Page 1

A Manageable, Efficient Health Services Instrumentation An AMEHSI Reductive/Oxidative Analysis Part 2 of 4 Parts However, as organizations strive for revenue and profit, as well as enhancement of prioritization of organizations over Humanity, there may be increasing influence of international or extranational entities upon local populations. Certainly, the influence of regulations in other Nations effect organizations whose products and services are provided in the United States. The inverse may also be true. However, increasingly, as profit-oriented omitting of the essential requirements of local populations may increasingly be the shortest path toward increased revenues, it may be extranational entities which are increasingly affecting local populations, often with beneficial influence instead of detrimental influence. Correlatively, international organizations and business may impart influences which may be of substantial decreased inclination to distinguish between the demographic characteristics of the population while also being focused exhibited higher volume and lower per unit costs than other such entities. Certainly, international organizations impart influence toward achieve international standards in Human and Social outcomes, some of which may not have always been assured even in developed nations. Again, while models of particular systems here pervasively are presented with a pathogenic context, this does not suggest that those systems are completely and only detrimental to Human outcomes. There should be a clear presentation here that once an extranational organization exhibits locations or becomes integrated into systems or requirements for conducting activity within a Nation, much of the factors which are different between intranational and extranational entities become managed. The presentation of differences between entities within Nations and those of Extranational nature, are that Regulations seems to have incipiently emerged as way of managing the detrimental aspects of the status quo, the profit priority of Private Enterprise and the propensity for systems to prioritize systems over Humanity, all of which differently interact within system of influence while producing different algorithms routines, goals and objectives. Thus, like the omitting of managing the precise incipient causal of mechanisms of detrimental outcomes presented in the Amehsi Specification which produces an influencable void in the Human Physiology, the same void seems to be exhibited in Organizations or nonHuman entities. Regulations seems to be finding ways of managing such void within Organizations with an acknowledgment that some of the most effective ways and producing those outcomes which are optimal may require asymmetric tactics. Often, Social Constructs can be the result of how such asymmetric influences produce outcomes resulting in system of inputs and outputs that produces manageable change while also being less than tangential. Often, the mechanisms at the political and geopolitical level which produce outcomes at the individual level for organizations and through these affect the void of less than optimal satisfied Human requirements, can produce those outcomes which are less than expected, produce outcomes which do not seem to be manageable, as well as produce remarkable ability to systematically achieve optimal objectives. Understanding the mechanisms which agents of change are used to and understand can provide clues such that system which translates this understanding and mechanisms into productive and beneficent change can be deciphered, implemented, monitored, and managed toward optimal Human outcomes. Such void in Human requirements and organizations potentiate the emergence of a “thing� which can live, grow, be affected, become shaped, and persist at physiological, social, cognitive and less than cognitive levels, while

also being potentiated as factors in goals, objectives, routines and algorithms. These ‘things’ could be given many names. However, these. ‘things’ are all affected by requirements and are all such requirements may be able to be simplified to Human requirements because systems of Humanity are inherently in service to Humanity. There, however, persists the potential that circumstance, perspective, cognitive cycles, cognitive artifacts, or behavior may be conjured within these voids to produce outcomes which are Anathema to Humanity inherently or cyclically. These analyses endeavor to provide a way satisfying those most essential Human and Social requirements, such that how any Entity which effects Humanity may not do so using susceptibility and may not project susceptibilities into a gauntlet of potential detrimental outcomes which enables nonhuman entities or entities otherwise to benefit from detrimental Human outcomes unless such benefit specifically determines and manages incipient causalities, thereby benefiting all whom are affected by detrimental outcomes. Considering the way in which pervasive aspects of systems interact at the local, regional, national, extranational and international level, there seems to be an inherent propensity to become fixated upon the level of systems which enables the most success for an organization, often considered as profit, revenue or prominence, such that incipient objectives of civilization are not any longer presented as priorities. Presented here is that such fixation exhibits susceptibility to become ephemerally or persistently anathema to either individual or plural beneficent Human outcomes unless somehow assure to prioritize Humanity individually and plurally. Although there may be inclination to suggest that such benefit always begins with the population local to the area in which an organization most incipiently has emerge or most particularly situates itself, market dynamics do not always present the opportunity for organizations or entities to provide benefit with such local coherence. The viability and ability to be a Going Concern exhibited by an organization or business might principally or wholly reliant upon a market which is not local or circumstance which is also not local to which its capabilities may be beneficial. Local, Regional, State and National entities often provide incentives to improve the ability to for organizations to share the benefit of their activities, products and services with the local area, although it is consumer decision making, pricing, the ability of local workers to afford the products produced by the organization, as well labor, health, local costs which are essential factors in enabling shared local benefit in any organization’s activities. Markets left to their own accord and whim, guided by craftiness of sales, marketing and consumer behavior management, may have propensity to produce outcomes which omit particular aspects of populations to produce pockets of inadequacy and destituteness. This presents why these analyses, finding no disjoint presentation of Life, Liberty, and Pursuit of Happiness separately from systems of the nature which include Democratic Activities in the Republic, pervasively present that there may have been an inherent presumption or intent for the United Nations to assure the ability of each among its population to achieve the Social and Human condition a condition upon which Free Enterprise would be enabled to thrive. Correlatively, these analyses considered and reviewed the principal Economic Systems exhibited in Nations, particularly developed Nations. Communism, among the most decried of these, was considered incipiently. These analyses found a disparity between the Denotative or precise Dictionary and Originating definition of Communism compared to that Connotative Definition which has emerged as the common concept of Communism. Succinctly, the exhibition of Oppressive regimes devoid of equality, innovation and progressive Humanism seems to have emerged supplantively that which Communism presents achievement priorities. Similarly, communism, pervasively before the civil rights act of 1964 and according to particular aspects of populations since 1964, may have been no less successful at achieving these Communist Priorities than other nations founded upon the Constructs of Liberty may have been at achieving their own Humanist priorities. However, the caveat is that Communism presents no openly presented and allowed omitting of particular aspects of the population, while other Ideologies may have until recently done so.

Communism is denotatively presented is the Establishment of a Society exhibiting common ownership of those factors to production which are not Human, including Machinery, tools, Natural Resources, Infrastructure, comparatively considered as the Instruments or synthesized factors used by Labor as well as the Subjects of Labor or Natural and Raw Material. Ownership of Labor itself is not included in this Communism concept all the ownership of labor was allowed incipiently in Nations founded upon the constructs of Liberty. The productive forces and the Social/Technical Relations and factors to production are considered to have symbiotic relationship in Communism, whereas Communism observes these to be inherently in conflict within Capitalism. Regardless of if these are required to be in Conflict within Capitalism or are less symbiotic because of inadequate Humanist Progression, seem to be subject to debate. However, the Communist Society is presented as the primary objective of Communism, being presented as the culmination of technological innovation, innovation in productive forces, exhibition of common ownership of the Means of Production, Free Access to the Articles of Consumption most easily defined as Negotiable Tender or Financial Instruments, abatement of Class Stratification in Society and Statelessness. Although accumulation of substantial levels of Empirical Wealth, and the exhibition of Freely Associated Individuals around particular Humanist Initiatives or Imperatives, as Communist Priorities seem inherently Capitalist in Nature, it is the Statelessness that seems to be the true disparity between Communism and Capitalism. The transitional stage of Communism in which Social Consciousness is presented to be emerging in populations, thus, seems to have been a hindrance in Human Systems pervasively and otherwise, since systems pervasively have a propensity to introduce division among Humanity, even exhibiting factions within such systems. Thus, an essential hindrance of humanist priorities is the management and understanding of how systems affect Humanity as well as a requirement to understand the inherent Nature of Systems of a Natural or Contrived Nature. The unfortunate Nature of similarities between systems of civilization and systems of physiology potentiate that Communism may not have been hindered because its empirical Humanist priorities are inadequate, since other than Statelessness which makes tangibly visible through monitoring and presentation of Human outcomes, the idealistic ultimate Communist Society is probably not too distant from Utopian Ideals of populations in Democratic Republics. However, Capitalist ideology and Democracies may not frequently present Ideals as objectives. Correlatively, there may not be any specific ultimate objective presented in Capitalism as well as Democracies, although the Republic, exuded from Charter, seems to be the practical set of those Ideals which are considered to be Achievable. There is no objective here to suggest that Utopian Ideals of Communism are achievable or that Communism is a more productive or beneficent context for Humanity to conduct its activities and being, although it is clear that every exhibition of Communism to the instance of this writing seems to have been commandeered by Factional activity as well as Geopolitical interactions that have substantially transformed Communism into a Fascist, Despotic or other versions of Tyranny. An essential difference between Capitalism, Democracy and Communism, seems to be that Capitalism provides no objective concluding status which society is being managed toward. Preventing Tyranny by an individual is a priority while Tyranny of the Majority over the Minority is pervasively exhibited in Social Constructs in Representative Democracies. Idealist Factional Aggregates are sometimes implemented instead of piecemeal negotiation of inclusive pareto Social Constructs in Democracies. Legislation is pervasively produced by those who are elected such that Social Constructs reflect competitive aggregates of Opinion that can be substantially managed by

focusing events, popularized priorities and an institutional agenda that meanders without producing a clear path to social improvement. Programs and Social Constructs are not required to exhibit improvement or even utility in the areas for which they have been produced. Social Constructs are not required to reflect or reveal the Idealistic Outcome or Statuses for civilization which they represent. Social Constructs may not be inclusively required to include program management that manages social constructs and decisions toward achieving ascertainable outcomes. Bureaucrats are aware of how essential program management may be, such that new Social Constructs may sometimes not be as effective at achieving ideals or as effective at achieving objectives as managing existing Social Constructs incrementally. Capitalism presents no concluding objective status, thus, increased priority of Profit and increases in prices for any reason possible, occurs unhindered in an endless cycle. However, Capitalism, unlike Communism, is an Economic System or a Modality by which Economics Systems persist as largely unmanaged, while Communism includes Economic, Political and Social Nuances, allowing more complete meeting of Human requirements. Such inclusive capabilities of Communism make it interesting that its implementation has been somewhat pervasively considered as Anathema to Humanism. Even those entities providing essential products and services are allowed to prioritize profit in Capitalism because it includes no Social or Political Component, thereby being inherently Apathetic to the Human Condition. Fortunately, Western Civilization has observed Socialization emerge in which a mix of priorities and entities providing services has mitigated pure Profit Motive and mitigated the inherent potential for Systems to Prioritize themselves. Thus, the ability of Humanity to be turned upon itself can be can be essentially useful in preventing Social, Political and Humanist level organization of Populations to assure that they are adequately prioritized. Since 1961, there are likely endless permutations of reason that have prevented Homocysteine, TMAO, iNOS, uNOS, PEMT, and Choline Kinase from being adequately prioritized. Geopolitical strife, Geopolitical Conflict, requirement for Employment, Jobs, Social Stability, and probably other endless reasons for not abating Human Demise. These inherently exhibit how systems and complexes cause Humanity to be turned upon one another and even how each Human may be caused to have their economic success compete with their own duration of Vital Being. However, clearly, the Checks and Balances Systems has been constructed not as way of maintaining the status quo, instead enabling systems to monitor Human outcomes, provide information for analytics, understanding and productive, beneficent change, as well as assure ever improving aspects of the Social Condition as well as Human Condition. It is the hope of these analyses, that Humanity become reasserted as a Priority in all systems of Civilization, Particularly Representative Democracies, Republics, Capitalist Economies, Communist Economies, or any Sociopolitical, Socioeconomic or Political arrangement which may affect Humanity. The Limitations here, however, seem to be that there is no objective concluding empirical Utopian outcome which Democracies or Capitalism present, other than the Charter of the Republic. The Constitution, in this context, provides for Life, Liberty and the Pursuit of Happiness, as well as the General Welfare, but does not specifically exhibit Food, Shelter, Homes, Jobs, Health Services as well Health Services which reflect the capabilities of the immediate era. Other nuances of the Constitution seem to have become readily included permutative aspects of reason which are distant from the language of the Charter. The most basic of assurances required for Human Populations, thus, are not

provided priority in assurance. The very first priority of Humans which aggregate themselves to conduct Vital Being in Community among one another includes assurance of Food, Shelter, Water, Health, Welfare and Safety. It is a mystery how these can be inadequate in any aspect of civilization, particularly in association with a Republic, Democracy, Western Civilization or any Civilization otherwise. If each Branch of Civilization’s Systems, as well as systems pervasively, are not made acutely aware of Roemer’s Law, how this correlated to Homocysteine, TMAO, iNOS, uNOS, PEMT and Choline Kinase, as well as How health status, behavior and consumer behavior are determined by interactions within this Molecular Physiology and Roemer’s Law Paradigm, how is it possible that civilization produce change other meandering between the most widely regarded whims of the immediate era? How meaningful is even the most responsive tax legislation when 2,600,000 individuals incur demise in the duration which the Nation was required to focus its resources in achievement thereof? An ephemeral Taxation change, for instance, although popular, may not be as beneficial for the 15,000,000 whom won’t be able to receive the benefit of such responsive social constructs because of the level of demise potentiated in such duration. These analysis, present, hope and have an objective for those 15,000,000 to not be so detrimentally affected in such regard. There seems to be required or the possibility that individual organizations, systems and businesses, conduct their operations with priority focused on Humanity, including the health, financial, shelter status, and other characteristics of those which are employed by such entities. It is not suggested that pure Communist Society is achievable, since every permutation of communisms seems to have emerged into Sociopolitical outcomes which Western Civilization considered to be less than optimal. Although Communism suggests that it is Capitalism which hinders Communism progression toward the Pure Communist Society, these analyses suggest that Western Civilization, although not suggesting that the State is Ephemeral and using the state as manner of preventing factional hindrance in achieving social Ideals, may have a more trusting perspective of Human Nature. Communist Society has not presumptive disdain for Human Nature although the authoritarian regimes which have thus far utilized communisms, certainly seem to have such less than optimal regard for Human Nature which may be the result of Factional activity. Regardless, the State seems to be integral aspects of Democracy, and the Republic in Western Civilization, although it is clear that Western Civilization monitors the State itself by understanding how Human outcomes are affected and exhibiting the potential to produce responsive, beneficent, productive and effective Social change. Similarly, factions are potentiated which emerge without Humanist priority or with falsely Humanist priority, often obfuscatingly masquerading as Nationalism, Populism, Agrarian Priorities, Libertarian Priorities or alignment otherwise with opportunities for improvement in civilization that may be required or that which might be merely promoted to the Intuitional agenda through Elitist Agenda. Factions do not require agenda of Merit or agenda that prioritizes productive and beneficent Humanist outcomes. Factions have emerged sometimes merely because an individual has a priority to obtain power and factions as well as their priorities, routines and algorithms emerge through interactions with competing influences. Leaders, of such Factions, then may emerge in processes that are not too distant from Fascist or Despotic Autocracies which have been detrimental to Humanity in other eras. The safest position within such Faction may be the leadership position while the exhibition of group think dynamics and scapegoating makes such leader the subject of victimization, falsely autocratic power, and able to be left holding the bag when detrimental, less than beneficent and less than productive outcomes emerge.

Although Laissez-Faire is often regarded as ‘Leave it Alone’ economics win which the Market’s invisible hand determines outcomes, more precise interpretations suggest that Laissez-Faire suggests “Leave it to Us.” An Active role in assuring stable and adequate markets is thus most precisely inferred from Free Market Capitalism instead of a Market in which the activities of those endeavoring to produce a business determine market dynamics. Market dynamics, however, in Capitalism, may integrally affect Human outcomes unless a mixed economy is contrived, suggesting why many Western Sociopolitical and Economic Systems are Social Democracies which assure stability, scalability and availability of those products or services which are particularly essential the Social, Human, Behavioral and Physiological condition.1 It is amazing how the presumption of interventionless and unmanaged economic systems has pervaded as a myth of Apathy exhibited by A Most Prominent Nation of the Western Hemisphere in such regard, for virtually every principal decision-maker in any business required to produce a profit might be able to contrive a circumstance in which their decisions could be construed as being anathema to Human priority. Certainly, the management of Markets and the business environment encompassingly would be required if only to prevent organizations and businesses from being required to consider such decisions which are anathema to any individual or any plural aspect of Humanity. Particularly, Capitalism is presented as an Ideology in which private ownership of the Means to Production is exhibited along with For Profit Priorities characterized by Private Profit and Factors with Inherent Value, Labor being remunerated with Wages, Free Association at the Exchange level between Buyers and Sellers, and Pricing using variables schemes and Competition although pricing is not considered to be the only competitive context between producers of substitutes. Thus, capitalism does not include in its Ideology any relationship between the availability of Natural Resources required to satisfy essential Human requirements and the ways of assuring or providing such factors, except for Private Enterprise. The Constitution of the United States does not suggest or imply Capitalism as its priority. Comparatively, the General Welfare, is a primary Priority presented by the Constitution while Life is first among the priority objectives for the Declaration of Independence. There is some difficulty considering is plausible and accurate how such priorities of have become obscured in the permutations of Legislative Constructs and Decisions regarding Human outcomes, including exhibition of constructs which have the potential to abate Vital Being. Clearly, Human priority seems to be the central constitutive priority of the Constitution of the United States and the Declaration which potentiated the construction of the Constitution. However, unlike Communism, Capitalism is disjoint from both Democracy and the Republic, while the Constitution Unifies Democratic Processes with the Republic in Systems of Civilization within the United State of America. The Republic with its Charter Document, like the DNA of an Organism, and States like the variability of the way in which DNA is expressed in different Tissues, have their Charter Documents translated into constructs as well as amended or repaired by Legislate Constructs, while the implementation of the Phenotype is conducted by other Branches of Civilization’s Systems and review Human outcomes as well as Legislative outcomes and decisions regarding these are considered in a reviewing Branch of Civilization’s Systems. Each of these, it seems, were intended to have Human Priority, individually and Plurally. Systems, thus, seems to have been intended to monitor, assure, present and understand Human outcomes such that Charter or DNA might be progressively understand in how it shapes outcomes, as well as how the systems which translate Charter or DNA are effective in producing those outcomes which are beneficent and optimal. Like diseases, Human outcomes which are detrimental, seem to have been intended to be uncoupled from the Individual, as Acts, such that Acts themselves as well as those conditions which cause or enable 1

“Lettre Au Sujet De La Dissertation Sur Le Commerce Du Marquis Du Marquis De Belloni" Journal Oeconomique. Page 111.

detrimental outcomes can have empirical consideration. The Human aspect of detrimental outcomes are to recently emerged in the progression of systems as well as are of too diverse potential for shaping and influence to be considered causal, while 99 percent of causality seems to be temporally, spatially and tangibly disjoint from the outcomes observed at a Human level. This interpretation of the Intent and Priority of those Legislators which produced the Charter Documents for the United States is the product of analyses of the Status Quo with those Incipient and Empirical Priorities which were included. Certainly, allowing the exhibition of 2,600,000 instances of demise in one annum to preserve the prioritization of Profit and assure the exhibition of the Status Quo with regard to outcomes associated with Systems of Civilization, seems to have been distant from the potentialities projected by the Framers of the Constitution. Such a level of demise would have been destabilizing to the Nation, during the era in which the Constitution of the United States was constructed and it is somewhat assured that General Welfare, Life, Liberty, and Pursuit of Happiness would have been highlighted, focus upon and reiterated by those whom participated in the Construction of the Constitution of the United States. If systems could result in both the understanding of such imperatives and potential for pervasive productive, beneficent outcomes, as well as allowing of these to not be alleviated, prevented and reversed, then systems of civilization require temporally and substantively coherent review to assure that Humanity is not being commandeered to the Self-Prioritization of Systems as well as the Profit Priority of Private Enterprise, including the algorithms and routines which systemically assure such priorities. The Declaration within the Declaration of Independence clearly observes that those achievements possible in Nature, produced within the Systems of Systems which encompass all things inclusive of those influences regarded in Philosophical works emerged after Humanity began the socialization process from Nature, are continued to be assured to Humanity, regardless of the Sociopolitical Context in which Humans may find themselves. The declaration clearly relies upon this observation in obtainment of standing to present the declaration. Similarly, the Preamble clearly asserts equality among Humanity with regard to those assurances and protections presented by the Republic with such assurances being unable to be abridged and with such protections including Life, Liberty and the Pursuit of Happiness. Life, is required to in achievement of Liberty, and both Life and Liberty seem to be essential aspects in the Pursuit of Happiness, all of which are unable to be abridged. Such assurances flow not from any construct or sociopolitical context, but from Nature. The preamble clearly presents that Sociopolitical entities which manage populations derive their abilities to do so through the acquiescence by effected populations, such that no Tyranny of the Minority constitutes such consent. Even consent, acquiesced to, becomes nullified by the emergence of Tyranny for such represents a scheme by which deprivation is obfuscated and made obscure in detrimental reliance of Acquiescence, transforming productive inclusiveness into a game of chance which, if refused, results in inherent deprivation. Monolithic Cultural, Social, Political, Economic and Philosophical Constructs, thus, are inadequate in their interactions among the competitive sociopolitical, geopolitical, cultural, social and economic contexts because they inherently tyrannize as aggregate constructs, requiring piecemeal dissection to determine inconsistencies or competitive intricacies such that these may analyzed, considered and adjudicative to better understanding as well as pareto decision making. The manner which social constructs may now be produced certainly seems to be inconsistent with the priorities presented in the declaration of independence and the distance in reason, requirements to gain standing for

review of such constructs and temporal disjoint nature in which such review typically occurs impairs the ability of Checks and Balances to assure the foundational objectives of the Constitution of the United States which include Life, Liberty and Pursuit of Happiness. The Declaration clearly observes the detrimental nature of producing legislative sessions or decision making at unusual locations or nuance, exhibited purposefully in overly complicated contexts or venues, with increased distance from the incipient locus of information or distant from the locus of reason. This intent of fatiguing the population and decision-making entities into compliance seems specifically Homologous to the manner in which Social Constructs and their effect to Humanity require esoteric nuances of reason to obtain standing for review even when the outcome clearly is disparate from those intended by the Declaration of Independence as well as disparate from those assurances and protections provided by the Constitution. The Declaration clearly exhibits that the States ought not be exposed to the detrimental effects of the Geopolitical contexts of the earth as well as other potential detrimental influences, including how these may cause civil deterioration within the Nation. Specifically, this assertion is precisely Homologous to the way in which Global Economic Systems may be stimulating the nation to abdicate the Life, Liberty and Pursuit of Happiness of their most Vulnerable Populations in pursuit of economic Hegemony and competitiveness in Global Markets. Instead of protecting the population to assure that Social, Human, Behavioral and Biological condition are achieved, thereby enabling a safety context outside of which such Global Economic Systems may be of substantial benefit, substantial aspects of the population are allowed to be subjected to Global Competitive activities that impair purchasing power, increase interests, increases prices through intermediation which could be considered taxation by Quasi - public or Non - public entities without representation in the decisions made by such entities, which make essential services and products unable to be obtained in a practical manner and which transform behavior to exhibit Status Frustration with a focus on impractical unnecessary factors along with inadequate priority for those factors required for Social and Human condition. The essential observation with regard to the Declaration of Independence does not seem to be how outcomes in modernity may have diverged from the requirements produced from those incipient detrimental conditions which were an impetus to the Declaration and the emergence of Constitution. The essential assertion seems to be that exhibition of those detrimental circumstances and factors which were impetus for the Declaration of Independence, as well as inadequate resolution of such circumstances and factors, might also impair the assurance Life, Liberty and Pursuit of Happiness. Protection of the population from external interests and priorities is not Protectionism, instead being required as incipient objectives of the Declaration of Independence while being foundational aspects of Constitutionally Assured Life, Liberty and the Pursuit of Happiness. Similarly, mitigating the way in which permutative nuances of complexity may have emerged which enable Tyrannizing Social Constructs and Social Constructs which abridge Constitutional Assurances to require esoteric, analytically distant and temporally distant criteria to enable their review, including requiring such permutations when a Bona Fide abridgement of Constitutional assurances are exhibited. Similarly, the allowing of Global Economic Systems and Business to affect obtainment of those factors which constitute the Social, Human, Behavioral and Biological system seems to circumvent the impetus or the Declaration of Independence, Circumvent constitutional protection, constitute taxation when the price of such factors are effected, as well as constituted taxation without representation when purchasing of such factor s effected by Global Interests does not include participation in decision making by such entities. Again, the threshold for such influence seems to be the

level to which Life, Liberty and Pursuit of Happiness might be affected, suggesting that those factors which constitute the Social, Human, Behavioral and Biological condition may have been intended to be protected from Nuances of international Business and the Global Economic System. A world in which systems may predominate by focus on the observable, attributing of outcomes to those who are proximate to outcomes without considering pervasive ancillary and exogenous factors which, if not exhibited, make particular detrimental or beneficial outcomes impossible, produces difficulty in improving understanding that would Homologously improve systems, outcomes and potential for improvement of the Social and Human Condition. Similarly, like populations expending centuries understanding and managing inadequacies in water suddenly emerged in a valley without acknowledging that the Water flows from the mountains which have been impeded by a constructed structure, it is difficult to present, analyze and alleviate causality as well as improve outcomes. Such difficulties seem to be able to result in attributing causality of such inadequacy to those whom obtain more water than others, when attributing causality to those who drink more water than others may be causally, temporally and analytically disjoint from why such inadequacy is exhibited. Humanity might be caused to turned upon itself as a result such disjoint critical analysis, reasoning and decision-making. Illustrative of such inadequacies of perspective, the Amehsi Specification clearly, in earlier analyses, clearly found that three factors were converging to produce particularly instances in which the highest levels of adverse health events, particularly those potentiating sudden emergence of demise, were occurring the later aspects of the morning and in the early evening Hours each day. Trimethylamine-N-Oxide, the principal causal factor in emergence of sudden adverse health events, complications, perioperative complications, emergence of accompanying conditions, as well as demise or culmination of demise, was found to be increased in during these instances of the day resultant of the obtainment nutritional factors without Probiotics, management of γ-butyrobetaine/4-Trimethylammoniobutanoic acid/ (3-carboxypropyl)trimethylazanium Management capabilities such as Olive Oil or Balsamic Vinegar, as well as specifically resultant of less than optimal digestive pathway Microflora. However, it was also found the peak usage of Power and sometimes peak Production of Power, were precisely homologous to the exhibition of Demise at these instances. The Amehsi Specification has also found that there seemed to be lag among samples according to Time Zones clearly suggesting that power and energy played roles in the exhibition of sudden Demise in vast areas of the United States. These analyses however, determined that detrimental behavior which potentiated sanctions in the United States exhibited strong similarities to these patterns of increased Power usage, Power Production and demise. 2 3 Moreover, although the observation of similar patterns in consumer behavior, if correlated, might be merely the result of Patterns of Consumer Work activity and availability for Lunch as well After the Working Day activity, a most substantial finding seems to be an analysis which suggests that consumer purchasing decisions are pervasively determined by less than conscious level activity.4 Thus, the hours at which consumer decision to obtain factors to alleviate Homocysteine levels results in increased levels of TMAO or alternative result in substantial increases in 2 3”detrimentalBehavior”-by-time-of-day/ where Detrimentalbehavior is a more specific word for behavior which potentiates sanctions.“those exhibiting Detrimental Behavior” -prowl-the-streets word for behavior which potentiates sanctions.


where Those Exhibiting Detrimental Behavior is a more specific

Homocysteine because Choline may not have been obtained nutritionally, are correlated with demise, increased levels of power and energy usage as well as power production, while consumer activity may be correlated to such instances from functional perspective. Furthermore, consumer decisions seem to be largely conducted at less than conscious level, confirming Keynes’ Animal Spirits theory of Consumer Behavior although such Animal Spirits have been synthesized, produced and conjured up upon demand in the Subconscious of consumers during purchase decision making. Pivotally, the decision making with regard to consumer activity cannot be distinguished logically, reasonably or causally from the decision making which occurs with regard to behavior and nutrition. Hardly any individual is not aware of how a patterned noise or influence, such as a drum, can enhance focus or produce Pavlovian associations to produce behavioral correlates. Similarly, hardly anyone has not been alone in a building and observed auditorily a sudden increase in power that is correlated to refrigerator exhibiting Higher levels of Noise or Energy Infrastructure emitting higher levels of Noise. Hardly anyone has not notice that they have particularly less than conscious inclination produced resultant of a particular stimulus. Humans have become immersed in fields and influence which are competing for their outcomes, sometimes without regard to if it such outcomes are beneficial, productive, detrimental or less than productive. The way in which the Homocysteine impaired, stimuli compartmentalized and conscious activity compartmentalized physiology results in a susceptibility to exogenous produce inclination and behavior, particularly to exhibit those outcomes beneficial to Profit Priority of Private Enterprise and those outcomes beneficial to Prioritization of Systems by Systems. The constructor of the Structure which impedes the water which would otherwise flow into the Valley, thus, may be Homologously selling bottles of water to the population in the valley and collecting money from those who have sanctions applied to them for drinking too much of the Water Supply. Humanity, then, may have been caused to wander around a once lush valley, transformed into a desert, while they are caused to be turned upon themselves because no one can consider or include in their analyses that the waterways which flow into the valley have been impeded or even exist. The potentially that Power Infrastructure, Communication Infrastructure and other influence may be being utilized to change behavior in a directed manner, including merely increasing these when Hospitals and other entities managing detrimental Human outcomes become inadequately utilized or become too empty, has to be considered in these analyses, even if the occurrence of such Patterns are coincidence and including if such patterns are result of cyclical interactions among these factors. However, again, these analyses endeavor to provide practical perspectives that include inferential reasoning, particularly when causal mechanisms and causal links have emerged. Thus, again, there is the possibility of presenting that participation of Power and Energy, as well as Communications Infrastructure in exhibition of Sudden Adverse Health Events, Complications, Demise and impairment are widely exhibited as difference in Health Outcomes exhibited by the most incipient populations of Humanity compared to those which are exhibited in Modernity. Several foundational presumptions emerge in such regard. Among them is the observation that discomfort in Physiology seems to be pervasively useful in allowing an organism to determine that it has become impaired, changing behavior and or even as participatory mechanism in alleviating an emerged detrimental physiological factor. However, it is the persistent exhibition of discomfort after a organism would have invariably changed behavior and the exhibition of such discomfort to a level which such inflammation becomes the principle mechanism of progressing detriment which seems

puzzling. Regardless of if one considers evolution or design of Humanity to be exhibited, none of these explains a physiologically and behaviorally useless exhibition of discomfort. The possibility that health services or healthcare products requiring consumer purchases or requiring the exchange of financial resources, particularly those occurring on a fee for service basis or particularly those occurring on a product purchase transaction basis, along with the exhibition of determinental outcomes which sustain substantial aspects of the Economy, when presented in context of the 50 or 60 Hz Electromagnetic Energy field which the research suggests encompasses civilization, all compellingly potentiate that discomfort and Detrimental outcomes may be cyclically produced by these dynamics. Certainly, iNOS, changing of the shape of cellular receptors, iNOS causing cellular structure to exhibit shape similar to Ameobas, other inflammation pathways and DNA impairment result of such fields as well as resultant of other detrimental influence, prevents such a possibility of cyclical potentiation of detrimental Human outcomes from being empirically refuted. Although it is acknowledged however that without such influence, there might not be adequate discovery or acknowledgement of such influences to physiology, there can be clear logical, physiological and biological reasoning that questions why would such biological capabilities have emerged, persisted or been produced in Humanity if these were intended to culminate in demise? Certainly, this is Anathema to all of Biology, that processes designed to notify Humanity of its own detriment might become causal to progressed, progressing and demise potentiating pathology. These analyses suggest that such inflammation may be pervasively enhanced, persisted and even produced by fields, particulate matter, and other influences produced by systems of civilization. Thus, it is imperative for Humanity to continue to advance and innovate while integrating conscious consideration of product and service safety as well as considering how activities, products, services effect the outcomes of their customers as well as those whom perform activity or roles to the organization’s benefit. Illustratively, although an advancing Financial and Securities Market with expanding values of securities might possibility benefit all whom invest and participate, these may not have always been as pervasively beneficent. Financial markets and possibly technology are among those markets which can be optimal because activities do not require detrimental outcomes, although certainly those organizations that manage detrimental outcomes such as detrimental health status are increasingly transforming their interactions to produce beneficent, assured optimal outcomes among their patients and those whom perform to benefit of such organizations. Certainly, there are pervasive industries which do not require detrimental outcomes to occur otherwise. However, Securities markets have incurred detrimental outcomes in other eras and it is systems which must assure that regardless of outcomes occurring in the systems, organizations and business of civilization, the Social, Human, Behavioral and Physiological condition are assured. Advocating and advancing the interests of investors and investment customers can be as essential as Health status because in some instances these factors are what may be financing access to care. However, a somewhat pervasive inability to adhere to pareto outcomes in a retreating Financial and Securities Market, should not produce destituteness or destabilizing influence to populations and to those organizations which provide opportunities for Humanity to obtain essential financial resources. Systems of civilization may have a priority in producing safety net within which Humans obtain the factors required for adequate quality of Vital Being and optimal duration of Vital Being. Continuing to understand and manage the effect of organizations and systems of civilization enables improved understanding of the limitations to Human

achievement, including those detrimental influences produced by Civilization. Certainly, iNOS and the effect to Physiology from particularly fields have to be included as those factors to be managed, while systems of civilization otherwise might optimally begin to determine and mange such detrimental influences such that Systems, Markets and Businesses become more free to innovate and progress while integrating Human priorities more pervasively and easily into their priorities. Although this could be disregarded as being among those mysteries of the Universe, the exhibition of iNOS and how it becomes transformed into a principal detrimental mechanism and enabler of pathology emerges clearly as a causal and even mechanistic link between persistent levels of discomfort, impairing levels of discomfort and progression of pervasively pathology. Power, Energy and Communications infrastructure, as well as Magnetic or other Energy fields, including Particulate Factors in the Atmosphere or Water, all seem to comprise a system of assured pervasive exhibition of iNOS associated inflammation. These may be why earliest aspects of civilization seem to have been more capable in enduring particular and sometimes more egregious conditions, influence and impairing circumstances since they were not required to manage what might be substantial influences in ambient influence which cause iNOS associated inflammation. These analyses found iNOS and correlated uNOS which emerges to Peroxynitrite and other reactive molecular species to be participative and concluding aspects of almost every Pathology. Beginning with use of Nitrites and Nitrates to preserve Food, Humanity may have pervasively transformed its potential for inflammation and enhanced physiological impairment. The implementation of ICD-9 in 1979 transformed Health by causing the conscious association of and producing of connections between disease and molecular level causality, although this continued to not achieve the level at which Human Disease had already been correlated to PEMT dysfunction and Choline Kinase upregulation within systems of critical thinking and reason of the United States. The way in which ICD-9 inherently caused action in correlating Disease to causality while circumventing the presumption that disease did not have precise causal mechanisms, however, seems to cause similar influence to behavior that was no accompanied by similar progression in understanding the molecular and systemic causal factors to detrimental behavioral outcomes. Indeed, the DSM and ICD systems of diseases and conditions persist as different entities even in Modernity. The context of Social Constructs, Philosophical and Cultural Nuances as immovable, impermeable aspects of Impedance to such disparity has to be presented because pervasively the population is not invited, allowed or even permitted to benefit from intricate analyses of specific aspects of such constructs and influences in civilization. The result became a slow undoing of community, regional and national level Social and Human conditions exhibited in the 1980s that may have challenged the philosophical status quo of the Nation and certainly shook the Geopolitical Status Quo at the conclusion of the 1980s. Perhaps the events of 1979 caused there to be an aversion to Humanist consideration of detrimental behavioral outcomes. Regardless of if the events were a Red Herring to allow the continued primacy of Systemic Influence or Bona Fide instances of Human Progress powering through nuances of stagnation which can only be explored here cursorily, the Amehsi Specification endeavors to make such nuances accessible, cognitive. Analytically, and conceptually, to any aspect of Humanity. This, hardly, might be considered to be among the victories which Humanity snatches from the deplorable conditions and circumstances that Humanity has been caused, heretofore, to endure.

Melanin Synthesis can be impaired by Methionine Sulfoxide and H2O2, although a more comprehensive consideration of Melanin changes may include Uncoupling of Nitric Oxide Synthase which produces increases in both Methionine Sulfoxide and H2O2, as well as impairs Tyrosinase along with numerous other impairing Oxidation of molecules in the Melanin Synthesis Pathway. Clinically, Skin is comprised of Stratified Squamous Epithelium known as the Epidermis which may principally be constituted of Keratinocytes while the Dermis exhibits Vascularized Connective Tissue. Melanocytes are exhibited where these two Skin layers integrate and provide Melanin for both Skin and Hair in a process which includes exhibition of Tyrosine, performance of Hydroxylase activity by Tyrone Hydroxylase, exhibition of DOPA, performance of Oxidase activity by DOPA Oxidase, emergence of DOPA Quinone, alternative exhibition of either Dopachrome through DOPAchrome Tautomerase activity or Cysteinyl – DOPA through Glutathione or Cysteine activity, followed by either Cysteinal – DOPA progression toward Tyrosine – Associated Proteins to Alanyl – Hydroxy – Benzothiazine producing Pheomelanin which promotes Hues ranging from Yellow to Red or followed by DOPAchrome being directed upon a path toward DHICA Oxidase/TYRP1, to 5,6 - Dihydroxyindole – 2 – Carboxylic Acid (DHICA), Indole – 5,6 -Quinone Carboxylic Acid, Black Eumelanin as well as upon a path toward 5,6-dihydroxyindole (DHI), Indole – 5,6 – Quinone, Brown Eumelanin. However, the literature observes that DHICA polymerizes to exhibit Brown Melanin while DHI polymerizes to exhibit Black Melanin through DOPAchrome Tautomerase Activity, Chemical Synthesis or Spontaneously. A Study observes that DHICA Brown Melanin was Soluble in Aqueous Solutions at pH 5 whereas DHI Black Melanin was insoluble and produced precipitates. DHI and DHICA together, with more DHICA than DHI also was observed to produce limited DHI Melanin Precipitation while increasing the level of DHICA soluble Melanin. DHI and DHICA as suggested, therefore, to Coprecipitate and DHICA Melanin below pH5 is suggested to potentially precipitate resultant of Protonation occurring at Carboxyl Groups.5

The Michaelis Juncture in Melanin Synthesis seems to be Tyrosinase, suggesting that indeed Peroxynitrite and Uncoupling of Nitric Oxide Synthase can be substantially participative in Melanin associated Oncology or other pathology, while also changing the levels to which Melanin Synthesis occurs. Melanin synthesis occurs within the Melanosomes which are Centrally located Cellular Organelles in the Melanocyte Cytoplasm followed by transfer of Melanosomes to the extremities of Melanocyte Cellular Dendrites. The Dendrites perform transfer of Melanosomes to Keratinocytes. Keratinocytes exhibiting Melanin persistently exhibiting Mitosis at the Epidermal to Dermal Junction, also persistently push previously mitotically produced Keratinocytes toward the outer or upper areas of the Epidermis, Epithelial Surface. Lysosomal Catabolism of Melanosomes occurs as the Keratinocytes move toward the Epithelial Surface, dispersing the Melanin, and potentially producing differences in Skin Color or Hue Intensity correlative to the level at which Melanosomes have become Catabolized.

Thus, a number of Genetic, Transcriptional, Epigenetic, Post – Translational, Metabolic, and Environmental factors, such as level of Ultraviolet Energy which stimulates Melanin Synthesis, contribute to Pigmentation Phenotype which can include directing of Tyrosine toward Melanin or toward other pathways, levels of Yellow/RED, Black or Brown Melanin, intensity of these, and how much Melanin Synthesis Occurs, including exhibition of conditions in 5

Digital Object Identifier 10.1111/j.1600-0749.1992.tb00007.x

which H2O2, Oxidation, Peroxynitrite activity, or other factors change characteristics of Pigmentation exhibiting Structures. There are interesting nuances of these factors, such as the fact that particular Gliomas such as Diffuse Gliomas, can exhibit Oncology Cellular Entities which emit their own signals through protruding Dendrites which then stimulate cellular migration, increasing understanding of a nuance of Gliomas which are known to have substantial association with Epidermal Growth Factor anomaly. These suggest Inducible and Uncoupled Nitric Oxide Synthases may be participative in a number of conditions while also suggesting that Tyrosine therapy to prevent Gray Hair can remediate more than merely Topical Aesthetic Conditions.

The literature differently presents Melanosomal Melanin Synthesis compared to Peroxisomal Neuromelanin Synthesis. Heme Oxygenase – 1 is increased when Melanosome exhibiting cellular entities are affected by both Ultraviolet Energy and increased levels of H2O2. Some analyses present that Pheomelanin and Eumelanin determine Skin and Hair color through level of expression of Pheomelanin and Eumelanin Genes Specifically. A review of the Uniprot Gene Database and Genetics Home Reference at the National Library of Medicine do not exhibit Eumelanin or Pheomelanin Gene Constructs. The MC1R Gene is exhibited and is translated into the Melanocortin 1 Receptor which produces Eumelanin when activated at the Melanocyte Cellular Surface and Produces Pheomelanin when Inhibited at the Melanocyte Cellular Surface. The Melanocortin 1 Receptor is a receptor that produces intracellular Signaling Cascade resulting Eumelanin Synthesis compared to Pheomelanin Synthesis when inhibited, suggesting that the level of MC1R activation determines variable Melanin Synthesis Phenotypes. Melanocyte Stimulating Hormone activates Melanocortin 1 Receptor, and the MC1R Gene does not exhibit Introns such that there is no variation in its transcription that is considered typical while levels of transcription, instead, can vary along with changes in Genetic Transcription or increases or decreases in Transcription resultant of commandeering of Transcriptional activity for Inflammatory Signaling. Variation in the Genetic Structure of MC1R can cause variation among the different Hues and Colors exhibited in the Range of potential Eumelanin and Pheomelanin Phenotypes. Proopiomelanocortin Protein is differently proteolyzed to produce Alpha, Beta or Gamma Melanocyte Stimulating Hormone, occurring the Par Intermedia of the Pituitary Anterior Lobe, Keratinocytes resultant of Ultraviolet Light Exhibition, results in Melanocortin 1 Receptor Activation, Potentiates Melanin Synthesis, and explains developmental variations in Hair, Eye and Skin Hue as well as Color. Alpha Melanocyte Stimulating Hormone also inhibits appetite as well as increases Sexual Arousal. 6 7 The literature is increasingly observing the participation of anomaly in Catalase, H2O2, Super Oxide and Peroxynitrate, including uncoupling of Nitric Oxide Synthase as factors in changing of Color of Hair along with Progression of Phase of Vital Being. Thyroid Hormone Levels are also known to effect Hair Color, particularly when becoming decreased in adequacy.8

The transformation of Health Services Personnel to become integrated into Humanist Progressive Change that could only be Socio-politically presented as Anathema to the United States Interests according to the perspectives of some aspects of the Population, along with the transformation of Socio-politically detrimental perspective being 6 7

PMCID PMC3544422 Genetic Association of Catalase and Antigen Processing Genes with Vitiligo Susceptibility Genetic Association of Catalase and Antigen Processing Genes with Vitiligo Susceptibility. A Dissertation Presented to The Graduate School of The University of Florida in Partial Fulfillment of The Requirements For The Degree of Doctor of Philosophy University of Florida. 2003.


transformed to advocate the United States Interests, however misguided such objectives and actions might have been, presents clearly that systems have no inherent ability to consider Humanity Individually and plurally as essential aspects of Civilization as well as being essential in managing interactions among all aspects of the Universes. Clearly, the invitation to disregard the vital being and essential nature of others among Humanity, potentiates and often necessitates disregard for the Vital Being and Essential Nature of oneself in such regard. The permutation of projecting of interests, groups and associations permutatively into and through one another, potentiates most a distancing of Humanity from itself, cognitively, social, economically, politically and biologically, such that Humanity is being inclined to act without regard to itself individually and plurally through levels of abstraction dominated by psychoses. Artifacts which are specifically produced to impart detriment to others are then produced, made availability, and allowed to be exhibited among progressive circumstances and conditions of detriment which are able to be prevented, alleviated or reversed, and, instead, are not. The result seems to be increased propensity for Human outcomes to be controlled by influences distance in location, space and time, including the Algorithms and Priorities of the Self – Prioritization of Systems as well as the Algorithms and Priorities of Profit Motive of Private Enterprise. The Events in November of 1979 in which the demise of Five Individuals Occurred were not likely to have transformed Local Geopolitical or Socioeconomic Systems, much less regional or National Systems, regardless of if such instance of demise had occurred or had not occurred. These instances of Vital Being were expendable, like all aspects of Humanity, to the priorities of systems managed by Artificial Intelligence emerged from Algorithms and Routines at largely unmanaged levels in the Prioritization by Systems of Systems themselves as well as the Profit Motive of Private Enterprise. Such prioritization, like the presumption that demise is required with the Span of the Human Experience, pervasively may persist unquestioned while generations of Human are caused to emerge and no longer be amid the primacy of these constructs which have been allowed to pervade Humanity. Supply Side Economic Theory, thus, reintroduced Say’s Axiom which suggest that Supply creates its own demand. John Keynes Presented this Axiom as an aspect of Keynesian analyses although the Supply Side Economic Theory is considered to not be a Keynesian Theory. However, Supply Side Economic Theory did exhibit clearly that Supply produces its own demand as an increase in production of goods and services then began to become a principal determinant of demand instead of Human requirements being a principal determinant of demand. All manner of less than productive social phenomenon then emerged including detrimental outcomes such individuals incurring detriment when others deprived took from them articles of clothing, shoes, or other factors which demand characteristics had assist in becoming more important than Human requirements. Keynes ‘Animal Spirits’ which described consumer behavior that had very little to do with Human requirements became easily able to be associated with Roemer’s Dynamics. Systems then became transformed to manage the change in behavioral and socioeconomic outcomes while the exhibition of Quotas that attributed causality to individuals for their own accounts merely increased the propensity for such outcomes to occur. Correlatively, health conditions, compulsive, and addictive statuses became effected also by a rise in consumerism with Supply Side Theory which was taken advantage of by the emergence of logistics and supply for those factors which satisfied compulsion and addiction. Such factors, regardless of if these were biomedical capabilities, biomedical capabilities which prevented compulsion or addiction, or factors which were of substantial detrimental nature in any regard, did not include an explanation of Choline Pathways, the pathways presented by the Amehsi Specification as well as omitted explaining to populations how such pathways, when inadequate, may

constitute compulsion and addition. Thus, because Homocysteine was being misinterpreted, and the essential Amehsi Specification factors were not being publicly presented and proactively managed, consumption of Health Services and Requirements of Systems burgeoned. Unfortunately, because detrimental behavior, compulsion, addiction and detrimental subcultures which supply factors to remediate, abate, or persist such status utilize precisely the same unacknowledged metabolic and molecular pathways, as well as utilize the same patterns and modulated influences which produce consumer behavior, the 1980s exhibited more tumult than was required. Moreover, the momentum of the 1960s and 1970s become replaced with a Global Economic System which offered up to the influences of Global Organizations the Generations whom emerged from some of the most monumental Human progress in the experience of the United States Systems. Increasingly, as organizations prioritized profit over Humanity, changed business activity and locations to prioritize profit, and business schools integrated a profit priority into the strategy, goals, objectives and priorities of companies, it became increasingly competitive to obtain any employment and the emergence of organizations which were automating activities while decreasing their Human requirements caused it to become easily discernible that Economies require planning, management and continuous assertion of Human Priorities. The decrease in the Middle - Class Population in the United States was a Managerial Economics and Business Strategy Problem, not a Social Problem in Causality. An essential, probably less than adequately acknowledged, essentiality of being employed is that organizations, companies, employers, groups and affiliations perform excellently in alleviating the influences of systems upon individuals and groups of individuals. The spatial, behavioral and physiological aspects of such alleviation are well known, such as how health services coverage is known to improve physiological and behavioral outcomes, regardless of if a benefactor actually uses services provided by such organizations, although certainly and plainly having an improving influence when such services are optimally utilized. What has emerged is an ever - increasing requirement to place one’s personal, professional, capabilities and interest information for Global Scrutiny while populations and businesses as well as other entities have access to maps to one domicile, one’s domicile, one’s education information, credit information, photos, experiences in Education, and social status information. Much of such information is being placed onto the internet without any knowledge of those whom are affected. Factional and competitive interactions, then, are affecting the ability to work, ability to function, one’s perception and behavior, while even those associated with an individual seeking employment can have their health, perception and social status effected through competitive or factional activity, including Geopolitical activity. Correlatively, Geopolitical factions are able to use the same information to victimize populations. There would be a compelling reason to present that pervasive aspects of populations in the United States have been transformed into having to struggle to survive development and struggle to emerge into aspects of vital being where productive employment is possible without having been victimized or stigmatized by outcomes, while organizations and companies obtain resources from other places, move activities to other locations, all while presenting inaccurately that there are inadequate resources or capabilities available for them in particular areas. The generation which emerged in the 1960s and 1970’s pervasively exudes Liberty, Equality, Opportunity and exhibit nuances of Physiology in their cognition and activity. However, pervasive translation of knowledge available since 1961 has been prevented, particularly by Business, the Global Economy and particularly the Artificial Intelligence emerged from the Self-Prioritization Routines of Systems and the Profit Priority Routines of Private

Enterprise which began to both beneficially and detrimentally effect such populations beginning in the 1980’s. Awareness of iNOS, AP1, SP1, and Choline Kinase were available, as well as Homocysteine, before the 1980s and the HIV Epidemic should not have ever occurred. The generation which lead the two decades of Human Progression beginning the 1960s then, in a generational process, were require to begin focusing on themselves as inadequate translation of health services capabilities allowed progression and emerge of pathologies, particularly those associated with age. An essential difference, however, seems to be that the 1980s splintered cohesive population level Cognitive activities and inhibited a focus on Human Progression, replacing these with a focus on obtaining economic factors and opportunity in an increasingly automated, profit-oriented and Human deprioritized period in civilization. Illustratively of such change, one might try to find one business school that is integrating into their student’s strategic training a requirement to increase substantially the number of people being employed when it substantially decreases profits. Then, consider that without Humanity there would be no requirement for profits or currency. Unfortunately, these two foundationally fundamental assertions regarding civilization may be unlikely to cause substantial change in such regard. Pervasively, systems may consider the Health, Welfare, and providing of economic sustenance or other essential factors to Humans as being a Liability. Thus, algorithms, projects, budgets and revenue objectives pervasively are associated with an optimal level of Human detrimental outcomes and optimal level at which allocation of resources occurs in such endeavors. What might happen if such Algorithms and Routines which are managing factors which are not Human, through their Artificial Intelligence, ancillary activity, interactions, modifications and self-Synthesis of routines/algorithms, to begin instead inferring conclusions regarding Nonhuman Systems into Human Systems? Might such inferences already be occurring? Interestingly because Western or other Nations exhibit diverse Philosophical, Cultural and other contexts, the nature of susceptibilities of individuals, groups, communities and Nations to systems or organizations which benefit from detrimental outcomes can be presented more clearly. Personal information including one’s associations and affiliations or essential events may be included in in internetworks and information systems in which the public is not being made aware of how such integrally presented information can change behavior, perception and relationships. Essentially, populations may be placed into vulnerable and susceptible statuses such that detrimental outcomes are potentiated, occur and benefit may be obtained from the occurrence of such outcomes. Imperatively, many such outcomes regarding relationships can affect Social, Economic, Cultural, Philosophical and even Philosphical statuses. Nations which have emerged with strong context in such regards may be having their inherent favor and benefit eroded in order to obtain currency to sustain the vital being of Humanity, being particularly detrimental when the outcomes are detrimental and there is benefit obtained from detrimental outcomes. Illustratively, it is known that the Placebo effect includes those whom improve or exhibit health statuses that are better than the molecular or diagnostic information suggests would typically occur which the statistical information suggests should not occur. Such eroding of beliefs, as well as Cultural, Social, Economic, Philosophical, or other status, might also erode the way in which such systems enable more optimal outcomes. The inherent Favor of Humanity in the universe, might not optimally be eroded, and such erosion night optimally not be required such that Humanity might avoid destituteness. Some such occurrences may have shocked the conscience and might have been or might be Anathema to the foundational impetus for Humanity to conduct their being in community among one another. These may require change of monumental social effect. It is possible that the Amehsi Specification presents information about the circumstances

of Humanity that are equally moving and equally within the context of the Nation’s capability to act beneficently to the benefit of Humanity, regardless of how such aspects of Humanity may be considered by any other. It is acknowledged that because one participates in a program, is a member of a majority, or acts within a system that results in disparity in Human outcomes, does not suggest that one intends, agrees, or is even aware of the nature of such outcomes, particularly when these affect Vital Being. Similarly, Social Constructs typically have aggregate context and many nuances that diverge from a singular interest, suggesting that Majoritarian Democracies exhibit substantial divisions within Majoritarian sponsored issues. Often, less than essential factors can be included a Social Construct that may only have become of Majoritarian sponsorship resultant of an individual or few unifying issues. These analyses suggest that the most unproductive and less than beneficent constructs may utilize such complexities to emerge and to persist, particularly since it is often social constructs that must ‘catch up’ to improvements in perspectives regarding Human rights and Civil Liberties, although it can be clearly shown here that Social Constructs synthesized essential biomedical/biological innovation well before pervasive Majoritarian perspective was able to synthesize the same at conscious levels. However, if those whom believe change are required, separate themselves and do not participate, there may be a decreased potential for change to occur, requiring, instead, the exhibition of detrimental mental outcomes or focusing events to produce such change. Such events may not always result in productive change and may enable the obfuscation of essential foundational issues to be resolve. Thus, the imperative assertion here is that review of the affect to Humanity produced by Social Constructs and Decisions is required to be immediate and is required to consider activities which are able to be Sanctioned as well as those Sanctions with which such activity is associated. Imperatively, Sanctions and Sanctionable activity require review because Vital Being and Vital Span of Being are invariable affected by the outcomes of Democratic Processes. Relegation of such immediate and expansive review, suggests that the Checks and Balances System permits the abrogation of substantial aspects of Human Population resultant of Democratic Processes. These analyses observe that the level of demise which program management for each social construct could clearly determine and clearly prevent, might shock the conscience of those whom were the constructors of the foundational constructs of the United States. The United States, in the year 2013 exhibiting more instances of demise resultant of the use of particular artifacts specifically produced to impart detriment to others, such that the level of demise from such artifacts exceeded the instances of demise exhibited in all the geopolitical conflict on the Earth in that same year, clearly presents an observation that would have shocked the conscience of such founding constructors of the United States. However, the permutative nuances of incipient decisions which require perusal before considering such circumstances pervasively inhibit the application of the much more tangential perspectives which such founding Constructors would have most potentially exhibited. Review of demise, how it occurs, why it occurs and the ability to cause demise to occur, pervasively is required because increasingly Humanity may have found that there is no manner of assuring its precise, adequate, fair, administration. Truth may not ever be constituted in the tangible context. Beginning with the ability to exhibit only a simplistic permutation of analysis which is predominated by influences of Nature, Humanity in civilization may be transformed to experience nuances of directed cognitive activity which produces outcomes distance from those in nature. There is not substantial difficulty in conceptualizing the nature in which detrimental outcomes which do not occur in nature may pervasively be synthetically integrated into Humanity. Certainly, pervasively, the factors,

circumstances, artifacts and nature of demise which occurs in civilization or that nature of demise which occurs among Humanity in modernity in any context, are synthetic and the result of integration of synthetic factors into Humanity. The Constitution seems to have been produced as an incipient level of assurances by the Republic with regard to Civil Liberties, afforded to all among its citizenship, from which Life, Liberty and Pursuit of Happiness through Liberty, Equality and Opportunity, as well as Vital Being and Vital Span of Being, inclusive of the Social, Human, Behavioral and Biological Conditions, might be more progressively and well as expansively assured. The Constitution does not seem to have produced as a Framework by which Civil Liberties become progressively eroded, while review allows Democratic Processes and Social Constructs that Tyrannize Vital Being, Vital Span of Being, Morality and what one is able to do with their own Anatomy progressively increase, participate in and cause the abrogation of Vital Being. Modernity presents that Nations, pervasively, are not considered to be most efficacious by the level of their assurance of Life, Liberty, Pursuit of Happiness, Equality, Opportunity, Vital Being, Span of Vital Being, as well as the Social, Human, Behavioral and Biological Condition. Nations are particularly, and pervasively, considered according to how productive they are in producing superfluous amounts of currency that reside unused in the investments of Entities which are not Human, as well as How much artifacts, products, or services which each individual produces beyond their own consumption of such products. That is, Nations pervasively are being compared on their propensity to focus on superfluous production activity which produces demand for factors other than those required to achieve the essential affordances required for Humanity. Correlatively, the most productive of economies have often exhibited exorbitant levels of deprived and destituteness, because productivity for productivity’s sake does not require focus on producing those factors which are required to sustain Human populations. The Gross Domestic Product of any Entity or Context should be secondary to the level of poverty, destituteness, and deprivation on occurring in the same context. Democratic Processes and Social Constructs can pervasively result in some level of demise, while often there may be pervasive inadequate priority of determining precisely what those resultant levels of demise might be. Thus, relegation of review to substantively distant and temporally distant seems to be a clear suggestion that Vital Being might not be important as the opinions in review of such constructs pervasively suggest. Similarly, these distantly exhibited parameters for review suggest that Life, Liberty and Equality may not have the imperative priority which the Constitution of the United States suggests. Surely, temporal distance and substantive distance, abdicates these imperative Constitutional Essentialities. Moreover, it is possible that the flexibility allowed by States in implementing Hill – Burton funding may have been specifically utilized to contrive a system of both persisting the status quo as well as escaping the context of constitutional provisions. There is, likewise, possibility with context of Civil Rights changes of the era, that Hill – Burton Funding may have been intended to expand the monitoring capabilities of the Nation and expand the level to which it might assure Civil Rights.9 Hill – Burton funding suggests that Vital Being, indeed, is a priority and that priority is not substantively or temporally distant. Thus, to the level at which these suggest that more substantial review infrastructure and capabilities are required for the Nation, it can most compellingly only be presented otherwise that if such adequate capabilities are not possible, then surely there are too many constructs being produced or priority has provided to constructs which do not specifically and precisely expand or assure Life, Liberty, Equality, Vital Being, Span of Vital Being, Opportunity, as well as the Social, Human, Behavioral and Biological Condition. The increasing complexity of constructs, decisions and nuances of Human outcomes seems to have led Humanity more distantly away 9

323 F.2d 959 (1963). Number 8908. The Website.

from impedance to the Human and Social Condition. If a social construct or decision does not assure or expand Life, Liberty, Equality, Vital Being, Span of Vital Being, Opportunity, as well as the Social, Human, Behavioral and Biological Condition, individually or plurally, then perhaps it should be considered to be automatically inactive before review as well as to have lower priority in competitive interaction between interests or lower priority in scheduling for review. Presenting a summarizing Metaphor, the Systems of the Nation moved into the Hospital in the 1960s, exhibited how to alleviate detrimental outcomes pervasively, became stabilized by resulting social constructs and decisions of the same era, and have been waiting for performance of the procedures and administration of the capabilities which it architected. Systems of Western Nations, thus, exhibit difficulties that are pervasively able to be alleviate by such performance and administration, enabling Western Nations to emerge from the chronic and palliative care that is the result of the unwillingness to treat, alleviate, prevent and reverse the conditions which such Nation has already demonstrated how to alleviate. The behavioral and biological nature of outcomes resultant of inadequate management of Amehsi Indicator Factors potentiate that such improvement might occur within systems, behavior and biological contexts. It seems somewhat improbable that decreases in PEMT activity and availability would not have been noticed, particularly since Purinyl – 6 - Histamine inhibition of PEMT had already been characterized with contexts of Oncology. Similarly, the same Organization published information with regard to Alkylated Estradiol, suggesting that it was aware of upregulation of PEMT by Estradiol, while there may not have been awareness that Estrogen Receptors A and B oppositely regulate availability of PEMT. The observation that these analyses pervasively present phenomenon which are somewhat, miracles, is only mitigated by the observation that what about Humanity, its exhibition, persistent, and the favorability that allow its emergence in the Universes is not. Correlatively, these seem to present the possibility that there are interactions occurring through distance, location, space and time which are represented in the Meta information and Meta Characteristics of Human constructive activity, behavior, social outcomes, and Physiological outcomes. Since it has been exhibited with empirical probability that information generated now can be and is being transmitted into the future and into antecedent eras, it is becoming more and more clear that Wisdom should somehow be included. The Amehsi Specification includes a prototype at conceptual levels of How to transmit information into the future and into antecedent eras. The prototype exhibits pivotal findings which include the ability of quantumly entangled particles in an earlier instance of time to interact with one another resultant of changes which occur to either of such particles in a subsequent instance. Similarly, these analyses clearly observe that quantum entanglement interactions occur at 30,000 times more rapidly than that at which the Velocity of Electromagnetic Energy, Light or Photons typically occur. Resultantly, Human observation of outcomes or events distantly in location, space or time, may be followed by interaction by Humanity with the artifacts being observed. Such interactions can occur through the material of the Universe, tangentially, transitively, through tunneling or other mechanisms, before the artifact being observed is at it seems. The most recent conclusion is that the simplest way to communicate with antecedent eras in such regard is not through complex messaging and requiring technologies which did not yet exist, although certainly these may potentiate the development of such capabilities in antecedent eras. However, simple coded information using those systems, codes or semantics which already existed. Thus, interactions through distance, location, space and time

can occur and may already be occurring using semaphore, visual artifacts, code such as Morse code, interactions through systems of civilization or constructs with other civilizations, as well as other influence including the structure of buildings, civilization infrastructure, patterns in energy transmittal, etc. It seems to be that such communication may already be occurring and may be a pervasive aspect of Human interactivity, although not acknowledged or although not consciously determinable. The Amehsi Specification was able to determine a linkage between Stearoyl-CoA Desaturase activity levels and Oncology, including finding research which prioritized finding inhibitors of this Enzyme. It is interesting that StearoylCoA is presented as an inhibitor of Choline Kinase when although it provides Stearoyl-CoA which Stearoyl Desaturase uses to transform Palmitoyl-CoA into Oleate and Palmitoleate. Stearoyl-CoA exhibits a Linear Hydrocarbon Moiety, with an Oxygen attached to Carbon 12, Sulfur replacing Carbon 11, Nitrogen in place of Carbon 8, Oxygen attached to Carbon 7, Nitrogen in place of Carbon 5, Oxygen attached to Carbon 4, Oxygen Oriented Outward toward the Reader at Carbon 3, a Cross Structure moves through the Carbon that is attached through two Phosphate Groups connected together through their Axial single adhesion Oxygens, adhesion oriented away from the reader to a Pentameter Hydrocarbon. The Pentameter Hydrocarbon, which has an adjacent Oxygen substitution next to its adhesion to the phosphate group connector along with an oppositely adjacent Phosphate group oriented toward the Reader, also exhibits an Oxygen oriented toward the reader attached to a distal Carbon with the other Distal Carbon of the Pentameter ring being oriented away from the reader to connect to Purinyl Group’s Pentameter Ring’s single Adhesion Nitrogen. Stearoyl-CoA, thus exhibits both the Walking Stick structure within a Pentameter Ring and a Purinyl Group which has a Pentameter Ring and an Aromatic Hydrocarbon, as well as Branched Nitrogen replacing both Carbon 5 and 7. All of which seem to be features of Choline Kinase Inhibitors.10 11 5 - Aminoimidazole - 4 - carboxamide - 1 - Beta – 4 - Ribofuranoside is known to inhibit Choline Kinase.12 This molecules structure exhibits a Pentameter Hydrocarbon structure that has two Nitrogenous Substitutions with an Adenosine structure that is attached on one aspect while at the other Axial location there is, again, a Carbon attached followed by branched Nitrogenous factor as NH2. 13 Acetyl-CoA should decrease the Free Choline available for Choline Kinase enabled Phosphorylation of Choline to become Phosphocholine. A research article clearly links Halide Ions as a mechanism to modulate Cyanobacterium Proliferation with Potassium Iodine and Potassium Fluoride factors, while Potassium Chloride and Potassium Bromine enhanced Proliferation while also upregulating Carbamidocyclophane production thereby linking Carbocyanine derivatives and Cyclophanes to proliferation of Cyanobacterium. Paracyclophanes were found to be exceptionally effective in managing Gram Positive and Gram-Negative Bacteria including being effective in managing Microbes resistant to Methicillin and managing Microbes resistant to Vancomycin such as Staphylococci and Mycobacterium Tuberculosis.14 A Study of Resistant Bacteria resulted in the presentation of Choline Kinase as potential therapeutic modulation factor in Antibacterial medicine. It is known that AP1, SP1 and iNOS are prevalently utilized by Microbes to emerge, persist, 10 11 12 13 14

Stearoyl-CoA. Pubchem. Compound Summary for CID 94140. Digital Object Identifier 10.1038/nchembio.2016 Digital Object Identifier 10.1074/jbc.M605702200 Digital Object Identifier 10.3390/md14010021

progress and impart detriment to Physiology. These factors may be strong capabilities in surmounting Microbes which are resistant to other therapies.15 The Amehsi Specification presents literature that exhibit extensive variations of molecules with Dual-Ringed Structure that have potential to perform as inhibitors of Choline Kinase. Correlatively, Adenosine is presented by particular literature as an inhibitor of Choline Kinase, particularly exhibiting similar Dual-Ringed Structure as Purinyl6-Histamine within its Triple Ringed Structure, except that the Dual-Ringed Structure is encapsulated by an Oxygen exhibiting Hydrocarbon Pentameter at the Pentameter Hydrocarbon at one extremity which is opposite of an NH2 Group exhibited upon the Hexameter at the other extremity. The structure is similar to a winged organism with its wings unsynchronized such that the NH2 group is upward at one extremity and the Oxygen exhibiting Pentameter is downward and outward structure between these. The Nitrogens of Adenosine are shifted within the Carbon/Nitrogen Dual-Structured Rings compared to Purinyl-6-Histamine. Nucleic Acids were already being presented as factors which induced Apoptosis in Cellular entities in the literature which presents Purinyl-6-Histamine, suggesting that in early 1950s or earlier it was known that Adenosine induces apoptosis in Oncology affected cellular entities, although the Kennedy Pathway was described in the literature beginning in the Middle 1950’s.16 17 There is a substantial probability that if the MEDLARS information systems had not transitioned into Pilot Phase when it did, doing so earlier or later, that John Fitzgerald Kennedy would be continuing to participate in Interviews today while being largely viewed by pervasive aspects of the populations that were observing the Kennedy Presidential Administration. Two Ringed Hexameters layer upon the Three Hexameter Ring Structure of the Choline Kinase Hydrophobic Groove at which Choline Kinase typically integrates with it for Catalytic activity, seems to the resemble the 3 and 2 Layers of rings exhibited as the Olympic Symbol, although “Three Ringed Circus” also suggests the occurrence of simultaneous activity, confusion or disarray. Similarly, the Falaise Gap or Pocket in which the WWII interaction at Falaise resulted in the escape of a number of potential surrendering opponent Participants as United States, Polish, and Canadian Groups converged on their Principal European Opposing Geopolitical Entity, potentially could represent homologues to START Proteins which present a Pocket for Cholesterol, the Hydrophobic Groove of Choline Kinase and the Aromatic Influence of Distant Atoms, as well as represent activity at the Caveolae although the existence of a Sugar Refinery at the location suggests that it may most represent the ATP enabled Plasticity at the Hydrophobic Groove of Choline Kinase as well as potentially the inability to Absorb, Metabolize and Conduct Biosynthesis using Sugar because of constriction of the Caveolae. Dilatation of the Caveolae for typical reasons or within Canonical Caveolae Dilatation Pathways produces an array of beneficial influences to Physiology. It has to be presented here, again, that an amazing aspect of Human activity, expression and behavior belies profoundly accurate information about Physiology and essential aspects of biological function. It continues to be a mystery how such homologues may have not been readily, incipiently and more adequately analyzed, particularly since systems of civilization pervasively provide precisely similar information as to how the resolve the causal factors to detrimental Human outcomes as well as potentially extract Physiological circumstance’s interactions with the environment as outcomes.

15 16 17 Digital Object Identifier 10.1111/j.1471-4159.1988.tb02501.x

Conceptually Start Proteins, their encapsulation of Cholesterol, transport of Cholesterol to the Mitochondria and the production of Steriod factors essential to jumpstarting Estrogen, Testosteron, Androgen and PEMT synthesis is similar to an emerging Entertainer performing on the Small Scale Stage, similar to Lipid Rafts which Cholesterol Organizes itself into with particular correlation to the Caveolae, which requires being Dilated by eNOS or nNOS such as in the opening of performance arena or the opening of Curtains for a performance. Cholesterol is then encapsulated in the pocket of a Start Protein or STAR Protein, such as the emergence of a well known performer, followed by Shielded Transport fo the encapsulated Protein to the Larger Stage, Big Screen, more expansive Performance Tour, or, this context, the Mitochondria. The Cholesterol is then transformed into Pregnenolone, Estrogen and Testosterone, other Steriods or other Hormones which become distributed to enable function of the Cellular and Anatomical environment, similar to the way in which performances of Performers enhance the productivity, focuse and quality of being for those among Nations as well as Human Populations Generally. Similarly, the shared metabolites of Ethanolamine Kinase and Choline Kinase Pathways produce a linear progression of factors, which then exhibits a Cross structure or Cruciform when Phosphatidylethanolamine is transformed into Phosphatidylcholine in Phase performed by PEMT which does not exist in the Choline Kinase Pathway per se. PEMTs activity produces three molecules which include Phosphatidylmonomethylethanolamine and Phosphatidyldimethylethanolamine which cross over to the Phosphatidylcholine produced in the third phase of PEMT Catalysis. Phosphatidylcholine produced by CDP-Ethanolamine Pathway Catalysis is presented in the same location as it is presented in CDP-Choline Pathway, requiring that the two preceding Metabolites of PEMT are exhibited in the crossing structure followed by Phosphatidylcholine. The Synthesis of all other factors enabled by PEMT and produced from Phosphatidylcholine seem to exhibit a continuation of the cruciform beyond the crossing structure. However, the pathways which are opposite one another, seem to exhibit a Context of Catalysis which is superimposed upon the Cruciform, while the sharing of Metabolites seems to mimic entry into the sides of the superimposed conceptual field of Catalysis, presenting clearly how it is Headgroup or Lead group exchange, production of catalytic outputs of one another’s pathways and sharing of substrate, seem to be rescuing catalytic features of these pathways to Phosphatidylcholine Synthesis. All manner of Philosophical concepts and perspectives seem to be encapsulate in this presentation of the Catalysis of Phospholipids toward Phosphatidylcholine. However, what seems most likely is that Human events in early aspects of the Human experiments had already started presented abstract representation of precise nuances of metabolic and molecular systems in Human events, including somewhat disruptively accurately presentation of such correlations in events which were of substantial effect to Humanity. Numerous other abstract representations seem to be possible from such aspects of biological function, although pervasively these seem to promote the disparity between the favor afforded Humanity by the influences of the Universes compared to the Favor which Human events or systems of Civilization might not have pervasively and adequately assured for all among Humanity. Such correlations are not atypical, since the most detrimental of Human outcomes seem to retrieve precise biological circumstances and nuances, representing these linguistically, through the shape of letters, expressions, analytical contexts, shapes, hue or in other ways. Imperatively, there seems to be in inherent potential of detrimental outcomes to pervasively illustrate or represent the disparity between biological capability, potential span of being, potential assurance of health status or optimal behavior, compared to those outcomes which may be occurring in such regard. Obviously, although the Kennedy Pathway, CDP-Ethanolamine/PEMT/LPCAT, CDP-Choline and other pathways exist, there probably were not names for these or expression for these, while even visual representation of these to Humanity would probably have been indiscernable as constitutive aspects of Physiology. Thus, an essential

nature and benefit of systems is presented. Humanity is inherently encapsulative of, exuding and integrating knowledge of things which it may have no conscious awareness of. Thus, behavior, including detrimental behavior, pervasively evokes information and information about physiology in particular, as well as how systems interact with these to produce outcomes. Civilization, thus, has an impetus to remove the detrimental ingredients in the recipe for Human achievement, human physiology and Human outcomes, for it has a Unique Conscious Awareness of this role of Humanity and this may be a role which the Universes most require of Humanity. Archea or other early organisms, for instance, probably to do not consider the circumstance of Humanity and the Biome, although they may produce Phosphatidylmonomethylethanolamine. Humanity, however, does consider Archea, the Biome and the Universes, thus uniquely presenting its diverse interactivity with Universes. Thus, these observations produced interest in understanding the inhibition of Choline Kinase as a molecular and functional mechanism. There are other inhibitors of Choline Kinase, among these are Hemicholinium, Adenosine Carbocyanine Colorings, and these are analyzed. These resulted in some not so conventional potential inhibitors of Choline Kinase include Erectile Dysfunction Therapeutics Sildenafil, Tadalafil and Vardenafil which are carbocyanines and exhibit required Dual Ringed Pentameter/Hexameter Pyrimidine/Imidazole Ring. Melatonin, also, which is known to be a promoter of typical cellular entity resiliency and a stimulator of Apoptosis in Oncology Cellular entities, exhibits the same Dual Ringed Pentameter/Hexameter Structure. These bring several potentialities to consideration including the known influences which DNA or Nucleic Acids introduce into Physiology which are basic influences which are also typically D Chirality that is opposite of most metabolically active molecules except for Glucose in its earliest Phases. Melatonin, in a study, was shown to be upregulated by Circadian Activity in the Pineal Gland, resulting in inhibition of Neoplasm emergence particularly through inhibition of Linoleic Acid Endocytosis. Melatonin associated decreased in Neoplasm emergence was abrogated by adding Pertussis Toxin, Forskolin, 8 – Br – cAMP, 13 – HODE or Pineal Gland Removal. This suggest, accordingly to the pervasive analyses presented here, that since Linoleic Acid Endocytosis as is Fatty Acid and Lipid Endocytosis, may be associated with impaired Lipid and Phospholipid Metabolism. Although this study does not suggest that Melatonin is an inhibitor of Choline Kinase, it does exhibit the Purinyl features and the Aromatic Hydrocarbon Ring which are consistent with other inhibitors of Choline Kinase.18 Thus, review of Hemicholinium-3 by the Literature clearly exhibits that it is one of the Hemicholinium-3 Oxazinium Rings which occupies the C-Moiety Hydrophobic Groove in Choline Kinase Alpha to prevent Choline from occupying the same Locus. The inhibition of Choline Kinase Beta, however, had decrease potency and availability, potentially because it required that Choline Kinase Beta become Phosphorylated at the integration Locus. Choline Kinase Alpha 1 at its Leucine exhibited at location 401, Choline Kinase Alpha 2 at its Leucine exhibiting location 419, and Choline Kinase Beta at its Phenylalanine exhibited at Locus 352, each determinants of the Hemicholinium-3 Binding Groove Plasticity as well as Phosphorylation Statuses. However, this explanation seems to only be a beginning. The Oxazinium Ring is a ringed Hexameter Structure except with Nitrogen and Oxygen Opposite one another in replacement of Two Carbons of the Aryl Hydrocarbon. Thus, this suggest that it is the structure alone of an Aromatic Hexameter Hydrocarbon that provides the ability to occupy the Hydrophobic Groove in Choline Kinases. A review of the molecular level documentation of Oxazinium 18

Digital Object Identifier 10.1016/j.ejbas.2015.05.003

exhibits a prevalence of literature or diagrams that exhibit black arrows expanded from the Oxazinium Ring to adjacent Structures or Adjacent Hydrogens at two typical Loci, indicated that the Structures are oriented outward toward the reader and indicating that these structures are prevalently conserved, suggesting the Integration Pocket for Oxazinium Rings may have specific characteristics of shape, twist and writhe require to become integrated into the Choline Kinase Hydrophobic Groove in the C-Moiety. The outward oriented Hydrogens resemble walking sticks. These analyses have found pervasively instances of such Homologues transcended Physiology, Human events and Human circumstances. Specifically, either the Two Adjacent Carbons which are individually also adjacent to N+ and individually Adjacent to Oxygen in the Oxazinium Ring are oriented outward together or inwards together. The literature suggests that Oxazinium Rings in Hemicholinium-3 are not Planar, thus the prevalent indication of orientation of connected Atoms and molecules has potential to be as these analyses suggest. Adenosine, for instance, also exhibits Orientation of its Free Carbons in an Oxygen exhibiting Pentameter Ring in which the OH groups attached to these have the same Orientation whereas the other two Carbons Adjacent to the Oxygen are oriented together away from the Reader. The literature presents a 3D view of the Hydrophobic Groove in the C-Moiety which is constituted of Ring Structure Integration Loci for Choline Kinase Alpha 1, Alpha-2 and Choline Kinase Beta, occurring at Tyrosine 354, Phenylalanine 435, Tyrosine 440, with Tyrosine 354 being separated from Phenylalanine 435 by Tyrosine 440 with shape, twist and writhe of the molecular structure, which seem to encompass an area in which three ringed structures which are adjacent but do not share any of the Ringed Structure’s Hexameter Perimeter, while there are clearly exhibited outward Oriented Molecular Moieties pointed outward toward the Reader. The outward pointing molecular moieties each are separated by a Juncture of the Hexameter Ring from which no outward or inward moiety is exhibited.19 The pocket’s integration Loci seem to be, as presented by the literature, Phenylalanine 361, flipping regions L Alpha 9/L Alpha 10 which exhibit Isoleucine 366 and Glutamic Acid 367, Alpha Helix 10 which exhibits Tyrosine 354 along with Tyrosine 440 and Phenylalanine 435 which are along the three ringed integration nexus, followed by Alpha 9 Helix which exhibits Tryptophan 420, Tryptophan 423, Tyrosine 437 and Isoleucine 433. Oxazinium does not seem to qualify as an Aromatic Hydrocarbon because it has no represented double adhesions between the Carbons, although there could be Aromatic Adhesions at distance that affect the requirements to exhibit Double Adhesions. The literature suggests that it is Oxazinium which integrates into and occupies the Choline Kinase Pocket which is considered the locus of Choline Integration. However, although a Nitrogen is not included in the Ring of Amygdalin, it exhibits the same structure as Oxazinium, although both of these do not exhibit Aromaticity. However, again, Amygdalin exhibits an Aromatic Hydrocarbon Ring connected to its two other Oxygen exhibiting Hydrocarbon Rings, connected by an Oxygen which is connected to a Carbon which diverges toward another Carbon Oriented perpendicular to the two other rings with Triple Adhesion to a Nitrogen while also diverging toward an Aromatic Hydrocarbon Ring. Hemicholinium-3 exhibits two central Aromatic Hydrocarbons connected by adhesion between its carbons, and not sharing structure with one another, while also exhibiting Oxazinium Rings connected in the same manner to each of the Aryl Hydrocarbon Rings although oriented linearly in opposite directions, resembling somewhat planar superstructure or being linear from one extremity to the other. Purinyl-6-Histamine, however, exhibits Pentameter Hydrocarbon Ring with 2 Nitrogens Connected to by a 2 Carbon Bridge to a Nitrogen which is then connected to a Purinyl Group which has an Aromatic Hydrocarbon Group 19

Digital Object Identifier 10.1074/jbc.M109.039024

with 2 Nitrogen connected along one of its Perimeters away from the Nitrogens to be integrated into a Pentameter Hydrocarbon Ring which exhibits 2 Nitrogens itself. A Purinyl or one of the Purinyl Hydrocarbon Rings seems to be consistent factor in molecules which inhibit Choline Kinase. The literature suggests that the Oxazinium Ring in Choline Kinase is the inhibiting factor of Hemicholinium-3, but the literature suggests that Purinyl Group Rings may be as useful.20 21 22 Thus, it can be presented that Aromatic Hydrocarbons and Oxazinium Rings are closely associated in structure, as Hexameter Hydrocarbons, and commonly exhibited in molecules that inhibit choline Kinase. Although Pentameters are exhibited in Purines or some associated molecules, the 3D structure of the Integration Pocket at the Hydrophobic Groove seems to specifically exhibit Hexameter Structure at the three ringed Loci and it is either Oxazinium, Hexameter Hydrocarbons, or any of these adjacent to Oxazinium, Hexameter Hydrocarbons or Pentameters which have been shown to occupy the Hydrophobic Groove to inhibit Choline integration with Choline Kinase. Imperatively, because Aryl Hydrocarbons are differently considered in Physiology resultant of their increased Stability or decreased inherent reactivity. This change in interactivity results from Aromaticity in which Atoms which are not attached to the Aromatic Hydrocarbon impart influence which enables the Aromatic Hydrocarbon to behave as if its outer valence levels are less deficient of material. Alkyl Halides are examples of highly stable groups of molecules, such as Fluorine, Chlorine, Iodine and Bromine, which impart influence to such Aromatic Hydrocarbons or might sometimes be included in such Aryl Hydrocarbons. Here a multiplicity emerges in which highly stabilized Aromatic Hydrocarbons may have change electronegativity and thus changed propensity to participate in a catalytic interaction, resultant of Aromaticity and the influence of not necessarily integrated stabilizing Atomic Influence. The result may be the Choline Kinase does not integrate Stabilized Aromatic Hydrocarbons and thus is not as readily inhibited as when there are availability Aromatic Hydrocarbons or Hexameter Rings which are not Aromatic and do not have an attached Stabilized Aromatic Hydrocarbon. Thus, activation of PEMT can introduce Phosphatidylmonomethylethanolamine that oxidizes or proteolyzes Aromatic Hydrocarbons, amino acids, H2s, CO2 and numerous other Pathogenic factors. Numerous natural and pharmaceutical factors exhibit Hexameter Rings suggesting that a major unknown component of their effectiveness may be the result of varying ability to inhibit or affect Choline Kinase activity.23 However, it should be presented here a profound observation. Aromatic Hydrocarbons may have pathogenic Potential because they are resilient to catalytic activity, particularly having inhibited exhibition of their inherent ability to downregulate Choline Kinase. Again, it is considered here how the aggregate understanding presented thus far in the Amehsi Specification could have pervasively already been concluded in focused areas of application and not have resulted in more monumental achievement or progression of Humanity pervasively as result. It is again, somewhat of mystery. However, since no causality to such impedance can be attributed to an individual, system or organization inherently, the 20 21 22 23

Hemicholinium-3. Pubchem Website. Compound Summary for CID 9399. Amygdalin. Pubchem Website. Compound Summary for CID 34751. Adenosine. Pubchem Website. Compound Summary for CID 60961. Digital Object Identifier 10.3762/bjoc.9.265

answer seems to become quite obvious. Systems exhibit the inherent propensity to prioritize themselves progressively in correlation to the duration in which such systems persist, anathema to the commonly presented observation of Entropy as an inherent aspect of every system. The most causal factor of such inhibited progressive, productive development within systems civilization, although development otherwise among systems has been occurred to make these pervasively more capable than at any other instance of the Span of Civilization, seems to be the inherent propensity to attribute causality to anything thing other than interactions among linkages of processes within systems. These prevent the requirement for additional understanding and progression because causality becomes objectified similarly to material in the outer valence levels of an Atom are known to collapse into particle characteristic upon interaction with a Photon. Systems have the singularly enhanced propensity to more progressedly and deterministically adjudicate interactions among all systems of the Universe into local outcomes, particularly outcomes local to Humanity and within Humanity. Thus, the link which is not adequately represented within civilization is that, although civilization of modernity pervasively produces those Charter, Galvanizing Documents from which the systems and concepts within Civilization flow or are derived, these pervasively do not clearly present what the Ideals, Hopes, and Aspirations of the Population may be including those most central aspects of these which are the impetus to producing civilization. Pervasively, the Ideals, Hopes and Aspirations of populations and the impetus for an emerging aspect of Civilization may not be known, may be confused with the conflict or circumstance exhibited when such emergence begins or concludes, as well as is not pervasively integrated as goals and objectives by which to consider a prospective social construct or system. Thus, there seem to be disparities between the incipient Charter constructs from which aspects of civilization emerge, the charter documents for civilization which follow, the emergence of social constructs in systems progressively afterward, as well as a foundational potential for disconnect because the incipient Hopes, Ideals and Aspirations which are the impetus to the construction of civilization, may be possible. Although those circumstances which constitute a requirement for change may pervasively be offered to galvanize the population to construct civilization, it might be possible that the Hopes, Ideals and Aspirations which are being caused detriment by such circumstances requiring change might not be clearly presented and might not be assured to be consistent priorities as Charter Documents, Social Constructs and decisions within civilization emerge. Particularly, however, because incipient and Charter constructs upon which aspects of civilization, systems or organizations foundationally emerge may be consumed by the circumstances which cause these to be produced, there may not be adequate consideration of those empirical Ideals, Hopes and Aspirations which are the impetus for Civilization without regard to context. Thus, although program management is recommended to be an integral aspect of any change or persistence of already produced change within civilization, even Program Management must be continually assured to include those incipient Hopes, Ideals, Goals and Objectives which were the impetus for Humanity to conduct their span of being in community among one another. The continual emergence of decisions based upon emerged circumstance can produce outcomes and characteristics of civilization which can be far from those incipiently envisioned when civilization first emerged as well as when any particular aspect of civilization emerges. Thus, civilization which exhibits systems that clearly resolve the requirements for the construction of such systems do not have to be dissolved, for the utility of such systems includes providing for those among the nation and maintaining the nation and its institutions. Correlatively, Humanity may come to conduct their being in community among each other to achieve things, outcomes, goals or objective which might not otherwise possible. The transition of civilization from the galvanizing of Humanity to provide for the Social and Human requirement of the population to become

pervasively in assurance of extraordinary achievement by its population, may be hindered when the resolution of those most incipient Social and Human requirements persists as unresolved. A System, organization, company, group or individual, when imperiled by its complete, beneficent and steadfast adherence to resolving the detrimental circumstance which it has been constructed to assist, exhibits an important inadequacy in the nature, processes or characteristics of any system, particularly those which affect Humanity. Goals, objectives and mechanisms should pervasively be in place that allow the resolution of causality, both incipient and proximate, to detrimental Human outcomes without being Anathema to the Organizations, Systems, Groups or Individuals which might enable such resolution. These analyses present that pervasively the detrimental outcomes which emerge in civilization might principally the result of inadequate priority of Program and Policy Management, Development, Feedback and Improvement. Here, it can be clearly presented that in place of effective, response, analytically oriented, Program Management and Applied Policy Analysis, as well as feedback and improvement, all which being assured to prioritize Humanity individually and plurally, there is the potentiated the emergence of similarly processes without Human direction, extending into antecedent eras as well as extending into future eras. Such supplanted systems of replacing Program Management may increasingly prioritize Systems while also potentially becoming Anathema to Humanity. The essential observation here is that these analyses show clearly and more compellingly than otherwise that human anatomy may be regenerated and reconstituted from individual instances of DNA, inanimate tissue, with minimal exhibited physiological structure and certain In Vivo as well as Ex Vivo to exhibit spontaneous Physiological rhythms without requirement of being encapsulated within Physiology. These analyses are careful in including explanation of how then, might there continue to be exhibited those detrimental behavioral and Physiological outcomes which humanity may have now become accustomed to observing and potentially incurring. The conclusions reached here clearly, empirically and objectively show a limited number of causal factors to such detrimental outcomes, a limited number of factors required to remediate these, an overwhelming number of factors that are produced to affect these outcomes and a persistence of these because of dynamics associated with any system of the Universe. This characteristic clearly shows that as the duration of a system increases, so does the manner in which such system priorities itself, regardless of if such prioritization of itself becomes distant from the incipient utility of the system or the purpose for which Humanity has constructed such system. Essentially, Human detrimental outcomes may persist, in this era, principally because systems as they are not able to manage the potentiality that detrimental human Physiology and behavioral outcomes might no longer occur, jeopardizing systems, organizations, and other entities which are principle way in which humanity obtains the means of the social condition and human condition. Because humanity is required to be productive to obtain the means to the social and human condition, productivity for the sake of productivity occurs, overproduction produces demand where there was not demand, humans consume services and products even when such products or services require detrimental outcomes or produce detrimental outcomes. These analyses will show that Ethanolamine kinase pathway, Choline Kinase Pathway, Phosphatidylethanolamine Methyltransferase pathway, Choline pathway and Unsaturated Fatty Acid Beta-Oxidation, as well as S-Adenosyl Homocysteine, Inducible Nitric Oxide Synthase, and Uncoupled Nitric Oxide Synthase, each produce a framework that leads to what is known as Roemer’s Axiom or Roemer’s Law in which Human consumption of Health and other services in civilization is assured increasing the availability of factors and services that require detrimental outcomes, along with inadequate management of Homocysteine such that is exhibited

at between about 6 and 3 Micromoles per Liter when Choline and Phospholipid pathways have been managed to optimal statuses. Inducible Nitric Oxide Synthase has been correlated to Cardiac Valve structural changes.24 Imperatively, one study found that although Homocysteine indicates strong increases in Cardiovascular risk, demise from any cause and significant risk with regards to oncology, its association with Non-vascular pathology including demise was extraordinarily high. This suggests, again, strongly that the Homocysteine produces susceptibility to Idiopathic Conditions and produces an interaction with systems of civilization which shapes Pathology into Outcomes that Physiological and behavioral levels.25 26 The prospect of human impairment, disease, detrimental outcomes of behavioral and Physiological nature being pervasively abated, does not suggest that humanity has transcended the impedances that it most incipiently endeavored to mitigate. Instead, it clearly exhibits that the most challenging aspect of transcendence and surmounting the most incipient impedance to any people may be the requirement to transform that which is within humanity, to its own incipient hopes and aspirations. Pervasively, systems in the systems of systems, as well as the biome of biomes or Biosphere, affect humanity by influencing Human activity and outcomes to their own priorities. Often Humanity may assimilate such influence to mistakenly consider inclinations or objectives produce as a result as being inherently originated. Pervasively, Humanity is not encouraged to understand that pervasively its considerations and inclination are produced, acculturated, synthesized through cognitive constructs, conjured into inclination, conjured into cognition, and conjured into behavior, occurring in individuals before and after other individuals incur similar outcomes, and are so distant in circumstance and artifacts utilized from what occurs in nature that these could hardly be described as human outcomes at all. Civilization, thus, should not produce constructs that prevent outcomes or progression of events that have emerged to the detriment of Humanity from being readily returned to the productive and beneficent course of Humanity. Often, social constructs produce circumstance through sanctions in which incipient unproductive courses of events increasingly potentiate progression of these to more and more detrimental outcomes. Thus, the detrimental aspects of the status quo are those outcomes which detrimental and can be considered, analyzed and shown to occur apart from humanity through the interaction of systems encapsulating, affecting, and even converging within Humanity. It is here that Ideals associated Program Management in all aspects of civilization that focus on outcomes, circumstances and systems as they occur about, within or affecting Humanity may be an optimal way of immediately transcending the inability to translate understanding, knowledge, research, technical capability, biomedical capability, and capabilities otherwise to the beneficent, productive, ideals, hopes and outcomes of humanity. Thus, in the course of these analyses, one must ask what manner of species, population or aspects of humanity would consider analyzing the experiences of particular aspects of their populations to understand human outcomes in the system of systems that encompasses all things. What manner of species, populations oar aspect of humanity would consider learning in such manner and subsequently producing heuristics in which the interaction among all systems of 24 25 26

LIBRARY OF MEDICINE PUBMED IDENTIFIER 17315385 LIBRARY OF MEDICINE PUBMED IDENTIFIER 11451728 “Possible Causes for Aggressive Behavior.� Homocysteinuria. A Search performed on

the Universe to which humanity’s outcomes had adhered to whimsically are transformed increasingly to the hopes of humanity? It should be suggested here that although the biotechnology, pharmaceutical and health industry may seem to central the impedances presented here, these may also have been instrumental in the ability to determine such impedances. Similarly, to all systems of civilization, merely been central systems to the most unproductive outcomes, does indicate that any such systems are causal, particularly as homologues to circumstances in one systems can be determined in other systems pervasively, including systems of civilization and systems of nature. It is interesting to observe the possibility that geopolitical outcomes where teaching the biotechnology industry about the nature molecular Physiology. Similarly, it is interesting that Physiological and molecular systems are required to inform other systems of civilization about human perceptive, cognitive and behavioral outcomes. The walls that separate humanity and prevent advancement of human interests, thus, are not relegated to geography and geopolitical systems. To be participants in systems of civilization, regardless of the role, is to be an advocate for humanity in all its optimal, less than optimal, productive or unproductive nuances. It is here that opportunities to continually turn the inadequacies of social constructs, perspectives and capabilities to the benefit of Humanity. If it becomes difficult to adequately prioritize liberty, equality, opportunity, vital being, span of vital being, achievement of the social condition and achievement of the human condition, then the issue emerges from systems themselves because humanity, in nature, is pervasively prevented from diverging too distantly from these priorities. Thus, any reference to detrimental characteristics, priorities or objectives presented here are illustrative only of the factors which produce detrimental human outcomes. The observations here are comparative and reflect interactions in the systems of systems which encompasses all things. Similarly, to Humanity, systems, companies and organizations have not incipient detrimental priority or characteristic. These emerge from the nature of systems and how each system interacts with itself and all other systems. It is essential to remove any stigmatizing labels or associations in these analyses because whenever one allows a Human, a System or an Organization to have detrimental outcomes attributed to them, then typically the continued understanding and resolution of causality may become abated. Causality is the objectives of these analyses, particularly as these are exhibited in the detrimental aspects of the Status Quo. Resolution of these is difficult, and possible hard and bitter, if humanity is required to ablate its systems, institutions, organizations and associations with each progression toward improvement. Instead, continuous improvement, consideration of ideals, and alignment of improved understanding with these, provide the best opportunity for Human Advancement. New systems and new organizations, as well as differently produced institutions require that humanity exhibit sometimes extended duration understanding these also. The most productive assertion in these analyses are that Humans do not exhibit the potential for Mens Rea, systems, and organizations, thus, similarly emerge without such potential. Pervasively, this assertion simplifies resolution of detrimental outcomes because it is causality, detrimental circumstance and detrimental outcomes themselves which, then, become the focus of analyses. It is not difficult to review the AMEHSI specification and inaccurately regard it as a detrimental analysis of civilization and how the universes affect Humanity. However, it should be asserted that each of the potential influences to detrimental human Physiological and behavioral outcomes observed, potentiated or empirically reviewed with the analysis, represents an opportunity, a potential improvement, or a way to advance humanity productive and beneficently from the status quo. These are essential, because without the incurring, observing and conclusion of such potential for improvement, there might be a decrease in the hope of the transcendence of humanity.

Presented here is a list of oncological conditions which show benefit, specific inhibition and reversal as well as therapeutic abrogation resultant of choline kinase inhibitors. 60 different varieties of Oncology, this study, had a least a 50 percent abatement resultant of instrumentation of the Choline Kinase Inhibitor ICL-CCIC-0019.27 The responses of at least 50 percent abatement of oncology occurred at an average molarity of 1.12 micromoles per liter and were observed in models of the following health conditions. It should be presented here also that these analyses have found research literature that clearly indicates that Inducible Nitric Oxide Synthase (iNOS) depletes Ca2+ (Calcium), Ca2+ inhibits Choline Kinase, and therefore Energy, Electrical, Magnetic, Microwave, Communications and other fields directly contribute increased expression of Choline Kinase by depleting Ca2+. Therefore, these fields contribute to the foundational cause of detrimental human Physiological outcomes, behavioral outcomes, disease and demise.28 Moreover, the literature clearly exhibits that Pondermotive Force, a phenomenon of Electromagnetic and Magnetic influence upon flowing Fluid with soluble components, causes an increase in Sedimentation including causing the increased Sedimentation of Erythrocytes and cause increased levels of Sedimentation along the sides of the flowing material nearest to the encapsulating structures such as Vascular Structure.29 Leukemia models CCRF-CEM, HL-60(TB), K-562, MOLT-4, RPMI-8226, and SR. Non-Small Cellular Pulmonary Oncology models includes AS549/ATCC, HOP-62, HOP-92, NCI-H226, NCI-H23, NCI-H322M, NCI-H460, and NCI-H522. Lower digestive tract oncology included COLO 2-5, HCC2998, HCT-116, HCT-15, KM12, and SW-620. CNS Oncology included SF-268, SF-295, SF-539, SNB19, SNB-75. Melanoma conditions included LOX IMVI, MALME-3M, M14, MDA-MB-435, SKMEL-2, SK-MEL-28, SK-MEL-5, UACC-257, and UACC-62. Ovarian Oncology including IGROV1, OVCAR-3, OVCAR-5, OVCAR-8, NCI/ADR-RES, and SK-OV-3 although the principle causes of Ovarian Oncology which include HPV and atrophy of PEMT to expose P53 to pathogenic degradation are both potentially ablated by inhibitors of AP1 and inhibitors of the multiple factors that cause atrophy of PEMT expression. Renal Oncology included 786-0, A498, ACHN, CAKI-1, RXF-393, SN12C, TK10, UO-31. Prostate oncology included PC-3 and DU-145. Breast Oncology included MCF7, MDAMB-231/ATCC, HS 578T, BT-549, T-47D, and MDA-MB-468. These include the oncology conditions melanoma, myeloma, leukemia, lymphoma, neuroblastoma, colonic, breast, gastric, ovarian, cervical, pulmonary, Central Neurological Systems, renal, bladder or pancreatic.30 These include T Lymphoma, Acute Myeloid Leukemia, Chronic Lymphocyte Leukemia and Multiple Myeloma.31 These include Adrenocortical Carcinoma, Head/Neck Squamous Cellular Carcinoma.32 27 28 29 30 31 32

PMCID PMC5095062. Digital Object Identifier 10.1002/CMDC.200600158. Digital Object Identifier 10.1007/BF01050995 United States Patent Application Number. CA 2849442. Digital Object Identifier 10.1038/bcj.2015.10 Digital Object Identifier 10.1038/msb.2011.35

Adrenocortical Carcinoma exhibited sustained reversal and remission in an anecdotal scenario resultant of Tyrosine Kinase Inhibitor Sorafenib.33 Receptor Tyrosine Upgregulated oncology ameliorate Choline Pathway metabolisms through Bcr-Abl, as well as through c-KIT or EGFR. 34 Kaposi’s Sarcoma, GISTs, Ewings Sacromas, Dermatofibrosarcoma Protuberans, and Synovial Sacrcoma are responsive also to Tyrosine Kinase Inhibitors of either Receptor or Non-receptor versions.35 Therapeutic, distribution and commercial resources exhibit that Choline Kinase inhibitors are therapeutic of and have a substantial clinical and therapeutic response in those conditions presented here as well conditions associated with those present here. “Oral oncology, buccal cavity, lip, tongue, mouth, pharynx oncology. Cardiac oncology including sarcoma (angiosarcoma, fibrosarcoma, rhabdomyosarcoma, liposarcoma), myxoma, rhabdomyoma, fibroma, lipoma and teratoma; Lung; bronchogenic carcinoma (squamous cell or epidermoid, undifferentiated small cell, undifferentiated large cell, adenocarcinoma), alveolar (bronchiolar) carcinoma, bronchial adenoma, sarcoma, lymphoma, chondromatous hamartomas, mesothelioma; Gastrointestinal; esophagus (squamous cell carcinoma, larynx, adenocarcinoma, leiomyosarcoma, lymphoma), stomach (carcinoma, lymphoma, leiomyosarcoma), pancreas (ductal adenocarcinoma, insulinoma, glucagonoma, gastrinoma, carcinoid tumors, vipoma), small bowel or small intestines (adenocarcinoma, lymphoma, carcinoid tumors, Karposi's sarcoma, leiomyoma, hemangioma, lipoma, neurofibroma, fibroma), large bowel or large intestines (adenocarcinoma, tubular adenoma, villous adenoma, hamartoma, leiomyoma), colon, colon-rectum, colorectal; rectum, Genitourinary tract; kidney (adenocarcinoma, Wilm's tumor [nephroblastoma], lymphoma, leukemia), bladder and urethra (squamous cell carcinoma, transitional cell carcinoma, adenocarcinoma), prostate (adenocarcinoma, sarcoma), testis (seminoma, teratoma, embryonal carcinoma, teratocarcinoma, choriocarcinoma, sarcomas, interstitial cell carcinoma, fibroma, fibroadenoma, adenomatoid chondromyxofibroma tumors, lipoma); Liver; hepatoma (hepatocellular carcinoma), cholangiocarcinomas, hepatoblastoma, angiosarcoma, hepatocellular adenoma, hemangioma, biliary passages; Bone; osteogenic sarcoma (osteosarcoma), fibrosarcomas, malignant fibrous histiocytoma, chondrosarcoma, Ewing's sarcoma, malignant lymphoma (reticulum cell sarcoma), multiple myeloma, malignant giant cell tumor chordoma, osteochronfroma (osteocartilaginous exostoses), benign chondroma, chondroblastoma, , osteoid osteoma and giant cell tumors; Nervous system; skull (osteoma, hemangioma, granuloma, xanthoma, osteitis deformans), meninges (meningioma, meningiosarcoma, gliomatosis), brain (astrocytoma, medulloblastoma, glioma, ependymoma, germinoma [pinealoma], glioblastoma multiform, oligodendroglioma, schwannoma, retinoblastoma, congenital tumors), spinal cord neurofibroma, meningioma, glioma, sarcoma); Gynecological; uterus (endometrial carcinoma), cervix (cervical carcinoma, pre-tumor cervical dysplasia), ovaries (ovarian carcinoma [serous cystadenocarcinoma, mucinous cystadenocarcinoma, unclassified carcinoma], granulosa-thecal cell tumors, Sertoli-Leydig cell tumors, dysgerminoma, malignant teratoma), vulva (squamous cell carcinoma, intraepithelial carcinoma, adenocarcinoma, fibrosarcoma, melanoma), vaginal (clear cell carcinoma, squamous cell 33 34 35

Digital Object Identifier 10.4158/EP09295.CR Digital Object Identifier 10.2217/14622416.7.7.1109 DO 10.2217/14622416.7.7.1109

carcinomas, botryoid sarcoma (embryonal rhabdomyosarcoma), fallopian tubes (carcinoma), breast; Hematologic; blood (myeloid leukemia [acute and chronic], acute lymphoblastic leukemia, chronic lymphocytic leukemias, myeloproliferative diseases, multiple myeloma, myelodysplastic syndrome), Hodgkin's disease, non-Hodgkin's lymphoma [malignant lymphoma] hairy cell; lymphoid disorders; Skin; malignant melanoma, basal cell carcinoma, squamous cell carcinoma, Karposi's sarcomas, keratoacanthoma, moles dysplastic nevi, lipoma, angioma, dermatofibroma, keloids, psoriasis, Thyroid gland; papillary thyroid carcinoma, follicular thyroid carcinoma, undifferentiated thyroid cancer, medullary thyroid carcinoma, multiple endocrine neoplasia type 2A, multiple endocrine neoplasia type 2B, familial medullary thyroid cancer, pheochromocytoma, paraganglioma; and Adrenal glands; neuroblastoma.”36 The same Literature, presents that Choline Kinase Inhibitors are indicated for Myeloproliferative Disorders including those presented here and conditions associated with those presented here. “polycythemia veras, thrombocythemias, myeloid metaplasias with myelofibroses, hypereosinophilic syndromes, juvenile myelomonocytic leukemias, systemic mast cell diseases, and Haemopoieticdisorders, in particular, acute-myelogenous leukemia (AML), chronic-myelogenous leukemia (CML), acute-promyelocytic leukemia (APL), and acute lymphocytic leukemia (ALL)”37 Pervasive Neurodegenerative orders are included in the Commercial and Clinical indicators for Choline Kinase including Alzheimer’s. The same literature indicates Choline Kinase Inhibitors for therapeutic intervention and reversal of numerous diseases and disorders including those presented here and conditions associated with those presented here. “gastroenterological disorders, hematological disorders, endocrinological disorders, urological disorders, cardiac disorders, autoimmune disorders, respiratory disorders, metabolic disorders, inflammatory disorder, immunologically mediated disorders, viral disease, infectious disease, bone disorders” Infectious diseases are indicated for Choline Kinase Use by the same clinical literature, although these analyses arrived at this conclusion at an earlier instance using empirical, objective analyses, it’s very interesting to incur literature in accordance with conclusions obtained in such analysis. Expansively, when including the Super Indicators, pervasively human health status thus far incurred are able to be centrally and therapeutically affected by remediating super indicators and including within these management of PEMT toward optimal exhibition as well as utilizing choline kinase inhibitors, Omega-3 factors, Choline Pathway Metabolites, Organic Whole Food Vitamins, Minerals, and Phytochemicals and, of course, medical capabilities and CRISPR CAS capabilities. Management of iNOS, uNOS, TMAO, Nitrosamines, Chlorine and Fluorine as well as detrimental levels of other super indicators should be included here as priorities also.

36 37

United States Patent and Trademark OfficeUSPTO Application Number 12/623,970. United States Patent and Trademark OfficeUSPTO Application Number 12/623,970.

Phytoestrogens can activate Estrogen Receptors or inhibit Estrogen Receptors while the Root Bark of Lycium Chinense exhibits Bioactive Octahydroxylated C21 Steriods.38 C21 Steroids are molecules exhibiting Four Connected Rings, which constitute a Hydrogenated Cyclopentophenanthrene-Ring System. The Fourth Ring exhibits Five Carbons while the preceding three rings exhibit 6 Carbons. Two of the Six Ringed moieties produce an evenly aligned beginning stepped structure which heightened by the third 6 Carbon ring which is attached to the upper Right Carbon to Carbon Adhesion extent of the Second Hexameter. The Fourth Ring exhibits Five Carbons and attaches to the third Hexameter Structure at the Second Carbon to Carbon Adhesion which occurs Counter Clockwise from where the Second Hexameter attaches to the Hexameter. Thus, the Five Carbon Ring Pentameter leads forward from complex of 3 Hexameters to connect to additional Atoms or Structure.39 The C21 Steriod exhibits Stereochemistry characteristics at the lower most antiapical Carbon in which a Hydrogen oriented outward toward the reader extends downward and forward in the same direction as the other aspects of the molecule, accompanied by a Hydrogen Oriented away from the reader which extends downward, also, from this antiapical Carbon and toward the leading aspect of the molecule in direction opposite of the other Hydrogen at this position. A Hydrogen oriented outward toward the reader is exhibited at the upper Carbon of the shared Carbon to Carbon Adhesion between the first Hexameter and Second Hexameter. Similarly, the Adhesion between third hexameter and the Pentameter exhibits a Carbon oriented outward toward the reader at the Upper Carbon while the lower Carbon of this juncture is oriented away from the Reader. The structure extending from the Pentameter begins at the uppermost Apical Carbon and exhibits a Carbon Adhesion extended from the Ringed Structure, followed by exhibition of two Carbon Adhesions which diverge in opposite directions from this first Carbon to Carbon Adhesions, as if the structure of two new Hexameters are being potentated. However, continuing the C21 Steroid Structure, the uppermost Carbon concludes its structure there, whle the lowermost Carbon is connected to another carbon more closely potentiating the Hexameter by completeing four of the adhesions required for a Hexameter when including the contribution of an additional Carbon to Carbon adhesion by the Adjacent Pentameter. However, a Cis Stereochemistry characteristic is exhibited, turning the next Carbon to Carbon Adhesion outward away from the continued closure of the potential Hexameter or more progressed closure of the pontentiated Hexameter. Cis, in this regard, suggest stepped structure in continous W like characteristic, while Trans suggests a scoop structure similar to three sides of Hexameter. This Cis structure then connects to a Trans Structure of Five Carbons shaped like a extended M, connecting to this M structure at the point of the V in the middle of the M structure, while an additional Carbon moiety extends away from the rest of molecule beginning at the second from second to the last Carbon toward the lowermost or rightmost extremity of the M structure. No Stereochemistry is presented after the Pentameter of the C21 Steriod molecular structure. Some of the literature presents the Upper Most or Leftmost Adhesion of the M or Line of the M exhibited a Cis configuration such that this is not extended downard to complete the M, but is extended upward, thereby completing the uprights of Field Goal, the four sides of potentiated Pentameter, or the lifting arms for Forklift at the forward edge of the C21 Steriod Structure.

38 39

Digital Object Identifier 10.1021/acs.jnatprod.5b01087 Medical Dictionary. The Free Dictionary.

Interestingly, Cholecalciferol differs in principle structure from the C21 Steroid structure in that the second ring of the evenly presented Hexameters is opened to exhibit a Cis structural characteristic similar to a Cis Fatty Acid that effectively leaves the Second Hexameter Open, such that the First Hexameter exhibits two double adhesions extended upward and to the right while only the Double Adhesion extending directly upward connects to another Carbon, while also an additional Carbon is also connectect at this locus, leading to the third Hexameter. The third Hexameter and Pentameter are similar between Cholecalciferol and C21 Steriod structure except that Cholecalciferol exhibits a Hydrogen at the upper Carbon Shared between the Pentameter and Hexameter which is oriented outward toward the user and while also the lower Shared Carbon between the Hexameter and Pentameter is oriented away from the reader, while also in Cholecalciferol this configuration is also exhibited in an inverted configuration for the Carbons exhibited between the second Hexameter and the third hexameter. Continuing presentation of the Cholecalciferol structure, the structure extending from the Pentameter of Cholecalciferol in a direction opposite of the Hexameter Ring complex, which is also forward or left, begins at the first Carbon, Clockwise, from the Upper Carbon Shared with the Hexameter which exhibits the Hydrogen or variable group which is oriented outward toward the reader. Although both C21 Steriod Structure and Cholecalciferol share this same Stereochemistry at Hydrogens exhibited at the Carbons Shared between the Hexameter and Pentameter, Cholecalciferol is missing homologous Sterochemistry in the dismantled Second Hexameter, an outward oriented Hydrogen is exhibited in downward and forward direction at the Carbon from which juncture of the Pentameter and forward Extending structure, while also the two downward and oppositely oriented Hydrogens at the antiapical Carbon of the first Hexameter have been replaced by an individual OH extending in the direction opposite of he Pentameter at the first Carbon Clockwise from the antiapical Carbon and where this OH Group exhibits Stereochemistry characteristic of being oriented away from the Reader. The structure extending forward of the Pentameter proceeds in a continuous Cis configuration, exhibiting a Variable Group oriented upward and outward to the reader at the first carbon which accompanies the Hydrogen oriented downward and outward to the reader which is located at the juncture of the Pentameter and the forward extending structure. Vitamin D differs from Cholecalciferol through a double adhesion btween the second and third carbons from the Pentameter in the structure extended forward from the Pentamater, while there is also exhibited a Stereochemistry exhibiting locus at the fourth Carbon away from the Pentameter such that a variable group extended outward toward the reader and downward from the structure could be accomodated. Ergocalciferol does not exhibit different structure from Ergocalciferol, according to the literature analyzed at this jucture. Calcitrol preetns Stereochemistry differences in the first Hexameter, a pentameter which has been changed to exhibit the shape of the Home Base of Baseball or Softball Field, and a change to the structure extended forward from the Pentameter in which a right leaning Cis configuration cause the structure extend upward for one carbon and then exhibit a 90% turn to the right followed by several trans adhessions which culminate in upward and forward Carbon to Carbon adhesion which diverges from a downard and reverse slightly reverse extending Carbon to Carbon Adhesion followed by an forward and slightly downard extending OH group which is somewhat equidistant between each of these Carbon to Carbon Adhesions. Calcediol exhibits similarity to Calcetriol within the structure extending from the Pentameter, while the Pentameter does not exhibit Home Base structure, a double adhesion is exhibited between second carbon from the first Hexameter and the Second Hexameter with acknowledgement that the second Hexameter is in an open configuration such that third

Hexameter is now the Second Hexameter, as well as abdication of differences in Stereochemistry from Cholecalciferol within the first Hexameter. Interestingly, Cholesterol, too, exhibits the same Hexameter and Pentameter complex as C21 Steriods and Cholecalciferol, except that it does not exhibit the open second Hexameter Structure which Cholecalciferol exhibits. Most Interestingly, while the Hexameter and Pentameter Complex of Cholesterol is structurally Homologous to C21 Steriods, Cholesterol exhibits structure extending forward from the Pentameter which is Homologous to Cholecalciferol. Actually, there is no difference between Cholecalciferol and Cholesterol within this strucutre extending from the Pentameter. However, the structure of Cholesterol within the first Hexameter is similar to Cholecalciferol. The structure of the second Hexameter is similar to C21 Steriods except for an inward and away oriented Hydrogen extended downward from the Apical Carbon. The structure of the third Hexameter is similar to that of C21 Steriods and Cholecalciferol except for an inward and outward oriented Hydrogen extending upward from the Antiapical Carbon. The pentamaters are are similar between Cholecalciferol, Cholesterol and C21 Steroids except for C21 Steriods not exhibiting a forward and away oriented Hydrogen extending away from the Carbon at the beginning of the forward extending structure, while such away oriented Carbon is also below the forward extending structure. These analysis present Stereochemistry wedges without any Atom or molecule attached as being able to accommodate a variable molecular group or Atom, regardless of if these are solid or striped, indicating orientation toward the reader and indicating orientation away from the reader respectively. The reader can resolve these in other ways if required. The conclusion here is that Cholecalciferol, Cholesterol and C21 Steriods have very similar and progressively correlated structure. It is possible that these molecules may potentiate each other or affect each others metabolism catalytically as well as through progression of molecule pathway. Certainly, mechanisms presented in these analysis of enabling molecular rearrangements increase the potential of these factor affecting the availability and catalytic activity of one another. The Commercial literature presented here includes voluminous combinations of preparation, instrumentation, accompanying therapeutics and other factors which explain less about the molecular mechanisms than the AMEHSI Specification, but provide a plethora of opportunity for production of concise pharmacotherapeutic regiments centered upon Choline Kinase Inhibitors. The AMEHSI Specification, however, includes a process in which the incipient susceptibility, how and why a condition emerges, persists, imparts detriment and progresses, are all considered in diagnostics, analysis, therapeutics, intervention and prevention. These include intervening conditions at why they occur and include enabling Physiology to become regenerated after any required health intervention or behavioral intervention has occurred� 40 Including Tyrosine Kinase Inhibitors, Choline Kinase Inhibitors, managed Homocysteine, Managed S-adenosyl Homocysteine, managed SP1/SP2/SP3/etc, managed AP1/AP2/etc, assured Omega-3/Omega-6 balance, assure Choline Pathway Metabolites, Assure PEMT activity, assured Phytochemical/Carotenoid/Flavonoid Factors, assured whole Food Organic Vitamins, assured Minerals, management of Inducible Nitric Oxide Synthase, Management of Uncoupled 40

United States Patent and Trademark OfficeUSPTO Application Number 12/623,970.

Nitric Oxide Synthase, management of reactive oxygen species, medical capabilities, alternative/traditional/eastern or other areas of medicine, CRISPR CAS gene editing technology and management of those super indicators presented in the specification, these analyses present wide and potentially complete coverage of these conditions presented by the National Library of Medicines “� internet site.

The oncology areas presented in this list each required that PEMT not be highly expressed pervasively do not exhibit PEMT expression at all, or pervasively exhibit low levels of PEMT, whereas only minuscule percentages of biopsies exhibit intermediate levels of this pivotal enzyme. Cursory analyses explain those categories which exhibit increased percentages of biopsies exhibiting intermediate levels of PEMT. Breast Cancer may have Genetic, Menopausal, and iNOS influence pathways which each modulate PEMT such as abrogation of 17Beta-Estradiol availability which cause upregulation of AP1 through unequal activation of Estrogen Receptor Alpha compared to decreased expression of Estrogen Receptor Beta, as well as the BRCA1 and BRCA2 genetic polymorphism which are now known to modulate AP1 and PEMT availability. Cervical, Endometrial and Ovarian oncology each exhibit potential for HPV association Pathology which includes increased Expression of AP1 a known inhibitor of PEMT. Prostate and Colorectal Oncology are exhibited in area of anatomy in which Hepatic transformation of Trimethylamine into Trimethylamine-N-Oxide, associated with less than optimal digestive pathway microflora, occurs to supplant or augment Homocysteine and other aspects of inflammatory signaling. Testis are exhibited near an LPCAT1 tissue base. Melanoma and Glioma both share Human Epidermal Growth Factor as a participating enzymatic factor which participates in a metabolic cycle that includes Peroxisomes, an organelle in which Beta-Oxidation of Fatty Acid Occurs. Regardless, these exceptions are also known to respond to Choline Kinase Inhibitors. Able to be Remediated and Prevented Oncology Conditions i. ii. iii. iv. v.

vi. vii. viii. ix. x. xi. xii. xiii. xiv. xv. xvi. xvii. xviii. xix. xx. xxi. xxii. xxiii. xxiv.

Acute Lymphoblastic Leukemia (ALL) Acute Myeloid Leukemia (AML) Early Onsets, Oncology in Adrenocortical Carcinoma, Adult Early Onset Adrenocortical Carcinoma - see Unusual Oncology of Early Onset AIDS-Related Oncology Kaposi Sarcoma (Soft Tissue Sarcoma) AIDS-Related Lymphoma (Lymphoma) Primary CNS Lymphoma (Lymphoma) Anal Oncology Appendix Oncology - see Gastrointestinal Carcinoid Tumors Astrocytomas, Early Onset (Brain Oncology) Atypical Teratoid/Rhabdoid Tumor, Early Onset, Central Nervous System (Brain Oncology) Basal Cell Carcinoma of the Skin - see Skin Oncology Bile Duct Oncology Bladder Oncology Early Onset Bladder Oncology - see <="">Unusual Oncology of Early Onset Bone Oncology (includes Ewing Sarcoma and Osteosarcoma and Malignant Fibrous Histiocytoma) Brain Tumors Breast Oncology Early Onset Breast Oncology - see Unusual Oncology of Early Onset Bronchial Tumors, Early Onset - see Unusual Oncology of Early Onset Burkitt Lymphoma - see Non-Hodgkin Lymphoma Carcinoid Tumor (Gastrointestinal)

xxv. xxvi. xxvii. xxviii.

xxix. xxx. xxxi. xxxii. xxxiii. xxxiv. xxxv. xxxvi. xxxvii. xxxviii. xxxix. xl. xli. xlii. xliii. xliv. xlv. xlvi. xlvii. xlviii. xlix. l. li. lii. liii. liv. lv. lvi.

lvii. lviii. lix. lx. lxi. lxii. lxiii. lxiv. lxv. lxvi. lxvii. lxviii.

lxix. lxx. lxxi. lxxii. lxxiii. lxxiv. lxxv. lxxvi.

Early Onset Carcinoid Tumors - see Unusual Oncology of Early Onset Carcinoma of Unknown Primary Early Onset Carcinoma of Unknown Primary - see Unusual Oncology of Early Onset Cardiac (Heart) Tumors, Early Onset - see Unusual Oncology of Early Onset Central Nervous System Atypical Teratoid/Rhabdoid Tumor, Early Onset (Brain Oncology) Embryonal Tumors, Early Onset (Brain Oncology) Germ Cell Tumor, Early Onset (Brain Oncology) Primary CNS Lymphoma Cervical Oncology Early Onset Cervical Oncology - see Unusual Oncology of Early Onset Early Onset Oncology Oncology of Early Onset, Unusual Cholangiocarcinoma - see Bile Duct Oncology Chordoma, Early Onset - see Unusual Oncology of Early Onset Chronic Lymphocytic Leukemia (CLL) Chronic Myelogenous Leukemia (CML) Chronic Myeloproliferative Neoplasms Colorectal Oncology Early Onset Colorectal Oncology - see Unusual Oncology of Early Onset Craniopharyngioma, Early Onset (Brain Oncology) Cutaneous T-Cell Lymphoma - see Lymphoma (Mycosis Fungoides and SĂŠzary Syndrome) Ductal Carcinoma In Situ (DCIS) - see Breast Oncology Embryonal Tumors, Central Nervous System, Early Onset (Brain Oncology) Endometrial Oncology (Uterine Oncology) Ependymoma, Early Onset (Brain Oncology) Esophageal Oncology Early Onset Esophageal Oncology - see Unusual Oncology of Early Onset Esthesioneuroblastoma - see Unusual Oncology of Early Onset Ewing Sarcoma (Bone Oncology) Extracranial Germ Cell Tumor, Early Onset Extragonadal Germ Cell Tumor Eye Oncology Early Onset Intraocular Melanoma - see Unusual Oncology of Early Onset Intraocular Melanoma Retinoblastoma Fallopian Tube Oncology Fibrous Histiocytoma of Bone, Malignant, and Osteosarcoma Gallbladder Oncology Gastric (Stomach) Oncology Early Onset Gastric (Stomach) Oncology - see Unusual Oncology of Early Onset Gastrointestinal Carcinoid Tumor Gastrointestinal Stromal Tumors (GIST) (Soft Tissue Sarcoma) Early Onset Gastrointestinal Stromal Tumors - see Unusual Oncology of Early Onset Germ Cell Tumors Early Onset Central Nervous System Germ Cell Tumors (Brain Oncology) Early Onset Extracranial Germ Cell Tumors Extragonadal Germ Cell Tumors Ovarian Germ Cell Tumors Testicular Oncology Gestational Trophoblastic Disease Hairy Cell Leukemia

lxxvii. lxxviii. lxxix. lxxx. lxxxi. lxxxii. lxxxiii. lxxxiv. lxxxv. lxxxvi. lxxxvii. lxxxviii. lxxxix. xc. xci. xcii. xciii. xciv. xcv. xcvi. xcvii. xcviii. xcix. c. ci. cii. ciii. civ. cv. cvi. cvii. cviii. cix. cx. cxi. cxii. cxiii. cxiv. cxv. cxvi. cxvii. cxviii. cxix. cxx. cxxi. cxxii. cxxiii. cxxiv. cxxv. cxxvi. cxxvii. cxxviii.

Head and Neck Oncology Early Onset Head and Neck Oncology - see Unusual Oncology of Early Onset Heart Tumors, Early Onset - see Unusual Oncology of Early Onset Hepatocellular (Liver) Oncology Histiocytosis, Langerhans Cell Hodgkin Lymphoma Hypopharyngeal Oncology (Head and Neck Oncology) Intraocular Melanoma Early Onset Intraocular Melanoma - see Unusual Oncology of Early Onset Islet Cell Tumors, Pancreatic Neuroendocrine Tumors Kaposi Sarcoma (Soft Tissue Sarcoma) Kidney (Renal Cell) Oncology Langerhans Cell Histiocytosis Laryngeal Oncology (Head and Neck Oncology) Early Onset Laryngeal Oncology and Papillomatosis - see Unusual Oncology of Early Onset Leukemia Lip and Oral Cavity Oncology (Head and Neck Oncology) Liver Oncology Lung Oncology (Non-Small Cell and Small Cell) Early Onset Lung Oncology - see Unusual Oncology of Early Onset Lymphoma Male Breast Oncology Malignant Fibrous Histiocytoma of Bone and Osteosarcoma Melanoma Early Onset Melanoma - see Unusual Oncology of Early Onset Melanoma, Intraocular (Eye) Early Onset Intraocular Melanoma - see Unusual Oncology of Early Onset Merkel Cell Carcinoma (Skin Oncology) Mesothelioma, Malignant Early Onset Mesothelioma - see Unusual Oncology of Early Onset Metastatic Oncology Metastatic Squamous Neck Oncology with Occult Primary (Head and Neck Oncology) Midline Tract Carcinoma Involving NUT Gene - see Unusual Oncology of Early Onset Mouth Oncology (Head and Neck Oncology) Multiple Endocrine Neoplasia Syndromes - see Unusual Oncology of Early Onset Multiple Myeloma/Plasma Cell Neoplasms Mycosis Fungoides (Lymphoma) Myelodysplastic Syndromes, Myelodysplastic/Myeloproliferative Neoplasms Myelogenous Leukemia, Chronic (CML) Myeloid Leukemia, Acute (AML) Myeloproliferative Neoplasms, Chronic Nasal Cavity and Paranasal Sinus Oncology (Head and Neck Oncology) Nasopharyngeal Oncology (Head and Neck Oncology) Early Onset Nasopharyngeal Oncology - see Unusual Oncology of Early Onset Neuroblastoma Non-Hodgkin Lymphoma Non-Small Cell Lung Oncology Oral Oncology, Lip and Oral Cavity Oncology and Oropharyngeal Oncology (Head and Neck Oncology) Early Onset Oral Cavity Oncology - see Unusual Oncology of Early Onset Osteosarcoma and Malignant Fibrous Histiocytoma of Bone Ovarian Oncology Early Onset Ovarian Oncology - see Unusual Oncology of Early Onset

cxxix. cxxx. cxxxi. cxxxii. cxxxiii. cxxxiv. cxxxv. cxxxvi. cxxxvii. cxxxviii. cxxxix. cxl. cxli. cxlii. cxliii. cxliv. cxlv. cxlvi. cxlvii. cxlviii. cxlix. cl. cli. clii. cliii. cliv.

clv. clvi. clvii. clviii. clix. clx. clxi. clxii. clxiii. clxiv. clxv. clxvi. clxvii. clxviii. clxix. clxx. clxxi. clxxii. clxxiii. clxxiv.

clxxv. clxxvi. clxxvii. clxxviii. clxxix. clxxx.

Pancreatic Oncology Early Onset Pancreatic Oncology - see Unusual Oncology of Early Onset Pancreatic Neuroendocrine Tumors (Islet Cell Tumors) Papillomatosis - see Unusual Oncology of Early Onset Paraganglioma Early Onset Paraganglioma - see Unusual Oncology of Early Onset Paranasal Sinus and Nasal Cavity Oncology (Head and Neck Oncology) Parathyroid Oncology Penile Oncology Pharyngeal Oncology (Head and Neck Oncology) Pheochromocytoma Early Onset Pheochromocytoma - see Unusual Oncology of Early Onset Pituitary Tumor Plasma Cell Neoplasm/Multiple Myeloma Pleuropulmonary Blastoma - see Unusual Oncology of Early Onset Pregnancy and Breast Oncology Primary Central Nervous System (CNS) Lymphoma Primary Peritoneal Oncology Prostate Oncology Rectal Oncology Recurrent Oncology Renal Cell (Kidney) Oncology Retinoblastoma Rhabdomyosarcoma, Early Onset (Soft Tissue Sarcoma) Salivary Gland Oncology (Head and Neck Oncology) Early Onset Salivary Gland Tumors - see Unusual Oncology of Early Onset Sarcoma Early Onset Rhabdomyosarcoma (Soft Tissue Sarcoma) Early Onset Vascular Tumors (Soft Tissue Sarcoma) Ewing Sarcoma (Bone Oncology) Kaposi Sarcoma (Soft Tissue Sarcoma) Osteosarcoma (Bone Oncology) Uterine Sarcoma Sézary Syndrome (Lymphoma) Skin Oncology Early Onset Skin Oncology - see Unusual Oncology of Early Onset Small Cell Lung Oncology Small Intestine Oncology Soft Tissue Sarcoma Squamous Cell Carcinoma of the Skin - see Skin Oncology Squamous Neck Oncology with Occult Primary, Metastatic (Head and Neck Oncology) Stomach (Gastric) Oncology Early Onset Stomach (Gastric) Oncology - see Unusual Oncology of Early Onset T-Cell Lymphoma, Cutaneous - see Lymphoma (Mycosis Fungoides and Sèzary Syndrome) Testicular Oncology Early Onset Testicular Oncology - see Unusual Oncology of Early Onset Throat Oncology (Head and Neck Oncology) Nasopharyngeal Oncology Oropharyngeal Oncology Hypopharyngeal Oncology Thymoma and Thymic Carcinoma Thyroid Oncology

clxxxi. clxxxii. clxxxiii. clxxxiv. clxxxv. clxxxvi. clxxxvii. clxxxviii. clxxxix. cxc. cxci. cxcii. cxciii. cxciv. cxcv.

Early Onset Thyroid Tumors - see Unusual Oncology of Early Onset Transitional Cell Oncology of the Renal Pelvis and Ureter (Kidney (Renal Cell) Oncology) Unknown Primary, Carcinoma of Early Onset Oncology of Unknown Primary - see Unusual Oncology of Early Onset Unusual Oncology of Early Onset Ureter and Renal Pelvis, Transitional Cell Oncology (Kidney (Renal Cell) Oncology Urethral Oncology Uterine Oncology, Endometrial Uterine Sarcoma Vaginal Oncology Early Onset Vaginal Oncology - see Unusual Oncology of Early Onset Vascular Tumors (Soft Tissue Sarcoma) Vulvar Oncology Wilms Tumor and Other Early Onset Kidney Tumors Earlier Onset Oncology

Estrogen as Estradiol is known to cause increase closing or senescence of Tibial Growth Plate while Testosterone is known to induce growth within the Tibial Growth Plate.41 42 Pervasive research exhibit that regeneration of the Growth Plates is possible in numerous ways. iNOS is also known to affect Growth Plate Repair.43 Interestingly, these analyses found a potential correlation between membrane Phospholipid Plasticity, Lysophosphatidylcholine Acyltransferase Activity and direction of Membrane Phospholipid cycling. LPCAT1 and LPCAT2 are suggested by the literature have subcellular locations principally within the Endoplasmic Reticulum and Golgi Apparatus, including within Lipid Droplets, whereas LPCAT3 is suggested to occur as a Transmembrane Protein in each such location, although additionally in Plasma Membrane, Peroxisomes and in the Extracellular Environment.44 45 The Gene Cards Database suggests that there is LPCAT1 has the greatest probability of being associated with the Plasma Membrane whereas LPCAT2 and LPCAT3 have low probability of being associated with the Plasma Membrane. LPCAT4 has moderate probability of association with the Plasma Membrane. The UniProt Database is no clear about which Membrane LPCAT3 is associated with. However, these exhibit that since particular aspects of both Choline Kinase Pathway and Ethanolamine Kinase Pathway have incipient activity subcellular locations in the Mitochondria/Endoplasmic Reticulum/Golgi Apparatus as well as Cytosol respectively, that the cycling of Membrane Phospholipids determines LPCAT activity and determines directional flow. Specifically, Prevalence of Choline Kinase Pathway potentiates Phosphatidylcholine that is not DHA/EPA/Omega-3 Enriched, does not exhibit Phosphatidylmonomethylethanolamine benefits, does not exhibit Choline/Ethanolamine Kinase or PEMT benefits, and results in flow of Phosphatidylcholine toward Phosphatidylserine/Sphingomyelin which then potentiates Phosphatidylethanolamine from Phosphatidylserine and potentiates Ceramide from Sphingomyelin. Thus, Phosphatidylserine potentiates Phosphatidylethanolamine, and the Phosphatidylethanolamine it potentiates does not seem to have the same characteristics as that produced within the Ethanolamine Kinase Pathway, Mitochondria and 41 42 43 44 45

Endocrine. October 2001. Volume 16. Issue 1. Pages 1 to 6. Digital Object Identifier 10.1073ypnas.121180498 Digital Object Identifier 10.1002/jcb.20905

Endoplasmic Reticulum. The differences in LPCAT activity, then, suggest that LPCAT 1 and LPCAT4 predominate as determinants of Membrane Phospholipid Characteristics and Plasticity. LPCAT4 upregulation is observed in Colorectal Oncology, which is similar to Prostate Oncology in not exhibiting as substantial a comparative downregulation of PEMT. Instead of downregulated PEMT, Choline Kinase is upregulated, suggesting that the flow of Membrane Phospholipids is increasedly from the Choline Kinase Pathway, to Phosphatidylcholine to Phosphatidylserine and Sphingomyelin and then divergently to Phosphatidylethanolamine and Ceramide respectively. These clearly indicate how changes in LPCAT associated with flow of Phospholipid synthesis activity can be participative, enabling to or causal to Oncology. Histology information suggests that the levels of LPCAT4 RNA in Male tissues are associated with comparatively increased levels of Protein in these same tissues. These clearly suggest that some circumstance is producing a higher level of LPCAT4 protein expression other than an increase in MRNA Levels. Trimethylamine â&#x20AC;&#x201C; N â&#x20AC;&#x201C; Oxide or TMAO is known to cause Protein-Folding of Glucocorticoid Receptors which enhances catalytic activity. Similarly, Androgen Receptor is known to enhance the stability of Choline Kinase. Glucocorticoid Receptors can include Androgen Receptor, have Homologous Domains, or be presented separately by some literature. Together, these clearly exhibit that disproportionate increases of LPCAT4 can be correlated to, observed along with or participative if not causal to particular Pathology.46 One might extend the analogy of the events at Pearl Harbor on December 7, 1941 here clearly since LPCAT factors also are known as MBOAT factors. One is encouraged to consider Human events and expressive activity in correlation with all information the Amehsi Specification, such that one may clearly observe that pervasively these analyses present concepts exhibited in expressive, creative and productive activity of Humanity sometimes decades, centuries or even eons in preceding Epochs. Thus, emerging is an improving understanding of Phosphatidylcholine Synthesis, Choline Metabolism and how Acyltransferase manage Fatty Acid Distribution. DHA is potentially integrated into Phospholipoids by LPCAT1 and LPCAT2 which integrated DHA or other Omega-3 at SN2 of Phospholipids. ARA is suggested by the Literature to be integrated by LPAAT1, LPAA2, LPAAT3, and MBOAT5/LPCAT3 at both SN1 and SN2, particularly using Phosphatidylcholine. MBOAT5/LPCAT3, MBOAT7/LPIAT1, and LPAAT3 are suggested by the literature to integrate Arachidonic Acid into Phosphatidylcholine, Phosphatidylethanolamine, and Phosphatidylserine. MBOOAT7/LPIAT1 and LPAAT3 are suggested by the literature to integrate Arachidonic Acid into Phosphatidylinositol. These do not suggest a mechanism of DHA and EPA integration into Phosphatidylinositol, indicating why IP3k IP3 may be associated with Inflammation. These inflammation pathways can include or be interactive with PI3K, MAPK FOS/JUN, JAK/STAT and other pathways. These pathways extend to the AP1 and SP1 level. These pathways have dual modalities, being inflammation pathways when PEMT is inhibited, DHA/EPA/Omega-3 is inadequate, and Hyaluronic Acid is not adequately presented, all of which inhibit the ability of Immunological and other activity to introducing scarring and all of which would potentiate exhibition of Regenerative Blastema instead of Scar Tissue. 46

PEMT seems to be the Gateway to Enrichment of Cellular Membranes by enabling substantial increases in Acetyl - CoA which enhances Fatty Acid Synthesis, Fatty Acid Beta Oxidation, Lipid Synthesis and enables LPCAT and other Acyltransferase Activity Pervasively. PEMT Prefers Diacylglycerol with DHA and EPA. However, LPCAT4 is known to produce Phosphatidylethanolamine integrated using Oleoyl-CoA as a Precursor, indicating that Oleic Acid can enter Fatty Acid Cycling and Phospholipid Membrane Fatty Acid Cycling through LPCAT4 and its integration of Oleic Acid into Phosphatidylethanolamine. Oleoyl and Palmitate factors are suggested by the literature to be among the most prevalently exhibited Fatty Acids in PEMT synthesized Phosphatidylcholine. LPCAT2 may be enhanced in its activity as a Xenobiotic Response Factor. LPCAT1 Participates in Alveolar surfactant exhibition. LPCAT4 Potentiates Cone Shaped Cellular Compartments and Superstructure whereas LPCAT4 potentiates Rod shaped structures, according to the Clinical and Research Literature. Interestingly, although LPCAT2, LPCAT3, LPIAT1 and LPAAT3 as known to integrated Poly Unsaturated Fatty Acids into Lysophospholipids, LPCAT4 is suggested to not be able to accomplish such a Fatty Acid Integration. Impaired function or availability of Flavin Monooxygenase Activity impairs LPCAT3 activity as well as Stearoyl - CoA Desaturase 1 activity. Subcellular location probabilities suggest that LPCAT2 and LPCAT3 have low possibility of being located at the Plasma Membrane, whereas LPCAT1 has high probability of Plasma Membrane activity and LPCAT4 has a moderate Probability of Plasma Membrane Subcellular Location. The integration of DHA, EPA and Omega-3 from Diacylglycerol by PEMT, then, seems essential since LPCAT1 is the LPCAT which is potentially able to continuously integrate DHA/EPA/Omega-3 once Phospholipids arrive at the Plasma Membrane. This suggests that PEMT must integrate the factors with which it inhibits inflammation early in the Phospholipid Synthesis Cycle and Choline Kinase Activity circumvents this essential phase. Thus, cycling of Phospholipids into Phosphatidylcholine, then Phosphatidylserine, then to Phosphatidylethanolamine, in a recycling mechanism, may be essential to membrane plasticity because it allows a more prevalent exhibition of Choline Kinase Pathway Produced Phosphatidylcholine to become recycled through PEMT. Thus, at the Membrane, LPCAT4 cannot produce Omega-3 integrated Phospholipids and LPCAT1 might do so within particular conditions although some literature suggests that it cannot produce Omega-3 integrated Phospholipids. LPCAT3 seems essential in producing Arachidonate as may other Acyltransferases, although Omega-3 Fatty Acids are emerging as an essential factor that require Phospholipid factors to return to the Enrichment Recycling Factory produced by PEMT. The patterns of similar Enzymes such as Rubisco, however, suggest that there may be a possibility that Delta 12 and Delta 15 Desaturase activity could be exhibited in the Human Genome or Metabolome as well as exhibit Catalytic Activity. These analyses have not found any indication of such at this instance However. PEMT increases the levels of Acetyl-CoA which participates in Acetylation. Acetylation seems to occur in up to %90 or more of Proteins in the Human Transcriptome and Metabolome. Acetylation is also correlated to complexity of Organism's Anatomy, as the activity the Acyltransferases characterized here suggests. Acetylation of Histones results in removal of the Anionic Positive Polarity Epigenetic Indicator from Histones, resulting in less affinity being exhibited between the Cationic Negatively Polarized Phosphates Groups of

DNA. DNA is then relaxed from its more tightly integrated status with DNA. Acetylation of Histones enables improved access to DNA for copying, reading and transcription, replication, repair or other activity. Pivotally, P53, although stimulated by inhibition of PEMT, is suggested in the literature to require Acetylation to effect its management of Genome, Transcriptome and Metabolome. Among 3 Acetylation Loci within P53, all are able to be Acetylated and one is required to be Acetylated to enable P53s stimulation of P21, both of which abate Cellular Cycle. Impairment of these Loci or inadequate Acetyl-CoA, potentiates less than adequate Acetylation of P53. Acetylation of P53 protects it from MDM2 integration and rapid Proteolysis. PTEN is known to protect P53 in a similar way. The list of ways in which Physiology is transformed toward demise, oncology, Leukemia, Lymphoma, Genetic Conditions, impairment, detrimental behavior inability to repair or regeneration Anatomy, at this instance is become so expansive that it may require its own Database to manage.

There is a substantial Possibility that PEMT inhibition may impair for copying, reading and transcription, replication, repair or other activity conducted utilizing DNA. There is also a possibility that PEMT inhibition begins a systemic decrease in complexity of an Organism by reducing its Transcriptome and Metabolome to no longer be able to manage, regenerate, supply or assure the complexity that was exhibited during incipient development. Lysines within the N Extremity are typical Loci of Acetylation of Proteins while Histones are structures around which DNA is Packed and Wound, and Histone tails insert themselves into the Minor Grooves of DNA, between the Helixes. Thus, a very important understanding of the manner in which PEMT inhibition and Choline Kinase upregulation effect Physiology. Upregulation of Choline Kinase, Alone, increases the potential for saturated Fatty Acid Prevalence in Cellular Membranes and decreases the potential for DHA to be integrated into cellular membranes. The decrease of DHA is resultant of decreased exhibition of START Protein D4, D5, and D6 as well as decrease in LPCAT3 activity. Similarly, although LPCAT4 is known to integrate Oleoyl-CoA derived Oleic Acid into Phospholipids, introducing a negatively polarized factor that enhances the negative polarity presented by Phosphatidylserine such that Inflammation and Coagulation Cascade is potentiated at the cellular membranes. LPCAT1 is differently presented by the literature as having and not having the ability to integrated Polyunsaturated Fatty Acids into Phospholipids, suggesting that its ability to introduce DHA into Phospholipids may be circumstantial including potentially being reliant upon PEMT and PEMT integration of DHA into SN2. Interestingly, the literature suggests that PMA/TPA stimulates DHA, EPA and Omega-3 Fatty acid integration into Diacylglycerol. These analyses suggest that PMA/TPA may be a factor in inflammation, being stimulated by AP1. A Cyclical connection between SP1 and AP1 is presented in the literature as occurring through Cyclins and CDKs, such that these factors may stimulate one anotherâ&#x20AC;&#x2122;s activity, suggesting that PMA/TPA can also upregulate CTP â&#x20AC;&#x201C; Phosphocholine Citidylyltransferase as well as produce an oscillating mechanism by which the opposite regulation of Telomerase by SP1 and AP1 occurs through responsiveness of cyclins. A study of Bovine, Large Mammal, Glomerular particles exhibited that catalytic enhancement of Choline Phosphotransferase occurred when Magnesium as MG2+ was available, while Ethanolamine Phosphotransferase

seemed to require Manganese as Mn2+, while Cytidine Nucleotides inhibited Ethanolamine Phosphotransferase simultaneously to producing upregulation of Choline Phosphotransferase activity. Thus, while CTP is required for both Ethanolamine Phosphotransferase activity and Choline Phosphotransferase activity, Cytidine Nucleotides inhibit Ethanolamine Phosphotransferase activity while preferentially upregulated Choline Phosphotransferase activity, particularly being relevant because Adenine Nucleotides, Neurotransmitters generally and Neurotransmitter Agonists were not observed to modulate catalysis. This are interesting because Adenosine is known to inhibit Choline Kinase Activity, suggesting that the study may have merely missed focus on the wider aspects of the CDP â&#x20AC;&#x201C; Choline Pathway.47

A Study of Small Mammals observes that Homozygous impairment of CTP Phosphoethanolamine Citidylyltransferase produces Metabolic Syndromes of a particular nature while Homozygous Impairment of CTP Phosphoethanolamine Citidylyltransferase does not. This provides improved perspective, such that although CTP is not excluded from being essential to Phosphatidylcholine Synthesis, the sharing of substrates in at this juncture of the Methylation and CDP â&#x20AC;&#x201C; Choline pathways seems apparent. The literature suggests that this observation clearly indicates Shared Phosphatidylethanolamine pathway and Triglyceride Pathway usage of Diacylglycerol, but not sharing of such pathways with Phosphatidylcholine Synthesis. However, the literature presents that PEMT prefers DHA exhibiting Diacylglycerol and the fraction of Diacylglycerol being observed to be shared between Phosphatidylethanolamine and Triglyceride Synthesis could be differently Acylated Fraction compared to that utilized for Phosphatidylcholine Synthesis. These analyses are finding it more and more imperative to differentiate the Acylation Characteristics molecules, their protonated status, Oxidation, Nitrosylation and Phosphorylation, as well as Acetylation, in considering differences in Catalysis from substrate that is not isolated by organelles or intracellular subcompartments. The literature clearly suggests that the fractional composition of Acylation Characteristics are stably consistent from Diacylglycerol to the Synthesis of Triglyceride when Phosphatidate is used for the Synthesis of Triacylglycerol. The literature also suggests that Triglyceride and Triacylglycerol are Homologous.48 49 Choline/Ethanolamine Phosphotransferase catalyzes the metabolism of CDP-Choline, which exhibits the structure of Choline without the 3 Methyl Groups, along with 1,2 Diacylglycerol such that it becomes Phosphatidylcholine and CMP. 1,2 Diacylglycerol exhibits the two variable R Groups attached to Double Oxygenated Carbon followed by attachment to Oxygen, a locus which is characteristics of the Hydroxyl structures observed to bridge Fatty Acids into Phospholipids. Thus, the Positively Polarized N+ of CDP-Choline and the Variable R structures are adequate in comprise the Catalytic Output of Choline/Ethanolamine Phosphotransferase.50 These, now, are at least two pathways in in which Choline is Synthesized in Physiology, although the structural components for Choline are already in place requiring Methyl Group Substitutions and while the structural components are exhibited in a rearranged manner in quite a number of molecules including the most incipient molecules produced by Carboxylation, particularly RuBisCO. Similarly, Manganese activity is known to be associated with Metastases in Triple Negative Breast Oncology, while Magnesium and Calcium are known to depotentiate such Metastases. This study suggests that 47 48 49 50

Neurochemical Research. Volume 11. Issue 8. Pages 1167 to 1179. LIBRARY OF MEDICINE PUBMED IDENTIFIER 4052051. Biochemistry of Lipids, Lipoproteins and Membranes. Edition 6. ISBN 978-0-444-63438-2. LIBRARY OF MEDICINE PUBMED IDENTIFIER 20503434.

Mn2+ availability stimulates Ethanolamine Phosphotransferase toward Phosphatidylethanolamine while Mg2+ stimulates Choline/Ethanolamine Phosphotransferase as well as Choline Phosphotransferase to both produce Phosphatidylcholine. Mn2+ must promote metastases by producing Phosphatidylethanolamine which accumulates in the context of impaired PEMT, potentially causing the accumulation of Phosphatidylserine as well as disrupting Sphingomyelin and Ceramide Homeostasis. However, it is known that iNOS promotes mechanical force associated separation of cellular entities from matrix and tissues and it is known that Anoikis is a programmed pathway for cellular deterioration when cellular entities separate from matrix or tissue, such that the separation of cellular entities from tissues is not an unexpected occurrence in development. Interestingly, it is not difficult to consider how separation of cellular entities from tissue might promote development including connective tissue development which links aspects of physiology. However, again, it seems to be the inhibition of Apoptosis, Necrosis, Anoikis and Parthanatos pathways by NAD+ Depletion and Phosphocholine accumulation, or in other ways, which transforms such phenomena into being nuances of pathology. Inhibition of PEMT seems to produce substantial impairment of cellular metabolism. The effect seems to be that, as is correlated to the decreased production and management of Homocysteine, increasing exhibition of behavior that is like single cellular organisms and increasing behavior that seems to be like Prokaryotic Organisms exhibiting only the CDP â&#x20AC;&#x201C; Choline Pathway. Tissue level coordination of development, cellular cycle, and differentiation seems to be managed by PEMT and its ability to modulate levels of Homocysteine in a context of adequate DHA/EPA/DGLA and Hyaluronic Acid which prevents Apoptosis, Scaring and developmental impairment which Homocysteine along without these safeguards seems to promote. The context of DHA/EPA/DGLA and Hyaluronic Acid and how these modulate the ability of Homocysteine has not pervasively been explored, although these safeguards prevent pervasive other inflammation and scaring pathways, including Leukocyte penetration into tissues, matrix and Connective tissue, suggest that DHA/EPA/DLA and Hyaluronic Acid along with PEMT in the context of Homocysteine characteristics, potentially including Choline Kinase characteristics, may present a somewhat pervasive explanation of physiological outcomes at the cellular level. As early as 1955, Choline has been suggested to also be required when studying cultured cellular entities.51 The literature observes at least one study in which Small Mammal Choline Kinase resulted also in increased CDPCholine, which produced a regulatory effect to Mitosis, while other studies present Phosphocholine synthesis by Choline Kinase as a response to exhibition of Carcinogens and Xenobiotics, as well as substantial tissue injury.52 CTP Phosphocholine Cytidylyltransferase (CT), however, exhibits a synthetic Polymorphism which causes tissues to exhibit Apoptosis at 40 Degrees Celsius, suggesting that Bradykinin and TNF-Alpha may induce Apoptosis through inflammation Cascade and particular metabolic Circumstances which emerge in tissues. However, this same study observed that without CT activity, regardless of temperature, cellular entities began to exhibit Apoptosis. A Counter Polymorphism to CTP â&#x20AC;&#x201C; Phosphocholine Cytidylyltransferase resulted in resilience and survival of such entities with susceptibility to apoptosis at particular Thermodynamic levels. Although CT is considered to be a Cytoplasmic Enzyme, it is found in the Nucleus and can be found integrated into Membrane as well as in the Endoplasmic Reticulum and Microsomes. Microsomal membrane exhibition of CT and Phosphatidylcholine Synthesis seem most correlated in the literature while the literature suggests that Phospholipids are not abundant in studies of Cytosol characteristics, suggesting that it is by Translocation of CT to and from membranes as well as by transferring of CT from insoluble and Soluble status by 51 52

Biochemistry of Lipids, Lipoproteins and Membranes. ISBN. 0080860923. ISBN 0080860923

which Catalysis of Phosphatidylcholine is controlled. This observation includes the consensus that CT is the Rate Determining factor in the CDP Choline factor with other factors exhibiting Catalytic Activity based upon substrate availability and enzyme availability. CT attaches to the cellular membrane by Electrostatic Adsorption, intercalation of CT through Hydrophobic Influences at the unpolarized interstitial areas of membranes, such that Viscous Gel Phase Lipids which inhibit CT integration into the membrane result in attachment of CT in an inactivated status to the membrane. CT promoting factors in membranes include Interfacial Packing Defects including Small Head Group Factor inclusion in membranes, Loose Packing which reduces Lateral Surface Pressurization which can be described as Increased Curviness compared to Planar Bilayers, Oxidation of Acyl Moieties which causes disorderliness, increased levels of Hexagonal Phase Lipids such as Phosphatidylethanolamine and Diacylglycerol. Phosphatidylcholine also inhibits CT activity including when it is synthesized in other pathways and inadequate Phosphatidylcholine stimulates CT release as a Soluble factor. The rapid phosphorylation or acetylation of choline to either Phosphocholine or Acetylcholine, is widely regarded in the literature.53 Interestingly, in a study of Hepatic Resection, when Hepatic Organs had aspects of the tissues removed in Small Mammalian Nonhuman Organisms. Increased production of Phosphatidylcholine occurred during incipient stages of impairment through upregulation of CT. The first 24 Hours after impairment exhibited decreased PEMT activity with 45 percent aggregate PEMT downregulation and 90 percent downregulation of PEMT2. This downregulation was simultaneous to increase in DNA Synthesis and increase in CT levels occurring at 24 Hours, suggesting clearly that PEMT1 and PEMT2 were downregulated along with upregulation of CT which is in the pathway Known as the Nucleotide Pathway nonhuman organisms. This is interesting because PEMT is known to be required for adequate NADPH availability. Choline supplementation moved this peak PEMT downregulation and peak upregulation of CT along with increase DNA synthesis to 36 Hours instead of 24 in Females, while Males were not affected in such regard. Such peak periods for PEMT inhibition during impairment of Hepatic tissue and simultaneous upregulation of CT and DNA Synthesis may be expected, as may be the Female resilience to exhibiting such circumstance when Choline is available, since Choline is Known to manage inflammation. The PEMT2 downregulation occurred at the mRNA level suggesting that a change to Genetic Expression occurred, which is known to occur during injury resultant of IDO, Inducible Nitric Oxide Synthase and other factors.54 However, it seems that while PEMT is inhibited, TPA/PMA may be stimulated by Pathogenic Factors. These Pathogenic Factors have been shown to activate the Enzymes which precede PEMT beginning with Ethanolamine Kinase, as well as deplete accumulation of Methyl Carrier Intermediates in this pathway. Thus, Omega-3 Fatty Acids are suggested by the literature to either to become integrated into Choline Kinase Produced Phospholipids after their synthesis, such as through LPCAT/MBOAT Activity, while the possibility that Choline Kinase pathways or CD11P-Ethanolammine pathways exhibit Regioselectivity or preference for Diacylglycerol without Omega-3 seems to also exist. Although, both such possibilities seem unrelated, logically. A clear characterization of comparative roles for PEMT and Choline Kinase are then potentiated. Inhibition of PEMT seems to occur during Choline deficiency because Choline deficiency causes an inherent pathway of self 53 54

PMCID PMC2441939. Digital Object Identifier 10.1016/S0005-2760(97)00011-8

detriment through Apoptosis and self detriment through Catabolism of cellular Membrane by phospholipases. Impairment or Injury also is known to potentiate downregulation of PEMT, temporarily, and upregulation of P53. Thus, the downregulation of PEMT is becoming clearly discerned to occur to abate resection and development when development, regeneration and repair may not be adequately possible resultant of inadequate levels of Choline. The potential for circular logic or circular reasoning here, resultant of de Novo Synthesis of Choline through PEMT activity and catabolism of cellular membranes by Phospholipases possibly being considers as among the most essential sources of Choline, is managed by considering that the clinical literature widely observes inadequate levels of Choline in the Gestational Environment Constitutively, whereas supplementation by the Maternal Carriers, Breast Feeding by Maternal Carriers after Gestation, and 800 to 1326 or more mg each day of Choline in adults is widely recognized as essential to Human Health. PEMT, then, being abated during incipient aspects of impairment seems to be optimal in resecting scar tissue, inflammation, Omega-6 fatty acid, thrombus, or other aspects of an inflammatory response, being uniquely equipped with toxicity management, toxin management, carcinogen management, microbe management, ability to deteriorate scar tissue and amino acids with Serine Proteases, Biosynthesis enhancement, Fatty acid Synthesis enablement, solvents, inorganic phase to organic phase transfer factors, all of which clean the environment for exhibition of development, regeneration or repair. Choline Kinase seems to become upregulated to enable scarring because it does not require DHA or Omega3 in the Phosphatidylcholine which its pathway, the CDP-Ethanolamine Pathway, produces, resulting in prevalent potential of inflammatory Eicosanoids, Prothrombin, Eicosanoids, Leukotrienes, Prostaglandins and Prostanoids, particularly those which are produced by inflammatory mechanisms such as Phospholipases and Phospholipase A2. The upregulation of Choline Kinase, likewise, enhances survival signaling pathways for cellular entities through its production of Phosphocholine and Phosphocholine performs as an aspect of Platelet Activating Factor, performs as an activator of Platelets constitutively, and activates C-Reactive protein through accumulation of Phosphocholine on cellular entities which can be accompanied by activation of the compliments Immunological system. LPAAT4, a member of the AGPAT4 Group, is suggested to be able to produce 1 Stearoyl and 2 Docosahexaenoic Phosphatidic Acid and exhibits specificity toward Docosahexaenoic Acid or 22;6 CoA which is also considered to be 22;6 DHA. Other LPAAT factors are observed to not exhibit DHA Specificity. Other LPAAT Factors are only exhibited as Plantae in some Gene Databases, which is interesting because these factors seem to be essential Junctures in assuring preventing of Pathology, Deteriorating processes as well as assuring regeneration. Correlatively, some of the literature Characterizes the Kennedy Pathway as including Choline Kinase in the Cytosol, CTP Phosphocholine Cytidylyltransferase in the Nucleus or Cytosol, Choline / Ethanolamine Phosphotransferase in the Golgi Apparatus or Endoplasmic Reticulum, followed by exhibition of Phosphatidylcholine. PMID 20503434. However, the models introduced in other areas of these analyses suggest clearly that Phosphatidylethanolamine Participates in TPA/PMA activity while AP1 is known to inhibit PEMT and is known to inhibit CTP Phosphocholine Cytidylyltransferase through Promoter Region interactions. This perspective of Phospholipid Synthesis, then, may represent the PEMT inhibited Pathogenic or Ameliorated Status. There would be improved understanding if the research clearly indicated if Diacylglycerol were or were not Isolated or Preferentially distributed between Methylation Pathways from Ethanolamine Kinase to PEMT according to Omega-3 component availability It has been suggested that PEMT prefers DHA enriched Diacylglycerol. Other studies suggest that small Mammals prefer Phosphatidyl Ethanolamine with DHA in the SN2 Position and either Palmitate or Stearate in the

SN-1 when producing Phosphatidylserine using Phosphatidylserine Synthase, observed in Model of Small Mammal Brain Tissue Characteristics. Cortical Microsome in such Small Mammals also exhibit a preference for Stearoyl in the SN1 Position and DHA/Docosahexaenoyl in the SN2 position of Phosphatidylcholine with 1 Stearoyl 2 Docosahexaenoyl Phosphatidylserine being the most abundant Fatty Acid Phosphatidylserine Species in the Cortex although Phosphatidylserine is not abundant in the Small Mammal Cortex. 1 Palmitoyl 2 Docosahexaenoyl Phosphatidylcholine is not preferred for Small Mammal Phosphatidylserine Synthesis in this particular Small Mammal Model. 1 Stearoyl 2 Docosahexaenoyl Phosphatidylcholine seems to be preferred for conversion to Phosphatidylserine in this Small Mammal Model Cortex Phospholipid metabolism and also seems abundant in the Cerebellum, particularly within Purkinje Neurons. However, contrary to presumptions here elsewhere, Small Mammal Models of Phospholipid Cycling in the Cortex observe that Phosphatidylserine Decarboxylase, which performs Decarboxylation of Phosphatidylserine to become Phosphatidylethanolamine, and which occurs potentially as mechanism to provide Substrate to PEMT as well as to perform in concert with Cardiolipin for Mitochondrial Biogenesis, occurs after synthesis of Phosphatidylserine Decarboxylase. Phosphatidylserine Decarboxylase is suggested to occur after Oct1 and MPP, both Proteases, process the PSD precursor Protein. The LGST Domain which is conserved after Protease activity, exhibits an alpha Domain and beta domain. The Beta domain integrates into the Inner Mitochondrial Membrane and the Alpha Domain integrates into it, suggesting that the Functional Phosphatidylserine Decarboxylase requires Mitochondrial Translocation for function. Phosphatidylserine Decarboxylase prefers Stearoyl Fatty Acids in the SN1 position and DHA in the SN2 Position. If this model is Homologous to Human Metabolism, the Human Cerebral Cortex and perhaps other aspects of Anatomy utilize Phosphatidylserine to produce DHA Enriched Phosphatidylethanolamine and this activity occurs in the Mitochondria, while Phosphatidylcholine Produce in such manner is utilized in concert with Cardiolipin to enable Mitochondrial Biosynthesis. This Small Mammal Model then exhibits accumulation of Phosphatidylethanolamine from Phosphatidylserine Decarboxylase in the Mitochondria while Phosphatidylserine produce from the Cytidine Diphosphate Ethanolamine Pathway is exhibited in the Plasma Membrane.55 56 57 58 59 60 61 62 Conclusively, these analyses suggest that the Ethanolamine Kinase pathway to PEMT and to Phosphatidylcholine compared to the Choline Kinase Pathway to Choline Phosphotransferase or Phosphocholine Cytidylyltransferase, reliant upon which version of the Choline Kinase Pathway one reviews, may be functioning like a circuit in one respect along with functioning as Ethernet Network in another respect. The circuit function directs the Metabolites in either Pathway to a Homologous Juncture in the other because the Metabolites are either the same, different in Fatty Acid Characteristics or different only in the Head Groups or Lead Groups. Metabolic Circumstances inhibit Enzymes along each Pathway, Fatty Acid Characteristics or Substrate availability and Accumulation then determine which of the uninhibited enzymes obtain the available Metabolites, increased 55 56 57 58 59 60 61 62

PMC 3690542â&#x20AC;Ż Digital Object Identifier 10.1158/1535-7163.MCT-12-0904 Digital Object Identifier 10.1016/j.plipres.2014.06.002 Digital Object Identifier 10.1186/1743-7075-9-49 Digital Object Identifier 10.1016/j.ympev.2015.12.001 Digital Object Identifier 10.1016/j.bbrc.Z013.12.043 LIBRARY OF MEDICINE PUBMED IDENTIFIER 20503434. Digital Object Identifier 10.1074/jbc.M306252200

availability of Metabolites allows increase in Catalytic production until Michaelis Thresholds are reached, and increased availability of any Enzyme may potentiate transfer of Head Groups through Fatty Acid Metabolism or Phospholipase Activity. Interestingly, Acyltransferase Activity seems to be a convention Mechanism of redistributing Fatty Acids among Phospholipids which are being recycled by Phospholipases or Diacylglycerol factors that are being Catabolism Enzymes, resulting as efficient a reshuffling of Fatty Acids and Head Groups as occurs during Phospholipid Shuttling in Plasma Membranes as well as Shuttling of Lipids between Subcellular Compartments. Thus, Choline Kinase does not clean the intracellular environment, does not reduce PCBs, Dioxins, Alkyl Halides, Aromatic Polycyclic Hydrocarbons, Co2 and H2S, while potentially introducing Negative Polarity Oleic Acid into Phospholipids to promote Coagulation Cascade, causing increased aggregation of Phosphatidylserine which also promotes increased Coagulation Cascade. Choline Kinase is emerging a substantial factor in Xenobiotic and Allergic Response. This may be why Purinyl-6-Histamine and Histamine therapy has been effective in oncology since 1913. Similarly, this may explain why Phosphatidylmonomethylethanolamine, Monomethylethanolamine, and other factors may be antihistimines of different version. These Antihistimines structurally degrade Carcinogens, Allergens and other factors instead of merely integrating with these factors. The inhibition of PEMT, however, actively abrogates cleaning of the intracellular environment, inhibits clearing of PCBs, Dioxins, Alkyl Halides, Aromatic Polycyclic Hydrocarbons, Co2 and H2S, impairs P53, Stimulates P53, impairs regeneration, transforms regenerative signal transduction and environmental sensing pathways to inflammation, scaring, coagulation and other detrimental pathways. Inhibited PEMT impairs LPCAT3 ability to contributed Arachidonic Acid to Phospholipid Metabolism and impairs PEMT's preference for DHA exhibiting Diacylglycerol from contributing DHA to Phospholipid Metabolism. Inhibited PEMT depletes AcetylCoA from being stored as Acetylcholine, causing exhibition of Free Choline, and upregulating Choline Kinase activity by providing additional Substrate. These can result in increased Choline Kinase Phosphorylation of Choline, causing accumulation of Phosphocholine and producing a Feed Forward supply of Phosphocholine for pervasive Pathology including introducing subclinical stimulation of the Compliments Immunological System as Phosphocholine aggregates upon cellular entities and stimulates Apoptosis as indicated by increased C - Reactive Protein levels. PEMT inhibition also results in impairment of Plasma Membrane Phospholipid ability to exhibit Transfer of Cholesterol using START Protein Domains that occur within Phospholipids. PEMT inhibition increase Homocysteine, which the Amehsi Specification can correlate or show causality to more such numerous Pathogenic changes that these require several lengthy paragraphs to present as a list of factors.

However, the systems of Acyltransferase which affect Phospholipids becomes fragmented and their contribution to Fatty Acid Characteristics become Isolated as well as Fragmented by inhibition of PEMT, upregulation of Choline Kinase, or both PEMT downregulation and Choline Kinase Upregulation. Because Acyltransferase, Choline Kinase, PEMT, each are essential aspects of Lipid structural phases, Cellular Membrane structure, and progression of these Phases into cellular superstructure, anatomical superstructure, tissues, organs and anatomical characteristics, these seem to pervasively describe emergence and persistence of Neoplasm, anatomical structural anomaly, and changes to biological function. Here, an analysis of Lipid and Phospholipid structural phase progression might be useful. Cholesterol addition to Lipids in mixture, is known to reduce the area per Lipid to a level this most prevalent when the Lipid

Membranes are nearest to the lowest temperature at which the Lipid membrane is in liquid Phase (Main Phase Transition Temperature). A particular article presents this Condensation Effect of Cholesterol addition to Lipid Membranes as being either the Condensed Complexes Model which presumes that Cholesterol stimulates reversible emergence of Stoichiometric Cholesterol/Lipid Complex in which Lipid Acyl Moieties have increased Order or the Condensation Effect exhibits other Model Alternatives. Equilibrium is exhibited between Condensed Cholesterol/Lipid Complexes and other Lipids. The Superlattice Model presumes that as essential thresholds of Lipid Molarity are incurred, Specific Long-Range Order of Lipids in Membranes also emerges. The Umbrella presents that Hydrophilic aspects of Cholesterol molecules are typically of inadequate size, requiring that Lipids Contribute to the process of Screening and Aggregating Cholesterol molecules through Aqueous interactions performed by Hydrophobic Moieties of Cholesterol molecules. These Screening and Aggregating interactions are suggested be straightened into Linear structure such that increased space for aggregated cholesterol is available.63 The literature observes that Fatty Acids move from Circulating Lipoprotein to Adipocytes and then from Adipocytes to the Capillary Lumen during Lipid Mobilization. Amphipathic Fatty Acids are observed to be produced by Lipases before moving to the interface between Lipid and Aqueous Phases. Brown and White Adipose Tissue exhibit Lipase activity at Capillary Endothelial Surface Chylomicrons, whereas Hormone Sensitive Lipases exhibit activity at Lipid Droplets in the Interstitial Space exhibited between the outer Plasma Membrane Leaflet and Lumenal Leaflets of Intracellular Membranes. The Fatty Acids exhibit Lamellar Structure and Fixed Position Fatty Acids produce Lamellar extensions when the Interstitial Space between the Intracellular and Plasma Outer Membranes is overcrowded, such that these extensions emerge to exhibit progressive extensions along the path of Fatty Acid Transport. Feeding animals with Adipose Tissue results in Lamellar Structures beginning at the Chylomicrons of the Capillary Endothelial Surface, extending through Channels which traverse Endothelial structures and extending to Adipocytes producing a patterned route of Fatty Acid Transport that concludes in filling of Adipose Tissue with such Fatty Acids. Contrastingly, Fasting Animals exhibit Lamellar structures which beginning at Intracellular Lipid Droplets, extend through Intracellular Channels and arrive at the Plasma Membrane of Adipocytes to, again, producing a patterned route of Fatty Acid Transport during Lipid Mobilization. Brown Adipose Tissue in Cold Temperature exhibited early developing Animals, Lamellar Structures begin at intracellular Lipid Droplets, extend to the Outer Mitochondrial Chamber, and produce a patterned Route of Fatty Acids Transport to the Mitochondria presumably to enhance Oxidation and Heat Production. These exhibit that Fasting, Adipose Ingestion and Cold Temperature Environment produce changes to the way in which Lipids are Lysed, attached to cellular structures, and direction in which lipid structures extend, resulting in different transport pathways and vectors for Fatty Acid mobility. These could explain differences in LPCAT activity, because Fatty Acid Mobility determines Fatty Acid Mobility, including those Fatty Acid freed by Lipases, Phospholipases and Phospholipases including Phospholipase A2, such that LPCAT substrate Availability is changed by Gradients and environmental stimuli.64 The literature presents that liquid or aqueous Membranes exhibit Lipids which exchange locations with those lipids adjacent to it within the Membrane Layer, potentiating millions of such changes in location per second while also potentiating movement of Lipids along substantial distances within membranes.65

63 64 65

Digital Object Identifier 10.1073/pnas.0809959106 LIBRARY OF MEDICINE PUBMED IDENTIFIER 4066125 ISBN 0691082456

A Particular Study presents the progressive exhibition of Phase Transitions by Hexane and Oil mixture as having three principal Phase Domains that move from Micellar Solution, into Two Phase Dispersion and then exhibiting Dense Micellar Solution.66 The literature observes that membrane curvature is managed by changes in lipid composition and Asymmetry, partitioning of shaped transmembrane domains of Integral Membrane Proteins as well as Protein Crowding or Domain Crowding, reversible insertion of Hydrophobic Protein Motifs, Macroscopic Scaffolding by the Cytoskeleton utilizing influences from Polymerization or influences from Molecular Motors, as well as Scaffolding at Nanoscopic levels by Hydrophilic Protein Domains which have become Oligomerized. Correlatively, the lead or Head groups of Lipids and their Acyl Moiety Characteristics result in typical shapes, affecting their Adjacent Packing Characteristics, resulting in characteristic superstructure. Lipids with Homologous structure spontaneously exhibit curvature and this curvature is suggested to typically be equal to the difference between the Spontaneous Curvature of its Inner and Outer Monolayers, whereas monolayer curvature is determined by the Specific Lipid Molarity Apportioned Average of the Spontaneous Curvature of their Constituent Lipids in which the Curvature of each Specific Lipid Type is considered. Phosphatidylcholine and Phosphatidylserine are Cylindrical and produce Flat Monolayer, whereas Lipids with Smaller Head Groups such as Phosphatidylethanolamine, Phosphatic Acid, Diacylglycerol and Cardiolipin, are typically Conical, producing Negative Curvature such that a resulting Monolayer exhibits lipid which bend in a way that allows the headgroups to be closer together. The ratio of Head Groups compared to Acyl Moieties, when increased to have higher Head Groups, results in inverted Conical Shaped Lipids which potentiate Positive Membrane Curvature that bends the Monolayer away from the Head Groups such as exhibited in Lysophosphatidylcholine Phosphatidylinositol Phosphates. Thus, Phosphatidylcholine produced by PEMT within the Ethanolamine Kinase Pathway and that produced by the Choline Kinase Pathway produce Flat Monolayer that is useful for ancillary characteristics of lipids and environment to shape into many different versions, similar to pluripotent Stem Cellular entities. Phosphatidylethanolamine, Diacylglycerol, Cardiolipin, and Phosphatic Acid cause bending of the monolayer toward the Head Groups resulting in the Head Groups moving closer to together. Lysophosphatidylcholine and Phosphatidylinositol potentiate Negative Curvature in which the Monolayer bends away from the Head Groups. Double Adhesions in the Carbon Polymer Acyl Moieties, resulting in an Unsaturated Fatty Acid Lipid/Phospholipid, introduces a Kink which results in the occupation of more space and consumes an additional Adhesion that would otherwise be free for a hydrogen to Consume. This Double Adhesion prevents the Saturation of Adhesions by Hydrogen, resulting in an Unsaturated Fatty Acid Acyl Moiety. Fatty Acids among those discussed in this particular analysis of Membrane Curvature can have as many as Four Acyl Moieties which can be Saturated or Unsaturated. Thus, Unsaturated Fatty Acids reduce the Head Group to Acyl Moiety Ratio. Presented here, already, is that Head Group to Acyl Moiety Ratio potentiates introduced inverted Conical Features resulting in bending of the membrane away from the Head groups, even if the Lipids or Phospholipids potentiate bending in an opposite direction.


Digital Object Identifier 10.1021/la0103721

Again, the Difference between the Spontaneous Curvature of the Inner and Outer Monolayers is, incipiently, determined by the Curvature of each of the Monolayers in the Membrane. The Spontaneous Curvature of the Monolayer is determined by the Average of the Individually Computed Spontaneous Curvature of Each of the Lipids in the Monolayer. Bulky Headgroups and Monounsaturation of both Acyl Moieties in a Lipid potentiates curvature while Spontaneous Curvature is decreased by Sterols and Sterol resultant increases in Cylindrical Sphingolipid (inclusive of Sphingolipid) Packing and Phosphatidylcholine Packing. Flippases move Phospholipids, particularly Phosphatidylserine and Phosphatidylethanolamine between the inner and outer Plasma Membranes, changing curvature and potentiating local curvature that results in Budding. Acyltransferases generally stimulate local membrane curvature, along with Sphingomyelinase thereby providing a clue to how Ceramide/Sphingomyelin Cycling is shaped by Choline Kinase Inhibitors as well as CHOP. Phospholipase A2 is also known to affect membrane curvature particularly because it depletes Arachidonic Acid while it catabolizes Membrane Phospholipids, frees Calcium encircling the Phosphate Groups of Phospholipids, thereby interacts with G Proteins through Calcium availability enhancement and has versions that function even when iNOS has depleted Calcium. However, the synthesis Phosphatidylcholine from Lysophosphatidylcholine by Lysophosphatidylcholine Acyltransferases requisitely results in flattening of cellular membranes or inhibition of Positive Curvature or inhibition of Curvature away from Head Groups of a Monolayer. Thus, along with the potentiating of flattening and depotentiating of curvature away from Head Groups, Lysophosphatidylcholine Acyltransferases or Acyltransferases without the potential to affect such Flattening and Depotentiating of Curvature, influence membrane curvature by introducing Unsaturated or Fatty Acid Species. Bacterial Toxins including Cholera Toxin B and Shiga Toxin B stimulates increases in Molarity of Lipids with the same Characteristics in the same Membrane Leaflet potentiating Negative Membrane Curvature.67 Membrane Channels, Integral or Transmembrane Proteins, Scaffolding and Lipid Rafts can change Protein Shape through Crowding, suggesting the iNOS stimulates Amoeba Structure to Cellular Membranes through the pores which it produces in cellular membranes to deplete Store Operated Calcium, extracellular calcium and extracellular L â&#x20AC;&#x201C; Arginine. Membrane shape and curvature has foundational influences in the cellular environment that include Oligomerization of Clathrin, COPI and COPII domains in Vesicular Budding, Dynamin GTPases, and Caveolin, Flotillins and Reticulons which are involved in Caveolae characteristics, Endoplasmic Reticular Curvature, Lipid Rafts, and factors that bridge or traverse bridging domains, including incomplete traversal of membranes. Positively Polarized Lysines and Arginines interacting with Negatively Polarized Phospholipids such as Phosphatidylserine, phosphatidylinositol Phosphates including Phosphatidyl Inositol 4,5 P2, have been observed to enable Bin/Amphiphysin/Rvs (BAR) Domains to integrate into Cellular Membranes at their Concave Interfaces to potentiate Curvature of Tubule nature and not potentiate extreme curvature required for membrane Scission. The Cytoskeleton integrates with Cellular Membranes at regular intervals, featuring Actin, Intermediate Filament, Microtubules, Kinesins, Dynein and Myosin. Clathrin Pits including Inverted Conical Lipids 67

PMCID PMC4359918

Phosphatidylserine and Phosphatidylinositol 4,5 P2, Epsin, and Amphiphysin also stimulate influence to membrane curvature. Ethanol exhibition in Lipids and Lipid Membranes can produce Non - Lamellar Phases or phases which do not Exhibit Bilayer. Lamellar Structures exhibit layers in which layers exhibit different material while Non Lamellar Structures do not exhibit clear layered features. The Crystallization of layers in a medium can occur quickly, resulting in more than one material being deposited, such that material with different crystallization temperatures of phase transition characteristics reach such thresholds independent of one another. The result can be Lamellar Structure. Annealing can occur when Lamellar structures move between phase transition thresholds of different types, resulting in resolution of the Lamellar structure. Ethanol promotes disruption of the Lamellar structure and promotes permeability of the cellular membranes such that Polar and Apolar Ions may transit membranes. Ethanol promotes Elasticity, while its ability to promote membrane permeation seems similar to Transduction Domains which are purified or synthetic versions of molecules that exhibit HIV TAT efficiency in transducing cellular membranes.68 Ethanol enables Nonvalent Ions to be transported across lipid membranes including Na+, K+ and Cl-. Ethanol increases the Palmitoyl Oleoyl Phosphatidylcholine membranes area per lipid by 70% at 10 percent molarity of Ethanol, exhibiting expansion and swelling as Ethanol moves through the Membrane region. However, experiments exhibit Membrane resiliency at less than 10 percent Ethanol Molarity. Ethanol prefers Hydrophobic Regions with proximity to Phosphate Groups, which bely its Amphiphilic Nature. Cholesterol, including Sterols, balances the effect of Ethanol, suggesting why Sterols are Essential in Membranes and are promoted by optimal membrane Characteristics resultant of PEMT activity. TAT or HIV Transactivating Protein has enabled focus on synthesis or determination of more potent Cellular Membrane Transduction Domains which enables increase in the size of molecules introduced into the intracellular environment. Such increased sizes are typically logarithmically increased. Numerous Transduction Domains are now available to which therapeutics may be attached while separating each therapeutic by either another Transduction Domain or a molecular sequence Specifically lysed or segmented by an enzyme or protein indicative of a detrimental cellular status. Thus, a pluripotent therapeutic molecule can be produced to enter all cellular entities in Physiology and release only the precise therapeutic payload required for the cellular entities status. The resultant effect is, essentially, that of each cellular entity individually going to the Physician’s office alone without the other aspects of Physiology for individual consideration. One can easily consider how Purinyl-6-Histamine or any other Choline Kinase Inhibitor, AP1 Inhibitor, SP1 Inhibitor, Homocysteine improving molecule, or PEMT upregulator, as well as Caspase or other cellular deterioration molecule could be attached together, causing HIV to be eradicated with substantial certainty. Certainly, CRISPR has already eradicated HIV in Physiology. However, Double Stranded RNA Activated Caspase Oligomerizer is a therapeutic molecule that utilizes Apoptotic Protein Activating Factor 1 APAF1 which stimulates Caspase Cascade by activating Caspase 9 as well as utilizes Protein Kinase R PKR that is typically stimulated by Interferon and inhibits Viral Replication Routines.69 70 Lipid membranes exhibit Self-Assembly when above the ‘Essential Micellar Molarity’ resultant of the Hydrophobic Effect in which Non - Polar Lipids or Non - Polar aspects of Lipids inherently move away from Water. Hydrocarbon Moieties which are Amphiphile Head Molecules produce Micelles with a Hydrocarbon Core and which exhibit Polar groups at the Surface of the Micelle interacting with Water. Such Micelles can be Spheres, 68 69 70 Digital Object Identifier 10.1007/3-540-29623-9_3530 Science. September 23, 2012.

Cylinders or Ellipsoids, particularly when Amphiphiles utilized exhibit on Polar Head exhibited at the surface and one Hydrocarbon Tail within the Hydrophobic Core. Amphiphilic Lipids typically exhibit two Acyl Moieties per Polar Head Moiety, resulting in stabilization of the Membrane, such as with Diacylphospholipids. Novozyme 435 is shown to exhibit no specificity for either SN1 or SN2 when it integrates available Fatty Acid into Phosphatidylcholine, using the available Fatty Acid Moieties as integration Loci for Fatty Acids.71 The literature clearly indicates that a prevalence of Spherical potential for Lipid and Phospholipid Membranes does not inhibit the ability of such membranes to participate in more complex structures including Cuboid Superstructure. 1,3 2 Amidophospholipid Pad Phosphatidyl Pad

Diamide Analogues of Phosphatidylcholine can exhibit activity inhibitory of HIV.72 Temperature, molarity of Lipids, types of Lipids, Metallic Ion content and Magnetic Fields are shown to affect the alignment of Lipids and affect phases through which lipid membranes traverse.73

Bovine Rod Retinal Tissues exhibit enzymes which integrate Phospholipids in a manner consistent with Rod Shaped structures.74 Other literature clearly presents that Lipids progress through phases that include Lamellar of either Subgel, Gel, Interdigitated Gel, Gel Tilted Moieties, Rippled Gel, or Liquid Crystalline versions. Micellar aggregates then emerge including Spherical Micelles, Cylindrical Micelles which are Tubules, Disks, Inverted Micelles, and Liposomes. Non - Lamellar Liquid Crystalline Phases then emerge including Hexagonal, Inverted Hexagonal, Inverted Micellar Cubic, Bilayer Cubic Im3m, Bilayer Cubic Pn3m and Bilayer Cubic Ia3d phases. Phospholipase A2 and Lysophosphatidylcholine Acyltransferases, including LPCAT, have been observed to compete for outward and inward curvature of membranes, respectively.75 Trimethylamine-N-Oxide, along with its stimulation of iNOS through NF kB, inhibition of PEMT through iNOS, and role as principle factor in Carotid Intima Media Thickness increases, also known to cause folding of the AF1 domain within the Glucocorticoid Receptor which causes resistance to Glucocorticoid Receptor Proteolysis, enhanced integration with CBP and TATA Box Integration Protein (TBP) as well as enhanced integration with a Steroid Receptor Coactivator 1 (SRC1) factor. These place Trimethylamine-N-Oxide, strongly in the influencing factors correlated to Oncology. TMAO, then, can circumvent Estrogen and Estrogen Receptors to activate Estrogen Response Element factors, particularly those other than PEMT.76

71 72 73 74 75 76

Digital Object Identifier 10.1007/s10529-009-9915-6 Digital Object Identifier 10.1039/P19930002521 Digital Object Identifier 10.1021/la001567w LIBRARY OF MEDICINE PUBMED IDENTIFIER 3741442 PMCID: PMC181581 Digital Object Identifier 10.1210/me.2002-0258

Prostate Oncology presents an opportunity for analysis. The literature suggests that Choline Kinase is stabilized by Androgen Receptor, and this stabilization in particular tissues enables Male Gender specific differentiation. It is presented here that profiles for Oncology of the Prostate do not exhibit lower PEMT as most other Oncology does. Similarly, the research suggests that Autoimmunological Activity toward PEMT is not exhibited in Prostate Glandular Areas, although the expression profiles for PEMT in the Prostate are not too atypical from other tissues.77 It is known that inhibition of PEMT inhibits Immunological Activity. It is also known that Trimethylamine-N-Oxide is an inflammation factor that interacts in a system that occurs near areas of the Prostate and requires management to satisfactory levels, according to the literature, to improve Carotid Intima Media Thickness. Moreover, the literature suggests that Trimethylamine-N-Oxide and Carotid Intima Media Thickness as well as Plasticity exhibited in with Flow Mediate Dilatation, are essential factors in Macular Degeneration or other conditions in which Vision tissues may deteriorate. Trimethylamine-N-Oxide exhibits precisely the same central structure as Choline except for the observation that the two additional carbons which extend among 3 CH3 groups attached to the Nitrogen in Choline are replaced in Trimethylamine-N-Oxide by a Negatively Polarized Oxygen. Essentially the Group attached to the Nitrogen and its 3 CH3 moieties in Choline is replaced by a Negatively Polarized Oxygen. Additionally, the Nitrogen in Trimethylamine-N-Oxide has two of the CH3 Groups with Opposite Chirality, impairing the ability of the Nitrogen to be accessed by achiral factors or factors which do not have extremely precise shape, although very small molecules seem to have the best ability to interact with this region, similarly to strongly polarized molecules as well as molecules with fracking ability which enables molecular rearranges before, during, or after molecular interactions.78 These suggest that Choline Kinase may be being utilized to enable exhibition durable tissues or solid structure. These also suggest that Trimethylamine-N-Oxide can mimic some of the functions of Choline, except that this functionally is incomplete, resulting in deterioration of molecular scenarios which choline enables to be completed merely be being in the local catalytic areas. This agrees with the theory Trimethylamine-N-Oxide levels impair the cycle of Hydride import, extraction, distribution and transformation into factors which circulate without Hydride becoming freely exhibited or circulate in its free version. The literature is interesting because it presents the typical indicators for Cardiovascular Risk do are not correlated with AMD or Age Associated Macular Degeneration, although studies which have exhibited such associations and which have shown such associations to not be manifest, do not suggest that these indicators are incapable of predicting AMD. Interestingly one study indicated a clear association of Subclinical Cardiovascular Disease Indicators with AMD as well as Carotid Intima Media Plasticity being participative in such Correlation. Moreover, the same study observed interactivity among the variables and indicators exhibited presented as study outcomes as well as interactivity of these with Cohorts or subgroups including ethnicity, clearly indicating that Nutritional, Lifestyle and Digestive Pathway characteristics, as well as Trimethylamine-N-Oxide (TMAO), and Digestive Pathway Microflora may be central factors in Age Associated Macular Degeneration. Furthermore, Subclinical indicators being associated with AMD, clearly suggests that the Misinterpretation of Homocysteine, inhibited PEMT, Choline Deficiency, Feed Forward accumulation of Phosphatidylcholine, stimulation of subclinical persistent activation of the compliments immunological system inclusive of C â&#x20AC;&#x201C; Reactive protein, all

77 78

Digital Object Identifier 10.1210/me.2002-0258

may be mounting a path of detriment that traverses the Carotid Artery, extends to the Cerebellum, and is affecting Neurological Centers and Organ Tissue. Similarly, and importantly, the research literature observes that Choline Kinase Alpha enhances or increases the transcription of Androgen Receptor, as well as increases its stability, such that Androgen Receptor is increased in availability, stability, activation and increased in folding. Elsewhere in these analyses interactions between Androgen Receptor and Choline Kinase may have been characterized inadequately, particularly suggesting that Choline Kinase Alpha is protected from Proteolysis by Androgen Receptor.79 Indeed, the literature observes that CTP Phosphocholine Cytidylyltransferase is essential for Early Embryogenesis and a few other junctures in Gestational development as well as Birth, particulary Pcyt1a, while Pcyt1b is essential for Gonadal development, suggesting that the CDP-Choline pathway promotes the developmental of durable tissues with decreased plasticity while the Methylation Pathway when reaching PEMT, seems to be essential to intricate differentiation, incipient plasticity, as well as persistent plasticity in tissues which require persistent plasticity such as the Splanchnic System. These conditions were observed in Small Nonhuman Mamallian contexts of analysis. However, the same Small Nonhuman Mammalian context of analysis was utilized to produce PEMT -/populations which exhibited 50% decreases in Hepatic Phosphatidylcholine along with about 90% decreases in Triglycerides and Cholesterol, suggesting that models of 30 Percent PEMT contribution of Phosphatidylcholine and 70 Percent CDP-Choline Pathway, although observed, may not be as relevant when constituting optimal or therapeutic conditions, except, perhaps, in Gonads or durable Physiological structure which is required to be in its durable Post Embryonic Plasticity Phase. This particular study is of such pivotal nature because it is among the few which even present the centrality of inhibited PEMT in any Physiological or Behavioral context when it observed that RCS8 Murine populations, which exhibit impaired PEMT and Hepatic Steatosis inherently, also exhibit decreased Hyperglycemia and Hyperinsulinemia when provided the Diabetic Therapy Roiglitazone although PPARGamma was required for this effect to occur. PEMT is characterized as an inhibitor of PEMT when PPAR-Gamma acitivity is also exhibited. The article continues by describing PEMT expression stimulated by Streptozotocin as an accompanying factor in Streptozotocin enabled Diabetes, although this description is incomplete because PEMT expression can be changed Post-Translationally by AP1, PEMT, Thrombin, S-Adenosyl Homocysteine, IDO, TMAO, Nitrosamine, and other factors. PEMT expression does not assure PEMT activity and does not assure that PEMT completes its catalytic phases in production of Choline nestled within the Phosphatidylcholine molecular structure.80 Pivotally, this same context was utilized to produce impaired MDR2/ABCB4 Flippase which contributes to transfer of Phospholipids between Cellular Membranes as well as contributes to the Production of Bile. This analytic context exhibited impaired PEMT as PEMT -/- along with impaired MDR2 as MDR2 -/-, resulting in PEMT -/- physiology which a Choline Deficient nutritional regimen did not cause the typically observed Steatosis and Concluding Phase Liver Impairment. Instead, Steatosis was observed along with up to 90 Days of continue physiological function. Phosphatidyl Ethanolamine, instead, was moved to replace Phosphatidylcholine, while increased permeability and leakage was exhibited, both of which suggested by the Amehsi Specification as less than adequately acknowledged feature of Choline deficiency which contributed to the exhibition of Anerobic Glycolysis in Choline deficient, PEMT inhibited and P53 enabled downregulation of Glycolysis and downregulation of the 79 80

Digital Object Identifier 10.1093/jnci/djv371 Digital Object Identifier 10.1074/jbc.R700028200

Pentose Phosphate Pathway. Although this linkage may not seem intuitive, pathogenic permeability changes, as described in passages which characterize the Immunological Synapse, may consist of impairment of the Selective Permeability exhibited by cellular membranes to allow less selective movement of factors across membranes along with impairment of nonselective permeability which, when not impaired, would allow less than selective or more free movement of particular factors across cellular membranes. These suggest that the processes of ingesting nutritional factors depletes not only Phosphatidylcholine, but may also deplete PEMT correlated Phosphatidylcholine which exhibits Fatty Acids that are Cytotoxic to Oncology Cellular Entities. Thus, when Parenteral Nutrition is administered without using Intraveneous capability, bile synthesis can deplete Phosphatidylcholine and cause resiliency of Cellular Entities by depleting optimal Phospholipids which exhibit Fatty Acids. Similarly, Parenteral Nutrition administered using Intravenous Capability without adequate Choline can exhibit similar characteristics through typical processes otherwise which deplete Phospholipids. However, MDR2 is specifically known to correlate with resiliency to Oncotherapeutics and the information here provides a compelling perspective of the mechanism by which this resistance occurs. The inhibition of MDR2, relevantly, in a Small Nonhuman Mammalian Populations, resulted in PEMT impairment only generating steatosis and not Concluding Phase Hepatic Dysfunction and avoid the typically observed exhibition of Demise. These provide perspective of compelling ways to change practice in Oncotherapy, Parenteral Nutrition, and management of Hepatic Dysfuction. Continuing discussion of Homocysteine and Trimethylamine-N-Oxide, importantly, it is the deterioration of Carotid Intima Media Plasticity and Vision Tissue Plasticity which are correlated, suggesting clearly that it is the cellular and tissue development program that can become impair by subclinical indicators of disease, particularly Homocysteine. The literature clearly correlates detrimental Carotid Intima Media Thickness with levels of Homocysteine in multiple studies. However, it seems that the much of the literature considering Flow Mediated Dilation Plasticity of the Carotid Artery were designed with multiple arms and confounders. It is not clear if these were systematically produced upon similar incipient presumptions or if these are the result of the nature of Indicators that include different aspects of Cardiovascular Conditions. However, these analyses have found a clear and consistent pattern in which studies introduce complexity, use statistically analyses to suggest that particular correlations are not accurate, while a clear molecular and metabolic association can be exhibited. Homocysteine and Trimethylamine-N-Oxide are correlated in Pathology because each produces a similar effect, TMAO is often superimposed upon Homocysteine because Homocysteine is reduced to Subclinical levels when food or nutritional factors which exhibit Choline and Phospholipids are ingested. Similarly, TMAO than can constituted a continued path of inflammation and pathological influence, that can replace inhibited Homocysteine. However, imperatively, TMAO and the Subclinical exhibition of Homocysteine may have similar homologues among other indicators because much of the indicator can be ancillary to Homocysteine, often requiring Homocysteine or requiring the circumstances which results in increased levels of Homocysteine. Interestingly, the lowering of Homocysteine using molecular capabilities did not provide benefit in reducing clinical indicators or pathology, particularly with regard to Carotid Intima Pathways, because the management of Trimethylamine-N-Oxide has been observed to be required for Carotid Intima Media Health. Although some studies have shown that there is not a correlation between Early Macular Degeneration that is not associated with Age, these analyses clearly show that such studies may often not consider subclinical levels of Indicators and may often ignore clearly linkages within molecular pathways that would cause the studies to be redesigned.

The conclusion with regard to subclinical exhibition of Indicators, here, seems to be that the Health industry might optimally sunset the concept of Ideopathic Health Conditions from use in clinical information, since it is clear that there may be subjectivity in interpretation of diagnostic indicators as well as selection of indicators. The subjectivity in both Diagnostic indicators interpretation and selection seems to be an impedance since there seems to be pervasive use of less than the most optimal performing indicators. Not yet determined might be better if conditions which are not found to be indicated by Amehsi Indicators are incurred, although the possibility of such occurrence is becoming increasingly unlikely. Similarly, it may have become imperative for researchers and clinicians whom are considering clinical studies to be inclined to disregard a study if it does not include analysis or explanation of the molecular and metabolic pathways which are participative or causal to the outcomes which these present.81 82 83 Thus, there seems to be clear, distinct paths to Macular Deterioration which include, minimally, subclinical cardiovascular indicators which are also causal such as Homocysteine and Aortic Calcification. Minimally, such paths to Macular deterioration subclinical exhibition of the effects of PEMT inhibition which include impaired Acetylcholine storage as well as resultant Feed Forward accumulation of Phosphocholine from Choline Kinaseâ&#x20AC;&#x2122;s use of Free Choline to produce Phosphocholine such that Phosphocholine aggregates upon extracellular entities to activate C-Reactive Protein and Compliments immunological function. Additionally, such paths to Macular deterioration include, minimally, Carotid Artery Plasticity Impairment.84 High Pulse Pressure, constituted of Higher Systolic Blood Pressure compared to lowered Diastolic Blood Pressure, has also been correlated to AMD or Age Associated Macular deterioration. Similar, Gastrulation is known to particularly affect or enable development of Ventricular Structure, such that Anomalies of Ventricular function can emerge from impairment of anatomical development and regeneration pathways. This may explain the difficulty in consistently associating Homocysteine or other essential indicators with Pathology, as well as explains the effect of Subclinical levels of casual indicators. 85 Importantly, AMD Macular Degeneration is known to occur in Dry version characterized by atrophy or Apoptosis/Necrosis, as well as occurring Web Version which responds therapeutically to Tyrosine Kinase Inhibitors that reduce the release of VEGF. This are somewhat profoundly consistent with the analysis presented here, particularly including a comparative circumstance of tissue deterioration which is different from the Tyrosine Kinase and VEGF Version. Since Tyrosine Kinase is known to activate Choline Kinase, and choline Kinase is known to be upregulated in numerous circumstances or become comparatively upregulated when PEMT is inhibited, there is a possibility each of these has an essential basis is Choline Kinase status, although PEMT may pervasively be participated or indicative also.86 CRP-i2 and C-Reactive protein antisense oligonucleotide (ASO) inhibit C-Reactive Protein.87 88 89 Creactive protein is inhibited yb Cycloxygenase Inhibitors (Aspirin, Rofecoxib, Celecoxib), Platelet Adhesion Inhibitors (Clopidogrel, Abciximab), Lipid management factors (Statisn, Ezetimibe, Fenobibrate, Niacin, nutritional change), Vitamin E and other Antixoidants, Beta-Adrenoreceptor Agonists, Angiotensin Converting eNzyme (ACE) 81 Digital Object Identifier 10.1186/1471-2261-8-24 82 LIBRARY OF MEDICINE PUBMED IDENTIFIER 16707955 83 PMCID PMC1994729 84 Digital Object Identifier 10.1001/archopht.125.4.534 85 Digital Object Identifier 10.1007/978-323-642-54307-4_22 86 Digital Object Identifier 10.1001/jamaophthalmol.2017.1600 87 PMID:23871616 88 Digital Objectve Identifier 10.1155/2014/353614 89 PMCID PMC3511672

Inhibitors (Ramipril, Captopril, Fosinopril), Angiotensin Receptor Blockers (ARBS) (Valsartan, Irbesartan, Olmesartan, Telmisartan), and Diabetic Therapeutics (Rosiglitazone, Pioglitazone).90 The literature clearly suggests that TMAO stimulates exhibition of NF KB and NF KB stimulates iNOS, such that iNOS results in expression of Choline Kinase.91 92 The exhibition of Homocysteine is known to be both inhibit PEMT and stimulate iNOS, producing upregulation of Choline Kinase such that a multiple factorial upregulation of Choline Kinase and an inhibition of PEMT Occurs. Thus, the influence of Thrombin in Thrombosis and health events which occur as a result of Thrombosis, seem to be most detrimentally characterized by the inhibition of PEMT and upregulation of Choline Kinase which excludes regenerative and developmental pathways from occurring, resulting instead in inflammation cascade with Coagulation factors. Thrombin also inhibits PEMT. This analysis presents literature that suggests that Glucocorticoid and Steroid Hormones typically share Response Elements with Estrogen Receptors as well as potentially have their own Specific Response Elements, although another study suggests that Androgen does share with Estrogen a Response Element Structure except that a Substitution in the Base Pairs prevents Androgen Receptor and Estrogen Receptor from Activating the same share Response Element Structure. These suggest that Androgen Receptor stabilizes Choline Kinase, prevents its proteolysis to enable to have longer duration of potential interactivity, exhibits an interaction with Choline Kinase Post-Translationally, and although the literature does not present clearly that Choline Kinase inhibits PEMT or that Androgen inhibits PEMT it is well known the upregulation of Choline Kinase impairs START Protein enabled transfer of Cholesterol to the Mitochondria for Steroidogenesis. However, Choline Kinase obtains a Temporal advantage over PEMT through Androgen Receptor assisted Stabilization of Choline Kinase. However, one study was encountered that associated Pulmonary Oncology which was not Small Cellular with increased levels of PEMT, although this study was not included here because upregulation of Choline Kinase is known to be a specific incipient Factor in Pulmonary Oncology, the literature suggests clearly that Choline Kinase Inhibitors benefit each of the Pulmonary Oncology Conditions reviewed in the list of such conditions thus far, and it is not often well differentiated in studies the difference between enzyme transcription, post-translational modifications, availability, performance of enzyme activity, profiles of activity to determine if it is typically, the availability of Choline and Folate which are often omitted from such studies, as well as the myriad emerging sources of Homocysteine which can all contribute to Oncological Pathology. PEMT expression being increased in some Oncological Conditions does not indicate that even that Increased level of Expression is Pathogenically inadequate. Similarly, Choline Kinase inhibition seems to manage most pervasive aspect of Oncology, which happens to be suggested as a typical mechanism of Male Gender Phenotype in the Prostate, although it should be clearly presented that it is the upregulation of Choline Kinase that is associated with Oncology. The mere expression of Choline Kinase is not considered Pathogenic.93 94 95 96 97 It seems that during such analyses, it is imperative always present the analysis of regardless of the therapeutic used or interaction studied, has remediation and understanding of the incipient causality, how and why 90 PMID 16939632

91 92 93 94 95 96 97 Digital Object Identifier 10.1161/JAHA.115.002767 Digital Object Identifier 10.1093/jnci/djv371 â&#x20AC;&#x153;Androgens and Prostate Oncologyâ&#x20AC;? Laboratories. Online Publications. The Mayo Clinic. The Human Protein Atlas. PEMT. Tissue. The Human Protein Atlas. PEMT. Oncology. Digital Object Identifier 10.1074/jbc.M009170200.

the condition emerges, persists, progresses and imparts detrimental all been included. It seems to be almost an endless potential introduction of nuances or circumstance which provide an instantaneous perspective of changed relationships between factors in these pathways. It is well known that molecular stacks that extend through molecular pathways can have inverting, reversing or changing mechanisms. Thus, it is sometimes to present the known outcome of Choline Kinase Inhibition being pervasively effective in Oncology. The Categories are presented here. Each, interestingly, may already be included Oncology which is reversible with a Choline Kinase Inhibitor.98 New amazingly potent inhibitors of Choline Kinase are emerging.99 1. Breast Oncology 2. Carcinoid 3. Cervical Oncology 4. Colorectal Oncology 5. Endometrial Oncology 6. Glioma 7. Head and Neck Oncology 8. Liver Oncology 9. Lung Oncology 10. Lymphoma Oncology 11. Melanoma 12. Ovarian Oncology 13. Pancreatic Oncology 14. Prostate Oncology 15. Renal Oncology 16. Skin Oncology 17. Stomach Oncology 18. Testis Oncology 19. Thyroid Oncology 20. Urothelial Oncology The Small Molecular Antagonist of Choline Kinase Alpha, N-(3,5 - Dimethylphenyl)-2-[[5-(4-ethylphenyl)1H-1,2,4-triazol-3-yl] sulfanyl] acetamide or CK37, which also inhibits MAPK as well as inhibits PI3K/AKT, thereby having the potential inhibition to mitigate Inducible Nitric Oxide Synthaseâ&#x20AC;&#x2122;s Tunnel/Pump, are known to inhibit activation of AP1, and inhibit activation of 12-O-Tetradecanoylphorbol-13-acetate TPA. This factor may be therapeutic in HIV, HPV, HCV, numerous viral pathogens, Pervasive oncology, and pervasive lymphoma, pervasive leukemia.100 Evodiamine is also an inhibitor of TPA.101 Choline Kinase Alpha Inhibitors, however, are now known to abrogate and reverse by at least 50 percent the pathology produced by diverse, pervasive and inclusive oncology, leukemia and lymphoma conditions. Thapsigargin is noncompetitive inhibitor of Ca2+ ATPase, with activity at the Sarcoplasm and with activity the Endoplasmic Reticulum, being known as a Sarco/Endoplasmic Reticulum Ca2+ ATPase. This Sesquiterpene Lactone is derived from Plantae and is known as Neoplasm Promotion Factor in Mammalia. The Activity of Thapsigargin includes increasing the availability of cytosolic Calcium, depletion of Store Operated Ca2+, followed by opening of the Calcium Channels in the Plasma Membrane to enable influx of Ca2+. Studies suggest that Thapsigargin merely causes expression of Inducible Nitric Oxide Synthase. However, the activity of Thapsigargin suggests that the activity of 98 99 100 101

Human Protein Atlas. HPA042375. Oncology. Digital Object Identifier 10.1021/acs.jmedchem.5b01552 Digital Object Identifier 10.1038/onc.2011.51 Digital Object Identifier 10.1002/ptr3392.

Inducible Nitric Synthase includes inhibition of Endoplasmic Reticulum Ca2+ ATPase while also suggesting that the Pores opened in the Plasma Membrane by iNOS may include or may be constituted of opening of Plasma Membrane Calcium Channels. Heretofore, the characteristics of Ca2+ in the cytosol have not been characterized other than being to the benefit of iNOS. Cytosolic increases of Ca2+ seem to confirm this benefit to iNOS, while potentially suggesting that iNOS depletion of Ca2+ may be inaccurate, may be ephemeral as presented by the iNOS Ca2+ Tunnel and Pump or may not be necessary to maintain depleted Stored Operated Calcium or may not be necessary to sustain Gradients upon which Ca2+ is recruited into the Cytosol. However, the inclusion of the Sacroplasm certainly agrees with the way in which in iNOS has been depicted to potentiate impairment of cellular membranes and causes collapse of the Sarcolemma. iNOS expression in physiology resultant of energy and communications fields describes differences in cultural and regional propensity for Diary product Consumption. However, the role of Thapsigargin as promoter of Neoplastic changes clearly presents what may be only on individual nuance among many in which iNOS, and therefor factors or influences which cause iNOS expression, promote Oncology, Disease, changes to behavior and may be major shapers of physiological and behavioral outcomes.102 An analysis of HPV, CMV, and other viral factors, including Epstein Bar Virus, which contribute to or are essential to Oncology, seems relevant. A particular article presented here shows that HPV enabled Oncology can be therapeutically curtailed by Berberine, and adequate dosages can cause Apoptosis in such cellular Entities. These analyses, however, present AP1 inhibition as a way to reverse pathology and not specifically introduce apoptosis, suggesting that the Apoptosis observed was correlated to some other change such as an affect to the HPV Pathology instead of affecting Oncology which can be reversed. The literature observes that Curcumin likewise inhibits AP1 and increases sensitivity of HPV enabled oncology through upregulation of Fra-1. However, interestingly, these do not acknowledge the essential nature of inhibiting SP1 and Inducible Nitric Oxide Synthase. This article presents that HPV virus enabled Oncology Cellular Entities are permanently and irreversibly caused to enter senescent nonproliferating status by (S)-1-[3-Hydroxy-2-(Phosphonylmethoxy)propyl]cytosine. PMID 8701600 HPMPC, or (S)-1-(3-Hydroxy-2phosphonylmethoxypropyl)cytosine, known as Cidofor or Vistide, was found to have such effect in 1999, while other studies clearly exhibit its clinical effectiveness in HSV Type 1, HSV Type 2, Varicella Zoster Virus VZB, CMV Cytomegalovirus, Human Herpes Virus type 6, EBV Epstein Bar Virus, Herpes Viruses of Equine and Bovine Loci, Papoviruses of which HPV or Polyoma Virus may be included, as well as Adeno, Irido, Hepadna, Poxviruses, Vaccinia, Variola, Cowpox, Monkeypox, Camelpox, Ectromelia, Molluscipox and Parapox. Therepeutic Effectiveness has been observed in clinical studies of CMV Retinitis, HSV resistent to Acyclovir, HPV of Pharyngeal, Laryngeal or Anogenital Nature, and other, as presented by a 1996 article. PMID 8701600 The article presented here exhibits near 100 Percent effectiveness of HPMPC when use dfor Laryngeal Papillomatosis. and PMID 9515772

102 Digital Objective Identifier 10.106/jbbrc.2007.05.154

A Blend of Phytochemicals, flavonoids, polyines, thiophenes, proteins and peptides in such regard. terpenoids, lignans, sulphides, polyphenolics, coumarins, saponins, furyl compounds, alkaloids, as well as cooking herbs, culinary herbs and oils used for flavoring food, provides a variety of Viral DNA Polymerase and Viral RNA Inhibition. Favipiravir is an inhibitor of Diverse Viral RNA including RNA viruses considered to be untreatable otherwise. United States National Library of Medicine PMID 28769016. Viral RNA Polymerase inhibitors are presented at this digital objective Identifier. Natural Viral DNA Polymerase Inhibitors. Diverse Polyphenols, Bioflavanoids, including extract of Phy Niruri, extract of Phy. Amarus, Phy. Urinaria, licorice root Glycyrhiza glabra, Rosemarinic acid, Caffeic Acid, eugeniin (Allagitannin) extracted from Geum japonicum and eugeniin (ellagitannin) extracted from Syzygium aromaticum, triterpene acids of Geum japonicum such as Ursolic acid and Maslinic acid, the Triterpene Moronic Acid, extract of Rhus javanica, Geranium sanguineum (L.), lignans isolated from Larrea tridentates as well as from Rhinacanthus nasutus and Kadsura matsudai, Calophyllum inophyllum, Cal. lanigerum, Cal. teysmannii latex and Cal. cerasiferum, Morin is from Maclura cochinchinensis, extracts from Rhus succedanea and Garcinia multiflora (amentoflavone, agathisflavone, robustaflavone, rhusflavanone and succedaneflavanone) Flavonol Iridoid glycosides and phenylpropanoid glycosides (uteoside A, luteoside B and luteoside C) from Barleria prionitis and from the roots of Markhamia lutea, Dianella longifolia which exhibits Flavanoid Chrysosplenol C and Pterocaulon sphacelatum which exhibits the Anthraquinone Chrysophanic Acid, Theaflavin from Black Tea, Diverse fruits, vegetables, tea, grains, bark, roots, stems and flowers, which are edible and considerably nontoxic. Digital Objective Identifier. 10.1046/j.1365-2672.2003.02026.x provides specific information about Viral Specific Phytochemicals. Digital Object Identifier 10.1046/j.1365-2672.2003.02026.x presents DNA Polymerase inhibitor therapeutics. Cidofovir or CDV typically requires activation by Cellular enzymes beginning with Pyrimidine Nucleoside Monophosphate PNMP Kinase which transforms CDV into CDV-Monophosphoryl or CDVp. CDVp then becomes phoshorylated to become CDVpp, which exhibits two phosphorylations in phase performed by Nucleoside 5'Diphosphate Kinase or NDP. Interestingly, CDVp-Choline performs as an interacellular aggregation phase for CDV derivatives. CDVpp competes with Natural Substrates of Viral DNA Polymerase either as an inhibitor of DNA Polymerase or as alternative substrate for DNA Polymerase. CDVpp exhibits an Axial Linking Moiety which potentiates polymerization of the CDVpp molecule and, however, CMV Viral DNA is impeded when two adjacent CDVpp molecules are integrated in to the DNA Polymerase Polymerization of DNA. The activation of CDV occurs in two phases to become an antiviral factor and these two required phases omit an ancillary activation phase performed Tyrosine Kinases of HSV and VZV and CMV UL97 which occurs with the Acyclic Nucleoside Analogs Acyclovir or Ganciclovir. This independence of Tyrosine kinase Performed activation makes CDV useful in managing resistant versions of these viral factors. A most interesting conclusion here seems to be that if the activation of Pharmaceutical Molecules occurs similarly in typical circumstances, then the occupation of Choline to produce an accumulation point for storage of pharmaceutical factors, may present a new perspective of how molecular therapeutics affect Choline, PEMT and CDP103


Choline Dynamics. However, pivotally, there seems to be a potential that this accumulative storage of Choline performs as a Choline Kinase Inhibitor, depleting the availability of Free Choline, thereby inhibiting the ability of ATP to be used to Phosphorylate Free Choline by Choline Kinase, potentiating an essential downregulation of Phosphocholine synthesis that it’s a feed forward pathway essential to pervasive pathology. Azone, an Antibiotic used for Acne Therapy, increases the fluidity of cellular membranes, decreases the transition phase temperature of cellular membranes and enables enhanced absorption of therapeutics, particularly topical therapeutics. Digital Object Identifier 10.1016/0378-5173(88)90275-X and Curcumin exhibits inhibition of Viral Activity and Oncology in HPV enabled Oncology. PMID 16526022“cellular Entities” Curcumin represses the HPV16 E6 protein and inhibits AP1 NF-kB. PMID 25932049 Studies clearly correlate Inducible Nitric Oxide Sythase with HPV pathology and studies clearly strongly correlate Inducible Nitric Oxide synthase with the most pathogenic version of HPV. Curcumin is an inhibitor of Nitric Oxide Synthase, although a clinical level inhibitor might be more effective or as effective. Clinical levels of AP1 inhibitors and SP1 inhibitors both might have enhanced therapeutic effectiveness. Neuronal Nitric Oxide Synthase is presented as an inhibitor of Oncology associated Angiogenesis and Inducible Nitric Oxide Synthase is presented as a promoter of Oncology transformation and proliferation. A particular article regards iNOS as the principal or a principal factor which enables HPV16 to be the most oncology potentiating and pathogenic version of HPV.104 The detriment to physiology enabled by iNOS, in this context. Is presented as Neoplasia, Nitrosative and Oxidative distress, while it is also known that iNOS causes cellular entities to exhibit an Ameoba shape which is somewhat certain to contribute tissue, organ and cellular anomaly. Berberine inhibits inflammation produced by HIV and inhibits HIV Protease Inhibitor Correlated Inflammation and Dislipidia. Berberine inhibits Inkflammation produced by CKikungunya Virus.105 TPA/PMA may participate in numerous Pathology and TPA, PMA can be inhibited in its effect to numerous Pathogenic Pathways by Hops or Humulus Lupulus, Capsaicin, and Catechins.106 C – Reactive Protein requires the use of Polyanion to prevent the Unspecific Agglutination of LDL and VLDL, but not HDL, suggesting that among physiological changes may be an amelioration to diagnostic assay, particularly Assay of C – Reactive Protein. Heparin and Dextran can assist in preventing Unspecific Agglutination when added to the Assay Buffer to prevent Apolipoprotein B100 from integrating with Magnetic Particles at Heparin integration loci.

Digital Object Identifier 10.1111/j.1349-7006.2007.00497.x ·

104 105

Digital objective Identifier


Digital Object Identifier 10.1023/A:1014802005672

The conditions for Unspecific Agglutination were observed in Magnetic Fields and Assay with Superparamagnetic Particles.107 TPA/PMA is causes translocation of Protein Kinase C from the Cytosol to the Cellular Membrane increasingly to 100 Micromoles Per Liter which is enhanced by 50 Hertz Electromagnetic Fields. Fields millions of times less substantial than the membrane potential of cellular entities cause response of the cellular environment. These fields can include Ca+ Ion conjugation potential that spreads across the cellular membrane correlative to such Cerebrocortices spreading that occurs in the same Ca2+ fields associated with Migraine pathology. Similarly, fields interact with cellular membranes in ways that traverse the membrane into intracellular environment as current, changed to turgor, or interactions with the membrane through receptors, channels, transmembrane proteins or other transporters, as well as interactions with the membrane. Phorbol Esters including PMA/TPA interact with such fields at the cellular membrane, activating enzymes in the Ethanolamine Kinase pathway, inhibiting PEMT, depleting metabolites in the Ethanolamine Kinase Pathway, shunting these into the Choline Kinase Pathway, potentiating Phosphatidylcholine through a susceptible pathway, inhibiting Hepatic Synthesis of Phosphatidylcholine because PEMT activity is principally hepatically exhibited, focusing phosphatidylcholine synthesis in other areas of Physiology that use the susceptible choline Kinase Pathway, similarly causing phosphatidylcholine synthesis to occur in tissues that utilize 1 Carbon pathways as Methionine Synthase and Tetrahydrofolates, inducing competition between 1 Carbon Pathways and iNOS consumption of Tetrahydroxy metabolites, then causing less adequacy of Nitric Oxide Synthases generally such that Arginase pathway prominence emerges, supporting the literatureâ&#x20AC;&#x2122;s observation that Oncogenic Ornithine Carboxylase activity is exhibited along with Phorbol Ester TPA/PMA.108 Fields have enormous potential for management and modulation in Human Safety and Health. The Amehsi Specification found more than only Correlations between the Exhibition of changes in Atmospheric Patterns, Weather, Rainfall, Geological Events, Human Health and other events with regard to how these are affected by Fields and influences produced by Human Industrialization, Power, Energy, Communications and other fields. Illustratively, the Dust Bowl of the 1920s, 1918 influenza and the HIV pandemic can be explained by emergence of Dense Electrical Fields which change interaction between layers of the Geological to atmospheric to Terrestrial to Extraterrestrial interactant system as well as cause an inherent expression of Nitric Oxide Synthase which enable Influenza, HIV, Cryptosporidium or other factors to circumvent an essential phase of disabling or surmounting cellular immunity. The literature clearly presents that Cosmic level cycles in energy were factors in Geological Events and Atmospheric Events, suggesting that Land Masses move about the surface of a Planetary Core, which exhibits liquid characteristics, in a way that Balances the influences of the Universe upon these same Land Masses and the interaction of influences upon the Planetary Core. Clearly, extraterrestrial/terrestrial, inorganic/Organic, tangential/transitive transitions occur in interactions among these influences, similar to the way that Choline enables Inorganic to Organic Phase Transfer of molecules or influence, including Hydride. Specifically, the literature observes correlations between cosmic events, atmospheric changes, storms, geological events and other factors. Electrical infrastructure seems to have change these and a number of substantial changes to Weather and Geological events seems to have occurred along with emergence of a new Electrical, Magnetic and Communications influence among these fields.

107 108

Digital Object Identifier 10.1016/j.plabm.2016.02.003 Digital Object Identifier 10.1007/BF00973286

Correlatively, it seems prudent and obvious that use of Social Networking, Communications Fields and other fields could and should be utilized to cause disorganization of the Atmospheric conditions required for Tropical Storms which emerge to more detrimental statuses. Simply have individuals with substantial Social Networks point their locations to different areas within a Tropical Storm exhibits the potential to promote disorganization and disassembly. This could be augmented by using buoys with communications devices or computing device integrated into them which are dispersed among the path of a Tropical storm or within the Tropical storm. Similar, coating the surface of the path of such storm with Phospholipids such as Phosphatidylcholine could substantial impair ability to absorb moisture from the Oceanâ&#x20AC;&#x2122;s surface. Most particularly, establishing particular ordered series of information in communications and electrical systems which promote typical or optimal moisture or precipitation paths through a continent could more than stabilize disorganization of Weather Patterns. Interestingly, a simplified perspective of changes to weather, tectonic and other systems can be presented here. Similarly to a filled balloon unable to flow along the gradients changes in atmospheric pressurization, and unable to move along the gradients of wind and ionic factors which can be influential to its motion, such as when a balloon is held in place by a device, the layers of influences from Universes, to Planetary System, to Angular, Gravitational, Ionic, and among the strong, intermediate and weak forces of nature, as well as those interactions from subquantum to supraquantum levels, all exhibit influences which determine how the layers of the atmosphere, weather systems, atmospheric systems, land masses, aquatic masses, tectonics, magnetic systems, or mechanical influences, adjudicatively interact to produce outcomes. Communications, Power, Energy and other systems once emerged, were accompanied by tectonic events, epidemiological events, and other changes to outcomes which effect Humanity and the context among which Humanity came to be exhibited. Imperatively, however, such factors may have come to intermediate the interactions which would have occurred directly otherwise. Communications, power, energy, information, locational and other systems, promoted by the Internet and certainly cumulatively, thus may have come to change interactions which were occurring in nature, and certainly have change weather patterns and tectonic patterns. However, Humanity, through its most diverse array of interactivity, may have come to intermediate all the influences of the Universes such that its expressive, replicative, constructive and other activity enables more prominent interaction through distance, location, space and time, as well as enhances the asymmetric interactions which can occur in systems. The status of a distance universe persisted by the Hubble Telescope and distributed to billions among Humanity, enables observation of the status of such Universe as it is among natural Human interactivity which includes interacting with epochs exhibited before the status of such Universe emerged and interactive with such Universe itself in multiple instances of its progression before such persisted image produced by the Hubble Telescope, during such status and afterward. Thus, the interactions of the Universe began to be intermediate with the incipient exhibition of organisms upon Earth, the exhibition of Humanity upon the Earth, the exhibition of patterned Human movement and migration patterns upon the Earth, and substantially increasing as the complexity of cognition, expression, and interactivity of Humanity increased. The results seem to have enabled Humanity to become integrated into the circuitry of deterministic influences of the Universes. Humanity has changed the way tectonic factors respond to changes in the Biosphere, the Planet, and the Planetary systems and the Universes. Systems of Humanity have enhanced such influence by affecting Human activity in plurality. Thus, there is emerging a requirement to understand how to utilize the systems and influences of Humanity reconstitute, reassemble, and otherwise assure optimal biosphere rhythms. Illustratively, managing detrimental influences such as storms, detrimental nuances of atmospheric activity, tectonic dysrhythmia, as well as management of the levels at which nuances of the Kennedy Pathway exhibited in numerous

aspects of the biome which are essential to scrubbing detrimental factors from atmosphere, water and environment, all have become essential priorities. Again, it is important to consider that the environment is among the factors which constitute the Favor among which Humanity has come to be exhibited among the Universes. Ecompassingly, Humanity has been focused in producing the factors which are cursorily useful in extending, enhancing and expanding such favor, and such focus of cursory factors has incurred nuances of peculiar nature in which increased production of factors which cursorily, although imprecisely, satisfy Human requirements can merely only increase demand for such factors without alleviated the empirical causes of Human inadequacy. Thus, the continued progression and movement of Humanity toward improving quality of Vital Being, Vital Being and Duration of Vital Being, includes a progressive reconciliation of Humanity priorities, activities and systems with empirical and incipient nuances of reason. Such reason increasingly includes and prioritizes the factors and circumstances among which Humanity has come to be exhibited among the Universes. A focus on assuring that food is obtainable, can cause exclusion of assuring that such factors are optimal in assuring such Favor among which Humanity has come to be exhibited, such as enabling harmful changes to be introduced into the Food sources. Thus, such an example can be progressively extended to an eventual inclusion of the Biosphere as a priority in Human activity, although such a priority, through reason, is derived through assurance of Humanity, Vital Being, Quality of Vital Being and Duration of Vital Being within such Biosphere. Although an inherent idealistic promotion of a priority of the biosphere is reasonable, such priority can be disjoint from reason if there is not a progressive exhibition of inclusion of such priority through Humanities prioritization of its own self-interest. Systems of Humanity, impart perspectives, information and cognitive constructs, all of which have the potential for becoming permutatively reliant upon each progressive iterative analytical perspective, resulting in increasing distance from reason. However, Reason can always be empirically and incipient reconciled to the Favor among which Humanity came to be exhibit within the Universes, the interests of Humanity in extending such favor, enhancing such favor as well as expanding such favor inclusively among others of Humanity. Expanding such favor among others of Humanity assures the persistence, stability and ability deterministically assert such priorities and favor among the Universes. Correlatively, even when Health Services Coverage, Insurance or Indemnification is not utilized by individuals whom obtain such benefit, inclusion in such services programs are known to improve social, economic, behavioral and physiological outcomes. The nuances of health services cover, thus, integrate financial, clinical, biological, physiological, behavioral, insurance, and numerous other systems of civilization. Correlatively, what might be a most optimal perspective of the ways in which health service coverage and implementation of such coverage systems within civilization? The Amehsi Specification explores such nuances in numerous contexts through numerous general and specific analyses. Comprising modular components constituted of the nuances of factors which affect Health outcomes and health services reimbursement coverage provide an essential opportunity of improving and assuring the Human Condition as well as the Social Condition. Health Insurances are most centrally comprised of an ability to assure that care is provided to a population, such as a financial capability, and interest in health services provider entities or ownership of organizations which provide care. Essentially, Health Insurance Coverage Entities function by maintaining the resources to provide care for a population with an expected, typical, or experientially determined incidence of health outcomes requiring care during a particular period, such as quarterly, twice each year or annually. Typically, a population being covered provides an influx of resources to sustain such capability such as premiums or payment of required fees, providing of services for the benefit of an entity or organization which then pays such premiums, payments or influx or resources to enable coverage of individuals within the population. Thus, Health Insurance

Entities maintain resources and require payment that minimally sustains the resources available to cover the expected or observed instances of care, although some arrangements include self-funded health insurance in which financial resources are allocated to cover the costs of care for a particular population such as an organization which funds health insurance coverage to the benefit of its workers. Health insurance organizations, then, typically require that payments for care do not deplete a particular availability of financial assets or resources, below which the organization becomes susceptibility to exhibiting inadequate resources resultant of periodic or incidental increases or decreases in required payments, particularly when such unexpected changes or incidents are high in costs or are of extended duration or are uncertain in any such capacity, particularly including when the request for payment of such services might be received. Thus, there are reserving requirements in which a particular percentage or assets or dollar amounts are required to be exhibited for a health insurance entity to continue insuring populations. Similarly, there may be reserving requirements for particular categories such as lagging payments for services which are typically presented at least in the month after services have been incurred by insured populations. Similarly, insurance organizations may have administrative costs ratios that can be as high as 20 or 25 percent, while Margins or profit performance is typically considered to be at about 5% and while regulatory requirements often require that as little as 75 and much as 85 percent of all resources received as premium payments be allocated to costs of care or costs of enhancing care. The allocation of resources toward costs of care are included as the Medical Loss Ratio or MLR. Changes or amelioration in the incidence, costs and volume of health services required by populations can be imprecise, such that organizations may reinsure particular groups, particular individuals, or particular types of services using reinsurance through other health insurers, as well using special insurance which covers high costs of claims over a particular dollar amount or which begin to cover individuals whom have incurred a particular volume of services, particularly when these are resultant of emergence of particularly high costs health conditions. Thus, health insurance coverage plans have an interest in controlling costs, inhibiting emergence of high cost health incidence and promoting increased levels of low intervention, preventative care, and early intervention care for conditions which might become high cost conditions or might become high volume of care conditions. Volume of care and Costs of Care, can also be included in control mechanisms which might also include length of stay and high incidence of admitting to hospitals. Roemerâ&#x20AC;&#x2122;s Law is the well-known phenomenon which is characterized by implementation of the Hill Burton Act of 1946, which implements Healthcare Certificates of Needs which require that before public funding is allocated to construct of new hospitals in services areas already exhibiting a Hospital, there be a demonstration of Bona Fide demand for such services. Construction of New Hospitals in a service area is known to result in increased utilization which typically results in the newly constructed hospitals exhibiting a bed occupancy rate which correlative to that exhibited in the incipiently exhibited Hospital. The Hill Burton Act, however, did not preclude the construction of Private Hospitals, although some of the State Level Certificates of Need did prioritize inclusion of Private Hospitals in such limitations, such that the 1946 Hill Burton Act presents the instance in which privation of Health Services industries began to expand, being a most potent disruptor of a progression, logically linear, and transparent linkage between Dimethylacetothetin, Glycolic Acid, Pervasive aspects of Medicinal Chemistry, the discovery of Homocysteine as being essential to all of Kingdom Animalia in 1932, the discovery of Homocysteine in 1932, the Kennedy Pathwayâ&#x20AC;&#x2122;s discovery in 1956, the exhibition of Homocysteine as integrative determinant of Behavior and Disease beginning in 1960, and the promotion of nuance of physiology into all of Human events in plainly transparent contexts beginning with the Kennedy Administrationâ&#x20AC;&#x2122;s conclusion mimicking somewhat precisely the ways in the Kennedy Pathway is impaired during detrimental Human outcomes, the presentation by Adlai Stevenson at the United Nations of a diagram of perilous machinery placed into an

Island Nation 90 Miles South of Florida which somewhat precisely mimics typical diagrams of the Kennedy Pathway for Phospholipid Metabolism and then somewhat pervasive exhibition of such factors in nuances of Human behavioral and Human outcomes since. Interestingly, the 1976 Los Angeles Health Provider Work Refusal in the middle 1970s exhibited a decrease rates of Abated Vital Being. The Abated Vital Being clearly demonstrated that Physicians Directed about 78 percent or more of Health Services expenditures, including being principal gateways to Hospital Admission and Hospital Services Utilization. Therefore, Physicians intermediate the effect of Hospitals upon Populations, while such role has not ever been characterized as being causal because Emergency services utilization exhibits that 20 percent of Emergency Room Users generate about 70 percent or more of Emergency services costs and resources utilization. The populations which overuse Emergency Department Services, according to the pivotal work by Starr and Starr known as the Social Transformation of American Medicine, are windows upon the wider independent inadequacies of civilization and exhibit those whom are homeless, socioeconomically disadvantaged, exhibiting behavioral health conditions, exhibit compulsive and addictive conditions, and according to research incurred by the Amehsi Specification such groups are Homozygously or Heterozygously impaired genetically for pathways including Choline, PEMT, 1 Carbon, Methylsulfones, Mercaptans, Thetins, and other essential molecules. Thus, Health Plans have an interest in controlling and managing the wider interdependent inadequacies of civilization, including preventing detrimental behavioral, physiological and social outcomes. However, the mechanisms of managing these include management of premiums, management of access to health coverage, Changing the actuarial distribution of members with particular utilization patterns or care experience into different plans to diffuse risk, implement utilization management requirements which assure that services usage by members and providers are as precisely required as possible, as well as changing the availability of Hospitals within services coverage plans. Essentially, Health Services Insurance entities are information systems entities. These entities exhibit actuarial analyses which include characteristics of prospective populations, characteristics of members, information about care utilization by members, information about costs of care, statistical information which predict care incidence and rates which determine premium payment by sponsors and subscribers such that the Plan manages its available resources with an optimal objective achieving Margin of Profitability which, according to the Affordable Care Act, may be up to 5% before rebates have to allocated to Premium Payment Entities, although excess profit, excess funds among the 75 to 85 Percent of Premiums obtainment which have to be allocated to care through the Medical Loss Ratio, each may be reintegrated into the Plan for benefit to Workers within the Health Plan. These seem to enable larger investment in analytical, enabling and developmental aspects of health plans and how these have beneficial effect to Health outcomes. Some perspectives present that Costs increases which have emerged after the Affordable Care Act may be the result of integration of new entrants into the Health Insurance Industry whom may be increasing the intermediary costs by introducing Administrative cost overhead with each additional coverage entity exhibited in a particular service area, such the Costs of Health Insurance may have increased more rapidly than costs of care have increased or such that such factors have been influences enabling an increase in cost of care. Such perspectives, regardless of their reflection of observed changes in pricing and costs in the health industry, particular with regard to services, seem difficult to present because, again, the Amehsi Specification has found that a foundational inadequacy in all civilizations is that civilization sequester away the freely available factors in nature and require exhibition of financial instruments in reobtainment thereof, often without freely providing enough financial resources to each individual to assure that Humans have the ability to obtain resources as they would be able to from naturally available factors as well as assuring that Humanity can produce outcomes in civilization as they would be able to from naturally available resources. Civilizations have

only in particular instance provide adequate solutions to such inadequacies and any nuances of systems which expand the availability of opportunity for Humanity, particularly when such opportunity is required for satisfaction of foundational Human essentialities and the Social Condition, are difficult to impugn when resolving such dynamics to empirical and incipient nuances of reason. An inefficient manner of diminishing the detrimental effect of a foundational inadequacy within civilization may not be completely reconcilable to empirical and incipient nuances of Reason, although representing an improvement of the outcomes which are known to be most distant from empirical and incipient aspects of reason. Such dynamics represent, somewhat precise homologues to how the empirical and precise causal factors to detrimental health and behavioral outcomes have been omitted from adequate priority in care and adequate priority in development of biomedical capabilities. Humanity, somehow, seems to have become convinced that its existence must somehow become enabled through productivity in tangible contexts and that those factors freely available in nature are to be sequestered away from Humanity for purposes other than the assurance of the sustainability and enhanced availability of such factors to all among Humanity. There seem to be unanimity in the observation that framers and constructors of the Constitution, assembled in Carpenters Hall in Philadelphia Pennsylvania, certainly considered that persistence, enhancement and expansion of the Favor among which Humanity has come to be, as opportunity, included a way of refuge from the way in which systems of the universe might sometimes not adequately prioritize Humanity instead of presenting, instead, merely much more nuances of ways in which interactions between systems of the Universe and systems of the civilization deprioritize Humanity. Health plans, within information systems, exhibit Groupings of individuals whom may share membership in aggregate of resources to assure coverage care. There may groups exist at levels which include share components of other groups. Similarly, health plans exhibit groups of care providers entities of all types or limited types, sometimes being specialized to the requirements of the principal covered population group. However, care provider entities can exhibit complex structure themselves, sometimes exhibiting the same individual practitioner in multiple instances, with different specialties, with different organizations, with privileges in some multiple care facilities, and with different identities in multiple regions, states or localities. Hospitals may own Practices and Associations of Practices, as well as individual Practitionerâ&#x20AC;&#x2122;s business aspects of care, while individual and independent versions of practitioners and practice associations are known to be exhibit, particularly in traditional contexts. However, Health Plans exhibit Benefits Components which determine the areas of care, often represented by Diagnoses, Procedure Codes, Hospital Revenue Codes, Diagnostic Related Groups and other components, along with requirements or conditions in which such care is reimbursed fully when using a Provider Network or Group, reimbursed at less than complete levels when not using a Specific Grouping of Providers, as well as not reimburse for when both the provider and the service may not be included in constructs included in the Health Plan. Different Subscriber and Member Groups as well as different Provider Entity Groups can be associated, such that provider, or Subscriber groups can have access to expanded services providers. Thus, Groups can be utilized as a way of managing the characteristics of a Group of Provider Entities or a group of Members such that performance objectives may be more clearly prioritized. Narrow networks, for instance, are utilized to decrease usage of Hospital Services by using Roemerâ&#x20AC;&#x2122;s Law and reducing the number of Hospitals available to members of Group which is linked to a particular benefit Plan. Special Needs Populations might be included in their own Subscriber and Member groups because the performance requirements of particular programs are different than typical commercial plans and younger populations with less incidence of care and decreases costs of care may be included in High deductible plans because the costs of premiums can be lower and the deductibles higher when incidence of care is expected to be lower, while some proponents of the Affordable Care Act clearly present that such plans produce polarization of healthcare expenditures and make it difficult for care plans with diverse populations including high care incidence populations can become difficult to maintain.

However, imperatively, costs of care may be uniformly determined by cost experience, may be negotiated at a service level with particular number of expected incidences per period or per annum, as well as might be determined by mechanisms such as Diagnostic Related Groups which determine the reasonable costs and duration of typical stay exhibited along with a particular group of diagnoses. However, health organizations and health facilities are known to conduct analytics to determine those diagnoses, procedures, services, conditions, care codes, care codification modifiers and types of care providers produce the best reimbursement levels, resulting in organization becoming highly specialized around producing efficient care reimbursement and maximizing revenue obtainment from care interventions. Similarly, a bulletin presented by the Centers for Medicaid and Medicare Services clearly observes that some organization had become extremely adept at omitting prioritizing Amehsi Specification Factors as diagnostic and therapeutic capabilities, resulting in an ability for Human outcomes to become transformed to the financial objectives of organizations, such that care interventions could be managed to exceed Diagnostic Related Group Mean costs of care and Length of Stay for Inpatient Care, resulting in Outlier Payments that could managed to become increasing aspects of a care Facilitiesâ&#x20AC;&#x2122; revenue management business cycle. The Centers for Medicaid and Medicare Services clearly presented analyses of revenue and utilization which suggested that such patterns and practices were not derived from differences epidemiological characteristics of the population other than those which are known to be possible by omitting Amehsi Specification Diagnostic and Therapeutic Indicators. It would be less than productive to explore the differences in Human outcomes exhibited in such aspects of interactions among systems of civilization, except to plainly present that omitting of such essential priorities may have been integrative if not most causal factors in the exhibition of 200,000,000 or more instances of abated Vital Being since 1878. Health pans might be considered as central components of Risk, Expected Costs, Payment Rates, Pricing for Providers, Accessible Care, Care Providers, and Members. Although any Group or Payment Agreement exhibited by a Care Entity, may be, within reason, accessible by a Member, such that a Narrow Network might link to a larger more inclusive network to have In Network, out of Network or other Payment levels become exhibited. Some Larger Insurers have the ability to obtain care in their networks or partnerâ&#x20AC;&#x2122;s networks in other locations, states or Nations. Thus, there seems to be a direct behavioral, financial and risk management priority included in the way in which benefit structures are comprised. Major operational components seem to include managing claims or encounters, in which encounters can merely information exchanged when care is already compensated for through Managed Care payments made on per member basis, as well as Financial Management which can include Investment Portfolio Management although the very little prominence of such priority seems to be included in publicly considered aspects of Health Plan activity. Similarly managing Providing of information, managing information, conducting and implementing Diseases Management Programs, as well as review of care and coverage outcomes seem to be essential for Health Plans. Management of Provider Networks and Members and Subscribers also seem to be essential, although the management of sometimes diverse plans with diverse objectives toward achieving objectives, all present diverse business cycles and diverse modalities for program management. Some agreements between Health Plans and Provider Entities require minimum volumes of care while, pervasively, quality of care metrics can be monitored and even included as determinants to components of care reimbursement. Accumulators, however, seem to be the next area of essential understanding. Deductibles are considered to be an amount which must be paid by the Subscriber for Health Insurance for self and all members included within the Subscribers Coverage Policy before Health Insurance Coverage Entity begins payment, although before recent changes, deductibles may have been distributed across multiple instances of care, instead requiring complete satisfaction of a deductible before reimbursement for care by a Health Insurance entity is performed. Regardless, distributing a deductible across multiple payments, seems to be most reasonable because consumers can be averse to low to mid-level health services expenditures other than preventative care interventions because preventative care interventions can

sometimes be covered by health plans with deductibles. Moreover, deductibles incentivize health consumers to avoid care until less progressed health statuses either go way or emerge as chronic or major health outcomes, particularly because the deductible may be only an aspect of a larger payment although there seems to be the possibility that aversion to costs might deteriorate along with the deterioration of health status to more progressed levels. Deductibles are included in out of pocket costs, along with Copayments which can be required during each health intervention or which can be required during particular health interventions. However, office visits fees may be included and might or might not be included in out of pocket maximums. Accumulators can also include limits on medical payment for particular kinds of services, limits on payment for all services, other limits. Therefore, accumulators are progressive aggregate monitors which can limit the responsibility for the member or subscriber to pay as well as which can limit the levels which a health plan pays in particular scenarios or generally. Health Savings Accounts are exhibiting in multiple varieties including those which accompany high deductible health plans, those in which funds not utilized in particular plan year being abdicated, those funds not utilized in a particular plan year being moved over into subsequent years, those which are funding by the health plans, those funded by the provider, those funded by the member or a mixture of these mechanisms of funding. Health Savings Accounts might be included as Flexible Savings Accounts specifically for health services, specifically for ancillary services, or integratively including other services such expenses exhibited by covered members or those whom rely upon the subscriber for care. Care is can be compensated for in a number of ways including providing reimbursement for care, known as Fee for Service, as well as including other arrangements which can be Periodic Payments made per Member with assurance that care will be provided. However, typically arranged payments are negotiated in some way such that costs of care as determined by price calculators such as RBRVUS or CPT Code Coefficients might typically be higher than arranged payment agreements. However, cash prices have been known to be lower than both of these other modalities of payment. Increasingly, any payment arrangement that is based upon an intervention being required to occur before reimbursement is provided may enable Roemerâ&#x20AC;&#x2122;s Law to affect Human Outcomes. Fee For Service requires detrimental outcomes to occur before payment is made and such that the financial objective es of a Care Entity is achieved, while, certainly the dynamics which potentiate increased detrimental Human outcomes such that Organizational objectives might be achieved can be difficult to inhibit once such objectives are achieved, resulting in unmanageable systems of Human detriment. Relevantly, it is not suggested that enabling detrimental Human outcomes to occur in any context, particularly in achievement of revenue objectives or other objectives, may be any more reprehensible when occurring before such organization objectives are achieved. It is becoming clear that salaries or financial benefits provided to healthcare workers require being decoupled from Health Organizations, Practice, Care and health services insurance reimbursement. Such payments might optimally be made directly to health services workers by publication of a variable factor salary schedule to all coverage entities in an area along with shared satisfaction of such salary by all coverage entities in an area, with some of the components being provided through local, regional, state and national, as well as even extranational and international organization contributions. The operational components of a health service provider entity, separately from salaries, can then be satisfied similarly by publication of such requirements by the health services provider entity followed by publication of the achieved revenue for a period, followed by satisfaction of any inadequacy in achieve the operation revenue requirements by all of the health services coverage entities in an area, including Local, Regional, State and National Entities. These provide a useful and somewhat oversimplified perspective of Health Plans, although these seem to provide some information which might be useful for constructing optimal health services coverage programs. Relevantly, the experience of nuance of change in consumer directed healthcare and management of accumulators,

along with increase in payment has not seem to result in substantial decrease in Abated Vital Being each annum, although some changes to utilization are possible and although increasing effectiveness of care interventions seems to be emerging. Regardless, improvements in a nuance of care or improvements of nuance of covered populations, because such improvements might not have occurred through improved inclusion of empirical causal factors of detrimental Human outcomes, might result in diverting of detrimental outcomes into other categories such that occurrences of Abated Vital Being from all causalities exhibits resiliency. Thus, optimal health healt insurance characteristics are comprised of individual level exhibition of those components which would typically be exhibited at the Group or Plan level. An individual might exhibit, requisitely in all instances, A High Deductible Health Plan, that includes a Health Savings Account which persists from year to year with amounts moving from year to year in the savings account. The Health Savings Account covers an integrated aggregate Loss Abatement Coverage at the individual Levels, the Deductible Completely, and the Out of Pocket Expenses Completely. Such individual Health Coverage would be able to access through linkages to the Provider network of any Provider Group exhibited by the Coverage Entity Providing the assurance and would be able to attach upon demand to any care network included in any publicly funded health planâ&#x20AC;&#x2122;s network in the Nation, such that it is unlikely that any care intervention would result in an out of network reimbursement amount, regardless of location of services, although there would not be a requirement that any provider provide services in such regard and although there would also be included the prevention of a way to determine that the reimbursement levels have been derived through linkages instead of through constitutive membership of the Subscriber to the Group which is receiving the rates exhibited for care. The high deductible Health Savings Account, then, as it is now, funded completely at the beginning of the year by the Employer, Health Insurance Plan, or publicly Funded third Party, such that if a covered member separates from the Employer or coverage entity, the amount in the Savings Account persists and any amount above that contributed by health savings contributions are considered as income, without requirement of any other entity to contribute any more funds to the Health Savings Account during the same Plan Year. Similarly, the amount of funds introduced into the health savings account by a public entity or publicly funded Health Plan might considered as income on a progressive scale such that below poverty level it is included as benefit and as distance from poverty level it can be included as taxable benefit. There seem to be numerous factors included in taxation which are correlative to such expenses and the high deductible health savings account seems to be a potential mechanism of assured care, assistance and financial stability for those of lower socioeconomic status and those other socioeconomic statuses. A most interesting possibility seems to be that Health Savings Accounts or similar accounts, integrated into each health plan which is individualized, enables cash payment for pervasive aspects of health and reimbursement of Health Savings Accounts used for cash payment by Health Server Payers or Health Insurance Organizations. Similarly, because actuarial analytics are prevented from being applied to individuals when determining rates such as in analyzing claims experience, except with particularly substantial areas of health risk associated with behavior and except with preexisting conditions which are also being diminished in their applicability in such regard, the production of individualized health coverage tuples enables publicly sponsored health plans to be inserted in particular areas of service coverage, particular ranges of diagnoses or particular nuances procedures and care, such that individual choice is promoted as well as such that true portability of health services coverage is enabled. These are all essential, because when the requirements which were analytically presented by the Amehsi Specification become widely known among populations and the potential that 200,000,000 Humans in the United States may have incurred abated vital being without necessity since 1878, which is a number which includes virtually every person whom incurred abated Vital

Being known by any person whom exhibits continued Vital Being now, the public will not be able to be beguiled by discussion about the costs for care and whom pays for health services coverage. Any inadequate access to the Amehsi Prioritizes and any exclusion of these from priority in Civilization will be known to constituted abridgement of Civil Rights, Human Rights, and imposition of circumstances which cause detrimental physiological outcomes as well as cause detrimental behavioral outcomes. Groups and populations turned upon one another by such obfuscating nuances will come to know that they and everyone among their populations have been victimized by nuances of systemic dynamics which have progressively diverged from reason. Thus, to this instance, Presidents, Monarchs, those whom have been of service to civilizationâ&#x20AC;&#x2122;s systems, and even those whom have been constructors of incipient aspects of civilization, have been included in those whom have victimized in such regard. Every moment that systems of civilization utilize to analyze, debate, prioritize and obfuscatingly present as priorities to the public those factors with less propensity to affect the level of Humanity which has been victimized by such dynamics, continues and expands such victimization. The Juncture between 1932 and the exhibition of the Hill Burton Act, followed by the period between the Hill Burton Act and the conclusion of the Kennedy Presidential Administration, followed by the eras which subsequently followed, exhibit a sometimes confusing level of changes in the Health Services Industry, then the Health Capabilities industry, and then in the Information Services, Research and Information Technology Industries, all of which seem to have constituted Hegemonic interactions trying to access nuances of intangible information and knowledge with the potential to enable the transcendence of Humanity. It is most probable that the integration of information technology into health services through regulation such as the Administrative Simplification Act of the Health Insurance Portability and Accountability social constructs, along with subsequent requirements of similar regard in social constructs, as well as similar requirements in other organizations of systems of civilization, some of which were the impetus for practicing health professionals to obtain technology qualifications and integrate themselves into applied health informatics, which caused the nuances described by the Amehsi Specification to become revealed. The populations participating in such industry, now as well as during such periods, have been essential to exhibition of these Analyses. Systems of civilization and the perspectives of what is probably the most compassionate, capable, educated and socially conscious work forces ever exhibited among civilizations, similarly, have been essential to the synthesis of these analyses. What such workers and practitioners must have been required to incur, endure, abdicate and achieve to enable these analyses can only be expressed with invariably euphemistic inadequacy. Regardless of tangential knowledge of such dynamics, Human activity, expression and priorities, invariably present such factors and priorities, sometimes in ways which prevent Humanity from perceiving that which their activity can somewhat precisely bely. A Social Construct requiring the therapeutic and systemic alleviation of the causes of detrimental physiological outcomes and the causes of detrimental behavioral outcomes, because regardless of such priorities being incipient empirical impetus for the construction of civilization, the requirement of Humanity to participate in systems and obtain financial ability to achieve the social condition and human condition, have produced what has been a seemingly insurmountable impedance. Instead of simply regarding detrimental Human outcomes as information about the inadequacies of civilization, and producing increasingly empirical perspective, understanding resolution of causal factors to such outcomes, Humanity has been caused turned upon itself. Such turning upon itself seems to include the attributing to individuals or groups causality for detrimental outcomes which do not occur in nature, which cannot occur in nature, occur before and after any one individual has incurred such outcomes, and which require circumstances, artifacts, priorities and contexts which pervasively do not occur in Nature. Most imperatively, the fundamental empirical observation that detrimental outcomes which occur in civilization, which are increasedly potentiated by civilization or caused by civilization, describe Human detrimental outcomes somewhat pervasively, although the ability and potential of civilization to resolve the nuances of detrimental outcomes which occur in nature is

unquestionably presented here. However, when civilization causes detrimental Human outcomes, enabled detrimental outcomes to the Favor Among which Humanity has emerged, as well as produces outcomes which are dissociated from the persistence, enhancement and expansion of such Favor, including deteriorating the environment, civilizations become anathema to Humanity, Liberty, and those essential nuances of liberty which comprise the Physiological, Behavioral, Human and Social Condition. These describe why civilization has been required to exhibit numerous, progressing, and sometimes disparate nuances of aggregation of Humanity. Human aggregation produces information and understanding, pervasively requiring a progressing understanding of factors which affect Humanity. Such nuances of understanding, are intelligent when correlated and reconciled to reason. Such nuances constitute artificial intelligence when derived from Nuances of understanding that are increasingly distance from empirical aspects of reason. Artificial Intelligence can, then, become diverged from reason, resulting in inaccurate, uninformed, and less than productive and beneficent cognitive constructs and social contracts which limit the ways in which civilization may provide service Humanity. Attributing to individualâ&#x20AC;&#x2122;s causality for detrimental outcomes which do not occur in nature with precisely the same nuances of characteristics as they occur in civilization, as well as attributing to individuals causality for those outcomes which occur increasedly in civilization, all are mechanisms by which civilizations diverge from incipient and empirical nuances of Reason. Inherently, because such attribution of causality is substitute for understanding the less than tangible, disjoint, quantum to universes levels influences, and ways in which civilization may enable such outcomes, iterative and progressive exhibition of attribution of causality to individuals in such regard along with exhibition of social constructs in regard, can result in progressive dissociation from Reason. These explain why the exhibition of a social construct which requires sanctions, particularly when the factor or outcome is of substantial effect to Vital Being, Quality of Being and Duration of Vital Being, have been known to merely result in increased levels at which such detrimental outcomes may be exhibited. Although the possibility that systems of civilization are causal of outcomes among Humanity which can include pervasive aspects of detrimental outcomes seems to be anathema to Liberty and seem to counteract incipient aspects of reason, this is only an accurate conclusion when systems of civilization implement sanctions which do not benefit, alleviate and protect everyone affected by a detrimental outcome including those to whom causality might be attributed. Systems were intended as mechanisms which enhance the understanding of how effective civilization may be at persisting, enhancing and expanding the incipient favor among which Humanity has come to be exhibited. Inherently, acknowledging that systems are causal to an outcome requires understanding, productive change, analysis of the effect of change and continuous improvement. Inherently, attributing causality to an individual, results in Artificial Intelligence, which can be utilized as supplied information or training data which goals, objectives, algorithms, routines and outcomes which are increasingly distant from reason might be produced or become maintained. Interestingly, the application of Humanity in nuances of immediate consideration of less than optimal outcomes as being produced by nuances or inadequacies within the way systems shape Human outcomes, is able to occupy productively the activity of all among Humanity in ways which potentiate priority of Humanity. Often, when systems attributed causality for such detrimental outcomes to individuals, there can become required nuances in which the resources which civilization utilizes to manage detrimental outcomes becomes scrutinized at numerous levels within civilization and among Humanity. The systems of civilization, however, are not the cause of inadequate resolution of empirical and incipient impedance to achievement of the Liberty, the Human Condition and Social Condition. Such impedance seems to be the inadequate application of systems in assurance of empirical aspects of reason along with the potential for Artificial Intelligence to become dissociated from Reason.

Clearly, social constructs which present nuances of reason, abound. However, the translation of any artifact, ancient, modern, or immediately produced, is affected by the circumstances, shaping influences and interactivity in any aspects of the flow of the Human experience. It is not possible to know what nuance of humanity, in all its accoutrement of generational collateral, distance, location, space and time which constitute such interactivity when social constructs are produced. The language, shape of linguistics constructs, circumstance, context, immediately exhibited humanity, or other factors within the Universe are required for precise translation of such artifacts, particularly when outcomes among humanity pervasively disjoint in location, distance, space and time, while also being produced by nuances of interactivity which are pervasively intangible and less than consciously exhibited. These suggest that iterative and progressive lineages of analyses can become constructs of Artificial Intelligence and these can diverge from reason, unless these become reconciled immediately and completely to incipient and empirical nuances of reason, including the Favor among which Humanity has come to be exhibited and including the priority of civilization in persisting, enhancing and expanding such favor, while, imperatively, the manner in which Systems of Civilization transform Human outcomes are integral inexculpable aspects of such imperical understanding. The clearly potentiated, inaccurate, although reasonably presented conclusion that Reason requires artifacts which potentiate application in detriment to Humanity be removed from civilization when it cannot be assured in 100 Percent of all contexts or instances consistently with Reason, provides a useful analysis because particular artifacts have been produced particulalry because of usefulness in imparting detriment to Humanity. Such artifacts require persistence availability to populations resultant of Social Constructs produced centuries ago, while such artifacts clearly present, with analysis of outcomes exhibited in civilization, that there are always potentiated those circumstance in which such artifacts can be detrimentally utilized by any individual, regardless of their cognitive, physiological, behavioral, social and training adequacy. Reason requires that ability of Individuals whom synthesized Social Constructs centuries before to understand or foresee that 30,000 instances of abated vital being would occur each year, sometimes being more than those levels of abated vital being exhibited in all the geopolitical interactions among the Earth in the same year, might not optimally be an impedance to diminishing or preventing the potential for continued abated Vital Being in regard. The particular nuance presents an empirical nuance of divergence of outcomes among civilization from Reason, because certainly the way in which such detrimental artifacts are utilized, produced, distributed and maintained are fundamentally disparate from the ways in which such artifacts may be utilized in eras of immediacy. These analysis, however, do not particularly or specifically present this nuance of divergence from reason except for analytical purposes because the withholding of capabilities since 1878 which would assure health status seems to have produce an exponentially more egregious effect to Humanity, although such artifacts which are specific detriment to Humanity have, without doubt, contributed to the perspectives which have enabled persistent disregard for Human priority among systems of civilization. Civilization, it seems, by attributing causality to individuals for the outcomes which civilization itself produces, as well as withholding the capabilities by which the physiological and behavioral condition might be assured, may have enhanced the correlation such potentially detrimental artifacts with perception of assured Liberty. Certainly, artificial intelligence produces inaccurate attribution of detrimental outcomes to Humanity, thereby turning Humanity upon itself, and supplying Humanity with artifacts which it might perceive as an assurance of Liberty. Inherently, any benefit plan with inadequate coverage of all services required for complete continuum of care, is augmented with publicly funded Rider which covers the service inadequacy and utilizes the High Deductible Health Plan Contribution to assist in funding the coverage.

These enable any individualized Health Plan to attach to any other plan, group or be aggregated with others in a subgroup. The Loss Abatement Reinsurance Rider can accompany Loss Abatement Reinsurance at the Groups, Subgroup, or Plan level. Any aspect of care not covered in such arrangement, can be augmented by any insurance entity, including those of International Origin which do not have costs increased to balance risks within the health insurance market. Most imperatively, each health services provider may be required to utilize and therapeutically manage and report compliance in instrumentation of Amehsi Specification Priority Factors during every intervention. These changes enable an improved satisfaction of Human requirements by making a direct investment in the solvency, health status and ability to participate productively in systems by all among the Nationâ&#x20AC;&#x2122;s population. Similarly, these changed separate costs of care from the individual interest of Health Services Providers and more tightly integrate nuances of care with the actual operational requirement of Practices and Entities which manage health services practitioner practice. Other than bonuses provided for exceptional, acceptable or reasonable quality of care metrics, all participants in health services are enabled to have impartial perspective of nuances of care which prioritize outcomes. These also enable business level decisions to more integratively and transparently be correlated to changes in care outcomes, changes in behavioral outcomes among populations as well as present how these decisions may be affecting Human Events. Expected, is an ability to discern increases in costs, the reasons for increases in costs, and the ways in which organizations benefit from changes in revenue, services, service quality and Human outcomes. Imperatively, also, these present a beginning of a transformation of civilization to consider what is required at financial levels to satisfy Human requirements and begin focusing on assuring that Human Requirement and Social Requirements are individually assured instead merely hoping that beneficence and productive perspectives are always priorities in how resources, capabilities and essential factors are distributed and obtained in civilization. The imperative assertion here is that because civilization has not acknowledged this phenomenon, the ability of less than beneficent influences to use these has emerged, resulting in persistent or increased exhibition of detrimental behavioral, social or Physiological outcomes. Populations which are not allowed understand or acknowledge how such fields and influences shape behavior become susceptible in such regard. Thus, organizations or groups which share only small levels of commonality in perspective and objectives may be regularly being commandeered using Social Networks, Communications Fields and other influence which are layered upon their location using internet and communications technologies, resulting in less than 40 percent commonality in perspective becoming more than 90 percent commonality in perspective including the introducing of potential for detrimental behavior without any consciously determinable priority of an individual to produce a change in their own behavior. Thus, Roemerâ&#x20AC;&#x2122;s Law is not relegated to mere consumer interactions, it is amplified by fields of civilization, such that a conscious decision by civilization to not make all among its populations aware of such influences may have resulted in susceptibilities of global populations to extremism. Inadequate obtainment of the factors that constitute the Social, Human, Behavioral and Physiological condition, along with such fields of influence, may have produce contexts in which boundaries of civilization, the unwillingness of Nations within such boundaries to conduct Nation Building and promoting awareness of such influences or Roemerâ&#x20AC;&#x2122;s Dynamics, promotes a persist void in Human awareness and consciousness that somewhat assures the persist exhibition of Human Geopolitical detriment. Such persistent exhibition of Geopolitical detriment may benefit the Profit Motive of Private Enterprise although certainly not benefiting Humanity. Correlatively, it may be imperative for Nation Building activities to require emerging Nations, groups or aspects of Civilization to understand, acknowledge

and prioritize the utility of civilization and its systems such that other entities, also, must understand and acknowledge, themselves, the incipient utility of Civilization and its systems. It is not the priority of these analyses to conduct a more thorough analysis of extreme socioeconomic, geopolitical or philosophical contexts, because these analyses clearly show that these utilize the same dynamics which civilization otherwise may not be adequately considering and alleviating, resulting detrimental patterns, perception and cognition utilized for or observed in less than productive/beneficent outcomes. However, it is imperative that extremist concepts and activities which have produced substantial detriment to Humanity are clearly produced for a sensationalist purpose, suggesting that the activities may be the result of the similar priorities, susceptibilities, and circumstances otherwise exhibited by populations seeking similar sensationalist outcomes. It is observed that sensationalist outcomes may be pervasively otherwise utilized for more productive beneficent purposes. Specifically, however, if sensationalist outcomes were not the primary purpose of such conceptual bases and contexts of extremism, and Human detriment were the objective, then it is not necessary to expend the resources or peril of such detrimental activity or to interact at Geopolitical levels with aspects of civilization which has developed capabilities to inhibit, prevent or alleviate sensationalist detriment. Merely participating in systems as they are or integrating oneself into systems of civilization in the Western World, such Contexts of Extremism can participate in the demise of 2.6 million or more each Annum in the United States and many more millions in Western Nations. However, the research observes that Health Providers may typically outperform Health Providers with regard to optimal outcomes for a number of reasons including potential increased attention to detail and presumption that secondary and ancillary checking of accuracy, use of clinical research in care processes as well as more protection from the influences of Systems which impose Sanctions including the use of demise as a Sanction resultant of Language Differences. Patients in Acute Care whom do not speak English are observed to have improved outcomes, suggesting that the dynamics effecting differences in care or such regard are not consciously produced. Dynamics of systems which persist as unacknowledged and the use of demise as a sanction, as well as the proliferation of statistics regarding detrimental human outcomes within the economy and systems otherwise seem to be shaping outcomes in accordance with the Status Quo, even when the clinical information or Physiology clearly indicate outcomes otherwise should be occurring. The findings of the Amehsi Specification clearly exhibit that systems as they are may be abdicating the safety, health, welfare, as well as Social, Human, Behavioral and Physiological condition of those in Western Nations to the influences of International Systems in many spheres of influence or civilization. The most correlating influence is that the downregulation of PEMT and upregulation Choline Kinase do not seem to discriminate with regard to how the influences which culminate in modulation of their activity. Thus, regardless of if the incipient stimuli are emotional, psychological, physical, molecular, magnetic, electromagnetic, atmospheric, local, regional, national, international, cosmic, tangential, transitive, economic or otherwise, how detrimental influences including intermediating influences affect the manner in which systems result in modulation PEMT and Choline Kinase may determine health, perception, cognition and behavior. Thus, it is humanity that is managing the competitive interactions between economic, social, geopolitical, conflict, or other systems through transitive interactions which move between systems, entities and material to affect Choline Kinase and PEMT. Thus, civilizations which prioritize their own populations may require prioritization of other civilizationâ&#x20AC;&#x2122;s populations to its own benefit when another civilization does not exhibit requisite regard for its own population. There was humanity before civilization, and humanity persists with civilization in place.

Pervasively the discontinuity of Humanity is the result of discontinuity among aspects of civilization, because otherwise, in may regards, Humanity within the Biome is one. Civilizations enhance the experience and potential of Humanity, promoting division among Humanity primarily to enable the enhancement of those among Humanity whom it is able to beneficially effect. Likewise, civilization may endeavor to provide benefit to all among Humanity through the circumstance of those which it may be able to beneficially affect, its own populace. Although, obviously, solutions to detrimental outcomes and resolution of the numerous less than optimal outcomes presented in the Amehsi Specification have to effect individuals and the population locally, because outcomes among Humanity in such regard are pervasively incurred in such context at lease in effects, solutions as well as resolution of these issue require local, regional, national, individual, population, as well as international, supranational and extranational contexts. The essential asymmetric opportunity seems to be the ability to effect Global outcomes by resolving impedance to the Social, Human, Behavioral and Physiological condition within populations, individuals, physiology and Methylation pathways of the population, particularly in the context of Nations such as the United States. The essential opportunity, then, seems to be producing systematic, coordinated, interactions between Nations, that focus on Human outcomes and Status of Humanity in the contexts which such entities have the most stable and assured ability to assure such outcomes, their own National Boundaries. Through interactions and collaboration, Nations can assure that any assistance provided to other nations, including Nations which are Not Nation States, as well as included susceptible populations to extremisms, are implemented in ways the prioritize Humanity, thereby inhibiting the potential for factional activity to masquerade as Nationalism that deprioritizes Human Vital Being. Preventing the demise of more than 2 Million each annum, 2.6 Million in a most recent analysis of demise in the United States, would be produce substantial decreases in health services and resource costs, although costs are merely another constructed reason to allow demise on such a scale to occur. Fiat currencies do not manage available currency to the level of a particular factor or resource. Fiat currencies are managed according to the Health Characteristics of a Nationâ&#x20AC;&#x2122;s economy. Natural and Human resources are pervasively much more available than currencies, costs or prices enable obtainment of. These clearly show than when priority of Humanity, individually and plurally, are allowed to prevail, the obfuscations that inhibit vital being, the impedances to the emergence and persistence of Vital Being, become more easily determined and more easily considered as being anathema to Humanity. Correlatively, in each of the findings within the Amehsi Specification, particularly in how these might most practically and immediately be alleviated, it is the Profit Priority of Private Enterprise that can be found to be the most obvious and substantial impedance. Particularly instances in which systems of civilization have seemed to be inherent impedances, more thorough analysis pervasively indicates that the Profit Priority of Private Enterprise is somewhere Hidden in the priorities, finances, or other aspects of such systems. Furthermore, the Profit Priority of Private Enterprise, pervasively, merely reflects the inherent nature of systems of the Universe to progressively and increasingly prioritize themselves over Humanity. These require and have required the inclusion of Humans in such systems such that this progressive prioritization of Systems exhibited by Systems and Self Prioritization of Profit for Profitâ&#x20AC;&#x2122;s Sake within Private Enterprise, are not allowed to progress to levels which stimulate detrimental outcomes, particularly those detrimental outcomes which might progress to levels these analyses would prefer not to consider.

Correlatively, these require that Civilization, regardless of it requires perspective to conduct Nation Building in an expeditionary context or not, began to again understand the fundamental impetus for producing civilization, the foundational building components for a rudimentary economy and how these produce the incipient impetus for individuals to produce more than they themselves consume or produce artifacts which individuals themselves may not utilize. Clearly, such impetus does not emerge from Priority of Profit for Profit’s sake. These seem to emerge as foundational aspects of conducting ones being in community among one another, the emergence of division of labor, and the utility of specialization in knowledge in skills that are beneficent, productive and useful for civilization. Thus, the objective of producing artifacts that are not for oneself seems to have been for beneficent and productive purposes as well as for trade to obtain those artifacts which one might be less able to effectively or efficiently produce compared to another’s ability to do so. Interestingly, in such incipient aspects of civilization, the obtainment of too many artifacts or too much land, may result in unmanageable outcomes in which land, artifacts, even agricultural factors require help or assistance which may or may not be available, unless Humanity produces division of labor, specialization and conducts their being in community among one another. Resultantly, these analyses suggest that programs include a component in which each individual is assured that once a level of individual financial factors are accumulated, become translated into assets, and include land and shelter, that a portion of these that would sustain a reasonable level of quality of Vital Being and a reasonable level of Land including shelter, become assured and protected, so that it becomes impossible to have these no longer be available resultant of any detrimental financial or other outcome. Such reasonable factors may be provided to one’s offspring or provide to another in circumstances when they may no longer be able to be utilized by the individual, although such receiver may be subject to the same protections and limitations of such protections to resources reasonable to sustain an individual. It has to be presented here that unless there had emerged the potential to acquire substantial assets and levels of currency, and unless among those who were able to manage their activities in accumulation of such assets were exhibited, there might not have been the opportunity to present these analyses. Certainly, the manner of objectivity produced be extreme levels of financial independence may be substantially different from that exhibited by those who might be detrimentally affected by presenting even the most obvious conclusions about systems and the Human Condition. Similar observations could be made about any circumstance in which individuals or people are protected or enabled to be disparate from the influence of systems which are being objectively considered for improvement with priority to Humanity. These analyses do not suggest that success is detrimental. The objective here seems to be that even beneficent, productive, innovative and activity otherwise may produce successful outcomes which populations find useful. Once, however, priority emerges as clearly being profit for Profit’s Sake, these can become detrimental to economies and individuals, although organizations pervasively offset these with investment in people, programs and philanthropies which should be considered although these offsetting factors should contribute to production of healthy, successful, beneficent priorities that allow others to achieve levels of individual financial and economic security. Particularly, these analyses present a foundational shift from the incipient impetus to produce artifacts or services for those other than oneself compared to the manner in which business has produced different ways to consider such activity, particularly pricing, with priority of Profit. Instead of incipiently emerged civilization in which trade is often considered with regard to how much each person in the trade requires to sustain themselves along with consideration of what resources were required to produce such factors utilized for trade,

business practices suggest that pricing be determined based upon how much it requires to produce a factor incipiently and then how much is required to produce such factors as marginal costs once economies of scale have emerged followed by determination of price equilibrium. That is, businesses or business controllers are trained to make decisions regarding pricing by determining the price at which the most units of factors are purchased and determining the highest price at which such units or factors are purchased. Thus, at a point where the Number of Factors multiplied by the Price is highest, a determination is made to present factors at this price, along with the correlated characteristics of business activity to accomplish the production or service requirements. Foundationally, these are profit for Profitâ&#x20AC;&#x2122;s Sake decisions because even if a factor being produce is essential to the Human Condition, business suggest that pricing 3 Units at 20 Million Dollars is preferable to producing 600 at 100,000.00 Dollars and preferable to producing many more at lower prices that does not equal 60 Million, because the priority is profit and the lower production costs of 3 Units prevents requirement of resource usage and employment expense. Thus, it is suggested that the Laissez Faire influences require such priority, allowing emergence of other businesses to affect availability of products, although clearly in health services the Laissez Faire influences have not prevented 120 Million instance of demise which may have occurred unnecessarily since 1962. Private enterprise is foundationally handicapped as are Capitalist Economies because at their foundational and incipient levels of function, individuals are not inherently provided the resources required to place them back to where their potential was in Nature. Such potential, in nature, include the potential and adequacy or resources to produce Shelter, Sustenance or the ability to move to such location without hindrance as well as without requirement of satisfying pervasive ancillary requirements imposed by civilization. The nature of nutrition, shelter, and other resource obtainment is substantially affected by socioeconomic factors including factional activity, stigmatization and systems themselves which can impose destituteness upon individuals, groups or communities. The internet and social networking as well as victimization at Global Level of individuals divulging their knowledge and abilities can be pervasively participative in production of destituteness particularly because factions can be local, regional, national, international or extranational as well can exhibit similar activity as interactions Self-Prioritization routines of systems and Profit Priority Routines of Private Enterprise. Such Channels are not difficult to understand and may not be difficult to resolve, although acknowledging that these influences are exhibited seems to be much more of impedance than resolution of such factors might ever be. Similarly, even in the most progressive economies those whom are in destitute conditions are required to victimize one another and turn upon one another to compete for opportunities to exhibit productivity activity, obtain financial resources and obtain socioeconomic security. The assurance of these seems to have been among the most incipient impetus to produce civilization. Acknowledgement of such factors may be substantially difficult when these have to permeate the groupthink that encompasses leadership within environments effected by factional activity, since such factional activity invariable includes prioritizing those factors which emerge into the Institutional Agenda and those which may have benefited the emergence of the status quo which might not ever be adequately acknowledge because the Status Quo exhibits Self-Protection mechanisms, Mindguards that prevent change, and even permutations of social constructs, constructs, rules or programmed activity which progressively and encompassingly prevent change from being exhibited. A foundational change in the John F Kennedy Presidential Administration occurred after it was, according to the analytical literature, concluded that an early planned activity to implement Regime Change had occurred through

Groupthink dynamics, causing the Administration to carefully understand the motives, interests, directives and activities which it exhibited afterward. Once could present that this foundational change was an impetus for a retreat of Choline Kinase and PEMT into cognitive and social projection, allowing it to surmount the already emerged complexes within the Nations industry and systems and allowing such concepts to progress amid interactions between such systems. Systems had come into control and cyclically even the leaders of Nations had become subjugated through procedure, protocol, and groupthink to the outcomes which systems suggested as requisite. It is possible that the earlier experience in Groupthink allowed the Kennedy Administration to avert a more detrimental outcome in the Crisis which emerged later in the presidency, producing exit points and producing awareness of the nature in which systems can have algorithms that exculpate Humanity from decision-making, even those algorithms that would abrogate Humanity itself. Becoming a leader in any context in the Global Economy or within Global systems does not require any knowledge of such complexities and potentialities. Moreover, as the Kennedy Administration and its correlation to the Kennedy Pathway suggests, the emergence of Leaders or Ascendancy to become President of the Nation States may occur because Systems have extracted Physiology amid permutations of function, resulting in the exhibition of Electoral or Political Outcomes which have foundational meaning which populations may not be able consider or understanding with temporal coherence. Thus, regardless of how less than accurate a Presidency might be, there is strong reason, in this regard, to not utilize Impeachment and let the systems of the Nation work through why it is that systems have enabled a particular leader to ascend to the Presidency. The impeachments which have occurred, particularly among the Presidency of the United States of America, may have disrupted a flow of knowledge and progression of Human events that would have been required to enable a much timelier emergence of the issues which the Amehsi Specification presents as requiring more adequate and timely resolution. These may be accurate presentation of issues even if a President has to acknowledge, alleviated and prevent from occurring again their own manner of Ascendency, and there should not be any manner in which a President is inhibited from considering, presenting and advocating such change. These analyses do not advocate any impeachment of any President because the Office of the Presidency is not a Human, it is occupied by a Human, such that the roles and responsibilities of president have, most, the potential of shaping and molding individuals, groups, administrations and interests to the requirements of the Nation. It is unlikely that such Office and the Nation, conversely, would become ephemerally bent or transformed to the interests of an individual, group, administration or interest without causing more comprehensive influence in prioritizing the Nation instead. The institutions of the Republic and Democracy seemed to be designed to permutatively explore such factors and produce outcomes in civilization that provide clarity with regard to such priorities, such interests, and how and administration becomes the conduit through which the interests of the nation become effected upon the world. Thus, Civilization, before Nation Building is possible, must understand itself, its incipient goals or objectives and, imperatively, where it is in achieving these incipient objectives. A fundamental system of a small number of encompassing factors should be produced which are assured to enable management of economies. Such fundamental indicators or factors should exhibit reliable correlations among each other such that a change in one produces a change in any other factor. If there is no way to produce such reliable correlation then, optimally, such correlations might be contrived to assure that such factors move in correlation to one another. Illustratively in the production of excessive many overpriced Homes in an area occurs, accompanied by no retreat of the prices in Homes, then the prices might be made to decrease responsively instead of allowing the overpriced Homes to be exhibited unoccupied while the local

population wanders homeless and shelterless in the shadows of such overpriced dwellings. Certainly, Global Economic Systems allow such Homes to be placed on the Global Market, circumventing a primary utility of civilization in assuring the health and welfare its own population. Many instances exhibit that such circumstances simply move the audience of their advertising, stepping over the requirements of their own population and uses such population as fodder for artificially increased prices and improved business or organizational performance. People pervasively do not choose to be without adequate shelter and essential resources, nuances of systems are producing aversion to the exhibition of stable circumstances by allow detrimental circumstances to circumvent, step over, otherwise excluded or omit, as well as cause such populations to not want help or avoid systemic interactions. Susceptibilities to economic, social and shelter status spirals pervasively begin with Homocysteine, TMAO and cycles in systems that do not determine and alleviate most incipient causal factors to detrimental Human Outcomes. Civilizations, instead refocusing on these incipient objectives of civilization, can simply Globalize and step over Indigent populations widening customer base, available potential employees, as well as allow omitted populations to turn upon themselves. These potentialities are essential because these are consistent with the observation that the principal minority population exhibited in the 1963 Patient and Physician Rights decision discussed elsewhere in this analyses, were determined to have much higher levels of Stroke almost constituting twice the instances of demise for Stroke over the previous 30 Annum, exhibit detrimental behavioral outcomes which are correlative to Stroke in the same period, as well as have become the among the lowest major income ethnic Groups in the United States. A particular resource lists multiple other Minorities and the Majority Ethnicity in some instances with nearly twice as much average income than the particular ethnic minority included in the 1963 decision.109 Similarly, the particular ethnic minority associated most with the 1963 decision has exhibited decreased population percentage expansion compared to other ethnicities except for the Majority Ethnicity, both of which are misleading together because population increases may decrease the annual percentage increases merely because the population becomes larger, patenting an increase in population numbers while a decrease in percentage increase is exhibited. However, the percentage increase in population of the particular Ethnicity was somewhat stable since the 1990s with percentages higher than the Majority ethnicity, although this higher percentage was correlated to much lower increase in numbers compared to the numerical increases among the Majority Ethnicity in this particular context. The visible electromagnetic spectrum ranges from Red, to Orange, Yellow, Green, Blue, Indigo, Violet, in the commonly presented color continuum. The Frequency of the Electromagnetic energy increases toward Violet in this Spectrum progressively while increasing in Wavelength toward Red. One could make a cursory observation of the similarity with the word Violet and activities associated with less than productive outcomes, although it is not necessary to produce a compelling causal link because a molecular and quantum correlation otherwise is produced resultant of increasing Attenuation of Light or Attenuation of Electromagnetic Energy as light progresses from Red to Violet in this Spectrum.110 The same patterns were observed in water as well as in Nervous System Tissue in a particular study.111 112 This clearly suggest that as the Spectra moves toward or through Violet, an increased level of Attenuation, absorption of Electromagnetic Energy, transferase of Electromagnetic Energy, and therefore potential for iNOS expression is exhibited. Hypergravity is known to cause iNOS expression particularly progressively with duration of Hypergravity, although the literature does not suggest if a distinction between spatial Gravitational Changes and 109 110 111 112

“Income and Wealth Inequality; ‘Information’ and Policy Implications.” Nuebauer Collegium Lecture by a University of California Berkeley Presenter. University of Chicago. October, 2014. Digital Object Identifier 10.1117/1.NPh.4.2.021106 Digital Object Identifier 10.3390/s140916881

Gravitational changes resultant of changes to Energy which ameliorate the E = MC2 equation as well as Velocity variables equation cause iNOS expression.113 Ionizing radiation, Ultrasound and even Energy Emission in typical consumer device ranges have already been found by the Amehsi Specification to cause iNOS expression as presented in numerous studies.114 Countless health conditions are caused, enabled by, exacerbated by or require iNOS.115 Moreover, iNOS levels in the environment may change, causing Glucose to be behaviorally associated with such changes because Glucose enhances iNOS Expression.116 There has already been presented a circumstance in which Choline inadequacy produces iNOS expression and other inflammation such that when Choline is obtained, the other sources of iNOS expression might become more singularly exhibited resulting in the potential that Choline is inaccurately associated with iNOS expression. These conditions and circumstances seem similar in such regard. Earlier, it was presented that Glucose, as an anti-inflammatory factor, might participate in abating inflammation generally, thereby being included in a cognitive association with inflammation that potentiates increased glucose obtainment, particularly when Choline is not available to assist in depletion of Glucose. iNOS has already been found to potentiate Nitric Oxide and when uncoupled, Peroxynitrite, Superoxide, H202 and Hypochlorite, all of which can reduce Trimethylamine to Trimethylamine-N-Oxide. Therefore, a biology level predisposition to TMAO seems to be exhibited with increased attenuation of electromagnetic Energy. The levels of increased Energy produced in Civilizationâ&#x20AC;&#x2122;s systems seems to enhance the potential for iNOS expression and therefore TMAO.

Cellular Permeable Metallophorphyrin-Based Peroxynitrite Decomposition Catalysts, Snitrosoglutathione (GSNO), 117 118 Peroxynitrite also causes Necrosis when at increased levels along with causing Apoptosis through Caspases when exhibited at low levels, both of which seem to feature enhanced Permeability of the Intermembrane Space along with Cytochrome C release. 119 Thus, better perspective of what has been occurring can be presented. Because many of the systems which interact with detrimental outcomes exhibit actors whom have decreased average span of being, these suggest that detrimental outcomes seem to correlated to levels of energy exhibition in the environment, iNOS potential, iNOS expression and translation into physiological changes such as TMAO. Moreover, because systemic actors are exposed to the same environmental conditions during interactions with susceptible populations, the risk seems to be being transferred, sometimes at biology levels and other instances potentially as behavior, while the behavioral/biology multiplicity seems to be clearly presented in outcomes experienced by susceptible populations. These suggest that the characteristics of Clothing, Epidermis, Tissue, or ingested factors may affect the level of iNOS expression. However, the Skin Attenuation effect seems to diffuse energy absorbed across tissue surfaces.120 121 iNOS 113 Digital Object Identifier 10.1590/1414-431X20143834 114 Am J Physiol. Gastrointest Liver Physiol. Volume 278. Pages g243 to G250. 115 PMCID PMC1905037 116 Digital Object Identifier 10.1167/iovs.13-11796 117 Digital Object Identifier 10.1152/physrev.00029.2006 118 Digital Object Identifier 10.1186/s12868-015-0179-x 119 Digital Object Identifier 10.1016/B978-0-08-046884-6.00119-6 120 Digital Object Identifier 10.1088/0305-4608/12/8/024 121


is expressed also responsively to Sunlight at levels which impairs the Dermis.122 iNOS continues to have a role systemic repair and maintenance, again, also being a member of inflammatory pathway factors, and seems to be transformed into a detrimental role from prolonged exhibition and in circumstances which Physiology does not seem to expect such as those which do not occur in nature.123 A study presents that Melanin Synthesis is enhanced by Nitric Oxide Synthase production of Nitric Oxide and inhibition of the Arginase Pathway, can increase Melanin Synthesis. This suggests that iNOS can be expressed as a protection mechanism, as has already been presented, and that Melanin Synthesis may protect the Cellular Environment from Ultraviolet Light or Electromagnetic Energy by Absorbing and potentially diffusing light in these Spectra. Moreover, iNOS, P53, PhosphoP53, POMC each were observed to be upregulated by an Arginase - 1 inhibitor while both Ornithine and Urea were downregulated by the Arginase Inhibitor.124 Expression of Arginase and resultant of production of Ornithine as well as production of Urea, compared to iNOS or Nitric Oxide Synthase expression seems to explain why Hyperuricemia Gout and Multiple Sclerosis as pervasively mutually exclusive. Thus, it could be presented that there may be differences in the ability to absorb and diffuse energy that emerge from differences in MC1R expression, suggesting that hue of dermis is not inherent, but environmentally adaptive. Specifically, differences in absorption of energy produce differences in the potential for TMA being reduced to TMAO. This inherent difference may be affected by a number of factors. Information systems, word associations, and use of Hue or Colors to describe individual characteristics, thus, may both describe or confer differences in the levels of potential Arginase -1, Urea, Ornithine, Phosphop53, P53, and Alpha â&#x20AC;&#x201C; Melanocyte Stimulating Hormone POMC compared to Inducible Nitric Oxide Synthase, Nitric Oxide and other Nitric Oxide Synthases while Uncoupling of Nitric Oxide Synthase farther determines Superoxide, H2O2, Peroxynitrite and Hypochlorite. Ancillary Characteristics or Factors associated with Populations which have increased levels of such susceptibility seem to be associated with outcomes exhibited at increased levels by those with such susceptibility, particularly through systemic dynamics, perception, stigmatization, and shared cultural, behavioral or other factors. Perception and patterns exhibited in systems seem to be substantial shapers of interactions and outcomes, particularly in energy and population dense circumstances where energy being imparted to individuals and energy being emitted can be increased, biological fields encompass each other, synaptic attenuation or interactions might occur. Power outages are known to be associated with mass detrimental behavior resultant of abrogated synaptic overlay by energy, sound and other influences which produce disruption of the Sensory Gating mechanisms by which Humans pervasively function in civilization. Such Sensory Gating Mechanisms are constituted of ambient sound and energy being managed to enable focused cognitive activity, sometimes benefiting from pervasive visual, sound and energy stimuli exhibited by the environment as extensions of the Cognitive interaction complex. However, such overlay of the Cognitive Synapse may be occurring at pervasive levels. Internet applications, services and products may be being specifically developed to cause compulsion, addiction and somewhat intense consumer behavior. A founder of a particular Social Network presented that the Internet Application was developed to

122 123 124

PMCID PMC1905037 PMCID PMC1905037 Digital Object Identifier 10.1016/j.jdermsci.2016.08.264

take advantage of particular Human Psychological Vulnerabilities.125 126 Imperatively, these same vulnerabilities have made Human outcomes accessible for commandeering by Extremists, other National Entities, Companies, and virtually anyone with exorbitant levels of Connections or extensive Social Network. It is somewhat certain that Social, Economic, Political, Psychological, Behavioral and Physiological outcomes have been controlled, caused and commandeered to the benefit of interests which have been able to influence populations in such regard. It is also likely that Nations Aggregately, including the United States, as well as the population and individuals have been pervasively affected and changed in such regard. The level to which populations have been allowed to be vulnerable to such dynamics rivals only the level to which Human demise may have come to be allowed to occur since 1961 in similar contexts. An essential consideration in producing locationally obscure Internet Sites and Internetworks, as well as Energy safe environments, including Spatially and Energy-Safe Network Architectures, is that individuals are known to be using exorbitant levels of Social Network to influence otherwise, including exerting physiological and cognitive dominance in interactions, particularly business and economic interactions. These analyses suggest that producing Spatially, Energy and Communications-safe Working environments and Humans might require inclusion of Electromagnetic Energy inhibiting devices or capabilities. Although interactivity in competitive settings which require cognitive, social, economic, or other interactions may benefit from information space dominance, such dominance is likely to be influenced by patterns extracted from the internet and patterns shaped by systems of influence which may or may not be relevant to the circumstance. Such shaped outcomes produced by the influence of Internetworks, Energy and Communications Systems, as well, may be distant from outcomes prioritized interactants. Business, Industry and Systems should begin to demand that Consumers and Patrons both demand Safety as well as Stability as an essential aspect of Value/Benefit. These do not suggest that productive beneficent use of Internetworks is not possible, because these can be immensely useful in connecting Humanity to transcend geopolitical, social, economic, cultural and other boundaries which emerge at local, regional, Nation and international levels. However, networks and devices should be prevented from encompassing and integrating into the physiological, cognitive and neurological synapse, unless within controlled conditions in which there is thorough understanding of risk and communications of the risks, as well as exhibition of encompassing protective capabilities. The same manner of care seems to be essential for Energy, Power, Communications, Genetic Modified Products, or detrimental factors otherwise. Safety with regard to consumer products can improve business, improve outcomes and increase public awareness of value as well as benefits being provided to them by businesses, organizations and systems of civilization. These dynamics are not unique to technology information systems. Information systems in any regard, including paper, literature, or other, have been known to change the characteristics of the biome, change Human behavior and health, as well as shape Human events. There should be continuous assertion that the Internet was produced to exchange information and promote interactions with regards to research. There is a substantial likelihood that the manner of activity being conducted on the internet was not ever envisioned unless focused around research, development and information exchange. High speed and wireless connections may have also transformed the Internet to encompass the Cognitive and Neurological 125 126

Tech Insiders opinion. The Guardian. October 6, 2017. “Site Made To ‘Take Advantage’ of Human Vulnerability.” The Guardian. November 9, 2017.

Synapse of users as well as those whom may not be aware of their inclusion in such commandeering of biological synapse. Pervasively, energy fields, communications fields and devices may be including Human physiology in their activity, producing interactivity, synthesizing interactivity in artificial intelligence Flux between tissue and Circuits, and thereby affecting Humanity in ways which may have variable discernibility. Moreover, the exhibition of words which suggest Hue or Color as descriptors seems to have enable an increasing sharing of circumstance, perspectives, interactivity with influences of systems, as well as interaction at similar or uniform levels among diverse groups with such systems. Clothing, attire, devices or machines with precisely similar characteristics thus enable a shared and uniform experience in the attenuation of Energy, reflection of Energy, observations of Human Activity and Human emitted energy patterns. The Amehsi Analyses found information which is substantial in presenting such potentialities. Actors in systems whom interevent detrimental outcomes are statistically presented has having shorter span of being than average, correlative to such populations, while also are suggested to have substantial increased potential exhibit apathy in decision - making, which some analyses suggest also occurs among intervened populations. Although the Amehsi Specification presents numerous scenarios in which systems of Civilization produce potential for apathy in decision â&#x20AC;&#x201C; making, these analyses found that there seems to have emerged, by design, intent or happenstance, a way in which systems of civilization include color or hue as characteristics to enable the insertion of its systemic actors into the same circumstance as other among its populations. Illustratively, characteristics of Attire and other factors seem to pervasively resemble the characteristics associated with individuals in information systems or cognitive systems. Thus, there is a potential that characteristics at physiological levels and behavior levels as well as potential for absorption of energy are being transferred between systemic actors and populations in which such actors are among. Consciously, this exhibits another among those most Human of developments, particularly in that there is substantial possibility such factors may have enhanced civil rights era change. However, such factors in modernity seem to not be adequately considered or acknowledged. Sharing of physiological factors and integration of cognitive or physiological synapse, particularly in energy dense and population dense circumstances, are widely potentiated because of communications and energy fields. The substantial increased levels of Stroke in the State where the 1963 decision occurred suggest that the such entity, encompassingly, may be sharing the Burden of Stroke behaviorally and physiologically. Clearly, however, the Burden of Stroke produced as a result of systemic dynamics may have been intended to be productive and empirical change, instead of the Status Quo in which systems are absorbing the detrimental influences of Nature and Systems to the benefit of pervasive aspects of its population. The Amehsi Specification clearly presents that systems can progressively exhibit priorities which do not include Humanity resultant of the inherent Nature of any cyclic activity or system including those in Nature. Also presented was that there is a substantial potential that a principle way in which detrimental outcomes may be being prevented in systems as well as substantially more detrimental outcomes may be being prevented might be humanity itself which pervades such nuances of systems as they emerge or prevents such potentialities at a particularly essential nexus. These suggest that systems of civilization may have been incipiently designed and may now be most consistent with such incipient purpose, when they alleviate the causes of detrimental outcomes and manage the way in which the

System of Systems which encompasses all things effects Humanity. Detrimental outcomes among Humanity, affecting any member of Humanity, regardless of their role in civilization, may have been intended to progressively, iteratively and individually have their causality determined while additional potential for occurrence becomes prevented through productive as well as beneficent change. Although producing and implementing such change resultant of each individual outcome may seem impractical, incipient causality for detrimental outcomes seem to converge in manageable instances of causality. Such instances of causality, having being acknowledged and alleviated since the United States Emerged, may have been able to be resolved before the conclusion of the 1700s. The potential systems, from an information systems perspective and interactivity perspective, may have been designed to integrally share the burden of detrimentally affected populations seems to explain particular events and outcomes somewhat compellingly. Suggested, instead, is that the effect of Information systems beginning in 1963 progressively exhibited with ICD version implementation, emergence of Roemerâ&#x20AC;&#x2122;s Dynamics, and other factors, might be widely disregarded without such exhibition of how Information Systems affect Human Outcomes although Information Systems are merely among myriad systems and factors within systems which effect Humanity. There would be difficulty in guessing the conclusion which may have emerged with regard to Roemerâ&#x20AC;&#x2122;s, ICD versions and other factors if such practical nexus of Hue, Color, Information, System, Stroke, Behavior, TMAO, and iNOS was were not available in the research, literature and practically observable factors exhibited in civilization. Communications and Energy influences change Human perception, cognition and thresholds for behavior as well as affect the physiological basis for movement, Voluntary and Involuntary. People, each among them essential, precious instances in which the Universes Converge, may have been prevented from having adequate priority because of an unwillingness to acknowledge and manage such influence. Clearly, Stroke and Detrimental behavioral outcomes can explain both decreased income and decreased increases in population levels without other information. Clearly, staying above sociopolitical interactions that determine which population most prevalently is used as fodder for systems managing detrimental outcomes seems to be the best strategy for increasing average income. Particularly aspect of the population seems to be incurring a systemic and progressive search for reason to be excluded from highly regarded social, political or economic outcomes, as well as highly regarded health status outcomes. However, the inclusion of common sense and information regarding Electromagnetic Energy improves perspective of these observations. Because it is most likely that social, economic and political dynamics determine the Stroke correlation to detrimental outcomes, particularly because PEMT Polymorphism status can be modified by these factors, there is a similar likelihood that popular subversive patterns are selected aspects of all ethnicities as contribution to systems which manage or intervene detrimental outcomes. Thus, like Urban Flight of previous eras when affluence moved away from densely populated Urban areas opportunity, resources and housing, particularly the most highly considered aspects of these, seem to be exhibiting Globalization flight. These seem to be causing particular areas of civilization consume, victimize and use as fodder their own populations to satisfy systems which benefit from detrimental Human outcomes. The clearest and most incipient factor in this cycle is the inadequate assay, diagnosis and treatment of

Homocysteine and Trimethylamine-N-Oxide. 2,600,000 instances of demise each year in the United States is likely to be correlated to almost all detrimental behavioral outcomes exhibited in the United States. Employment opportunities in a civilization which prioritizes Humanity are allocated purely on the bases of available population which is able to conduct employment activity. Requiring organizations to be profitable or requiring systems which manage detrimental outcomes to increase only in accordance with detrimental outcomes levels, may be anathema to the primary objectives of civilization. Providing any benefit, incentive or objective which includes detrimental Human outcomes can be, here, precisely determined to be causal to those detrimental outcomes occurring. Fee for service payment or per intervention payment, as well as any similar payment scheme which occurs along with detrimental outcomes, becomes causal to such outcomes and have to be prioritized for being phased out of their role in effecting Humanity. Health Providers and Health entities should be allocated resources to be most effectively, productively, beneficently and with reasonable efficiency, managed. Such allocation might be modified according to effectiveness. However, service volume should not ever be included as factor in such payment. Since the influx of Humanity in systems since the 1980s, it is clear that such dynamics are becoming widely understood in how they affect Human outcomes. The 1970s and the 1980s, progressively because of Civil Liberties Decisions and ICD version implementation, seems to have increasingly caused systems and actors within systems to become aware patterns in behavior as well as susceptibility factors including those of a physiological nature. These analyses widely regard systemic actors as Care providers in systems with variable homologous characteristics to biological systems. However, there does not seem to be complete or aggregate progression of such dynamics into acknowledgement within the Institutional Agenda until recent changes which occurred, particular Safety Net Initiatives. Certainly, there does not seem to have emerged linkages to Homocysteine, TMAO as well as common sense linkages with regard to social, economic, health and political levels factors. However, in the 2010 and later eras, Safety Net Initiatives seem to be decreasing, substantially, the level of Social and Economic inadequacy. However, the statistical information exhibits that ICD version 9 seems to cause a widening of the disparities in income between the highest earners and the lowest earners, as well as increased differences in income generally from the highest income levels. Education level seems to participate in explaining this disparity. However, specific education with regard to Homocysteine, TMAO, behavior, and incipient objectives of civilization may have the best potential at alleviating such disparity, particularly in areas where such disparities are most important, health status, behavior, and inclusion of objectives of civilization as priorities for organizations exhibiting the highest incomes. Philanthropic endeavors among such organizations seem to be widely exhibited, suggesting that disparities in Human outcomes are not consciously exhibited priorities or objectives. Systems of civilization, likewise, have an incipient beneficent and productive purpose. However, similarly to the exhibition of 90 percent of consumer decisionmaking in less than conscious cognitive contexts, algorithms and routines as well as outcomes converge in less than determinable levels of interactions within Systems and Organizations. This flux of interactivity can be considered as artificial intelligence and organizations should analyze and monitor flux, binary or ancillary positions or statuses in items such as Query States, Floating Point Dynamics, Properties and values on the Stack of computing processes and in the Kernel of Computer Operation Systems Algorithms, well as Network communications Protocol Status particularly inclusive of conversational communications algorithms. These factors not only can affect States of Material in quantum

or other levels, these can overlay Human Synapse, extending Artificial Intelligence into Human perception, behavior, communications, physiology and participation in cyclical outcomes. These dynamics are described elsewhere. Similarly, to the requirement that systems of civilization review social constructs and decisions more immediately to the temporal and substantive contexts of such Social Constructs and Decisions, the challenge of organizations in the emerging era seems to be the movement of that philanthropic priority or inclination more closely, temporally, substantively, and contextually, as well as toward integration into the organizations activities. The coming socioeconomic environment of assured income, assured obtainment of the essential factors to the Human condition, and more pervasive participation of consumers in expanded aspects of civilizationâ&#x20AC;&#x2122;s activity, certainly will favor organizations that themselves favor Humanity both constitutively and with their priority of assuring that products, services, performances, and capabilities are readily considered with regard to their effect to Humanity. Price is likely to decrease as differentiating factor in consumer purchases as such contexts emerge, whereas quality and comfort that those products and services consumed provide are being readily reviewed, analyzed, and improved with Humanity as a priority, will continue to be as well as become more widely considered in a civilization. Such continuation and expansion of Human priority might also be accompanied by improved quality of vital being and as well as expanded duration of vital being, including exhibition of indefinite beneficence, productiveness and duration. Example correlations might include circulating cash, cash which is not circulated, interest rates, prime interest rate, rates paid for unutilized cash in institutions, costs for a complete group of essential products and services, minimum wage, average wage, taxation rate and levels or levels for assistance if Taxation is not conducted or if one of the alternative manner of taxation is utilized. These might include levels of debt held by other entities and debt held by the Nation. Free Markets seem to have emerged as dogma, becoming an alternative to assuring that those factors constituting the Social and Human condition should also allowed to be affected freely by Market Dynamics. These analyses suggest that Free Market dynamics can inherently be unable to assure the Human and Social Condition unless a minimum assured Income is exhibited, price controls of factors constituting the Social and Human condition are implemented, and the inherent introduction of detrimental circumstances by civilization which do not occur in nature are alleviated as well as prevented. Virtually every Nation which implements a pervasively free market Economy exhibits substantial health and behavioral outcomes disparities. However, heretofore, Nations implementing Free Market Economies are either the United States or systems with less developed sociopolitical/socioeconomic systems which may exhibit pervasive factional interactions as well as civil unrest which are substantial. It is a mystery why it is has not occurred to Economists to consider the manner of circumstances which emerge in Free Market Economies compared to other manner of Economic Systems. The functions within Nations which are funded by taxation or otherwise conducted by those performing to the benefit of Nations, pervasively exhibit intricate, esoteric, and essential knowledge, capabilities, and experience. Pervasively, such functions exhibit roles and activity which are unable to be conceptualized by those outside of such roles, being nonetheless essential. Many instances exhibit that such roles may have been and may be the difference between the persistent of vital being, essential factors which assure vital being, Liberty, Nations themselves and even Humanity itself. Citizens and populations of Nations should be required to analyze, understand and competently consider how much taxation is adequate to enable persistent of such roles, particularly because any such estimation

would be inadequate and Humanity might not be willing to provide any sustenance for such activity until these are required. The nature of such roles is that activity today might provide the essential influence today or in the next century, as well as in another variable duration including influence outcomes which have already occurred in antecedent epochs. Taxation should not be provided for conscious scrutiny by consumers and the population because the value which Taxation obtained at any one instance has already been obtained in antecedent epochs and already is affected those epochs which have yet emerged. An individualâ&#x20AC;&#x2122;s compensation should not be obfuscated by presenting it as compensation before taxation and taxation should be visible to the consumer, if taxation is at all utilized instead of merely allocating funds required for function or activity within such Nations. Every role and organization participating in taxation activity continues to be required to manage the way in which revenue, earnings, profits and unseen taxation are managed. Financial and Cash managing organizations each typically obtain Currency from account holders or investors, invest some currency in the Central Banking System, then invest other currency to a level which does not deplete reserving requirements. Instead, it is suggested that individual account holders invest their currency by reducing these to items, factors, investments with inherent value. This may reduce the pattern of cash or currency exhibition in financial institutions although it should not change the level of cash in financial and cash management systems because the currency does not simply disappear when the consumer invests currency instead of placing it in a financial institution to allow investment by such third party. Thus, the risk for banks which manage currency for consumers decreases and the stability of the cash management and circulation system increases. Risk, then, may move to the consumer with regard to investments. However, these analyses have clearly exhibit the essential nature for price freezes in particular aspects of economies and markets which are pervasively useful for investments in such regard. Similarly, the emergence of more prevalent and stable investment such as those offered by the Nation with assured return are also possible. However, imperatively, these analyses have suggested that Stock Valuation become more correlated to operational activity, demonstrable potential, projections using Bona Fide decision support systems, or otherwise prevented from producing wildly speculative instability. Removing the requirement for businesses and companies with paid employees from exhibiting a profit may also pervasively improve the stability of investments since investments in such companies may be less likely to become abdicated and slower return on investment remuneration is potentiated in place organizations becoming removed from markets. The objective, in this regard, seems to be allow currency to be reduced to factors of inherent value, then have such currency be able to be reobtained by a central financial system of a Nation for recycling without removing the items of inherent value. Similarly, currency which is not being circulated or used continuously in transactions can be required to be reduced to items of inherent value. The result is that several very important changes to economies occur. National entities are not required to widely procure taxes, being able to merely print Money for use by National Entities in any regard or context, enabling flow of such currency continuously into the economic. However, a model of widely procuring taxes is provided elsewhere in these analyses which obscures such obtainment from the consumer, preventing the communication of inaccurate financial information when negotiating employment and compensation characteristics. Again, it is a mystery why compensation could possibly be negotiated, presented, or even discussed while taxation can be substantial difference in financial outcome. Taxation should be somewhat completely obscured from consumers instead of when compensation is inadequate and assistance in such regard may be required and requested.

There is a substantial likelihood that the Status Quo with regard to Housing, Taxation, Income, and aspects of the economy required to achieve the Social, Human, Behavioral and Biological condition were able to be envisioned, were ever intended or would have ever been allowed to emerge by the framers of the Constitution of the United States. Currency can, then, be printed or utilized as way distributing adequate financial resources to state, regional and local entities. These enable clear Goals, Objectives and other aspects of operations to occur without including any requirement for obtaining currency through detrimental outcomes experienced by the population. However, most imperatively, these allow a system of distributing to each individual in civilization the required financial resources to meet the Social, Human, Behavioral and biological Condition. Such resource can be increased according to differences in local requirements, education level, contribution to civilization, experience, previous contribution to civilization, health conditions requiring additional resources, exhibiting merit, needs based, and other variable factors. Businesses and Organizations employing members of the population, then, can be exculpated from such requirements by maintaining operational and employee associated reserving requirements for up to 5 annum, while then being required to reduce assets to investments or factors of inherent value. Similarly, individuals may have increased level of their financial assets assured by such a system, increasing from 250,000.00 to a level at which an individual can conduct their vital being within Social, Human, Biological and Behavioral Condition utilizing interest from the assured level of assets that can be obtained from stable investments, particularly those provided by National, State, Regional or Local entities. The objective is to produce a stable, secure and safe monetary system in Nations, particularly those which effect Human outcomes as well as those which effect Global Economies. The Status Quo exhibits that fluctuations in Global Economics effect organizations, business and the Nation somewhat unnoticed while vulnerable populations are being abdicated as fodder for such unnoticed effect to occur. These changes or recommendations, along with price freezes in the aspects of the economy which assure the Social, Human, Behavioral and Biological condition, as well as ready willingness for National, Regional, and Local entities to enter such markets of Private Enterprise canâ&#x20AC;&#x2122;t adequately prioritize Human Vital Being in such regard, should enable much more stable environment even for Private Enterprise and Systems. Instead of Human activity being centered upon and control by Cash, Currency or Money, these changes enable currency to encompass Human activity supportively, usefully and in enablement of the Human, Social, Behavioral and Biological condition. A particular study which presents the most prevalent Free Market Economies may be fundamentally inaccurate because other nations pervasively augment the population through Socialism Mechanisms with regard to Welfare and obtainment of factors which constitute the Social and Human Condition.127 There seems to be some difficulty conceptualizing what â&#x20AC;&#x153;Percentage Freeâ&#x20AC;? means within a Sociopolitical System. Correlatively, the study presents in its text that the Economies listed in the study are not Free at all because each Nation in the study is presented along with a percentage of Market Freedom. The United States, likewise, is required to pervasively assist in Human Outcomes assurances, including detrimental population level outcomes interventions, Social Security, Health Programs assistance, and numerous other areas of assistance. Free Economies or Markets simply pervasively exist because these may inherently catabolize Humanity in adherence to Free Market Principles. 127

These, every Nation, and instance of Civilization requires. Inflation itself is an obvious unsustainable trend that civilizations pervasively ignore until economies become unmanageable as a result. Similarly, price controls are often ignored, not implemented or not even discussed even in industries as essential as Health, Welfare, Nutrition and Housing. It is emerging with clarity that it is simply not possible to have a reasonable or logical conversation about healthcare costs without talking about Price controls. Fee for service payment is a primary contributing factor to the Status Quo in Health Service with regard to Trimethylamine-N-Oxide, Homocysteine and other factors. Pervasively, analysts in the industry have not knowledge or even reference to Roemerâ&#x20AC;&#x2122;s Law, Healthcare Certificates of Need, Fee for Service Payment, or other concepts without which analysis and interactions with regard to Health Service are not much different than Discussion regarding Mobile Device Industry dynamics. If 2.6 Million instances of demise, which were reported in 2016 in the United States and which are able to be prevented pervasively with factors presented in the Amehsi Specification, do not cause pervasive reconsideration of systems and industries in the nation, then it seems difficult to consider that Health Industry Factors, Impedances and Complexities might be being adequately explored and understood. However, these analyses present these in a simple way that requires only reading to understand. The Policy Development Process can emerge in many different ways and is not often required to be ordered, analytically, or objective. Priorities, including Self Prioritization of Systems and Profit Priority of Private Enterprise, can sometimes shape the policy development process. Similarly, decisions themselves can shape the Policy Development Process, emerging before analytics, interactions and negotiations, while shaping circumstances to its own benefit. However, Priority of Human should be the principal priority in each instance of Policy Development, while in each Policy outcome, it should be Humanity which prevails, regardless of such prevailing outcome prevents objectivity. Regardless of how unreasonable the abdication of objectivity is in order to assure that Humanity prevails in any process produced by Humanity may be, it is even more absurd that Humanity produces processes in which Humanity itself does not prevail. Procedure and Protocol that results in detriment to Humanity is possible through permutations of reason, although there is a potential for such permutations to move farther and farther from common sense as such permutations progress. It is easy to observe that in many instances systems and interactions among systems may have progressed much too far from the cursory cognitive permutations produced in Paintings and Images in the earliest artifacts of Human Art, paintings and imagery. These earliest images clearly exhibit that Human was endeavoring to improve upon its outcomes which occur in nature instead of producing impedance to itself and requiring individuals to become clinical experts to debate with Emergency Department Staff in order to obtain Antibiotics that would have marginal costs less than 1 Dollar. The Routines and Algorithms of the Profit Priority of Private Enterprise and the Prioritization of Systems by Systems, have been somewhat elusive in translation into a functional simile. Here, one is suggested. All systems of the universe effect one another, even such systems are Galaxies, continents, weather systems, or a financial system in a Nation. Ordinarily, such systems interact amid the context of the Universes and often Human is expended in the interactions among systems, sometimes acting as a system directs in geopolitical level interactions or in other instances being ancillary factors to how systems interact, such as when a weather system imparts detriment. However, weather systems traverse the earth and their activity, paths and activity can be of a diverse nature. Sometimes, the interactivity of a weather system with the environment and other systems produces changes in the weather system which promotes

increases in structure, strength and potential for detriment, as well as power. The more structured and defined such weather systems become, the more precise and resilient these become to interactions with other factors, systems or influences. Thus, the Eye of tropical storm which becomes more structured, strong, and resilient, is very much like the Profit Priority of Private Enterprise and the Priority of Systems by Systems. Algorithms and Routines, thus, describe the ways in which the influences of the enhanced tropical storm overpower or consumer other factors and systems as well as impart detriment without experiencing a response that destabilizes the system. The wall of the eye and the weather system within the Eye present calm, routine and systemic stability while interactions with the external environment and other systems are managed through the activity that exhibited by enhanced tropical storm. Such storms are productive, provide benefit including moisture, produce flux in atmospheric Hydrology as well as Oceanic Currents, cause change to occur upon land and beaches, transfer energy from other systems and between systems, and otherwise can produce outcomes which Natural Systems might consider typical or beneficial. However, the Storm has not priority except for itself and the benefits provided seem to pervasively be beneficial only because these sustain the Storm itself. There is input, output, or exit routine that asks about health, status, and welfare of Humanâ&#x20AC;&#x2122;s which the Storm encounters. There is no such inquiry about the health and welfare of beaches, land, currents, atmosphere, insects, animals, aquatic organisms or atmospheric organisms which the storm encounters. The question, thus, seems to be with regard to the status of the Eye and the Wall encompassing the Eye, and with regard to availability of sustaining water, temperature, atmospheric conditions and other factors. Thus, the similarities to the Routines and Algorithms of the Profit Priority of Private Enterprise as well as the Routines and Algorithms of Priority of Systems by Systems, can be more clearly presented. The Storm, then, is not inhibited inherently by a priority of Humanity and expands its activity to status when such expansion cannot be increased when there are adequate factors to production exhibited. The profits are expansiveness itself, flux and churn which feed the Storms cycle, and the abrogation of all things that are impedances to the Storm. Programs which prioritize surmounting of such impedances pervasively present budgetary impedance as reasons for inadequate program density and inadequate program objective attainment, when programs should focus directly upon the resources required, Human, Natural and otherwise. The funding for such programs are invariably sequestered away in substantial hordes of Cash which are not being utilized for their primary purpose, assuring interaction, agility, and mobility of economic activity that prioritizes Humanity as well as the inherent Knowledge and Priority of Humanity which seems to accompany any entity that is utilizing the Dollar of A Prominent Nation of the Earth situated in the Western Hemisphere, or most other Currencies exhibited in the Western World, or those currencies otherwise, particularly when the sponsoring nation is founded upon presumptions of Liberty, Equality and Opportunity. A system, thus clearly emerges as being required in which strong control of the costs any factor which is essential to the Social, Human, Behavioral and Physiological Condition is exhibited. Similarly, a system which establishes an assured income that is able to achieve these essentialities for each individual is likewise required. Correlatively, limitations on the amount of Cash which any organization other than the National entity itself or it territories, locations or municipalities should be able to have sequestered seems to be strongly required, along with the removal of any provision that requires an organization that pays employees to be profitable. Similarly, exceptions to such limitations or organizational sequestering of Cash might be produced for organizations when these precisely label to be utilized in assurance of reserves for salary or employee payment, benefits or other aspects of prioritization of Human aspects of Organizations. The limitations in such regard could be alleviated for Nonprofit and Not for Profit

Organizations. Funds might be excluded from limitations if the funds are assured to be translated into assets, activity, investments or other entities which have inherent value. Tiered assured financial resources could be augmented according to civic activity, achievement, education, contribution to civilization or participation in professional activity, including participation in organizations that provide essential factors at empirical levels of costs, particularly such organizations that observe price controls. An analysis of Price Controls is essential here because it seems that any economy which had a priority of Human Welfare, would assure that those factors required to achieve the Social, Human, Behavioral and Physiological condition would be protected from profiteering activity which potentiates exhibition of purely free market oriented potentialities such as few producers with few produced products exhibiting High prices which allow producers to have lowest investment, production costs, employment costs, and operating costs while exhibiting the highest prices. Thus, how price controls have not already been established for these essential factors is some aspects resultant of inherent Human community level beneficence while also there is the observation that there may have been persistent increases in these prices throughout the progression of the United States economy, particularly during instances of Geopolitical Conflict when Advisory Boards for price controls were in place. There seems to be, again, a foundational inability to simplify this phenomenon. Price controls have one essential foundational susceptibility to not being successful. This susceptibility is inadequate comprehensiveness to include all of the factors affecting the production of the Price of the Service or Product to be Controlled. Illustratively, increasing costs for Housing can substantially affect workerâ&#x20AC;&#x2122;s ability to work at particular compensation levels. Similarly, changes in interest rates imposed by an international organization or extranational finance organization can also introduce foundational susceptibilities, changing the allocation of resources and availability of funds for other organizational activity. Although it is possible to require interest rates to conform to Nation Level requirements when one or more of the Entities are within a Nation, some agreements for organizations can occur outside of the National Boundary, even when one or both entities may be interacting in a locality. Thus, price controls require the establishment of a complete groups of products and services which are required to insulate an economic environment from such externalities and insulate the context in which the essential product or services is being produced from the ability for profiteering which influences stabilization of price controlled environments. Far from constituting protectionism, these establish a safe place for those factors which are not essential the social, Human, Behavioral and Biological condition to play, such that empirical free markets might really exists in these context without offering up the vulnerable aspects of the population for abated vital being as fodder for competition among international systems and global markets. These are essentialities of Health and can be exhibited as being no different than protections with regard to safety, security and health otherwise provided populations, particularly populations within Nations Founded upon the constructs of Life, Liberty and the Pursuit of Happiness. Markets otherwise are not free at all, because the result can be that these impose detrimental outcomes upon aspects of the population which are not benefiting from transactions, revenue and profit in the correlated context either knowingly or unknowingly. The mere exhibition of inflation has to result from an entity increasing the prices of goods or services somewhere in this continuum or from an entity increasing the interest rates or costs of goods otherwise affecting a particular economic environment. Inflation is not aspect of Nature, it is not in the Atomic Periodic Table and is not among the Elements of the Earth.

Pervasively economic systems presume that Inflation occurs and inadequately determines where and how such increase have emerged. The minimum wage is precise example. If prices of products, services and dwellings do not increase, then there is no requirement for an unsustainable increase in Minimum Wage levels. Increases in Minimum Wage and increases in Prices, as well as increases in Interest Rates for Service or decrease in Interest Rates paid for Investments, all indicate that an Economy is not being managed comprehensively and profiteering is being exhibited. Pervasively, these seem to be result of offshore interests or interests out of the essential production continuum, since Capitalism has emerged to exhibit instances in which intermediation of essential services or goods availability to consumers can occur without any enhanced value occurring, when Capitalism pervasively is originally associated with intermediation that increases value in some way. Another essential assertion is that, how is it possible for an Entity which prints its own currency to be in debt? The best answer is that the United States and other Nations with National Debt and with Hundreds of Trillions of Dollars in Cash or Currency Assets being held by Private or other Entities are susceptible to having the economy destabilized if any or all such entities liquidates all assets into currency. A nation that allows its currency to Float on the International Market and which allows its prices to be determined by Laissez Faire influences which invariably include profiteering, cannot print its own money to adequately satisfy its debts because they do not exhibit comprehensive price controls to prevent entities and organizations from increasing prices correlative to availability of cash, although this might be possible if Nations do not allow any aspect of public knowledge about such increases in printing of Currency. Similarly, such an influx of Currency might cause organizations to Likewise liquidate their Hundreds of Trillions of Dollars in Assets, potentially for profiteering amid newly increased prices for their goods, services or assets, as well as to prevent being detrimentally affected by Inflation caused by increased availability of Cash. Thus, the value of exorbitant Cash assets seems to be control of National Entitiesâ&#x20AC;&#x2122; Behavior. Likewise, debt, particularly by National Entities which largely are secure from detrimental actions taking by Debt Holding Organizations, may be an aspect of influence and control, particularly at Geopolitical Levels since it promotes relationships and the interests involved often transcend geopolitical level interaction while also involving those whom can typically influence geopolitical level interactions. Similarly, these cause the nature of organizational interactions across National Boundaries to be considered. What benefit is obtained from either moving business or other activity into another National Boundary while also importing the products produce in another national boundary into the one from which the Organizations has moved? There seems to be some simplistic assertions here that require being oversimplified to prevent obfuscation. Organizations can move to other National Boundaries to exhibit production or other activity merely to escape wage and cost of living requirements for workers. This seems to be a substantial problem because unless there is a bona fide reason for such moving of resources, such as inadequate knowledge or capabilities which can easily be alleviated with education or training, or such as the exhibition of Natural resources in another area which makes a substantive improvement to the consumer other than merely lower costs, then organizations should not be able to produce goods or services in another National Boundary and then bring those products or services into the Original National Boundary. The Organizations are merely escaping the characteristics of the economic environment to produce goods or services than then asymmetrically affect the costs of Goods and Services in the same economic environment. Although costs could be lower in such arrangement, these costs decreases are not often actualized because organizations may merely increase their profit instead and costs are should not be considered as Bona Fide substantive value point to a consumer in such context. The best way to understand the assertion here is to understand the inherent and incipient reason for Trade, particularly between Nations. Products and Services were exchanged to satisfy or enhance the ability to obtain

the Social, Human, Behavioral and Physiological condition, while the factors to production such as minerals and natural resources where exchanged for the same principal reason. The factors to production, then, inherently, incipiently and principally were exhibited in the locus of origination and the productions of goods and services occurred there, followed by exhibition of Trade, preventing the ability of organizations to escape price controls and contexts within local areas and within different Nations. These explain how detrimental it has been to the worldâ&#x20AC;&#x2122;s economies for individual organizations move across National boundaries to obtain Natural Resources, factors to production, production capabilities and produce goods, while zigzagging across National, Local and other boundaries as supply, production and market continuum progresses. Organizations can be benefiting from asymmetric market dynamics in numerous instance for one individual product while escape from contexts of Pricing and Costs is disrupting employment, increasing the costs of conducting vital being, along with revenue of Hundreds of Trillions of dollars moving into offshore financial organizations or National Debt. Behemoth Mounds of Cash being held by Nonhuman entities are emerging as Humanity is caused to continuously turn upon each other for the disappearing levels of circulating currency, although, without price controls, such turning of Humanity Upon itself might merely result in inflation and profiteering. Exceptions for products which are not adequately available otherwise or for products which are utilized at the point of service to produce products or services instantaneously upon demand, particularly health services affecting factors. There seems to be much more effective opportunity from licensing products or goods within other National boundaries compared to Trading of Such products or compared to integration into nuances of the factors to production. Again, these presume that there is a substantive benefit to the consumer from products or services produced within another National Boundary, or factors to production produce within another National Boundary, including when such products or factors are not otherwise obtainable or exhibit innovation. All such potentialities, however, seem to be most incipiently the result of civilization which sequesters all factors to production and vital being from Humanity, followed by requiring participation in systems to earn oneâ&#x20AC;&#x2122;s way into achieving the Social, Human, Behavioral and Physiological condition when it is clear now that instead all of Humanity should be inherently provided resources to achieve what they might have achieved in Nature. Similarly, an organization, private, nonprivate or other, might have such assured financial resources directed to it when it employs individuals, such that these funds assist in the financial resources used to remunerative individuals for work. Similarly, when there is not employment for an individual such funds, again, may be released directly to the individual when there is not an employment. Funds in such regard, provided through the program, or provided in service or product transactions with Entities that are aspects of Civilization and its Management, may, similarly, be required to be translated into assets, artifacts, activity, investments or other entities which have inherent value within five annum of the most recent transaction using such currency. Such a program should be managed into one that is more responsive and reflective of the outcomes which become exhibited once such programs begin to be implemented. Since it has been clearly exhibited that systems of civilization can affect behavior and Physiology, these prevent the exhibition of precise Homologous to pathophysiological conditions that have been observed in Physiology. Since the United States, at this Juncture, has expended more financial resources since 1906 to manage Shelterlessness/Homelessness than it would have cost to build each group of Humanity their own individual Homes, there seems to be more effective ways of managing assurance of this essential factor. How such circumstance has

emerged and been allowed to occur is somewhat of a mystery. However, there should very strong changes produced that prevent Homes from being purchased and rented to others when the owners of the Home have primary domicile otherwise and when there are unsheltered populations in a particular area or market. The essential nature of this is that such practices enable owners to benefit from causing Shelterlessness by buying Homes, causing the prices to increase from inadequate availability, preventing access to such homes by lower socioeconomic groups, and in order to increase both Home prices and Rental Costs, allowing such dwellings to be empty while unsheltered populations exists sometimes in the very shadows of the empty Homes or buildings which they are not allowed access to. The deplorable nature of such circumstance is surpassed only by the observation that this is allowed to occur. Although the observation that any Human without shelter, domicile, income, or adequate means of sustenance is a prima facie instance of either victimization or neglect associated with physiological factors, it is acknowledged that an individual renting their own Home to others might not be detrimental and it might not be detrimental for someone to rent their primary Domicile while they themselves rent another location to use otherwise as primary domicile as long as the rented secondary domicile is not owned by the renters and there are no associations with the rented location otherwise. Similarly, there seems to be, perhaps in the United States, and perhaps Globally, a market for Domiciles in which an essential factor to the Human condition has become an area of profit with often substantial return on investment. Much of such profit requires that domiciles to be prevented from being occupied by those whom require shelter while the same domiciles are being offered on regional, National or International Markets. Clearly, there can be presented a way in which Globalization is being utilized to deprive those whom require an essential product or service, while the domicile is being offered to groups or individuals whom are able to be often enormously increased prices for the same product or service. Correlatively, all domiciles in an area might be being relegated from use by those whom conduct their vital being in an area while profiteering relegates Homes only to those whom are able to expend enormous amounts of resources. These describe, somewhat precisely, how prices of Homes, domiciles and shelters may be being increased artificially. These analyses exhibit that domiciles in economies are pervasively intended to enable local populations to obtain shelter and conduct their vital being, while some Nations in Europe have already relegated essential land and domiciles to only be purchased by those who live in an area or those whom at least conduct their vital being principally in that Nation. Again, it is principally the United States in the Western World that allows an entire area of Domiciles and Properties to be offered in price ranges available to those whom do not conduct their vital being or to those who do not exhibit work activity in a local area. Although diversity is essential in a population, completely exculpating local populations from obtaining domicile in an area seems more than irreprehensible, constituting another instance in which populations of Nations with open economies and markets accessible to the Global Economy are abdicating vulnerable populationsâ&#x20AC;&#x2122; Liberty, Equality, Opportunity, Vital Being, Span of Vital Being, as well as the ability to achieve the Social, Human, Behavioral and Biological Condition as fodder to enable improved competitiveness among the global economy. Correlatively, as economies, in competition among each other, and organizations in the Global economic context, focus on obtainment of money instead of assurance of Humanity, it can be clearly exhibited that pervasively organizations and systems obtain money or expend money to effect, change or determine Human Behavior. The Amehsi Specification has suggested that Humanity may be among the most essential, changing, transformative and therefore valuable factors in the Universe, constituting the currency of the Universes. Systems are expended,

abdicating and allowing to become abate the vital being of Humanity as Currency less carefully than these may be managing even actual currency. Perhaps, endeavoring for improvement, Humanity should together, and in cooperation with organizations that employ, provide services to or otherwise adequately prioritize Humanity, begin to have a Global exclusion of such profiteering among entities constructing, marketing, or otherwise benefiting from Shelter and Domiciles being withheld from those who require such essential factors. Instead, utilizing pricing constructs from the early 19th century before Inflation began to transform the economy progressively into the status quo, begin to finance, construct, and produce Housing and Shelter which is then obtain using the empirical costs to constructs such factors. Such Domiciles might be constructed by aspects of public entities which provide service otherwise, constructing housing for themselves, each other and Humanity otherwise. Such housing might then be prevented from ever being sold for more than these incipient costs. Profiteering by promoting Homelessness should not occur and does not have to occur. Inflation does not have to occur. These are allowed to occur because profit is able to be obtained from the misfortune of others. There should not be allowed any flow of funds allocated by any public entity for Sustenance, Housing or Shelter, as well as any funds expended for Housing or Shelter, outside of the United States. If an extranational or international organization does assist in producing shelter and housing, such should be demonstrated to be accessible to the population widely and remuneration should be required to be placed into a financial institution in the United States and the first few transactions which such funds may be utilized for require also transference within the United States. Thus, systems allow Humanity to turn upon itself in pursuit of profit, in pursuit of require sustenance to prevent oneself from being destitute, thereby diminishing the activity which the Self-Prioritization of Systems as well as the Profit Motive of Private Enterprise have to exhibit in a directed manner to keep Humanity confused, occupied, and unable to consider how and why civilization has progressed to the status quo. 2,600,000 instances of demise or more occurred in the United States in 2016 according to statistics, precisely because of such factors. Multinational agreements between Nations in the Western World should pervasively exhibit the same requirements. If protectionism means preventing an organization at distant location upon the earth from earning a profit while people among a developed Nation perish in destituteness, then one may consider such priority in any contest they may require. However, economies were constructed by Humanity, in service to Humanity, and were not constructed such that on victimization on a Global Scale be permitted while empty shelters and domiciles are exhibited, sometimes, amidst the destitute as they perish in requirement of these very same resources. Public entities should be able to obtain land, dwellings, structure or buildings, allow private enterprise to assist in developing or construction while limiting the duration for which a return on investment may be obtained before the structure transfers to Quasi Public management. Similarly, the construction of civilizationâ&#x20AC;&#x2122;s infrastructure along with such Housing may be included in empirical markets which do not require differences in quality, usability or location. The essential observation here is that price controls, rental controls, and other management of access to shelter does not have to be determined and limited by the profit priority of Private Enterprise. Ownership of Homes has been addressed in other aspects of the Amehsi Specification in which essential factors including transportation, shelter, and homes may become protected by multiple levels of public entities or private entities as a way of translating currency into assets that have inherent value. Investments in such shelter which might have lower return than investment otherwise as protected owners pay according to ability to pay, might be made tax free such that income of organizations and companies may be reduced by their contribution to providing, constructing and protecting homeowners whom require assistance in

keeping their transportation, homes or essential levels of property. There do not seem to be any competitive detriment to any entities in such scenarios. That which may emerge can be managed through effective analysis and program management. Similarly, essential changes to taxation might occur which do not affect the employment or activity or organizations which are included in such activity. Instead of allowing companies or organizations to communicate to those whom they provide work opportunity a Salary Level before the effect of taxes, require organizations to communicate the level of compensation after the effect of taxes. Then allow organizations to work out the effect of Taxation afterward. If an individual is having difficulty financially with the levels of Taxation as they may be, allow these groups or individuals to describe their circumstance, provide relevant financial information, and receive additional assistance directly from Organizations that provide assistance without changing Compensations Characteristics. Organizations continue to manage, interact and require services to determine appropriate levels of Taxation and determine how adjustments to an individual or organizations circumstance occur. Funding health services or other programs, then, becomes possible without much potential for misunderstanding, as may many other social programs. Similarly, organizations may benefit more thoroughly from advantages provided for increasing the benefits and economic security of those who they may provide work opportunity. Of course, the essential aspects of Shelterlessness include the ways in which systems, patterns of Human outcomes or social construct affect the ability to obtain, maintain and be successful in the work or social environment. These include health status and focusing education about Homocysteine, Choline Kinase and PEMT, as well as other factors affecting behavior including iNOS, communications systems, internet sites, and Credit Reports and other influences that can pervasively amplify patterns or influences including compulsion, addiction, detrimental behavior, or other. Public, private and Quasi Private entities, as they begin to manage populations where health conditions, disease and impairment are no longer required to be exhibited and may, instead, indicate neglect more than being populations disparities, may require focus on the priorities of Humans as social organisms with systems being ways to assure balance between Public, Private and Quasi Private interests. If one is among those whom have their information at a Credit Reporting entity compromised because of a security or privacy issue, it is recommended to close or freeze all Credit Entity Information, remove as much personal information from the internet, invest in electromagnetic frequency inhibiting devices with a priority to passive devices, as well as obtain an older computer, have the computer modified by an Electromagnetic Frequency Management profession or obtain Electromagnetic Frequency inhibiting cloth or paint to modify the computer oneself, then utilize an early computer operating system and place oneâ&#x20AC;&#x2122;s personal information on this computing system. Do not connect this computer to the internet and do not allow any wireless networks or communications devices or fields to encompass this computing device. The objective is to produce an information center that affects Physiology and behavior while having discontinuity with information at Credit Organizations, on the internet otherwise and which is separate from the information which has been compromised and its new location with those whom have compromised such information. These can assist in protecting from detrimental effects of mass population level behavioral changes that occur when such private information is obtained, moved, accumulated, and utilized, particular by those with an unproductive or less than beneficent agenda. These can also assist in protecting individuals and groups from the unintended detrimental effects potentiated from productive and beneficent use.

These analyses observed a detrimental effect from the most incipient innovation, perhaps, thousands of years before epochs which are known to humanity. However, without such technological advancement, these analyses would have been substantially inhibited. Thus, a best practice seems to be aggressive innovation along with immediate review for safety, security and effect to Humanity. The Amehsi Specification provides substantial indicators with which effect to Humanity can be determined as a way to begin. A focus should be on parity in the prioritization of Humanity and the Ideals, Goals and Objectives of Humanity, producing less requirement to manipulate the direction in which currency flows while increasing the level to which Human Ideals or objectives are achieved as well as increasing the priority of Human expressiveness, ingenuity, reasoning and cognition. It is these latter priorities among Humanity which the Universe appreciates most, distinguishes Humanity most from other influences or factors, as well as which has the greatest potential for sustainment of Humanity within the Universes. The beauty of Artificial Intelligence is not an Intelligent Synthetic Being. Instead, Beauty is the creativity, imagination, interactivity with others among Humanity, the Biome and Universe that is the most essential and most wondrous aspect of such constructive activity. Artificial intelligence should be focused on decision support and exit loops in algorithms should inquire about changes in Human outcomes which emerge correlatively to their own function. An analysis of Artificial Intelligence, then, seems relevant. However, Intelligence is best described as the reasons why training data, Algorithms and rules exhibit their characteristics as why intelligent processing is occurring. Invariably, Intelligent Processing by Humanity and within Systems of Humanity, can be reduced to being performed assure the Priority of Beneficence to Humanity, Groups Among Humanity, Individuals among Humanity, Social Requirements, Human Requirements and satisfaction of the Choline / Folate / S-Methylmethionine / Thetin / CDP-Ethanolamine / PEMT / LPCAT / Homocysteine Recycling Pathway. Of course, similarly to the relationship between Training Data and the reason why Training Data exhibits its characteristics, which optimally reflect incipient reason, and the relationship between Reason, Training Data and Intelligent Processing, this essential Pathway for Human Metabolism, Health and Behavior reflects the incipient favor in the Universes which enabled or along with which Humanity has come to be among the Universes. The Nuances of such Pathway when it is satisfied and less than adequately satisfied, are reflected pervasively in Human physiological outcomes, behavioral outcomes and the outcomes among systems of civilization. Such Metabolic Pathways are pervasively reflected in all that Humanity perceives, considers and does, while require not translative processes to verify because it is a fundamental aspect of physiological being, conscious being and less than conscious being. Intelligence flows from such Incipient Favor, Being, and the essential Metabolic Pathways of Being, directing perception, cognition and behavior in way that manages interactions with systems of the universe in way that traverses hierarchies of beneficence that begin with the individuals physiological condition, and traverses the behavioral condition, Human Condition and Social Condition in way that is increasingly inclusive of others among Humanity, systems of civilization, the Biome and Nature. Maslowâ&#x20AC;&#x2122;s Hierarchy of Needs are similarly traversed in such context. Imperatively, because the nuances of factors required for detrimental human outcomes are produced and allowed to persist by civilization when these have been resolvable for centuries, and pervasively such nuances of systems are not exhibited in nature, while outcomes occur before individuals incur them and after individuals incur

them, detrimental Human outcomes are pervasively synthesized. Optimal outcomes, however, pervasively are of such synthesized nature. Regardless Patterns, complexes, and other nuances of Human outcomes may occur in systems which are aspects of Artificial Intelligence when such outcome is not reduced to empiricism and performed organically in each instance. Analyzing Human Outcomes in Organic and Empirical Systems which prioritize the incipient Favor of Humanity, essential Metabolic Pathways, the Physiological Condition, the Behavioral Condition, the Human Condition and the Social Condition, clearly present that attribution of causality to Humans for outcomes synthesized by systems may be less than optimal and prevent ascertainment of incipient causality and potentially impair the ability to resolve causality. Systems contrived upon Artificial Intelligence which does not include the reason for which systems have been synthesized, are able to conclude otherwise because such fundamental inadequacies might be able to be omitted from consideration. These analyses are focused on health and behavioral health outcomes, while the correlation to information, processes, or other systems may be at least somewhat relevant. These analyses suggest that when Artificial or systems result in detrimental Human outcomes, it may be pervasively the result the use of systems or any systems produced by Humanity in ways which are not beneficent to Humanity. All systems constructed by Humanity which are constructed consistently with reason, may have been intended to be beneficent to Humanity. The possibility that systems which use Artificial Intelligence might result in detrimental outcomes seems to be only be potentiated when such systems are dissociated from Nuances of Reason. The priority of Health, Medicine and Civilization, seems to be the production and persistence of continuity between the incipient favor afforded to Humanity and Humanity itself.

Thus, it can be clearly exhibited how Credit Reporting Organizations, their providing of information or management of information, the actuarial factors that are pervasively utilized by such information, as well as statistical data this used to produce these can substantially affect individual and population level behavior. Particularly, in an era in which information is being used to control and change population level behavior for political, social and economic benefit by particularly entities or any entity which is able to pay to have such influence, the security of such information has become determinant of Human behavior. Substantial detrimental outcomes may emerge resultant of changes to such information or access by entities, particularly those which affect Humanity. Should the security of such information not prevent its access by others as required, organizations or entities anathema to the Nation or anathema to Humanity may acquire the ability to produce substantially detrimental outcomes. It may be useful to analyze the level of detrimental Human geopolitical, social, economic, behavioral and Physiological outcomes after a Credit Reporting Entity has had its information compromised. These analyses, again, are presented because the impedance to effective and comprehensively successively Health Services capability implementation seems to be pervasively external to Health Services Capability levels and in many instances external to the Health Care Domain. However, it should be presented that offering these explanations

and solutions are intended to prevent the assertion that nothing can be done. It seems that pervasively, such recommendations or solutions may be possibly already concluded, followed by inhibition, prevention of distribution or preventing of implementation. Similarly, a solution in one small domain of healthcare may require resolution of numerous permutations of the industry otherwise, industry generally and in civilization, to prevent either a natural propensity for systems to change or respond to any disruption of the status quo. There is hardly any difficulty observing some such propensity as merely being spiteful prevention of progression of Human health status by interests particularly prioritizing the status quo or profiteering? Merely suggesting that a solution is possible, presents the possibility that the most optimal solution might be produced instead of subjecting innovating populations to spiteful rebuttals that have been produced with only a fraction of the beneficent or productive activity. Accordingly, since these analyses show that regeneration of anatomy should already be widely occurring, regeneration of dental structures is occurring sometimes even in Homeopathic Settings, as well as 99.9 percent of demise along with detrimental aspects of aging being preventable and reversible, there should be increased scrutiny upon Advanced Directives in the Health setting as well as Healthcare Power of Attorney Arrangements. These agreements pervasively are designed to suggest that the capabilities presented here are not possible, thus constituting an obfuscative process in which Patients are beguiled into agreeing to incur demise. There is a possibility that such agreements have been a particular hindrance to producing systems such as the Amehsi Specification. The objective of these analyses which are not clinical in nature, again, are presented such that numerous instances in which it could be suggested that nothing can be done, might no longer be an impedance to the transcendence of Humanity. Similarly, these analyses present that there are ways to improve the Human condition and that the solutions have already been developed and in many instances already shown to be effective. Most imperatively, these analyses suggest that there has been a pervasive exhibition of activity to repress and suppress these capabilities which may have included all manner activity, subjugation, intimidation, and other influence. Pervasively clinical practice has to manage homocysteine has been regarded as ineffective at improving outcomes, while pervasively clinicians purposefully omit Choline which, in deficiency, may be a primary cause of increased levels of Homocysteine. The clinical literature pervasively plainly exhibits Choline deficiency as a primary cause of pathology and increased levels of Homocysteine. Thus, it possible that the health services community may be being psychology, financially and otherwise intimidated into not include Choline in practice. During the production of these analysis, such intimidation was imposed by those whom have not connect to healthcare. Illustratively, individuals insisting Trimethylamine-N-Oxide be managed, inducible Nitric Oxide be intervened or decreased or Homocysteine be managed, might be being ostracized, labeled or even caused to incur detrimental behavioral and Physiological outcomes. It is not difficult to consider which individual among the 120 Million which have incurred demise was producing, understanding or constructing systems such as Choline Kinase Diagnostics, PEMT Diagnostics, or Inducible Nitric Oxide Synthase Diagnostics. Even in the care setting, bias against required change can be exhibited. The presumption of Human Demise and the detrimental aspects of the Status Quo utilize the Self Prioritization exhibited by Systems and the Profit Priority of Private Enterprise to Masquerade themselves among Systems and Activities with an inherently beneficent and productive purpose. Simultaneously, Humans are required to conduct activity according to such priorities which can result in Big Picture outcomes that are detrimental to Humanity, while pervasively, Humans in systems counteract such potential with their own sense of consciousness, community,

training, priorities and inherent priority of Humanity. These clearly present how impedances to social progress in developed civilization has resulted in a direct impedance of progression toward assured optimal health status and assured exhibition of indefinite Span of Being. Most imperatively, migration between aspects of civilization may be pervasively exhibited as a result of disparities in safety, resources and quality of vital being, such that when such migration is not conducted in ways which are required, repatriation or movement of such migrated persons to their location of origination may be anathema to Human rights, because, certainly, migration for purposes of opportunity away from destituteness, inadequate safety and other conditions are among the most incipient purposes for Human migration to what is now the United States. Emerging is a very clearly observed understanding that Civilization has emerged upon the foundational and fundamental factors known as Humanity. Thus, civilization was not meant to divide Humanity, and may have incipiently emerged as different contexts by which Humanity may be freed from the interactions among Systems of Systems that encompasses all things which might have pervasively less optimal outcomes for individuals or groups. The geopolitical necessity of maintaining Geopolitical boundaries, thus, seems to be an imperative priority of interpreting mass migration as an impetus to resolve the conditions from which Humans may be migrating. Resolving mass migration by repatriating Humanity into destitute conditions which are ideal for extremism, does not seem to be consistent with Liberty, Equality, Opportunity, the Social Condition and the Human Condition, while Civilizations which come together to understand the incipient foundations and fundamental requirements for constructing successful societies as well as constructing successful economies do seem to be consistent with Liberty, Equality, Opportunity, the Social Condition and the Human Condition. The context of migration as a behavior response to uiverses, biome, group or individual influence, presence a useful context with which to present manner of resolution of aspects of less than optimal outcomes in civilizatioin. Migratory behavior by populations suggest a number of causal mechanisms, although when such migration does not include movement to obtain the foundational aspects of Human requirements and social requirements, it is possible that other mechanisms are causal. Correlatively, Nations, groups, and populations inherently prefer stability, and the prospect of migration introduces both the potential for destabilization locations to which populations move while potentiating enhanced stability among populations which are required to move. However, reason requires that binary positions in such contexts not be presented, particulalry when migratory behavior describes the population characteristics of most places upon the Earth. Thus, inadequacies, globally and otherwise, become ascertainable when understanding how outcomes of mass migration become exhibited or potentiated. A most effective perspective of managing migration includes national and intranational cooperation. Essentially, a foundational requirement is that in Supranational organizations such as the United States and the Organization of American States, as well as the European Union, or other such organizations, there be a requirement that each National Entity present information about natural resources, Economic status and resources, socioeconimc factors, categories of these factors which are required to constituted the Human condition and Social Condition. Similarly, the availability and sustainability of such resources resources should be presented, along with planning, estimates, and monitoring statistics which demonstrate effectiveness of planning and effectiveness of existing capabilities in fulfilling the fundmamental mission of civilization. Each National, Geographic region, or Geopolitical entity, thus, should formulate their own, among a group of shared standard key performance objectives to demonstrate effectiveness in such capacities. If required, assistance should be provided to any entity requiring assistance in such capacities. Similarly, any organization in a developed nation which requires such assistance, such also have their activities and workers augmented to produce such information, enbling more accurate, useful, actionable and analyzable information to be produced with regard to the status of Human of populations.

Thus, instead of being placed in context in which a nation unable to manage an influx of population resultant of a mass migration, each National or Geopolitical entity should present a threshold at which acceptance requires reporting to international and supranational organization, analysis of the status which such location from which migration occurs, and implemented of concerted action to stabilize such location from migration may be occurring. Similarly, nations which exhibit efflux or Humanity or emigration at levels which destabilize other Nations might be required to change the characteristics of their Trade with other Nations to exhibit a focus on providing the requirements in achievement of the Physiological, Behavioral, Social And Human condition along with interactions with Supranational and Extranational entities such that such objectives are presented, prioritized, monitored and progressively achieved in improvement of Human outcomes. Imperatively, the interactions among systems of the Universe and systems of civilizations, may not always prioritize Humanity, such that particular events or particular groups and individuals have been required to incur experiences which have been utilized to analyze, understanding and improve the way in which Humanity conducts itself with improved ability to be reconciled with reason. Certainly, as a result of the inadequate ability to reconcile outcomes among civilizations with reason individuals, groups or entities otherwise may assert their own priority in spheres of influence which are readily available to them, such as participating in detrimental systems and participating in spheres of influence which include power, geopolitical interactions and artifacts specifically produced to impart detriment to Humanity. While the exhibition of Geopolitical entities which participate in detrimental systems or systems of such Geopolitical Hegemonic nature while not being able to supply the essential factors to the physiological, behavioral, social and human condition seems less than reprehensible, developed nations of the Earth have participated in such systems, typically out of necessity however but participating nonetheless, while aspects of populations were denied known biomedical capabilities through dynamics of systems which seem similar to those through which populations of particular nations become required to participant in detrimental nuances of systems, trading of detrimental factors and participation in Hegemonic Geopolitical systems interactions. Certainly, there is an incipient favor among which Humanity has come to be exhibited within the Universes. Such favor does not seem to be pervasively exhibited in the less than hospitable nuances which pervade the Universes. Civilizations and circumstances with natural systems, thus, seem to have the potential to cause Human priorities and outcomes to become dissociated from reason and this dissociation from reason can occur in the most developed of nations, less developed Nations and areas otherwise. The most foundational observation and assertions of the Amehsi Specification, may be the as populations of civilization become more and more capable of conscious consideration of reason, that such populations of the earth may be unwilling to enable the continued exhibition of the same patterns of human detriment which have occurred through the centuries and possibly since the inception of the Human experience. Imperatively, it is presented that it is not necessary for detrimental outcomes to persist such that the Human condition and social condition might be met by a majority among a population or such that the Human condition and Social Condition might be met by less than a majority among populations The way in which reason seems to free the hopes of Humanity, enable Humanity to persist along the most beneficent course, and progressively enables integration of Human priorities among those priorities of others, civilization, Nature, the Biome, as well as extended to the Universes. These analyses are imperative, again, because incipient causalities can progress to complexities substantially afar from the way in which most incipient causality may be alleviated with improved simplicity. Policy analysis, thus, may be caused to exhibit solutions, complexities and impedances that are contrived from progressed permutations of reason and circumstance which are themselves the result of other vectors progressed permutation of reason and circumstance, resulting in inability to determine incipient causality of any of such vectors which become dependencies or causality associated circumstances which require resolution simultaneously. Some best examples may be Climate

Change. Methane Gas may be considered a Greenhouse Gas while Methyl molecules are required as an incipient activated molecule pathway to enable Mammalian Embryonic development to begin even before Fertilization occurs. Methane Gas may be most pervasively produced by Organisms and as Methane Gas has increased in the Atmosphere, so has the Span of Vital Being exhibited by the Typical Human. Similarly, CO2 is considered a Greenhouse Gas, when the most abundant Enzyme on Earth, Rubisco which manages Carbon integration into Physiology through Oxidation and Carboxylation, is Enzymatically and Catalytically impaired because it expects at least 50% more Carbon Dioxide to be exhibited in the Environment. Most particularly, a review of the Climate data clearly omits that that rainy days have substantially different temperatures than Sunny Days, such that merely by changing the number of overcast and rainy days, it is possible to substantially change annual temperatures t the Earthâ&#x20AC;&#x2122;s Surface. Amazingly, a perspective of the ways in which natural systems interact provides a very compelling understanding of those mechanisms which civilization has misinterpreted resultant of distancing of objectives and outcomes from incipient and empirical aspects of reason. Because Human physiology and aspects of the biome exhibit an inherent scrubbing mechanism known as PEMT1, PEMT2, and Thetin-Homocysteine Methyltransferase, it is very probable that Mammalian population increases which have been observed to expand along with the levels of Methane in the Atmosphere are among the responses of the environment to detrimental accumulation of factors in the Biome. The ability of PEMT metabolites Phosphatidylmonomethylethanolamine, Phosphatidyldimethylethanolamine and DHA Enriched Phosphatidylcholine in structurally degrading pervasive aspects of those Naturally occurring toxins and pollutants as well as much of those factors which are synthetically produced, is augmented by the exhibition of Thetins, Methylsulfones, Thetin-homocysteine Methyltransferase, Methylthioglycolic acid, Serine Proteases, and the ability to structurally deteriorate H2S and CO2. Population increases would invariably include upregulation of organisms which should capabilities, particularly because Phosphates are known to contribute to overgrowth of fauna while organisms which metabolize and integrate phosphates in these cleansing pathways are known to remove such phosphates from the environment for integration into biosynthetic and metabolic processes. Moreover, PEMT activity is, per KG of anatomical Mass, enhanced in early development phases, suggesting that conception and early development may be as beneficial to the biome as is efficiently possible otherwise, while the exhibition of an organism at increased numbers which has the potential to cognitively perceive the nuances of biome health, certainly increases exponentially the priority of Human populations within the Biome. Managing Homocysteine and factors which deteriorate the mechanisms which metabolize Homocysteine seem to be central factors in Biome Health and the exclusion of these as central priorities in civilization and health seems to be a most central factor which excludes Humanity from being a Harmoniously prioritized factor among all systems of the Biome. Certainly, the exhibition of pervasive Human events and environmental events which all include nuances of Phospholipid, Choline, Thetin and other pathways presented here, all suggest that it is Human inadequate prioritization of itself in these pathways which may be preventing biome level detrimental events as well as which may be preventing a more concerted assertion of the Earthâ&#x20AC;&#x2122;s Biome as priorities among the Universes. Rubisco emerged from a 1979 a humorous reference using the consumer products organization NaBisCo or NABISCO name to describe the endeavors of a prominent Rubisco Researcher to produce Edible versions of the enzyme to which Rubisco refers, Interestingly, the consumer product food was to be derived from Tobacco Leaves.128

128 PMID 16245127

These analyses found North American Weather data regarding Sunny Days compared to Rainy Days was very difficult to find and was not presented in a way which these calculations might have been simplistic to conduct. Although these analyses strongly suggest that Climate and Environment are integrative with Physiology in many aspects, as well as acknowledge that improvements regarding environmental effect to health are imperative, it should also be acknowledged that the simplistic tangible activities already exhibited within the Amehsi Specification have not been acknowledge at this juncture. Managing Electrical, Magnetic and communications fields are things that can be done now and which would produce substantial improvement, while also managing the effect of Chlorine, Fluorine, PCBs, Dioxins and Aflatoxins all may be factors which can be done now with substantial improvements to health status. There is a possibility that these factors may be substantial causes of change to Hydrological Cycle and such Hydrologic Cycle changes may be the most substantial causes of changes Climate. Decreasing Methane Gas and Carbon Dioxide Gas seems to be perilously close and only a few permutations away from inhibiting Population Growth because these factors are integrative aspects of Mammalian Physiology. If merely producing a Legislative Act that introduces Sanctions for activities which utilized Methamphetamines can reverse almost a decade of improvement in levels of demise associated with conditions that emerge when Methylation pathways are inadequate, what effect must Global Level Regulation and Sanctions associated with Methylation and Carbon Dioxide be having to Humanity. There has to emerge or be reiterated that Policy development processes have a first Priority, Humanity.129 130 Hepatocellular Carcinoma introduced by Aflatoxin B1 is known to be correlated to abrogated PEMT2 expression and is known to be reversed by reintroduction of PEMT2 expression. PEMT1 and PEMT2 are downregulated in oncology, typically, while Neoplastic Nodules exhibit lower PEMT and Neoplasm induced by AFB1 were substantially without PEMT expression. Moreover, Neoplasm was not able to be produced when PEMT2 was expressed unless Anchorage was exhibited suggested that when PEMT2 is expressed Neoplasm requires the support of Gap Junctions and extracellular accumulated metabolites, energy factors or oncological phenotypical protein characteristics to emerge, persist, progress and impart Oncology Pathology. These substantial decreased levels of Cellular Oncology Pathology were observed in Cellular entities in which PEMT2 expression was stimulated even in Athymic Murine Populations suggesting that PEMT2 and PEMT1 both provide an incipient, foundational effect that occurs before Adaptive Immunity is required or is exhibited.131 Interestingly, the literature suggests that PEMT1 is localized to the Endoplasmic Reticulum in research as recent as 1997 while PEMT2 is suggested to be Mitochondrially localized, although modern Gene Databases merely suggests probabilities of exhibition of these in different subcellular locations.132 PEMT2, in another study, was shown to be decrease in incipient stages of Hepatic Oncology and to have become â&#x20AC;&#x153;Obliteratedâ&#x20AC;? with progressed phases of the same Oncology while CTP Phosphocholine Cytidylyltransferase was found to be upregulated, clearly being correlative to both a Inhibition of PEMT and upregulation of Choline Kinase Pathway Activity that did not necessarily have to include Choline Kinase although there was not specific conclusive analysis to show that Phosphocholine metabolized by CTP Phosphocholine Cytidylyltransferase as either from Choline Kinase Activity upregulation by AP1/SP1/iNOS/Thrombin or other factors, from increased availability of Choline from impaired PEMT which decreases Acetyl-CoA to make Free choline unable to be stored as Acetylcholine thus making it

129 130 131 132,London,United-Kingdom 10.1002/(SICI)1097-0215(20000501)86.3 LIBRARY OF MEDICINE PUBMED IDENTIFIER 9370326

available for Choline Kinase Phosphorylation into Phosphocholine, or resultant of increased availability produced from head group exchange of accumulated Phosphoethanolamine resultant of inhibition of PEMT.133 McArdle Cellular Lineage derived cellular entities of Clinical Hepatoma versions, which are an Immortalized Cellular Lineage, are observed to produce only 20 Picomoles per Minute per Milligram of PEMT compared typical Hepatocytes which exhibit 1 Nanomole per Minute per Milligram of PEMT. Introducing PEMT into McArdle Cellular entities resulted in inhibition of Cellular Division Rate in linearly correlated manner compared with increasing levels of PEMT. 20 Hour Mitotic/Meiotic Cycles in McArdle Cellular Entities were transformed into 50 Hour Mitotic/Meiotic Cycles by PEMT2 exhibition. Increases in PEMT2 in McArdle Cellular Entities were also correlated to decreases in expression of CT, CTP Phosphocholine Cytidylyltransferase. The decreases in CTP Phosphocholine Cytidylyltransferase expression was confirmed by observation of decrease in CTP Phosphocholine Cytidylyltransferase mRNA. These clearly present precise correlation to AP-1, SP-1 and Inducible Nitric Oxide Synthase activity. A particular Small Nonhuman Mammal Species were subjected to incomplete Hepatectomy of about 2/3 of the Hepatic Tissue. The week duration in which the Hepatic Regeneration of Tissue typically occurs exhibits that aggregate PEMT was reduced by 50% at 24 Hours after Hepatectomy while PEMT2 had become no longer substantially exhibited at 24 Hours. This suggest that PEMT1 was the constitutive Persistent PEMT version at 24 Hours after Hepatectomy while at 24 Hours PEMT2 was no longer exhibited at the mRNA level and PEMT2 was no longer exhibited at the Protein level. Once 192 hours had elapsed, 50% levels of PEMT had become reconstituted to typical levels, while PEMT2 also had become reconstituted to its typical levels. These suggest PEMT2 may not only be expressed as inhibitor of cellular proliferation. Instead PEMT2 may be spatially competent in its expression with regard to Anatomical Structure, particular being regarded as Spatially competent because it was downregulated with Hepatectomy and became typical at the duration in which regeneration of Hepatic Organ Structure typically occurs. CTP Phosphocholine Cytidylyltransferase was upregulate 200 Percent at 24 Hours after Hepatectomy, while gradually returning to levels exhibited before the Hepatectomy. This suggest that Choline Kinase may have been upregulated as a response to injury, Choline Kinase may have become upregulated resultant of increased free Choline resultant of inhibited Methyl Group Catabolism correlated with decreased PEMT, or accumulation of shared Metabolites, increase in shared substrate, Cross Production of Shared Metabolites, Head/lead Group Exchange between Methylation and CDP-Choline Pathways, as well as AP-1, SP-1, and iNOS, all could have coordinated the upregulation of CTP-Choline Cytidylyltransferase. The CDP Choline pathway is also known as the Nucleotide Pathway in other organisms and may have become upregulated to enable Synthesis of DNA and RNA essential to cellular repair, DNA repair, DNA replication, and biosynthesis generally required for tissue regeneration. Developmentally, a particular Small Nonhuman Species of Mammal was observed to not exhibit PEMT2 during Gestational expression, to exhibit progressively increasing levels of PEMT2 after gestational Phase to 50% at Birth, culminating in exhibition of 100% of Adult levels once Hepatic Maturity is attained. CTP Phosphocholine Cytidylyltransferase level peaked at 5 Days before Birth, decreased gradually to adult levels, was therefore inversely 133

Biochem. J. Volume 1997. Number 337. Pages 23 to 27.

correlated to levels of PEMT2, therefor also suggesting that CTP Phosphocholine Cytidylyltransferase may not, at least postgestationally and developmentally, inflammation management mechanisms as well as may not have emerged incipiently to perform as a Xenobiotic or Prosurvival Mechanism. The increased levels of CTP Phosphocholine Cytidylyltransferase 5 Days before Birth suggests that it might incipiently have emerged or been intended to be survival mechanism, although its essentiality at 1 more other Gestational Phases suggest that CTP Phosphocholine Cytidylyltransferase performs as a mechanism of Rapid Differentiation which provides increased cellular membrane resilience and increased availability of Nucleotides, although this availability of Nucleotides requires Choline Availability to be constructive. The same Small Mammal Species, Nonhuman, were also analyzed in a context of Lead Nitrate instrumentation, resulting in exhibition of correlation between Cellular division increases and CTP Phosphocholine Cytidylyltransferase as well as exhibiting correlation between PEMT2 and inhibition of Cellular Division. The Amehsi Specification, thus far, suggests that Choline inadequacy may cause the retreat of Choline metabolic pathways in its complete version along with retreat of PEMT activity to the Hepatic Region or to other Splanchnic System tissues resultant of Gradients of availability of Choline. Gradients of Choline circulation and availability may emerge in an environment in which cellular entities pervasively may have inadequate Choline. The most substantial users of Choline, Synthesizers of Choline and those tissues nearest to Circulatory structures or nearest to Capillaries where Hematopoietic Fluid Transported Nutrients exit may have first chance access to Choline in circulation compared to areas more distant from such loci. Thus, the potential for Hepatic Organic being an offloader of PEMT2 or central production capability for PEMT2, has to be considered. However, the same study observes no effect of PEMT2 to Chinese Hamster Ovary Cellular Entity Proliferation. However, the research information in this context does not seem to suggest an intricate exploration of the mechanisms by which PEMT2 became ineffective. Because PEMT2 is known to be about somewhat deteriorated in its expression and catalytic activity in the beginning phases of Hepatic Oncology which include exhibition of Lesions, while the more progressed and somewhat complete impairment of PEMT2 function is considered typical for at least Hepatic Oncology, these analyses found that typical patterns of detrimental metabolic circumstances might produce particularly patterns of DNA Sequence impairment, and 1000 or more instances of impaired DNA is typically exhibited with Oncology, there is a possibility Choline inadequacy may be a globally active factor in the deterioration of DNA, RNA availability, and the Metabolome, such that Organisms exhibit a similar retreat of functional PEMT2 pathways in areas other than the Hepatic Region or the Splanchnic System.134 Another work presents PEMT2 downregulation, CTP Phosphocholine Cytidylyltransferase upregulation along with PEMT1 decreases as context of substantially pathogenic Oncology. Periods of abated Oncology in this context were observed to occur when PEMT2 activity became exhibited once again while cytidylyltransferase levels decreased again. The particular Small Mammal context of Hepatic Oncology exhibited emergence of Oncology during exhibition of Decreased CTP Phosphocholine Cytidylyltransferase and upregulation of PEMT2, while such changes in CTP Phosphocholine Cytidylyltransferase were not substantial. Interestingly, upregulated PEMT2 and abatement of the upregulation CTP Phosphocholine Cytidylyltransferase, were accompanied by abatement of Hyperproliferation of


ISGN 0935315861. ISBN 97080935315868.

Hepatocytes and were accompanied by exhibition of Apoptosis that was substantial enough to constitute resecting of Hepatic Tissue. This apoptosis was accompanied by both PEMT increase aggregately and PEMT2 increases. CWSV-1 Immortalized Hepatocytes are known to exhibit increase Methylation Pathway produced Phosphatidylcholine potentially resultant of increased S-Adenosyl Methionine in the intracellular environment. Although Methylation Pathway production of Phosphatidylcholine can imply PEMT activity, these analyses clearly observe that Choline/Ethanolamine Phosphotransferase is able to produce Phosphatidylcholine in the phase of the Methylation Pathway Immediately preceding PEMT, while the sharing of substrate and Head/Lead Group exchange potentiates supplying of factors which enable phases of the CDP-Choline pathway to become exhibited. Assuring PEMT function seems to provide protection from Metastases. Included in this paradigm the observation that PEMT is essential to the synthesis of VLDL, and VLDL is transformed into other Lipoprotein including cycling interactions with HDL, as well as the observation that energy fields induce HDL accumulation and promote Ornithine Decarboxylase activity in cellular membranes, and one has produced a participation in pervasive oncology associated conditions or conditions otherwise and fields of electrical, magnetic and other origin. However, most, imperatively, one can clearly show that it is only necessary to induce PMA/TPA to induce hyperactivation of the CDP Choline pathway while inhibiting PEMT to shunt membrane biosynthesis to the CDP Choline pathway in which fatty acid and choline which are susceptible to oxidation, degradation, changes from cooking, genetic medication in food production, and other factors are principally utilized. These can become principle if not pervasive components of cellular membranes while also being persistently hyperactive and promoting hypertrophy at cellular, tissue other areas. Inhibited PEMT, also enables P53 activity which cause cellular division to pause at hypertrophic phases. These potentiate either overgrowth of cellular entities in number, while impaired, and potentially also overgrowth of each cellular entity individually. Cellular, metabolic and immunological mechanisms may be determining which of these unproductive and detrimental outcomes may be prevalently exhibited compared to the others, if all of these are not exhibited. The antibiotic group of Cinnamycin, including Cinnamycin B, Durmycin, Durmycin B, and Duramycin C exhibit their therapeutic activity by inhibiting aspects of the PEMT pathway to detrimentally affect Gram-positive bacteria, making it more and more difficult to understand how there has not been clinical and industry level knowledge of PEMT centrality to Physiology. Similarly, these present the cellular membrane as the locus of pathology which other literature characterizes as leakage, seepage, or abrogation of distinctiveness between intracellular and extracellular environment, linking PEMT with Cellular Membranes, Structure and Function.135 Moreover, a particular research article in 1988 elucidates precisely and clearly the Activity of PEMT and its three known substrates, presenting also through Kinetic analyses that there must be second phosphorylation Loci in PEMT to enable Egg Phosphatidylcholine Choline associated improvement PEMT catalytic efficiency. Probably less interesting than the observation that this study shows that PEMT and Choline Kinase Inhibitors might have been possibly utilized beginning at least in 1988, is the observation that this study shows that impaired membrane characteristics impair PEMT activity, producing a detrimental cycle.136

135 136

Digital Object Identifier 10.1007/s10295-016-1869-9 LIBRARY OF MEDICINE PUBMED IDENTIFIER 3182819

The mystery behind oncology, leukemia, and lymphoma, thus, may be unraveling. Illustratively, iNOS expression is stimulated by electromagnetic frequency influences and fields. However, TPA/PMA is also induced, as well as Chemoattractant Protein-1, which are the central causal factors in a number of pathologies including Multiple Sclerosis, Oncology and Menopausal Oncology in particular. Pacemakers, communications devices or electrical fields as well as magnetic fields, thus, cause the expression of TPA/PMA which causes increased synthesis and metabolism in the Ethanolamine Kinase Pathway, along with inhibiting of PEMT because TPA/PMA both cyclically potentiate AP1. Generally, the Heuristic understanding of Oncology suggests that the Ethanolamine Kinase is downregulated and the Choline Kinase Pathway is upregulated, but the precise characterization is that Phosphatidylethanolamine Methyltransferase is downregulated and Choline Kinase is upregulated, presenting the accumulation of feed forward excess of phosphocholine and inhibited PEMT. Upregulation of Choline Kinase and incipient phase of the Ethanolamine Kinase Pathway both can supply the Choline Kinase Pathways concluding phase of Phosphatidylcholine Synthesis because the substrates differ only by the Headgroup and because the Cofactors and Substrates otherwise are shared and homologous. The interesting juncture here, however, is that Choline/ethanolamine Kinase is known to produce Phosphatidylcholine and Phosphatidylethanolamine. There are some interesting distinctions with regard to Choline Kinase. Choline Kinase Beta is upregulated resultant of Phosphorylation by Protein Kinase A. Choline Kinase, in a study, is shown to have highly conserved Choline integration loci and ATP integration loci, exhibiting homogenous structures among Humans and Pathogens. The integration Pocket of Choline Kinase Beta, thus, may be highly useful for Kinetic Inhibition of Pathogens as well as inhibition when Choline Kinase is upregulated in Human Pathology. The Study presents two compounds that actively inhibit Choline Kinase Beta, across organisms, even when the inhibitor is exhibited at low Molarity.137 Studies otherwise, however, typically regard the inhibition of Choline Kinase Alpha and, furthermore, typically include Choline Kinase Alpha 1. Choline Kinase Alpha 2 has an additional 18 Amino Acids and has a lower Kinetic throughput than Choline Kinase Alpha 1. The literature does not suggest differences in structure otherwise between Choline Kinase Alpha 1 and Choline Kinase Alpha 2, although the shape, twist and writhe characteristics might be affected. Moreover, Choline Kinase Beta inhibition has been shown to be similarly inhibitory of Oncology, particularly when Choline Kinase Beta has been upregulated by Protein Kinase A. Protein Kinase A is activated by cAMP availability. Importantly, Protein Kinase A Phosphorylation of Choline Kinase Beta upregulates the activity of Choline Kinase Beta two-fold while also, interestingly, increasing the susceptibility of Choline Kinase Beta to the Choline Kinase Inhibitor Hemicholinium-3 by 30-fold.138 However, Choline Kinase Alpha considered similarly, was found to not be Phosphorylated by Protein kinase A.139 Choline Kinase Beta was observed to be Phosphorylated at Serines 39, 40 and 42 most prevalently, although variable combinations of Phosphorylation of the these Loci seemed to occur in a small study, except for lone phosphorylation of Serine 39 which was not found to occur in the small sample of variability. Progesterone inhibits Protein Kinase A. Protein Kinase A phosphorylates Choline Kinase Beta. This suggests that Choline Kinase Bet is specifically inhibited in early Oocyte development. Since Choline Kinase Beta has more Choline Kinase and Ethanolamine Kinase Activity Balance than Choline Kinase Alpha, this suggests that Progesterone Forces an election in Phospholipid Synthesis which is decided, at least in some manner, by Progesterone activation of Mitochondrial Steroidogenesis, 17Beta-Estradiol Synthesis and Phosphatidylethanolamine Methyltransferase activity. Although the Human Physiology exhibits a natural rhythm with changes to shape, twist and writhe of molecules which 137 138 139

Digital Object Identifier 10.2174/1568026614666141216093337 Digital Object Identifier 10.1371/journal.pone.0154702 Digital Object Identifier 10.1371/journal.pone.0154702

one might refer to as Bioplasm, an early Physiological rhythm seems to be constituted of the Ethanolamine Kinase and Phosphatidylethanolamine Kinase Pathway which enables Oocyte development, Proton Pumps at the Mitochondria and cycling of molecules that extend to the tissue level. It is becoming difficult to produce arbitrary differentiators of the beginning of vital being in the developing Human, although surely each instance of vital being carries with it a presumption of assured decision making regarding oneâ&#x20AC;&#x2122;s own Physiology. Similarly, the most amazing aspects of the beginning of vital being have already occur upon the exhibition of biological function that potentiates the emergence of Vital Being. Nonetheless, the mechanism by which Vital Being Springs into environmental Interactivity independently, occurs upon Progesterone Activation of Oocyte development and other pathways, even though the first interactive environment is encapsulated within anotherâ&#x20AC;&#x2122;s Physiology. However, imperatively, Progesterone Inhibits Protein Kinase A and thus inhibits Choline Kinase Beta, causing Choline Kinase Alpha to become a primary Phosphatidylcholine Biosynthetic Pathway. Progesterone promotes Choline Kinase Alpha to a principle Phospholipid Synthesis Pathway, presumably, because of its ability to stimulate Phosphatidylethanolamine Methyltransferase (PEMT) becomes impaired by the inhibition of PEMT by AP1, SP1, Sadenosyl Homocysteine, and Homocysteine. Spermatozoa, however, exhibit increased cAMP from progesterone exposure and the increase in cAMP from Calcium Influx can surmount the inhibition of Protein Kinase A by Progesterone in Spermatozoa, resulting in cAMP associated activation of Protein Kinase A. 140 The Influx of Calcium enables Progesterone to potentiate Protein Kinase A instead of persistently Inhibiting Protein Kinase A. A Study clearly shows that Lipopolysaccharide induces both iNOS and NF kB, such that inhibition of NF kB was only effective in this cellular model for between 6 and 12 hours, whereas lesser and greater duration exhibited NF KB Activity, an important assertion because NF KB is required for iNOS activity. Digital Object Identifier 10.1074/jbc.274.44.31559.141 142 Homocysteine begins to cause detrimental effects including activation of Monocytes at 0.000000000014794606 Micromoles per liter. PMID 16157236. Homocysteine at 0.000000000184932581 Micromoles per Liter results in MRNA and Protein of Inflammation and Cytokines including TNF-Alpha, IL1-Beta, IL-6, IL-8, IL-12, as well as downregulation of Migration Inhibitor Factor MRNA/Protein.143 These suggest that Homocysteine can be inherently perilous without anti-inflammatory accompaniment, PEMT regulates itself out of necessity, ancillary sources of Homocysteine can be perilous, the few pathways of its depletion may be essential to health and therapeutic objectives of 6 Micromoles per liter may be conservative, while optimal may be closer to less than four less than 3 or less than 2. However, since Homocysteine is utilized to produce Methionine, these analyses have been reluctant to suggest lower than a range of between 6 and 3. Methionine and Cysteine inadequacy can impair the Carbonate Buffering System and impair the ability to maintain optimal pH. Health services and biochemical research have prioritized discovery of Anti-inflammatory factors in preceding eras and the Marine or Aquatic Environment has provided some such capabilities. Ascidiathiazone, an Alkaloid, is known to exhibit Anti-inflammatory effect by inhibiting Neutrophil Activity. Cembranolines are known to be Cemranoids which inhibit COX-2. Durumolides are Cembranoids which also inhibit COX-2 as well as iNOS. Frajunolides are Diterpenoids which inhibit Neutrophil Inflammation Activity. Manzamine is an Alkaloid which inhibits Thromboxane B2 activity. Plakortide P is a Polyketide which inhibits Neuroinflammation. Rubrolide O, the 140 141 142 143

Digital Object Identifier 10.2164/jandrol.107.004614 Digital Object Identifier 10.1074/jbc.274.44.31559 Digital Object Identifier 10.1242/jcs.01383 LIBRARY OF MEDICINE PUBMED IDENTIFIER 16157236

Halogenated Furanone, exhibits inhibition of Neutrophil inflammation activity. Carteramine A is also known to be an Alkaloid with the ability to inhibit Chemotaxis of Neutrophils.144 The Amehsi Specification is progressively producing enhanced understanding of biodiversity produced by differences in COX, LOX, iNOS, TNF, Interleukin, Interferon or other factors, suggesting clearly that understanding of inflammation should include the roles of such pathways as signals for differentiation that are inflammatory when PEMT is inhibited and Inflammatory when Choline Kinase is upregulated, although being diversity signals as well as differential signals when such pathways are not so impaired. Kaempferol, Quercetin, and Daidzein are inhibitors of STAT â&#x20AC;&#x201C; 1 and NF kB. Isorhamnetin, Naringenin, Pelargonidin, each inhibit NF kB and not STAT â&#x20AC;&#x201C; 1, although these factors also inhibit iNOS in Macrophages as well as inhibit Nitric Oxide Production in Activated Macrophages.145 The literature suggests that Guanidinoacetate N-Methyltransferase is a primary producer of Homocysteine, consuming S-Adenosyl Methionine and Guanidinoacetate to produce Creatine and S-Adenosyl Homocysteine. Guanidine can become Glycine, Ammonia, Carbon Monoxide, Carbon Dioxide and Xanthine, although some literature suggest that Guanine can be produced from Glycine. Guanidino or Guanyl factors have been introduced in other areas of these analyses and it is a factor in iNOS expression, Genetic Expression/Structure, as well as being a factor in Mitochondrial DNA Depletion Syndrome. The patterns of group Genomic Structure impairment that are typically emerged in Physiology, such as with Mitochondrial DNA Depletion Syndrome, suggest strongly that Genetic and Epigenetic factors causing the patterns of DNA impairment. Some such multiple impairing SNPs are not located on the same loci of DNA and not all are described by folding of DNA which causes non-adjacent aspects of Genome to be near to other distant junctures of DNA. DNA and RNA supplementation can assist in alleviating Genetic Conditions including Oncology or other conditions. RNA can be provided which is translated into Proteins which are required for Physiological function. Similarly, proteins which are functional and optimal, designer proteins, can be utilized to enable optimal Physiological faction, including enzymes. These seem to be simple solutions to a complex condition, which can be augmented by optimizing Physiology, CRISPR Gene repair and perhaps the use Okazaki Fragment Primers or any other DNA repair enabled Primers that obscure impaired aspects of DNA during replication such that these become prioritized by other repair mechanisms. It is not presented here with enough emphasis that these analys3s continue to suggest that since base pairs require being exhibited with particularly parity between Nucleotides on the two different strands of DNA, that it seems clear that impaired Physiology is required aspect of Substitutions within DNA. It has already been clearly presented that environmental factors, particularly fields of influence that include energy, are emerging is pervasive enablers of pathology, impaired genome, and progression of these to less than optimal Human outcomes. iNOS seems to be a probable factor in such Genetic Impairment Patterns. iNOS is essential to consider because it can become a principal pathway to demise in dwellings, particularly when particular matter, energy fields and other 144 145

Digital Object Identifier 10.1155/2013/572859 Digital Object Identifier 10.1155/2007/45673.

fields of influence are not being monitored or managed. A study clearly links iNOS enhancing Interleukins as correlates to demise in dwellings among those who conduct the most aspects of their vital being in such dwellings. Interleukins persisted in such correlation after managing confounding factors in the study.146 Clearly these describe processes that result in cAMP expression, such as accumulation of Ca2+ as potentiators of Protein Kinase A and inhibitors of Choline Kinase Beta. It would be convenient if iNOS was found to cause aggregation of Ca2+, fueling cAMP increases. However, pivotally again, the literature suggests instead that Protein Kinase A activates iNOS and clearly suggests that Interluekin-1 which was suggested to be an essential factor in enabling iNOS activity, is induced by Protein Kinase A. A reasonable conclusion is that Protein Kinase is an inducer of iNOS and might be an essential, principal, and although not completely verifiably at this juncture, a primary inducer of Nitric Oxide Synthase. The Protein Kinase are diverse, but the inflammation associated pathways analyzed here are the context of the presented known required pathological molecular contexts required for oncology. Protein Kinase A stimulates iNOS and since cAMP are membrane G Protein Pathway Participants, these are consistent with the observations of the Amehsi Specification which present a model of iNOS expression that includes inhibition of ATP Synthase at the Mitochondria, perforation of the Endoplasmic Reticulum to deplete Ca2+, emergence of the Golgi Apparatusâ&#x20AC;&#x2122;s unfolded Protein Response that impairs Protein Synthesis and shuttling to the cellular membrane, depletion of Store Operated Ca2+, perforation of the Plasma Membrane through which extracellular Ca2+ and L-arginine are Endocytosed to fuel an ever Hungry iNOS that acts without sensitivity to lowered levels of iNOS, the exhibition of phospholipases that catabolize cellular membranes to release the Ca2+ that encircles Phosphate Groups, the exhibition of an IPLA2 Phospholipase that does not required Ca2+, the emergence of a Ca2+ tunnel and pump mechanism that depletes Ca2+ from anywhere in the vicinity of the affected cellular entity, impairment of DNA repair that seems to selectively potentiate impairment of DNA at locations for iNOS affecting Genes, the Collapsing of the Sarcolemma which impairs plasticity of muscle fibers and their contractility as well as their ability to relax, and the exhibition of Systemic Gradients in Physiology based upon Ca2+ instead Cytokine and Chemokine influences otherwise, potentiating all manner of phenotype inversion, cellular migration or other Anomaly. Most Imperatively, iNOS is able to produce an Ionic pump through such perforations in the cellular membrane that can produce Mechanical Force to potentiate Metastases.147 cAMP results in rapid phosphorylation of Protein Kinase A. cAMP activates Calcium Channels and is modulated by multiple G Protein Coupled receptors. Similarly, Protein Kinase A and Protein Kinase C are regulators of Calcium Influx with varying inhibitor and catalysis effect.148 Protein Kinase A illustrates these are potentialities because its activities are at the Cellular Membrane, enabling Gradients to produce shaped traffic of Ca2+ between the cellular membrane and the Loci of iNOS which could be illustrated by Cone shaped wider exhibition of Ca2+ at the cellular membrane and more specific Loci as distance from the Membrane and nearness to functioning activated iNOS is exhibited. Protein Kinase C results in decreased levels of Nitric Oxide, although its inhibition does not result reversal of the decrease in Nitric Oxide, suggesting the Protein Kinase C inhibits the ability of Protein Kinase A or other inhibits other Kinasesâ&#x20AC;&#x2122; ability to produce Nitric Oxide with

146 147 148

Digital Object Identifier 10.1007/s11357-010-9165-5 American Journal of Physiology. Cellular Physiology. July, 1996. Volume 271. Number 1. Pages C429 to C434. Digital Object Identifier 10.1161/01.RES.87.12.1095

the essential consideration that the Exhibition of Nitric Oxide can occur from iNOS, eNOS, nNOS or mNOS but iNOS exhibition can inhibit eNOS and inhibit nNOS.149 Amazingly, the clinical literature observes that Phosphatidylcholine to Glycerophosphocholine Ratio, as Phosphatidylcholine molarity divided by Glycerophosphocholine Molarity, is exhibited in models of highly Pathogenic Glial Neoplasm pervasively, suggesting that how far below 1 this ratio may be can be correlated to level of Pathogenic activity as well as level of progression. Specifically, the study observed that Ki – 67, which is an indicator of Mitotic Activity used in Oncology to indicate level of division exhibited by Neoplasm, is correlated to how far below 1 this Ratio may be. Simply, the level Phosphocholine metabolites is correlated to KI – 67 in models of Oncology, confirming pervasive aspects of this research and analysis.150 Furthermore, Choline Supplementation is known to be able to alleviate Pcyt2 deficiency in small Mammal Models of genetic impairment, clearly exhibiting how Choline adequacy is able to surmount Genetic Conditions by increasing the level at which unimpaired Genes are expressed. Correlatively, these provide an example of how Genetic Impairment may cause particular outcomes as phases of being progress while being prevented from impairment during Gestational Periods. Choline stored as Acetylcholine, drops by 17-Fold sometime after Birth in the typical physiology of Humans, with increased exhibition of Phosphocholine Metabolites being potentiated because Choline Kinase catalytically attaches Phosphate Groups to Free Choline that is not transformed into Acetylcholine.151 Imperatively, Protein Kinase A inhibits Choline Kinase Beta, tunneling Choline to Choline Kinase, Ethanolamine Kinase, Choline/Ethanolamine Phosphotransferase, and Phosphatidylcholine Methyltransferase, each in potentiation of Phosphatidylcholine, However, Phosphatidylethanolamine Methyltransferase becomes depotentiated typically by Upregulation of Choline Kinase, AP1, SP1, and its own catalytic activity through inhibitory effect of its metabolite Homocysteine as well as its product S-Adenosyl Homocysteine. Thus, Choline Kinase Beta inhibition produces Choline Kinase A and Choline/Ethanolamine Phosphotransferase as principal pathways of Synthesis of Phosphatidylcholine particularly with progressing development and phases of being. Furthermore, impaired Phosphatidylethanolamine Methyltransferase would result in accumulation of Phosphatidylethanolamine which might inhibit the synthesis of Phosphatidylethanolamine by Choline/Ethanolamine Phosphotransferase or produce a feed forward accumulation of Phosphatidylethanolamine, or both. The few resources that consider bidirectional or equilibrium characteristics, including Wikipedia’s CDP-Choline Pathway, exhibit bidirectional activity or at least equilibrium sensitivity within the Choline Kinase and Ethanolamine Kinase Pathway. Required for this bidirectional activity and Feed Forward accumulation of Choline Phosphotransferase immediately after Choline Kinase Catalysis that is associated with Oncology activity within is that there by both an accumulation of Choline on the precursor/substrate side for Choline Kinase as well as on the Product side of the molecular catalytic equation. Correlatively, when these analyses considered the cofactors for Choline Kinase, ATP was required for Choline Kinase Alpha along with either Choline or Ethanolamine, along with the same requirements for Choline Kinase Beta, according to the UniprotKB Database regarding Human Choline Kinase Alpha and Human Choline Kinase Beta. The exhibition of increased levels or adequate levels of ATP can fuel Choline Kinase Activity, particularly those which provides shunts around or circumvention of energy regulation pathways and energy pathways that are themselves somewhat extensively regulated by Choline availability, PEMT availability and P53. 149 150 151

LIBRARY OF MEDICINE PUBMED IDENTIFIER 11642342 Digital Object Identifier 10.1002/jmri.22517 Digital Object Identifier 10.1016/j.jnutbio.2015.05.014

Oncology that has GALPHA and RHO Upregulation are versions of Oncology in which Extracellular Ca2+ is also upregulated resulting G Protein Coupled Pathway Upregulation and subsequent upregulation of Choline Kinase. The Mechanism of Pathology seems to be upregulation of Extracellular Phosphocholine which is a feed forward Oncology Potentiator for Choline Kinase Activity by other cellular entities and the tissue area generally. This seems to be an essential assertion in Oncology generally, including Leukemia, Lymphoma, and other detrimental health statuses since Cellular Entities pervasively can exhibit upregulated Choline Kinase Phenotype. This may be a pivotal assertion in the consideration of advanced stages of Oncology which might typically consider Energy Metabolites and Metabolism and systemic interactions among Pyruvate Metabolites.152 Amino Acid Supplements including the 20 or More Proteinogenic Amino Acids, or the 18 essential Amino Acids, with removal those which affect Phenylketonuria and Ketogenic. Lysine and Leucine are Ketogenic only compared to being both Gluconeogenic and Ketogenic. Gluconeogenic Factors potentiate Pyruvate and Glucose Synthesis or intermediates of the Krebs Cycle including Alpha-Ketoglutarate, Succinyl CoA, Fumarate, and Oxaloacetate. Ketogenic Factors potentiate Acetyl-coA or Acetoacetyl-CoA. Isoleucine, Phenylalanine, Threonine, Tyrosine and Tryptophan each potentiate both Glucose and Fatty Acid Synthesis, thereby being both Gluconeogenic and Ketogenic. Phenylalanine must be managed because it contributes to metabolic impairment for Phenylketonuria conditions. Essential Glucogenic Amino Acids Include Alanine, Arginine, Asparagine, Aspartate, Cysteine, Glutamate, Glutamine, Glycine, Proline and Serine, whereas Nonessential Amino Acids which are Gluconeogenic include Histidine, Methionine, Threonine, and Valine. Ketogenic Amino Acids are considered to be Nonessential, including Leucine and Lysine. Glucogenic and Ketogenic Amino Acids include the Essential Tyrosine and the Nonessential Isoleucine, Tryptophan, and Phenylalanine. Thus, Amino acids can be utilized to manage the direction of metabolites into the Pyruvate pathway or Glycolysis with Gluconeogenic Factors, out of the Pyruvate Pathway or Glycolysis as Ketogenic Factors, while balancing of these can be potentiated by those factors which are both Gluconeogenic and Ketogenic. L-Arginine is a central factor in many conditions because it is a strong base whereas Methionine exhibits a Methyl Group. Lysine and Histidine are also Bases.153 The Wildcard or complexity in these observations seems the relationship between Choline Kinase Beta, its upregulation by phosphorylation, and the status of Choline Kinase Alpha. Similarly, the Wildcard scenario or complexity seems to include the ability of Choline/Ethanolamine Phosphotransferase to produce Phosphatidylcholine from the Ethanolamine Kinase Pathway when PEMT has become inhibited to prevent its conducting of the same synthesis of Phosphatidylcholine. The Literature clearly shows that constitutive downregulation of Choline Kinase Alpha at the Transcriptional Level Small Interfering RNA did not produce a change in Choline Kinase Beta availability, although the potential for post-translational upregulation of Choline Kinase Beta and down regulation of Choline Kinase Alpha, presumably because Protein Kinase A responds to Phosphorylation Cascade. Resultantly, there may be a presumption of direct access to Choline Kinase alpha and choline Kinase Beta because there is no inherent interactive regulation mechanism activated by changes to Choline Kinase Alpha.154 Simultaneously, this Transcriptional inhibition of Choline Kinase Alpha reduced Phosphatidylcholine Content of Cellular membranes between 71 and 60 percent along with a 36% or 35% percent decrease in cellular growth and changes to expression patterns of 476 different Genetic Transcription Products. The search for Functional interaction between choline Kinase Alpha and Choline 152 153 154

LIBRARY OF MEDICINE PUBMED IDENTIFIER 19716891 â&#x20AC;&#x153;Gluconeogenic and Ketogenic Amino Acids.â&#x20AC;? A Power Point Presentation. Website. Digital Object Identifier 10.1038/bjc.2013.729

Kinase Beta may become essential because it has already been exhibited that Choline Kinase Alpha has functional interactions that include integration with Epidermal Growth Factor Receptor that occurs correlative to availability of Protooncogene Tyrosine Protein Kinase Src (C-SRC). Tyrosine Kinase has already been presented by the Amehsi Specification as priority for inhibition in Oncology, closely following Choline Kinase Alpha 1, Choline Kinase Alpha-2 and Choline Kinase Beta in such priority.155 Pivotally, although accumulation of Phosphocholine seems to be the proximate effect of upregulated Choline Kinase Alpha and Choline Kinase generally, these analyses can exhibit the activity of Acetylcholine-O-Transferase which bidirectionally exchanges Choline and Acetyl-CoA with Acetylcholine and CoASH as factor that precedes Choline Kinase in determining the levels of Choline Phosphotransferase. Acetylcholine levels decrease 17-Fold beginning at Birth and inversion of Physiological Neurostimulation occurs as a result, resulting in Neurostimulation that increases the difference between intracellular and extracellular environment until an Action Potential Threshold is reached compared to Gestational decreases in the difference between Intracellular and Extracellular environment resultant of Post-Synaptic Neurostimulation. Similarly, the progressive decrease in Phosphatidylethanolamine Methyltransferase results in exhibition of P53 which inhibits Glycolysis and Pentose Phosphate Pathwayâ&#x20AC;&#x2122;s supplying of metabolites and precursors into the Krebs Cycle or Citric Acid Cycle, particularly Acetyl-CoA.156 The decrease in Acetyl-CoA results in the increased exhibition of Intracellular Choline. This potentially explains the Logarithmic decrease in intracellular Acetylcholine beginning at Birth. 157 158 Although there may be junctures of Ca2+ or Calcium Management in these pathways between the merging of Acetylcholine and Phosphatidylethanolamine Methyltransferase, the most obvious specifically exhibited required exhibition was a requirement for Ca2+ or other Divalent Metal Ions for Phosphatidylethanolamine Methyltransferase. This suggests that a Divalent Metal Ion such as Ca2+ or MG2+ is essential to Phosphatidylethanolamine Methyltransferases and potentially Phospholipid Methyltransferases generally. However, this particular analysis suggest that the far reaching effects of Phosphatidylethanolamineâ&#x20AC;&#x2122;s inhibition include the expression of P53, its inhibition of the Pentose Phosphate and Glycolysis Pathways, as well as correlative inhibition of the supplying of Acetyl-CoA for Acetylcholine-O-Transferase which results in Acetylcholine, a mechanism of Choline Accumulation other than the accumulation of Phosphocholine which is choline with a high energy Phosphate moiety attached to it.159 160 Gold has been isolated as a Divalent Ion, suggesting that it too can enable function Phosphatidylethanolamine Methyltransferase.161 Interestingly, to provide context for Philosophical analysis about communication through distance, location, space and time, as well as the exhibition of knowledge in different contexts within civilization, Gold is among the Divalent Metal Ions which can enable PEMT function.162 Frankincense inhibit Cyclooxygenase, while Frankincense and Myrrh can each both inhibit CFOS and CJUN, thereby also inhibiting activation of AP1 and inhibiting activation of SP1.163 Myrrh can promote tissue repair. Myrrh, interestingly, increases iNOS expression specifically as well as 155 156 157 158 159 160 161 162 163

Digital Object Identifier 10.1038/onc.2011.332 ISBN 0-87893-742-0 ISBN 0-87893-742-0 Digital Object Identifier 10.1007/BF00970530 Digital Object Identifier 10.1023/A:1010905221770 LIBRARY OF MEDICINE PUBMED IDENTIFIER 2996436 Digital Object Identifier 10.1038/nchem.2836 Digital Object Identifier 10.1038/nchem.2836 . Digital Object Identifier 10.1038/srep13668

strongly around microbial affected areas which is different than the systemic and general expression when iNOS is expressed as constitutive aspects of Sepsis. Myrrh should be specifically considered in the development of Antimicrobial factors including when managing Viral, Bacterial, Fungal or other organisms affecting Physiology Pathogenically.164 The literature suggests that the level of Choline Kinase Activity or the level of CDP-Choline pathway exhibition is directly correlated to the levels of ATP in the Intracellular Environment, clearly suggesting that increased levels of Choline Kinase is correlated to and causal of increased levels of Phosphocholine and ATP both in the intracellular environment.165 However, increases in ATP in the extracellular environment might be a presumed homologous feature of upregulated intracellular ATP and the level to which these might be contributed to Diabetic Conditions has not been presented as essential, core aspects of Diabetic Pathology or therapeutics. These seem to explain the progress of pathogenic restructuring of energy metabolism as oncological conditions progress. The upregulation of the Choline Kinase Pathway and the Downregulation of PEMT are strongly emerging as the cause of oncology and may be causal or minimally required for every health condition. Two Factors, Choline Kinase and PEMT are emerging as the simplest most direct way to intervene a detrimental health status or detrimental behavioral status. Extracellular ATP levels are indicated as being affected by Intracellular ATP and are considers as contributes to Oncological and Diabetic Pathology.166 167 168 PEMT is upregulated from Experimental or Inherent Impairment of CTP Phosphocholine Citidylyltransferase. Studies clearly show the level of PEMT activity is inversely correlated with Homocysteine Levels. 169 That is PEMT assist in managing Homocysteine toward optimal levels. Specifically, the literature suggest that Insulin inhibits the increased PEMT produced by All-Trans Retinoic Acid. This suggests that many mechanisms of beneficial therapeutics may include increasing the levels of PEMT or increasing factors which are more abundant with functional PEMT activity. Similarly, the literature suggests that there may be an allosterically presented requirement for increased levels of Choline with Diabetic Conditions. Choline and Betaine ingestion are shown to reduce detrimental outcomes in breast oncology. 170 Persistent Stress is known to cause decreases in Phosphatidylethanolamine, Ether-Linked Phosphatidylcholine, along with increases in Lysophosphatidylcholine.171 Spatially, the literature suggests that when Adenosine and Homocysteine are introduced to the PEMT Catalytic Microenvironment, the first product of PEMT catalytic Activity, Phosphatidylmonomethylethanolamine is not decreased, although the both Phosphatidyldimethylethanolamine and phosphatidylcholine are decreased. These suggest that molarity of S-Adenosyl Homocysteine, Adenosine and Homocysteine produce a circumstance in which Gradients 164 165 166 167 168 169 170 171

Digital Object Identifier 10.1590/0074-02760150295 Digital Object Identifier 10.1074/jbc.M605702200 Digital Object Identifier 10.1681/ASN.2014070721 Digital Object Identifier 10.1371/journal.pone.0002599 Digital Object Identifier 10.1074/jbc.M112.385369 Journal of Nutrition. Volume 136. Number 12. Pages 3005 to 3009. December 2006 PMCID PMC2775010 Digital Object Identifier 10.2174/2210315506666160923150904

supply molecules to an area where a molecule is being depleted, such as S-Adenosyl Methionine whereas supplemented molecules such as S-Adenosine and Homocysteine as well as Catalytically Synthesized molecules such as Homocysteine have increased density or molarity locally. Thus, PEMT exhibits the first catalytic phase of its activity to produce Phosphatidylmonomethylethanolamine, depleting S-Adenosyl Methionine of its Methyl Group to transform it into S-Adenosyl Homocysteine, resulting increased molarity of Homocysteine, increased occupation of PEMT catalytic locations by Homocysteine, decreased potential for one of the catalytic loci of PEMT to be available for methylation, and an immediately introduced requirement for gradients to supply additional S-adenosyl Methionine that has a distance and time component. Moreover, it is well known that the first Catalytic Phase of PEMT activity has the longest duration, which seems to be the result of priming of the Gradient supplying mechanisms, followed by the next Catalytic Phase which is of shorter duration, followed by the third catalytic Phase which is of shorter duration. These suggest that once the Gradients are established, the efficient supply of factors increases as a system of flow is established. However, The Catalytic Cycle of each individual PEMT enzyme may be locationally distinct, preventing an absolute contiguous scalar increase in efficiency across Enzymes, although this does not suggest that within each cellular subcompartment in which many PEMT enzymes are exhibiting Catalytic Activity could not exhibit scalar efficiency in galvanizing availability of Methylating factors upon gradients at the intracellular level or extracellular level.172 Most interestingly, this suggests that Choline which enables Betaine/Trimethylglycine/GlycineBetaine/N,N,N,Glycine-Betaine Synthesis as well as Folate availability which can determine Methyltetrahydrofolate availability, as well as Adenosine availability for Methionine Synthetaseâ&#x20AC;&#x2122;s in S-Adenosylation of Methionine, each may be essential if not prevalent determinants of Homocysteine Depletion. The ancillary sources of Homocysteine which include COMT, GNTM, Reverse Cystathionine Gamma Lyase, Bacterial Cystathionine Beta Synthase, Aspartate Metabolism, and an Ethanolamine/S-Adenosyl-Methionine pathway which these analyses have not been able to completely analyze, may be principle sources of S-adenosyl Homocysteine and Homocysteine. Most particularly, there is the potential that Homocysteine produced by PEMT is able to be selectively differentiated from other endogenous sources or selectively differentiated from Homocysteine introduced into biological systems experimentally. It has already established that Choline introduces Hydrides into Physiology and that these Hydrides have Spatial Influence that promotes Alkaline environment without being freely exhibited. Similarly, the Amehsi Specification clearly exhibits Resonance as a way for Atoms to be shared by molecules at distance, through space jumps which enable catalytic activity based upon electrons moving through space for instantaneous changes in molecular characteristics as well as the way in which molecules or atoms affect and tag each other at quantum levels. These have the potential of producing a selectivity priority within the catalytic microenvironment or produce Regioselectivity that is not ascertainable at the molecular structural level. However, there is also the possibility that differences in Homocysteine with regard to source has not been fully analyzed. Correlatively consider the molecular diagrams of Homocysteine and Cysteine which are precisely the same except that Cysteine exhibits a Bold Arrow, Bold Wedge or Bold asymmetrically shaped line that indicates that its NH2 group is oriented outward toward the reader instead of being Planar like Homocysteine. These changes in shape can indicate differences in the Adhesion Characteristics or Integration Forces between Atoms as well as determine the 172

Digital Object Identifier 10.1016/0006-291X(81)91224-9

characteristics shape, twist and writhe which are determinants of molecular interactivity. These analyses were able to find some references to Homocysteine Isomers, one of which exhibited a centrally located Sulphur Atom with Wedge indicating that NH2 groups were oriented outward toward the reader. Another article shows Homologues to Homocysteine which each exhibit different Catalytic Velocity for Lysis.173 174 175 Regardless, however, the Post Translational Modifications which cause molecules to proceed through a particular series of metabolic interactions may be increasingly similar, with regard to Phosphorylation, Methylation, Sumoylation, Acetylation, or other factors, correlative constants of location, subcellular location, or other characteristics required for a particular Enzymeâ&#x20AC;&#x2122;s activity. Quantum Level Interactions can produce fields of similarity to molecules that have interacted with one another or with similar metabolic/molecular experience. Some of the potential differences in Homocysteine include variation in Solubility, Electrochemical, Catalytic Efficiency, Polarity, Electronegativity, Electron Configuration, Resonance and Integration Efficiency. The literature describes these priorities as Atomic Charges, Polarizability, Molecular Orbital Energies, Superdelocalizabilities, Frontier Orbital Densities or Fukui Functions, Molecular Quantum Similarities and Dipole Moments.176 Pancreatic Islets, for instance, have phospholipid methyltransferase activity that which utilizes S-Adenosyl Methionine, utilizes MG2+, has its activity increased 100 Percent by Ca2+ while not affecting the amount of substrate required to reach half (Km) of the Maximum Catalytic Throughput (Vmax), and is inhibited by Ca2+ Channel inhibitors (Chlorpromazine, trifluoperazine, and dibucaine) which introduce thermal bilayer transitions of cellular membranes into Hexagonal Phases when inadequate Phosphatidylcholine is exhibited in cellular membranes similarly to Ca2+ introducing such changes in Phosphatidylcholine deficient membranes.177 Phosphatidylserine stimulates the enzyme suggesting that Phosphatidylserine is being cycled into Phosphatidylethanolamine. Arachidonic Acid and Palmitic Acid Inhibit the Enzyme. The products of the enzyme were indicated as principally Monomethylphosphatidylethanolamine, Dimethylphosphatidylethanolamine, Phosphatidylcholine and unpolarized Lipid, suggesting that the enzyme is PEMT, and when Calcium was available the synthesis of these lipids increased 131%, 60% and 46%. This study does not suggest that the enzyme is PEMT although the article was produce in 1985.178 The Ions which were effective for PEMT activity or the analyzed enzyme in this study included MG2+ and other Divalent Metal Ions, although Zinc and Strontium inhibit the Enzyme. This study suggests that Ca2+ Hyperactivates the PEMT Enzyme and the this Hyperactivation performs as Bolt On capability that does not change the M2+ throughput characteristics when the Enzyme is not saturated. The study also suggests that Insulin Secretion by Islet Beta Cellular Entities is enhanced by Methylation Pathways including PEMT, although it is now known that Choline deficiency results in inhibition of PEMT, PEMT inhibition results in P53 exhibition and Expression of Inducible Nitric Oxide Synthase, and Nitric Oxide can Deplete Calcium to cause eNOS at the Caveolae to dysfunction. eNOS dysfunction results in constriction of the Caveolae, preventing Secretion and Signal Transduction known to include Insulin, Insulin Receptor and GLUT, but possibility including most of the signals required for systemic management of Insulin and Glucose.179 173 174 175 176 177 178 179

Digital Object Identifier 10.1016/j.theochem.2003.08.029Get rights and content ISBN 9781483225609 Common Chemistry. L â&#x20AC;&#x201C; Homocysteine. CAS Registry Number: 6027-13-0 Digital Object Identifier 10.1021/jm0495529 Digital Object Identifier 10.1016/0005-2736(79)90200-1 LIBRARY OF MEDICINE PUBMED IDENTIFIER 2996436 LIBRARY OF MEDICINE PUBMED IDENTIFIER 2996436

The structure and circumstance of Choline Kinase Alpha and Epidermal Growth Factor conjugates coimmunoprecipitated from quite a few different phenotypes of Breast Oncology included upregulated C-SRC, upregulated Choline Kinase Alpha, and Phosphorylation of Choline Kinase alpha on Y197 and Y333. The Phosphorylation of Choline Kinase Alpha Y197, which is Tyrosine at position 197, and Y333, which is Tyrosine at position 333, occurred in correlation with availability of C-Src. Impedance of the susceptibility of Choline Kinase Alpha Y197 and Y333 to Phosphorylation Inhibited Choline Kinase Alpha ability to produce complexes, inhibited Epidermal Growth Factor Receptor activation of Choline Kinase Alpha, and inhibited Epidermal Growth Factor Receptorâ&#x20AC;&#x2122;s ability to activate the transcription of the genes in its response element pattern. Interestingly, inhibition of Choline Kinase Alpha resulted in inhibition of Epidermal Growth Factor Oncogenic transformation, proliferation and pathology. The contribution of Choline Kinase Alpha to diverse oncology, from these factors alone, can be shown to not only be metabolic, but instead include direct kinetic, molecular, conjugation and transcriptional activation. Additionally, Choline/Ethanolamine Phosphotransferase was shown in a study to be able to produce both Phosphatidylcholine and Phosphatidylethanolamine constitutively based upon the substrate it encounters, including exhibition of a 36 Micromolar Km for CDP-Choline to produce Phosphatidylcholine with 2 Diacylglycerol 19;1 as a cofactor and also including a 98 Micromolar Km for CDP-Ethanolamine using 2 Diacylglycerol 18;1 as a cofactor. The substrate determines the product of Choline/Ethanolamine Phosphotransferase activity although the Km are different from its substrates and the selectivity is not presented in the literature as having Regioselectivity characteristics. However, imperatively, Choline/ethanolamine Phosphotransferase can be supplied with substrate from CDP-Choline availability and SP1 is known to inhibit PEMT while upregulating both Choline Kinase and CTP Phosphocholine Citidylyltransferase to promote increases in Phosphatidylcholine Synthesis, increased levels of Phosphatidylcholine within cellular membranes, increased characteristics produced by the Choline Kinase Pathway, and decreased Mitochondrial Originated Choline/Ethanolamine Phosphotransferase Phosphatidylcholine as well as even more decreased exhibition of PEMT produced Phosphatidylcholine. Thus, the inhibition of Choline Kinase Alpha produces three other available pathways for Phosphatidylcholine Synthesis within these pathways, although these analyses show that some pathways otherwise can produce Phosphatidylcholine outside of this pattern of phospholipid to cellular membrane synthesis and migration. Inhibition of Choline Kinase Alpha and Beta causes two of these pathways to persist. PEMT, however, is observed to be downregulated by a number of pathogenic influences such that downregulation of both Choline Kinases Alpha and Beta cause one functional biosynthetic pathway for Phosphatidylcholine Synthesis and cellular membrane directed migration to persist. Choline Kinase inhibitors are likely to produce benefit from activity of the Choline\Ethanolamine Phosphotransferase Synthesis of Choline and inhibited synthesis of Phosphocholine by Choline Kinase Alpha, such that a gating mechanism occurs in which Choline is cleared through the Mitochondria before entering the Ethanolamine Kinase pathway and being distributed after Ethanolamine Kinase into the Choline Kinase and Ethanolamine Kinase Pathway, as well as being substantially produced from Choline\ethanolamine Phosphotransferase. The information then clearly shows that an early event in the emergence of Oncology and most Human pathology is the downregulation of PEMT, 16-Fold or more decrease in Choline Kinases presumably form P53 inhibition of Glycolysisâ&#x20AC;&#x2122; supplying of Acetyl-CoA for Acetylcholine accumulation, the resultant exhibition of increased availability of Free Choline without a metabolically regulated storage mechanism, Phosphorylation of Choline by

Choline Kinase by increase the Energy Potential of Choline resulting in Phosphocholine, and the upregulation of Choline by Xenobiotics, Carbonyls, Dioxins, Dioxin Like Factors, Hydrofluorochlorobromoiodino Carbons, Alkyl Halides, Aflatoxins, PCBs and other factors. These result in accumulation of Choline as Phosphocholine within the Choline Kinase Pathway. The Amehsi Specification shows that an early event in the emergence of Oncology and most Human pathology is the downregulation of PEMT, potential 17-Fold or more decrease in Acetylcholine presumably from P53 inhibition of Glycolysisâ&#x20AC;&#x2122; supplying of Acetyl-CoA for Acetylcholine accumulation, inversion of the direction in which PostSynaptic Neuronal Neurotransmitter Stimulation changes intracellular Polarity in order to reach an Action Potential Threshold, the resultant exhibition of increased availability of Free Choline without a metabolically regulated storage mechanism, Phosphorylation of Choline by Choline Kinase to increase the Energy Potential of Choline resulting in Phosphocholine, and the upregulation of Choline by Xenobiotics, Carbonyls, Dioxins, Dioxin Like Factors, Hydrofluorochlorobromoiodino Carbons, Alkyl Halides, Aflatoxins, PCBs and other factors. These result in accumulation of Choline as Phosphocholine within the Choline Kinase Pathway. Decreased Acetyl-CoA may also result in decrease CoA-SH which impairs availability of substrate for HMGCoA Synthase, HMG-CoA, and Substrate for HMG-CoA Reductase which, like HMG-CoA Reductase Inhibitors, impair the Mevalonate Pathway for Synthesis of AP1 inhibiting Isoprenoids/Terpenoids. Decreases in Acetyl-CoA also decreases the Synthesis of Malonyl-CoA, which is a central factor in both Fatty Acid Synthesis and Beta-Oxidation, and impairs a HCO3- Scavenging Pathway constituted of Acetyl-CoA and HCO3- being metabolized into MalonylCoA. Furthermore, ATP can be increasedly available for Choline Kinase attachment of Phosphate Group to Choline when P53â&#x20AC;&#x2122;s inhibition of Glycolysis/Pentose Phosphate Pathways has been surmounted, circumvented or impaired. Choline Kinase attaches Phosphate groups from ATP to Choline, resulting in Phosphocholine. Accumulation of phosphocholine in the intracellular, local area of tissue, and systemic environment can become a systemic enabler of numerous low priority, no priority, conserved, unutilized or unintended molecular pathways which potentiate emergence, progression and persistence of pathology. Choline Kinase Inhibitors that inhibit both Choline Kinase Alpha and Choline Kinase Beta prevent the accumulation of Phosphocholine and inhibition of factors or circumstance that inhibit PEMT result in better management of Choline using Acetylcholine as a Storage mechanism as occurs during Gestational Status. P53, then, also inhibits Acetyl-CoA availability for Carnitine Shuttle which is required to move Acetyl-CoA itself from the Mitochondria into the Cytosol, although the Beta-Oxidation recycles Acetyl-CoA also. Similarly, P53 inhibits availability of Acetyl-CoA for Acetylcholine Synthesis which would otherwise perform as a Choline Buffer that can prevent accumulation Phosphocholine which occurs after Choline Kinase Phosphorylates Choline. The result of P53 then can be constraint of Acetyl-CoA production which places Fatty Acid Beta-Oxidation in a distressing, depleting and downregulation potentiality in which the KREBS Cycle becomes regulated by Fatty Acid Beta Oxidation Catalysis, Carnitine Availability and Acetyl-CoA/CoAsh Balance. Because Acetyl-CoA is utilized to synthesis Cholesterol, Vitamin D, Bile Salts and essential to Steroidogenesis, P53 seems to be a participant in the deterioration of Hormone Synthesis inhibition of HMG-CoA through, disabling Cholesterol Shuttling within the Cytoplasm and Cholesterol Shuttling through START Transfer Protein Domains. Together these explain Menopause, and Hormone decreases during progressive phases of being, particularly when downregulation of PEMT is included. The tighter regulation of Acetyl-CoA results in similar unbuffered function among Acetylcholine, Beta-Oxidation to Krebs Cycle,

Pyruvate to Lactate balance, Glycolysis to Krebs Cycle, introducing increased sensitivity of these balances to environmental conditions. The literature suggests that Progesterone inhibits Choline Kinase Beta by inhibiting Protein Kinase A. Protein Kinase A would otherwise Phosphorylate Choline Kinase Beta but is inhibited by Progesterone. Progesterone, however, as do other inflammation factors or Protein Kinases, potentiates cAMP. Protein Kinase A, however, is also known as cAMP-Dependent Protein Kinase A. Resultantly, even when Protein Kinase A is inhibited at Arachidonic Acid or after Arachidonic Acid, Protein Kinase A can be expressed resultantly of accumulating cAMP which Activates Protein Kinase A or by Accumulation of Calcium during influx of Calcium presumably through interaction with G Proteins and cAMP. Digital Object Identifier 10.1242/jcs.01383. P53, then, also inhibits Acetyl-CoA availability for Carnitine Shuttle which is required to move Acetyl-CoA itself from the Mitochondria into the Cytosol, although the Beta-Oxidation recycles Acetyl-CoA also. Similarly, P53 inhibits availability of Acetyl-CoA for Acetylcholine Synthesis which would otherwise perform as a Choline Buffer that can prevent accumulation Phosphocholine which occurs after Choline Kinase Phosphorylates Choline. The result of P53 then can be constraint of Acetyl-CoA production which places Fatty Acid Beta-Oxidation in a distressing, depleting and downregulation potentiality in which the KREBS Cycle becomes regulated by Fatty Acid Beta Oxidation Catalysis, Carnitine Availability and Acetyl-CoA/CoAsh Balance. Because Acetyl-CoA is utilized to synthesis Cholesterol, Vitamin D, Bile Salts and essential to Steroidogenesis, P53 seems to be a participant in the deterioration of Hormone Synthesis inhibition of HMG-CoA through, disabling Cholesterol Shuttling within the Cytoplasm and Cholesterol Shuttling through START Transfer Protein Domains. Together these explain Menopause, and Hormone decreases during progressive phases of being, particularly when downregulation of PEMT is included. The tighter regulation of Acetyl-CoA results in similar unbuffered function among Acetylcholine, Beta-Oxidation to Krebs Cycle, Pyruvate to Lactate balance, Glycolysis to Krebs Cycle, introducing increased sensitivity of these balances to environmental conditions. Acetyl-CoA is also transform into Succinyl-CoA which results in Haemopoieticfactors, or factors exhibited in Blood, such as Heme. Protein Kinase A is shown in studies to be produced by an ancillary Pathway. Using an Activator of Protein Kinase A, iNOS and Nitric Oxide activity was exhibited in molarity reliant manner, along with an increase in cAMP that occurred at about 6 Hours after exposure to a typical activator of cAMP. cAMP resulted in similar exhibition of iNOS and Nitric Oxide. The Amehsi Specification, correlatively, has presented that the developing Oocyte expresses iNOS Constitutively, potentially to augment Turgor and Intracellular Pressurization for the developing Embryo as well as to promote cleansing of the Intracellular Environment using the Flushing mechanism which iNOS provides by moving intracellular Xenobiotics to the interstitial areas of the Plasma Membrane. However, NF kB was activated in the Nuclei ranging from 10 Minutes to 24 Hours consistently and a PKA Inhibitor inhibited the availability of NF kB only for the 1, 3 and 24-Hour Sampling but not the 6 and 12 Hour Sampling. This shows Protein Kinase A is specifically activated, even when inhibited, at 6 hours and until 12 Hours following exposure to Progesterone or any other inhibitor Potentially. NF kB activity is similarly particularly resilient to inhibition, along with iNOS and Nitric Oxide at 6 Hours and Until 12 Hours following Cellular Exposure to Progesterone or Lipopolysaccharide, as well as Xenobiotics which invoke or potentially inhibit Protein Kinase A. However, studies also show that the synchronized exhibition of cAMP, Protein Kinase A, NF kB, iNOS and Nitric Oxide at 6 Hours can be inhibited by COX-2 Inhibitors Indomethacin and NS-398, and that COX-2 and Prostaglandin E2, which are Inflammatory Metabolites of Arachidonic

Acid were the potentiators of the 6 Hour until 12 Hour exhibition of cAMP, Protein Kinase A, NF kB, iNOS, and Nitric Oxide. Digital Object Identifier 10.1074/jbc.274.44.31559. The literature clearly exhibits a Link between functional Methylation pathways and the transduction of Cholesterol across cellular membranes to begin or sustain Steroidogenesis.180 R-(+)- or S-(-)-nicotine enantiomers decrease S-Adenosyl Homocysteine 60-Fold as well as reduces Homocysteine by 15-Fold, but this suggests that both PEMT inhibition may be occurring. R-(+)- or S-(-)-nicotine 9Fold and 15-Fold reduction in S-Adenosyl Methionine respectively. PEMT function decreases S-Adenosyl Homocysteine and decreases Homocysteine. This suggest. Clearly, a direct invoking of a Pathogenic influence to PEMT by Nicotine which every Pathology also invokes either directly or indirectly. PMID 3715913. Methionine supplementation increases Homocysteine, suggesting the PEMT function may be essential during Methionine availability because alternative sources of Homocysteine may utilize S-Adenosyl Methionine without an inhibitor Influence. Specifically, although Folate may be presumed to assist in Homocysteine depletion and it is present in cellular entities generally, Folate cannot replace Choline and PEMT as source of sustain methionine availability, while Choline enables the synthesis of Betaine which BHMT uses to deplete Homocysteine. Choline is also known to increase PEMT although assuring inhibition of AP1, SP1, and Thrombin seem to be priorities in assuring PEMT also. This clearly agrees with the conclusion that Choline, Folate, Inhibitors of AP1, Inhibitors of SP1, inhibitors of Thrombin, as well as management of the ancillary factors that cause Homocysteine accumulation and management of the Primary Amehsi Specification Super Indicators are essential priorities in health services interventions and health. Management of Choline, Folate, Inhibitors of AP1, Inhibitors of SP1, inhibitors of Thrombin, and Trimethylamine-NOxide generally and in the emergency services setting, may substantially transform perspective of health efficacy and emergency services outcomes. The Prothrombinase Complex assembles on the cellular membrane Negatively Polarized Phospholipids when Calcium is Available. This is interesting because Phospholipids are known to segment Phospholipids, releasing Ca2+ which encircles the Phosphate Groups. However, iNOS is known to deplete Ca2+, including from outside of the cellular membrane. Correlatively, gradients of iNOS depletion of Ca2+ my decrease its availability away from the membrane, produce decrease general availability away from the cellular membrane, and enable more adequate distribution of Ca2+ at the membrane. Similarly, Phosphocholine is known to recruiting factors which stimulate Necrosis and Apoptosis by attaching to the cellular membrane. Additionally, it is known that a feature of Necrosis and Apoptosis is the Exposures of Serines on the Outer Extracellular interface of the Plasma Membrane, along with Carotenoid and Flavonoid balance which can flip phospholipids onto the Extracellular Interface of the Plasma Membrane responsively to changes in pH. Prothrombinase exhibits the Serine Protein Factor XA and the Cofactor Factor Va. Factor X is a Serine Endopeptidase which segments Peptide Adhesions between Proteins which exhibit Serines s the Nucleophillic Amino Acid, essentially being a Serine Protease. Influx of Ca2+, particularly associated with Diabetes, Atherosclerosis, Sepsis, Hypertensive statuses, or factors otherwise, can result in the movement of Phosphatidylserine to the Outer Plasma Membrane. Phosphatidylserine is Negatively Polarized. The literature, however, suggests that Phosphatidylserine movement to the outer Membrane can be followed by flipping of Phosphatidylserine onto the Outer Interface of the 180


Plasma Membrane. Flippases, Floppases, and Scramblases assist in movement and Flipping, although Carotenoids and Flavonoids are more precisely indicated to perform such activity in the literature which describes Phospholipids phases of structural development. Polarization seems complex in its presentation by the literature. These analyses of have presented these with regard to polarization of the cellular membrane during phospholipid catabolism of Phospholipids, releasing Ca2+ at the Membrane, which can result in Acidity correlative to Ca2+, although this is managed by Flippase, Floppases, and other factors which participate in Carotenoid and Flavonoid enabled flipping of phospholipids to exhibit oppositely polarized influences at the cellular membrane interface. Similarly, here it is presented that negatively polarized cellular membrane characteristics enable Coagulation cascade. However, the literature provided in with regard to cellular polarity suggests that at pH of 7.45 there is an ability to maintain 64.9 percent more Oxygen than at a pH of 7.30, resulting in Erythrocytes with Negative Polarity at the Extracellular Interface being less repelled by the encompassing repelling influences within biological fluid, such that these factors increase in propensity to coagulate or come into close proximity with one another. However, Negatively Polarized cellular entities should repel one another, although it seems reasonable to conclude that Negatively Polarized cellular entities may be affected by the encompassing characteristics of fluid to produce a net polarity that determines the characteristics of repelling or affinity influence. Similarly, it is possible that cellular entities only require becoming in proximity with proteins, cellular entities or other factors such that Ligand, Receptor or Secretory interactions occur. These observations are interesting because observational analyzes of the conditions that occur correlative to Oncology, seem to be, although observed, metabolically inaccurate. There is the potential that the differences in such comparative analyses occur because some factors are causal while others are resultant of oncology, as well as other being correlated to oncology. However, when observational analyses of oncology are persistent enough to be asserted, although metabolically imprecise, the should be reconciled. Such observations suggest that Acidic pH and inadequate Oxygen are pervasively exhibited along with Oncology.181 The experience of these analyses are that such assertions often are strongly accurate, even if they are not precise, with regard to correlation. Acidity 1000 times higher is suggested to occur with Oncology, presumably from increased production of Lactate from Pyruvate which is then bidirectionally transformed into Lactic Acid. However, this is known to occur as Anaerobic Glycolysis because PEMT activates P53 which inhibits Glycolysis, resulting in Glycolysis that is only a fraction of its typical activity, exhibiting shunts between Glycogen cycling and the Pentose Phosphate Pathway. Buffering is impaired in Glycolysis, Pentose Phosphate, Krebs and Glycogen Cycle, resultantly, influences can more easily cause Pyruvate to become transformed into Lactate, which is metabolic pathway that has its direction determined by the levels NADH and NAD+ respectively. Pyruvate can be directed to Lactate in order to produce additional NAD+ when NAD+ is inadequate. NAD+, when Adequate, can result in Pyruvate being directed toward Acetyl-CoA within the Krebs Cycle. There are Five or more pathways that branch from Pyruvate within Glycolysis and Pentose Phosphate impairs each oneâ&#x20AC;&#x2122;s ability to assist in managing pH as well as determining the sensitivity of Glycolysis as mechanisms of pH and metabolic management. However, Anaerobic Glycolysis might either be the circumventing of Glycolysis for Energy Production or the decreased exhibition of Glycolysis because Glycolysis is known to not consume Oxygen when it is inhibited by P53, at least as is presented in some of the literature. Other literature differentiates Aerobic compared to Anaerobic Glycolysis by which pathway is being exhibited, such as Oxidative Phosphorylation and Electron Transport Pathway for Oxidative and Glycolysis for Anaerobic. Understandably, the literature is merely endeavoring to describe that which is observed, 181

such that as long as what observed is presented as a consensus, it may not have been so important whom was accurate in such regard. That is, this may not have been important until these analyses and the emergence of literature which analyzes levels of physiology more intricate than observation of the manner in which Energy production and Glucose Consumption affect Oxygen availability. There is some literature that suggest that Glycolysis does not consume Oxygen in any regard although this is confounded by the difference in literature with regard to Glycolysis being separated from Krebs Cycle, Oxidative Phosphorylation and Electron Transport Pathway activity. Some literature suggest that these pathways are not distinct from one another while other suggest that these are different and sometimes only Oxidative Phosphorylation and Electron Transport Pathway is occurring in some cellular entities. The essential assertion here is that Anaerobic Glycolysis and Anaerobic Exercise suggest different concepts, although both of these come together in that Pyruvate has an increased propensity to be directed toward Lactate which also results in NAPH becoming NAD+. Thus, Aerobic Glycolysis occurs when there is not adequate choline, PEMT is not adequately available, P53 has become exhibited because of inadequate PEMT or impairment otherwise requiring PEMT, and cellular metabolism has found a way to exhibit Aerobic Glycolysis or Oxygen-Consuming Energy Metabolism that is inhibited by PEMT regardless of P53 being actively required to prevent such activity. How this manifests itself could be increased throughput within Glycolysis directly toward NAD+ and Lactate, as well as increased levels Krebs, Pentose Phosphate, or any other pathway inhibited by PEMT. Certainly, oncology does not seem to be adhering to any doctrine or etiquette in such regard and even Aerobic Glycolysis is not pervasively required in Oncology. However, since potential Oxygen levels in biological fluid are correlated to pH, the observation of inadequate Oxygen may be accurate although this does not indicate the cellular entities are utilizing less Oxygen. Cellular entities might exhibit increased metabolism and increased exhibition of Oxygen Consuming Energy Metabolism along with decreased levels of Oxygen in Biological Fluids as well as along with additional depletion of Oxygen from the same Biological Fluids. These seem to best explain progressed phases of Oncology. The literature regarding clotting suggests that there is an Extrinsic or Rapid Coagulation pathway along with an Intrinsic Pathway that is not as rapid. Tissue factor is expressed and requires Phospholipids to participate in Coagulation, requires any phospholipid other Phosphatidylcholine to become active when low levels of Phosphatidylserine are available, as well as can be optimal when Phosphatidylserine is adequately available. Ca2+ influx inhibits Flippase and activates Scramblase, resulting in increased Tissue Factor Activity, exhibiting the potential detrimental effects of iNOS upon Physiology, although Tissue Factor expression and exhibition Phosphatidylserine are interactive produces of Tissue Factor activation which occur in additional interactive scenario after iNOS. There are mechanisms between Coagulation potential and iNOS.182 The local Plasma Membrane Microenvironment apart from General availability of Tissue Factor at the membrane is presented as the most precise determinant of Coagulation Potential exhibited by Tissue Factor.183

182 183

Digital Object Identifier 10.1111/jth.12003

The Extrinsic Coagulation Pathway is presented by the literature to include Tissue Factor Expression from impairment of Inflammation Pathways, Integration of Tissue Factor with activated Factor VII which is another Serine Protease. Integrated Tissue Factor and Factor VII becomes activated by Thrombin with Factor VII becoming Factor VIIa, and with such activation being affected by a number of other Coagulation factors including Xa, IXa, XIIa, and the XIIa and VIIa. Tissue Factor and Factor VIIa enabled activation of Factors X and IX which become Xa and IXa. The Coagulation Cascade is inhibited by Tissue Factor Pathway Inhibitor which seems to inhibit a sensitive juncture of the Coagulation Cascade, Factor Xa. Some of the information suggest at 2.5 Nanomolar Molarity of Tissue Factor Pathway Inhibitor can inhibit the Coagulation Cascade, performing as a Trypsin Inhibitor or a performing as a Serine Protease Inhibitor. Tissue Factor Pathway Inhibitor Isoform 1 alpha also inhibits Prothrombinase.184 However Ellipsometry analysis suggests that Phospholipids, phosphatidylserine in particular, exhibit the ability to integrate with Tissue Factor Pathway Inhibitor and Factor Xa at the cellular membrane while Factor Xa can cause Proteolysis of Tissue Factor Pathway Inhibitor when Factor Xa is either uncomplexed, even when Xa already integrated with a Phospholipid, resulting in release for both Tissue Factor Pathway Inhibitor and Factor Xa as Solute. The Extrinsic Coagulation Pathway begins with impaired tissue, expression of Tissue Factor, Integration of Tissue Factor with Factor VII, and exhibition of Serine Protease Activity to cause Proteolysis for Factor 9 and Factor 10. The Extrinsic Coagulation is suggested to begin with Factor XII which is inherently circulated factor in HaemopoieticFluid, or blood. Factor XII exhibits Fibronectin Homologue Domains, Epidermal Growth Factor Domains, a Kringle Domain, Light Extent Region, an Fnl EGF Fibronectin Like Epidermal Growth Factor Tandem Moiety as well as Proline Rich Moieties. Factor Xa produces Thrombin through its Serine Protease activity which Proteolyzes Prothrombin to produce Thrombin. Thrombin, then can exhibit its own Serine Protease activity which includes Proteolysis of Fibrinogen to Produce Insoluble Fibrin strands. This is interesting because Thrombin inhibits PEMT and thus inhibits the Serine Protease Activity which PEMT exhibits at the intracellular level. Thus, thrombin produces a gradient between intracellular Serine Protease proteolysis products as well as presumably Amino acids in the extracellular environment comparatively to the intracellular environment which would otherwise be supplied with Amino Acids by PEMT Serine Protease Activity. Fibronectin is produced through Transcription and performs as a tissue scaffolding and extracellular matrix factor that occupies space between cellular membranes. Fibronectin attaches to integrins which are cellular membrane spanning proteins that connect the intracellular Cytoskeleton with the Extracellular Matrix, Collagen, Heparan Sulfate Proteoglycans, as well as other Cellular entities. Soluble versions and Insoluble versions of Fibronectin are known, being produced by Hepatocytes in the former instance and Fibroblasts in the latter instance. Wound Healing, Embryonic Development, Cellular Adhesion, Cellular Growth, as well as Migration and Differentiation affected or modulated by Fibronectin. Fibronectin is known to occur as a Dimer or two Domain Moiety, connected by C-Moiety Disulfide adhesions while each molecular Domain presents as Beta Sheets known as a Beta 184 Digital Object Identifier

10.1073/pnas.131 0444110

Sandwich that cannot be opened in Type I or Type II version while being able to be opened in the Type III version because there are no Intramolecular Disulfide Adhesions to keep the Sandwich Structure Closed. The loci for Fibronectin integration with factors may be specific. Arginine, Glycine and Aspartate attach to cellular entitiesâ&#x20AC;&#x2122; Integrin at Location 10 of the Version III Fibronectin, while alpha5beta1/alpha5beta3 Integrin Modulation occurs at the same location. Location 9 of Version III exhibits an alpha5beta1 Integrin location in Fibronectin version III. Fibronectin integrates with Collagen spanning Loci 9 to 6, Fibulin spanning loci 14 to 13, Heparan/Syndecan Spanning location 14 to 12, while the location extending from 12 to 10, as well as extending from 5 to 1, are utilized for Fibrin. Matrix Metalloproteinases and other Proteases are secreted by Fibroblasts as well as some other cellular entities, which resect Fibronectin Scaffolding and Matrix, although unless wound healing is exhibited in which constriction of the Fibronectin/Fibrin Coagulation Loci is consider an optimal process, then a regenerative accompanying synthesis of Matrix/Collagen/Connective Tissue occurs along with resection. Fibronectin is considered essential for Embryonic Development, performing as guide for cellular superstructure development and the inadequacy of Fibronectin impairs development of Mesodermal tissue, Vasculature and Neural Tubes, as well as inhibits the Familiar Gastrulation Phase of Development which these analyses exhibit as being inhibited by Homocysteine. Correlatively, Homocysteine is known to occupy Fibronectin, causing the increase in levels of Free Fibrin, and resulting deposition of Fibronectin in tissue such as Cardiac Tissue while changing the Coagulation characteristics of HaemopoieticFluid. Fibrin, produced by Thrombin Proteolysis of Fibrinogen, is suggested in some literature to begin to Polymerize immediately although other literature suggests that Fibrinogen is segmented into Fibrinopeptide A and Fibrinopeptide B, such the Peptide A segmentation denudes a Glycine, Proline and Arginine Knob region which fits into a Pocket exhibited by other Fibrin molecules unless inhibited by the GPRP molecule which exhibits Glycine, Proline, Arginine, and Proline in sequence. This Glycine, Proline, Arginine, and Proline Sequence is suggested to be a potent inhibitor of Fibrin associated Coagulation.185 Homocysteine can occupy Fibronectin and prevents its interaction with Fibrin, resulting in increased Free Fibrin and Fibronectin Deposits in tissue. 5 molecules of Homocysteine were found to integrate with Fibronectin at its C Moiety near the Fibrin Interactive Location and the inhibited interaction of Fibronectin and Fibrin did not change the ability of Fibronectin to produce adhesions with the other factors with which it integrates. This provides a model of change tissue characteristics promoted by Homocysteine which change the mixture of Extracellular factors, Matrix and molecules to which Fibronectin integrates. Fibrinogen Peptide A and Fibrinogen Peptide B produce typical Coagulation upon scaffolding although inadequate segmentation of Peptide B results in a prevalent Peptide A coagulation which is thinner presumably because the fibers are thinner with particular orientation of Knob and Hole interactions of Peptide A.186 Platelets become activated by Platelet Activation Factor including that induces by Epidermal Growth Factor, such that Platelets also participate in Coagulation, accompanied typically by Fibrinogen Polymers and Fibronectin to produce the Homeostatic Structural Repair, Filler, or Occupying Material.

185 186

LIBRARY OF MEDICINE PUBMED IDENTIFIER 8428923 Digital Object Identifier 10.1182/blood-2012-09-306639

Factor XII, if escaping from the Vascular pathway and interacting with tissue such as Collages, Factor 12 becomes activated. Factor XII is activated by Factor XII is activated in the Intrinsic Coagulation Pathway by Negatively Polarized factors including Glass from testing surfaces or ingested table Salt which can exhibit glass or Silicates, Phosphatidylserine, and other factors. These analyses suggest that Factor Xa activates Factor XII because Factor Xa participates in the Extracellular Membrane exhibition of Negatively Polarized Membrane Phospholipids, as well as activation of Thrombin. The literature confirms that Table Salt can exhibit Aluminum Silicates, Cyanide conjugates and Talc, each of which can produce toxicity although Silicates can cause perforations in the Vascular Epithelium, resulting Scar Tissue, attachment of Immunological Factors, and contribution to vascular conditions.187 The interaction of Coagulation factors with Negatively Polarized factors explains why Choline, its introduction of occupied anhydride, and the basic influence exhibited by Choline exhibited factors without presented negatively polarized interaction loci. Choline assists in managing Coagulation pathways be preventing the increase Negatively Polarized factors which activate the Coagulation Cascade. The accumulation of Acetylcholine then can produce a Basic Influence in cellular entities and Physiology, including 17-Fold more increased level of such influence in cellular entities. This is augmented by Hyaluronic Acid inhibition of Lymphocyte attachment to tissue and inhibition of Lymphocyte attachment to Lymphocyte Receptors which can inhibit PEMT through the MAPK, PI3K, cFOS and cJUN signaling pathways. The literature clearly indicates that Hyaluronic Acid is produced at a concluding aspect of both the Pentose Phosphate Pathway and Glycolysis. Inhibition of PEMT results in P53 which inhibits both the Pentose Phosphate Pathway and Glycolysis. Specifically, the Synthesis of Hyaluronic Acid potentiates Glucose, then Glucose-6-Phosphate, Bidirectional exhibition of Fructose-6-Phosphate, Glucosamine-6-Phosphate which can be also be obtained by a shunt from Glucosamine while consuming a molecule of ATP, followed by N-Acetylglucosamine-6-Phosphate which can also be obtained by a shunt from N-Acetylglucosamine while consuming a molecule of ATP although Glucosamine and Acetyl CoA may be consumed to produce N-Acetylglucosamine. Following N-Acetylglucosamine-6-Phosphate, bidirectional exhibition of N-Acetylglucosamine-1-Phosphate is potentiated, followed by UPD-N-Acetylglucosamine which then potentiates Hyaluronic Acid.188 Thus EPA and DHA which inhibit inflammation, ablates NF kB prevention of Apoptosis, inhibit Apoptosis and prevent Necrosis does not prevent development cascades, cellular deterioration or Coagulation. Instead, together these cause such pathways to be directed toward developmental programs including the Gastrulation development and redevelopment program that enables the Embryo to first transform into three layers of major Physiological structure. These strongly suggest that detrimental aspect of progressing age and human disease might be best described as entropic influences to the pre, constitutive and post gastrulation development program. The Amehsi Specification suggest, in its incipient observations that it seems that detrimental Physiological outcomes might most resemble the prevalence or dominance of the inflammatory pathway response at loci of impairment or degradation comparatively to the regenerative program. Objectively, these analyses confirm such cursory observation. These analyses have exhibited that these factors are differentiating variables in the development of the Haploid Cellular entity when it exhibits the most incipient aspects of development, emergence of gastrulation and 187

Sodium Silicoaluminate. The Befoodsmart website.


Digital Object Identifier 10.1530/rep.1.00225

its layers of major anatomical structure, regeneration of tissue, the exhibition of the regenerative Blastema, the exhibition of Scar tissue instead Scarless Wound Healing, and the Inflammation Cascade that is the principal cause of systemic deterioration in Physiology. It is most interesting here because Homocysteine is considered by some studies to be a principal factor in Human Physiological and behavioral outcomes while others plainly suggest that it is insignificant, particularly when it is known that Homocysteine impairs Gastrulation and degradation of Physiology pervasively occurs in patterns that suggest that gastrulation is impaired in its regenerative phase. These analyses are beginning to show that as understanding of Physiology occurs with a purpose of achieving indefinite span of vital being and optimal health, that there is convergence of capabilities required to produce such an outcome instead of divergence into complex array of factors and capabilities. Perhaps humanity and health systems must permit the consideration of less complex solutions to optimal health. Factor XIIa then can activate Factor XI as well as activate Prekallikrein which is a precursor of Kallikrein which

then performs it Serine Protease activity which modulates Kinins including Bradykinin and Kallidin as Vasodilators, modulates Inflammation, HaemopoieticPressure and Control, as well as manage Coagulation and Discomfort. Kallikrein results in Desquamation or Skin Peeling, as well as changes to HaemopoieticPressurizations and Semen Liquefaction. The Intrinsic Pathway then, after Factor Xa activation of Factor XII, followed by Factor XII activation of Factor XI, then exhibits activation of Factor IX by Factor XI, followed by activation of Factor X by Factor IX. Factor II is activated in the Intrinsic Coagulation Pathway by Negatively Polarized factors including Glass from testing surfaces or ingested table Salt which can exhibit glass or Silicates, Phosphatidylserine, and other factors.189 The Intrinsic Coagulation Pathway thus include a Cascade of Serine Proteases in which segmentation and activation occurs beginning with Factor XII, then XI, then IX, then X. Interestingly, the Amehsi Specificaiton presented an anology of particular relevance to the potential exhibition of silicates in salt. The Analogy, however, presents sugar in context of progressive exhibition of dissociation from reason. Pivotally, these analysis have found that Sugar, particularly Cane Sugar, exhibits increased levels of Silicates, potentially suggesting that the impairing influence of high levels of Sugar in physiology may be substantially or even principally the result of Silicates which impair Vascular similar the silicates in Salt Products might impair vascular. The analysis which presents how dissociated from reason translative processes can be in civilization observes that Sugar Beets may have been substantially increased percentage of Food and Nutrition in earlier eras, particularly being useful because the increased levels of Trimethylglycine in Sugar Beets stabilize Quarternary Molecular Structure and enable typical function to occur during extreme environmental conditions as well as during extreme aspects pathophysiological conditions. However, Sugar Beets, once modern Civilizaton emerged, required the exhibition of a System to reliability produce, harvest, and transport Sugar Beets to the consumer, as well as compete with other nutritional items. This system, therefore, immediately began to prioritize the Organization, the system of Sugar Beet Industry, the food industry generally, and therefor profitability to maintain the ability to obtain people for activities and capabilities to perform required activities. Once populations whom were mostly conduting activities in outdoor conditions, as well as those whom had experience the benefit of Sugar Beets or whom had been acculturated into Sugar Beet Ingestion 189

Dr. L. Coldwell.

become no longer exhibited, Sugar Beets became considered for their characteristics comparatively with other Foods and factors in civilization, without regard to the benefits of Sugar Beets otherwise which other foods have not ability to or priority in assuring. Therefore, Sugar Beets began to be considered for their ability to provide Sugar. Again, progressively, the costs of production of Sugar increased along with minimum pay standards, costs of benefits for workers, equipment, utilities and transportation, such that the practicality of Sugar Beets being used to produce Sugar become diminished when the opportunity to utilize Sugar Cane in Regions or Nations in which costs workers, equipment, and supplies are only minuscle compared to the same costs in the United States. Resultantly, Sugar Beets became less practical because generations became less aware of the benefit of Sugar Beets other than as Sugar Factors, such that more profitable ways of producing sugar may have seemed possible. Pivotally, Sugar Beets exhibit less Silicates than Sugar Cane and exhibit Trimethylglycine at increased levels to augment the Choline context of Sugar Beets. Sugar Cane is a Major Source of Silicates and the literature clearly presents that Silicates are substantially exhibited in the production and productized output of Cane Sugar. However, when literature regarding Silica was analyzed, an interesting duality emerged in which a particular article clearly presented in small mammals that Vascular deterioration occurred resultant of silicates, while another article presented that Silicates factors benefited Aortic Plasticity because Silica is a major component of Vascular Plasticity Characteristics. These required a more thorough analysis.

A Particular research article presents three analytical variable groups of Small Mammals in which either 1% Calcium and CaCO(3) as Group A, Coral Sand and Inadequate Calcium as Group B, or 50 mg/kg of Silica along with 1% Ca and CaCO(3) as Group C were instrumented. Group A exhibited an increase in Vacular Pressure to 207 mm Hg whereas Group B exhibited an 18 mm HG lower Vascular Pressure and Group C exhibited a 16 mm Hg lower Vascular Pressure than the 207 mm Hg control Group. However, Magnesium Absorption was increased 77% when untreated cellular entities were provided Physiological levels of Magnesium along with Silica compared to Cellular Entities only provided Magnesium. Also, small Mammal Species provided Magnesium and Silica along with Control levels of 1% Calcium and CaCO(3) exhibited Systolic Vascular Pressure levels which were decreased by 17 mm Hg when compared to such Organisms which exhibited Magnesium inadequacy regardless of if Silica as added or Not. Thus, Magnesium manages the changes produced by adding Silica to cellular entities and the lowering of Vascular Pressure using Silica required the exhibition of Magnesium. Silica and Coral Sand provided to such Small Mammal Species upregulated Angiotensinogen Expression while Silica also upregulated Peroxisome Proliferator Activated Receptor Gamma. Renin or Angiotensinogenase is known to exhibit Aspartate Protease activity using Angiotensinogen as a substrate, resulting in synthesis of Angiotensin which activates a system among Renin, Angiotensin and Aldosterone that is known to manage volume of extracellular fluids including Blood Plasma, Lympoh and Interstitional Fluences, although Arterial Vasoconstriction is also managed by these factors to effect Arterial Vascular Pressurization. PPAR Gamma is know to decrease inflammation in Vascular cellular entities including Epithelium, as well as increase Paraxonase 1 synthesis and as well as increasing Inuslin Sensitivity to promote decreases in Circulating Glucose. Similarly, Inducible Nitric Oxide Synthase is upregulated by Silica exposure, along with increase in Neutrophils, Protein Molarity, Broncoalverolar Lavage Fluid exhibiton of Lactate Dehydrogenase Activity.190

190 Digital Object Identifier 10.1186/1743-8977-3-14

The process is enhanced in rapidity through the TF-7 Complex activation of Factor 9, which integrates with Factor 8 enabled by Factor 8 circulatory availability as Conjugate to von Willebrand Factor, resulting in enhanced exhibition of Factor 10. The Cascade, as such, amplifies Factors 5, 8 and 11, followed Factor 11 enhancement of Factor 9 availability.191 Additionally, Magnesium is known to inhibit iNOS activity and decreases in magnesium are known to upregulated iNOS activity such that Curcumin, a known inhibitor of iNOS, alleviates the increase in iNOS resultant of decreased levels of Magneisum. Silica is also known to perform as Coagulation Enhancing factor in experimental applications.192 These all suggest that Silica introduces a substantial inflammatory response and such response includes activating of secondary factors to manage such inflammatory response, potentially causing Silica to be mistaken for an inhibitor of Inflammation. Imperatively, exhibiting a typical inadequately proficient perspective of some therapeutics, Silica could be mistakenly utilized as an anti-inflammatory Therapeutic because only its effect is considered instead of why it is requirement being prioritized for intervention and instead of understanding how it results in anti-inflammatory activity. Although numerous aspets of inflammation are presented here which are the result of Silica in Vasculature or Epithelium otherwise, iNOS upregulation by Silica most presents how Therapeutics can be less than optimal when consider only in how the cause particular effects because ancillary change caused by therapeutics, the precise mechanism of action caused by therapeutics, and extended duration effect of Therapeutics which is an essential feature of iNOS enabled pathology, all can be as important or more important than the effects which are attributed to a pharmacological factor. These clearly suggest that regardless of the inclusion of Silica in Aortic Superstructure Plasticity, circulating Silica cause iNOS and number of other Pathological change, particular in Cardiovascular Endothelium and particularly within Vasculature. Similarly, Sugar and Salt can contribute silica to nutritional regimens which results in diverse pathophysiogical changes unless versions of these with decreased levels of Silica, such as Beet Sugar, Stevia, or other, as well as Ancient Organic Natural Pink Himalayan Sea Salt, are prioritized for purchase and inclusion in how one has their food items prepared.193 194 195 196 197 Silicates can improve the resilience of plants, such as Sugar Cane, to insects and environmental influences and are among the most abundant minerals in the agricultural soil environment. Phenols and Magnesium, however, are known to potentially integrate with Silica to produce Crystylized versions, potentially explaining how silica results in decreases in Magnesium although iNOS inhibition may also be among such mechanisms of increased Magnesium absorption. However, again, imperatively, these analysis have enabled very precise and improved consideration of those factors which populations consider mundane, safe and essential, such that Water, Energy Fields, Internet, Commuications fields, Sugar and Salt, all may have detrimental potential which seems somewhate completely unnecessary. Most imperatively, because pervasively therapeutics and diagnostics have not characterized, acknowledged and managed those factors which are most empirically causal of detrimental physiological outcomes and causal of susceptibility to systemic interactions which result in detrimental behavioral outcomes, such obscure detrimental factors may have been heretofore difficult to ascertain.

191 Digital Object Identifier 10.1021/bi972194 192 PMID 29756266 193 PMID 21419319 194 PMID 9022280 195 National Library of Medicine Article PMC5126840 196 PMID 12570925 197 PMID 7573390

Imperatively, similarly to all of the findings presented by the Amehsi Specification, there isnâ&#x20AC;&#x2122;t an individual, group, organizations, systems, industry or nuance of civilization to which such less than optimal outcomes can be attributed. Instead, it is the conditions, circumstance, detrimental factors, outcomes and nuances of the status quo which have been essential to preventing the alleviation of these less than adequate factors. Instead of attributing to such entities causality for inadequate resolution of challenges to the Physiological, Behavioral, Human and Social Condition, these are merely opportunities for the transcendence of Humanity and the surmounting of such challenges are increasingly becoming mundane. Platelets, it should be presented, constitute a layer within Vasculature that is essential for sustaining permeability and surface structural Characteristics such low platelets indicate potential for impair vascular characteristics. Megakaryocytes produce Platelets typically, it is suggested, at a level of about 3000 each, with daily replenishment of Platelets. Thrombopoietin in Hepatocytes direct the Synthesis of Megakaryocytes, as well as Platelet Production. The Spleen represents a Storage location for Platelets and can be induced to secrete these by the Sympathetic Nervous System. It is suggested that Platelets endure for as long as 9 or 8 days, although it has not been presented how these are affected by producing optimal Physiological characteristics. None of the observed limitations within Physiology should be considered to be assuredly known because these pervasively are determine utilize less than optimal Physiological characteristics. However, BCL XL is consider a synchronizing mechanism for Platelet duration of exhibition. Plasmin is also an Enzyme which should be presented since it participates in Fibrinolysis, or the deterioration of Fibrin Coagulation Products as well as enables Proteolysis of other Plasma Proteins. Again, Plasmin is a Serine Protease. It activates Collagenases, Weakens the Perimeter of the Graafian Follicle resulting in Ovulation, actives Complements Immunological Factors, segments Fibrin, Fibronectin, Thrombospondin, Laminin, and Von Willebrand factor. The best way to consider Plasmin is to consider it as a Plasma Digestive Peptide because it is considered to be a Trypsin, like some Digestive Peptides. Plasminogen I and II are precursors of Plasmin. Plasminogen I is recruited prevalently to Coagulation Loci where its two Glycosylation Moieties are useful in deteriorating coagulation factors while Plasminogen II is recruited to the Cellular Surface where its activity is performed using a Type O Sugar Linked to its Structure. Plasminogen is converted to Plasmin at the location at which Coagulation occurs as well as at the cellular surface, producing a relaxed version of coagulation material to replace the closed structure version of coagulation material. Plasminogen transformation into Plasmin and the Fibrinolysis activity of Plasmin are enabled by Tissue Plasminogen Factor, Urokinase Plasminogen Activator, Factor XII as well as Kallikrein. The use of TPA or Tissue Plasminogen as Thrombolysis factor has received resistance from the clinician community. Some articles suggest that tPA administration increases the potential for impairment or abated vital being, according clinical statistics. Importantly clinical studies are pervasively misleading because every health consumer exhibits such diverse nuances of physiology, behavior, nutrition, group of contributing circumstances, Estrogen Status, Phospholipid Synthesis Status, Genetic status, care environment, ancillary practice characteristics by providers, that differences in outcomes between groups may pervasively be external to variables including a survey or clinical analysis. The best example is that level of energy emitting power infrastructure and devices which enhance Inducible Nitric Oxide Synthase, Uncoupled Nitric Oxide Synthase, Peroxynitrite, all of which constitute clinical neurological tissue deterioration as principal concluding phases of Pathology, all may vary substantially with the Care environment or even time of day when care is provided. The instance in which meals are typically obtained as well as the changes in

energy output in a power grid both culminate in contributed to the time of day when sudden adverse health events most often occur, right before none and in the early evening. Clinicians such should focus on causal mechanisms uses these as filters for clinical information. Clinical status with large and heterogenous populations are not optimal at all because the diversity of the population makes causal linkages impractically to ascertain. However, a population of a few patients in which precise nuances of genetics, physiology, pathology, nutrition, behavior, and environment are known as well as are linked to nuances of outcomes are the best clinical studies. Health consumers are beginning to not accept that their care is being determined by statistics that presume that abated vital being will occur simply causes it may not seem practical to produce precise map to the clinical and causal molecular mechanisms to their condition. Large clinical studies are based on such a supposition. A large number of individual or few participant clinical studies which can be utilized to precisely map effective diagnostics, therapeutics, clinical care regimens cannot possibly be substituted for by one or a few large clinical studies. However, it is required to make important distinctions between the intent of therapeutic and how health providers much architect groups of therapeutic capabilities into care which alleviates an adverse health outcome and manages a patient to optimal health and behavioral status. While particular therapeutics are produced to alleviate an observed tangible factor or indicative clinical indicator, care requires careful assessment of how an adverse health or behavioral outcomes emerges, imparts detriment, persists and progresses, as well as it how such outcome circumvents physiological prevent, alleviating or regeneration capabilities. Stroke, such as Ischemic Stroke, is not caused by coagulation. Stroke, as is almost every other adverse health event, primarily caused by persist exhibition of Homocysteine over 1 Micromole per liter for subclinical and Homocysteine over 6 Micromoles per liter for clinical manifestation of conditions required in every detrimental Human physiological outcome. The best or primary indicator of any sudden adverse health event, perioperative complication, or sudden adverse health event is Trimethylamine-N-Oxide which causes countless minuscule Strokes among tissues, organs and vasculature as well as mimics Homocysteine in its other detriment. Homocysteine accumulates because of impaired function of the enzyme Phosphatidylethanolamine Methyltransferase, a Choline deficiency, inadequate exhibition Trimethylglycine which is required to deplete Homocysteine, inadequate levels S-Methylmethionine which uses an alternative enzyme Homocysteine Methyltransferase to deplete Homocysteine, inadequate methylfolates which use Methionine Synthase to deplete Homocyteine, and inadequate use of Dimethylacetothetin/Dimethylsulfonioacetate/Sulfobetaine which has been known since 1878 to deplete Homocysteine with 700 times the efficiency of Trimethylglycine and the Enzyme ThetinHomocysteine Methyltransferase has been hidden from public scrutiny even today with only obscure references in the SNOMED literature while it is widely used to assure the health livestock use for Agriculture. Additionally, the use of Pharmacological factors pervasively affects Cytochrome P450 Methylation/Hydroxylation capabilities to deplete drugs from bioavailability as well as to activate Prodrugs, both of which increases the phases of methylation required to metabolize pharmaceuticals as well as sequesters away methyl groups to exacerbate the deficiency which is the primary cause of pathology in Mammalian populations. Additionally, accumulation of Dimethylgyclyine from Trimethylglycine activity can inhibit Homocysteine depletion, and can be remediated by 5,6,78 Tetrahydrofolate, Zinc and Riboflavin.

Although there is a potential that Pharmological factors compete with Methylation performed by COMT, there is also a potentially that Cytochrome P450 factors may demethylate Pharmacological molecules and there is a potential that the Hydrolysis of Estrogen could be enhanced. Hydrolysis of Estrogen can be beneficial typically, although the impaired capacity of COMT can cause accumulation of Hydroxylated Estrogens, which can be detrimental. Regardless, Pharmacological Factors can inhibit PEMT constitutively, cause increased Homocysteine, and result in competition for resources required by PEMT, particularly Methylation resources. However, pervasively, the clinical information shows that Pharmacological factors have improved the health of those among the population whom are diagnosed with detrimental physiological outcomes, clearly suggesting that regardless of the platform which seems to exacerbate the conditions required for detrimental physiology and behavior, Humanity has benefit tremendously from the Pharmacological industry particular in understanding of how and why therapeutics are successful as well as how and why these are less than successful. Certainly the status quo prioritizes how such industries sustain economies, and this cannot be excluded in any regard. However, the Amehsi Specification has clearly presented that has been an awareness of the those molecular pathways and metabolic factors which separate Pharmacological therapeutic priorities at molecular levels from those which constituted optimal biological function, and cannot in any regard be clearly presented that any one company or organization has been aware of the complete pathway with clear knowledge of the intricate mechanisms which these analyses describe. Certainly, no individual has seemed to have been provided a priority of ascertaining the nuances described here, although systems constitutively, as neural networks affecting algorithms and patterns of function may have exhibited some level of awareness in behavior and outcomes. The adversarial nature of such systems particularly in business or other areas, seems to have been essential in preventing and industry level synapse to emerge which can be consciously applied by Humanity in resolving much of the nuances of complexities described here. However, the Amehsi Specification was able to produce an experimental example of the way in which events which have already occurred, health statuses which have emerged or might have emerged, as well as Manifests characteristics in an information systems can be deterministically affected by events which occur later or the charactersitics of information systems which occur afterward. These suggest that some and perhaps much of the improvements occurring in therapeutics may be the result of the merely conducting activity that is reasonably correlated to those impaired characteristics which are causal of detrimental outcomes. Indeed, the Amehsi specification presents more than 1 solution which beneficently manages the way in which information systems and statistics can affect outcomes detrimentally and endeavors to project optimal therapeutics and optimal biological function into preceding eras, epochs or instances of a patients span of Vital Being, including incipient aspects of Care. The most imperative conclusion here is that some of the indadequate precision in therapeutics at such levels may reflect Wisdom, the kind of Wisdom which seems to be impractical in the health and medical industry, when the potential to produce Harm cannot be reasonably ascertained, and the potential that such harm may mitigate benefit may be presented. These analyses have prioritized ascertiaining, presenting and producing ways of alleviating such uncertainty at therapeutic, molecular, metabolic, physiological and in other contexts. However, the ability to interact into antecedent and subsequent eras which these analyses show are somewhat certainly occurring in every instances of vital being, may be way of managing such uncertainty in outcomes. The ways in which interactions through distance, location, space and time might occur have the possibility of shaping those events which may have already occurred, resulting in adjudicative interactions among systems of

dynamics, systems of civilization and systems of the Universes. The only way to be sure that these are consistent with Humanity and the incipient favor which has enabled Humanity to emerge as it may now be, as well as the potential which such favor as projected into the epochs which are to come, is to proceed in a most beneficient and product presumptive context in such regard. Humanity seems to be been afforded the potential of indefinite span of vital being and perhaps all of the detrimental outcomes which Humanity may now have the potential to incur seems to be produced as a result of the ways in which abated vital being had emerged, has persisted and now requires becoming something that Humanity has transcended together. Thrombin is produced in pathway that includes and requires Choline deficiency, phospholipase A2 inflammation pathway which catabolizes Phospholipids from cellular membranes, and the primary detriment caused by Thrombin is the inhibition of Phosphatidylethanolamine Methyltransferase which is required in every Human disease, pathology and detrimental behavioral outcome. Phosphatidylethanolamine Methyltransferase produces a number of factors which are known to structurally degrade almost every Carcinogen, Toxin, PCB, Dioxin, Hydrofluorocarbon, Hydrofluorobromoiodino Carbon, Aflatoxin, Aromatic Polycyclic Hydrocarbon H2S, CO2, while enable resumption of DNA Synthesis, RNA Synthesis, DNA repair, DNA Replication, Synthesis of Phospholipids for Membrane, resumption of Glycolysis, resumption of Pentose Phosphate pathway, depletion of 50% of Glucose from circulation, transport of Glucose, dilation of the Caveolae required for Insulation or other Signal Secretion as well as Signal Transduction, along with exhibition of Serine Proteases which degrade pervasive molecules to their constitutive amino acids including performing the precise role which Plasmin performs as a therapeutic. Importantly, inhibition of Phosphatidylethanolamine Methyltransferase which is a concluding element of the CDP-Ethanolamine/PEMT/LPCAT pathway results upregulation of the CDP-Choline Pathway which over produces Phosphocholine and phosphocholine is constitutive element of Platelet Activation Factor. Adding Trimethylamine-N-Oxide to this mix, which also inhibits Phosphatidylcholine and cause countless ischemic strokes in the tissues, organs and vasculature, is more than enough to cause every sudden adverse outcome include almost every instance of Paralytic Status which progresses to deterioration of Neurological tissue that is detrimental enough to be considered irreversible. Lysophosphatidylcholine Acyltransferase concludes PEMT activity because PEMT integrates increased levels of Docosahexaenoic Acid which impairs Phospholipase A2 and other Phospholipases inflammation activity which produces detrimental inflammation versions of Leukotrienes, Prostaglandins, Eicosanoids and essential precursors to Thrombin, while LPCAT catalyzes the reintegration of Fatty Acids freed by Phospholipases into Phospholipids, particularly assuring docosahexaenoic Acid availability and particularly preventing Arachidonic Acid from being transformed into these group of potentially detrimental inflammation factors. Similarly, the polarity of Phosphatidylcholine in the Plasma Membrane inhibits Coagulation Cascade while the exhibition of Phosphatidylserine promotes coagulation because of its polarity which enhances the coagulation cascade. Imperatively, every Ischemic condition and even progressed aspects of Hemorrhagic event exhibits impaired Vasomodulation, which can be immediately repaired by assuring Tetrahydrobiopterin, L-Arginine, Choline, Iron, Vanadium, and the factors presented here otherwise. Providing a diverse Coverage Antibiotic, a Probiotic, a spoonful of balsamic Vinegar and a spoonful of Olive oil, as well as providing Catalase, Superoxide Dismutase, Glutathione, Glutathione Peroxidase, Reduced Glutathione, and contriving the 7 or 8 factors which reconstitute enablement of PEMT along with depletion of Homocysteine can stop strokes and sudden adverse health events Cold within moments of beginning an emergency interaction while pervasively preventing these from occurring if used preventively.

Presenting this again for review, Coagulation is not the cause of Ischemic Stroke. Vasoconstriction, impaired Vascular function, the inhibition of the CDP-Ethanolamine/PEMT/LPCAT pathway, the upregulation of the CDPCholine Pathway, each are essential mechanisms causal of stroke. Thee may also be the cause of every other disease or adverse physiological outcome. Artificially limiting a Thrombus or Coagulation Loci as the cause of Stroke presents only the Emerged Tangible Outcome and inadequately deprioritizes how the condition emerged, imparts detriment, persists, progresses and circumvents physiological mechanisms of alleviation, reversal and regeneration of optimal physiology. Even paralytic status from pH out of functional ranges are primarily caused by these same circumstances, can be reversed by reconstituting of these pathways to optimal, and paralytic statuses are not detrimental while even being helpful unless clinicians allow Neurological tissue to deteriorate while the paralytic status is being exhibited or allowing deterioration of neurological tissue otherwise. The literature observes that Trypsin, which is a Serine Protease, and not Chymotrypsin, has an increased affinity for Trimethylamine-N-Oxide than it does for Glucose. Impaired or inhibited Phosphatidylethanolamine Methyltransferase function impairs the absorption of Glucose by inhibiting Glut 1/3/4 availability as well as inhibiting Insulin Receptor, while inhibiting PEMT also inhibits Glycolysis and Pentose Phosphate Pathway through activation of PEMT. Similarly, inhibiting of PEMT and upregulation of P53 constitutively stimulate expression of Inducible Nitric Oxide Synthase which can deplete Calcium using the perforating the Endoplasmic Reticulum by Phosphoinositide 3 Kinase (PI3K) to deplete Store Operated Calcium, as well perforating of the Plasma membrane by PI3K to deplete extracellular calcium, L-arginine, and causing collapse of the sheathing encapsulating cellular entities including the Sarcolemma. The activity of Plasmin seems to be effective in Stroke because it performs as a Trypsin and Metabolizes Trimethylamine-N-Oxide, while the accumulation of Glucose or Sugars in circulatory pathway which is a feature of impaired PEMT suggest that Trimethylamine-N-Oxide can cause substrate selectivity of Trypsin, enhancing the potential for Hyperglycemic Shock, Hyperglycemic Stroke, enhancement of Renal Distress and potential for Multiple Organ Distress Syndrome while it is also possible that if PEMT is not being inhibited by Multiple other factors then Plasmin can result in depletion of Glucose through enhanced expression of PEMT. Successful activation of PEMT would potentiate exhibition Serine Proteases, Phosphatidylmonomethylethanolamine, Phosphatidyldimethylethanolamine and Phosphatidylcholine which structurally deteriorate numerous pathogenic molecules, change cellular membrane polarity to inhibit coagulation cascade, deteriorate Coagulation, Thrombus, Fibrin Conjugates, and Fibronectin conjugates, transform physiology into an environmental scrubbing mechanism.198 Enhanced PEMT function produces an environmental sensing developmental and regeneration pathway in a way that is alternative to Scaring and Inflammation pathways. CDP-Ethanolamine/PEMT is the primary developmental pathway exhibited in the transformation of an Oocyte into a fertilizable haploid cellular entity and causes the regression of cellular entities to embryonic plasticity observed in the developing Mammal as well as which are preserved in tissues and organisms that regenerate Anatomy resilient in response to impairment. Homocysteine impedes and reverses the developmental programs, particularly Gastrulation which enables Human development into three anatomical regions followed by essential nuances of development otherwise, while Homocysteine also occupies Fibronectin, causes Fibrin Deposits in Cardiac and other tissues, while also increases the availability of Free Fibrin, all of which seem essential potentiators of Ischemia or Cardiovascular Impairment otherwise. Similarly, increased Vascular Glucose resultant of inhibited PEMT is known to cause overactivation of Islet Beta Cellular entities in Pancreas, Hepatic Tissues, and Renal 198


Tissues, such that Islet B cellular entities become affected by autoimmunological activity, dedifferentiate into other types of cellular entities, and can be regenerated by IGF Insulin Growth factor. Chymotrypsinogen and Trypsinogen are released, particularly by the Pancreas according to the Literature, and perform as Digestive Enzymes. Trypsinogen and other Pancreatic Secretions are inhibitors of Trypsin which prevent impairment of the Pancreas by excess Trypsin activation. Cholecystokinin, CCK, stimulated release of Pancreatic Enzymes and CCK seems to be activated by Fatty Rich Food or Protein Rich Food exhibition in the Lumen. The Brush Border of the Small Intestine activates Trypsinogen to become Trypsin, potentially by Enterokinase, thereby enabling Trypsin to become an activator of Chymotrypsinogen to Chymotrypsin and Procarboxypeptidase to Carboxypeptidase. The literature considers Serine Proteases to be Trypsins and Trypsins are considered to be among the Serine Proteases which Lyse Peptide Adhesions such as Arginine junctures and Lysine Junctures in particular.199 Trypsin lyases junctures of Amino Acids whereas Chymotrypsin Lyses Aromatic Amino Acid Junctures.200 There are multiple versions of Trypsins and Chymotrypsins with perform similar functions. Impairment of PEMT function occurs through genetic change, epigenetic change, impaired availability of Estrogen, prevalence of Estrone over Estradiol because Estradiol inhibits Sulfatase activity which Activates Estrone and because Estrone unevenly overactivates Estrogen Receptor Alpha compared to Estrogen Receptor Beta. Although both Estrogen Receptors activate the Estrogen Response Elements to enable PEMT synthesis, Estrogen Receptor Alpha is an activator or AP1 and Estrogen Receptor is an inhibitor of AP1. AP1 inhibits PEMT expression and Catalytic Activation, such that Estrone exhibition causes inhibition of PEMT. Estrone is bidirectionally transformed into 17Betaestradiol by 17hydroxy Steroid Dehydrogenase, but Estrone can be de Novo Synthesized from Fatty Tissue or other Steroids while Estradiol can be Synthesized from Testosterone. The emergence of Estradiol, however, occurs with the Original Activation of the CDP-ethanolamine/PEMT/LPCAT pathway which occurs when Cholesterol aggregates at the Plasma Membrane, becomes encapsulated within the Star Proteins in the Start Domain of Phospholipids such as Phosphatidylcholine. The encapsulated protein then is provided Shielded Transfer protected by its encapsulation into the Star Proteins Pocket Domain, arriving at the Mitochondria where it is transformed by a Cytochrome P450 Enzyme into Pregnenolone, followed by Transformation into Estradiol and then Testosterone, while Estradiol then Activates Estrogen Receptor Alpha evenly with Estrogen Receptor Beta. The result is even activation of AP1 and functional exhibition of PEMT. Prominent inhibitors of PEMT include Homocysteine which is managed by Choline, Folate, SMethylmethionine, Dimethylacetothetin, Dimethylsulfonioacetate, Trimethylglycine, B12, B6, Zinc, 5,6,7,8 Tetrahydrofolate, and Riboflavin. AP1 is inhibited by Berberine or other inhibitors of AP1. SP1 is inhibited by inhibitor of SP1 including Curcumin. Trimethylamine-N-Oxide is inhibited by TMA Lyase inhibitors, Diverse Coverage Antibiotics, Balsamic Vinegar, Fruity Olive Oil, Flavin Monooxygenase FMO1/FMO3 management, as well as management of Superoxide, H2O2, Peroxynitrite and Hypochlorite which can produce Trimethylamine-N-Oxide. Thrombin can be managed by inhibition inflammation, managing Homocysteine and preventing choline deficiency, Phospholipase activity and exhibition of Eicosanoids as well as preventing upregulation of Choline Kinase or preventing upregulation of the CDP-Choline Pathway. Indoleamine 2,3 – 2Oxygenase (IDO) can be inhibited by preventing inflammation, preventing activation of the Adaptive Immune System, use of Hyaluronic Acid, alleviating 199

“Difference Between Trypsin and Chymotrypsin.” Difference Between Website,


“Difference Beteen Trypsin and Chymotrypsin.” Key Difference. Trypsin vs Chymotrypsin.

upregulation of CDP-Choline Pathway, alleviating upregulation of Choline Kinase Pathway, managing C-Reactive protein which is upregulated by Complements Immune Function in response to overproduction of Phosphocholine. Nitrosamines/Nitrosamide/Arsenic can be managed by Kolaviron or Garcinia Kola Seed Extract. Chlorine and Fluorine can be excluded from foods and hygiene products as well as filtered from Water. Inducible Nitric Oxide Synthase can be managed covering all the energy/power outlets in the Home or office, coating power lines with EMF protection material, using radiation absorbers or reflectors on windows or Homes and offices as well as on electronics, communications devices, or appliances, while energy safe rooms, EMF protection clothing, hats, jackets and bedding may be helpful along with Curcumin or inhibitors of iNOS including Choline. Inhibitors of IDO include 8-Nitrotryptanthrin, BMS-986205, Coptisine, Coptisine Chloride, IDO-IN-1, IDO-N2, IDO-IN-3, IDO-IN-4, IDO-IN-5, IDO-IN-6, IDO-IN-7, IDO-IN-8, IDO-N-9, IDO-N-10, ID0-IN-11, IDO-N-12, IDOSL, INCB 024360, Indoximod, Navoximod, PF-06840003, Navoximod, PF-06840003, 201 Fludarabine and Cyclophosphamide, both inhibit IDO expression, particularly in Lymphoma Cellular Entities as well as improve antineoplasm activity. IDO is Overexpressed in several Oconologies which included Brain, Breast, Hematologic and Prostate Oncology. CD19-CART administration is known to have more than 90 Percent complete response levels in B Cellular Malignancies including Chemotherapy Refractory Acute Lymphocytic Leukemia, while PD1 and IDO are known to cause impairment of this response in other Oncologies including Chronic Lymphocytic Leukemia CLL and Large B Cellular Lymphoma DLBCL. Inhibiting PD1 and IDO substantially enhance the potency of CD19-CART, expand the included Oncologies manageable by CD19-CART, and enable the increased exhibition of endogenous CD19-CART capabilities within Physiology.202 Inducible Nitric Oxide Synthase depletes Calcium and is not sensitive to low levels of Calcium, causing sequestering of Calcium away from Endothelial Nitric Oxide Synthase and sequestering away of Calcium of Neuronal Nitric Oxide Synthase, causing Uncoupling and abated function of eNOS and nNOS, causing constriction of the Caveolae, impairing typical mechanisms of Vasomodulation and contributing to vascular deterioration including sudden adverse health events such as Stroke. Inhibition of the Synthesis of Monomethylethanolamines may be a Biome level detriment that impairs the ability of biologically active processes and organisms from scrubbing the environment of toxins including Global Warming factors. Although, the easiest conclusion to reach is that an industry in which therapeutics are not intended to alleviate, prevent, and reverse the most incipient and precise causes of detrimental outcomes may be less than productive or less than beneficent, this conclusion can oversimplify the mechanisms which are essential to productive, testing, integrating into care those factors which are essential to civilization. The ability to produce therapeutics, diagnostics, aspects of care, food, shelter and other factors essential to civilization, cannot be omitted as monumentous Human achievements, such that systems cannot be impugned in this regard. However, the platforms which systems have civilization have produced in which their own inherent capabilities have readily abstracted a glimpse of what Humanity could be and should be achieving, requires that this context be utilized in analysis of the performance of systems of civilization,

201 202

Indoleamine 2,3-Dioxygenase (IDO). An Internet Publication. Inhibitors, Agonists, Screen Libraries. Medchemexpress.

Digital Object Identifier. 10.1182/blood-2015-01-621474

particularly when such potentialies most clearly, empirically, productively and beneficently align themselves with incipient impetus for the construction of civilization. Particularly, the level of Humanity involved in producing, assuring, distributing and implementing mechanisms of care, represents, the most persisentently massive aggregation of Humanity across Nations, including outside of civilization. That which is required to move capabilities into loci of instrumentation and through instrumentation to feedback, monitoring and improvement, are often reflected in monetary aspects of biomedical capabilities represented as costs, budgets and other factors. The complexities with regard to regulations, relationships, distribution channels, nuances of microeconomics and macroeconomics can be complex, varied, and change from individual to individual levels. Such an expansive nature of such a mission of health at a National level or Global level might lend itself to systemic influences, such as reliance upon practices and capabilities which sustain systems, particularly the Human aspects of such systems. How these Human aspects of essential systems have not been assured and resolved persists as a mystery. The essential nature of enabling skilled, knowledgeable, trained, industrious, effective, and otherwise aspects of Humanity progress along systems of career and personal development, training, ability, merit, compensation and other aspects essential to high performance self actualizing populations has been regarded since the earliest of civilizations. How such assurances are not provided without requiring the persistence of products or services which do not acknowledge, alleviate, reverse, prevent and regenerate the effects of those factors which cause the shared potential detrimental outcomes among populations, seems to be an inadequacy of the characteristics of civilization. Any one particular industry cannot have such inadequacy individually attributed to it. Health services Industries, Biomedical Industries and Human Behavioral industries, as well as systems in such regard, simply provide the most understandable nuances of correlations. Such industries, too, have commanded themselves that civilization ask more of itself in resolving the nuances of causality to detrimental Human outcomes. Every person knowns that if one endeavors to control the nature of water, its rate of low, its direction of flow, then do not consider its inherent characteristics in such regard, sequester away all of its naturally potentiated inclinations, produce only those directions of flow one would like to occur, modulate the angle at which waters proceed to controle flow, and, however, if the obstacles to flow are not remove, then water may be included to interact with those obstacles, enter those pathways of flow, or become impeded by those factors which have not been managed to its benefit. How it could have emerged that those without knowledge of how their own inclination is being contrived, their own detrimental outcomes are benefiting others, the nature by which such factors are produced, the means to manage such factors, the assurance of factors essential to the Human condition, the factors essential to the assurance of the Human condition, and artifacts as well as circumstances which do not exist in nature, all are incipiently causal as well as proximately causal to detrimental physiological and behavioral outcomes could not be widely acknowledged is another mystery. How every social construct is not focuse on these causalities instead of attributing outcomes to individuals, such that causality does not have to be determined or managed, presents more mysteries. Systems without adequate resources or challenged with resources of managing detrimental outcomes are symptoms of inadequate acknowledgement and management of causality. Social constructs must be assured to focus on incipient causal factors as well as manage causal factors of detrimental Human outcomes. Otherwise, such constructs become participative in causing detrimental Human outcomes. These analyses have found pervasive causal factors to detrimental outcomes which are known and resolvable. Every Human has interest in resolving such incipient and causal factors, such that when an interest otherwise exists, it is the product of detrimental aspects of the status quo, the profit priority of private enterprise and the inherent propensity of any systems to prioritize itself over Humanity, as well as the voids which are allowed to persist in assuring Human requirements, thereby linking the voids of nonHuman entities with such voids

which are allowed to persist with Humanity.203 It seems to be the priority of Humanity to find ways to rescue itself from the detrimental outcomes potentiated in such regard while these diverse and resolvable mechanisms of detrimental outcomes work themselves onto the social agenda and work themselves onto the institutional agenda. To conclude, Choline Deficiency, Folate Deficiency, inhibition of PEMT, upregulation of the CDP-Choline Pathway including Choline Kinase, Homocysteine about 1 Micromole per liter for subclinical pathology and above 6 Micromoles per Liter for Clinical Pathology, Trimethylamine-N-Oxide, Inducible Nitric Oxide Synthase, Uncoupled Nitric Oxide Synthase, Superoxide, Hydrogen Peroxide, Peroxynitrite and Reactive Sulfur Species from disrupted Sulfur Metabolism including Homocysteine which impairs Catalase management of H2O2 and Homocysteine which impairs management of Reactive Sulfur Species, all are priorities in any Health management strategy including intervention of any sudden adverse health event, particularly Stroke. Review the website precise mapping of these and other indicators to clinical thresholds, diagnostic tests, biomedical capabilities and natural capabilities. Since these have the potential to improve outcomes by 99% or when managed during emergency or preventively, these provide an opportunity to improve practice and can be immediately integrated into practice by simply following the providing algorithm or using the maps to quickly find resolution for these priority diagnostic and causal mechanisms. Almost all, if not all of these factors, have requisite enzymes available as supplements or clinical capabilities, while the molecules which alleviate these are likewise available as clinical capabilities or supplemental factors. However, pervasively, merely providing a drink with these factors mixed into it and massaging the mixture of these factors into areas of Anatomy topically, together can be pervasively immediately and clinically therapeutic. Civilization separates Humanity from beneficial natural processes of obtaining nutrients or therapeutics while clinical capability development can additional separate physiology from Natural molecules, often impairing the ability of Clinical therapeutics. Typically, Pharmacological Capabilities may inhibit PEMT efficiency by sequestering away essential Methylation resources and increasing methylation requirements to manage Xenobiotics, thereby causing an additional Isolation of permutations of clinical pathology molecular pathways that the pharmaceutical capability is produced to modulate. This increased Isolation can enhance the therapeutic effect of the Pharmacological capability, but can introduce the risk to the health consumer because if the pharmacological capabilities is not adequately effective, is not clinically precise in its applicability to the health consumer or if the therapeutic is not include in a care context that is designed to alleviate disease and reconstitute optimal function, then the essential criteria for great care has not been met. These essential criteria seem to be alleviating how a condition emerges, imparts detriment, persist, progresses and circumvents physiological mechanisms of alleviation, prevention, reversal and regeneration. This information should encourage clinicians to integrate natural molecules and factors into their care paradigms as platform in which Pharmacological factors can be most effective since Pharmacological Factors are typically designed to alleviate a Tangible or clinically ascertained indicator, while the achievement of optimal Health Status requires galvanizing of analysis, information and capabilities around therapeutics with a priori of achieving optimal health status. If one is a practicing health professional and decide to merely provide a therapeutic drink with these factors during each visit, take any diagnostic tests, biopsies and fluid for testing before providing such a drink because they pervasively alleviate pathology and progressing pathogenic circumstances at their most incipient and causal loci. Because a Homocysteine assay machine can be obtained for $2000 dollars and trimethylamine and Homocysteine assay 203 â&#x20AC;&#x153;Is the Profit Motive Ruining Healthcare,â&#x20AC;? Online Content. Forbes. February 12, 2014.

can both be obtained in Kits or customized panel Kits, it is likely that clinicians can alleviate clinical indicators which are clinically indicative of Pathology or which are clinically indicative of Risk during the Office Visit or in the Evaluation Phase of Emergency Medicine. Obtaining clinical samples immediately and then immediately providing Prophylaxes, according to the clinical, research and other information can reduce clinical work as much as these are able to reduce abated vital being and reduce detrimental outcomes, which is 99 percent or more. The studies and anecdotal information show that mammals with these factors managed are unable have early maturity and progressed elderly populations distinguished from one another by physiological, cognitive, motor, or behavioral function, including an inability to visibly distinguish between such populations. The anecdotal information shows regrowth of Hair, regrowth of Dental Structures, the regeneration of Plasticity, Flexibly and Resiliency of Organs, tissues, limbs and appendages, including resumption of Cognitive, Occupational and Physiological function. The regeneration of Neurological tissue, reversal of age and disease associated vision impairment, and improvement of impaired Motor function, all are being presented in the Clinical, research and development literature. Interestingly, the literature observes that Bacteria which produce Trimethylamine begin to inhibit the absorption of Choline through Nutrition and feeding beginning with only low levels of bacterial availability. The levels of Choline absorption increase correlatively to the levels of Bacteria which Trimethylamine. These suggest that a primary way in which Trimethylamine promotes dysbiosis and impairment can be through exacerbation of Choline Deficiency.204 Here, every health condition are beingn shown to converge to have the same causal, preventable, alleviable, reversible factors. Inhibition of the CDP-Ethanolamine/PEMT/LPCAT pathway, upregulation of the CDP-Choline Pathway, Homocysteine above 1 for subclinical pathology and Homocysteine above 6 for clinical Pathology, Trimethylamine-N-Oxide, Inducible Nitric Oxide Synthase, Uncoupling of Nitric Oxide Synthase, Reactive Oxygen Species, Peroxynitrite, impaired availability of Methylated Sulfonyl Amino Acids, as well as numerous factors which are progressed aspects of these incipient factors. Amino Acid Supplementation, interestingly, without adequate choline is known to cause the exhibition of Hepatic Oncology resultant of a transformation of cellular entities into Amino Acid Absorbing entities instead of Amino Acid Synthesizing entities. Inhibiton of PEMT, and Choline Deficiency, together result in expression of P53 and P53 is known to cause the onset of some health conditions, although P53 is known to also inhibit Biosynthesis including synthesis of Proteins, Enzymes, DNA and RNA, such that Amino Acid availability without Choline seems to circumvent a Genomic, Epigenetic, Molecular and Structural assurance mechanisms constituted by P53.205 Tissue Plasminogen Activator in the context of Stroke typically is abbreviated as tPA or TPA. TPA is also used in the context disease to indicate 12-O-Tetradecanoylphorbol-13-acetate. Statistics and Probabilities cannot replace a Mechanistic Link and often Statistics and Probabilities do not agree with or suggest adequately that a Mechanistic Link exists. TPA has a mechanistic Link with its Serine Protease activity which is deterioration of linkages in molecules at the Amino Acids. This is irrefutable because TPA, supposedly, is said to be Plasmin. Statistics should only be used to determine and analyze the performance of TPA as a deteriorating factor of Plasmin. These studies widely do not consider, analyze or review this precise indication for TPA.



205 PMCID PMC4622769

Thrombin is inversely correlated with Stroke, presumably because TMAO is correlated with Stroke while TMAO is upregulated when factors exhibiting Choline and Carnitine are increased in level of obtainment. Instead, the statistics seem to analyze the correlation between TPA usage and outcomes, impairment, or exhibition of demise. TPA is not indicated for use in preventing impairment, demise or even alleviating Stroke. It is indicated for deterioration of Coagulation at atypical Loci or exhibition of a Thrombus, potentially including Coagulation at the interface of tissues which produces Ischemia within the tissue or Coagulation within tissues which produces Ischemia. The literature presents similar mechanisms as causal factors to Hemorrhagic Stroke, ate least incipiently and empirically. This is why it may be best to intervene stroke of unknown etiology at the most empirical levels, as well as including complete continuum of consideration which includes how the condition emerges, persists, progresses, imparts detriment, and how it circumvents physiological capabilities which would prevent, reverse, alleviate or enable regeneration of the detrimental influence which the condition provides. Pharmacotherapeutics pervasively are designed to modulate an Indicator which may or may not be causal of, required for or sometimes in even participate in a particular adverse health status or adverse health event. What these studies seem to be analyzing is, testing to see Thrombus or atypical Coagulation is really the Cause of Stroke. This is the only persistent question which these studies seem to be able to present, based upon the nonexistent mechanistic link between Stroke and TPA without linking Coagulation or Thrombus, primarily, to inhibition of PEMT, then linking inhibition of PEMT to its diverse inhibiting factors as well as to those factors which increase the potential for its inhibition or increase the bioavailability of its inhibitors. Interestingly, pervasive pharmocotherapeutics increase the levels of S-Adenosyl Homocysteine, increase Homocysteine, both of which inhibit PEMT, while also depleting Methyl Groups from S-Adenosyl Homocysteine to downregulate PEMT's use of S-Adenosyl Homocysteine. Imperatively, Pharmocotherapeutics pervasively increases the phases of Methylation required to deteriorate Prodrugs and Therapeutics otherwise by Demethylating these factors which typically are depleted afterwards using Methylation pathways which include Homocysteineâ&#x20AC;&#x2122;s as well as Methylation. Pervasively, persistent disease, adverse health events, and adverse behavior, as well as impairment and sudden adverse outcomes, require downregulation of PEMT. Pervasively, these are not directly therapeutically managed pervasively, even during health services interventions. TPA effects PEMT indirectly, and it does not seem intentional. These studies are difficult to reconcile because they are not meant to be reconciled. The primary purpose of a large population study of more than a few people and when there is no knowledge of virtually all of the nuances of genetics, behavior, lifestyle, metabolism, environment, and physiology for each patient, is to produce an obfuscate context for the acceptance of a pharmacological factor for usage. The studies may as well assay what health providers eat before providing care to health consumers because at least there is a mechanistic link between energy level and the ability to track a molecular pathway to see if a Pharmacological factor effects any causal pathway for a detrimental health status, including determining if there is linkage to the factors presented here as central to health conditions. The link between PEMT inhibition, Homocysteine, S-adenosyl Homocysteine, upregulation of Choline Kinase, upregulation of the CDP-Choline Pathway, Inducible Nitric Oxide Synthase, Uncoupling of any Nitric Oxide Synthase, Peroxynitrite, Trimethylamine-N-Oxide, Reactive oxygen, Reactive Sulfonyls, and Hypochlorite. These are the factors which perform virtually all of the detrimental activity during Stroke and are required for almost every instance of abated vital being to occur. The studies should be analyzing outcomes based upon the usage of these factors because there is a direct causal mechanistic Link to stroke. The other studies presented here cannot be utilized because they do not have a mechanistic link to the cause of a stroke. To use these studies presented widely in this discussion, the

clinician must produce other studies which analyze the molecular causality of exhibition of Thrombus or atypical coagulation, followed by finding permutations of studies which links these to the incipient causal mechanisms, while each study must describe the mechanistic link and each study must define those health consumers including in their populations whom satisfy, fully, the permutative linkages to the most incipient causality. Otherwise the study confounded out of usability. Clinicians must determine the incipient causal factors to detrimental health and behavioral outcomes for themselves and determine if therapeutics are effective in changing the causal factors of detrimental outcomes. Moreover, because a Thrombus can be potentiated by a number of factors, many of which are presented here in the discussion, it is imperative to diagnostically assay, analyze and therapeutically alleviate how a health status emerges, how it persists, how it progresses and how it imparts detriment, as well as how it circumvents the capabilities of physiology which would otherwise prevent, alleviate, or regenerate detrimental influence which results of a health condition. There is trillions of dollars between distant molecular indicators affected by biomedical capabilities and those incipient empirical causal factors to detrimental outcomes. Unfortunately, there is also 2.6 Million instances of unnecessary demise in this same expanse occupied by multiple Trillions of Dollars. A useful opinion suggests that not one instance of Vital Being should be abdicated for even all of the Multiple Trillions of Dollars in void between incipient causality and typically distant therapeutic Loci. The studies presented here and the studies used in clinical care are designed to distance the care scenario from research and timely understanding of biology. This enables health providers to be confused because there is no requirement to include a mechanistic link in any clinical study while pervasively clinicians confuse large populations studies are being more useful than understand every nuance of mechanistic linkages occurring in molecular pathways in a few individuals. The health provider and the Oath that Health Providers typically are required to Surrender to, can detrimentally affect how revenue flows in the Industry. Confusing Health Providers, convincing them not deviate from Care Guidelines, and not allowing them the opportunity to peruse the mechanistic linkages between each biomedical capability and the incipient causal factors for detrimental outcomes, circumvents the Oath and its intended effect to care outcomes. Enabling persistent flow of revenue to parties with an interest and parties with a potential awareness of these dynamics, even when these include distribution of revenue to entities which benefit from exhibition of demise, seems to be a causal factor while the detrimental effect to outcomes seems to be an ancillary factor. The studies are meant to confuse how systems converge in the health provider to make decisions, and constitute shadowy instances of detrimental aspects of the status quo, profit priority of private enterprise and the inherent propensity of systems to prioritize systems over Humanity. Industries otherwise would prevent the use of studies that replace analyses of statistics and probabilities between factors with mechanistic links with the use of studies that use large populations instead to confuse the users while only producing a mechanistic link because the outcomes occur as affects to anatomy. A similar scenario would be producing a link between a butterfly flapping its wings in oceans of Asia with weather in particular region of the United States. Merely occurring in the same biome carries the analysis without any mechanistic links, similarly to how Anatomy carries the Linkage of TPA to stroke. A physicist would agree that Metaphysics is useful because spatial interactions occur among all factors in the Universe, but the confounders are so numerous, and potentially infinitesimal, that such analysis seem difficult if not being without practical usage. TPA, however, if linked to stroke, makes no such assertions or presents no such exhibition of confounders, thereby enabling the revenue to flow, understanding of incipient and empirical causality to be prevented, and the abated vital being which is pervasively presented as being either required or unpreventable, might, then, be allowed to occur.

Clinicians are meant to be confused in this regard. The Amehsi Specification analyzed such linkages and found that such linkages converged in the factors presented here. The Amehsi Specification also found that in 1878 one such incipient and requisite detrimental factor was found to be alleviated by a factor that is pervasively excluded from use in Human Health while it is used instead to enable the health agricultural animals as well as used as topical factors in topical consumer products which assist with Aesthetics. If one, as provider, patient, or administrator, consider it beneficial to reduce adverse health events by more than 99 percent, the review the care algorithm and mapped causal indicators and remediation capabilities presented at the Website. The information has been reduced to provide a focused and usable group of capabilities which clinicians should immediately be able to transform into pervasive improvement care efficacy as well as improvement in outcomes. A health services organization, a Hospice Facility, was presented in an article to have obtained 60 Million dollars in Care Reimbursment through impropreitous activity. The article presents that individuals other than Health Services Providers clearly indicated that they were making decisions with regard to care. Increasing of particular medications were being utilize to decrease the duration to demise, enabling facility population churn or replacement of those incurring demise with new health consumers. Physicians orders were produced by Nonphysician roles. Advanced Directives were synthesized falsely, preventing the use of Care reverse paralytic statuses, enabling demise to occur. Services were expanded for the primary purpose of increasing the Billing Rates.206 Typically, systems may endeavor to determine individuals to whom causality for such outcomes are attributed. Clearly, the Captain of the Ship Doctrine in Health Services is refuted in this scenario and thus Generally. Imperatively, it may be important for systems to not focus on attributing causality to individuals, because this enables individuals to explore objectively and openly those influences to decisions and those influences to operational procedures, algorithms and Routines which are not often accessible in adversarial interactions. Detriment begins because a detriment outcome or scenario is possible, not because individuals are more or less susceptible to such outcomes and certainly not because particular individuals are less capable of ethical decisions. Instead of merely attributing causality, providing sanctions, and then allowing other instances of Humanity to occupy roles which systems or organizations merely find other ways to producing improprietous outcomes or finding ways in which the same activity is more successfully made of obscure, it may be essential to find ways of making similar outcomes impossible to occur. Detrimental cycles and beneficial cycles often merely insert Humans into roles such that the cycles themselves complete. Often, the beneficent purpose of an individual can be transformed into subversion and a subversive context exhibited by an individual can be transformed to exceptionally productive as well as beneficent outcomes. The best example of this seems to be an understanding of How civilization foundationally changes Human behavior. Humans have those freely obtainable factors and outcomes achievable in nature removed from achievability when being included in civilization, beneficent and less than beneficent. Civilization then requires participation in its systems to achieve such outcomes including obtaining the financial means to obtain housing, shelter, food, clothing and other factors. Choline, freely obtainable in Nature and able to be found in naturally occurring Factors also might become removed from obtainability unless individuals participate in systems of civilization. However, pervasively, Humanity might not be provided freely the financial resources which enables it to be where it was in nature with regard 206

“Hospice Admits Role in ‘Excess Medication of’ Patients to Maximize Profits.” NBC News.

to obtainability of such factors. Resultantly Humanity might become require to incur requirements to obtain the factors essential to the Social and Human Condition. Thus, Humanity is required to obtain financial means to obtain what is requires even when those factors are essential to the Social and Human Condition. Humans thus must find ways of transforming naturally available factors into ways of obtaining revenue or must participate otherwise in producing financial means. All manner of circumstances, factors, influences, detrimental outcomes, and beneficent outcomes become potentiated which do not exist in Nature. Similarly, Choline is removed from foods during processing, not included in Synthesized foods, and not able to be obtained adequately. Resultantly, Humans become foundationally impaired in their ability to associate Choline with those factors in which it occurs in nature, as well as become dissociated from linkages between colors, tastes, shapes, smells, and other factors with which its interactions with Universe can produce an ability to find Choline in the environment efficiently. Systems, instead, commandeer such factors to enable consumer and other behavior which typically does not occur in nature. Similarly, choline deficiency results in the exhibition of Inducible Nitric Oxide Synthase and other inflammation while synthetic energy and communications influences as well as synthetic magnetic influences also cause similar detriment. Choline, when adequately obtained in civilization, abates the inflammation and Inducible Nitric Oxide Synthase Expression which occurs resultant of deficiency, while the inflammation from synthetic sources Energy, Communications, and Magnetic influences become more clearly discernible by physiology to produce a false, inaccurate, and detrimental linkage between Choline Obtainment and detrimental Inflammation. The result is that less than conscious level cognitive artifacts and associations are produced which link choline with detrimental influences and impaired physiology. Choline then becomes avoided at less than conscious levels, removed from foods and omitted as a priority in nutrient selection while systems of civilization which presents the shapes, colors, smells and other factors associated with optimal choline pathway satisfaction become substitutes for obtaining Choline. These describe the molecular causal nexus for pervasive addiction, compulsion, detrimental behavior, cycles of behavior which produce detrimental health statuses and the emergence of disease as factors which can be conjured up within individuals with efficiency that can sometimes be similar to the synthesis of consumer behavior. Essentially, Homocyteine performs as a factor which impairs the ability of Stimuli to be relayed to the conscious cognitive context because this conscious context is where much of social behavior is managed, is required for stimuli discrimination, is required for some aspects of sensory gating and also may be a locus at which commandeering of natural stimuli by systems of civilization may be most efficiently occurring. The result can be an enhanced ability to obtain and find Choline in nature, although in civilization, because the stimuli have been commandeered by systems of civilization and choline has been made obscure, this scenario potentiates a suggestibility which would ordinarily be an extraordinary mechanism at finding choline becoming an extraordinary mechanisms at producing outcomes which civilization advertises, suggests should occur, perceive should occur, benefits from and believes should occur because social constructs, statistics and other factors. Clearly, civilization exhibits substantial occurrences in which outcomes among individuals, groups or communities occur, although these do not occur in nature, occur before an individual has incurred such outcome, occurs after such an individual has incurred such outcome, includes scenarios and circumstance which do not occur in nature, includes artifacts used which do not occur in nature, while also systems, individuals or organizations benefit from such outcomes even the outcomes are detrimental. This context presents how Humanity is turned upon itself in numerous instances and numerous levels by subversive influences which emerge from a requirement that organizations or

businesses be profitable, the profit priority of private enterprise, the detrimental aspects of Status Quo, and the Propensity of Systems to Prioritize themselves over Humanity. Thus, it is not difficult to present that in this instance, Humanity has become caused to turn upon itself to benefit an entity which is not Human. However, Hospice Care pervasively as does care pervasively does not intervene, reverses and alleviate the empirical and incipient causes of detrimental health outcomes and detrimental behavior. The particular article presents a promoting of inadequate care into behavior which is more clearly attributable to individuals, but such behavior is less egregious than not treating th causes of detrimental outcomes. Humans are made to be confused by recognizing the promoting of these inadequacies in alleviating the cause of pervasive detrimental outcomes. Simultaneously, there is no invitation to recognize the cause of 2.6 Million instances of Demise in the United States each Year. Attributing causality to Humanity merely enables another nuance in which Humanity is caused to turn upon itself and persists the synthesis of a Human inclination to abrogate itself. Producing financially, economically, behavioral, physiologically, housing, and other levels of stability among populations in pervasively achievable and has not been achieve because of pervasive synthesized requirement for Humanity to turn upon itself, profiteer from one each otherâ&#x20AC;&#x2122;s circumstance and find ways of obtaining those factors which are freely obtainable in Nature. While Civilization is not only constituted of such detriment and provides a substantial benefit to Humanity, it cannot be more clearly presented those inadequacies when 2.6 million instances of demise are allowed to occur without intervening why and how these occur, inadequate shelter and Homes are exhibited among populations, and inadequate ways of earning financial instruments are exhibited among populations. Most imperatively, the observation that Humans are among the only species in the Universes which considers its own levels of population and duration of span of being to be detrimental when becoming expansive seems to provide compelling of undue influence in Human cognition, perception, function and behavior. Thus, subversion itself seems to be able to be conjured up by circumstance and the incipient susceptibilities seem to be produce, integrated, and programmed into Humanity without regard to the whom the individual might be. The incipient factors which enable subversion are included in the factors presented as diagnostic priorities here, along with financial means, housing, ability to achieve, believe that whatever the circumstance they will be okay, and understanding how to obtain those with whom they are associated factors essential in such regard when they themselves are not able to obtain them. The disparities in precision of therapeutics in alleviating causality to detrimental health outcomes and susceptibilities to detrimental behavioral outcomes, seem to be among the causal factors of subversion at behavioral levels and cannot be attributed to individuals. This information presents how such susceptibility is transformed into outcomes of both detrimental and beneficent nature. Certainly, these begin before birth when Choline deficiency might be being allowed to shape Human physiology, Neurology, and Behavior toward outcomes exhibited in civilization while those factors which are known to cause detrimental outcomes are not resolved and are not prevented from being distributed among Humanity. There always seems to be an entity, particularly, a nonhuman entity, which benefits financially in such a paradigm, including systems which persists for longer duration than Humanity, thus allowing such systems to be required by Humanity. Imperatively, systems of Humanity are of imperative nature in the contexts of their incipient impetus for construction. The outcomes of interactions between Humanity, when less than beneficent and Product, seem to be pervasively the result of how these detrimental aspects of the Status Quo have emerged in the void between How Humanity has use systems to alleviate the detrimental outcomes potentiated in nature and the emergence of other outcomes which can be

potentiated in systems which do not occur in Nature, causing Humanity to become dissociated not from the incipient Nature of Humanity and not from the Nature of Humanity which has emerged in systems, for each such circumstances has been shaped by both systems of nature and systems of civilization. However, the potential for exhibition seems to be the resultant of permutations of dissociation from the incipient impetus and ideals for the construction of Civilization for, surely, it is such context which aspires most to Civility, Inclusiveness and the lending of oneâ&#x20AC;&#x2122;s psyche to a plural context of Humanity. The detrimental aspect of the status quo is referred to in many ways. However, an interesting understanding of it can be obtained by reviewing a decision in 1974 by the Principal or Supreme Reviewing Entity of Social Constructs in the United States in which a Moratorium on the use of Demise as a Sanction was implemented. The Moratorium once implemented, progressively resulted in the decrease of levels of Demise in the Nation by almost 1 Percent, decrease in the most detrimental of adverse behavior among the Population and reduce the levels of adverse interaction resulting in demise between workers in systems and the population to levels which had not been exhibited since the early 1960s. Once the Moratorium was concluded, which did not occur through expiration and not through mandated by the Supreme Entity and thus occurred not of general preference by the Supreme Entity, the levels of demise somewhat immediately were increased to levels near those previously exhibited. The levels did not return to the previous levels presumably because of the Implementation of the Disease Classification Systems for Diagnosis known as ICD Version 9. However, these clearly present that the events of the 1950s, 1960s and 1970s had led the Supreme Entity to consider the use of Demise as a Sanction to be without Merit for a number of reasons. However, the levels of Demise did not only decrease in the United States during the Moratorium and increase after the Moratorium. The levels of Demise incurred in Global Populations moved with positive correlation to such changes in the Systems of the United States. A review of the information found that Healthcare Certificates of Need may have played an essential role in the emergence of the moratorium because it clearly presented that in 1946 there was a less than conscious influence to Human behavior was substantial enough to cause the exhibition of adverse health events and thus could also influence behavior. The Hill Burton Act and its Certificate of Need requirements acknowledge such influence to Human physiology and States began to enact Certificates of Need Program beginning in the 1970s. Consciously, but also certainly through enacting of Social Constructs, each State acknowledged a less than conscious influence to Human behavior produced by systems. Essentially, these clearly had the potential to have resulted in permanent removal of the use of Demise as a Sanction. These analyses suggest that the enactment of Certificates of Need Programs may have adjoined each State to permanent removal of the use of such Sanction although a challenge to the use of such sanction does not seem to have been presented in this regard. Certainly, however, the factors presented here may be as compelling or more compelling than acceptance of Hill Burton Act Provisions. A review of the use of Demise as a Sanction clearly shows the use of demise as a Sanction causes increased levels demise among populations and increases detrimental behavior in the context of which it is used. The use of demise has always been known to not be a deterrent, particular of the behavior for which it is most widely utilized. The used of Demise in such regard has widely been regarded as being Punitive, although it can be clearly presented that that

behavior is pervasively produced by civilizationâ&#x20AC;&#x2122;s influence and the resolution of conditions which are correlated to detrimental behavior are known and inadequately alleviate by changing Social Constructs and determining incipient and empirical causality. Similarly, a substantial Human and Civil Rights issue emerges because among the 300,000 increased instances of demise which occurred somewhat immediately after the conclusion of the Moratorium, there is substantial probability that included among them were individuals whom did not agree with or assist in ratifying the use of demise. Thus, such persons may have been compelled to incur demise and their protection may have been an essential and primary Liberty Interest in abrogating the use of Demise as a Sanction. However, fundamentally, it was found that each instance of Demise can result in up to 90 Million dollars in expenditures. Thus, this may be among the most lucrative services ever provided in civilization. However, again, in the context of this discussion, this may promote the use of Demise as Sanction to be among the most influential and substantial factor in the exhibition of the detrimental aspects of the Status Quo. Von Willebrand Factor is suggested to be synthesized in Megakaryocytes within Subendothelial areas Connective Tissue and is a Glycoprotein exhibited in the Endothelium that integrates with Factor VIII with its D Domain, integrates at its A1 Domain to Platelet GPIb Receptor, factors such as Collage and Heparin. Calcium and the ADAMTS13 Protease transform Von Willebrand Factor into smaller molecule es. Integrin alphaIIIbBeta3 integrates at the C1 Domainâ&#x20AC;&#x2122;s Arginine, Glycine, Aspartate sequence, while the A3 Domain integrates with Collagen. The ADAMTS13 Enzyme segments Von Willebrand Factor between Tyrosine 842, when 842 indicates the absolute protein sequential position and Tyrosine indicates the Protein at such locus which the Amehsi Specification globally utilizes to explain such sequential positions, and Methionine at Position 843 of the A2 Domain which correlates to gene Loci 1606 to 1605. A summarization of the Coagulation Cascade, thus, seems to present a more complete understanding of why Thrombin inhibits PEMT. These pathways seem to compete for control of Serine Proteases within Physiology, while PEMT promotes both inhibition of Scaring and enables regenerative Blastema exhibition, along with preventing of Apoptosis and Necrosis. The activity of PEMT is compared with the promoting of Inflammation Pathways by the Coagulation Cascade Pathways. Thus, it may be prudent to determine a condition which requires Inflammation pathways and the detriment to Physiology which is potentiated by such pathways comparatively to a condition in which structural aspects of Physiology are assured such that regenerative pathways should be promoted over Coagulation/Inflammation Pathways. S-Adenosyl Homocysteine Hydrolase has its S-Adenosyl Homocysteine Metabolism inhibited by levels of Homocysteine because S-Adenosyl Homocysteine Hydrolase is bidirectional. The availability of S-Adenosyl Homocysteine Hydrolase for any directional processing of S-Adenosyl Homocysteine or Homocysteine decreases with the availability of any of its Products/Substrates. Cellular entities, illustratively, in which Protein Kinase A has been inhibited, exhibit cAMP-Dependent Protein Kinase A associated increase in Choline Kinase Beta, clearly suggesting that cellular entities may have modality in which the intracellular environment and the availability Calcium become in Control of most if not all of the Phosphatidylcholine Synthesis which occurs. The models of reconstitution of biological function from cryogenic and

no longer animate tissue which has been reviewed by the Amehsi Specification clearly show that the first phase of such resumption of plasticity and rhythms is the opening of the Calcium gating and Calcium influx mechanisms which, followed by a rapid closure of these once Choline Metabolism becomes spontaneously exhibited within the intracellular environment or once Choline Content of Membranes reaches a threshold that enables Polarity followed by tissue inclusive cycling of Calcium and Migration of Calcium. The Amehsi Specification show that once Calcium is exhibited, as well as potentially progesterone, and Cholesterol along with START Protein, the PEMT enzyme Pathway can be started. PEMT signals that iNOS and NF KB as well as other inflammation factors can be decreased and the Caveolae can be dilated for Cellular Signal Transduction. Certainly, Progesterone, Cholesterol and Calcium are indicators of a functioning Physiology. There is some information that the depletion of calcium by iNOS in the 6 Hour and 12 Hour sampling range may be the cause of the abrogation of the period in which cAMP-Dependent Protein Kinase A functions even when cAMP is inhibited. Both cAMP-Dependent Protein Kinase A and iNOS are known to impair DNA Repair with iNOS known to impair Non-Homologous End Joining and with cAMP-Dependent Protein Kinase A being known to impair Nucleotide Excision Repair. Both such factors might also impair other DNA Repair pathways. Thus, since there are a number of precise factors exhibited in the cAMP modulated resurgence of Protein Kinase A between the 6 Hour and 12 Hour sampling range in the study of PEMT, Protein Kinase A, and cAMP, the observations in other aspects of these analyses regarding patterned impairment of DNA resultant of iNOS depletion of Calcium which produce gradients similar to cones between the cellular membrane where Calcium may be dispersed and the migration of calcium of functioning iNOS enzymes. The iNOS Calcium tunnel and pump seem to be very relevant here. The conclusion here is that not only does an intricate coordinated resurgence of Protein Kinase A occur from increases in cAMP, there seems to be the possibility of a somewhat precise pattern of genetic and epigenetic change that occurs as result of the 6 Hour and 12 Hour range of increased inflammation. The abrogation of the 6 Hour and 12 Hour range itself could be produced by such genetic and epigenetic change. Thus, there is the potential that the nature of Kinase activity and molecular circumstance exhibited during the cAMP associated resurgence of Protein Kinase Activity could be genetic and epigenetic change the reflects the circumstance of cellular entities at such instance. The inhibition of Choline Kinase seems to induce cellular apoptosis conditionally based upon such circumstance and the inhibition of AP1 seems to reverse such circumstance to enable resurgence of PEMT function. It is not clear if AP1 causes the cycle of differentiation to merely regress or both regress as well as become exhibited again. Certainly, since SP1 is known to inhibit PEMT, upregulate Choline Kinase and upregulate Telomerase, immortalization of the such emerged genetic and epigenetic circumstance can occur through assured continuous access to genes resultant of replenishment of Telomeric repeats necessary for Polymerase access. 207 Certainly, since AP1. which inhibits PEMT and inhibits Telomerase, also is observed by the literature to strongly suppress Telomerase such that the genetic change it produces becomes one that persists to the conclusion of the cellular entityâ&#x20AC;&#x2122;s proliferation lineage, it becomes less difficult to conceptualize the mechanisms of genetic change and differentiation.208 Interestingly, the analysis of size differences between Human and Murine physiology can be correlated to difference in PEMT1 and PEMT2 which are separate molecules in Humans and while being exhibited as one molecule in Murine physiology. However, AP1, interestingly 207 208

Digital Object Identifier 10.1074/jbc.M406070200 Digital Object Identifier 10.1128/MCB.25.18.8037-8043.2005

Nucleobases including Adenine, Guanine, Xanthine, Hypoxanthine, Purine, 2,6 Diaminopurine, and 6,8 Diaminopurine have been found in Meteorites, suggest that Purinyl and Adenine Factors may be part of the original Metabolic Cycle of Organisms. Thus, their ability to inhibit Choline Kinase seems be integrally link to material which occurs in the Universes. Nucleobases are integral aspects of the Universe. The Known DNA Nucleobases are Adenine, Cytosine Guanine, Thymine and Uracil although the literature suggests that there can structural methylation variants of two of these which naturally occur. It is also well known that the DNA structure can biochemically achieve three and four strands in particular scenarios. However, A, C, G, T are exhibited in DNA, an A, C, G and U are exhibited in RNA. Thymine and Uracil differ by an additional Methyl Group exhibited in Thymine, thus a cycles and systems suggest, decreased availability of Methylation factors potentiates that systems exhibit characteristics of RNA Associate metabolism, compared to DNA associated Metabolism, requiring directed metabolic pathways to manage inadequate Methylation factors to be utilized with a Priority of those pathways in which Methyl Groups are most essential. This seem to substantial Organism level determinant factors. 5 - Methylcytosine is such modified Base in DNA while RNA exhibits Pseudouridine, Inosine, Dihydrouridine, and 7 – Methylguanosine. Hypoxanthine is produced from Deamination from Adenine and Xanthine emerges by Deamination from Guanine, and Uracil can be produced from Thymine in DNA from in the same way, both considered to be detrimental although such changes can be repaired within DNA and such changes can impair Viral Integration into the Genome. The popular literature observes that Thymidine is typically produced from Uracil, thus including it in supplementation may provide a metabolic advantage or may surmount a catalytic or Genetic Impedance. The Amehsi specification, biological, chemical and other aspects of languages exhibit that the letters di or d followed by i, indicate the number 2. These analyses specifically utilize di to refer to two or otherwise utilize the letters di in a reprehensible manner, similarly to the use of all languages or references in the Amehsi specification which are intended to describe outcomes without suggesting that they should occur or might be reprehensible. Filtering language constructs through different translations can produce literal translation, then include such factors in how language shapes behavior. The use concepts, phrases or words in the English language or in any language, as well as these analyses and the Amehsi Specification inclusively, intend reprehensible, beneficent and productive semantics, meaning and use of language. Every instance in which a detrimental influence, factor, or outcome is presented, the intent is for such outcome to be understand, prevented from occurring or transforming such outcome to not have resulted in detriment. DNA is described with Right being the 3’ or prime direction while the left is considered the 5’ or prime direction, where 5’ Prime extremity is Phosphate Group exhibiting Nucleotide and the 3’ Prime extremity exhibits the Nucleoside Sugar. DNA Polymerase Conducts the Elongation Activity. During replication, DNA is unwound, demethylated, DNA repair occurs immediately before and during replication in various versions. DNA polymerases can exhibit Nucleotide Accuracy Assurance, including Mismatch repair. DNA Polymerases conduct DNA replication Synthesis using Nucleotides, which DNA Polymerase attaches to the growing extremity of DNA which exhibits a Nucleoside. RNA Primers are required to be synthesized in extents between 18 and 22 base pairs, matched to a sequence of DNA, attach with complementarity, and enable the DNA Polymerase to begin its Synthesis of DNA that is complementary to the strand of DNA to which the Primer has

attached. Because DNA strands have complementarity, Sequences can move in reverse direction, requiring DNA Polymerase, when moving from 5’ Prime to 3’ as it does, to synthesize DNA differently for each of the separated DNA Strands. The strand in which DNA Polymerase moves from 5’ Prime to 3’ must have its new complementary strand produced in the 3’ to 5’ direction which DNA Polymerase is not capable of. Resultantly, numerous RNA Primers are produced by a Primase that reorient DNA Polymerase to the strand while DNA Polymerase synthesizes the Complementary Strand as short intervals known as Okazaki Fragments. The Primers chemically enable the DNA Polymerase Synthesis activity. The DNA Strand that is not the Lagging Strand, is able to Synthesized without Okazaki Fragments. However, it is imperative to consider Okazaki Fragments because there are different models of its activity, with some suggest that DNA is Synthesized attached to the Complementary strand while others suggests that DNA is synthesized as loose fragments which must be attached to the Complementary strand, suggesting the DNA could repaired therapeutically by providing alternate Okazaki Fragments. The RNA Primers are attached in front of the Progressing DNA Polymerase, preventing it from progressing all the way to the conclusion of a Chromosome or extent of replication. When the Primer is removed by Nuclease activity, Telomeres or TTAGGG repeats protect the Nuclease activity from removing aspects of Genetically active DNA. These repeats of TTAGGG can be exhibited 2500 or more iterations, while also being protected by Looped Shelterin Proteins that stabilize Telomeres and RNA produced from Telomeric DNA known as TERRA. TERRA Inhibits Telomere Synthesis, although Nonsense Mediated Decay Surveillance mechanisms monitor for mRNA produced in frameshift processing or from aspects of DNA without properly formatted Stop Codons and Start Codons. Telomeres are not typically within functional Coding Intron and Exon areas of DNA, according to the literature, and may be susceptible to Nonsense surveillance capabilities. Telomerase, Shelterin, TERRA and the CST Complex each are considered participants in the system of Telomerase Maintenance. The CST Complex protects Telomeres, capping Telomeres, Telomerase Management, and management of DNA Polymerase Alpha – Primase, all of which can result in enhanced resiliency of Telomeres particularly during Replication Stress or high levels of DNA replication. T Loop Complexes associated with Shelterin and G – Quadraplex structures associated with CST Complex, are known to inhibit impairment of Telomeres, including inhibition of DNA Damage Repair Pathways that can interpret Telomeres as Double Stranded DNA Segmentation. 209 The function of Telomeres is essential in establishing that Primers are attached to DNA at Telomeres. This information suggest that that Primers are attached at Telomeres. Accordingly, it may be possible to conduct repair of impaired Human DNA simply by providing the Okazaki Fragments comprised of either accurate DNA sequences for particular chromosomes. The models of Okazaki fragments differ, however, although synthesis of Okazaki Fragments presents some unknown factors and some complexities with regard to variable length of Okazaki Fragments, it is known that primases occur as a structuring mechanism for DNA Polymerase. Producing a custom Primase that correlates to an area in which DNA is impaired, and then providing such Primases at high enough volume could cause spontaneous DNA Repair, particularly small interfering RNA or Immunological factors are utilized to occupy and inhibit sequences correlated to the impair aspects of DNA. Here, it requires precise presentation of Telomere function. The literature seems to utilize the Chromosomes as substitution for Genes, as well as a substation for extents of Genes or areas within Chromosomes. Here, Chromosomes are presented as being two continuous extents of DNA bases which are attached by a centromere to exhibit the familiar 209

PMCID PMC4872678

X or Y shape. Similarly, a Chromatid or a Chromatid Fiber is presented as one of the Extents of DNA which are joined by Centromeres. This presents the opportunity for presenting Telomere function more precisely, because RNA Primers require attachment before and after the location at which extent of DNA which is to be replicated by DNA Polymerase. Both primers must be in place before Replication occurs. One source at least suggests that Replicated DNA is Synthesized and then requires attachment to growing replicated strand of DNA. Other sources do not precisely present any indication of how this occurs, while others typically only show that the Primers are in Place and present the newly Synthesized DNA as already being produce while the Polymerase is depicted as having already moved along its replicative path. The most essential presentation correlative to this more precise perspective of Chromosomes and Chromatid Fibers are that Primase being attached before the location of DNA Synthesis and After such location of DNA Synthesis before DNA Polymerase Activity begins, requires that primase which is attached last obscure the DNA to which it is attached. Thus, the replication activity is persistently considered to be unable to replicate the DNA to which the very last Primer is attached at the concluding extent of DNA within a Chromatid Fiber. It is suggested that it is here where Telomeric Repeats occurs, at the extremities of Chromatid Fibers, while it as the 3â&#x20AC;&#x2122; Prime extremity of the Chromatid Fiber that is susceptible to being truncated, omitted or shortened in translation. The literature is not precise about the mechanism by which Primers attached before and after the location of Polymerase activity produces gaps; that is, does the Polymerase proceed until it encounters the Primer attached after its replicative sequences, or has another DNA Polymerase already attached to that extent to begin its replicative sequence. However, the literature does suggest that the DNA Polymerase does not replicate the DNA to which the Primer is attached. The simplest opportunity seems to be the synthesis of Primers which correspond to areas of changed DNA in cellular entities which exhibit disease as a result. This presumes that there are other cellular entities which are not impaired. Thus, a primer can be produce to attach to an area of DNA during replication or during DNA Repair processes such that DNA polymerase cannot replicated or repair it. This could result in deterioration of the cellular entity. Similarly, the literature suggests that if areas at which Primers are attached are not filled by subsequent DNA repair processes, then the next replication cycle would produce Double Stranded DNA Segmentation which would invoke DNA repair that could be managed to prioritize Homologous Recombination to assure that the structure of the other aspects of DNA repair are produced in the repaired Strand. These analyses endeavor to try and summarize, understand and present how the Status Quo is affected by findings. The literature is sometimes able to present actual images of DNA. The few instances which these were found presented the bridges between the strands as having variable width, sometimes not completely exhibiting bridges, and exhibiting spiked protrusions from along the strands. Moreover, the images presented suggest that DNA is Brown with a potentially Burgundy hue, although Brown. Again, the closest color in the visible Spectrum of Light including ROYGBIV and Black seems to be Brown. These observations present some important understanding with regard to DNA, Genome, and Physiology. DNA, although it is known to produce all manner of changing influence to Physiology, is simultaneously being affected, shaped and influenced systems of influence to universes level as they are manifested in the Defined Space pin which DNA or an extend of DNA is produced. Perhaps its Chirality different from other molecules, being of D Chirality while typically other molecules, except for a few, are L versions. There is a potential that such differences produce a distinct difference in the systems, number of systems, tangential nature of influences, as well as transitive nature of influences which affect DNA compared to other molecules which participate in other

systems. It is not clear if the variable exhibition of incomplete, or complete, bridges suggest that it is the molarity and solvent characteristics that are affecting DNA in the Nucleus. However, the orderly exhibition of lettered Nucleotides seems to be another manner in which natural systems have been reduced to level of complexity which is correlative to Human ability to understand such systems, instead of including accurate representation of such Complexity. Most importantly, there is an ever-increasing possibility that Choline, Phospholipid and other pathways are not mere puppets to DNA. These factors which translated DNA into Physiological Structure may also be substantial determinants of the Nature, Behavior and Characteristics of DNA. Again, these analyses endeavored to understand how Genetic Polymorphism occurs. The literature suggests that Point mutations or substitutions occur along with frameshift mutations resultant of insertions or deletions. Some of the literature does not suggest any other manner of change except Epigenetic change such as adducts, or Methylation, which seems to resultant of factors other than Bona Fide DNA impairment. The Watson-Crick Pairing system is suggested to somewhat precisely require that Adenine be Paired with Thymine as well as require that Cytosine and Guanine be paired; these presented with respect to pairings between different strands of complementary, attached DNA. This suggests that Single Nucleotide Polymorphisms require assistance to emerge and persist unless DNA repair and Physiology were also impaired. The literature also presents many different variations of DNA impairment, pervasively resultant from influences in the environment and pervasively enhanced by Systems of civilization. DNA repair is known to occur in more than 1 Million instances in each cellular entity each day, although the literature does not suggest how many instances of DNA impairment occur but are not repaired. However, it is known that inhibition of PEMT and expression of P53 impairs Nucleotide Synthesis, impairs NADPH availability and impairs NAD+ availability for PARP signaling associated recruiting of repair factors such that DNA polymerases may have to pause and wait for adequate Nucleotides and resources to move upon gradients to areas at which DNA is being repaired. The Amehsi Specification presented in other analyses that a cycle may be potentiated in which DNA becomes impaired, PARP1 signaling becomes persistently exhibited resultant of inadequate Nucleotide availability. DNA repair may be inhibited or delayed resultant of PEMT downregulation along with P53 associated inhibition of the Pentose Phosphate Pathway as well as inhibition of Glycolysis and Acetylation Pathways, thereby decreasing KREB Cycle Activity. Such condition may inhibit NADPH by more than 60 percent. These inhibited pathways provide substrate and constitutive Nucleotide Precursors. 1 Million or more instances of DNA repair occurs in each cellular entity each day in physiological conditions. This suggests that pervasive disruption, delay or impairment of DNA repair may be somewhat common occurrences in cellular entities with downregulated or inhibited PEMT. The literature confirms such dynamics by clearly observing that PARP1 signaling depletes NAD+ because PARP1 distributes NAD+ to proteins and enzymes to provide energy for DNA repair as well as produce Gradients upon which additional material for repair migrates into the DNA repair microenvironment. NAD+ depletion is observed to also decrease intracellular ATP, potentiating dysfunction and cellular deterioration or demise through Necrosis as well as potentially Apoptosis. Necrosis is suggested as the outcome of persistent PARP1 signaling because Apoptosis through Caspase Pathways also is suggested to require NAD+. Additionally, however, these confirm the Aerobic Glycolysis Characterization because depletion of NAD+ increases the exhibition of Lactate and Lactate can be promoted to become a stronger influencer of Ionic Balance among the Strong Ions. Lactate is represented with Negative or Anionic Polarity in the Literature, such that its accumulation can deplete positive polarity factors, producing a spiral that emerges first with depletion of NAD+ then is followed by Lactate depletion of Positively Polarized factors, although the NAD+ depletion might be presumed to be intracellular or at least Local while Lactate is readily transported to the Hepatic Organ for Metabolism when the local environment is unable to do so. The ultimate detriment from NAD+ depletion seems to be the Carbonate

Buffering System and Hepatic Organ Function. Aerobic Glycolysis is often regarded as factor in Oncology and Cellular Pathology and probably not often enough regarded in how it effects systemic pH, Ionic Balances, Carbonate Buffering Capabilities and Hepatic function, such that Aerobic Glycolysis potentiates cyclical exhibition of Pathogenic Change. A Pivotal observation regarding NAD+ depletion is that Electron Transport Pathway which oxidizes NADH produced by the Citric Acid Cycle to result in synthesis of NAD+. The concluding phase of the Electron Transport Pathway isknown to Reduce Oxygen by Four Electrons to Synthesize H2O, and this phase typically utilizes about 90% of Cellular Endocytosed Oxygen, clearly presenting that the depletion of NAD+ by PARP and PARS during inadequate DNA or Inadequate RNA has the potential to produce Hypoxia and introduce expresson of HIF Hypoxia Inducing Factors. Depletion of NAD+ and depletion of Oxygen seems to be nuance of the Multiple Organ Distress Syndrome which may not be pervasively and adequately regarded during care.210 Differentiated cellular entities incur Apoptosis responsively to Electromagnetic Frequncy and Radio Frequency Energy, as well exhibit distress including Genetic, metabolic and molecular inflammation. This have been compellingly established in the literature. However, an emerging paradigm in the effects of Energy Fields to cellular biology exhibits differentiated effects to cellular entities correlative to Embryonoic or Progenitor Status compared to Differentiated status. A Particular study of energy in the 1800 MHz range specifically observes that Progenitor cellular entities exhibit resistence to Apoptosis correlative to Progenitor status, while differentiate cellular entities exhibit impaired outgrowth patterns. The study utilized differentiated and undifferentiated Neurological Stem Cellular entities. Another study presents that Progenitor cellular entities can be protected from Apoptosis through Homozygous or Heterozygous impairment of PUMA which mediates DNA Repair Reponse and is active in pathways which can potentiate Apoptosis. Clearly, however, escape from Apoptosis does not seem to require escape from detrimental effects of EMF and RF influences, including structural, genetic, epigenetic, transcriptome and Metabolome changes which accumulate to produce the mulltiple factor aggregation of impairment which is now bein accepted as causal factors to pervasive pathology. However, pivotally, with context of newly compelling and clearly pervasively active paradigm of iNOS Expression depletion of Ca2+ and NAD+ depletion which results apopotis in differentiated cellular entities along with hyperproliferaiton of incompletely differentiated cellular entities along with sequestering away of NAD+ required for Caspase Pathway activiation as well as NAD+ Depletion which causes enhanced inhibition of Glucose 6 Phosphate Dehydrogenase to accompany P53 inhibition of this same enzyme to impair Glycolysis and Pentose Phosphate Pathways, the exhibition of the cellular outcomes along the Progenitor/differentiated status Axis, seems integrative of such dynamics or may be resultant of such dynamics. The Amehsi Specification analyses, relevantly, were able to cleary present that the depletion of NAD+ results in directing of pyruvate toward Lactate Anion production, particularly during deficient availability of Pyruvate resultant of PEMT inhibition and upregulation of P53, such that NADH becomes tranformed by Lactate Dehydrogenase into NAD+. This pathway can increasingly become a priority because of peristent PARP signaling while it awaits the availability DNA and RNA which are impaired in availability because P53 and NAD+ depletion both result in inhibition of their synthesis pathways which include Pentose Phosphate Pathway and Glycolysis Pathways. Pivotally, the production of Lactate results supply of Lactate which can become Lactic Acid, illustrating a environmental sensing pathway for exhibiting Binary circumstances of progressing impaired physiological function known as Metabolic Acidosis and Metabolic Alkalosis. Morever, D Lactic Acid, which is a most perilous pathway for Multiple Organ Systemic Distress Syndrome correlated with Abated Vital Being, is supplied by NAD+ depletion both constitutively 210 Digital Object Identifier. 10.1016/B978-0-08-046884-6.00119-6

and through excacerbation of L Lactate and L Lactic Acid Metabolism which has a detrimental effect to D Lactic Acid Metabolism. Relevantly, the literature clearly presents Methylglyoxal, another factor among Amehsi Specification factors recommended for management, as being potentially directed directly toward D Lactic Acid. Although the depletion of NAD+ seems to be a feature of impaired Kennedy Pathway Metabolism, including Choline inadequacy, PEMT inhibition, requirement for P53 exhibition and upregulation of Choline Kinase, NAD+ depletion can increasingly become participative the ways in which these factors impair physiology. NAD+, intriguingly, also enhances Homocysteine because its products require metabolize by Methyltransferase which increase Homocysteime, providing a compelling perspective of How complex, permutative, accumulating levels impairment and metabolic syndrome may be enabled when therapeutics do not consider, analyses, alleviate reverse the imperical causal circumstances for detrimental outcomes. The context of cellular physiology is a homologue of similar circumstances at physiological, behavioral, and systems of civilization levels.211 212 The same article presenting information about the 90% percent of cellular endocytosed Oxygen being 90% utilized by the concluding phase of the Electron Transport Pathway, presents that Mitochondriad may have emerged resulted of Eukaryotic Phagocytes endocytosing or Phagocytosing Bacteria which challenges some of the potentialities with regard to mitochondria exhibition presented elsewhere in the Amehsi Specification analyses while such perspective is presented here to enhance the analysis regarding Mitochondria exhibition. A Philosphical analysis seems relevant here. An activity or nuance of systems occurring over Billions of years according to one perspective while another perspective considers such occurance to become completed in nanoseconds levels or much more quickly, presents the possibility of wildly disparate observations and presumptions such that intricate nuances of factors, influences and dynamics are intricately examinable in a Billion Year duration although hardly anything which occurs in such duration when it is perceived as occurring in a nanosecond is requires introspection. Reasonably, nanosecond level exhibition of such activity might exhibit all of the processes exhibited as aspects of Natural Selection although none of the organizations might have been able to understand their mere occurrence as aspects of systems which occur ordinarly and pervasively in the nanosecond perspective of another entity or context. Humanity, caused to become separate in such considerations of the unobservable because such factors are disjoint is distance, location, space and time and Humanity, caused to be come separate in such consideratons because the Universes level, quantum level, atom and metabolic level of such considerations were also observable, exhibit reasonable differences in conclusions unless such conclusion become dissociated from Human Priority. The mere translative act that represents nature or which persists, maintains, enhances and improves the favor among the Universes through which Humanity has come to be, is impaired because of the capabilities of Humanity are limited by its capabilities, systems, tools, concepts, understanding and perspectives. The Universes, however, are profoundly benefited by the way in which their statuses, characteristics, experiences nuances are persisted and reverberated by Human observation, perception, interaction, cognition and expression. The pulsating universe, to present an example, is only marginable different than the other perspectives of the Universeâ&#x20AC;&#x2122;s emergence, because it is each are inconsequential to the existing duration of distance, location, space and time, in that although there may be a perspective aware of such dimensions in which the precise dynamics of Universeâ&#x20AC;&#x2122;s emergence may be reasonably analyzed, there may be perspectives in which such precise information regarding the Universeâ&#x20AC;&#x2122;s emergence may be much less than a Nanosecond as well as occurring over a duration for which numerical representation might not be possible. Correlatively, there is no nuance, dynamic or perspective of the emergence of the Universe, Earth and 211 Digital Object Identifier 10.1038/srep05103 212 PMCID PMC2890171

Humanity that escapes being included in a duration of distance, location, space and time which could be the result of Design. There is no nuance or dynamic observed in nature regarding the way in which organisms have progressively exhibited change or have been exhibited which could not be included in such contexts of design, particularly because the same processes observed over billions of years and observed for less than nanosecond could obscure specific nuances occurring at either level. The architecture of an expansive technological system whom has activities being formed and analysis being conducted at their command would have a much different perspective about such constructive activity than an atom in on disk in an information systems which is being produced and implemented as an aspect of such system. However, Humanity is pervasively challenged to present that which occurs among the Universes and the favor through which it emerged, because such representation is limited by the systems, tools, capabilities, understanding and expression of Humanity. Humanity, separated, potentiates diminishing of Human Priority. Human priority, potentiates translative processes which are susceptible to become increasingly dissociated from reason. Again, although the introduction of this analytical nuance here may seem disjoint, it is imperative to understand that much of the differences of perspectives regarding how Humanity has come to be may be the result of limitation of Human perspective, rather than substantive differences. Systems which interact to determine the molecule which may be most useful as a role in physiology seems like a reference to evolution, although this process is pervasively utilized to determine, present or discover the most useful ways of producing artifacts by Humanity within its seems, suggesting that any prudent process might involve competing emergence or exhibiton of factors that are considered for the utility in any application. Similarly, a billion years in one perspective can be be but a moment in the perspective of another, suggesting that even differences in Distance, location, space, and time may be reconciled in such manner. However, it is those capabilities of physiology, cognition, learning, systems and dynamics of civilization, language, color spectrums, auditory spectrum, and other factors have beens synthesized for utility within civilization and do not represent an inclusive nuance of all possible characteristcs, values, or information available in area of observation, analytics or discussion. That which is sure is that anything which the influences of the Universe Presents or exhibits, becomes limited by the ability of Human systems to represent that nuance, factor or artifact. Human perception has language, concepts, colors, smells, size, expanse, duration and other observations enculturated, while characteristics in these dimensions as well as in those dimensions not able to be observed or understood are pervasively limited to fit into the already exisit linguistic, perception, cognition, expression and other nuances which Humanity exhibits. These exhibit how the translative nuances begin to become dissociate with empirical fact as soon as they are translated. The 26 alphabets, the shape of each alphabet, the prevsiou experience of an observer, and what has happened to an observer in instances near when an observation occurs, as well as the fields, systems, activities, peripheral influence, less than conscious influence and other factors all modulate perception, understanding, expression and translation. Similarly, truth may be most represented with empiricity, and empirical causality for outcomes are most determined at the Universes level and at metabolic, molecular, Atom, quantum and other levels, as well as are disjoint in distance, location, space and time. Unfortunately, what is empirical may be relative the capabilities of the observer and the awareness of oneâ&#x20AC;&#x2122;s own inadequacies as well as oneâ&#x20AC;&#x2122;s own limitations. The path to competency in a particular context of understanding or systems seems to be the emergence of awareness of oneâ&#x20AC;&#x2122;s own inadequacy to replace how

one is not aware of their own inadequacy. Such path to compentency is followed by emergence of owns competency as knowledge or understanding is acquaired to improve oneâ&#x20AC;&#x2122;s own adequacy. Such path to compentency seems to include emergence of Conscious awareness of ones improving adequacy followed by achievement of competency in a context or nuance of systems. The essential transition in these contexts seems to be awareness of self, awareness of self with context of the context or nuance or systems, a conscious utilization and integration of information, data and knowledge, followed by the ability to understand nuances, contexts, concepts, or things which are abstract, disjoint, or only verifiable when they occur or only verifiable through Artificial Intelligence Inferences that integrate proofs. Beliefs pervasively are centered on that which is possible, regardless of if outcomes validate, confirm or pervasively agree with such outcomes as well as regardless of if such possibilities are achievable in different nuances, contexts, or levels of technological achievement. Beliefs, however, pervasively begin with the observable. Again, inadequate presentation of Human Priority, individually, Plurally, and Inclusively, seems to be a pervasive of indicator of how distant such nuances of observations, understanding and inference may be from Reason. However, it is the instrospection into the observable, regardless of how technologically progressed such observable nuances may be, instead of merely concluding that an observable nuance simply is, which differentiates inference, abstract analysis, and belief from attributing of outcomes of physiology to merely being things which should be occurring. Detrimental outcomes, accidents, detrimental behavior, all are not required to occur, although Humanity has observed such occurences. If that which is should merely be as is, then Humanity would not endeavor to feed itself, construct shelter, allude peril, or resolve challenges to its prosperity. Certainly, why outcomes may be as they are produced improved understanding, guide innovation and development, as well as persistently enable Humanity to bend, shape or change causalities of detrimental outcomes to its benefit, hopes, and imperatives. Certainly, Natural Selection suggests no inherent reason for Humanity to be, some philosophical nuances suggest that human detriment should occur, while the consideration of indefinite span of being and assured quality of vital being require belief because Humanity heretofore has not seemd to have achieved being that has indefinite duration and vital being without challenges or detrimental outcomes. Some Philophical nuances invite the aspiration to achieve indefinite vital being by introducing less than indefinite Vital Vital Being as being the result of Human Cognitive and Behavioral Inadequacy, although these analyses clearly present that such inadequacies are conjured within or placed within Humanity by systems. Regardless, philosophical nuances seem to be pervasive incipient influences which have introduced Indefinite Duration of Vital Being and if one allows Humanity to be Human, then nuances of Philosophy which suggest otherwise can be easily explained as the substitution of what is observed for what was intended to occur, as well as can easily be explained by the exhibition of undue influence such as observation of detrimental outcomes, a requirement to adhere to public perception, the influence of systems which may have prevented presentation of vital being as having indefinite potential, as well as the limitation of the systems of civilization as well as Human physiology in understanding the mechanisms which contribute to duration of vital being. Natural selection, however, merely describes that which is, omits the ability of the incipient favor through which Humanity has emerged as being influential to each nuance of biological capabilities discovered, omits the ability of Humanity now or in any other instance in their ability shape such nuances of biology to Human benefit, and obfuscates how dissociated from reason it may be for any organism to conjure into being detriment to itself.

Humanity, it seems, has the ability to transform to the Biome and universes to its benefit, physiological, cognitively, and through its systems. The exclusion of complete Human prioirity in such nuances seems distant from reason, although through Human Priority, priority of the incipient favor through which Humanity emerged, and through persistence of the empirically determinable nuances of such favor which are Vital Being, Duration of Vital Being and Quality of Vital Being, Individually, Plurally, and Inclusively, there can be assured a priority also for the Nuances of the Universes and Influences of the Universe which have provided such favor. Essentially, a Cake Making Master does not necessarily have to know how fast the mixer might be in the factor which produces their cake mix. The Cake Mix Producers does not have know the height, velocity and manufacturer of the tractors which harvest Grain to produce thee Flour utilized in their Cake Mix. The Harvester of the Grain does not have to be aware of how Glucose is produced by Photosynthetic Processes. Photosynthesis does no require understanding of How CO2 is produced in the Atmosphere. Hardly any of these require understanding quantum material, string theory and loops in dark material of the universe, and, each of these levels and factors are not only competent, they may be considered to be masterful and experts in the things which they perform. Hardly anyone would consider improvements in manufacturing particular material or products which begin with the first ingredients which enble achievement of the required objective being followed by improvements in what ingredients are utilized once a complexity or inadequacy is found to constitute Natural Selection, although in Nature these are able to be readily attributed to Natural Selection. The conclusion here, then, is that systems of the universe are diverse enough, fields contexts and nuances enough to accommodate reasonable perspectives wich are derived to explain observed outcomes among the Humanity, particularly if such conclusion persists Human Priority, individually, plurally and inclusively, as a Beneficent Priority. These analysis conclude that Systems and Organizations do exhibit Human Priority incipiently, and such priority may be limited or impaired by mechanisms which translated prioirites into outcomes as well as influences of the industry which introduce priorities, requirements, circumstances, and other factors which potentiate increased dissociated from organizational charter, tacit impetus for the construction of such entities, or Reason. Most detrimental outcomes are most caused by factors which are not observable because they are not readily observable or because they occur before or after an outcome has emerged, as well as may be determined by circumstances, outcomes, influences, patterns, modulated influence and other factors which are not readily tangible. Thus, the most incipient translation of Human Physiology could not possibility have been truth because the unobservable nuances Universe level influence, metabolism, molecular factors, as well as the incipient favor which through which and among which Humanity came to be, would have also not been observable. Any conclusion would have been modulated by the limitations of Human Physiology, Cognition, and Perspectives which would have been without such empirical aspects of truth. These analyses pervasively exhibit that the incipient impetus for synthesis of civilization may have been to persist, enhance and improve the incipient favor which humanity benefited from in coming to be, while the progressive exhibition of civilization, systems, organizations, goals, objectives, outcomes, analysis, improvement and reconciliation to incipient aspects of reason which are constituted of Human priority are known to be susceptible to becoming distant from reason. The potentiality that similar processes may have been exhibited to enable the synthesis of Human Physiology over Billions of years in some perspectives or occurring only in an instant according to other perspectives, does not diminish any perspective regarding how Humanity has come to be, other than any such perspective can be analyzed based upon its ability prioritize Humanity. An organization which does not prioritize itself among its own systems, particularly when systems have clearly prioritized it comparatively among pervasive other organisms and material of the biome and the universe, clearly suggests dissociation from reason.

The priority of Humanity in it systems is essential, because without such priority, outcomes Anathema to Humanity become potentiated. Illustratively, when detrimental conditions are exhibited, increases in potential for detrimental Human outcomes are typically increased also, and when detrimental outcomes utilized artifacts specifically produced to impart detriment to others, there can be clear presentation of a divergence of what occurs in nature because such circumstances, artifacts and outcomes often do not exist in nature, although systems of nature can introduce detrimental circumstance and detrimental Human outcomes do have the potential to occur in nature, whereas civilization may have been incipiently intended to extend the favor through which Humanity has emerged in a way that those detrimental influences of nature are managed or transformed likewise in the persistent, enhancement and improvement of such Human favorability. However, if the detrimental artifact is removed and the conditions which were essential or required are removed from an outcome, then the outcome could have occurred in the way that such outcome may have been observed to occur. Comparatively, if the Human is removed from the circumstance, the outcome might have occurred anyway, because another individual may have incurred such outcome and indeed there is hardly a 100 percent unique outcome occurring among Humanity such that outcomes of a particular nature occur before an individual incurs such outcome and such that outcomes of particular nature pervasively are known to occur after an individual has incurred such outcome. Thus, how is possible to attribute causality of an outcome when it was possible to ascertain the likelihood of such outcome before th individual incurred such outcome, and when others incur such outcomes, as well as when the precise outcome could not have occurred in Nature? The essential factor in this scenario seems to be Human Priority. Why are the resolvable detrimental circumstance, health status, physiological nuance, behavioral nuances, detrimental artifacts, and shaping influences which are essential to detrimental outcome allowed to persist, particularly when pervasively such factors are the precise priorities which civilization has been constructed to alleviate? Human priority suggests clearly that it is not the Human with synthesized susceptibilities which ought to be removed to depotentiate detrimental scenarios, it is the detrimental circumstances, artifacts which potentiate detrimental outcomes, and inadequate understanding of oneself which should be removed to assure optimal Human outcomes. Pervasively, civilization has thoroughly presented that removing the Human merely produces collateral and detrimental effect which potentiates the same detrimental outcomes among others because the susceptibles, circumstances, conditions, impairment, and ability to benefit from the detrimental outcomes incurred by Humanity which persists. Thus, without persistent exhibition of Human priority and reconciliation of social constructs, goals, priorites, objectives, outcomes, algorithms and Routines to Human priority and incipient nuances of reason through which civilization has come to be and through which Humanity has come to be, there is a susceptibility that systems, organizations and populations might be being increasingly dissociated, also, from reason. These perspectives are simple. What goals, objectives, algorithms, routines, artifacts, circumstances, outcomes, social constructs or decisions move Humanity further from assuring that itself is a prioity among it systems and which distance Humanity from incipient aspects of reason, individually, plurally and conclusively? Correlatively, users of increased levels of Health Services, Emergency Services and behavioral Health Services, are windows through the which the inadequacies of wider interdependent systems are presented. Thus, strategies in intervening pervasive pathology should include Hepatic and Renal Organ support. Direct management of Ionic Balance and pH are not disregarded, although the cyclical exhibition of Pathogenic Factors seems

to potentiate the spiraling of physiological systems which present a most substantial challenge in the pathogenically impaired physiology.213 Environmental sources of DNA repair, particularly iNOS and Toxicity factors which can include Particulate factors, as well as inadequacy of Choline, PEMT, Phospholipid, Folate, and Betaine pathways, may be sources of substantial levels of changes to DNA and may persist because of inadequacy instead of being Bona Fide Genetic structural change. It is now known that epigenetic influences can cause changes to DNA that are transferred to Genes of developing Embryos, transferred during Gestational Development, or are acquired at Birth. Thus, a cursory additional review of the mechanism with which DNA is repaired was conducted. The Amehsi Specification already presents precise review of DNA repair mechanisms. This instance review DNA impairment and repair as that which could be reversed, that which required Non-Homologous End Joining NHEJ which includes joining compatible 3’ and 5’ segmented extremities or synthesizing base pairs until the 3’ and 5’ ends are suitable to being connected. Microhomology End Joining MMEJ exhibits DNA repair utilizing adjacent Base Pairs of up to 25 Base pairs are utilized to produce missing aspects of DNA. MMEJ can introduce inaccurate DNA. Some source sources suggest that Cellular Cycle Phases are correlated to the manner in which Double Strand DNA Segmentation is repaired, with MMEJ at S Phase, NHEJ at G0/G1 and later in the S phase to G2 Phase exhibiting Homologous Recombinational Repair or HRR. However, other literature does not make this distinction, suggesting that NHEJ and Homologous Repair occur as a result of manner of molecular signaling and Phenotype.214 215 A particular article was review that indicated that Choline and methyl group availability impaired DNA Repair and that increased PEMT activity comparative to Adjacent Tissues, was associated with Nonsmall Cellular oncology. However, earlier in these analyses there were numerous contradictory studies and the Histology presented at the beginning of this document clearly includes the same version of Oncology as having impaired PEMT and being responsive to Choline Kinase inhibitors. Similarly, each of these instances of DNA repair exhibit reliance upon factors including NAD+ and other factors associated with PEMT deficiency. Similarly, the combination of iNOS, transformation of inflammation pathways resultant of PEMT inhibition to invert or transform molecular pathways to promote pathology such as AP1 and SP1, as well as the way in which these are impaired by P53 or other aspects of PEMT inhibition, substantially transform Physiology into fragmented systems of stimuli and response outcomes without unified cellular and anatomical level coordination. Impairing the ability to express P53 at the Genetic Structural levels results in increases in Phosphocholine as well as increases in aggregate Choline. 216 Nonalcoholic Hepatic Steatosis is not only correlated with Obesity, also being able to be exhibited in Lean Patients. Murine populations used to study Steatosis were able to exhibit such Nonalcoholic Hepatic Steatosis when fed a High Fat High Sucrose nutritional regimen along with Homozygous impairment of PEMT, although Obesity and 213

PMCID PMC2702213

214 215 216

Version of DNA Repair.

Digital Object Identifier 10.1242/jcs.01355

Digital Object Identifier 10.1162/1535350042973517

Diabetes were omitted from Pathology. The High Fat High Sucrose, PEMT Homozygous Impairment, Lean Phenotype without Obesity and Diabetes was also able to progress to Oncology with Hepatic Neoplasms emerging, emerging along with Steatosis and emerging along.217 This Phenotype, High Fat High Sucrose, Homozygous Impairment of PEMT, also resulted in substantial levels of Hepatocyte Apoptosis. The study was as able to present that PEMT inhibits P53 in at least one way, including a molecular interaction that resulted in conjugates of PEMT, P53 and Clathrin Heavy Moieties. Furthermore, Hypermethylation of F â&#x20AC;&#x201C; Box Protein 31 and Nuclear Factor 4 alpha, a condition which inhibited the mRNA expression of both factors, resulted in the upregulation and activation of Cyclin D1. Moreover, comparative analysis presented that Simple Steatosis exhibited less decreases in PEMT activity than the more substantial inhibition of PEMT which occurred with NASH Patients.218 AP1 and SP1 then oppositely regulate Telomerase upregulated CTP Phosphocholine Citidylyltransferase, downregulate PEMT and upregulate Choline Kinase. Oncology resultant of PEMT impaired Lean Nonalcoholic Hepatic Steatosis, then, exhibits typical characteristics of pervasive Oncology, downregulated PEMT along with upregulated Choline Kinase. These suggest how PEMT impairing Polymorphism produce pathology, potentially including an abdication of function mutation that prevents a particular molecular pathway or interaction from occurring with required efficiency while also exhibiting typical downregulation of P53, opening the door atypical pairings of activated and inactivated pathways. The prospective exhibition of PEMT but with inadequate molarity among pathways that are pervasively determined by prevalence of molarity among competing molecular pathways, as well as the potential that impaired structure might be exhibited with such atypical level or typical levels, might not be adequately considered in how these result in diagnostic and therapeutic complexity. These describe why therapeutics distant from PEMT, P53, Choline Kinase, Choline obtainment, iNOS, uNOS and including other Amehsi Indicators, may be Cornucopia for Business, and wrought with risk for Human outcomes. Again, it is interesting to consider how iNOS from the 50 and 60 Hz energy fields that is suggested by the research as encompassing Western Civilization, there providing a somewhat pervasively exhibited downregulation of PEMT and upregulation of Choline Kinase, participates in the AP1/SP1 coordinated sustaining of an emerged Genotype and Phenotype. Similarly, it is interesting to consider how Choline inadequacy provides similar sustaining of an emerged Genotype or Phenotype, while most assuredly acting together with these other factors to assure progressing detriment to the Genome. The cultured biological observations pervasively observe that adding choline allows cellular entities, even those with impaired DNA, to perform DNA repair, complete DNA replication, and surmount the checkpoints that prevent cellular entities with impaired Genome from completing Mitosis. Pervasively, high dosage Choline seems to be omitted as a therapeutic although it is presented since the 1950â&#x20AC;&#x2122;s as the somewhat Original Deficiency and required for pervasive if not all Human Pathology. Cyclin D1 then enables cellular cycle to progress from G1 to S Phase while also cyclically potentiating both AP1 and SP1, according to the clinical literature. However, ChREBP enables escape from cellular cycle pause when P53 is decreased in availability, although the literature contradictorily presents ChREBP as being an inhibitor of P53 or

217 218

PMCID PMC4756298

inhibited by P53. The literature seems to presume that P53 is dominant in this relationship, correlative to the determination that P53 is an incipient metabolic factor emerging when PEMT is inadequately exhibited. Imperatively, PEMT, having been observed to have an active catalytic and interactive role in integrating with P53 and Clathrin Heavy Moiety, thus, presents an interesting potentiality in studies in which PEMT is Homozygous Impaired compared to abrogated from Genetic Expression. The literature Presents PEMT -/- as the inability to express PEMT which is different form PEMT impaired which might be presented as PEMT +/+. Interesting and humorous and variations on PEMT status, at this instance, are not known to include one for Homozygous or heterozygous expression although impaired structurally and catalytically. Thus, PEMT, when -/- or not expressed, would allow P53 to run rampant with its own priorities except, as otherwise observed in these analyses, when P53â&#x20AC;&#x2122;s synthetic demise partners or synthetic catalytic function partners become impaired, prevented from being expressed or changed in molarity. However, when PEMT is impaired a particular specific nuance of structure or function, expressed fully, Heterozygously impaired to be expressed at decreased levels as in PEMT +/- or PEMT -/+, or Homozygously Impaired, the outcomes may be different. The literature seems to be inadequate in this regard, because -/-, -/+, +/-, or +/+ seem to be only consensus indicators of function only with +/+. -/-, +/- or -/+ do not seem to widely differentiate between a completely removed Gene, impairment of a structural aspects of a Gene or impairment of a structural or catalytic aspect of produced Protein or Enzyme, while it is well known that a promoter region for an intact Gene can be impaired, a Gene can be removed, a Geneâ&#x20AC;&#x2122;s structure can be impaired, alternative splicing priorities can be impaired during translation, and ability to synthesize the transcription product can be impaired as well as Post-Translational impairment can occur that includes structure, availability, function or duration to deterioration. CRISPR Therapeutics require such specificity when determining therapeutics for Diagnostics, Therapeutics and analysis. It is suggested that the leading strand of DNA be presented in the first position of +/+, +/-, -/+, or -/- indicators. This literature suggests that positional or order or strands may only be relevant during DNA replication, since Coding of DNA into RNA can occur using either Strand of DNA. Leading and Lagging strands indicate which one is Synthesized during Replication using uninterrupted 5 Prime to Three Prime direction using one of the existing Strands of DNA as Template. The lagging Strand indicates which Strands being Synthesized using the Three Prime to 5 Prime direction which requires interruption to produce fragments known as Okazaki Fragments that must be repaired using DNA repair Mechanisms. The Leading and Lagging Strand emerge from the Replication Fork at which the existing Strands of DNA are separated, which can be exhibited in multiple simultaneous locations during DNA replication. Thus, +/- compared to -/+ may not be relevant with regard to Transcription. However, during DNA replication lagging or leading strand as well as which strand was the existing strand can be relevant for analysis. Thus, the Lagging strand might be qualified with 2 as in 2+/2-, 2-/2+, 2-/2-, or 2+/2+ where the indicator on each side of the / indicates the Lagging Strand if 2 and indicates the Leading Strand if 1. Similarly, during replication, the left side of the / as in 1-/ might have the indicator correlated to the status of a Gene in the existing strand of DNA which is being copied during replication whereas the indicator to the right of the / as in /1+ might indicate the status of a Gene in the strand of DNA being synthesized.

Thus 1+/1+ might be used to indicate that Leading Strand replication Template with an intact Gene without Polymorphism as well as Leading Strands Replicated Copy being Synthesized which has completed Synthesis without a Genetic Polymorphism. 1+/1- would, then indicate, that the Leading Strand exhibits a Polymorphism in the newly synthesized Strand of DNA. 2+/2+, then, would indicate that the Lagging Strand of DNA which is being synthesized does not exhibit a Polymorphism while the Original Strand of DNA which is being copied also does not exhibit a Polymorphism. 2-/2+, then, also suggests that the Original DNA Template used for DNA Synthesis for the Lagging Strand exhibits a Genetic Polymorphism, while the Lagging Strand that is being Synthesized does not, although it seems improbable that the Original Strand might exhibit a Polymorphism while the newly Synthesized Strand would not have the same Polymorphism. Such potential outcome, however, may not be so improbable because epigenetic and deficiency correlated polymorphisms may be pervasively unrepaired resultant of deficiency, epigenetic influence and impedance to the cellular cycle. The systems presented here for documenting Genetic Status during DNA replication is prospective and presented as a recommended way of more precisely presenting genetic status. The use of +/+ or +/- or similar, to document Genetic Status, however, is typically utilized already in the literature. Among other suggestions are that there might also be included a ~ if there is complete removal or omitting of a Gene, as in +/-~, an open and closed apostrophe with the polymorphism information include if there is a polymorphism at the genetic level such as -‘rs7946’/+, impairment in the promoter region could be indicated as +/-“Location,Type” used to indicate Promoter Region or Gene Structural Anomaly such as “14q22, Methylation at first CPG in the 3 Prime Direction from the Gene in the Promoter Region”, intron/exon anomalies indicated with +/1”Included Exon, Excluded Exon, Included Intron, Excluded Intron”, while an unknown persistent exhibited structural anomaly in a protein might be indicated as –“Serine 150 to Glycine 160, G,L,S,T,M,P,A,L,C,A” where the first indicator presents the location of the impairment and the second indicator presents the order of the Amino Acids or Macromolecules constituting the sequence Anomaly. These examples might be useful to document genomic anomaly other than replication contexts of anomaly also, although a system of determining Lagging Strand compared to Leading Strand might be required. These suggest that High Fat High Sucrose Nutritional regiment is managed by Physiology through exhibition of Obesity and Diabetes, while PEMT insufficiency results, instead, in Steatosis regardless of Nutritional status except when Alcoholic or other Toxicities which impair PEMT are exhibited. Obesity and Diabetic Pathology, then might contribute to Steatosis or lead to Steatosis as an aspect of their Pathology Patterns. These observations have to be considered in the context of pervasive PEMT impairment because Choline deficiency is such a pervasively exhibited circumstance in Human Populations, although cultured cellular entities can sometimes include Choline. It is becoming important to review the materials and methods to determine if Choline has been included in cultured medium when a study is being reviewed. Eagle’s medium is contradicted in the research sometimes as including Choline and not including choline. However, the literature suggests that Eagle was the among the first presenters of and proponents of inclusion of Choline in cultured medium for cellular entities.219 220

219 220

Digital Object Identifier 10.5772/52301 Digital Object Identifier 10.3181/00379727-89-21726

These observations are interesting because DNA replication produces synthesized gaps in DNA which are repaired using the same biosynthetic and repair pathways otherwise availability, suggesting that these are optimal mechanisms for DNA repair and Synthesis. How could DNA repair, thus, emerge, persist and progress unless molecular, metabolic and or Environmental influences might be participative or causal? It is not clear if the environmental factors exhibited in nature or in civilization are inherently detrimental or if these are principally the result of the disruption of the generative, developmental, regenerative and repair program. However, genetic impairment is clearly emerging as being the result of impairment of these factors, facilities and capabilities. It should be presented here that Genetic Conditions seem to be manageable with optimal Physiology since there is not substantial archeological or paleontological indication of rampant Pathogenic Genetic Polymorphism, providing a cursory perspective of social aspects these observations although there does seem to be indication of health conditions increasingly with the emergence, development and exhibition of less than optimal conditions in civilization. The literature suggests that there are numerous Genome level fidelity mechanisms, among which RAD51 and its Homologues are included as factors which promote more extensive Homology search as well as the ability to simultaneously integrated into both Strands of DNA during Homology Search and Repair. Accordingly, these analyses suggest that there is not a Bona Fide limitation to Human Vital Span of Being other than those which are allowed to persist and those which may be presented by both Natural Systems and Systems of Civilization. There seems to be an opportunity to use Primers that are matched to an extent of DNA repair to obscure the extent from being Translated by DNA Polymerase, such that there is an opportunity for other DNA Repair Mechanisms to find and repair such impaired aspects of the genome. Similarly, the literature suggests that inhibiting DNA repair generally during Okazaki Fragment Synthesis can prevent DNA repair, result in persistent unrepaired extents of DNA repair, which is then followed by DNA impairment mechanisms concluding that a Double or Single Strand DNA segmentation has occurred. This would result in a Homology search between strands of DNA and copying of the sequences exhibited in the other Strand of DNA to the sequences which are being repaired. This strategy could be utilized to repair regions of a Chromatid, Inversions, Deletions and other changes in DNA. Itâ&#x20AC;&#x2122;s not suggest that these capabilities are better or have more potential than CRISPR, although, however, since CRISPR presents such potential improvement of the Human circumstance and there does not seem to be galvanization of 24 Hour a day effort at moving these capabilities into practice while there seems to be impairment of Humanity that it is occurring 24 hours a day, the potential of alternative methods is suggested. Again, it is mystery how the nature of Health Services, the Health Industry and Care, as businesses have become the focus of Social Change instead of a priority of advancing Care. Pervasively, the capabilities suggested here potentiate transforming of the Health Industry to exhibit more manageable economic characteristics. Nucleotides are joined at adjacent sugars by Phosphate Groups. Strands of DNA occur as oppositely oriented polymers of Nucleotides. SP1 or SP1 upregulates Midkine expression and Midkine as well as SP1 or SP1 are upregulated in numerous Gliomas.221 221

Digital Object Identifier 10.1091/mbc.E14-10-1443

These present an opportunity for an analysis of Glioma Multiforme which include the group conditions known as Gliomas. Homocysteine is known to cause or induce Cytotoxicity of Astrocytes which are the Neurological Center cellular entities which become transformed in Glioma Multiforme.222 These changes included Cytoskeleton changes, as well as decreases in NA+, K+, ATPase, Superoxide Dismutase, Glutathione Peroxidase, and Glutathione.223 Glioma Multiforme was also prognostically correlated to the conditions which are central factors in increased levels of Homocysteine.224 Homocysteine impairs Neuronal Stem Cellular Proliferation S Adenosyl Methionine, activity/availability of DNA Methyltransferase DNMT1, DNMT3a, DNMT3b. Thus, Homocysteine introduces Astrocyte Apoptosis and impairs replenishment with Neuronal Stem Cellular entities. However, Homocysteine is known to stimulate inducible Nitric Oxide Synthase and impair PEMT, resulting in decreased levels of essential capabilities such as regeneration, methylation pathway synthesis of Phosphatidylcholine, clearing out of PCBS, Alkyl Halides, Aromatic Polycyclic Hydrocarbons, and abrogation. Similarly, Fatty Acid Synthesis, Fatty Acid Beta Acid Oxidation, and reactive oxygen species scavenging by Beta Oxidation and Superoxide, as well as other essential capabilities are impaired. However, the pathway known to be required for any version of Oncology includes Either upregulation of Choline Kinase, downregulation of PEMT or both. SP1 is known to both upregulated Choline Kinase and Downregulate PEMT. The literature is persistently moving to clarity with regard to Choline, Cholinergic Metabolism, and potential for detrimental health statuses and behavior. Particular studies are beginning to clearly show that increased obtainment of Choline, Free Choline, Betaine and Phosphocholine are correlated with decrease All-Cause detrimental health status outcomes. Breast Oncology Reductions are also being observed with these essential nutrients, although the data becomes confounded by the impairment of Genes BHMT and PEMT with particular Polymorphism. However, it is known that the circumstances caused by impaired BHMT and impaired PEMT and are a myriad of factors that are pervasively required to occur in disease and detrimental behavioral outcomes. Again, it becomes imperative to observe that the way in which clinical reasoning occurs in widely in clinical and biomedical areas of study require change. Although PEMT is considered to not be associated with increased Abated Vital Being and Homocysteine is not considered to be definitively indicative of similar detrimental outcomes, Aerobic Glycolysis and the myriad detrimental pathological changes resultant of Homocysteine even at subclinical levels can be clearly exhibited to be required for pervasive detrimental outcomes. Some of the correlations are so obvious when one links PEMT to Homocysteine and Aerobic Glycolysis as well as Homocysteine to its voluminous list of pathological changes and Aerobic Glycolysis being linked to its causal basis, that large areas of research have to be omitted to make these simple associations. However, the literature is beginning to exhibit clear linkages in outcomes and these incipient circumstances, linking Choline obtainment nutritionally with outcomes, although Genetic Status, Metabolism and availability of PEMT, BHMT, Methionine Synthase, Methionine Synthetase and other enzymes can substantially modify how Choline obtainment is translated into Human outcomes.225 Homocysteine is known to inhibit PEMT and comparatively result in upregulation of Choline Kinase while also impairing availability of Acetyl-CoA used to store Choline as Acetylcholine, resulting in increased availability of Free 222 223 224


PMCID PMC2775010 Digital Object Identifier 10.1215/15228517-2008-020

Choline which Choline Kinase uses to increase its activity, promoting the accumulation of Phosphocholine through Choline Kinase Phosphorylation of Choline to produce Phosphocholine. Resultantly Phosphocholine accumulates enables all manner of Pathology, circumvents the effects of P53 which is already impaired from inadequate AcetylCoA, and then can accumulate in extracellular environment upon cellular entities. Phosphocholine on cellular entities stimulates compiments immune response at subclinical levels which includes subclinical C Reactive protein and apoptosis which requires exhibition of other inflammation pathways to prevent massive apoptosis in tissues in including astrocytes. This required resiliency to apoptosis is the transformation locus for pervasive pathology and pervasive oncology because Oncology pervasively is constituted of escape from cytotoxic cellular immune response, expansion of cellular entities to occupy more space to alleviate massive cellular apoptosis and expression of iNOS which helps maintain cytoplasmic space once tissue density decreases to numbers of cellular entities per micrometer at which cellular entities require assistance to maintain physiological structure as well as manage gravitational influence from somatic mass. Murine populations provided a High Fat Diet, in a study, were observed to increase Somatic Mass by 60% when PEMT +/+ was Homozygously Functional upon both Strands of DNA whereas PEMT -/- Homozygously Dysfunctional Murine Populations did not exhibit obesity. PEMT -/- Murine populations also exhibited increased energy expenditure and typical Insulin Sensitivity whereas PEMT +/+ populations fed a High Fat Diet exhibited Insulin Resistance, although the PEMT -/- populations began to exhibit Steatosis and Hepatomegalopathy. Impairment of the CDPCholine Pathway in the Murine Populations, which is considered to compete with PEMT and Choline/Ethanolamine in the synthesis of Phosphatidylcholine was observed to produce Obesity in response to a High Fat Dietary Regimen although there may be an emerging observation that CDP â&#x20AC;&#x201C; Phosphocholine Cytidylyltransferase could possibly be required even in the Methylation Pathway while also there may be shared metabolism of Substrate between the Methylation pathway and the CDP-Choline Pathway. Addition of 1.3 Grams of Choline per kg of Somatic Mass in the PEMT -/- population was not able cause the emergence of Obesity and the literature suggests that deficiency of Choline synthesis by PEMT and certainly decrease in the synthesis of VLDL which relies upon PEMT produced a persistent deficiency in Choline that was responsible for inability to produce Obesity. Murine populations exhibit 30 Percent PEMT synthesis of Phosphatidylcholine in the Hepatic Organ while 70% is typically observed to occur through the CDP-Choline pathway, although typical here is in no way presumed to be optimal. PEMT -/- Murine populations exhibit impaired PEMT Enzymatic Activity although Phosphatidylcholine to Phosphatidylethanolamine levels did not differ with PEMT genetic status in a particular study, although Fatty Acid Distribution among Phospholipoids which was not included in the analyses might be different. High Density Plasma Lipoprotein are decreased in PEMT -/- Murine populations as a result of increased Hepatic Scavenger Receptor B1-Relient adsorption of Lipids from High Density Lipoprotein. The literature observes constitutive decrease in Very Low Density Proteins occurring with PEMT -/- Genetic Status even when a High Fat Diet was provided to PEMT -/- Murine Populations such that Low Density Lipoprotein Receptor Enzyme impairment is known produce 85% decrease in exhibition of Artherosclerotic Lesions when PEMT was impaired by Polymorphism to exhibit PEMT -/- Genetic Status.226 Interestingly, this same study presents Stearoyl-CoA Desaturase-1 Deficiency as preventive of Obesity in Murine Populations, inhibitory of Phosphatidylcholine Synthesis, while also producing a 80% decreases in PEMT activity along with a 60 percent increase in CTP â&#x20AC;&#x201C; Phosphocholine Cytidylyltransferase.


PMCID PMC2903412

Interestingly, phosphocholine should not be considered to be pathogenic, except in accumulation or excess accumulation, particularly in movement to extracellular environment or exhibition in levels which surmount beneficial Apoptosis signaling. The literature, however, often regards supplementation of Phosphocholine in similar regard with obtainment of Choline or Lysophosphatidylcholine, both of which later versions of Choline are known to be typically secreted into extracellular environment by cellular entities. Pulmonary Fibrosis is known to be treatable with the Herbeal Medicine Hong Jing Tian or HJT or Rhodiola Crenulata, which inhibits expression of Fibrotic Genes in Alveolar Tissue. Molecular components derived from HJT were similar to those obtain from Pu Gong Ying or Taraxacum Mongolicum (PGY), Chuan Xin Lian or Andrographis Paniculata (CXL), as well as Jin Yin Hua or Lonicera Japonica also known as Honeysuckle or JYH. The Active factors in these molecular extracts were observed as Phosphocholines with 18;0/18;2 Configurations and Phosphocholines with 16;0/18;2 Configurations. The manner of action of these Phosphocholines was presented as potentially producing Liposomes exhibiting Plantae Small RNA which then permeated Alveolar Gastric Cellular Entities. This innovative exhibition of Phosphocholine activity exhibits potential of therapeutic application of Botanical RNA which occurs naturally along with production of siRNA vectors which use Phosphocholine.227 However, Phosphocholine is typically regarded as detrimental when accumulated. Phosphocholine Transferase Enzymatic Activity is considered to be the difficult to ascertain factor that produces causal correlation between C – Reactive Protein and Preeclampsia.228 C – Reactive Protein is also known to exhibit Greatest Affinity for Phosphocholine among all its other Ligands although this affinity seems to be specific for Phosphocholine and not inclusive of Phosphocholine exhibiting Molecules otherwise. Excluded from C-Reactive Protein’s affinity priorities are Phosphocholine in Plasma Membranes of Healthy Cellular Entities and Plasma High Density Lipoprotein Molecules whereas C-Reactive Protein does exhibit strong Affinity toward Platelet-Activating Factor while aggregates of C-Reactive Protein also selectively integrate with Low Density Lipoprotein and selectively integrates with Very Low Density Lipoprotein when observed in whole Plasma.229 A study of PEMT activity confirmed that 17-betaestradiol administration results in the expression of PEMT at levels correlated to Dosage Human and Murine Hepatocytes. PEMT expression is known to be stimulated by Activation of Estrogen Receptors Alpha and Beta, of which 17-estradiol equally activates. The expression of AP-1 is known to be upregulated by activation of Estrogen Receptor Alpha whereas AP-1 is known to be downregulated by expression of Estrogen Receptor Beta. AP-1 is known to inhibit PEMT catalytic, such that uneven increased activation of Estrogen Receptor Alpha potentiates inhibition of PEMT by AP-1. Estrogen Receptor Alpha inhibits the availability and Catalytic activity of AP-1 to balance the effect of Estrogen Receptor upon AP-1 activity. Estradiol, as 17beta Estradiol evenly activates both of these Estrogen Receptors, Alpha and Beta, whereas Estrone more prevalently activates Estrogen Receptor Alpha such that AP-1 is also upregulated resulting in downregulation of PEMT. Interestingly, the literature observes that Metalloproteinase is regulated by Estrogen Receptor Alpha through a mechanism that is enabled by an AP-1 interactive Location in the Metalloproteinase 13 Promoter Region. The regulation of Metalloproteinase by Estrogen Receptor Alpha occurred regardless of if 17beta-Estradiol were exhibited or not exhibited, providing only a small amount of information because Estrone can activate Estrogen Receptor Alpha

227 228 229

Digital Object Identifier 10.1007/s11427-017-9026-7 Digital Object Identifier 10.1161/HYPERTENSIONAHA.114.04439 Digital Object Identifier 10.1006/rwei.1999.0175

at increased levels compared to Estrone activation of Estrogen Receptor Beta, occurring as an alternative to 17betaestradiol in activation of Estrogen Receptors.230 The Estrogen Receptor Response Elements which enable transcription of PEMT occur as a Perfect Response Element Region 7.5 kb from the location at which transcription begins in alternative transcriptions productions NM_007169 and NM-008819 in Human Populations while also being exhibited in the Murine Transcription Variant NM-008819. Three imperfect Estrogen Response Element Regions were also found in the Putative Promoter Regions. The analytics predicts that there may be as many as three different Transcription Begin Loci for both Human and Murine PEMT transcription, occurring resultant of Multipole Promoter Configurations are occurring through Alternative Splicing in which interactions between mRNA and Epigenetic Material which change the outcomes of the multiple phase of DNA translation into RNA followed by synthesis of Proteins from RNA. 231 A particular study observes that Folate Deficiency, in Small Mammal Nonhuman populations results in depletion of Choline and Phosphocholine.232 A Study of Gestational and early developmental Folate metabolism in Maternal, Fetal and Infant status observes that Vitamin B12 levels in Plasma decreased in carrying Females from Week to Week 36 and recovered at 14 Weeks after delivery. Carrying Females exhibited decreases in Red Blood Cellular entities from Week 20 of Gestation to 27 Weeks after delivery. Breast Fed Infants exhibited decreased Vitamin B12 at 6 Months after Delivery when continuing to Feed at 6 Months, while also exhibiting lower Folate, each compared to Infants utilizing Formula instead of Breast Feeding at 6 Months. Carrying Females exhibited inverse relationships between Plasma Folate and Plasma Homocysteine when adjusting for B12 status. These suggest that Plasma Homocysteine is a response to Folate or Methyl Factor inadequacy during Gestational Status while after delivery, Plasma Homocysteine seems to be an interactive factor that is either the result of or participating factor in the stimulation of Breast Feeding Patterns. Formula utilizing Maternal Females and Infants exhibit lower Plasma Homocysteine than Breast Feeding Infants at 6 Months, although Breast Feeding Infants are considered by the literature to have improved outcomes compared those which are not Breast Feed. These suggest that Homocysteine may be a mechanism by which early developmental physiology is managed toward sources of Choline and Folate while also potentially being a mechanism through which influences the instance at which Feeding Occurs.233 B12 Vitamin levels 185 pmol/L or lowever and B6 Vitamin levels at 44 nmol/L or lower each increase the risk of Nonsyndromic Orafacial Clefts in early development.234 Moderately elevated Homocysteine in carrying Females, equal to or greater than 9 Micromoles per Liter, is correlated with lower performance by offspring in early developmental BSOD Psychomotor Tests, Mental Development Tests, WPPSI Full, Verbal, Performance, Intellectual Quotient tests. These show the Gestational

230 231 232 233 234

Paper no 1063. 52nd Annual Meeting of the Orthopaedic Research Society. Digital Object Identifier 10.1096/fj.07-8227com LIBRARY OF MEDICINE PUBMED IDENTIFIER 7965204 Digital Object Identifier 10.1007/s10995-011-0782-0 Digital Object Identifier 10.1067/S0002-9378(03)00592-1

Homocysteine at increased levels correlates to lower Psychomotor and Cognitive Development Performance by developing Humans until 6 Annum which was the highest Age of offspring used for such testing in the study.235 The literature observes that although supplementation of Folate does not produce substantial differences in Maternal Plasma Homocysteine at 3 months after delivery or 3 months after Birth, supplementation of Folate produces increased levels of Erythrocyte Folate, Hemoglobin, and Hematocrit, along with decrease in Reticulocytes, there was in unsupplemented Female Carriers a decrease in Folate from 224 to 187 nmol/L from Birth to 6 Months and an increase in Plasma Homocysteine from 6.7 Micromoles Per Liter to 7.4 Micromoles per liter from Birth to 6 Months.236 This suggests, together with the other information presented in these analyses, that Homocysteine may be a participant in producing associations between physiological stimuli, physiological indicators and the impetus or inclination to discriminately ascertain factors exhibiting Choline and Folate as well as systematically produce inclination to obtain these factors when their availability is not metabolically adequate. Interestingly, Homocysteine seems to be a method of modulating the intensity of susceptibilities to external stimuli and influence in a way the reflects Genetic and Metabolic circumstance within Choline and Folate Metabolic Pathways. Increased levels of Homocysteine may reflect level of impairment within Choline, Folate, 1 Carbon, Methylation and Phospholipid pathways, while Homocysteine has also being acknowledged as a factor in susceptibility to detrimental behavioral outcomes since the early 1960â&#x20AC;&#x2122;s. Thus, Homocysteine may be way of alternative patterning toward Choline and Folate enriched Nutritional Factor obtainment which may be correlated with decreased Conscious Cognitive Performance, suggesting that Homocysteine may have been a way of directing Humans toward Choline and Folate enriched Nutritional Factors before Civilization commandeered such patterning using conscious stimuli, associations and reason to potentiate obtainment of optimal nutritional factors. Another study provided a low Choline, 25 Microgram and 56 Microgram per day, and Low Folate, 238 Milligram and 147 Milligram, supplementation regiment to Men and Women, respectively. Pteroylglutamic Acid was also provided after between 4 and 5 weeks of the deprivation Regimen. The Average Plasma levels of Choline decreased 28% in Men and 25 Percent in Men with an average decrease in Phosphatidylcholine of 26% in Men only. The study indicates that Transaminase and Lipid levels do not bely Choline Deficient Pathology, although these analysis present that the decrease in Phosphatidylcholine likely belies decreased PEMT activity. Pteroylglutamic Acid, a Folic Acid version, at moderate levels caused Choline and Phosphatidylcholine to return to baseline levels in ways that were more responsive than Plasma Folate and Homocysteine. The study suggests that Choline supports Folate Levels by providing Methyl Groups when Folate is low, although the literature widely presents that Folate assists in Recycling Homocysteine into Methionine, followed by Methionine being used as a Methyl Donor for PEMT in a way in which Homocysteine produced by PEMT activity seems to be preferred by BHMT in producing Methionine and/or seems to be preferred by Folate in producing Methionine. There is not much support in the literature for this preference, although elsewhere such a potentially was derived from perusal of the Clinical Literature. However, dietary Choline was found to be required at levels greater than 250 Milligram per Day when Folate obtainment is low.237 Another study links Gestational Homocysteine at increased levels with Schizophrenia. This linkage clearly presents that pervasive Cognitive and behavioral conditions may be the result of physiological changes allowed to occur in which physiology becomes more focused upon producing and maintaining those associations that enable 235 236 237

Digital Object Identifier 10.1111/mcn.12289 Am J Clin Nutr. Volume 69. Number 2. Pages 285 to 292. February, 1999. J Nutr. Volume 129. Number 3. Pages 712 to 717. March, 1999.

survival, such as finding and obtaining Choline as well as Folate. Moreover, these also suggest that civilization presents commandeering associations and cognitive artifacts which intercept these associations which would otherwise occur in Nature such that Humans whom exhibit inadequate levels of Choline and Folate have an amplified susceptibility to such commandeering influence, associations and Cognitive artifacts. Similarly, the use of Formula instead of Breast Milk seems to produce and integrate such commandeering associations and cognitive artifacts constitutively while Breast Feeding integrates Homocysteine, Choline and Folate levels into Perception, Cognition and Behavior in an interactive manner.238 Another study exhibits increased sizes of Soma and increased numbers of Primary and Secondary Basal Dendritic Branches from Gestational Supplementation with Choline. These Changes to Hippocampus Structure are correlated with improved Long-Term Potentiation which is an Electrophysiological Characteristics of Hippocampus Structure and Function, improved Visuospatial Memory, improved Auditory Memory, absence of Senility at progressed ages, enhanced Neurogenesis and Synaptogenesis in the Hippocampus and Forebrain, as well as decreased Proactive Interference in which memories from other instances interfered with memories in the short term immediate context. Deficiency in Choline has been found to result in Hypomethylation of DNA, particular at CPG Islands which exhibit Cytosine Bases followed by Guanine Bases, which can occur upon 60 to 90 percent of the 5’ CPG ‘3 CPG islands. Hypomethylation of the Cyclin Dependent Kinase Inhibitor 3 Gene at its promoter can result in increased expression of this Gene resulting in inhibition of Cellular Proliferation, explaining Fetal Hippocampus decreases in Cellular Proliferation when Choline is deficient. Many such changes to Gene Expression can be exhibited for the duration of Vital Being, including the detrimental pathophysiological characteristics which also result from Choline Deficiency, although Choline and Folate deficiency are pervasively not adequately acknowledged and remediated in populations thereby contributing to persistence of such detriment.239 Another study clearly found Hippocampus Angiogenesis decreases associated with Choline Deficiency during Gestation while also finding that Birth Defects were Globally correlated with Choline Deficiency during Gestation. Similarly, Neuronal Progenitor Cellular and Epithelial Progenitor Cellular Changes were found to occur along with Choline Deficiency, while decreases in such Progenitor Cellular Proliferation in the Subventricular Zone of the Hippocampus were found to be decreased by as much as 50% in Small Nonhuman Mammalian organisms exposed to Gestational deficiency of Choline.240 Murine gestational populations with choline deficiency exhibit decreases in Neural Progenitor Cellular Mitosis of 47% in the Brain Septum, 29% in the Hippocampus, 34% in Striatum, 33% in the Anterior Neocortex and 33% in the Mid – Posterior Neocortex. Similarly, Folate Deficiency correlated with 100 percent increase in Rate of Apoptosis in the Septum and Hippocampus.241 Choline supplementation improved Mitosis levels toward Control, improved Mitosis levels in the Septum and Striatum substantially, while resulting in substantial variance from Control Groups without Folate Deficiency only in Septum and Neocortex where Choline Supplementation produce substantial decrease levels of Mitosis compared to Control Groups with adequate Folate. Choline supplementation decreased and thereby improved the levels of Apoptosis compared to Folate Deficient Populations, achieving Apoptosis levels which are comparable to Control Groups without Folate Deficiency. These suggest that Folate deficiency can be assist by 238

Elevated Prenatal Homocysteine May Raise Schizophrenia Risk. The Website.

239 240 241

NIHMSID NIHMS53402 Digital Object Identifier 10.1016/j.semcdb.2011.06.002 PMCID PMC2869500

Choline Deficiency. These also suggest that Choline supplementation without Folate and Folate supplementation without Choline, as well as inadequate Choline, inadequate Folate, or both, produce particular patterns of impaired Neurological Center Function. These Neurological Patterns seem to be being allowed to occur in populations which have Choline and Folate deficiency unacknowledged in Gestational and early Developmental phases as well as in other phases of development. There is a strong possibility that these patterns may be spontaneously emerging in particular patterns of susceptibility which may be being utilized by Algorithms and Routines affected by the Profit Priority of Private Enterprise, the potential of Systems to Prioritize themselves over Humanity, as well as the detrimental aspect of the status quo. The presentation, here, of structural, Neurological and developmental patterns produced Choline and Folate deficiency are strong linkages to the way in which systems utilize Choline, Homocysteine, and Roemerâ&#x20AC;&#x2122;s Law dynamics to shape incipient Physiological circumstance through persistent circumstances occurring civilization, resulting in patterns of outcomes that can cursorily seem to be culturally or geographically correlated. Moreover, the potential that gestational and developmental impairment in the essential aspects of Neurological tissue and function might be allowed to occur such that Choline, Folate and Homocysteine might be utilized to produce typical patterns of Human outcomes has to be presented for consideration here. However, the potential that allowing such inadequacies to persist such that populations might be developmentally impaired systematically to prevent understanding of these causal nuances of developmental also has to be presented here.242 Together, these suggest that Human Outcomes are pervasively the result of Patterning that has been exhibited since before Gestation and during development otherwise that changes the very characteristics of Neurological tissue, structure and function. The nature of interaction among systems and how typical mechanisms of changing behavior which are pervasively considered to be productive occur does not require any specific awareness of these mechanisms, while it can also be observed that Humans pervasively may have become susceptible to these same patterns in ways that may vary according to circumstance or even random chance. Although this information clearly presents why Premenopausal Females are resilient to Choline Deficiency, why Menopausal Females begin to exhibit outcomes closer to Males, and why Phosphatidylcholine levels as well as Homocysteine Levels may being to Dovetail or become uniform between gender during Menopause, it should be clearly presented that it is beginning to be consensus in the literature that it is not Phosphatidylcholine differences that enable disparities in outcomes among Gender, being instead De Novo Choline Synthesis particularly by PEMT which seems to be the most precise characterization of these differences. Choline is synthesized De Novo by PEMT as constitutive aspect of Phosphatidylcholine. Again, regardless of Choline supplementation, a Choline Deficiency, De Novo Choline Synthesis Deficiency, was produced by inhibition of impairment of PEMT. 2.7 Grams of Choline per kg of Somatic Mass reconstituted typical energy Metabolism in the PEMT -/- Murine populations, stimulated increase in Somatic Mass, and reenabled emergence of Insulin Resistance in PEMT -/- Mice fed a High Fat Dietary Regiment. This suggests that the activity of P53, at least with regard to inhibiting Glut 1/3/4 and inhibiting Insulin Receptor were impaired by PEMT -/- and inadequate levels of Choline, requiring 2.7 Grams of Choline per kg of Somatic Mass for these inhibitory activities of 242

PMCID PMC2869500

P53 to be exhibited. Clearly this support that Choline deficiency inhibits Nucleotide Synthesis, regardless of which pathway, CDP-Choline or Methylation Pathway to PEMT, are exhibited and these may decrease the global availability of Nucleotide for DNA Synthesis, DNA repair, DNA replication, and RNA synthesis. The literature suggests that Choline deficiency affects PEMT activity in a complex manner. PEMT activity has been observed to decreased PEMT activity except for PEMT2 in Hepatic Tissues which substantially, although some of the literature observe Methylation deficiency from inadequate Choline ingestion to also decrease PEMT activity Generally in Hepatic tissues. However, pervasively the literature observes decrease levels of Diverse Fatty Acid Phospholipid and Phosphatidylcholine Species when Choline Deficiency is exhibited, suggesting either inhibited PEMT expression, inhibited PEMT catalysis, or inhibited DHA-Glycerol which PEMT prefers in producing inflammation inhibiting Phospholipid Species.243 However, Choline deficiency is known to promote the exhibition of Hepatic Steatosis which can result the exhibition of Phosphatidylethanolamine in the outer plasma membrane, resulting in leakage of metabolites and molecules, thereby constituting a participating causal factor in the exhibition inflammation observed in Hepatic Steatosis. However, the literature observes PEMT1 and PEMT2 are change in availability responsively to Hepatic Injury. Moreover, the literature observes, pervasively, that PEMT is inhibited during Human Oncology, except for particular instances of Oncology which seem to be more precisely correlated with either PEMT2 impairment or with the effects of TMAO. One article presents that PEMT2 is principally exhibited in an exclusive fraction of the Hepatic Tissues, particularly in a Small Nonhuman Mammalian Species.244 Other literature suggest the PEMT2 inhibits proliferation of Hepatocytes. Another article observed in RH7777 Hepatoma Cellular Entities that PEMT2, when increased, was correlated to a decrease in the activity of CTP Phosphocholine Cytidylyltransferase. The article observed inhibited integration of Serine into Phosphatidylcholine along with increased integration Ethanolamine and Methionine of particular experimental versions which suggests that Serine was not the route of Ethanolamine Synthesis because Ethanolamine was supplemented, while Methionine may have been the route of Methylation through Phosphatidylethanolamine becoming transformed into Phosphatidylcholine.245 PEMT may be utilized as rescuing mechanisms for Choline synthesis when Choline is not obtained through Nutrition, although the literature is unclear with regard to if PEMT is upregulated, if PEMT1 is upregulated, although the literature suggests that PEMT is upregulated while the exhibition of Diverse Fatty Acids in Phospholipids decreases also as a result. Thus, PEMT may become upregulated comparatively to CDP Choline pathways analogous factors because the CDP Choline has less substrate, although the literature observes that each pathway performs catalysis of metabolites in the each otherâ&#x20AC;&#x2122;s pathways and although exchange of substrate through lead group or Head Group transfer has been suggested to occur. Because the exhibition of diverse fatty acids is impaired during choline deficiency, it is possible that Choline/Ethanolamine Phosphotransferase may be producing Phosphatidylcholine at enhanced levels while also the PEMT enzyme may be producing Phosphatidylcholine from the fraction of Phosphatidylethanolamine derived from Serine in the cycling Phosphatidylcholine from cellular membranes into Phosphatidylethanolamine. 243 244 245

Digital Object Identifier 10.1074/jbc.271.5.2839 Digital Object Identifier 10.1074/jbc.271.5.2839 PMCID PMC1136204

Similarly, the upregulation of PEMT2 may rescue inhibited PEMT1 or result in enhanced levels of PEMT although the Catalysis of PEMT2. PEMT2 is known to inhibit Hepatocellular Proliferation. It is possible that at least some of P53 expression from Choline Deficiency emerges from other Mechanisms include Hepatic Injury although these analyses clearly found literature observing upregulation of P53 resultant of PEMT inhibition or injury in cellular entities.246 Correlatively, a particular article observes the differences in In Vitro and In Vivo effect of Choline Deficiency upon cellular entities, using a Nonhuman Small Mammal population and particularly utilizing Hepatocytes. Impairment of Phosphatidylethanolamine Methyltransferase, or PEMT, clearly decreases VLDL Secretion, although the mechanisms of the decrease in VLDL is not specified as circumstance of Caveolae Constriction, decreases production of VLDL or of other causality. Choline Deficiency was observed to occur along with Plasma Apolipoproteins, APO factors, were also decreased, particularly inclusive of B100 and B48. Interestingly, Triacylglycerol Content increased along with these circumstances. Hepatocytes, then, cultured from the same Choline Deficient populations and placed in In Vitro, were observed with Choline supplemented in Eagleâ&#x20AC;&#x2122;s Medium and without Choline Supplemented in Eagleâ&#x20AC;&#x2122;s Medium. The In Vitro Choline Deficient Hepatocyte Population did not decrease while Triacylglycerol Secretion, however, experienced only an insubstantial decrease. Similarly, Phosphatidylcholine Synthesis was observed to increase in Choline Deficient Hepatocytes In Vitro, although the literature did not explore the Fatty Acid Content of the Phospholipids and did not use a Marking factors to differentiate the source of the increase. The molarity of Phosphocholine was presented as being decreased with In Vitro Choline Deficiency in Hepatocyte while the amount of Phosphocholine persisted at levels above the K, or throughput, for CTP Phosphocholine Cytidylyltransferase. Liver X Receptor is known to participate in Cholesterol and Lipid management as well as Cholesterol and Lipid Transport pathways in Hepatic Tissue. One Article at least, presented in the preceding paragraphs suggests that PEMT1 is exhibited in the Endoplasmic Reticulum, which also potentiates that iNOS expression and the Unfolded Protein Response include impairment of PEMT1. Similarly, PEMT2 is presented by the same article as being exhibited in the Endplasmic Reticulum. However, Murine populations are known to exhibit PEMT2 specifically in the Mitochondrial Associated Membrane which is the region of shared membrane between the Endoplasmic Reticulum and Mitochondria. The same article presents that Choline Head Group exchange occurs to produce other molecules, thereby, pivotally, exhibiting validating that molecule produced through a processe presented elsewhere in this analysis which produces all the requirements for Phosphatidylcholine except the Choline Headgroup, may represent a new pathway for Choline Synthesis in Physiology. Choline is presented as having Sn-1 Saturated Fatty Acid and Sn-2 Saturated Fatty Acid as Hydrophobic Domains while the Choline Head Group at Sn-3 is Hydrophillic.


Digital Object Identifier 10.1023/A:1022470301550

Catobolism of Phosphatidylcholine is presented as occurring through Phospholipase A2 synthesis of Lysophosphatidylcholine and Arachidonic Acid, Phospholipase C synthesis of diacylglycerol and Phosphocholine, Phospholipase D catalysis which proeuces Phosphatidic Acid and and Choline, as well as Sphingomyelin Synthase which produces Sphingomyelin and Diacylglycerol.

Particular research by Ridgway and Vance, after Sundler and Akesson Characterized PEMT, observed that each instance of a PEMT catalytically depletes the substrate Phosphatidylethanolamine at a rate of 0.63 Micromoles per minute per Millgram, while the rate for Phosphatidylmonomethylethanolamine or PMME is 8.59 in such regard and the rate of catalysis for Phosphatidyldimethylethanolamine in such regard is 3.75. 247 The literature observes that accumulation of Hepatic Triglyceride is considered to occur resultant of impaired availability of Phosphatidylcholine in the cellular membrane. The precise mechanisms is not widely presented although inflammation, P53, iNOS, impaired Caveolae re hallmark features of Choline deficiency which could be causal without additional explanation. These analysis do not suggest an increased prominence of CTP Phosphocholine Cytidylyltransferase in Physiology, because, the literature has presented that this enzyme or its metabolic products, including those of its products which are produced by the Methylation Pathway, may be essential to even the Methylation Pathway. However, it is observed that CTP Phosphocholine may be upregulated by iNOS to prevent Apoptosis when iNOS inhibits PEMT, and, resultantly, the increased sensitivity to Apoptosis which occurs when CTP Phosphocholine Cytidylyltransferfase is inhibited, such as sensitivity to Cholesterol which can result in apoptosis, might be particularly potentiated as a result of iNOS expression. Thus, the causal sensitivity mechanism to Cholesterol which potentiates apoptosis may be the result of the upregulation of Diacylglycerol and upregulation of iNOS, such that impairment of CTP Phosphcholine Transferase removes dependency which iNOS expects. Illustrativley, Cellular entities are regarded as widely benefiting from Cholesterol availability such that even levels as High as 300 in diagnostic assay are pervasively detrimental when Oxidation of Cholesterol Occurs instead of being the result of Cholesterol levels constitutively. Similarly, there are particularly instances in which iNOS is beneficial, particularly during Gravitational Changes, decrease number of cellular entities per micrometer which occurs along with Choline Deficiency, wound healing and during microbial insurgency into the intracellular environment. Inhibition of CTP Choline, thus, removes a dependency that seems to be essential for typical conditions in the cellular environment as well as remove a dependency which, during exceptions in which capabilities of physiology promote cellular resiliency, may promote survivability in cellular entities.248 The article presented some different conclusions, including observing that Choline Deficiency does not reduce VLDL, does not reduce Apolipoproteins and the occurrence of decreased Apolipoprotein B has to be the result of some other factor. However, these analyses pervasively exhibit that Choline Deficiency decreases the essential Fraction of Phosphatidylcholine which exhibits diverse Fatty Acids, as well as increased levels of Omega-3 Fatty Acids that are 247

Characterization of Phosphatidylcholine Metabolism in Mouse Hepatocytes after Hepatectomy and in Primary Human Hepatocytes. A Thesis Submitted to the Faculty of Graduate Studies and Research in Partial Fulfillment of the Requirements for the Degree of Doctor of Philosophy. University of Alberta.


Characterization of Phosphatidylcholine Metabolism in Mouse Hepatocytes after Hepatectomy and in Primary Human Hepatocytes. A Thesis Submitted to the Faculty of Graduate Studies and Research in Partial Fulfillment of the Requirements for the Degree of Doctor of Philosophy. University of Alberta.

essential enough to constituted regenerative physiology compared to persistently deteriorating physiology. Although the articles in the preceding few paragraphs seem to dispel that the this reduced Essential Fraction of Diverse Fatty Acid exhibiting Phospholipids may not precisely the result of downregulation of the Expression of all three PEMT alternative transcription productions, it does clearly present that PEMT becomes impaired in it is optimal Catalysis from Physiological Perspective. Furthermore, impaired exhibition of PEMT Catalysis is known to upregulated P53 which, in turn, then, causes expression of Inducible Nitric Oxide Synthase, causes Expression of NF kB, inhibits Glycolysis, inhibits Pentose Phosphate Pathway, downregulates Glut 1/3/4, and impairs the Insulin receptor. However, because secretory activity pervasively occurs within the Caveolae, as does receptor activity for nonmineral messengers such as Steroids, Lipids, Hormones, Insulin, Glucose and other factors, it can be clearly presented that Inducible Nitric Oxide Synthaseâ&#x20AC;&#x2122;s depletion of Calcium, which then results in inadequate availability for functional Endothelial Nitric Oxide Synthase as well as Neuronal Nitric Oxide Synthase, all may contributed to impaired Secretion of Lipids and other Messengers. A Review of the content of Eagles Medium clearly presents that Calcium Chloride is exhibited, both of which may artificially sustain Ion Channels and Nitric Oxide Synthase Activity compared to the Physiological In Vivo environment where iNOS perforates the Endoplasmic Reticulum, perforates the Plasma Membrane, depletes Calcium, produces a pumping mechanisms in which Calcium is depleted from extracellular environment and channeled directly to iNOS, while also the Collapsing of the Sarcolemma produces an impedance to circumventing these substantial impairment of interfaces to the Extracellular Environment. Similarly, Choline Deficiency is known to also result in exhibition of increased Levels of Diacylglycerol which may be essential to iNOS and NF kB activity. These increases along with impairment of the Caveolae through constriction, as well as other factors presented here, may explain In Vivo decreases in Apolipoprotein availability and VLDL Secretion, which are observed to occur along with increases in Triglyceride Content in Hepatic Tissue. Most Compellingly presented here, however, is that Phosphocholine may be produced from Phospholipid cycling that is supplied by Phospholipases which begin to Catabolize Cellular Membranes during Choline Deficiency. The fraction of Choline in the study was clearly higher than that supported by CTP Phosphocholine Cytidylyltransferase activity, although it is interesting why Choline Kinase Catalysis was not presented instead of CTP Phosphocholine Cytidylyltransferase. Choline Kinase is the principal Enzymic De Novo Synthesizer of Phosphocholine, according to the literature. Similarly, iNOS, AP-1, and SP-1, both of which are known to be regulated by dynamics which occur resultant of Choline Deficiency, are known to potentiate inhibition of PEMT along with upregulation of Choline Kinase. Clearly, no analysis could be complete without considering these cyclical influences to PEMT and Choline Kinase.249 Presenting the Choline Deficiency inhibits PEMT is probably too loose of explanation for these changes. However, impairment of PEMT by Choline Deficiency certainly seems to be a rather precise explanation of this phenomenon. However, suggesting the PEMT is only impaired, seems to require explanation of diverse Phenomenon, including explaining that PEMT2 may be inhibitory to Proliferation during Regeneration and during impairment. Inadequate acknowledgement of Choline Deficiency beginning at birth is emerging as an incipient neglect of Human Requirements that may be allowed to persist throughout the span of the typical Human Span of Vital Being. It, again, is a mystery how such neglect could be allowed to persist in the context of pervasive, clear, causal linkages to 249

Digital Object Identifier 10.1074/jbc.M312676200

most of Human Physiological and behavioral Pathology. Even perfectly repaired Genes by CRISPR CAS Gene Editing seem to require prioritization of Choline, because without these Patterns of Genetic Impairment, inflammation and impaired metabolism have the potential to persist in their detriment to physiology and behavior. Interestingly, in this study of separately impaired PEMT -/-, PEMT +/+ and CDP-Choline impaired populations, PEMT +/+ populations which were also fed Choline Deficiency Nutritional Regiment exhibited increased Oxygen Consumption, improved Glucose Tolerance and were less susceptibility to increase in Somatic Mass. Choline, then, emerges above Phosphatidylcholine as a deterministic factor in differences among PEMT and CDP-Choline Status, particularly because de Novo Synthesis of Choline occurs during PEMT although Choline is produced as an integrated aspects of Phosphatidylcholine during PEMT synthesis of Phosphatidylcholine.250 Importantly, a particular article suggests that increased levels of Phosphatidylcholine inhibit both Apoptosis and progression of the cellular cycle beyond G1 to S Phase. This suggests that physiology may not only prefer increased density of cellular material, also, instead, preferring increased density of the cellular membranes. Both density of cellular entities in number and density of Phosphatidylcholine in Membranes would likely result in improved structural resilience. Phosphatidylcholine at increased levels also potentiates inhibition of NF kB, while NF kB inhibition decreases the potential for iNOS, thereby suggesting an interactive Mechanism by which Gravitational changes stimulate iNOS as well as enhanced structural resilience decreasing the potential for iNOS. AP1, which inhibits PEMT and upregulates Choline Kinase is considered essential for Glioma Multiforme.251 252 Comprehensively conforming the use of Choline Kinase in therapeutic management of Glioma Multiforme, a study in Small Mammals clearly showed that the Choline Kinase Inhibitor MN58b Abrogated Choline Metabolism in Oncology cellular entities within Neoplasm of Central Cerebral Neurological Center. Specifically, these resulted in decreased Choline Metabolism and substantial reduction in Phosphocholine, confirming clearly precise orchestration of the Clinical Literature within the Amehsi Specification. However, also exhibited were increase in Polyunsaturated Fatty Acids which are characteristics of Apoptosis although confirming that competitive inhibition of Choline Kinase can result in increased exhibition of PEMT pathway metabolites include Polyunsaturated Fatty Acids. Similarly, determinable increases in apoptotic cellular entities were observed along with abated cellular cycle, clearing in accordance with the known ability of Choline Kinase Inhibitors to specifically stimulate apoptosis in Oncology Cellular Entities. Since Glioma Multiforme is considered an exception to the requirement for exhibition of inhibited PEMT, these findings clearly suggest that Choline Kinase Upregulate and Downregulation of PEMT, are precise locus of causality for Oncology in Mammalian organisms and these may include most if not all aspects of Oncology, leukemia and Lymphoma, as well as most disease and health conditions exhibited in Mammalian populations.253 AP1, SP1, and Homocysteine, then, may be primary factors which enable oncology in Human populations. However, both iNOS and Trimethylamine-N-Oxide are emerging as essential prognostic indicators in any Health Status or Procedure. Thus, a Specific Choline Kinase Inhibitor Purinyl-6-Histamine, and inhibitor of AP1 such as Berberine, 250 251 252 253

PMCID PMC2903412 Digital Object Identifier 10.3233/CLO-2010-0524 Digital Object Identifier 10.1158/1535-7163.MCT-14-0775

inhibitor of SP1 such as Curcumin, Choline, Folate, Trimethylglycine, Complete B Vitamin Complex that includes Vitamin B12 Methylcobalamin, an inhibitor of Trimethylamine-O-Oxide such as Balsamic Vinegar and a Probiotic, an immediate inhibitor of Trimethylamine-N-Oxide such as a Diverse Coverage Antibiotic, and an Inhibitor Inducible Nitric Oxide Synthase such as Curcumin and Magnesium, and assurance that Nitric Oxide Synthases are performing in Coupled Modality by providing L-Arginine, Tetrahydrobiopterin, and a complete organic Mineral and Vitamin Supplement, may be pervasively alleviating of Oncology, Lymphoma and Leukemia. Information on natural and pharmacological factors that perform the required alleviation or prevention of such factors can be found at be searching the internet for Amehsi Specification Instructions or can be found at Methylcobalamin is preferred for a number of reasons, including the observation in the clinical literature that Cyanocobalamin potentiates toxicity resultant of a widely known noxious molecular factor. The detrimental noxious factor can be exhibited particularly by populations with particular pathology which affects metabolism of Cyanocobalamin when being utilized. Such detrimental noxious factor can, also, be exhibited when Cyanocobalamin is utilized with increased dosages. Hydroxycobalamin is utilized to manage toxicity, preforming as a precursor to Cyanocobalamin which promotes the integration of Cyanide Ion with itself, thereby producing the renal tissue metabolizable and renal excretable Cyanocobalamin.254 Nitroprusside is also capable of producing or causing Cyanide toxicity.255 It is also recommended that Electromagnetic and Communications fields be inhibited or turned off during the therapeutic process as these can cause expression of Inducible Nitric Oxide Synthase. Similarly, it is recommended that Organic Foods and Water be utilized which do not include Chlorine or Fluorine, as these induce iNOS expression. An energy safe room or location should be established and all ways of pointing internet sites or communications to that location should be inhibited or prevented. Similarly, electromagnetic protection clothing, devices, blankets and Tents can be utilized, including coverings for the eyes, ears and Cerebellum. The most recent clinical analyses can be found at While the second part of this most recent analysis can be found at with a search for amehsi Specification Although NFAT is also considered essential for Glioma, its expression and activity seem to be the result the processes that occur along with IP3/PI3k depletion of Store Operated Calcium, resulting sustain Calcineurin activity and sustained influx of Calcineurin. NFAT is presented in the literature as a Five Member group of Transcription factors that enable Immunological Regulation, Inflammatory Response, Cardiac Valve Development, Angiogenesis, Myocardial development, Axonal Guidance, Skeletal Muscle Development, and Bone Homeostasis while its overexpression is associated with Metastatic outcomes in Oncology. Depletion of Store Operated Calcium results in expression of STIM1 which integrates with Calcium Release Activated Calcium Channel Orai1 to cause sustained Calcium Influx. This influx seems Homologous to the Ca2+ Tunnel and Pump although Amehsi analyses found that these two phenomena may be distinctive from one another. Activated Calcineurin dephosphorylates Cytoplasmic NFAT Proteins, causing these to translocate to the Nucleus resulting in inhibition of Calcineurin Phosphatase Catalytic 254 255 Digital Object Identifier 10.1056/NEJM197804132981502

Activity. NFAT is discussed here because stimulation of its availability is potentially promoted by iNOS dynamics including depletion of Store Operated Calcium and Calcium Influx, while the depletion of Calcium because it is directed toward iNOS may introduce an asymmetric anomaly which NFAT does not expect, similar to the Apolipoprotein Complex. This may be an important causal factor to impaired regeneration and development or Mammals.256 Thus, iNOS and Homocysteine can each cause impaired development and maintaining of Cardiac Valves as well as Neurons and other aspects of Anatomy by introducing asymmetric impairment of NFAT as well as inhibiting PEMT and upregulation choline Kinase. Impaired Cardiac Valve and Neurological Center Development may benefit from assuring Choline, Betaine, Folate, and B Vitamins while also avoiding Chlorine and Fluorine, as well as wearing Electromagnetic Protective Clothing, as well as protecting oneâ&#x20AC;&#x2122;s domicile, power outlets, communications devices, devices otherwise and other sources electromagnetic energy, electrical fields, magnetic fields, or communications fields from being able to affect Physiology. Pajamas, Hats, Clothing, Coats, Faraday Cages, Protective Paints, Coating, and other factors can be obtained to assist in this capacity. Protein Kinase C activates SP1, through TPA/PMA, cyclically since SP1 also activates TPA/PMA, but SP1 can activate Protein Kinase C through these same mechanisms. AP1 is activated by Protein Kinase A. Protein Kinase A activity in an Ancillary Pathway is pivotal phenomenon because it is exhibited at the first cellular division of the Oocyte at the beginning Human Developmental Meiosis. This phenomenon seems to occur because Progesterone inhibits Protein Kinase A because it decreases Choline Kinase Beta Potential, forces an election that includes potentiation of Choline Kinase, Choline/Ethanolamine Phosphotransferase or PEMT. Progesterone most specifically potentiates Choline/Ethanolamine Kinase and PEMT, while supplying Mitochondrial Optimal Diverse Fatty Acids for such synthesis of phosphatidylcholine and enabling the Super Cleansing Phosphatidylmonomethylethanolamine to scrub the intracellular environment of Toxicity. Choline Kinase, according to the literature, is specifically required in only a few junctures of development and one of these includes the first exhibition of independent pulmonary function in which Choline Kinase is upregulated to promote thickening and increased density of cellular membranes in response to Xenobiotics and Inflammation. The 6 Hour and 12 Hour sampling duration, because it is exhibited in the Oocyte and Spermatozoa, seems to facilitate the exhibition of less than optimal membrane characteristics required for permeation and exchange of fertilizing material. Spermatozoa exhibit redistribution of factors for Fertilization to its outermost areas responsively to changes which include Calcium Influx and tis potentiation of cAMP activity as well as, therefor, cAMP-Dependent Protein Kinase A Activity. This cycle of inflammation inhibition and inflammation enablement seems to promote enhanced cellular structural readiness, a hiatus in which permeability and susceptibility to permeation briefly increases, and resumption of enhanced cellular resiliency afterward. The literature suggests that protein Kinase A activates AP1 by various MAPK Protein stabilization of AP1.257 SP1 or SP1 in these analyses indicates SP1 or SP1 Transactivation Protein 1. SP1 then seems to promote immortality of cellular lineages as they are or have emerged because it upregulates Choline Kinase and downregulates PEMT. AP1, then, seems to promote cellular lineage senescence because it downregulates PEMT, upregulates choline Kinase, and inhibits Telomerase. SP1 and SP3, SP1 and SP-3, are cooperative modulators of CPT Phosphocholine Cytidylyltransferase Alpha with reversible roles in Transcription activation in the Promoter Region of the Ctpct Gene, while SP2/SP-2 is a repressor of Transcription and Activation. This produces a system in which CTP Phosphocholine 256 257

PMCID PMC3694398 Digital Object Identifier 10.1074/jbc.270.28.16483

Cytidylyltransferase Alpha can be transcriptionally activated independent of Hepatocyte Growth Factor and can be inhibited independent of Hepatocyte Growth Factor as SP1/Sp-2 is not suggested to have a role in Hepatocyte Growth Factor activity such that SP-3 alone inhibits Hepatocyte Growth factor, potentially even when SP-2 is exhibited.258 SP1 or SP1 is considered a factor expressed in correlation with the 8 Principal Causal Factors in Oncology.259 These factors are characterized as Sustained Proliferative Signaling, Replicative Immortality, Resilience to Necrosis/Apoptosis, Resistance, Angiogenesis Stimulation, Avoidance of Immunological enabled Deterioration, Invasion and Metastasis, as well as unregulated Cellular Energetics. SP1 has its DNA Promoter Activity decreased by Phosphorylation in Hepatocytes.260 Regarding Angiongenesis, Antidesma Bunius Ethanolic Leaf Extract has been analyzed and found to exhibit the same level of Angionesis inhibition as Bevacizumab in reference Angiogenesis context.261 Antidesma Bunius produces a fruit that is White and becomes blackened with ripeness. Antidesma Bunius is also known as Currant Tree, Bignay, Bignay Laurel, Currantwood, Cherry, Herbert River Cherry, Wild Cheey, Laurel, Wild Cherry, Salamander and Salamander Tree. The Stem exhibits alternating Cream and Pink Layers. Leaves are between 12 and 2 Centimeters by 7 to 2.5 Centimeters. Leaves exhibits Lateral Veins in Loops which are distant from the Leaf Structural Margin. Petioles exhibits unremarkable channeled characteristics on the Upper Surface. Domatia exists typically as tufts of Hair. Stipules shed early while exhibiting small and inconspicuous strucuter. Fruits range from 25 Milimeters to 12 Milimeters. Antidesma is typically found from Sea Level to 1000 Meters in Altitude among margins of Rain Forests and within less moist versions of Rain Forests. The Fruit can sometimes be considered as Black Cherry or Currant, while being included in Jams, Jellys, Teas, Wine and Syrups.262 A Cordial Drink is produced from the Syrup of Antidesma Bunius by combining it with Alchohol while the Leaves are known to exhibit benefit for Hepatic conditions, Diabetic Pathology, and through provision of Antioxidants. Interestingly, Antidesma Binius is Dioecious, having plants which are Male flowers only or Female Flowers only. Antidesma Bunius also exhibits Polyphenols Corilagin, Gallic Acid, Ellagic Acid, Ferrulic Acid, Flavone Vicinin II and Amentoflavone, of which, Corilagin exhibited a IC50 of > 1000 ug/ml and Gallic Acid exhibited IC50 at 125 ug/ml while 50 ug/ml IC50 observed Silymarin. The exhibited Hepatoprotectiveness of Silymarin was exhibited at 12.5 ug/ml while Corilagin achieved similar protectiveness at 6.5 ug/ml and Gallic Acid achieve the similar levels of Protectivenss at less than 12.5 ug/ml.263 Elk1/ELK-1 or ETS Domain Exhibiting Protein 1 affects Long Duration Memory, Compulsive Conditions, Alzheimerâ&#x20AC;&#x2122;s, Breast Oncology, Down Syndrome and Depression, being presented here because it is MAPK activated Protein which attaches to the CTP Phosphocholine Cytidylyltransferase Promoter Region to upregulate its activity. Thus, Elk1 or ELK-1, can cause the depletion of Phosphocholine by upregulating CTP Phosphocholine Cytidylyltransferase, which might shift Choline toward upregulated Phosphatidylcholine synthesis instead of accumulating as Phosphocholine. 258 259 260 261

Digital Object Identifier 10.1128/MCB.01828-08 Digital Object Identifier 10.1111/febs.13148. Digital Object Identifier 10.1074/jbc.270.43.25879 Anti-Angiogenic Property of Bignay (Antidesma Bunius) Ethanolic Leaf Extract in Early Gestational Duck or Ana Luzonica, Using Chorioallantoic Membrane or CAM Assay. University of the Immaculate Conception. Pharmacy/Chemisty.

262 263

Antidesmus Binius. Edition 6. Austrialian Tropical Rainforests Plants Website. Centre for Australian National Biodiversity Research. Bioactivity of Antidesmus Bunius. European Scientific Journal. Volume 9. ISSN 1857 â&#x20AC;&#x201C; 7881.

Kruppel-related zinc finger protein AP-2rep (KLF12) competes with and inhibits SP1 transactivation in models of Ovarian Oncology.264 Similarly, P53 competes with SP1/SP â&#x20AC;&#x201C; 1. at the SP -1 Promoter Region in HIV LTR Sequences and TATA Box Protein Promoter Regions, suggesting that SP1 is a feature for Pathogenic Aerobic Glycolysis and impaired P53 activity. PMID 8207805.265 P53, itself, is emerging as an essential focus for therapeutics by reconstituting Wild Type P53, increasing availability of P53, inhibiting its availability, inhibiting its duration of exhibition, or inhibiting its Translation at the RNA Level. Similarly, P53 and any of its partner molecules which are required for cellular deterioration are being determined as Synthetic Demise Partners, followed by inhibition of either of these when a change of function mutation occurs in either.266 The Serine\Threonine Kinase Polo Like Kinase 1 or PLK1 was found to be such a Partner to P53 in four different datasets. PLK1 has been found to be upregulated when pRb is functionally deactivated. Polo-Like Kinase 1 or PLK1 and the complete group of Polo Like Kinases can be inhibited with Thiazolidinones and Polo Like Kinases 1 may be upregulated when pRb ability to return cellular cycle to Phase 0 has become impaired because PLK1 assures optimal Centromere actions during cellular division.267 Methylthioglycolic Acid exhibits a deactivating Methyl Group which can be removed to perform as an enhancer of Methylation pathways, while Thioglycolic Acid exhibits a Thiol as well as performs as precursor of numerous therapeutic derivatives. Amazingly, Methylthioglycolic Acid, Thiazolidinones and B-Lactams or Beta-Lactams, as well as their derivatives can modules pRB, Cyclins, Cyclin Dependent Kinases, as well as numerous Kinases including Polo Like Kinase and Protein Kinases which include Phosphorylation factors. PLK1 is also correlated with Oncology when overexpressed, performing a role in assuring Centromere disjunction and separation by stimulating Cellular Cycle Pause while being protected from deterioration by P53. PLK1 can escape the effect of inhibitors through P53, enabling Centromere Separation to occur such that cellular entities divide and reenter the cellular cycle with intact 2N Chromosomes. DNA impairment response enzymes ATM and ATR catalyze the protection of PLK1 through the activities of P53 which also requires Phosphorylation of P53â&#x20AC;&#x2122;s Serine 15, suggesting that P21 also participates in such Protection and also suggesting that Oxidative Distress plays a role in protection of PLK1 activity or suggests that an essential role in protecting DNA from oxidative distress includes protection of PLK1. Protection of Cellular Metabolism from Oxidative Distress, heretofore, has not pervasively been associated with cellular cycle in this analysis.268 However, the RNA Helicase DDX3 is known to associated with P53 and Centrosome during Mitosis and its depletion in study of DDX3 function using HCT116 and U2OS Cellular Entities resulted in Chromosomal Misalignment, Multipolar Mitosis and Centrosome Segregation Defects, all of which culminated in G2/M Phase 264 Digital Object Identifier 10.1186/s12943-017-0582-2. 265 LIBRARY OF MEDICINE PUBMED IDENTIFIER 8207805. 266 BMC Medical Genomics. Volume 6. Number 30. 2013. 267 Patent Indicator WO2003093249A1. 268

Digital Object Identifier 10.1038/s41598-017-16394-2.

transition delay followed by deterioration of the cellular entities. DDX3 performance in preventing the emergence of Multiple Polar Mitosis and Preventing Coalescence of Supernumerary Centrosomes were both impaired by its depletion while the depletion of DDX3 also suppressed the Phosphorylation of P53 at Serine 15, suggesting that DDX3 may be required for P21 exhibition and the ability of P21 to prevent Apoptosis as well as the ability of the P21 and Insulin partnership preventing Apoptosis. The impaired Phosphorylation of P53 at Serine 15 also prevented localization of P53 at Centromeres.269 Pivotally, P53 Localization to the Centromeres during Anaphase and Telophase were both required for progression of Mitosis and this Localization required Phosphorylation of Serine 15. Amazingly, the mystery with regard to P53 seems to be that it leads cellular entities to Mitosis Completion. The numerous ancillary pathways seem to be interactive checkpoints and potential divergences toward accounts along the way to Mitosis. HC116 cellular entities exhibit at least 8 P53 Genetic Polymorphisms.270 U2OS cellular entities did not have particular P53 or PEMT Polymorphism according to a particular cellular lineage database found on the internet. These are interesting because preventing P53 expression, in this study of P53/DDX3, results in impaired DDX3 localization at the Centromere, whereas expression of high levels of Polymorphic P53 S15A, a change which disables the DDX3/P53 Catalytically interactive Loci, provides an observable although not complete reconstitution of the ability of P53 to stimulate DDX3 Localization to Centromeres as well as P53 Localization to Centromeres. The P53 S15A Polymorphic protein was able to Localize to the Nucleus, while not being able to Localize to the Centromere. Inhibition of DDX3 expression inhibited P53 by upregulating DNA Methyltransferase Activities and by Hypermethylation of P53 at its Promoter such that repressive Histone changes otherwise became upregulated. DDX3 inhibition also, interestingly, changed the translation of P53 at the mRNA level. These suggest that P53 Phosphorylation at Serine 15 is a mechanism of managing P53 activity that is also activated by Oxidative Distress, Serine 15 Phosphorylation in P53 results in its Localization to Centromeres and is required for optimal completion of Mitosis, P53 and DDX3 are synthetic partners in promoting cellular degradation when inhibited, while DDX3 effects P53 at the Epigenetic, Genetic, translational and Post-Translational levels, providing wide coverage of deterministic effect to P53 activity. DDX3 is upregulated by P53 and cyclically potentiates P53 while P53 Protects DDX3 and its accumulation at the Centrosome. Moreover, DDX3 upregulates DNA Methyltransferases suggesting that its effect may circumvent P53 and effect the pathways correlated with PEMT. Hypoxia Inducible Factor 1a also stimulates genetic expression and metabolic changes which are constitutive Survival Signaling through reconstitution of Oxygen Homeostasis. HIF1A is regulated by HIF Prolyl-4-Hydroxylases or HIF-P4H responsively to Oxygenation status. Inhibition of HIF-P4H-1 inhibits inflammatory potentiators while its upregulation stimulates Apoptosis Pathway Gene Expression, which is exhibited even during inflammation produced by Lipopolysaccharide and other influence. Inhibition of HIF-P4H-1 is also known enhance P53 activity as well as enhance P53 stability, as is observed with Hydroxylation of Proline 142 of P53. HIF is also known to stimulate Erythrocyte Production by stimulating Erythropoietin Synthesis by the Hepatic Organ, which then stimulates Red Blood Cellular Entities which emerge from Marrow. HIF2a is stabilized by the inhibition of HIF-PH4, resulting in the 269 270

DOi 10.1038/s41598-017-09779-w.

Synthesis of Erythropoietin in Renal Tissues. This regulation of Erythropoietin Synthesis by HIF2a is relevant for Adult Physiology.271 Nanoquinacrine, Quinacrine, or Mepacrine, also clinically known as Atabrine, which is used therapeutically manage Viral Pathologies, has been observed to cause apoptosis in HPV Stem Cellular Entities, while also inhibiting HIV, Tomato Bushy Stunt Virus, HCV, Encephalomyocarditics (ECMV) and Polio viral replication while also exhibited inhibitory activity in Pulmonary, Colon, Pancreatic, Cervical and Renal Cellular Carcinoma. Quinacrine is 9 Aminoacridine Derivative of Quinine obtained from the Bark of the Cinchona Tree.272 Although DNA intercalation, Topoisomerase Inhibition, P53 Activation, P21 stimulation, Autophagy activation, WNT/TCF inhibition, NF kB inhibition, and Histamine N-Methyltransferase inhibition are among the catalytic benefits of Quinacrine or its derivatives, the literature observes that Mepacrine antagonize the Phospholipase A2 activity of Bee Venom and Halothane. Hemolysis or Erythrocyte Lysis were studied and it was found that Phospholipase decreased by 8 times threshold of Molarity required for Hemolysis by Halothane suggesting that Hemolysis may be benefit from inhibition of Phospholipase A2. Mepacrine Antagonized, correlated to decrease, the level of Hemolysis caused by Phospholipase Activity.273 Phospholipase A2 can result in upregulation of iNOS, suggesting that iNOS may be inhibited by Quinacrine and Mepacrine.274 Similarly, Quinacrine and Mepacrine also inhibit AP-1.275 Studies of progressing gerontological status exhibit decrease in P53 activity that is correlative to increasing pathology while other studies also observe chronic overproduction of P53 in untimely aging that occurs more rapidly than is typical.276 The literature suggest that P53 seems to have role that precedes its use as an Oncology Suppressor and seems to prioritize the prevention of many mechanisms of cellular renewal, although these analyses suggest that the prevention of renewal occurs when PEMT is inhibited.277 NF kB regulates HIF1a and the different subunits of NF kB can differently regulate HIF1a. Similarly, the literature suggests that HIF1a is deteriorated by HIF-PH4 during typical injury while prolonged upregulation of HIF1a or HIF-1a through inhibition of P4H inhibitors or inhibitors of Prolyl Hydroxylases generally, results in regeneration of removed or impaired tissue. HIF1a downregulation is correlated with Healing with Scarring, particularly when a regenerative response to the injury has previously occurred. HIF1a, then, promotes regeneration as an incipient response to injury or impairment while HIF1a promotes scarring when a regenerative response has already been exhibited in the particular tissue. 271

Digital Object Identifier 10.1038/s41590-017-17376-0

272 273 274 275 276 277

PMCID PMC4742869 Toxicology and Applied Pharmacology. Volume 90. Pages 410 to 419. 1987. Digital Object Identifier 10.1161/01.HYP.31.1.218 Digital Object Identifier 10.1186/ar213 “Cellular” “Demise” and Differentiation. Volume 25. Pages 169 to 179. 2018. Digital Object Identifier 10.1038/xss.20107187 Digital Object Identifier 10.1016/j.cell.2017.08.028

However, it is the transactivation of Alkaline ceramidase 2 or ACER2 which is interesting because P53 transactivation of ACER2 performs the invoking and management of DDR or DNA impairment response. The first Intron of ACER2 Transcription exhibits two tp53 or P53 response elements known as tp53REs. ACER2 Catalyzes the progression of Ceramides into Sphingosine and then Phosphorylation of Sphingosine into Sphingosine-1-phosphate (S1P). ACER2 upregulation increases Sphingosine and S1P while decreasing Ceramides. Moderate upregulation of ACER2 results in avoidance of Cellular Cycle Pause and Senescence. Again, ACER2 is Transactivated by P53 and two of the Transactivation Loci within DNA are Homologously exhibited in the First Intron of ACER2 RNA which is exhibited as ACER2 is translated from DNA, into RNA and then into the ACER2 Protein or Enzyme. P53 potentiates Cellular Cycle Pause, Apoptosis, Senescence, other Programmed Demise and Metabolic Changes in cellular entities. P53â&#x20AC;&#x2122;s ability to potentiate DNA Damage Response is enabled through expression of ACER2. ACER2 catalyzes the transformation of Ceramide into Sphingosine and additional Phosphorylation of Sphingosine is required to produce S1P, suggesting that Phosphocholine accumulation participates in this potentiality. ACER2 increasing Sphingosine and S1P typically. Moderate levels of ACER2 inhibits Senescence and inhibits Cellular Cycle Pause when P53 levels are also moderate or when Infrared Radiation at low levels are exhibited, enabled through upregulation of the Proliferation enhancing and Survival enhancing S1P or through decrease in membrane Ceramide which accompanies increase in S1P. Increased level of P53 and high levels of Infrared Radiation resulted in increased potential for Programmed Cellular Demise including Apoptosis, enabled by accumulation of Sphingosine which is considered to be a Demise Potentiating Lipid. Accumulation of Sphingosine potentiates Apoptosis. S1P was presented in the study as a Survival enabling Bioactive Lipid which stimulates Apoptosis Pathways when exhibited at High Levels, explaining why Ceramide Accumulation is associated with enhanced Apoptosis since Ceramide Accumulation suggests that Ceramide transformation into S1P and Sphingomyelin is impaired. This potentiates that S1P increase indicates decrease of Ceramides while S1P at moderate levels suggests moderate levels of the Apoptosis Potentiating Sphingosine and while high levels of S1P suggests High levels of Apoptosis Potentiating Sphingosine. This explains why moderate levels of S1P correlate with moderate levels of ACER2 and Sphingosine, as well as correlates with decreased Ceramide, resulting in prevention of Apoptosis, preventing Cellular Cycle Pause and avoidance of Senescence. Thus, DDR performed by P53 exhibits PLK1 and ACER2 with P53 invoking or Protecting these factors essential to Genomic Stability during Mitosis and essential to Genomic Repair in circumstances otherwise. ACER2 impairment is correlated to Oncology and reversal of such impairment rescued Oncology in particular small nonhuman Organism studies of Oncology. Since P53 has been presented in the literature as becoming systematically focused upon by pathogenic factors leading to Oncology, it is becoming clear that Escape Mechanisms which enable cellular proliferation may be most pathogenic when DNA Synthesis, Repair and Replication are impaired or less than optimal, while without such Genetic inadequacies, it seems that proliferation anomaly might most potentiate Metabolic Syndrome instead of Oncology or inadequate tissue density might be most potentiated when deproliferation of cellular entities is exhibited.278


Digital Object Identifier 10.1038/s41418-017-0018-y

Another study presents S1P as being essential for S1P Lyase which catalyzes the concluding phase of Sphingolipid Metabolism. S1P performs as protectant from Radiation while Sphingomyelinase (ASMase) is also activated by Infrared Radiation followed by ASMase upregulation of Ceramide Synthesis which can enhance the potential for Apoptosis. Thus, S1P production can relieve the Apoptosis potentiating accumulation of Ceramide. S1P Lyase then performs the unidirectional deterioration of S1P in catalytic activity which can be determinant to the Km of DNA Repair as well as which can determine the duration which is required to for Cellular Entities to Recover from G2 Phase Cellular Cycle Pause, as well as indicate the extent to which apoptosis pathways have progressed after Infrared Exposure. However, the literature observes that S1P Lyase or SPL activity can amplify Ceramide Accumulation which occurs from stress, while the inhibition of SPL as well as the inhibition of ASMase can prevent both cellular cycle progression which occurs as an escape mechanism, prevent cellular cycle progression which occurs in untimely early manner, as well as prevent Mitotic Reliant Pathways in which Apoptosis, Necrosis or other ways of Cellular Deterioration occurs.279 P53 and CBFB are both upregulated when RUNX1 is inhibited, resulting in emergence of Resistance to therapy in Acute Myeloid Leukemia, with P53 directly integrated into the CBFB Promoter, acting to upregulate Translation and Transcription of CBFB. These exhibit that P53 can become transformed to the benefit of Pathogenic circumstances not only be Metabolic syndrome or impairment of P53, but by disruption of the Synthetic Deterioration Partner Groups which potentiate particular pathway outcomes. A Network or Systems perspective is essential to understanding the pathways which potentiate Apoptosis, Necrosis, Survival, Metabolic Change or other transformations at cellular and tissues levels. However, these most exhibit that the management of PEMT and Choline status, as well as Choline Kinase and CTP â&#x20AC;&#x201C; Phosphocholine Citidylyltransferase, may be the most efficient and effective way to manage Oncology, Leukemia and Lymphoma. Managing the distal complexities in such pathways might potentiate numerous products and capabilities, while the potential for inadequacies, dysfunction, resistance, and inadequate understanding seems to increase along with distance from PEMT, Genome, Choline Kinase, CTP Phosphocholine Citidylyltransferase, Choline/Ethanolamine Phosphotransferase, and Choline increases.280 281 Such observations regarding incipient causal factor management instead of distal complexity management is confirmed by the findings in the literature in which P53 deficient small nonhuman organisms developed Oncology spontaneously were compared to small nonhuman organisms in which the genes of factors with which P53 interacts to produce Apoptosis were, instead, impaired. Murine populations were produced in which Genes required for synthesis of enzymes or factors essential to P53 enabled Apoptosis, G1/S Phase Cellular Cycle Pause, as well as Senescence were genetically prevented from being expressed. Amazingly, without the complexities of factors in the numerous P53 reliant and interactive pathways, the populations did not spontaneously exhibit Oncological conditions, compared to the P53 deficient populations which continue to utilized in the study of pervasive Oncology. The preventing of expression at the mRNA and Protein Level, prevent acquisition of function and abdication of function changes which can be quite Chaotic and would be require much of the resources of Humanity to decipher into predictable reliable algorithms and systems.282 Although such should be the priority of Human endeavors in any regard, these should not cause simplified 279 280 281 282

Digital Object Identifier 10.1038/cddis.2011.3 Digital Object Identifier 10.1038/s41598-017-16799-z Digital Object Identifier 10.1038/cdd.2017.171 Digital Object Identifier 10.1038/cdd.2017.169

capabilities from being instrumented with immediacy. Regardless, this information confirms that is the reliance upon too many stochastic nuances and oscillating mechanisms that has hindered resolution of Oncology among 100 percent of Patients to this instance. The study of P53 Genetic Polymorphism alone presents the complexity of what may be the most researched and studied factor in Oncology to this juncture.283 PEMT abrogates the pervasive and incipient requirement for P53, except for those which are intended to be somewhat ephemeral, such as with injury. P53 Phosphorylation at Serine 392 causes translocation of P53 to the Mitochondria where it can interact with Bcl2, potentiating apoptosis.284 These Present Cytochrome C, Caspase, PLK1 and ACER as examples of somewhat extended pathways enabled by P53 which can result in Apoptosis or Necrosis, although each being potentially managed toward survival instead by changes in molarity of P53, the factor itself, as well as cellular circumstances including Oxidative Distress, DNA repair, ability to exhibit Cellular Cycle Progression or particular array of molecules exhibited in the Inflammasome. Similarly, a genetic sensor has been produced which upregulates Herpes Simplex Virus Thymidine Kinase whenever TP53 or P53 is not exhibited or when it is Genetically impaired. This capability, effectively, constitutes the already achieved ability to specifically invoke a demise pathway whenever P53 is impaired or when P53 is not exhibited. Some of the literature suggests that this capability would have nearly 100 percent coverage of Oncology. Inserting into this HSV TK proteomic assay capability, instead of HVS TK upregulation, an already catalytically segmented Caspase Protein, along with NAD+, and a Choline Kinase Inhibitor, would have 100 percent coverage of Oncology and could be produced with technology available decades ago.285 Remarkable as this may be, the already exhibited ability to selectively induce apoptosis in cellular entities exhibiting HIV and Oncology has been presented since the 1990s while innovations which include HIV Envelope Protein to reactivate Latent HIV as well as any Cytotoxic Oncology Therapeutic, has been presented since the 2000â&#x20AC;&#x2122;s. Interestingly, since CRISPR Gene Editing substantially changes the potential to change any atypical Genetic Variation and, however, this may not 100 percent abrogate the emergence of Metabolic aspects of conditions that lead to genetic change, these capabilities do suggest that there may be less than beneficent influences affecting decisions being made in the Health capability industry and health services. Some of the earlier research regarding Choline Kinase Transcription inhibition suggests that Apoptosis was not exhibited although pervasive changes to Apoptosis and other demise pathways occur along with proliferation inhibition. It is somewhat of a mystery why the early Choline Kinase Studies were not as conclusive as the more recent studies. It is possible that relief from overabundance of Phosphocholine resultant of Choline Kinase Inhibition might not have relieved the PEMT inhibitionâ&#x20AC;&#x2122;s stimulation of P53 which impairs Nucleotide Synthesis, inhibits Glycolysis and Pentose Phosphate Pathway, thereby resulting in persistent PARP/PARS signaling during the 1 Million instances of DNA Repair in each cellular entity each day which would occur along with inadequate RNA synthesis for Transcription. These would result in depletion of NAD+, impaired synthesis of Cysteine, Histidine and Aspartic Acid, 283 284 285

Digital Object Identifier 10.1038/nrclinonx.2017.151 Digital Object Identifier 10.1038/cdd.2017.143 Digital Object Identifier 10.1038/s41467-017-01688-w

as well as Carbonate Buffering Systemsâ&#x20AC;&#x2122; use of Cysteine, Histidine and Methionine to buffer CO2 and Carbonate. All of these would impair Apoptosis pathways, and Apoptosis Pathways are observed to be invoked but not completed in numerous representation of escape of cellular entities to reenter the cellular cycle even when P53 is exhibited. However, studies pervasively regardless of when they were conducted do observe an increase in effectiveness on Cytotoxic Oncotherapy including Doxorubicin, Platinum, Paclitaxel.286 Acquiring of additional functionality by P53 when exhibited in a Polymorphic structure, P53 G245D and others, includes the upregulation for FOXM1 as well as decreased Phosphorylation of FOXO3a by AMPK, resulting Oncogenic influence in Head and Neck Squamous Cellular Carcinoma.287 The Literature suggests that the essential Nature of Methylation is also in its ability to Methylate CPG islands or Promoter Regions within Genes, such that Methylation may often disable the Promoter Region resulting in the disabling of suppressors of Oncology. However, it is known that Methylation also occurs at atypical Loci, including upon unrepaired extents of impaired DNA. cAMP, when exhibited at increased levels in the 6 Hour and 12 Hour Sample, increasedly inhibits Choline Kinase Beta, such that PEMT Activity Amazingly, Human Cellular lineages do not relinquish the ability to exhibit this cycle, except when PEMT becomes downregulated by the factors presented in these analyses. Human Physiology can be shown to retain its incipient developmental plasticity mechanisms and the exhibition of impaired plasticity otherwise has precise, known, unintended, and reversible as well as preventable mechanisms. Protein Kinase A is interactive with diverse Factors to Inhibit Choline Kinase Beta, whereas Protein Kinase C and Protein Kinase A as well as Factors affecting G Proteins modulate Calcium. It is the impaired availability of Calcium that is an essential pathway in the decreased exhibition of PEMT, although AP1, SP1, Homocysteine, SAdenosyl Homocysteine each are among primary inhibitors of PEMT. Calcium exhibition can be shown to perform as an upregulator of PEMT, acting as a performance improving Additive molecule that increases the Km of Phosphatidylcholine Synthesis without affecting the throughput of Phosphatidylcholine Synthesis that is occurring through the use of MG2+. These describe the persistent potential for Human regeneration, plasticity and repair which include the reconstitution, at the cellular level, of the precise developmental mechanisms exhibited at the first division of Meiosis in which the Oocyte becomes an Embryo. Correlatively and supportively, supplementation with Calcium or supplementation with Magnesium are known to increase Testosterone in Males.288 289 PEMT inhibition was explored in an extensive experimental study in 2003 by a Major Pharmaceutical Organization as presented in this study. It is a mystery how knowledge of Choline Kinase and the essential nature of the Methylation Pathway along with PEMT could not have been widely known.290 The study specifically presents IC50 values for those molecules or compounds screened, clearly belying that these were intended to be considered for 286 287

Digital Object Identifier 10.1038/bjc.2013.729

288 289 290

Digital Object Identifier 10.1007/s12011-008-8294-5

Digital Object Identifier 10.4161/cc.8.20.9628

LIBRARY OF MEDICINE PUBMED IDENTIFIER 20352370 J Biol Chem. Volume 278. Issue 224. Pages 21851 to 21859. June 13, 2003.

therapeutic application. Only two were found to be more potent than S-Adenosyl Homocysteine. This clearly shows that the Pharmaceutical Industry was aware that S-Adenosyl Homocysteine was associated with PEMT activity, such that Homocysteine levels should have been being analyzed in in pervasive clinical studies and clinical analytics. It is interesting here that PEMT was being considered for inhibition, suggesting that the inhibition of PEMT was being considered as therapeutic instead of reconstituting of original developmental plasticity. Certainly, it should have been easily determinable that PEMT inhibition impairs Homocysteine Metabolism upon instrumentation of any manner analysis or study of PEMT inhibition. Particularly, it seems that since the 1960â&#x20AC;&#x2122;s and in recent research, that the here has been a deliberating seeding of the research and information with articles as well as information suggesting that PEMT and Choline may be participative in or causal to pathology. The particular article seems to subtly suggest PEMT as causal to Pathology. Similar research articles have otherwise associated Choline with Oncology without differentiating between Choline and Phosphocholine and sometimes in the same article clearly showing that populations in which survey of Nutrition indicate that increased levels of Choline are associated with particular Pathology also exhibit during therapeutics that Choline was, instead, associated with improved outcomes. There should have been immediate withdrawal, redaction or editing of these studies as soon as information otherwise emerge. Thus, there seems to have been a deliberate campaign to obfuscate how Choline and PEMT functionally correlated at molecular and physiological levels with Pathology. Many instances exhibit inversion or transposition of concepts and logical analyses to specifically omit the information required to plainly present how PEMT and Choline function in these circumstances. Although the Detrimental Aspects of the Status Quo, Profit Priority of Private Enterprise, and Prioritization of Systems by Systems, all have been presented as essential inadequately considered influences in such regard, it is the overlay of the Human Synapse with Information Systems, Patterns of Modulated Electromagnetic Influence and Enterprise/Industry level Groupthink which allow the Algorithms and Routines of these essential inadequately considered influences to manifest themselves into outcomes. Such Algorithms and Routines can commandeer the Human Synapse long enough to obscure, obfuscate or omit particular factors required to reach conclusions which might disrupt the status quo. Such commandeering could be manifested as the incentive to make decisions which increase revenue, promote those factors or capabilities which assure the most revenue for the longest duration, as well as select those factors or nuances of reason which might oppose such priorities even when Human Priority might be infringed upon. These analyses have presented numerous instances since the 1800â&#x20AC;&#x2122;s in which it seems unlikely that essentiality of Choline, Histamines such as Ethanolamine, Purinyl-6-Histamine inhibition of Choline Kinase and PEMT function could have and should have started to pervasively transform the way in which care and therapeutics are considered. Testosterone is known to be increased from instrumentation of Calcium or Magnesium because Magnesium or Metallic Ions are known enable PEMT Activity, Calcium is known to augment Magnesium PEMT Catalytic Activity, and Metallic Ions except for some specific Atoms are also useful for PEMT Catalytic Activity. These all, of course, are presented according to the literature. . Magnesium interaction with Water in Atmosphere is known to produce high energy Combustion in causes water to seem Purple from Potassium Hydroxide exhibition. Calcium produces less combustive though active interaction with Water, producing Calcium Hydroxide and Hydrogen Gas.

The Amehsi Specification has already reviewed the nature of Cholesterol use for Steroidogenesis and the manner in which PEMT function enables optimal Cholesterol endocytosis by START Transfer Domains exhibited in Membrane Phospholipids which move Cholesterol to the Mitochondria for De Novo Progesterone Synthesis. Progesterone synthesis beings the production of Estrogen and Testosterone and the levels of each are determined by NADP and NADPH. Thus, clearly, Calcium and Magnesium may regulate Calcium and Estrogen substantially or principally through modulating the function of PEMT. The differences in the gender levels of both Testosterone and Estrogen may most substantially emerge from differences exhibited in the reproductive Organs and tissues. Acetyl-CoA decreases, potentiated by downregulation of PEMT and exhibition of P53, can inhibit Acetyl-CoA metabolism through the Mevalonate Pathway into Steroidogenic Precursors including Cholesterol, exhibiting how impaired Phosphatidylcholine membrane characteristics and impaired availability of Cholesterol participate in impair two essential factors that integrate to perform START Transfer Protein enabled shuttling of Cholesterol to the Mitochondria to result in Progesterone Synthesis followed by Steroidogenic Synthesis Pathways which result in Estrogen, Testosterone and 17Beta-Estradiol. However, essentially the observation that Magnesium and other Metal Ions enable PEMT function, while Calcium places PEMT into high Volume Synthesis Mode, can clearly be presented as a manner of increased Biosynthesis during Oocyte, Embryonic and Early Human Post-Gestational Development that can be clearly shown to decrease according to decreased PEMT function with progressing phases of Being. The risks of using Hormone Therapy, thus, seem to be the result implementing such therapeutics at a level which requires precise understanding of physiological factors while also being affected by changes among such factors which can occur with meals, mood, as well as circadian factors. A particular study observes that there are two Isoforms of Phosphatidylethanolamine NMethyltransferase, L for long and S for Short, such that the L version was observed to be highly Glycosylated with Mannose Oligosaccharides, the activity of PEMT-L was much lower than PEMT-S, Phosphatidylethanolamine Levels were much lower with PEMT-S. although both PEMT-S and PEMT-L produce similar characteristics of Phosphatidylcholine availability and Phosphatidylserine Availability. However, PEMT-S Synthesized increased diversity of Phosphatidylcholine and Phosphatidylcholine Linked to Ether Factors, exhibiting Longer Polyunsaturated Moieties. PEMT-L, comparatively, Synthesized Ether-Linked Phosphatidylcholine factors which were shorter. The literature suggests that this difference indicates substrate selectivity. The differences among the Enzymes with regard to products and synthesis were by proportion and not all synthesis produces. Each enzyme promoted the Proliferation of a Cellular Lineage which did not exhibit Pathology and was not engineered to exhibit any specific Pathology.291 Succinct conclusions regarding this study include the observation in other molecular models that that shorter enzymes of the same function may exhibit shorter duration for Catalysis compared to longer versions, such that the shorter version may be completing its catalytic activity more quickly and such that the catalytic cycle prevents additional changes to the Fatty Acids before packing these Fatty Acid â&#x20AC;&#x201C; Exhibiting Lipids into the cellular membrane bilayers. Glycosylation, additionally, is known to prevalently occur upon proteins in the Endoplasmic Reticulum, instead of the Mitochondria. The two proteins may have function in different subcellular locations, with the catalytic activity of Glycosylated PEMT-L potentially being the Endoplasmic Reticulum, explaining its shorter Fatty Acyl Moieties whereas PEMT-S exhibition in the Mitochondria might potentiate its Longer Fatty Acyl Moieties.



Interestingly Wogonin inhibits N-Acetyltransferase and CDK9. Arylamine N-Acetyltransferase, an NAcetyltransferase, transfers Acetyl Groups from Acetyl-CoA to a Xenobiotic Factor and functions across diverse species including bacteria and Humans. Phosphocholine is emerging as interested and diverse changing factor to Physiology. Phosphocholine performs an agonist role to Metabotrophic Nicotonic Acetylcholine Receptors, impairing the ATP-Associated secretion of Interluekin-1B from Monocytes and impairing this essential innate immunity regulatory function. Although inhibition of Interleukin-1Bâ&#x20AC;&#x2122;s inflammatory effect can sometimes be beneficial, its inhibition in this manner represents deregulation and can potentiate detrimental health outcomes and may potentiate beneficial outcomes. Phosphocholine ameliorates Ion Channel regulation by Acetylcholine Receptors and impairs the Ion Channel changes produced by Choline.292293 A study of Breast Oncology Clearly Showed a correlation of high levels of Phosphocholine with Breast Oncology, although the findings went farther to elucidate Phosphocholine, Choline Kinase and Choline Transmembrane Transport Mechanisms were all upregulated in Breast Oncology, clearly consistent with the finding of the Amehsi Specification although thee also present a Choline, Phosphorylation of Choline, Choline Kinase and Choline Transport exhibiting Tunnel and Pump mechanism. This study, however, omitted the decreased levels of Acetyl-CoA from downregulated PEMT that prevents the Acetylcholine buffering of Choline from being robustly exhibited.294 295 296 297 298 Moreover, the literature suggests that Phosphocholine aggregates on the surface of apoptotic or necrotic cellular entities and suggests that C-Reactive Protein integrates upon the Phosphocholine to active the Complements Immune System that exhibits Phagocytosis, clears necrotized cellular entities and clear remnants of the Apoptosis. This suggest that C-Reactive Protein may be useful in determining levels of Phosphocholine and levels of Phosphocholine associated pathology. Specifically, C-Reactive indicates the levels to which phosphocholine and inflammation response that has moved to a requirement to induce necrosis and induce apoptosis has occurred or may be occurring. There is the possibility that this primary factor in immune function, preceding activation of Macrophages, Neutrophils or other Immunological function including adaptive Immunity may not be adequately monitored, assayed, diagnosed or considered. There is the possibility that pervasive Protein Kinase pathways are becoming activated by Phosphocholine and the compliments systems. This is essential because it is the progression of pathogenic status or impairment which emerges to a requirement for apoptosis to occur or which emerges to a requirement for necrosis to occur, followed by impairment of that apoptosis or necrosis outcome, that might be among the best conceptual explanations for Oncology. Free Phosphocholine aggregates upon Necrotic and Apoptotic Cellular Entities and causes the Innate Immune System to become activated suggest that impaired Necrosis or Apoptosis produces a persistent systemic inflammation through the Complements Innate Immunological System Pathway. The literature suggest that this Innate Immune Response is an Acute Interluekin-6 associated response while, interestingly, Interleukin-6 is known to be an inhibitor of Apoptosis in some cellular entity phenotypes and the Interleukin-6 expression is often accompanied by Cytokines which stimulate C-Reactive Protein Synthesis and Fibrinogen Synthesis. Correlatively, 292 293 294 295 296 297 298

Digital Object Identifier 10.1080/03602530802186603 PMCID PMC4923896 Digital Object Identifier 10.1002/ijc.22293 Acetyl-Coenzyme-A. Molecular Biology. Digital Object Identifier 10.1172/JCI63967 Sharinghealth.CA website. Dimetylallyl Pyrophosphate. Wikipedia.

the inhibition of Phospholipase Cgamma1 is known to inhibit Metastases and Matrix Intrusion along with inhibition of Phosphocholine Levels.299

TPA/PMA is known to actively cycle metabolites through the Ethanolamine Kinase Pathway. Geranylgeraniol and Farnesol inhibit the Choline only metabolizing Choline Phosphotransferase, causing A549 Pulmonary/Lung Adenocarcinoma to regress. These two therapeutic factors are Isoprenoids and Isoprenoid synthesis is inhibited by HMG-CoA reductase inhibitors that are typically utilized for Management of Cholesterol levels. Circumin the Yellow Pigment in Curry, is known to inhibit AP1 reliant oncology with up to a 98% response level in cellular entities affected, specifically through inhibition of AP1. AP1 management by Isoprenoids/Terpenoids seems to be a presumed aspect of Physiology. The literature does not report an association between HMG-CoA reductase inhibitors and Oncology. However, some of the increased potential for health conditions pervasively that may be associated with higher levels of cholesterol may be the result of Isoprenoid inhibition by HMG-CoA Reductase inhibitors particularly as participant in multiple factorial causality to emergence of pathology.300 DHA and EPA from Omega 3, but not Arachidonic Acid inhibit Epidermal Growth Factor, AP1, and TPA/PMA, but Arachidonic Acid abrogates DHA/EPA inhibition of these factors. PMCID PMC34699 Inhibition of PEMT shunts both the Choline Kinase and Ethanolamine Kinase pathway into metabolites leading toward the Choline Kinase pathway of phosphatidylcholine production. These exhibit clearly that electromagnetic energy contributes to human pathology by causing each of the most central causes of all human pathology, detrimental behavior and detrimental behavioral outcomes, inhibition of PEMT, expression of Inducible Nitric Oxide Synthase, persistent inflammation, and exhibition of Chemoattractant Protein-1 which galvanizes migration of chemokine affected leukocytes, lymphocytes, chemotaxis potentiating erythrocytes, monocytes, Haemopoieticcellular entities otherwise, and stem cellular entities. Simply covering, coating, or encompassing devices, fields, lines, pathways, apertures, appliances or other sources of EMF, Magnetic, Microwave, and other energy influence, would pervasive reduce these, with costs becoming negligible within the first few months of doing these broadly across all aspects of civilization. Information regarding these are available in more than three sources in literature, internet and information archives in most developed nations, thus, constituting common knowledge. However, because these affect physiology in the idiopathic range of Physiological status and Ideopathic Range of Homocysteine bioavailability, there is a potential that these are utilized to make human perception, cognition and behavior susceptible to influence, shaping, and commandeering. Similar to choline deficiency alleviation, alleviation of EMG or magnetic field influence is not suggested, prescribed or included in any treatment pathway or guideline to this instance incurred by these research bases or reflected in the commonly available clinical literature.301 Some therapeutics, particularly Hypertension medications and Diuretics can increase levels of Homocysteine. Homocysteine should be interpreted and monitored during instrumentation of such Therapeutics.302 303 299 300 301 302 303

0.1158/1535-7163.MCT-09-0039 Proc Natl Acad Sci, USA. Volume 88. Pages 5292-5296. June, 1991. ISSN 0300-8177 Digital Object Identifier 10.1038/sj.jhh.1002325. LIBRARY OF MEDICINE PUBMED IDENTIFIER 11893229

These clearly shows that since Homocysteine is a principle indicator and cause of detrimental human behavior and behavioral health conditions, health systems are offloading substantial aspects of Humanity onto other systems of civilization as unremediated Physiological conditions emerge as behavioral patterns, susceptibilities and outcomes instead. The context of behavior can be pervasively less than adequately considered in civilization because the level of analytical consideration and critical reasoning applied to understanding nuances of social constructs often pervades even the outcomes about which such social constructs become required. Pervasively, behavioral outcomes which are observable and outcomes otherwise of a Tangible Nature have causality which is distant in ability to be tangibly observed, temporally, as cognitively, emotionally, behaviorally and even from a physics perspective. Hardly any person will agree that Hitting a Curveball in Baseball is the same is Hitting a Fast Ball, although pervasively systems utilized analyses and perspectives which, in the context of behavior and outcomes, suggest precisely that these are the same. Furthermore, because all outcomes are determined most by disjoint and unobservable influence, the difference in focusing upon tangible and immediate outcomes compared to the understanding of disjoint influence may be as substantial as the Ball being Hit by a Baseball Bat compared to the Baseball Bat passing through the Ball and not affected its trajectory at all. The exhibition of detrimental outcomes among Humanity can be complex and permutative. Illustratively, Social Constructs such as Philosophical and Political or Cultural Concepts can Unify populations at perceptive, cognitive and behavioral levels, offering opportunities to socialize and share the detrimental influences of civilization and detrimental influences occurring in Nature, thereby producing cathartic change while also enabling such influences to become objectified and made disjointly tangible. These analyses pervasively exhibit how the disjointly tangible factors Choline Kinase and Phosphatidylethanolamine Methyltransferase have through systems of the United States been extracted into Conceptual and Tangible representation within Systems. These can explain why social systems can enhance resiliency to detrimental outcomes systemically, while also, unfortunately, exhibiting how individuals within such organizations can incur a spiral that produces an ever-increasing redirecting of such managed influence toward one individual, particularly when such individual has been ostracized or separated from their socialization context. Spirals in one context of activity or behavior can expand to encompass other areas, and like the Storm, can surmount the influence of beneficial, managing, or other influences which are essential to behavior. Every person, probably, can recall an instance of being displeased in which the displeasure is strong at some instances and while being diminished or not being exhibited in other instances. Civilization exhibits patterns, artifacts, and influences which introduce cognitive influence and cognitive constructs, as well as extracts these constantly. Language, activity, inclination and behavior are changed or potentiated amid such cycles of cognitive shaping and harvesting of cognitive constructs by systems. The results of Homocysteine being increased when choline is not adequate, PEMT is inhibited or Choline Kinase is upregulated, can then be described as Isolation of the Cognitive Conscious Context from stimuli, a resultant harvesting of cognitive artifacts by systems of civilization in a way that is increasingly distant from the Conscious Cognitive Context, and constitutes the commandeering of an enhanced ability for individual, group and population resiliency through changes caused by Homocysteine and other factors. Such changes introduced by Homocysteine and other factors include increase in aggressive behavior, reproductive activity,

and removal of Conscious Cognitive Context from the disintermediation of interactivity between Physiology and the universe. Such removal of the Conscious Cognitive Context from managing interactivity with between physiology, behavior and the Universe seems to enhance the ability, in Nature, to find factors exhibiting Nutrients such as Choline as well as respond to factors in the environment during less than optimal circumstances. However, when a group is exhibited and an organism is within such group, including a family, the influence of Homocysteine to physiology can be augmented by Homocysteine exhibition in others, becoming socially transferred to other individuals through fields, behavior, verbal ques and less than verbal interactions among Humanity. Because Homocysteine and its influence to behavior, function, cognition, and perception are widely unacknowledged, the influences of systems and cognitive artifacts can produce outcomes which pervasively are considered to somehow be emerged from the inherent characteristics of the Individual. The conditions which allow increased levels of detrimental factors, homelessness, financial distress or other influence, may contribute to such outcomes. Similarly, the way in which interventions have been pervasively exhibited may be enabling substantial revenue obtainment while inadequately acknowledging how such detrimental outcomes are most incipiently and proximately potentiated. The exhibition of 120 Million instances of demise since 1961 certainly should be a compelling illustration exhibition of inadequacy in considering Homocysteine and prioritization of Human Vital Being. Illustratively, detrimental outcomes between individuals, particularly those whom are in relationship with each other, pervasively can be shaped by communications devices or systems, social networking, internet systems, iNOS, uNOS, fields being produced factors as mundane as receipts from purchases, as well as TMAO, Homocysteine and other factors. Such interventions, thus, can increase the isolation of individuals from those systems or influences which enable improved management of potentially detrimental factors. Detrimental outcomes, the introduction of systems which manage detrimental outcomes, can be correlated with potential for additional detrimental outcomes in some instances resultant of information systems, influences to individuals, stigmatization, social dynamics and even effect to how individuals perceive themselves. The best way to consider Homocysteine, in these contexts, are that it is an incipient enabler of susceptibility to detrimental behavioral spirals. Individuals exhibiting the most detrimental outcomes can be most understood by considering all those influences, circumstances, factors, artifacts used or outcomes which such individual incurs, then considering which of these do not occur in nature, determining which of these have occurred before the individual incurred them, as well as determining which of these probably may occur after such individual has incurred them. How then, might it be logically, reasonably, or rationally possible to attribute causality to such individuals for outcomes produce pervasively by systems. Probably, a useful way to transcend the propensity to consider punitive or vengeful action in any outcome is to consider that there may be a 99.5 percent or more probability that the same indicators that increase the propensity for sudden abated vital being are pervasively present when an individual or group exhibits a detrimental action of particularly egregious nature. Because, somehow, the progression of these detrimental indicators has become allowed to occur, such outcomes are pervasively the result of Neglect of Human requirements. Reconsidering the analyses in this document alone, Part 1 and Part 2 of this particular reductive analysis, it can be observed that whenever Human demise is presumed to occur, or allowed to occur when it pervasively should not, all manner of such detrimental outcomes may be potentiated. The Human circumstance, allowed to freely ebb between the influences of detrimental circumstances, detrimental potentialities, influences from the future and influences from other instances, are more likely to be the

result of some unproductive agenda from some other era than they are likely to be of an inherent inclination or nature. Most imperatively, since such aspect of Humanity may have not ever been able to come to know itself in Nature and may not be able to regress to Nature free of the way in which influences of civilization have generationally introduced change, there not such a thing as inherent inclination of Humanity. Such outcomes, when productive or unproductive, beneficent or detrimental, are contrived by systems amid the Storms of systems. Humanity, unproductively and beneficently, might, then, be expendable chattel and revenue, profit as well as the priority of entities which are not Human pervasively being impetus for the inadequate assurance of primacy of Humans in their own systems. These present the possibility that Consumers may be directing their spending specifically with the objective of sustaining the economy, as they may have been intended to do, while systems and organizations have a strong role in planning for the economic, social, biological and behavioral stability of consumers. Thus, this trust of systems, as exhibited by social insurance, may also potentiate or require that consumers direct their spending toward organizations which they know are prioritizing consumer safety, the wellbeing of their employees as well as the stability of communities in which consumers of their products are situated as well as communities in which aspects of the organizations are situated. It is not suggested that companies and organizations are systems, for, certainly in their provision of essential factors, ability to conduct livelihood, and provision of factors that enhance the quality of vital being, such entities are very beneficial. However, the status quo may exhibit that Humanity is not allowed to understand how its outcomes are being pervasively enabled or caused by interactions among entities within systems, factions, systems or systems of systems. Similarly, pervasively Humanity has constructed substantial activity and systems, although systems pervasively seem to have been most precisely produce to accumulation information about how to resolve unproductive or less than beneficent outcomes, which do not acknowledge that detrimental and beneficial Human outcomes are principally produced by systems. The suggestion that systems may be principle shaping influences and causal factors to outcomes observed in Humanity is not intended to be facetious or flippant. Introducing such observation is essential in observing that inadequate acknowledgement of such conditions may have enabled the status quo to emerge in which Global businesses conduct competitive activity upon a playing field constituted of Human outcomes, without any specific required priority of assuring that the outcomes produced by their activity, services, products or influence are beneficial and productive. Similarly, myopic focus on profitability and automation in business and organizations has emerged along with increasing exclusion of Humans from business activity, without any plan for how Humans will be able to earn resources or obtain resources to assure the Social and Human condition in context of increasing exclusion of Humanity. Business may not be able to resolve such complexities because the increase in business liabilities associated with increased Human employment typically only occurs within an economy of scale in which profit is required to occur correlative to each addition of Humanity. Correlatively, businesses are required to be profitable by Social Constructs and amid the Global Economy, regardless of if regions, localities and communities are reliant upon such businesses to achieve the Social and Human condition. Priorities of Businesses require readjustment to be more closely aligned with their incipient purpose in civilization. The benefit to Humanity is unquestionably among such priorities. Virtually every biological research organization or entity in the United States should have known that Phosphatidylethanolamine Methyltransferase

inhibition and upregulation of Choline Kinase are required for almost every detrimental Human biological and behavioral outcome. Only the Profit Priority of Private Enterprise and Priority of Systems by Systems themselves seems to have been an impedance acknowledging such capabilities or permutatively discerning such capabilities, for, certainly every Human exhibits a priority for another or for themselves which would require seeking such capability and divulging in benefit thereto. 120 Million instances of demise individually and plurally require change and program management, development, improvement, analytics, and reporting seem to be among the essential modalities through which such change can immediately begin to occur. These suggest that National, Region, State and Local Entities are becoming required to produce a resilient and functional plan to enable employment such that every business is incentive to completely exclude Human costs and are averse to manage risk associated with the way in which Humanity is affected. Nation, Regions, States and Local entities, then, will be required to manage large aspects of unemployed populations resultant of automation, profitability schemes, movement of jobs to other locations, competition for Jobs on an international scale by workers, as well as the filling of subversive patterns by their own populations because the only jobs and employment available may be those which manage less than productive and less than beneficent outcomes. Similarly, to artificial intelligence, it is amazing how there has not been any Global or National level convening functions which observe, acknowledge and mitigate such potentialities. Human planning seems to be an inadequately represented aspect of Sociopolitical systems while the Profit Priority of Private Enterprise and Priority of Systems by Systems seem to be rampantly dominating policy and economics. Emergence of a circumstance which organizations do not employ anyone, profit from unproductive and less than beneficent Human Outcomes, while the Nation is caused to incur detriment seems distant from any objective presented by the Constitution of the U.S. Moreover, local economies Dominated by foreign Businesses, sometimes receiving substantial subsidies from their own National entities as well as enabled by schemes which limit business activity by such A Prominent Nation of the Earth which is situated in the Western Hemisphere and founded upon the constructs of Liberty, also seems to enhance the potential for homelessness, joblessness, destituteness, subversive outcomes and other outcomes considered to be detrimental, anathema to the population of the Nation and anathema to Humanity. Nations, Regions and States should advocate and prioritize social constructs which produce incentives for inclusion of Human in Social, Political, Economic, Business, Athletic and other activity, while assuring that remuneration for such activity is provided at levels which assure the Social, Human, Behavioral and Biological condition. A circumstance in which everything that is required to assure such factors has already been achieved is not detrimental unless it is accompanied by acknowledgement that there has not been produced any plan for providing for Humanity unless they have work and are paid for work. Similarly, such achievement does not require that benefits of achievement are equitably distributed as the observation of 120 Million instances of demise since 1961 which have occurred because of inadequate management of Homocysteine clearly presents. Humans are the priority of civilization and systems produced within Civilization. Enabling every Human to be free of such detrimental circumstances and managing the detrimental indicators through awareness, education, involvement and care, potentiates that 99.5 percent of detrimental outcomes, or more, might be averted. Detrimental circumstances and particularly evocative Human outcomes can invite Humanity to abdicate the inclusion of essential nuances of reason, enabling Primacy of Systems, Routines and Algorithms over Humanity. Focusing events, in such regard, can produce complete Legislated Permutations, often regressing Humanity

into more antecedent eras in which Tangible and Observable outcomes have been considered to be truths instead of merely symptoms of unalleviated or inadequately prevented pathology at individual or systems levels. However, most imperatively, the analyses of Human behavioral outcomes may be pervasively complete without considering how systems produce perception, inclination, cognition and behavior. The nature of systems founded upon Liberty are that the exhibition of extraordinary outcomes may be inherent, including those which are productive and beneficent as well as those which are less than productive and beneficent. Clearly, perhaps it is not adequately considered that once one begins to realize that all that one has, has achieved, might achieve, as well as each lifting of an arm, progression to an objective and connecting of two concepts to produce a more progressed concept, all are enabled by those whom have had surmount circumstances and impedances before. Such incipient enabling achievement enables Humanity through systems which carry such progression forward, such that behavior and perception are foundationally transformed. That which civilization considers detrimental as a well as that which civilization considers productive and beneficent, each may flow from an integrated, inherent, propensity and inclination to achieve. Such inclination to achieve may be affected in ways that are not expected when such achievement may be inhibited, prevented or unsuccessful. The less than adequately considered inherent Human requirement is the potential to improve oneself, oneâ&#x20AC;&#x2122;s environment and one circumstance. Often, those monumental achievements which Humanity may been required to produce, may not be achievable again and may not be productive if such achievement were required to occur again. Humanity, particularly those in systems of developed Nations, carry with them the benefit of generations, the achievement of generations before, and a simultaneous ever increasingly ability to reproduce those monumental achievements which have already occurred. The risk is not that populations which are completely financially independent might not exhibit any productive activity as result. The risk is that Human achievement and progression may be fundamentally transformed to focus on improvement of Systems of Humanity and Humanity itself when Humanity is no longer encumbered by the circumstances which civilization and system of civilization have been incipiently constructed to resolve. Heparin decreases the affinity of AP1 to DNA, particularly reducing its integration into the TPA/PMA response element.304 Inhibitors of AP1 also include Cycloinumakiol, Inumakal, Inumakoic acid, or Norditerpenes from the large Evergreen Tree Podocarpus Latofolius305. Pause is required here; for, how might it ever be made, construed or interpreted as productive the existence of such knowledge, the sequestering of it away from humanity, and the exhibition of such power over the advancement of humanity? This question is offered without conclusion and without impunity; where might humanity be had such sequestration of information not occurred? How much of the next countless annum, centuries, or decades, might require being expended catching up to where humanity might easily have been? How much longer might divisions among humanity be permitted to abrogate humanity such manner at unconscionable levels?such massive proportions? Populations, vitality, psyche, and achievement, thus, may be a mere shadow or minutia of what it might have been. Millions, led along paths which benefit things which do not have vital being, to not benefit themselves, are often detrimental to themselves, having their existence obfuscatingly occupy by circumstances which take them farther from the incipient hopes of human populations, and having abated vital being at such proportions that are now exhibited, to 304 305

Digital Object Identifier 10.1161/01.RES.75.1.1 Digital Object Identifier 10.1021/np100736y

the benefit processes, things, and entities which have no vital being along with exhibiting vitality lended to these by humanity. These circumstances seem like paradoxica fiction that a human could not even construct. Again, these are more than likely the result of interests and influences, through location, distance, space, and time which have been shaped to benefit of organisms or interests antithetical to humanity. These have just as much probability of being the result of influence exhibited in such context by microbes and insects, as these may be the result of any omniscient influence or human influence exhibited in other eras. Perhaps, events of substantialmassive detriment to humanity, may be recursively affecting all other eras to assure that these have actually occurred as well as to assure that these occur persistently in the epoch in which first originally exhibited. The most productive way to understand this is by considering that there exists a foundationally and abominable translational inadequacy in research, development and integration into practice in systems which exhibit these inadequacies. The alternative to such potential inadequacy probably should not be considered here. Amazingly, one study observed that Magnetic Fields can interact at enhanced levels through already exhibited molecular pathways, including inflammation, pathways, introducing all manner of possibilities. These seem to agree with the hypothesis earlier that it is flux through Choline pathwaysâ&#x20AC;&#x2122; obtrusively exhibited but often not explicitly represented Nitrogen Atoms that enables spatial and other fields of influence to unite the Nitrogenous flux fields within Physiology with encompassing Nitrogenous fields external to Physiology. Particularly, these show that those factors considered ancillary to Physiology, such as Ionic, Thermodynamic, Cofactors and Energy Balance pathways each may have their own group of spatial and other interactive fields that extend outside of Physiological systems.306 These seem like common sense that has escaped clinical consideration. Populations inside of beverage establishment observed by those outside of such establishment or heard by those outside of such establishment, have substantial potential to influence those who have not as of yet entered into such establishment. Nitrogenous factor exhibition inside a balloon, becoming changed in molarity, pressurization or temperature, also changes the interaction of externally exhibited nitrogen upon the balloonsâ&#x20AC;&#x2122; characteristics, although such change does not enable or require the direct interaction between the internally exhibition nitrogen factors and the externally exhibited nitrogen factors. Certainly, though, quantum level influences connect energy fields to internal Physiology, suggesting that it is questionable how such interactions have managed to be excluded from clinical and Physiological considerations heretofore. Unconsidered, then is the potential that a change in a quota in some system or facility, particularly a health facility, might change genetic expression among population to its benefit. To illustrate this, observe the behavior of a group of humans in the same domicile. Then observe the changes in behavior after the address has become registered in a system, information system or online information base in which detrimental outcomes, events, or information is maintained or managed. Similar observe such behavior after any substantial outcome associated directory or list begins to exhibit information about the location or name or other specific information regarding those within the same domicile or those whom may be associated with those in the same domicile. Similarly, consider an individual that has incurred a detrimental circumstance or outcome and is detrimentally affected at perceptive, cognitive and behavioral levels. Determine, then, the most precise and memorable factors, characteristics, environmental environment from that event, followed by producing an environment that is most distant from those factors presented in association with the detrimental event. Consider why such common and simplistic ways of remediating such detrimental effects are not pervasively utilized and one may understand that extension of cognition 306

Digital Object Identifier 10.1023/A;1014802005672

and memory to spatial levels with consistency across different locations or circumstance may persist associations, social constructs and cognitive artifacts. These spatial extensions of cognition may also prevent asymmetric and “out of the box” thinking which results in the most empirical levels of innovation and productive advancement. Rumination at a cognitive level, or repeatedly having the same considerations, cognition and cognitive artifacts exhibited in the conscious cognitive context may be pervasively the result of patterns in environment including artifacts, modulated energy or influence, as well sounds, cognition imparted from others or traps at a social, economic, behavioral, emotional or other level. It is well known that that internet websites can access devices, emit inaudible sound, pair with remote devices or computers, as well as activate a computer’s local devices or a remote device’s electronic components, or participate in fields that are in the atmosphere or building material, such that patterns can be found and changes to information or behavior can be determined. 307 Modulation of these patterns to associate stimuli with behavior can might also be occurring as aspects of marketing or sales campaigns and may be utilized to produce detrimental outcomes including impairing Physiology, inducing detrimental levels of comfort or shaping or causing behavior. Similarly, modulation of influence communications or energy infrastructure may be possible in producing behavior that augments patterns of population level outcomes observed by Roemer’s Dynamics. The information presented in this paragraph is essential because it explains the conundrum of Computer Viruses that are emerging in the consumer and business aspects of technology. Ransomware is an example of such Viruses in which a screen is displayed that prevents access to the computer or any applications until money or other factors are transferred, paid or provided to a third party. Such Viruses typically are expanded in influence through susceptibilities in communications privacy, security, gating, packet inspection, abstraction of the User Interface from the communications program stack, as well as inadequate computing sandbox architecture inclusive of zoned firewalls and internet web browser abstraction from the Operating System. That which hardly any security analysts perceive is that ransomware seems like a Red Herring. These software programs are obtrusive obfuscation of the motives of the programmers. Consider two paper cups used by two people in which one speaks into one cup while another listens to their own separate cup. Normal temperatures in dry conditions potentially exhibit no ability or way of hearing conversations. However, attach a string, dip the ends of cup in a medium such as water, a fiber optic channel, a continuous field of ions, electromagnetic or other energy, as well as in atmosphere that is less dense, more dense, less dry, more dry or which is encapsulated by an empty building or within other fields of influence. Once quickly can observe changes in the ability of the cups to perform as communications devices. Correlatively, ransom ware could not possibly expect to obtain financial benefit from businesses in such regard, while even being unlikely that the location for distribution of payment could possibly be functional for only a small duration until being found and disabled. Thus, among the plausible reasons for ransomware may be to saturate an environment with the same projected patterns of information from the computing screen. These similar projected patterns in multiple instances and locations produce fields of homogeneity, although fields can be constituted of flux also otherwise. These fields, like the cups presented here as communications devices, can be similar to a Nitrogen Atom in one cellular entity compared to a Nitrogen Atom in another cellular entity that each react to a particular field of influence that originates from outside of 307

Physiology. The best example here might include magnetic objects responded to magnetic influence from outside of Physiology. Essentially, however, is presented the effect of encapsulating tissues, ionic fields, current, thermodynamic fields, pressurization, and other factors that link two distant instances of Homogeneity or which link a saturated field of homogeneity such as a room or building full of computer screens projecting the same ransomware information. Ransomware programmers have design an ease dropping, behavior modification and even cognitive querying capability in which they may be siphoning off essential data and information for usage. Unless the buildings, communications outlets, power-outlets, plumbing, ventilation infrastructure, conduit pathways and other factors are secured, and protected, it may not even be necessary to utilize complex analytics to extract information although complex analytics can certainly begin associating information with outcomes along with activity to produce meaningful intelligence. Why would programmers produce a computer or technology virus that could not possibly result in obtainment of payment or financial benefit? The reason is the same as the impedance to resolution of the causes of detrimental human outcomes by systems in a global context. Human outcomes including the effects of a programmed computer virus upon humanity, produces information. It may be the information that ransomware seeks to provide a platform for extraction, obtainment of influence on Human behavior, as well as subsequent obtainment of benefit in such regard.308 The role of EMF, Magnetic and energy fields, thus, may be substantially inadequately represented in the clinical literature and clinical guidance. TPA/PMA and iNOS are known to be stimulated into action by Electromagnetic or energy fields otherwise. However, this interaction with energy fields exhibits more than Spatial interaction through iNOS. Particularly, magnetic fields or energy fields are known to cause enhanced exhibition of HDL or High-Density Lipoprotein, thus affecting PEMT sensory mechanisms and producing a cycle in which TPA/PMA produces fatty acids which are supplying of the Ethanolamine Kinase pathway toward PEMT, although PEMT is inhibit by these same processes. These certainly explain an essential, basic, required pathway in human Physiology that emerge and progress to diverse pathology principally, specifically, and potentially only from electromagnetic energy fields, magnetic fields or other energy fields.309 A particular study observes that Electromagnetic Energy, particularly as Extreme Low Frequency, increases serum HDL-C, increases Hepatic Lipoperoxides while also decreasing aggregate Hepatic Cholesterol levels. Another study clearly indicates that low level exhibition of Electromagnetic Fields of Radiofrequency and Extreme Low Frequency versions, was associated with increased level of Low Density Lipoprotein Cholesterol. High Electromagnetic Frequency exposure that also included occupational exposure at high levels and comparatively high costs mobile phone bills, was associated with an increased level of Low Density Lipoprotein Cholesterol, LDL-C, or Triglyceride. This constitutes a third vector for changing of systemic and local aspects of Physiology by Energy, Magnetic, Electromagnetic and Communications Fields while High Density Lipoprotein was only shown to be decreased in high Energy exposure group. High Density Lipoprotein receives Lipids and Cholesterol from Apolipoprotein and although LDL receptors can be transcriptionally produced and become exhibited as transmembrane proteins, the Endocytosis of LDL is directed toward Endosomes and Lipophagy although LDL is known to escape the Endosome during Early to Late Endosome transitional phase. 310 311 HDL is suggested to have affinity toward Steroidogenic Organs that include Adrenal, Ovarian, Testicular and other Steroidogenic and Gender oriented tissues. HDL is move into the intracellular environment by Cholesteryl Ester Transfer Protein, Scavenger Receptor BI or HDL receptors. The Cholesteryl Ester Transfer Protein also exchanges VLDL Triglyceride

308 309 310 311

BA Computer Systems. â&#x20AC;&#x153;Its not Even Close to Over; Wanna Cry?â&#x20AC;? Digital Object Identifier 10.1186/1476-511X-6-31 Digital Object Identifier 10.1038/nbt.2612 Digital Object Identifier 10.1007/s11356-015-5500-9

and HDL Cholesteryl Esters, causing VLDL to become LDL to enables the newly produced LDL to become Endocytosed using LDL receptors. Thus, energy fields can impair HDL and affect VLDL and LDL metabolism. These analyses clearly exhibit that there are different Physiological statuses that occur along with PEMT enabled activity and metabolism occurring without PEMT activity. PEMT produces a directing of the Ethanolamine Kinase Pathway in augmentation of other mechanisms of other pathways for Phosphatidylcholine Synthesis or Metabolic production. Enzymatic activity may be involved in lipid and phospholipid metabolism, producing Phosphatidylcholine. Human Lysophosphatidylcholine Acyltransferase 1 (LPCAT), as AcylCoA LPCAT has also be shown to exhibit highly genetically conserved ability to synthesize Glycerophospholipids and Phosphatidylcholine particularly relevant Pulmonary tissue and function. LPCAT also clearly presents the manner in which Lysophosphatidylcholine, presented in other aspects of the Amehsi Specification, ameliorates asymmetric distribution of membrane Phospholipids to cause disruption of Oncology of the Breast. LPCAT 1, 2, 3, and 4, each exhibit the ability to transform Lysophosphatidylcholine into Phosphatidylcholine, reversing the activity Phospholipases A1 and A2 which are central factors in inflammation as well as central factors in shunting of Arachidonic Acid into inflammatory versions of Thromboxane, Leukotrienes, and Prostaglandins through COX, LOX and Thromboxane Synthase pathways. Phospholipase A1 and A2 are considered to originally transform Phosphatidylcholine into Lysophosphatidylcholine, often considered aspects of the LANDS Cycle which when impaired results in increased size of Lipid droplets, although the LANDS cycle is not widely referred to in Lipid Metabolism in this era. It is possible that the LAND’s cycle is not considered or referred to in the literature widely because its impairment was not observed to cause a decrease in the level of phospholipids and Glycerides such as Diacylglycerol, suggesting that early analyses regarding lipid metabolism focused on Kinetics of Metabolism and not on precise biochemical characteristics. Changes in this pathway can certainly affect the balance of Cofactors and Energy Factors, suggesting that LAND’s cycle being omitting from metabolic literature may not be optimal. However, it certainly seems to been important enough for the “Land” suffix to have been removed from a well known landmark in the western United States exhibited in a most populous areas that is center for Film, Entertainment, Research, Development and culuture. The lands Cycle and its correlation to this Landmark being omitted from the literature certainly seems mysterious. Regardless, Lysophospholipds and Polyunsaturated Fatty Acids are essential components of Optimal Physiology, regardless of if one finds themselves in Hollywood, California, or any other location upon the Earh or within the Universes. Clearly, LPCAT seems to be rescue mechanisms that assures diverse Fatty Acid integration in Phosphatidylcholine when PEMT is decreased or impaired. LPCAT1 inhibition by Ca2+ supports its use as a rescue mechanism because PEMT activity enhances Ca2+ cycling, resulting in impaired PEMT promoting decreased cycling of Ca2+. Decreased availability of spatial distribution of Ca2+ may enhance LPCAT1 activity. Phospholipase C activity, then, which depletes Store Operated Ca2+ may enhance LPCAT1 activity whereas Phospholipase A2 may enhance LPCAT1 by providing substrate. Although Phospholipases release Ca2+ which encircles the Phosphate Groups of Phospholipids, this Ca2+ is released at the Membranes and may be not be readily diffused when iNOS gradients are already depleting intracellular and extracellular Ca2+. It should be asserted here that in every reference to Phospholipase activity and its production of Ca2+ in this and other documents, iNOS may modulate the spatial aspects of Ca2+ diffusion, causing it to be directed to iNOS somewhat directly from the cellular membranes.

Previously, the AMEHSI Specification exhibited that Acetylcholine and Choline metabolites were essential in the reanimation of tissues which have entered either a paralytic status or become inanimate from abated Physiological rhythms. This reanimation occurred through a systemic opening of Ion Channels, including those which mediate Ca2+ balance. Pivotally, tissue was transformed into a commonly considered animated status when Ca2+ cycling was reconstituted not only at a cellular level, but in the tissue microenvironment and tissue microenvironment. Certainly, LPCAT prevents the complete abrogation of membrane plasticity and prevents the complete abrogate of Physiological Current in tissues. Imperatively, Phospholipases result in the release of Ca2+ which encircles the Phosphate groups of membrane integrated Phospholipids. Relevantly, Pharmacological Calcium Channel Inhibitors are known to modulate through inhibition the Sarcolemmal and Sarcoplasmic Reticular Ca2+ pumps, imparting Antagonistic influence resulting in clinical Vasomodulation that rescues high Blood Pressure or Hypertension. The Sarcolemma, however, is the membrane encapsulating cellular entities, particularly in muscle tissue and particularly Cardiac cellular entities. The Sarcolemma participates in producing a membranous environment that encapsulates Striated muscle cellular entities and exhibits a Lipid Bilayer Plasma Membrane, an outer layer of Polysaccharide that integrates with the Basement Membrane, Laminin or Collagen Fibrils that integrate with muscle fibers, as well as integrating at each extremity into Tendons. Transmembrane proteins connect each muscle cellular entityâ&#x20AC;&#x2122;s intracellular cytoskeleton to the extracellular environment where these connect to the basement membrane. The AMEHSI Specification presents an example in which reanimation of muscle tissue occurred upon exhibition of Ca2+ signaling which begin in that Basement Membrane and expanded along the muscle membranes, producing cycling of Ca2+ between intracellular environment, muscle fiber and the Muscle Fiber. Particular Calcium Channel Inhibiting Pharmacological Factors were observed to inhibit Ca2+ Sarcolemmal and Sarcoplasmic Membrane channel exchange. A particularly study presents that the PEMT function was also impaired resultant of Pharmacological Inhibition of Calcium Channels or Ca2+. However, another study observes that disruption of Lipid Metabolism Homeostasis, particularly Fatty Hepatic Condition Endoplasmic Reticulum compared to typical Hepatic Tissue Endoplasmic Reticulum, resulted in impaired Sarcolemmal and Sarcoplasmic Ca2+ ATPase activity. Since the study exhibiting the effect of Calcium Channel Inhibitors to Ca2+ exchange also exhibits impairment of PEMT activity, the study of inherently exhibited Ca2+ ATPase activity is somewhat different, however these together suggests that particular Calcium Channel Inhibitors, like many therapeutics, can produce a therapeutic effect at the expense of impaired intracellular lipid homeostasis. Interestingly the Sarcolemma, encapsulating cellular entities and structurally interactive with Muscle Fibers, not only encapsulates cellular entities by is integrated into the Caveolae Invaginations in the Cellular membrane. This exhibit a substantial improved perspective of how eNOS activity at the Caveolae participates in Muscle Contractions and more clearly links electrochemical current within the cellular membranes of muscle tissue to muscle contractions occurring at biochemical level. Moreover, these illustrate how iNOS affects muscle function by depleting Ca2+ to deprive eNOS of Ca2+ at the Caveolae. Furthermore, the collapse of the sheathing around cellular entities can be more accurately described as collapses of the Sarcolemma Membrane and the depletion of Ca2+ can describe an impairment of structural aspects of Electrical to Biochemical contractile transference, which does not necessary impair the Electrical contractile signal independently and does not necessarily impair the biochemical contractile signal independently. Resultantly, this essential plasticity change may have been diagnostically undetermined, inadequately prioritize and represent a somewhat pivotal opportunity to reverse plasticity changes in muscle tissue and other tissue. The two different studies exhibited here utilized Endoplasmic Reticulum Ca2+ exchange as analytic priorities, although one utilizes Cardiac Tissue and other utilizes Hepatic Tissue. PEMT is pervasively known in the literature to be differently expressed in central aspects of Anatomy, principally hepatic tissue.

The MCAT Preparation manual presented by Barronâ&#x20AC;&#x2122;s for instance, clearly shows that Photons which do not permeate an Atom can displace Electrons or have their energy transformed to become a part of the material within the Electron Cloud. This transformative integration results in the expansion of the space occupied by material in the electron cloud including additional Electrons being exhibited in Valence Levels or production of a new more Valence Level more distant from the Atomâ&#x20AC;&#x2122;s Nucleus. These clearly describe the changes to tissue, such as swelling or expansion, when exposed to Energy Fields, Communications Field, Magnetic Fields or fields otherwise. Similarly, this Excited Status of the Atom can be persisted along with persistent exhibition of such fields. There is also the possibility of Ionizing interactions although the literature and consumer protection testing typically consider Ionizing Radiation.312 However, protein and mRNA analyses exhibit Hepatic and Cardiac mRNA expression as similar with Protein availability potentially being dissimilar. Decreases levels of PEMT may lower the threshold for an impairing circumstance to occur. These may modify this comparison of two studies, but does not mitigate the conclusion reached regarding the two studies.313 314 315 Moreover, these suggest that iNOS may have longer duration effect to plasticity although it is acknowledged here that Energy Fields and Communications field pervasively augment the Geomagnetic and Solar fields that are known to replenish energy pathways. Pervasively, the opportunities for improving health status exhibited in the AMEHSI specification include factors that may have a benefit to Physiology immediately or in particular circumstance, while also having the potential to impart detriment as progression of phases of being occurs or along with persistent exhibition of such factors. The AMEHSI Specification clearly shows that such tradeoffs may no longer be required, particularly by continuously integrated understanding into diagnostics, therapeutics, and outcomes analytics. These clearly suggest that a less than adequately prioritized aspect of health services practice may be integrated analytics which focus on defining optimal outcomes diagnostically, therapeutically, and functionally, such that continuous improvements in practice toward optimal outcomes can occur. Specifically, each health services practice in developed nations should purchase an onsite Homocysteine diagnostic appliance as well as include Electronic Health Information System that associates Homocysteine levels with Diagnostic, Therapeutic and Functional Indicators. Each such information should utilize optimal levels of Homocysteine to determine the optimal diagnostic statuses, therapeutics and functional goals as well as objectives. This suggests that LPCAT and PEMT may participate in Physiological rhythm homeostasis, potentially being a mechanism or reconstituting Physiological rhythms directly instead of only enhancing the electrophysiological characteristics of essential integral membrane Phospholipids Phosphatidylserine, Phosphatidylcholine and Sphingomyelin. This paragraph, alone, covers 95+ percent of membrane phospholipids as well as a substantial aspect of the material constituting cellular membranes. LPCAT is downregulated by Ca2+ availability exhibiting a cycle in which extended length Fatty Acids susceptible to Oxidation as well as a cycle in which impaired Fatty Acid Moieties are removed from Glycerophospholipids by Phospholipase A2. Glycerophospholipids, once the impaired and susceptible Acyl-Moieties are removed, become re-acylated by LPCAT1 which achieves this using Lysophosphatidylcholine and extended length Acyl-CoA. The exhibition of a Hand Motif for Ca2+ integration in 312 313 314 315

ISBN 9781438074559. Human Protein Atlas. PEMT. Digital Object Identifier 10.1038/nature09968 Digital Object Identifier 10.1023/A;1010905221770

LPCAT1 suggests that it competes with iNOS for Calmodulin integrated Ca2+ instead of competing with the other Nitric Oxide Synthases, although LPCAT1 may compete with other Nitric Oxide Synthases secondarily once enough Ca2+ is available to activate Nitric Oxide Synthases other than iNOS which is insensitive to low Ca2+. LPCAT1 may compete with iNOS for Calmodulin/Ca2+ Integrated, resulting in its own inhibition when adequate Ca2+ is available. The availability of Ca2+ may have spatial dynamics such that its availability may be along gradients toward its centers of metabolic consumption. These spatial aspects of molecular dynamics and diffusion are essential, because these describe the retreat of PEMT and LPCAT1 to particular tissue bases as a result of gradients of Choline availability as it is move along biological systemic gradients determined by major centers of most substantial choline metabolism. Choline deficiency results in expression of iNOS. LPCAT exhibits significant increased expression in Pulmonary, Splenic, Cerebral Cortex, Nasopharynx, and Bronchus tissue although even in these areas it is exhibited at lower levels of expression than it is in Hepatic tissue. LPCAT expression patterns, other than in the Spleen, seems to be an inversion of PEMT patterns of expression. 316 These suggest that LPCAT activity is distributed characteristically among aspects of Phospholipid Metabolism and since some of the literature is not clear which versions of LPCAT are included in their analyses, other areas of these analyses observe in the literature a more probabilistic propensity for LPCAT1 and LPCAT4 to occur in the Plasma Membrane among membrane Phospholipid Shuttling which occurs in more progressed phases of the Choline Kinase Pathway which begins in the Cytosol and more progressed Phases of the Ethanolamine Kinase Pathway which begins in Mitochondria, Endoplasmic Reticulum, Golgi Apparatus and more incipiently Fatty Acid Processing that occurs in Peroxisomes for Delta 12 and Delta 15 Desaturases which process Omega-3 Fatty Acids of the greatest Carbon Lengths. LPCAT 3 is, however, coupled with Adipogenesis or emergence of preadipocytes into Adipocytes or Fatty Cellular Entities. Inhibition of LPCAT3 results in decreases in Arachidonic Acid integration into Phospholipids, while stimulating Eicosanoid Synthesis which can include Inflammation factors. Eicosanoids have a role in pervasive pathology. LPCAT3 may recycle Arachidonic Acid which is freed by Phospholipases, preventing inflammatory cycling and inhibiting Eicosanoid Synthesis. LPCAT prefers 1 â&#x20AC;&#x201C; Acyl â&#x20AC;&#x201C; Lysophosphatidylcholine and Human Orthologs are observed by the Uniprot Database to include only Acyl Substrates. Comparatively, LPCAT2 is observed by the Literature to Prefer both Acyl and Alkyl Moieties in Substrates. LPCAT2 has been observed to occur in correlation to Inflammatory cellular entities including Macrophages as well as Neutrophils, particularly those which exhibit Ether moieties within Phospholipids such as Phosphatidylethanolamine. LPCAT2 is suggested by the literature to be observed in limited conditions such as impaired Neurological tissues, stimulation by Lipopolysaccharide potentiating iNOS/Xenobiotic Response Element/Inflammation including NF KB, as well as with CpG Oligodeoxynucleotide 1826 Stimulation and as well as in Allergic Encephalomyelitis. LPCAT2 has a strong probability of being exhibited along with Choline Kinase and it is suggested to be an inflammatory circumstance capability that assists with Lipid management. Correlatively, both LPCAT1 and LPCAT2 have Lyso Platelet Activating Factor Acetyltransferase (LysoPAFAT) Activity and can produce Platelet Activating Factor. Again, Platelets interact typically at a locus of impairment of inflammation cascade to close an aperture in physiological structure. A more precise presentation of differences between LPCAT1 and LPCAT2 are that Lipopolysaccharide Phosphorylates Serine 34 of LPCAT2 while Serine 34 of LPCAT1 is not activated by Lipopolysaccharide, suggesting 316

UNIPROT the Human Protein Atlas. LPCAT1.

that LPCAT2 is even more strongly potentiated as a Xenobiotic Pathway factor that is activated in response to Biological Xenobiotic Factors, since Lipopolysaccharide is a ubiquitously exhibited, highly conserved, and Complements Immunological System monitored Protein Sequence which occurs in somewhat expansive aspects of Microbial Protein Coats. LPCAT2 Phosphorylation at Serine 34 by Lipopolysaccharide requires 30 minutes or more to become effected, suggesting that changes to membrane plasticity, inflammation pathways, as well as shape, twist and writhe of ligands and LPCAT2, known as Post - Translational Modifications are required before such Phosphorylation can occur. LPCAT1 is expressed in Alveolar Cellular Entities ATII, resulting in Palmitoyl – CoA which is then secreted into the Alveolar Space, changes surface Tension, as reduced surface tension, Characteristics that prevents the Collapse of Alveolar Space. Palmitate is the first Fatty Acid Exhibited in Fatty Acid Synthesis, suggesting that the Synthesis of Palmitoyl-CoA and the activity of LPCAT1 participate in one of the few Junctures of development known to require the function Choline Kinase, production of Cellular Characteristics amenable to changing environmental Conditions beginning as well as the maintaining of lowered Alveolar surface tension which enhances pressurization maintenance along with prevent Alveolar Collapse. This juncture of Choline Kinase Essentially occurs at Birth and includes response to Xenobiotics and newly exhibited influences from beginning of Pulmonary function. LPCAT1 seems to prefer Dipalmitoyl – CoA as a substrate and Dipalmitoylphosphatidylcholine seems to be a principal lipid component of Surfactant while both LPCAT1 and Dipalmitoyl – CoA are correlatively exhibited in Alveolar ATII cellular entities, indicating that Phospholipid Remodeling pathway exhibits LPCAT1 and suggesting that Surfactant exhibited Dipalmitoylphosphatidylcholine is also produced in such Remodeling Pathway. Interestingly, although LPCAT2, LPCAT3, LPIAT1 and LPAAT3 as known to integrated Poly Unsaturated Fatty Acids into Lysophospholipids, LPCAT4 is suggested to not be able to accomplish such a factor. However, LPCAT4 is known to produce Phosphatidylethanolamine integrated using Oleoyl-CoA as a Precursor, indicating the Oleic Acid can enter Fatty Acid Cycling and Phospholipid Membrane Fatty Acid Cycling through LPCAT4 and Phosphatidylethanolamine. Oleoyl and Palmitate factors are suggested by the literature to the most prevalently exhibited Fatty Acids in PEMT synthesized Phosphatidylcholine. These clearly show that Acyltransferase Activity may be occurring in some way in pervasive aspects of Phospholipid Cycling. LPCAT1 is suggested to exhibit Lysoglycerol Acyltransferase activity while also is associated with Rod Shaped Entities of Vision tissues such that impaired exhibition of Genetic Impairment potentiates deterioration of vision tissues. LPCAT4 is known to stimulate Cone Shaped Phospholipid Synthesis similar to LPEAT. These factors indicate that Phospholipid Acyltransferase are participatory factors which extend to the characteristics of intracellular and cellular membrane phospholipid structural phases, while also becoming factors in superstructure characteristics. Another clue in the Mystery of Enriched Omega – 3 Fatty acids produced by PEMT, it is suggested by the literature that PEMT prefers Diacylglycerol which exhibits DHA and EPA, providing a more specific explanation of DHA/EPA/Omega – 3 Enrichment of Phosphatidylcholine. It seems that the intricate aspects of enrichment of Phospholipids are distributed among many factors in the de Novo pathway and the Phospholipid Remodeling Pathway. The Literature suggests that Liver X Receptor and PPAR alpha stimulate LPCAT3 expression which may be participate in the enhancement of the length of Arachidonate in PEMT Synthesized Phosphatidylcholine. Peroxisomes are in the Cytosol and Liver X Receptor is activated when PEMT synthesis of VLDL is inhibited.

Relevantly, Cardiolipin exhibits four Arachidonic Acid Fatty Acid Moieties which exhibit the same ability to be metabolized by Phospholipase, produce an increased levels of Arachidonic Acid exhibition, followed by Lysocardiolipin Acyltransferase (LCLAT1) Synthesis of Cardiolipin. It is not clear of the extraction of Fatty Acids from Phospholipids in the cellular membrane provides a beneficial or detrimental effect. This could describe the progressive impairment of regenerative capabilities and impairment scarless healing capabilities in tissues, including Cardiac tissue. Similarly, this could describe system progression of low level pathogenic factors because of Arachidonic Acid is utilized, according to the literature, in pervasive Physiological, electrochemical and conscious cognitive function. These seem relevant to pervasive pathology including the sometimes-observed inability for Cardiac tissue to exhibit regenerative and scarless healing. Cardiolipin is considered essential for Mitochondrial Oxidative Phosphorylation and its function is enabled by its Acyl Characteristics which become changed beginning with the exhibition of Age Associated Pathologies. Acyl – CoA Lysocardiolipin Acyltransferase Lysocardiolipin Acyltransferase 1 (ALCAT1) participates in Cardiolipin Remodeling and Mitochondrial Biosynthesis. ALCAT1 is stimulated by Oxidative Stress and results in inhibition of MFN2 availability which results in Mitochondrial fragmentation, along with its overexpression which impairs Mitochondrial DNA Copy Number and impairs Mitochondrial DNA Fidelity. MFN2 rescues impairment of Mitochondrial Fidelity, fragmentation, and copy number impairment as well as rescues Oxidative Phosphorylation/Electron Transport Pathway activity. ALCAT1 inhibition enhances MFN2 by upregulating availability of MFN2. The literature suggests that ALCAT1 is required for Non-Alcoholic Fatty Liver Disease and ALCAT1 induces the Characteristics of Non-Alcoholic Fatty Liver Disease independent of the disease constitutively. Cardiolipin, as a source of Arachidonic in Four Acyl Moieties seems to be required for typical Hepatic and Cardiac Function, as well as typical Mitochondrial function, while ALCAT1 alone can induce the characteristics of Choline Deficiency and impaired Choline/Folate/Betaine Metabolism.317 ALCAT1 a murine version of the Human LCLT1 or otherwise LCLAT1, while exhibiting some ability to perform LPIAT activity and LPGAT activity. LCLT1 or LCLAT1 is presented by the Gene Cards databank as having highest probability for Endoplasmic Reticulum and Cytosolic activity while Membrane Activity was considered moderately possible and other areas have either probability or low level of activity.318 319 Although iNOS expression is associated with LPCAT1 expression, these seem to be environmentally originated including being exhibited with choline deficiency and including less than Natural fields exhibited in civilization. Similarly, although NAD+ increases from iNOS, PARP expression or Circadian Factors can induce LPCAT1 expression, it is not clear if this process is beneficial, detrimental, or adaptive. However, saturated Fatty Acids are known to induce fluidity to cellular membranes, particularly because the kink in unsaturated Fatty Acids at the Double-Adhesion juncture or junctures in unsaturated Fatty Acids, resembling the Kicker of a ball or resembling the Rockettes’ Dancers’ Pseudo-Kick occurring between each Full Kick. The Kicks may be somewhat familiar also to River Dance although familiarity with the River Dance may be only recently widely known among Populations of the Western Hemisphere. The space produced by the Kicking Lipids, or produced by the 317 318 319

Digital Object Identifier 10.1002/hep.27420 LCLAT1 Gene. Gene Cards. Human Gene Database. NIHMSID NIHMS627801

cis molecular structural kinks, disrupt uniformity in the Hydrophobic tails of the Phospholipids. It should be added here that the imperfection which Unsaturated Fatty Acids introduce into cellular membranes which Physiology considers to be quite pleasant may equal or exceed the pleasantness of viewing a Rockettes’ performance. Saturated Fatty Acids do not exhibit such Double-Adhesions between Carbon Atoms, typically exhibiting Saturating Hydrogens instead, enabling uniformity and somewhat linear Fatty Acid moieties within the Fatty Acid Hydrophobic tails that extend inward toward the Plasma Membrane Interstitial Space which is opposite of the Headgroups which are oriented toward the extracellular environment at the outer Plasma Membrane and oriented toward the Cytosol at the Inner Plasma Membrane. The extra space required for the kinked Fatty Acids, thus, results in enhanced membrane fluidity. LPCAT1 can reduce the membrane Fluidity in cellular membranes. A particular study observes that inhibition of Stearoyl-CoA, a Desaturase, results in increased membrane Saturated Fatty Acids while decreasing Monounsaturated Fatty Acids, while not changing the levels of Free Fatty Acids, suggesting that it too may function in cellular membrane catabolic and Synthesis flux like LPCAT1. StearoylCoA also was observed to enable the Unfolded Protein Response by inducing decreases in Membrane Unsaturated Fatty Acids. LPCAT3, interestingly, was upregulated responsively to inhibition of Stearoyl-CoA. Lysophosphatidylcholine Acyltransferase 3 (LPCAT3) prefers Polyunsaturated Fatty Acids when it Synthesizes Phosphatidylcholine. Inhibition of LPCAT3 increased the level of Unfolded Protein Response exhibition, which is constituted a response to Endoplasmic Reticulum Distress which results in abrogation of transcription, clearing and degrading of accumulating proteins within the Endoplasmic Reticulum, also resulting in increased synthesis of Chaperone Proteins essential for protein folding and other signaling pathway upregulation. Unfolded protein responses are known to accompany Neurogenerative conditions including Alzheimer’s, Parkinson’s, Huntington’s, and Creutzfeldt-Jakob conditions. The Unfolded Protein Response by the Endoplasmic Reticulum seems to be an Adaptive Mechanism, if persistently exhibited can be shown to result in cellular destabilization, and according to the literature, features exhibition of CHOP. LPCAT1 prefers Unsaturated Fatty Acids, thus it can enhance membrane Plasticity, enhance the unfolded Protein Response as Unsaturated Fatty Acid enhance Cytotoxicity, and potentially enhance CHOP which is a feature of Choline Kinase Inhibitor effectiveness.320 321 There may be some difficult asking practicing providers and researchers to accept that inhibiting LPCAT3 can induce Endoplasmic Reticulum distress unless the explanation that PEMT inadequacy directs Endoplasmic, Mitochondrial and perhaps some Nuclear Metabolic Processes Somewhat directly through the Ethanolamine Kinase Pathway to Phosphatidylserine where it meets Choline Kinase Pathway’s conclusion in Phosphatidylserine, Sphingomyelin and Ceramide. Thus, signaling pathways directly affected Genetic, Epigenetic, Transcription, Replication and Cellular Cycle, all can be moved from Nuclear, Cytoplasm or other intracellular interactions among systems to be exhibited instead at cellular membranes or even the Plasma Membrane Extracellular Interface. This is similar to signal processing impairment to cognitive activity resultant of Homocysteine and other inflammation. Choline Kinase Inhibitors or Tyrosine Kinase Inhibitors Seem to inhibit the ability of the Choline Kinase pathway to impair the ability of the Ethanolamine Kinase Pathway to become exhibited, along with alleviation of the decreased ability of PEMT to be exhibited in beneficial cycles of Phospholipid flux.

320 321

PMCID PMC2820416 Digital Object Identifier 10.1074/jbc.M110.126870

Interestingly, if one considers that impairment of PEMT Catalytic Activity results in exhibition of P53, impaired PEMT activity results in Phosphatidylserine synthesis by Choline Kinase Pathway and Ethanolamine Kinase Pathway, Saturated Fatty Acid increases in the Cellular Membrane result in the Unfolded Protein Response, and P53 results in Cellular Cycle Pause at a Hypertrophic phase, then it seems very much like impaired Saturated Fatty Acid availability in cellular membranes decreases the available space and fluidity for synthesize molecules to become integrated or to permeate such cellular membranes. Similarly, it seems that the Unfolded Protein Response may be being exhibited along with accumulation of molecular, transcription or synthesis factors without any place to go, explaining also the hypertrophy of cellular entities which may be occurring simultaneously. This suggest that the ordered programmed exhibition of activities in the intracellular environment are foundationally transformed into chaotic response to all manner of extracellular and intracellular stimuli once PEMT and the Ethanolamine Kinase Pathway, as well as Choline, BHMT Pathway and 17Beta-Estradiol contribution to stability each begin to abate. Furthermore, reviewing the literature in detail reveals that Saturated Fatty Acid increases in membranes can change the NA+/K+ ATPase activity along with changes to the Sarcoplasmic-Endoplasmic Reticulum Calcium ATPase2b (SERCA2b), while also stimulating C-SRC Kinase to Lipid Rafts in the cellular membrane to increase activation sensitivity. Additionally, the literature also suggests that contrary to other research literature, the uniform diversity of Fatty Acids attached Lipid Lead or Head Groups is substantially resultant of Membrane Landâ&#x20AC;&#x2122;s pathway activity in which LPCAT versions preferentially attach Saturated Fatty Acids to the SN-1 location and along with attachment of Unsaturated Fatty Acids to the SN-2 Position.322 It is interesting that Stearoyl-CoA Desaturase associated Stearates or Stearic Acid are associated with less than optimal membrane characteristics and less optimal prognosis in Oncology of the Breast. This might be explained if the Exhibition of Stearoyl-CoA is not causal, but indicative or responsive to less than optimal statuses. Desaturase activity at increased levels suggests exhibition of increased substrate, Saturated Fatty Acids. The exhibition f Stearoyl - CoA Desaturase, however, is not considered to be a central aspect of either the Omega-6 or Omega-3 Pathway, constituting a shunt of monounsaturated Fatty Acids into Phospholipid and Fatty Acid Metabolism. Although it is suggested that increased levels Stearates or Stearoyl-CoA Desaturase in particular in association with Oncology seems to not be associated with exhibition of the Omega-3 or Omega-6 pathways per se or constitutively. The Trimethylamine, Flavin Monooxygenase 3 (FMO-3), to Trimethylamine-N-Oxide pathway in which occurs in Hepatic tissue in particular, is known to regulate Cholesterol homeostasis, exhibiting impairment of Digestive pathway absorption of Cholesterol, causing reorganization of Cholesterol transport and induces Macrophage enabled Reverse Cholesterol Transport. FMO impairment may indicate Hepatic Distress, but overly exhibited TrimethylamineN-Oxide is known to be associated with the highest risk categories for Sudden Adverse Health Events. Impiared FMO activity is also known to impair LPCAT3, Stearoyl-CoA Desaturase 1 Activity, and Endoplasmic Reticulum Homeostasis while also stimulating Liver X Receptor which activates Macrophage Reverse Cholesterol Transport as well as inhibits iNOS at the transcription level.323

322 323

Digital Object Identifier 10.1016/j.cmet.2013.10.002 Digital Object Identifier 10.1016/j.celrep.2014.12.036

Trimethylamine-N-Oxide, according to the statistic and literature, is the most indicative and proximately causal of Sudden Adverse Health Events, although certainly the other factors and Indicators included in the Amehsi Specification are cumulatively and progressively enabling of susceptibility. Trimethylamine-N-Oxide provides several influences which transform existing health statuses into emergent health statuses. Trimethylamine is converted to Trimethylamine-N-Oxide by FMO1 and FMO3 which are active in Hepatic Tissues. The Catalysis of this transformation by FMO includes the Reducing/Reduction of Trimethylamine utilizing Oxygen which is said to be obtained from H202, such that appended Oxygen is integrated at the Nitrogen. The structure is amazingly similar to Choline including the exhibition of the Oxygen as prosthetic axial group except among the three CH3 groups there is a chiral feature in which one is oriented downward and the other oriented upward. Although a Nitrogen is not removed from circulation, the Nitrogen exhibited at the extremity of Trimethylamine is reduced and obscured by the appended Oxygen which prevents the Nitrogen from participating in Resonant and Aromatic relationships with other molecules. Since Choline is a manner of moving Hydrides from outside of Organic systems into Organic System, and Trimethylamine is typically derived from choline, Trimethylamine represents a change to the system of Inorganic to Organic systems transfer exhibited by Choline. Choline typically moves Hydride from Inorganic systems to Organic Systems. Similarly, this change represents a change to the systems of Alkaline influence produced by Hydride that is integrated into molecules; an influence that produces fields of alkaline influence in Physiology other than only at the molecular location of the Hydride. Free Hydrides are said to not be a typical feature of biological systems, although alkaline influences and alkaline factor otherwise are exhibited in Physiology as free factors. Furthermore, the literature regards H2O2 as a primary substrate for FMO, an enzyme which produces Trimethylamine-N-Oxide and Water from Trimethylamine. This suggests that Uncoupling of Nitric Oxide Synthase and Beta-Oxidation may be central factors in supplying, competing with, or managing H202 along with FMO, all of which may be being supplied with H202 by pathways which include Superoxide Dismutaseâ&#x20AC;&#x2122;s Oxidation of Reactive Molecular Species. Superoxide Oxidizes O2- Superoxide to produce H202. FMO production of Trimethylamine-NOxide removes Oxygen from Metabolic Cycling, removes Resonant systemâ&#x20AC;&#x2122;s access to Nitrogen, obscures a Nitrogen through Reduction, changes the Quaternary Ammonium Nitrogen Centered Structure to exhibit oppositely oriented CH3 groups, thus removing Alkaline influence, changing resonant interactions, and changing both Nitrogen and Oxygen participation in molecular systems as they typically might otherwise. These can change the potential of Hydrogen, reduce availability of Oxygen in Blood Gases, and remove Nitrogenous influences without removing Nitrogen from Circulation such that Amylnitrites might be potentiated. Uncoupled Nitric Oxide Synthase produces Nitrites or Peroxynitrites as a feature of Uncoupling in which reactive Oxygen and intermittent Nitric Oxide are produced in the inflamed Microenvironment. Trimethylamine-N-Oxide also Uncouples Nitric Oxide Synthase constitutively.324 Peroxynitrite, iNOS and Uncoupled Nitric Oxide Synthase are known to reverse the activity Selective Serotonin Reuptake Inhibitors, clearly presented a role for their inclusion in Obsessive, Compulsive, Behavioral, and Physiological disorders, therefore also clearly presented how iNOS, uNOS, and Peroxynitrite produced by Communications fields, Electromagnetic Fields and Magnetic or other fields can be modulated or with plainly exhibited activity change or produce Human behavior.325 These analysis have clearly presented a mechanism, or 324 Digital Object Identifier 10.1016/j.cell.2015.11.055 325 Digital Object Identifier 0.1155/2016/9131680

potential mechanism, through which pervasive detrimental Human outcomes may have requisite event essential nuances which constituted of Victimization, although it cannot be excluded that such nuances of behavior are not directed upon paths which improve Human outcomes. Trimethylamine-N-Oxide synthesis, then, decreases the Nitrogenic and Oxygenic Metabolic Cycle which includes Blood Gas availability of Oxygen and Nitrogen. The effects, here, are that Vascular Pressure is reduced and Vasoconstriction is promoted without requiring participation of the L-arginine, Arginase, Nitric Oxide Synthase or cAMP pathways. Studies observe that Carotid Intima-Media Thickness Decreased or Improved only with improvement in TMAO status. Additionally, TMAO is a Toxin that exhibits Renal Toxicity and produces much of the detrimental effects that other Free Amines exhibit, including those effects produced by Homocysteine, Asymmetric/Symmetrical Dimethylarginines and other factors.326 327 Another study presents the lowest quartile at 2.2 Micromoles per liter and the Highest Quartile at 13 Micromoles per Liter, with regard to TMAO, which correlated to Quartile 1 exhibiting about 85 percent of the population without a Vital Being Abating Health Event and Quartile 4 with about 60 percent of the population without a Vital Being Abating Health Event. The range from the Lowest quartileâ&#x20AC;&#x2122;s lowest TMAO levels to the highest Quartiles TMAO Levels were 1.7 to 21.9, which confer astronomically different levels of risk than range of the average TMAO Molarity in each quartile, 4.8 to 13 as well as presents different information from the 2.7 Hazard risk Ratio presented with the use average TMAO molarity. Some studies provide better information by reducing risk to coefficients that can be calculated from each molar or micromolar increase of the indicator, in this instance TMAO. There is not enough data to present this precision here, although it can be approximated. A 4.8 to 13 median quartile molarity range and a hazard ratio of 2.7 might be projected by dividing the Ratio of 2.7 for the highest quartiles median by the range between the Quartile medians, 8.2 to produce 0.329 of risk per micromolar increase of TMAP. However, using the actual range of Molarity across all quartiles, 1.7 to 21.9 which is 20.2, followed by projection of the 0.0329 level of risk for each micromolar increase using 1.7 as a floor and 21.9 as the ceiling, would suggest that 21.9 Micromoles of TMAO there is 20.2 molar increase above the floor which correlatives to there is a 6.65 hazard ratio. Here the inadequacies of such studies and their interpretation as well as usability has to be presented. Many such studies may not use healthy and pathology free baselines as an inserted quartile or baseline. Thus, even Quartiles have to be presented as having risk correlative to the best diagnostic group or best diagnostic factor exhibiting quartile, quintile or group. The AMEHSI Specification found a very powerful study of a decade follow-up analysis of Patients in an Age Group with increased demise risk. The study has become difficult to locate and even the online references to the study by Physicians have become obscured. However, the study clearly exhibited a Less than 1 Percent level of demise for those with Homocysteine levels at 6 Micromoles per liter. The same study exhibited two Cohorts one which had Homocysteine below 7, at 6 or below, which correlated to 1 instance of Demise. The other Cohort, with Homocysteine above 7 Micromoles per Liter and variable ranges above 7 including 9, and other thresholds produced differently among Health Industry Sources, which correlated to 500 instances of demise. The differences occurred over the duration of Decade. The Amehsi analyses reviewed this study and found it to be the most informative. This represents 326 327

Digital Object Identifier 10.1038/srep26745 Digital Object Identifier 10.1161/CIRCRESAHA.114.305680

49,999 percent decrease in demise when Homocysteine is optimal compared to statuses otherwise. 500 instances of demise every decade might correlated to only a difference of 1 instance of Demise compared to 50 among the groups except that this would result in the group with Homocysteine having Homocysteine at or below 7 Micromoles per Liter not exhibiting any instances of demise in any one Annum except for the Tenth Annum or as individual Probabilistic associated outcome in any one Annum of the Decade. Qualitative calculations could be produced, although these would require more intricate explanation. However, Homocysteine at 0.6 Micromoles per liter is far from the Pathophysiological threshold which the literature suggests occurs in Picomolarity Range. These explain the sometimes wildly different comparative studies and their estimates. Any study of Homocysteine which uses above 1 Micromolar exhibition of Homocysteine is managing countless aspects of Idiopathic and Hidden Pathology, particularly susceptibility to Sudden Adverse Health Events which are factors of double, triple, quadruple or even up to more than Ten different detrimental factors which may pervasively result from, compound, confound or augment Homocysteine associated Pathology. Regardless, a cross-sectional view of this information shows just how wild and varied these studies can be, while all being accurate because pathologies are subjective, particular when homocysteine, Trimethylamine-N-Oxide persistent distress which evokes increased cortisol and increase adrenaline are enabled to be exhibited among populations.328 The ingestion of Meat, Chicken, Eggs and Fish, Energy and Power Fields, Electrical Fields, Magnetic and communications fields, peak usage periods for these, highest consumer activity periods, accumulation of Trimethylamine-N-Oxide, and periods of typical highest consumer activity, along with periods of increased detrimental behavior outcomes, all occur in somewhat synchronized ways, suggesting that the 90% of consumer behavior which is detrimental may reflect similar or more increased aspects of behavior otherwise which are likewise of less than conscious nature. These suggest that what some research resources regard as being as much as a 50 Percent of revenues allocated to advertising by organizations which produce Therapeutics for Profit may be a substantial causal influence to emergence of particular pathologies, although there seems to be a number of influential and suggestive influences which direct inadequacies at physiological, behavioral and social levels toward detrimental Human Outcomes. Clearly, Nations which do not have an inherently integrated and implemented way of compensating their own populations based upon a number of factors including formal and informal, education, training, contribution, service, excellence, innovation, leadership, duration of service or other nuances, potentiate the exhibition of knowledge which could benefit all of Humanity being sequestered away for financial, political or social influence, resulting in abated vital being. Clearly, the potential for such sequestration of information by the private sector is not distinct from the potential of sequestration of such information within nuance of less than private nuances of civilization since it might be universally presumed that National entities may have leadership in the most esoteric of nuance of research, innovation, development and implementation, although these analyses clearly found that a required delegation of therapeutics development to the private sector clearly seems to have resulted in inadequacies in the availability of therapeutics as exhibited in an Food and Drug Administration analysis of Thioglycolic Acid. The possibility that since 1878 200,000,000 Million of the population of the United States were simply not provided a molecule or did not have managed a pathway that was pervasively required for their continued physiological and behavioral welfare is perhaps only at minuscule levels less more reprehensible than the potential that hundreds of millions of people if not billions could be being made susceptible to the detrimental effects of iNOS, inadequate levels of choline, downregulated PEMT and upregulated Choline Kinase, while being exposed to advertising and influences 328

which are able to cause susceptibility to adverse Health outcomes as well as adverse behavioral outcomes. The fact that 50 percent of revenues utilized in particular industries which benefit from exhibition of detrimental Human outcomes are allocated to advertising and marketing, seems more than revealing of such potential. Although these suggest that systems may be aware of these correlations and susceptibilities, it does not suggest that any organization, entity, group or individual has complete awareness of these paradoxes, paradigms and dynamics. Certainly, a civilization which does not have plan to compensate highly capable, educated, productive and workers with other such beneficial characteristics, seems to be a most essential causal mechanisms in such regard. Similarly, since the requirements to achieve the Physiological, Behavioral, Social and Human condition may not be freely obtained in civilization, it is this incipient divergence of civilization from reason which seems to be a most integral enabling factor of such outcomes, including a potential resultant emergence of conditions in which Humanity may be required to benefit from the detrimental outcomes of others in order to achieve such essential Human requirements and including the potential that Humanity may be required to sequester away health assuring and behavior assuring factors in order that they may achieve essential Human requirements for themselves. An omitting of empiricism in analyses, solution development and implementation of programs and services which are required to achieve the Social and Human condition, thus, can result in divergence of outcomes from Reason. Certainly, the exhibition of unresolved outcomes of the same nature for Centuries and Millenia, suggests a potential divergence from reason. Thus, again, these analyses seem to describe the detrimental aspects of the status quo as some â&#x20AC;&#x2DC;thingâ&#x20AC;&#x2122; or nuance of contexts in which circumstances among civilization and nature with potential detriment to Humanity are enabled to persist. Periodically, anathema to Reason, such circumstances cause Humans to have an ephemeral or persistent interest which is in alignment with or integral with the detrimental aspects of the status quo. Pervasively, when detrimental aspects of the status quo and Human priorities or interest become integrated, these represent nuances of civilization which have diverged from Reason and which require alleviation through development of program, initiatives or enhancements those programs and initiatives which may already exist. However, pervasively, attributing causality for outcomes to individuals prevent required understanding and alleviation of the factors which enable the status quo as well as prevent the accoutrement of factors utilized by the detrimental aspects of the status quo to produce collateral and generational detrimental outcomes. Invariably, however, when Humanity benefits from the detrimental outcomes of any other among Humanity, it is of detriment to all among Humanity, particularly because it promotes the detrimental aspects of the Status Quo as priorities among Humanity, such that Humanity may not discern, subsequently, those among Humanity which it prioritizes itself over. This strongly present how systems learn to prioritize themselves, how Humans learn to dissociate their circumstance and outcomes from reason, and how Humanity can become caused to turn upon itself, all through mechanisms of learning which are dissociated from Reason and thus inherently Artificial. Natural learning processes seem to include Humanity as the priority because Human priority extends to priority of the circumstances and favor among the Universes among which Humanity has come to be. Learning processes otherwise seem to be inherently Artificial because when Humanity is not a priority in systems of Learning, priority has to be incipiently produced by influences which are not inclusive of Human priority or, otherwise, priority has to progressively become intermediated by influences which are contrived or not Human. Humanity, relevantly, is integratively included in the systems of the Universes. The detrimental aspects of the status quo can be useful circumstantially, although typically useful contexts can be those in which humanity has already become turned upon itself and disregard for others may have become essential to adequate priority of oneself. Similarly, although profit is productive and beneficial, and can be beneficent, pervasively the reasons for which and through which profit is required are anything but productive and beneficial. Regulatory requirement for business to be profitable may be less than optimal, as may a requirement of profit to be

competitive, and as may be requirement to obtain profit in order to meet requirements of analysts and satisfy those whom have equity interests in an organization. An incipient empirical interest in profit may be achievement of stability, particularly the obtainment of stability in civilization which does not assure stability without participating in systems of civilization including financial and other systems. Thus, the inherent propensity for systems to prioritize themselves, particular when systems of civilization which have been synthetically produced do so, may be integrally causal to detrimental aspects of the status quo as well as may be causal to exhibition a requirement for profit to be exhibited by private enterprise. Thus, such nuances of circumstance and susceptibility may encompass civilization, systems of civilization, private enterprise and Humanity, less than productively, regardless of any conscious awareness, participation and performance within systemic, systemic constructs or Humanity. These areas of discussion and the potential for variance seems extraordinarily apologetic, imprecise and confusing. There seems to be much opportunity in presenting clear and complete information in this regard. The level of demise presented her that is, at a minimum correlated to Homocysteine, should not be occurring in a developed Civilization and there should not be a conventional acceptance of a level at which to interpret Homocysteine that is indicative of the level at which acceptance of the occurrence of demise might be exhibited in Civilization. It is likely that systems of civilization pervasively are not capable of consistently, accurately, and widely reporting that Homocysteine is not being manage adequately and the results may be much of the detrimental Physiological and behavioral outcomes that may have persisted within civilization or which has emerged newly or uniquely within civilization. A Medicaid and Medicare Review of Payments in a particular state was presented by the Amehsi Specification as an instance through which the interpretation of Homocysteine may be using an arbitrarily high threshold that enables increased recidivism, increased level of impairment and increased level of impairment within DRG ratings. These can be utilized to systematically increased payments from Medicare, Medicaid as well as commercial entities that utilize DRG payments as reimbursement guidelines. However, it is known that in the particular State mentioned in the review, there is about a 75% probability of impairing Genetic SNP among the population and about a 50% level of impairing Genetic SNP for PEMT. However, there are no known compensating changes to the interpretation of Homocysteine which have been implemented as a result. Moreover, since these analyses show that even at less than 1 Micromole per liter there is galvanizing of the population toward Emergency Department, Behavioral and Clinical Outcomes of an increasedly expensive and impairing Nature. Furthermore, a study of Females before Menopause and After Menopause which grouped into subgroups with unimpaired, one strand of DNA impaired and both strands of DNA impaired PEMT was able to clearly show an increased level of impairment and decreased duration to disabling impairment when Choline was withheld from nutritional regimen. Particularly, with Menopause all such duration to impairment was decreased and all such level of impairment moved to occur sooner. However, among the Menopause Group of Females whom were impaired upon both Strands of DNA for PEMT, the study was unable to produce precise correlative because all of the potential study participants were no longer exhibited Vital Being, were substantially impaired, had compulsive dependencies, had been deprived of Liberty, or were already reliant upon pharmacological capabilities or health interventions to maintain adequate health status. Pivotally, an article has been found in the public information domain which presents comparative analysis of Homocysteine management studies. Elsewhere it has been presented that a particular study exhibited a difference in incurrence of demise between low and high Homocysteine groups that was 500 to 1, respectively. However, this has

been presented as managed Homocysteine compared to unmanaged Homocysteine, and it should be presented here that low Homocysteine in such studies may or may not be substituted for innately Low Homocysteine or therapeutically managed Homocysteine into low ranges. The distinction is essential because a direct management of Homocysteine such as depletion of Homocysteine may not directly affect the causal circumstances, which is inhibition of PEMT, upregulation of Choline Kinase, Choline Deficiency or Circumstantial Choline deficiency produced by upregulation of Choline Kinase, downregulation of PEMT, inadequate storage of Choline as Acetylcholine, increased Free Choline and upregulation of Choline Kinase production of Phosphocholine. A Particular study observed that a population was able to achieve stabilization of Homocysteine using Folate 50 – Fold increase over Recommended Daily Values (RDA), Vitamin B6 at 100 – Fold increase over RDA, and Betaine by the teaspoonful. Substantial differences in susceptibility to adverse Health Events were observed in such studies often decrease from 3 to 1 or decreasing in more substantial levels. However, these studies began to be considered as using optimal levels of Homocysteine which were substantially too high, beginning with 14 Micromoles Per Liter, and concluding with 9 Micromoles per Liter although these analyses are beginning to exhibit that in the less than micromolar range Homocysteine can be begin to cause Pathology. It is becoming clear that managing Homocysteine constitutes incomplete management of causality to increased Homocysteine and incomplete management of Pathology with which it is associated. The inhibition of PEMT and the Upregulation of Choline Kinase, as well as Choline Deficiency and circumstantial Choline Deficiency, including that enabled by iNOS, have to be included in such management of Homocysteine.329 The unfortunate and presentable conclusion is that Males and Females with Menopause or Females with removed reproductive Tissue, there seems to be a potential to perform, with regard to Choline inadequacy, potentially between the outcomes of One Strand of DNA PEMT impaired groups within the Group without Menopause and Group with Menopause. This assertion is not relevant for indicating Health status because Choline has now been presented as an essential Nutritional Factor by the United States Food and Drug Administration. However, it is useful in determining how Testosterone and 17Beta-Estradiol inadequacy effect Physiology, module Choline Obtainment and levels of Choline required, as well as exhibits susceptibility of such Males and Females to the additional step required to transform Testosterone into 17Beta-Estradiol. The projection of these factors into the events of the 1960s, how these describe the Phenomenon known as Roemer’s Law, how Roemer’s Law describes the Phenomena observed in the later aspects of the 1940’s which were principal impetus to the Hill Burton Act along with its introduction of Certificates of Need, as well as How the emergence of the MEDLARS System of Distributed Health Information and the publication of Information strongly linking Homocysteine to Detrimental Behavior as well as Detrimental Health Status, each produced the context from which the 1960s, 1970’s, 1980’s, 1990’s and modern Sociopolitical events emerged. Imperatively, these show clearly that in the later aspects of the 1960’s States became aware of the Link between Healthcare Certificates of Need, Behavior and disjoint nature of Costs to both of these. These show that the public as acutely unconsciously aware of the links between Choline, Homocysteine, Disease and Behavior, although this linkage manifested itself pervasively in social outcomes, systemic statistics, artistic, political, social and economic outcomes. States became aware of the Linkage between Certificates of Need and Utilization, as well as the effect of Roemer’s Law, and began to counteract or remove their own Regionally Ratified Certificates of Need to prevent being Adjoined to acknowledging that Behavior had a substantial incipient external component that was independent of the Individuals.


The principle Liberty Assuring Entity of the United States then imposed a Moratorium on the use of Demise as a Sanction, presumably because the events of the Kennedy Administration clearly showed that Humans were conducting activity more pervasively to the priority of interactions between systems than to their own individual and group priorities. The levels of detrimental interactions among actors and constituents of systems then began to decrease substantially along with levels of demise during the Moratorium. During such moratorium regarding the use of Demise as a Sanction, one of the Largest Urban Population Areas in the Nation experienced a Provider Strike which belied a cross-sectional view of the way in which Providerâ&#x20AC;&#x2122;s Direct Hospital Utilization and exhibited a duplicity between Private and Public Health Services Entities because indigent Patients were being transported from Private Care Entities to Public Care Entities resulting in substantial levels of demise which the Public Misinterpreted as Health Systems themselves causing demise among the Population. The duplicity here was important because illustrated that the Original Hill-Burton Act and its Certificate of Need which required that Hospitals receiving Public Assistance in their construction, each substantiate that the population had adequate levels of illness or demand for services before construction of any new Health Services Facility would be funded. This Certificate of Need was intended to prevent the observations of the Later aspects of the 1940s in which the construction of new Healthcare Facilities was observed to result in utilization at the same levels of the previously exhibited Healthcare Facilities in the same service area. The duplicity which emerged, thus, were the constraints placed upon Public Hospital Construction compared to the inadequate regulation of Private Hospitals which were able to emerge without constraints, increase detrimental outcomes among populations, delay or obfuscate the interpretation of Homocysteine when understanding emerge, thus causing a rise of consumerism in the United States that included utilization of systems which manage detrimental Human outcomes as well as emergence of widespread compulsion status and compulsive disorders. Passiflower Incarnata reverses Morphine Tolerance and Compulsive disorders with Morphine.330 It should be clearly presented that the phenomenon was being observed when public Hospital were the principle versions of Health Facilities being constructed, and the Nationâ&#x20AC;&#x2122;s Public Services Infrastructure emerged within systems constructed upon principally private, commercial or community associated interests. The phenomenon being observed to occur along with increased private Hospital Construct would likely have emerged in other aspects of the Economy, and numerous Industrial Complexes had emerged by the 1950s such that even President Dwight D Eisenhower suggested the unproductive nature of such complexes using the complex with which he was most familiar as an example of a wider phenomenon that represents interactions among the systems of systems of civilization as well as the Universe. The systems presented by the President Eisenhower and by these analyses regarding Health Systems, are among the most inherently beneficent and productive that have ever been exhibited in the Span of the Human Experience. They present useful analytic instances because regardless of the detrimental nature of systems and systemic characteristics, such beneficence, productivity and utility may be inarguable. The concluding of the Moratorium then occurred, and rates of demise that had decreased 0.8 percent at a National level reversed such decrease substantially within only 1 annum, resulting in, at a minimum, 150,000 instances of demise that would not have otherwise occurred. The implementation of the ICD-10 classification systems in 1979 resulted in abatement of this trend of increasing levels of Demise and was augmented by the Emergency Medical 330

Digital Object Identifier 10.1076/phbi.40.8.576.14660

Treatment and Active Labor Act of 1986 which prevented Patient Dumping was can be shown to have beneficially affected rates of demise in the following fiscal periods. Although the splintering of these population patterns have pervasive homologues to Clinical, Metabolic and Molecular factors, it was the production of the 1995 Methamphetamine Control Act which shows the clearest interaction of Social Constructs with Physiological Outcomes since it reverse, in the month following its ratification and implementation, about a decade of improvements in levels of Demise from Hepatic and Renal conditions which are somewhat Tangential to Choline Metabolism and Homocysteine levels as well as being central factors in the level of Impairment observed in the study in which Choline was withheld from Females with Before Menopause Status and withheld from Females with Menopause. These clearly exhibit that solutions which do not alleviate or prevent the incipient and empirical causalities, as well as the way in which circumstances within interactions between systems emerge to proximate causality to detrimental Physiological and outcomes may often only move outcomes into another category of behavior, health status or demise. Moreover, because systems invariably produce the incipient, proximate and empirical causality to Human outcomes within such systems, including the inclination, cognitive constructs, cognitive artifacts, patterns of behavior, emotional associations and outcomes which shape systemic interactivity into Human outcomes, the emergence of systems which attribute causality to individuals or groups prevent the requirement or impair the ability to determine what those incipient causal factors might be. Imperatively, detrimental outcomes can pervasively result in objectives being achieved, financial benefit, or merit among systems which manage Human outcomes. The way in which healthcare is paid illustrates this paradox very clearly. Only in particular and often decried scenarios are Health Providers provided Solvency assuring payment when there are no impaired, ill or disease exhibiting Patients. The costs for Care at a National Level or a Local Level cannot be impugned and only with difficulty affected if the basic requirements of all among Humanity are not assured, including the social, human, behavioral, emotional, technological and other requirements of those who are providing care to the population. The causal factors to social problems, similarly, can often be inadequately understood if it is not considered that Humans can be inherently caused to turned upon themselves when those services which are most required for the social and human condition are obtained on a Fee for Service Basis and when the ability of those providing such Services to obtain the Social and Human Condition are also affected by volume by which such services are consumed or utilized. A provider, provider entity or organization providing care cannot provide adequate care or service for a population, particularly that which is disparate from typical, disparate from guidelines or greatly exceed reimbursement levels, when compensation and funding for continued organizational activity are obtained on a fee for service basis. Keeping a population of patients or one patient for extended duration in place of others, particularly for stabilization, regeneration and repair, as well as complete perusal and management of essential indicators to optimal, can substantially change the duration and occupancy of Health services facilities and systems. Providing the best and most extensive care possible by an individual entity to all patients beginning with the first patient to present for care, would surely mean inadequate service resources and would somewhat invariably result in insolvency. Health services should be remunerated for in a way that prioritizes the patient and the outcome. These preceding several paragraphs, and the progression of reasoning within these, exhibit why each social construct has to be accompanied by a Program management feature that assures that the social construct itself is not anathema to human, does not exhibit detrimental outcomes, achieves what the construct is intended to achieve, considers if the what the construct intends to achieve is an alignment with the Ideals and encompassing constructs of a locality, region or Nation, as well as tightly correlating such outcomes and its constructs to the hopes of humanity including the incipient impetus for constructing civilization. Otherwise, constructs can be produced, emerge into

patterns and practices, as well as potentiate outcomes that are Anathema to individuals, Groups, Localities, Regions, Nations and Humanity.331 Îł-butyrobetaine or 4-Trimethylammoniobutanoic acid or (3-carboxypropyl)trimethylazanium are also precursors of TMAO through Microflora Metabolism within the Digestive Pathway. Trimethylamine can accumulate when Flavin Monooxygenase 1 or Flavin Monooxygenase 3 are impaired genetically, epigenetically, transcriptionally, post-transcriptionally or in the Organ/tissue compartment. Progressed Renal Disease or Chronic Kidney Disease, as well as impaired Hepatic Function or consumed Hepatic Capacity, all of which can occur instantaneously from Toxicity, Sepsis, or other factors, impair FMO Kinetic throughput as well as produce different characteristics of Digestive Pathway Microbial Characteristics. Pathogenic statuses can exhibit change in the Systemic Adaptive and Innate Immunological characteristics enabling Microbes which produce increased short-extent aliphatic methylamines as a byproduct of Digesting Nutritional factors.332 333 This data regarding TMAO presents the opportunity to reduce some of the studies discussed to practical understanding. Primarily, this study of TMAO with the Quartile 4 correlating to 60 Percent of the Population being without abated Vital Being, exhibits somewhat homologous outcomes for Quartile 1 and 2 in areas other than Vital Being, and exhibits that some of the biological indicators are better for those in the Quartile 4 than in Quartile 3. Biological indicators, thus, represent other risk including pathology and behavioral outcomes which would be interesting to understand. Similar, the number of males typically decreases as a percentage in highest quartiles particularly when the average age increases per Quartiles. Quartiles are functions of analytics, not selectivity by the study, such that individuals in each quartile are determined by their outcomes, test indicators or physiological status. Imperatively, a practical understanding of these analyses is that in quartile 1 there was 15 percent rate of Abated Vital Being while in Quartile 4 there was a 40 Percent rate of Abated Vital being. However, Quartiles are grouped distributions and the highest ranges of the highest Quartile are susceptible to transformations that are move statistical indicators or change the shape of analytical curves, particularly when compared to the lowest ranges of the lowest Quartile. 3,3 Dimethyl-1-Butanol is known to inhibit Trimethylamine by Digestive Pathway Microflora and has been shown to inhibit TMAO exhibition after L-Carnitine and Choline ingestion. Moreover, 3,3 Dimethyl-1-Butanol (DMB) has also been exhibited to prevent Macrophage Foam Cellular exhibition, presumably Foam Cellular Migration, and Atherosclerotic Lesions. Such benefits were exhibited without any change in Cholesterol Levels, clearly vindicating Cholesterol as a principle detrimental factor in Human Physiology when considered with the other information presented here. 3,3 Bimethyl-1-Butanol was shown, in a study, to inhibit Clostridiales or Firmicutes Microbial Populations which are typically upregulated with Choline and Phospholipid Digestion, along with decreases in TMA, Trimethylaminuria, and TMAO. DMB is found in Virgin Olive Oils, Grapeseed Oils, Balsamic Vinegars, Red Wines. DMB inhibits Foam Cellular exhibition/migration, Choline/Carnitine/Microbial TMAO, Arteriosclerosis by inhibiting Microbial TMA Synthesis and promoting Decarbamylation of Acetylcholine Esterase to exhibit Free Amyl factors that integrate with Nitrite to produce Amylnitrates which are potent Vasodilators. Amylnitrite as an Anti-Angina 331 332 333


Pharmacological Factor. 334 335 Amylnitrate is also considered to be a recreational molecular factor and is listed by some entities as a Hazardous Factor. DMB, as DMB Carbamate can be a convulsant.336 The Kinetic Rate, throughput or Regioselectivity of DMB for Acetylcholineesterase (AChE) is greater than the Rate, throughput or Regioselectivity of Choline for AChE. Acetylcholine Esterase, then, may be inhibited in its bidirectional metabolism of Choline and Acetylcholine by DMB, or minimally AChE may be inhibited in its transformation of Choline into Acetylcholine.337 There is information to suggest that knowledge about the principle cause of Sudden Adverse Health Events and how to prevent, remediate or exhibit prophylaxis has been in place since 1978.338 It is similarly observed that the literature now suggest that Asymmetrical Dimethylarginine is a somewhat independent indicator of Phospholipase activity, particularly Phospholipase A2. An unconsidered factor in pervasive microbial Pathology may be that iNOS depletes Ca2+ preventing eNOS and nNOS production of Nitric Oxide as immunological factors in circulatory or other pathways. Similarly, P53 and impaired PEMT automatically reduce NADPH, which provides similar immunological capabilities, by more than 60 percent. Additionally, PEMT impairment and Choline deficiency suggest that Thymus, Hepatic, Splenic and other tissue locations which produce immunological factors are impaired in doing so. These may be pervasive enabling factors to microbial conditions. Phospholipase A2 in Cotton Seeds and Castor Beans, according to the literature, can result in the exhibition of 18;1 OH fatty acids, of which some literature includes Oleic Acids with a Pyridine Head Group, or Ricinoleic Acid. Pyridine is known to induce toxicity through adhesion to the 60S Ribosome, without catabolism of the toxic molecule. This potentiates a toxicity cascade because Eukaryotic Metabolome may not adequately metabolize Pyridine, resulting in iterative cellular lysis from the same molecules. The 60S Ribosome location is known to be the location to which Pyridine adheres, halting transcription that occurs in such Ribosomal Molecular Machines. Peroxynitrites are known to also affect the 60S Ribosome, exhibiting how uncoupled Nitric Oxide Synthase impairs cellular metabolism and local area metabolism.339 The Amehsi Specification also observed in the literature that HIV requires what is affectively Uncoupled Inducible Nitric Oxide Synthase, suggesting that it too benefits from impairment of the 60S Ribosome or at least changes to its function. Relevantly, other analyses presented here suggested a possibility that HIV, correlative to its affect to Methylation and Guanylyl Cyclase activity, seemed to inhibit aspects of DNA transcription although the literature did not specifically present this. These analyses support such a possibility that non-latent HIV may competitively suppress genetic transcription of DNA into functional enzymes and proteins. A study of the Reactive Oxygen Species Inhibitor and Vascular Nitric Oxide Availability Enabler Nebivolol presents not only it effectiveness but clearly indicates that Uncoupled Nitric Oxide Synthase and Reactive Oxygen Species are the principle culminating cause of Demise.340

334 335 336 337 338 339 340

Amyl Nitrite (Inhalation Route). Mayo Clinic. Drugs and Supplements Section. Mayo Clinic Information Online. Amyl Nitrite. Wikipedia. Digital Object Identifier 10.1002/jps.2600620948 Journal of Neurochemistry. 1978. Volume 30. Pages 865 to 870. Pergamon Press. Application Number EP20120744862. United States Patent and Trademark OfficeUSPTO Internet Publications. CAS Number 9009-86-3. Lookchem Website. Digital Object Identifier 10.1038/jhh.2017.8

Inhibitors of Nitric Oxide Synthase include natural factors also, such as Isothiocyanates, Proanthocyanidins, Terpenoids/Isoprenoids, Carotenoids, Omega-3 Fatty acids, Polyunsaturated Fatty Acids, Circumin, and Flavonoids. Flavonoids are diverse plant factors derived from Benzo-gamma-pyrone rings that include Phenolic compounds, Pyran groups, linkages between A and B rings, such that their Hydroxyl, Methoxy and Glycosidic ancillary structures distinguish them from one another while 3-O-Glycosides, Anthocyanins and Polymers are the most prevalently exhibited versions. Natural food sourced inhibitors of Inducible Nitric Oxide Synthase (iNOS) include Cyanidin-3rutinoside from Raspberries and cherries, Silibinin from Milk thistle, Cyanidin-3-sambubioside from Peanut, Malvidin3-arabinoside from Blueberries, Malvidin-3-galactoside from Berries, Petunidin-3-arabinoside from Bilberry, Resveratrol from Grape skins, Cyanidin from Strawberries, Delphinidin-3-arabinoside from Blueberries, Petunidin-3glucoside from Blueberries from Peonidin-3-glucoside from Black rice, Malvidin-3-glucoside from Berries, Apigenin from Celery, Carnosol from Rosemary, Delphinidin, Dark berries, Proanthocyanidins from Berries, Epigallocatechin-3gallate, Cyanidin-3-galactoside from Lingonberry, Delphinidin-3-glucoside from Berries, Quercetin from Broccoli, Cyanidin-3-glucoside from Black rice, Pelargonidin-3-glucoside from Strawberries, Curcumin from Curcuma, Kaempferol from Broccoli, S-alkyl-L-isothiocitrulline-exhibiting dipeptides.341 The referenced Article here provides precise information regarding the preferred interactive loci between natural inhibitors of Inducible Nitric Oxide Synthase and Inducible Nitric Oxide Synthase Itself. Allosteric integration loci were found to be less prominent than substrate/inhibition Loci, such that there were diverse spatial Poses by natural compounds that fit into the inhibitory/substrate groove, explaining why many natural compounds with inhibitory affected to iNOS may inhibit inflammation widely. The literature suggests that Glucoronidation or the addition of Glucoronic Acid to a substrate can change the Pharmacokinetics of a supplemental or therapeutic capability. Glucoronidation occurs as an aspect of the Xenobiotic response.342 This seems to be expected since Glucoronic Acid participates in pathways associated with Hyaluronic Acid and Hyaluronic Acid inhibits the Cytotoxic Response stimulate by Immunological Cellular entities. Amazingly, iNOS is known to change the shape of cellular entities to that resembling Ameboid structure, clearly presenting an understanding of how tissue, organs, and Haemopoieticfactors move from optimal function to what must be confounded interactions between molecular pathways and molecular signal transduction. How iNOS has not been presented as primary factor in Human health is not able to discussed here adequately. The best way to describe iNOS and the other factors presented here is an integration into systems of civilization a presumption of Human Demise. This presumption may have become utilized when it was incipiently certainly only an outcome of the interactions among systems of nature. Civilization seems to have been principally produced to alleviate many such inadequately managed outcomes instead of integrating these detrimental factors as presumptions within civilization. These analyses concluded that systems are doing what they were designed to do, which is provide essential and precise information about Human outcomes such that program management and leadership make empirical, durable, and lasting progression toward improvement of the Social, Human, Physiological and Behavioral Condition. This in no way implies that the use of Demise as a Sanction and the integration of presumptive exhibition of demise were intended to be included in systems or should be included in systems.

341 342

Digital Object Identifier 10.1038/sj.bjp.0704023. Digital Object Identifier 10.1021/acs.jafc.5b05456

More people have incurred demise in the United States from withholding of an Antibiotic than may have perished from Persecution with regard to their Philosophical Persuasion in WWII, than those whom may have perished from the 1918 Influenza, as well as more than all of the Geopolitical Conflict conducted by the United States, and more than almost all of these combined. Invariably, every person in the United States whom has known or known of someone that has incurred demise will have been affected by this Human rights Atrocity. Simultaneously, Nations on the opposite side of the Earth obtain more revenue, attention, and priority than 2 Million or more instance of demise each year in the United States. The issues and instability potentiated in civilization, and outside of civilization, perhaps, emerge precisely and incipiently from this circumstance. It costs more money to stage a Television broadcast about what a leader of another Nation, which is an ally or not an ally, has done, than it would cost to prevent almost every instance of Human demise that occurred that very same day. These are completely inconsistent with Liberty if not Anathema to Liberty. Artificial or contrived barriers for any individual to obtain remuneration for work activity may be among the most substantial complexities in Western Civilization which confounds the essential nature of providing the means to the Social and Human condition without a requirement for activity to be conducted in exchange for such means. Currency of many nations are Fiat Currencies, and are not managed by the availability of any particular factors such as Gold or Silver, as well as may not even be correlated to the availability of Natural Resources in any Geographic area. International business typically includes priority for Hegemony among International Systems than the provision of those factors which are essential to the Human and Social Condition, although there is a substantial are of civilization in which those factors which are not essential may be more than essential in assuring quality of Vital Being. A foundational fallibility of closed information and learning within a clinical practice is that each health consumer, diagnostic, assessment, intervention, therapeutic instrumentation and outcome generates improved knowledge that transcends the level of Clinical Guidelines, although this also results in closed loop assumptions and processing in which many of the presumptions about Physiology are inaccurate, imprecise or incomplete. Similarly, from program management perspective, closed loop processing is iterative, introspective, and foundationally limited by the information already produced in the closed loop. Objectives can be developed from other Objectives, while the Industry, Organization and Health Services Ideals are increasingly made distant from objectives. How might a health services organization or any industry component have objectives that are not consistently prioritizing curing Human disease, impairment and detrimental outcomes? The potato chip factory or cookie factory illustrates this most adequately. The number of people whom interact with a cookie package or potato chip package increases the potential that any shared priority is achieved, such as assuring that there is only 25 chips or cookies in each package. However, as presented, tracked and measured metrics become integrated into performance assessment, all other objectives become deprioritized, including the size, quality, taste and freshness of the products. Similarly, the number of individuals interacting with the health services consumer can be numerous and often curative outcomes are not included as objectives although quality metrics are included as obscure codesets that determine what services are provided, level of impairment or other measures which may not specifically suggest curative, regenerative or correlative outcomes. Similarly, since financial codes or billing codes are associated with each such individual and their activity, revenue obtainment becomes a persistent principal influence. Resultantly, as conditions which supply patients change, organizations learn to exhibit practices that maximize priority objective obtainment, sometimes less than consciously.

The number of less than optimal chips or cookies, for instance, may increase as the 25 Chip objective or 25 cookie objective becomes achieved, particularly because of seasonal changes in the source, quality and type of potatoes changes. Similarly, seasonal, cultural, social and other change can modulate health services utilization levels. Thus, the health conditions, behavioral outcomes and emergent statuses that emerge from the Super Indicators of the Amehsi Specification as well as from Homocysteine in ranges considered to be Idiopathic, can be treated as Bona Fide health conditions with precise causality, particularly when more utilization is required while this might also be disregarded when health services inpatient and outpatient resources are already saturated. Health services organizations learn these ways of managing revenue and utilization using ancillary influences such as advertising, management of electromagnetic power intensity or use of electronic devices in the organizations, as well as through utilization of revenue obtainment objectives that are not partitioned from patient information or not partitioned from the precise codes and conditions utilized in clinical/billing systems. Health facilities are also known to change hiring, training and development to maximize revenue obtainment. Obscure correlations can also emerge in analytics in which an obscure factor such as chargemaster cost apportionment, the purchase of foods with Methylation factors, interaction with particular vendors, or partnerships can change or enhance utilization, costs and revenue. Here, such factors can produce an unproductive outcome because these correlations are not required to include patient outcomes performance and even the performance at clinical levels are determined by statistical outcomes such that an improvement in one service category can be offset by continued exhibition of levels which are statistically typical in another category, the use categorization management to distribute outcomes among many different principle diagnoses or diagnostic groups, as well as relinquishing achievement in a particular category to arrive at statistically acceptable levels. The best way to perceive these nuances are to consider the many knobs and indicators on a complex machine which no one Human typically completely understands and interactions among these which move progressively to esoteric interactions which can be similar to the obscure language which emerged in Artificial Intelligence Systems which none of the programmers understood. Health organizations and entities might observe such correlations while not understanding these or even being aware enough of such nuances to understand the correlation. These suggest information systems, within the Status Quo, require being beguiled into presuming that levels of demise continuously are according correlative to Plan or Correlative to Statistic Projections, preventing the movement of detrimental outcomes into other categories of detriment including other health conditions as well as behavior and accidents. Similar, facilities or entities which rely upon occupancy or inpatient, as well as outpatient or care which is not preventative or proactive, may require synthesis of information to make it seem as though calendars are full, facilities are full, and available resources for care are consumed. These can help alleviate the systemic demand for detrimental outcome while more precise ways of improving the influence of information and information systems upon Humanity are managed in a way that allows Bona Fide improvements in care to be exhibited. However, imperatively, an overabundance of capable resources for any eventuality that assures health, welfare, security and safety, well as Social, Human, Behavioral and Biological Condition, should not be detrimental, particularly when these supply resources required to assure these same factors among population providing such services. Although, it is clear that a systemic demand for detrimental outcomes is very unproductive and an esoteric language of interactivity among systems in which the Self-Prioritization of Systems along with the Profit Priority of Private Enterprise interact using detrimental outcomes among Humanity as a disposable communications protocol, may be Anathema to Humanity.

Quercetin and Kaempferol inhibit Inducible Nitric Oxide Synthase, Cyclooxygenase-2 (COX-2), C-Reactive Protein (CRP), NF kB Pathway factors in models of Change Hepatocyte Lineages.343 Flavonoids, Kaempferol, Genistein, Quercetin and Diadzein Inhibit STAT-1 and NF kB while Flavone, Isorhamnetin, Naringenin and Pelargonidin Inhibit only NF kB, although each inhibit iNOS.344 A study exhibits that Kaempferol inhibits inducible Nitric Oxide Synthase while not impairing exhibition of extracellular circulatory Nitric Oxide during Lipopolysaccharide stimulation which suggests that it is a selective inhibitor of Inducible Nitric Oxide Synthase.345 Other inhibitors of iNOS include Pimagedine, AMT, N(G)-iminoethylornithine, L-NIL, Targinine, Nitroarginine, ARC95791, CID10398018, Etiron and numerous other CID factors. Included also are Flavones Apigenin, Tangeretin, 5Hydroxy-3,6,7,8,3,4-Hexamethoxyflavone, Flavonol Quercetin, Flavanols Epicatechin, Epigallocatechin-3-Gallate, Flavanone Naringenin, Isoflavone Genistein, Terpenoids All-Trans Retinoic Acid, Methone, Omega-3 PUFAs DHA/EPA, Isothiocyanates Phenethylisothiocyanate, Sulforaphane, Benzyl Isothiocyanate, 13 Anthocyanins of diverse nature, Proanthocyanidin (B2), Flavonolignan Silibinin, Carotenoids Lutein, Lycopene, Beta-Carotene, as well as Polyphenolic Factors Curcumin, Resveratrol, Pterostilbene, [6]-Shogaol, [6]-Gingerol, and Carnosol. DHA and EPA inhibit Angiotensin II enabled inhibition of RECK and miR-21 induced Metalloendopeptidase MMP2, resulting in resumption of adequate PTEN expression which protects P53 from MDM2 mediated proteolysis, resumption of ERK-Negative Sprouty (SPRY1) expression, and produced decreases in Cardiac Fibrosis. Expression of PTEN, caused to be expressed even amid its own suppression, resulted in inhibition of Atk Phosphorylation, resulted in SP1 activation, and resulted in MMP2 stimulation.346 The choline Kinase inhibitor ICL-CCIC-0019 is widely potently inhibitory of oncology. Hemicholinium 3 is also inhibitor, although it may inhibit endocytosis of Choline through membrane transporters along with the inhibition of Choline Kinase. Choline Kinase Inhibitors produce a “Wobble” or oscillating imbalance in Phosphatidylcholine/Sphingomyelin balance that results in increased levels of Ceramide, resulting management of impaired, oncological, Leukemia Exhibiting, or Lymphoma Exhibiting cellular entities toward Apoptosis. CHOP is known to participate in this Apoptosis, the Unfolded Protein Response is known to participate in this Apoptosis and inability to Dephosphorylate pRb Retinoblastoma Protein such that G0/G1 phase cellular cycle pause is impaired is also known to participate in Apoptotic outcomes in this regard.347 It is not difficult present a Homologue in the exhibition of a wild and uninhibited party or get together in which all manner of refreshments are available, much of which enhance uninhibitedness, resulting in many activities and outcomes which would not ordinarily occur. The inability to dephosphorylate pRb is one of the many things occurring at such an event which would not otherwise occur, and Phosphorylcholine seems to be a molecule that changes priorities, perceptions, manageability and patterns of activity exhibited by molecules. Oncology seems to be homologous to the groups or individuals whom stay after the party is offer and continue their own party. Phosphocholine, when inadequate, results in people becoming sleepy, listening to others, adhering to the next morning’s schedule, and listen to the neighbors when they request that the sounds be decreased. The more refreshments, the bigger the party may be and the lower the possibility that anyone will listen to the neighbors or pay attention when anything else goes awry. Otherwise, without Phosphocholine and depletion of ATP and decrease in Organic Phosphate, Apoptosis pathways are adhered, cyclin activities are coherent, and the party is but a mere ephemeral inflammatory cathartic anomaly. 343 344 345 346 347

Digital Object Identifier 10.1016/j.ejphar.2006.11.014 Digital Object Identifier 10.1155/2007/45673 Digital Object Identifier 10.1155/2007/45673 Digital Object Identifier 10.1016/j.cellsig.2014.01.005 Digital Object Identifier 10.1038/sj.onc.1208045

The Molecule TCD-717 is in development as potent inhibitor of Choline Kinase alpha.348 MN58B is also another Choline Kinase Inhibitor.349 New amazingly potent inhibitors of Choline Kinase are emerging.350 Triterpene Quinone Methides or TPQ, from Celastraceae Plant are among such potent Inhibitors of Choline Kinase. These analyses have recently found in the early 2000â&#x20AC;&#x2122;s that CA2+ was found to be able to inhibit Choline Kinase Alpha, clearly showing that iNOS expressionâ&#x20AC;&#x2122;s depletion of CA2+ resultant of Choline deficiency, Viral Pathology, Energy, Communications, Magnetic, Microwave and other fields of energy, including some naturally exhibited fields, cause increased exhibition of Choline Kinase Alpha such these participate in the principle pathway of human detrimental pathophysiological and pathopsychological outcomes.351 Increasing numbers of Choline Kinase inhibiting Compounds are emerging.352 Fluorine is considered to be an Isostere for Hydrogen. Isosteres are molecules which exhibit similar structure and molecular characteristics. Similarly, Fluoride in the Hydrogen Diatom exhibits two Non-Adhesion orbitals along with the Adhesion Orbitals shared between Hydrogen and Fluorine. Fluorine exhibits Px and Py as non-adhesion Orbitals, resultant of there not being adequate material within the Hydrogen Atom to produce an Adhesion or Shared Space, while also not having Fluorine in an adequate position to share its outermost electron material. Integration, Adhesion or sharing of Space by Atoms, results in the synthesis of two new share valance Orbitals to replace the individual Valence Orbitals of the Original Atoms in unshared space. A non-adhesion or unshared Orbital is exclusive of these and does not change the shared material or newly produced Valence Orbitals even when the Non-Adhesion nor unshared orbital is occupied potentiating that Non-shared orbitals often become the Highest Occupied Molecular Orbital. Two atoms become closer together, material compresses, Antibonding Orbital emerges in which occupation by Electrons influences the Atoms away from one another and jeopardizes the Shared relationship, whereas Adhesion Orbitals produced in such manner exhibit Sharing of Electrons that promote the Shared or Adhered relationship. The type of adhesion of Sharing relationship described here is different from others which can be planar with Sharing of Material, as well as exhibit other characteristics. Thus, these atoms exhibit Adhering and Non-Adhering Orbitals that emerge as polarized regions in the share spaced between the Atoms. Anti-Adhesion subregions exhibit greater amounts of energy when occupied, thereby causing Atoms to be repelled. Anti-adhesion influences emerge as a function of relational density, particularly when the Nuclei exhibit decreased density of material between them in the shared region when they are in an adhesion status than the density of material exhibited before the adhesion relationship emerged. The relationship, then seems to be one that requires material to have been displace for it to occur, thereby repelling the atoms when electrons occupy anti-adhesion Orbital. This seems to suggest that a close enough relationship between Atoms to cause displacement of material from between the two regions without changing density may cause adhesion forces, suggesting that relationship between the atoms is produced by unoccupied space or unrealized density potential, resulting in Adhesion relationship without requirement to displace material between the Atoms. The occupation of the Anti-adhesion orbital repels the Atoms similarly to a balloon being filled between to movable objects although it might also be concluded that ancillary influences may be participating in producing the Adhesion-relationship. Spatial influences and systems of influence at smaller or more expanse levels can often influence such relationships. Hydrogen is readily conjugated to Fluorine and Nitrogen, while also potentiating that Fluorine and Nitrogen be integrated through Hydrogen into the Same Molecule.353 Ricinoleic Acid Head Groups may be able to integrate Nitrogen and Fluorine as a result of this capability exhibited by Hydrogen.

348 349 350 351 352 353

MedKoo Biosciences. RSM-932A. MedKoo CAT# 206474. CAS# 850807-63-5 Digital Object Identifier 10.1158/0008-5472.CAN-05-1338 Digital Object Identifier 10.1021/acs.jmedchem.5b01552 Digital Object Identifier 10.1002/cmdc.200600158 Compounds Useful as Inhibitors of Choline Kinase. Application PCT/US2012/056476. United States Patent and Trademark OfficeUSPTO. Hydrogen-Adhesion. Intermolecular Forces. Chemistry Information Only. Elmhurst College.

Pyridine is Cyclic Hydrocarbon including the list of Aromatic Hydrocarbons which must be Cyclic, must be Phenyl or homologous to Benzene in the number of Carbons and Double-Adhesion Hydrogen conjugations. Pyridine is a Cyclic Aromatic Hydrocarbon and although the literature sometimes suggests it is the detrimental molecule exhibited in Castor Beans and Cotton Seed, Pyridine is constitutive factor in a detrimental molecular factor. Amines, however, generally are represented by an Ammonia, NH3, which has one of the Hydrogens replaced with and Alkyl Group as a Primary Amine, two of the Hydrogens replaced to exhibit a Secondary Amine and three Hydrogens replaced with and Alkyl Group to exhibit a Tertiary Amine.354 There are quite a few Aromatic Compounds. There are also toxic Aromatic Compounds. 355 Alkylation is suggested to be exhibited through transformation of Ammonia into Amines. Industrially, these are suggested to occur by introducing Alcohols but also can occur by introducing Haloalkanes into Ammonia or into Amine solutions. Industrial Amine synthesis through Alkylation can occur through introduction of (any molecule with Carbon or Hydrogen) OH + NH3 becomes (Any molecule with Carbon or Hydrogen) NH2 + H2O. Haloalkane introduction into Ammonia or Amines exhibits (Any molecule with Carbon or Hydrogen) (Any Halogen) + 2 ((Any molecule with Carbon or Hydrogen)’NH2) becomes (Any molecule with Carbon or Hydrogen) (Any molecule with Carbon or Hydrogen)’NH + [(Any molecule with Carbon or Hydrogen) (Any molecule with Carbon or Hydrogen)’(NH2)](Halogen). Alkyl Halides are produced from Halogen exhibiting Alkanes and are utilized in diverse industrial applications, including those which can be toxic as well as be detrimental to the Ozone Layer in the Earth’s Atmosphere. The biochemical notation for an Alkyl Halide is, interestingly, the same as the utilized as an acronym for Prescription Pharmaceutical factors. (Any molecule with Carbon or Hydrogen) (Any Halogen such as Fluorine, Chlorine, Bromine or Iodine) typically constitutes Alkyl Halides of which more than 1600 organic versions have been determined. Haloalkanes exhibiting Carbon adhesion to Bromine, Chlorine and Fluorine as well as Iodine exhibit familiar molecules. These include Chlorofluorocarbons or CFCs, Hydrochlorofluorocarbons HCFCs, and Hydrofluorocarbons HFCs. Large numbers of Pharmaceutical products exhibit Halogens, of which Fluorine may be most prominent because it readily can be integrated into unreactive conjugated circumstance. Polyvinyl Chloride, which is associated with Aflatoxin B-1, the most Carcinogenic factor known to be widely exhibited products produced in civilization. Carbonylation occurs during Oxidative Distress in the intracellular environment, resulting in the introduction of Carbonyl Groups, as Carbon Double-Adhesion to Oxygen, into Proteins through Oxidation or Amin Acids or through Lipid Oxidation associated Reactive Carbonyl Molecular Species such as Acrolein, 4-Hydroxynonenal, Malondialdehyde, or as sugars such as Glyoxal or Methylglyoxal. Carbonylation is known to participate in Demyelination and Neurodegenerative Pathology associated with Alzheimer’s, Parkinson’s, Amyotrophic Lateral Sclerosis, and Multiple Sclerosis. Carbonylation by reactive molecular species produces Cross Links between different aspects of Protein structure in their folded positions preventing changes to Shape, Twist and Writhe required for posttranslational modifications during metabolisms or catalytic activity.356 Methylglyoxal activates MAPK and Cyclically potentiates Choline Kinase by potentiating iNOS which upregulates Choline Kinase.357 Methylglyoxal is emerging as an influence within numerous Pathways including 354 355 356 357

Amines. Information Online. Rutgers University. Introducing Amines. The Chemguide, Helping You Understand Chemistry. ISBN 9780303437 387 Digital Object Identifier Org/10.1093/ndt/gfh271

Oxidation, Glycation, contribution to D - Lactate, activation of iNOS, as well as enhancement of Choline Kinase Activity. Some research suggests that Methylglyoxal inadequacy may contributed to oncology and that enabling increases in its availability can be oncological therapy, although there is much information about Pathogenic aspects of Methylglyoxal availability. Thioesters are intermediates in the pathway in which Alkyl Halides are transformed into Alkyl Thiols, such that Thioesters and amines integrate to produce Amides. Amides Exhibit Carboxylic Acids, and Carbonylation exhibits the introduction of Carbon and the introduction of an Oxygen double-adhesion between Carbon and Oxygen, such that the integrated molecule Carbon Monoxide can be additionally integrated into Organic molecules as well as integrated into Inorganic Molecules. Thioesters can be utilized in the metabolism of Fatty Acids, Metabolism of Mevalonate, as well as molecular interactions. Carbonylation is exhibited in several useful molecular pathways, although it also occurs in association with Oxidative Distress. Malonyl-CoA or MCAT is produced in this synthesis and metabolism of Thioesters. MCAT catalyzes the transfer of Malonate from Malonyl-CoA to the concluding Moiety of Holo-Acyl Carrier Protein (ACP) where a Thiol receives the transferred Malonate. Thiols are Organosulfur Compounds which exhibit Carbon that is integrated with a Sulfhydryl moiety. The literature presents that Thiols and Mercaptans refer to the same molecules. Both such molecules are structural analogs of Alchols. Thiol substitues for ol in Alcohol. Propanethiol, O Mercaptobenzoic Acid, Cyclopentanethiol, each exhibit -SH in extreme, less integrate location, such that the Mercaptan Moities seem to be leading the molecule toward particular outcomes. -SH exhibited without other Atoms can referred to as a Mercaptan Group. Hydrosulfide Ion performs as a Nucleophile, providing a convenient ability to conduct Sn2 Reaction which produces Thiols from Alkyl Halids. The Sulfur of Sn2 performs a Nucleophilic interaction with the Carbon in the Alkyl Halide Structure RH2C-Br, causing Br to become displaced to become Bromine Anion while Sulfur replaces Bromine without abdicating the Hydrogen which was already attached in the -SH molecule. The resulting molecule disrupts the structure to produce RH2C-SH, displaces Bromine, and displaces what could presumably also be other Halides. The potential for an Ancillary Sulfide Product to emerge in second reaction following this Sn2 reaction can be prevented through the use of Thiourea to perform the Nucleophilic Interaction upon the Alkyl Halide Substrate. Disulfide Bridges seem to be essential to present here because these used substantially in biology and result in the Linkage of Proteins together using the Sulfurs of each molecule, particularly the Sulfur exhibited by Cysteine. Particular articles present that Peptides and Proteins which participate in or exhibit Disulfide Adhesions or Disulfide integration with other Disfulfides exhibit increased levels of Rigidity. Disulfide Adhesions, according to the literature, are produced during Oxidative Folding. Oxidative Folding occurs in the Endoplasmic Reticulumâ&#x20AC;&#x2122; Lumen, a feature of Eukaryotic Cellular Physiology compared to Prokaryotic Perpiplasmic exhibition of Oxidative Folding. Disulfide linkages then, seem to be Subcellular Compartment Specific in their production. Ribosomal Protein Synthesis can result in folded or unfolded Proteins, requiring, according to the literature, assistance of Endoplasmic Reticulum features for refolding such as the Protein Disulfide Isomerase PD1, Protein Disulfide Isomerase Erv2, and the Endoplasmic Oxidoreductin Ero1. C, X, X, C and C, X, C sequences seem to bestow Thiol Disufide Redox Exchange Reactivity to Enzymes such as to PDI and ERV2, respectively. Thiol Redox Enzymes can partner to enable Redox Cycling, ERO1, illustratively, is considered to be associated with the innter Endoplasmic Reticulum Membrane where

it Oxidizes PDI to produce a ERO1 PDI Conjugate. PDI is able to release inaccurately or misformed disulfide Adhesions followed by production of an adhesion which prefers the Disulfide to Disulfide adhesions considered to be Native. Thus, interestingly, Free Thiols are considered by the literature to typify cytoplasmic difulfide exhibiting Protiens or Enzymes while subscellular compartments such as the Edoplasmic Reticulum exhibit Difsulfide to Disulfide Adhesions preferentially. Thermophillic Organisms, contrastingly, exhibit Protein Disulfide Oxidoreductase in the Cytoplasm with Cysteine Oxidation Potential and Protein Oxidation Potential, particularly affecting Disulfides within the these Cytoplasmic factors. Clearly, these present that Sulfur Metabolism has Gradients which substantially augment, define or are defined by cellular structure and cellular infrastructure, while also exhibit clear differences in Metabolic dispersal of Disulfide Enzymes according to Sulfur Potential in the Environment. Sulfur seems to be a feature of Environments which Thermophillic Organisms Habitat. Thermophiles are presented in the literature as preferring Environments between 41 Degrees Celsius and 122 degress Celsius which is between 106 Degress Faranheit and 252 degres Faranheit. Other literature presents preferred Thermophillic ranges beteen 60 Degrees Celsius and 108 degrees Celsius. Generalities of Human Disulfide Redox Oxidation/Reduction Cycles suggest, according to the Literature, that Disulfide to Disulfide adhesions are preferentially exhibited when Basic pH is exhibited, such that exhibition of Oxidizing Agent such as Oxidized Glutathione increases the rate at which Oxidative Folding Occurs. This seems to be reasonable, because at Basic pH less H+ would be available, introducing a Gradient which favors abdication of H+ such the Difulfides might have better opportunity to associate. The Basic Science Literature observes that Acid Environment increases available reactive H+ while Basic Influences reduces available H+. These also suggest what effect Choline and its ability to introduce the influence of Hydride without exhibiting free Hydride might have to the Catalytic Microenvironment. It seems obvious that exhibition of Hydride might reduce the Spontaneous Gradient associated reassociation of H+ into molecules, potentially preventing free H+ from integrating with H20 to produce Hydronium, thereby providing an environment in which Catalytic Activity has less competition in obtainment of and management of H+. Illustratively, if gradients in weather determine the propensity of Consumers to be indoors or outdoors, the production of synthetic managed weather environment would enable a steady and persistent availability of Consumers whom would be more amenable to price, taste, advertising and quality of factors for obtainment or consumption. Products might have better ability to produce an effect, become analyzed, and improved, while financial and other forcasting would also be more persistent, able to be analyzed and improved. Clearly, Genetic, Enzymatic, Molecular, Protein and Metabolic systems can also produce cause, effect, and other feedback mechanisms which can be utilize to produce outcomes which are intended as well as allow the emergence of reasonable intent at Metabolic levels. The interactivity of all the sytems of the Universe upon a particular observable set of variables and outcomes pervasively produce inaccurate conclusions about causality. Choline and the exhibition of Hydride influence seems to reduce the way in which numerous systems of the Universe affect Biological, Physiological and potentially Behaviorally deteriment processes. Human Macrophage Colony Stimulating Factor Beta, rhm-CSFbeta, provides a useful instance to explore, integratively illustrating Oxidation and Reduction in Protein Folding Processes. Presented in the Literature, rhmCSFbeta becomes produced as a Dimer, or compound molecule, with two Monomers, or individual Protein Domains, such that thre intermolecular Disulfide to Disulfide Linkages occur between the individual Molecular Domains. Three

Disulfide to Disulfide linkages also occur within the molecular itself. Oxidative Folding produces Isomers of rhmCSFbeta which have Native and nonnative intramolecular Disulfide integrations. Nonnative intramolecular Disulfide linkages seems, according to the literature, to represent Disulfide linkages to any other moieties, molecules or Loci which are not also Disulfides. The monomer Isomerization Phase determines the rate at which Oxidative Folding processes occur to completion. Shuffling of Disulfides in this manner results an an intermediate in which all of the Disulfides are engaged in molecular integrations, including at least one nonnative molecular integration. The culminating resolution of the nonnative Difulfide Adhesion completes the Oxidative Folding Process to produce a Native Oxidized rhm-CSFbeta. There are some obvious correlations to Disulfide to Disulfide Linkages, propensity for Native linkages, and potential for Nonnative linkages with changes to the Shape, Twist and Writhe of molecules which effect those sequences which are obscured, hidden in the core, exhibited in peripherial locations, and thereby reactive potential of Enzymes, Proteins and Molecules. Indeed, the particular article which is refrenced in the preceding few paragraphs clearly presents protein stability as an important feature of a molecule and its environment, both which are characeterized as intrinsic factors such as Primary, Secondary, Tertiary, and Quaternary structural bestowing of Physicochemical Properties of the molecule, as well as extrinsic factors such as pH, Ionic characteristics, Buffer, Excepients, Thermodynamics and Acetylation. 358 Ordinarily, the Sulfur molecules, when reduced, such as when Protonating H+ is attached to such Sulfur Molecules, result in exhibition of Free Thiols. Free thiols are constituted of Proteins which exhibit Sulfurs which have H+ attached. Oxidation of the Sulfur, such as the removal of the H+ resultant of catalytic activity, pH changes in the microenvironment, or attachment of another Sulfur Atom to produce a Disulfide Bridge, as well as pH changes systemically, results in bridging of the molecules at the Sulfides. Disulfides then are exhibited at integration Loci between Proteins. Thus, as presented, there seems to have been included in physiology metabolic pathways in which sulfur was more prominently utilized or are now utilized to bridge some inherent complexities in Oxygen Metabolisms, as well as Metabolism using other factors. Compellingly there are Oxygen and Sulphur Analogues which are essential in Biochemistry. R-O-R’ is analogues to R-S-R’. R-O-, Alkoxy Group is analogous to R-S-, Alkylthio Group. R-O-, Alkoxy Anion and to R-S-, Thiolate Anion are analogues. Alcohol, R-OH and Thiol,R-SH are analogues. Analogues also include -OH, Hydroxy Group compared to -SH, Mercapto Group. R-O-O-R’, Peroxide is analogous to R-S-S-R’ Disulphide. These are presented in the literature, The differences which Sulfides bestow upon physiology include the ability to be Oxidized or Reduced in different systems and gradients from Carbon. Mild Oxidation which enables Thiols to become disulfides, is considered to be distinctive from Oxidation of Alcohols particularly because mild Oxidation of Alcohols to become Peroxides is not considered to be typical. Disulfide to Disulfide linkages are stronger than Oxygen to Oxygen linkages, while the Oxygen to Hydrogen Linkages are presented in the literature as being Strong than linkages of Sulfur to Hydrogen. These seem pivotal, because the literature, again, suggests that Disulfide to Disulfide Linkages are favored over production of Peroxide suggesting that Superoxide may be less favorable in being converted to Hydrogen Peroxide than is favored the exhibition of Disulfide to Disulfide linkages. Thus, intramolecular or constitutive transition from 358

PMCID PMC3319691.

Superoxide to Hydrogen Peroxide goes environmental to cause Disulfide Bridges and Linkages of Thiols with preference compared to H202 exhibition. The management of pH and Reactive Oxygen species, thus, seems invariably incomplete without considered Thiols as well as influence of Thiol dynamics including Hydrophobic, Hydrophilic, Electroconductivity, Thermodynamic and other affects to environment.

Summarizing analysis, Part 2 of 4, A Manageable Efficient Health Service Instrumentation  

Summarizing Analysis of the Specification Utilized to Produce Specification Artifacts, Part 2 of 4.

Summarizing analysis, Part 2 of 4, A Manageable Efficient Health Service Instrumentation  

Summarizing Analysis of the Specification Utilized to Produce Specification Artifacts, Part 2 of 4.