Quantum Ultimatum Science Magazine by Caterham School

2022 - 23 ISSUE

THE ANNUAL MAGAZINE OF THE MONCRIEFF-JONES SOCIETY

Endorser: Nicholas Hart during the most challenging time in NHS history. The engagement from a packed Humphrey’s Lecture Theatre was only matched by the depth of thought that the pupils in the audience applied to their probing questions. It was wonderful to witness a group of young people demonstrating a huge passion for science, underpinned by the nurturing environment of the Moncrieff-Jones Society which fosters a profound interest and knowledge whilst promoting confidence in public speaking. Truly inspiring!

t was an honour and a privilege to be invited back to school, as a guest speaker, for the Moncrieff-Jones Society Annual Christmas Lecture. Although an old Caterhamian, it was uplifting and wonderful to experience the change over 35 years, which was not only in terms of the educational estate, but also the teaching culture. However, this was overshadowed by the level of engagement, enthusiasm and understanding of the diverse group of pupils that I met. With my friend and Guy’s & St Thomas’ Hospital colleague, Suneil Ramessur, we spoke about ‘COVID-19: After the Clapping Stopped’. We reported on our lives, and that of the critical care and anaesthesia teams, during the Covid-19 pandemic and described the central role that our hospital played 2

This edition of Quantum Ultimatum is a collection of articles that has been distilled from the arduous work that pupils have undertaken throughout a demanding year. It is a product of endless reading, learning and writing. I am delighted to provide the strongest level of endorsement for this magazine and proud to support the Moncrieff-Jones Society. It comes with relief that, with the issues we have faced in recent years, our next generation of scientists are so well equipped to flourish and face up to new challenges. Finally, I would like to show my appreciation and gratitude to Mr Quinton for his constant commitment and relentless motivation, which has driven the Moncrieff-Jones Society to be the jewel in the crown of Caterham School. The scientific restlessness and infectious enthusiasm of the science teachers at Caterham School is exemplary. I hope you enjoy reading this next edition of this impressive publication. Nicholas Hart MB BS BSc MRCP PhD FFICM FERS Deputy Medical Director Heart Lung Critical Care Group Guy’s & St Thomas’ NHS Foundation Trust

President’s Introduction at Caterham, simply because we love it. As always, the autumn term saw five brave Upper 6th formers present their research on a whole host of topics ranging from superconductivity to ADHD. The term ended with a fantastic Christmas lecture on what really happened during the pandemic, for which I cannot thank Professor Hart and Dr Ramessur enough. The new year brought 6 Lower 6th talks. Giving a presentation at the Moncrieff-Jones Society is most certainly daunting, and to volunteer to do this to an audience of members in the year above is incredibly impressive, and every speaker has my full respect.

Dear Reader, It is my pleasure to welcome you to the 16th edition of Quantum Ultimatum. It has been another amazing year for the Moncrieff-Jones Society, which continues to provide an environment for students to present on their passion and inspire an audience to delve further into the very mechanisms of life.

To run a society as successful as Moncrieff-Jones is definitely not a job for one person, and I could never have done it without the immense efforts of those around me. Of course, I must thank our speakers and the audience, but there are also so many figures coordinating things behind the scenes. I would like to thank O-Teen for his support as vice-president and Mr Evans for helping run meetings. Lastly, I must thank Mr Quinton, for your faith in me as a president, especially since it will be your last year here- it has been an absolute joy to work alongside you this past year. I am so grateful for the person you have helped me become. I will carry your passion with me through everything that I do. Yours, Isabel Singleton

Anyone who has ever attended or given a talk knows it is no easy task to research a topic, present on it, and then be questioned by students and teachers alike, and yet talks are always over-subscribed, and the room always overfull. This is testimony to the culture of scientific excellence we have created here 3

Contents Annual Christmas Lecture. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5 Upper Sixth Talks. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 6 Junk DNA Sophia Liu . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 8 Room Temperature Superconductivity Paramita Shen . . . . . . . . . . . . . . . . . . . . . . . . 12 How an Enzyme’s Active Site Functions Elliot Major . . . . . . . . . . . . . . . . . . . . . . . . . .16 Organo-metallic Chemistry Avery Chen . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 20 The Functioning of Neurotransmitters and ADHD Natasha Smith . . . . . . . . . . 24 Lower Sixth Talks. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 30 Membrane Technology Lisa Hu . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 32 Dynamic Phototherapy Marcus Kwok . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 36 AI Image Generators Xavier Parker. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 40 Ageing Jack Butler. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 44 Optogenetics Vladimir Fediunin . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 48 The Harmonic Series Phillip Morgan. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 52 The Darwin Society . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 56 Physics Extension O-Teen Kwok . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 57 Chemistry Race Alex Mylet . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 58 The Wright Society . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 59 Prep School Science Short Competition . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 59 Society Review Mr Dan Quinton . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 60 Past MJS Presidents, Vice Presidents & Endorsers . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 61 References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 62

Annual Christmas Lecture

We had the honour of hosting Prof. Nick Hart and Dr. Suneil Ramessur for this year’s Christmas lecture, both of whom were very involved with the COVID-19 response at Guy’s and St Thomas’ hospitals. The talk was entitled “When the Clapping Stops” and discussed what really happened during the pandemic and the ramifications it has had on healthcare now. Too often healthcare news and information about the NHS is masked by what the media wants us to see, so it was truly eye-opening to hear from doctors who witnessed the pandemic first hand. As medical director of the heart, lung and critical care group, Prof. Hart directed the critical care response for 1300 patients. In the lecture he talked about how he used data science to facilitate this, and to predict the course of the pandemic. As the deputy clinical lead to theatres, anaesthetics and perioperative medicine, Dr. Ramessur was on the COVID-19 tactical team, where he helped to design the anaesthetics response to the pandemic, as well as being directly involved in frontline clinical

care. He talked of the additional precautions the anaesthetists had to take in terms of PPE to ensure staff safety. With an increase in need for patients to be put on ventilators, a huge burden of the pandemic fell onto the anaesthetics team. The team took 5 main interventions to ensure the best chances of recovery for COVID-19 patients. They made sure patients had a regulated fluid balance and a safe oxygen saturation. Treatments included antiviral medication, anti-inflammatory medication, and anticoagulants. Although it now seems we have come out the other side of the pandemic as a society, this isn’t necessarily the case for healthcare professionals. Other health needs were neglected in the summit of it all, and now the NHS is faced with a huge backlog, forced into taking extreme measures like the HIT approach in the anaesthetic’s department. Moreover, this is all being carried out by an already exhausted workforce. All in all, the talk was truly inspiring as we listened to two incredibly selfless and dedicated individuals reflect on their own experiences during the pandemic, and how much they sacrificed to provide outstanding care for those who needed it most in the nation’s hour of need. 5

Upper Sixth Talks Junk DNA Sophia Liu The genetic code is the blueprint for all the coding blocks that makes up of what we have known as the human body. Although it only has four different bases, but its complexity has always been a subject to undergo scientific investigation. Especially on epigenetics and junk DNA, this lets us discover a vast number of vital roles for gene regulation that could eventually be the key to unlock the mysteries for unsolved genetic diseases which I’m excited to find out about.

Room Temperature Superconductivity Paramita Shen I chose room temperature superconductivity as my Moncrieff Jones topic because it is one of the most cutting-edge physics research. With no resistance and diamagnetism, superconductors’ magical properties have enormous potential to change people’s lives. After exploring it in depth, I found that the stories and theories behind it are far more complicated and exciting than I thought. From the first superconductor that Onnes discovered to the highly anticipated high-temperature superconductor yttrium-barium-copper-oxygen, from the BCS theory to the unfinished superexchange theory, room temperature superconductivity is still an ever-changing subject, waiting for new breakthroughs.

How an Enzyme’s Active Site Functions Elliot Major The active site is discussed at both GCSE and A-level however it is not discussed in much detail. This is the region of the enzyme which carries out catalysis on the substrate. The mechanisms by which bond formation and breaking could be carried out on the substrates while still at temperatures low enough and pH’s mild enough to support human life intrigued me. I wanted to know more about these remarkable molecules and gain a better understanding of what occurs at their active sites to enable these reactions to take place. This is why I chose to talk about this area of biology.

Organometallic Chemistry Avery Chen My first-ever encounter with organometallic chemistry is the involvement of Grignard reagents in the formation of C-C bonds where a nucleophilic attack is performed through C, which is the opposite of what C usually does i.e. being the electrophilic centre. I wondered how other organometallic compounds would react. Another thing that was rather mysterious to me was the metal-carbon bond that all organometallic compounds contain and hence the name – sometimes they are said to be covalent but other times ionic, both looked counter-intuitive to me back in the time. My curiosity drove me to explore more on this topic which, as I later realised, was an area of chemistry more fascinating than I had thought. Therefore, I wanted to share what I had learnt about it via a Moncrieff-Jones talk.

The Functioning of Neurotransmitters & ADHD Natasha Smith I chose neurotransmitters and ADHD as they are two rich areas of study that intertwine beautifully to begin to show the fantastical interactions in our brains, and how slight changes can drastically affect our behaviour when interacting with the right environment. Neurotransmitters, in my opinion, have the potential to lead to breakthroughs in the neuroscience field. Such as theoretically being used to reverse engineer drugs, or help understand the chemical nature of disorders, which might lead to the ability to detect and consistently identify disorders and initiate the beginnings of personalised medicine, as people can be proscribed the medication which is most effective for their neurology and neurochemistry.

Junk DNA Sophia Liu

The term ‘Junk DNA’ was first used by geneticist Susumu Ohno back in 1972 when it describes all noncoding sections of a genome. When the Human Genome Project (HGP) was completed two decades ago in 2003, DNA was put into numbers. The big discovery was that over 98% of DNA in a human cell is junk but 2% in the entire genome which codes for protein. Shortly after the HGP, the Encyclopaedia of DNA Elements (ENCODE) project was launched to find out all the functional regions of the human genome. It revealed that millions of these noncoding letter sequences do serve a functional role, with some being even more crucial than DNA’s main role of producing proteins.

X-inactivation One example of an RNA molecule that does not serve as carrier of a protein is Xist. It is responsible for switching off one of the X chromosomes in females so that both genders have the same amount of X chromosome-encoded protein expression in their cells. This process is known as the X-inactivation. Although Xist RNA is very long with 17000 bases, the longest run of amino acid made was under 300 as its sequences also act as stop signals when protein chains build up. As the RNA never leaves the nucleus, this concludes why no proteins will ever be formed from Xist. The Xist RNA will just stay intact towards the inactive X chromosome. As more Xist RNA are produced, they coat the whole chromosome and silence any gene expression. Another junk DNA involved in the X inactivation process is the antisense RNA of Xist named Tsix.It regulates on one X chromosome to be active whilst the other to be inactive by ensuring that Xist will not be expressed on the same chromosome. This process requires a quick and intense physical relationship

between the two X chromosomes where they roughly touch each other to choose which X chromosome to stay active. This is a very crucial decision to make before rounds of cell division in the embryo for further development so that there will not be extra proteins produced. X-inactivation is solely dependent on junk DNA thus revealing the importance of nonprotein-coding DNA.

Genomic Imprinting Imprinting is the process that differentiates between certain genes on the maternal and paternal chromosomes resulting in the expression of only the copy of those genes in the offspring . This demonstrates a parent-of-origin effect where certain regions of DNA carry epigenetic modification that indicates where it is from the maternal or paternal parent during the formation of egg and sperm cells. This is dependent on a region of junk DNA called ICE (imprinting control element) as it drives the expression of long non-coding RNA to switch off gene expression. This system has evolved to balance out the competing demands of the male and female contributions to the genome. A lot of crosstalk exists with the epigenetic system and the junk DNA as methylating the junk DNA that forms ICE is the main pathway of switching a gene off. The importance of imprinting is shown through two similar, yet different diseases called the Angelman

disease and the Prayer-Willi disease. Both diseases are caused by a deletion in chromosome 15 but the difference between the two depends on whether the deletion is contributed by the paternal or maternal chromosome. With the gene is not inherited from the “right” parent; establishment, and maintenance of the imprint in early development can easily go wrong. Hence resulting in an ICE region being inappropriately methylated or non-methylated or even switched on and off when it should not be. This showcases the importance of these so-called ‘junk’ DNA in regulating development pathways.

Untranslated regions Located at the start and the end of an mRNA are untranslated regions (UTRs). Although they do not contribute to the amino acid sequence, they have a role in protein expression. An example shown is a DNA sequence change in UTR where ACG become ATG, this may cause a new start codon to appear when the ribosome starts the protein chain too early. The junk RNA eventually becomes protein-coding RNA and adds extra amino acids causing the protein to become faulty.

A point mutation in junk DNA and protein-coding gene expression Morphogens are proteins that govern patterns of tissue development. For example, it controls the number of fingers we have. Some people have extra fingers which makes researchers suspect it must be a genetic change caused in the SHH gene, which regulates embryonic morphogenesis. However, research has found that the extra finger was caused by a single base change from C to G in a junk DNA region that is located thousand bases away. That region serves the role of being the enhancer (ZRS) where the mutation causes the enhancer to lose its function, causing morphogen levels to not be able to reach critical levels in the brain. Transcription factors are also unable to bind to the promoter on the gene. This chain effect causes the gene to never be switched on. One interesting fact is that there is a strong correlation between the base pair variant and the expression level of a second gene, but not the original gene. This is due to the fact that the enhancer of the original gene is constantly interacting with the promoter of the second gene. Any changes in the enhancer will be able to alter the expression level of the target gene despite being half a million base pairs away.

Another interesting mutation occurring at the UTR that can also be fatal is a single base change at the end of the mRNA. At the UTR, there is a six-base motif AAUAAA that acts as a polyadenylation (PolyA) signal for the mRNA processing enzyme to recognise and cut the mRNA which adds multiple adenine bases to the end of the mRNA chain for stability. Although the poly A signal is not translated, a point mutation from AAUAAA to AAUGAA can cause an autoimmune disease called IPEX syndrome. The polyA signal no longer targets for cutting gene enzyme but instead switches on the FOXP3 gene which loses control of the regulatory T-cells and the body starts attacking its immune system. After the ENCODE project, it has been more well known to scientists and the public about the dark genome that also serves a function that it is not ‘junk’ as described decades ago. Could there be new approaches to drugs that use these ‘junk’ DNA to target pathways that regular drugs can’t reach? After all, one person’s trash can be another person’s treasure.

Room Temperature Superconductivity Paramita Shen

Lossless energy transfer, controllable nuclear fusion, can be popularised once successful. Room temperature superconductivity must be one of the technologies closest to changing the destiny of mankind among all the unsolved mysteries in the scientific community. If the ultimate goal of high energy physics is a grand unified theory, then it is the holy grail of condensed matter physics. What’s fascinating about it is that today’s physics is inconclusive about its nature, and our search for it is still a reckless trial and error. If low temperature superconductivity is from 0 to 1, then room temperature superconductivity is from 1 to infinity. It is a monument that no matter how many people fail.

Room temperature superconductivity Superconductivity, the first macroscopic quantum phenomenon observed by man, has always been one of the major focuses in physics. The exciting characteristics of 0 resistance and complete diamagnetism gave superconductors a huge potential in application, and they indeed changed our life. MRI, quantum computer and magnetically levitated train could have never existed without them. However, the strict condition of low temperature still severely restrained their use. Therefore, room temperature superconductors have now become a tempting but untouched trophy standing in front of condensed matter physicists. With all supports form various areas and decades of research, this technology still appears to be out of reach. How can it be?

Regular superconductivity: the beginning Let’s start with regular superconductivity that’s currently been used. The widely accepted explanation for this counterintuitive phenomenon is the BCS theory, which revolves around the concept of Cooper pairs. At extremely low temperatures, thermal disturbances become weak enough, so the originally mutually repelling electrons can be combined in pairs due to the exchange of phonons. In other words, an electron pulls the surrounding atomic nucleus towards itself due to the attraction of opposites charges, and then leaves at a high speed. This causes the latter electron to attract the more condensed nucleus left behind by the previous electron, thus forming a weak bond which makes them a cooper pair. This causes electrons to change from fermions 13

with semi-odd spins to composite bosons with integer spins, making them Bose-Einstein condensate. Since bosons do not obey the Pauli exclusion principle, so all Cooper pairs are at the quantum state with the lowest energy level, avoiding the scattering of energy caused by lattice defects. The macroscopic performance, therefore, is 0 resistance.

High temperatures superconductivity: crisis and hope Since the liquid helium used for cooling is too expensive and difficult to maintain, scientists immediately turned their attention to high-temperature superconductivity. Although the BCS theory perfectly explains the formation of low-temperature superconductivity, it sets an impenetrable ceiling for further research. After calculation, the model predicts that in order to provide a valid environment for superconducting, the critical temperature of any 14

superconductor must be lower than 40K, which is called the McMillan limit. Experimental physicists have questioned the calculations and tried to get past this hurdle. They decided to test out the entire periodic table, including both conductors and insulators, as well as compounds, and found about ten thousand different superconductors, with most of them having a critical temperature lower than 20K. The turning point occurred in 1986, 21 years after the McMillan limit was proposed, Ba-La-Cu-O high-

temperature superconductivity was discovered, and its critical temperature was 35k. In the second year, by changing only one element, Y-Ba-Cu-O superconductivity raised this value to 93k, smashing the ceiling, and even entering the liquid nitrogen temperature zone. This greatly reduced the cost of superconductivity, and became the first material discovered by humans worthy to be called hightemperature superconductor. The second was the iron-based superconductor ReFeAsO1-xFx found in 2008, which obtained a critical temperature of 4055K. Unlike the fragile copper based superconductor, this one is a malleable metal, suitable for construction. These two are the only normal-pressure hightemperature superconductors discovered so far.

Room temperature superconductor: the mystery Although the 100-meter long iron-based superconducting wire for scientific research was completed at the Chinese Academy of Sciences in 2016, 50K is still too far from the target room temperature of 300 k, even farther from being able to be put into civilian use. In addition to continuing research under normal pressure, many physicists choose to create ideal room-temperature superconductors by pressurising materials, and metallic hydrogen is one of the highly anticipated ones. Yet natural metallic hydrogen can even be found in Jupiter’s core,

and the pressures needed to make it are so high that it’s very unstable. But compounds of hydrogen can be quite feasible. In 2015, German scientists Drozdov and Eremet discovered H3S superconductivity, using diamond anvils. It was found to have superconducting transition temperature of 202k at 2.2 million atmospheres. The highest temperature obtained so far is the C-H-S superconductivity discovered by Dias and others in the United States in 2020. The critical temperature of 288k, i.e. 15 degrees Celsius was obtained at 2.67 million atmospheres, almost reaching room temperature superconductivity. But keeping the pressure this high becomes

a dilemma on another level. Just last year, it was claimed that demonstrating the successful retention of pressure-enhanced and induced superconducting phases or semiconducting phases without pressure in single crystals of superconducting FeSe and nonsuperconducting Cu-doped FeSe was found possible.

The Future Unlike the blooming of experimental physics, theoretical physics has hit a wall in hightemperature superconductivity. After P.W. Anderson was awarded the Nobel Prize in 1977 for bringing magnetism, not just electricity, into the consideration of high-temperature superconductivity, the principle of this weirder-than-weird phenomenon no longer had a widely held consensus. How superconductivity eliminates so much interference between electricity and magnetism is still a mystery without a conclusion. But there is still good news for experimental physicists who are still keen for trial and error. For example, using deep learning and artificial intelligence, to calculate feasible potential superconducting materials faster, greatly improving the efficiency of screening. Perhaps when room temperature superconductivity is truly realised, fully superconducting tokamak can be widely used to completely solve the energy crisis of mankind, and even future interstellar travel. 15

How an Enzyme’s Active Site Functions Elliot Major

Enzymes utilise regions known as active sites in order to catalyse reactions within and outside of cell in order to produce molecules of use to the cell. Two example of these enzymes are urease and lanthanide dependent-methanol dehydrogenase and in this article I will discuss one of the proposed reaction pathways for each of active sites of these enzymes.

Urease Urease is a nickel metalloenzyme which catalyses the hydrolysis of urea into ammonia and carbamic acid. It is not found in animals however it is found in bacteria such as Heliobacter pylori, it can have negative effects both on the soil and on people. In the soil its presence can lead to an increase in soil pH affecting agriculture as it releases ammonia into the soil which is toxic to plants. In people ureases are used pathogenic bacteria such as Heliobacter pylori to survive and the enzymes presence breaks down urea inside the body affecting homeostasis and leading to disease. It can break down urea at a rate 1014 times faster than the rate of spontaneous breakdown of urea.

The intermediate at the active site then breaks down producing an ammonia molecule and deprotonating a histidine residue[3]. The carbamate dissociates from the active site breaks down into an ammonia molecule and carbon dioxide molecule.

Overall Mechanism of Urease

The enzymes active site contains two Ni2+ cations. Each ion is bound to a water molecule and two histidine residues, a hydroxide and a carbamylated lysine residue (a lysine residue where the amine end has reacted so that it is CONH2 rather than NH2) bridge the two ions together. One ion is also bound to an Aspartic acid residue. The nickel ion that is not bound to an aspartic acid residue is referred to as Ni1 while the nickel which is bound to the aspartic acid residue is referred to as Ni2. One suggested mechanism is the hydrolysis mechanism where the carbonyl oxygen of urea displaces the water molecule bound to Ni1. Upon binding to Ni1 an aspartic acid residue deprotonates a histidine residue, this histidine residue then deprotonates the urea[1]. Another unbound histidine residue then deprotonates the water bound to Ni2 producing a bound hydroxide which then attacks the urea. This results in the substrate then deprotonating the first histidine residue, this causes other amino acid residues to be deprotonated[2]. 18

Lanthanide-dependent methanol dehydrogenase: Recent investigations have revealed the presence of lanthanide containing proteins responsible for the oxidation of methanol in some bacteria the enzyme has a cofactor, pyrroloquinoline quinone. The role of a cofactor is to be the chemical group which carries out the reaction with the substrate. The cofactor is turned into its active form by the actions of the active site. This type of methanol dehydrogenase which requires lanthanide elements to function is called XoxF-MDH. Compared to MxaF-MDH which has calcium as its metal ion in its active site; XoxFMDH differs by having an aspartic acid residue at its active site replacing an alanine residue found at the active site of MxaF-MDH. This change in amino acid residues at the active site is important in allowing the lanthanide ions to coordinate to the active site. A key difference between calcium and the lanthanides is that lanthanides are stronger Lewis acids meaning they accept an electron pair more readily than calcium, speeding up the reaction. In addition the lanthanide form of the dehydrogenase had a higher affinity for methanol, further improving the reaction rate.

while another hydrogen is taken by an aspartic acid residue from the hydroxyl group. This generates the methanal[1]. The methanal is then released from the active site and protonated aspartic acid residue is deprotonated by the cofactor[2], a ketoenol tautomerisation then forms pyrroloquinoline quinol[3].

2 Overall Mechanism of XoxF-MDH

The active site structure of XoxF-MDH consists of a lanthanide ion coordinating with a glutamic acid residue, an asparagine residue and two aspartic acid residues as well as pyrroloquinoline quinone. The oxidation state of the lanthanide ion at the active site is the 3+ state. The enzyme works well with the light rare earth lanthanides (Lanthanum to Europium) these being the more abundant lanthanides in nature. One proposed mechanism is the hydride transfer mechanism, a hydrogen is taken from the carbon of methanol by the PQQ

3 19

Organometallic Chemistry Avery Chen

Organometallic chemistry is the chemistry of compounds that contain metal-carbon bonds. The metal-carbon bond can be ionic or covalent, mainly depending on the difference between the electronegativities of the metal and carbon. Such compounds can have simple structures such as the ones of organolithiums and Grignard reagents and can be as complex as ferrocene, an example of sandwich compounds, the name due to their shapes. Transition metal organometallic compounds undergo a wide range of reactions, which enables them to be used as catalysts in synthetic processes. For example, in the Boots-Hoechst-Celanese synthesis of Ibuprofen, the oxidative addition, reductive elimination and migratory insertion of organometallic compounds allows a 100% atom economy. Hence, organometallic chemistry is not only an interesting area but is also of great industrial interest. My article introduces you to Grignard reagents and organometallic catalysts in Ibuprofen synthesis.

Grignard reagents During the past 100 years the Grignard reagents probably have been the most widely used organometallic reagents. They are organomagnesium halides and are often written as RMgX, where R is the organic part and X is a halide. It is named after Victor Grignard who discovered it at the University of Lyon in France in 1990 and was awarded a Nobel Prize in chemistry in 1912 for this discovery, as Grignard reagents are easy to prepare and have broad applications in organic and organometallic synthesis. Grignard reagents are used to catalyse reactions such as the formation of alcohols, ethers, and epoxides. A common way to make Grignard reagents is by reacting magnesium with alkyl halides in ether solvents to form solutions of alkylmagnesium halide. This reaction is an example of oxidative insertion, where magnesium is inserted into the new carbon-halogen bond. There is a change in the oxidation state of the magnesium, from Mg(0) to Mg(II).

Grignard reagents act as nucleophiles at the carbon of the metal-carbon covalent bond. As we can see in Pauling electronegativities [Figure 1], carbon is more electronegative than Mg as it is compared with all metals. This means that carbon attracts electrons towards itself along the covalent bond and has a partial negative charge. This contrasts with the case in other carbon-heteroatom bonds like C-F, C-O, C-N, where the carbon acts as an electrophile as these heteroatoms are more electronegative than carbon. The nature of the metal-carbon bond makes Grignard reagents highly reactive and useful for various chemical synthesis, e.g. the synthesis of carboxylic acids and alcohols. When Grignard reagents react with carbon dioxide, the electrophile in this reaction, carboxylate salts are produced. After the acidic work-up or quench, carboxylic acids are obtained. The mechanism is shown in Scheme 1. In similar manners, the additions of Grignard reagents to methanal give primary alcohols, the additions to other aldehydes give secondary alcohols, and the additions to ketones give tertiary alcohols. These reactions are all examples of nucleophilic addition to ligands (molecules, ions, or molecular fragment bonded to a central metal atom).

Equation 1: Formation of Grignard reagents

Figure 1: Pauling electronegativities

Scheme 1: Grignard reagent reacts with carbon dioxide to form carboxylic acid

Organometallic compounds as catalysts Organometallic compounds are long known to be highly efficient catalysts. The fact that they can be homogeneous or heterogeneous makes them suitable catalysts in a wide range of reactions. As such, organometallic reagents have played the key role of promoting key steps in the total synthesis of numerous molecules, many of which are biologically active, including Ibuprofen synthesis.

reductive elimination (step c), which regenerates the catalyst and produces acid chloride 82. Hydrolysis of 82 (step d) yields Ibuprofen and HCl, which then reacts with alcohol 80 to produce 81.

The use of organometallic catalysts in the BootsHoechst-Celanese process for Ibuprofen synthesis [Scheme 2] increases the atom economy from only 40% in the Boots synthesis to close to 100%, assuming the ethanoic acid by product in the step a is recycled.

Scheme 2: The Boots-Hoechst-Celanese process for Ibuprofen synthesis

As shown in the synthetic scheme, step b and c both involve organometallic compounds. In step b, a heterogeneously-catalysed hydrogenation of a carbonyl group to give the corresponding alcohol. Either palladium on charcoal or Raney-nickel can be used as a catalyst. Step c is an example of an alcohol carbonylation, the catalytic cycle of which is shown in Scheme 3. In this step, the precatalyst PdCl2(PPh3)2 is converted to Pd(CO)(PPh3)2 under the reducing conditions of the reaction. Once the catalyst is generated, benzyl chloride 81, generated from a secondary cycle involving steps d and e, enters the cycle and undergoes oxidation addition (step a). Migratory CO insertion (step b) precedes

Scheme 3: Catalytic cycle for the carbonylation step of the Boots-Hoechst-Celanese Synthesis of Ibuprofen

Outlook Organometallic chemistry is a very broad and interesting subject due to the versatile nature of organometallic compounds. Research has been done on exploring the catalytic use of these compounds and the synthesis of metal organic frameworks, which are porous compounds that have potential in the storage of gases such as hydrogen and carbon dioxide, and as heterogeneous catalysts. Overall, because organometallic compounds are such useful catalysts, they have been and will continue to be important for meeting the green chemistry standards. 23

The Functioning of Neurotransmitters & ADHD Natasha Smith

ADHD is a fascinating condition that has often been miss represented and sometimes overlooked for the complex and very real struggle that it can be for people. The diagnosis has been growing in recognition in recent years but many of its portrayals in media do not encompass the disorder and instead push the stereotype of ADHD which is the more commonly know hyperactive form. With its growing awareness there has also been surges in research to understand the causes behind the diagnostic symptoms. Most frequently seen such as problems with time comprehension, maintaining focus and mental effect, and working memory deficits. One such theory is the dopamine theory and follows on from research in neuroscience about the functioning of neurotransmitters and their importance and impact on the brain. From serotonin to glycine to TCH, neurotransmitters are incredible, also being complex in their synthesis, releasing and neuronal effects. 24

Neurotransmitters are incredibly important and underrated molecules that are responsible for transmitting chemical messages in the brain and influencing the nervous systems reaction to stimuli. The discussion surrounding neurotransmitters in media is often highly simplistic and misinformed, causing misconceptions to be more commonly known than the truth. One of the major misconceptions around neurotransmitters is their relationship with medicinal drugs and psychiatric problems. Such as the usage of SSRIs, selective serotonin reuptake inhibitors, as a pharmaceutical treatment for depression has lead to the idea that increasing serotonin levels or having high serotonin levels in the brain helps people be happy or similarly the idea that ADHD is caused by the improper releasable of dopamine because a treatment is stimulant medication. This is far from the truth, for example, higher natural levels of serotonin can be a risk factor for depression when expressed in particular environments, this is known as the serotonin paradox. Furthermore, it is widely known that pharmaceutical treatments that interact with neurotransmitters have many side effects, but the

reason for the side effects is not discussed enough. The reason is that a single neurotransmitter has multiple functions it is responsible for and drugs currently cannot target that specific areas where the treatment is needed and instead the drug affects the entire brain. This leads to side effects as the other functions the neurotransmitter controls, that were not intended to be altered by the pharmaceutical treatment, is manipulated as the neurotransmitters levels in the whole nervous system is changed. This sentiment is encompassed by the statement “Our brain is not a bag of chemical soup” made famous by a TED talk by David Anderson. To dismantle the misconstrued ideas surrounding neurotransmitters there must be more information distributed about the types, synthesis, synaptic transmission, pathways and defining which neurotransmitters control what processes and what is the true effect when the levels and balance in the brain is altered, purposefully or otherwise.

Fundamentals of neurotransmitters There are classes of neurotransmitters and then subclasses within that specific the composition and functioning of the neurotransmitters. The classes are unconventional class which includes nitric oxide and carbon monoxide, endocannibinoids such as THC, neuropeptides like pituitary peptides and brain gut peptides and the largest class is called the small molecules. The most well known neurotransmitters are part of the small molecule class, including dopamine, serotonin and epinephrine (Adrenaline). There are three subclasses in the small molecule class: amino acids,

monoamines (biogenic amines) and acetylcholine. The further sub-class known as the catecholamines are grouped due to their synthesis all deriving form L-tyrosine. Glutamate and GABA are known as the workhorse neurotransmitters or the universal neurotransmitters. This is because GABA is the universal inhibitor and Glutamate is the universal excitatory neurotransmitter. Inhibitory neurotransmitters, hyperpolarise the next neurone, reducing the likelihood of an action potential being continued. Conversely, excitatory neurotransmitters depolarise the next neurone, increasing the chance that the neurone will continue the action potential transmitted. Also, our of 100 billion neurones in the brain there are 8 billion GABA specific neurones and 20 billion Glutamate specific neurones. While dopamine and serotonin only have 250,000 specific neurotransmitters each. Every neurotransmitter has a primary function that is is associated with it, for example dopamine. Dopamine is found in four central pathways in the brain, the mesolimbic, the mesocortical, the nigrostriatal and the tuberoinfundibular. Through out these four pathways the key function of dopamine is to create conditions for plasticity and for the person to experience pleasurable feelings that encourage

the action to be repeated. In simplistic terms it is the key neurotransmitter in learning and motivation. To understand how this works and then to be able to link it to disorders such as ADHD, we require an understanding of synaptic transmission.

Synaptic transmission For synaptic transmission to occur an action potential must reach the axon terminal for a neurone, this causes a change in membrane potential as the membrane is depolarised. At the axon terminal there are voltage gated calcium ion channels that are opened due to the depolarisation. This leads to calcium ions influxing into the axon terminal. The calcium further depolarises the neurone and stimulates the release of calcium dependant fast exocytosis vesicles that are stored in vesicle pools by the synaptic membrane of the presynaptic neurone. The calcium ions bind the the SNARE complex on the vesicle, which is a combination of multiple proteins that hold the vesicles in place to be exocytated. The SNARE complex is comprised of the SNAP 25 complex, which includes synaptobrevin and syntaxin-1 in a coiled assembly, and various other synaptic proteins such as synaptotagmin. At the post synaptic neurone there are specie complimentary receptors for the neurotransmitter; there are two types of receptors ionotropic and metabotropic. Ionotropic receptors are directly connected to a ion channel which allows an influx of either sodium ions or chloride ions, depending 28

on if the neurotransmitter is acting as an excitatory or as an inhibitory neurotransmitter respectively. Metabotropic receptors are connected to G- proteins which cause a secondary messenger cascade inside the cell which, in the case of dopamine creates the cellular environment for plasticity.

Dopamine theory and ADHD Dopamine has regularly been cited when discussing the potential causes of ‘attention deficit hyperactive disorder’ (ADHD), this is because of the dopamine theory. Dopamine theory is the theory that states that the disregualtion in the levels of dopamine can be the root biological cause behind three disorders, ADHD when dopamine is dysregulated , Parkinson’s when there is a cut in the nigrostarial pathway and schizophrenia when there is too much dopamine in pathways. Majority of supportive evidence for dopamine theory is because the pharmaceutical treatment is stimulant and non stimulant medication which both increase levels of dopamine and norepinephrine in the brain, thus increasing ability to remember and concentrate, which are two key characteristics in ADHD. As discussed before, the medical treatment for a disorder does not indicate the actual cause. There have been

studies conducted that have found that when nonADHD participants took stimulant medication along side ADHD participants, there was a very similar increase in dopamine and norepinephrine levels in the brain, as well as similar increases in ability to concentrate and memory. There was not a statistically significant difference between the two groups to suggest that ADHD participants were effected more by the increase in their dopamine levels and therefore suggest the original levels being the cause of the concentration issue. So, there is an ongoing discussion as well as research to discover the other potential causes for the symptoms expressed and displayed in ADHD. ADHD also has many misconceptions surrounding its symptoms and the personal experience. Worldwide there is an estimated 5% of 4 to 7 year olds diagnosed and currently 2.8% of the adult population diagnosed. ADHD is categorised as a neurodivergency by the DSMv, with there being three types: inattentive, hyperactive and combination. To be diagnosed there must be a major disturbance to functioning in three settings over at least 6 months, with the behaviours stemming from childhood and not being by choice. Some of the diagnostic symptoms include difficulty organising tasks, difficulty sustaining tasks or play activities, often avoids tasks requiring sustained mental effort, easily distracted, feeling restless, like they are driven by a motor. Some of the personal experience but non diagnostic symptoms include time blindness, struggle with emotional control and hyper fixations. Overall, ADHD like many other disorders are widely known but misunderstood and that is similar to neurotransmitters and specifically the neurotransmitter ADHD is linked to, dopamine. But scientific progress is being constantly made and is quickly uncovering information that could help explain the processes behind many neuroscience questions.

Lower Sixth Talks Membrane Technology Lisa Hu After working with a group of specialists in membrane technology last summer, I became deeply interested in this field. Organic compounds are quite abstract — they are different from elements, which are tangible. By synthesising those compounds into a concrete membrane, we can see how the minute change in concentration and the structure of the molecules can affect the final product on a larger scale. To me, membrane technology is like a delicate sonata composed by all the aspects in science. And I, as the conductor, want to introduce this piece to you.

Dynamic Phototherapy Marcus Kwok I was introduced to photodynamic therapy by coming across it online, in which the treatment was introduced as a “cancer treatment that has the side effect of giving humans a slight level of night vision”. Interested by it, I dug deeper to find out how it does that. I therefore chose to do my Moncrieff-Jones talk to share this type of treatment which is not as well-known as other leading ones like chemotherapy. With its high effectiveness and limited side effects, photodynamic therapy will surely continue to rise in use to become a major type of cancer therapy.

AI Image Generators Xavier Parker After working with a group of specialists in membrane technology last summer, I became deeply interested in this field. Organic compounds are quite abstract — they are different from elements, which are tangible. By synthesising those compounds into a concrete membrane, we can see how the minute change in concentration and the structure of the molecules can affect the final product on a larger scale. To me, membrane technology is like a delicate sonata composed by all the aspects in science. And I, as the conductor, want to introduce this piece to you.

Ageing Jack Butler I decided to do my Moncrieff-Jones talk on the science of ageing because it is something every human experiences, but despite this there is no agreed upon theory on why we age. After doing some research I was impressed with the sheer number of theories, so I decided to determine for myself what the main one was. I was also fascinated with the idea of life extension technology and if it would be possible to drastically extend lifespans, and the societal and moral impacts of ageing significantly past our current lifespans.

Optogenetics Vladimir Fediunin I was introduced to photodynamic therapy by coming across it online, in which the treatment was introduced as a “cancer treatment that has the side effect of giving humans a slight level of night vision”. Interested by it, I dug deeper to find out how it does that. I therefore chose to do my Moncrieff-Jones talk to share this type of treatment which is not as well-known as other leading ones like chemotherapy. With its high effectiveness and limited side effects, photodynamic therapy will surely continue to rise in use to become a major type of cancer therapy.

The Harmonic Series Philip Morgan I chose the topic of The Harmonic Series because I have a passion for music and science. When previously I thought of them as almost opposites, as a creative and study, art and fact. Upon exploring them further, they blend. There is reasoning and logic behind the art, and creativity behind the patterns. There is so much to explore, from Pythagoras to Fourier Transformations. The Harmonic Series appears everywhere and can be explored through almost any perspective, mathematical or artistic. Personally, I am an aspiring musician and scientist, and I make it my goal to understand everything I can from as many perspectives as I can, so of course the blend which previously was unforeseen by me, has risen through this topic. 31

Membrane Technology Lisa Hu

Less than fifty years ago, a simple cellulose acetate (CA) membrane which can filter out contaminants in water became one of the most popular methods used in water treatment. Because of its multidisciplinary nature, it is used in a plethora of industries, including domestic and industrial water treatment, pharmacology, medicine, energetics etc. Among all types of membranes, Thin-film composite (TFC), composed by active layers and a supportive layer, due to its outstanding ability in rejecting unwanted substances and high durability, became the focus point of most of the membrane scientists. Inspired by the bilayer phospholipid and other biotic characteristics, they decided make improvements such as adding surfactants to the active layer.

What is a piece of membrane We first encountered the idea of a “membrane” in Biology, the cell membrane. We were told that it selectively allows substances to pass through. Membrane technology, on the other hand, developed this idea to a further extent. First applied in industry around in 1960s, within nearly 50 years of rapid development, we humans have been enjoying the benefits brought by this technology in a plethora of aspects. In general, membranes are classified based on their average pore size, morphology, and the amount of pressure applied. The smaller the pore size, the less permeable it is, the more substances it can reject. Therefore, to let the water molecules to travel against the concentration gradient, higher pressure needed to be applied. For example, the membrane used for dialysis which has a mean pore size of 0.005-0.01 micrometre lies under the ultrafiltration criteria, while the membrane used for water treatment with a mean pore size less than 0.001 micrometre lies under the reverse osmosis category.

Another way of classifying membranes is using their morphology. Membranes are either solid or liquid, and further divided on whether they are symmetric and porous or not.

Exposition: Thin Film Composite Thin film composite, in short TFC, lies under the anisotropic composite membrane category in the membrane classification based on their morphology. It can be considered as a molecular sieve constructed in the form of a film from two 34

or more layered materials. Due to its excellent salt rejecting ability, widely in water treatment and dialysis, we investigate the structure of a TFC membrane. The active layer, which in most cases are the thin polyamide (PA) film, is responsible for the intrinsic water permeability and salt rejection. By synthesising diacid chloride and diamine monomers through interfacial polymerisation, an asymmetric porous membrane is formed. The supportive layers, which is responsible for providing the mechanical integrity of the membrane, are usually macroporous polymers including polyacrylonitrile (PAN), polysulfone (PSF), polyethersulfone (PES). Way more than only supporting the active layers, the supportive layer can largely influence the water flux by changing its physiochemical properties.

Recapitulation: The active layers The active layer is responsible for rejecting salt and other unwanted contaminants when filtering a solution. This is done due to the small but dense pores in the cross-linked polyamide polymers through liquid-liquid phase interfacial polymerisation (IP). IP takes place where two immiscible phase interfaces. The most widely used industrial PA membrane is synthesised through interfacial polymerisation of m-phenylene diamine (MPD) in aqueous solution and trimesoyl chloride (TMC) in organic solution. When filtering out

solutions, since passing through the PA membrane is the rate determining step, by changing the density, the size of the pores and the thickness of the film, the permeability, antifouling performance, and selectivity can be influenced significantly. It is agreed that by increasing the hydrophilicity of the membrane, the water flux will increase. However, there is a trade-off effect, meaning that by increasing the water flux, the permeability is weakened. For instance, by introducing surfactants, such as the anionic sodium dodecyl sulfate (SDS) through the IP of TMC and piperazine (PIP), a self-assembled network of amphiphiles at the water/hexane interface is established, forming a PA film with uniform pore size distribution through the IP, and consequently the amount of cross-linking in between the polymers is increased significantly, which increased reasonably the salt rejection percentage. However, only those anionic surfactants can improve the contaminants rejection performance; cationic surfactants such as cetyltrimethylammonium bromide (CATB) is ineffective in helping to form a PA membrane with homogeneous pore sizes.

diffuses slower within the pores toward the interface due to the polar interactions between the fictional groups of the PVP and MPD itself. Therefore, more PA is formed inside the hydrophilic and porous substrate, leading to a thinner and smoother PA overlay. Besides, the pore size of the supportive layers can influence the performance of the PA film. The larger the pore size, the larger amount of MPD existing inside the pores, the more PA layer formed inner pores, the lower degree of cross-linking in PA, leading to worse salt rejection performance. Also, since more MPD is stored inside the pores, large perturbations are promoted by the intense movement of MPD towards the organic phase, advection takes place over convection. The early formed PA is pushed out and bent, forming a rough surface, which affects the morphology of the PA membrane.

Development: The supportive layers The supportive layer is responsible for providing the mechanical integrity of the TFC. Polymers including PES, PAN, PSF have been widely used in TFC. However, more than just providing a stable structure for the active layer, the difference in the chemical structures of the supportive layer can influence the performance of the TFC significantly. It is studied that under similar situation, the water flux of PES-based TFC is higher than PSF-based TFC, since the diffusion of the diamine monomers when interfacial polymerising is the rate-determined step, the hydrophilicity of the supportive layer will affect the diffusion rate of the diamine monomers, influencing the amount of cross-linking in the active layers. Therefore, by adding pore-forming agents, such as PEG or PVP in the dope solution, MPD

Coda: Future developments There are certain problems that have not yet been solved in membrane technology, including the annoying fouling of the membrane and its weak sustainability. As more meticulous tools are invented and the awareness of protecting the environment is growing, we can try fabricating more interesting and unprecedented membranes with the newly synthesised compounds. What about adding nanomaterials to the membranes? What about using those membranes in filtering out desirable ions in brine? In short foreseeable future, we will have the answer to those questions. 35

Dynamic Phototherapy Marcus Kwok

Photodynamic therapy is based on using photosensitizing agents, drugs activated by light to kill cancerous or abnormal cells. With its ability to treat cancers, precancers and other skin diseases such as Actinic Keratosis, as well as its limited side effects in comparison to other leading treatments such as radiotherapy and chemotherapy, it is a much favourable alternative to treat conditions on surfaces of tissues. Patients are either injected with medication containing photosensitizers or it is applied to the area, which is selectively retained by abnormal cells. After an incubation period, which allows oxygen free radicals to form, blue or red light is shone to the area to activate photosensitizer molecules and cause the production of cytotoxic oxygen molecules which destroys tumours from within.

Photodynamic therapy(PDT) is a type of cancer treatment that uses a photosensitizer, a drug activated by light to kill cancer cells. It is used to treat cancers like squamous cell skin cancer and precancers like actinic keratosis, characterized by a rough scaly patch of skin from prolonged sun exposure. Due to its reliance on light reaching the area to be treated, it is limited to treating conditions that are on or just under the skin, like advanced cutaneous T-cell lymphoma, which is marked by itchy, scaly red rashes or lesions, or tumours on the lining of internal organs e.g., the lungs, as the light used cannot pass through more than around 1 cm of tissue.

Procedure To prepare for photodynamic therapy, the area is first washed and dried, and it is advised that patients shave the area 2 days before the procedure as excess hair can limit the effectiveness of the treatment. Then, a curette is used to scrape away tops of precancers or crusty patches (developed from years of sun exposure) on the skin, so medication applied has a thinner layer to penetrate through. After the incubation period, during which the photosensitizer molecules are absorbed by the abnormal cells, blue light (used more in the US) or red light (used more in Europe) is shone onto the area for a bit less than 20 minutes.

How it destroys tumours Photodynamic therapy (PDT) relies on the energy transfer from excited photosensitizer molecules to molecular oxygen during a photooxygenation reaction, which produces highly reactive and cytotoxic singlet oxygen (1O2). Commonly used photosensitizers include photofrin II, a first-generation photosensitizer, and many 2nd generation photosensitizers are being used in clinical trials, like chlorins, which show an increased accumulation in cancer cells and are less phototoxic than 1st generation ones. The singlet oxygen molecules are crucial in causing tumour destruction through inducing apoptosis 38

and dirupting membranes. PDT also causes microvascular damage and the induction of vascular stasis in tumours through altercating and damaging endothelial cells, cells on the inner lining of blood vessels. Endothelial cell damage leads to establishments of thrombogenic sites, where clots of blood form within blood vessels, which initiates a series of responses including rapid production of platelets, release of vasoactive molecules, which normally control blood vessel relaxation or contraction and leukocyte adhesion. These all combine to produce the result of blood flow stasis, causing tissue hypoxia in the tumour and its death due to lack of oxygen.

New advancements in mechanisms of PDT

Photofrin II

Using Protoporphyrin IX loaded polymersomes Despite its promising nature, some skin cancers have shown a level of resistance to PDT. A mechanism shown by resistant melanomas is the low encapsulation of photosensitiser molecules and a low uptake ratio in cells, leading to a reduced accumulation of photosensitiser molecules and PDT’s effect on killing melanoma cells. To improve the ability of PDT to kill melanoma cells, Protoporphyrin (PPIX) loaded polymersomes were used. PPIX is a constituent of haemoglobin and cytochrome C, a heme protein, and absorbs wavelengths of around 400 nm, which photo-excited state triggers the formation of singlet oxygen molecules that lead to cancer cell death. The reason for choosing PPIX in the study was because it degrades slower in cancer cells, lasting up to 1224 hours in cancer cells compared to 2-4 hours in normal cells. This is due to the lack of ferrochelatase in cancer cells, an enzyme that usually converts PPIX into a heme protein in normal cells. However, PPIX is hydrophobic which could lead to a reduced

efficacy. Therefore, polymersome nanoparticles were researched into possibly being a carrier, as they have a low toxicity to healthy fibroblast cells, have an enhanced stability and longer circulation times than other delivery vesicles like liposomes. Positive results from the study in Wenzhou Medical University in China showed that this could be a possible and promising treatment for delivering the photosensitizer molecules efficiently in antitumor applications.

granulocytes to the area, inducing inflammation, recruiting other types leukocytes like monocytes to the area, as well as activating natural killer cells and facilitating an influx of innate immune cells to the tumour. This inlfux of innate immune cells is done by the activation of the complement system—a system of plasma proteins that interacts with pathogens and marks them to be destroyed by phagocytes, as well as a rapid increase of inflammatory cytokines, which are both factors that lead to the influx of innate immune cells.

Loading a polymersome

Using cold atmospheric plasma post-treatment Cold atmospheric plasma (CAP) is an ionized gas which contains electrons, charged particles, radicals, reactive oxygen species (ROS) and UV photons. These components, which are not seen in simple post-treatment light sources like UV light, have all shown the potential to enhance and promote cellular activity or disrupt and destroy cells. Most importantly, the ROS present can create oxidized stress and aid in damaging and destroying cancer cells. Moreover, CAP creates small pores in the membranes of cancer cells, increasing its permeability and therefore leading to a greater uptake of photosensitiser particles.

Activation of the immune system Opposed to other types of cancer treatment, like chemotherapy, which suppresses the immune system, PDT can activate the immune system. It does this through triggering an influx of

A SEM image of a natural killer cell

Enhancing night vision A strange side effect of PDT is that some patients reported being able to see better in the dark after their treatment. This is due to the role of rhodopsin, a light sensitive protein and chlorin e6, a photosensitizer. During PDT, chlorin e6 transforms the oxygen in eye tissue in the highly reactive singlet oxygen, which reacts with the retinal to allow infrared light to trigger a biochemical reaction in rhodopsin. This leads to the release of neurotransmitters for the brain to interpret to form images, although it is usually only triggered by visual light. This triggering by infrared light was seen in a simulation by the University of Lorraine, though the exact mechanism of the reaction between the singlet oxygen and the retinal is still unknown. 39

AI Image Generators Xavier Parker

Optogenetics is a field of research that combines optics and genetics to control the activity of neurons using light. The basic principle of optogenetics is to introduce light-sensitive proteins, called opsins, into neurons using genetic techniques. Opsins are found in various organisms, including bacteria, algae, and animals, and they can respond to different wavelengths of light. By choosing the appropriate opsin and the corresponding light source, scientists can activate or inhibit the neurons expressing the opsin, and observe the resulting changes in behavior or physiology. Optogenetics has several advantages over traditional methods of manipulating neurons, such as electrical stimulation or pharmacological agents. First, it allows for precise spatial and temporal control of neuron activity, which is essential for studying the dynamics of neural circuits. Second, it is reversible, which minimizes the risk of tissue damage and enables longitudinal studies. Third, it can be used to target specific cell types, such as excitatory or inhibitory neurons, or even subtypes of neurons, such as those involved in a particular behavior or disease. Overall, optogenetics is a powerful tool for investigating the brain and developing new therapies for neurological disorder

Neural networks/machine learning AI image generators would not be possible without neural networks. Neural networks can be thought of as a function: they take in an input and give back an output. The only difference to a traditional function is that a neural network will adapt and produce more accurate results. A neural network is made up of neurons, with these neurons connected to other neurons. If I am struggling with my maths homework and I go to two friends, friend A and friend B, to get help. I do not trust that friend A can actually help me with my maths so I put less weight on his advice, but I do believe that friend B is good at maths, so I put a greater weight on his advice. Neurons do the same thing, they put a greater weight on the other neurons which they think are important to them and add up all the different values. Neurons also have one more variable associated with them, a bias. Going back to the maths homework analogy, friend B gets an answer to the question, but I know that he is always 1 off, so I add 1 to my result. Neurons do the same thing: they add their own bias to get a result they are happy with.

Gradient Descent and Backpropagation Gradient descent and backpropagation are the specific algorithms used to change the weights. So, I hand in my maths homework and it turns out that all the questions that friend B helped me with were wrong but some of the questions friend A helped me with were correct. So, I adjust how much I value their help. Neurons do the same with their weights. They take the correct result, y, and the neural network result, ŷ, and calculate the loss by loss = (y - ŷ)2. The neural network can then plot a graph. The aim 42

of gradient descent is to find the minimum point of the cost (average loss across all the biases and weights). The resulting graph will be in more than 2 dimensions and look like a group of mountains. The method the computer uses to find the minimum is comparable to rolling a ball down a hill and then all the weights and biases can be adjusted by seeing how far the ball has rolled.

Normal distribution A Normal distribution is a graph where the highest point will be the mean, it will be symmetrical around this highest point. Additionally, the standard deviation determines how spaced out the values are from each other.

Reverse process To go backwards and go from having a picture with noise to having a picture without noise, you can use a neural network to predict the previous image. What they found worked was getting the image to predict the noise and then using the equation

is a neural network predicting the where the noise that was added at that timestep that has been given the picture and the timestep as inputs. This equation produces the previous image before noise was added for that timestep.

Noise Each pixel in an image can be represented with a set of 3 numbers (each one ranging between 0 and 255). Two images can be put together by a computer easily. They used normally distributed noise, which is where if the frequency of the values of the pixels are plotted, then the result is a normal distribution. If you plot an image with normally distributed noise with a mean 0 and standard deviation 1, you get picture (4). Defining the variables as a straightline graph starting at around 0.001 and by the end of the noising process will be on 0.02, and by defining where t is the current timestep of adding noise. Finally, (the

means that you multiply every

from the first value up to the current value). From these variables the equation can be used to instantly generate any amount of from an original image noised image will look just like picture 4. Because of the variables used, the final amount of noise will always end up looking like picture 4, although to a computer it will be different values, to us it will always look the same.

When the forward noising process is done over enough timesteps, it becomes random noise like picture 4. When there is no original picture, the image generator is used to make original pictures. The reverse process can start with random noise, mean 0 and standard deviation 1, and work backwards to produce a new picture.

Training The neural network predicts the noise that has been added, so using the equation then algorithm is very simple:

. Using this, the training

1. Get a picture from the training data 2. Choose a random timestep 3. Generate some random noise using (picture 4) 4. Perform gradient descent on the neural network using 5. Repeat until happy with model

Ageing Jack Butler

Ageing is the time dependant deterioration of systems in our body eventually resulting in death. Ageing occurs due to cell senescence, degradation of cellular structures and processes that can lead to production of free radicals and in some cases toxins, causing chronic inflammation which damages the body. Biological theories of ageing suggest that cell senescence is caused and regulated by the body for an evolutionary advantage. Chemical theories of ageing suggest that cell senescence is caused by random accumulation of damage to biomolecules through chemical processes.

The Hayflick limit Differentiated cells in animals undergo only a limited number of cell divisions, unless they become transformed to cancer cells by mutation, this is due to telomeres. Telomeres are the specialised repetitive DNA sequences at the ends of linear chromosomes that serve to maintain the integrity of the chromosome. They consist of small sections of DNA that are repeated around 3000 times. In humans the sequence is TTA GGG. Telomeres shorten due to incomplete synthesis of the lagging strand of DNA, when the telomere is ‘used up’ the Hayflick limit is reached. The theory of Replicative Senescence suggests that cell deterioration occurs once the Hayflick limit is reached, causing deterioration of major organ systems as cells can no longer divide. Telomerase, the reverse transcriptase for maintaining the length of telomeres is only present in foetal tissues or cancer cells, all somatic cells lack telomerase activity hence why senescence occurs in our cells but not in cancerous cells. 45

proteins such as Elastin and collagen leads to the loss of elasticity and wrinkling of the skin.

Programmed ageing theories

Chemical ageing theories Chemical theories of ageing suggest that ageing is caused by random, cumulative damage to essential biomolecules such as DNA, RNA, proteins, lipids etc. Through 2 key theories: The Free Radical Theory of Ageing (FRTA) and The Glycation and protein cross linkage theory of ageing. The FRTA: The main free radicals, molecules with unpaired electrons, in the body are reactive oxygen species such as H₂O₂, OH, HO₂, O₃ or HOCl. They are found in the body due to being a by-product in mitochondrial electron transport in the synthesis of ATP. ROS oxidise biomolecules causing cumulative damage that eventually causes cell senescence. This is especially prevalent in mitochondrial DNA which is very susceptible to oxidative damage due to: having a high concentration of reactive oxygen species in the mitochondria, mitochondrial DNA having no protective histones and it’s limited capacity for DNA repair. Damage to mitochondrial DNA , which codes for proton pumps and ATP synthase will decrease a cells capacity for aerobic respiration causing senescence. Damaged mitochondria produce higher concentrations of ROS. Glycation: Glycation is the process in which carbonyl groups in reducing sugars, such as glucose, covalently bond themselves to free amide groups in proteins. This can cause cross linking of proteins, which react more readily with reactive oxygen species to cause damage, and to produce advanced glycation end-products that contribute to protein browning especially in areas such as the lens, which can lead to cataracts. Glycation of skin 46

Programmed ageing theories suggest that there is a genetic reason for ageing. For example: Sirtuins, 7 genes that are nicknamed the ‘longevity genes’ are responsible for regulating cellular health by: triggering apoptosis, regulating autophagy, stimulating mitochondrial biogenesis and repairing damaged DNA. They are only activated during periods of cellular stress, known as hormesis, Sirtuins are regulated by the co-enzyme NAD+ , however NAD+ levels decline over time, due to increased levels of the NADase CD38. CD38 levels increase due to chronic inflammation. This leads to decreased expression of Sirtuins, hence causing cell senescence. Autophagy (recycling of damaged organelles during a period of cellular stress), a process induced by Sirtuins is a key programmed process in regulating age by removing dysfunctional organelles such as mitochondria, and removing aggregated proteins that contribute to age related diseases such as Alzheimers.

Is there an evolutionary reason for ageing? Natural selection designs organisms for optimal survival and reproductive success, so it would seem that ageing is an evolutionary disadvantage. One evolutionary theory of ageing is that environmental factors such as disease, starvation or predation prevent organisms from reaching old age, hence there is little evolutionary pressure to have genetic changes focusing on longevity, and by the time

organisms are affected by ageing, they will have already reproduced, passing on their genes. An alternate theory suggests that cell senescence occurs to prevent the spread of cancer, with telomeres preventing indefinite mitosis, cancerous cells can only spread if the gene coding for telomerase is activated by mutation, hence it is an evolutionary advantage for an organism to age, because cells that become senescent over time have a lower chance of mutation to cancerous cells. And hence organisms that age are more likely to survive and so mutations that cause ageing are passed down.

Anti-ageing techniques Anti-ageing techniques come in 2 strains: lifestyle changes such as exercise and caloric restriction, or pharmaceutical regulation with endogenous substances such as NMN, or drugs such as Acarbose and Resveratrol

Lifestyle changes: Alcohol and cigarettes contain free radicals that oxidise biomolecules causing damage and, hence ageing. Exercise activates the sirtuins by causing hormesis and hence people who exercise regularly have increased vitality. Caloric restriction is a proven age extension techniques

that increased the lifespan of mice by around 18 months, the equivalent of extending human lifespan to 150 years. This is due to reducing metabolism and thus the rate of production of free radicals, limiting oxidative damage. Caloric restriction has had success in increasing the lifespan of Rhesus monkeys however similar studies have not been carried out on humans as it requires complete restriction of calories to an unsustainable level. Caloric restriction induces high levels of autophagy, in order to conserve its resources, which increases maximum lifespan greatly. Similar effects can also be achieved through intermittent fasting. Pharmaceutical regulation: NMN is a NAD+ precursor, that increases levels of NAD+ in the body. It reduces the effects of Sirtuin regression, which is proven to reduce the symptoms of ageing. However, it must be taken regularly in order to have effect due to the increase in NADase levels as we age. High doses decrease the amount of methyl groups available in our body, which decreases methylation of our DNA which increases oxidative damage. Acarbose is an α-glycosidase inhibitor, used to treat type 2 diabetes, that reduces the take up of sugars by the small intestine by inhibiting enzymes that breakdown starch. This mimics the effects of caloric restriction, stimulating autophagy without significant fasting. Resveratrol is an antioxidant found in plants such as grapes that are grown in stressful conditions such as sandy soil. Resveratrol triggers the Sirtuins in a process known as xenohormesis causing increased autophagy and cellular maintenance without fasting, slowing ageing. Overtime there have been very many different theories on why we age, with current theories suggesting that Sirtuin regression via oxidative damage is the main cause of ageing. And hence the best anti-ageing techniques are NMN or caloric restriction mimicked through acarbose or intermittent fasting in order to have high levels of autophagy to slow the ageing process. 47

Optogenetics Vladimir Fediunin

In the 21st century, human science is primarily the science of the brain and its functions. Modern methods of fMRI and microelectrode stimulation have provided us with an opportunity to understand the structure of this, perhaps, most mysterious of organs and to use its own language in our studies. But quite recently the world has been presented with an absolutely different method, offering neurons their own language - light. Let’s talk about optogenetics. Back in 1979, Nobel laureate Francis Crick voiced the main problem in studying brain activity: to influence one type of neurons without affecting others . As the possessor of an incisive mind, he rejected in his lectures the methods of electrical stimulation and pharmacological influence as insufficiently precise, and suggested that light would be perfect for this purpose. But at the time, the technology to make cells respond to light was still unknown. Consciousness, personality, intelligence - all these are created by neurons. So, if we want to study these aspects of humans (or other animals), it is necessary to understand what happens with nerve cells of the object of research. The main problem is that there are too many of these nerve cells, and it’s impossible to keep track of all the neurons at once. In addition, nerve cells tend to form clusters, so it is mostly problematic to separate the action 50

of one neuron from another, and to act on each cell individually. Neither MRI nor EEG are accurate enough to show activation of individual neurons. In other words, it is not easy to register the activity of a single cell without affecting neighboring neurons. It is even more difficult to specifically change this activity. The years went by. Biology, physics, genetic engineering, medicine developed. In 1975, Walther Stoeckenius and Dieter Oesterhelt from the University of California, San Francisco, isolated the light-sensitive protein bacteriorhodopsin from Chlamydomonas reinhardtii, which allows bacteria to move toward or away from the sun. Genetic engineering has also evolved, and since the work of Stanley Cohen and Herbert Boyer in 1973, it has been possible to obtain recombinant proteins by inserting sections of DNA into the cell genome. In early 2000 Georg Nagel successfully used the lightsensitive protein canalrodopsin to control cell activity.

So what is optogenetics? Optogenetics is a method of studying excitable cells that uses proteins that are embedded in the cell membrane and activated by light. Most animals have such proteins (opsins) in their vision organs and some plants, such as green algae. In order to build

photo-activated proteins into neuronal membranes, we have to bring genes of opsins from other organisms into the neurons. Today, this tool for studying the nervous system has received a number of applications that were originally unavailable. One of the most common protein used in optogenetics is channelrhodopsin(relative of retinal rhodopsin). Like the eye pigment, channelrhodopsin(ChR2) reacts to light exposure, only in a slightly different way: it increases the influx of positive ions into the algae cell, so the cell depolarizes. Since we have a protein capable of changing the membrane potential of a cell, and we have its gene, why not introduce this gene into an electrically excitable cell and see what will happen? The method of optogenetics is scientifically elegant. Bioengineers create a section of a gene construct consisting of a promoter and a gene encoding the necessary opsin (a light-sensitive protein) and encase it in a viral capsid. After the bioengineers, doctors and neurophysiologists take over, choosing the area of their scientific interest in the brain, where the virus will be injected (so far all studies have been conducted only on animals). Then the transfection process takes place (something like a viral infection), and the gene enters the neuron.(see fig.1) Although viral vectors are occasionally created from pathogenic viruses,

they are modified in such a way as to minimize the risk of handling them. This usually involves the deletion of a part of the viral genome critical for viral replication.To stimulate ChR2 on the surface of neuron light source in form of miniature optic fibre with a wavelength of about 480 nm will be used. In order to see if neuron is activated by photostimulation we will use microelectrodes implanted in the brain together with the light source. Figure 1:

Don’t trust anyone. Not even yourself! Scientists at the Massachusetts Institute of Technology (MIT), led by Susumu Tonegawa, wondered, “Can memories be artificially manipulated?” . Laboratory mice were fitted with a fiber optic system delivering light to the dentate gyrus of the hippocampus (gyrus dentatus), whose neurons were “trained” to respond to light.(fig2) This rather modestly sized area of the brain is considered to be responsible for memory consolidation (transfer of information from short-term

memory to long-term memory), especially emotionally colored memory. The mouse was placed in a neutral, safe environment - a box with bare walls. After some time, which is necessary for consolidation of memory about this environment, the mouse was placed in another box and a conditioned reflex was developed. Going a little further than a light bulb and dripping saliva, Tonegawa’s group illuminated the dentate gyrus with a laser, immediately followed by an electric shock. In doing so, activation of the dentate gyrus cells caused the mouse to recall the first box. “Thus,” says Xu Liu, one of Tonegawa’s colleagues, “we wanted to artificially link the triggered memories of the first box with the danger in the second box” (Fig. 3). Subsequently, when the mouse was placed in the first box again, it froze in anticipation of the discharge, indicating the association of the first safe box with the fear of electric shock. False memories appeared.

Figure 2:

Figure 3:

This technology is not only used as a research tool. Nowadays optogenetics can be applied for the treatment of neurological diseases. Retinitis pigmentosa is a neurodegenerative eye disease where loss of photoreceptors can lead to complete blindness. In a blind patient, we combined intraocular injection of an adenoassociated viral vector encoding opsinswith light stimulation via engineered goggles. The goggles detect local changes in light intensity and project corresponding light pulses onto the retina in real time to activate optogenetically transduced retinal ganglion cells. The patient perceived, located, counted and touched different objects using the vector-treated eye alone while wearing the goggles. During visual perception, multichannel electroencephalographic recordings revealed object-related activity above the visual cortex. The patient could not visually detect any objects before injection with or without the goggles or after injection without the goggles. This was the first reported case of partial functional recovery in a neurodegenerative disease after optogenetic therapy(may 2021). 51

The Harmonic Series

Phillip Morgan

The Harmonic Series is the science and maths behind music. Its patterns weave itself through everything. It is why we use the tuning system we use today; it is what gives instruments their character. We can use it to explain why chords make us feel a certain way. Along with other unexpected uses too! One does not have to be a musician to appreciate the beauty of the sequence.

Resonance Resonant frequency is fundamental to understanding why things sound the way they do. What is resonance? A helpful metaphor is to imagine someone pushing a swing. The person pushes the swing as the swing reaches them. If they did not, the swing would eventually stop swinging as energy is lost to the environment. The person is providing energy into the swing at the perfect time to add to the energy of the swing, rather than take it away, say, if the person pushed as the swing was still in motion towards them. This is resonance. The synchronisation of input and waves that are already present, which in turn amplifies the waves. This is often demonstrated by the Ruben’s tube. Here, a wave propagates through the tube (in flammable gas and air) and some energy is lost to the environment by the time it reaches the other end, where the wave reflects and comes back, much like the swing. Until it hits the loudspeaker’s diaphragm which acts like the person pushing the swing and adds energy to the wave sent back the other way. Now that we have a resonant frequency, what happens when we multiply it by two? When two waves interfere, the resultant amplitude is the vector sum of the individual amplitudes. This is known as the principle of superposition. In the diagram, there is a standing wave due to the superposition of two travelling waves of the same frequency travelling in opposite directions.

Here is the link to a helpful animation: https://www. desmos.com/calculator/qdepo1olam

Harmonics Now that we have a resonant frequency, what happens when you double, triple (etc.) the frequencies? We will yet again get standing waves again; because there is symmetry in air pressure on the left of the tube and right. We can multiply the frequency by any integer value and the waves will still resonate. These are known as harmonics. The harmonic series is:

Each term can be used to represent a wavelength of a harmonic. As:

Where v is the velocity of a wave (which we can assume is constant for sound in air) so

This enables us to translate resonant frequencies and wavelengths. Why is this significant? Take an empty bottle and blow over the lip of it. The sound coming from your mouth is white noise. A mixture of seemingly random frequencies. However, the resonant frequencies are amplified and emerge from the mix of white noise. This translates to all wind instruments, and by extension brass and string. Everything that has a natural resonant frequency will amplify its harmonics. Most of the sound is now harmonic, of course, you can still hear the inharmonic frequencies of the air rushing from your lips and this blend of different harmonics and inharmonic noise that give every instrument their timbre (sonority and characteristic). The note that we perceive is the loudest harmonic, which is almost always the lowest, the “fundamental”

or the first term in the harmonic series (the first harmonic) as a rule of thumb. However, with most rules, it is possible to break.

The Fourier Analysis Say we have the waveform of an instrument; how do we tell which harmonics are present? We can deconstruct the frequencies using the Fourier analysis. The Fourier analysis is like looking at a colour made from a mixture of primary colours and telling us which ones are used and in what proportions. The Fourier Theorem states that any periodic function can be computed by a series of sinusoidal waves. Below is the waveform of a sine wave of 440Hz and 493.8Hz interfering with each other.

I chose these frequencies because in music, they make a tritone interval, known as the Devils interval for how dissonant it sounds. Yet, this does not fool the Fourier Analysis. Time progresses from left to right on this graph. The “air pressure” is distance from the x axis. If we use a polar coordinate system, time can progress in a circle, and pressure can be the distance from the origin. If we change the scale to the right length, the waves will stack on top of each other perfectly. We can measure this by imagining the line plotted is a wire and measuring the distance from the centre of gravity of that wire to the origin. Here is the link to another animation:https://www. desmos.com/calculator/5tdaxnh2li On the left, the wave wraps 440 times per second. In the middle the wave wraps 454 times per second and on the right the wave wraps 493.8 times per second.

What I love about science at Caterham is the opportunities to enthuse about it beyond the constraints of the A-Level specification, so when Mr Quinton brought up the idea of introducing an extension session for some of the most enthusiastic Lower 6th pupils (and daring 5th years), I was thrilled. This seemed to be the perfect opportunity to discuss cutting edge topics and share a love for biology. Each half term, some Upper 6th pupils go about researching topics that link directly to the Lower 6th syllabus but to the standard of university level biology. Be it biochemistry, neuroscience, or medicine, we have had the joy of discussing the things we are most passionate about in biology. We launched The Darwin Society in October, with a brilliant session delivered by Chelsea on the cytoskeleton. Chelsea discussed microtubules, microfilaments and intermediate filaments, explaining their roles in cell division and cell motility. Since then, we have heard talks on a wide range of topics from a deep dive on the roles of amino acids, medical scandals, and glucose straight chains. Most recently, the Lower 6th have started to give talks on areas of biology they are passionate about. As ever, presenting to an audience of the year above is daunting, and yet they speak with confidence and explain complex concepts with ease. The Society’s success has gone above all expectations. There is fierce competition for talks and attendance is second to none. The standard of presentations is brilliant, and I am always left in awe 56

at the speaker’s knowledge on their topic, especially when faced by the rigorous cross-questioning that follows every talk. As the year ends, I have the bittersweet job of handing over my role and leaving the department. The biology department has given me so many opportunities to grow and develop my knowledge of the subject, and I find it a privilege to leave having helped to add the society to the school. I am leaving The Darwin Society in the very capable hands of Marcus and Winston, who have already done an amazing job to coordinate the forthcoming terms and have even organised for external speakers to present at the society. All in all, it has been a joy to see so many budding scientists develop a culture of curiosity and the need to know more.

Physics Extension Physics extension was, no doubt, one of the best highlights of my sixth form life. Not only did it offer a weekly dose of intellectual stimulation, but also a thrilling adventure through our universe, from the expanse of stars and galaxies to the interactions between subatomic particles. Led by Dr Scott and Mr Martinez, physics extension is a 90-minute lecture every Wednesday after school. We were enlightened on a wide range of topics, including classical mechanics (coordinate systems, frictional forces, rocket and avalanche physics, moments of inertia, angular momentum), thermodynamics (Zeroth, First and Second Laws, enthalpy, Carnot cycle, Helmholtz and Gibbs free energies), statistical mechanics (Boltzmann distribution, UV catastrophe and Planckian distribution), and quantum mechanics (Bohr’s model of an atom and Schrödinger’s equation). Reaching far beyond the A-level syllabus, these lectures equip us with strong mathematical abilities and problem-solving

O-Teen Kwok

skills for rigorous university studies. Also, the lectures are supplemented with experimental demonstrations, step-by-step equation derivations and frequent group discussions, which help illustrate abstract concepts and theories in an engaging way. Although the sessions are designed to challenge our aspirational sixth form physicists and engineers, they are open to all. It was most encouraging to see chemists and even lower year students occasionally joining us, exploring the wonders of physics. We may come to the lecture with different levels of understanding in physics, but it is certain that we all leave the room with equally inspired minds. I would like to give a massive thanks to Dr Scott and Mr Martinez, as well as every passionate scientist who made the sessions possible. Remember, physics is a lifelong journey of discovery. Embrace the wonder that physics has to offer, and you will discover a fascinating world of limitless possibilities and boundless potential! 57

Chemistry Race

Alex Mylet

otherwise, they had to go back and reattempt the question. Teams were allowed to bring as much physical reference material as they wanted, but the only digital devices allowed were calculators. The textbooks and data books we brought proved helpful for looking up certain compounds, reactions, and organic groups.

On Saturday 4th February, a team of five of Caterham’s strongest chemists competed in the 4th Chemistry Race at the Department of Chemistry at the University of Cambridge. The team consisted of Avery, Luke, and me from Upper Sixth, and Lisa and Phil from Lower Sixth accompanied by Mr Keyworth, competing under the team name Alex and his Besties. Leading up to the event, we assigned ourselves specialities to focus our preparation on. We therefore learnt content both on the A-Level syllabus and beyond it, as well as attempting questions from both past Chemistry Races and also from various chemistry Olympiad competitions. With the aim of answering as many questions as possible in a two-hour period, each team worked on six questions at a time, with a team member running down to the front of the lecture theatre to submit their answer to each question. If the team got the answer correct, they got the next question; 58

The questions tested chemistry knowledge, mathematical ability, and problem-solving ability. Topics in questions included Atomic Force Microscopy, the ingredients of toothpaste, the number of sigma bonds in buckminsterfullerene, heating a bath using the energy released from the reaction of sodium hydroxide and hydrochloric acid, filling party balloons using alphaparticles released from the radioactive decay of Polonium-210, and the ionic radii of group 1 metal ions held inside organic molecules. During the competition, there was a live scoreboard. We started around 10th and slowly crept up over the course of the race, until the scoreboard disappeared with about half-an-hour left. After the race, while the organisers double-checked the results, we went for lunch. Then we went back to the lecture theatre for the results: we came 6th at Cambridge (missing out on prizes by one spot), and 9th overall (there was also a concurrent race, with the same questions, occurring at Oxford University’s Department of Chemistry).

Prep School Science Short Competition The Wright Society was formed in 2020 by Max Fogelman and Mr Quinton, alongside the societies’ patron: Dr Wright. It is the home of aspiring medics, dentists and vets at Caterham School and has members from Oxted and Warlingham school too. Currently the President is Holly Cook and Vice President is Sally Henley. Our mission is to support our peers in achieving places at medical school, as well as inspiring students lower down the school to consider a career in medicine. All students receive guidance with their application process and benefit from a practical approach to learning - through peer guided presentations on topics in the L6th as well as preparing for their UCAT/BMAT exams. The U6th, as of December have been taking part in mock interview practice which have helped them prepare for their upcoming interviews.

This year we had the honour of introducing a science video competition to the prep school. Students’ task was to research a scientist or scientific discovery that changed the world and make a video talking about their findings. We were stunned by the amazing quality of the videos, as well as the depth of scientific knowledge displayed. There was an impressive number of topics, ranging from Isaac Newton, x-rays, and blood circulation. The entries exhibited all the qualities we were seeking:creativity, focus, rigour, sophistication and presentation so it was intensively difficult for us to make the final decision. The top prize was awarded to Elliot Webster (Climate Change and Evolution). The 3 highly commended prizes went to Mia Mehmood (The Molecular Structure of DNA), Alexander Jones (Nikola Tesla), and Seb Chapman (Fundamental Particles). Finally, a big well done and thanks to everyone who entered. We look forward to hearing the achievements of all these incredible young scientists!

Society Review Mr Dan Quinton

With some sadness this is the last time I will write a page for Quantum Ultimatum. Leaving Caterham after a quarter of a century, I have so many great memories but none prouder than the formidable Moncrieff-Jones Society. The MJS has been a massive part of my life here at Caterham and is therefore very dear to my heart. There have been some incredible Presidents and Vice Presidents along the way, many of whom are now big names in Science such as Ross Hendron who runs his own BioTech company, recently featured in the FT, and Luke Bashford one of the world’s leading neuroscientists. Quantum Ultimatum is the magazine of the MJS - I started it in 2007 with the then legendary team of Luke Bashford (President) and Edd Simpson 60

(VP). The magazine was just a photocopied booklet in those days but nevertheless innovative, new and cutting edge. To hold this current edition and see just how far we have come makes me so proud. I’d like to thank all the past teams I have worked with for MJS, but none more so than Is Singleton and O-Teen Kwok this year. Is has been a truly inspirational leader and helped take the MJS to new heights. Her dedication to the society and the hours she has willingly and unquestioningly put in is awe inspiring and an example to her generation. I hand the reins over to Mr Evans who has helped me so closely during recent years, and wish him luck, and know he will take care of something so precious to me. I look forward to coming back in years to come to see where MJS goes in the future.

Past Moncrieff-Jones Society Presidents & Vice Presidents 2007-2008

2012-2013

2017-2018

President: Luke Bashford (University College London)

President: Rachel Wright (St Peter’s College, Oxford)

President: Kamen Kyutchukov (University College London)

Vice President: Edd Simpson (University of Leeds)

Vice President: David Gardner (University of Nottingham)

Vice President: Natalie Bishop (University College London)

2008-2009

2013-2014

2018-2019

President: Tonya Semyachkova (Balliol College, Oxford)

President: Holly Hendron (St Peter’s College, Oxford)

President: Daniel Farris (University of Exeter)

Vice President: Raphael Zimmermann (University of East Anglia)

Vice President: Annie-Marie Baston (Magdalen College, Oxford)

Vice President: Rowan Bradbury (University of York)

2009-2010

2014-2015

President: Alex Hinkson (St Catherine’s College, Oxford)

President: Ollie Hull (Merton College, Oxford)

President: Michael Land (University of Warwick)

Vice President: Alexander Clark (Robinson College, Cambridge)

Vice President: Cesci Adams (University of Durham)

2010-2011

2015-2016

President: Oliver Claydon (Gonville and Caius College, Cambridge)

President: Thomas Land (University of Southampton)

Vice President: Sally Ko (Imperial College, London) 2011-2012

President: Glen-Oliver Gowers (University College, Oxford) Vice President: Ross-William Hendron (St Peter’s College, Oxford)

Vice President: Emily Yates (University of Birmingham) 2016-2017

President: Hannah Pook (St John’s College, Oxford) Vice President: Vladimir Kalinovsky (University College London)

2019-2020

Vice President: Ben Brown (Bristol University) 2020-2021

President: Alex Richings (Imperial College London) Vice President: Max Fogelman (University of St Andrews) 2021-2022

President: Jason Cho (University College London) Vice President: Rainis Cheng (University of Hong Kong)

Past Endorsers of the Moncrieff-Jones Society Dr Jan Schnupp Lecturer in the Department of Physiology, Anatomy and Genetics at the University of Oxford Dr Bruce Griffin Professor at Surrey University, specialising in lipid metabolism, nutritional biochemistry and cardiovascular disease Dr Simon Singh Popular author and science writer including the book “Trick or Treatment”

Dr Mark Wormald Tutor of Biochemistry at the University of Oxford

Dr Max Bodmer Marine Biologist and lecturer at Lincoln and Nottingham University

Dr Alexis Bailey Surrey University, Department of Biochemistry and Physiology Leader of the Drug Addiction Research Team

Dr Jansen Zhao Senior Researcher in the Computer Science Department at ETH Zürich

Dr Nick Lane Reader in Evolutionary Biochemistry at University College London Mike Bonsall Professor of Mathematical Biology at St Peter’s College, Oxford

Mr Shahnawaz Rasheed Consultant Surgeon at The Royal Marsden and Senior Lecturer at Imperial College London Mr Mark Hitchman Managing Director at Canon Medical Systems 61

Sophia Liu’s reference

https://www.nationalgeographic.com/science/article/thecase-for-junk-dna https://www.scienceabc.com/pure-sciences/is-98-of-ourdna-really-junk.html The Complex Truth About ‘Junk DNA’ | Quanta Magazine. Quanta Magazine. (2022). Retrieved 4 September 2022, from https://www.quantamagazine. org/the-complex-truth-about-junk-dna-20210901/. Carey, N. (2015). Junk DNA. London, ZULU: Icon Books Ltd. Rehfeld, A., Plass, M., Krogh, A., & Friis-Hansen, L. (1AD, January 1). Alterations in polyadenylation and its implications for endocrine disease. Frontiers. Retrieved September 4, 2022, from https://www.frontiersin.org/ articles/10.3389/fendo.2013.00053/full https://medlineplus.gov/genetics/understanding/ inheritance/updimprinting/#:~:text=In%20genes%20 that%20undergo%20genomic,to%20certain%20 segments%20of%20DNA. Panning, B. X-chromosome inactivation: the molecular basis of silencing. J Biol 7, 30 (2008). https://doi. org/10.1186/jbiol95 https://www.ncbi.nlm.nih.gov/pmc/articles/ PMC5084913/#ref-list-1title Paramita Shen’s reference Phys. Rev. 167, 331 (1968): Transition Temperature of Strong-Coupled Superconductors http://prola.aps.org/abstract/PR/v167/i2/p331_1 Bardeen, J.; Cooper, L. N.; Schrieffer, J. R. (1957). “Microscopic Theory of Superconductivity”. https://doi. org/10.1103%2FPhysRev.106.162 Hole-doped room-temperature superconductivity in H3S1-xZx (Z=C, Si), YanfengGe, FanZhang Ranga P.Dias, Russell J.Hemley, YuguiYao https://doi. org/10.1016/j.mtphys.2020.100330 First-principles demonstration of superconductivity at 280 K in hydrogen sulfide with low phosphorus substitution Yanfeng Ge, Fan Zhang, and Yugui Yao, Phys. Rev. B 93, 224513 – Published 16 June 2016 https://doi.org/10.1103/PhysRevB.93.224513 Liangzi Deng, Trevor Bontke, Rabin Dahal , Yu Xie, Bin Gao, Xue Li, Ketao Yin, Melissa Gooch, Donald Rolston, Tong Chen, Zheng Wu, Yanming Ma, Pengcheng Dai, and Ching-Wu Chu, Pressure-induced high-temperature superconductivity retained without pressure in FeSe single crystals, 2021, https://www.pnas.org/doi/10.1073/pnas.2108938118 Davide Castelvecchi. First room-temperature superconductor excites-and-baffles-scientists. Nature 586,349(2020) https://www.nature.com/articles/d41586020-02895-0 George A. Sawatzky, Superconductivity seen in a nonmagnetic nickel oxide https://www.nature.com/articles/d41586-019-02518-3 Menlo Park, Calif. First report of superconductivity in a nickel oxide material https://www6.slac.stanford.edu/news/2019-08-28-firstreport-superconductivity-nickel-oxide-material.aspx Bednorz, J. G. ; Müller, K. A. Possible high Tc superconductivity in the Ba-La-Cu-O system https://ui.adsabs.harvard.edu/ abs/1986ZPhyB..64..189B/abstract

Avery Chen’s reference

Clark, J. (2015, October). Grignard reagents. Chemguide. Retrieved August 2022, from https://www. chemguide.co.uk/organicprops/haloalkanes/grignard. html Clayden, J., Greeves, N., & Warren, S. (2012). Organic Chemistry (2nd ed.). Oxford University Press. Cossy, J. (2015). Grignard Reagents. De Gruyter.

Grignard Reagents Market. (2016, December). NAFTA and Europe Industry Analysis, Size and Forecast, 2016 to 2026. Retrieved August 2022, from https://www. futuremarketinsights.com/reports/nafta-and-europegrignard-reagents-market Hartwig, J. (2009). Organotransition Metal Chemistry: From Bonding to Catalysis (1st ed.). University Science books. Ouellette, R. J., & Rawn, J. D. (2015). Haloalkanes and Alcohols Introduction to Nucleophilic Substitution and Elimination Reactions. Organic Chemistry Study Guide, 135–167. https://doi.org/10.1016/b978-0-12-8018897.00009-1 Seyferth, D. (2009). The Grignard Reagents. Organometallics, 28(6), 1598–1605. https://doi. org/10.1021/om900088z Spessard, G. O., & Miessler, G. L. (2015). Organometallic Chemistry (3rd ed.). Oxford University Press. Elliot Major’s reference Boer, J.L., Mulrooney, S.B. and Hausinger, R.P., 2014. Nickel-dependent metalloenzymes. Archives of biochemistry and biophysics, 544, pp.142-152. Carter, E.L., Flugga, N., Boer, J.L., Mulrooney, S.B. and Hausinger, R.P., 2009. Interplay of metal ions and urease. Metallomics, 1(3), pp.207-221. Benini, S., Rypniewski, W.R., Wilson, K.S., Miletti, S., Ciurli, S. and Mangani, S., 1999. A new proposal for urease mechanism based on the crystal structures of the native and inhibited enzyme from Bacillus pasteurii: why urea hydrolysis costs two nickels. Structure, 7(2), pp.205-216. Picone, N. and den Camp, H.J.O., 2019. Role of rare earth elements in methanol oxidation. Current Opinion in Chemical Biology, 49, pp.39-44. Biochemistry Second Edition Wiley Donald D. Voet Judith G. Voet Lumpe, H., Pol, A., den Camp, H.J.O. and Daumann, L.J., 2018. Impact of the lanthanide contraction on the activity of a lanthanide-dependent methanol dehydrogenase–a kinetic and DFT study. Dalton Transactions, 47(31), pp.10463-10472. Argaman, Nathan & Makov, Guy. (1998). Density Functional Theory -- an introduction. American Journal of Physics. 68. 10.1119/1.19375. https://www.ebi.ac.uk/thornton-srv/m-csa/entry/997/ https://www.ebi.ac.uk/thornton-srv/m-csa/entry/87/ Natasha Smith’s reference Saltiel H, Thomopoulos P. Dopamine et hormones antéhypophysaires. Physiologie et pathologie [Dopamine and pituitary hormones. Physiology and pathology (author’s transl)]. Ann Endocrinol (Paris). 1981 Dec;42(6):497-516. (Accessed August 2022) Saline.S (2022) ADHD Statistics: New ADD Facts and Research, ADDitude, available at https://www. additudemag.com/statistics-of-adhd/ (accessed August 2022) Katzman MA, Bilkey TS, Chokka PR, Fallu A, Klassen LJ. Adult ADHD and comorbid disorders: clinical implications of a dimensional approach. BMC Psychiatry. 2017 Aug 22;17(1):302. (Accessed August 2022) Levy, F. Synaptic Gating and ADHD: A Biological Theory of Comorbidity of ADHD and Anxiety. Neuropsychopharmacol 29, 1589–1596 (2004). Accessed at https://doi.org/10.1038/sj.npp.1300469 (accessed September 2022) Pereira-Sanchez, Victora,b; Castellanos, Francisco X.a,c. Neuroimaging in attention-deficit/hyperactivity disorder. Current Opinion in Psychiatry 34(2):p 105-111, March 2021. | (accessed September 2022) Purves D, Augustine GJ, Fitzpatrick D, et al., editors. Neuroscience. 2nd edition. Sunderland (MA): Sinauer Associates; 2001. Neurons Often Release More Than One Transmitter. Available from: https://www.ncbi.nlm. nih.gov/books/NBK10818/ (accessed September 2022) Curatolo, P., D’Agati, E. & Moavero, R. The neurobiological basis of ADHD. Ital J Pediatr 36, 79 (2010). (Accessed September 2022)

Sears SM, Hewett SJ. Influence of glutamate and GABA transport on brain excitatory/inhibitory balance. Exp Biol Med (Maywood). 2021 May;246(9):1069-1083. (Accessed September 2022) Madras BK, Miller GM, Fischman AJ. The dopamine transporter and attention-deficit/hyperactivity disorder. Biol Psychiatry. 2005 Jun 1;57(11):1397-409. (Accessed September 2022) Lai, T.K.Y., Su, P., Zhang, H. et al. Development of a peptide targeting dopamine transporter to improve ADHD-like deficits. Mol Brain 11, 66 (2018). (Accessed September 2022) Südhof TC. Composition of Synaptic Vesicles. In: Siegel GJ, Agranoff BW, Albers RW, et al., editors. Basic Neurochemistry: Molecular, Cellular and Medical Aspects. 6th edition. Philadelphia: Lippincott-Raven; 1999. Available from: https://www.ncbi.nlm.nih.gov/ books/NBK28154/ (Accessed September 2022) Mason, Peggy, ‘Synthesis, Packaging, and Termination of Neurotransmitters’, Medical Neurobiology, 2 edn (New York, 2017; online edn, Oxford Academic, 1 Feb. 2017),( Accessed October 2022) Xu J, Luo F, Zhang Z, Xue L, Wu XS, Chiang HC, Shin W, Wu LG. SNARE proteins synaptobrevin, SNAP-25, and syntaxin are involved in rapid and slow endocytosis at synapses. Cell Rep. 2013 May 30;3(5):1414-21. (Accessed October 2022) Antonucci F, Corradini I, Fossati G, Tomasoni R, Menna E, Matteoli M. SNAP-25, a Known Presynaptic Protein with Emerging Postsynaptic Functions. Front Synaptic Neurosci. 2016 Mar 24;8:7. (Accessed October 2022) Pramod AB, Foster J, Carvelli L, Henry LK. SLC6 transporters: structure, function, regulation, disease association and therapeutics. Mol Aspects Med. 2013 Apr-Jun;34(2-3):197-219. (Accessed October 2022) Kristen A. Stout, Amy R. Dunn, Carlie Hoffman, and Gary W. Miller The Synaptic Vesicle Glycoprotein 2: Structure, Function, and Disease Relevance ACS Chemical Neuroscience 2019 10 (9), 3927-3938 ( Accessed October 2022) Silver.L, (2022) An expert on attention deficit and learning disabilities talks about the biology behind ADHD and why it’s sometimes so difficult to diagnose and treat symptoms in children, ADDitude, available at https://www.additudemag.com/adhd-neuroscience-101/ (Accessed October 2022) Bringmann A, Grosche A, Pannicke T, Reichenbach A. GABA and Glutamate Uptake and Metabolism in Retinal Glial (Müller) Cells. Front Endocrinol (Lausanne). 2013 Apr 17;4:48. (Accessed October 2022) Curatolo, P., D’Agati, E. & Moavero, R. The neurobiological basis of ADHD. Ital J Pediatr 36, 79 (2010). (Accessed November 2022)

Lisa Hu’s reference

Baker, R.W. (2012). Membrane technology and applications. Chichester John Wiley & Sons. Chen, L.-Q. (2019). Chemical potential and Gibbs free energy. MRS Bulletin, [online] 44(7), pp.520–523. doi:10.1557/mrs.2019.162. Environment, U.N. (2017). Tackling global water pollution. [online] UNEP - UN Environment Programme. Available at: https://www.unep.org/explore-topics/water/ what-we-do/tackling-global-water-pollution. Enzler, S.M. (2017). History of water treatment. [online] Lenntech.com. Available at: https://www.lenntech.com/ history-water-treatment.htm. Han, X., Wang, Z. and Wang, J. (2022). Preparation of highly selective reverse osmosis membranes by introducing a nonionic surfactant in the organic phase. Journal of Membrane Science, 651, p.120453. doi:10.1016/j.memsci.2022.120453. Hołda, A.K. and Vankelecom, I.F.J. (2015). Understanding and guiding the phase inversion process for synthesis of solvent resistant nanofiltration membranes. Journal of Applied Polymer Science, 132(27), p.n/a-n/a. doi:10.1002/app.42130. Kim, H., Choi, J-S. and Lee, S. (2012). Pressure retarded osmosis for energy production: membrane materials and operating conditions. Water science and

technology : a journal of the International Association on Water Pollution Research, [online] 65(10), pp.1789–94. doi:10.2166/wst.2012.025. Li, D., Yan, Y. and Wang, H. (2016). Recent advances in polymer and polymer composite membranes for reverse and forward osmosis processes. Progress in Polymer Science, 61, pp.104–155. doi:10.1016/j. progpolymsci.2016.03.003. Liang, Y., Zhu, Y., Liu, C., Lee, K.-R., Hung, W.-S., Wang, Z., Li, Y., Elimelech, M., Jin, J. and Lin, S. (2020). Polyamide nanofiltration membrane with highly uniform sub-nanometre pores for sub-1 Å precision separation. Nature Communications, [online] 11(1), p.2015. doi:10.1038/s41467-020-15771-2. Liu, F., Wang, L., Li, D., Liu, Q. and Deng, B. (2019). A review: the effect of the microporous support during interfacial polymerization on the morphology and performances of a thin film composite membrane for liquid purification. RSC Advances, 9(61), pp.35417– 35428. doi:10.1039/c9ra07114h. Lu, X., Arias Chavez, L.H., Romero-Vargas Castrillón, S., Ma, J. and Elimelech, M. (2015). Influence of Active Layer and Support Layer Surface Structures on Organic Fouling Propensity of Thin-Film Composite Forward Osmosis Membranes. Environmental Science & Technology, 49(3), pp.1436–1444. doi:10.1021/ es5044062. Mansourpanah, Y., Alizadeh, K., Madaeni, S.S., Rahimpour, A. and Soltani Afarani, H. (2011). Using different surfactants for changing the properties of poly(piperazineamide) TFC nanofiltration membranes. Desalination, 271(1-3), pp.169–177. doi:10.1016/j. desal.2010.12.026. Mokarizadeh, H., Moayedfard, S., Maleh, M.S., Mohamed, S.I.G.P., Nejati, S. and Esfahani, M.R. (2022). The role of support layer properties on the fabrication and performance of thin-film composite membranes: The significance of selective layer-support layer connectivity. Separation and Purification Technology, 278, p.119451. doi:10.1016/j. seppur.2021.119451. Nunes, S.P., Culfaz-Emecen, P.Z., Ramon, G.Z., Visser, T., Koops, G.H., Jin, W. and Ulbricht, M. (2020). Thinking the future of membranes: Perspectives for advanced and new membrane materials and manufacturing processes. Journal of Membrane Science, 598, p.117761. doi:10.1016/j. memsci.2019.117761. Purkait, M.K., Sinha, M.K., Mondal, P. and Singh, R. (2018). Introduction to Membranes. Interface Science and Technology, 25, pp.1–37. doi:10.1016/b978-0-12813961-5.00001-2. Shapiro, J. (2018). An Easy Guide to Understanding Surfactants - International Products Corporation. [online] International Products Corporation. Available at: https://www.ipcol.com/blog/an-easy-guide-tounderstanding-surfactants/. Song, Y., Fan, J.-B. and Wang, S. (2017). Recent progress in interfacial polymerization. Materials Chemistry Frontiers, [online] 1(6), pp.1028–1040. doi:10.1039/C6QM00325G. Wang, C., Wang, Z., Yang, F. and Wang, J. (2021). Improving the permselectivity and antifouling performance of reverse osmosis membrane based on a semi-interpenetrating polymer network. Desalination, 502, p.114910. doi:10.1016/j.desal.2020.114910. Wei, Y.-M., Xu, Z.-L., Yang, X.-T. and Liu, H.-L. (2006). Mathematical calculation of binodal curves of a polymer/solvent/nonsolvent system in the phase inversion process. Desalination, 192(1-3), pp.91–104. doi:10.1016/j.desal.2005.07.035. Yip, N.Y., Tiraferri, A., Phillip, W.A., Schiffman, J.D., Hoover, L.A., Kim, Y.C. and Elimelech, M. (2011). Thin-Film Composite Pressure Retarded Osmosis Membranes for Sustainable Power Generation from Salinity Gradients. Environmental Science & Technology, 45(10), pp.4360–4369. doi:10.1021/ es104325z.

Xavier Parker’s reference

Soho-Dickstein (2015) Deep Unsupervised Learning using Nonequilibrium Thermodynamics https://arxiv.org/ pdf/1503.03585.pdf

Ho, Jane, Abbeel (2020) Denoising Diffusion Probabilistic Models https://arxiv.org/pdf/2006.11239.pdf Nichol, Dariwal (2021) Improved Denoising Diffusion Probabilistic Models https://arxiv.org/pdf/2102.09672.pdf Nichol, Dariwal (2021) Diffusion Models Beat GANs on Image Synthesis https://arxiv.org/pdf/2105.05233.pdf Yannic Kilcher (2021) DDPM – Diffusion Models Beat GANs on Image Synthesis (Machine Learning Research Paper Explained https://youtu.be/W-O7AZNzbzQ Adam Dhalla (2021) The Complete Mathematics of Neural Networks and Deep Learning https://youtu.be/ Ixl3nykKG9M 3Blue1Brown (2017) Gradient descent, how neural networks learn https://youtu.be/IHZwWFHWa-w Angus Turner (2021) Diffusion Models as a kind of VAE https://angusturner.github.io/generative_ models/2021/06/29/diffusion-probabilistic-models-I.html Lilian Weng (2021) What are Diffusion Models? https:// lilianweng.github.io/posts/2021-07-11-diffusion-models/

Marcus Kwok’s reference

Eldridge, L. (2013). What It Means If You Have Precancerous Cells. [online] Verywell Health. Available at: https://www.verywellhealth.com/what-areprecancerous-cells-2248796. ‌ octorpedia (2018). Light Therapy | Photodynamic D (PDT) [Dermatology]. YouTube. Available at: https:// www.youtube.com/watch?v=SFbnvlYQ1hA [Accessed 28 Jul. 2021]. ‌ ww.cancer.gov. (2011). Photodynamic Therapy for w Cancer - National Cancer Institute. [online] Available at: https://www.cancer.gov/about-cancer/treatment/types/ photodynamic-therapy.

‌ unt, D.W. and Chan, A.H. (1999). Photodynamic H therapy and immunity. IDrugs: the investigational drugs journal, [online] 2(3), pp.231–236. Available at: https:// pubmed.ncbi.nlm.nih.gov/16160933/ [Accessed 23 Jan. 2023]. ‌ i, X., Kwon, N., Guo, T., Liu, Z. and Yoon, J. (2018). L Innovative Strategies for Hypoxic‐Tumor Photodynamic Therapy. Angewandte Chemie International Edition, 57(36), pp.11522–11531. doi:10.1002/anie.201805138. ‌ eginato, E. (2014). Immune response after R photodynamic therapy increases anti-cancer and antibacterial effects. World Journal of Immunology, [online] 4(1), p.1. doi:10.5411/wji.v4.i1.1. ‌ ollnick, S.O., Owczarczak, B. and Maier, P. (2006). G Photodynamic therapy and anti-tumor immunity. Lasers in Surgery and Medicine, [online] 38(5), pp.509–515. doi:10.1002/lsm.20362. ‌ tudy.com. (2015). What Are Cytokines? - Definition, S Types & Function - Video & Lesson Transcript | Study. com. [online] Available at: https://study.com/academy/ lesson/what-are-cytokines-definition-types-function.html. ‌ ield, D. (2020). There’s a Cancer Treatment That N Gives People ‘Night Vision’, And We Finally Know Why. [online] ScienceAlert. Available at: https://www. sciencealert.com/scientists-have-figured-out-how-acancer-treatment-gives-patients-night-vision [Accessed 23 Jan. 2023]. ‌ sychology Wiki. (n.d.). Visual phototransduction. P [online] Available at: https://psychology.fandom.com/ wiki/Visual_phototransduction [Accessed 23 Jan. 2023]. ‌ atalina Island Marine Institute. (2021). Night Vision: C Rhodopsin Seeing in the Dark! [online] Available at: https://cimi.org/blog/night-vision-rhodopsin-seeing-inthe-dark/. ‌ ogers, K. (2019). Rhodopsin | biochemistry. In: R Encyclopædia Britannica. [online] Available at: https:// www.britannica.com/science/rhodopsin.

Fuchs, J. and Thiele, J. (1998). The Role of Oxygen in Cutaneous Photodynamic Therapy. Free Radical Biology and Medicine, [online] 24(5), pp.835–847. doi:10.1016/S0891-5849(97)00370-5.

‌ unaydin, G., Gedik, M.E. and Ayan, S. (2021). G Photodynamic Therapy—Current Limitations and Novel Approaches. Frontiers in Chemistry, 9. doi:10.3389/ fchem.2021.691697.

Wang, M., Geilich, B., Keidar, M. and Webster, T. (2017). Killing malignant melanoma cells with protoporphyrin IX-loaded polymersome-mediated photodynamic therapy and cold atmospheric plasma. International Journal of Nanomedicine, Volume 12, pp.4117–4127. doi:10.2147/ijn.s129266.

‌ rofound-answers.com. (n.d.). How do leukocytes p destroy pathogens? – Profound-Answers. [online] Available at: https://profound-answers.com/how-doleukocytes-destroy-pathogens/ [Accessed 23 Jan. 2023].

‌ ischer, D.E. and Ahmed, F. (2006). D POLYMERSOMES. Annual Review of Biomedical Engineering, 8(1), pp.323–341. doi:10.1146/annurev. bioeng.8.061505.095838. Maytin, E.V., Kaw, U., Ilyas, M., Mack, J.A. and Hu, B. (2018). Blue light versus red light for photodynamic therapy of basal cell carcinoma in patients with Gorlin syndrome: A bilaterally controlled comparison study. Photodiagnosis and Photodynamic Therapy, 22, pp.7–13. doi:10.1016/j.pdpdt.2018.02.009. ‌ ww.sciencedirect.com. (n.d.). Photooxidation - an w overview | ScienceDirect Topics. [online] Available at: https://www.sciencedirect.com/topics/earth-andplanetary-sciences/photooxidation Fuchs, J. and Thiele, J. (1998). The Role of Oxygen in Cutaneous Photodynamic Therapy. Free Radical Biology and Medicine, [online] 24(5), pp.835–847. doi:10.1016/S0891-5849(97)00370-5. ‌ itra, S., Cassar, S.E., Niles, D.J., Puskas, J.A., M Frelinger, J.G. and Foster, T.H. (2006). Photodynamic therapy mediates the oxygen-independent activation of hypoxia-inducible factor 1α. Molecular Cancer Therapeutics, 5(12), pp.3268–3274. doi:10.1158/15357163.mct-06-0421. ‌ i, X., Kwon, N., Guo, T., Liu, Z. and Yoon, J. (2018). L Innovative Strategies for Hypoxic‐Tumor Photodynamic Therapy. Angewandte Chemie International Edition, 57(36), pp.11522–11531. doi:10.1002/anie.201805138. Masoud, G.N. and Li, W. (2015). HIF-1α pathway: role, regulation and intervention for cancer therapy. Acta Pharmaceutica Sinica B, [online] 5(5), pp.378–389. doi:10.1016/j.apsb.2015.05.007. ‌ leveland Clinic. (n.d.). Granulocytes: Definition, C Types & Function. [online] Available at: https:// my.clevelandclinic.org/health/body/22016-granulocytes.

‌ alk‐Mahapatra, R. and Gollnick, S.O. (2020). F Photodynamic Therapy and Immunity: An Update. Photochemistry and Photobiology, 96(3), pp.550–559. doi:10.1111/php.13253. ‌ organ, B.P. and Conversation, T. (n.d.). Coronavirus M treatments: keep your eye on anti-complement drugs— they look promising. [online] medicalxpress.com. Available at: https://medicalxpress.com/news/2020-11coronavirus-treatments-eye-anti-complement-drugsthey. html#:~:text=Complement%20is%20a%20highly%20 inflammatory%20system [Accessed 23 Jan. 2023]. Haralambiev, L., Nitsch, A., Einenkel, R., Muzzio, D.O., Gelbrich, N., Burchardt, M., Zygmunt, M., Ekkernkamp, A., Stope, M.B. and Gümbel, D. (2020). The Effect of Cold Atmospheric Plasma on the Membrane Permeability of Human Osteosarcoma Cells. Anticancer Research, [online] 40(2), pp.841–846. doi:10.21873/ anticanres.14016. ‌ e Keijzer, M.J., de Klerk, D.J., de Haan, L.R., van d Kooten, R.T., Franchi, L.P., Dias, L.M., Kleijn, T.G., van Doorn, D.J., Heger, M. and Photodynamic Therapy Study Group (2022). Inhibition of the HIF-1 Survival Pathway as a Strategy to Augment Photodynamic Therapy Efficacy. Methods in Molecular Biology (Clifton, N.J.), [online] 2451, pp.285–403. doi:10.1007/978-10716-2099-1_19. FINGAR, V. H. (1996). Vascular Effects of Photodynamic Therapy. Journal of Clinical Laser Medicine & Surgery, 14(5), 323–328. https://doi. org/10.1089/clm.1996.14.323 ‌ ww.horiba.com. (n.d.). What is Singlet Oxygen? w [online] Available at: https://www.horiba.com/int/ scientific/technologies/fluorescence-spectroscopy/whatis-singlet-oxygen/ [Accessed 23 Jan. 2023]. ‌ ing. (n.d.). why can polymersomes carry both B hydrophilic and hydrophobic molecules. [online] Available at: https://www.bing.com/

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