HURJ Volume 21 - Fall 2015

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a letter from the editor


The Hopkins Undergraduate Research Journal was the first interdisciplinary undergraduate research journal on the Homewood campus. Within the pages of this issue, you will encounter a sampling of the incredible research engaging Hopkins students in the sciences, humanities, social sciences, and engineering. For each biannual issue of HURJ, the editorial staff selects one topic of interest to highlight in the magazine’s Focus section. This fall, we received submissions on “learning from the past.” As you will find upon browsing the articles inside, historical trade patterns and political elections inform contemporary affairs. Our Spotlight, Science & Engineering, and Humanities & Social Sciences sections showcase research endeavors that fall outside our chosen theme. This semester, we bring you articles on a fascinating range of subjects, including cross-cultural identity, social non-conformism, and Roman pilgrimage culture. The articles in this Fall 2015 issue of HURJ reveal the diverse research interests of Johns Hopkins University students. I am proud of this publication as a testament to the boundless academic and intellectual talents of my peers. I would like to give special thanks to the HURJ staff and contributors for their hard work. Enjoy!

Jessica Terekhov Editor-in-Chief

hurj editorial board Editor-in-Chief Jessica Terekhov Focus Yunchan Chen Cyrus Zhou Humanities & Social Sciences Emily Karcher Harry Burke Science & Engineering Annie Cho Aneek Patel Apurv Hirsh Shekhar Spotlight Jaya Jasty* Veronica Reardon* Layout Sarah Sukardi Treasurer Yunchan Chen Publicity Aneek Patel Copy

hurj fall issue 2015 contributors Kyoung-A Cho Jane Miglo Lauren Pomerantz James Shamul

Maria Belen Wu Arpan Ghosh Taylor Alessio Elisabeth Fassas

Sungbae Paul Park Anna Silk Melaku Arega Kain Kim

* Recognized for Participation in HURJ Spring 2015

about hurj: The Hopkins Undergraduate Research Journal provides undergraduates with valuable access to research undertaken by their peers. The journal features four sections: a main Focus, Spotlight, Science & Engineering, and Humanities & Social Sciences. Students are highly encouraged to submit their original work.


The views expressed in this publication are those of the authors and do not constitute the opinion of the Hopkins Undergraduate Research Journal.

contact us: Hopkins Undergraduate Research Journal Mattin Center, Suite 210 3400 N Charles St Baltimore, MD 21218


Fall 2015:

Learning from the Past

table of contents fall 2015 focus: Chinese Trade and Investment in Latin America: Neo-Colonialism or Alliance? Maria Belen Wu The Indian National Election Arpan Ghosh

spotlight: Jubilee!: A Look into Early Modern Roman Catholic Pilgrimage Culture Taylor Alessio Severed Ties and Future Aspirations: Youth Perspective on the Cypriot Conflict Elisabeth Fassas

table of contents humanities & social sciences: Decisions to Escape the Margins: A Look into Runaway Youths and Teen Suicide in Light of the Imagination of the City Sungbae Paul Park Consider the Headline: The Portrayal of Muslim Immigration in Media Sources Anna Silk

science and engineering: Hypoxia-Induced Regulation of Macroautophagy in Cancer Melaku Arega Role of Exogenous Ă&#x;-Carotene in Cerebral Ischemia/Reperfusion Injury in Vivo Kain Kim


hurj fall 2015: issue 21

Chinese Trade and Investment in Latin America: Neo-Colonialism or Alliance?

Maria Belen Wu, Class of 2018, Dr. Carla Ramon Berjano International Studies

China’s involvement

quite modest. During the reign of Mao Zedong as the Chairman of the Communist Party of China (1966economy has grown dramatically since the nation be- 1976), Chinese foreign policy supported the theory of gan a process of reform and globalization in 1978. Back the “third world,” but that was largely the extent of any in 1980, China was ranked twentieth in importance in relations. Although diplomatic relations between China world trade, while, at present, China is the world’s sec- and Cuba were established in September 1960, one year ond largest trading country. In the 1980s, China em- after the Cuban Revolution, relations with the rest of barked on a progressive and carefully designed de- the region took a bit longer. In fact, most international activity occurred around US Presivelopment process that focused dent Nixon´s visit to Beijing in early initially on coastal zones, foreign 1972. Chile was the first to establish direct investment and technolodiplomatic relations with China in gy adaptation. With unused and 1970; Peru did the same in 1971, and cheap land supply, low labor costs At present, China is Argentina and Mexico a year later. and foreign capital, China became The last Latin American country to the world’s second the “world’s factory.” In 2001, after do so was Costa Rica in 2007. a long negotiation, China became in the global

largest trading country.

a member of the World Trade Organization (WTO), which would further enhance its prominence in the world economy. Moreover, China´s growth was apparent from its two identities as a major world producer and consumer. The provision of resources and energy became crucial for the preservation of dramatic production growth rates. Tremendous growth fueled increased demand for goods, particularly for food. The provision of raw materials and energy, thus, became a fundamental aspect of China´s relationship with the rest of the world, and especially with developing Latin American countries. A dramatic upsurge of trade relations and financial investment has reasonably raised concerns over an asymmetrical relationship on the Latin American end. However, speculation and fear of Chinese neo-colonialism threatens to hinder the untapped potential of mutual benefit yet to be seen from such strategic alliances in the developing world.

Relations between China and Latin America Historical ties Before 1978, Chinese relations with Latin America were


Current relations Within the last decade alone, several important events influenced the relations between Latin America and China. The first one involved the Chinese government’s release of the White Paper for interregional relations in 20082. Another important step was Chinese Prime Minister Wen Jiabao’s visit to the region in 2012; the event highlighted the launch of a proposal for stronger cooperation in economic and political issues between China and Latin America. Last year, the so-called “1+3+6” strategy for the 2015-2019 period was launched during the first China-CELAC Summit held in Brasilia. China has subsequently established free trade agreements with Chile, Peru and Costa Rica. These are strong indications of the Chinese government’s desire to enhance cooperation and strengthen its links with the region. Currently China is the second largest country of origin for Latin American imports and the third largest for Latin American export products. The United States continues to be Latin America´s first import and export market, while the European Union continues to be the second main export destination, but since 2010 has been displaced to third place for imports, after China. According to CEPAL3, between 2000 and 2014, Chinese

spotlight hurj fall 2015: issue 21

share in regional exports increased from 1 to 9 percent while its imports increased from 2 to 16 percent. Likewise, the significance of Latin America for the Chinese market has also increased. In 2000, Chinese exports and imports to and from Latin America accounted for 3 percent and 2 percent, respectively, of total Chinese trade; by 2013, this had increased to 6 percent and 7 percent, respectively.

Trade between Latin America and China: The Breakdown4,5


Three Asymmetries in Trade Relative Sizes China accounts for twice as much – 12.75 percent – of total Latin American trade, with 4.5 percent exports and 8.2 percent imports. Items of Trade Latin America´s four main export products to China are ores, food products, fuels and minerals, which comprise over 80 percent of total exports to China; Latin America primary imports from China, however, include electrical machinery and equipment. Concentration of Trade The top 20 export products to China constitute almost 97 percent of total Latin American exports. In particular, the top 5 products comprise over 80 percent of total exports (83.2 percent). These products are ores, slags and ash (26.6 percent), oil seeds and other products (21.04 percent), mineral fuels (21.02 percent), copper (11.49 percent) and pulp of wood (2.99 percent). Meanwhile, imports from China remain much more diversified.


focus Foreign Direct Investment (FDI) in Latin America6

hurj fall 2015: issue 21 cerns over China´s negotiations with Latin America. Chinese aid can be redirected rather than channeled into assigned areas, with intervention being unlikely given China’s policy of non-interference. According to the World Economic Forum, Latin American countries rank among the most corrupt in the world, so when it comes to Chinese investment in the region, local corrupt practices are a main concern.

Opportunities from Continued Alliance

Source: authors´own, with data from Trademap.

Figure above: Five countries concentrate most of Chinese FDI in the region, with Venezuela at the top (51 percent), followed by Brazil and Argentina (20 and 17 percent respectively) and to a much lesser extent Ecuador (10 percent) and Bahamas (3 percent).

Main Concerns The statistics merely state the obvious: Chinese involvement in the Latin American economy has proven consistent. The asymmetries in trade of goods and services discussed above reflect the two regions’ contrasting levels of industrialization. Most neo-colonialist concerns arise from the massive amounts of incoming FDI, as well as the side effects of financial operations. Such concerns about Chinese presence stem from three main standpoints: foreign ownership of land, generation of local employment and local corruption. The issue of “land grabbing” by China in Latin America involves transactions that are mainly conducted within the private sector. By and large, the Chinese government seems to be encouraging investment in several aspects of the production chain, trying to access different sectors, markets, industries, such as banking and logistics. The most popular critique of Chinese investment in the region is the resulting competition between foreign and local labor forces. Many Chinese companies that have been involved in investments across several sectors financed by Chinese banks usually import Chinese management, technical expertise and, in some cases, even Chinese workers. In Latin America, the countries most dependent on Chinese employees are by and large small Caribbean nations, whose markets are smaller and have weaker bargaining positions. In addition, their local labor force is relatively smaller and often lacks necessary skills. There is growing attention, however, to the local workforce. This is due to several factors – for instance, the fact that fewer Chinese employees are willing to work abroad due to the considerably poorer wages and labor conditions. Additionally, Chinese firms have come to brand themselves as “professional,” international, and more attuned to concerns voiced in foreign regions, particularly from trade unions. Local corruption is another issue that often sparks con-


For China China’s incentive for entering into Foreign Trade Associations (FTAs) and FDI projects had very little to do with gaining access to Latin American markets, which are nominal relative to China’s other export markets. Rather, China entered into these agreements for political and strategic reasons.7 First and foremost, China saw the opportunity to balance the historically dominant role of Western powers in Latin America. Adding to the flourishing Sino-Latin American economic ties, extra-regional trade and investment are further being promoted through proposals such as the “One Belt, One Road” initiative, the New Silk Road, and the Chinese-led Asian Infrastructure Investment Bank (AIIB). Chinese economic and political measures have already prompted a series of counter-balancing measures from other developed countries, who similarly advocate boosting trade or reestablishing relations with developing countries and their regional organizations. To begin with, the United States’ recent restoration of diplomatic ties with Cuba was, among many other political strategies, an attempt to remedy existing anti-Americanism in the country and the rest of Latin America.8 This brings the US a step closer towards ending the trade embargo still in place and eventually improving both diplomatic and economic connections to Cuba and Latin America. Another initiative is the proposed Trans-Pacific Partnership spearheaded by the United States and Japan and formed by twelve countries on the Pacific Rim, excluding China. This trade agreement is not mainly about cutting tariffs, but rather about setting new rules for global commerce; by leaving China out of negotiations, the United States has to a certain extent rigged them in its favor. “If China doesn’t promote its own ideas for trade, it will be influenced by those of others,” says Zhou Mi, a researcher in a think-tank under China’s commerce ministry.9 Evidently, China must remain close with its Latin American allies in the face of such a competitive global atmosphere. For Latin America The advantages to strengthening trade ties are most apparent for China, which assumes a neocolonialist profile in result. Nevertheless, there is also a significant series of advantages for Latin America in choosing to continue its alliance with China. As previously mentioned, China and other world powers increasingly compete for

spotlight hurj fall 2015: issue 21 involvement in Latin America. Instead of assuming a position of dependence, Latin America can reap its own benefits and liberate itself from both Western financial institutions like the World Bank, and from massive Chinese financial inflows. There are clear signs that wider options abound for the region in terms of financial and humanitarian aid. At the 2015 EU-CELAC Summit in Brussels last June, leaders of the European Union expressed renewed interest in deepening ties with Latin America and forging a partnership for the next generation, mainly through establishing sub-regional schemes within Latin America and the Caribbean. The summit called for more cooperation on peace and security, as well as for an agreement to step up cooperation on climate change, the post-2015 development agenda and the war on drugs. The EU announced the projected establishment of an EU Trust Fund in support of the Colombian post-conflict phase, and envisioned future efforts to increase transatlantic connectivity, investment in joint education programs, and trade-boosting projects.10 China is making similar offers of aid, with the key difference of its non-interference policy. While the policy itself is a double-edged sword that often involves transparency and corruption issues, the massive amount of Chinese financial investment in Latin America has contributed to improvements in infrastructure, transport and areas like education and healthcare. In addition, Chinese loans and currency swaps for debt restructuring have provided necessary, immediate relief for countries like Argentina and Venezuela. This has resulted in loan-for-oil arrangements with the latter country, which repays much of its loan with the proceeds from long-term oil sales to China. Ecuador has struck similar deals, and Petrobras, Brazil’s state-controlled oil firm, negotiated a $10 billion credit line from the China Development Bank in 2009.11 Of course, it is no surprise that Chinese money is welcome in unstable financial markets, and Latin American countries must look towards long-term solutions more assertive roles in future deals. Another added benefit to the continued alliance with China is the prospect of participation in the AIIB. Despite limited Latin American involvement so far – since only Brazil forms part of the multilateral investment

focus bank – opportunities for collaboration still abound. More schemes for economic inclusion and collaboration are yet to be drafted, and 18,486 AIIB shares are yet to be allocated. Therefore, Latin America does have a measure of influence over the actions of global powers and should develop its negotiation strategies in order to better promote its own needs.

Neo-Colonialism or Alliance? It is imperative to consider the asymmetries in trade between China and other developing nations objectively. Patterns of trade and concentrations of products traded are natural consequences of the Chinese model of economic development. It is crucial for Latin American countries to find a more proactive role in future negotiations in order to achieve more comprehensive benefits for all regions involved. Most importantly, by reinforcing a dynamic of interdependence, Latin American countries can harness the influence they actually possess in negotiations with China and put this leverage to strategic use.

References: “East of Africa (and West of China): Chinese Business in Africa” (2010), Harvard Business School, Case Study prepared by Dr. Carola Ramon-Berjano under the supervisión of Dr Marcus Schuetz. “America Latina y el Caribe y China. Hacia una nueva era de cooperación económica”, CEPAL, 2015. “Infographic: China-Latin America Trade,” Americas Society/Council of the Americas, Elizabeth Gonzalez, 9 January 2015 TradeMap. “China-Latin America Finance Database,” Inter-American Dialogue, Kevin P. Gallagher and Margaret Myers, 2014. “China and Latin America – Problems Or Possibilities,” Julie Klinger, Berkeley Review of Latin American Studies, Spring 2013. Why the United States and Cuba are cosying up”, The Economist, May 26 2015. “The Trans-Pacific Partnership: Into the home stretch”, The Economist, July 25 2015. “EU and Latin American and Caribbean leaders agree to deepen their partnership,” European External Action Service, June 12 2015, http://www., (accessed August 5, 2015) “Flexible friends,” The Economist, April 12 2014, http://www.economist. com/news/americas/21600686-china-lends-disproportionately-countries-lack-other-options-flexible-friends, (accessed August 5, 2015)



hurj fall 2015: issue 21

The Indian National Election Arpan Ghosh, Class of 2017 International Studies

The Indian National Election of Asia’s oldest de2014 catapulted mocracy into a new political era. After a grueling five-week campaign, the candidate of the right-wing Bharitya Janata Party (BJP), Narendra Modi, was elected Prime Minister of India on May 26. This marked the first election in the country’s 67-year history in which voters supported, in a staggeringly clear mandate, a non-Congress affiliated party1. The BJP captured 336 of 545 Lok Shaba seats, or an unprecedented 61.7% of the total2. This sharp turn to the right could spell not only the ascendance of the BJP but also the end of the left wing, dynastical Nehru-Gandhi style of governance that has dominated India since its birth in 19473. This paper will examine the factors that helped produce such an unprecedented–and unexpected-victory for both Modi and the BJP-led National Democratic Alliance (NDA). By analyzing the political climate of India before Modi’s win, this paper will attempt to show how such a climate shaped Modi’s campaign, and to analyze the effectiveness of the strategies used by the BJP and Modi’s campaign staff in achieving such a decisive, clear-cut victory. The Landscape Modi’s 2014 victory is a powerful example of how quickly representative democracy can be altered by electorate discontent4. The United Progressive Alliance (UPA) – the leading coalition since the late 1990s and the 2000s, which includes the popular Indian National Congress (INC) Party – had ruled India during a time of economic prosperity, with an average annual growth of 8.2% in the Gross Domestic Product. However, the years following the global 2008 recession did not bode well for India’s economy5. Except for in 2010, India’s yearly GDP was far below the previous decade’s average: 7.4% in 2008 and 2009, 6.8% in 2011, 6.5% in 2012, and an abysmal 4.4% in 2013. Due to such depressing growth, India’s very large young adult population (half of the country’s 1.3 billion people are under 25) faced a low demand for jobs especially in the manufacturing sector, where profits weakened by 2% from 2011 to 2012. On top of a weakening GDP, the inflation rate continued to rise substantially, jumping to 6.27% in 2006 – a 158% rise from the previous year’s rate of only 3.97%6. Over the next several years, inflation continued to rise, reaching a 10-year all-time high of 11.9% in 2010. The inflation rate also brought down the value of the rupee (India’s


national currency), which slipped to an all-time low of 68.75 INR against the U.S. Dollar, decreasing the value of Indian foreign investments and thereby discouraging foreign as well as domestic investment7. In the face of such warnings, the Indian government found it incredibly difficult to persuade both foreign and domestic investors to partake in efforts to revitalize the economy, and the UPA found it even more difficult to pass new legislation due to strong opposition from its own moderate politicians. For the Indian electorate, which had its expectation of growth raised by the successes of the pre-2008 period, the combination of economic and political stagnation came as a shock and produced backlash against the UPA-Congress majority. Large sections of the Indian electorate began to question the ruling party’s vision and policies, made even worse by revelations of government mismanagement and corruption. As a result, an angry and restless Indian populace became open to political suggestion and persuasion on a mass scale not seen, perhaps, since independence. Gujarat – A Diamond in the Rough Modi’s positive governing record as Chief Minister of Gujarat during the post-2008 crisis also played a key role in catapulting him to political center stage8. The state of Gujarat, located in India’s northwestern region, has roughly the same size and population as the UK. Since Modi’s inauguration in 2001, Gujarat has arguably become the country’s biggest industrial hub, dominating in industries ranging from agriculture to electrical engineering and even maritime services9. The state leads the country with a per annum growth in agricultural GDP of 9.8%, which is almost three times larger than the national average of 3.4%10. Modi was also able to deliver GDP growth of over 12% in the midst of a national recession between 2007 and 2012. In terms of per capital income level, Gujarat is number three in the country, behind Haryana and Maharashtra11. In terms of electrical capacity, every major city in India typically rations its power supply by shutting down service every few hours, since all of India suffers from a severe lack of electrical energy. Under his government, Modi was able to implement “Jyotigram Yojana,” an initiative that paved the way for international and domestic companies to create a sustainable infrastructure that currently provides a 24-hour supply of electricity to Gujarat’s major cities and 18,000 rural villages. Gujarat is the only state in India that has achieved this impressive status. At the same time, Gujarat’s power plants have the capacity to produce such massive amounts of en-

hurj fall 2015: issue 21 ergy that the state has sold its excess to the neighboring states of Maharashtra and Madhya Pradesh12. By focusing on infrastructure, Modi tackled several issues that faced Gujaratis at various socioeconomic levels – in spite of the argument that lower-income farmers and villagers benefitted the most, thus stimulating Gujarat’s agrarian economy. On top of achieving domestic growth, Gujarat has drawn attention from international corporations like America’s IBM and China’s tech giant, Lenovo, who have established branches in the state13. How exactly did Gujarat become an economic powerhouse in India? Modi was able to produce such drastic developmental changes in Gujarat due to his pro-business, “less government and more governance” attitude. Moreover, with the Gujarat “model” spreading across India, Modi was able to portray himself not only as a financial guru with visionary ideas to jumpstart India’s economy, but to establish a track record as a qualified chief executive ready to become Prime Minister. Modi argued that foreign investment should be encouraged rather than resisted, and that a sustainable and globally respected economy could only emerge as a function of infrastructural development similar to that in Gujarat14. Modi’s campaign also made much of the impressive economic data from his tenure in Gujarat. Numerous state-level statistical indices, including quality of life, agrarian output, and average income, placed the state in the top five, further validating Modi’s approach. During his political rallies and interviews, Modi suggested that such immense gains could be a reality for all of India, whereas electing Rahul Gandhi would only perpetuate national stagnation. In the end, an overwhelming majority of voters believed him. Corruption as a Factor in Electorate Discontent Economic disappointment and discontent may have been enough to convince many Indian voters to switch their historic allegiances; however, another key issue in the minds of voters was political mismanagement and gross corruption by Gandhi and within the Congress party15. In the previous decade, countless news organizations and party insiders had helped find several Congress party members guilty of re-appropriating federal and state funds for personal uses, as well as express-

focus ing favoritism in delegating authority. These corruption scandals led many Indians to label the Congress party as weak, unable to combat corruption and graft, and thus a hindrance to the progress of the nation. A study conducted in 2013 suggested that around 30% of federal and state elected representatives faced criminal charges, many of them involving corruption, as well as murder and rape16. Although many BJP members also faced corruption allegations, those were never perceived as so endemic. By contrast, much of the Indian public, as well as the BJP, criticized the Congress party for safeguarding corruption and shielding its leaders from impeachment and prosecution. Millions of Indians, as well as politicians from local parties once allied with the Congress party, united to form new parties devoted to ending corruption, and focused their attention on election candidates who not only vowed to fight corruption, but also seemed politically able to do so17. For many Indians, Rahul Gandhi represented a coalition of Congress-party members who were skilled at circumventing corruption allegations rather than eliminating crimes. Therefore, the electorate believed Gandhi’s strict allegiance to the Congress party would translate to the national level, where Gandhi would act almost sympathetically towards political actors found guilty of graft or similar allegations. On the other hand, Narendra Modi, who faced civil allegations of his own as a Member of Parliament (MP) for Gujarat, successfully dissuaded the public. Despite multiple race-based allegations, especially towards Muslims, Modi was able to escape relatively unscathed. Rahul Gandhi and Arvind Kejriwal’s efforts to portray Modi as a gruesome leader complicit in the murders of Muslim minorities in India failed. It became increasingly clear during the months before the election that the majority of the electorate was concerned with job growth and the economy, and not with efforts to impugn Modi’s character based on old and unproven allegations18. Technology and Social Media Modi’s victory can also be attributed to the efforts of his campaign staff in using technology to reach as many Indians as possible. In previous years, access to the In-



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ternet belonged to the few privileged enough to own speeches, or edited reports for their daily and weeka computer and find relatively reliable electricity and ly broadcasts. Modi was the first candidate in the hisconnectivity. However, as access to computing devices tory of Indian elections to exploit American-style “citbecame a financial and viable option for larger num- izen journalism” and “crowd sourcing” in this fashion. bers of Indians, especially through the introduction of By contrast, both Gandhi and Arvind Kejriwal, each of smartphones and cheap netbooks, young adults start- whom held numerous mass campaign rallies, failed to ed leaving a digital footprint of their own through pop- establish a competitive presence on broadcast televiular services like Twitter, Facebook, Google +, and the sion or in newspapers. By losing the social media war, recently defunct but incredibly popular Indian platform, Modi’s opponents also failed to compete effectively in Orkut. These services quickly emerged as platforms the traditional media war. for commercial advertising, e-commerce, and social networking; however, they also contained explosive, if Religion and the Campaign latent, political potential as avenues for reaching and Modi’s campaign success also resulted from his surmobilizing voters19. prisingly effective use of religion as a symbol of moral Namenda Modi’s 2014 election campaign was the first strength and unity rather than sectarian division25. In in India’s history to understand the potential of the theory, Modi’s religion–especially his Hindu nationalism, new media. Modi hired his longtime supporter and in- and his ethnic and regional roots in Gujarat-should have formation technology/social media connoisseur Hiren been an asset to Gandhi and the other candidates, alJoshi as his Officer on Special Duty (OSD IT) to over- lowing them to portray Modi and the BJP as too narrow see a team of over 2,000 volunfor a modern, secular country. That teers managing online information formula had worked for the ConThe campaign dissemination20. gress party and the Gandhis since quickly took advantage of India’s the time of independence. Modi’s campaign was Modi’s campaign was able to transgeneration of millennials by delivering powerful and positive messages what could have been a major able to transform what form to voters across the country right political liability into an asset. Hininto their handheld devices, bar- could have been a major duism, in fact, is a major unifying raging them with political slogans, in India but is rarely appealed political liability into an factor videos, info-graphics, and statistics to by the Congress party due to its asset. demonstrating the BJP’s superiorimodern, secularizing ethos. Modi ty to the Congress party. Targeting decided to take advantage of his youth was especially critical since personal Hindu background to porthis demographic had so enthusiastray himself as a spiritual and relitically backed Gandhi and the Congious individual and thereby sharpgress party in the recent past. Utilizing social media so en his public image in contrast to Gandhi. For example, effectively, in contrast to Gandhi’s own lackluster and when Modi travelled to Varanasi in the state of Uttar outmoded media efforts, helped brand Modi as the dy- Pradesh for a political rally, he began with a traditionnamic new face for change in Indian politics21. al religious ritual from a temple near the Ganges River, To provide some perspective on the shear breadth of a sacred site for Hindus26. His demonstrated devotion Modi’s online footprint, his Twitter followers increased to Hinduism provided an antithesis to the secular Confrom just a few thousand followers in 2009 to roughly gress party. Many voters, perhaps, imagined that India 400,000 by November 201122. Modi also demonstrated needed a divine mandate amidst high inflation and othsupport for cultural and linguistic diversity created not er economic concerns – a mandate that could be fuljust one Twitter handle for English speakers, but a total filled by Modi himself. of nine handles to cover the nine most spoken languag- Essentially, Modi described himself as an individual sent es in India. By 2010, Modi’s Twitter followers had jumped by God to fix the problems caused by a secular United to over a million, and by July 2014, he had amassed more Progressive Alliance and Congress party. He antagothan five times that many23. By contrast, Rahul Gandhi nized the Congress by emphasizing its numerous acts did not even own a Twitter account, and his Facebook of wrongdoing. Modi successfully swayed many voters page never became operational for political purposes, off the fence through his political prowess and his image of moral righteousness, seemingly granted him by crippling his online campaign advertising. On his personal website, Modi posted dozens of vid- none other than the gods themselves. eos of his rallies and campaign appearances across That said, Modi’s campaign was careful not to exaggerthe country, including videos produced, uploaded, and ate its portrayal of Modi as a “savior.” While plucking the maintained by his supporters that were therefore copy- chord of Hindu religious sentimentality, Modi kept the right-free24. This not only allowed Modi’s most eager overall focus on his experience as a leader and his abilconstituents to shape his campaign from the “bottom ity to identify with voters of all backgrounds. His “chaiup,” it also provided TV stations all across India with wala- chai pe charcha” campaign events, during which a video database from which to air sound bites, full


hurj fall 2015: issue 21 he spoke with small groups of voters while drinking chai (tea), served to brand him as a down-to-earth and personable leader who could relate to the average, financially-strapped or impoverished Indian27. Modi was able to highlight his humble beginnings by alluding to his childhood occupation as a tea vendor, suggesting that anyone could become successful in India. This broad narrative proved as successful in garnering votes from middle-aged Indians in rural areas as from younger tech-savvy voters in cities. Modi’s approach – broadly secular but tinged with emotive appeals to Hindu religiosity – reflected his sophistication in dealing with and balancing the diverse mindsets of different voter groups. While grounded firmly in the past and traditional principles, Modi seemed uniquely suited to lead India into a more dynamic and modern future. Conclusion and Implications Narendra Modi and the Bharitya Janata Party won decisively in 2014. There is no doubt that this domination has brought a dramatic change to Indian politics, one that may be difficult to reverse in the short term. However, the Congress party has not disappeared. The National Democratic Alliance and the BJP do not control the upper house, or the Rajya Sabha, of India’s parliament. To secure complete parliamentary control, the BJP will need to undertake sustained coalition-building over the next several years. What Modi can do, and has already started to do, is govern from a position of strength at the national level without having to constantly appease regional parties after the example of past United Progressive Alliance governments. Moreover, in dealing with BJP-led states like Uttar Pradesh and Gujarat, Modi will succeed in bringing decisive reform. In theory, these reform efforts can be modeled for other states, extending the BJP’s brand and influence. What will happen to the Congress party? Five years ago, few could have accurately perceived that a popular party essentially created by Jawaharlal Nehru and Mahatma Gandhi could be diminished into such a small minority in the Lok Sabha. If the BJP fails to deliver on promises made during the campaign, and India’s economic troubles continue, the Congress party could well experience a revival; however, no one should underestimate the damage already done to the party’s standing and credibility with voters. If Modi and the BJP succeed, even slightly, in bringing needed change, the Congress party could well be nearing its end. Regional parties all over India could experience a similar fate. Even in West Bengal, a one-time exclusive bastion of Communist Party, the BJP has made unprecedented inroads, leading some analysts to predict a pending collapse of the Indian left. The BJP also managed to infiltrate southern India, an area mostly domi-

focus nated by regional factions focused heavily on cultural identity issues. These factions, too, have become aware of the BJP as a force to be reckoned with, suggesting the magnitude of discontent with the Indian status quo and the potential for shifting age-old political alliances forged during the period of Congress party dominance. In the future, every challenger to Modi and the BJP will need to study the extraordinary success of the 2014 campaign. Both domestic and international media has painted an image of the Congress party and Rahul Gandhi as inefficient, powerless, and corruption-packed. On top of the party’s massive electoral defeat, Gandhi himself has suffered from vast attacks on his character, and many pundits have suggested that he may not have a political future. At a minimum, Gandhi and his party will need to reinvent themselves politically, especially among the young adult demographic. In part, this will involve changing their campaign style by relying far more heavily on social media. Moreover, they must be willing to spend far more money on election campaigns, an idea that is controversial with the Indian electorate despite the BJP’s recent victory. Modi and the BJP have clearly helped “Westernize” Indian elections. How that will appear to the electorate in time remains to be seen. Time will also tell whether Modi and the BJP can deliver on their far-reaching promises of governmental reform and economic prosperity. However, it can be inferred that Modi has almost singlehandedly transformed how Indian elections will operate henceforth. In fact, Modi’s campaign will be studied, dissected, and analyzed by political scientists for years to come, and it is unlikely that Indian elections will ever occur in the pre-2014 mode again. References: India Election Historic for Many Reasons. Perf. Tanvi Madan. The Brookings Institution. 19 May 2014. Experts Discuss Historic BJP and Narendra Modi Victory in India’s Elections. Tanvi Madan. Perf. Milan Vaishnav, Sadanand Dhume, Richard Rossow, Druva Jaishankar. Brookings India Project. The Brookings Institution. Srivastava, Kanchan. “Muslims Prosper in Gujarat and Kerala; UP, Bihar the Worst.” Domestic News and Analysis India. DNA, 22 Mar. 2014 Kotwal, Ashok, and Arka R. Chaudhuri. “Gujarat’s Growth for Growth’s Sake.” Election 2014. Indian Express, 3 Apr. 2014. Limaye, Yogita. “India’s Economic Growth Slows down.” BBC News. 28 Feb. 2014. Web. 31 Aug. 2014. Malik, Ashok. “Capitalist Hero: How Modi Made Reforms Work for Gujaratis.” Hindustan Times, Arya, Anita, and Niti Mehta. “Performance of Gujarat economy: An Analysis of Growth and Instability.” (2011). Malik, Surabhi. “From Narendra Modi’s Team, Some Stats: 437 Rallies, 5827 Events, 3 Lakh Kilometres - NDTV.” NDTV Elections 2014. “‘Power-full’ Gujarat Gives 24-hour Electricity.” The Times of India. 4 Mar. 2013. Malik, Ashok. “Capitalist Hero: How Modi Made Reforms Work for Gujaratis.” “Corruption Could Be a Curse Congress Must Battle in Elections.” NDTV. Thomas Reuters, 17 Oct. 2013. India Election Historic for Many Reasons. Perf. Tanvi Madan. The Brookings Institution. India Decides 2014. Dutt, Barkha, and Vikram Chandra. NDTV. Did Modi Win India in the Style of US Presidential Elections?” Hum Log. NDTV.



The Papal

Jubilees of Renaissance Italy left an indelible mark on Rome and Catholic culture. Although historians cannot travel back in time to experience the opulence and sanctity of the anni santi, Johns Hopkins has a magnificent collection of books and objects that act as windows onto the past, and allow us to reconstruct the fascinating culture of Early Modern Roman Catholic pilgrimage specifically during the years of Jubilee. These windows through time provide insight into the religious, political, and social life of the period: the objects were produced for a audience ranging from humble pilgrims to Renaissance Popes, and the books recorded for posterity the wonder, grandeur, tradition, and religion of the Holy Years. Rome displaced Jerusalem as the ultimate Catholic destination when the Holy Land became less accessible after its conquest by the Ottoman Turks. The traditional spiritual benefits of pilgrimage were enhanced by the sale of Holy Year indulgences, which some likened to rebaptism in the ability to remit sin and damnation. The urban fabric of the city of Rome itself had grown to awe-inspiring heights with the revival and expansion of the ancient city and the construction of the largest church in the world: the new St. Peter’s basilica at the Vatican. Despite the ever-present challenges of physical danger, poor living conditions, food shortages, periodic lawlessness, and the threat of plague, pilgrims flocked to Rome in the hundreds of thousands in search of personal salvation, renewed sacred experiences and spaces, and the saving power and promise of holy relics—above all, the tomb of St. Peter himself. The first Papal Jubilee began in February 1300 under Pope Boniface VIII in an effort to reinvigorate, renovate, and glorify Rome with new works of art and architecture intended to define the city for centuries to come. The early Modern Popes continued this tradition; Sixtus V continued an ongoing Renaissance campaign to impose order on the medieval city, in part by resurrecting the ancient obelisks of the imperial Roman past in order to glorify the Vatican by making it visible from multiple vantage points. This incredible feat of engineering was completed by Vatican architect Domenico Fontana. Soon obelisks across Rome created awe-inspiring vistas of the central piazzas and guided the crowds of pious travelers to the important station churches. Domenico Fontana recorded his engineering triumph in the book, Della trasportatione dell’obelisco Vaticano: et delle fabriche di nostro signore Papa Sisto V, of which there is a copy in the Johns Hopkins Special and Rare Books Library. The book includes full-page engravings of the new apparatuses used to move the obelisks – like complex systems of gears and pulleys and death-defying ladders – and of the thousands of laborers and hundreds of horse teams needed to complete the project. Domenico Fontana’s legacy inspired many, and the changes he made to the piazzas of Rome remain to this day. In the nineteenth century, his work on the movement of the obelisks touched the mind of Nicolò Zabaglia, a self-taught master mason who made his life’s work the restoration


hurj fall 2015: issue 21 of the Holy City. His interest in the glorification of Rome brought him to the works of Fontana, whom he honored in his book on engineering, Castelli e ponti, printed in 1734. This book, like Fontana’s, makes use of full-page engravings. These images display the incredible and unimaginable scaffolds and ladders used in the construction and reconstruction of the Holy Places of Rome. These scenes appear to be impossible, and represent an imagined view of how Fontana was able to complete the Vatican building projects. Fontana and Zabigila’s books do not only represent a concerted effort to re-imagine and re-engineer the city, but also a keen interest in recording these changes for prosperity, as well as to be forever remembered within the history of the Eternal City. The tradition of building and renovating St. Peters Basilica persisted throughout the Renaissance. The book, Basilicae veteris Vaticanae descriptio avctore Romano eiusdem Basilicae canonico, by Petrus Mallius and Paolo De Angelis uses this long history as a decoration on the double page frontispiece. A visual “timeline” of sorts shows the construction of the original Basilica by the Emperor Constantine until the time of its completion. In the center of the architectural structure is a representation of the new Basilica, small, so as to not draw attention away from the location’s long history. This timeline presents readers with another way to understand the complex history of the creation and reinvention of the Vatican complex. This guide to the history of the Vatican again typifies a preoccupation with the careful recording of history. Here, this sacred history is guarded by St. Peter himself, whose portrait appears on the opposite page. Buildings weren’t the only things produced in celebration of the Holy Years. Records of the Holy Years were produced as souvenirs or as memorials of the celebrations. One such record in the Johns Hopkins collection, Tesori dell’Anno Santo, archives the Jubilee of Urban VIII in the year 1625. The book describes the magnificence of the late-antique basilicas, the hospitality of the Pope, and the ceremony of the opening of the Porta Santa at St. Peter’s. It also numerically estimates the number of pilgrims who made the journey to Rome in each month of 1625. A staggering, perhaps hyperbolic count showed that precisely 588,633 pilgrims made their way to the eternal city in that year. In addition to month-by-month totals of pilgrims, the book calculates the amount of alms given in specific churches and holy locations. This type of record gives historians insight into the crowds and sights of a holy year. In addition to books, other types of holy souvenirs were produced in celebration of the Jubilee. These objects rarely survive the ravages of time and use, because many were acquired for their apotropaic healing qualities. Through communion with relics of the saints and Christ himself, pilgrims believed that they could be healed or protected from the perils of modern life, including war and the Black Death. Thanks to their inclusion in books, some of these ephemeral pilgrimage tokens made it into Johns Hopkins Special and Rare Books collection. One such artifact, a handkerchief printed in 1685, is the only one of its kind in existence. This small token was plau-

A Look into Early Modern Roman Catholic Pilgrimage Culture

Taylor Alessio Class of 2016 Art History

from della trasportatione dell’obelisco Vaticano: et delle fabriche di nostro signore Papa Sisto V



from Nuova pianta et alzata della città di Roma con tutte le strade piazze, et edificii de tempii

hurj fall 2015: issue 21 with gold thread, that once held the foot of Saint Anne, mother of the Virgin Mary. It is listed on the broadsheet among those held at the Cathedral. Attached to the pillow with a red ribbon is a manuscript proving the object’s authenticity, sealed by the overseeing clergy. The pillow, like the handkerchief from Turin, is a contact relic that was likely given to important pilgrims, such as other members of the clergy. Although we cannot journey back in time to witness the magnificence of a Renaissance Holy Year, the books and objects in the Johns Hopkins Rare Books Library act as a time machine through which the fabric of pilgrimage culture can be pieced back together. From books that chronicle changes in Rome and describe pilgrims’ experiences, to objects that reflect the craze for relics, this small collection can provide modern historians a view of the ostentation, celebration, and religious consequence of Papal Jubilee Years.

sibly created for the grand revelation References: of the Shroud of Turin at its new Domenico Fontana, Della trasportatione chapel, completed by the accomDomenico Fontana’s dell’obelisco Vaticano: et delle fabriche di nosplished Guarino Guarini in 1685. The tro signore Papa Sisto V (Rome, 1590). Shroud itself is one of the most im- legacy inspired many, and Petrus Mallius, Paolo De Angelis, & BernardiTani, Basilicae veteris Vaticanae descriptio portant relics in all of Christendom, the changes he made to niavctore Romano eiusdem Basilicae canonico as it is one of the few relics known to (Rome, 1646). the piazzas of Rome recontain the corporeal ‘body’ of Christ Giovanni Battista Falda, Giovanni Giacomo de in the form of sweat and blood. The Rossi, & Georgio Widman, Nuova pianta et main to this day. alzata della città di Roma con tutte le strade, relic’s connection to Christ’s passion, piazze, et edificii de tempii…fabriche antiche et combined with the relic’s potency, modern…nel Pontifcato di Papa Innocentio XI made it an exceptionally popular pil(Rome, 1676). grimage stop. The object is dominatMarsilio Honorati & Frabcesco Caualli. Tesori dell’Anno Santo: ceremonie ed by two angels holding up the Shroud as it was seen in aprire La Porta Santa… 1625, da Urbano Ottauo (Rome, 1649). Nota delle relique insigne (Ancona, 1675). in 1685. Surrounding the holy relic are important scenes Anonymous, Embroidered cushion placed under the foot of St. Anne (Ancona, 1751). from the passion narrative, specifically scenes that include Anonymous, Printed silk handkerchief with the Shroud or Turin (Turin, the apotropaic relics, the shroud and the Veronica. Pilgrims ca. 1685) who made the difficult journey through the Alps to Turin would have been able to take home with them some of the apotropaic power of the Shroud by purchasing this handkerchief and touching it to the actual shroud’s reliquary, thereby creating contact relics. When the two materials met, some of the relic’s superabundant power could be transferred to the token, which the pilgrims could then bring back with them to give to loved ones, use for healing purposes, or offer soldiers for protection during war. Considering the power of the relics and their ability to draw pilgrims from across Europe, churches began to hunt and amass monumental collections. A broadsheet from the Cathedral of San Ciriaco in Ancona names some of the holiest relics on a “List of the most distinguished relics over many others, and holy bodies…” The list includes objects from the passion: a portion of the true cross; the point of the spear of Longinus; a thorn from Christ’s crown; and objects related to the Virgin. The proliferation of relics reflects the insatiable hunger for contact with holy people, the passion, and Christ himself. A contact relic created in the Cathedral of San Ciriaco was recently added to Johns Hopkins’ Library and attests to from Della trasportatione dell’obelisco Vaticano: et delle fabriche di the culture of relics that flourished in the jubilee years of nostro signore Papa Sisto V the Renaissance. The relic is a small silk pillow, embroidered


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Severed Ties and Future Aspirations: Youth Perspective on the Cypriot Conflict Elisabeth Fassas, Class of 2017 Biology


the context of our highly globalized and interconnected

world, the ethno-political tensions that plague the island nation of Cyprus offer an acute representation of the stifled progress inhibiting the growth of the country’s economic and social infrastructure. While the Greco-Turkish relations in Cyprus and throughout the Aegean Sea have remained contentious throughout the twentieth and twenty-first centuries, the importance of these tensions arises in their development in each subsequent generation raised within the context of conflict. The political division of the island fosters generation-old animosities whose repercussions remain relevant for the youth. This youth’s educational and employment opportunities are currently quite literally divided in half, as the island is physically divided in half, on the basis of cultural and religious affiliations. The question then arises as to whether the ideals that have succeeded in

maintaining these divisions retain any practical importance in the lives of today’s Cypriot youth. I travelled to Cyprus to do research that aims to evaluate the extent to which youth of both Greek and Turkish descent has inherited the stories of its parents and grandparents, and subsequently, the possible animosities and prejudices that these experiences foster. Upon crossing the border on one of my many trips, I met Mehmet, a 25- year-old Turk (not Turkish-Cypriot) who clearly identified himself as such despite having spent the past 21 years of his life in the Turkish Northern Republic of Cyprus. He explained his interesting position as a Turkish youth born and raised in Turkish Cyprus. I should mention that my questions did not raise the distinction between Turkish and Turkish-Cypriot identities, but that I was rather introduced to the profound nuance of the difference. “I have lived in that house [he points] for 21 years, but Turkey is my country.” The following interview has been translated from Greek into English: Elisabeth: Can you tell me about what happened here in 1974?


spotlight Mehmet: Big fish eats the little fish. Just like it happens in nature. We people are no different. Cyprus is the little fish. Everyone else is the big fish—Turkey, Greece, England, the USA. Elisabeth: You speak excellent Greek. Did you go to school on the Greek side? Mehmet: The Greek side? Oh no, no. I have never been over there. [Here I should mention that Mehmet’s store was less than half a mile away from the checkpoints from which I had just entered]. I am not allowed over there with my passport from the TNRC. Elisabeth: Are you able to travel to countries in the European Union? Mehmet: Of course. I have travelled to Turkey many times.

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soldiers stationed in Cyprus under a Greek-Cypriot agreement for protection against the possible threat of another Turkish invasion. I sat around a small round table with four Greek soldiers and three young Greek women who had left Greece and come to Cyprus in order to study law at the University of Nicosia. All of them had lived in Cyprus for a period of less than six months, and they enjoyed their coffees while reminiscing about the vibrant Greek cities they left behind. In ostensibly describing to me why there is “no place like Greece,” they mentioned Turkish presence on the island. I was not surprised to hear them use profanities against the Turks, given the historical animosities between the two cultural groups. However, I did not expect to find that these historical animosities were just that—founded almost exclusively in the Greek-Turkish history taught As our conversation shifted from a political focus to Greek and Greek-Cypriot children in elementary and a social one, I noticed very profound identifications middle school, and then exaggerated from historical meant to distinguish different “catefacts to a series of unfounded claims. gories” of people from one anoth“How can you expect these saver. Many people passing by, whose ages to have any respect for our interest was undoubtedly piqued I noticed very profound lands and for our people—because by the image of one of their own Greece and Cyprus are sister naidentifications meant tions—when they don’t even have sitting and discussing politics with a strange girl in Greek, stopped to to distinguish different respect for their own citizens?” contribute to our conversation on Dimitri, a 19-year-old soldier from “categories” of people Patras, Greece asked me earnestnumerous occasions. “Hey, I know a guy who married one of yours,” one ly. He quickly proceeded to explain from one another. man informed me. Others spoke to his point. “Well, just take a look at me about the Charles Hebdo shootShariah law,” he said, “and how they ings that had recently taken place oppress their woman. A man who in Paris, and spoke to me about the can’t even respect the rights of his inherently peaceful nature of Islam. mother as a functioning member of When I turned to leave after hours of lively conversation society, of course, has no problem coming into a foreign with many people, Mehmet stopped me and insisted on and [sic.] raping our mothers and our sisters. All those clarifying one final point: “I have a problem only with tribunals ‘investigating’ should take a break from all the Greek-Cypriots,” he said, “not with Greece or Turkey or history and look at pure common sense.” Cyprus, although I do wish I could cross the checkpoint. “Just look at what they did in Paris,” Petros, another solMy problem is an issue of trust. I don’t know what they dier from Crete, chimed in. As quickly as it had begun, think over there. Do they hate us? Do they like us? Do the casual conversation about Greek-Turkish relations they care? I don’t know their opinion and that is a prob- within Cyprus shifted to a wider – and perhaps more lem.” relevant to these young men – conversation about the I had the unique opportunity of interacting with Greek positions of Turkey and Greece within the European context: Should Turkey be admitted into the European Union and Eurozone? Should it have to change the religious associations of its government before it is? As I hope I have illustrated here, the issue of the Greek-Turkish conflict and its continued presence on the island still remains at the forefront of political and personal concerns for Turkish-Cypriot youth. Its passports and identification cards, issued by a country that lacks official recognition from every world power except Turkey, limits occupational and travel opportunities. As Mehmet so poignantly described, Turkish-Cypriot youth is forbidden from crossing the checkpoint established within its own city. Greek-Cypriot youth by contrast, can traverse the border freely with the appropriate documentation. It is these physical restrictions, I have come


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to understand, that place the Greek-Turkish conflict and the issue of the island’s division at the political forefront for Turkish-Cypriot youth. Also, the alleviation of this particular division has distanced Greek-Cypriot youth from a tangible reminder of conflict, allowing their political focus to shift to more contemporary issues and their social prejudices to remain stuck in the hateful and largely uninformed discourse of the twentieth century.


humanities and social sciences

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Decisions to Escape the Margins: A Look into Runaway Youths and Teen Suicide in Light of the Imagination of the City Sungbae Paul Park, Class of 2014 Anthropology Homogenized Ideal of the Normative Family and Productivity The ‘50s-era war-torn and agrarian-based economy of the Republic of Korea experienced unprecedented growth in the 1960s-90s. After an economic crisis in 1997, South Korea swiftly recovered and became the 15th largest economy by nominal GDP, according to The World Bank. The country is home to the world’s leading industrial corporations and has seen remarkable growth in its labor force, stock capital, and productivity. An integral part of this growth, I argue, was the rhetoric of ‘One People’ or Danil-Minjok, which connotes a nation-state of one ethnic group with little to no ethnic diversity, and which fostered a homogenous ideal of the normative family and productivity. I do not argue that this cultural uniformity had a direct influence on the economic boom. Instead, I suggest that this idea is very much interwoven into the imagination of Korean productivity and, consequently, related to the ideal of the normative family. The rhetoric of ‘One People’ is rife in social science textbooks, in advocacy efforts for re-unification with North Korea, and in efforts to bolster the economy, as well as birth rates. Each and every citizen was expected to be a productive member of society by upholding the ideal of the normative family – that is, to form nuclear families and have children – and belonging to the capitalist labor force. Anne Allison similarly argues that Fordist Japan had embraced a principle of “reproductive futurism,” and she focuses on what happens to a nation-state when, slipping in its ability to (re)produce, it consigns itself to the exclusion of any futurity. However, my object of inquiry here is different. Instead of focusing on pervasive social precariousness, I focus on individuals in the margins who seek to escape the social structures vested with this ideal of productivity and the normative family. By drawing attention to South Korean runaway youths and students who commit suicide, I take a look into the lives of individuals who struggle against both the idealistic social structure and the policies supporting these ideals. According to the “Current Report on Runaway Youth” from the Ministry of Gender Equality & Family, the run-


away population increased by fifty-seven percent from 2007 to 2011. As of 2011, 29,281 youths have run away due to: conflict with parents (51.3 percent); the desire to play (29.2 percent); the desire to have a free lifestyle (25.5 percent); the displeasure of school or studying (18.5 percent); and the pressure to get good grades (13.3 percent). Although survey reports reveal only a limited facet of the complex reasons surrounding the decision to run away, I would like to note here the interconnectedness of the two domains of home or family and school. Academic success is not confined to the space of the school; it permeates a youth’s and his or her respective parents’ values as a member of the family or home. On the other hand, Korean Statistics (KOSTAT) reports that the largest cause of death for youth aged 15 to 24 is suicide. When considered on a global scale, this number becomes far more alarming. According to the Organisation for Economic Co-operation and Development (OECD) library, suicide in South Korea ranks first among OECD countries. South Korea has 33.5 deaths per 100,000, Hungary comes in a distant second, with 23.4, and many other countries have numbers in the

Modern Seoul, South Korea

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humanities and social sciences

teens or single digits (in 2010). This statistic indicates him to a secluded motel, which serves as a home to that nearly 44 people take their own life every day in this gachool-fam. Renting out two rooms right next to Korea. For the youth, “grades and admission to higher each other, five runaway youths live together as a famieducation” was the number one reason for considering ly: two boys, their girlfriends, and 16-year-old girl Hyunsuicide (53.4 percent), followed by “domestic conflict” Ah, who has recently joined them. The boys leave the (12.6 percent) and “loneliness” (11.2 percent). These sta- motel to grab dinner for the fam. Though nomads, these tistics are often referenced by media and government youths are not completely denied the ability to choose reports to articulate anxieties about the future of Korea. what they eat. They pick out specific brands of ramen These numbers help to draw Korean public attention noodles and different tastes of gimbab, respecting each to the morality of Korean society as a whole, instead member’s preference. For example, Jung-in, an 18-yearof blaming suicide on victims. They paint a picture of old female member of the fam, never eats the ramen runaway and suicidal youth as having problems both at noodle brand named Shin-Ramen, because it reminds home and in school. In this short essay, I will articulate her of her stepmother’s violence and disrespect for her how these problems can be understood in light of the father. The adolescents are well aware of each other’s ideal of the normative family and stories and pain. They have escaped productivity. In the Korean imaginegligence and violence – whether nation, having a normative family is The adolescents are well sexual, verbal, or physical – in their inextricably related to having a sefamilies in order to find security aware of each other’s and connectedness. Although their cure income as a productive member of the labor force. Productivity does not follow the normastories and pain. They ‘family’ in work then becomes rooted in the tive ideal, these youths seek filial minds of the youth as equivalent to have escaped negligence qualities like unconditional care, academic success. In turn, it creates acceptance, and connectedand violence... in order love, a highly competitive society for adness among themselves. to find security and olescents pressured to get into top For runaway children, it is hard to universities in order to succeed in find elements of stability or securiconnectedness. the domestic sphere and secure ty. First, their homes are transitory, stable work. Thus, the notions of often moving between streets, mothe home and school are interwotels, and friends’ houses. Also, withven, such that success in one domain cannot happen out proper identification cards or papers, they cannot without success in the other. Those who do not meet secure stable jobs, whether full-time or part-time. Even expected standards in pursuing this homogenized ide- the fam itself is often unstable: fights, break-ups, and al of successful personhood are seen as inadequate or economic difficulties drive the groups to disintegrate or lacking, and some end up running away or taking their seek members more fit for the group, whether socially lives. or economically. If there is any consistency in the runIn order to discuss how the ideal of productivity affects aways’ lives, it involves poverty and hunger. these youths’ everyday experiences, a thorough and Due to this precariousness, a social system of immedisystematic ethnography is required. This essay, howev- ate gain emerges and a reorientation of moral values er, focuses on a very specific reality of gachool [run- occurs. In the SBS documentary, 16-year old Nara says, away] youths portrayed in a documentary. I hope that “Other people pity us, right? But we don’t think that this analysis will shed some light on the everyday strug- way. We just need to be happy, right? We just need to gles of these youths – how their everyday sustenance is be happy and not die, that’s how I have been thinking.” jeopardized and how they find ways of reproducing the Another boy accounts his experience of sleeping with social order. In rejecting society’s notion of successful an elderly man for money. He says, “You just close your personhood (academic success, normative family, and eyes and get it over with. It sucks but you can get by satisfying employment), the runaway youths must find the next few days without much trouble.” Moral values other ways to tether themselves to their new social fab- constantly shift to accommodate the needs of the self ric and create meaning in their everyday lives. as well as those of the fam. Many individuals engage in informal or socially unaccepted means of making monEveryday Lives of Runaways ey, thereby creating divisions in their personal identities. Korean public television broadcasting station SBS aired Normative activities such as going to school – let alone a special episode titled “Where is My Home?” on August pursuing the ideal of the normative family and produc26th, 2012. In the segment, a journalist waits six hours tivity – are not possible for runaways. To the youths, to meet up with a gachool-fam, which translates to ‘run- the city represented oppression and control and every away fam(ily),’or a group of runaway youths who live day involved pressure to achieve in school and conflict together. After constantly changing the rendezvous lo- with parents – either about school or other problems, cation via text message, two boys aged 18 and 20 meet including negligence and violence. The pressure to do up with the journalist at the “S” train station and take well in school affected relationships with teachers, fam-


humanities and social sciences ily members, part-time employers, and friends. Without parents or teachers telling them what to do – but more importantly, how they should be – the runaway youths become free and gain control of their own decisions. While the city remains a single locality and social area, two separate spaces now exist in the imagination of the runaway youths. In a way, the city had scrutinized and controlled every action of these adolescents before they ran away. Parents and school had measured their personal worth, but running away liberated them from observing eyes. If they smoke, drink, or lead promiscuous lifestyles, no one pays attention. In several symbolic senses, they can walk in the city completely unnoticed. To clarify, I do not wish to romanticize the decision to run away from daily life. As mentioned in the beginning, one cannot ignore the prevalence of poverty, health concerns, and exposure to crime and exploitation. Still, the image of two spaces within one city and the sensation of freedom exemplify the ways in which runaway youths imagine the cityscape. This notion of freedom can only remain intact with basic needs – such as a place to sleep, a sense of security, and things to eat. I highlight the gachool-fam as a context in which these ideas can proliferate. Within the gachool-fam, runaway youths reproduce social order as an attempt to secure stability and create a new social fabric. To one another, members of the fam assume the roles of mothers, fathers, and siblings. The archetypical roles of family members are reconfigured and divided among the members of the fam. I have approached documentary film for a better sense of the everyday experience of living in the margins. By joining gachool-fams, people in the margins make meaning out of their daily experiences. By creating a notion of personhood outside the ideal of the norm, they claim: “We runaways together form a family that understands each other.” Although it is evident that those in the margins struggle to find meaning, the documentary portrays reintegration as their only hope. It expresses faith in government policies, prevention, and awareness seminars, and the resulting image of the city is that of control. The city or state is portrayed as the necessary guardian and protector of social order, combating the breakdown of kinship networks. This resonates with the image of the city painted by Park, Burgess, and McKenzie, who write, “It is probably the breaking down of local attachments and the weakening of the restraints and inhibitions of the primary group, under the influence of the urban environment, which are largely responsible for the increase of vice and crime in great cities…” Is the documentary correct about those in the margins having suffered from so many problems because their family networks have failed? Do we now wait on city and social policies to address the needs of those in the margins? Is control the necessary price of belonging to such a social order? If so, we must first expect the city to recognize the indi-


hurj fall 2015: issue 21 vidual deaths and everyday pains of those who make the decision to escape the ideal of the normative family and productivity. References: World Bank. Accessed Dec. 13th, 2013. <>. Eichengreen, Barry J., Dwight H. Perkins, and Sin. From miracle to maturity : the growth of the Korean economy. (Cambridge, Mass: Harvard University Asia Center, and distributed by Harvard University Press, 2012). Allison, Anne. 2012. “Ordinary Refugees: Social Precarity and Soul in the 21st Century” in Anthropological Quarterly 85(2): 345-370. Kim, Kwangjin. “Runaway Youths Increased by 57% in the last 4 Years... Nearing 30,000 People.” Bokji Times, Oct. 04, 2012. <http:// =timesNews&boardNo=134933568967385&command=READ&categoryId=1318851243100>. (accessed December 14, 2013). “Runaway Family - Where is my Home.” SBS Special. SBS Aug. 26 2012. compact disc. Park, Robert, E. W. Burgess, and Roderick McKenzie. The City. (Chicago: University of Chicago Press, 1984) 25.

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humanities and social sciences

Consider the Headline:

The Portrayal of Muslim Immigration in Media Sources Anna Silk, Class of 2018 International Studies In Europe today, the fluidity of migration across borders, oceans, and continents has become highly reflective not of shifts in the global dynamic, but of national attitudes. The issue of Muslim immigration and integration has ballooned into questions of European and national identity, Europe’s value systems, and the relationship between religion and the governments of the European Union. The dichotomy between the representation and reality of Islamic presence in Europe is striking. Through newspaper headlines, magazine articles, television programs, and visual campaigns, the media influences public perception and shapes European opinion on a daily basis. However, this information is often skewed towards a biased and negative perception of Islamic culture. The headscarf debate in France is a perfect case study for examining the influence of the media on depictions of Muslim immigration issues in the European context. European media disseminates biased information that perpetuates tension and a lack of understanding on issues of Muslim immigration and integration. Disillusionment The European media fuels general public disillusionment about Islamic culture and practices. The slanted cultural understanding promoted by different media formats leads to contorted perspectives on the Muslim immigration debate. As Benedict Anderson points out in “Imagined Communities: Reflections on the Origin and Spread of Nationalism,” the community of the nation “is imagined because the members of even the smallest nation will never know most of their fellow-members, meet them, or even hear of them, yet in the minds of each lives the image of their communion”1. The media acts on this imagined quality by painting a picture of Muslim identity that resonates with readers even if not indicative of the religion’s true values and culture. Tamara Vukov discusses the role of the Canadian media in drawing an association between terrorism and Muslim immigrants and explains how these “mediatized threats” aided in the government’s political agenda of a restrictive immigrant policy6. The media represented Muslim immigrants as security concerns, which image has affected Canadian government policy by taking advantage of the assumption that most Canadians had little familiarity with the details of Muslim

immigrant culture, and so creating an imagined, collective conception of Muslim terrorists. The Snopes Muslim Demographics webpage challenges the misrepresentation of the influx of immigrants. The site features a video that argues that the Muslim immigrant birthrate will overwhelm Europe, but points out that this prediction is at odds with the true demographic reality. The video compares the French birthrate of 1.8 children with that of Muslim immigrants – 8.1 children5. Snopes explains that the numbers cannot be accurate because France does not collect racial or religious statistics, and that the video misrepresents and antagonizes Muslim immigrant family values. Overstatements about the percentage of the Muslim population in nations like Belgium and the Netherlands create an image of a Europe “overwhelmed” by an unstoppable onslaught of Muslim immigrants that threaten the “Christian character” of the West5. The website mentions the work of Martin Walker, who writes that, in fact, Muslim birth rates are decreasing around the world. Snopes underlines the fact that “much of the information presented in the video is incorrect, unsubstantiated, or misrepresented”5, much like many media claims at large. Media sources tend to exploit extremes, to the effect that European society tends to regard Muslim immigrants on a spectrum of “good” or “bad”4. Mamdani defines the “good” Muslim as someone who does not overtly display religious ideology and shares Western values; a “bad” Muslim is deemed too extreme and not sympathetic to Western beliefs4. The media portrayal of exaggerated fact and fiction cleaves the Muslim immigrant community and forces a categorical division between accepted and condemned behavior. Impact The media has a large impact on the audience it reaches, and contributes to public awareness of current events and issues. The 2005 Dutch cartoon fiasco, centered on the Jyllands-Posten newspaper, highlights the serious implications and consequences of media coverage3. Vukov’s article mentions media in connection with “affective epidemics” in culture or society6. These epidemics of ideas, and usually fears, are based on something that “cements the feel of everyday life,” seeping into the public consciousness and coloring perspective6. The publication in a Dutch newspaper of twelve cartoons depicting questionable stereotypes of Islam sparked major public outcry in the European community3. In the political sector, Muslim ambassadors appealed to the Danish prime minister to counter the


humanities and social science

The Jyllands-Posten newspaper, which included 12 editorial cartoons, many of which depicted Muhammad

negative, biased attitude of the Danish media on topics of Muslim faith and culture3. Ander Fogh Rasmussen denied their motions to discuss the situation by citing the media’s right to free speech3. While their publication was justified on legal grounds, the cartoons fuel misapprehensions about Muslim stereotypes and fed into Vukov’s “epidemic” of associations. As Vukov writes, “the affective amplification that news media discourses engage in (what Hall et al. [1978] call the ‘amplification spiral’) plays a crucial role in articulating immigration, criminality and fear together by means of affective resonance”6. After the cartoons were published, unrest and discord broke out in Muslim communities around the world and protests occurred outside Danish embassies in Muslim nations3. Ambassadors pointed out that this was not the first case in which the Danish media had negatively represented the Muslim community: they cited a 2005 radio show that encouraged the killing of Muslims throughout the nation3. With such a steady stream of antagonism projected by the media, the European public has few other sources through which to form opinions or attitudes about Muslim immigration and integration issues in its respective nations.


hurj fall 2015: issue 21 Case Study The French headscarf debate France exemplifies the role of the media in framing the debate between national laïcite and Muslim presence and integration. In Why the French Hate Headscarves, John Bowen analyzes the media image of the headscarf as a symbol of Muslim immigrants’ lack of integration into the French national identity. Bowen recalls being surprised to find many negative accounts of the headscarf issue in a French bookstore. He saw titles like, Islamist Totalitarianism Attacks Democracies, and A Voile over the Republic, all suggestive of the Muslim community as “attacking” the French nation and identity2. French citizens visiting the same bookstore would potentially be negatively affected by the media maelstrom around the debate. Media coverage of the headscarf has effectively viewed an item of clothing with hostility and suspicion2. Bowen mentions the release of the documentary, Trappes at Prayer Time, which focused on a French town succumbing to the supposed “evils” of communalism2. Frédéric Brunquell explored the neighborhood, interviewing women who embraced the headscarf and school officials who denounced it2. The conclusion he made as described in the program was that, for Muslim women, the veil symbolizes male repression rather than the evocation of faith. This contradicts his conversation with Miriam, who remarks that her voile is her own personal testament to God and claims that she does not wear it out of any male-imposed requirement2. Brunquell’s manipulation of the situation portrays the headscarf as not only a violation of laïcite culture, but also a matter of gender oppression, despite Miriam’s testimony. One reporter who did notice the bias reflected that “Brunquell had correctly reported the facts but slanted them to build an image of secrecy and control”2. The wearing of the headscarf in schools is also explored in multiple documentaries and television programs. School principle Thérèse Duplaix ran one such show on France 3, showcasing scenes of tension caused by Muslim students attempting to “spread” Islamic ideology. Bowen mentions that the school community responded with outrage after the episode aired, citing that it was filled with “‘dishonesty’”2. Another striking example of a television program that misrepresents the role of the headscarf role in Muslim culture is France 3’s France-Europe-Express show2. Focusing on discussion of the voile, the panel chosen for the talks consisted of all anti-voile advocates except Dr. Abdallah Milcent, who was criticized repeatedly for supporting the right of girls to wear the headscarf2. Portraying Dr. Milcent as “an object of scorn” forces the French people to consider whether supporting the voile might estrange them from popular opinion2. Creating a media environment already prone to bias is not effective in helping French society understand the issue at stake. Anti-voile advocates believe that the headscarf is too public and overt a symbol of Islam to allow at school, a laïc space of secularism2. The scarf is depicted as sup-

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humanities and social science

porting communalism and heightening a sense of “difference” between the French national identity and Muslim immigrant culture2. However, the headscarf itself is a modest form of attire for the Muslim community, worn by women as a private symbol of faith2. By focusing so much attention on the scarf, the media creates a sense of distance between what is deemed traditional French society and so-called “alien” Muslim culture, further sundering any effort to promote integration, tolerance, and acceptance. Bowen concludes that the French media’s slant towards an unfounded and unfair representation of Muslim women and headscarves will continue to influence public opinion and act as an obstacle to integrative progress. He writes that it seems as if “only the bareheaded women and the secularist men are worth listening to for their opinions on society” and that, unfortunately, “viewers and readers also would have concluded that Muslim men and women come in three categories: Islamists, violent adolescents, and secularists”2. A shift in media politics is necessary to promote a more objective and fact-based view of the situation. Adjusting media practice in representations of the headscarf debate would form a more open and informed French public that would then be more capable of fixing, rather than fixating on, the issue. Media influence is a powerful influence on twenty-first century public opinion and thought. Harnessing its broad scope will prove truly revolutionary in altering popular opinion on any number of local, national, and global issues. Muslim immigration in Europe is likely to continue and grow over the coming decades, and integration will remain a significant and essential step towards achieving both political and attitudinal acceptance. Reading a newspaper headline, watching a television program, or listening to a radio station will remain relevant pastimes. It is up to the media to become a source of information that considers different perspectives of a news story. In this way, European society will begin to advocate political and cultural change that would benefit both Muslim immigrants and European residents and create a healthier continental community. References: Anderson, Benedict. Imagined Communities: Reflections on the Origin and Spread of Nationalism. London, UK: Verso, 1991. Bowen, John R. Why the French Don’t Like Headscarves. Princeton, NJ: Princeton University Press, 2007. Larson, Ruth Engelbreth. “The Danish Cartoon Affair.” Counterpunch. Mamdani, Mahmood. “Good Muslim, Bad Muslim: A Political Perspective on Culture and Terrorism.” American Anthropologist 104, no. 3 (2002): 766-75. “Muslim Demographics.”, Tamara. “Imagining Communities Through Immigration Policies, Governmental Regulation, Media Spectacles and the Affective Politics of National Borders.” International Journal of Cultural Studies 6, no. 3 (2003): 335-53.


science and engineering

hurj fall 2015: issue 21

Role of Exogenous ß-Carotene in Cerebral Ischemia/Reperfusion Injury in Vivo Kain Kim Class of 2019, Chemical and Biomolecular Engineering Introduction Ischemic injury occurs when the blood supply to a certain area of brain is cut off, often because of an embolism or other blockage in the blood vessels. Eventually all ischemic tissue becomes necrotic; restoration of blood supply should minimize the damage, but reperfusing tissue after thrombosis led to the awareness that the extent of injury often paradoxically increases when blood supply is restored. This exacerbation of damage – reperfusion injury – is widely attributed to the activity of free radicals that overwhelm the cells’ usual defenses, leading to uncontrolled oxidation of vital cell components. Studies of reperfusion injury present no clear solutions as of yet, most likely because of the wide array of experimental protocols. Of the potential therapies that attempt to limit the free radical generation on reperfusion, none have had consistently beneficial results in controlled trials (R&D, 2013). Mitochondrial fission is an early event in ischemic stroke and is caused by one of these free radicals, Nitric Oxide (NO). NO causes S-nitrosylation of Drp1 proteins in the mitochondria, resulting in mitochondrial fission. Mitochondrial fission is unregulated during ischemic stroke, and causes cellular stress and thus apoptosis. In contrast, it has also been suggested that NO may actually act as a protective factor in ischemia-reperfusion injury since it increases blood flow, and has beneficial effects on cell signaling and the inhibition of nuclear proteins. Nevertheless, controversy exists to this day as to the role of NO. Elucidating the biochemical and molecular mechanisms of reperfusion injury has been an active area of investigation, as any insight would be of significant benefit during both percutaneous and pharmacological reperfusion techniques (Kobayashi, 1995). Beta-carotene is an antioxidant that can inhibit iNOS, the enzymes that catalyze the production of NO. Beta-carotene metabolizes in the feces and so is easily excreted from the body; it diffuses through the blood brain barrier (BBB) with ease. Moreover, most drug reports state that beta-carotene is administered orally, which is why an oral gavage will be used in this experiment rather than direct injection to the brain. By introducing beta-carotene early to stroke patients, the amount of neural death has the potential to be reduced significantly, because ß-carotene has been shown to downregulate ischemia/reperfusion-induced oxidative damage in areas of renal tissue (Hosseini, 2009), the gastric mucosa (Seyyed, 2012), and the liver (Codoñer-Franch, 2008). Depending on the area of the brain affected, neuronal death can either be fatal or can impair speech, vision, or other sensorimotor functions;


quick actions to preserve neurons can make a huge difference in a patient’s life. This research explores the benefits of ß-carotene after blood flow has been restored to the ischemic injury. It is predicted that if ß-carotene is administered to rats suffering ischemia-reperfusion injury, then the extent of NO activity will significantly decrease and thus reduce levels of cellular stress and apoptosis, as well as other symptoms that accompany ischemic stroke. Laboratory albino rats will be used as an in vivo model and biological vehicle for the research; it is important to note that the procedures and tissue involved in this experiment were provided under a larger, separate protocol approved by the hospital facility and that no animals were euthanized for the sole purpose of this research. Methods Surgery Two experimental conditions are followed throughout the experiment: group 1, transient ischemia without beta-carotene treatment; and group 2, transient ischemia with beta-carotene treatment. 8 rats are utilized in the experiment and the baseline (pre-surgery) data of the rats serve as the control. Ischemia/reperfusion surgery is conducted through transient transcranial middle cerebral artery occlusion to cause stroke-like symptoms in which a sudden disruption of blood flow to parts of the brain occurs. The technique of modeling ischemic stroke by transient transcranial MCAO is similar to that of permanent transcranial MCAO, with the middle cerebral artery (MCA) being reperfused after a defined period of focal cerebral ischemia. After exposure and ligation of the common carotid artery (CCA), a rescue suture is placed on the common and the pterygopalatine is temporarily ligated. Then the common and internal artery is clamped off when an arteriotomy is done to the left external carotid artery and thyroid artery. A 3-0 nylon suture is then strung into the opening left after arteriotomy of the external into the internal artery (removing the clamp on the internal in the process to allow the suture to be strung all the way to the brain). The suture around the pterygopalatine is then removed. Reperfusion injury is induced by withdrawal of the suture two hours later (Buchan, 1992). Three blood samples are collected through retroorbital bleeding from each rat- one before surgery, one 24 hours after surgery, and one before euthanizing the rat. The rat must be anesthetized for this procedure. Pressure is placed on the top and bottom lids of one eye to keep the eye open and the globe pushed forward

hurj spring 2014:issue issue 21 18 hurj fall 2015: slightly. A glass microcapillary tube is placed in the medial canthus of the eye at a 30° - 45° angle toward the back of the eye. Firm, steady forward pressure is used and the tube is rotated between the thumb and forefinger to cut through the conjunctiva at the back of the eye and enter the retroorbital sinus at which time blood flows into the tube. After collecting the sample, the eyelids are closed and pressure is applied with a piece of gauze until hemostasis has been achieved. A small amount of ophthalmic ointment containing an antibiotic is placed on the eye after bleeding has stopped to act as a bandage and help prevent infection (LSSU, 2014). Collected blood samples are centrifuged to extract plasma and are stored on dry ice at -20 ºC. The rats designated for treatment are administered beta-carotene via oral gavage 15 minutes prior to performance of surgery. Such timing allows ß-carotene to be fully introduced into the bloodstream of the rat by the time the second blood collection is taken 24-hours post-surgery. The ß-Carotene is dissolved in corn oil for administration due to the fact that it is only lipid soluble and that corn oil is a nonreactive vehicle. Testing Plasma samples are then tested for presence of free radical Nitric Oxide via ELISA assay, a standard quantitative sandwich enzyme immunoassay. A standard curve is plotted relating the intensity of the color (O.D.) to the concentration of the standards. The iNOS concentration in each sample is interpolated from this standard curve. Immediately following euthanization, slices of representative brain tissue approximately 2 mm thick are obtained ipsilaterally and contralaterally from a superficial portion of the ischemic core section of the frontoparietal infarct. The slices are then kept in a 37ºC heater in TTC staining. The slices are left to stain for thirty minutes. Once staining is complete, two slices of the brain are fixed onto slides for further examination under the microscope for leukocytes. Severe white matter disease defined by standard criteria in acute ischemic stroke patients is associated with disability at 1 year and can be assessed quickly using visual rating scales (Leonards, 2012). Appearance of white matter on one side of the brain indicates successfully induced cerebral ischemic stroke. Comparative digital imaging of the brain post-surgical treatment determines the extent of ischemic injury that took place. A binocular biological digital optical microscope was used to image stained/flattened fixed brain tissue and observe for presence of leukocyte recruitment post-ischemic brain injury. The latter reflects inflammation tissue injury associated with brain I/R. Recovery Animals frequently become hypothermic when anesthetized due to inhalation of cold gases, exposure of body cavities to the room air, and loss of normal thermoregulatory mechanisms and behaviors. Hypothermia depresses all physiologic functions, including respiration

science and engineering science and engineering and cardiac function, and slows the metabolism of anesthetics, resulting in prolonged recoveries. Hyperthermia is less common, but may still occur because of excessive application of heat, hot surgery lights or malignant hyperthermia in genetically-predisposed animals. Body temperature is thus monitored frequently using a thermometer during all procedures and throughout anesthetic recovery (Kent Scientific, 2006). Breathing is periodically checked for any respiratory problems; if any issues are present the rat is administered pure oxygen until it is resolved. This observation period lasts approximately an hour and the rat is put back in its cage when fully active again. For a week, the rats are continually observed for any signs of weight loss or distress; any symptoms are recorded and carefully monitored. The rats are administered an analgesic (ibuprofen) through their feeding tube if any immediate problems arise. The rats are housed in standard caging equipment, the cage being replaced every other week. The cages are docked in a system that regulates temperature and only allows filtered air into the cages. Rats are each supplied with nesting blocks and housed in pairs or groups of three for enrichment. Additional behavioral testing is also performed on the rats; rats undergo tests two days prior to the surgery to establish a baseline and another two times after the surgery. The wire test requires rats to crawl around wires that are suspended over a bucket of water. It is observed how many times the rat stumbles while crawling over the wires; a common symptom of ischemic stroke is sudden numbness or weakness in the arm, face, or leg, especially involving one side of the body. Such instability is predicted to induce increased occurrences of stumbling, loss of balance, and lack of coordination. Results & Discussion Blood samples were drawn through retroorbital bleeding and centrifuged to extract plasma; activity of free radical Nitric Oxide was measured by iNOS ELISA and is shown above for the three different time periods of blood collection- before surgery was performed (baseline collection), 24 hours post-surgery, and post-surgery pre-euthanization. Six rats total underwent surgery, half with treatment and half without. Baseline collections for groups without ß-Carotene treatment served as the control. NO levels for different rats at each point in blood collection were averaged and are displayed in Figure 1. Values for rats without treatment were normalized to the values for the rats with treatment. The data is represented by +/- SD (n=3).

Figure 1. Levels Administration.






science and engineering (Kriz, 2006).

Figure 2. Stumbles Prior to Surgery

Figure 3. Stumbles during Wire Behavioral Testing

Figure 2 above shows stumbling prior to surgery. The data is represented by +/- SD (n=6). Asterisk marks are statistically significant (p < 0.05). Figure 3 shows stumbling before euthanization. Rats in both groups (with/without ß-carotene treatment) were tested days before euthanization. The data is represented by +/- SD (n=6). Asterisk marks are statistically significant (p < 0.05).

Several cases of evidence indicate successful induction of ischemic stroke through reperfusion surgery. Cerebral white matter is highly vulnerable to the effects of focal ischemia and indicates that stroke was successfully induced in one side of the brain; reperfusion-operated animals showed drastic contrast between cerebral matter on the dorsal half of the brain after TTC staining, a process that stains living neurons purple, leaving brain cells affected by the ischemia/reperfusion injury white (see Figure 4).

Figure 4.

Previous research shows ischemic white matter disease impairs executive functioning, information processing speed, and gait. This matches up accordingly with the behavioral testing performed on the rats, which showed the animals’ drastic reliance on the left (non-affected) side of the body to support their weight. Comparative differences in numbers of leukocytes of the immune system for the unaffected and affected sections of the brain denote inflammation in the tissue (see Figures 5 and 6). Experimentally and clinically, stroke is followed by an acute and a prolonged inflammatory response characterized by the production of inflammatory cytokines, leukocyte and monocyte infiltration in the brain


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Figure 5. Light microscope cell imaging portraying presence of leukocytes (indicated by arrows) in ventral side of brain slices (40x magnification).

Figure 6. Light microscope cell imaging portraying the lack of presence of leukocytes in brain slices (40x Magnification).

It was predicted that the level of NO would rise for both treated and untreated rats from pre-surgery to the 24hour mark, a period in which the surgical induction of stroke would cause the sudden activity of free radicals that would then rise or fall accordingly at the pre-euthanization point, at which the stabilizing effects of the ß-carotene should have occurred. The results contradict this first supposition: NO levels fell for both rats with and without treatment, although those that received ß-carotene experienced a lesser fall in levels of NO. At the pre-euthanization point, however, the rats without treatment underwent further decreasing in levels of NO, while those with treatment were subjected to a sudden rise in NO levels to a point higher than it was at the pre-surgery mark. Such data represents the direct opposite of what was hypothesized: instead of the rats receiving treatment experiencing a decrease in NO quantity, they underwent a significant influx of free radical activity. Behavioral testing indicates a similar result; the rats were suspended on a wire grate above a tub containing 2.5 liters of water to test their ability to use both body sides efficiently to navigate the “maze”. Heavy dependence on the left side of the body indicated an effective ischemia injury (see Figure 7). Prior to surgery, the number of times rats in each group stumbled are seemingly random and have no apparent trend, with no statistical significance to note. However, the number of times the rats stumbled or lost their balance on the grate is significantly augmented at the pre-euthanization point in the group that was given ß-carotene. This shows that the treated rats were affected more drastically by the reperfusion injury. Again, this is contradictory to what was previously hypothesized.

hurj fall 2015: issue 21 Preceding research studies have been conducted with rats suffering from reperfusion injury in which forms of beta carotene have been introduced via an external vehicle, such as through dietary or nutritional supplements, but not in which ß-carotene was introduced to directly infuse into the bloodstream to affect free radical activity post-ischemia reperfusion injury. In addition, studies of ß-carotene effects in ischemia/reperfusion injury rarely focus on cerebral events. Most studies generally emphasize the role antioxidants play in such a destabilized biological environment, and the consensus in previous studies show that such agents do combat against ischemia-reperfusion injury, at least in areas of renal tissue, the liver, or the heart. However, the findings of this study seemingly go against the claim stated most other publications that poor plasma status of carotene is associated with higher mortality for ischemic stroke.

Figure 7.

Conclusions/Future Research The results obtained conclusively oppose the hypothesis that if ß-carotene is administered post-reperfusion in rats with ischemic stroke, the levels of endogenous NO will decrease significantly. The rats that received treatment experienced an increased rise in NO levels in comparison to those that did not receive treatment, and the post-surgery behavioral testing indicates decreased levels of performance in the ß-carotene group as well. Thus, it can be inferred that the ß-carotene had a negative impact on the physiological and behavioral trends of the rats. These results were highly unprecedented, as previous studies have supported that antioxidants like ß-carotene have a supplemental effect in management of chronic inflammatory or degenerative conditions similar to ischemic stroke. This nevertheless presents a fresh take on the effects of beta-carotene, mostly studied as a nutritional supplement to this point, and how it could instead exert detrimental effects on symptoms of ischemic stroke. Any mention of ß-carotene being administered via oral gavage during surgically induced reperfusion injury could not be found in previous literature; the dose quantity and timing of administration was thus an educated inference founded on similar protocols, which could have affected the validity of our data. In agreement with prior literature, an intervening factor could be nitric oxide itself, and how it can actually play a protective role as well as a detrimental one. Though most evidence indicates that oxygen-derived free radicals such as NO contribute to the cellular damage caused by ischemia reperfusion, other studies have de-

science and engineering scribed endogenous NO as having the protective ability to increase blood flow and scavenge oxyradicals in sites such as the rat liver (Kobayashi, 1995). S-nitrosylation is intimately linked with reperfusion injury, helping to explain the salutary actions of statins, estrogen, and mitochondrial respiratory chain inhibitors. Endogenous NO induces S-nitrosylation and mediates the p38-signaling pathway by NMDAR, resulting in mitochondrial fission, which in turn causes cellular stress and thus apoptosis (Qi, 2013). It has been shown that exogenous NO can reverse the harmful effect of endogenous NO by suppressing S-nitrosylation of ASK1 and exerting neuroprotection during ischemia-reperfusion, thus presenting itself as a possible form of stroke therapy (Liu, 2013). Further investigation concerning the double-sided role of nitric oxide and its potentially protective applications as an endogenous free radical is ongoing. Understanding ischemia/reperfusion injury is crucial in clinical interventions following medical emergencies such as strokes or heart attacks, as well as in developing new therapeutics. These processes are also central to successful outcomes of organ transplantation. Moreover, in an era defined by increased usage of health supplements like vitamins, some of which may contain ß-carotene, it is crucial to identify any possible side reactions that may occur. References: Black, Sandra. (2008, December 8). “Understanding White Matter Disease Imaging-Pathological Correlations in Vascular Cognitive Impairment.” Buchan, A. M., D. Xue, A. Slivka (1992, February 1). “A new model of temporary focal neocortical ischemia in the rat”. Chandrasekharan Guruvayoorappan, Girija Kuttan. (2007, April 13). “β-Carotene down-regulates inducible nitric oxide synthase gene expression and induces apoptosis by suppressing bcl-2 expression and activating caspase-3 and p53 genes in B16F-10 melanoma cells”. Codoñer-Franch P, Muñiz P, Gasco E, Domingo JV, Valls-Belles V. (2008, July). “Effect of a Diet Supplemented with alpha-Tocopherol and beta-Carotene on ATP and Antioxidant Levels after Hepatic Ischemia-Reperfusion”. Gey, K.F. (1993, January). “Poor plasma status of carotene and vitamin C is associated with higher mortality from ischemic heart disease and stroke Basel Prospective Study”. Hosseini F., Naseri MK, Badavi M., Ghaffari M, Shahbazian H, Rashidi I. (2009). “Protective effect of beta carotene pretreatment on renal ischemia/reperfusion injury in rat”. Kobayashi H., Nonami T., Kurokawa T. (1995, December). “Role of endogenous nitric oxide in ischemia-reperfusion injury in rat liver.” Kriz, J. (2006). “Inflammation in ischemic brain injury: timing is important”. Lee WH1, Kang S, Vlachos PP, Lee YW. (2009, April 23). “A novel in vitro ischemia/reperfusion injury model.” Leonards CO, Ipsen N, Malzahn U, Fiebach JB, Endres M, Ebinger M. (2012, Aug 30). “White matter lesion severity in mild acute ischemic stroke patients and functional outcome after 1 year”. Liu, D.H., Yuan, F.G., Hu, S.Q. (2013, January 15). “Endogenous nitric oxide induces activation of apoptosis signal-regulating kinase 1 via S-nitrosylation in rat hippocampus during cerebral ischemia-reperfusion.” LSSU Care & Use Manual (2014). “Blood Collection.” Phillips L, Toledo AH, Lopez-Neblina F, Anaya-Prado R, Toledo-Pereyra LH. (2009, Feb 22). “Nitric oxide mechanism of protection in ischemia and reperfusion injury.” Qi SH, Hao LY, Yue J, Zong YY, Zhang GY. (2013, April). “Exogenous nitric oxide negatively regulates the S-nitrosylation p38 mitogen-activated protein kinase activation during cerebral ischaemia and reperfusion”. R&D Systems. (2013). “Ischemia/Reperfusion Injury.”


A Review:

Hypoxia-Induced Regulation of Macroautophagy in Cancer

Melaku Arega Class of 2017 Molecular and Cellular Biology

hurj fall 2015: issue 21

An emergent

property of solid tumors, hypoxia plays a key role in several hallmarks of malignant cells including metabolism and angiogenesis1. The oxygen concentration in most normal tissues is found within a range of 5-7 percent2. If the oxygen concentration in tissues dips below 3%, the tissue is said to be hypoxic. There are two well-documented types of hypoxia: acute (perfusion-limited) hypoxia and chronic (diffusion-limited) hypoxia2. Acute hypoxia is denoted by a fluctuation in sudden depletion and availability of oxygen in tissues. In tumors, acute hypoxia is a direct consequence of poor vasculatures constructed by malignant cells. Tumor neovasculature exhibits precocious capillary sprouting, convoluted and excessive branching, abnormal levels of cell proliferation and apoptosis resulting in erratic blood flow (Figure 1.1)3. Chronic hypoxia, on the other hand, is related to how far from the nearest blood vessel away a tissue occurs. In tumors, cell proliferation often exceeds neovasculature and oxygen supply for the malignant cells, leading to hypoxic conditions2. Thus, in chronic hypoxia, there exist spectrum of cells at all oxygen concentration located depending on their distance (Figure 1.1)2.

science and engineering domain (ODD)6. Hydroxy-HIF-1α is then recognized by Von Hippel-Lindau tumor suppressor protein (pVHL). This interaction leads to ubiquitylation and subsequent degradation of HIF-1α1. When minimal levels of O2 are present, O2-dependent PHD is not able to hydroxylate HIF-1α and pVHL does not recognize HIF-1α. HIF-1α escapes degradation and, instead, combines with ARNT and translocates across the nuclear membrane. In the nucleus, HIF-1α binds to an enhancer called hypoxia response element (HRE) and functions as a transcription factor1. Along with its co-activator, p300/CBP, HIF-1α promotes production of hypoxia-driven gene products1. Hypoxia and Autophagy Hypoxia in malignant cells also reprograms cellular metabolism via a HIF-1α mediated pathway by enhancing expression of glucose transporters (mainly GLUT1) and all enzymes in the glycolytic pathway (see Figure 1.2)1. The combinatorial effect of these enzymes is the preference for glycolysis over aerobic respiration6. Therefore, hypoxia is associated with insufficient amount of energy in cells due to reprogramming of metabolism in the favor of glycolysis7. Hypoxic tumors cope with insufficient energy by inducing pathways that recycle cellular nutrients of the cell. One emergent area of importance in hypoxia research is the role of autophagy in providing cellular nutrients under stress, specially its role in hypoxic tumors.


Figure 1.1 – Capillaries injected with red dextran dye (red) are traced in normal tissue (left) and tumors (right). Normal tissue capillaries thoroughly carry the red dye whereas tumor capillaries lose the dye because of leakage. Tumor capillaries exhibit compromised poor vasculature.

Hypoxia in Cancer: Hypoxia Inducible Factors Hypoxia inducible factor (HIF) is a heteromeric, DNA binding transcription factor consisting of two homodimers called HIF-1α and HIF-1β. HIF-1β is also called aryl hydrocarbon receptor nuclear translocator (ARNT)4. ARNT, as its name suggests, translocates proteins across the nuclear membrane. ARNT can also bind proteins other than HIF-1α such as aryl hydrocarbon transcription factor1. The HIF protein is synthesized from three gene products: HIF1A encoding HIF-1α; EPAS1 encoding HIF-2α, and HIF3A encoding HIF-3α; HIF-1α is the protein discussed in this review5. HIF Pathway in Normoxia and Hypoxia During ample O2 supply, an Fe2+ ion, O2, and 2-oxoglutarate dependent-enzyme called prolyl hydroxylase (PHD) covalently modifies HIF-1α via hydroxylation at specific proline residues within oxygen-dependent degradation

Triggered by several cellular stresses including hypoxia, autophagy is a catabolic process of sequestering cellular interiors such as protein aggregates and intracellular organelles into a double membranous organelle called autophagosome—after which sequestered cargos undergo lysosome-mediated degradation8. Autophagy functions to control the cytosolic biomass, organellar abundance, and protein aggregates (Figure 1.3). Autophagy is induced upon varying intracellular and extracellular cues such as: amino acid deprivation, ER stress, oxidative stress, organelle damage, growth factor withdrawal, infections, and hypoxic stress9. Autophagy regulation is implicated in many disease including neurodegeneration (Parkinson’s disease, Huntington’s disease, and Alzheimer’s disease) cancer, liver disease and myopathies10.


science and engineering Autophagy is classified into three major types: microautophagy, chaperon-mediated autophagy (CMA), and macroautophagy. Microautophagy involves a simple invagination of the lysosomal membrane into which cargos are taken up into the lysosome and subsequently degraded by hydrolases in the lysosome. CMA is the sequestration of specifically targeted proteins that are imported directly into the lysosome. Macroautophagy—referred to as autophagy hereafter—is a bulk degradation of proteins and organelles that is carried out via autophagosome and the later fusion with the lysosome11. Autophagy and Cancer: Double-edged Sword One autophagic function found at the organismal level in mammals is its function as a tumor suppressor12. It is now clear that autophagy also has a role in mitochondrial quality control, regulation of oxidative stress, and protein aggregate clearance13. All of these functions contribute to tumor suppression by avoiding a build up of cellular stresses that could lead to genomic instability or a build up of p62 that could lead to inflammation, two enabling characteristics of malignant cells14,15. On the other hand, autophagy is also a key tumor facilitator for established tumors16. Established tumors endure stress conditions such as hypoxia, oncogene-induced oxidative stress, and metabolic stress. Thus, autophagy is necessary for management and evasion of such stresses, especially in Ras activated tumors17. As a result, autophagy has a “double-edged sword” function in tumorigenesis and tumor progression16. Seeing that most solid tumors are hypoxic, what role does hypoxia induced autophagy play in tumor suppression or tumor facilitation? This is an important and emerging area of research because understanding this signaling pathway is key to designing therapeutics to inhibit or induce autophagy in depending on its varying role in target tumors. II. Hypoxia-Induced Autophagy In Malignant Cells Hypoxia has been reported to upregulate autophagy induction18. Papandreou et al showed that oxygen deprivation induces microtubule-associated protein 1A/1Blight chain 3 (LC3) processing as well as the formation of autophagosomes, both features of autophagy induction19. LC3 processing is a marker for a cell undergoing autophagy. A. mTORC1 The mammalian target of rapamycin complex 1 (mTORC1) is molecular hub that integrates diverse cellular signals and regulates cell survival, proliferation, and growth by initiating protein synthesis20. Most importantly for the purposes of this paper, inhibition of mTORC1 is critical for induction of autophagy. 1) REDD1 Regulated in development and DNA damage response 1 (REDD1) is HIF-1α dependent protein in hypoxia that leads to mTORC1 inhibition and thus, autophagy21. Under


hurj fall 2015: issue 21 hypoxic conditions, REDD1 transcription is upregulated rapidly and sharply in C6 rat glioma cells22. REDD1 is necessary and sufficient for inhibition of mTORC1 in certain cells23. The inhibitory effects of REDD1 are due its ability to sequester 14-3-3 protein via its 14-3-3 binding motif23. Under normal conditions, 14-3-3 proteins bind to and inactivate the tuberous sclerosis complex 1/2 (TSC1/TSC2) via PI3K/Akt signaling pathway. TSC2 is a GTPase-activating protein for the small GTPase Rheb. Activation of TSC2 by REDD1 leads to decreased levels of GTP-Rheb and subsequent inhibition of mTORC1 and initiation of autophagy because GTP-Rheb is required for direct activation of mTORC17. 2) AMPK AMPK is a master regulator of energy metabolism in the cell and it is activated upon an increase in the AMP:ATP ratio24. Prolonged hypoxia leads to energy deprivation because cells rely mostly on anaerobic metabolism; as a result, AMPK is activated7. During hypoxic stress, AMPK activity is also LKB1 dependent, a Ser/Thr kinase directly upstream of AMPK. LKB1 phosphorylates and activates AMPK under hypoxia, which subsequently phosphorylates and activates TSC2 (Figure 1.5)7,25. Activation of the TSC1/TSC2 complex leads to mTORC1 inhibition and autophagy induction7. On the other hand, AMPK has also been reported to directly phosphorylate and activate ULK126. B. BNIP3/NIX: HIF-dependent transcriptional regulation of BNIP3 and NIX Hypoxia-induced autophagy has been shown to upregulate the transcription of BNIP3 and NIX in a HIF-1αα dependent manner27. HIF-1α consists of two transactivation domains: C-TAD and N-TAD. N-TAD is responsible for the transcription of BNIP3 while both C-TAD and N-TAD transactivate NIX28. BNIP3 contains two hypoxia response element (HREs) upstream of its promoter: HRE1 and HRE229. Under hypoxic conditions, HIF-1α binds at HRE2 and promote transcription of BNIP330,31. HIF-2α has been reported to negatively regulate BNIP3 transcription32. Activation of BNIP3 and NIX by HIF-1α is essential for hypoxia-induced autophagy in certain cell lines20. BNIP3 is able to regulate mTOR by directly binding to Ras homolog enriched in brain (Rheb) (Figure 1.5)33. Rheb is a small GTPase superfamily that is directly upstream of the mTORC133. Hypoxia-induced BNIP3 binds to and sequesters Rheb. BNIP3 decreases GTP-bound Rheb levels thereby inhibiting mTORC1. The physiological relevance of mTORC1 inhibition by BNIP3 is unknown so far21. BNIP3 and NIX can also induce autophagy via their BH3 domain in hypoxia27. BNIP3 can heterodimerize with Bcl-2 anti-apoptotic protein, which binds and sequesters an essential autophagic protein Beclin 1 through its BH3-only domain protein30,34. The BH3 domains of BNIP3 and NIX can disrupt the Bcl-2-Beclin 1 complex without inducing cell death27. Thus, the proposed a model is one in which BNIP3 and NIX could compete

hurj fall 2015: issue 21 Beclin 1 for binding Bcl-2 via their BH3 domains. III. Conclusion: Possible Therapeutics Thus far, we discussed several ways hypoxia-induced activation of autophagy malignant cells by HIF dependent and HIF independent mechanisms. In HIF driven hypoxia-induced autophagy, BNIP3 and NIX are transcriptionally upregulated. These BH3 proteins release Beclin 1, an essential autophagy protein, by competing for sequestering Bcl-2 or Bcl-xL anti-apoptotic proteins. HIF-1α induced REDD1 and BNIP3 also inhibit mTOR and promote autophagy by sequestering 14-3-3 protein (activate TSC1/TSC2) and GTP-Rheb respectively. In HIF independent hypoxia-induced autophagy AMPK pathways leads to inhibition of mTOR via TSC1/TSC2 activation. Autophagy and hypoxia are two hallmarks of solid tumors discussed thus far. Consequently, understanding hypoxia as well as hypoxia-induced autophagy could potentially lead to therapeutic treatments that selectively exhibit cytotoxic effects and confer sensitivity in malignant cells. The phenotypic effects of hypoxia result in poor response to radiation therapy and chemotherapy. Correction of hypoxia is important for better results. EPO, which controls production of red blood cells, restores tumor oxygenation. EPO given to patients before radiation therapy has been to shown to give better response to therapy although it is quite expensive35. An alternative approach is the use of hypoxia-activated prodrugs, which exhibit oxygen sensitive reduction chemistry such that they are inactive under normoxia36. One such prodrug, tripazamine, has shown efficacy in non-small-cell lung tumors37. As discussed, autophagy is a tumor suppressor in early tumors whereas it is a tumor facilitator in established tumours14–16. So, inhibition or induction of autophagy could be toxic towards malignant cell under varying conditions. Interestingly, bioactive defense molecules called phytoalexins show antitumor activity38. Resveratrol from grapes and cucumin from turmeric are implicated in inducing pro-apoptotic ER stress in leukemia and autophagy in breast cancer respectively39,40. Phytochemicals may have clinical potential for treatment of cancer; however, their exact mechanism of action is currently unknown. However there are major challenges in designing treatments due to the controversial cell specific cytoprotective and cytotoxic roles autophagy plays in cancer. Can autophagy induce non-apoptotic cell death? It is possible that cells under severe hypoxic stress upregulate autophagy as a protective mechanism to cope with stress, but autophagy eventually fails to rescue these cells from severe stress and end up with an inevitable cell death. However, if autophagy can indeed cause cell death, what is the mechanism for autophagic cell death? What upstream signals determine whether the cell undergoes protective autophagy or autophagic cell death? Elucidation of the precise mechanism of autophagy will help us address these important questions.

science and engineering References: Harris, A. L. Hypoxia--a key regulatory factor in tumour growth. Nat. Rev. Cancer 2, 38–47 (2002). Joiner, M. Basic Clinical Radiobiology Edited by. (2009). Nagy, J. a., Chang, S. H., Shih, S. C., Dvorak, A. M. & Dvorak, H. F. Heterogeneity of the tumor vasculature. Semin. Thromb. Hemost. 36, 321–331 (2010). Greer, S. N., Metcalf, J. L., Wang, Y. & Ohh, M. The updated biology of hypoxia-inducible factor. EMBO J. 31, 2448–2460 (2012). Wang, G. L., Jiang, B. H., Rue, E. a & Semenza, G. L. Hypoxia-inducible factor 1 is a basic-helix-loop-helix-PAS heterodimer regulated by cellular O2 tension. Proc. Natl. Acad. Sci. U. S. A. 92, 5510–5514 (1995). Semenza, G. L. HIF-1: upstream and downstream of cancer metabolism. Curr. Opin. Genet. Dev. 20, 51–56 (2010). Schneider, A., Younis, R. H. & Gutkind, J. S. Hypoxia-induced energy stress inhibits the mTOR pathway by activating an AMPK/REDD1 signaling axis in head and neck squamous cell carcinoma. Neoplasia 10, 1295–1302 (2008). Jin, M. & Klionsky, D. J. The Core Molecular Machinery of Autophagosome Formation. (2013). doi:10.1101/cshperspect.a008821 Lum, J. J., DeBerardinis, R. J. & Thompson, C. B. Autophagy in metazoans: cell survival in the land of plenty. Nat. Rev. Mol. Cell Biol. 6, 439– 448 (2005). Mizushima, N., Levine, B., Cuervo, A. M. & Klionsky, D. J. Autophagy fights disease through cellular self-digestion. 451, 1069–1075 (2009). Chen, Y. & Klionsky, D. J. The regulation of autophagy - unanswered questions. J. Cell Sci. 124, 161–170 (2011). Liang, X. H. et al. Induction of autophagy and inhibition of tumorigenesis by beclin 1. Nature 402, 672–676 (1999). Jin, S. Autophagy, mitochondrial quality control, and oncogenesis. Autophagy 2, 80–84 (2006). Karantza-Wadsworth, V. et al. Autophagy mitigates metabolic stress and genome damage in mammary tumorigenesis. Genes Dev. 21, 1621– 1635 (2007). White, E. Deconvoluting the context-dependent role of autophagy in cancer. Changes 29, 997–1003 (2012). Wang, H.-G. Autophagy and cancer. Experimental & Molecular Medicine 44, (Springer Science, 2013). Guo, J. Y. et al. Activated Ras requires autophagy to maintain oxidative metabolism and tumorigenesis. Genes Dev. 25, 460–470 (2011). Schaaf, M. B. E. et al. The autophagy associated gene, ULK1, promotes tolerance to chronic and acute hypoxia. Radiother. Oncol. 108, 529–534 (2013). Papandreou, I., Lim, a L., Laderoute, K. & Denko, N. C. Hypoxia signals autophagy in tumor cells via AMPK activity, independent of HIF-1, BNIP3, and BNIP3L. Cell Death Differ. 15, 1572–1581 (2008). Wu, H., Huang, S. & Zhang, D. Autophagic responses to hypoxia and anticancer therapy in head and neck cancer. Pathol. - Res. Pract. 211, 101–108 (2015). Wouters, B. G. & Koritzinsky, M. Hypoxia signalling through mTOR and the unfolded protein response in cancer. Nat. Rev. Cancer 8, 851–864 (2008). Shoshani, T. et al. Identi cation of a Novel Hypoxia-Inducible Factor 1-Responsive Gene,. Society 22, 2283–2293 (2002). Wolff, N. C. et al. Cell-type-dependent regulation of mTORC1 by REDD1 and the tumor suppressors TSC1/TSC2 and LKB1 in response to hypoxia. Mol. Cell. Biol. 31, 1870–1884 (2011). Carling, D. The AMP-activated protein kinase cascade - A unifying system for energy control. Trends Biochem. Sci. 29, 18–24 (2004). Inoki, K., Zhu, T. & Guan, K.-L. TSC2 mediates cellular energy response to control cell growth and survival. Cell 115, 577–590 (2003). Egan, D. F. et al. Phosphorylation of ULK1 (hATG1) by AMP-activated protein kinase connects energy sensing to mitophagy. 331, 456–461 (2011). Bellot, G. et al. Hypoxia-induced autophagy is mediated through hypoxia-inducible factor induction of BNIP3 and BNIP3L via their BH3 domains. Mol. Cell. Biol. 29, 2570–2581 (2009). Dayan, F., Roux, D., Brahimi-Horn, M. C., Pouyssegur, J. & Mazure, N. M. The oxygen sensor factor-inhibiting hypoxia-inducible factor-1 controls expression of distinct genes through the bifunctional transcriptional character of hypoxia-inducible factor-1α. Cancer Res. 66, 3688–3698 (2006). Mellor, H. R. & Harris, A. L. The role of the hypoxia-inducible BH3-only proteins BNIP3 and BNIP3L in cancer. Cancer Metastasis Rev. 26, 553–566 (2007).


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