HURJ Hopkins Undergraduate Research Journal
Spring 2012 | Issue 14
examining environmental insecurity
from energy to economics 1
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a letter from the editors
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In light of technological advancement, climate change concerns and recent political events and natural disasters, it is important to consider the social, political, economic and scientific dimensions of environmental security. The concept of ‘environmental security’ encompasses various sub-elements such as responding to environmentally-caused conflicts and protecting the environment due to its inherent moral value. Since then, much attention has been focused on discussing environmental threats to the security of individuals, nations and the world. This issue of the Hopkins Undergraduate Research Journal seeks to investigate various aspects of environmental security and sustainability efforts, with articles on the promise of solar power and environmental security and policy in Senegal, the Middle East, North Africa and Russia. These pieces provide an assessment of the status of environmental policy around the world and analyze prospects of how to deal with climate change in the coming decades. This issue of HURJ was made possible by the hard work and motivation of the undergraduate writers and the dedication of the HURJ staff members. We would also like to thank the Student Activities Commission for their continued support. We hope that you enjoy this Spring 2012 issue of the journal.
With our best,
Leela Chakravarti Editor-in-Chief, Content
Paige Robson Editor-in-Chief, Layout
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table of contents spring 2012 focus: examining environmental insecurity pg. 12 ....... E ne rg y S e c ur it y in t he Midd l e E ast and Nor t h Af r i c a
Af te r t he Arab Spr ing
Nicole Salter
pg. 16 ....... T he Kre m l in’s Ene rg y St rate g y
Rahul Sabbineni
pg. 20 ....... S ol ar Powe r : T he Pat h to U.S. Ene rg y Inde p endence
Joseph Leanza
pg. 25 ....... E nv ironme nt a l S e c ur it y in S e ne ga l : T he Inters e c t i on
of D e fe ns e, D e vel opme nt , and Dipl omac y
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Mark Brennan
table of contents spotlights on research 8
Defining Autism: What’s Beyond the Diagnosis? Kimia Grace Ganjaei
10 Flotillas, Sledgehammers and Cyprus: The Worsening of Israel-Turkey Relations and its Effects on the Political Sphere of the Middle East Calvin Price 11 Off to See the Wizard: Graduate Student Life at Hopkins Isaac Jilbert
humanities 29 Stalin-Era Writers & the Russian Individual Shantini Persaud 31 British and American Experiments in African Colonization: Unsuccessful Ventures in Eliminating the Slave Trade and Slavery Catherine Rose 34 Franciscan Influence in the Walters Art Museum’s Crucifix with Mourning Virgin and St. John the Evangelist Rebecca Krishnan-Ayer 38 The Queen’s Two Heads: Victoria Disraeli Gratia Indiae Imperatrix Chet Connor
science & engineering reports
41 The Effect of Inhibition on Lactosylceramide Synthase on Polycystic Kidney Disease Jeong Hoon Park 44 Inverted Catalysts: Heavy Metal Oxide Nanoparticle Additions to Nanoporous Gold Katherine Charov & Alex Dang 47 Targets for Glioblastoma Multiforme (GBM) Immunotherapy Sung Jin Jeong 50 Investigating the Impact of Microtubule Inhibitors on EWS-FLI1 Trafficking Andi Shahu 53 Delineating the Role of BRF2 in Breast Cancer Pathogenesis Jean Fan
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hurj 2011-2012 hurj’s editorial board Editor-in-Chief, Content Leela Chakravarti Editor-in-Chief, Layout Paige Robson Content Editors Wallace Feng Mary Han Isaac Jilbert Andi Shahu Elina Tonkova Layout Editors Edward Kim Sydney Resnik Chief Copy Editor Jessica Stuyvenberg PR/Advertising Deng Pan Faculty Advisor Dr. Michael Yassa
hurj spring issue 2012 contributors Mark Brennan Katherine Charov Chet Connor Alex Dang Jean Fan Kimia Ganjaei Sung Jin Jeong Isaac Jilbert Joseph Leanza
about hurj:
The Hopkins Undergraduate Research Journal provides undergraduates with a valuable resource to access research being done by their peers and interesting current issues. The journal is comprised of five sections - a main focus topic, spotlights, and current research in engineering, humanities, and science. Students are highly encouraged to submit their original work.
disclaimer: The views expressed in this publication are those of the authors and do not constitute the opinion of the Hopkins Undergraduate Research Journal.
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Jeong Hoon Park Rebecca Krishnan-Ayer Shanti Persaud Calvin Price Catherine Rose Rahul Sabbineni Nicole Salter Andi Shahu
contact us: Hopkins Undergraduate Research Journal Mattin Center, Suite 210 3400 N Charles St Baltimore, MD 21218 hurj@jhu.edu http://www.jhu.edu/hurj
hurj spring 2012: issue 14
can you see yourself in hurj? share your research! now accepting submissions for our fall 2012 issue focus -- humanities -- science -- spotlight -- engineering contact hurj@jhu.edu
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spotlight
Defining Autism:
what´s behind the diagnosis? Kimia Grace Ganjaei, Class of 2013 Behavioral Biology
Introduction Autism is an ominously prevailing neurological disorder, now affecting an estimated one in every 110 children born in the United States, and we have yet to thoroughly map out the biological correlates of the disease (Center for Disease and Control Prevention, 2010). It has been noted that autism is rising at epidemic rates (Rice, 2009). Autism awareness in the U.S. and globally has increased greatly over the past decade, either because of the substantial rise of diagnoses, or because of the rise of the disease itself. Though there are now more services available for autistic children than there were twenty years ago,something is troubling about these advances. . There is something that is still fundamentally wrong with the concept of “autism.” Often, doctors will diagnose children with autism around 18 months of age, but what they are really describing are symptoms of a disorder that we do not truly understand. Behavioral symptoms such as lack of eye contact, incredible difficulty with social interactions and auditory processing, and repetitive behaviours, like rocking and scripting, fall into an “autism spectrum,” ranging from disorders like Down´s Syndrome to Asperger´s Syndrome. The symptomatic diagnosis of “autism” barely reaches the deeper biological essence of the disorder. We cannot truly understand what causes autism through this analysis; it is as though we are digging for diamonds with our hands. It is necessary to use different tools to clarify two central components of the etiology of autism: 1) the neurological and epigenetic correlates of autistic behavior, and 2) what could be the possible environmental cause of these developmental changes in the autistic brain.
The Neurobiology of Autism Looking at the neurobiology of autism can provide a retrospective analysis of the deficits in transcription and hormonal signalling, and lead topossible clues as to what environmental factor could initiate such changes. Past research has identified distinct neurological and hormonal differences in autistic subjects compared to those without austism. In several studies of postmortem samples, autistic subjects showed abnormal neuronal migration in the cerebellum, brain stem, and cortex (Kemper & Bauman, 1998). These regions are very primitive brain structures; the abnormalities suggest malfunctioning brain development during the early gestational period (Kemper & Bauman, 1998). Improper development of the cerebellum can result in lower muscle tone, impaired coordination, and cognitive deficits, all of which characterize symptoms of autism (Courchesne & Saitch, 1994). When developmental issues occur in such more primitive brain structures early in embryonic development, there may be a cascade of abnormal development in other brain areas involving auditory processing, social interaction, and other cognitive tasks.
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Developmental hyperserotonemia (DHS) is a hypothesis that suggests that elevated serotonin levels in the developing fetal brain may cause autism (Patricia Whitaker-Azmitia, 2005). An affected serotinergic system directly relates to tendencies in autistic behavior, such as abnormal sleeping patterns. This may be related to irregular levels of melatonin, a hormone synthesized from serotonin. Levels of melatonin, which is responsible for initiating sleep, peak at night or in the dark. Serotonin reuptake inhibitors (SSRIs) have also been shown to reduce obsessive-compulsive behaviors and repetitive tendencies, and these drugs are widely administered to autistic patients today. Serotonin has further connections with other hormones that are possibly relevant to autism. It plays a role in the regulation of the hormones oxytocin and vasopressin, suggesting that autism may consist of greatly complex, multifaceted, neuro-hormonal patterns. It has been hypothesized that increased sensitivity to abnormal levels of vasopressin—which is characteristically responsible for aspects of male social bonding and attachment—may correlate with the fact that vastly more boys are affected by autism than girls (Carter, 2006). Researchers are also interested in levels of endogenous steroids in the intrauterine environment. There is speculation that the prenatal maternal stress response, which increases cortisol levels during gestation, may also be related to elevated anxiety in many autistic individuals (Kinney et al, 2008).
Causes of Autism: Looking at Genes The cause of autism does not seem to be a single genetic mutation; there is no consistent correlation between different studiesin phenotypic patterns within families (Rapin & Katzel, 1998). It is more likely that environmental causes exacerbate a genetic susceptibility to the disorder through a multifaceted gene-environment interaction. This idea is based on current research of Hox genes, a group of genes expressed during embryonic development that are highly reliant on environmental interactions. In addition, a study of eight particular loci on the X chromosome show genes associated with synaptic and neuronal development likely to be associated with autism. This suggests that autism may be X-linked, and helps to explain why more boys are affected than girls (Deisher, 2010).
Causes of Autism: Possible Environmental Causes More research on potential environmental causes of autism needs to be done. Unless we target the responsible external factor for autism, the number of cases will continue to increase dramatically. As of right now, there are only a few consistent links between specific chemicals and autistic behaviors. Previous studies have identified several neurotoxic chemicals that may initiate an epigenetic cascade of events that potentially lead to decreased synaptic connections in social brain areas, and deficiencies in other neuronal pathways. One that seems to have a particularly strong correlation with autism is Thimerosal, which contains ethyl mercury. This is a controversial topic because Thimerosal is a vaccine preservative, which, though it has been removed from most vaccines since about 2000, causes worry that parents will avoid getting their children vaccinated out of fear of autism (Schechter & Grether, 2008). Though the association between vaccinations and autism is not proven, this does not rule out that other incidents of exposure to mercury derivatives will not have neurotoxic effects. For example,
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mercury is found in many foods such as fish and high-fructose corn syrup, which is highly consumed in the U.S. (Loveland & Tunali-Kotoski, 2005). There are nearly identical consistencies between mercury poisoning and autism; these consist of anxiety, social difficulties, identical neurotransmitter irregularities, autoimmune deficiencies, and elevated glutamate levels, often related to autistic susceptibility to seizures (Bernard et al, 2001). Recent studies have also shown greater levels of blood mercury and evidence of metal metabolism disorder in autistic subjects (Desoto & Hitlan, 2007; Geier et al, 2010). Studies of hazardous air pollutants and other chemicals in relation to autism have yet to be studied enough to be considered potential causes. If research is pointing towards examining the intrauterine environment, then environmental exposure during pregnancy should be targeted for research now.
Suggestions for Further Research It is difficult to truly understand autism, from both a personal and a scientific view. It may be useful to simplify the approach by isolating neural correlations of very specific autistic behaviors and hypothesizing as to what environmental factors may play a role. For instance, fMRI studies during moments of scripting or repetitive motor movements may provide a better understanding of the neurobiology of autism. Of the 3,000 synthetic chemicals children are exposed to today, studies like this could narrow the focus onto which ones contribute to the familiar yet mysterious name of “autism.” References: 1. Bernard, S., Enayati, A., Redwood, L., Roger, H., and Binstock, T. 2001. Autism: a novel form of mercury poisoning. Med. Hypotheses. 56:462– 471. 2. Carter, Sue. Sex differences in oxytocin and vasopressin: Implications for autism spectrum disorders. Behavioral Brain Research 176 (2007) 170186 (2006). 3. Courchesne E. Townsend, J. Saitch O. The brain in infantile autism: posterior fossa structures are abnormal. Neurology 44:214-228 (1994). 4. Desoto, M. C., and Hitlan, R. T. 2007. Blood levels of mercury are related to diagnosis of autism: a reanalysis of an important data set. J. Child Neurol. 22:1308–1311. 5. Hadjikhani N. Serotonin, pregnancy and increased autism prevalence: Is there a link?. Med Hypotheses (2009) 6. Kemper, T.L., Bauman M. Neuropathology of infantile autism. J Neuropathal Exp Neurol 57:645-652 (1998). 7. Rice, C. 2009. Prevalence of Autism Spectrum Disorders—Autism and Developmental Disabilities Monitoring Network, United States, 2006. 8. London, Eric; Etzel, Ruth. The environment as an etiologic factor in autism: A new direction for research. Environ Health Perspect 108(supp3): 401-404 (2000). 9. Loveland, K., and Tunali-Kotoski, B. 2005. The school aged child with an autism spectrum disorder. In: The Handbook of Autism and Pervasive Developmental Disorders, 3rd Edition. Volume 1 (Volkmar, F., Paul, R., Klin, A., and Cohen, D., Eds.), Hoboken, NJ: John Wiley & Sons, Inc., pp. 10. Rapin. Isabelle, MD; Katzman, Robert, MD. Neurobiology of Autism. Annals of Neurology Vol 43, Issue 1, pp. 7-14 (1998). 11. Ratajczak, Helen. Theoretical aspects of autism: Causes—A review. Journal of Immunotoxicology, 2011; 8 (1): 68-79 (2010). 12. Schechter, R., and Grether, J. K. 2008. Continuing increases in autism reported to California’s developmental services system: mercury in retrograde. Arch. Gen. Psychiatry. 65:19–24. children. Pediatrics 107:1221–1226. 13. Whitaker-Azmitia PM. Behavioral and cellular consequences of increasing serotonergic activity during brain development: a role in autism? Int J Dev Neurosci 2005;23:75–83.
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hurj spring 2012: issue 14
Flotillas, Sledgehammers, and Cyprus:
The Worsening of Israel-Turkey Relations and its Effects on the Political Sphere of the Middle East
Calvin Price, Class of 2012 International Studies Ever since the Israeli raid on the “Gaza Freedom Flotilla” on May 31, 2010, which resulted in 10 wounded Israeli soldiers and the deaths of nine Turkish citizens, the relationship between Turkey and Israel, once seen as a pillar of stability in the Middle East, has become extremely icy. Turkey’s recall of its ambassador to Israel, along with protests and harsh words from government officials, especially Prime Minister Recep Tayyip Erdoğan, have been extremely controversial on the international level1. The peaceful relations between the two countries had been a glimmer of hope for acceptance of Israel within the greater Islamic community and for peace in a region torn with violence. The Turkish government has since increased its naval presence in the Eastern Mediterranean, ostensibly to promote free travel in international waters, though maybe also due to the developing maritime economic relationship between Israel and Cyprus2, a country that has long been at odds with TurkeyW due to Turkey’s de facto control over the northern part of the island of Cyprus. While violent confrontation is highly unlikely, the flexing of muscles of the region’s two main powers allied with the West could very well hurt Israel’s goal for greater acceptance among its Muslim neighbors and could decrease the stability of an already unstable region. Turkey’s government has, since Atatürk, been highly secularized, specifically with a great deal of power given to the military to overthrow the leaders when they are deemed to be pursuing “unconstitutional” powers. However, after the arrests of major military leaders in 2010 due to the alleged “Sledgehammer” plot to overthrow the current government, the Turkish military has basically become completely subservient to the civilian government3. This situation has led to fears among some Israeli politicians and their supporters that, with Turkey’s primary secular institution losing its power, the Turkish government will become increasingly Islamist, which has already led to claims that Turkey supports Hamas and other anti-Israel groups.4 While Turkey would likely never deny Israel’s right to exist, the lack
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of support for Israel by the oldest majority-Muslim democracy in the region could influence the new (hopefully) Democratic states that are arising out of the “Arab Spring” revolutions to take a similarly cool approach with Israel. This could potentially ruin an excellent chance for Israel to improve its relations with many of its neighbors that it now has, at the very least, some political common ground with. However, despite the increasing political tensions between Turkey and Israel, there is still real hope that the relations between the countries will improve. Maybe most importantly, from 2010 to 2011, which is the same period that diplomacy completely fell through, the economic relations between the two countries strengthened greatly. In the first quarter of 2011, Turkey was Israel’s third largest export market, a six-place jump from the previous year and higher than countries such as Germany, with which Israel has traditionally had extremely strong diplomatic and economic relations.5 With the international pressure on both countries to improve their relations, and with strong economic ties that would hurt both countries extensively to lose, there remain many good reasons for the states to make up, but if they do not, then the international situation in the Middle East is likely to change for the worse. References
1. Tavernise, Sabrina. Israeli Raid Jeopardizes Relations with Turkey. In New York Times. 31 May 2011. Viewed 22 October, 2011. http://www.nytimes.com/2010/06/01/ world/middleeast/01turkey.html 2. Villelabeitia, Ibon. Analysis: Turkey’s Gunboat Diplomacy Makes Waves in Region. In Reuters. 8 September 2011. Viewed 20 October 2011. http://www.reuters.com/ article/2011/09/08/us-turkey-israel-gamble-idUSTRE7871WZ20110908 3. Tuysuz, Gul and Sabrina Tavernise. Turkey’s Top Military Leaders Resign. In New York Times. 29 July 2011. Viewed 22 October 2011. http://www.nytimes.com/2011/07/30/ world/europe/30turkey.html?_r=2 4. Katz, Yaakov. Shin Bet: Hamas operating in Turkey, China. In The Jerusalem Post. 9 August, 2011. Viewed 22 October, 2011. http://www.jpost.com/MiddleEast/Article. aspx?id=237108 5. Moise, Tal. Turkey Israel’s 3rd Largest Exporter in Q1. In Globes Online. 30 May, 2011. Viewed 20 October, 2011. http://www.globes.co.il/serveen/globes/docview. asp?did=1000650116&fid=1725
hurj spring 2012: issue 14
spotlight
Off
to see
the Wizard: Graduate Student Life at Hopkins Isaac Jilbert, Class of 2012 International Studies To undergraduates, graduate school is the Land of Oz where all our dreams will come true. Whether it is medical school, law school, or an MBA, we all believe that if only we can get that acceptance letter, our lives will be complete because whether it’s a great job, lots of money, or getting your parents off your back, graduate school is the solution. However, I too believed this, until I sat down with Dan Pasciutto, a graduate student in sociology, to find out about his trip to see the wizard, and what lessons he could share with undergraduates. It turns out that graduate school isn’t the yellow brick road that we are led to believe it is. Many routes lead to graduate school, but for Dan, four years in the army working on mechanics and logistics preceded even his undergraduate work at the University of Riverside, California. While in the reserves, he was able to complete his undergraduate work and entered graduate school at Johns Hopkins right after. Furthermore, starting as an undergraduate major in business, it was never his intention to find himself in graduate school. After taking an introductory sociology class, Dan found himself working as an undergraduate researcher on World Systems theory for Christopher Chase-Dunn (a former Hopkins professor then working at UC Riverside). World Systems theory looks at the world as the unit of analysis and finds global patterns that repeat themselves throughout history. When Professor Chase-Dunn eventually asked what Dan was doing after graduating, his response was “I dunno, I’m getting a degree in business, I’ll go get a job.” Unsatisfied with this response, ChaseDunn responded, “Why don’t you go to grad school? Change your frickin major to sociology and apply to grad school.” Everyone experiences graduate school differently, yet nearly everyone loses faith at some point. The question is whether faith is regained. Some quit graduate school and find themselves working as truck drivers before returning to the field to publish highly acclaimed works. Dan explained that he “reached a point where I couldn’t write because I didn’t feel like I knew what the hell I was doing. I couldn’t meet the deadlines that the department was asking me to meet just because I couldn’t write…I’d stare at it all day and couldn’t write anything.” Some departments in America have as much as 50% of their students drop out and it isn’t unheard of for students to wake up in the middle of the night due to stress. Graduate school is unlike undergraduate school where papers and tests occur and a grade is given and the process ends. Rather, as a graduate student you are constantly being
evaluated, but without feedback, which creates an entirely different type of stress. “Most of graduate school isn’t taking a class….graduate school is this process where ok, do your classes, write your prospectus, defend your prospectus, get your data, it’s like there’s this never ending tunnel….” But Dan made sure to stress that graduate school isn’t at all bad as he made it seemed to be in the beginning of our conversation. Rather, even though he wanted to leave the program at one point, I was assured by Dan that “I certainly have no regrets about coming back.” A piece of advice he left me with was: if you want to attend graduate school, “finding someone in the faculty you can work with really well… is pretty essential. If you don’t have someone to rely on, it becomes very problematic.” If you are able to deal with the stress and truly are passionate about what you are doing, then graduate school will be a very rewarding experience. Graduate school is more like finding the wizard than it is actually going back to Kansas. If you truly are passionate about what you are learning, then it’s the last task before going back home; however, Dan was quick to point out “If you come in with this idea, ‘I’m gonna change the world’, you get very disillusioned very quickly.” Graduate school, and particularly the end, makes you realize how much of the process was about the journey and not the actual destination. There are many ways to find your way home, but it’s up to everyone to decide what type of journey t h e y ’d like to t a k e to get there.
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Image courtesy of www.harry-potter--merchandise.com
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hurj spring 2012: issue 14
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Energy Security in the Middle East and North Africa After the Arab Spring Nicole Salter, Class of 2012 International Studies
Much of the world depends on oil and natural gas reserves in the Middle East, making this region critical to the world’s energy security. Reliance on Middle Eastern oil, a nonrenewable resource, has been growing; this has resulted in price increases and has made any disruption to oil production felt throughout the world. The Arab Spring, referring collectively to the 2011 uprisings in Tunisia, Egypt, and Libya, as well as smaller demonstrations in other countries in the Middle East and North Africa, resulted in major political disruptions throughout the region and aroused concern for the Middle East’s oil supply. While the 2011 revolutions did not have a lasting effect on the world’s energy security, they had the potential to threaten the world oil supply, particularly in Libya where oil and natural gas production significantly decreased. Most importantly, they underlined the world’s unsustainable and insecure dependence on oil in the Middle East.
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2005:
Oil and natural gas are the world’s most important energy sources. The Middle East has been the largest supplier of oil since the 1930s. In 2006, oil exports from the Middle East comprised about 22 percent of the U.S.’s imports, 36 percent of Europe’s, 40 percent of China’s, 60 percent of India’s, 80 percent of Japan and South Korea’s, and 45 percent of Canada’s. As of 2009, oil supplied about 40 percent of the world’s energy overall. The majority was used for transportation, with the Middle East supplying 37 percent of it, in addition to the 18 percent of the world’s natural gas. The most prominent oil-producing countries in the Middle East and North Africa are Saudi Arabia, Iran, Iraq, Kuwait, UAE, and Libya.1 Similarly, large natural gas reserves are in Qatar, Iran, Yemen, and Algeria.2 Demand for and consumption of oil has been continuously increasing throughout the past decade. Simultaneously, production has been decreasing, driving prices significantly upwards since 2003. By 2005, prices had accrued up to $66 per barrel, and in 2008, oil prices reached a historical high of $147 per barrel in July.4,5 Though the United States remains the largest consumer of oil, American demand for oil has been decreasing. However, demand has been rising elsewhere, particularly in developing states such as India and China where there has been a large increase in the number of automobiles. Oil consumption will increase as even more people acquire cars; the International Energy Agency predicts that by 2030 there will be over 1.25 billion cars worldwide whereas in 2009, there were about 700 million cars.6 Accordingly, world oil consumption is expected to rise by about 60 percent, with a yearly oil consumption growth rate of 7.5 percent in China and 5.5 percent in India.7 Lacking oil on their own territories, China, India, and other Asian countries will import 80 percent of their oil requirements; 80 percent of this amount will come from the Middle East and Africa.8 Previously, Middle Eastern oil supplies were most important just to the U.S. and Europe; now this region is becoming an even more important provider since more countries rely on the region for oil. The growing world demand for oil affects everyone because it results in rising prices for all. Rising prices are exacerbated by decreasing oil exports from other suppliers. Beginning in 2003, strikes in Venezuela shut down oil production. Previously, it had been considered “among the most reliable of oil exporters since World War II.”; since the strikes, Venezuelan exports have remained below their post-strike levels.9 The United States’ invasion of Iraq has resulted in Iraqi exports decreasing by 30 to 40 percent.10 Additionally, Hurricanes Katrina and Rita shut down 27 percent of U.S. oil production, as well as 21 percent of the U.S.’s refining capacity.11 Decreasing oil production in other parts of the world amplifies the importance of Middle Eastern oil. The Organization of the Petroleum Exporting Countries (OPEC) accounts for 79 percent of world crude oil reserves and 44 percent of the world’s crude oil production.12 However, between 2005 and 2007, OPEC members had no growth in production to meet the rise in world demand.13 This lagging production, combined with the decreases in exportation from other areas, has resulted in the elevated prices we face today. Considering how significant the amount of oil reserves in the Middle East is, the status of this oil will remain critical in the balance of the world’s energy security and leave those dependent on it in constant uncertainty. With the world depending so much on Middle Eastern oil, any disruption to the Middle East oil supply could be catastrophic. The demonstrations and revolutions in the Middle Eastern and North African states in early 2011 threatened to bring about this dreaded debacle. The 2011 uprisings began when Tunisians overthrew President Zine El Abidine Ben Ali in January 2011. The Tunisian revolution sparked uprisings and demonstrations throughout the region as people attempted to oust their long-
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$66 per barrel
2005-
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term dictators in various countries, most notably in Bahrain, Yemen, Libya, and Egypt. Demonstrations to overthrow President Hosni Mubarak of Egypt began in January 2011, ushering in concerns for oil security, as well as oil price increases. The price of Oil and Natural Gas in the Middle East and North Africa increase follow- Map Source: U.S Congressional Research Service, which was based on U.S ing the Egyptian revolution was mostly due to speculations about the future of oil security. Egypt is an oil-producing country; however, Egypt consumes most of the oil that it produces.14 Therefore, the shutdown of oil production in Egypt was not a major concern and not the reason for world oil price increases. However, Egypt controls the Suez Canal, which is used to transport many commodities, including oil. The fear was that if the demonstrations led to a shutdown of the Suez Canal, then trade would be disrupted and shipping prices would increase, causing oil prices to increase accordingly.15 After seeing how the Tunisian revolution sparked the revolution in Egypt, many believed that the entire region would revolt against the numerous authoritarian regimes. Fear of political unrest spreading to oil-exporting countries such as Iraq, Kuwait, or Saudi Arabia – particularly concerning as it is the second largest producer of oil behind Russia – drove up speculations for oil.16,17 The drastic price increases came from fear in just the possibility of protests and the possibility of ensuing major disruption in Middle Eastern oil, and thus the world supply of oil. The dangers of our dependence is underscored by this reaction because it shows just how significantly such a disruption would affect our way of life, particularly in terms of transportation. Concerns over energy security were exacerbated by uprisings in Libya, starting in February 2011 when protestors sought to depose Muammar Gaddafi. The Libyan revolt halted natural gas exports and significantly decreased oil production. Europe was most affected by Libya’s production decreases since more than 85 percent of Libya’s exports go to Europe.18 After Libyan production of natural gas was completely cut off, Europe suffered a 12 percent price increase in gas.19 Oil production in Libya did not come to a complete halt, but about 80 percent of Libya’s oil production was in rebel-held territory which resulted in the loss of about a million
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2008:
$147 per barrel
barrels per day – down from the 1.6 million barrels it was producing per day before the revolution – in the world market from February through August.20, 21 The loss of one million barrels per day is about a 62.5 percent decrease in exports. As a result, oil prices soared to $120 per barrel,22 whereas in December S. State Department information.3 2010 the price had been close to $90 per barrel.23 Other countries stepped in to help with this minor energy crisis, forming a temporary solution to the energy problem. Russia increased its exports to Italy to help offset the loss of natural gas.24 Saudi Arabia increased its production of oil to about 9 million barrels per day, an increase of about 700,000 barrels from its exports in 2010, in an attempt to stabilize the world prices.25 However, Saudi Arabia and Libya produce two different “types” of oil. Libya’s oil is considered “sweet”, while Saudi Arabia’s is considered “sour” due to its heavier and higher sulfur content. “Sweet” crude oil is better suited for producing diesel fuel, which is very popular in Europe.26 Therefore, Saudi Arabia’s oil is often not an acceptable substitute, keeping the price of “sweet” crude oil high. The repercussions of events in Libyan should be reversed as natural gas and oil production picks back up, given that the fighting in Libya has now ended. The protestors gained control of Libya in August and they are currently setting up a new government. As order is slowly restored to the region, the price of oil is expected to come down. The new Libyan regime certainly will bring oil and natural gas exports back up because these exports are Libya’s main income and will be needed to support the new government. However, prices are still likely to remain higher than the pre-revolution levels because new regimes usually signal potential for instability on the world market since no one knows if the new regime will survive. Despite the lack of permanent consequences, the minor energy crisis that resulted from the revolutions highlighted the world’s dependence on Middle Eastern oil. While Europe was particularly affected with the oil and natural gas shortages, the rest of the world felt the price impact at the gas station. In the U.S., prices rose from $2.87 per gallon in November 2010 to $3.10 per gallon by the end of January 2011 and
up to $3.64 per gallon in July.27, 28, 29 Dependence on Middle Eastern oil is a dangerous path as demand for it cannot be sustained. Oil will not last forever, even in the Middle East and North Africa where it is currently plentiful; current estimates regarding reserve-to-production supplies of oil left in the Persian Gulf will only last 80 to 100 more years.30 Unfortunately, the world does not appear to be taking the 2011 Arab revolutions as a warning about the future of energy security. The concerns that arose during the uprisings are slowly fading away as the fighting has died down. Yet the reality of the world’s uncertain and unrealistic dependence on Middle Eastern oil remains. Many companies and organizations have begun looking into the possibilities alternative energy sources have to offer. However, the urgency in such projects is lacking; many are discouraged by the expenses in such research while we still have relatively cheap oil. Keeping the Arab Spring in mind, the pursuit of alternative energy, either by investing in research or petitioning Congress and other respective governments to help with funding, is critical. References 1. Gal Luft. “Dependence on Middle East Energy and its Impact on Global Security.” S. Stec and B. Baraj (eds.). Energy and Environmental Challenges to Security. Springer Science and Business Media B.V. (2009), 198. 2. Guri Bang. “Energy Security and Climate Change Concerns: Triggers for Energy Policy Change in the United States?” Energy Policy. (14 March 2009), 1647. 3. Michael Ratner and Neelesh Nerurkar. “Middle East and North Africa Unrest: Implications for Oil and Natural Gas Markets.” Congressional Research Service, (10 March 2011), 1. 4. David Ellis. “Record Energy Prices and Your Wallet.” CNN Money. (11 August 2005). 5. Bang, 1647. 6, 7, 8. Luft, 198. 9. Daniel Yergin. “Ensuring Energy Security.” Foreign Affairs, Vol. 85, No 2, (March-April 2006), 73. 10. Yergin, 73. 11. Yergin, 74. 12. Turquoise Partners. Iran Investment Monthly, Vol. 4, No 50. (November 2010), 7. 13. Bang, 1647. 14. Michael Ratner. “Implications of Egypt’s Turmoil on Global Oil and Natural Gas Supply.” Congressional Research Service, (11 February 2011), 2-4. 15. Ratner, 3. 16. Ratner, 6. 17. Ratner and Nerurkah, 2. 18. Clifford Krauss. “Why the Disruption of Libyan Oil Has Led to a Price Spike.” The New York Times, (23 February 2011). 19. Ratner and Nerurkah, 6. 20. Jad Mouawad and Clifford Krauss. “Tremors from Libya Contribute to Oil Price Cycles.” The New York Times, (27 February 2011). 21. James Herron. “Libya Oil Output Down 75%, Eni Says.” The Wall Street Journal. (24 February 2011). 22. Herron. 23. Paul R. La Monica. “The ‘tax’ you can’t avoid: Oil prices rising.” CNN Money. (6 December 2010). 24 Ratner and Nerurkah, 6. 25. Mouawad and Krauss. 26. Krauss. 27. “Average gas prices—November 8, 2010.” Customer Reports.org. (8 November 2010). < http://news.consumerreports.org/cars/2010/11/average-gas-prices-november-8-2010. html>. 28. “Average gas prices—January 31, 2011.” Customer Reports.org. (31 January 2011). < http://news.consumerreports.org/cars/2011/01/average-gas-prices-january-31-2011. html>. 29. “Average gas prices—July 11, 2011.” Customer Reports.org. (11 July 2011). < http:// news.consumerreports.org/cars/2011/07/average-gas-prices-july-11-2011.html>. 30. Luft, 199.
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The Kremlinâ&#x20AC;&#x2122;s Energy Strategy Rahul Sabbineni Class of 2015
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hurj spring 2012: issue 14
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focus The Russian Federation’s presence in the international community is largely dependent on positive political and economic outcomes related to its energy policy. The Federation has the largest natural gas reserves and the eighth largest oil reserves in the world, allowing it to structure its economic growth around gains in energy production and trade. The Kremlin has focused on conflating Russia’s vast energy resources with its larger strategic political objectives, expanding influence on Europe and Central Asia. It is undeniable that Russia is a major actor as a consequence of its geopolitical foundations; the tactics that drive the Federation’s energy policies, however, are more contentious in both results and means. While Russia’s energy strategy is successful in pushing forward the Kremlin’s political objectives, it lacks the domestic sustainability needed to continue relying on energy resources as a means of projecting power in the global community. Investigating the feasibility of the Kremlin’s grand strategy necessitates an analysis of the dual perspectives on Russia’s energy policy: the use of resources as a coercive weapon, and the mutual codependence of Russia and the European Union as trading partners. Analyzing these two perspectives reveals the merits and flaws of each interpretation, thus calling into question the efficacy of the Kremlin’s strategic objectives. The dominant view held by many theorists is that Russia has used its energy resources to obtain political benefits and continue its overarching agenda in Eastern Europe. Such usage is constituted by four chief criteria: 1) turning off energy supplies or increasing prices to obtain political concessions, 2) exploiting existing debts for energy supplies or economic weakness in energy consuming countries, 3) unfairly seizing the assets of US or European energy companies operating in Russia, or 4) encouraging a broader assertiveness in Moscow’s foreign policy.1 These four criteria characterize the usage of Russia’s energy resources as a coercive tool, asserting energy dominance as a means of shaping a favorable political environment. From the perspective of states dependent on Russian energy, the potential of mutuality in this dependence is often ignored because of the coercive threat posed by conflicts over pricing and Russia’s political goals. In a geopolitical framework, the skepticism and paranoia of the European Union is partially justified, given the tremendous dependence of European nations on Russian energy reserves. Russia has the largest natural gas reserves in the world, supplying 38.7% of the EU’s imports, increasing the impression of its dominance over the European continent.2 Meanwhile, many EU nations have complete or majority energy dependencies on the Russian Federation, leaving energy concerns subject to the political attitude of the Kremlin.3 The fear of Russia’s energy threat capacity is promulgated further by Putin’s continuation of foreign policy aggression and conflicts over energy resources between Russia and several European states. The Federation cancelled oil deliveries to Ukraine in 2006, following the election of a pro-EU government in Kiev. It also cancelled oil deliveries to the Czech Republic on July 18th, 2008, the day the Czech Republic signed an antimissile radar system agreement with the United States. The construction of the Nordstream pipeline, completed in 2011, which sends natural gas and oil directly from Russia to Germany, bypassing Eastern Europe, was seen as an attempt to divide European interests on the Russian issue. Indeed, Putin’s general foreign policy strategy upon taking office was to use Germany as a means of pushing Russia’s political interests in Europe.4
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focus Putin’s foreign policy activism and the usage of Russia’s energy weapon, despite imposing a threat to several European states, did not achieve outcomes solely favorable for Russia. Many of the threatened countries were not forced to accept higher prices, and deliverances of oil continued without major attention. While major crises developed in the case of Ukraine, the EU was able to diplomatically attain solutions that prevented Russia from getting a broad strategic advantage. The Kremlin has defended its cancellations by blaming Ukraine and other Eastern European states for refusing to accept reasonable prices and siphoning oil from alternate routes. However, the huge price disparity between the consumers of Russia’s energy supply seems to suggest a different story. Russia pays 100 USD per trillion cubic meters for gas purchased from Turkmenistan, while selling gas to Georgia for 230 USD per trillion cubic meters.Though Gazprom’s inefficiency accounts for a certain range of costs, Georgia’s high prices are a consequence of its alignment towards the west rather than transportation difficulties.5 While these coercive strategies have been largely ineffective, the Russian energy weapon has succeeded in implementing its “divide and conquer” strategy, utilizing price discrimination and wedging European Union member-states against each other. Solidarity diminished greatly in the EU following tensions surrounding the 2004 acceptance of the accession bids of several Eastern European countries, whose economic standards barely met the limits of the acquis chapters. Russia, while not responsible for crumbling solidarity against Russian energy policy, preyed upon the dichotomy, exploiting the fragility of Eastern European economies and the reluctance of Western European countries to aid their Eastern counterparts. The strategy polarizes the bureaucratic policy processes of the EU, causing inaction and allowing Russia to possess a tactical advantage over energy deliverance grievances. The EU’s inability to establish an enforcement mechanism on its policies only allots more room for Russia to wedge the member-states for the best strategic result. Through the usage of bilateral deals, Russia was able to turn both Germany and Italy against the collective policy agenda of the EU in the Nordstream and South Stream pipeline deals, respectively. Germany had previously rejected having a direct connection to Russia’s Shtokman field, opting to work through a collective energy policy with France, which posed a challenge to the Russian strategy.6 However, the Nordstream saw to the subversion of Ukraine in favor of a generous direct connection to Germany, not only reversing German policy but also increasing tensions between Ukraine and Germany. The strong economic partnership with Germany will challenge future collective European action against Russia. In Croatia, Serbia, and Bulgaria, Russia has reached rapid bilateral deals, furthering Russia’s competitive edge against non-Russian exports from Central Europe. Unable to compete with the corruption and kompromat tactics of the Kremlin’s strategists, former Russia intelligence figures, the EU responded with inaction and delay.7
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hurj spring 2012: issue 14 With no enforcement mechanism for its policies and the integrity of its design in question, the EU put forward the Lisbon Treaty, which collectivized many of the EU member-states’ policies through binding legislation. The Lisbon Treaty directly affected EU energy and defense concerns, with implications for security and a joint energy policy. Under the Treaty, the harmonization of security forces and battlegroups was made possible, eliminating the Western European Union and furthering EU solidarity even if its most reaching provisions were contingent on future EU Council progress. Additionally, energy was named a shared competence in which common acts become legally binding: “When the Treaties confer on the Union a competence shared with the Member States in a specific area, the Union and the Member States may legislate and adopt legally binding acts in that area”; additional provisions for threats to energy supply and energy security were also included.8 Combined with the inception of Phase II of the EU-Emissions Trading System and the 20-20-20 plans, which aim to reduce emissions and energy consumption, the integration of renewable energy and phasing out of dependence seems possible. While this will help the energy portfolio of the EU, the absence of a clear, common energy policy will lead to further exploitation and manipulation by Russia. Still, to view Russian policy as purely an aggressive energy threat is to ignore the codependence of Russia and the EU. Russian economic growth is equally tied to its relationships with Central Asia and the European Union, given the importance of the energy sector to the Russian economy. Russian energy concerns – Russia saw itself vulnerable because of its dependence on transit energy exports – after the Yeltsin administration indicate the flaws of this perspective. The fear that foreign nations would use this for political and economic blackmail was apparent in the 2003 energy plan. The Russian government worked to further the usage of its own ports, building export terminals and restricting foreign interference. New routes eliminating the possibility of transit dependence have been developed to Central Asian states, building a new relationship between Russia and the Commonwealth of Independent States.9 Despite many successes, Russia’s energy strategy fails in pushing forward economic diversification and increased revenue by coercion. The Russian economy is completely dependent on the success of its energy sector; despite the Putin Administration’s calls for economic diversification, it remains the dominant source of revenue for the Russian Federation. Any fluctuation in the price of oil causes issues for the Russian budget and a mutually assured economic loss in the event of cancellation: the consuming nation fails to obtain energy and Russia fails to earn revenue. On average, a $1 per barrel change in oil prices results in a $1.4 billion change in Russian government revenues in the same direction.10 Additionally, there is a significant loss of revenue caused by the inefficiencies of Gazprom, Russia’s largest liquefied natural gas extractor, and other state owned corporations. The Swedish economist Anders Åslund
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estimated that Gazprom lost up to 50% in revenue by virtue of its structure. Aslund’s estimates are backed by a significant depth and history of operational inefficiencies. For instance, when Gazprom constructed Blue Stream, Gazprom’s costs for the construction of the pipeline were three times greater than on the Turkish construction side. Additionally, the completion of Nordstream and Southstream added 25 billion dollars of costs to a company that already faced overwhelming debt.11 The inefficiencies of nationalized corporations and the dependence of the Russian economy on energy prices and other transit states, challenge the benefits of political outcomes realized by the Kremlin’s energy strategy. The most recent energy strategy, running through 2030, refers to global struggles over energy resources in an attempt to continue economic expansion.12 However, the relative success of past coercive practices and the continuation of mutual dependence reveal several weaknesses, making feasibility of this plan unclear. Although the Kremlin’s energy strategy has been effective in polarizing the European Union, domestic challenges riddle the plan and obscure energy dominance. Lacking in economic diversity, the Federation was barely able to balance the budget when oil reached 70 USD a barrel in 2010. If Russia does not take further steps to diversify its economy, tackle the corruption and ills of nationalization that reduce the productivity of its energy sectors, the strength of the Kremlin, which uses its energy resources as a political weapon, will fall dramatically.13 Russia may be able to extract favorable political outcomes in Europe with coercion, and maintain a façade of strength, but beneath this is a state struggling to retain its status in the challenging climate of the international order. References
1. Russian Energy and European Security: A Transatlantic Dialogue, Paul J. Saunders, February 2008 2. Energy Dialogue EU-Russia, Tenth Progress Report, Presented by Andris Piebalgs and Sergey Shmatko November 2009 3. U.S. Department of Energy, Energy Information Administration, “Russia,” Country Analysis Brief, April 2007, p. 10, Table 4 4. See i 5. Zeyno Baran, EU Energy Security: Time to End Russian Leverage, Washington Quarterly, Autumn 2007 6. EUROPE STRUGGLES TO THWART RUSSIA’S DIVIDE-AND-CONQUER POLICY, Jamestown Foundation, Eurasia Daily Monitor Volume: 3 Issue: 194, October 20, 2006 7. Russia-Europe Energy Relations: Implications for U.S. Policy, Keith C. Smith, Center for Strategic and International Studies, February 2010 8. Article II, Treaty of Lisbon amending the Treaty on European Union and the Treaty establishing the European Community, signed at Lisbon, 13 December 2007 9. Russian Energy Policy Toward Neighboring Countries, Steven Woehrel, Specialist in European Affairs, September 2, 2009 10. Energy Information Administration. Russia Country Analysis Brief, February 2005 11. Gazprom’s New Weakness Offers Opportunity, Anders Aslund, Center for Social and Economic Research Network, June 2009 12. Energy Strategy of Russia for period up to 2030, Ministry of Energy of the Russian Federation, Moscow 2010 13. The Geopolitics of Russian Energy: Looking Back, Looking Forward, Robert E. Ebel, Center for Strategic and International Studies, July 2009
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hurj sping 2012: issue 14
Solar Power:
The Path to U.S. Energy Independence
Joseph Leanza, Class of 2012 International Studies
America finds itself faced with two inseparable hurdles on its path to clean and independent energy: climate change and energy insecurity. Overcoming these obstacles in an economically favorable manner calls for integration of a multi-sector, multi-solution plan that will span at least the next fifty years. The need for secure carbon-neutral energy must be addressed, while staying within the bounds of capacity, feasibility, and security criteria. Among the options for such a renewable system, solar power emerges at the forefront, promising nearly limitless secure domestic energy in the near future. In 2006, the United States used 25% of the world’s energy, 14 trillion watts, and produced 85% of it with fossil fuels. The US emits almost 6000 million metric tons of CO2, about 40% of which results from electricity generation.1 Extrapolating to 2050, normal economic growth is projected to increase US energy consumption to 50 trillion watts.2 Business as usual will see America scaling up coal and natural gas plants to meet energy needs. California Institute of Technology physicist Nathan Lewis asserts that only nuclear, carbon sequestration or solar technologies could feasibly scale to reflect this trajectory. Unfortunately, the United States would need to construct one nuclear plant per day for the next fifty years to satisfy energy needs with only fission energy, and fusion technology is currently out of reach. Carbon sequestration, by which plants collect emissions and store them underground, is still unproven, and such a solution would rely on unstable underground reservoirs. That leaves solar, an abundant source as more solar energy hits the earth each hour than all energy consumed in an entire year.3 The two varieties of solar energy, concentrated solar power (CSP) and photovoltaics, are therefore the obvious choice to generate clean energy. CSP plants use mirrors to focus the sun’s heat to produce steam to drive turbines. Because solar plants cannot generate electricity at night, molten salts associated with the plants can store the heat for nighttime use. CSP plants are most competitive when scaled up, and are effective only under direct irradiance. Photovoltaic panels, however, work under both diffuse and direct irradiance, generating energy by converting the sun’s energy into direct current electricity.4 Questions of economic feasibility are of utmost
20
importance when considering a transition in energy generation. Typical cost quantification fails to address the negative environmental effects of CO2 emissions, such as climate change and ocean acidification. Indeed, the Intergovernmental Panel on Climate Change warns of severe environmental effects atmospheric CO2 concentrations exceed 450-510ppm.5 Therefore the external costs of carbon emissions will be moderate to high. Additionally, incentives and taxes, as well as transmission, distribution, and environmental costs are excluded from the cost analyses. Coal-fired power plants generate electricity at an average of $25-50 per megawatt hour. Gas-powered plants have lower capital costs than coal plants, but due to input costs generate electricity at $37-60/MWh. These generation costs are directly reflected in consumer costs, and are subject to variable (and rising) transportation and commodity prices.6 Depending on solar intensity and plant scale, all solar-generated electricity averages about $150/MWh.7 Thus, presently adopting both expensive and inexpensive solar technologies would roughly double generation costs. That said, once the infrastructure is in place, operators pay only for maintenance. Transforming electricity generation from coal or natural gas to CO2 will abate significant amounts of CO2 yet cost an average of $225/ton.8 Beside costs, technological feasibility concerns many policymakers. The efficacy of solar thermal technology is well-documented, and become increasingly efficient and effective. At the time of writing, the National Renewable Energy Laboratory has created the most advanced photovoltaic cell at 40.8% energy input to output efficiency.9 Such cells would produce electricity at an unsubsidized 8-10 cents per kWh, but will not hit the market for a number of years.10 To put efficiency in perspective, 2.5kWh/m2 of solar energy per day fell on the UK. At a PV efficiency of only 5% the country could supply its entire electricity demand by using only 3% of its land area. Moreover, by integrating modules into buildings, the country could avoid clearing additional land.11 At a greater efficiency – the market-best is Sunpower’s 315 panel at 19.3% the land area required would obviously be far lower. Two geographic factors also inhibit solar’s effectiveness. First, the United States grid is unable to transmit solar-produced direct current electricity. Acciona
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focus estimates that, in order to cover American electricity needs, additions to the US grid must traverse 100,000-500,000 miles at a cost of $1.5 million per mile.12,13 Second, sunlight does not fall uniformly on the US. Where the angle of incoming sunlight is closer to 90 degrees, the contained energy is much higher. Additionally, areas with fewer trees and clouds allow plants to capture more sunlight. With this in mind, CSP plants, which require direct irradiation, are limited to the southwest. Photovoltaics are similarly better suited for southern latitudes, but are still effective in the north because they can generate electricity with both direct and diffuse irradiation. The critical limit on solar power is the need for electricity storage on cloudy days and at night. Solar thermal plants have circumvented the issue with heat-transfer fluids and molten salts. Conventional fuel cells for solar panels are prohibitively expensive, but many technologies under development hold promise.14 For instance, researchers at MIT have developed a new fuel cell catalyst that resembles photosynthesis and should be cost-competitive within ten years.15,16 Employment concerns have additionally stymied clean energy adoption. In 2007, the U.S. oil and natural gas industry directly supported 2.12 million jobs, and added about $450 billion to GDP. Coal mining and plant operation supported an additional 150,000 employees.17,18 That said, oil, coal and gas would certainly experience employment losses from the proposed energy transition. But the losses, according to the Congressional Budget Office, will mean a shift to employment in clean energy sectors rather than an increase in national unemployment.19 Recent data show that from 1998 to 2007, jobs in clean energy grew by 9.1% compared with a 3.7% national employment growth rate. Solar was responsible for 62.5% of jobs in the clean energy sector, and is projected to continue leading renewable growth through 2020.20 Jobs will become directly available for solar researchers, engineers, and technicians. Additionally, indirect jobs will be available for architects, builders, skilled laborers, commodity suppliers, and electric power utility workers.21 Beyond a feasibility analysis, economic, energy, and environmental security must be addressed. In terms of energy, with respect to recent developments in the Middle East and North Africa – high petroleum and home heating prices will likely persist. With affordable oil and gas expected to peak in as few as twenty years, economical and domestic electricity generation is of paramount importance.22 Furthermore, foreign companies are outpacing American renewable industries, with companies from Germany and Spain having built a significant portion of new American renewable installations. The Spanish Acciona Energy Conglomerate built and owns a 95% stake in Nevada Solar One. Although “...the Department of Energy projects that CSP such complants will be cost-competitive by 2020, and p a n i e s c r e a t e continues to contract with researchers to develop A me r i c an c on s t r u c CSP technologies.” tion jobs, the corporate economic boom is felt on other continents. Investments in renewable energy today will not only jumpstart clean technology sectors, but will also investments in American infrastructure. Policies to promote renewable energy research, manufacturing, and adop-
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tion are no-regrets measures to increase US economic security. In terms of security, prices, regional instability, and international competition all have implications for transportation, home heating, and electricity generation fuels. The United States has a robust domestic coal industry, but in 2009 imported over 15% of consumed natural gas. Most natural gas imports come from Canada, but much like oil, the gas imports from politically “Alternative energy investments now wou unstable for alternative transportation options, such areas, such as Mexico, vehicles, thereby limiting America’s trade d Eg ypt, Nigeria, and Trinidad, are subject to interference. Intra-continental transportation of natural gas is reliant on pipelines to Mexico and Canada, which are further subject to crime, weather, and degradation.23 Prices and supply of oil are also variable and subject to international disputes.24 Alternative energy investments now would set the foundation for alternative transportation options, such as hydrogen-powered vehicles, thereby limiting America’s trade deficit and oil imports. One can envision a clean energy system, paired with electric or hydrogen transportation fuel, solidifying energy independence. The environmental security issues expected from atmospheric carbon loading will intensify as emissions increase. The Intergovernmental Panel on Climate Change generally warns that carbon loading of the atmosphere will catalyze catastrophic climate change.25 Environmental groups are concerned that solar plant construction may destroy unspoiled desert habitats in the southwest.26 However, the National Renewable Energy Laboratory in Golden, Colorado has determined that enough land is available in the southwest that environmentally sensitive areas can be entirely avoided.27 Even so, when factoring in mining, the land impact is lower for solar energy than for coal-powered plants.28 Best estimates indicate that a CSP plant covering a 100 x 100 mile tract in the southwest U.S. could entirely meet U.S. electricity demand.29 Land clearing can even be avoided by integrating photovoltaic panels into already utilized land such as roofs and parking lots. As efficiencies improve, solar will easily maintain environmental security without adversely affecting individual ecosystems.30 Current policies offer seventeen national financial incentives for renewable energy complemented by an array of state and local incentives.31 The American Reinvestment and Recovery Act supports these measures with $21 billion dedicated to tax incentives for renewables, a $30 billion fund delegated to clean energy programs, and $3.4 billion in government grants for a smart-grid that to transport renewably generated electricity.32,33 Spain and Germany have successfully ensured competitive market access for renewable electricity with respective 39 cent/kWh and 53 cent/kWh solar feed-intariffs, a policy that the United States would do well to consider.34,35 In sum, while solar plants avoid fuel expenditures, cost still inhibits solar installations regardless of scale. That said, the Department of Energy projects that CSP plants will be cost-competitive by 2020, and continues to contract with researchers to develop CSP technologies.36 As solar technologies reach fruition, market growth and economies of scale will help PV and CSP plants compete with conventional electricity sources subsidy-free.37 Until then, the government
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focus 6. U.S. Energy Information Administration Independent Statistics and Analysis.
will need to maintain supports. The International Energy Agency es- Natural Gas Navigator. U.S. Energy Information Administration. http://tonto.eia.doe.gov/ timates CSP generation costs of less than 6 cents/kWh, prices equiv- dnav/ng/hist/n3045us3m.htm. (Accessed March 24, 2010) 7. International Energy Agency Secretariat. Projected Costs of Generating Electricalent to that of coal and natural gas.38 Moreover, about 15% of all ity 2005 Update. International Energy Agency. http://www.iea.org/publications/free_new_ global venture capital investments are in clean energy, indicating pri- Desc.asp?PUBS_ID=1472. (Accessed February 19, 2010) vate-sector confidence in renewables.39 With the US interest rate at a 8. Hughes, Evan 2000. Cost of Greenhouse Gas Mitigation. Treepower Working seemingly permanent minimum, the time is right for capital-intense Group, November 11. http://docs.google.com/viewer?a=v&q=cache:ZXxfjlvYLKgJ:www. investments into renewable energy. treepower.org/globalwarming/CO2-EPRI-EvanHughes.pdf+cost+per+ton+of+CO2+avo ided+with+solar&hl=en&gl=us&pid=bl&srcid=ADGEESgKCiEcHARIxuRA7SrXpMlY Several obstacles in technology XEHoOGAHc3Nr6_9HP28DCEyWYjkYzE6UwIHos35wwVq2yxfwvAg5YaO8E_QAvTand cost have yet to be overcome. In pb8WkwGP-Lf2vid3E7ZGDwqxXKSojbscMhxEOsd-v2vh5gYWCY&sig=AHIEtbSXf7x the meantime, if policymakers de- RMv8FFx7To6l5bZQMnPY5MQ uld set the foundation 9. National Renewable Energy Laboratory Newsroom. NREL Solar Cell Sets World sire investments in renewable energy, Efficiency Record at 40.8 Percent. National Renewable Energy Laboratory, August 13, 2008. h as hydrogen-powered the public, government, and industry http://www.nrel.gov/news/press/2008/625.html. (Accessed March 11, 2010) must connect their goals. The public 10. Solar Energy Weblog. Efficiency With Photovoltaic Cells. Solar Energy. http:// deficit and oil imports.” appears ready, with an estimated 70% www.gstriatum.com/solarenergy/2009/04/efficiency-with-photovoltaic-cells/. (Accessed willing to accept a 5% increase in elec- March 24, 2010) 11. Jackson, Tim and Mark Oliver. The viability of solar photovoltaics. Energy Policy vol. tricity for “green” production.40 Nine 28, no. 14 (November 2000), http://www.sciencedirect.com/science?_ob=ArticleURL&_ policy options are outlined below. udi=B6V2W-4177N2J-1&_user=10&_coverDate=11%2F30%2F2000&_rdoc=1&_ The Scientific American report “A Solar Grand Plan” projects fmt=high&_orig=search&_sort=d&_docanchor=&view=c&_searchStrId=1268110167&_ that subsidies totaling $420 billion through 2050 will be sufficient rerunOrigin=google&_acct=C000050221&_version=1&_urlVersion=0&_userid=10&md 5=17a69d1b255ff21581ce56cd3e8c936b. (Accessed March 2, 2010) to give solar power a 69% market share of electricity generation.42 12. Scientific American Energy and Sustainability. U.S. Plan for 2050. Scientific Solar is not a silver bullet and is too costly to cover all US electric- American, December 16, 2007. http://www.scientificamerican.com/article.cfm?id=usity generation. However, energy efficiency measures and a portfo- plan-for-2050. (Accessed March 1, 2010) 13. Kanellos, Michael 2007. Shrinking the Cost for Solar Power. CNET News, May lio of renewable technologies will reduce both the necessary mar11.http://news.cnet.com/Shrinking-the-cost-for-solar-power/2100-11392_3-6182947. ket share and subsidy requirement for solar. Costs will also decline html (Accessed March 1, 2010) over time, and investments will simultaneously stimulate solar panel 14. National Renewable Energy Laboratory TroughNet. Parabolic Trough Thermal manufacturing, CO2 reductions, long-term economic savings, and Energy Storage Technology. National Renewable Energy Laboratory. http://www.nrel.gov/ csp/troughnet/thermal_energy_storage.html#systems. (Accessed March 1, 2010) energy independence. Solar 15. Trafton, Anne 2008. ‘Macertainly does appear ready jor discovery’ from MIT primed to to accommodate 50% of US unleash solar revolution. MIT News, 1. Institute policies to develop large, durable tracts of land in the July 31. http://web.mit.edu/newsofenergy needs, at an estimatfice/2008/oxygen-0731.html. (AcUS southwest with solar plants and connect them to the rest of the ed cost of $300 billion over cessed March 10, 2010) the next 40 years, about $7 country with a direct current smart grid. 16. Trafton, Anne 2008. ‘Mabillion per year. A transition jor discovery’ from MIT primed to 2. States should also be held to renewable generation minimums, unleash solar revolution. MIT News, of this scale could alone cut but maintain autonomy in policy implementation. July 31. http://web.mit.edu/newsofelectricity-related emissions 3. Increase push and pull investments in research, development, fice/2008/oxygen-0731.html. (Acby more than half. With adcessed March 10, 2010) and installation of CSP, PV, storage, and other renewables. ditional wind, nuclear, and 17. NMA American Resource. 4. A feed-in-tariff to ensure long-term competitiveness of new U.S. Coal Mine Employment by State, hydroelectric electricity plants, which will have the co-benefit of stimulating CSP and PV Region, and Method of Mining. Nageneration, America could tional Mining Association. http:// manufacturing. easily power herself with www.nma.org/pdf/c_employment_ 5. A gradual coal plant moratorium over five years and beginning in 100% clean energy by 2050. state_region_method.pdf. (Accessed
References
2010, such as that proposed in H.R. 5575 [110th Congress]. 6. A federal price on carbon emissions. 7. Electric generation performance standards or mitigation requirements for power plants.41 8. Federal and state cooperation on renewable and environmental portfolio standards.lxii 9. Policies to ensure that substantial credit is given for early action.
1. “Country Shares of CO2 Emissions.” Citizens and Scientists for Environmental Solutions. Union of Concerned Scientists. http://www. ucsusa.org/global_warming/science_ and_impacts/science/each-countrysshare-of-co2.html 2. Lewis, Dr. Nate. 2008. Where in the World Will Our Energy Come From? Lecture for the von Karman Lecture Series, February 28 & 29, in Pasadena, California. http://www.jpl.nasa.gov/events/ lectures/feb08.cfm. 3. Lewis, Dr. Nate. 2008. Where in the World Will Our Energy Come From? 4. Quaschning, Volker, and Manuel Blanco Muriel. 2001. Solar Power – Photovoltaics or Solar Thermal Power Plants? VGB Congress Power Plants 2001, http://volker-quaschning.de/downloads/VGB2001.pdf. (Accessed March 6, 2010) 5. Intergovernmental Panel on Climate Change Assessments. IPCC Fourth Assessment Report: Climate Change 2007. Intergovernmental Panel on Climate Change. http:// www.ipcc.ch/publications_and_data/publications_and_data_reports.htm#1(Accessed March 2, 2010)
March 10, 2010) 18. Sourcewatch.org. Coal and jobs in the United States. Source Watch. http://www.sourcewatch.org/ index.php?title=Coal_and_jobs_in_ the_United_States. (Accessed March 11, 2010) 19. CBO Economic and Budget Issue Brief. The Costs of Reducing Greenhouse-Gas Emissions. Congressional Budget Office. http://www. cbo.gov/ftpdocs/104xx/doc10458/1123-GHG_Emissions_Brief.pdf. (Ac-
cessed March 27, 2010) 20. Pew Center on the States and Pew Environment Group. The Clean Energy Economy – Repowering Jobs, Businesses, and Investments Across America. The Pew Charitable Trusts. http://www.coecon.com/Reports/GREEN/Clean_Economy_Report_Web.pdf (Accessed March 4, 2010) 21. Austin Community College Report. Occupational Profiles for the Solar Industry. Interstate Renewable Energy Council. http://www.austincc.edu/ce/renewable/solar.pdf. (Accessed February 28, 2010) 22. Hirsch, Robert L., Roger Bezdek, and Robert Wendling. “Peaking of World Oil
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hurj spring 2012: issue 14 Production: Impacts, Mitigation, & Risk Management.” Department of Energy Publication (2005): 1-91. http://www.netl.doe.gov/energy-analyses/pubs/Oil_Peaking_NETL.pdf. 23. U.S. Energy Information Administration Independent Statistics and Analysis. U.S. Natural Gas Imports by Country. U.S. Energy Information Administration. http://tonto.eia.doe.gov/dnav/ng/ng_move_impc_ s1_m.htm. (Accessed February 25, 2010) 24. Krauss, Clifford 2010. Oil and Gasoline Prices Begin to Creep Up. The New York Times, March 8. 25. Intergovernmental Panel on Climate Change 9th Session of Working Group III. Summary for Policymakers. Intergovernmental Panel on Climate Change. http://www.ipcc.ch/pdf/assessment-report/ar4/wg3/ ar4-wg3-spm.pdf. (Accessed March 9, 2010) 26. Zweibel, Ken, James Mason, and Vasilis Fthenakis. Jan. 2008. Solar Grand Plan. Scientific American Vol. 298, Issue 1. 27. Basin and Range Watch. Defending the Desert. http://www.basinandrangewatch.org/. (Accessed March 4, 2010) 28. Zweibel, Ken, James Mason, and Vasilis Fthenakis. Jan. 2008. Solar Grand Plan. 29. Acciona North America. Nevada Solar One Project Overview. Acciona Energy. http://www.acciona-na.com/About-Us/Our-Projects/US-/Nevada-Solar-One.aspx. (Accessed March 2, 2010) 30. Scientific American Energy and Sustainability. U.S. Plan for 2050. Scientific American, December 16, 2007. http://www.scientificamerican. com/article.cfm?id=us-plan-for-2050. (Accessed March 1, 2010) 31. N.C. Solar Center. Database of State Incentives for Renewables & Efficiency. N.C. State University. http://www.dsireusa.org/summarytables/ index.cfm?ee=1&RE=1. (Accessed March 4, 2010) 32. Pew Center on the States and Pew Environment Group. The Clean Energy Economy – Repowering Jobs, Businesses, and Investments Across America. The Pew Charitable Trusts. http://www.coecon.com/ Reports/GREEN/Clean_Economy_Report_Web.pdf (Accessed March 4, 2010) 33. Epstein, Lita 2009. Green projects, electric cars and solar power on agenda for Obama and Biden. AOL Daily Finance, October 27. http:// www.dailyfinance.com/story/green-projects-electric-cars-solar-poweron-agenda-for-obama-biden/19210978/. (Accessed February 20, 2010) 34. Segade, Lourdes 2010. Solar Industry learns lessons in Spanish Sun. The New York Times, March 8. 35. Mendonça, Miguel and James Corre. Success story: Feed-In Tariffs and Renewable energy in Germany. e-Parliament in Action. http:// www.e-parl.net/eparlimages/general/pdf/080603%20FIT%20toolkit.pdf. (Accessed March 2, 2010) 36. U.S. DOE Energy Efficiency and Renewable Energy Solar Energy Technologies Program. Concentrating Solar Power. U.S. Department of Energy. http://www1.eere.energy.gov/solar/pdfs/43685.pdf. (Accessed March 4, 2010) 37. Jackson, Tim and Mark Oliver. The viability of solar photovoltaics. Energy Policy vol. 28, no. 14 (November 2000), http:// www.sciencedirect.com/science?_ob=ArticleURL&_udi=B6V2W4177N2J-1&_user=10&_coverDate=11%2F30%2F2000&_rdoc=1&_ fmt=high&_orig=search&_sort=d&_docanchor=&view=c&_searchStrId=1268110167&_rerunOrigin=google&_acct=C000050221&_version=1&_urlVersion=0&_userid=10&md5=17a69d1b255ff21581ce56cd3 e8c936b. (Accessed March 2, 2010) 38. Schott North America. Schott White Paper on Solar Thermal Power Plant Technology. Schott Inc. http://www.us.schott.com/csp/english/download/schott_white_paper.pdf. (Accessed March 15, 2010) 39. Pew Center on the States and Pew Environment Group. The Clean Energy Economy – Repowering Jobs, Businesses, and Investments Across America. The Pew Charitable Trusts. http://www.coecon.com/ Reports/GREEN/Clean_Economy_Report_Web.pdf (Accessed March 4, 2010) 40. Deloitte Center for Energy Solutions. Deloitte Survey: Energy Regulators In A Green State Of Mind. Deloitte. http:// www.deloitte.com/view/en_US/us/Insights/centers/centers-center-for-energy-solutions/press-release/b995cb51ed812210VgnVCM100000ba42f00aRCRD.htm. (Accessed March 14, 2010) 41. The Center for Climate Strategies State Action Plans. Brief Descriptions of State Climate Actions: Energy Supply. The Center for Climate Strategies. http://www.climatestrategies.us/ ewebeditpro/items/O25F17650.PDF. (Accessed March 21, 2010) 42. Zweibel, Ken, James Mason, and Vasilis Fthenakis. Jan. 2008. Solar Grand Plan.
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hurj spring 2012: issue 14
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Environmental Security in Senegal: The Intersection of Defense, Development, and Diplomacy Mark Brennan, Class of 2012 International Studies
There is a tendency to securitize areas of concern in American policy. It ranges from energy security in building an oil pipeline from Canada, to cyber security in reference to internet infrastructure, to the Executive Branchâ&#x20AC;&#x2122;s regular citation of national security to justify actions in court, prisons, and the marketplace. Despite such a broad range of securitization subjects, environmental security remains a largely overlooked underdog. America should reevaluate its relegation of the environment as and under-supported area of study and concern. The centrality of this issue for American defense, diplomacy, and development can be highlighted by establishing the themes it has in common with other securities. Within this framework, insurance of environmental security in the developing world shows itself to be key not only in the short-term American diplomatic toolkit, but also an investment in long-term defense and diplomacy. Several common themes unite all areas of security, with internationalism and economics in the spotlight. Together, they create a lens that clearly shows environmental security as among the traditional areas of study. Using Senegal as a case study shows how current investments
to ensure an ecologically conscious developing world and sustainable development can pay large dividends in the areas of climate change, transboundary air pollution, and waste disposal. The securitization of the environment is undoubtedly one of the best advances in American foreign policy. The broad spatial and temporal dimensions of environmental security make it an inherently international subject. Just as Americans concern themselves with border security alongside Mexico and Canada, environmental security is inherently international, and perhaps more complicated, because trans-border air and water pollutants cannot be kept out with an avant-garde passport system. Environmental pollution will grow as an international phenomenon as the world continues to globalize, urbanize, and industrialize. In the United States, more than 80% of deposited mercury is from a foreign country.1 Black carbon, a pollutant and climate change gas produced by developing countries, has the potential to wreck havoc on polar ice cover, consequently causing international ramifications.2 The physical impacts of polar ice melt, in terms of land lost to submersion along the Gulf Coast in the United States, would be large and permanent.
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hurj spring 2012: issue 14
Such a potential consequence obviates the long-term as- lution and foreign environmental security concerns can be mitigated pects of environmental security, solidifying its impor- through capacity building investments by the United States. These intance within discussions of more general ‘national security’. clude regulations and technology, drafting laws, assisting with legal and Economic implications of environmental security further its simi- judicial enforcement, all of which can apply immediately to pollution, as larities to others, such as cyber security for Wall Street’s cyber infrastruc- well as to climate change. It is important to note that the same institutionture or economic modeling that supports energy securitization. Security al processes that might reduce mercury emissions or SO2 can be applied intends to protect vested interests, and in a capitalist society, these often to greenhouse gases, which will undeniably impact American agriculture have monetary and environconnotations. mental security. Table 1: Economic & Population Data10 Just as domestic Thus, ensuring environmental environmental 2009 2000 2005 policy is desecurity in the signed to address developing world 8.70 billion 12.79 billion 4.69 billion Economic (USD) environmental is a key tool in 9.51 million Population 10.87 million 12.11 million externalities, it is both the shortcertainly in the term AmeriEnergy Use (kg of oil 257 --252 interest of the can diplomatic equivalent per capita) United States toolkit, and the Electric power consumption to minimize long-term de--106 163 the externalifense and diplo(kWh per capita) ties that come macy toolkit. from internaP r e s tional sources of ent day efpollution. Given its commonalities with popularly acknowl- forts to ensure an environmentally conscious developing world by edged areas of securitization, environmental security ought promoting sustainable development can pay off on large scales. If deto be integrated into American defense and diplomacy. veloping countries attain the institutional capacities to mitigate polTreatment of the environment as a defendable entity, like land, lution – including greenhouse gas emissions – binding treaties to rebrings up international security issues. For instance, particulate mat- duce global emissions, for example, would be more feasible. Thus, ter emissions from the Far East, mercury from Latin America, and the question naturally becomes, what can the United States do to get carbon emissions from Europe impact the American environment. this payoff? More specifically, what domestic institutions would be Such trans-boundary pollution shows how one country can infringe the key players in an international environmental security initiative? upon the security of another, an important and complex discussion. Within Washington there exist three government entities that inFor example, the eastern United States currently has a cap-and-trade teract to examine environment through a strategic lens: The Departsystem to reduce the otherwise large economic externality produced ment of Defense (DOD), Department of State (DOS), and Agency for by cement and power production. However, it is more complicated International Development (AID). Other key collaborating groups that to establish a system to provide reparations for Mexican power plant sometimes lead projects include the U.S. Trade Representative, the Deemissions on the southwestern United States; it is orders of magni- partment of Agriculture, Department of Interior, and the U.S. Environtude more difficult to establish a regime in which countries would mental Protection Agency. These internal governmental actors represent pay for the cost of their sulfur dioxide deposition in the United States. the environmental approach to American foreign policy, via internaTrans-boundary concerns take a new level of importance when tional organizations and bilateral relations. The United States is already examining climate change. The impact of American and the interna- a major funder of many international environmental organizations and tional communities’ greenhouse gas emissions are the most pressing treaties, though often not a signatory or party because domestic limitaenvironmental security issue that we face today.3 The National Oce- tions preclude its participation. Most prominently, the United States govanic and Atmospheric Administration notes in 2011 alone the cost of ernment (USG) has used memorandums of understandings attached to weather and climate disasters was about $35 billion dollars, connect- Free Trade Agreements; North American Free Trade Agreement and ing the disasters to elevated green house gas emissions worldwide.4 Central America Free Trade Agreement-Dominican Republic both The U.S. Climate Change Science Program and academic systems have environmental programs, administered by the federal government. models suggest a variety of further domestic impacts, from flooding These often entail collaboration between USG agencies and departments around the Florida Panhandle, to decreased agriculture productivity. and their foreign counterparts, in exchanges of technical information. Developing countries, with less political and economic capaciAlongside the federal government, American NGOs also perties to approach environmental damage and degradation, can be se- form environmental work abroad; among these there are for-profit riously affected by pollution or waste. Such countries often lack the and non-profit NGOs capable of environmental capacity building.6,7 institutional and regulatory capacities that the United States has had Notably, the State Department often looks for market-friendly solusince the 1970s. Rather, many developing countries focus on eco- tions to environmental issues, and local for-profit and non-profit organomic growth and development. This focus has lead to several re- nizations facilitate and implement these solutions. This for-profit apcent protests over environmental degradation, most notably the proach can be seen most apparently in the Global Alliance for Clean unrest in Northern China over the Jinko Solar chemical factory, Cookstoves that the State Department has recently promoted. Ultiwhere local workers protested against the pollution from the plant.5 mately, these groups produce American international policy at all levels. With this in mind, this article asserts that trans-boundary polThe United States stands to gain from a proactive stance on en-
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hurj spring 2012: issue 14
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vironmental security, which touches on two key areas of defense and diplomacy. First, it influences domestic environmental security via trans-boundary pollution. Second, the long-term and short-term impact of poor environmental governance in foreign countries can impact American national security interests. Within the defined American institutional framework, Senegal specifically motivates environmental cooperation with the United States. Senegal is a hub of NGO activity for West and Central Africa. It is a democratic Muslim state, and has a relatively free market, engaging in international trade, though domestically some markets are not competitive (i.e. cell phone service, electricity). Further, Dakar qualifies as an attractive foreign government to the US government, especially as the USG plans to continue to expand its influence in Africa while maintaining strong ties to the global Muslim population. All indicators point to a successful working environment and any investment that betters Senegal’s environment – or Senegal’s capacity to approach future environmental problems – is an investment in American security. Because Senegal is a developing country, it would be significant if, because of its ability to environmentally govern, it were to decide that a climate change treaty is adventitious.8 The other side of the coin is that bettering the Senegalese environment is a fundamentally humanitarian action, and would mean positive involvement for the United States.
The United States has a long history of sharing technical and policy knowledge, and it would be interesting to see how it might provide technical and consultative support to Senegal. This exchange has great potential especially because Senegal recognizes the energy security and environmental implications of its dependence on petroleum. Specifically, Senegal could hypothetically use American assistance in an emissions inspections and regulations programs for taxicabs and power plants. Energy combustion is a pressing area for intervention as it is often unregulated, and is one of the largest apparent issues in Senegal. Petroleum combustion powers the major cities and transportation networks. In Dakar this occurs in car engines and in the power plants surrounding the city. When viewed from the ‘security’ lens, these two sources are relevant because they greatly shape general ambient air quality. The issue at hand ties industrial and residential systems together as consumption from both sectors drives the dirty and unsustainable energy system. Economic and population projections suggest that neither industrial nor commercial nor residential consumption will decrease, and so the solution lies in a proactive program. Examination of the major environmental impacts of a nation dependent on imported petroleum shows room for benefits of an emissions reduction program inspired by the American SO2 or NO2 reduction programs. (Table 1.) Petroleum-fired coal power plants ring the eastern side of the pen-
Table 2: Combustion of petroleum in diesel taxis, another processes that contribute to urban air pollution.
Sunday 430pm Small Mermoz 27
Sunday 330pm Medium Boabab 71
Sunday 330pm Highway Carak 73
Sunday 1210pm Medium Mermoz 19
Sunday 1030pm Small Mermoz 21
Sunday 1030pm Medium Mermoz 45
Sunday 1010pm Highway Mermoz 76
Non‐Diesel Taxi
2
8
3
0
‐‐
‐‐
‐‐
Car
17
45
88
12
10
27
41
Bus
0
1
13
0
0
0
0
Motorcycle
2
11
12
3
2
0
1
Horse
0
1
0
1
0
0
0
Weekday 900am Small Boabab
Weekday 900am Medium Boabab
Diesel Taxi
21
148
216
48
2
19
‐‐
Non‐Diesel Taxi
‐‐
‐‐
9
‐‐
0
4
‐‐
Car
9
128
392
14
6
32
‐‐
Bus
0
0
54
0
0
1
‐‐
Motorcycle
3
23
49
0
2
8
‐‐
Horse
0
0
0
0
1
2
‐‐
Diesel Taxi
Weekday Weekday Weekday Weekday 840am 900am 1205pm 1215pm Highway Small Small Small Carak Mermoz Boabab Boabab
Tabulation of cars, diesel taxis, non-diesel taxis, buses, and motorcycles from the start time till 20 minutes from the start time on small and medium roads and one highway. 27
focus insula of Senegal, providing power for the peninsula and much of the countryside through an elaborate electric grid. They are also important sources of local emissions, though slightly outside of Dakar. In the urban lull between the capital and its suburbs it is possible to see where Senelec, the national energy provider, operates its power plants. These power plants, according to Mr. Harris, CEO of SOS Environment in Senegal, are responsible for much of the country’s electricity. The power sector is problematic, however, and a major overhaul is in order. Throughout June 2011 Dakar experienced significant power outages. Unrest spread throughout Dakar as Senelec struggled to electrify the city. Concern is mounting among Senegalese that the electric grid will become more unsustainable, which is seen as indicating a greater political problem. USAID noted they have no immediate plans to become involved in cleaning or greening Senelec’s power plants. However, the Senegalese Ministry for Environment has acted in the past to reduce pointsource emissions, showing consciousness of impact. Most notably, the government mandated that SOCOCIM’s infamous cement plant east of the Dakarian peninsula undertake a pollution prevention program. The plant is in a location where the growth of trees in the surrounding area is still stunted. Power plants are less destructive but still are significant sources of pollution in the Western part of the country. A possible initiative would be for the United States to collaborate with the Senegalese in modifying the power plants like SOCOCIM modified its cement plant and reducing emissions. The United States Office of Environment and Trade often works in mediating between an American Department and the corresponding Department or Ministry in another country, and could easily step in for this case. (Table 2.) Vehicle emissions present another pollution issue. In Dakar and most urban areas throughout Senegal there is a transportation system of buses, taxis, motorcycles, and personal cars. Most significantly, however, many Senegalese depend on a fleet of aging taxis. The majority of cars on the road at any given time are taxis, but cabs are slightly more complicated than power plants to regulate because they are not fixed points of emissions. The government has acknowledged the dilapidated state of the taxi fleet, facilitating the purchase of new nondiesel cabs for the Islamic Summit Conference in the capital. But a brief statistical survey confirms the abundance of older taxis on the roads. Though the Senegalese government has recently started a biofuel initiative9, the corporation farming and experimenting with jatropha is still learning how to efficiently extract the fuel from the fruit and this initiative is in its infancy. This suggests any short-term change of emissions will come from policy directives to reduce emissions of the cars that are on the road, not strategic long-term fuel supply shifts. Interestingly, there is a slight distinction between the color schemes of cabs in Dakar and the amount they pollute. Cabs from the Islamic Summit Conference which stayed on the streets are known to be cleaner, and painted a pure yellow, while other cabs are orange and black. An emissions inspection could be implemented, and high polluting cars retain the orange and black
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hurj spring 2012: issue 14 paint scheme, while cleaner cars move towards all orange paint. A fee could be levied for any driver that repainted his car without meeting the appropriate emissions criteria, and incentives offered for cars to retrofit and reduce emissions. Cars that meet emissions criteria could charge more in fares. In terms of transportation emissions, this would be an effective way of targeting a large portion of the sector. In discussing Senegalese-American cooperation, a member of the United State’s Department of Defense quoted the proverb: “a rising tide helps all ships.” This is particularly appropriate for any collaboration between the United States and Senegal on areas of petroleum consumption. The USDOD has a presence in Senegal. Among other tasks, it ensures efficient allocation of American resources in the region and sub regions, with a focus on democracy, human rights, and natural resources. A program to improve public health, by bringing attention to a severe dependency on petroleum, would touch on many of these areas. Simultaneously, having a developing world ally in the United Nations Framework Convention for Climate Change with a progressive, emissions-conscious regulatory policy in its capital city might be invaluable for the United States one day. When examining this hypothetical example of an initiative that would improve Senegalese ambient air quality while furthering securing American interests in the region, it is important to remember defense interests often manifest themselves through development; at the most fundamental level, a stable, healthy Senegal is an asset for the United States. Though the potential for environmental cooperation between the United States and Senegal is immense, possible collaborations between the United States and many developing countries are abundant. The potential for low-cost high-yield environmental cooperation across the globe is a truly powerful tool in the American diplomacy toolkit. The areas for synergies in defense and development are large, and the technical expertise of the United States – when asked for – is a priceless asset. To openly leverage the environment in a productive, mutually desirable sense will ensure the United States stays ahead in twenty-first century development, defense, and diplomacy. This will help ensure management, by the US and by the world, of long-term environmental issues that will have broad impacts and economic ramifications, and will surely dominate twenty-first century international relations. The author extends his thanks to the JHU Bander Award for International Research for making this research project possible. 1. “EPA’s Roadmap for Mercury | Mercury | US EPA.” US Environmental Protection Agency. Web. 03 Oct. 2011.<http://www.epa.gov/hg/executivesummary.htm>. 2. “Progress Report and Recommendations for Ministers.” Artic Council Task Force on Short Lived Climate Forcers. Web. 23 Oct. 2011. <www.state.gov/documents/organization/164926.pdf>. 3. “Global Change Scenarios: Their Development and Use.” United States Global Change Research Program. Web. 23 Oct. 2011. <http://www.globalchange.gov/>. 4. Lott, Neal. “NCDC: Billion Dollar U.S. Weather/Climate Disasters.” NCDC: * National Climatic Data Center (NCDC) *. Web. 23 Oct. 2011. <http://www.ncdc.noaa. gov/oa/reports/billionz.html>. 5. “China Shuts Factory after Pollution Protest - Telegraph.” Telegraph.co.uk - Telegraph Online, Daily Telegraph and Sunday Telegraph - Telegraph. Web. 23 Oct. 2011. <http://www.telegraph.co.uk/news/worldnews/asia/china/8773738/China-shuts-factoryafter-pollution-protest.html> 6. Information from Saul Garlic, CEO ThinkImapct 7. Information from Tostan 8. A review from public documents of the major environmental treaties currently being considered by the global community suggest that larger developing countries are reluctant to sign any legally binding treaties. The “common but differentiated responsibility “ divide has become an entrenched issue in international politics. 9. Information from Dr. Ismael Fofana 10. “Data Profile: Senegal.” The World Bank. Web. <http://ddp-ext.worldbank.org/ext/ddpreports/ ViewSharedReport?&CF=&REPORT_ID=9147&REQUEST_ TYPE=VIEWADVANCED>.
hurj spring 2012: issue 14
Stalin-Era Writers Shantini Persaud, Class of 2012
humanities
&
Public Health Studies Braving the cold and the extensive damage incurred by her feet, a slight (albeit, proud) woman whose life and family had been torn apart by Josef Stalin’s Terror stood in line to hear news of her imprisoned son. She had in her hands a care package of food and other staples that took her months of saving and scrimping to compile. This woman was characteristic of the millions who suffered under Stalin. Later, she would recount: On that occasion there was a woman standing behind me, her lips blue with cold, who, of course, had never in her life heard my name. Jolted out of the torpor characteristic of all of us, she said into my ear (everyone whispered there) - ‘Could one ever describe this?’ And I answered - ‘I can.’ This is the introduction to Anna Akhmatova’s anti-Soviet work Requiem that was written during the Great Purge (1936-1938). In this time period, Josef Stalin, the dictator of the Soviet Union, arranged the mass executions of human beings to solidify his political power. With friends, relatives, famous artists, writers, and politicians imprisoned and murdered, the fear that permeated the public must have been difficult or nearly impossible to bear. To further suppress dissent, Stalin condemned all literature that celebrated human individuality and only allowed literature that supported Socialism. However, Stalin’s overwhelming power could not stop several anti-socialist writers from defying him. Boris Pasternak and Anna Akhmatova, two mainstays of Russian literature and poetry, created works that triumphed the importance of the individual over the state. In 1934, Stalin and the state-sponsored Congress of Writers established the term “Socialist Realism” as the guideline that all Soviet writers should follow. It would turn out to be more of a broad mandate in practice. In Thank You, Comrade Stalin!, historian Jeffrey Brooks describes how this policy benefited the regime: “Over time, socialist realism became associated with aesthetic conventions and literary formulas, but it always represented a grossly unequal arrangement in which writers worked under the authority of cultural bureaucrats to promote the government’s changing agenda”.1 The meaning of a Russian canon was thus modified in order to suit the needs of the Soviet powers. Socialist Realist writers devalued the human individual and described the Russian people as a gross entity, encompassing the Russian land and all of its contents. The Socialist Realist poet Sergei Mikhalkov wrote a set of children’s poems that praises socialism. “Everything our homeland has/Is possessed by all the people. /They keep the books on fields and woods/…/Mineshafts, minepits, factories. /As a lesson for other nations /The people run them all themselves”.2 Mikhalkov never uses the word “I,” revealing a movement to delete the sense of individuality starting at a very young age. Thus, the idea of writing being “Partiinost,” or conforming to the ideals of the Soviet Party, was the major criterion of Socialist Realism. All writers had to follow this cri-
the Russian Individual
terion; the consequence of disobedience was persecution and death. Akhmatova and Pasternak differed from Stalin’s vision. For them, for the purpose of literature was to directly connect with the audience and to lift the individual above the state. In fact, Akhmatova and Pasternak refused to adopt Stalin’s Partiinost guidelines and, in the face of persecution, they continued writing in their home country. Akhmatova wrote her greatest work, Requiem, from 1935 to 1940. Since it was forbidden to have anti-Socialist writings in her possession, Anna often recited her poems with a friend such that they both could commit her writings to memory (Feinstein). The poems of Requiem cover Akhmatov’s emotions and thoughts during a time when many of her family members and friends had been robbed of their lives. Part of the epilogue reads: I have learned how faces fall, How terror can escape from lowered eyes, How suffering can etch cruel pages Of cuneiform-like marks upon the cheeks. I know how dark or ash-blond strands of hairha Can suddenly turn white. I’ve learned to recognise The fading smiles upon submissive lips, The trembling fear inside a hollow laugh. That’s why I pray not for myself But all of you who stood there with me Through fiercest cold and scorching July heat Under a towering, completely blind red wall. Akhmatova’s writing exudes a deep intimacy with the human being, both physically and emotionally. By detailing her own thoughts and sentiments, Akhmatova allows readers to sympathize with her condition and reminds people about the preciousness of life. Writing as an individual about how she suffered and loved made her work relatable to the millions of others who endured similar hardships under Stalin’s reign. Akhmatova became very close with Boris Pasternak, the prolific writer who would go on to win the Nobel Prize in Literature. Pasternak composed poetry and wrote several novels. His most famous novel is Dr. Zhivago which was published in 1957 and detailed the life of the protagonist Dr. Zhivago during the Russian Revolution and the Russian Civil War. Pasternak was in and out of favor with the Soviet regime, but Dr. Zhivago ran countered to Socialist Realism movement, and as such, he published it abroad. It is at first glance an epic love story, laced with anti-war sentiments. Upon further inspection, however, the story is a criticism of Stalinist government. The very style of the novel recalls pre-revolutionary writing in the tradition of Dostoevsky (part of the traditional Russian canon), and includes many Orthodox references. Pasternak promotes the value of the human individual as much as Akhmatova does. In a passage towards the end of the novel, the main character, Zhivago muses on the significance of history: “A forest does not move; we cannot catch it, cannot surprise it changing place. We always find it immobile. And it is in the same immobility that we find the eternally growing, eternally changing life of society, history, in its unobservable transformations”.3 Here, Pasternak implies that while Stalin’s government has changed the day-to-day operations of Russians, the Russians themselves are still unchanged human be-
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humanities ings. He goes on to describe how revolutions and leaders come and go, but the essence of the people remains the same. One cannot help but think that Pasternak is making these statements through Zhivago, in emphasizing the singularity of humankind in the face of oppression. Furthermore, Pasternak’s Zhivago proclaims that “No one makes history, it is not visible, just as it is impossible to see grass grow”.3 Zhivago explicitly criticizes the Stalin government, saying what many before have thought but have been too afraid to utter: the Stalin regime, despite its radical reforms, does not have the omnipotent abilities that it proclaims. Here lies a fundamental difference between Pasternak and the Stalinsponsored Socialist writers. Although Socialist Realist writers quietly toed the line, Pasternak and his peers defied the fundamental ideology of their intellectual jailers. Pasternak does not bend his writing to the will of the regime, and, by daring to oppose its fundamental ideology, Pasternak undermines the importance of the Socialist State and, as a result, raises the importance of the human individual. At the end of “Dr. Zhivago”, Pasternak includes a collection of poems that are deeply emotional. Their subject matter encompasses nature, love and Christianity, among others. Pasternak’s intimate descripFigure 1: Portrait of Anna Akhmatova tions of physical features are simple and yet paint very realistic and deep portraits of human beings, again emphasizing the value of the human individual. Although its physical form and medium have changed in the decades since Stalin, writing continues to be a powerful tool in the defense of the human spirit. Those who face censorship still use writing as a way to reach others and express themselves no matter the consequences. A very recent example of this occurred during the 2010-11 political turmoil in Egypt, where the government blocked Internet access. Those within the country turned to new voice technology by Google to post updates on the Internet. These firsthand accounts were critical in informing the
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hurj spring 2012: issue 14 world of the struggles going on within Egypt. Although the times were radically different and the technology would have been unfathomable a century ago, the cause of the people of Egypt did not differ from that of Akhmatova’s or Pasternak’s. These two Russian writers set a precedent of fearless, defiant writing that became extremely important and inspirational to oppressed people of the future. As in Pasternak’s metaphor, the seasons in the forest have changed, but the forest has come through mostly untouched. The people are still people, unwavering in their ability to overcome adversity, using writing as one of their greatest tools. References 1. Brooks, Jeffrey. Thank You, Comrade Stalin!: Soviet Public Culture from Revolution to Cold War Princeton, NJ: Princeton Univ., 2001. Print. 2. Von Geldern, James, and Richard Stites. Mass Culture in Soviet Russia: Tales, Poems, Songs, Movies, Plays, and Folklore, 1917-1953. Bloomington, IN: Indiana Univ., 1995. Print. 3. Pasternak, Boris Leonidovich. Doctor Zhivago. Trans. Richard Pevear and Larissa Volokhonsky. New York: Pantheon, 2010. Print. 4. Yevtushenko, Yevgeny Aleksandrovich, Albert Todd, and Max Hayward. Twentieth Century Russian Poetry: Silver and Steel : An Anthology. New York: Doubleday, 1993. Print
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British and American Experiments in African Colonization: Unsuccessful Ventures in Eliminating the Slave Trade and Slavery Catherine Rose, Class of 2012 History The earliest known mention of the potential for colonizing free people of color came from an anonymous New Jersey resident in 1714, who said that all slaves should “be set free…[and] sent to their own country.”1 This man’s idea came to fruition one hundred and twenty years later when both Britain and the United States had established colonies in Africa for the purpose of sending free people of color to the land of their ancestors. Although both nations experimented in colonization, Britain intended to end the slave trade, while proponents of colonization in the United States saw colonization as a vehicle for emancipation. In both nations, men believed that free blacks were only nominally free and would have more opportunities to succeed in an environment free of racism.2 After the American Revolution, with different intentions in mind, groups of people in both the United States and Britain believed that by establishing a colony in Africa, they could end institutions that had been in place for centuries. While men in Britain believed colonization would bring an end to the traffic of humans across the Atlantic, men in America saw colonization as a means to end the entire institution of slavery. The discrepancy in goals can be attributed to the different roles each nation played in the Atlantic slave trade and in slavery itself. In the late eighteenth and early nineteenth centuries, Britain was one of the most powerful nations in the world. British theorist Malachy Postlethwayt said in 1746, “The Negro-Trade and the natural consequences resulting from it may be just esteemed in the inexhaustible fund of wealth and naval power to the nation.”3 The products produced by slave labor produced immense capital, making Britain a world power and making it hard to argue for abolition. British abolitionists found greater support when they focused their efforts on a different goal, ending the trafficking of Africans across the Atlantic. In the late eighteenth century, philanthropic societies became popular in Britain. There were approximately five thousand free blacks in London in the 1780s, and probably double that in all of Britain because of the British Proclamation during the American Revolution, which promised freedom to all slaves who fought for the loyalists. Free blacks in London were mostly members of military bands, either in the Royal Artillery or other regiments, and those that were not in uniform were either prostitutes or beggars, who could not find legitimate work.4 The actions taken towards colonizing the free black population were a result of the movement in Britain to form societies for the benefit of the repressed, the poor, and the destitute. Henry Smeathman was one of the first British advocates for colonization in Africa as a means to end the slave trade. Smeathmen did an immense amount of research on the social structure of termites and noticed that termites repress individuality for the good of the community and have a highly specialized labor force, precisely what Smeathman believed was lacking in African society. He concluded
that Africans were lazy, indolent, and lacked any sort of domestic economy from his observations. To solve these problems, Smeathmen thought that the British should buy slaves from slave ships en route to the Americas, settle them on the west coast of Africa, and have them work to repay the cost of their freedom. Like termites, they would not be enslaved, but they would work hard and in an organized fashion. Once the settlement was established, Smeathmen believed that the British poor, refugees from America, and free blacks from the Americas would want to settle there in spite of the fact that they were already free. They would be drawn to the idea of going somewhere where the color of their skin would not be the first thing people noticed about them. He pitched his ideas to his powerful Quaker friends with the ultimate goal of ending the slave trade by planting “a sprig of science and liberty on the oppressed coasts of Africa.”5 Another key player in the British colonization movement was Granville Sharp, who took over the movement when Smeathmen died in 1786. By establishing a colony in Africa, Sharp believed that a legitimate trade of goods between England and Africa could be established and people would realize that Africa had more to offer than human labor. Further, civilized colonists in Africa could spread the ideals of Christianity and teach the local people that slavery was wrong, stopping them from providing slaves to Europeans. For Sharp, the colony was about bringing Christianity and British influence to Africa in order to spread these ideals and bring about an end to the slave trade.6 On April 9, 1789, the British Navy transported four hundred and fifty nine passengers to the colony Sharp had named the “Province of Freedom,” in Sierra Leone.7 Although Sharp’s colony ultimately may have failed, British colonization of free blacks in Sierra Leone did not end with the
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Province of Freedom. Freetown, a new copy built in place of the those who do justly, love mercy, and walk humbly with their god.”16 Province of Freedom, became home to eleven hundred free blacks, In 1790, another Virginian, Ferdinando Fairfax, began to adwho had been freed by the British proclamation and had been liv- vocate colonization to end slavery because he did not think it was ing in Nova Scotia since the American Revolution.8 Following the possible for blacks and whites to live in harmony. He proposed interNapoleonic Wars, Britain continued to settle former slave soldiers, marriage as a means to create equality, but admitted very few people and maintain, to this day, a naval base in Freetown, Sierra Leone, would find it an appealing possibility. Unlike Jefferson, Fairfax beoriginally established to patrol the coast for illegal slave ships.9 lieved that emancipation was a violation of property rights and the There is one instance of American participation in the British only legal way for emancipation to occur was to ensure masters that colonization experiment in Sierra Leone before the establishment their freed slaves would not be a danger to them or to their comof the American Colonization Society and the settlement of Libe- munity. He proposed that Congress secure a piece of land in Africa ria.10 Massachusetts had outlawed slavery and freeing slaves was for free blacks and believed that slaveholders would be more likely becoming more and more popular in the northern United States. to free their slaves because fear for their safety. As an incentive to Samuel Hopkins, a prominent member of the Providence Society for Congress, he noted that America would reap the benefits of having a the Abolition of the Slave Trade, described his plans in a letter to tropical colony with valuable resources they would otherwise have to Granville Sharpe, who had just established the Province of Freedom, pay more to acquire. Even though Jefferson and Fairfax disagree on inquiring as to the progress of his colony and whether he would emancipation, they both believe that colonization would end slavery.17 be able to send blacks from America there as well. Sharp agreed The influence of Jefferson and Fairfax is evident in cases of prito Hopkins’ proposition, but when Hopkins sent a man to further vate colonization ventures made before the formal establishment of explore the opportunity, Sharp was no longer a part of the colony the American Society for Colonizing the Free People of Colour in the and Freetown had been established on United States. The most influential intop of the failure that was the Province stance of private colonization, however, of Freedom.11 This is one of the only occurred in 1815, when Paul Cuffee The concept of colonization as a examples of Americans attempting to brought thirty-eight free blacks to the means to end slavery in the United work with the British venture to end British settlement in Sierra Leone.1819 States ultimately failed, but it the slave trade. This early venture does After the War of 1812, benevonot reflect the wish of the American lent societies appeared all over the Unitsucceeded in sending thousands of Colonization Society to end slavery ed States for the purpose of aiding the free blacks to Africa. that emerged a few decades later, but poor and irreligious. Reverend Robert it is representative of the benevolence Finley of New Jersey was a well-known many Americans had toward blacks clergyman in New Jersey and the direcand Africa. Tensions between the nations were high so soon after tor of theological seminary at Princeton University. He was drawn the Revolutionary War, but citizens from each nation agreed on colo- to the idea of colonization because he believed three things would be nization of free people of color enough to attempt to work together. accomplished. The United States would be free from its growing free Thomas Jefferson was one of the first advocates of colonization black population, Africa would gain a group of partially civilized inin the United States. Although he was a slave owner, Jefferson felt dividuals with knowledge of Christianity, and the free blacks would strongly that slavery was evil and that it needed to cease to exist in the be in a better situation, free from prejudice in the United States.20 United States. He feared that the growing Negro population would Many Americans were concerned about being in close proxreverse the roles of slave and master and said, “I tremble for my imity to a large free black population and Mills and Finley believed country when I reflect that God is just: that his justice cannot sleep that many Americans would be more inclined to free their slaves if forever.”12 It was only a matter of time until God punished American they were not in contact with free blacks. The Haitian Revolution whites for the pain they had inflicted on Africans and their descen- proved that free black populations could be dangerous and colodants for centuries.13 In his “Notes on the State of Virginia,” Jefferson nization became a more legitimate solution in the United States. says, “Among the Romans emancipation required but one effort. The After the meeting in Princeton, Mills toured the Atlantic states to slave, when made free, might mix with, without staining the blood spread the word about the formation of a colonization society.21 22 of his master. But with us a second is necessary, unknown to history. The first general meeting of the society took place on DecemWhen freed, he is to be removed beyond the reach of mixture.”14 In ber 21, 1816 in Washington, D.C., where they officially named this passage, Jefferson supports emancipation out of fear of God’s themselves The Society for the Colonization of Free People of Colpunishment for Americans, but acknowledges that ending slavery or of America. They discussed the importance of atoning for the presents challenges because of the racial nature of slavery in the wrongdoings Americans had committed in Africa by promising United States. Jefferson believed free blacks had to be removed from equality, a homestead, and free passage to Africa and the ability to society before God delivered retribution on American slave owners.15 eliminate a dangerous population and bring Christianity and civiMany more would make similar thoughts public in subsequent years. lization to Africa. The first objective appealed to southern slaveDuring Jefferson’s presidency, a Philadelphia Quaker, John Par- holders and the second appealed to northerners who, not as tied rish proposed domestic colonization as a means to end slavery and to slavery, were more concerned about morality and the wellbeing relieve Americans of their sins. The government would provide a of the colonized people. The society, much like British proponents homestead to every black family in the western wilderness and slave of colonization, recognized the role this colony would play in exowners would take comfort in the fact that their former slaves would terminating the trafficking of slaves. They believed slaveholders be far enough away to not threaten the family that they once served. would be deterred from securing human cargo in an area where Only after they were freed from this “dreadful evil,” Parrish said, there was a civilized Christian colony and that the colonists would could the nation could enjoy “that Sabbath which is prepared for all be able to promulgate the idea that selling people into slavery was
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hurj spring 2012: issue 14 morally wrong and Africans would end their participation in the trade. The main objective of the society went beyond abolishing the trade and in the words of Mills: “it is confidently believed by many of our best and wisest men that, if the plan proposed succeeds, it will ultimately be the means of exterminating slavery in our country.23 The concept of colonization as a means to end slavery in the United States ultimately failed, but it succeeded in sending thousands of free blacks to Africa. The United States signed a contract to secure land in Liberia following the Act of 1819. From 1820-1821, very few people were sent to Liberia, but by 1830, almost 500 people had been freed and sent to the colony, and another 1,100 free blacks from the United States or slaves recovered from ships en route to the Americas were also living in Liberia. In 1830, President Andrew Jackson chose to reinterpret the Act of 1819 and ceased federal aid to the American Colonization Society, but voyages continued. Following Nat Turner’s Rebellion, which added to white fears of a free black population and to black fears of an angry white population, 1,300 slaves and free blacks relocated to Liberia. The Fugitive Slave Act, passed in 1850, gave free blacks another reason to leave the United States. Many free northern blacks were worried about being claimed as slaves and forced to work in the south. President Lincoln supported colonization, but did not think that it could end slavery, because it was impossible to remove the entire black population of the United States. The heyday of the American Colonization Society ended with the onset of the Civil War, but it was not formally dissolved until 1964.24 Like Britain, the United States failed in achieving its goal by way of colonization, but all slaves in the United States were eventually freed by the passage of the 13th Amendment after the Civil War in 1865. Colonization presented a viable means to achieve two different goals in two different nations. People in Britain saw colonization as a way to end the slave trade. There were no slaves in Britain itself, and those who were enslaved within their empire produced too much capital for any majority of British people to support abolition. The major moral issue in Britain was their involvement with the trafficking of Africans across the Atlantic, which they believed colonization would remedy. In the United States, the biggest moral issue concerning slavery was the fact that Americans were actively enslaving blacks. Even if people did not feel guilt for their sins, they did fear the possibility of God’s punishment. They could not abolish slavery for fear of an incident similar to the Haitian Revolution or Nat Turner’s Rebellion, so the Colonization Society formed around the idea of removing the free black population a safe distance away, while also providing for the free blacks in their new home. They believed they could end slavery by convincing slaveholders that they would be safe after they granted freedom to their slaves. People in Britain and the United States had different goals for their experimentation with colonization because they had different levels of involvement and interaction with blacks and their movement across the Atlantic and enslavement in the Americas. Bibliography
Abasiattai, Monday B. “The Search for Independence: New World Blacks in Sierra Leone and Liberia, 1787-1847.” Journal of Black Studies 23 (1992): 107-116. Bergh, Albert Ellery, ed. The Writings of Thomas Jefferson: Volume 2. Charlottesville: University of Virginia Library Electronic Text Center, 2000. Accessed November 7, 2010. http://etext.lib.virginia.edu/toc/modeng/public/JefBv021.html Blyden, Nemta Amelia. “Back to Africa: The Migration of New World Blacks to Sierra Leone and Liberia.” OAH Magazine of History 18 (2004): 23-25. Brookes Jr., George E. “The Providence African Society’s Sierra Leone Emigration Scheme 1794-1795: Prologue to the African Colonization Movement.” The International Journal of African Historical Studies 7 (1974): 183-202.
humanities Brown, Christopher L. “Empire Without Slaves: British Concepts of Emancipation in the Age of the American Revolution.” William and Mary Quarterly 56 (1999): 173-306. Burin, Eric. Slavery and the Peculiar Solution: A History of the American Colonization Society. Gainesville: The University Press of Florida, 2005. Coleman, Deidre, Romantic Colonization and British Anti-Slavery. Cambridge: Cambridge University Press, 2005. Hickey, Donald R. “America’s Response to the Slave Revolt in Haiti 1791-1806.” Journal of the Early Republic 2 (1982): 361-379. Hochschild, Adam Bury the Chains: Prophets and Rebels in the Right to Free an Empire’s Slaves. New York: First Mariner Books, 2006. Hutton, Frankie. “Economic Considerations in the American Colonization Society’s Early Effort to Emigrate Free Blacks to Liberia.” The Journal of Negro History 68 (1983): 376-89. Matthewson, Tim. “Jefferson and Haiti.” The Journal of Southern History 61 (1995): 209-248. Sherwood, Henry Noble. “The Formation of the American Colonization Society.” The Journal of Negro History 2 (1917): 209-28. Staudenraus, P.J. The African Colonization Movement 1816-1865. New York: Columbia University Press, 1961. United Nations Integrated Peacebuilding Office in Sierra Leone. “History.” Accessed December 1, 2010. http://unipsil.unmissions.org/Default.aspx?tabid=4442.
References
1. Eric Burin, Slavery and the Peculiar Solution: A History of the American Colonization Society (Gainesville: The University Press of Florida, 2005) 7. 2. Abasiattai, “The Search for Independence,” 107. 3. Christopher L. Brown, “Empire Without Slaves: British Concepts of Emancipation in the Age of the American Revolution,” The William and Mary Quarterly 56 (1999): 273. 4. Hochschild, Bury the Chains, 143-144. 5. Deidre Coleman, Romantic Colonization and British Ant-Slavery (Cambridge: Cambridge University Press, 2005), 29, 32, 52-53, 57-58. 6. Hochschild, Bury the Chains, 146, 148-150. 7. Abasiattai, “The Search for Independence,” 108. 8. Brooks, “The Providence African Society’s Sierra Leone Emigration Scheme 1794-1795,” 190. 9. “History,” United Nations Integrated Peacebuilding Office in Sierra Leone, accessed December 1, 2010, http://unipsil.unmissions.org/Default.aspx?tabid=4442. 10. Burin, Slavery and the Peculiar Solution, 8. 11. George E. Brooks, Jr. “The Providence Society’s Sierra Leone Emigration Scheme 1794-1795: Prologue to the African Colonization Movement,” The International Journal of African Historical Studies 7 (1974): 184-186, 195-196. 12. Staudenraus, The African Colonization Movement, 2. 13. Staudenraus, The African Colonization Movement, 1-2. 14. Albert Ellery Bergh, The Writings of Thomas Jefferson: Volume 2 (Charlottesville: University of Virginia Library Electronic Text Center, 2000) accessed November 7, 2010, http://etext.lib.virginia.edu/toc/modeng/public/JefBv021.html. 15. Staudenrauss, The African Colonization Movement 1816-1865, 2. 16. Staudenrauss, The African Colonization Movement 1816-1865, 4. 17. Staudenrauss The African Colonization Movement 1816-1865, 2-3. 18. Henry Noble Sherwood, “The Formation of the American Colonization Society,” The Journal of Negro History 2 (1917): 209-10. 19. Cuffee was a very talented Quaker seaman from Massachusetts and of African and Indian descent. Cuffee had never been a slave himself, but even as a free black man, he preferred colonization to living among whites. Cuffee died before he could continue his work with the then established society, but there is no doubt that his privately funded voyage set the tone for the establishment of the society and their endeavors. Staudenrauss, The African Colonization Movement 1816-1865, 15-19. 21. Staudenraus, The African Colonization Movement 1816-1865, 18. 22. The fear of many Americans of free blacks can be attributed to the Haitian Revolution. The French colony, St. Domingue, was the largest and wealthiest colony in the Caribbean in 1789. In 1791, it was the world’s leading producer of sugar and coffee and accounted for half of all the slaves in the Caribbean. The French Revolution weakened the relationship between the nation and her colony, allowing for the uprising of slaves in the North Plain, who killed their masters and set fire to their plantations. The original revolt spread across the island and Toussaint Louverture, a free black man, organized the blacks and Haiti became a free republic in 1804. Because the United States had a large population of blacks, both slave and free, they became fearful of a similar incident. Sherwood, “The Formation of the American Colonization Society,” 221-224. 24. Burin, Slavery and the Peculiar Solution, 15, 17, 19, 30, 32-20.
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Franciscan Influence in the Walters Art Museum’s Crucifix with Mourning Virgin and St. John the Evangelist Rebecca Krishnan-Ayer, Class of 2013 Art History, French Literature Originally displayed above the altar of a church between the nave and the sanctuary, Crucifix with Mourning Virgin and St. John the Evangelist can be dated to the medieval period (Fig. 1).1 This Gothic style crucifix now hangs in the Walters Art Museum in Baltimore, Maryland. It was crafted using tempera paint and gold leaf on panel2 between the years 1275 and 1300 in Florence or Arezzo, Italy by an anonymous Italian artist of the Florentine school of painting.3 The work is a single-sided painted panel cross, confirming that it was not used for church processions, but rather for display at the altar.4 The Virgin Mary and St. John the Evangelist flank Christ on the left and right rectangular end pieces of the cross’ arms, respectively.5 Both Mary and St. John the Evangelist face slightly inward, drawing attention to the highly stylized Christ located in the center vertical section of the cross. The two figures mourn his death, their hands clutching their faces in grief. Edges of the panel have weathered from insect damage and portions of the gold leaf inscription in the upper terminal of the vertical section have disintegrated.6 The traces of the inscription have been restored and read, “IHS. NAZARE DEORUMNUS. REX. IU,” which translates to “Jesus of Nazareth, King of the Jews.”7 The artist rendered Christ in the form of Christus patiens, or suffering Christ, which was a convention that began around 1240.8 This emphasis on Christ’s suffering, coupled with the “christocentric” (Christ-centered) nature of the piece, suggests influence of the Catholic Franciscan order, which helped disseminate a number of Christus patiens icons during the Italian duecento.9 While some aspects of the Walters crucifix’s origins remain uncertain (namely, the author and the exact place of origin), the most compelling evidence that points to the Walters crucifix’s Franciscan influence is that author of The Development of the Italian Schools of Painting: From the 6th until the end of the 13th Century and art historian Raimond Van Marle insists the Walters crucifix is in fact Franciscan by dating the crucifix to the latter half of the thirteenth century and by pointing out the similarities between Walter’s Christ and other Franciscans depictions of Christ around that time.10 The first depictions of Christ crucified, such as those found on the doors of the Santa Sabina church in Rome, emerged around the turn of the fifth or sixth century.11 The Italian conquest of Constantinople and the resultant cultural fusion of Eastern and Western Europe spurred an analogous synthesis of artistic conventions in both the East and the West, giving rise to the maniera greca style, or “in the Greek manner.”12 When Constantinople fell, the rise of the Mendicant orders, such as the Franciscan and Dominican orders, contributed to this exceptional melding of artistic style. These religious orders, founded by St. Francis of Assisi and St. Dominic of Osma respectively, helped evolve a new series of artistic conventions in religious painting. The Franciscan order in particular began gaining momentum as thirteen-century Italian painting started to
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adopt Eastern features, and the Order profoundly affected the art of the time period.13Van Merle remarks that Franciscan art “found expression in the decoration of churches, in pictures of saints, and in the painted Crucifix, the veneration for which had been greatly increased and had even acquired a fresh aspect as a result of the miracle of the stigmata.”14 Hence, although Byzantine attributes resurfaced in the decorations of the church, Franciscan ideals undoubtedly began penetrating art as well, augmenting the importance of the painted Crucifix and the representation of Christ’s stigmata. Art Historian Anna Derbes cites an underlying characteristic of Franciscan art: “Devotion to the passion was central to Franciscan piety, a defining attribute both of Francis and of the order he founded. In fact, the term ‘Franciscan spirituality’ has become virtually synonymous with the veneration of Christ’s suffering on the cross.”15 Between the late eleventh century and early twelfth century, Franciscan compassion for the suffering Christ in the form of Christus patiens began to take hold in crucifixes and passion narratives.16 Christus patiens, intended to educe sympathy from the viewer, replaced the former and more traditional Christus triumphans, which depicted Christ triumphant over death with considerably less emphasis on the stigmata.17 With the proliferation of the Franciscan order came a distinctive artistic genre of church adornments and a markedly different incarnation of Christian devotional practice.18 This aspect of Franciscan art is readily apparent in Crucifix with Mourning Virgin and St. John the Evangelist. Franciscans venerated St. Francis as a thaumaturgy, capable of inducing miracles, thus narrative panels displayed in Franciscan churches often adopted this subject matter.19 Much of Franciscan art centered on the religious aspect of the posthumous miracles, one of the conditions of sainthood, as well as St. Francis’ miraculous stigmatization.20 This explains the emphasis on Christ’s suffering and stigmatization in Franciscan crucifixes. Proponents of the Franciscan order aimed to disseminate the ideas of St. Francis and broaden their base of believers through images that demonstrated Francis’ four posthumous miracles or through images that closely equated Christ with St. Francis.21 As such, Passion narratives and crucifixes assumed a prominent role in the Franciscan church. As Belting notes, “St. Francis of Assisi had developed a model for the cult of the Crucified, whom he wanted to resemble even in his sufferings.”22 The Franciscan Order laid the framework for a longstanding and prolific model of crucifix with the commissioning of Giunta Pisano’s panel cross in 1236 (Fig. 2).23 Giunta was well renowned as a master of the Pisan school, and he crafted this piece for St. Francis’ burial church.24 Raimond Van Marle extols him as “the master who best interpreted the Franciscan conception of the crucifix.”25 The crucifix itself was given by Elias of Cortona in 1236, the next in command to St. Francis in the Franciscan Order and establisher of the church.26 The crucifix served as a “triumphal cross in the present Lower Church.”27 Hans Belting refers to Giunta’s crucifix as “the archetype of the further development because of its site, the church of S. Francesco at Assisi39” or the one work that set the precedent
hurj spring 2012: issue 14 for numerous succeeding Franciscan panel crosses.28 Robert Oertel too suggests the archetypal nature of the this crucifix when he states: Although there were Byzantine precedents for the figure of Christ in this form and with this expression, it was through Guinta Pisano that it became the standard type of Italian Duecento crucifixes. Giunta himself made no further alterations…Even as late as the end of the century a master like Cimabue could add nothing to this solution.29 Not only does the crucifix represent the substitution of Christus triumphans with Christus patiens, but also it is demonstrative of the more minimalistic style of the new model of crucifix. Following canons initiated by the painter of the Franciscan church in Prescia, Buonaventura Berlinghieri, Giunta eliminated the custom of side narratives altogether, shifted the focus to Christ as the central subject, and elected to include only Mary and St. Fig. 1. Crucifix with Mourning Virgin and St. John the John, the witnesses Evangelist, 1275-1300. Tempera and gold leaf on panel, of Christ’s crucifix- 98 11/16 x 89 9/16 x 1 9/16 in. Walters Art Museum, ion. Furthermore, Baltimore. these conventions can be seen in the oldest one of Giunta’s panel crosses, the crucifix of Santa Maria degli Angeli near Assisi (Fig. 2), which possesses features that mirror that of the Walters crucifix as well. Giunta’s consequential crucifix bears a striking resemblance to Crucifix with Mourning Virgin and St. John the Evangelist. The Fig. 3. Romagnole School, Crucifix (Franciscan), Thircentury. Paint on glass, 82 5/8 x 74 7/8 in. Convent inscription “Je- teenth of S. Francesco, Villa Verucchio, Italy. sus of Nazareth: King of the Jews” adorns the upper terminal of both crucifixes. Both works depict Christ in the form of Christus patiens, his eyes closed, his emaciation exaggerated, and the stigmata prominently rendered. The artist of these pieces portrayed Christ in a stylized manner, from the geometrical anatomy to the patterned hair and beard. The perizoma, or loin-
humanities cloth,30 Christ wears in both crucifixes are equally diaphanous, and the cruciform halo is of similar scale and degree of relief. Even the colors of tempera paint applied to the panels are alike, with the juxtaposition of deep background colors (namely scarlet, burgundy, black) against the luminescence of the gold borders and light flesh tones. Perhaps the most notable similarity is that just as in the Walters crucifix, Giunta’s crucifix includes the mourning Virgin and St. John on the ends of the arms, underlining the emergence of Christus Patiens as a standard convention. Since the Franciscan-commissioned Giunta crucifix can be considered “archetyp[al]”31 of Franciscan panel crosses, then its remarkable similarities with the Walters crucifix confirms that the Walters crucifix contains distinguishable Franciscan elements too. Giunta’s commissioned crucifix is not the only Franciscan crucifix that shares congruent features with “Crucifix with Mourning Virgin and St. John the Evangelist.” The Walters crucifix’s close resemblance to a thirteenth century Romagnole school Franciscan crucifix (Fig. Fig. 2. Giunta Pisano, Crucifix, 1236. Basilica di 3) is astounding—the S. Maria degli Angeli, Assisi, Italy. curvature of Christ’s body, expressions of Mary and St. John, stigmata, and even the scale of the crucifixes are all alike. The artist of the Walters crucifix also modeled his design after the crucifixes of the great Florentine painter, Giovanni Cimabue.32 In particular, Cimabue’s crucifix from the Florentine Santa Croce church (Fig. 4), a Franciscan church, arguably inspired Fig. 4. Giovanni Cimabue, Santa Croce many elements of the Crucifix, 1280-1285. Florence, Italy. Walters crucifix.33. The rendering of Christ’s arms and legs, as well as the figure of St. John are especially comparable in these two crucifixes.34 The Santa Croce cross can be dated to around 1280-1285, and as Derbes claims, is “well known to students of duecento painting for its startling departures from the conventions seen in earlier painted crosses.”35 This crucifix, like Giunta’s Franciscan crucifix done in 1236, marks the momentous shift in the scheme of panel crosses. Because the Walters crucifix shares a noteworthy resemblance with both these works,
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the Walters crucifix, too, can be regarded as having been shaped by crucifix.43 Derbes claims that the ensuing Franciscan “appeal” in this shift between the Romanesque and rendering the perizoma so delicately may Gothic Franciscan manner of rendering have been because it presented an almost crucifixes. Not only do these works typify nude representation of Christ.44 The idea the gradual movement into a more “natuof a naked Christ would have been widely ralistic representation” of Christ, but they embraced in Franciscan liturgical practice also embody crucifixes of the Franciscan since “the naked Christ was a ‘key figure’ style.36 The origins of the Santa Croce crufor Francis.”45 St. Francis’ biographer, Bocifix can be traced to Florence, like the naventure, and other Franciscan writers Walters crucifix, confirming the prospect utilized the concept of the naked Christ in that one of these pieces must have influterms of Franciscan ideology to again asenced the stylistic traits of the other on sociate Christ with St. Francis.46 Bonaventhe basis of proximity. In considering the ture supported the display of an unclothed artistic influence of the Franciscan Santa Christ because “just as Francis stripped to Croce crucifix on the Walters crucifix, it renounce his father’s wealth, Christ’s nuis only logical to assume that such distincdity likewise proclaimed his poverty, and tively Franciscan ideals were reciprocated. thus validated the vow upon which Francis Cimabue’s crucifix from the San Dofounded the Order.”47 Cimabue accordingly menico church in Arezzo (Fig. 5), made made the Santa Croce cross with Francisaround the same time as the Walters crucan ideology in mind, and in manipulating cifix between 1270-1275 presents analothe effect of the perizoma, he insinuated the gous evidence of Franciscan commission.37 image of a naked Christ.48 Building on this Christ’s stylized, protruding abdomen and manipulation of Christ’s loincloth, a “refthe figure of Mary in the Walters crucifix erence to Franciscan poverty,” as Derbes chiefly recall characteristics of Cimabue’s terms it, the Franciscan crucifix also came San Domenico crucifix. Again, one nota- Fig. 5. Giovanni Cimabue, Crucifix, c. 1270. Tempera to exhibit a less ornate and more subdued ble comparison between these works is the on gold panel, 336 x 267 cm. Arezzo, Church of San style.49 The Santa Croce cross embodies Domenico, Arezzo, Italy. conscious attempt on behalf of the artist to this notion—gold contours on the drapery articulate the translucency of Christ’s perof the subjects’ garments, typical of precedizoma. Ferdinando Bologna iling crucifixes, were discarded, lustrates the difference between along with intricate designs surCimabue’s San Domenico crucirounding Christ on the panels.50 38 fix and his Santa Croce crucifix. These artistic formulae The San Domenico piece reflects function as a testament to Franinfluence from crucifixes by ciscan austerity, and they are Coppo di Marcovaldo, but also certainly present in the Walters reveals a reiteration of Byzantine crucifix. The Walters crucifix techniques.39 On the contrary, evinces little ostentation, and the Cimabue’s Santa Croce crucifix artist utilized solid colors and signifies the “first example of a a limited addition of design to broad relaxation of manner” in underscore Christ’s eminence. crucifixes, with a rejection of the While the Walters work may informer Byzantine gold perizoma corporate significant amounts of in favor of a transparent one.40 gold, this was probably not apThe result of this replacement plied with the intention of ostenis an increased concern with tation, but rather practicality and depicting the rudimentary and liturgical purpose—it was necemotionally vulnerable form of essary that the crucifix be seen Christ, Christus patiens,41 as evifrom farther distances within denced in the Walters crucifix. the church. It would still seem Some of the first depictions plausible then that this crucifix of Christ’s translucent perizoma contains Franciscan influence. can be traced to mosaics at HoIn any case, Crucifix sios Lukas in Byzantium and with Mourning Virgin and St. in Byzantine icons located in Fig. 6. Giotto di Bondone, Saint Francis’s Miracle of the Crib at Greccio, 1295-1305. John the Evangelist exempliMt. Sinai, and the convention Fresco, 90.55 x 106.30 in. Assisi, Italy. fies the Christus patiens form persisted much later during the with its strong emotive qualiduecento, eventually encounties and emphasis on Christ’s tering Franciscan art.42 Cimabue replicated this idea of an almost overwhelming lack of vitality. It maintains discernible similarities transparent loincloth covering Jesus, beginning with his Santa Croce with the crucifixes created by Giunta and Cimabue for Franciscan
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hurj spring 2012: issue 14 churches and with those made by anonymous Franciscan artists. This in turn indicates that the artist of the Walters crucifix must have then drawn inspiration from Franciscan artistic traditions. Though much still remains to be deciphered regarding the origins of this piece, the incredible artistic skill required in its creation is unmistakable. If indeed the Walters crucifix were of the Franciscan order, its value would be significant, given that “the Franciscan Order played a decisive role in the development of Italian painting.”51
References
1 Zeri, Federico, Italian Paintings in the Walters Art Gallery, vol. 1, ed. Ursula E. McCraken (Baltimore: Walters Art Gallery, 1976), 4-5. 2 Ibid. 3 Ibid. 4 David Bomford and others, Art in the MakingL Italian Painting Before 1400 (London: The National Gallery Publications Ltd., 1989), 57. 5 Zeri, Italian Paintings in the Walters Gallery, 4-5. 6 Ibid. 7 Ibid. 8 Raimond Van Marle, The Development of the Italian Schools of Painting: From the 6th until the end of the 13th Century, vol. 1, The Development of the Italian schools of Painting (The Hague: Martinus Nijhoff, 1923), 307. 9 Anne Derbes, Picturing the Passion in Late Medieval Italy: Narrative Painting, Franciscan Ideologies, and the Levant (New York: Cambridge University Press, 1996), 16. Derbes claims,“For much of the thirteenth century, the Franciscans were in fact the most prolific patrons of all the orders.” 10 Ibid. 11 James J. Rorimer, “A Twelfth-Century Crucifix,” The Metropolitan Museum of Art Bulletin 30, no. 12 (Dec., 1935): 236, http://jstor.org. 12 Derbes, Picturing the Passion in Late Medieval Italy, 12. Derbes states, “Thirteenth-century Italian painting has traditionally been labeled the ‘maniera greca” (a disparaging term from the beginning) and its style described as ‘ItaloByzantine’; these terms are still used today.” 13 Van Marle, The Development of the Italian Schools of Painting, 258. 14 Ibid. 15 Derbes, Picturing the Passion in Late Medieval Italy, 17. 16 Ibid. 17 Ibid. 18 Derbes, Picturing the Passion in Late Medieval Italy, 23. 19 Gregory W. Ahlquist and William R. Cook, “The Representation of Posthumous Miracles of St Francis of Assisi in Thirteenth-Century Italian Painting,” in The Art of the Franciscan Order in Italy, ed. William R. Cook (Leiden: Koninklijke Brill NV, 2005), 214. 20 Ibid. 21 Ibid. 22 Belting, Likeness and Presence, 362. 23 Ibid. 24 Oertel, Early Italian Painting to 1400, 39. 25 Van Marle, The Development of the Italian Schools of Painting, 362. 26 Ibid. 27 Ibid. 28 Ibid. 29 Oertel, Early Italian Painting to 1400, 40. 30 Martin Davies, The Italian Schools before 1400, revised by Dillian Gordon (London: National Gallery Company, 2001), 82. 31 Belting, Likeness and Presence, 362. 32 Zeri, Italian Paintings in the Walters Art Gallery, 4-5. 33 Ibid. 34 Ibid. 35 Derbes, Picturing the Passion in Late Medieval Italy, 27. 36 Ibid., 28. 37 Oertel, Early Italian Painting to 1400, 49. 38 Ferdinando Bologna, Early Italian Painting: Romanesque and Early Medieval Art, ed. Roberto Longhi (Dresden: Edition Leipzig, 1964), 79. 39 Ibid. 40 Ibid. 41 Ibid. 42 Derbes, Picturing the Passion in Late Medieval Italy, 30. 43 Ibid. 44 Ibid.
humanities 45 Ibid. Derbes mentions that the image of Christ appearing nude on the cross appeared in many Franciscan literary works. 46 Ibid. 47 Ibid. 48 Ibid. Derbes affirms on p. 30, “The Santa Croce cross thus evokes the words of Bonaventure, who repeatedly described Christ ‘suspended destitute and naked.’ Though Christ is not literally naked in the Santa Croce cross, the translucent loincloth approximates nudity as closely as decorum would allow in the thirteenth century.” 49 Ibid. Derbes describes Monica Chiellini’s interpretation of the Franciscan nude Christ: “Noting, in the Santa Croce cross, the elimination of the gold striations in the cloaks of Mary and St. John, and the relatively subtle treatment of the decorative panels, [Chiellini] proposed that these features may be a Franciscan adaptation, deliberate muting of the ornate to make the image ‘less regal and sumptuous.’” 50 Ibid. 51 Ibid.,16.
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The Queen’s Two Heads: Victoria Disraeli Gratia Indiae Imperatrix Chet Connor, Class of 2012 History BA/MA “Shut-up—Lion! What is the use of growling any longer? Time is gone by; majorities are mighty; Disraeli is determined; the advice will be given; the Proclamation issued; and Victoria, Queen of England, will be henceforth Victoria, Empress of India,” declared Punch upon learning the House of Commons was going to pass Prime Minister Benjamin Disraeli’s “mess,” or the Royal Titles Act of 1876, following the Easter recess.1 The fight over the Royal Titles Bill had been fierce. For the past three months, Punch, England’s most widely circulated periodical of political satire, had often savagely rallied against the Bill in the name of protecting the liberal English democracy that characterized 19th century Victorian England from the potential tyranny of oriental despotism. In the drama of the Royal Titles Act of 1876, Mr. Punch, the eponymous hooked nose caricature of satirical print fame, becomes the protagonist of the story. Benjamin Disraeli, the “unEnglish” Prime Minister suspected of being a crypto-Jew (a Jewish person who claims to be part of the Christian faith but actually remains loyal to Judaism) is cast as the oriental villain tempting Queen Victoria to assume the crown of Imperatrix. The plot calls for the sardonic Mr. Punch to betray this enemy “Hebrew magician’s” designs on England’s beloved Queen through a series of caricatures by Punch’s John Tenniel titled “The Queen with Two Heads” and “New Crowns for Old Ones!”2— both published as part of the periodical’s satirical campaign against the Royal Titles Bill that stretched from March to May of 1876. Punch’s use of humor and satirical imagery through two of its most influential comics “New Crowns for Old Ones!” and “The Queen with Two Heads” promotes the magazine’s Liberal agenda designed to disparage the Conservative Disraeli government and delegitimize Victoria’s desires to add Empress of India to her Royal Titles. Between March and May of 1876, Punch relentlessly depicts Benjamin Disraeli as either an oriental, un-English Jew plotting to impose an eastern Empire upon liberal England or a rouge political craftsman seeking to add another head to the Queen’s Royal body so that it is suited to wear both the Crown
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of Empress and Queen. Victoria, on the other hand, represents the role of a passive monarch, impotent before the Prime Minister’s seductive charm or magical powers of creation, despite her alleged pursuit of the Royal Title. This two-fold attempt to portray the Queen as an ineffectual figure whose only role was to represent liberal English democracy allowed the liberal satirists to shift blame to Disraeli, whose seditious character could serve as a scapegoat for corrupting liberal democracy in England with the despotism associated with the idea of empire. For Prime Minister Benjamin Disraeli, the Royal Titles Act could not have come at a more inconvenient time. Although it was Disraeli who introduced the Bill to Parliament, it was Queen Victoria who felt it necessary to add “Empress” to her Royal Title due to her perceived waning influence following an increase in democratic and republican tendencies in England.3 The initial proposition did not delimit where the Royal Title would be in effect until Disraeli, in an effort to forestall controversy, assured that the title of Empress would not be implemented in the United Kingdom. Victoria was to be a QueenEmpress: Queen of England and Empress of India. The implications, at any rate, of an Imperial Title for Victoria in India were grave. The proclamation of “Empress” generated a title that could not only impress her Indian subjects, but also supplement her title as Queen amongst European powers.4 In political terms, however, the fealty of the Indian princes to the Empress created an official British hegemony over the subcontinent that put its resources, both financial and military, under the direct control of the Empire with the exclusion of Parliamentary control. Empire was a complete disregard for the indulgent self-proclaimed liberal tolerance of Victorian England. The Queen’s insistence upon the new Royal Title left Disraeli with little choice but to go forward with in pursuing the Act despite the recent war scare that arose from the tough Eastern Question that England faced when mediating between the Russian and Ottoman Empires. In fact, the threat of war with Russia to defend the Ottoman Empire brought to the forefront much skepticism about Disraeli’s loyalties to England. As a Jewish convert to Christianity at age 13, there were many attacks on the Prime Minister’s character as being that of an “un-English” crypto-Jew or an outsider, a “wandering
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Jew.”5 His defense of the Ottoman Empire, accused of brutal repression against Eastern Christians, provoked ire amongst his fiercest critics. The introduction of the Titles Bill did not help improve his situation due to its seemingly contrary nature to England’s self-identification. Punch’s motivating principle for attacking Disraeli comes from the simple fact that he was a Conservative Prime Minster that had unexpectedly defeated the Liberal Government of William Ewart Gladstone, the foremost champion of liberalism in 19th century England. Much of the debate, as Punch frames it, revolves around the Prime Minster’s compliancy with the Crown’s wishes over those of the people. The line of attack is a patent dismissal of Disraeli as an Englishman when the question of “Queen or Empress?” arises. When “Dizzy” says, “Empress,” Punch criticizes the claim as having “little force of logic, or reason of history.”6 His proposal, in a word is anti-English. Gladstone, on the other hand, says “Queen” with “emphasis all the more effective for the pulse of patriotism and force of feeling that beat and glowed under his words.”7 Punch wanted an English candidate that respected British traditions and institutions in a way that Disraeli, as a suspected crypto-Jew with an oriental sympathy, could never have understood because of the unclear and shifting nature of his loyalties. Due to its high readership (40,000 copies sold weekly)8 and lasting fame, the way in which Punch portrays both Prime Minster Benjamin Disraeli and Queen Victoria throughout the 1876 Royal Titles affair is of great historical importance. Punch could not (or more aptly would not) directly attack the Queen for her ambition. The Victorian use of laughter, according to historian Donald J. Grey, “was to ridicule in order to correct, or at least to unsettle, things and ideas which those who laugh take very seriously.”9 Punch was gentle with Queen Victoria in its determination to prevent her from becoming the Empress Victoria largely because of the traditionally polite nature of Punch’s satire and the deference traditionally shown to the monarchy. In the May 6 issue, Punch declared he “won’t believe in ‘Victoria Imperatrix’ till he has it under her Royal hand” with the hope “she may have had her Royal eyes opened to the real state of the case at the eleventh hour, and may shrink from the change of title after all!”10 Although Victoria herself was not greatly criticized, Punch attacked Disraeli with a savagery that was uncommon for the era and the periodical itself. Disraeli was the Hebrew, seditious traitor that created an Imperial Title and forced it upon an unsuspecting democratic nation. The burden of governance had come to rest in the repre-
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sentative body of Parliament had been betrayed by its own head. To have the most important of that legislative body offering up a new—seemingly more powerful—Imperial Crown to place upon the Queen’s head smacked of an usurpation of England’s democratic parliamentarian principles and a return to monarchical autocracy in the control of the empire. The most noticeable commonality depicted in both “The Queen with Two Heads” and “New Crowns for Old Ones” is Disraeli’s active movements that present the Queen in a passive manner by comparison. In “The Queen with Two Heads,” published on April 1, 1876, the Prime Minster is the maestro of the Titles Act with stencil and brush in hand adding an extra head to Victoria’s Royal body. Although one of Victoria’s heads still wears the Crown of the United Kingdom, the Imperial Crown supersedes it. This additional head reflects Disraeli’s attempts to “take the sting out of the Bill by explaining that the Queen would, under no circumstances, assume the style of Empress in England. Victoria in fact, is to be Empress, ‘Limited’—to India…” as Punch reported in the same issue,11 but it still represents an actus reus on the body politic. The work is that of Disraeli alone against the will of the English people, who are collectively represented by the figure of John Bull. This act reduces the Queen to little more than a portrait that the Prime Minister alters according to his own designs. The isolation of Disraeli in this action is apparent. He has removed himself from the Body Politic of English democracy that John Bull represents in order to carry out this political design. He is alone on a ladder with his back turned and is thus ignorant to Mr. Bull’s exclamation, “You can’t improve on the Old ‘Queen’s Head!’” Punch endeavors to show Disraeli as a figure alone on this imperial venture myopic to all around him as he labors to make Victoria the Empress of India. The Prime Minister has decided to “touch-up” upon the traditional institution and in the process distorted it into what amounts to be a foreign monstrosity that John Bull and England cannot accept. John Tenniel, the Punch caricaturist responsible for both images, exaggerates the isolation of Disraeli and the passivity of Victoria to even greater extremes in the April 15 issue of “New Crowns for Old Ones!” Disraeli here is depicted as an oriental—no doubt an allusion to his Jewish ancestry—with kabalistic symbols on both the hem of his robe and the magic Aladdin’s box at his belt. He is depicted as a slightly hunched figure leaning in to seduce the Queen with a false, flashy Imperial Crown to replace the old, regal English one. The caricature captures the stereo-
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humanities typical peddler plying his magical wares to an unsuspecting victim. He extends his right hand, already expecting Victoria to give up her title as Queen, and he delicately presents the new Crown. Victoria, opposite him, is in her austere black with a sullen look, unable to make eye contact. The expression captures the notion that perhaps she recognizes she is betraying her people by accepting the new title. There is guilt in her eye as she offers up the old Crown. The contrast exemplifies an aspect of Punch’s campaign to discount the Imperial Title as an oriental temptation that conflicts with traditional English values that the Queen embodies. Disraeli greets the viewer in both images with his slightly suspicious, curling smile, his wispy goat-like beard, curly dark hair, and prominent nose that denote him as an “un-English” character. Despite being depicted in typical English attire suited to that of a Prime Minister in the April 1st image, he is equally at home in this oriental garb that only further isolates him from being “English.” Disraeli, according to Oxford scholar Robert Blake, was baffled by the accusation of being “un-English” because he was unsure as to what that term (along with the word “unconstitutional”) precisely meant.12 In the case of Disraeli, it is often apparent exactly what satirists meant to say. In “Asian Mysteries,” an “Aladdin the Younger” writes Mr. Punch decrying, “Queen Victoria, who, for a thousand years, has worn a Crown more wonderful than even the Lamp of Aladdin or the Seal of Solomon…has been persuaded to listen to an old Hebrew magician, who has offered her a veritable talisman of sovereignty for a new one.”13 The text, a companion to Tenniel’s infamous image, furthers the disparagement of Disraeli’s Englishness by replacing it with his veritable character as “Hebrew magician.” A “Hebrew” offering the Imperial Crown to Victoria further reinforces the act as a foreign one far removed from what Punch considered to be properly English. “For his own part, he must admit that of the two D.G.’s he prefers the old one—‘Victoria Dei Gratia Angliae Regina,’ to ‘Victoria Disraeli Gratia Indiae Imperatrix’” was the summation of Punch’s feelings on the Royal Title Act as proposed by Benjamin Disraeli.14 This substitution of Dei Gratia Anglicae Regina (Latin for “Queen of England by the Grace of God”) for Disraeli Gratia Indiae Imperatrix (faux Latin for “Empress of India by the Grace of Disraeli”) is damningly subtle in its implications for how Punch viewed Disraeli’s actions. God made Victoria Queen of England. She has a legitimate Divine Right of Rule given to her by the Christian God. That providential God did not make her an Empress. For Victoria to assume such a title could only be by the “Grace of Disraeli”—a bold insult to Britain’s historical and cultural traditions that carried with it an implication that Disraeli, an “un-English” Jew that does not believe in the same Christian God, would betray those sacred traditions. Despite Punch’s cleverest attempts at humor to dissuade the passage of the Royal Titles Act of 1876, the advice was given; the Proclamation was issued; and Victoria, Queen of England, was henceforth known as Victoria, Empress of India. Punch failed to save the Old Queen’s head from the hated hand of Disraeli. That new Aladdin who Mr. Punch had so vilified succeeded in trading in the Old Crown for the Imperial Title. The implication of Disraeli’s triumph only served to reinforce his critics’ perception of him as a Jew more aligned with oriental sympathies. Punch was not the only political satire that portrayed or would go on to portray Disraeli as a cryptoJew with a hidden anti-English or anti-Christian agenda. Disraeli’s ministry withstood four more years of endless satire and criticism from Punch and other prominent political publications following the Royal Titles Act until William Gladstone ushered in a new Liberal Government in 1880. The attacks on Disraeli and his faith never abated until his death in 1881. Even then, there was an unsubstantiated rumor that he made a deathbed reconversion to Judaism.15 The implications of Disraeli’s ethnicity and race showed a virulent strain of anti-Semitism that permeated the “tolerant” and “polite” nature of Victorian society, forcing even the
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hurj spring 2012: issue 14 traditional stereotypes of caricature to an uncompromising cruelty. The role of political satire was entrenched in the British political scene for the rest of the 19th and early 20th centuries, and Punch retained its supremacy as the preeminent political satire but never again did a satire represent a leading politician so viciously “un-English” as it had done with Disraeli throughout the Titles Act of 1876. Disraeli, with the creation of an Indian Empire, had desacralized Victoria, Regina Dei Gratia, and created Victoria, Imperatrix Disraeli Gratia. Dizzy’s sacrilegious imperial design upset Punch’s notion of the modern British monarchy. With savage bias, Punch’s humor did not just ridicule Disraeli; it degraded him. Acknowledgements Jeffery Brooks, for the original inspiration to find humor in history, and Wallace Feng, for an uncommon patience during many rewrites. References 1. “Punch’s Essence of Parliament,” 6 May 1876, Punch, or the London Charivari, Vol. LXX, p. 173 2. Figure 1 and 2 respectively 3. L. A. Knight, “The Royal Titles Act and India”, The Historical Journal, Vol. 11, No. 3 (Cambridge, 1968), p 488 4. Margaret Homens, Royal Representations: Queen Victoria and British Culture, 18371876, The University of Chicago Press, 1998, p 233 5. Anthony S. Wohl, “Ben JuJu”: Representations of Disraeli’s Jewishness in the Victorian Political Cartoon, Jewish History, V. 10, No. 2 (Vassar, 1996), p. 102 6. “Punch’s Essence of Parliament,” 18 March 1876, Punch, or the London Charivari, Vol. LXX, p. 98 7. Ibid 8. Ibid, p. 90 9. Donald J. Gray, The Uses of Victorian Laugher, Victorian Studies, 10:2 (1966:Dec.) pp. 146-147 10. “Punch’s Essence of Parliament,” 6 May 1876, Punch, or the London Charivari, Vol. LXX, p. 173 11. “Punch’s Essence of Parliament,” 1 April 1876, Punch, or the London Charivari, Vol. LXX, p. 120 12. Robert Blake, “Gladstone, Disraeli, and Queen Victoria”, The Centenary Romanes Lecture, November 4, 1992, Oxford. 13. “Asian Mysteries,” 15 April 1876, Punch, or the London Charivari, Vol. LXX, p. 146 14. “Punch’s Essence of Parliament,” 25 March 1876, Punch, or the London Charivari, Vol. LXX, p. 110 15. Bernard Glassman, Disraeli’s Jewishness, and: Benjamin Disraeli: The Fabricated Jew in Myth and Memory, University Press of America (2003), p. 98
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science & engineering reports
The Effect of Inhibition on Lactosylceramide Synthase on Polycystic Kidney Disease Jeong Hoon Park1, Dr. Subroto Chatterjee2 1 Department of Biology, Johns Hopkins University 2 Department of Pediatrics, Johns Hopkins Medical Institutions Abstract The pathway to angiogenesis was targeted in order to halt the formation of blood vessels to inhibit the development of polycystic kidneys. D-PDMP is a compound in development that is known to target a specific site in the pathway of angiogenesis. By inhibiting the crucial enzymatic site in angiogenesis, D-PDMP mitigates the proliferation of polycystic kidneys. This study explores the effect of D-PDMP by measuring levels of different lipids that are responsible for inducing angiogenesis. Introduction Kidneys serve vital roles that range from filtering wastes to regulating blood pressure. They are responsible for important homeostatic functions in many mammals, namely humans. Polycystic kidney disease (PKD) is a genetic disorder that is often characterized by the formation of numerous fluid-filled cysts of various sizes within the kidneys (Figure 1). The development of cysts enlarge the kidneys by 4 to 5-fold of their normal size, reshaping much of their original structure. Alteration of the normal anatomy of kidneys results in reduced function, ultimately leading to kidney failure. Much like how organisms need food to live, tumors, cancers, and cysts all require an input of nutrients for growth and sustainability. Their supply system is the very blood vessels that provide necessary elements to different parts of the body; however, in order to steal the nutrients from the system, tumors and cysts need to build new blood vessels through a process known as angiogenesis. Previous studies have shown that an important glycolipid that induces angiogenesis is lactosylceramide (LacCer)2,3. Upon activation by vascular endothelial growth factor (VEGF), lactosylceramide synthase (LCS) transfers galactose from UDPgalactose to glucosylceramide to form LacCer.4,5 LacCer then signals a series of downstream effectors that ultimately lead to the production of platelet endothelial cell adhesion molecule-1 (PECAM-1) and subsequent angiogenesis (Figure 2).6,7 This sequence of events is necessary to provide growing cysts with essential nutrition. While the angiogenic pathway is responsible for supplying PKD cells with important nutrients, another pathway is responsible for cell proliferation; this is responsible for the growth and re-formation of the kidney cells. This complex pathway signaling involves three important proteins; mitogenactivated protein kinase (MAPK), phosphate-AKT (pAKT), and mammalian target of rapamycin Figure 1: The polycystic kidney roughly retains the same shape as the healthy kidney.1
(mTOR)8,9. Close examination through western blotting of these proteins confirm the fact that the angiogenic pathway directly stimulates cell proliferation, and not by any other variables.6
Figure 2: Angiogenic pathway of PKD. Courtesy of S. Chatterjee
Inhibition of LCS is possible by either gene deletion using the corresponding siRNA, or administration of the inhibitor D-threo-1-phenyl-2-decanoylamino-3-morpholino-1-peopanol (D-PDMP). D-PDMP is known to inhibit both glucosyl-ceramide synthase and LCS.10 By inhibiting the production of both the substrate (glucosyl-ceramide) and the enzyme (LCS) that yields LacCer, we are able to inhibit formation of new blood vessels that feed PKD cells upstream in the angiogenic pathway. If LCS is inhibited using D-PDMP, we should see evidence of PKD mitigation due to the lack of formation of new blood vessels. Materials and Metho ds Five mice (V/V heterozygous, male) were used in this experiment. Three of them were fed D-PDMP (10mg/kg weight of mice) solubilized in vehicle composed of 5% Tween -80 in phosphate buffered saline; two were given vehicle only via oral gavage. Mice were fed D-PDMP or vehicle daily for 30 days. The mouse kidneys were then excised, the tissues weighed and one half of the kidney homogenized in an organic solvent (chloroform methanol 2:1 v/v supplemented with internal standards e/g. C2 ceramide and C12 fatty acid both at 10ug/ml). The lipid extracts
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were dried in nitrogen and sent to the liquid chromatography tandem mass spectrometry (LCMS) facility. Results: The LCMS results collected from the five mice were graphed for comparison of their levels in Ceramide, Monohexosylceramide, Dihexosylcermide, and Sphingomyelin. All four types of lipids are known to play critical roles in the production of LacCer. Analyzing their levels of presence would indicate the accuracy of D-PDMPâ&#x20AC;&#x2122;s effect on the pathway to LacCer production.
level of glucosylceramide. However, both the vehicle-treated and the drug-treated mice showed some imprecision in its data. Due to such scattered data, standard error mean for both the vehicle and the drug treated mice were calculated to be 31% and 30% respectively. Level of Ceramide:
Level of Dihexosylceramide:
Figure 5: LCMS data analyzed for the level of ceramide
Figure 3: LCMS data analyzed for the level of dihexosylceramide
Since LCMS does not distinguish between lactosylceramide and digalactosylceramide, the combined data is presented together. According to the angiogenic pathway of PKD in Figure 2, if there is any inhibition of the drug D-PDMP at the level of LacCer synthase, the subsequent production of LacCer should decrease and would show a lowered level of LacCer. According to Figure 3, the drug treated mice showed 33% lower level of LacCer compared to those mice that were fed with vehicle. L e vel of Monohex osylceramide:
Figure 4: LCMS data analyzed for the level of monohexosylceramide (Glucosylceramide)
Monohexosylceramide in this case is glucosylceramide, a substrate that is consumed along with UDP-Galactose by LCS to form LacCer. According to Figure 2, with inhibition of LCS by D-PDMP, there should be a compilation of the two substrates, which is indeed reflected in Figure 4. The drug treated mice showed 17% higher
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Ceramide is the basic lipid molecule that goes through a series of reactions other than the pathway described in Figure 2 to be converted into glucosylceramide. This pathway involves glucosylceramide synthase, which converts ceramide into glucosylceramide. As D-PDMP inhibits glucosyl-ceramide synthase at the same time as LCS, the level of ceramide should reduce along with the level of glucosylceramide. According to Figure 5, the drug treated mice have 33% higher level of ceramide in comparison with the vehicle mice. This observation suggests that in vivo the target for D-PDMP action is at the LCS level and not the glucosyl-ceramide synthase level. The standard error mean calculated was quite high for both vehicle and drug treatments with values of 38% and 34% respectively. Like that of monohexosylceramide, the high standard error mean values show that the collected data was scattered and was quite imprecise. Level of Sphingomyelin:
Figure 6: LCMS data analyzed for the level of sphingomyelin
Sphingomyelin, which is absent in Figure 2, is a sphingolipid formed from phosphorylcholine and ceramide. Since it is the successor of ceramide, the level of sphingomyelin should also show some increase. However, according to Figure 6, the level of sphingomyelin in drug treated mice show 42% lowered level of the sphingolipid, a statistic that is still be explored.
hurj spring 2012: issue 14 Discussion It can be concluded that compound D-PDMP successfully inhibits the enzyme LCS. The lipids of interest were monohexosylceramide, dihexosylceramide, ceramide, and sphingomyelin. The results from this study indicate the high level of effectiveness of the compound D-PDMP on its target sites. Both lower levels of LacCer and higher levels of ceramide and glucosylceramide in drug-treated mice show that the drug inhibited LCS, ultimately leading to the depletion of LacCer production. The level of dihexosylceramide directly interpreted into the level of lactosylceramide, the glycolipid that induces angiongenesis and subsequent tumor growth. The statistical analysis allowed us to deduce that the data was indeed the result of the D-PDMPâ&#x20AC;&#x2122;s specific inhibition on LCS; the standard error mean was low, signifying precision of the data points. The t-test value was small, indicating high significance of the data. On the other hand, the data of monohexosylceramide and ceramide were not as assuring as that of the dihexosylceramide. Both data sets of the two former lipids showed high standard error mean and t-test values, forcing us to question the validity of the data. We predicted that the level of sphingomyelin would increase, due to the fact that ceramide is a precursor. However, the level of sphingomyelin decreases by 42%, as observed in Figure 6. From these results, we hypothesize that sphingomyelin might be consumed in a different pathway other than that described in Figure 2 for the drug treated mice.
science & engineering reports 9. Radin, N.S., Shayman, J.A., Inokuchi, J., Metabolic effects of inhibiting glycosylceramide synthesis with PDMP and other substances. Adv. Lipid Res. 1993; 26: 183-213.
References 1. NIDDK scientists and outside experts. (2010, September 2). Polycystic Kidney Disease In National Kidney & Urologic Diseases Information Clearinghouse (NKUDIC). Retrieved August 5, 2011, from http://kidney.niddk.nih.gov/kudiseases/ pubs/polycystic/Figure 6: LCMS data analyzed for the level of sphingomyelin Rajesh, M. Kolmakova A., Chatterjee, S.: Novel role of lacotsylceramide in vascular endothelial growth factor mediated angiogenesis in human endothelial growth factor mediated angiogenesis in human endothelial cells. Circ. Res. 97(8), 796-804 (2005). doi:10.1161/01.RES.0000185327.45463.A8. 2. Wei, W, Popov V, Walocha, JA, Wen J, Bello-Reuss, E: Evidence of angiogenesis and microvascular regression in autosomal-dominant polycystic kidney disease kidneys. A corrosion cast study. Kidney International 70: 1261-1268, 2006. 3. Chatterjee, S. Assay of lactosylceramide synthase and comments on its potential role in signal transduction. Methods Enzymol 2000;311:73-81. 4. Song, X., Giovanni V. D., He, N., Wang, K., Ingram, A., Rosenblum, N.D., Pei, Y.:Systems biology of autosomal dominant kidney (ADPKD): computational identification of gene expression pathways integrated regulatory networks. Human Molecular Genetics 18(13): 2328-2343, 2009. 5. Chatterjee S, Pandey,A. Ying and Yang of Lactosylceramide metabolism:Implications in cell functions. Biochim.. Biophys Acta 1780(3) 370-382 2008. 6. Kolmakova,A Mohan,R., Zang,D Pili,R and Chatterjee,S. VEGF recruits lactosylceramide to induce PECAM-1 expression and angiogenesis in vitro and in vivo. Glycocojugate J 26:547-558(2009), 7. Chatterjee, S., Shi W.Y., Wilson, P., Mazumdar, A.: Role of lactosylceramide and MAP kinase in the proliferation of proximal tubular cells in human polycystic kidney disease. J Lipid Research 37: 1334-1344, 1996. 8. Wahl PR, Serra AL, Le Hir M, Molle KD, Hall MN, Wuthrich RP. Inhibition of mTOR with sirolimus slows disease progression in Han: SPRD rats with autosomal dominant polycystic kidney disease (ADPKD). Nephrol Dial Transplant. 2006 Mar;21(3): 598-604.
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Inverted Catalysts: Heavy Metal Oxide Nanoparticle Additions to Nanoporous Gold Katherine Charov1, Alex Dang2 1 Chemical and Biomolecular Engineering, Johns Hopkins University 2 Materials Science and Engineering, Johns Hopkins University Abstract We examine different nanoparticle heavy metal oxides for their potential use as additions to nanoporous gold structures. Previous work concerning the production of nanoporous gold is built upon, and several methods for incorporating heavy metal oxide particles into such structures are devised. The reason for this work is as follows: we are interested in creating an improved catalyst for the water gas shift reaction. Our proposed solution is a so-called, “inverted catalyst”, in which metal oxide particles are dispersed on a surface of nanoporous gold. Introduction As independence from fossil fuels becomes more important, many alternative methods of energy production are being explored. Fuel cells are of particular interest as they present a sustainable source of electricity with little or no emissions; in hydrogen fuel cells there are zero emissions. Currently, there are a variety of different methods to produce hydrogen gas for fuel cell applications. Of these, the steam reformation of methane is one of the most prevalent methods used in industry. It has the benefit of being relatively easy to carry out, while using reactants that are readily available in large quantities. However, as seen below, this method has one large disadvantage1, because for every three moles of hydrogen gas produced, one mole of carbon monoxide is also produced:
To get rid of the carbon monoxide in the product stream, this reaction is often coupled with the water gas shift reaction2, in which the carbon monoxide reacts with more steam to form even more hydrogen along with carbon dioxide:
Together, both reactions yield a net reaction which both produces an appreciable amount of hydrogen and does not produce toxic by-products:
Catalysts, which help increase the rate of a chemical reaction without being consumed, have been the active subjects of research for a long time. Currently, the common choice of catalyst for the water gas shift reaction is a transition metal oxide. The water gas shift reaction is important in removing carbon monoxide, which 1 There are other disadvantages to this method, such as the high temperature required for methane and steam to react. This reaction is typically run at about 1000 °C. 2 This reaction does not require as high of a temperature to occur, thus, it is typically run at about 150 °C.
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is otherwise an impurity within the fuel cell and limits efficiency. In the past, gold-cerium and gold-titanium oxides have been researched as catalysts. However, in an attempt to increase the catalytic activity of these metals, inverse catalysts consisting of gold nanoparticles interspersed on such heavy metal oxides have been researched. Research has shown that, although gold by itself is inert in the water gas shift reaction, with additions of these nanoparticle oxides, the gold becomes extremely active1. While this method certainly works, it has a few drawbacks, the chief one being that it does not have a large amount of surface area, which limits its efficiency. Materials and Metho ds S o l u t i o n 1 : F e 3O 2 P a r t i c l e s In this process, mixtures of varying concentrations of gold, silver, and iron were melted together using a hydrogen torch in air, and rapidly cooled to form a solid solution. Besides creating an alloy, this melting served another purpose: oxidizing the iron to form iron oxide. The ingot was then rolled to an approximate 40 μm thickness, annealed (to reduce work hardening) and subsequently dealloyed by free corrosion in concentrated nitric acid. During the melting process, we aimed to form iron (III) oxide within the ingot and that, following dealloying, a nanoporous structure featuring oxide particles interspersed throughout the structure would be left. All samples were analyzed with a scanning electron microscope. S o l u t i o n 2 : Ti O 2 P a r t i c l e s I n this process, nanoporous gold was first prepared, as detailed by Erlebacher et. al.2, and then subjected to treatment with titanium isopropoxide3 solution in an argon atmosphere. Titanium isopropoxide reacts with water to form a titanium dioxide precipitate. Specifically, varying concentrations of titanium isopropoxide were diluted in approximately 40 mL ethanol (200 proof), creating a pure titanium isopropoxide, 1:10, 1:100, 1:1000 parts titanium isopropoxide to parts ethanol solution. A 10 μL drop of the solution was placed on the nanoporous gold surface, and then imme3
Formula: Ti[OCH(CH3)2]4. Note: extremely toxic to humans.
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diately subjected to a 10 μL drop of water directly on top of it. Following this, air was passed over the surface until the nanoporous gold was once again dry. This procedure was repeated 10 times per sample, and all samples were observed with SEM. Initial observations showed that the gold samples that were subjected to high concentrations of titanium isopropoxide (pure, 1:10, and 1:100) had large amounts of a crystalline white substance on their surfaces. Results Iron ( I I I ) O x i d e Par ti cl e s This process had one innate problem: although silver and gold are perfectly miscible at almost any composition, silver and iron are not, and therefore phase separate. This was known at the beginning of the experiment, however, so these mixtures of gold, silver, and iron were made into solution with the hydrogen torch with the hope that the intense heat from the torch would evenly mix and distribute the iron oxide particles. However, although the silver was eventually dissolved, the fact that this occurred after the melting process meant that the iron would nonetheless be clumped together. This was experimentally observed as all of the samples, which contained varying concentrations of iron at 5, 3, 1.5, 0.6, and 0.3 mole percent, showed evidence of phase separation under the SEM as there were always well-defined particles of iron oxide clustered together on the nanoporous gold (see Fig. 1a).
Figure 1b: SEM image (8 000 X, LEI) of 0.6% iron sample after electrochemical dealloying. Note once again the large clusters of iron particles, denoted by the arrows.
isopropoxide is unreactive with ethanol. However, once mixed with water, a precipitate forms according to the following reaction:
By this process, in theory, the TiO2 precipitates out of solution and falls onto the surface of the gold substrate, while the alcohols (the 4 (CH3)2OH and ethanol) vaporize because of the passing ir. Under the SEM, TiO2 particles were seen on all samples except for the 1:1000 sample4, as confirmed by EDAX. However, on the pure and 1:10 samples, the TiO2 particles were much too large to be deemed suitable for catalysis (see Fig. 2a). The 1:100 sample was much more promising though, since TiO2 particles with an average diameter of 100 nm were seen on the surface of the nanoporous gold. While this is a promising find for this experiment, this result is still not ideal since most of the observed TiO2 particles were found clustered on the surface of the substrate, and not evenly dispersed.
Figure 1a: SEM image (50 000 X, SEI) of 1.5% iron sample after free corrosion in nitric acid. Note the large clusters of ironparticles, denoted by the arrows.
Following this initial set of observations, we explored the option that our melting process simply failed to mix the iron, silver and gold together adequately; we returned to consider how we might mix the metals together more effectively. Another set of samples of the same composition were prepared, except this time using the radio frequency induction furnace under flowing argon, followed by rapid quenching. Also, another set of samples of the same composition were dealloyed electrochemically. However, the same results for both cases were seen under the SEM, where the iron oxide particles were clumped together instead of evenly dispersed (see Fig. 1b). Consequently, this project was put on hold. Ti t a n i u m D i o x i d e P a r t i c l e s The motivation behind using this technique was to “force” metal oxide particles to precipitate onto the surface of the gold. Titanium
Figure 2a: SEM image (1 000 X, LEI) of titanium dioxide sample with 1:10 parts titanium isopropoxide to ethanol solution. Note the large amounts of titanium dioxide on the surface. The average cluster size is approx. 10 μm in diameter. 4 This may have been due to the micropipette that was used, since sometimes, when transferring very small amounts of liquid, none of the liquid inside the pipette tip comes out.
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science & engineering reports Another set of samples of the same concentrations were prepared by letting them sit in a humid atmosphere overnight after 10 μL of titanium isopropoxide / ethanol solution was placed on the surface. However, the same results were seen under the SEM. To fully investigate what is happening at concentrations below 1:100, samples at 1:200, 1:400, 1:600, and 1:800 concentrations are currently being prepared, however, more experiments need to be performed.
Figure 2b: SEM image (2 500 X, SEI) of titanium dioxide sample with 1:100 parts titanium isopropoxide to ethanol solution. Although there are titanium dioxide clusters on the surface (blue arrow), there are also free, scattered, titanium dioxide particles. Further experiments will try to try to create more of these scattered particles and fewer clusters.
Discussion Although the iron oxide experiment did not yield very promising results, the results from the titanium dioxide experiment show that there may be a way of evenly dispersing metal oxide particles on a nanoporous gold substrate. Further experiments will hopefully confirm this. However, there remain a number of options to explore. It should not be forgotten that the main goal is to successfully add nanoparticles to the pores of a NPG structure, not just to the surface. What remains to be tested, among other factors, is size of oxide particles created. If the size of particles can be controlled, there is a better chance of being able to successfully incorporate the particles within the structure, instead of placing them on the surface. Currently, solutions of titanium isopropoxide and ethanol at 1:200, 1:400 and 1:600 concentrations are being tested. Additionally, other research by Ibrahim and Sreekantan3, has shown that titanium dioxide particles can be created using a sol-gel method in which the size of particles can be controlled by altering the pH of the solution used to make the particles. It remains to be tested whether creating titanium dioxide particles with desired size, depositing them on the surface of NPG and annealing such a sample will also yield positive results. Perhaps in using the sol-gel method, we could create particles of a size that is most compatible with the NPG structure we can readily make via free corrosion. The success of this work as well as other research in heavy metal oxide catalytic activity in the water gas shift reaction is encouraging. Fuel cells have already shown incredible promise in providing an alternative energy source and it is important to keep working towards making them as efficient as possible. As fossil fuels become less and less desirable, alternative energy sources like fuel cells are more important than ever.
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hurj spring 2012: issue 14 Acknowledgments The authors would like to thank Felicitee Kertis and Jonah Erlebacher for their help and patience.
References 1. Activity of CeOx and TiOx Nanoparticles Grown on Au(111) in the Water-Gas Shift Reaction. J. A. Rodriguez, S. Ma, P. Liu, J. Hrbek, J. Evans, and M. Pére. Science 14 December 2007: 318 (5857), 1757-1760. [DOI:10.1126/science.1150038] 2. Erlebacher, Jonah et. al. “Evolution of Nanoporosity in Dealloying.” Nature 410. (2001): 450-453. Web. 9 May 2011. 3. Ibrahim, Siti Aida, Sreekantan, Srimala. “Effect of pH on TiO2 Nanoparticles via Sol-Gel Method.” Advanced Materials Research Vol. 173 (2011) 184 – 189.
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Targets for Glioblastoma Multiforme (GBM) Immunotherapy Sung Jin Jeong1 1 Chemical and Biomolecular Engineering, Johns Hopkins University Lethality of GBM GBM, a member of high-grade gliomas (HGG), is one of the most lethal types of brain tumors. Even with surgery, radiotherapy, and chemotherapy, the median life expectancy of GBM patients is generally less than one year from the point of diagnosis and most of these patients die within two years.1 GBM is incurable because the GBM cells have high tendency to invade the surrounding normal brain, which prevents a complete tumor resection.2,3 Relationship B etween Immune System and GBM Making the life expectancy of GBM patients longer is possible through immunotherapy which targets the protumor immunosuppressive factors and helps the immune system to recognize and destroy tumor cells.6 It can be a possible treatment because GBM and immune system are related. When GBM is present in the human, there are several cytokines, proteins, and chemokines that suppress antitumor immune system and helps tumor to grow (protumor immunosuppression).2,3,4,5,6,7 Those are Vascular Endothelial Growth Factor (VEGF), Signal Transducer and Activator of Transcription 3 (STAT3), Janus Kinase 2 (JAK2), Transforming Growth Factorbeta (TGF-β), IL-10, Forkhead Box P3 (FoxP3), Nuclear factor κB (NF-κB), Cyclooxygenase-2 (COX-2).2,3,4,5,6,7 These can help tumor to expand blood vessels to gain more nutrients and oxygen, resist to chemotherapy, inhibit T-cell activation and proliferation, and promote cell cycle progression and survival.2,3,4,5,6,7 Since these factors are responsible for the proliferation of GBM, they are the possible targets for immunotherapy. If one or more of the targets are inhibited, the immunotherapy will slow the proliferation of GBM, thus impeding tumor growth and resulting in longer life expectancy for GBM patients. Ty p e s o f I m m u n o t h e r a p y There are several types of immunotherapies: adoptive immunotherapy, passive immunotherapy with monoclonal antibodies, and active immunotherapy.5,8 These types of immunotherapy can be used to treat GBM. In adoptive immunotherapy, autologous tumour-reactive T cells are activated and expanded ex vivo, and then injected into the tumor patients, which will induce antitumor response in vivo.8,9 In active immunotherapy, antigen sources are used to treat tumor patients. Possible antigen sources are intact tumour cells, tumor protein lysates, tumour-derived mRNA, peptides eluded from tumour MHC class I molecules, and synthetic peptides. Antigens can be injected directly in the presence of different adjuvants or can be presented on Dendritic Cells (DCs), which has an important role in triggering immune reaction.8 Therfore, active immunotherapy aims to stimulate the adaptive immune system in vivo.9 Monoclonal antibody (mAb) can decrease expression level of a specific cytokine, protein, or factor that the antibody targeted. Monoclonal antibody can stimulate the immune system to attack GBM cells through activation of cytotoxic pathway, complement mediated cytotoxicity, and apoptotic signaling and growth inhibitory pathways.8,10 Since monoclonal antibodies are highly specific
and show limited toxicity, it can be a promising immunotherapy.10 Ta r g e t s o f G B M i m m u n o t h e r a p y As previously mentioned, there have been several targets of GBM immunotherapy. The roles of each target in GBM and the result of each immunotherapy will be discussed in this section. VEGF VEGF is in the pathway of TGF-β that is responsible for expanding GBM blood vessels, and has been identified as a critical regulator of angiogenesis.10 VEGF acts as an inhibitor of cell adhesion molecule (CAM) expression in the nonglioma animal model and in experiments on endothelial cells derived from normal tissues.3 Bevacizumab, an anti-VEGF antibody, has shown various effects on GBM.11 Marked decrease in contrast agent leakage and a limited reduction in tumor reduction has been observed after Bevacizumab treatment.10 In one study, weekly antibody injections were performed for 3 weeks. The average initial tumor size was 23.1 +/- 9.6 mm3. Three weeks after the treatment, the control group’s tumor had grown to an average size of 322 +/- 176 mm3, while the treated group has grown to an average size of 230 +/- 76 mm3.11 The tumor doubling time of the treated group increased by about 16% compared to control group, which suggests that tumor growth rate slows down during treatment.11 The results indicated that the antibody induces slight reduction in tumor progression.11 Bevacizumab reduces tumor blood flow, blood volume, and affects vessel permeability parameters.11 Tumor blood flow of treatment group in the same study was reduced by 17%.11 In the treatment group, 46% reduction of blood volume per unit of tissue and nutrients to the tumor was observed.11 These results suggest that there was reduced supply of oxygen and nutrients to the tumor.11 Furthermore, permeability surface, extraction fraction, and the tissue to blood backflow constant were reduced by the treatment.11 From the data, the researcher observed that the loss of CE after the anti-VEGF treatment was not only from reduced vessel permeability but also from a reduction of blood flow.11 In GBM, based on the data, anti-angiogenic treatment leads to reduced blood supply and consequently reduced oxygenation of the tumor bed.11 Anti-VEGF treatment reduces vessel density and strongly increases cell invasion.11 Researchers found that the antibody induces a reduction of large and medium size blood vessels, decreases tumor heterogeneity, and increases parenchymal tumor cell infiltration dramatically.11 They assume that the reason for loss of endothelial cell proliferation in treated group’s tumors is a consequence of reduced tumor oxygenation.11 Increased tumor hypoxia and activation of the PI3K and Wnt-Signaling Pathyway is observed after anti-VEGF treatment.10 The antibody, according to the GBM xenografts model, increases tumor hypoxia and activates alternative angiogenic pathways and molecular functions associated with stem cell biology and the invasive phenotype.11
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TGF-β
NF-κB
TGF-β has tumor suppressor function in regular tumor.11 However, in high-grade glioma, such as GBM, TGF-β inhibits T-cell activation and proliferation, represses production of lytic enzymes, and drives development of naïve T cells into regulatory T cells (Tregs).3,12 Tregs are necessary to protect against immune disease under normal physiological condition. However, in GBM patients, Tregs are suggested as a major contributor to depressed cellular immunity.3 Zhang et al. tested TGF-βRI serine/threonine inhibitor LY2109761 to U87MG and T98 GBM xenograft subcutaneous mouse models.12 Zhang et al. not only did monotherapy of LY2109761, TMZ, or radiotherapy but also did triple therapies that used LY2109761, TMZ (a chemotherapeutic agent), and radiotherapy. Among those therapies, using all three therapies showed subsequent delay in both tumor models.12 As it is shown in figure 1 {A}, in U87MG model, the mean time to tumor progression (TTP) of control group was 11.1 +/- 1.79days; TTP of LY2109761 treatment group was 32.0 +/- 6.28 days; TTP of triple treatments group was 95.9 +/- 2.39 days.12 As it is shown in Figure B, in T98 model, TTP of LY2109761 treatment group was 16.5 +/- 2.53 days; TTP of triple treatments group was 30.78 +/- 6.16 days.12
NF-κB is involved in control of oncogenesis, tumor progression, and shows resistance to chemotherapy treatment of various cancers.7 NF-κB binds to DNA, which modulates the expression of various genes that plays a role in inflammation, apoptosis resistance, cell invasion, angiogenesis, proliferation and metastasis.7 Since NF-κB is involved with various types genes that are responsible for proliferation of tumors, it may be a potential target for GBM immunotherapy. For instance, NF-κB inhibitors, BAY11082 and MG132 significantly decrease GBM viability.7 First, knocking down NF-κB-p65 member (p65) induces apoptosis in GBM cells.7 By knocking down p65, inhibiting NF-κB DNA-binding activity, and decreasing bcl-xL protein (an antiapoptiotic NF-κB target gene product) levels, NF-κB downregulation occurred, which induced cell death in p65 silenced cells.7 From the knockdown of NF-κB-p65 member, viability of GBM cells decreased 45-55%.7 Second, p65 accumulated more in GBM cells than non-tumor astrocytes. GBM cells exhibited a 5-10 fold increase in the basal activity of NF-κB compared to that of primary astrocytes.7 COX-2 When cytokines and growth factors are present during inflammation, COX-2 can be induced.13 In brain tumor, COX-2 is overexpressed with poor prognosis.13 Selective COX-2 inhibitors (NS-398, SC-236) are effective to reduce human GBM cell viability in vitro.13 Kang et al. used celecoxib, which is selective COX-2 inhibitor, to U87MG, LN229, and U373MG cells.13 As it can be seen in the figure 2, Celecoxib reduced GBM cell viability in concentration-dependent manner.13 When functional p53, which increases sensitivity to celecoxib, was inhibited in GBM cells, anti-proliferative effect of celecoxib was significantly reduced.13 Celecoxib significantly induced DNA damage and inhibited DNA synthesis, corresponding with p53 activation.13 In U87MG cells, celecoxib accompanied with p21 activation induced G1-phase cell cycle arrest while cell cycle progression of U87MG-E6 and U87MG-PFT was not affected.13 In addition, celecoxib induced G1 cell cycle arrest in LN229 cells, but not in U373MG cells.13 In all cell types except LN229, apoptosis level was not changed by celecoxib regard less of p53 status.13 In short, celecoxib reduces viability of GBM cells, which leads to p53 dependent G1 cell cycle arrest.13 S TAT 3
Figure 1: In Vivo growth of Ub7MG and T98 tumor xenografts, BALB/c nu/nu mice with U87MG {A} and T98 {B} human glioblastoma.12 The LY+TMZ+RT treatment group has slowest tumor growth rate in BALB/c nu/nu mice with U87MG {A} and T98 {B} human glioblastoma.12
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In human gliomas, STAT3, a member of the JAK/STAT3 signaling pathway, is constitutively activated and overexpressed.2 The activation level of STAT3 and the malignancy of the tumor are correlated.2 Activated STAT3 promotes cell cycle progression and survival, stimulates angiogenesis, and impairs immunologic responses to cancer cells.2 STAT3 is a pleiotropic transcription factor which is involved in a wide variety of physiological processes. STAT3 can be activated by numerous cytokines, growth factors, and oncogenic proteins, such as VEGF, epidermal growth factor (EGF), plateletderived growth factor (PDGF), basic fibroblast growth factor bFGF, IL-6, Src, and Ras.2 Inhibiting the STAT3 signaling pathway may be useful as an anti-invasive therapeutic approach against GBM.2 Effects of STAT3 pathway inhibition was shown in vitro, when JAK-2 inhibitor tryphostic AG490 was used.2
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AG490 inhibits STAT3 phosphorylation in human GBM cells. Treatment with AG490 reduced the levels of constitutively activated STAT3 by inhibiting phosphorylation of STAT3.2 Complete inhibition occurred after 48 hours of exposure to the drug at a concentration of 100uM. AG490 treatment did not have an effect on baseline level of latent protein of glioma cell lines, which suggests that constitutive STAT3 activation in malignant glioma cells is largely fueled by signaling through the JAK-2/STAT3 pathway.2 AG490 inhibits migration of human GBM cells.2 In order to clarify whether inhibition of JAK-2/STAT3 signaling with AG490 can impede the migratory potential of GBM cells, an in vitro wound-healing assay was used.2 Twelve hours after the injury, cell migration to the wound was observed. After AG490 treatment, inhibition of migration was observed.2 AG490 inhibits invasion of human GBM cells.2 After 48 hours of 100uM AG490 treatment, the invasiveness of the GBM was reduced.2 The results suggest that STAT3 is involved in migration/invasion of human GBM cells.2 AG490 reduces transcription of MMP genes and reduces enzymatic activity of MMPs in human GBM cells.2 The reduced expression level of MMP-2 transcripts was shown in a dose-dependent manner.2 Also reduced expression level of MMP2 and MMP-9 mRNA was shown in dose-dependent manner.2 Discussion GBM is still incurable and the cause of GBM is unknnown1,2,3 However, our research implicitly demonstrates that if the right target for effective immunotherapy are found, the life expectancies of GBM patients may increase. We have found that there are targets such as IL-23 and IL-17, that can cause pro-tumor immunosuppression.14 If more cytokines, angiogenesis factors, and proteins of GBM are discovered and thoroughly examined, understanding the mechanisms and treatment of GBM is possible. We believe that as our understanding of GBM increases, we will be able to combine the current best treatment option (i.e. surgery, radiotherapy, and chemotherapy) with immunotherapy: A potential synergic effect from such a treatment can benefit patients with GBM.12,15 Although some immunotherapy was shown to be effective without toxicity in preclinical animal models, the success in animal model does not guarantee a success in human clinical trial since humans are different from animal (i.e. genes are quite different).15 If immunotherapy in clinical trials can have the same efficacy and non-toxicity as immunotherapy in preclinical trials, GBM patients may have a better chance of being cured. References 1. Stuppp, Roger et al. Radiotherapy plus Concomitant and Adjuvant Temozolomide for Glioblastoma. The New England Journal of Medicine. 2005. PMID: 15758009 2. Senft et al. Inhibition of the JAK-2/STAT3 signaling pathway impedes the migratory and invasive potential of human glioblastoma cells. Journal of NeuroOncology. June 2010 3. Lohr, Jennifer et al. Effector T-cell Infiltration Positively Impacts Survivial of Glioblastoma Patients and Is Impaired by Tumor-Derived TGF-beta. Clinical Cancer Research. 2011; 17:4296-4308. April 8, 2011 4. Lohr, Jennifer et al. Effector T-cell Infiltraion Positively Impacts Survivial of Glioblastoma Patients and Is Impaired by Tumor-Derived TGF-beta. Clinical Cancer Research. 2011 5. Wei, Jun and Wu, Adam et al. Hypoxia Potentiates Glioma-Mediated Immunosuppression. PLoS ONE. Volume 6. Issue 1. January 2011 6. McLaughlin et al. Inhibition of Secretion of Interleukin (IL)-12/IL-23 Family
Figure 2: Concentration-dependent response of celecoxib on viability of human glioblastoma cells. Cell viability decreases when concentration of Celecoxib increases in all cell types shown below.13 Cytokines by 4-Trifluoromethyl-celecoxib Is Coupled to Degradation via the Endoplasmice Reticulum Stress Protein HERP. Journal Of Biological Chemistry. 285(10): 6960-6969. March 5, 2010. 7. Zanotto-Filho et al. NFκB inhibitors induce cell death in glioblastomas. Biochemical Pharmacology 81:412-424. 2011 8. Vauleon et al. Overview of Cellular Immunotherapy for Patients with Glioblastoma. Clinical and Developmental Immunology. 2010. PMID: 20953324 9. Gattinoni and Powell et al. Adoptive immunotherapy for cancer: building on success. Nature reviews. Immunology. May 6, 2011. Volume 6(5): 383-393 10. O’Mahony and Bishop et al. Monoclonal antibody therapy. Frontiers in Bioscience. May 1, 2006. Volume 11:1620-1635 11. Keunean et al. Anti-VEGF treatment reduces blood supply and increases tumor cell invasion in glioblastoma. PNAS. 108(9): 3749-3754. March 1, 2011 12. Zhang et al. Trimodal Glioblastoma Treatment Consisting of Concurrent Radiotherapy, Temozolomide, and the Novel TGF- β Receptor I Kinase Inhibitor LY2109761. NEOPLASIA. June 2011. Volume 13(6): 537-549 13. Kang et al. Enhanced sensitivity of celecoxib in human glioblastoma cells: Induction of DNA damage leading to p53-dependent G1 cell cycle arrest and autophagy. Mol Cancer. 2009 Aug 25;8:66 14. Xu et al. Regulation of Antitumor Immune Responses by the IL-12 Family Cytokines, IL-12, IL-23, and IL-27. Clinical and Developmental Immunology. Vol. 2010, Article ID 832454 15. Curtin and King et al. Combining Cytotoxic and Immune-Mediated Gene Therapy to Treat Brain Tumors. Current Topics in Medical Chemistry. 5(12): 11511170. 2005
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Investigating the Impact of Microtubule Inhibitors on EWS-FLI1 Trafficking Andi Shahu1, Patrick J. Grohar1, Laurie Griffin1, Lee J. Helman1 1 Pediatric Oncology Branch, Center for Cancer Research, National Cancer Institute, Bethesda, MD Abstract The aberrant oncogene EWS-FLI1 has been identified as a key target gene in the treatment of Ewing’s sarcoma. A drug screen conducted prior to this study identified analogues of microtubule inhibiting drugs as potential small molecule inhibitors of EWS-FLI11. It was hypothesized that microtubules participate in transporting the EWS-FLI1 protein from the cytoplasm into the nucleus of Ewing’s cells, and that microtubule inhibitors prevent this trafficking. This relationship was investigated through in-vitro studies of a wellcharacterized Ewing’s sarcoma cell line and the effect of treatment with the chemotherapy on these cells. The results suggest an inherent sensitivity of Ewing’s cells to microtubule inhibitors. However, they also indicate that these drugs do not affect EWS-FLI1 trafficking from the cytoplasm into the nucleus. We conclude that while these microtubule inhibitors may be effective against Ewing’s sarcoma cells, they do not prevent EWS-FLI1 trafficking. Introduction The Ewing’s Sarcoma Family of Tumors (ESFT) is the second most common childhood bone cancer, with an incidence of 2.1 cases per million children2. The cancer typically presents between the ages of 10 and 20, and is most commonly found in the arms, legs, chest, and pelvis. ESFT is an extremely aggressive neoplasm; X-rays reveal lower bone density near the site of the tumor, an appearance frequently described “moth-eaten.” Common symptoms of the cancer include inexplicable fevers, pain, pathologic fracture, swelling, and formation of a lump at the site of the tumor2. There is often a delay in diagnosis because patients ignore the pain or attribute it to other causes such as “growing pains” or athletic injuries. The standard of care for Ewing’s sarcoma is multimodal therapy, which involves chemotherapy, surgery and/or radiation therapy. The drugs vincristine, cyclophosphamide, doxorubicin, ifosfamide, and etoposide2 make up the most common regimen of chemotherapy. It is important to note here that one of these drugs – vincristine – is a microtubule inhibitor. While the standard of care for the cancer is effective if diagnosed early enough, significant toxicities result from therapy. These toxicities include cardiotoxicities, second malignancies, myelosuppresion, nausea, suppression of the immune system, and disfigurement resulting from surgery2. Despite aggressive therapy, survival for ESFT patients is only 60-65%3. In addition, patients with high-risk disease (such as metastatic or relapsed disease) have a particularly poor prognosis, which has exhibited limited improvement over the last several decades of research. Thus, the goal of this research is to target and inhibit genes that are necessary for tumor survival. All Ewing’s cancers have chromosomal translocations involving the EWS gene and a member of the ETS family of transcription factors4. The most common gene fusion results in oncogenic transcription factor EWS-FLI1. The EWS-FLI1 translocation is a reciprocal translocation between chromosome 11 and 22. The EWS Transactivation Domain is fused to the FLI1 DNA Binding Domain, creating an oncogene that codes for the EWS-FLI1 fusion protein4. The fusion protein is believed to function as an aberrant transcrip-
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tion factor that alters the function of hundreds of target genes, causing the cell to become malignant5. These target genes initiate an oncogenic program that promotes cell proliferation, metastasis, and angiogenesis. Multiple studies have shown that inhibiting expression of EWS-FLI1 in turn inhibits proliferation of EWS-FLI1 cells. Thus, EWS-FLI1 is crucial to the survival of Ewing’s cells, and that EWS-FLI1 is a viable target for treatment of the cancer. Prior to this study, our lab conducted a drug screen to identify small molecule inhibitors of EWS-FLI11. Several of the top hits from this screen were analogues of known microtubule inhibitors. Microtubule inhibitors, which target the microtubule network by either stabilizing or destabilizing it, are commonly used in cancer therapy6. Cancer cells are more sensitive to the drugs, but as with other forms of chemotherapy, other rapidly dividing cells are also affected. Nevertheless, the results of the drug screen suggested a drug a relationship between EWS-FLI1 and microtubules. For the purposes of the study, five common microtubule inhibitors were chosen: vincristine, vinorelbine, vinblastine, paclitaxel and docetaxel. All of these have been used in chemotherapeutic treatment of various cancers6. Vincristine, vinorelbine, and vinblastine are mirotubule destabilizers and prevent microtubules from assembling6. Paclitaxel and docetaxel are microtubule stabilizers and inhibit microtubule disassembly6. Based on the well-characterized functions of the microtubule inhibitors, we hypothesized that microtubules participate in cytoplasmic-nuclear trafficking of EWS-FLI1 protein following its translation. It would then follow that microtubule inhibitors would prevent this trafficking. Various assays, detailed below, were performed in order to investigate this potential relationship. Materials & Metho ds Cell culture. Cell lines TC32 (Ewing’s sarcoma) and U2OS (Osteosarcoma) were maintained in RPMI 1640 with 10% FBS, 100 units/ML Penicillin and 100 μML Streptomycin and 2 mM L-Glutamine. These cell lines were incubated at 37°C under 5% CO2 and passaged until use. Cell proliferation assays. Cells were plated in standard
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The cell proliferation in TC32 (Ewing’s) and U2OS (Osteosarcoma) that received 72-hour drug treatment resulted in reduced cell viability, as shown in Figure 1. The TC32 cells were more sensitive to the microtubule inhibitors than the U2OS cells. The proliferation of the Ewing’s cells was inhibited to a much greater degree than the proliferation of the U2OS cells by each of the drugs, although paclitaxel seemed to be less potent than the other drugs. Furthermore, Western blot studies of protein lysates obtained from TC32 Ewing’s cells treated with the five drugs for 18 hours were performed to evaluate the protein expression of the EWS-FLI1 and ID2 (a downstream target gene of EWS-FLI1). Vinblastine was the only drug that appeared to decrease the expression of EWS-FLI1. However, protein expression of the EWS-FLI1 downstream Figure 1. TC32 cells are more sensitive to the microtubule inhibitors after 72 hours than U2OS cells. The target ID2 was reduced after treatment with all of the microtubule inhibitors (Figure 2). Docetaxel and vinproliferation of TC32 cells treated with (A) 10 nM vincristine, (B) 10 nM vinorelbine, and (C) 10 nM vinblastine is significantly more inhibited than the proliferation of U2OS cells. TC32 cells are also more blastine appeared to have the greatest inhibitory effect. sensitive to the taxanes than U2OS cells. In addition, luciferase data indicated 96-well plates; 5000 cells per well were plated in these plates and that NR0B1 promoter activity was decreased after 18-hour treatallowed to recover overnight. They were treated with the drug ment with four of the five microtubule inhibitors (Figure 3). The the following day. Cell viability after drug treatment was cal- activity of the CMV reporter also decreased, consistent with lowculated using CellTiter 96® (Promega, Madison, WI) and plot- er cell viability observed at the same concentration and time of ted against a standard curve for each of the two cell lines in or- treatment (data not shown). Finally, the 24-hour fractionation der to estimate cell numbers. Cells of both cell lines were treated experiments, in which nuclear and cytoplasmic fractions were with one of the five microtubule inhibitors for either 24, 48, or extracted from cell lysates, showed that neither docetaxel nor 72 hours. Only the data for the 72 hour time points is shown. vinorelbine affected the localization of EWS-FLI1 (Figure 4). The Western blot analysis. TC32 cells were treated with one relative protein expression of FLI1 was higher in the nuclear fracof the five drugs, lysed in LDS buffer, collected, and quantitated tions than in the cytoplasmic fractions without treatment (as exvia a BCA assay (Pierce, Waltham, MA). The lysates were sepa- pected, since EWS-FLI1 is a transcription factor). However, there rated on a 4-12% bis-tris gel (invitrogen) in MES buffer via elec- was no difference in this localization of the protein after treatment trophoresis and transferred to nitrocellulose. The blot was then with either of the two drugs. Protein expression of other relevant probed with primary antibody and visualized on film with the proteins such as SP1, α-tubulin, β-actin, S6, and ID2 was also anrequisite HRP conjugated secondary antibody using a Chemoluminescent Kit (Pierce) following the manufacturer’s protocol. Fractionation experiments. TC32 cells were treated with vinorelbine or docetaxel, then lysed with cytoplasmic extraction reagent to extract cytoplasmic protein. The remaining nuclear pellets were lysed with nuclear extraction reagent, according to the manufacturer’s protocol. These samples were stored frozen on dry ice and stored at -80°C. A western blot analysis was performed (as described above) to determine protein levels in the nuclear and cytoplasmic fractions. Luciferase assays. The promoter for NR0B1 was cloned from genomic DNA into PGL 4.18 and used to transfect TC32 cells. Single cell clones were generated as in the drug screen study1. The CMV-Luc cells were also generated using the CMV promoter and PGL 4.18. TC32 NR0B1-Luc and CMV-Luc cells were maintained Figure 2. Western blot showing suppression of the EWS-FLI1 target using the same procedures for the normal TC32 cell line. Cells were ID2 when treated with various microtubule inhibitors. TC32 cells plated in 96-well plates, and treated with the drugs the following treated were treated with the various microtubule inhibitors were day. Bioluminescence was measured at 6 and 18 hour time points. collected at 18 hours and probed with anti-ß-actin, anti-Fli1, and Cell viability was calculated using CellTiter 96® (Promega) and plotanti-ID2 antibodies. Vinblastine was the only drug which appeared to decrease the expression of EWS-Fli1. Protein expression of downted against a standard curve for each of the two cell lines in order stream target ID2 was reduced after treatment with any of the five to estimate cell numbers. Luciferase Steady GloTM Assay Reagent microtubule inhibitors. Docetaxel and vinblastine had the greatest effect on the expression of the ID2 protein.
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alyzed, but these results provided no discernable new information about the effect of the drugs on the cells or the different fractions.
hibit expression of the EWS-FLI1 oncogene itself, treatment with several of the drugs suppressed expression of downstream target gene ID2. This suggests that the drugs modulate the activity of EWS-FLI1 and decrease the expression of some downstream targets. Treatment with the microtubule inhibitors also suppresses expression of the NR0B1 promoter, but there is limited selectivity between the NR0B1 and CMV, suggesting a more general effect on transcription. It remains unclear whether or not the microtubule inhibitors cause a direct suppression of the NR0B1 reporter. Confocal microscopy done outside of this study suggested an interaction between EWS-FLI1 and microtubules. Although some of this data seemed to point to a relationship between microtubules and EWS-FLI1, the Western blots from the nuclear-cytoplasmic assay suggested that microtubule inhibitors do not affect EWS-FLI1 trafficking from the cytoplasm to the nucleus. Thus, while the drugs are cytotoxic to Ewing’s sarcoma tumor cells, prevention of EWS-FLI1 trafficking is probably not their mechanism of action. It is still unclear if these drugs interfere with the activity of EWS-FLI1. Despite this negative result, we have shown Figure 3. The EWS-FLI1 downstream target, NR0B1 promoter activity was significantly decreased after 18 that the EWS-FLI1 fusion transcription factor is hour treatment with four of the five microtubule inhibitors. At high concentrations CMV promoter activ- an excellent candidate oncogene for the developity decreased consistent with a corresponding decrease in cell viability (data not shown). ment of molecularly targeted therapies for Ewing’s sarcoma5. The development of molecularly target therapies for various types of cancers for which the genetic basis is known will play a key role in the future of this field of research, as more effective and less toxic therapies are sought out. This is partially due to the fact that the drugs currently being used are generally cytotoxic and target all rapidly dividing cells. The research and development of molecularly targeted therapies can address this question, as it can provide ways to more specifically and effectively target these cancers. In the case of Ewing’s sarcoma, an understanding of the exact functions and mechanisms of EWS-FLI1 will lead to the development of molecularly-target therapies. The development of specific therapies Figure 4. Nuclear cytoplasmic fractionation experiments indicate no change in the localization of the EWS-FLI1 transcription factor with microtubule inhibitor treatment. TC32 cells were treated with either through rigorous research and testing of potential docetaxel (A) or vinorelbine (B) and western blots were performed in order to determine relative protein inhibitors of key genes such as EWS-FLI1, will allevels in nuclear and cytoplasmic fractions at 24 hours . Neither docetaxel or vinorelbine changed the low for personalized cancer treatment based on localization of EWS-FLI1. C – cytoplasmic fraction; N – nuclear fraction; S – solvent control. genetic profiling of individual patients’ tumor cells.
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Discussion
References
The drug screen conducted prior to this study is a good example of modern approaches to finding molecular targets of cancers such as Ewing’s sarcoma. Some of the potential inhibitors of EWS-FLI1 by the screen were in fact microtubule inhibitors. The five drugs used for this study were chosen because they or their analogs were identified through the screen. The results of the cell viability experiments suggest an inherent sensitivity of Ewing’s cells to microtubule inhibitors, consistent with the known sensitivity of this tumor to this class of chemotherapy observed in the clinic. Furthermore, although microtubule inhibitors did not in-
1. Grohar, P. J., Woldemichael, G. M., Griffin, L. B., et al. Identification of an Inhibitor of the EWS-FLI1 Oncogenic Transcription Factor by High-Throughput Screening. J Natl Cancer Inst, 103, 962-978 (2011). 2. Lahl M., Fisher V., Laschinger K. Ewing’s Sarcoma Family Tumors: An Overview from Diagnosis to Survivorship. Clin J Oncol Nurs, 12(1), 89-97 (2008). 3. Leavy, P.J., Collier, A. B. Ewing sarcoma: prognostic criteria, outcomes and future treatments. Expert Rev Anticanc, 8, 617-624. (2008). 4. Arvand A., Denny C. T. Biology of EWS/ETS fusions in Ewing’s family tumors. Oncogene, 20, 5747-5754. (2001). 5. Riggi N., Stamenkovic, I. The Biology of Ewing sarcoma. Cancer Lett, 254(1), 1-10. (2007). 6. Jordan, M. A., Wilson, L. Microtubules as a target for anticancer drugs. Nat Rev Cancer, 4, 253-265. (2004).
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Delineating the Role of BRF2 in Breast Cancer Pathogenesis Jean Fan1, Yunkai Yu2, Paul Meltzer, M.D.2, Liang Cao, Ph.D.2 1 Montgomery Blair High School, Silver Spring, MD 2Genetics Branch, National Cancer Institute, Bethesda, MD Abstract Amplification of 8p11-12 is present in 10-15% breast cancers and is associated with poor prognosis. However, while putative driving oncogenes have been proposed, genes within this amplicon have yet to be definitively implicated in cancer growth, survival or pathogenesis. BRF2, a gene located within this amplicon, encodes a general transcription factor involved in RNA polymerase III-mediated transcription. A recent report suggests its homologue, BRF1, may promote cellular transformation. Here, the role of BRF2 is evaluated in breast cancer growth and development. A strong correlation between BRF2 gene amplification and BRF2 protein overexpression, a trait consistent with an oncogenic role, was established through immunoblot analysis, previous CGH, and expression array studies. Lentiviral-mediated gene transfer delivered BRF2-shRNA into breast cancer cells with 8p11-12 amplification and subsequently established long-term stable cell lines with shRNA constructs targeting BRF2 leading to marked reduction of BRF2. BRF2 inhibition resulted in impeded growth and proliferation rates as well as increased cell death. These findings suggest that BRF2 is a relevant oncogene in the 8p11-12 amplicon and may play a role in breast cancer growth and pathogenesis.
Introduction In breast cancers, 8p11-12 is the second most common region of genetic amplification, exhibited in 10% to 15% of breast cancers (AdĂŠlaĂŻde et al., 1997; Courjal and Theillet, 1997; Ray et al, 2004). In recent studies, 8p11-12 amplification has been associated with poor prognosis (Gelsi-Boyer et al., 2005). Patients with the 8p11-12 amplicon exhibited a significantly lower proportion of metastasis-free survival compared to patients without the amplicon (Fig. 1). This association suggests a malignant long-term consequence of oncogene amplification within 8p11-12 on breast cancer survival and a potential link between genetic amplification and pejorative disease evolution (Gelsi-Boyer et al., 2005). Despite the frequency and importance of the 8p11-12 amplicon, the relevant oncogene or oncogenes have yet to be identified. And while putative oncogenes have been proposed, further analysis is required in order to provide direct evidence of their oncogenic roles (Theillet et al., 1993). Garcia et al. (2005) examined 80 breast and ovarian tumors
Figure 1: 8p11-12 amplification and cancer prognosis. The orange Kaplan-Meier curves illustrate the metastasis-free survival (MFS) of 319 patients with and without the 8p11-12 amplification. The proportion of MFS decreases more dramatically with time for patients with the 8p11-12 amplification compared to patients without the 8p11-12 amplification. Similar results can be seen with the blue Kaplan-Meier curves representing A2 amplification. P values were calculated using the log-rank test. (GelsiBoyer et al., 2005)
and cell lines using high-resolution array comparative genomic hybridization(aCGH) and gene expression analyses in order to identify a segment of minimal common amplification of approximately 1-Mb size that is likely to contain key oncogenes driving the 8p11amplicon. BRF2 was one of four putative oncogenes cited as par12 ticularly interesting candidates for further evaluation. Gelsi-Boyer et al. (2005) also identified four distinct amplicons, A1, A2, A3, and A4, within 8p11-12 using a CGH. BRF2, common to the boundaries of amplicons A1 and A2 (Fig. 2), displayed expression levels significantly correlatedwith the expression of neighbor genes, suggestive of an oncogenic role. A2 amplification has also been associated with poor prognosis (Fig. 1). It is therefore important to generate biological data for the identification of candidate 8p11-12 genes that are important for their growth and survival. BRF2, located at 8p11.23, has been previously suggested as a candidate gene for the 8p11-12 amplicon (Garcia et al., 2005; Gelsi-Boyer et al., 2005). Yet, no biological data exist to elucidate the roles of BRF2 in breast cancer. By definitively determining the relevant oncogene or oncogenes for the 8p11-12amplicon, we hope to improve long-term breast cancer prognoses through the identification of novel target drugs. We hypothesized that BRF2 may play an oncogenic role in the development and progression of breast cancers exhibiting 8p11-12 amplification. By analyzing a panel of breast cancer cell lines with the 8p11-12 amplicon, we showed a strong correlation between BRF2 genetic amplification and BRF2 protein overexpression, a trait consistent with an oncogenic role. In addition, we employed shRNA-mediated long-term gene knockdown to reduce or silence BRF2 gene expression. Knockdown of BRF2 in HCC1500 breast cancer cells resulted in a substantial decrease in BRF2 synthesis. Furthermore, cell growth and cell proliferation rates were hindered markedly by the BRF2 knockdown while cell death was promoted. Our results suggest that BRF2 is a strong candidate driver oncogene for the 8p11-12amplicon and may contribute significantly to breast cancer pathogenesis.
Metho ds & Materials Cell Lines and Grow th Conditions Breast cancer cells lines BT483, CAMA1, HCC38, HCC1500, HCC1900, MCF7, MDA231, MDA435, UACC2087, ZR75, SUM44,
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hurj spring 2012: issue 14 ter 24h, cells were infected with lentiviruses with scramble or BRF2 shRNAs for 72 hrs. Infected cells were selected with 1μg/mL puromycin for about 2 weeks.
Figure 2: Genetic map of 8p11-12 with genes and identified amplicons A1, A2, A3, and A4 mapping in the interval of interest. The amplicon boundaries are indicated with lines and cores with enlarged lines. (Gelsi-Boyer et al., 2005)
and SUM52 were obtained from the NCI Genetics Branch Cell Repository (Bethesda, MD). Cells were maintained in recommended 1xRPMI-1640 or DMEM supplemented with 10%v/v FBS, 100U/ml penicillin and 100μg/ml streptomycin. All cell lines were incubated at 37°C under 5% CO2 and passaged at confluence until use. Immun obl ot An aly si s : Cells were homogenized in 1ml ice-cold PBS (Biosource) and suspended in 10mL RIPA+ buffer (Thermo Scientific Pierce) supplemented with 1%v/v 1xprotease inhibitor cocktail (Roche Diagnostics) and AEBSF and 2%v/v NaF, Na3VO4, Na2P2O7, phosphatase inhibitors I and phosphatase inhibitors II (Sigma). Protein concentrations of cleared lysates were quantified using the Pierce BCA Protein Assay kit (Thermo Scientific Pierce) following the manufacturer’s protocols. Protein concentrations were normalized in RIPA+ buffer, mixed with 1xNuPAGE LDS sample buffer (Invitrogen) and subsequently boiled for preservation. Lysate proteins were fractioned by SDS-PAGE on a 15-well Bis-Tris-HCl-10% polyacrylamide gel (Invitrogen) under standard conditions, blotted onto an iBlot nitrocellulose membrane (Invitrogen) according to manufacturer’s protocols, and blocked in 5% NFDM/TBST (Bio-Rad Laboratories). Reactive bands were labeled with primary antibodies against BRF2 (Proteintech Group Inc.) at 1:1000 dilution and primary antibodies against GAPDH (Cell Signaling) at 1:1000 dilution overnight at 4°C. After 2h incubation with 1:2000 dilution of secondary HRP-anti-Rabbit (Cell Signaling), reactive bands were developed using SuperSignal West Pico Chemoluminescent Kit (Pierce) following the manufacturer’s protocols and visualized on chemiluminescent film (Kodak). shRNA Plasmid Preparation: Plasmids containing lentiviralshRNA vectors targeting BRF2 were obtained from Open Biosystems. Bacterial colonies were generated on LB agar plates with ampicillin and incubated at 37°C overnight. Single colonies were inoculated into LB broth supplemented with ampicillin and incubated at 37° tilt overnight with 250 RMP shaking. Plasmid DNA was purified using the QIAGEN Plasmid Purification Midi Kit following manufacturer’s protocols. Generation of Lentiviruses: Bacterial plasmid DNA was purified using the QIAGEN EndoFree Plasmid Purification Maxi Kit following manufacturer’s protocols. Lentiviruses were generated from purified plasmid DNA following Invitrogen protocols. Infe c ti on : A total of 2.5x104 target cells were seeded into 6 well plates. Af-
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Grow th Assay : Approximately 2.5x103 cells were seeded into 96 well plates. At specified time points, cell growth was determined via ATP assay following manufacturer’s protocols.
Results and Conclusions Detection of elevated BRF2 protein in cell lines with 8p11-12 amplicon (C GH) and increased mRNA (expression array): Since BRF2 is an essential component in the RNA pol-III transcription factor complex and subsequently plays a vital role in mRNA processing and protein transcription, elevation in expression of BRF2 following BRF2 amplification may influence translation and proliferation rates and lead to cancer. To detect elevated expressions of BRF2, we analyzed a panel of breast cancer cell lines including BT483, CAMA1, HCC38, HCC1500, HCC1900, MCF7, MDA231, MDA435, UACC2087, ZR75, SUM44, and SUM52 with immunoblot analysis. Some of these cells lines have been previously shown to exhibit amplification at 8p11-12 as determined by comparative genomic hybridization (CGH) and elevated 8p11-12 mRNA levels as determined by mRNA expression arrays. Immunoblot results detected the highest levels of BRF2 in cell lines HCC1500, BT484, and UACC2087, respectively (Fig. 3). Our results provide the first piece of evidence to demonstrate that amplification of 8p11-12 leads to increased BRF2 protein expression in this panel of breast cancer cell lines.
Figure 3: Immunoblot analyses of BRF2 expression in a panel of breast cancer cell lines where GAPDH is used as a loading control. Approximately 11.25μg of each cell lysate was loaded into each lane. Immunoblot data appears consistent with expression ratios from previous studies.
Long-ter m Lentiv iral-Mediated G ene Silencing BRF2 in HCC1500: Lentiviral-mediated shRNA gene transfer achieved stable BRF2 knockdown in HCC1500 breast cancer cells for both BRF2-shRNA constructs. Stable cell lines were generated following a 2 week selection with puromycin to eliminate non-infected cells.Immunoblot
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analysis showed decreased BRF2 levels for both BRF2-shRNA-infected HCC1500 cell lines compared to the scramble control (Fig. 4), confirming effectiveness of BRF2 shRNA-1 and BRF2 shRNA-3 in silencing BRF2 geneexpression. Effec ts of BRF2 Knockdow n on Grow th in HCC1500 Breast Cancer Cells: To evaluate the BRF2 knockdown on the growth and proliferation of breast cancer cells, growth rates of BRF2 knockdown HCC1500 breast cancer cells were compared to the growth rates of control HCC1500 breast cancer cells over a period of 7 days. Control scramble HCC1500 cells grew and proliferated accordingly. However, BRF2 knockdown HCC1500 cells failed to grow and proliferate in vivo and subsequently decreased in cell count. The decrease in cell count may also be indicative of an increase in cell death rate by BRF2 knockdown (Fig. 5). This data suggests that elevated BRF2 expression is important for growth and proliferation of breast cancer cells with high degree of amplification, and thus may play a role in breast cancer development and pathogenesis.
Figure 5: Cell number counts as determined by ATP assay over 7 days after plating. Mean cell numbers are plotted + SD for 6 independent HCC1500 BRF2 shRNA-3-mediated knockdown cells and HCC1500 BRF2 scramble shRNA control cells. BRF2 shRNA-1-mediated knockdown cells have been omitted due to insufficient initial cell count.
Discussion
Amplification of 8p11-12 is commonly exhibited in breast cancers and is associated with poor prognosis. However, relevant oncogenes have yet to be definitively identified. We hypothesized that BRF2, a gene within the 8p11-12amplicon, may play an oncogenic role in the development and progression of breast cancer exhibiting 8p11-12 amplification. Our data confirmed elevated BRF2 expression in a panel of breast cancer cell lines exhibiting 8p11-12 amplification (Fig.3). The magnitude of BRF2 amplification was also found to be strongly correlated with BRF2 overexpression (Fig. 3). To fully evaluate the role of BRF2 on breast cancer growth, we performed BRF2 gene silencing on HCC1500 breast cancer cells, which exhibited high levels of BRF2 amplification and BRF2 overexpression. Long-term stable lentiviral-mediated gene silencing was achieved in HCC1500 breast cancer cells with two independent BRF2-shRNA vectors (Fig. 4). We estimate that both Figure 4: Immunoblot analysis for BRF2 expression in BRF2 knockdown infected HCC1500 cells. Approximately 30 μg of each cell cell lines expressed lysate was loaded into each lane. shRNAs have convincingly about 10% of the decreased BRF2 levels, confirming the gene knockdown. original BRF2 in HCC1500, thus reducing the level of BRF2 to that comparable of breast cancer lines without BRF2 amplification. Preliminary analysis of the growth of HCC1500 cells with BRF2 knockdown showed a large reduction of cell proliferation as well as increased cell death as indicated by ATP-
based cell proliferation assay and clonogenic assay (Fig. 5). Due to the interesting phenotypes associated with BRF2 knock-down in breast cancer cells with BRF2 amplification and overexpression, further investigations are warranted. In summary, the results from our experiments suggest that BRF2 may play an oncogenic role and be a putative driver oncogene for the 8p11-12 amplicon. Therefore, targeting BRF2 and its associated downstream machinery in patients exhibiting 8p11-12 amplification may have therapeutic potential. Our discovery may facilitate the understanding of breast cancer pathogenesis in the ultimate search for a cure. References
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