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CIRCUMVENTING ANTIGEN LOSS TO POTENTIATE CANCER IMMUNOTHERAPY Cancer cells become resistant to monoclonal antibody (mAb) therapy when they lose the cell surface antigens that mAbs target. To circumvent immune escape and maximize the efficacy of mAb therapy, new approaches to mitigate or perhaps even counteract antigen loss are necessary. Herein, we discuss three major mechanisms of antigen loss: trogocytosis, internalization and transcriptional down-regulation, and strategies to thwart cancer resistance caused by antigen loss.; First, we designed, generated and evaluated a novel type of antibody-drug conjugate that combines a cytotoxic payload with the Fc region of IgM antibodies to capitalize on the overexpression of the IgM Fc receptor by chronic lymphocytic leukemia (CLL) cells. This Fc-derived drug conjugate was selectively toxic for primary leukemic B-cells but not autologous normal T-cells ex vivo and in a murine xenograft model of CLL. This work provides proof-of-principle for targeted drug delivery by Fc-derived drug conjugates into cells that overexpress the IgM Fc receptor.; Second, we evaluated interactions between the kinase inhibitor ibrutinib and anti-CD20 mAbs. We demonstrated that ibrutinib causes transcriptional down-regulation of CD20 on CLL cells, but also preserves complement labeling of CLL cells through CD55 down-regulation and protects CLL cell surface CD20 by inhibiting trogocytosis. Thus, we uncovered putative mechanisms by which kinase inhibitors may augment mAb function.; Third, to allow for retargeting of CLL cells that lost antigen, we generated mAbs directed against the complement component C3d. We demonstrated that anti-C3d mAbs specifically bind to and eliminate CLL cells that are labelled by complement proteins during in vivo anti-CD20 mAb administration. Furthermore, we observed the anti-C3d mAbs can amplify their binding to CLL cells by mediating de novo complement deposition. These data suggest that anti-C3d mAbs represent a universal means of potentiating mAb therapy and eliminating residual cancer cells that have lost antigen.; Together, these findings improve our understanding of antigen loss and could translate into more effective mAb cancer therapies. Specifically, the work presented herein may lead to the development and optimization of combination therapies that can yield deeper and more durable responses in cancer patients. Ph.D.
Dalit Christians and Caste Consciousness in Pakistan This study explores caste discrimination in Pakistan against untouchable (Dalit) converts to Christianity. During the nineteenth century in India, many Dalits converted to Christianity to escape caste persecution. In the 1870s in Punjab, a mass movement to Protestant Christianity flourished among the Dalit Chuhra caste. The Chuhras were the largest menial caste in Punjab and engaged in degrading occupations including sweeping and sanitation work. By the 1930s, almost the entire Chuhra caste converted to Protestant Christianity. In 1947, during the partition of India, the majority of Chuhra converts in Punjab became part of the Protestant community in Pakistan. After Partition, many uneducated Chuhras were confined to menial jobs in the sanitation industry. Today, the stigma of Dalit ancestry is a distinct feature of social discrimination against Chuhra Christians in Pakistan.; `Caste consciousness' in Pakistan is connected to norms of purity and pollution. While not as pronounced as India, purity and pollution in Pakistan relates to the concept of pak (clean) and na-pak (unclean). Because of degrading occupations as sweepers and sanitation workers, many Chuhra Christians in Pakistan are associated with `pollution.' This leads to multiple forms of social discrimination. Chuhra Christians respond to caste persecution through various modes. Through an analysis of church sermons, I argue that Chuhra Christians create `counter-narratives' as a form of protest against caste discrimination. These `counter-narratives' focus on veiling caste identity and creating a new genealogical history for their community that is not connected to Dalit ancestry. These counter-narratives also affect the development of `folk theology' which focuses on the concept of izzat or `respect.' Church sermons reveal that izzat has a theological dimension and shapes Chuhra Christian self-understanding in Pakistan. Ph.D.
A Place Between Two Places: The Qur'an's Intermediate State and the Early History of the Barzakh For those who believe in a future resurrection of the body, there naturally arises the question of what happens after death but before the end of time. This condition is the intermediate state. For most Muslims, the intermediate state is called the barzakh. It is a fantastical and frightening time in the grave, often equated to Purgatory in Christianity. Muslims throughout history and today have discussed this belief and expressed it in many forms. In the theological turmoil of the early Islamic Middle Ages, it even became a touchstone of orthodoxy: to be a true Muslim was to believe in the barzakh. But where does the medieval/modern belief in the barzakh come from? While the word barzakh does appear in the Qur'an three times, it is never explained there in detail. The Qur'an's primal audience is expected to understand this word without further comment. Using the methodologies of comparative religion and oral compositional forms (ring structure, chiasms, parallelisms), this project aims to show what the Qur'an meant by barzakh in the 7th century. A long study will be given on the Qur'an's eighteenth sura, al-Kahf. Fifteen other suras will be examined as well. I will argue that the Qur'anic barzakh is an eschatological cosmology designed specifically to nullify saint cults and the cult of the divine Christ by putting the dead into a sleep state. From here, the belief in the barzakh will be shown passing through early Islamic history and culminating in the distinctive eschatological claims of the Islamic Middle Ages. Ph.D.
AVATARES DE LA AGENCIA Y RESISTENCIA INDIGENA: TITU CUSI YUPANQUI (15??-1571) Y ESTERCILIA SIMANCA (1976)
AVATARES DE LA AGENCIA Y RESISTENCIA INDIGENA: TITU CUSI YUPANQUI (15??-1571) Y ESTERCILIA SIMANCA (1976) The dissertation proposes a comparative analysis of two indigenous authors who wrote more than four centuries apart: Inca Titu Cusi Yupanqui from 16th century Peru, and a 21st century female Wayuu writer, Estercilia Simanca from Colombia. The focus of the research is the indigenous perspective of colonialism in America; both writers were witnesses to particular circumstances and wrote about them in Spanish. Their texts are forms of agency and resistance against colonial/postcolonial oppression respectively. For the indigenous perspective, the European arrival to the “New World” in 1492 meant the destruction of their culture, ways of life, and in many cases death itself. Yet, indigenous peoples were not passive victims of that history. During the 16th century, Titu Yupanqui’s people confronted and fought against the invaders, and in the 21st century, Estercilia Simanca’s community continues to resist its disappearance. These two indigenous writers severely condemn the colonizers, and my research aims to demonstrate how these two authors play an important role in the preservation of their cultures, and to underscore the relevance of the studying and teaching of indigenous authors. Ph.D.
Towards a Transnational Aesthetic in Latin American Literature This thesis looks at the representation of national and transnational spaces in contemporary Latin American literature. In doing so, it argues that contemporary writing expands both the geographical imaginary of the physical spaces of the state and more significantly, frequently alters the conceptual envisioning of nation through unsettling its conventionally understood links to history, language, and identity. I develop the notion of literary transnationalism as an emerging aesthetic, defined by its handling of space, time and social cohesion. I argue that the region's contemporary literature moves away from the clean parameters of nation and into bi-national, multi-national, de-national, post-national, extra-national, and virtual domains. This framework includes: 1) migration-related texts 2) multi-territorial texts that traverse many geographies 3) nationally ambiguous or undefined texts, including Marc Augé's non-places 4) and texts imbedded in extra-national and virtual realms. I define space as a finite system of representation with imagined limits, be they geographical, national, linguistic or digital.; In order to study the spatial aesthetics of transnationalism, I begin by looking at three migration-themed texts from Brazil in my first chapter, Luiz Ruffato's Estive em Lisboa e lembrei de você (2009), Wilson Bueno's Mar Paraguayo (1992), and Oscar Nadasato's Nihonjin (2011). Specifically I argue that contemporary migration-themed novels disrupt narrative time-space cohesion by obscuring the frontiers between the national and the transnational. In the following chapter, I study the interplay among speed, mobility and power in Roberto Bolaño’s 2666 and its theatrical adaptation by Spanish director Àlex Rigola. Seeing the two works in dialogue, I focus on the place of stasis and non-mobility as a counterpoint to speed and their implications for transnationalism. In the third chapter, I turn to Bernardo Carvalho’s Teatro (1998) and Gilberto Noll’s Harmada (1993), exploring the contrast between spatial ambiguity, and ruins and decaying spaces. I propose that ruin acts as an affront to the flattening processes of globalization in the two novels. To conclude, I examine two collections of literary blogs in Spanish and Portuguese, the Brazilian publishing house, Companhia das Letras’ Amores Expressos blogs, as well as Elboomeran(g) a vast literary blog in Spanish. Employing both close and distant readings, I show how online literary writing elucidates the poetics and spatial fluidity vital to contemporary transnationalism. Ph.D.
A longitudinal study on the role of lexical stress and motivation in the perception and production of L2 Spanish stop consonants
A longitudinal study on the role of lexical stress and motivation in the perception and production of L2 Spanish stop consonants This study investigated the perception and production of two L2 stop consonants, examining the importance of lexical stress and motivation to learners' ability to discriminate and produce Spanish /b/ and /p/. Longitudinal data was collected from 26 English-speaking adults enrolled in a second-semester Spanish course at the time of recruitment. On five occasions over a year-long period spanning nearly three semesters of Spanish instruction, participants completed a discrimination task and two production tasks: a sentence formation task and a sentence reading task. Once per semester, they also completed a language contact questionnaire, a quantitative motivation questionnaire operationalizing aspects of the L2 Motivational Self System (Dörnyei, 2009), and a qualitative questionnaire eliciting information on their language learning goals and beliefs.; For each of four contrasts crossing stress and position in the word, I calculated d' as a measure of participants' ability to discriminate the stops (Macmillan & Creelman, 2005). On the production data, I took VOT measurements from word-initial targets and C:V intensity ratio measurements, which index degree of lenition (Hualde, Simonet, & Nadeu, 2011), from word-medial targets using Praat software (Boersma & Weenik, 2012).; In characterizing the findings, both accuracy and stability were taken into account. Learners developed short-lag /p/ more quickly than lead-lag /b/, but the lead-lag category proved more resilient after a brief hiatus from Spanish during Winter Break. In contrast, there was little development of word-medial stops at the group level, though some individuals succeeded in producing targetlike C:V intensity ratios, indicating that they had acquired the phonological distribution of stops and approximants in Spanish. Consequently, phonetic detail (i.e., VOT) may be easier to acquire than phonological alternations (i.e., lenition).; Regarding stress and motivation, the primary predictors of interest, the former was more related to performance and the latter to development. Participants' discriminated stops more readily in stressed syllables and produced medial /b/ with greater degrees of lenition in unstressed syllables. In terms of motivation, a stronger ideal L2 self was negatively related to VOT development. This finding suggests that at lower instructional levels, learners likely prioritize grammar and vocabulary, potentially excluding pronunciation from their motivational systems. Ph.D.
CIRS Newsletter 18 Center for International and Regional Studies]
Legionaries Living in Lutetia: A Study of the Socio-Economic Effects of the Roman Army during the Principate
Legionaries Living in Lutetia: A Study of the Socio-Economic Effects of the Roman Army during the Principate Wagner, Brian
Jihad and Jihadn’t: Emerging Parallels in Twentieth-Century Holy War Propaganda Layfield, Philip
Living and Imagining City Spaces: The Case Study of Beirut Harb, Mohamad Khalil “Schein und Sein,” is a baroque German proverb that literally translates to image and reality or the illusionary and the real. The dichotomy between the image and the real, the imagined and the lived, served as the initial inspiration for my project on the city of Beirut. Between the image and the reality, the notion of space unfolded and that was the crux of my research. This project has been a synchronic one, studying and capturing Beirut in a moment in time with all its contemporary complexities. The famous American novelist and essayist, Christopher Morley, once said “all cities are mad: but the madness is gallant. All cities are beautiful, but the beauty is grim.” This is the city, a place of paradoxes, a place of beauty, a place of contradictions, evidently a space. Whether we romanticize a city, or criticize a city, we tend to forget that in the end it is a space. In particularly, it is an amalgam of spaces that are imagined, lived, contradicted and resisted. From certain spaces, the imagination of the city arises and from certain spaces, a different lived experience of the city arises. This dichotomy of spaces is witnessed in Beirut, a city that exhibits a paradoxical relation between its image and its various spatial realities. In this research, I used Beirut and its spaces as a model and a means to an end. I probed to see how groups conceive, imagine and live city-spaces. When looking at the image of Beirut, we see one that is part of the global order of world cities; a cosmopolitan capital that provides all that is available in international exclusivity and its accompanying lifestyles. This globalist spatiality can be lived in certain enclaves of the city, albeit limited ones. While the image exists, a different set of realities and lived experiences in Beirut and its spaces also exist. These lived experiences are different from the image and project a new, locally-oriented reality. With this in mind, I asked two central questions for this research: Is the image of Beirut the product of an affluent upper class that imagines the city-space in a certain way? Moreover, is there a different lower-income group that lives and generates a different spatial reality in the city? Through attempting to answer these questions and through attempting to thickly describe Beirut in a moment of time, I identified a new model for studying city-space. This model is the Urbanista and the Biarti model. In this research, I will present this model and demonstrate the spatial dichotomies it generates in cities. Throughout the research, I will be using the Urbanistas, as the main label to describe the group that imagines the city and that positions it with the global order of metropolitan cities. It is the group that is responsible for the “image” and who lives the image in their globally connected spaces. I will also be using the Biartis, as the main label to identify a locally oriented group that lives the city in a particular way. This group accords a lifestyle that is so very different from the image of Beirut and that produces a city-space of its own. Evidently, space cannot come about on its own and it requires groups that live it and imagine it. A city is not a city without its inhabitants and through the Urbanista and the Biarti model, we will see that what we think is a unified city, is actually a set of fragmented spaces that are lumped under one label.
Community Action toward the Desegregation of the DC Public Schools, 1947-1954 Liotta, Allison
The 2009 Iranian Presidential Elections in Comparative Perspective in Iran and the International System Anoush Ehteshami & Reza Molavi, ed.
The 2009 Iranian Presidential Elections in Comparative Perspective in Iran and the International System Anoush Ehteshami & Reza Molavi, ed. Zaccara, Luciano Much attention in the West has focused on Iran as a problem country. This book challenges the representations of Iran as a hostile regional power led by ideologues, and goes further by discussing how international relations are viewed from inside Iran itself, outlining the factors which underpin Iranian thinking on international relations and considering what role Iran, as a large and significant country in the Middle East, ought to play in a fairly constructed international system. The book is written by leading scholars and policy makers from inside, as well as from outside, Iran and includes academics with unparalleled access and insights into the world-views of the Iranian leadership. Subjects covered include: the rationale of Iran's Islamic constitution, including its electoral system, and the impact this has on international relations; Iran's view of the ideal international system, including the place therein of ethics, justice, and security; Iran's international interests, including energy needs; and relations with the West, including the clash between Iranian and Western views of the world order.
Saudi Arabia: Family, Religion, Army and Oil in Political Regimes in the Arab World: Society and Exercise of Power Ferran Izquierdo Brichs, ed.
Saudi Arabia: Family, Religion, Army and Oil in Political Regimes in the Arab World: Society and Exercise of Power Ferran Izquierdo Brichs, ed. Soler, Eduard; Zaccara, Luciano One of the implications of Orientalism is that the Arab world, as a homogenous entity, is often analysed as an anomaly within the international system. This book argues that, despite their differences, societies across the globe ultimately construct their own history according to very similar dynamics and tensions. The methodological approach of this book, using different countries within the Arab world as models, offers the reader an analysis of relations between the elites and their opposition in a variety of settings. A definition of the political structure of each country is drawn from this analysis before potential future scenarios, as according to country specific experts, are proposed. This model provides a useful contribution to students and scholars of political science and international relations. Through providing a comparative study of the political regimes currently operating in the Arab world; their elites, civil society, power resources and political resistance, this book illustrates that despite the image of homogeneity sometimes portrayed by the Arab world, it is the multiplicity of models and heterogeneity of regimes that constitute reality.
Custom in Islamic Law and Legal Theory, the Development of the Concepts of ‘Urf and ‘Adah in the Islamic Legal Tradition.
Custom in Islamic Law and Legal Theory, the Development of the Concepts of ‘Urf and ‘Adah in the Islamic Legal Tradition. Shaban, Ayman This book explores the relationship between custom and Islamic law and seeks to uncover the role of custom in the construction of legal rulings. On a deeper level, however, it deals with the perennial problem of change and continuity in the Islamic legal tradition (or any tradition for that matter).
Muslim Communities in Post-Cold War Europe Nonneman, Gerd
Iran under Ahmadinejad: a European View Nonneman, Gerd
Security in the Wider Middle East: a question of avoiding self-fulfilling prophecies Nonneman, Gerd
Constants and Variations in the British Gulf Relations Nonneman, Gerd A decade after the War for Kuwait and two decades after the Iran-Iraq War, the wider Gulf region remains mired in internal, regional and international conflicts. Iran, Iraq, and the Arab Gulf States presents analytical perspectives - including solution-oriented assessments to identify major causes for actual and potential conflicts throughout the Gulf. The twenty-six papers assembled in this volume identify trends for the next decade. Studies on Iranian, Iraqi, Saudi and Arab Gulf States' political agendas on the domestic, regional and international fronts are included, along with assessments on pending legal issues, including border disputes, relations among the Gulf states themselves, as well as their complex and evolving ties with several Western powers. The study closes with four 'trends' chapters looking at the 2000-2010 period.
The Gulf States and the Iran-Iraq War: Pattern Shifts and Continuities Nonneman, Gerd Iraq and Iran are the two most important states in the Gulf region, given their population size, military strength, and the potential threat they pose to other states in the region. This book enhances our understanding of the troubled relationship between Iran and Iraq, placing it in historical context, examining the rapid deterioration leading to the eight-year war that started in 1980 and the effects of that trauma, and exploring the ongoing issues that currently bedevil bilateral relations. The authors cover such central issues as how each side has sought to use opposition groups in the other state to weaken it, ethnic divisions, the role of outside states (especially the United States), and a fascinating account of how the war affected a generation of Iraqis and Iranians. The role of the U.S. in the region and how U.S. policy has affected the two states are also considered. This book provides a basis for understanding the background of a tumultuous relationship that is entering a new era.
The Three Environments of Middle East Foreign Policy Making and Relations with Europe Nonneman, Gerd In the post-9/11 climate, the role of Middle Eastern and North African (MENA) states in Europe’s regional security environment and international politics has become more than ever a focus for attention, but remains ill-understood. This book provides a framework for the analysis of Middle Eastern foreign policies in general, and for understanding these states’ relations with Europe in particular. The book fills a gap in the literature on Euro-Middle Eastern relations by adopting a south-to-north perspective, using the tools of Foreign Policy Analysis to examine the determinants of the foreign policies of the MENA states themselves: only thus can one hope to arrive at a genuine understanding of what underlies these states’ evolving policy orientations and behaviour towards Europe. The volume starts by laying out a conceptual framework for analysis, and examining the domestic, regional, and international environments that condition MENA foreign policies. Actual policy output is then systematically investigated through a wide range of country case studies ranging from the Maghreb and the Mashreq to the Gulf and Turkey. Europe is treated throughout both as a target of those foreign policies, and as part of the environment that shapes them. The result of a two-year project sponsored by the European University Institute’s Mediterranean Programme, the book helps bridge the divide between Middle East expertise and the discipline of International Relations. The systematic comparative analysis of MENA states’ foreign policy with special reference to Europe throws new light on questions about ‘Third World’ foreign policy.