Analysis of memory B cell responses and isolation of novel monoclonal antibodies with neutralizing breadth from HIV-1-infected individuals.

BACKGROUND: The isolation of human monoclonal antibodies (mAbs) that neutralize a broad spectrum of primary HIV-1 isolates and the characterization of the human neutralizing antibody B cell response to HIV-1 infection are important goals that are central to the design of an effective antibody-based vaccine. METHODS AND FINDINGS: We immortalized IgG(+) memory B cells from individuals infected with diverse clades of HIV-1 and selected on the basis of plasma neutralization profiles that were cross-clade and relatively potent. Culture supernatants were screened using various recombinant forms of the envelope glycoproteins (Env) in multiple parallel assays. We isolated 58 mAbs that were mapped to different Env surfaces, most of which showed neutralizing activity. One mAb in particular (HJ16) specific for a novel epitope proximal to the CD4 binding site on gp120 selectively neutralized a multi-clade panel of Tier-2 HIV-1 pseudoviruses, and demonstrated reactivity that was comparable in breadth, but distinct in neutralization specificity, to that of the other CD4 binding site-specific neutralizing mAb b12. A second mAb (HGN194) bound a conserved epitope in the V3 crown and neutralized all Tier-1 and a proportion of Tier-2 pseudoviruses tested, irrespective of clade. A third mAb (HK20) with broad neutralizing activity, particularly as a Fab fragment, recognized a highly conserved epitope in the HR-1 region of gp41, but showed striking assay-dependent selectivity in its activity. CONCLUSIONS: This study reveals that by using appropriate screening methods, a large proportion of memory B cells can be isolated that produce mAbs with HIV-1 neutralizing activity. Three of these mAbs show unusual breadth of neutralization and therefore add to the current panel of HIV-1 neutralizing antibodies with potential for passive protection and template-based vaccine design.

Shifting Loyalties: World War I and the Conflicted Politics of Patriotism in the British Caribbean

This dissertation examines how the crisis of World War I impacted imperial policy and popular claims-making in the British Caribbean. Between 1915 and 1918, tens of thousands of men from the British Caribbean volunteered to fight in World War I and nearly 16,000 men, hailing from every British colony in the region, served in the newly formed British West Indies Regiment (BWIR). Rousing appeals to imperial patriotism and manly duty during the wartime recruitment campaigns and postwar commemoration movement linked the British Empire, civilization, and Christianity while simultaneously promoting new roles for women vis-à-vis the colonial state. In Jamaica and Trinidad and Tobago, the two colonies that contributed over seventy-five percent of the British Caribbean troops, discussions about the meaning of the war for black, coloured, white, East Indian, and Chinese residents sparked heated debates about the relationship among race, gender, and imperial loyalty.

To explore these debates, this dissertation foregrounds the social, cultural, and political practices of BWIR soldiers, tracing their engagements with colonial authorities, military officials, and West Indian civilians throughout the war years. It begins by reassessing the origins of the BWIR, and then analyzes the regional campaign to recruit West Indian men for military service. Travelling with newly enlisted volunteers across the Atlantic, this study then chronicles soldiers' multi-sited campaign for equal status, pay, and standing in the British imperial armed forces. It closes by offering new perspectives on the dramatic postwar protests by BWIR soldiers in Italy in 1918 and British Honduras and Trinidad in 1919, and reflects on the trajectory of veterans' activism in the postwar era.

This study argues that the racism and discrimination soldiers experienced overseas fueled heightened claims-making in the postwar era. In the aftermath of the war, veterans mobilized collectively to garner financial support and social recognition from colonial officials. Rather than withdrawing their allegiance from the empire, ex-servicemen and civilians invoked notions of mutual obligation to argue that British officials owed a debt to West Indians for their wartime sacrifices. This study reveals the continued salience of imperial patriotism, even as veterans and their civilian allies invoked nested local, regional, and diasporic loyalties as well. In doing so, it contributes to the literature on the origins of patriotism in the colonial Caribbean, while providing a historical case study for contemporary debates about "hegemonic dissolution" and popular mobilization in the region.

This dissertation draws upon a wide range of written and visual sources, including archival materials, war recruitment posters, newspapers, oral histories, photographs, and memoirs. In addition to Colonial Office records and military files, it incorporates previously untapped letters and petitions from the Jamaica Archives, National Archives of Trinidad and Tobago, Barbados Department of Archives, and US National Archives.

A Politics of the Unspeakable: The Differend of Israel

Israel's establishment in 1948 in former British-Mandate Palestine as a Jewish country and as a liberal democracy is commonly understood as a form of response to the Holocaust of WWII. Zionist narratives frame Israel's establishment not only as a response to the Holocaust, but also as a return to the Jewish people's original homeland after centuries of wandering in exile. Debates over Israel's policies, particularly with regard to Palestinians and to the country's non-Jewish population, often center on whether Israel's claims to Jewish singularity are at the expense of principles of liberal democracy, international law and universal human rights. In this dissertation, I argue that Israel's emphasis on Jewish singularity can be understood not as a violation of humanism's universalist frameworks, but as a symptom of the violence inherent to these frameworks and to the modern liberal rights-bearing subject on which they are based. Through an analysis of my fieldwork in Israel (2005-2008), I trace the relation between the figures of "Jew" and "Israeli" in terms of their historical genealogies and in contemporary Israeli contexts. Doing so makes legible how European modernity and its concepts of sovereignty, liberalism, the human, and subjectivity are based on a metaphysics of presence that defines the human through a displacement of difference. This displaced difference is manifest in affective expression. This dissertation shows how the figure of the Jew in relation to Israel reveals sexual difference as under erasure by the suppression of alterity in humanism's configuration of man, woman, and animal, and suggests a political subject unable to be sovereign or fully represented in language.

Climate change, water resources, and the politics of adaptation in the Middle East and North Africa

Through an examination of global climate change models combined with hydrological data on deteriorating water quality in the Middle East and North Africa (MENA), we elucidate the ways in which the MENA countries are vulnerable to climate-induced impacts on water resources. Adaptive governance strategies, however, remain a low priority for political leaderships in the MENA region. To date, most MENA governments have concentrated the bulk of their resources on large-scale supply side projects such as desalination, dam construction, inter-basin water transfers, tapping fossil groundwater aquifers, and importing virtual water. Because managing water demand, improving the efficiency of water use, and promoting conservation will be key ingredients in responding to climate-induced impacts on the water sector, we analyze the political, economic, and institutional drivers that have shaped governance responses. While the scholarly literature emphasizes the importance of social capital to adaptive governance, we find that many political leaders and water experts in the MENA rarely engage societal actors in considering water risks. We conclude that the key capacities for adaptive governance to water scarcity in MENA are underdeveloped. © 2010 Springer Science+Business Media B.V.

Informatic Opacity: Biometric Facial Recognition and the Aesthetics and Politics of Defacement

Confronting the rapidly increasing, worldwide reliance on biometric technologies to surveil, manage, and police human beings, my dissertation Informatic Opacity: Biometric Facial Recognition and the Aesthetics and Politics of Defacement charts a series of queer, feminist, and anti-racist concepts and artworks that favor opacity as a means of political struggle against surveillance and capture technologies in the 21st century. Utilizing biometric facial recognition as a paradigmatic example, I argue that today's surveillance requires persons to be informatically visible in order to control them, and such visibility relies upon the production of technical standardizations of identification to operate globally, which most vehemently impact non- normative, minoritarian populations. Thus, as biometric technologies turn exposures of the face into sites of governance, activists and artists strive to make the face biometrically illegible and refuse the political recognition biometrics promises through acts of masking, escape, and imperceptibility. Although I specifically describe tactics of making the face unrecognizable as "defacement," I broadly theorize refusals to visually cohere to digital surveillance and capture technologies' gaze as "informatic opacity," an aesthetic-political theory and practice of anti- normativity at a global, technical scale whose goal is maintaining the autonomous determination of alterity and difference by evading the quantification, standardization, and regulation of identity imposed by biometrics and the state. My dissertation also features two artworks: Facial Weaponization Suite, a series of masks and public actions, and Face Cages, a critical, dystopic installation that investigates the abstract violence of biometric facial diagramming and analysis. I develop an interdisciplinary, practice-based method that pulls from contemporary art and aesthetic theory, media theory and surveillance studies, political and continental philosophy, queer and feminist theory, transgender studies, postcolonial theory, and critical race studies.

Event memory: A theory of memory for laboratory, autobiographical, and fictional events.

An event memory is a mental construction of a scene recalled as a single occurrence. It therefore requires the hippocampus and ventral visual stream needed for all scene construction. The construction need not come with a sense of reliving or be made by a participant in the event, and it can be a summary of occurrences from more than one encoding. The mental construction, or physical rendering, of any scene must be done from a specific location and time; this introduces a "self" located in space and time, which is a necessary, but need not be a sufficient, condition for a sense of reliving. We base our theory on scene construction rather than reliving because this allows the integration of many literatures and because there is more accumulated knowledge about scene construction's phenomenology, behavior, and neural basis. Event memory differs from episodic memory in that it does not conflate the independent dimensions of whether or not a memory is relived, is about the self, is recalled voluntarily, or is based on a single encoding with whether it is recalled as a single occurrence of a scene. Thus, we argue that event memory provides a clearer contrast to semantic memory, which also can be about the self, be recalled voluntarily, and be from a unique encoding; allows for a more comprehensive dimensional account of the structure of explicit memory; and better accounts for laboratory and real-world behavioral and neural results, including those from neuropsychology and neuroimaging, than does episodic memory.

Experimental manipulations of the phenomenology of memory.

We investigated the effects of visual input at encoding and retrieval on the phenomenology of memory. In Experiment 1, participants took part in events with and without wearing blindfolds, and later were shown a video of the events. Blindfolding, as well as later viewing of the video, both tended to decrease recollection. In Experiment 2, participants were played videos, with and without the visual component, of events involving other people. Events listened to without visual input were recalled with less recollection; later adding of the visual component increased recollection. In Experiment 3, participants were provided with progressively more information about events that they had experienced, either in the form of photographs that they had taken of the events or narrative descriptions of those photographs. In comparison with manipulations at encoding, the addition of more visual or narrative cues at recall had similar but smaller effects on recollection.

The Politics of Gender Socialization

This manuscript is comprised of three papers that examine the far-reaching and often invisible political outcomes of gender role socialization in the United States. These papers focus primarily on two areas: political confidence amongst girls and women, and the effects of gender on survey measurement and data quality.

Chapter one focuses on political confidence, and the likelihood that women will run for political office. Women continue to be underrepresented at all levels of political leadership, and their lack of political ambition, relative to men, has been identified as a primary cause. In this paper, I explore the relationship between an individual's masculinity and femininity and her development of political ambition. Using original survey data from the 2012 Cooperative Congressional Election Study (CCES), I first empirically demonstrate that gender (masculinity/femininity) and sex (male/female) are unique elements of identity and, moreover, are both independently related to political ambition. I then explore the relevance of gender for the study of candidate emergence, testing whether and how masculinity and femininity might be related to political ambition are supported empirically. While the results suggest that masculinity is positively associated with the development of political ambition, the relationship between femininity and candidate emergence seems to be more complicated and not what prevailing stereotypes might lead us to expect. Moreover, while the relationship between masculinity and political ambition is the same for men and women, the relationship between femininity and political ambition is very different for women than it is for men. This study suggests that gender role socialization is highly related with both men's and women's desire to seek positions of political leadership.

Chapter two continues this exploration of gendered differences in the development of political ambition, this time exploring how social attractiveness and gendered perceptions of political leadership impact the desire to hold political office.Women are persistently underrepresented as candidates for public office and remain underrepresented at all levels of government in the United States. Previous literature suggests that the gendered ambition gap, gender socialization, insufficient recruitment, media scrutiny, family responsibilities, modern campaign strategies, and political opportunity structures all contribute to the gender imbalance in pools of officeholders and candidates. To explain women's reticence to run, scholars have offered explanations addressing structural, institutional, and individual-level factors that deter women from becoming candidates, especially for high positions in the U.S. government. This paper examines a previously unexplored factor: how dating and socialized norms of sexual attraction affect political ambition. This study investigates whether young, single, and heterosexual women's desire for male attention and fear of being perceived as unattractive or "too ambitious" present obstacles to running for office. The results of these experiments suggest that social expectations about gender, attraction and sexuality, and political office-holding may contribute to women's reticence to pursue political leadership. Chapter two is a co-authored work and represents the joint efforts of Laura Lazarus Frankel, Shauna Shames, and Nadia Farjood.

Chapter 3 bridges survey methodology and gender socialization, focusing on how interviewer sex affects survey measurement and data quality. Specifically, this paper examines whether and how matching interviewer and respondent sex affects panel attrition--respondents dropping out of the study after participating in the first wave. While the majority of research on interviewer effects suggests that matching interviewer and respondent characteristics (homophily) yields higher quality data, little work has examined whether this pattern holds true in the area of panel attrition. Using paradata from the General Social Survey (GSS), I explore this question. My analysis reveals that, despite its broader positive effects on data quality, matching interviewer and respondent sex increases likelihood to attrit. Interestingly, this phenomenon only emerges amongst male respondents. However, while assigning female interviewers to male respondents decreases their propensity to attrit, it also increases the likelihood of biased responses on gender related items. These conflicting outcomes represent a tradeoff for scholars and survey researchers, requiring careful consideration of mode, content, and study goals when designing surveys and/or analyzing survey data. The implications of these patterns and areas for further research are discussed.

Together, these papers illustrate two ways that gender norms are related to political outcomes: they contribute to patterns of candidate emergence and affect the measurement of political attitudes and behaviors.

Optimizing the Correction of Memory Errors

People are always at risk of making errors when they attempt to retrieve information from memory. An important question is how to create the optimal learning conditions so that, over time, the correct information is learned and the number of mistakes declines. Feedback is a powerful tool, both for reinforcing new learning and correcting memory errors. In 5 experiments, I sought to understand the best procedures for administering feedback during learning. First, I evaluated the popular recommendation that feedback is most effective when given immediately, and I showed that this recommendation does not always hold when correcting errors made with educational materials in the classroom. Second, I asked whether immediate feedback is more effective in a particular case—when correcting false memories, or strongly-held errors that may be difficult to notice even when the learner is confronted with the feedback message. Third, I examined whether varying levels of learner motivation might help to explain cross-experimental variability in feedback timing effects: Are unmotivated learners less likely to benefit from corrective feedback, especially when it is administered at a delay? Overall, the results revealed that there is no best “one-size-fits-all” recommendation for administering feedback; the optimal procedure depends on various characteristics of learners and their errors. As a package, the data are consistent with the spacing hypothesis of feedback timing, although this theoretical account does not successfully explain all of the data in the larger literature.

The neuropsychology of autobiographical memory.

This special issue of Cortex focuses on the relative contribution of different neural networks to memory and the interaction of 'core' memory processes with other cognitive processes. In this article, we examine both. Specifically, we identify cognitive processes other than encoding and retrieval that are thought to be involved in memory; we then examine the consequences of damage to brain regions that support these processes. This approach forces a consideration of the roles of brain regions outside of the frontal, medial-temporal, and diencephalic regions that form a central part of neurobiological theories of memory. Certain kinds of damage to visual cortex or lateral temporal cortex produced impairments of visual imagery or semantic memory; these patterns of impairment are associated with a unique pattern of amnesia that was distinctly different from the pattern associated with medial-temporal trauma. On the other hand, damage to language regions, auditory cortex, or parietal cortex produced impairments of language, auditory imagery, or spatial imagery; however, these impairments were not associated with amnesia. Therefore, a full model of autobiographical memory must consider cognitive processes that are not generally considered 'core processes,' as well as the brain regions upon which these processes depend.

Dedication and Display of Portrait Statues in Hellenistic Greece: Spatial Practices and Identity Politics

This dissertation models a new approach to the study of ancient portrait statues—one that situates them in their historical, political, and spatial contexts. By bringing into conversation bodies of evidence that have traditionally been studied in discrete categories, I investigate how statue landscapes articulated and reinforced a complex set of political and social identities, how space was utilized and manipulated on a local and a regional level, and how patrons responded to the spatial pressures and visual politics of statue dedication within a constantly changing landscape.

Instead of treating sites independently, I have found it to be more productive—and, indeed, necessary—to examine broader patterns of statue dedication. I demonstrate that a regional perspective, that is, one that takes into account the role of choice and spatial preference in setting up a statue within a regional network of available display locations, can illuminate how space shaped the ancient practice of portrait dedication. This level of analysis is a new approach to the study of portrait statues and it has proved to be a productive way of thinking about how statues and context were used together to articulate identity. Understanding how individual monuments worked within these broader landscapes of portrait dedications, how statue monuments functioned within federal systems, and how monuments set up by individuals and social groups operated along side those set up by political bodies clarifies the important place of honorific statues as an expression of power and identity within the history of the site, the region, and Hellenistic Greece.

Contributions Of the Human Medial Prefrontal Cortex To Associative Recognition Memory: Evidence From Functional Neuroimaging

Neuroimaging studies of episodic memory, or memory of events from our personal past, have predominantly focused their attention on medial temporal lobe (MTL). There is growing acknowledgement however, from the cognitive neuroscience of memory literature, that regions outside the MTL can support episodic memory processes. The medial prefrontal cortex is one such region garnering increasing interest from researchers. Using behavioral and functional magnetic resonance imaging measures, over two studies, this thesis provides evidence of a mnemonic role of the medial PFC. In the first study, participants were scanned while judging the extent to which they agreed or disagreed with the sociopolitical views of unfamiliar individuals. Behavioral tests of associative recognition revealed that participants remembered with high confidence viewpoints previously linked with judgments of strong agreement/disagreement. Neurally, the medial PFC mediated the interaction between high-confidence associative recognition memory and beliefs associated with strong agree/disagree judgments. In an effort to generalize this finding to well-established associative information, in the second study, we investigated associative recognition memory for real-world concepts. Object-scene pairs congruent or incongruent with a preexisting schema were presented to participants in a cued-recall paradigm. Behavioral tests of conceptual and perceptual recognition revealed memory enhancements arising from strong resonance between presented pairs and preexisting schemas. Neurally, the medial PFC tracked increases in visual recall of schema-congruent pairs whereas the MTL tracked increases in visual recall of schema-incongruent pairs. Additionally, ventral areas of the medial PFC tracked conceptual components of visual recall specifically for schema-congruent pairs. These findings are consistent with a recent theoretical proposal of medial PFC contributions to memory for schema-related content. Collectively, these studies provide evidence of a role for the medial PFC in associative recognition memory persisting for associative information deployed in our daily social interactions and for those associations formed over multiple learning episodes. Additionally, this set of findings advance our understanding of the cognitive contributions of the medial PFC beyond its canonical role in processes underlying social cognition.