VictorJuiz/thesis huggingface dataset:
How Do We Know What is the Best Medicine? From Laughter to the Limits of Biomedical Knowledge
Keywords: philosophy of medicine
medical knowledge
epistemology
evidence-based medicine
story-based medicine
unorthodox medicine
placebo
anecdote
complexity
laughter

Medicine has been called a science, as well as an art or a craft, among other terms that express aspects of its practical nature. Medicine is not the abstract pursuit of knowledge. Medical researchers and clinical practitioners aim primarily to help people. As a first approximation then, given its practical focus on the person, the most important question in medicine is: what works? To answer that question, however, we need to understand how we know what works. What are the standards, methods and limits of medical knowledge? That is the central focus and subject of this inquiry: how we know what works in medicine. To explore medical knowledge and its limits, this thesis examines the common notion that laughter is the best medicine. Focusing on laughter provides a robust case study of how we know what works in medicine; it also, in part, reveals the thin, perhaps even non-existent, distinction in medicine between empirically-grounded knowledge and intuition. As there is no single academic discipline devoted to laughter in medicine, the first chapter situates and charts the course of this unusual project and explains why inquiry into laughter in medicine matters. In the following chapters, we encounter claims from distinguished sources that laughter and humor are the best medicine. These claims are examined from a variety of perspectives including not only the orthodox view of evidence-based medicine, but also from narrative, evolutionary and complexity views of medicine. The rarely explored serious negative side of laughter is also examined. No view provides a firm foundation for belief in laughter medicine. A general conclusion from this inquiry is that none of the approaches effectively tame the complexity of medical phenomena; indeed each starkly reveals a greater complexity than found at first glance. A narrower conclusion is that providing a basis for claims about laughter in medicine poses its own specific challenges. A third conclusion is that, as things stand, none of the existing approaches seems up to the task of determining whether something such as laughter is the best medicine.
The Synthetic Utility of Allylic Trifluoroborate Salts: Reactions of Ketones and Indoles using Montmorillonite, Indium and Lewis Acid
Keywords: Trifluroborates
Indium

Chapter 1 briefly covers the development and utility of allylboron reagents in organic synthesis. Transition models proposed for addition to carbonyl groups and imines are discussed and selected examples of the utility of these reagents to the synthesis of complex molecule covered. In chapter 2 the allylation and crotylation of ketones using allyl- and crotyltrifluoroborates and montmorillonite K-10 are described. The method is scalable and utilizes a reliable catalyst with high functional group tolerance. A conventional work-up is not required for further purification, since the boric acid by-product of the reagent remains trapped in the cavity of the K-10. The method is quite robust and provides an operationally straightforward procedure for the allylation of a range of ketones using the air and moisture stable potassium allyltrifluoroborate. In Chapter 3, the first indium-mediated highly chemo- and diastereoselective allylation of α,β- epoxyketones using allyltrifluoroborate was developed. It was shown in the case of simple ketone substrates, the loading of indium can be reduced to catalytic quantities without a diminishment in yield. The stereochemical nature of the epoxy homoallylic alcohols was ii unequivocally established through Payne rearrangement. Mechanistic studies indicate that the reaction proceeds through an allylindium species; although the nature of the indium species was not fully elucidated. Finally, in chapter 4 regioselective allylation and diastereoselective crotylation of various indoles are discussed using BF3·Et2O as a promoter. It was shown that the electronic effects of the substituents on the indole ring had little effect on the outcome of the reaction. However, steric factors were more influential on the yields and reactivity of the substrates. Stereospecific addition of the E- and Z-crotyltrifluoroborates could also be achieved under the reaction conditions, providing the corresponding anti and syn products, respectively.
Sovereignty, the State of Exception and Counter-culture: Toward a Transnational Critique of State Power in 20th and 21st Century Anglophone Fiction
Keywords: Contemporary Fiction
State Power

This dissertation examines the way in which contemporary fiction is highly concerned with sovereign power and the state of exception, as described by Giorgio Agamben in State of Exception. While in the last decade Agamben’s work has provided a new locus for the study of state power, I argue that disquiet over the reach of state power into everyday life has existed in fiction since at least the 1980s. Reading James Joyce, Margaret Atwood, Salman Rushdie, Kazuo Ishiguro, Don DeLillo and William Gibson alongside Agamben’s theories of state power and the state of exception sheds light on fictional representations of modern developments in power, the state and the corporate world. Through close analysis of philosophical and fictional texts, I draw out the complex politics of contemporary novelists and underscore the importance of both fictional and theoretical representations of contemporary political power. The dissertation consists of four chapters. Chapter One examines what I contend is new about Agamben’s work on power which is that, unlike Foucault, he accounts for the kind of power that may produce a concentration camp, and examines the place of this power at the heart of contemporary politics. Through analyses of James Joyce’s Ulysses and Margaret Atwood’s The Handmaid’s Tale¬ I examine the ways in which Agamben’s theories move us towards a clearer understanding of representations of state power in contemporary fiction. In Chapter Two I discuss sovereign power in Rushdie’s postcolonial India and England, and I describe how the national identities of citizens of, or migrants to, those countries take shape in a society whose very fabric is affected by power that is frequently unrestricted by the law or by democracy. In Chapter Three I consider the “aftermath” of sovereign power in the work of Kazuo Ishiguro. In particular, I argue that he represents the extent to which sovereign power conditions culture and society, and how contemporary art and intellectual thought have failed as effective countermeasures to the power that may produce the state of exception. In the final Chapter, I consider the ways in which violence constitutes a form of resistance to sovereign power in the novels of William Gibson and Don DeLillo’s White Noise; further, I assess Gibson’s new narratives of space as potential counters to the state of exception. While Agamben’s work provides an opportunity to highlight the extent to which sovereign power and the state of exception are at work in contemporary novels, I contend that fiction represents these phenomena and their significance more completely than Agamben is able to. The use of figurative and experimental language and narrative techniques is highly effective in conveying the nuances and the experiential realities of state power, thereby moving the reader’s understanding beyond the abstract and the conceptual.
The Chisel and the Lens: Picasso, Brassaï, and the Photography of Sculptures: 1933–1948
Keywords: Pablo Picasso
Brassaï
Photography of Sculptures

While Pablo Picasso internationally exhibited his paintings, he chose to expose his sculptures only through photographs. Picasso’s commitment to the photographic display of his sculpture comes to light through his fifteen year collaboration with Brassaï, the first photographer to collaborate regularly with the artist and the only one to engage thoroughly with Picasso’s sculptural oeuvre. This collaboration culminated in hundreds of images published largely on two occasions – a photo essay published in the avant-garde Journal Minotaure in 1933 and a catalogue covering almost fifty years of Picasso’s sculptural production published in French in 1948 and in English in 1949. These photographs, as well as unpublished prints, uncropped versions of the published photographs, and the contact sheets Brassaï assembled as he was photographing Picasso’s oeuvre are contextualized in light of contemporary theories regarding the presentation, representation, and dissemination of art. This case study sheds light on the way in which strategies of display shape art’s meaning, as well as the artist’s public image, reputation, and legacy.
American Impotence: Narratives of National Manhood in Postwar U.S. Literature
Keywords: National Manhood
Politics
Masculinity
Postwar
Novel
Ralph Ellison
John Updike
Robert Coover
Bret Easton Ellis
Joan Didion

“American Impotence” investigates a continuity between literary representations of masculinity and considerations of national identity in the works of five postwar novelists. In particular, I illustrate the manner in which Ralph Ellison’s Invisible Man, John Updike’s Couples, Robert Coover’s The Public Burning, Joan Didion’s Democracy and The Last Thing He Wanted, and Bret Easton Ellis’s American Psycho challenge the patterns of daily life through which a single figure is imagined to be the essential agent of American polity: namely, the self-made individualist, characterized by manly virtues like dominance, aggression, ambition, mastery, vitality, and virility. More specifically, this project examines the manner in which the iconicity of men helps sustain a narrative of “imperilled masculinity” that at once privileges an impossible identity, situated in the representative nucleus of postwar democracy, and forecloses other modalities of political life. Observing the full meaning of the word “potency,” I elucidate the interrelationships between narrative forms, masculine norms, and democratic practice. Ellison’s work ties the maturation of African American boys to the impossibility of full participation in civic life, for instance, while in Updike’s Couples the contradictions of virile manhood manifest in the form of a fatalism that threatens to undo the carefully cultivated social boundaries of early sixties bohemianism; in a variety of ways, The Public Burning and American Psycho represent the iconic nature of masculinity as a psychic threat to those men closest to it, while Didion’s female protagonists find themselves flirting with the promises of a secret agency linked to imperial adventures in Southeast Asia and Central America. In the cultural context of the Cold War, these novelists demonstrate how intensified participation in national fantasies of potency and virility is inevitably disempowering; as an alternative, this dissertation seeks to consider impotence as dissensus detached from the mandates of hegemonic masculinity.
The Role of Chloride Channels in Regulation of Pulmonary Artery Smooth Muscle Cell Proliferation
Keywords: Pulmonary arterial hypertension
Pulmonary artery smooth muscle cell
Proliferation
Chloride channel
Cell volume
Membrane potential
RNA interference
Lentivirus
CLC channels
CLC-3
DIDS
DCPIB

Pulmonary arterial hypertension (PAH) is a rare but fatal disease with an annual mortality rate of 15% despite current therapies. Uncontrolled proliferation of pulmonary artery smooth muscle cells (PASMCs) results in adverse vascular remodeling contributing to PAH. Understanding the mechanisms of PASMC proliferation may identify new targets for treatment. Chloride currents/channels (ICl) are expressed in PASMCs and their roles in proliferation have been suggested based on their importance in resting membrane potential and cell volume regulation. The present study explored the role of ICl in proliferation in rat and human PASMCs. We found that either nonspecific ICl inhibitors (DIDS or NPPB) or a putative specific blocker of swelling-activated ICl (ICl,swell) reduced proliferation of PASMCs cultured in serum-containing media. Patch-clamp studies showed that proliferating PASMCs had increased baseline ICl and ICl,swell in association with depolarized membrane potentials. Quantitative real-time RT-PCR studies identified expressions of CLC-3, a candidate gene of ICl,swell, and several other CLC genes in proliferating PASMCs. While selective knockdown of CLC-3 with lentiviral shRNA reduced PASMC proliferation, it had no effect on ICl,swell. These findings are consistent with the conclusion that ICl regulate proliferation of PASMCs and suggest that selective ICl inhibition may be useful in treating pulmonary arterial hypertension.
The Characterization of Nemadipine and Migrazole as Small Molecule Tools for Use in the Nematode Caenorhabditis elegans
Keywords: small molecules
C. elegans
nemadipine
migrazole

Small molecules are powerful reagents for biological investigation. They provide an alternative to genetic perturbation and may offer more control over a target’s activity. C. elegans has recently gained prominence as a platform to discover new chemical tools. Through large-scale screens for compounds that induce phenotypes consistent with the disruption of conserved pathways, we identified two previously uncharacterized molecules of interest that we named nemadipine and migrazole. Here, I describe my efforts to understand their mechanism of action. Nemadipine is structurally analogous to 1,4-dihydropyridines (DHPs), which target the Cav1 calcium channel and are used clinically to lower blood pressure. Phenotypic and genetic evidence suggest that nemadipine targets the worm Cav1 channel, EGL-19. To identify the target of nemadipine in an unbiased manner, I performed a forward genetic screen for mutants resistant to its effects. The majority of the mutants from my screen had polymorphisms in EGL-19, providing additional evidence that it is the target of nemadipine. I also found that nemadipine is the only DHP that robustly elicits phenotypes in the worm. Therefore, I used this unique chemical to investigate the in vivo interactions between DHPs and the Cav1 channel. I identified residues in EGL-19 important for DHP-sensitivity in worms and showed that some of these residues are also important for mammalian DHP-interaction. Other labs have since exploited nemadipine’s in vivo properties to demonstrate new biological insights for EGL-19. Chemical genetic analyses indicated that migrazole disrupts multiple signal transduction pathways. This, together with experiments that I performed in yeast, suggests that migrazole may affect multiple pathways by perturbation of protein transport. To identify migrazole’s target, I performed a forward genetic screen for mutants resistant to migrazole’s effects. However, I was unable to identify the target of migrazole through analysis of the mutants I isolated. This result illustrates that while forward genetic screens can be very successful for target identification, their effectiveness is likely dependent on the nature of the compound-target interaction. My work shows that all aspects of developing a small molecule into a tool for biological analysis, from its discovery to its characterization, can be accomplished using C. elegans.
Brechtian Cinemas: Montage and Theatricality in Jean-Marie Straub and Danièle Huillet, Peter Watkins and Lars von Trier
Keywords: Bertolt Brecht
Jean-Marie Straub
Danièle Huillet
Peter Watkins
theatricality
montage

In this dissertation I investigate the stylistic shift in the cinema of selected filmmakers whose work is rooted in Bertolt Brecht’s dramatic theory: Jean-Marie Straub and Danièle Huillet, Peter Watkins, and Lars von Trier. Through the work of these filmmakers, I trace the ongoing change in the cinematic applications of the theory. By and large, the change consists of a lessening of the role of montage – a technique that occupies a paramount place in Brecht’s theatrical and filmic practice – in favour of the objects within the camera’s field of view and the sounds within the microphone’s range. Since the ultimate effect for which the Brechtian filmmaker aims is that of Verfremdung, theatrical stylisation – itself estranging within the context of cinema – appears as a natural corollary of the described shift in emphasis. I also suggest a causal connection between the aforementioned shift and the growing self-consciousness of the style employed by meainstream cinemas (of which Hollywood is the foremost representative), which often manifests itself in the use of unorthodox editing patterns. Accordingly, I propose that we can attribute the contemporary Brechtian filmmaker’s growing reliance on mise-en-scène elements as a source of Verfremdung largely to the major film industries’ adoption of montage and other specifically cinematic codes that make a film’s style overt. Not surprisingly, perhaps, the Brechtian filmmaker – whose political stance is inherently antagonistic to that exemplified by most mainstream cinema, reacts to the normalisation of foregrounded film style by employing the opposite strategy.
Bridging the Genomics Gap: The role of Large-scale Genotyping Projects in the Developing World and the Importance of Genomic Sovereignty
Keywords: genomics
sovereignty
science & technology
innovation
qualitative
case study

In recent years, there have been several proposals for large-scale human genotyping projects in the developing world. The dissertation presented here explores the motivations, opportunities and challenges of initiating locally led, large-scale genotyping projects documenting human genomic variation in the developing world. I analyze two case studies: the Indian Genome Variation Consortium in India and the University of Cape Town, Department of Human Genetics and the African Genomics Education Initiative in South Africa. These case studies, together with similar projects in Mexico and Thailand provide compelling reasons for pursuing these projects: the potential to address local health needs and reduce health care costs; the opportunity to stimulate economic development through investments in genomic sciences, and the availability of unique population resources. In an effort to capture the value of these investments and promote an equal stake in international collaborations, Mexico and India have developed guidelines and laws to protect local human genetic material as a sovereign resource, referred to here as ‘genomic sovereignty’. Critics have suggested that it can impede international collaborations and reduce access to external funding. I provide an in depth analysis of genomic sovereignty and how it may contribute to each country’s aim of achieving health equity through investments in genomics, its relation to heritage and patrimony, and its potential limitations. The debate is critical, as the knowledge generated from large-scale human genomic research will need to be interpreted in larger international collaborative efforts before it can lead to health benefits. Qualitative case study methodology is employed and the primary data source consists of interviews conducted with key informants. The research described here provides a source of empirical description and analysis that is informing the framing of policies, principles and practices on how research infrastructure and capacity are being established for human genomic sciences in developing countries.
Nineteen Thirty-four: Generic Hybridity and the Search for a Democratic Aesthetic
Keywords: 1934
Democracy
Generic Hybridity

This dissertation poses a fundamental question: why does a concern about the value of literary writing emerge during a felt crisis in public speech, especially in times of war? My focus is 1934, the year that Hitler became Führer and Socialist Realism was formulated in the USSR. In this year, Mikhail Bakhtin and Erich Auerbach developed the foundations of their narrative theory, while Virginia Woolf, T. S. Eliot, and Wyndham Lewis embarked on new ventures in genre. Despite their differences, I argue, these writers all sought to challenge the linguistic basis of political power by developing new forms that engage readers in independent, active ways. Woolf, Eliot, and Lewis responded to totalitarianism with experiments in generic hybridity, believing that inter-generic dialogue could promote social dialogue and democratic modes of thought. My introduction analyses the political and aesthetic implications of German and Soviet propaganda in 1934. Chapter 1 establishes a theoretical frame through two works written in exile from these totalitarian regimes. Bakhtin’s “Discourse in the Novel” and Auerbach’s Mimesis both posit the centrality of genre to political freedom, but Bakhtin’s binary of monologic poetry and dialogic prose contrasts with Auerbach’s arguments for the political potential of mixed forms. Chapter 2 shows how similar concerns about pluralist voicing inform debates concerning the “death of poetry” in England; nonetheless, I conclude that the political poetry of Thirties Poets often privileged ideology over dialogism. Three chapters then explore the emergence of hybrid genres in Woolf, Eliot, and Lewis. I argue that Woolf’s unpublished “Ode to Cutbush” is a prose-poetic hybrid that employs poetic rhythm and free indirect discourse to instill democratic values of empathy and tolerance; that Eliot’s first completed play, The Rock, invokes the ideological complexities and unresolved political contradictions of his journalism and editorial practice to incite the audience’s active collaboration; and that Lewis’s novelistic poem One-Way Song attempts to escape the increasingly monologic voice of his political writings and return to the polyphonic style and polyvalent thinking of his earlier work. My conclusion demonstrates these writers’ continuing commitment to the democratic potential of generic hybridity during World War II.
Disambiguating Rebirth: A Socio-rhetorical Exploration of Rebirth Language in 1 Peter
Keywords: 1 Peter
rebirth
socio-rhetorical

Rebirth language has traditionally been associated with the initiation rite of baptism and relegated to discussions within this limited framework. Analyses of 1 Peter—where rebirth language is particularly dominant—have focussed almost exclusively on a baptismal framework for understanding this language. However, a detailed reading of the letter does not reveal any association between rebirth and Christian rites of initiation. Whatever action, activity or idea triggered the use of this language, its role in the letter has never been adequately explored. This study employs socio-rhetorical analysis to examine the role of rebirth language within the letter of 1 Peter and within its larger cultural and textual context. Rebirth language is employed in the key opening section of the letter and, within the framework of familial language, serves as a central distinctive of the letter’s recipient-focussed argument. As part of the familial metaphor, rebirth highlights the readers’ identity as children whose πατήρ (“father”) is God. A comprehensive analysis of all other extant (first century) texts employing rebirth language, reveals that, while 1 Peter’s use of such language shares some points of contact with other expressions of rebirth, the meaning of rebirth in 1 Peter is not directly tied to any related language. More likely, 1 Peter contains cultural allusions to the developing idea of rebirth that is also shared—in different ways—with other extant materials. No other source, however, contains the same usage and implied meaning of rebirth language as 1 Peter. Instead, 1 Peter’s author, building upon the powerful father-child analogy, intends to shape his readers’ self-perceptions using this language to provide a sense of identity without encouraging extensive alienation from the larger society. 1 Peter’s use of rebirth language builds upon and intensifies the cultural familial metaphor in order to help firmly establish the recipients’ Christian identity in the midst of their associations and interactions within their social context.