VictorJuiz/thesis huggingface dataset:
Investigations Of The Determinants of Functional Outcomes In Schizophrenia: Cross-sectional And Longitudinal Examinations Of The Role Of Negative Symptoms
Keywords: Schizophrenia
Negative Symptoms
Motivation
Apathy
Cognition
Functional outcomes

Despite significant advances in the field, functional impairment continues to be a characteristic feature of schizophrenia. Negative symptoms, and in particular motivational deficits, along with cognitive dysfunction have consistently been linked with functional impairments in schizophrenia. However, most investigations of functional outcomes have focused on discrete symptoms, or alternatively on broad symptom domains. Further, recent findings have suggested that a lack of motivation may contribute to the cognitive impairment seen in schizophrenia. This series of investigations sought to: 1) advance our understanding of the determinants of cross- sectional and longitudinal community functioning in schizophrenia by examining the concurrent contribution of negative symptoms, cognition, and other important symptoms to longitudinal functioning in schizophrenia over one year; and 2) clarify the relationships between motivation, effort exerted during cognitive testing, and cognitive performance in schizophrenia. We hypothesized that: 1) motivational deficits would serve as the most important and stable determinant of community functioning, with cognition offering additional predictive value; and 2) motivational deficits would exhibit a differential relationship across various cognitive domains, with those exhibiting reduced effort during testing evincing more severe motivational deficits. Seventy stable adult outpatients with schizophrenia or schizoaffective disorder underwent clinical, cognitive, and functional evaluations at baseline, 6 months, and 12 months. Using stepwise and hierarchical regression analyses, motivational deficits emerged as the most predictive and reliable determinant of cross-sectional and longitudinal community functioning, accounting for up to 58% of the variance in functioning. Other symptom domains exhibited substantially less predictive value for functioning. Motivational deficits also exhibited a differential relationship across cognitive domains, with a particular relationship with verbal fluency. Further, effort during cognitive testing appeared to be related to both cognitive dysfunction and motivation, suggesting that the use of performance validity tests in schizophrenia may not be an appropriate index of mental effort. Overall, these findings highlight the central role motivational deficits play in determining outcomes in schizophrenia, as well as their impact on cognitive dysfunction in this illness. Importantly, in spite of advances in treatment, this work points to the essential need for interventions to address these motivational deficits if we hope to improve outcomes in schizophrenia.
Authoring Death: Mourning Masculinity in American Autobiography
Keywords: masculinity
disease
autobiography
death
gender
corporeality
body
Hemingway
Tennessee Williams
Roth
Schnabel

This dissertation investigates the anxiety surrounding identity and notions of selfhood in contemporary American life writing. Male corporeality is too often conflated with robust health, and treated as an afterthought in the analyses of gender and identity. My work addresses this critical lacuna by probing the “unhealthy” male bodies that permeate American autobiographies. I scrutinize the many instances in American life writing where the male subject experiences his own corporeality as diseased or dying. The autobiographical treatment of death and decay, this thesis argues, relieves the life writer from an individualistic relationship with his body, and contributes to the decomposition of the very boundaries that separate the self from the other. My work thus pivots on a paradox: even though the autobiographer’s corporeality frees him from isolating notions of singularity, the autobiographical “I” cannot help but be capricious and inconsistent, since his desire for freedom is so profoundly mired in convention. By exposing the different ways the autobiographical text manifests the writer’s failing corporeality—even when he struggles to conceal it—I look to challenge the myth of the self-made and invulnerable man of American autobiography. Through a reading of Ernest Hemingway’s A Moveable Feast (1964), Chapter One considers how silence and omission are sometimes the only ways traumatic memories can be represented. The second chapter examines the leaky and diseased bodies that permeate Tennessee Williams’s Memoirs (1975), connecting the playwright’s nausea with the gendered contradictions that undermine the coherence of “masculine” subjecthood. Chapter Three explores the “subterranean” presence of women in Roth’s The Facts (1989) and Patrimony (1991) that undermines the writer’s discrete self. I conclude my dissertation with a discussion of filmic life “writing,” and the political potential of “adapted autobiographies.” This chapter studies Julian Schnabel’s Diving Bell and the Butterfly (2007) as a form of “death writing,” and explores the ways the filmmaker transforms the corporeal boundaries that initially separate self and other into the connective tissue that links the many “I”s/eyes of the film.
Aspects de l'écriture du moi chez Loti et Leiris : problématique du moi et de l'autre dans La Mort de Philae et Journal 1922-1989
Keywords: Loti, Leiris, La Mort de Philae, Journal 1922-1989
écriture autobiographique, journal personnel/intime, récit de voyage,
l'altérité, l'énonciation, rapports texte-image
morphologie du moi diaristique, l'image textuelle, la prose poétique

Les écritures du moi et l’altérité sont deux champs d’études qui paraissent à première vue opposés. Cette thèse part du constat que la rencontre du moi et de l’autre favorise une interaction, voire une osmose entre ces deux entités. Nous examinons cette tension dialectique du sujet autobiographique tiraillé d’une part, entre son moi et l’autre et d’autre part, entre lui-même et ce moi devenu autre. Et ce, à travers deux récits problématisant cette question sur les plans narratif, discursif et iconique : La Mort de Philae de Loti et Journal 1922-1989 de Leiris. Malgré les affinités qui lient ces écrivains, leurs œuvres divergent a priori quant aux degrés d’implication du sujet d’énonciation au sein de ces textes autobiographiques. Si le narrateur lotien a tendance à l’extraversion, le sujet leirissien est porté à l’introspection. Cependant, l’expression du moi dans le journal de Leiris n’est guère dissociable de l’influence qu’exerce le regard d’autrui sur l’image que le diariste se fait de lui-même. En fait, le changement opéré chez les deux écrivains s’inscrit dans le temps quoique de manières différentes. Quant aux images insérées dans lesdites œuvres, elles sont majoritairement des photographies. Cependant, leur mode d’insertion dans le texte de Loti relève de l’illustration, pratique qui intervient après la création verbale de l’œuvre, alors que les images introduites dans le journal de Leiris ont été choisies par le diariste pendant le processus de la création. D’ailleurs, Loti se distingue par ses descriptions poétiques qui constituent des images textuelles rivalisant avec les images iconiques insérées par l’éditeur. Toutefois, ces images sélectionnées dans la collection iconographique léguée par Loti illustrent pertinemment son livre. Pour sa part, Leiris insère dans son journal des images dont la diversité est représentative de la nature de l’œuvre diaristique elle-même et dont la majorité trace obliquement le portrait du sujet diaristique. En bref, notre thèse vise à étudier les mécanismes textuels et visuels qui sous-tendent la construction d’une image de soi et de l’autre, tout en mettant l’accent sur les stratégies discursives mises en œuvre dans ce processus de découverte de soi, de l’autre et de soi à travers l’autre.
Guardians Entrapped: The Demise of the Turkish Armed Forces as a Veto-Player
Keywords: Civil-Military Relations
Europeanization
institutional change
Democratic Control of Armed Forces
Turkish Armed Forces
Justice and Development Party
Turkey

This study examines how and why Turkey's civil-military relations regime transformed since the soft coup of 28 February 1997. It argues that major changes in the international security structure -the renaissance of democratic control of armed forces, the change of US foreign policy in the Broader Middle East and the process of Europeanization- opened a window of opportunity for demilitarization in Turkey. The recognition of Turkey's EU membership candidacy at the Helsinki Summit of December 1999 and the required alignment of Turkey's civil-military relations with that of EU best practices were the most important external factors that altered Turkey's domestic political opportunity structure in favor of change. Voter re-alignment in the November 2002 elections, the emergence of a single-party government with a strong will to change the domestic balance of power in its own favor, and the domestic mobilization of opposition to the military mediated between the EU's external pressure and domestic change. The military, in turn, failed to veto reforms that targeted its own prerogatives as such an action would generate substantial cost to its ideational interests including loss of prestige, credibility, and legitimacy as a result of being perceived as obstructing Turkey's century-old Westernization-cum-modernization process. An analysis of the behavioral, attitudinal, and institutional dimensions of democratic control shows that in the post-Helsinki period Turkey has not attained democratic control of the armed forces, but instead has shifted from the tutelary regime category to the defective democratic control category. Regarding the implications of this institutional change for the trajectory of Turkey's democratization, the study does not provide as optimistic a view as those advanced by the country's liberal and Muslim intellectuals. By conceptually differentiating between civilianization and democratization, this study argues that although the Turkish regime has become substantially civilianized in the last decade - i.e., political power has shifted markedly into the hands of civilians- the extent of the regime's democratization failed to match this level of civilianization.
Romantic Authorship and the Failures of Familiarity
Keywords: Romanticism
Reception History
Lady Caroline Lamb
William Hazlitt
Charlotte Smith
Literary Annuals
familiarity

Focusing on familiarity in the late-eighteenth and early-nineteenth centuries, this dissertation examines how Romantic authors--especially those who published (semi-)autobiographical works--engaged both the complex legacy of sensibility and the rapidly changing literary marketplace. Exploring how and why authors' evocations of familiarity failed to encourage readers' and critics' sympathy brings to the fore how the desire to feel close to contemporary authors was haunted by anxieties about vulgarity and banality. I analyze the strategies that authors used to relate (semi-)autobiographical information in a critical climate concerned that literature was, in many ways, becoming all too personal. Assessing what Pierre Bourdieu terms 'the literary field' of the Romantic period, I demonstrate how fears about over-familiarity explicitly and implicitly shaped the content of Romantic texts and, just as important, their reading. My first chapter analyzes Charlotte Smith's Elegiac Sonnets. Smith's prefatory defences in Elegiac Sonnets offer one of the period's most detailed justifications of formulaic, familiar language, and I explore how Smith answered criticisms that her emotionally-repetitive works were insincere. My second chapter analyzes William Hazlitt's autobiographical work Liber Amoris in the context of the detailed theories of familiarity outlined in his essays and the moral philosopher Adam Smith's theories of sympathy. Examining Liber Amoris's representations of familiarity alongside Hazlitt's earlier theories of familiarity gives us a new perspective on both his essays and his most challenging work. Analyzing the negative reception of Lady Caroline Lamb's famous autobiographical novel Glenarvon, my third chapter demonstrates how notions of gender difference conditioned determinations of familiarity's proper limits. My final chapter argues that literary annuals sought to place readers on familiar terms with their famous editors and contributors by commercializing the culture of coterie manuscript exchange. I show that evocations of the type of familiarity associated with manuscript culture began to fail in the 1830s because the annuals became too common. Drawing on extensive archival research, this dissertation tracks the troubled reception histories of the works focusing each of its chapters. Overall, these case histories reveal familiarity and its failures to be key factors in the reception of literature in the Romantic period.
Just Do It! Self-Determination for Complex Minorities
Keywords: Self-Government
Métis
First Nation
Fransaskois
Minority Rights

This thesis explores how Indigenous and linguistic communities achieve self-determination without fixed cultural and territorial boundaries. An examination of the governance practices of Métis, Francophones and First Nations in Saskatchewan reveals that these communities use innovative membership and participation rules in lieu of territorial and cultural criteria to delineate the boundaries within which to exercise political power. These practices have allowed territorially dispersed communities to build institutions, adopt laws and deliver services through province-wide governance structures. In addition to providing an empirical basis to support non-territorial models of self-determination, this study offers a new approach to governance that challenges state-centric theories of minority rights by focusing on the transformative power communities generate through stories and actions.
The Role of Surfactant Protein D in Neutrophil Extracellular Traps-Mediated Innate Immunity
Keywords: Innate Immunity
Neutrophil
Neutrophil Extracellular Traps
Infection
Surfactant Protein D
Pulmonary

Neutrophils extracellular traps (NETs) efficiently trap and kill invading microbes, but also inflict damage to the host. However, the mechanisms and the host factors that regulate NETosis are not clearly understood. Surfactant protein D (SP-D) is a soluble innate immune molecule present on mucosal surfaces, and functions as a pattern-recognition molecule. For my doctoral research project, I hypothesized that SP-D augments neutrophil-mediated innate immune defense by regulating NETosis and also by enhancing the anti-microbial functions of NETs. There are two previously identified pathways for NETosis: NOX-dependent and NOX-independent pathways. The results show that the NOX-dependent pathway of NETosis requires the activation of Akt and JNK, which are downstream of ROS production by NOX, to suppress the pro-apoptotic pathway. Furthermore, SP-D redirects NETosis to apoptosis by suppressing JNK activation. SP-D does not, however, affect the activation of Akt, ERK or p38 kinases. Also, this suppression of NETosis by SP-D is dose dependent, and is subject to the availability of SP-D. The presence of other soluble ligands such as bacterial LPS attenuates the ability of SP-D to suppress NETosis. SP-D, thus, may act as a barometer to control the extent of NETosis/NETs required to combat infection while minimizing tissue damage. The NOX-independent pathway has also been described previously, but its mechanism remains poorly understood. This study shows that the NOX-independent pathway, shown by its insensitivity to the inhibition by DPI, is induced by the calcium ionophore, A23187. Moreover, the NOX-independent pathyway, unlike the NOX-dependent pathway, is mediated by the activation of the calcium activated small conductance potassium (SK) channel, and it requires intact mitochondrial potential. Also, Hepoxilin A3, a derivative of arachidonic acid, can induce both the NOX-dependent and -independent pathways. Experiments using mice show that the endotracheal instillation of LPS into the mouse airways results in NET release by the recruited neutrophils in the airways, in vivo. Once NETs are formed, SP-D simultaneously interacts with NET DNA and the carbohydrate targets, and enhances bacterial trapping by NETs. Collectively, the data show that SP-D regulates NETosis and also enhances the innate immune potential of NETs.
Molecular and Biophysical Targeting of Malignant Brain Tumours
Keywords: glioblastoma
medulloblastoma
nanotechnology
Aurora kinases
tumour biology
focused ultrasound

Primary malignant brain tumours are notoriously difficult to treat due to their infiltrative nature, unrelenting proliferative capacity, tumour heterogeneity, and the inability of novel drug or molecular targeted therapies to efficiently cross the blood-brain barrier (BBB). Using cell line and xenograft models of glioblastoma (GBM) and medulloblastoma we have studied the therapeutic potential of blocking the kinase activity of Aurora kinase B, a master regulator of multiple processes in mitosis. We demonstrate that the growth of intracranial xenografts of p53 mutant GBM or Myc amplified medulloblastoma can be impaired by Aurora B inhibition, while sparing normal neural tissue and thereby allowing prolongation of survival. Mechanism of action studies have further informed our in-vivo dosing strategies and indicate possible new synthetic lethal gene targets for Myc amplified medulloblastoma. Targeting biologically active macromolecules to achieve tumour control at the invasive margins, where recurrences are most often observed, may enhance the therapeutic efficacy of anti-mitotic agents. We developed a novel technology for the delivery and targeting of multi-functional nanoparticles to the invasive front of intra-axial tumours. Transient, safe, and reversible BBB disruption was achieved with MRI-guided transcranial focused ultrasound to deliver spherical gold nanoparticles to normal brain parenchyma or tumour margins. Furthermore, we characterized the interaction of multi-functional gold nanoparticles with glioblastoma cells using surface enhanced Raman scattering spectral microscopy, live fluorescence microscopy, electron microscopy, and in-vivo imaging. Lastly, we were able to demonstrate the targeted delivery of anti-epidermal growth factor antibody modified NIR-SERS capable silica encapsulated gold nanoparticles to regions of transcranial ultrasound mediated blood-brain barrier disruption. This serves as a stepping stone to future combination therapy in which mitotic inhibitors selected by genetic profiling of malignant brain tumours may be used in conjunction with MRI-guided trancranial focused ultrasound delivery of multifunctional nanoparticles targeting invasive and proliferating cells.
From “Moron” to Maladjusted”: Eugenics, Psychiatry and the Regulation of Women, Ontario, 1930s-1960s
Keywords: 0453

In the early 1900s, the eugenics movement spurred a number of major developments in Ontario, among them the committal of large numbers of women to the Ontario Hospital, Cobourg under diagnoses of mental defect. A tool of reproductive control, institutionalization was meant to inhibit “feebleminded” women’s procreative capacities. Despite the absence of enabling legislation, evidence suggests eugenic sterilizations also occurred in the province. Drawing on the detailed patient case files of women confined to the Cobourg facility from the mid1930s to mid1960s, this dissertation re-examines the history of eugenics in Ontario to demonstrate not only its profound impact in the decades prior to the Second World War, but also its enduring effects in the postwar era. To illustrate eugenics’ lingering impact, the study explores the interconnections between diagnoses linked to intellectual disabilities and emergent postwar psychiatric classifications of personality disorders to show how eugenics and psychiatric regulation were re-framed after the 1940s and applied to broader groups of women. Examining disability as both a category of analysis and a discursive construct, the dissertation argues that eugenicists re-scripted the notion of mentally ‘unfit’ into a concept of ‘maladjustment’ in the postwar years, and then applied it more broadly to justify and advance inequitable social relations across a range of social identities. Eugenics operated both materially and discursively as a mechanism through which particular configurations of gender, race, class, and sexuality, along with disability, were established and regulated. It was ultimately in and through early-twentieth-century eugenics that the ‘bio’ and ‘social’ collided, facilitating new notions of citizenship, modes of state governance, and the emergence of the modern bio-political state.
Bazooka and atypical Protein Kinase C regulate dynamic actomyosin networks during Drosophila amnioserosa apical constriction
Keywords: Cell biology
actin and myosin
Par complex
polarity
drosophila
morphogenesis
development
dorsal closure
amnioserosa

Cell shape changes drive tissue remodeling. Polarized activity of actin and myosin drive apical constriction, as seen for example in Drosophila embryonic amnioserosa cells during dorsal closure (DC). My first aim was to characterize interactions between apical actomyosin networks and the cell polarity regulators Bazooka (Baz, the Drosophila Par-3), Par-6, and atypical Protein Kinase C (aPKC) (the PAR complex) during Drosophila DC. I found that both actomyosin networks and the PAR complex are enriched at the apical surfaces of amnioserosa cells and that actomyosin contractility is driven by cyclical assembly and disassembly of actomyosin networks. The pulsatile actomyosin networks translocate across persistent apical surface PAR complex puncta. To assess whether the PAR complex interacts with actomyosin, I characterized myosin dynamics with PAR loss- and gain-of-function perturbations. Baz enhances, whereas Par6/aPKC inhibits actomyosin. These studies suggest that PAR proteins regulate pulsatile apical actomyosin networks mediating constriction of amnioserosa cells. My next aim was to characterize actomyosin networks during a shift in their dynamics. Amnioserosa constriction transitions from pulsatile to persistent from early to late DC. Since oscillatory networks result from delayed negative feedback, I examined whether such regulation exists in these actomyosin networks. The actomyosin inhibitor aPKC is recruited to the apical surface by actomyosin and, in turn, aPKC recruits Baz. To examine the significance of Baz – aPKC dynamic interactions, I ectopically stabilized their interactions. This served to inhibit the antagonism of actomyosin networks by aPKC, suggesting that Baz can act as a competitive inhibitor of aPKC. I found that interactions between Par-6 and Baz increase during DC, suggesting an increase in aPKC inhibition during DC progression. To examine whether decreased inhibition can tune oscillatory actomyosin networks, we collaborated with Qiming Wang and Dr. James Feng (University of British Columbia) to test this oscillation in silico. Computer modeling suggests that decreasing delayed negative feedback can transition actomyosin oscillations towards stabilized constriction. Together, these results demonstrate the requirement of Baz – aPKC interactions for their localization and for dynamic regulation of aPKC by a competitive inhibitor. Finally, my research reveals a regulatory circuit to tune actomyosin behaviour during development.