VictorJuiz/thesis huggingface dataset:
Vice and Self-examination in the Christian Desert: An Intellectual Historical Reading of Evagrius Ponticus
Keywords: Evagrius Ponticus
moral psychology

This thesis offers an analysis of the vice tradition of the fourth-century monk Evagrius Ponticus. While Evagrius, like others before him, understands that virtue and vice have an affective component, and that these affections are reactions to mental images, for Evagrius these images are veridically thinner than what we find in earlier discussions of passion in ancient philosophy. As a result, vice is less a matter of false reasoning and false perception than it is a matter of the excessive dwelling on representations connected with events of one’s personal history, to the point that the passions aroused at the time of those events become globalized dispositions. Evagrius’s concern with how memories lead us to dwell on these “bad thoughts” proves to be point of contact with psychoanaly which many modern authors, including Michel Foucault, have detected; yet a close analysis of what Evagrius takes to be involved in self-examination reveals that Foucault’s account of the “technologies of the self” fails to take into account Evagrius’s interest in the distinction between the endowed self, that self which is examined, and the ideal self, the goal of the ascetic activity.
Preventing Suicides in the Toronto Subway System: A Program Evaluation
Keywords: suicide prevention
program evaluation

Despite the wealth of information on suicide prevention issues and the widespread implementation of suicide prevention strategies, program evaluation efforts have been limited. Lack of sound program evaluation remains one of the most significant barriers to identification and implementation of effective intervention and prevention strategies. The purpose of this study was two-fold: to conduct a summative evaluation of the gatekeeper suicide prevention program implemented at the Toronto Transit Commission, and to concomitantly, appraise the efficacy and effectiveness of the Kirkpatrick evaluation model as an analytical framework to guide suicide prevention program evaluations. The study used a two-phase, sequential mixed-method approach of converging quantitative and qualitative methodologies. The quantitative study employed a repeated measures design and examined the immediate and long-term effects of the gatekeeper program on attitudes, knowledge, intervention abilities. The qualitative study consisted of semi-structured interviews and explored participants’ effective and utility reactions to the gatekeeper training program. The results of this study indicated safeTALK and suicideAWARE training programs increased participants’ knowledge of suicide and suicidal behaviour, enhanced positive attitudes toward the suicidal individual, suicide intervention, and improved intervention skills. The empirical findings from this study support the premise that the Kirkpatrick evaluation model could be adapted for use in gatekeeper program evaluations. The model provides a highly relevant, well-rounded, rigorous approach to suicide prevention program evaluations.
Function and Regulation of Septins During Mammalian Cell Division
Keywords: cytokinesis
septin
phosphorylation
SEPT9

Septins are a family of GTP-binding proteins implicated in mammalian cell division. Since these proteins form heterologous complexes and filaments in interphase cells, it has been assumed that depletion of any or all septins in a given cell type will give rise to the same phenotype. I demonstrate that while all septins expressed in HeLa cells localize to the cleavage furrow and midbody during cytokinesis, and co-immunoprecipitate throughout cell division, they do not all have identical roles during this process. Specific depletion of SEPT2 or SEPT11 caused defects in the early stages of cytokinesis, ultimately resulting in binucleation. Similar results were observed upon simultaneous depletion of all septins. In sharp contrast, SEPT9 was dispensable for the early stages of cell division, but was critical for the final separation of daughter cells. I demonstrate that SEPT9 mediates the localization of the vesicle-tethering exocyst complex to the midbody. Immunofluorescence microscopy suggests that SEPT9 may act to compartmentalize the exocyst at the site of abscission, analogous to the role performed by septins in Saccharomyces cerevisiae. I provide evidence that the N-terminal region of SEPT9, which is absent from the shorter SEPT9 isoforms, plays an important role in abscission. I describe a long-anticipated link between a mammalian septin and the cell cycle machinery by showing that the N-terminal region of SEPT9 is phosphorylated at threonine 24 upon mitotic entry by cyclin-dependent kinase 1. This creates a binding site for the WW domain of the peptidyl-prolyl isomerase Pin1. I provide evidence that Pin1 induces a conformational change in the N-terminal region of SEPT9 that is important for the completion of cytokinesis. I propose that mitotic regulation of SEPT9 by Cdk1 and Pin1 regulates an interaction between SEPT9 and an unidentified protein that is critical for abscission.
The Transgressive Stage: The Culture of Public Entertainment in Late Victorian Toronto
Keywords: public entertainment
commercial amusements
gender
race
class
political history
advertising
circus
J. W. Bengough
Blackface Minstrelsy
Sarah Bernhardt in Canada
Oscar Wilde in Canada
aesthetic movement
theatre
cultural history
Victorian Toronto
Canadian History
Antisemitism

“The Transgressive Stage: The Culture of Public Entertainment in Late Victorian Toronto,” argues that public entertainment was one of the most important sites for the negotiation of identities in late Victorian Toronto. From the vantage point of the twenty-first century, where theatre is strictly highbrow, it is difficult to appreciate the centrality of public entertainment to everyday life in the nineteenth century. Simply put, the Victorian imagination was populated by melodrama and minstrelsy, Shakespeare and circuses. Studying the responses to these entertainments, greatly expands our understanding of Victorian culture. The central argument of this dissertation is that public entertainment spilled over the threshold of the playhouse and circus tent to influence the wider world. In so doing, it radically altered the urban streetscape, interacted with political ideology, promoted trends in consumption, as well as exposed audiences to new intellectual currents about art and beauty. Specifically, this study examines the moral panic surrounding indecent theatrical advertisements; the use by political playwrights of tropes from public entertainment as a vehicle for political satire; the role of the stage in providing an outlet for Toronto’s racial curiosity; the centrality of commercial amusements in defining the boundaries of gender; and, finally, the importance of the theatre—particularly through the Aesthetic Movement—in attempts to control the city’s working class. When Torontonians took in a play, they were also exposing themselves to one of the most significant transnational forces of the nineteenth century. British and American shows, which made up the bulk of what was on offer in the city, brought with them British and American perspectives. The latest plays from London and New York made their way to the city within months, and sometimes weeks, of their first production. These entertainments introduced audiences to the latest thoughts, fashion, slang and trends. They also confronted playgoers with issues that might, on the surface seem foreign and irrelevant. Nevertheless, they quickly adapted to the environment north of the border. Public entertainment in Toronto came to embody a hybridized culture with a promiscuous co-mingling of high and low and of British and American influences.
Communication and the Construction of the Ideal in the West
Keywords: utopian literature
utopian thought
communication change
ideal society
symbolic thought
literacy
Plato
Thomas More
St.Augustine
Francois Rabelais
Francis Bacon

This dissertation examines the conceptualization of the ideal society in Western culture in relation to changes in communication modes. The utopian discourse is defined by a concern with the relationship between language and reality. I explore this concern as a reflection of the theoretical disposition invited by changes in communication modes, which are perceived as crises of representation. Plato and Thomas More’s enlightened communities in the Republic and Utopia reflect comparable idealistic perspectives on education. In my view, this optimism stems from the social reality of growing literacies with the advent of the alphabet and printing, respectively. I contend that these writers are animated by an ethical impulse to teach their readers that language is representation. From the vantage point of this knowledge, each individual may employ language symbolically in order to create and perpetuate a moral and spiritual mode of thought. I argue that the discourse of the ideal is the symbolic expression of humanity’s engagement with death, the ultimate existential concern made acute by the aspect of historical discontinuity in the crisis of representation. Plato and More exhibit comparable efforts to open to their readers the superior space of critical reflexivity which they themselves inhabit. From this conceptual, pre-representational space of conscious choice, language is subjected to achieving spiritual progress. I introduce the concept of post-utopia, which describes a pragmatic moment when the relationship between author and the ideal society is brought into the foreground and reinforced as a way of addressing concerns with textual authority. I examine these developments in Augustine’s De Civitate Dei, François Rabelais’s episode of the Abbaye de Thélème in Gargantua, and Francis Bacon’s New Atlantis. These authors draw on the ideologies of representation inherent in utopian discourse, and position the authorial figure as link between scriptural teleology and history, ensuring spiritual and societal betterment in the textual cultures of late antiquity and early modernity. The figure of the author emerges as a symbol of history and of man’s ability to assume the limits of the mind and of language.
Facilitating Clinical Trials of Parenteral Lipid Strategies for the Prevention of Intestinal Failure Associated Liver Disease (IFALD) in Infants
Keywords: Intestinal Failure
Clinical Trials
Parenteral Nutrition
Intestinal Failure Associated Liver Disease
Omega-3 fatty acids
Bayesian Statistics

Objective: The objective of this thesis was to facilitate clinical trials of the optimal lipid based approach (e.g.: omega-3 containing lipid emulsions or minimization of conventional lipid) for the prevention of Intestinal Failure Associated Liver Disease (IFALD). This was achieved through 3 related projects. Project 1: The first project examined the risk of advanced IFALD associated with exposure to conventional intravenous lipid in a logistic regression model. The study demonstrated that each day of conventional lipid (> 2.5 g/kg/day) was associated with a significant increase in the risk of advanced IFALD [Odds Ratio: 1.04 95% CI: 1.003 – 1.06]. Project 2: The second project surveyed experts in Intestinal Failure regarding their beliefs of the efficacy of lipid minimization and lipid emulsions containing omega-3 fatty acids relative to conventional emulsions. The goal of the project was to develop prior distributions of the treatment response for these therapies that can be used in Bayesian analyses of clinical trials. Our results demonstrated consistent expert opinion that the novel lipid based approaches are superior to conventional therapy. Estimates of the treatment effect were similar for the two approaches (median elicited treatment response, relative to conventional lipid, was a relative risk of 0.53 for omega-3 lipid and 0.45 for lipid minimization). Project 3: The final project was a pilot randomized controlled trial of an omega-3 emulsion. The study demonstrated that the randomized design is a feasible strategy for evaluating lipid based approaches for the prevention of IFALD. A Bayesian preliminary assessment of the results of the trial, suggests a high likelihood that the trial will demonstrate a difference between the conventional and omega-3 emulsion evaluated in the trial. However, since the analysis was blinded, the direction of the difference is not known. Conclusion: This thesis will contribute to the design and analysis of high quality and feasible randomized trials that will allow investigators to address the optimal lipid based approach to the management of IFALD.
Modeling Multi-factor Financial Derivatives by a Partial Differential Equation Approach with Efficient Implementation on Graphics Processing Units
Keywords: multi-currency swaps
multi-currency options
Power Reverse-Dual Currency
PRDC
Partial Differential Equation
PDE
Alternating Direction Implicit
ADI
Graphics Processing Units
GPU
parallel computing
finite difference

This thesis develops efficient modeling frameworks via a Partial Differential Equation (PDE) approach for multi-factor financial derivatives, with emphasis on three-factor models, and studies highly efficient implementations of the numerical methods on novel high-performance computer architectures, with particular focus on Graphics Processing Units (GPUs) and multi-GPU platforms/clusters of GPUs. Two important classes of multi-factor financial instruments are considered: cross-currency/foreign exchange (FX) interest rate derivatives and multi-asset options. For cross-currency interest rate derivatives, the focus of the thesis is on Power Reverse Dual Currency (PRDC) swaps with three of the most popular exotic features, namely Bermudan cancelability, knockout, and FX Target Redemption. The modeling of PRDC swaps using one-factor Gaussian models for the domestic and foreign interest short rates, and a one-factor skew model for the spot FX rate results in a time-dependent parabolic PDE in three space dimensions. Our proposed PDE pricing framework is based on partitioning the pricing problem into several independent pricing subproblems over each time period of the swap's tenor structure, with possible communication at the end of the time period. Each of these subproblems requires a solution of the model PDE. We then develop a highly efficient GPU-based parallelization of the Alternating Direction Implicit (ADI) timestepping methods for solving the model PDE. To further handle the substantially increased computational requirements due to the exotic features, we extend the pricing procedures to multi-GPU platforms/clusters of GPUs to solve each of these independent subproblems on a separate GPU. Numerical results indicate that the proposed GPU-based parallel numerical methods are highly efficient and provide significant increase in performance over CPU-based methods when pricing PRDC swaps. An analysis of the impact of the FX volatility skew on the price of PRDC swaps is provided. In the second part of the thesis, we develop efficient pricing algorithms for multi-asset options under the Black-Scholes-Merton framework, with strong emphasis on multi-asset American options. Our proposed pricing approach is built upon a combination of (i) a discrete penalty approach for the linear complementarity problem arising due to the free boundary and (ii) a GPU-based parallel ADI Approximate Factorization technique for the solution of the linear algebraic system arising from each penalty iteration. A timestep size selector implemented efficiently on GPUs is used to further increase the efficiency of the methods. We demonstrate the efficiency and accuracy of the proposed GPU-based parallel numerical methods by pricing American options written on three assets.
Promyelocytic Leukemia Nuclear Bodies: A Meeting Place For Genomic Loci
Keywords: chromatin organization
nuclear structure and function

The nucleus is a highly compartmentalized organelle where specific cellular activities are confined to discrete domains. One such domain is the promyelocytic leukemia nuclear body (PML NB). PML NBs are protein-based structures that make numerous contacts with neighboring chromatin domains. To elucidate the function of PML NBs, research has been focused on identifying the protein complement of PML NBs. More than 60 proteins have been shown to localize to PML NBs, implicating the bodies in numerous cellular activities such as transcription regulation, apoptosis, tumor suppression, and the antiviral response. This approach has not yielded a general model for PML NB function. Instead I have chosen to focus on the chromatin contacts made with PML NBs. Using live-cell microscopy, my observations support the hypothesis that changes in chromatin topology affect the structural integrity of PML NBs. Moreover, I have developed a technique, called immunoTRAP, which allows for the extraction of chromatin specifically associated with PML NBs. Analysis of these chromatin associations reveal that specific genes associate with PML NBs and these associations are cell type specific. Therefore, PML NBs make specific contacts with neighboring chromatin domains and these contacts are integral to PML NB morphology. Thus making PML NBs a meeting place for a specific set of genomic loci.
Development of Microfluidic Devices for Drug Delivery and Cellular Biophysics
Keywords: Microfluidics
Controlled Drug Delivery
Cellular Biophysics
Single-Cell Analysis
Diabetes
Cancer

Recent advances in micro technologies have equipped researches with novel tools for interacting with biological molecules and cells. This thesis focuses on the design, fabrication and application of microfluidic platforms for stimuli-responsive drug delivery and the electromechanical characterization of single cells. Stimuli-responsive hydrogels are promising materials for controlled drug delivery due to their ability to respond to changes in local environmental conditions. In particular, nanohydrogel particles have been a topic of considerable interest due to their rapid response times compared to micro and macro-scale counterparts. Owing to their small size and thus low drug-loading capacity, these materials are unsuitable for prolonged drug delivery. To address this issue, stimuli-responsive implantable drug delivery micro devices by integrating microfabricated drug reservoirs with smart nano-hydrogel particles embedded composite membranes have been proposed. In one proposed glucose-responsive micro device, crosslinked glucose oxidase enables the oxidation of glucose into gluconic acid, producing a microenvironment with lower pH values to modulate the pH-responsive nanoparticles. In vitro glucose-responsive drug release profiles were characterized and normoglycemic glucose levels in diabetic rats with device implantation were also recorded. The biophysical properties of single cells have recently been demonstrated as an important indicator of disease diagnosis. Existing technologies are capable of characterizing single parameter either electrical or mechanical rapidly, but not both, which could only collect limited information for cell status evaluation. To address this issue, two microfluidic platforms capable of simultaneously characterizing both the electrical and mechanical properties of single cells based on electrodeformation and integrated impedance spectroscopy with micropipette aspiration have been proposed. In one proposed microfluidic device, a negative pressure was used to suck cells continuously through the aspiration channel with impedance profiles measured. By interpreting impedance profiles, transit time and impedance amplitude ratio can be quantified as cellular mechanical and electrical property indicators. Neural network based cell classification was conducted, demonstrating that two biophysical parameters could provide a higher cell classification success rate than using electrical or mechanical parameter alone.
Novel Molecular Mechanisms Controlling Pancreatic β-cell Function and Hepatic Glucose Homeostasis
Keywords: Pancreas
Liver
Transcription
Free fatty acids

The key defects characteristic of hyperglycemia in T2D include increased hepatic glucose production, a diminution of insulin secretion, and an absolute impairment in peripheral insulin action. The objective of my thesis was to investigate the molecular mechanisms leading to fatty acid induced β-cell dysfunction and determine the role of a novel transcriptional coregulator in the regulation of hepatic glucose homeostasis. The first part of my work focused on the chronic effects of fatty acids on human pancreatic β-cell function. Using microarray technology I established an important role for fatty acids in the pathogenesis of β-cell dysfunction. Accordingly chronic exposure of islets to oleate resulted in a significant reduction in glucose-stimulated insulin secretion and to an increase in the rate of reactive oxygen species generation. Additionally, pre-treatment of human islets with oleate led to a significant increase in the rate of oxidation of this fatty acid and to a significant decrease in glucose oxidation. My data indicate that chronic exposure of human islets to fatty acids activates inflammatory and metabolic pathways that lead to oxidative stress. In addition, the first part of my work demonstrated that fatty acids induce oxidative stress in vitro an effect that is preventable to a large extent by the use of antioxidants. In this setting and recapitulating the human islet data, fatty acids are causally linked to impaired insulin secretion, and the induction of oxidative stress. Our report demonstrated that oxidative stress plays a key role in the decrease in β-cell function induced by chronic lipotoxicity. My work also demonstrated that fatty acids are causally linked to the induction of endoplasmic reticulum stress in human islets. Finally, in the second part of my work I provide novel evidence for the role of PHIP in the regulation of hepatic gluconeogenesis. My work is the first to demonstrate that PHIP suppresses hepatic gluconeogenesis in vitro and in vivo. PHIP is amongst the few proteins that have ever been reported to suppress gluconeogenesis to date. PHIP thus represents a novel target for pharmaceutical intervention of diabetes and the suppression of hepatic glucose production.