VictorJuiz/thesis huggingface dataset:
Analysis of Mitochondrial Signaling in the Regulation of Programmed Cell Death

The involvement of mitochondrial signaling in mammalian PCD regulation has been examined extensively via biochemical analyses and cellular studies in vitro. However there still exist considerable gaps in our knowledge regarding its contribution in specific tissues and cell types during mammalian development in vivo. In addition, given the numerous pathologic conditions associated with aberrant PCD, modulation of this signaling process represents an attractive target for therapeutic intervention. In this thesis I have therefore examined the regulation of mitochondrion-mediated PCD signaling as it pertains to several forms of developmental and injury-induced cell death. In the first component of the thesis I have examined the differential sensitivity of Bcl2 on the survival of motor neuron populations from two distinct developmental origins (alpha and gamma motor neurons), demonstrating that gamma motor neurons are preferentially affected in Bcl2 null mice. Thus, Bcl-2 plays a critical in vivo in regulating subtype-specific motor neuron survival during development. In the second study I have demonstrated that a major portion of the neuroprotective effect exerted by the immunophilins cyclosporin A and FK-506 are mediated through calcineurin signaling; rather than MOMP-mediated events as previously held. Additional findings of this study demonstrated the first neuroprotective effects of the pyrethroid insecticide cypermethrin and calcineurin-mediated control of Bad phosphorylation. Such findings establish a link between calcineurin signaling and mitochondrion-mediated cell survival. The above studies established critical features of mitochondrion-mediated PCD in regulating survival of several neuronal subpopulations. I therefore followed these studies with an examination of how post-mitochondrial PCD signaling is regulated following MOMP permeabilization. Specifically I examined regulation of the Smac-IAP-caspase axis, investigating how combinatorial deletion of Casp3 and Diablo alter PCD progression in mouse embryonic fibroblasts. Using a series of injury stimuli in the context of biochemical and cellular analyses I have developed a model of how endogenous Smac/DIABLO regulates executioner caspase activity. Collectively these studies elucidate key aspects of mitochondrial signaling during both developmental and injury-induced PCD in vivo.

Keywords: programmed cell death
mitochondria
development
acute neural injury
Bcl-2
calcineurin
caspases
inhibitor of apoptosis proteins
Smac/DIABLO
genetic modification
immunophilin ligands
neuroprotection
gamma motor neurons
Advisor: Henderson, Jeffrey T.
The Ethics of Simplicity: Modernist Minimalism in Hemingway and Cather

This study investigates how minimalist narrative techniques in American modernist literature oblige us, as readers and critics, to be self-reflexive about the ethical basis of interpretation. Through a concentrated narratological analysis of Hemingway’s and Cather’s fiction, I identify three major elements of what I term the “simple text”—thinness, smoothness, and spaciousness—and I show how each category engages a hermeneutic ethics. By gesturing towards accessibility and straightforward comprehension while also producing moments of indeterminacy that subtly resist the reader’s inferences, the simple text challenges the reader to conceive interpretation both as a positive exercise of individuation and imagination and, simultaneously, as a potentially unethical mode of critical violation and imposition. My introduction contemplates the ethical foundations of Hemingway’s and Cather’s famous aesthetics of omission to argue that such simplicity conveys a complex theory of reader engagement. Chapter One defines “thinness” by examining “thin characters” in A Farewell to Arms and My Ántonia—characters whose simplicity makes them paradoxically unreadable in a way that foregrounds the nature of our accountability towards others. The second chapter, focusing on In Our Time and Death Comes for the Archbishop, defines “smoothness” as a simple paratactic patterning that challenges our critical desire to generalize meanings from particular experiences. While the smooth surface invites our interpretive touch, its structural integrity resists marking and inscription. The final chapter details the element of “spaciousness,” showing how open and simple settings in The Old Man and the Sea and The Professor’s House inspire, in the protagonists, moments of self-conscious interpretation of the nonhuman other and solicit a practice of accountable freedom. I argue that the foregrounding of such spaces proffers a subtle yet pointed critique of American individualism, but this critique is learned only through our encounter with the text’s interpretive limits. The study concludes by suggesting how these strategies both respond to and participate in specific criticisms of American democracy that circulated during the modernist period.

Keywords: American Literature
Narrative Theory
Ernest Hemingway
Willa Cather
Ethics
Simplicity
Advisor: Cuddy-Keane, Melba
Ironic Acceptance – Present in Academia Discarded as Oriental: The Case of Iranian Female Graduate Student in Canadian Academia

The purpose of this research is to examine the experiences of first-generation, highly educated Iranian women who came to Canada to pursue further education in a ‘just’, ‘safe’, and ‘peaceful’ place. The research has revealed that these women who were fleeing from an ‘oppressive’ and ‘unjust’ Iranian regime face new challenges and different forms of oppression in Canada. This dissertation examines some of the challenges that these women face at their place of work and/or at graduate school. The research findings are based on narratives of eleven Iranian women who participated in in-depth interviews in the summer of 2008. These women, whose ages range from 26 to 55 and are of diverse marital status, all hold an academic degree from Iran. They were also all enrolled in different graduate schools and diverse disciplines in Ontario universities at the time of the interviews. The research findings indicate that their presence in Canada became more controversial after the September 11, 2001 attack on the World Trade centers in New York. Historically, the social images imposed on Middle Eastern women derive from the Orientalism that arose following the colonization of the Middle East by Western imperialists. The perpetuation of such images after the 9/11 attack has created a harsh environment for the participants in this research. After 9/11 most immigrants from the Middle East were assumed to be Muslim and Arab, which many North Americans came to equate with being a terrorist. In order to analyze the participants’ voices and experiences, I have adopted a multi-critical theoretical perspective that includes Orientalism, anti-colonialism and integrative anti-racist feminist perspectives, so as to be equipped with the tools necessary to investigate and expose the roots of racism, oppression and discrimination of these marginalized voices. The findings of this research fall under six interrelated themes: adaptation, stereotyping, discrimination, being silenced, strategy of resistance, and belonging to Canadian society/ graduate school. One of the important results of this research is that, regardless of the suffering and pain that the participants feel in Canadian graduate school and society, they prefer to stay in Canada because of the socio-political climate in Iran.

Keywords: Middle Eastern women
First generation Iranian immigrant
Racialized female graduate students
Androcentric Canadian higher education
Neo-liberalism and Canadian higher education
Orientalism
Racism
stereotyping
adaptation
discrimination
marginalization
belonging
being silenced
Iranian immigrant educated women in Canadian graduate school
9/11 and Oriental women in Canadian school
Oppression
Muslim women
Advisor: Wane, Njoki
Impact of CYP2A6 Genetic Variation on Nicotine Metabolism and Smoking Behaviours in Light Smoking Populations of Black-African Descent

Populations of Black-African descent have slower rates of nicotine and cotinine metabolism, smoke fewer cigarettes (~10 cigarettes/day), and have higher incidences of tobacco-related illnesses compared to Caucasians. Cytochrome P450 2A6 (CYP2A6) is the main enzyme involved in the metabolism of nicotine and its proximal metabolite cotinine, as well as tobacco-specific nitrosamines. Genetic polymorphisms in CYP2A6 contribute to the large variability observed in rates of nicotine metabolism. Reduced CYP2A6 activity has been associated with fewer cigarettes smoked, higher quit rates, and lower lung cancer risk in predominantly moderate to heavy-smoking (~20–30 cigarettes/day) Caucasians. CYP2A6 genetic variants and their impact on smoking behaviours have not been well studied among individuals of Black-African descent. The main objectives herein were to identify and characterize new CYP2A6 variants that may explain the slower rates of metabolism, and determine whether CYP2A6 variation is a predictor of smoking phenotypes in this population. Furthermore, we examined whether previously validated biomarkers of tobacco exposure have limitations among individuals of Black-African descent given their low and sporadic smoking patterns. A new CYP2A6 variant (CYP2A6*23) was found in individuals of Black-African descent recruited for a nicotine pharmacogenetic-pharmacokinetic study. CYP2A6*23 reduced activity towards nicotine and coumarin in vitro and was associated with slower rates of CYP2A6 kinetics in vivo. In a clinical trial of African-American light smokers, CYP2A6 slow metabolizers were more successful at smoking cessation compared to normal metabolizers, although no differences in cigarette consumption were found. Two common biochemical markers of tobacco smoke exposure, cotinine and exhaled carbon monoxide, were weakly correlated with self-reported cigarette consumption. These biomarkers were not substantially affected by variables previously shown to alter amount smoked and/or rates of cotinine metabolism such as gender, age, body mass index or smoking menthol cigarettes. However, CYP2A6 slow metabolizers had significantly higher cotinine without smoking more cigarettes. Identification and characterization of novel variants adds to our understanding of nicotine pharmacokinetic differences between racial/ethnic minority groups and improves accuracy of CYP2A6 genotype groupings for genetic association studies. Furthermore, better insight into the biological factors associated with smoking behaviours will aid in the development of more efficacious targeted treatments for this understudied population.

Keywords: Pharmacogenetics
Nicotine
CYP2A6
Advisor: Tyndale, Rachel
Molecular Barcoded Plasmid Yeast ORF Library: Linking Bioactive Compounds to their Cellular Targets and Mapping Dosage Suppressor Networks

In this thesis I describe a functional genomics resource in which each yeast gene, with its native promoter and 3’UTR, is cloned on a uniquely barcoded low-copy vector. We refer to this resource as the Molecular Barcoded Yeast ORF (MoBY-ORF) library 1.0. Each gene carried by MoBY-ORF 1.0 should mimic its native expression and thus is best suited for complementation cloning. The vector backbone of MoBY-ORF 1.0 is compatible with the mating-assisted genetically integrated cloning (MAGIC) system for recombination cloning in bacterial cells, which allows the transfer of the ORF fragment and its barcoded cassette to other vector backbones. Taking advantage of the MAGIC system, we created a multi-copy version of the library, which we refer to as MoBY-ORF 2.0. I used MoBY-ORF 1.0 to map drug resistant mutants by complementation cloning with a barcode microarray readout. I investigated several drugs with known targets in my proof-of-principle experiments and showed the feasibility of this method. I identified a single mutation that causes resistance to two different natural products, theopalauamide and stichloroside. By doing so, I was able to link these two chemicals to their cellular target, ergosterol. In fact, theopalauamide represents a new class of sterol binding chemical. I also describe the use of MoBY-ORF 2.0 to clone dosage suppressors of conditional temperature-sensitive mutants. By doing so, and combing our own data with published literature, we showed that dosage suppression interactions often overlap with protein-protein interactions and negative genetic interactions but not positive interactions; however the majority of dosage suppression interactions are unique and thus they represent an unique edge on a global functional interaction map. We also describe the first genome-wide dosage suppressor interaction map of budding yeast.

Keywords: Budding yeast
Functional genomic
Advisor: Boone, Charles
Subfilter Scale Modelling for Large Eddy Simulation of Lean Hydrogen-enriched Turbulent Premixed Combustion

Hydrogen (H2) enrichment of hydrocarbon fuels in lean premixed systems is desirable since it can lead to a progressive reduction in greenhouse-gas emissions, while paving the way towards pure hydrogen combustion. In recent decades, large-eddy simulation (LES) has emerged as a promising tool to computationally describe and represent turbulent combustion processes. However, a considerable complication of LES for turbulent premixed combustion is that chemical reactions occur in a thin reacting layer at small scales which cannot be entirely resolved on computational grids and need to be modelled. In this thesis, subfilter-scale (SFS) modelling for LES of lean H2-enriched methane-air turbulent premixed combustion was investigated. Two- and three-dimensional fully-compressible LES solvers for a thermally perfect reactive mixture of gases were developed and systematically validated. Two modelling strategies for the chemistry-turbulence interaction were pursued: the artificially thickened flame model with a power-law SFS wrinkling approach and the presumed conditional moment (PCM) coupled with the flame prolongation of intrinsic low-dimensional manifold (FPI) chemistry tabulation technique. Freely propagating and Bunsen-type flames corresponding to stoichiometric and lean premixed mixtures were considered. Validation of the LES solvers was carried out by comparing predicted solutions with experimental data and other published numerical results. Head-to-head comparisons of different SFS approaches, including a transported flame surface density (FSD) model, allowed to identify weaknesses and strengths of the various models. Based on the predictive capabilities of the models examined, the PCM-FPI model was selected for the study of hydrogen-enrichment of methane. A new progress of reaction variable was proposed to account for NO. The importance of transporting species with different diffusion coefficients was demonstrated, in particular for H2. The proposed approach was applied to a Bunsen-type configuration, reproducing key features observed in the experiments: the enriched flame was shorter, which is attributed to a faster consumption of the blended fuel; and the enriched flame displayed a broader two-dimensional curvature probability density function. Furthermore, reduced levels of carbon dioxide (CO2), increased levels of nitrogen monoxide (NO), and a slight increase in the carbon monoxide (CO) levels in areas of fully burned gas were predicted for the enriched flame.

Keywords: Combustion
Large Eddy Simulation
Computational Fluid Dynamics
Subfilter Scale Modelling
Advisor: Groth, Clinton P. T.
Gulder, Omer L.
Interference Control in Memory and Fluid Intelligence

This thesis investigated the role of interference in general cognitive functioning. Study 1 explored the relationships among interference control, memory, and fluid intelligence. Studies 2 and 3 explored the possibility that interference is controlled by suppressing the interfering information rather than, for example, facilitating the target information. Study 1 tested the hypothesis that individual differences in the ability to regulate interference are responsible for the correlation between memory tasks and fluid intelligence. Participants completed common measures of working memory, long-term memory, fluid intelligence, and interference regulation. In structural equation models, controlling for interference regulation ability largely accounted for the correlation between the memory tasks and fluid intelligence. These results suggest that efficient interference control is critical to cognitive functioning. Study 2a tested the hypothesis that interference is regulated by suppressing competing responses. In Phase 1 of a three-phase paradigm, participants performed a vowel-counting task that included pairs of orthographically similar words (e.g., allergy/analogy). In Phase 2 participants solved word fragments (e.g., a _ l _ _ gy) that resembled both words in an earlier pair, but could be completed only by one of these words. Phase 3 measured the consequence of having resolved interference in Phase 2 by asking participants to read a list of words, including the rejected competitors, as quickly as possible. Relative to participants in control conditions that did not require interference resolution these interference condition participants were slower to name competitor words. Study 2b showed that while competitors are suppressed during interference resolution, a complementary facilitative process does not directly enhance accessibility of targets. Finally, Study 3 tested the hypothesis that older adults have impaired suppression abilities. Older adults were tested in the same paradigm used in Studies 2a and 2b. In contrast to younger adults, older adults showed no suppression of competitors. This result supports the theory that some age related memory deficits stem from impaired suppression processes.

Keywords: memory
Interference
aging
intelegence
Advisor: Lynn, Hasher
The Development of Working-class Organic Intellectuals in the Canadian Black Left Tradition: Historical Roots and Contemporary Expressions, Future Directions

This thesis explores the revolutionary adult education learning dimensions in a Canadian Black anti-racist organization, which continues to be under-represented in the Canadian Adult Education literature on social movement learning. This case study draws on detailed reflection based on my own personal experience as a leader and member of the Black Action Defense Committee (BADC). The analysis demonstrates the limitations to the application of the Gramscian approach to radical adult education in the non-profit sector, I will refer to as the Non-Profit Industrial Complex (NPIC) drawing on recent research by INCITE Women of Colour! (2007). This study fills important gaps in the new fields of studies on the NPIC and its role in the cooptation of dissent, by offering the first Canadian study of a radical Black anti-racist organization currently experiencing this. This study fills an important gap in the social movement and adult education literature related to the legacy of Canadian Black Communism specifically on the Canadian left.

Keywords: Black Working-Class Organic Intellectuals
Learning and Development
Advisor: Sawchuk, Peter H.
Territory of the Sages: Neo-Confucian Discourse of Wuyi Nine Bends Jingjie

This dissertation examines the effects of jingjie 境界 discourse on the development of Neo-Confucianism in 12th-18th century China and Korea. Jingjie, a multilayered term whose meanings include “territory,” “spiritual realm,” and “poetic landscape,” has largely been studied as a philosophical idea and aesthetic trope. These investigations, however, often overlook the connection between jingjie’s diverse meanings and the term’s role in the production of territorial knowledge. Using the method of discourse analysis, this study explores jingjie as a discourse of territoriality that constructed and represented forms of space, power, and identity through the process of horizontal and vertical territorialization, traversing geopolitics, philosophy, and poetry. The development of Neo-Confucianism can be traced through the intricate interplay of the multiple discourses of jingjie, particularly in the conception of sagely learning and living. The “jingjie of the sages,” proposed by Neo-Confucians as a new subject of inquiry and goal of learning, was conceived as a moral and spiritual territory to be claimed and reached, a poetic territory to be experienced, and a geopolitical territory to be restored. The most pronounced expression of Neo-Confucian jingjie discourse is found in the discursive development of Wuyi Mountains and its Nine Bends Stream (Wuyi Jiuqu 武夷九曲). Well-known because of its association with Zhu Xi 朱熹 (1130-1200 AD), Wuyi Nine Bends jingjie as a geopolitical territory developed into both the physical and symbolic centre of Cheng-Zhu learning, and was recreated throughout China and Korea as a sign of legitimate orthodoxy and as a base for factional expansion. As a poetic territory, Wuyi emerged as an important site of shared cultural memory, forging bonds between Neo-Confucians across generations. The discussion of Wuyi as a philosophical jingjie revolved around the interpretation of Zhu Xi’s poem “The Boat Song of Wuyi’s Nine Bends 武夷九曲櫂歌,” which became the source of hermeneutic debate that lasted for several centuries and contributed to an important philosophical literature. On the whole, by examining the development of Neo-Confucianism in light of the traditional discursive context of jingjie, this study reveals how the philosophical, political, and cultural movement was conceived and understood by the Neo-Confucians themselves as the joining together of different modes of territoriality, thus providing a richer, more nuanced and complex picture of the development of Neo-Confucianism in China and Korea from 12th-18th centuries.

Keywords: Jingjie
Neo-Confucianism
Advisor: Sanders, Graham
Municipal School Curricula Knowledge Dynamics in Brazil's Northeast

The global spread of the neoliberal paradigm has propelled a recent worldwide trend of educational decentralization/centralization policies. Such policies constitute a contradictory ensemble that has shifted authority and accountability across national, provincial or state, municipal, and school levels. They have also been marked by contestation over the extent to which curricula are nationally standardized or locally defined. Education reform in Brazil in this regard has been shaped by a confluence of neoliberal and critical theoretical currents: enhance the nation’s economic competitiveness in the global market and redress pressing societal issues. Using Basil Bernstein’s concepts of classification and framing together with critical educational scholars’ conceptualizations of knowledge and knowledge in the official and enacted curriculum as conceptual and theoretical frameworks, this comparative ethnographic case study examines the nexus between curriculum, knowledge, and pedagogy in municipal schools in Brazil’s Northeast. In doing so it addresses gaps in comparative educational research on curriculum knowledge along with how educational decentralization/centralization policies are implemented in practice. The central thesis is that municipal school curricula knowledge dynamics—the classification and framing of knowledge in the official curriculum and the relation of such with what knowledge is legitimized in classrooms, how such is transmitted and analyzed, and why—in Brazil’s Northeast encompass a multilevel web of contradictions. This web spans incongruent ideologies, opposing elements of autonomy and accountability, conflicting pedagogical principles and practices, and a chasm between curriculum ideals and urban periphery municipal school realities.

Keywords: curriculum
knowledge
pedagogy
municipal schools
Northeast Brazil
neoliberalism
educational decentralization/centralization policies
urban periphery
ethnographic case study
critical theoretical framework
classification and framing
sub-national comparison
Advisor: Gérin-Lajoie, Diane