VictorJuiz/thesis huggingface dataset:
Young, Queer and Trans, Homeless, and Besieged: A Critical Action Research Study of How Policy and Culture Create Oppressive Conditions for LGBTQ Youth in Toronto's Shelter System

This dissertation is about lesbian, gay, bisexual, transgender, transsexual, and queer (LGBTQ) youth and the shelter system. This work focuses on the denial of home and safety to queer and trans youth. Over approximately two years, different groups of people came together to discuss what is holding up and sustaining the homophobia and transphobia in the shelter system, how homophobia and transphobia occurs and is managed in the shelter system, and how broader policy issues serve to create oppressive contexts for LGBTQ youth. This is a Critical Action Research study that was informed by Critical Ethnography and Institutional Ethnography. In order to investigate what disjunctures occur for LGBTQ youth in the shelter system and how those disjunctures come about, this dissertation draws upon one-on-one interviews with LGBTQ youth experiencing homelessness, shelter Executive Directors, City of Toronto management, and training facilitators; focus groups with frontline shelter staff; and training observations. This study suggests that it is both the excessive bureaucratic regulation and the lack of necessary bureaucratic regulation in highly significant areas, that play a key role in creating the disjunctures that occur for queer and trans youth in the shelter system. This dissertation describes the findings of this study in five major themes, which include: Homophobia and Transphobia in the Shelter System, LGBTQ Youth Invisibility, Inadequate, Invasive and Otherwise Problematic Rules, Lack of Knowledge, and Inconsistent Conformity to Formal Rules. A Digital Storytelling project was created with one youth and was used as a Knowledge Mobilization strategy for this study. The film helped generate extensive media attention and facilitated change in the shelter system, at the City of Toronto, and at a policy level. This research study has made it possible for the voices of LGBTQ homeless youth to be heard in the context of a critical public health and social justice problem. Detailed policy and practice recommendations and changes to the Toronto Shelter Standards are provided at the end of this dissertation and are meant to help Toronto's shelter system become safe, accessible, and supportive of LGBTQ youth.

Keywords: homelessness
homophobia
LGBTQ
shelter services
transphobia
youth
Advisor: Burstow, Bonnie
PXR-mediated Regulation of Placental Drug Transporters Impact on Fetal Exposure to Lopinavir

Globally, there are close to 20 million women living with HIV. An increasing number of these women are of child bearing age. Current guidelines recommend treatment of all pregnant women with highly active antiretroviral agents to both maintain maternal health and to prevent the vertical transmission of the virus. Maintaining a balance between adequate levels of antiretroviral in the fetal system and preventing fetal toxicity are key to the success of this strategy. Despite increasing use, little is known about the transplacental accumulation of these agents. ABC drug transporters at the placental surface are believed to play an important role in the protective function of the placenta. This thesis explored the involvement of Pregnane X Receptor (PXR), an established regulator of drug transporters in the liver and intestine, in the regulation of placental drug transporters and the impact of PXR genotype and associated differences in placental transporter levels on fetal drug accumulation of lopinavir, a key antiretroviral used extensively in pregnant women. We examined the role of the nuclear receptor at the placental interface in PXR knockout and wildtype mice. Pegnenolone-16-á-carbonitrile (PCN) treatment failed to induce PXR and target genes in the placenta in contrast to the liver. Furthermore, an inverse relationship between placental PXR expression and the expression of Pgp, Mrp 1-3 and Bcrp was observed in the placental tissue. PXR heterozygotes were bred in order to generate pregnant dams with varying expression of placental transporters in individual fetal units within the same dam. This model was used to study the impact of fetal genotype and placental transporter expression on fetal exposure to lopinavir within the same dam. A two fold higher fetal accumulation of lopinavir was observed the PXR null placentas as compared to the wild types. An inverse relationship was observed between the placental expression of Mdr1a and fetal exposure to lopinavir (p

Keywords: ABC Transporters
Lopinavir
Placenta
PXR
Advisor: Piquette-Miller, Michekine
Development and Pluralization of the Media of Security Sensitive Ethnic Minority Groups: the Experience of South Eastern European States

This thesis is about the media of security sensitive ethnic minority groups in South Eastern Europe. Why some of them enjoy developed media spheres whereas others are media-deprived? Why operating in similarly structured liberal contexts, the media spheres of some minorities develop as pluralist and liberal, whereas those of others as non-pluralist and authoritarian? In search for answers to these questions, this dissertation compares the media of Turks in Bulgaria, Albanians in Macedonia and Hungarians in Romania. It proposes a model of development of pluralist media spheres of security sensitive ethnic minorities, incorporating variables from three levels of analysis (group, state and system), namely, political cohesion of ethnic minority groups, their level of education, status of interethnic relations, media funding mechanisms, external system pressure and grand polity design.

Keywords: ethnic minorities
ethnic minority media
ethnic parties
ethnic party systems
media
media pluralism
Advisor: Deibert, Ronald J.
Free Radical Determinants of Teratogenesis: Oxidative Damage and Biochemical Signalling by Reactive Oxygen Species

Prenatal exposure to xenobiotics can lead to the production of reactive oxygen species (ROS) that alter signal transduction or oxidatively damage cellular macromolecules such as DNA and protein. During development, ROS play an important role in physiological signalling, suggesting that tight regulation of oxidative stress is imperative for normal development. My research employed two models: one to examine the role of ROS-mediated signalling in teratogenesis and the other to examine the role of oxidative DNA damage and repair. Using the industrial plasticizer and environmental contaminant, bisphenol A (BPA), I found that a single high dose exposure during early fetal development can increase ROS production, causing protein and DNA oxidation in fetal brain, accompanied by postnatal increases in hyperactivity and loss of fear conditioning and olfactory discrimination. BPA-exposed mice have increased neocortical cell proliferation that may involve activation of the PI3K/Akt/mTOR pathway based on the observed increase in oxidation of phosphatase and tensin homolog (PTEN). To elucidate the importance of DNA damage during embryonic development, I generated a conditional knockout mouse line for the breast cancer susceptibility gene (Brca) 1. While individuals with decreased BRCA1 develop normally, they have a greater risk of developing breast and ovarian cancers, and Brca1 null mice are not viable, suggesting that the gene is essential for normal development. Using the pro-oxidative drugs ethanol (EtOH) and methamphetamine, we have shown that heterozygous BRCA1-deficient mice develop normally but are more susceptible to ROS-initiated embryopathies in embryo culture. Furthermore, BRCA1-deficient females show greater susceptibility to ROS-initiated neurodevelopmental deficits than their BRCA1-normal littermates. ROS adversely affect embryonic and fetal brain development via both altered biochemical signalling and oxidative damage, the latter of which is modulated by conceptal DNA repair. Further identification of the complex interactions involved in the dynamic balance among ROS production and detoxification, and downstream repair of macromolecular damage, may provide insight into personal risk for developmental deficits.

Keywords: Bisphenol A
DNA damage
Ethanol
Methamphetamine
Oxidative Stress
ROS signalling
Advisor: Wells, Peter G
Athens in Rome, Rome in Germany: Nicodemus Frischlin's 1586 Translations of Aristophanes

This thesis presents a critical analysis of Nicodemus Frischlin's 1586 Latin translations of Aristophanes' Plutus, Clouds, Acharnians, Frogs, and Knights. This analysis uses criticism from the fields of translation studies to get to the heart of the cultural milieu for which Frischlin produced these translations. One major question this thesis will seek to answer is why, exactly, a German humanist would think it a good idea to translate and popularize the works of an author typically thought to be too obscene and topical to be of any value to the Christian readers of the European Renaissance. This thesis answers this question by undertaking the necessary analyses of the rapidly shifting political, religious, and educational boundaries in Frischlin's Holy Roman Empire at the close of the 16th century. Within this fragmented state, Frischlin's work reached many different groups and effected them in different ways, and so this thesis also attempts to trace these varied reactions through the different political and cultural contexts in which Frischlin worked at different stages, exposing the literary and poetic expectations of the multiple audiences who read and happily re-published his work. Chapter one introduces the subject, with basic background information on the general consensus concerning Aristophanes at the time Frischlin began his work. Chapter two handles the question of translation directly, establishing the methods Frischlin employed in producing his translations, and the means by which we can best criticize and understand them. Chapter three examines Frischlin's relationship to the educational curricula of his day, and the purpose his translations served within those evolving curricula. Chapter four analyzes the relationship of Frischlin and his translation to the governmental structures within which he had to work and seek patronage. Chapter five seeks to establish what lasting impact Frischlin's approach to Aristophanes had on later generations of scholars and artists. Chapter six concludes the dissertation by summarizing the preceding arguments and suggesting directions that similar research can and should take in the future.

Keywords: Aristophanes
Comedy
Nicodemus Frischlin
Renaissance
Rudolf II
Translation
Advisor: Revermann, Martin
Bartlett, Kenneth
Functional Characterization of UVRAG and ANP32B in Immune Cells Using Gene-deficient Mice

This dissertation is a functional characterization of UVRAG and ANP32B in the immune system using gene deficient mice. Focus 1: UVRAG is a putative tumour suppressor with potential roles in autophagy and endocytic trafficking. Despite a plethora of in vitro data, the in vivo role of this gene remains poorly understood. Here, we report the generation and characterization of the T cell specific UVRAG deficient mice. These mice exhibited normal T cell development but impaired homeostasis in the periphery, rendering them unable to clear LCMV infections. We demonstrate that UVRAG may be dispensable for T cell autophagy but it is required for the homeostatic survival and proliferation of naïve T cells. Taken together, our data provide insights into the control of autophagy in T cells and identify UVRAG as a new regulator of naïve T cell homeostasis. Focus 2: ANP32B belongs to a highly conserved and broadly expressed family of ANP32 proteins that have been implicated in many cellular functions. Based on previous analyses of mice bearing targeted mutations of Anp32a or Anp32e, there has been speculation that all ANP32 proteins play redundant roles and are dispensable for normal development. Here, we report that ANP32B expression is associated with poor prognosis in human breast cancer. Using ANP32B-deficient mice, we demonstrate a hierarchy of importance for the mammalian Anp32 genes, with Anp32b being the most critical for normal development. In addition, we reveal important roles for ANP32B in differentiation, homeostasis and activation of immune cells. Together, these are novel findings implicating ANP32B in mammalian development and immune cell function.

Keywords: Autophagy
EAE
Endocytic Trafficking
Knockout mice
LCMV infections
T cell homeostasis
Advisor: Mak, Tak W
Na+ Transport and Toxicity in Plants

Soil salinity is an urgent and global agricultural problem, affecting more than 80 million hectares of arable land. While sodium can be benign and even beneficial to plants at low concentrations, severe toxicity symptoms are found in many species at high, saline, concentrations. Toxicity is initiated by the entry of Na

Keywords: Compartmental analysis
Ion transport
Radiotracers
Salinity
Sodium
Toxicology
Advisor: Kronzucker, Herbert J
Phosphotyrosine Signalling and Regulation of the Fibroblast Growth Factor Receptor 3 in Multiple Myeloma

Protein phosphorylation on tyrosine residues is a critical post-translational modification involved in most cellular processes. Reversible tyrosine phosphorylation events are controlled by the opposing action of protein tyrosine kinases and protein tyrosine phosphatases. Activation of transmembrane receptor tyrosine kinases by ligand binding initiates tyrosine phosphorylation cascades, thus allowing the transmission of signals from the extracellular space to intracellular effectors. The FGFR3 is one such receptor tyrosine kinase involved in numerous biological processes and its dysregulated activity is involved in developmental skeletal disorders as well as malignancies such as the bone marrow cancer multiple myeloma. The lack of comprehensive understanding of FGFR3 signalling as well as its involvement in multiple myeloma, a refractory and deadly disease, led me to investigate its signalling network in myeloma cells by mass spectrometry. Following label-free quantification of phospho-peptides co-modulated with inhibition or activation of FGFR3, I propose an outline of the FGFR3 network, thus considerably increasing our knowledge of the components involved in FGFR3 signalling in myeloma as well as the tyrosine residues phosphorylated within this network. Additionally, this initial screen identified several activated tyrosine kinases, including FGFR3, which contained the D/EYYR/K motif within the activation loop of their kinase domain. This sequence has been proposed as a recognition motif for the protein tyrosine phosphatases PTPN1 and PTPN2. Lentiviral-based, shRNA-mediated knockdown of either of these phosphatases resulted in increased tyrosine phosphorylation of the FGFR3 activation loop. However, each of these phosphatases displays preferential targeting of different FGFR3 populations, depending on the glycosylation state and therefore localization of the receptor. Moreover, loss of these phosphatases differentially affects FGFR3 protein levels in various myeloma cell lines. Taken together, these results provide new knowledge about the signalling network of FGFR3 in multiple myeloma as well as revealing aspects of the mechanisms involved in its regulation by PTPN1 and PTPN2.

Keywords: kinase
mass spectrometry
phosphatase
phosphorylation
protein
tyrosine
Advisor: Moran, Michael F
Anti-vascular Endothelial Growth Factor Therapy in Mouse Models of Vascular Dysplasia and Chronic Colitis

Hereditary hemorrhagic telangiectasia (HHT) and inflammatory bowel disease (IBD) are associated with pathological angiogenesis. Vascular endothelial growth factor, VEGF, is a major angiogenic modulator implicated in HHT and IBD. Hence, we hypothesized that VEGF-targeted therapy might be beneficial in these disorders. HHT is an inherited vascular dysplasia characterized by arteriovenous malformations in organs leading to severe complications. HHT is caused by mutations in Endoglin (ENG; HHT1) or Activin receptor-like kinase 1 (ALK1; HHT2) genes, coding for transforming growth factor (TGF-) superfamily receptors. We studied the angiogenic phenotype of Endoglin and Alk1 heterozygous mice and determined their response to anti-VEGF therapy. We demonstrated that lungs, but not liver, heart or colon, showed dysregulated angiogenesis, characterized by reduction in peripheral microvessel density (MVD). An increase in angiostatic thrombospondin-1 (TSP-1) and vascular destabilizing factor angiopoietin-2 (Ang-2), was associated with reduced MVD in Eng+/- and Alk1+/- lungs respectively. Surprisingly, anti-VEGF treatment increased peripheral pulmonary MVD and normalized levels of TSP-1 and Ang-2, suggesting that the treatment restored the angiogenic balance by distinct pathways in HHT1 and HHT2 models. IBD is characterized by severe, relapsing gut inflammation, leading to multiple complications. Pathological angiogenesis in chronic colitis is persistent, excessive and abnormal. We tested the effect of anti-VEGF therapy in chronic colitis using the Eng+/- mouse model subjected to dextran-sodium sulphate, characterized by severe, chronic intestinal inflammation and pathological angiogenesis. We demonstrated that pathologic angiogenesis is characterized by high colonic MVD and increased in vivo microvascular hemodynamics, as assessed by ultrasound. Interestingly, colitic Eng+/- mice showed an inflammation-induced rise in colonic endoglin, several pro-inflammatory cytokines and myeloid chemotactic factors. They had a further increase in G-CSF and amphiregulin, when compared to wild type mice. This suggests that endoglin might have a triple role, as a protective regenerative factor and as a marker of inflammation and angiogenesis in colitis. Importantly, anti-VEGF therapy showed effects associated with resolution of in vivo and in vitro inflammation and pathological angiogenesis in the Eng+/- model of chronic colitis. Our findings establish the foundation for future translational studies in patients with vascular dysplastic and chronic inflammatory diseases.

Keywords: Angiogenesis
Anti-VEGF therapy
HHT
IBD
VEGF
Advisor: Letarte, Michelle
Kerbel, Robert
Genetic Analysis of Retinopathy in Type 1 Diabetes

Diabetic retinopathy (DR) is a leading cause of blindness worldwide. Several lines of evidence suggest a genetic contribution to the risk of DR; however, no genetic variant has shown convincing association with DR in genome-wide association studies (GWAS). To identify common polymorphisms associated with DR, meta-GWAS were performed in three type 1 diabetes cohorts of White subjects: Diabetes Complications and Control Trial (DCCT, n=1304), Wisconsin Epidemiologic Study of Diabetic Retinopathy (WESDR, n=603) and Renin-Angiotensin System Study (RASS, n=239). Severe (SDR) and mild (MDR) retinopathy outcomes were defined based on repeated fundus photographs in each study graded for retinopathy severity on the Early Treatment Diabetic Retinopathy Study (ETDRS) scale. Multivariable models accounted for glycemia (measured by A1C), diabetes duration and other relevant covariates in the association analyses of additive genotypes with SDR and MDR. Fixed-effects meta-analysis was used to combine the results of GWAS performed separately in WESDR, RASS and subgroups of DCCT, defined by cohort and treatment group. Top association signals were prioritized for replication, based on previous supporting knowledge from the literature, followed by replication in three independent white T1D studies: Genesis-GeneDiab (n=502), Steno (n=936) and FinnDiane (n=2194). No SNP reached genome-wide significance in survival meta-GWAS for SDR. In a case-control meta-GWAS, however, SNPs in

Keywords: diabetes complications
Diabetes Mellitus
Type 1
diabetic retinopathy
Genome-Wide Association Study
GWAS
Polymorphism
Single Nucleotide
Advisor: Paterson, Andrew D
Textual Transgressions: Confessional Discourse in Late Twentieth-century Canadian and Québécois Writing

Through close readings of six works of confessional fiction from Canada and Québec, this dissertation argues that the subversive use of confessional discourse can serve as a powerful platform for social critique. It challenges Michel Foucault's thesis that confession, a practice that he regards as fundamental to our major social institutions such as religion, law, and medicine, is allied to a history of domination and as such serves to trap the subject within existing dynamics of power. Rather than regard confession as an instrument of repression, I reformulate it as a speech act that the subject can embrace in creative ways to resist and subsequently undermine constraining social narratives. My first chapter provides the theoretical basis for this argument, outlining the four main assumptions that underlie confession--the unified subject; guilt/shame; the need for forgiveness; the desire to be readmitted into the community--and introducing the strategies by which writers parodically undercut them. In Chapter 2, I apply this discussion to two texts that portray religion as a repressive force, Margaret Atwood's

Keywords: Canadian Literature
Confession
Foucault
Modernism
Quebec
Rhetoric
Advisor: Havercroft, Barbara
Securing Health: HIV Securitization in the UN system

This dissertation examines the efficacy of securitization as a strategy for drawing attention and resources to an issue, with specific reference to the efforts of elite actors in the United Nations to position HIV as a security threat by placing it on the United Nations Security Council (UNSC) agenda and thereby catalyse change in the global HIV response. The dissertation argues that while this move initially catalysed a far-reaching discussion, including calls for improved treatment access, the longer-term impact of international HIV securitization has been mixed. Although HIV securitization in the UN has come to include exceptional practices within the security sector, it did not have a significant effect on treatment access or the global response writ large. HIV securitization produced at once exceptional yet limited effects. To explain these effects, this dissertation first argues that HIV securitization in 2000 was deeply shaped by older racialized and gendered discourses about Africa, disease and security, and was constrained from the outset by these prior threat constructions. Second, it argues that threat construction is predicated on binary categories that produce difference, and then hierarchies based on that difference. This produces consistent constraints that shape subsequent threat response, rendering securitization inherently limited as a transformative strategy. The analysis is developed via a framework reimagining securitization as a policy process. Analytically, conceptualising securitization as a series of policy stages enables structured tracing of the origins, evolution and effects of securitization. Theoretically, the framework unites several strands of securitization theory, levels of analysis and categories of actors in a single framework. The conception of securitization as a policy process advances securitization theory by uniting discursive and practice-based approaches to securitization, but by illuminating inherent limitations of securitization as a means to emancipatory ends, it pushes theorists and practitioners to think and act beyond securitization.

Keywords: global health
HIV/AIDS
securitization
security
United Nations
Advisor: Handley, Antoinette
Hoffmann, Matthew
The RavA-ViaA Chaperone-like System Targets Specific Respiratory Complexes in Escherichia coli

MoxR AAA+ ATPases are widespread throughout bacteria and archaea. They perform chaperone-like functions in the maturation of specific target proteins, or aid in cofactor insertion. In

Keywords: Escherichia coli
Fumarate reductase
MoxR AAA+ ATPases
NADH:ubiquinone oxidoreductase I
RavA
ViaA
Advisor: Houry, Walid A