VictorJuiz/thesis huggingface dataset:
Functional Deficiency of Dicer in Atherosclerosis: A Role for Hemodynamic Shear Stress Regulation of the miRNA Biogenesis Pathway

Endogenous microRNAs act as post-transcriptional gene regulators. miR-145 is significantly reduced in both human and murine atherosclerotic lesions; we have shown that re-expression of miR-145 in an atherosclerotic murine model was associated with a reduction of lesion size. Dicer is an RNase-III enzyme which cleaves pre-miRNA into mature miRNA. The regulation of Dicer and its effects on microRNAs in atherosclerosis remains undefined. Multiple atherosclerotic murine models demonstrate downregulated Dicer expression and is associated with global dysregulation of microRNAs. Investigating the mechanism behind Dicer deficiency is key to understanding atherosclerosis development. Endothelial cells (EC) from specific regions of the aorta in wild-type mice experiencing laminar or disturbed/non-laminar blood flow show differential Dicer expression. Dicer expression and function is regulated by hemodynamic shear stress in vitro. Furthermore, the presence or absence of endothelial Dicer affects expression of flow-responsive genes. We posit that Dicer deficiency can potentially prime atheroprone regions in diseased vasculature.

Keywords: Atheroprone
Atherosclerosis
Dicer
Endothelium
Hemodynamic
microRNA
Advisor: Marsden, Philip A
"Abandoned in every sense”: Dispossession, Depletion, and the Reproduction of Colonial Relations through Transnational Mining in the Peruvian Andes

In 2016, the ten indigenous campesino communities of the district of Chamaca, Peru temporarily seized a copper mine owned and operated by a transnational mining company, HudBay Minerals. To understand such mining conflicts in Chamaca, this thesis examines how colonial logics and power relations underpin contemporary development policies of the Peruvian state. In particular, I analyze how the historical entanglements of race, indigenous land tenure and labor, and mining inform contemporary extractivist policies. Drawing on three months of ethnographic research, I argue that the HudBay mining enclosure, justified by such policies, reproduces the colonial power structure in three ways: through 1) dispossessions that deplete indigenous social reproduction; 2) the entrenchment of the colonial gender system; 3) state and corporate legal abandonment that recreates hacienda-indigenous relations. En 2016, las diez comunidades campesinas originarias del distrito de Chamaca, Perú tomaron las instalaciones de la minera transnacional—HudBay Minerals—por cuatro días. Para entender los conflictos mineros en Chamaca, esta tesis examina cómo las lógicas y relaciones de poder coloniales respaldan la política de desarrollo contemporánea del Estado peruano. En particular, analizo cómo las conexiones históricas entre las estructuras raciales, la tenencia de la tierra y la labor de las poblaciones indígenas, y la minería informan la política extractivista del presente. Luego de tres meses de investigación etnográfica, sostengo que el cercamiento minero de HudBay, establecido por tal política, reproduce la estructura colonial en tres maneras: por 1) las desposesiones que agotan la reproducción social de los pueblos originarios; 2) el afianzamiento del sistema de género colonial; 3) el abandonamiento legal por parte del Estado y la empresa, que recrea las relaciones y economía de hacienda.

Keywords: Coloniality
Indigenous rights
Latin America
Mining conflicts
Natural resource extraction
Political ecology
Advisor: Mollett, Sharlene
Public Spaces of Precarity: Labour Geographies of Informal Recycling in Toronto

This thesis explores the everyday working lives and workspaces of Toronto’s informal recyclers, who earn a living collecting and returning discarded beverage containers from bins and public spaces. Drawing on in-depth interviews and photovoice methods, the research finds that although informal recycling is pursued as a response to precarious conditions in the neoliberal city, it constitutes a precarious form of work in itself. Recyclers’ experiences of precarity are intimately connected to the public spaces of work they inhabit, through material, affective, and regulatory dimensions. In negotiating spaces of precarity, recyclers deploy a refined repertoire of embodied skills and spatial tactics, challenging perceptions of informal recycling as ‘unskilled’ work. With recent changes by the provincial government to the landscape of alcohol sales in Ontario, the future of informal recycling is uncertain. Policy recommendations are therefore proposed.

Advisor: Leslie, Deborah
Prostaglandin E2 and its Receptor Subtype EP4 are Functionally Relevant in Ankylosing Spondylitis Disease Pathogenesis

Introduction: PGE2/EP4 are good candidates to explore in AS pathogenesis as they have been shown to be involved in all three of these pathways. Methods: ELISA was used to discern PGE2 levels in the serum of AS progressors and nonprogressors.Taqman assays evaluated SNPs in the PTGER4 gene in this group. Flow cytometry was used to evaluate the surface expression of EP4. LEGENDplex analysis was employed to discern cytokine secretion from monocyte subsets in response to PGE2/EP4 agonist. Results: PGE2 serum levels were significantly increased in AS progressors vs. non-progressors and were an independent predictor of disease progression. The CC genotype of the rs6896969 PTGER4 SNP was significantly elevated in disease progressors. PGE2 had a mild effect on cytokine production from AS classical monocytes vs. HCs. Conclusion: PGE2/EP4 are involved in radiographic progression in AS. Further experiments are needed to discern its activity in the IL23/IL17 axis and bone remodelling.

Keywords: Ankylosing Spondylitis
Arthritis
Rheumatology
Advisor: Haroon, Nigil
The Regulation of Inclusion: An Exploration of School Culture, Pride Narratives, and the Limits of Queer in the National Imaginary

The following study provides a critical examination of the current landscape of 2SLGBTQ+ (two-spirit, lesbian, gay, bisexual, trans, queer) inclusion for high school students in several major Canadian provinces. In order to locate particular strengths and limitations within the predominant framework of inclusion, this study uses a comparative analysis to highlight the (dis)connections between institutional narratives of inclusion (i.e., school policies; school climate surveys; political discourse; and mainstream Pride narratives) and individual accounts of inclusion in school (i.e., 2SLGBTQ+ perspectives and experiences). Findings highlight the various ways in which the prevailing framework of inclusion remains heavily influenced by heteronormative, colonial, and ableist standards of belonging, which consequently, continues to exclude 2SLGBTQ+ voices and lived experiences. The included perspectives from 2SLGBTQ+ youth, families, and educators offer unique opportunities to both re-examine and reconceptualize how prevalent notions of ‘inclusion’ and ‘well-being’ are being reproduced, operationalized, and experienced by all students in school.

Keywords: Education
Equity
Inclusion
Pride
Queer
Two-spirit
Advisor: Sztainbok, Vannina
Parekh, Gillian
Deep Graph Embeddings in Recommender Systems

Recommender Systems are intelligent machine learning systems that help customers discover a ranked set of personalized products from a dynamic pool of diverse choices. We can formally view recommender systems objective as ranking edges in a bipartite graph consisting of user and item nodes. Deep Graph embeddings have shown great success in a variety of applications. In this thesis, we aim to explore the application of deep graph embeddings for recommendation. We first understand the embeddings from numerous recommendation perspectives. Next, we compare graph embeddings against existing seminal recommendation algorithms on standard recommendation tasks. Then, we design a new evaluation metric that we argue is important for the e-commerce setting. Finally, we extend graph embeddings to improve performance on the recommendation tasks. To conclude, our experiments support using deep graph embeddings for recommendation tasks and indicate that it could be useful to bias recommender models towards long-tail items.

Keywords: Deep Learning
Economics
Geometric Deep Learning
Information Retrieval
Machine Learning
Recommender Systems
Advisor: Sanner, Scott
Understanding the Impacts of Connected Autonomous Vehicles on Pedestrians with Visual Impairment

This thesis develops a policy-framework that can be used for minimizing communication issues between connected autonomous vehicles (CAVs) and visually impaired pedestrians. The existing literature on CAVs is highly focused on different perspectives of the possible users of these technologies. Since, this research uses a dataset collected through a tailor-made stated adaptation survey among visually impaired pedestrians. The dataset includes the current mobility issues of this community, their perceptions about CAVs, and a wide range of socioeconomic attributes. Some evidence-based recommendations are provided on communication techniques, based on the key findings of a series of structural equation models (SEM) and ordered logit models estimated using the survey data. The results reveal that the low-noise issue of electric engines influences visually impaired pedestrians’ safety and security in the contexts of CAVs. It shows that respondents who rely on mobile applications and technology-based devices for navigating purposes tend to trust in CAVs.

Keywords: Communication and Mobility Issues
Connected Autonomous Vehicles
Visually Impaired Pedestrians
Vulnerable Road Users
Advisor: Habib, Khandker Nurul
Does Age Matter? Mental Health Implications and Determinants of When Youth Present to a Gender Clinic

Background: Gender-affirming medical care (GAMC) improves the psychological functioning of transgender adolescents and adults. Purpose: 1) To assess the relationship between age at presentation to GAMC and rates of mental health comorbidities. 2) To identify factors influencing when youth present to GAMC. 3) To determine whether older presenting youth face more barriers to care. Methods: 1) Cross-sectional chart review of new patients to a gender clinic. 2) Sequential exploratory mixed methods study involving semi-structured interviews and subsequent questionnaire design and distribution. Results: Older age at presentation was associated with psychoactive medication use. Late pubertal stage was associated with depressive and anxiety disorders. Younger presenting youth recognized gender incongruence earlier and were more likely to have LGBTQ+ family members. More older presenting youth endorsed familial religious affiliations. Conclusions: Later presentation to GAMC is associated with higher rates of mental health comorbidities and may be driven by later recognition of gender incongruence.

Keywords: Access to care
Gender-affirming care
Gender incongruent youth
Mental health
Pediatric endocrinology
Transgender youth
Advisor: Palmert, Mark R
Molecular Dynamics Study of the Solvation and Mechanical Properties of Elastin-like Peptides

Elastin is a disordered structural protein that imparts extensibility and elastic recoil to major arteries, lungs, and other elastic human tissues. Elastin-based peptides are biocompatible and able to self-assemble, making them suitable for biomimetic materials. Recent studies have begun to uncover the role of entropic effects, including the hydrophobic effect and conformational entropy, in the structural ensemble of elastin-like peptides. In this study, we use atomistic molecular dynamics simulations of peptides based on the hydrophobic domains of elastin to investigate their solvation and mechanical properties. The modulus of elastin-like domains obtained from equilibrium fluctuations is commensurate with elastic measurements from simulations as they are pulled to full extension and subsequently allowed to collapse. Our findings indicate that the hydrophobic eﬀect is a signiﬁcant driving force for elastic recoil, and suggest that the isolated hydrophobic domains are not responsible for the low resilience of elastin-based materials.

Keywords: Elastin
Intrinsically Disordered Proteins
Molecular Dynamics Simulations
Advisor: Pomès, Régis
Regulatory Role of Bile Acids in Dietary Fat Absorption and Intestinal Lipoprotein Production

Postprandial dyslipidemia is a key feature of insulin resistance that involves the overproduction of chylomicrons from the intestine after a meal, resulting in an excess number of atherogenic lipoprotein remnants. Bile acids have been recognized as signaling molecules with the ability to regulate peripheral lipid metabolism and energy expenditure. Here I examined the utility of intraduodenal bile acid administration for lowering postprandial lipemia and chylomicron production in the Syrian golden hamster model. Bile acid administration was shown to decrease postprandial lipemia by slowing down gastric emptying and decreasing mRNA expression of genes involved in fatty acid absorption and chylomicron assembly. Furthermore, bile acid administration was able to regulate VLDL secretion in the fasting state and decreased postprandial lipemia in insulin resistant hamsters. Altogether, the findings arising from these studies support the potential utility of targeting bile acid receptors in the treatment of postprandial dyslipidemia often seen in insulin resistant states.

Keywords: bile acid
chylomicron
dyslipidemia
intestinal
lipoprotein
postprandial
Advisor: Adeli, Khosrow
Understanding Global Giant Radiating Mafic Dyke Swarms from the ~2.45 Ga Matachewan Event

The 2.45 Ga Matachewan Large Igneous Province (LIP) of the southern and central Superior Craton consists of radiating mafic dykes, layered-mafic intrusions, basalt lavas and lesser felsic units. The LIP likely represents a mantle plume-driven, intracontinental rift event. Eleven new ID-TIMS U-Pb baddeleyite ages for the Matachewan dyke swarm reveal that dyke emplacement mostly occurred during one burst of magmatic activity semi-continuously from ~2461 to 2450 Ma. A small-volume early pulse is also recorded at 2479.1 Ma on the eastern flank of the swarm. Crustal contamination of a mantle-derived gabbroic magma possibly occurred during staging at lower crustal levels. Paleomagnetic studies of precisely-dated dyke samples suggest a single polarity reversal is constrained at ~2452 Ma, although a second, late reversal is possible. Precise correlations are strengthened with coeval mafic magmatism in Wyoming and Karelia cratons, suggesting they represent complementary components of a rifted supercontinent formerly involving the Superior craton.

Advisor: Hamilton, Michael A
"Trying to Figure Out Where We Belong": Narratives of Racialized Sexual Minorities on Community, Identity, Discrimination, and Health

Lesbian, Gay, Bisexual, Transgender, and Queer people of colour are regularly exposed to unique and contextual forms of prejudice and stigma, which have been linked to stress and increased likelihood of mental and physical health problems. In order to better understand the experiences of this multiply marginalized population, we interviewed eleven LGBTQ-POC to examine how they describe their identities, communities, health, and experiences with stigma. This study reveals new information about community intersection and the microaggressions experienced by queer people of colour, and provides theoretical support for previously identified issues concerning identity relationships and wellbeing. Common issues discussed by respondents include disconnect from communities, relationships between identities, coming out, exoticization, and stress and anxiety. Three primary concepts that are introduced and discussed in this study include:

Keywords: intersectionality
LGBTQ
minorities
people of colour
stress
Advisor: Andersen, Judith
Carlson, Erika
Rethinking Repetition: Selective Scanpath Recapitulation Supports Mnemonic Performance on a Change Detection Task

Stimulus repetition improves processing efficiency and performance on a variety of mnemonic tasks. When images are successfully retrieved from memory, the accompanying pattern of fixations or "scanpath" is highly similar to that elicited during encoding. However, it remains unclear how scanpath repetition promotes efficiency gains on goal-directed tasks. The present study used eye-movement monitoring to test the predictions of scanpath theory against a repeated change detection task. Fixations at repeated-viewing were highly similar to first and final novel- viewing fixations, suggesting that speeded search results from a strategic collapsing of the encoding scanpath based on goal-productivity of novel-viewing fixations. Moreover, older adults repeated more initial encoding fixations than younger adults, designating a specialized role for memory in repetition of the recognition sequence. Results support and extend theories of eye- movement-based repetition effects to account for efficiency gains on change detection as a function of goal-relevance and memory.

Keywords: change detection
eyetracking
memory
repetition
scanpath
Advisor: Ryan, Jennifer
Buchsbaum, Bradley
Remote Spatial Memory in Major Depressive Disorder (MDD)

Spatial memory can be divided into episodic (perceptually detailed) and semantic (coarse, map-like) components. When examining remote spatial memories (routes or environments learned long ago) several previous studies have noted that the episodic component seems to be impaired in patients with hippocampal damage, while the semantic component is preserved. Spatial memory in major depressive disorder (MDD), another group found to have hippocampal defects, has sparsely been studied; any studies that do examine this question tend to focus on new spatial learning. The focus of the current study was to examine remote spatial memory in MDD using a novel online paradigm that is composed of traditionally paper-and-pencil spatial and autobiographical measures. We found no differences between healthy and depressed groups on measures of semantic spatial memory. The depressed group appeared to have alterations on the measure of episodic spatial memory, but the nature of this alternation is unknown.

Keywords: cognitive neuroscience
hippocampus
internet testing
memory
spatial memory
Advisor: Levine, Brian
Global Dysregulation of miRNAs via Dicer Deficiency in Atherosclerosis

Molecular and phenotypic changes of vascular smooth muscle cells are key components of atherogenesis. miRNAs control, at least in part, this phenotypic transition via desuppression of pro-inflammatory factors. Although specific miRNAs have been implicated in atherosclerosis, a mechanism for their dysregulation remains unknown. Global expression profiling of miRNAs via microarray in healthy versus atherosclerotic murine aorta displayed an overall 30% reduction of miRNA abundance in atherosclerosis. We observed a decrease in Dicer, a key enzyme for miRNA biogenesis, in atherosclerosis. In accordance with this finding, we observed an accumulation in the Dicer substrate precursor-miRNAs despite a decrease in mature levels. Surprisingly, we found Dicer expression in healthy mice to be basally lower in atheroprone areas of the vasculature. Therefore, we propose that global regulation of miRNAs via Dicer deficiency is an important facet of atherogenesis, and desuppression of atherogenic transcription factors such as Runx2 via downregulation of miR-133 in disease.

Keywords: atherosclerosis
Dicer
hemodynamic
miRNA
post-transcriptional regulation
Advisor: Marsden, Philip A
ALC Populations in Ontario – A Data Driven Approach to Targeted Policy Design for Specific Patient Populations using a Time-variant State Space Model

Hospital overcrowding is a major policy issue across Ontario, Canada. Nearly 15% of all acute care hospital bed-days were used by ALC patients between April-2012 and April-2017. Patient level data on all patients in Ontario with at least one ALC day during the study window was made available by the MOHLTC. A whole system model is proposed and can used to test the impact of policies on demand for included services, while accounting for the multidimensionality of the ALC problem. A policy where 15% of patients, who would otherwise await placement in ALC to a LTCH, are discharged to community care was found to unblock 100 acute care beds at peak. A second policy examined the changes to service use patterns if ALC patients with dementia and delirium were discharged at twice the current rate, to find that between 200-250 beds would be released.

Keywords: ALC
Advisor: Carter, Michael
Pain Sensitivity is Associated with Moral Judgment

Moral psychologists often identify harm perception as a core consideration in moral deliberation. Since pain tends to be a ubiquitous form of harm, pain experiences are likely to activate cognitive harm templates. We examined whether pain sensitivity was associated with individual differences in moral judgement. In Study 1, higher pain sensitivity was positively associated with greater perceived relevance of binding foundations and greater support of all moral foundations. Pain sensitivity predicted greater condemnation of moral transgressions involving binding foundations and greater approval of utilitarian behaviour on moral dilemmas. However, it was unclear whether this effect on moral dilemmas was driven by salience, utilitarian content, or goal-oriented language. Study 2 manipulated question wording in dilemmas without changing details of dilemmas themselves. Participants with higher pain sensitivity indicted higher approval of the behaviours described in moral dilemmas regardless of question wording, suggesting that salience, not utilitarian content, was driving these results.

Keywords: Moral Beliefs
Moral Judgements
Pain Sensitivity
Advisor: Lee, Spike S. W.
Automated Localization of Breast Ductal Carcinoma in Situ in Whole Slide Images

Duct segmentation in whole slide images (WSIs) is an important step needed to analyze breast ductal carcinoma in-situ (DCIS), an early form of breast cancer. Here, we trained several U-Net architectures – deep convolutional neural networks designed to output probability maps – to segment DCIS in WSIs and validate the optimal patch field of view necessary to achieve superior accuracy at the slide-level. A U-Net trained at 5x achieved the best test results (DSC = 0.771, F1 = 0.601), implying the U-Net benefits from seeing wider contextual information. A custom U-Net based architecture, trained to incorporate patches from all available resolutions, achieved test results of DSC = 0.759 (F1 = 0.682), showing improvement in the model’s duct detecting capabilities. Both architectures showed comparable performance to a second expert annotator on an independent test set. This is preliminary work for a pipeline targeted at predicting recurrence risk in DCIS patients.

Keywords: DCIS
Digital pathology
Machine learning
Segmentation
Advisor: Martel, Anne L
Effects of and Mitigation Strategies for Fast Voltage Transients on Current and Future FPGAs

As FPGAs grow in size and speed, so too does their power consumption. Power reduction techniques such as dynamic voltage scaling and clock gating can potentially be applied to FPGAs, however, it is unclear whether they are safe in the presence of fast voltage transients caused by large changes in on-chip signal activity. We measure the impact transients have on applications and present a mitigation strategy to prevent them from causing timing failures. We create transient generators that can significantly reduce an application's measured maximum frequency, by up to 25%. We also show that transients are very fast and hence transient mitigation must occur within the same clock cycle as the transient. We create a clock edge suppressor that detects a transient event and delays the next clock edge to prevent timing failure. Additionally, we present new architectures that would make future FPGAs more robust to voltage transients.

Advisor: Betz, Vaughn