VictorJuiz/thesis huggingface dataset:
Privation of Inclusion, Cordon Minoritaire and Racist Oppression in the Public Sector: A Hermeneutic Exploration of the Ugly Side of Beautiful British Columbia

This dissertation offers a hermeneutic exploration of racialized employees’ lived experiences with racial discrimination at publicly funded places of employment in British Columbia, Canada. Presented in three-paper format, the first article, Self-Identifications and Perceptions of a Phantasm through the Looking-Glass: Tracing Race in Embodied Perceptions, presents a critical illustration of the multitude of ways in which race, as a putative classificatory construct, is phantomic. This paper, through explicating the multifaceted range of meanings produced about race, will also engage in an examination of embodied perceptions of race in these varied and painful articulations. The second paper, Privation of inclusion: An exploration of racialized public servants’ experiences with sabotaged recruitment processes in BC, offers an examination of privation of inclusion at work. Taking the position that the dualistic inclusion-exclusion paradigm fails to capture participants’ lived realities with inclusive exclusions and exclusive inclusions, this article presents privative inclusion as a third space between inclusion and exclusion as a more robust framework for understanding how participants were marked and targeted for differential treatment. The third paper, The body, the stranger and cordon minoritaire: An exploration of racialized civil servants’ lived experiences with contained mobility at work, offers an examination of a particular manifestation of racial discrimination: that of quarantine-like containment of mobility at work. Examining undue restrictions and mobility limitations imposed on participants, this article will use three metaphors – stranger for racialized individuals, body for workplaces and cordon minoritaire as the process of containing the mobility of strangers within the body. Cordon minoritaire is presented as a novel analytical framework to illustrate the ways in which racialized workers’ professional freedoms and career mobilities were restricted in order to quarantine White ecosystems of employment. Consequently, cordon minoritaire machinations created perniciously unequal conditions and fundamentally unjust treatments – depravities that are at odds with whimsical notions of Canada as tolerant, multicultural and morally superior to its neighbour south of the border, the United States of America. Ultimately, and collectively, the three papers included in this dissertation offer nuanced and detailed accounts of microprocesses that perpetrated and perpetuated racial oppression at work, in the BC public sector.

Keywords: Canada
discrimination
employment
public service
racial discrimination
racism
Advisor: Williams, Charmaine C.
Organotellurium Probes for Mass Cytometry

Cellular heterogeneity presents one of the most fundamental challenges in our ability to study health and disease. While the existence of cell-to-cell variation in cell systems and tissues has been acknowledged for a long time now, the characterization of cell phenotypes and their biological functions has been limited. One of the most well-established single-cell techniques is mass cytometry (MC)– a technology where multiple cellular biomarkers are measured simultaneously with heavy metal-labelled antibodies in a high-throughput fashion. Equipped with single mass unit resolution, MC allows quantitative single-cell analysis of more than 45 parameters in parallel. In addition, Imaging Mass Cytometry (IMC™️) has been developed to utilize the same metal-tagged probes used in MC for biomarker quantitation in tissue sections with subcellular resolution. Tellurium-based reporters have emerged one of the most important and diverse categories of MC and IMC™️ probes. Specifically, tellurophenes are stable, biocompatible scaffolds that successfully leverage the polyisotopic nature of tellurium, enabling measurements of dynamic cellular states previously inaccessible with traditional MC reagents. This thesis explores three new applications of tellurophene-based reporters in MC and IMC™️. First, a polymeric tellurophene construct was synthesized for the purposes of increasing the parametrization of single-cell suspension MC assays. Antibodies tagged with tellurophene-bearing polymers identified cells expressing the targeted antigen while an isotopically enriched mass tag was prepared for multiplexed immunoassays. Second, a tellurophene-based reagent was developed for immunostaining of low abundance antigens in tissue sections with IMC™️. The staining agent was compatible with alkaline phosphatase-conjugated antibodies allowing robust, sensitive detection of low expression biomarkers via enzymatic amplification. Overall, the staining method complemented IMC™️ workflows and was an improvement over contemporary methods. Finally, tellurophenes are also known to function as effective biomimetics of small aromatic rings. This property was exploited to synthetically incorporate a MC reporter in a clinically approved therapeutic (teniposide). The tellurium labelled derivative exhibited similar inhibitory and cytotoxicity activities to the cognate drug in vitro. MC analysis of drug-treated cells allowed monitoring of cellular uptake. The ability to visualize tissue distribution and cellular accumulation of drug with IMC™️ was assessed in a human pancreatic cancer xenograft model.

Keywords: mass cytometry
single-cell
tellurium
Advisor: Nitz, Mark
Characterizing the Shear Stress-mediated Identity of hiPSC-derived Endothelial Cells

Human induced pluripotent stem cell-derived endothelial cells (iPSC-ECs) are a promising endothelial cell (EC) source for vascular therapy. They are especially alluring for applications where niche EC types are desired as their lack of tissue-specific maturation may lend plasticity that allows for specification towards distinct endothelial subtypes. Although shear is a crucial component of functional endothelium, few studies have examined the response of iPSC-ECs to shear stress or its impact on iPSC-EC identity. To assess the suitability of iPSC-ECs for tissue engineering applications, this thesis investigated the effects of physiologically-relevant fluid shear conditioning on a commercially available iPSC-EC source; the work herein focused on endothelial properties relevant to the generation of a vascular bypass graft, namely arterial-venous identity, shear sensing, barrier function, and inflammation. The iPSC-ECs were evaluated against similarly conditioned mature endothelial benchmarks and overall presented as more arterial than the mature arterial and venous EC controls in vitro; however, both steady and pulsatile shear conditioning prompted a shift towards venous identity relative to static culture. Pathway analysis from RNA-sequencing of the sheared iPSC-ECs revealed dysregulation of several genes involved in arterial specification processes, although the mechanism(s) driving venous identity with shear remain unclear. Using mature ECs as benchmarks, potential deficiencies in gene expression patterns of endothelial shear sensing elements were identified; validation studies assessing protein expression revealed impaired phosphorylation of junctional mechanosensors. Expression patterns of tight junctions, gap junctions, and adherens junctions as measures of endothelial barrier function, as well as genes related to inflammation were also found to be differentially expressed in the iPSC-ECs compared to mature EC benchmarks. Ultimately, although the iPSC-ECs showed some similarity to the mature EC controls, they did not completely align with any one endothelial benchmark for the metrics assessed in this work. These findings enable us to better define iPSC-EC identity, situate the cells among mature EC cultures, and inform potential applications within tissue engineering involving exposure to fluid flow.

Keywords: arterial-venous specification
endothelial cell
induced pluripotent stem cell (iPSC)
RNA sequencing
shear stress
vascular tissue engineering
Advisor: Simmons, Craig A
Santerre, J Paul
Assessment of the Integrity of Fish Communities In The Great Lakes Area: A Bayesian Perspective

The Great Lakes are a well recognized national ecological feature and are a prized natural resource. As a basin as well as individual water bodies, the Great Lakes have undergone significant environmental changes. Fish communities have been impacted significantly by these environmental changes. As a result, the main aim of this thesis is to assess the overall state and integrity of fish communities across the Canadian portion of the Great Lakes. This was done by applying novel Bayesian modeling techniques to evaluate the spatio-temporal trends of mercury and polychlorinated biphenyls (PCBs), well-known global legacy contaminants, in several fish species across all of the Canadian Great Lakes. Another goal was to identify contamination “hot spots” and create consumption advisories across all four major water bodies. Furthermore, this study assesses the rate of tumour occurrence in areas of concern (AOCs) and proposes a cohesive framework to determine tumour rates across these heavily polluted regions. Lastly, this study makes use of the Hamilton Harbour as a case study to propose and implement a probabilistic framework which aims to determine the state of a system based on current data and knowledge that could be used towards environmental policy and management decisions. The main achievement of this research is to provide a very thorough interdisciplinary analysis of the aquatic environment of the Great Lakes, by evaluating the ecosystem’s history, chemistry and biology. The Bayesian methodology applied in this research accounts for environmental uncertainty. Rather than using uncertainty as an excuse to not give answers, the models implemented make use of uncertainty to formulate risks in an informative way that can be used in a management practice (fish contamination, fish tumours, eutrophication etc). The Great Lakes are interconnected to one another, while also being distinct ecosystem regions and although their current state and the state of the fish communities has improved significantly over the past forty years, further research and monitoring should be implemented to adapt and match changing future scenarios.

Advisor: Arhonditsis, George GA
Automatic Tumour Typing based on Patterns of Somatic Passenger Mutations

In cancer, a tumour’s cell of origin is the strongest determinant of its clinical behaviour. While cell of origin is typically clear at the time of diagnosis, 3-5% of cancer patients present with a metastatic tumour and no obvious corresponding primary tumour. Despite advances in molecular testing, imaging, and pathology, the primary tumour site cannot be inferred in the majority of these cases. Recent large- scale analysis of cancer genomes has uncovered strong associations between cancer type and somatic mutations, prompting the use of somatic mutations as a tool for identifying cancer type. While existing approaches have attempted to use cancer-associated mutations, which may be more common in specific cancer types to infer the primary tumour type from the metastatic tissue, these methods have had only limited success. A more promising alternative is to use the association between patterns of somatic passenger mutations and cancer type, by exploiting the relationships between both regional mutation density and cancer type, and mutational processes and cancer type. Somatic point mutations accu- mulate in regions of closed chromatin, and so mutation density provides information about chromatin state, which in turn offers hints about the underlying cell type. As some mutational processes are highly cell-type specific, mutational processes also provide clues about cancer type. In this thesis, I describe a number of deep learning systems for automatic tumour typing based on patterns of somatic passenger mutations. I then address challenges for translating the classifier into clinical scenarios through the use of multiple algorithmic improvements. First, I make use of modern advancements in deep learning to extend the classifier to accurately discriminate between 29 cancer types. I then use a number of sta- tistical methods for assessing the uncertainty in the model’s predictions, and for improving uncertainty quantification. Finally, I make use of information theoretic metrics to use the model’s predictive uncer- tainty to automatically detect cancer samples that come from rare cancer types that the model was not trained to classify. These studies demonstrate the utility of passenger mutations as a tool for identifying cancer type, and address challenges for translating the deep learning classifier into clinical settings.

Keywords: Cancer diagnosis
Chromatin
Deep learning
Somatic mutations
Uncertainty estimation
Advisor: Morris, Quaid D
Imaging Nociceptin Receptor Expression in Cannabis Use and Psychosis using Positron Emission Tomography with the radioligand [11C]NOP-1A

Nociceptin/orphanin FQ (N/OFQ) is a neuropeptide transmitter in the brain that can suppress neurotransmitter release, including dopamine and glutamate. Therefore, dysregulation of nociceptin opioid peptide receptor (NOPr) signaling can result in neurotransmitter imbalance, suggesting its putative role in substance use disorder and psychosis. Furthermore, N/OFQ has been demonstrated to be involved in the brain’s stress response and in cognitive function. This study presents the first investigation of NOPr in these diseases using the highly specific ligand [11C]NOP-1A and positron emission tomography (PET). Study participants with long-term cannabis use and diagnosed as Clinical High Risk (CHR) and First Episode Psychosis (FEP) were included in the present work. The target regions of interest (ROI) include hippocampus, striatum, medial prefrontal cortex and dorsolateral prefrontal cortex. [11C]NOP-1A binding in the clinical groups was not significantly different compared to healthy volunteers. Cannabis users did not differ in [11C]NOP-1A binding from healthy volunteers and there were no significant group by ROI interactions. [11C]NOP-1A binding was not significantly different between FEP and healthy volunteers with no significant group by ROI interaction. [11C]NOP-1A binding was not significantly different between CHR and healthy volunteers with no significant group by ROI interaction. Interestingly, [11C]NOP-1A binding was associated with cognition in healthy volunteers. We report an interaction between group and immediate and delayed memory scores, such that as memory score increases, [11C]NOP-1A binding in the healthy volunteers decreases. This finding is line with preclinical animal studies that demonstrate N/OFQ agonist treatment or NOPr activation inhibits working memory abilities. In addition, [11C]NOP-1A binding is associated with self-reported stress in cannabis users and CHR. We report an interaction between group and chronic stress such that as stress score increases, [11C]NOP-1A binding in the cannabis users and CHR decreases, but increases in HV. This finding is line with studies that have demonstrated that stress mobilizes the nociceptin receptor system. Our results suggest that cannabis users and CHR patients, which are known to have abnormal stress responses, are unable to upregulate NOPr to counteract stress. Therefore, this may suggest NOPr as a novel target for interventions in these populations.

Keywords: Cannabis Use
Nociceptin
PET Imaging
Psychosis
Advisor: Mizrahi, Romina
Examining Associations between Sociodemographic, Behavioural, Environmental, Risk Determinants and Multimorbidity

Multimorbidity, defined as having 2 or more chronic conditions, is a global phenomenon with high prevalence in Canada and the province of Ontario. Multimorbidity has been associated with various social, health and economic costs. While research has been conducted determining key indicators and their associations with multimorbidity; studies using a comprehensive list of determinants, including environmental factors have been far fewer. The overall aim of this thesis was to evaluate potential relationships between sociodemographic, lifestyle behavioural, environmental determinants, and risk conditions, identified by the Chronic Disease Indicator Framework. The first study examined the association between various dimensions of marginalization and multimorbidity. The second study examined multiple indicator variables and their associations with multimorbidity and healthcare utilization costs. The third study examined neighbourhood walkability as part of the built environment, and impact of various exposures, in a time to event analysis (becoming multimorbid) for a period of 16 years. Study findings suggest that nearly a third of the Ontario population are multimorbid. Of the four dimensions identified by the Ontario Marginalization Index, material deprivation was highly correlated with multimorbidity and higher cost chronic conditions. Out of all determinant variables, age, self-perceived health, body mass index and income, were significantly associated with multimorbidity and showed the largest magnitudes. Cost of care has risen by 21% during the study period, with greater morbidity, number of conditions, and healthcare utilization costs, associated with the lowest income populations. There was an observed relationship between most walkable neighbourhoods and lower body mass index. The least walkable neighbourhoods had significantly higher risk for multimorbidity. The high-risk approach currently adopted by the health establishment, which targets patients with health risks and markers for future illness, has not been effective at slowing multimorbidity in the population. A more progressive population strategy is needed, that features more radical measures of prevention to help reduce the rise in chronic illness across the life course. The built environment may be a valuable part of a wider prevention strategy. Walkable neighbourhoods that promote greater physical activity may aid in prevention, by reducing obesity at the population level to reduce incidence of multimorbidity.

Keywords: Built environment
Chronic disease
Multimorbidity
Physical activity
Advisor: Upshur, Ross
The Role of Episodic Memory and Simulation in Judgments Concerning Prosociality

How do our memories and imaginations influence our social behaviour? How do they contribute to our sense of identity? The present work addresses these questions in three sets of studies. The recollection of specific past events (episodic memory) and the vivid imagining of hypothetical scenarios (episodic simulation) are strongly related and rely on a brain network including the medial temporal lobe (MTL) as one of its critical nodes. Research shows that episodic simulation influences various forms of decision-making. The present work extends this research to populations and paradigms yet to be investigated. In the first set of studies, we extend a paradigm in which episodic simulation has been found to increase prosocial intentions in healthy, young adults, by testing older adults and individuals with MTL resections. Since these populations are known to imagine (and remember) events less vividly, we predicted, and found, that their prosocial intentions are less affected by episodic simulation. In the second set of studies, we predicted that episodic simulation would influence behaviour in an economic game, and found that it can both increase and reduce cooperative behaviour. In the third set of studies, we explored whether people’s ratings of their own trait empathy would be affected by the retrieval of behaviourally relevant episodic memories while filling out a questionnaire. We tested healthy,young adults, as well as older adults and individuals with MTL resections. As predicted, we found that episodic memory affected self-reported trait empathy in young and neurologically healthy adults, but not in the other groups. Taken together, our findings suggest that episodic memory and simulation may amplify judgments pertaining to self-knowledge and social behaviour, at least for young, neurologically healthy adults. As older adults and people with MTL damage may rely more on brain regions mediating conceptual knowledge (semantic memory) to make such judgments, future work should examine whether changes in functional connectivity are associated with the altered relationship between episodic processes and social judgments in these populations. Finally, our work suggests that episodic memory and simulation should be taken into greater account in research and theory development on prosocial behaviour and personality measurement.

Keywords: empathy
episodic memory
hippocampus
imagination
medial temporal lobe
prosocial behaviour
Advisor: Moscovitch, Morris
McAndrews, Mary Pat
The Role of Large-amplitude, Basin-scale Internal Waves in Driving Physical Processes that Influence Water Quality and Biological Responses in Medium to Large Stratified Lakes and Harbours

Most large, deep lakes stratify, allowing internal waves to develop in the interior. The distribution of water-quality constituents are strongly influenced by internal waves in these systems. When changes in water-quality parameters, such as temperature and dissolved oxygen, negatively impact fishes and other aquatic organisms, they must respond, or suffer the adverse consequences. Using field observations and 3D hydrodynamic modelling, this research addresses three important aspects of how large-amplitude internal waves at the thermocline drive physical processes and influence biological responses in stratified lakes. Firstly, I demonstrate how large-amplitude internal waves in a deep, narrow embayment produce a pumping mechanism, driving exchange with the main basin. I further show how Coriolis forces drive a residual circulation, enhancing exchange rates. The combined exchange processes effectively flush the embayment much faster than hydraulic flushing from tributaries alone. These exchange processes are relevant for determining the dynamics of water-quality parameters used as indicators to evaluate lake health and fish habitat. Secondly, I illustrate how basin morphometry and wind direction can structure the internal wave field and internal swash zone of an enclosed basin. As the thermocline sloshes along the sloping lakebed, it produces an internal swash zone of high temperature and dissolved oxygen variability. Consequently, upwellings of the hypoxic hypolimnion result in frequent hypoxic events through the internal swash zone, reducing availability of preferred habitat for hypoxia-intolerant species. Due to basin morphometry and wind direction influences on internal swash zone structure, these effects are greatest at the mild-sloping, narrow, upwind end of the basin. Finally, I observed that large-amplitude internal waves impact the nighttime distribution of coldwater pelagic fishes in a stratified embayment. When their preferred temperature range coincides with the thermocline, the rise and fall of internal waves alters the location and availability of preferred thermal habitat. I observed the upper bound of the fishes’ depth varied in concert with vertical thermocline oscillations, suggesting fishes respond to changes in their physical environment to remain within their preferred thermal habitat. These findings emphasize the need to account for internal waves when interpreting and designing fisheries surveys, as thermocline movements can influence fishes’ distribution.

Keywords: Environmental fluid dynamics
Environmental water quality
Internal swash zone
Internal waves
Lakes
Advisor: Wells, Mathew G