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Exploring the link between dioxin exposure and diabetes risk: contributions of the islet aryl hydrocarbon receptor
No full textType 2 diabetes (T2D) is a chronic condition where insulin-secreting pancreatic β-cell mass and function is compromised. Etiology is traditionally linked to genetic predisposition and lifestyle; however, research indicates that exposure(s) to persistent organic pollutants (POPs) also contribute to incidence. Dioxins are particularly noxious POPs that include the widely studied toxicant 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). TCDD exposure activates the xenobiotic metabolism pathway via the aryl hydrocarbon receptor (AHR). In hepatocytes the AHR has been shown to crosstalk with the hypoxia inducible factor 1α (HIF1α) pathway, but AHR-HIF1α crosstalk has not been previously studied in islets. To investigate the connection between dioxin exposure and T2D pathogenesis, my thesis examines both epidemiology and molecular effects of TCDD in islet cell models. In Chapter 1, I conducted a meta-analysis on epidemiology studies examining dioxin exposure and T2D incidence to look for sex-specific associations. I found significant associations between dioxin exposure and T2D for both sexes, and sex-specific associations when I considered mode of exposure. In Chapter 2, I explored whether AHR-HIF1α crosstalk exists in pancreatic islets. I exposed human donor islets and human embryonic stem cell (hESC) derived islets (SC-islets) to TCDD +/- hypoxia and measured gene expression changes associated with both pathways. I found the HIF1α pathway reproducibly dominated the AHR pathway in SC-islets, but crosstalk was more variable in human islet donors. In Chapter 3, I explored the role of the AHR in human pancreas development. First, I investigated when during hESC differentiation does TCDD exposure upregulate genes indicating AHR activation. I found TCDD exposure activates the AHR at the pancreatic progenitor stage of development and onwards. Secondly, I generated, characterized, and validated 3 AHR knock-out (KO) hESC lines to explore if knocking-out the AHR impacts differentiation. Following differentiation all 3 clone lines showed a modest decrease in Glucose-6-phosphatase catalytic subunit 2 (G6PC2) gene expression compared to the parent line. My thesis shows that the AHR pathway is capable of molecular crosstalk in islets and is involved in moderating G6PC2 expression in nascent pancreatic β-cells. Therefore, AHR activation by TCDD impacts pancreatic islet health in multiple ways and requires continued study
Indigenous Canadians take the Stand: The Influence of Age and Race on Mock-Juror Perceptions and Verdict Decisions
No full textThis study examined if race and age interact to influence juror perceptions of eyewitness memory and defendant guilt. Eyewitness age (i.e., 12-vs. 18-years-old), eyewitness race (i.e., Indigenous vs. White), and defendant race (i.e., Indigenous vs. White) were manipulated using a mock-trial transcript. Participants (N= 275) were recruited from psychology courses and Amazon’s Mechanical Turk platform. Contrary to the hypotheses, Indigenous eyewitness testimony resulted in more guilty verdicts, higher guilt ratings, less favourable perceptions of the defendant, and more favourable perceptions of the eyewitness. Mock-jurors were more punitive toward White defendants and held more favourable perceptions of Indigenous defendants. Racial bias scores moderated the relationships between eyewitness race, defendant race, and the interaction of eyewitness-defendant race for verdict decisions and perceptions of trial party members. This research contributes to the understanding of racial bias in juror decision-making research and can be used to inform jury selection and best practices in the Canadian legal system
A Consolidated List of FSM Mutation Operators
No full textMutation analysis is extensively used for the comparison of state-based testing
methods that work from a finite state machine (FSM); It consists in seeding faults in the FSM
model using mutation operators, one fault at a time, executing already constructed test suites
on the correct FSM and the mutated FSMs and comparing executions to identify proportions
of mutants revealed by test suites, a.k.a. the mutation score. Although a common
experimental practice, there is still a lot to discover about FSM mutation operators so that
we can adequately rely on experimental results that employ them, starting with the
identification of a common set of operators. Indeed, published results that rely on FSM
mutants employ a varied, incomplete, and sometimes ill-defined set of operators, making
comparisons of empirical results difficult. In this paper, we report on our effort to coalesce
a complete set of precisely defined operators. The paper also illustrates, with the W method
for test case construction, and several real-world FSMs, how the operators can be used
First observation of solar neutrino absorption on 40Ar using the DEAP-3600 detector
No full textThis work presents the first observation of neutrino absorption interactions on liquid argon. It was performed using data collected with the \DEAP\ detector located at SNOLAB, which is a second generation dark matter direct detection experiment \SI{2}{\kilo\meter} underground. The mass of liquid argon contained in the detector was \SI{3.2}{\tonne} and a total of \SI{849}{\day} of data was collected between 2016 and 2020. To enable this analysis, a measurement of the local muon flux was required to constrain the production of muon-induced backgrounds. The muon flux was measured to be which allowed constraints to be placed on both prompt and delayed muon-induced neutron production. Muon-induced backgrounds are relevant for not only this work but also for analyses searching for low energy nuclear recoils or those that require constraints on neutron radiative captures on detector materials. The search for neutrino interactions resulted in an observation of 5 events with an expectation of 0.32 background events. This allowed the background-only hypothesis to be rejected with a statistical significance of 4.7. Thus, this work is the first strong evidence for neutrino absorption on \textsuperscript{40}Ar using solar electron neutrinos. It is the first direct evidence for neutrino interactions in a dark matter detector
The Climate Dilemma : The Fossil-Fueled Politics of Us vs. Them
No full textThis thesis aims to compare how recent Canadian far-right political parties’ messaging around climate change and fossil fuel extraction compares to that of fossil-fuel industry-associated and citizens’ advocacy groups. Both sets of groups have long been associated with climate denial and delay. While the political parties engaged in significantly more denial of climate science, both groups were committed to a strongly capitalist framework that emphasized our economic competition with other nations and a lack of trust in their sincerity and commitment to climate action. This is presented as amplifying the need to be cautious about taking potentially anti-competitive measures which might undermine Canada’s ability to provide for our citizens through fossil-fueled wealth. Both groups also emphasized that Canada is a world leader in social and environmental factors, achieved to date not primarily through regulation, but through the commitment of the Canadian oil and gas industry to progress
Impact of Time-Dependent Ageing Effects on Geotechnical Properties of Soft Geomaterials
No full textEffective management of deep deposits of clayey tailings and similar soft material hinges on understanding of their consolidation properties. While the large strain consolidation theory is conventionally used, prolonged consolidation process in deep deposits may be influenced by time-dependent effects such as creep and ageing, leading to substantial changes in settlement and density profiles. Ageing increases the undisturbed undrained shear strength and pre-consolidation pressure, can potentially accelerate reclamation efforts, but can reduce the residual shear strength. Despite being evident in soft soils and clayey tailings, the ageing phenomenon remains poorly understood and challenging to predict from any standard geotechnical measurements. This research, therefore, aims to advance the understanding of inherent ageing effects in soft geomaterials. Fine-grained post glacial Eastern Canadian marine Leda clay was used to study the general features of ageing, with findings applied to understand the ageing behaviour in clayey tailings. Ageing effects are quantified using oscillatory rheometry, fall cone shear strength, oedometer tests, and a specialized consolidation apparatus. Experiments conducted on soft Leda clay and treated clayey tailings for more than 100 days revealed consistent trends in undisturbed undrained shear strength and elastic shear modulus development, correlating with concepts from colloidal science literature to identify the rate and magnitude of ageing. In Leda clay samples, across a wide range of water contents (2 to 1.2 x LL) and effective stresses (self-weight to 30 kPa), both the rate and relative increase in shear strength, after the end of primary consolidation (EOP), appear to be relatively constrained. Analysis of data from this study and literature suggested a maximum ageing strength of about five times the strength measured at or near EOP, with the rate of ageing also being fairly constrained for a wide range of soils and clayey tailings. Additionally, the increase in undisturbed undrained shear strength due to ageing correlated with changes in compression behaviour, showing a nearly linear relationship between normalized strength /elastic shear modulus and the yield stress ratio. Moreover, the flocculation conditions favouring ageing over the consolidation process in treated clayey tailings samples were identified through the undisturbed strength development, dewatering behaviour, and floc size
Global Equitable Vaccine Distribution: A Plan for Next Time
No full textThis thesis project argues that we ought to ensure a global equitable distribution of vaccines (GEDV) during a pandemic, using lessons learned from the Covid-19 pandemic. In my first chapter I argue that wealthy nations are the ones most responsible for ensuring GEDV based on their capacity and self-interest in the matter. In my second chapter I explain that wealthy nations stockpiled vaccines for themselves because of their nationalist values that prioritize the health and safety of their own citizens. In my final chapter I propose a hypothesis that we ought to try something different next time a pandemic happens, and I offer a possible solution which I call the efficient altruism principle, which states that wealthy nations ought to ensure GEDV because doing so is within their own self-interest. Achieving herd immunity through vaccination will end the pandemic sooner and, therefore, save more lives and money overall
The Politics of Citizenship as a Durable Solution for Refugees in Tanzania: A Comparative Case Study of Naturalization of the Rwandese Refugees (1980-1995) and Burundian Refugees (2008-2023)
No full textIn 1980, the Government of Tanzania granted citizenship to some 36,000 Rwandese refugees who had been in Tanzania since the early 1960s. Then, in 2008, Tanzania granted citizenship to more than 160,000 Burundian refugees who had been since 1972. Both groups were settled in the northwestern regions of Tanzania. Yet, the experience of these two groups as citizens of Tanzania has been marked with differences, with the former Rwandese refugees seen to have been more successfully integrated into Tanzanian society compared to Burundian refugees. What explains this variation in their experience of being members of the national community? In an attempt to explain such variation, this dissertation situates itself in the interdisciplinary field of refugee and forced migration studies, specifically the literature that considers local integration into a host country as a durable solution for refugees. To address gaps in the literature on the politics of local integration, this dissertation draws on literature from citizenship studies and post-colonial African comparative politics to develop a conceptual framework to explain the variation in experience of these two groups of refugees in Tanzania, thus contributing to the literature on the politics of local integration. Drawing on the results of semi-structured interviews, archival research, observation and content-analysis, this dissertation argues that while both groups have gained permanent legal status in Tanzania, and have therefore been de jure locally integrated, refugees from Rwanda were more successfully integrated compared to Burundian refugees in relation to their inclusion in Tanzanian society. The most prominent factors that explain this variation include: change in political context of naturalization, refugee hosting fatigue, securitization of the Hutu label, and refugee’s relationship between the political centre and periphery of the Tanzanian state. I also argue that with the passage of time, the integration of former refugees from Burundi will be more successful as long as concerted efforts are made by former refugees themselves, the government, and host communities to address the integration challenges identified in this research. Findings from this study are significant for the literature and practice on durable solutions
Uncovering the Limits of Detection of Artificial Intelligence using Synthetic Lesions in Positron Emission Tomography
No full textThe use of artificial intelligence (AI) for detection of lesions has been proposed to aid clinicians in detection tasks. However, before AI can be used clinically, the limits of detection must be studied to characterize AI performance. In this work, a library was constructed containing well-characterized spherical synthetic lesions in real positron emission tomography (PET) and x-ray computed tomography (CT) patient data, which had been previously reported free of lesions by expert physicians. These lesions were manually defined and automatically synthesized using the Lesion Synthesis Toolbox (LST). This library was used to study two FDG PET lesion-detection AI algorithms by their ability to detect lesions by size and intensity metrics, including lesion intensity, contrast, and contrast-to-noise ratio. The work demonstrates the utility of synthetic lesions for characterizing the limits of detection of AI and necessary tools available to other researchers