VictorJuiz/thesis huggingface dataset:
Characterization of the E3 Ubiquitin ligase EEL-1 in DNA Damage-induced Germ Line Apoptosis in C. elegans

E3 ubiquitin ligases are important regulators of several cellular processes, including apoptosis. To determine the extent to which E3 ligases regulate DNA damage-induced apoptotic signalling in C. elegans, a high-throughput RNAi screen was performed in our laboratory. We identified the E3 ubiquitin ligase EEL-1 as a positive regulator of DNA damage-induced germ cell apoptosis. ARF-BP1, the mammalian EEL-1 ortholog, negatively regulates both the tumour suppressor protein p53 and the anti-apoptotic protein Mcl-1. In C. elegans, we found that eel-1 regulates DNA damage-induced germ cell apoptosis by a mechanism downstream of cep-1/p53 and upstream of ced-9/mcl-1. My results show that unlike ARF-BP1, EEL-1 does not regulate CED-9/Mcl-1 protein levels, suggesting a novel mechanism of apoptosis regulation in C. elegans for this E3 ligase. Unexpectedly, eel-1 causes synthetic sterility in ced-9 loss-of-function mutants that is suppressed by ablation of the Apaf-1 orthologue ced-4, suggesting an additional role for these genes in oogenesis.

Keywords: C. elegans
apoptosis
E3 ubiquitin ligases
Advisor: Derry, Brent
Describing and Assessing the Views of Transplant Professionals in Ontario about Directed Organ Donations from Deceased Donors: A Qualitative Study

In Ontario, the organs of deceased donors are usually allocated to those recipients who are ranked highest on the province’s waiting list for transplant surgery. However, on rare occasion, a donor, or the donor’s family, will request that an organ be given to a designated recipient or designated group of recipients. The ethical acceptability of these so-called “directed donations” of organs from deceased donors is debated in the transplant literature. The purpose of this study was to elicit the views of a group of transplant professionals in Ontario on the question, “Under what circumstances, if any, should a donor or the donor’s family be allowed to choose the recipient of the organ?” Qualitative in-depth interviews were conducted with 14 Ontario transplant professionals from a range of clinical disciplines. An analysis of these interviews revealed several practical and ethical considerations that the transplant professionals believed to be important in assessing the acceptability of directed donations.

Keywords: directed donation
organ donation
qualitative
bioethics
Advisor: Secker, Barbara L.
From Opposition to Government: Continuities and Ruptures in Discourses and Practices in Local Democracy

This inquiry examines the ruptures and continuities in local democratic practices in opposition and in government. I conducted research in seven rural municipalities in Chalatenango, El Salvador where leaders of oppositional community-based organizations entered municipal politics 15 years ago. This new generation of municipal officials established forums for citizen participation that incorporate patterns of citizenship learning and participation developed in oppositional civil society. The democratic outcomes of these municipal spaces for citizen engagement are mixed, however: they improved the quality of citizen participation in municipal governance, but circumscribed autonomous forms of citizen participation. The influence of partisan political and institutional state interests are the principal factors that account for this outcome. At the same time, civil society and local government in Chalatenango exist in a relationship of mutual influence. This suggests that efforts to foster democratic citizen participation should complement support to institutional innovation with efforts to strengthen civil society.

Keywords: El Salvador
local democracy
Advisor: Schugurensky, Daniel
Dietary Patterns and Incident Type 2 Diabetes mellitus in an Aboriginal Canadian Population

Type 2 diabetes (T2DM) is a growing concern worldwide, particularly among Aboriginal Canadians. Diet has been associated with diabetes risk, and dietary pattern analysis (DPA) provides a method in which whole dietary patterns may be explored in relation to disease. Factor analysis (FA) and reduced rank regression (RRR) of data from the Sandy Lake Health and Diabetes Project identified patterns associated with incident T2DM at follow-up. A RRR-derived pattern characterized by tea, hot cereal, and peas, and low intake of high-sugar foods and beef was positively associated with diabetes; however, the relationship was attenuated with adjustment for age and other covariates. A FA-derived pattern characterized by processed foods was positively associated with incident T2DM in a multivariate model (OR=1.38; CIs: 1.02, 1.86 per unit), suggesting intake of processed foods may predict T2DM risk.

Keywords: Type 2 Diabetes
Aboriginal Canadian
Dietary Patterns
Factor Analysis
Reduced Rank Regression
Advisor: Hanley, Anthony James Gordon
Transformation of Muscle Architecture at the Fiber Bundle Level to Fit Parametric B-spline Volumes: Extensor carpi radialis brevis and longus

Most models of the musculoskeletal system incorporate individual or groups of muscles as a series of line segments, assuming all fiber bundles within a muscle have the same length and moment arm, and do not account for architectural differences throughout the muscle volume. The purpose was to develop an algorithm to fit digitized fiber bundle data from one specimen into muscle volume and intramuscular nerve distribution data from seven other specimens of extensor carpi radialis longus (ECRL) and brevis (ECRB). Coherent Point Drift (CPD) algorithm was successfully adapted for this purpose. The intramuscular nerve distribution and fiber bundle architecture was modeled in all the muscle volumes. ECRL was found to have two neuromuscular compartments, superficial and deep, while ECRB was found to have two, three or four, in a proximal to distal direction depending on the number of primary nerve branches.

Keywords: muscle architecture
fitting
fiber bundle architecture
modeling
Advisor: Agur, Anne M. R.
Vascular Endothelial Growth Factor Functionalized Agarose Can Efficiently Guide Pluripotent Stem Cell Aggregates Toward Blood Progenitor Cells

Embryonic stem cells (ESCs) are derived from the inner cell mass (ICM) of the embryo that have great potential for regenerative therapies because of their ability to self-renew and differentiate into almost all cell types. However, this developmental potential is influenced by the local cellular microenvironment, including cell surface bound ligands. In this study, we synthesized an artificial stem cell niche wherein vascular endothelial growth factor A (VEGFA) was functionally immobilized in an agarose hydrogel. Immobilized VEGFA treatments were able to upregulate mesodermal markers, brachyury and VEGF receptor 2, by day 4 and were CD34+CD41+ by day seven. Subsequently, VEGFA immobilized treatments were able to generate colony forming cells by day fourteen. This work demonstrates our ability to use functionalized hydrogels to guide ESCs toward blood progenitor cells and serves as a useful tool to replicate aspects of the embryonic microenvironment.

Keywords: Agarose
Hydrogel
Embryoid Bodies
VEGFA
Blood Progenitor Cells
3D
Differentiation
Serum-Free
Advisor: Shoichet, Molly
Zandstra, Peter W.
Assessing the Hydraulic Transient Performance of Water and Wastewater Systems Using Field and Numerical Modeling Data

A large proportion of water and wastewater systems have traditionally been analyzed and designed without the consideration of the nature, risk, and potential consequence of hydraulic transients. Recent advancements in numerical hydraulic modeling have spawned a specialty hydraulic field based on numerical transient analysis. The current practice within this field often lacks physical understanding and can be misguided by both the current knowledge, technology based limitations, and by the sole reliance on numerical models. This thesis aims to provide insights into some of the shortcomings of current practice and to develop the importance and application of field data based confirmations. The thesis examines the advances in the current field oriented technology for recording transient pressures, and provides examples and insights on how this data can be used both in conjunction with numerical modeling and on its own as a first step to a proposed frequency based transient risk assessment methodology. The thesis establishes definitions and a preliminary methodology for a Transient Risk Index.

Keywords: hydraulic transients
numerical modeling
Advisor: Karney, Bryan William
The Role and Regulation of Factor Inhibiting HIF (FIH) in Normal and Pathological Human Placentae

Factor inhibiting HIF (FIH) negatively regulates hypoxia inducible factor-1 (HIF-1) transcriptional activity, selectively controlling certain HIF-1 target genes, such as vascular endothelial growth factor (VEGF) and prolyl hydroxylase domain 3 (PHD3), but not others. PHD3 and VEGF are important for placental development and function and are overexpressed in preeclampsia (PE). The purpose of this study was to examine FIH in both normal and pathological human placentae. I hypothesized that FIH regulates VEGF and PHD3 in the placenta and that this rheostat is altered in PE. Results show that FIH suppresses PHD3 and VEGF in JEG-3 cells; this effect was abrogated by FIH gene silencing. Moreover, my data indicate that seven in absentia homologue-1 (Siah-1) targets FIH for degradation in the placenta; this degradation is enhanced in PE and likely contributes to aberrant VEGF and PHD3 expression. Overall, my data suggest an important role for FIH in the pathogenesis of PE.

Keywords: Placenta
Preeclampsia
Hypoxia Inducible Factor (HIF)
Factor Inhibiting HIF (FIH)
Advisor: Caniggia, Isabella
Carrying on with Living: The Impact of Pulmonary Rehabilitation on the Health Behaviour of Older Adults with Chronic Obstructive Pulmonary Disease

Introduction: This study explored the health behaviour of older adults with COPD. Objectives included: 1) to explore the process of successfully managing COPD; 2) to identify health behaviour strategies utilized; 3) to identify factors influencing health behaviour change; 4) to understand the impact of pulmonary rehabilitation (PR). Methods: Eleven community-dwelling older adults were interviewed following PR. Interviews were coded and analyzed using constant comparative analysis, comparing and contrasting incoming data with emerging theory. Findings: Two distinct models were developed representing participants’ experience with COPD and health behaviour change: Struggling with Living: Life with COPD before Pulmonary Rehabilitation; and Carrying on with Living: Life with COPD following Pulmonary Rehabilitation. Conclusions: Older adults with COPD engaged in a limited repertoire of health behaviour strategies which were relatively ineffectual prior to participation in PR. PR had a major impact on health behaviour strategies, and on the external and personal factors influencing health behaviour.

Keywords: COPD
health behaviour
pulmonary rehabilitation
older adult
Advisor: Cott, Cheryl
A Novel Approach to Ambulatory Monitoring: An Investigation into Everyday Walking Activity in Patients With Sub-acute Stroke

Walking is an essential task important to recovery after stroke. However, there is a limited understanding regarding the characteristics of walking in in-patients with stroke. The objectives of this thesis were to: 1) develop an instrument capable of acquiring temporal characteristics of everyday walking; 2) investigate the quantity and control of everyday walking; and 3) profile the task-specific link between walking and cardiorespiratory response. In study 1 we developed and validated a wireless monitoring system (ABLE system). Study 2 revealed low quantities of everyday walking (4816 steps; SD 3247) characterized by short bout durations (59.8s; SD 23.4) and asymmetric walking. In study 3 we observed a modest task-related response in HR(19.4% HRR); however, the intensity and duration of everyday walking did not approach the guidelines for aerobic benefit. Monitoring in-patient walking can help guide clinical decision making in developing methods to maximize recovery after stroke.

Keywords: stroke
ambulatory monitoring
accelerometry
gait asymmetry
Advisor: McIlroy, William E.
Recombinant HBsAg Vaccine in Persons with HIV: Is Seroconversion Sufficient for Long-term Protection?

The recombinant Hepatitis B surface antigen vaccine inadequately protects those living with HIV from Hepatitis B virus infection. This study utilized saved serum samples from a retrospective cohort of persons with HIV and documented vaccine-induced HBsAb seroconversion to determine factors associated with persistence of protective levels of HBsAb (≥10mIU/ml). HBsAb levels fell below 10mIU/ml in 27% of the cohort after a median follow-up of 43 months. HIV viral load suppression (<50copies/ml) at the time of vaccination was the major factor associated with persistence of protective levels of HBsAb (OR 3.83, p <0.01). Among individuals who lost protective levels of HBsAb, booster doses of vaccine re-instated the development of protective levels of HBsAb. Delaying or repeating HBV vaccination until after suppression of HIV viral load is achieved should be considered HBV antibody levels should be followed over time and boosters given with loss of protective levels of HBsAb.

Keywords: HIV
Hepatitis B Virus
Vaccination
Immunity
Advisor: Walmsley, Sharon
Using a Financial Model to Determine Technical Objectives for Organic Solar Cells

Organic solar cells (OSCs) are of interest because the technology offers a significant opportunity to reduce the overall costs of solar energy. OSCs can be very inexpensive to produce given that they rely on non-commodity materials and can use existing manufacturing techniques that are not labour- and capital-intensive. In this research, a financial model, named TEEOS (Technological and Economic Evaluator for Organic Solar), is developed and is used to determine financial indicators, such as simple payback period. These indicators are used to determine technical objectives for the OSCs. Two sample cells are evaluated in Toronto, Canada using historical data. The results show that the cell with a higher efficiency and wider absorptive wavelength range produces a payback period of approximately nine years, while the other cell has a payback period well over 45 years. Stochastic modeling techniques are also used to better replicate electricity price and weather fluctuations.

Keywords: Solar Energy
Organic Solar Cells
Payback Period
Toronto
Net Present Value
Advisor: Lawryshyn, Yuri Andrew
Bender, Timothy
The Victimhood of the Powerful: White Jews, Zionism and the Racism of Hegemonic Holocaust Education

This paper focuses on issues of Jewish identity, whiteness and victimhood within hegemonic Holocaust education. I argue that today, Jewish people of European descent enjoy white privilege and are among the most socio-economically advantaged groups in the West. Despite this privilege, the organized Jewish community makes claims about Jewish victimhood that are widely accepted within that community and within popular discourse in the West. I propose that these claims to victimhood are no longer based in a reality of oppression, but continue to be propagated because a victimized Jewish identity can produce certain effects that are beneficial to the organized Jewish community and the Israeli nation-state. I focus on two related Holocaust education projects – the March of the Living and the March of Remembrance and Hope – to show how Jewish victimhood is instrumentalized in ways that obscure Jewish privilege, deny Jewish racism and promote the interests of the Israeli nation-state.

Keywords: Israel
Palestine
Holocaust
Apartheid
Whiteness
Jewish Identity
anti-racism
Zionism
Advisor: Nestel, Sheryl
Seeking a Kaleidoscopic Lens: A Holistic Analysis of the Psychedelic Field

The psychedelic field has generated a vast body of work in terms of psychology, art, spirituality and understandings of the mind and consciousness. Having engaged with the field for the last ten years, I have been curious as to why issues of race, gender and class are not included in the analysis and theories that are generated from the field. My background in feminism, queer studies, anti-racism, critical theory and social justice, as well as my interest in consciousness and psychedelics, led me to conduct a literature review and analyze it with a critical framework. The literature showed an overwhelming gap in the field in regards to inclusion and analysis of issues pertaining to race, gender and class. This gap needs to be addressed and I look forward to conducting fieldwork in the future such as interviewing people about their experiences of race, class and gender and its intersection with psychedelics. I hope to contribute to the field in terms of creatively and productively including an analysis of race, class and gender to the psychedelics field.

Keywords: Psychedelics
Ayahuasca
Critical theory
Hippie
Race
Class
Gender
Tourism
Advisor: Wane, Njoki
Climate Change Impacts on the Molecular-level Carbon Biogeochemistry in Arctic Ecosystems

The goal of this thesis was to characterize and quantify changes to Canadian Arctic organic matter (OM) induced by a physical disruption to the permafrost active layer by employing molecular-level techniques such as biomarker extraction and NMR to help elucidate its contribution to carbon turnover and global climate change. The initial biomarker characterization study determined that the extractable plant lipids were unaltered originating from the deposition of new vascular material or permafrost melt where a high alteration of lignin-derived OM was observed suggesting a long residence time in the ecosystem. Analysis of samples where there was a new and historical physical disruption to the permafrost landscape showed an initial increase in bacterial biomass biomarkers, and was corroborated with increased bacterial protein contributions and peptidoglycan signals in the NMR spectra. It is hypothesized that this increase in bacterial biomass resulted in a faster rate of degradation, possibly leading to OM priming.

Keywords: biogeochemistry
soil organic matter
sedimentary organic matter
biomarkers
gas chromatography-mass spectrometry
nuclear magnetic resoances spectroscopy
Advisor: Simpson, Myrna J.
The Effects of Purine Nucleoside Phosphorylase (PNP) Deficiency on Thymocyte Development

PNP is a crucial enzyme in purine metabolism, and its inherited defects result in severe T-lineage immune deficiency in humans. I hypothesized that PNP deficiency disrupts the development of late CD4-CD8- double negative (DN) thymocytes and induces mitochondrial-mediated apoptosis of CD4+CD8+ double positive (DP) thymocytes. By using PNP-deficient (PNP-/-) mice as well as an OP9-DL1 co-culture system simulating PNP-deficient conditions, I demonstrated that PNP deficiency interferes with the maturation of DN thymocytes at the transition from DN3 to DN4 stage. Although PNP deficiency does not affect the generation or proliferation of DP thymocytes, PNP-/- DP thymocytes were observed to undergo apoptosis at a higher rate. My results suggest that apoptosis is induced through a mitochondrial mediated pathway. Additionally, re-introduction of PNP into PNP-/- thymocytes protected the cells from the toxic effects of deoxyguanosine by preventing the formation of deoxyguanosine triphosphate, indicating that the toxic metabolite in PNP deficiency is deoxyguanosine.

Keywords: Thymocyte development
immune deficiency
purine metabolism
Purine nucleoside phosphorylase
Advisor: Grunebaum, Eyal
Sulphation and Sulphate Decomposition in Roasted Nickel Concentrates

The sulphation and sulphate decomposition occurring during the oxidation of nickel concentrates were studied by thermal analysis. Samples of industrial nickel concentrates were heated in inert gas to temperatures between 400°C and 850°C and oxidized isothermally in air or in a 4%O2-96%N2 mixture. During isothermal oxidation of the concentrates, SO2 evolved from the roasting reactions led to partial formation of metal sulphates. Following the oxidation and sulphation of the sample, the decomposition of the formed sulphates was studied. This was completed either by heating the sulphated sample to 950°C to thermally decompose the sulphates, or by lowering the partial pressure of oxygen while holding the sample at the isothermal oxidation temperature. The sulphation of the sample was found to follow the parabolic rate law, implying diffusion as the rate controlling-step. The thermal decomposition of the sulphates occurred at a near constant rate, implying zero-order kinetics.

Keywords: sulphation
sulphate
nickel concentrate
roasting
sulphate decomposition
nonferrous pyrometallurgy
Advisor: Utigard, Torstein A.
Spaces of Belonging: Filipina LCP Migrants and their Practices of Claiming Spaces of Belonging in Toronto

Much current literature on women and migration tends to approach the study of migrant domestic workers as victims of global capitalism—or according to Parrenas’s evocative phrase as “servants of globalization”—from one of two vantage points. The first vantage point focuses attention on how the conditions of exit in various sending countries make overseas domestic servitude one of the few employment opportunities available for many women (Parrenas 2001). The second draws attention to the ways in which these migrant women experience stratification—along the lines of gender, race, and class—as part of their settlement experiences in their host countries (Pratt 1998). Both of these vantage points reinforce aspects of the “servants of globalization” discourse in that they pay relatively little attention to the coping practices of migrant domestic workers. In order to extend the thesis beyond the “servants of globalization” discourse, this thesis examines the coping practices that migrant Filipina domestic workers develop in their efforts to create communities of affirmation, care, and belonging.

Keywords: International Migration
Live-In Caregiver Program
Global Care Chains
Advisor: Silvey, Rachel
Leslie, Deborah
Predicting Vulnerability of Fishes

Conservation biology would benefit from methods that identify species at risk in a proactive manner, rather than through post-hoc conservation assessments. This study examines the utility of four potential indices for predicting vulnerability in fishes: total body length; trophic level; intrinsic vulnerability score; and, resilience. Statistical analysis was done to determine if correlations existed between any of these four indices and known levels of risk in marine and freshwater Canadian fishes. Results show the success of two of these indices to predict risk: fished species over 78.33 centimeters total length, or with intrinsic vulnerability scores over 57.41 are more highly vulnerable to becoming at risk. Over 20% of Canadian fished species of unknown conservation status are therefore currently vulnerable, and possibly at risk of extinction. This study shows vulnerability indices allow a rapid prioritization of fishes at risk of extinction, and can thus help achieve proactive conservation even in the absence of population decline data.

Keywords: conservation
fishes
Canada
vulnerability
assessment
body size
resilience
trophic level
Advisor: Gross, Mart