VictorJuiz/thesis huggingface dataset:
Association Studies of Personality Traits, Problem Gambling, and Serotonergic Gene Polymorphisms

Problem gambling is the subclinical form of pathological gambling and both are characterized by difficulties in the limiting of money and time spent on gambling. Genetic and personality factors have been implicated in gambling disorders (PG). As PG is classified as an impulse-control disorder, the serotonin (5-HT) system has been suggested to be involved. We sought to better understand the complex relationship between personality traits, PG, and 5-HT genes. We investigated ten 5-HT candidate genes for association with PG and personality traits. We also examined personality traits for association with PG. We found that MAOA and HTR3A haplotypes were associated with Agreeableness and Conscientiousness personality domains, PG was associated with high Neuroticism and low Conscientiousness scores, and the MAOA gene may play a role in PG. Our findings contribute to the better understanding of how 5-HT genes may be involved in the neurobiological mechanisms underlying PG and personality.

Keywords: Serotonergic Gene Polymorphisms
Genetics
Problem Gambling
Personality
Advisor: Kennedy, James
Characterizing the Role of Stromal Cell Derived Factor 2 Like-1 (SDF2L1) in Pancreatic β-Cells

Type 2 diabetes is characterized by insulin resistance and pancreatic β-cell failure. Insulin resistance leads to increased insulin demand, which can lead to increased proinsulin misfolding in the endoplasmic reticulum (ER). The accumulation of the misfolded proteins in the ER can cause ER stress, which can lead to pancreatic β-cell dysfunction. Cells respond to ER stress by the unfolded protein response (UPR), which increases protein folding capacity and causes degradation of misfolded proteins. Using a pancreatic β-cell model of induced misfolded proinsulin expression (proinsulin-C96Y tagged with GFP) we discovered that one of the most highly induced genes was stromal cell-derived factor 2 like 1 (SDF2L1). SDF2L1 is an ER localized soluble protein with an as yet unknown function. In this thesis I examined the potential role of SDF2L1 in pancreatic β-cells in ER stress conditions.

Keywords: SDF2L1
ER stress
Advisor: Volchuk, Allen
Role of Intercellular Interactions between Mast Cells and Gingival Fibroblasts in Mediating Inflammation

The mechanisms that mediate acute exacerbations in chronic inflammatory diseases such as periodontitis are not understood. IL-8 is a potent chemoattractant for neutrophils in acute inflammatory lesions. We investigated the role of fibroblast-mast cell interactions on short-term IL-8 release. Human gingival fibroblasts were co-cultured with human mast cells (HMC-1). After co-culture, the concentration of IL-8 was measured by ELISA. HMC co-cultured with fibroblasts increased IL-8 secretion by >6-fold, which required intercellular contact and was blocked by the gap junction inhibitor BGA. Thapsigargin-induced elevations of intracellular calcium increased IL-8 levels by 15-fold. Chemotaxis of human neutrophils was significantly enhanced in response to conditioned medium from co-cultures. Calcein-dye transfer showed intercellular, gap junction communication between HMC and fibroblasts that was dependent in part on β1 integrins. We conclude that mast cells adhere to fibroblasts and promote IL-8 secretion, thereby enhancing neutrophil chemotaxis and possibly the perpetuation of the inflammatory response.

Keywords: mast cell
fibroblast
inflammtion
Advisor: McCulloch, Christopher
Design of Raman Active Phopsholipid Gold Nanoparticles for Plasmonics based Tumour Detection and Imaging

Cancer is the leading cause of death worldwide and one third of its burden can be decreased with early detection. Surface enhanced Raman spectroscopic (SERS) based imaging is a promising new technique for non-invasive detection of tumours due to its ultra-sensitivity and multiplexing capabilities. For in vivo SERS molecular imaging, a biocompatible, robust and targeted nanoparticle is required to attain high sensitivity and specificity. In this thesis, a SERS capable gold nanoparticle was rationally designed by encapsulation with a phospholipid bilayer which conferred biocompatibility, colloidal stability and versatility to changing surface chemistry. Moreover, validation of this SERS probe with a specific targeting ligand for carcinoma cells was studied through the targeting of a commonly overexpressed cancer receptor, epidermal growth factor receptor. Using this phospholipid design, optimizations with differing chemistries, targeting ligand or modifications for additional functionalities can be achieved for further development as a viable in vivo molecular imaging tool.

Keywords: Gold nanoparticles
Surface enhanced Raman spectroscopy
phospholipid
nanoparticle design
cancer imaging
Advisor: Zheng, Gang
Wilson, Brian Campbell
Vehicle Routing Approaches for Solving an Order Cutoff Assignment Problem

We define an order cutoff for a retailer as a time in the day such that orders sent to the depot before this point will be delivered by tomorrow, and orders submitted after will be delivered by the day after tomorrow. The later a retailer’s cutoff, the sooner it receives its orders which helps it to maintain ideal inventory levels. Generally, not all retailers in a supply chain can have the latest cutoff since transportation takes a significant amount of time. This thesis tries to assign optimal order cutoffs to retailers. We call this an order cutoff assignment problem and we solve it using three different mathematical programming approaches. The approaches are exhaustive route generation and selection, a series of mixed integer programs, and branch-and-price. 60 sample problems were solved and results showed that branch-and-price is often the most effective method.

Keywords: distance constrained vehicle routing problem
branch-and-price
column generation
mixed integer programming
constraint programming
order cutoff assignment problem
Advisor: Lee, Chi-Guhn
Hardness of Electrodeposited Nano-nickel Revisited

In the past, hardness measurements on nanocrystalline metals were limited to Vickers micro-hardness and nano-indentation tests, mainly due to sample size/thickness limitations. On the other hand, most industries require hardness values on the Rockwell scale and make extensive use of hardness conversion relationships for various hardness scales. However, hardness conversions currently do not exist for nanocrystalline metals. With recent advances in electrodeposition technology, thicker specimens with a wide range of grain sizes can now be produced. In this study, the relationships between Vickers and Rockwell hardness scales have been developed for such materials. In addition, hardness indentations were used to gain further insight into the work hardening of nanocrystalline and polycrystalline nickel. Vickers microhardness and nano-indentation profiles below large Rockwell indentations showed that polycrystalline nickel exhibited considerable strain hardening, as expected. On the other hand, for nanocrystalline nickel the micro-Vickers and nano-indentations hardness profile showed low strain hardening capacity.

Keywords: Hardness
Nano-Nickel
Advisor: Erb, Uwe
Effect of Channel Stochasticity on Spike Timing Dependent Plasticity

The variability of the postsynaptic response following a presynaptic action potential arises from: i) the neurotransmitter release being probabilistic and ii) channels in the postsynaptic cell involved in the response to neurotransmitter release, having stochastic properties. Spike timing dependent plasticity (STDP) is a form of plasticity that exhibits LTP or LTD depending on the precise order and timing of the firing of the synaptic cells. STDP plays a role in fundamental tasks such as learning and memory, thus understanding and characterizing the effect variability in synaptic transmission has on STDP is essential. To that end a model incorporating both forms of variability was constructed. It was shown that ion channel stochasticity increased the magnitude of maximal potentiation, increased the window of potentiation and severely reduced the post-LTP associated LTD in the STDP curves. The variability due to short term plasticity decreased the magnitude of maximal potentiation.

Keywords: Spike Timing Dependent Plasticity
Ion Channel Stochasticity
Short Term Plasticity
Advisor: Bardakjian, Berj
Functional Characterization of the Chromosomal MazEF Toxin-Antitoxin Addiction System in Streptococcus mutans

Chromosomal toxin-antitoxin (TA) modules have been proposed to function as regulators of cell growth in response to environmental perturbations. The objective of this study was to characterize the MazEF TA system of the human pathogen Streptococcus mutans. Our data showed that the mazEF genes form a bicistronic operon. MazF toxin had a toxic effect on cells and this effect can be neutralized by coexpression of its cognate antitoxin MazE. Furthermore, we demonstrated that MazE and MazF proteins interact with each other in vivo, confirming the nature of this TA as a type II addiction system. We also demonstrated that MazF is a toxic nuclease arresting cell growth through the mechanism of RNA cleavage and that MazE inhibits the RNase activity of MazF by forming a protein complex. Our results suggest that the MazEF TA might represent a cell growth modulator facilitating the persistence of S. mutans in the oral cavity.

Keywords: toxin antitoxin system
streptococcus mutans
Advisor: Lévesque, Céline
Serving up Change? Corporate Social Responsibility as a Tool for Social Change: A Case Analysis of the UNESCO-WTA Tour Partnership for Global Gender Equality

This research project critically questions the power relations inherent in the use of corporate social responsibility (CSR) as a tool for international development. My case study focuses on the partnership between UNESCO and the Women’s Tennis Association (WTA), which advocates for global gender equality. This discourse analysis seeks to expose the social inequities that may result from CSR by using the theoretical framework of Orientalism and the methodologies of postcolonial feminism and intersectionality. The results suggest that an outdated understanding of gender as the axis of discrimination hinders the attainment of gender equality. Furthermore, Girl Effect type initiatives that promote third-wave feminism are observed to reproduce social inequities through the perpetuation of global capitalism. Key recommendations include a reconceptualization of gender (equality) that accounts for the intersectionality of identities, holistic context specific solutions, and the use of socio-cultural analysis for CSR programming.

Keywords: corporate social responsibility
gender equality
UNESCO
tennis
international development
Orientalism
Advisor: MacNeill, Margaret
Natural Killer Cell Line Therapy in Multiple Myeloma

Multiple myeloma (MM) is an incurable plasma cell malignancy. NK cells have demonstrated anti-MM activity in allogeneic transplants and donor lymphocyte infusions, and may provide a more effective therapy for MM. This work demonstrates cytotoxicity of NK-92 and KHYG-1 against MM cells in chromium release and flow cytometry cytotoxicity assays. At a 10:1 effector to target ratio, the cytotoxicity of NK cell lines against MM cells is 50-90%. Blocking NKp30 significantly reduces the cytotoxicity of NK-92 and KHYG-1, while blocking NKG2D and DNAM-1 only reduces the cytotoxicity of NK-92. Notably, NK-92 and KHYG-1 have shown preferential cytotoxicity against the clonogenic population, killing 89-99% in a methylcellulose cytotoxicity assay. Preliminary results in a xenograft bioluminescent mouse model show that NK-92, but not KHYG-1, reduces the tumor burden detected by bioluminescence imaging and bone marrow engraftment by flow cytometry. Therefore, NK cell lines may offer a more effective therapy for MM.

Keywords: natural killer cells
multiple myeloma
cancer
clonogenic
cancer stem cells
NK-92
KHYG-1
bioluminescent
Advisor: Keating, Armand
Rearticulating Nature: Ecosystem Services in British Columbia and the United Nations Convention on Biological Diversity

This thesis applies mixed ethnographic methods at field sites in British Columbia and the United Nations to explore the spread and uptake of the "ecosystem services" idea in different institutions of environmental governance. I explore intensifying efforts by ecosystem services proponents to rearticualte living nature in various ways and with various objectives around the concept. As the idea manifests in a wide array of different policies and practices, I attempt to characterize a process of 'discursive refraction,' and argue ecosystem services represents a kind of chimera, appearing differently to the disparate practitioners interpreting, responding to, and beginning to use it. Consequently, the idea takes on diverse forms and functions in those institutional settings where it appears. I conclude that the discourse of ecosystem services remains a locus of ongoing contestation, which significantly complicates the relationship between what its proponents intend for it, and its ideological, institutional, and ecological consequences.

Keywords: Ecosystem services
Advisor: Prudham, W. Scott
A Retrospective Study of Root Canal Therapy in Non-vital Primary Molars

Purpose: This retrospective study was performed to assess the clinical and radiographic success rates of a non-vital formocresol and zinc oxide eugenol (ZOE) primary molar root canal therapy (RCT) technique. The effects of this treatment on the permanent successors and on exfoliation times were also investigated. Methods: The study included 161 patients with 211 primary molars treated by RCT by a single operator in a private pediatric dental office in the Toronto area. Results: A clinical success rate of 90.0% and a radiographic success rate of 77.3% were obtained. Enamel defects were found in 6.8% of permanent successors and in patients who were significantly younger at the time of root canal therapy treatment (p = .001). Treated molars exfoliated on average 5.8 months sooner than contralateral teeth (p<0.001). Conclusions: Formocresol and ZOE RCT is a viable treatment for necrotic primary molars and yielded very high clinical success rates with moderate radiographic success rates.

Keywords: Root Canal Therapy
Primary molars
formocresol
zinc oxide eugenol
Advisor: Sigal, Michael
Andrews, Paul
The Company One Keeps: The Khadr II Litigation in its International and Comparative Legal Context

This thesis examines the extent to which the judiciary can intervene into the executive branch’s power over foreign affairs. This thesis focuses on the Supreme Court of Canada’s decision in Canada (Prime Minister) v. Omar Khadr, 2010 SCC 3 where Omar Khadr requested the judiciary to order the executive branch to request his release from American custody in Guantanamo Bay, Cuba. The Supreme Court refused Khadr’s request, but issued a declaratory order stating that Khadr’s rights had been violated by the Canadian government. This thesis places this decision, and its follow-on litigation, in its international and comparative context by examining the international law of diplomatic protection as well as three cases, one from the United Kingdom, one from South Africa and one from West Germany. After examining the context, this thesis concludes that the Supreme Court’s decision, although flawed, was reasonable.

Keywords: Constitution
Judiciary
Executive
Remedies
Advisor: Kent, Roach
The Role of FGF21 in Pancreatic Islet Metabolism

The endocrine-like factor FGF21 is a potent regulator of nutrient metabolism. Systemic FGF21 administration to obese animals improves glucose tolerance, lowers blood glucose and triglycerides, and decreases fasting insulin levels. Although FGF21 improves the survival and function of islet β-cells, the mechanisms are currently unknown. This thesis examines mechanisms of FGF21 in the regulation of pancreatic islet metabolism. Biochemistry studies showed FGF21 decreased Acetyl-CoA carboxylase (ACC) and Uncoupling protein-2 (UCP2) protein expression in mouse islets. Autofluorescence microscopy showed difference in NAD(P)H responses when challenged with TCA cycle intermediate citrate. FGF21-treated islets showed significant decreased mitochondrial energetics when acutely stimulated with high concentrations of glucose and palmitate. This decrease in energetics correlated with increased generation of NADPH. Importantly, insulin secretion was lowered but not abolished in this state. These data confirm that FGF21 alters pancreatic islets metabolism during high glucose and high fat loading and reduces insulin during nutrient stress.

Keywords: FGF21, FGFR1, KLB, Islet, Diabetes, Autofluorescence Imaging, Microfluidics, two-photon imaging, NAD(P)H
Advisor: Rocheleau, Jonathan
Evaluating the Ability of eQUEST Software to Simulate Low-energy Buildings in a Cold Climatic Region

Building Simulation is widely used for understanding how a building consumes energy and for assessing design strategies aimed at improving building energy efficiency. The present research study uses eQUEST, a popular simulation software. Various simulations are done here to analyse and critically comment on the best design strategies to be used in order to vastly reduce the energy consumption of a recently constructed small (1800 m2 floor area) commercial building in Brampton, Ontario, which is a heating dominated region. The limitations faced with eQUEST while simulating the modified design are critiqued. A complete understanding of the building science and heat flow through the building envelope has been applied to modify the building in question. After all the changes applied, the overall heat load of the building was reduced to 15 kWh/m2/yr and the overall energy consumption reduced by 60 percent.

Keywords: Building Simulation
eQUEST
Low-Energy Commercial Buildings
Cold Climatic Region
Advisor: Harvey, L. D. Danny
Compounded Discrimination and the Gonzalez v. Mexico Case: Introducing an Anti-Essentialist Framework for Compounded Discrimination/Violence against Women Cases at the Inter-American Court of Human Rights

In Gonzalez et al. v. Mexico, a case decided by the Inter-American Court of Human Rights in 2009, a context of discrimination and violence against women was known to target particular subgroups of women, of which the claimants were constituent, distinguished inter alia by their age, socioeconomic and, in some cases, migrant status. Despite this, the judgment of the Inter-American Court focused almost exclusively on sex discrimination and violence against women as a broader social phenomenon. With this judgment forming the background for the critique, the author will develop an anti-essentialist framework for the analysis of discrimination and violence against women claims where the discrimination was compounded by various identity factors. Intended to assist the Inter-American Court with its articulation of norms and standards in such cases, the ultimate value of this framework should be measured in terms of the assistance it can offer the Court at the reparations stage.

Keywords: women's human rights
compounded discrimination
international law
inter-american court of human rights
Gonzalez
anti-essentialism
violence against women
Advisor: Cook, Rebecca J.
Desperately Seeking Representation: An Investigation into Visible Minority Electability under Vancouver’s At-large Electoral System

The results of Vancouver’s 2008 municipal election led to critiques that South Asian candidates, and possibly all visible minority candidates, face reduced electability under Vancouver’s at-large electoral system than they would under a different municipal electoral system. This thesis employs numerous quantitative research methods to assess whether visible minority candidates do face reduced electability under the at-large system compared to a ward system proposed for Vancouver in 2004. The extent that Vancouver’s 2008 election results fulfill three U.S. Supreme Court conditions for establishing minority vote dilution is also assessed as part of this thesis research.

Keywords: Electoral Geography
Visible minorities
Multiculturalism
At-large electoral system
Advisor: Walks, R. Alan
Siemiatycki, Matti
Dignity and Equality: Law’s Reasonable Claimant and Human Dignity under Section 15

The concept of human dignity is an essential and inextricable element of equality rights. In Law v. Canada the Supreme Court united around the concept of dignity to determine section 15(1) cases. This test was abandoned in R v. Kapp, deciding that dignity was too abstract and subjective. This paper argues that the problems with the Law test did not come from the concept of dignity itself, but rather from the reasonable claimant test which focused on subjective feelings and legislative intentions. This paper presents an alternative conception of human dignity, which proposes that substantive equality should be a matter of equal concern based on two principles of human dignity: the principle of equal intrinsic value and the principle of personal responsibility. The analysis must be truly contextual, focused on the objective consequences of discrimination and the circumstances that create and foster inequality.

Keywords: Equality
Dignity
Advisor: Reaume, Denise
Changes in Social Inequality in Smoking-attributable Adult Male Mortality between 1986 and 2001 in Four Developed Countries

Social inequalities exist in smoking-attributable mortality rates of males. Change in these social inequalities in the past two decades in developed countries remains uncertain. This study was conducted in Canada, France, Poland, and Switzerland to quantify differences in smoking-attributable mortality rates, at ages 35-69 years, among different social strata in recent years and to examine the changes in social inequalities in these rates between 1986 and 2001. Analyses included 377,878 deaths from a total population of 13,482,210 males of these four countries. Smoking-attributable mortality rates reduced in all strata over the comparative time periods, in all countries, except France. This work specifically focuses to fill the gap in knowledge about whether tobacco control has reached the poor or lower social strata in developed countries. This study will enable follow up research including quantification of effects of the specific tobacco control policies in each country.

Keywords: Smoking
Social inequality
Advisor: Jha, Prabhat
Prevalence, Predictors, and Outcomes Associated with Late Start of Chronic Kidney Disease Care Amongst Adults with End-stage Renal Disease

Using Ontario health administrative data, we identified 12,143 adults with chronic kidney disease (CKD) who received outpatient nephrology care prior to start of renal replacement therapy (RRT) in order to study the effect of care-related factors in predicting late start of predialysis care (PDC, defined as first outpatient nephrology visit <6 months prior to RRT start) and to explore covariates which further quantify the PDC received. Lack of an usual provider of primary care (OR 0.76; 95%CI 0.66, 0.87) predicted late start of PDC. In addition to late start of PDC, number of nephrology visits (OR 0.97 per visit; 95% CI 0.96, 0.98), and having seen a nephrologist in only 1 or 2 of the 6 months prior to RRT start (OR 1.33; 95%CI 1.18, 1.51), were also independent predictors of one-year mortality, suggesting that other measures of PDC are needed to better characterize the care received.

Keywords: end-stage renal disease
dialysis
chronic kidney disease care
late referral
nephrology care
mortality
predictors
survival
Advisor: Hux, Janet