VictorJuiz/thesis huggingface dataset:
The Role of FGF21 in Pancreatic Islet Metabolism
Keywords: FGF21, FGFR1, KLB, Islet, Diabetes, Autofluorescence Imaging, Microfluidics, two-photon imaging, NAD(P)H

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.
Evaluating the Ability of eQUEST Software to Simulate Low-energy Buildings in a Cold Climatic Region
Keywords: Building Simulation
eQUEST
Low-Energy Commercial Buildings
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.
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
Keywords: women's human rights
compounded discrimination
international law
inter-american court of human rights
Gonzalez
anti-essentialism
violence against women

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.
Desperately Seeking Representation: An Investigation into Visible Minority Electability under Vancouver’s At-large Electoral System
Keywords: Electoral Geography
Visible minorities
Multiculturalism
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.
Dignity and Equality: Law’s Reasonable Claimant and Human Dignity under Section 15
Keywords: Equality
Dignity

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.
Changes in Social Inequality in Smoking-attributable Adult Male Mortality between 1986 and 2001 in Four Developed Countries
Keywords: Smoking
Social inequality

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.
Prevalence, Predictors, and Outcomes Associated with Late Start of Chronic Kidney Disease Care Amongst Adults with End-stage Renal Disease
Keywords: end-stage renal disease
dialysis
chronic kidney disease care
late referral
nephrology care
mortality
predictors
survival

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.
Towards Achieving Highly Parallelized Publish/Subscribe Matching at Line-rates Using Reconfigurable Hardware
Keywords: FPGA
fpga-ToPSS
Publish Subscribe Matching
middleware system
event procesing system
content based router

We present fpga-ToPSS (Toronto Publish/ Subscribe System), an efficient FPGA-based middleware platform geared towards high-frequency and low-latency event processing. fpga-ToPSS is built over reconfigurable hardware---FPGAs---to achieve line-rate processing by exploiting unprecedented degrees of parallelism and potential for pipelining,only available through custom-built, application-specific and low-level logic design. Furthermore, our middleware solution hosts an event processing engine that is built on a hardware-based packet processor and Boolean expression matcher. Our middleware vision extends to a wide range of applications including real-time data analytics, intrusion detection, algorithmic trading, targeted advertisement, and (complex) event processing.
Retinal Origins of Vigabatrin Toxicity in Infantile Spasms
Keywords: vigabatrin
toxicity
electroretinogram
infantile spasms

Vigabatrin (VGB) is an anti-epileptic drug used to treat children with Infantile Spasms (IS). The 3.0 flicker amplitude of the electroretinogram (ERG) is currently used to monitor visual function changes in infants on VGB. To find a more specific marker of permanent changes due to VGB, sedated ERGs were performed on 31 IS patients and 13 retinally normal controls to isolate components of the cone pathway. ERG growth curves, for each component, recorded from children with IS were generated using data recorded pre-VGB treatment and for controls. Only the cone off response (from Off bipolar cells) and cone photoreceptor sensitivity were associated with decreased flicker amplitude. Twenty nine percent of patients had an abnormal cone off response. No patient had an abnormal cone off response at baseline. No patient with an abnormal cone off response recovered normal function. The cone off response could serve as a marker VGB retinal toxicity.
Assessing the Cytoprotective Properties and Central Nervous System Expression Profile of Mammalian Sirtuin SIRT3
Keywords: mitochondria
SIRT3

Sirtuins are a family of nicotinamide adenine dinucleotide - dependent enzymes, which have gained recent interest due to their ability to directly or indirectly regulate cell metabolism, oxidative response mechanisms and cellular senescence. A mitochondrial sirtuin SIRT3, although still relatively under-investigated, regulates mitochondrial processes through deacetylation of metabolic enzymes and components of electron transport chain. We hypothesized that SIRT3 is a mitochondrial cytoprotective factor that exerts its function by decreasing reactive oxygen species levels, and protecting cells from oxidative stress. HEK-293 cells over-expressing SIRT3 exhibit reduced mitochondrial membrane potential and reactive oxygen species levels under basal conditions. In addition, cells over-expressing SIRT3 are less sensitive to hydrogen peroxide and glucose deprivation/glucose reperfusion induced-cell death. Since SIRT3 expression in the brain has not yet been investigated, its expression pattern in the rodent brain was characterized. Our results showed that SIRT3 mRNA and protein levels are robustly expressed in different regions of the adult rodent brain and their expression increases with age. Furthermore, SIRT3 is expressed predominantly in astrocytes in cultures derived from rat primary E18 cortical cells. These results suggest that SIRT3 possesses cytoprotective potential, and that its actions in the brain regulate astrocyte physiology.
Glitch Reduction and CAD Algorithm Noise in FPGAs
Keywords: FPGA
CAD
Glitch
Power
Noise
Algorithms

This thesis presents two contributions to the FPGA CAD domain. First, a study of glitch power in a commercial FPGA is presented, showing that glitch power in FPGAs is significant. A CAD algorithm is presented that reduces glitch power at the post-routing stage by taking advantage of don't-cares in the logic functions of the circuit. This method comes at no cost to area or performance. The second contribution of this thesis is a study of FPGA CAD algorithm noise {random choices which can have an unpredictable effect on the circuit as a whole. An analysis of noise in the logic synthesis, technology mapping, and placement stages is presented. A series of early performance and power metrics is proposed, in an effort to find the best circuit implementation in the noise space.
EMI Reduction in Discrete SMPS Using Programmable Gate Driver Output Resistance
Keywords: SMPS
EMI
Power Electronics
Integrated Circuits
Gate Driver

A gate driver IC with programmable driving strength to reduce electromagnetic interference (EMI) in SMPS is presented in this thesis. The design builds on previous segmented gate driver designs that have been used to improve light load efficiency. The presented solution is to dynamically adjust the output resistance Rout at the arrival of each gate pulse to minimize EMI while maintaining low switching loss. Dynamically adjusting Rout is not possible with conventional gate driver designs. Thus, a segmented gate driver is designed and fabricated in the AMS 0.35μm 40V HVCMOS process. Unlike traditional snubber circuits, the proposed method does not require extra discrete components that dissipate energy. Experimental results indicate up to a 7dBμV improvement in peak Conducted EMI (CEMI) between 20 MHz and 30 MHz and a 150μV/m improvement in peak Radiated EMI (REMI) between 88 MHz and 216 MHz.
Investigating the Anti-viral Property of Verotoxin and its Receptor Gb3 in Preventing Primary HIV-1 Infection
Keywords: HIV-1
Verotoxin
glycosphingolipid
Gb3

Verotoxin produced by Enterohemorrhagic E. coli is comprised of a catalytic A subunit and a receptor Gb3 binding B subunit pentamer. VT causes protein synthesis inhibition by ribosomal inactivation in Gb3 positive cells via receptor mediated endocytosis and retrograde transport to the ER. We propose that verotoxin is a novel inhibitor for HIV-1 infection. Experiments conducted using VT treated Jurkat-C T cells and PHA/IL-2 activated human PBMCs reveal the anti-HIV-1 property of VT is receptor Gb3 independent since the catalytic A subunit alone is sufficient for inhibition. Possible mechanism of action involves mild inhibition of protein synthesis and cell proliferation. Recent findings in our lab suggest Gb3 is a natural resistance factor for HIV-1 infection, which was further investigated by selecting a Gb3 low subpopulation in THP-1 cells using VT treatment. Selected THP-1 cells were completely resistant to HIV-1 infection, however decreased surface CXCR4 expression may be a cause.
Computational Fluid Dynamics (CFD) Evaluation of Non-planar Stent Graft Configurations in Endovascular Aneurysm Repair (EVAR)
Keywords: stent graft
hemodynamics
crossing the limbs
helical flow
AAA
abdominal aortic aneurysm
EVAR
endovascular aneurysm repair
CFD
computational fluid dynamics

Crossing of stent graft limbs during endovascular aneurysm repair (EVAR) is often used to assist cannulation and prevent graft kinking when the aortic bifurcation is widely splayed. Little has been reported about the implications of cross-limb EVAR, especially in comparison to conventional EVAR. Using computational fluid dynamics, this work numerically examines the hemodynamic differences between these two out-of-plane stent graft configurations against a planar configuration commonly found in literature. Predicted values of displacement force, wall shear stress, and oscillatory shear index were similar between the out-of-plane configurations. The planar configuration predicted similar wall shear stress values, but significantly lower displacement forces than the out-of-plane configurations. These results suggest that the hemodynamic safety of cross-limb EVAR is comparable to conventional EVAR. However, a study of clinical outcomes may reveal reduced thrombosis incidence and long-term structural implications for the stent graft in cross-limb EVAR.
Study of Peri-operative Complications in Persons with Disabilties under Dental Treatment under General Anesthesia at the Mount Sinai Hospital
Keywords: general anesthesia
complications
disabilities
dentistry
satisfaction
dental treatment
special needs

This was a two part study. Part one was a retrospective chart review to ascertain the prevalence and predictors of peri-operative complications in PWD receiving their dental care under general anesthesia (GA). Part two was a prospective survey of parents/caregivers regarding their satisfaction with the service as well as to ascertain the prevalence of post-operative symptoms incurred by patients. In Part 1, the prevalence of complications in PWD was 4 times higher than the 6% stated in the literature for the general population. Time under GA, and no previous history of dental care under GA were significantly related to complications. In Part 2, 100% of patients experienced post-operative symptoms; nonetheless, 92.7% of parents/caregivers were satisfied with the service provided. There prevalence of complications in the PWD in this study was high. Prior to treatment under GA, adequate pre-operative medical evaluations must be completed and time under GA minimized.
The Margin of Appreciation in Context of Freedom of Religion in the Interpretation of the European Court of Human Rights
Keywords: margin of appreciation
freedom of religion

This thesis addresses numerous key points on the application of the margin of appreciation principle in relation to Article 9 (2) of the European Convention on the Protection of Human Rights and Fundamental Freedoms ('Convention').1 In general terms, the margin of appreciation doctrine means that the State is allowed a certain measure of discretion, subject to European supervision, when it takes legislative, administrative, or judicial action in the area of a Convention right.2 The margin of appreciation is given to Contracting States to allow variation amongst them in terms of interpretation of the rights guaranteed.
Exploring Gendered Relationships Between Aboriginal Urbanization, Aboriginal Rights and Health
Keywords: Aboriginal health
Aboriginal urbanization
Aboriginal rights
mixed-methods

Aboriginal urbanization has increased dramatically in Canada over the last half century. Aboriginal rights may be an important factor in shaping Aboriginal peoples’ experiences of urbanization, as they are largely restricted to those living on reserves. Through their impacts on social determinants of health, these differences in spatial access to Aboriginal rights may have implications for the health of Aboriginal peoples living in urban areas. Using mixed quantitative (statistical analysis of the Aboriginal Peoples Survey) and qualitative (in-depth interviews with Aboriginal women and men in Toronto) methods, this thesis explores relationships between Aboriginal urbanization and Aboriginal rights, focusing on how they may differentially impact the health of Aboriginal women and men living in urban areas. Findings suggest that the perceived lack of respect for Aboriginal rights in urban areas is negatively related to health, and that Aboriginal women and men may experience these impacts differently.
The Direct Interaction of Tubulin With Transient Receptor Potential Melastatin 2
Keywords: TRPM2
Tubulin

Transient Receptor Potential Melastatin 2 (TRPM2) is a widely expressed, non-selective cationic channel with implicated roles in cell death, chemokine production and oxidative stress. This study characterizes a novel interactor of TRPM2. Using fusion proteins comprised of the TRPM2 C-terminus we established that tubulin interacted directly with the predicted C-terminal coiled-coil domain of the channel. In vitro studies revealed increased interaction between tubulin and TRPM2 during LPS-induced macrophage activation and taxol-induced microtubule stabilization. We propose that the stabilization of microtubules in activated macrophages enhances the interaction of tubulin with TRPM2 resulting in the gating and/or localization of the channel resulting in a contribution to increased intracellular calcium and downstream production of chemokines.
Synthesis of 1,2,3-Triazole-fused Heterocycles via Palladium Catalyzed Annulation of 5-Iodotriazoles
Keywords: triazoles
palladium catalysis
Heck reaction
dirct arylation
organic chemistry

Increasing attention has recently been directed toward 1,2,3-triazole-containing compounds. With their unique properties and excellent stability, 1,4-disubstituted triazoles are readily accessible via the copper catalyzed azide alkyne cycloaddition (CuAAC). As compounds containing fused triazoles become common in pharmaceutical targets and biologically active substances, new strategies to synthesize this class of molecules are highly desirable. An efficient and highly modular approach toward the synthesis of three different heterocyclic motifs containing fused 1,2,3-triazoles is reported. The synthesis involved a Pd-catalyzed annulation of 5-iodo-1,2,3-triazoles, which were prepared by a Cu(I)-catalyzed cycloaddition of iodoalkynes and azides. This work demonstrates the versatility of iodotriazoles in Heck reactions and in direct arylations.
The Roles of the Voa Subunit of the Vacuolar H+-ATPase in Dense-core Vesicle Acidification, Transmitter Uptake and Storage
Keywords: V-ATPase
Voa
transmitter uptake
acidification

The Vo sector of the vacuolar H+-ATPase is a multi-subunit complex that forms a proteolipid pore. The largest subunit in this complex is the a subunit which has four isoforms (a1-a4). The isoform(s) critical for secretory vesicle acidification has yet to be identified. Using a cell line derived from rat pheochromocytoma in which Voa1 and/or Voa2 had been down-regulated this study revealed that Voa1, and to a lesser extent, Voa2 are critical for acidifying dense-core vesicles (DCVs). The acidification defects resulting from down-regulation of Voa1 and Voa1/ Voa2 were suppressed by the expression of knockdown-resistant Voa1. Defects in DCV acidification resulted in reductions in their transmitter uptake and storage. Lastly, Ca2+-dependent peptide secretion appeared normal in Voa1 and Voa1/ Voa2 knockdown cells. . This study demonstrated that Voa1 and Voa2 cooperatively regulate dense-core vesicle acidification as well as transmitter uptake/storage, while they may not be critical for dense-core vesicle exocytosis.