VictorJuiz/thesis huggingface dataset:
The Epigenetic Regulation of Endothelial Cell-enriched genes in the Vascular Endothelium

The mechanisms which control the gene expression profile of a particular cell type are critical for maintaining homeostasis and physiological processes. A role for epigenetic processes in the regulation of gene expression of an endothelial cell (EC)-enriched gene, namely endothelial nitric oxide synthase (eNOS), has been previously demonstrated. The extent to which epigenetic mechanisms, particularly proximal promoter DNA methylation, plays a role in regulating other EC-enriched genes is not well understood. To investigate whether proximal promoter DNA methylation was important for regulating the expression of EC-enriched genes, we utilized high-resolution sodium bisulfite genomic sequencing, pyrosequencing analysis and DNA immunoprecipitation to assess the methylation status of several EC-enriched gene promoters. We identified differentially methylated regions (DMRs) at the majority of EC-enriched gene promoters in ECs versus non-ECs. Inhibition of DNA methyltransferase activity resulted in an induction in mRNA expression of EC genes in non-EC types, indicating the importance of proximal promoter DNA methylation in gene silencing. We further investigated the role of the newly rediscovered cytosine modified base, 5-hydroxymethylcytosine (hmC), in the vasculature. We developed a quantitative assay - high performance liquid chromatography electrospray ionization tandem mass spectrometry with multiple reaction monitoring (HPLC-ESI-MS/MS-MRM) - to measure both 5-methylcytosine (mC) and hmC in mouse tissues, during embryonic development and in the vasculature.

Keywords: DNA methylation
epigenetics
gene expression
vascular endothelium
Advisor: Marsden, A Philip
Identification and Analysis of Halogenated Contaminants Formed in Thermal Decomposition of Halogenated Materials

Fires release a wide array of contaminants that contribute to detrimental environmental and health effects. The thermal decomposition of halogenated materials in fires produces complex mixtures that include unidentified environmentally persistent and toxic halogenated contaminants. Resulting complex mixtures pose an analytical challenge in assessing the hazards of a fire site where burn conditions and contents are unknown. Non-targeted analytical approaches can facilitate identification of novel compounds in complex mixtures to direct further study. This thesis investigates the thermal decomposition mechanisms and products of halogenated materials using non-targeted analytical techniques, and assesses the environmental relevance of these thermal processes. Mass defect filtering of high-resolution mass spectra is an effective approach to visually resolve and interpret complex chemical information. This non-targeted approach was used to characterize the thermal decomposition products of polychlorotrifluoroethylene (PCTFE) and polyvinylidene fluoride (PVDF). High-resolution mass spectra, obtained by Fourier transform ion cyclotron resonance mass spectrometry (FTICR-MS), were interpreted using mass defect plots based on unique mass scales. Novel halogenated compounds were identified, including perchlorinated/fluorinated polycyclic aromatic hydrocarbons (X-PAHs, X=Cl,F), and polyfluorinated polycyclic aromatic hydrocarbons (F-PAHs). Congener profiles of thermal decomposition products provided evidence of associated decomposition mechanisms. The potential of non-targeted analyses to characterize complex environmental samples was further exemplified through studies examining the environmental relevance of combustion-derived contaminants. Using mass defect plots as a screening tool, a variety of brominated contaminants, including polybrominated/chlorinated dibenzofurans (PXDFs, X=Br/Cl), were identified in air and particulates collected from simulation fire studies. Mass defect filtering, in combination with comprehensive two-dimensional gas chromatography high-resolution time of flight mass spectrometry (GCxGC-HRToF) and gas chromatography tandem mass spectrometry (GC-MS/MS) was used to identify bioaccumulative contaminants in aquatic species exposed to soil from an industrial fire site. Compounds identified as bioaccumulative included polybrominated/chlorinated, anthracenes/phenanthrenes and pyrenes/fluoranthenes (X-PAHs, X=Br,Cl). The majority of environmental analyses is targeted and thereby only examines a small subset of compounds present in the environment. This work demonstrates the potential of non-targeted techniques to screen complex environmental samples for halogenated contaminants. This is particularly applicable to combustion-derived mixtures, the complexity of which varies with fire conditions and contents.

Advisor: Scott, A Mabury
Dynamic Models and Methods in the Consumer Packaged Goods Industry

Dynamic structural models capture forward looking behavior on the part of economic agents. While these models can bring new insights, the computational cost of estimating these models can be prohibitive. In the three chapters of my dissertation, I use dynamic models to capture qualitative insights into the consumer packaged goods industry, while introducing methodological innovations that expand the range of problems where dynamic models can be estimated. In the first chapter, I seek to explain counter-cyclic pricing, the phenomenon where the price of seasonal goods increases in periods of high demand. I do this by modeling consumers who may purchase without search. Consumers are more likely to purchase without search in low demand periods, which decreases estimated price sensitivity. I test this explanation using a dynamic, structural inventory model where consumers make decisions on whether to search, which reveals price promotions. I estimate this model by developing a cyclic-successive approximation algorithm, which removes the computational burden of adding cyclic variables to the state space of any dynamic model.Several recent papers develop methods to identify discount factors in dynamic models. However, in some cases, the estimation of discount factors is a computational challenge. The nested pseudo likelihood method of Agguiregabiria and Mira (2007) allows the value function to be calculated without costly contraction mapping evaluations. However, when the discount factor is being estimated, this computational efficiency is lost. In the second chapter of my dissertation, I restore this computational efficiency through an application of the eigendecomposition.The third chapter is a joint work with Ron Borkovsky, Avi Goldfarb, and Sridhar Moorthy, in which we capture the inherently dynamic nature of brand value. Firms invest in brand equity through advertising, and the value of this equity will depend on the expected decisions of rival firms. Measuring brand value then requires one to account for the current state of the market, and the evolution of the market in the future. We apply our approach by estimating brand values in the stacked potato chips industry by adapting the Pakes-McGuire quality ladder to allow firms to have a stochastic advertising decision.

Keywords: Dynamic Methods
Dynamic Models
Seasonality
Structural Methodology
Structural Models
Advisor: Avi, Goldfarb
Chemical-assisted Femtosecond Laser Writing of Lab-in-fiber Sensors

Three-dimensional (3D) patterning inside optical fiber was shown to be a powerful tool for embedding refractive index and microfluidic structures inside the flexible glass fiber for enabling novel sensing opportunities with lab-in-fibers (LIFs). A femtosecond laser was tightly focused into optical fibers using an oil-immersion lens to eliminate extreme optical aberrations from the cladding-air interface. The laser interactions were then optimized to bring ~12 nm rms surfaces for the first time inside the fiber cladding by precisely conforming planar nanograting structures when assembled by the writing laser. Further, the unprecedented integration of cladding waveguides, X-couplers, fiber Bragg gratings (FBGs), microholes, mirrors, optofluidic resonators, and microfluidic reservoirs defined the building blocks for facile interconnection of inline core-waveguide devices with fiber cladding optofluidics. Laser templating was restricted to the single mode fiber (SMF) cladding or formed inside all-fused silica coreless optical fibers to meet with buried laser-formed waveguides that were fused to SMFs for novel seamless inline probing while avoiding undesired concave surface profiles and negative lensing losses associated with writing optofluidic templates across the germanium-doped SMF core waveguide.With these components, more advanced, integrated, and multiplexed fiber microsystems were demonstrated for fluorescence detection, Fabry Perot interferometer (FPI) refractometry, and simultaneous sensing of refractive index, temperature, and bending strain. Tapered access ports were found to minimize fiber mechanical weakening and thereby avoid fiber breakage during optofluidic sensing. Optical resonator arrays (ORAs) were then explored to deepen fringe contrasts beyond that available with a single FPI for opening new prospects for fiber inline pass-band optical filters and broadband reflectors. Finally, wavefront splitting interferometers (WSIs) were targeted to improve fringe contrast and peak resolution beyond that available with FPIs and offer a significant theoretical improvement in refractometer sensitivity.The advanced laser processes optimized here may provide a new base for photonics, microfluidics, and optofluidics fabrication in a LIF platform with multiplexed functionality and rapid prototyping capabilities of fully integrable 3D optofluidic systems. The proposed LIF devices define new micro-systems for temperature, strain, pressure, refractive index, and bend strain sensing that may find application in the acoustic, aerospace, automotive, biological, chemical, civil, or medical fields.

Keywords: Chemical Etching
Femtosecond Laser Processing
Lab in Fiber
Lab-on-Chip
Optical Fiber
Optofluidics
Advisor: Peter, R Herman
The Pharmacology of Periconceptional Folic Acid Supplementation

Periconceptional folic acid supplementation is associated with a reduction in the risk of neural tube defects, other birth defects, as well as positive maternal outcomes during pregnancy. Current healthcare recommendations regarding the timing and dosage of prenatal supplementation are based on studies in non-pregnant women of childbearing age. The overall objective of this thesis is to characterize risk factors associated with the periconceptional period, validate the effectiveness of folic acid supplementation based on pregnancy-related pharmacokinetics, analyze the current folate status of women in Toronto, as well as explore recruitment strategies for clinical trials in pregnant women. The first study was a two-arm, randomized, clinical trial assessing the long-term folate kinetics in pregnant women supplementing with either 1.1mg (regular dose) or 5mg (high dose) of folic acid. This study evaluated dose-dependent and gestational age-dependent changes in the pharmacokinetics among pregnant women, which have not been previously studied at these doses of supplementation. We found non-linear folate pharmacokinetics in the 5mg group, as well as altered pharmacokinetics in both dose-groups due to pregnancy-related changes. The second study was based on secondary analysis emerging from the randomized clinical trial, where we tackled the challenges associated with recruitment of pregnant women (a vulnerable population) into a study on folic acid supplementation at a time when a high degree of supplementation awareness already exists among women in Toronto. We used social media as a novel tool for recruitment, and found a 12-fold increase in recruitment rate. The third study was a systematic review and meta-analysis investigating the effect of oral contraceptive use on blood folate concentrations among women. We found that oral contraceptives had a folate-lowering effect and recommended continued folate supplementation among oral contraceptive users. Finally, in our fourth population-based cohort study, we evaluated blood folate concentrations among women in Toronto and found that 93% of women of childbearing age had optimally protective blood folate concentrations against neural tube defects.Recommendations for periconceptional folic acid supplementation should be re-evaluated based on population-level data, and be tailored to individual risk factors such oral contraceptive use or altered folate demands during pregnancy.

Keywords: folic acid
fortification
periconceptional period
pharmacokinetics
pharmacology
pregnancy
Advisor: Gideon, Koren
What Would Jesus Wear? Dress in the Synoptic Gospels

For early followers of Jesus, the body was not a "fixed" entity, yet bodily fixity was a constant concern. The primary way to "fix" the body, or to negotiate and locate identity, was through dress. Dress in the ancient Mediterranean context enabled a different kind of embodied knowledge than contemporary conventions of dress, and in order to understand passages in the synoptic gospels that use items of dress in the flow of their narrative, these garments must be examined in context. The first chapter of this dissertation outlines a methodology of dressed bodies that integrates bodily experience with social practice. This methodology provides the framework for subsequent discussion. The second chapter examines the preponderance of cloaks in the gospels, particularly the gospel of Mark, from a material perspective, arguing that cloaks are not symbolic of inner or other meanings, but are constitutive of meaning in and of themselves. The third chapter focuses on absent clothes and naked bodies, specifically the absent clothes of the disciples according to Jesus' instructions for their travel and work. Jesus commands the disciples to go naked in a dressed society, to identify with a typically rejected state. Finally, chapter four focuses on Mark 14:51-52 and the mysterious flight of the naked man into the night, arguing that it not so mysterious after all: the young man, losing his cloak at the violent scene of Jesus' arrest, leaves it behind in order to flee, joining many other ancient men and women who lost their cloaks in similar situations. When the realities of ancient dress are taken into account, occurrences of dress in the gospels make new sense. The gospel writers use dress as the material means to concretize the identity and qualities of Jesus and his followers.

Advisor: John, S. Kloppenborg
Shaping the World in One's Image: An Essay on the Nature and Value of Achievements

This project is a philosophical exploration of the common sense notion that achievements are among the things that make a life go well. Parts I and II develop an account of achievements as competently reached goals and discuss in virtue of what some such goals are more of an achievement than others. Part III argues that, given the account of achievements developed in parts I and II, we have good reason to think that the common sense idea is true: achievements are intrinsically valuable. We can see that this is so by reflecting on the fact that achieving our goals realizes certain valuable relations of harmony between mind and world.

Keywords: achievement
value theory
Advisor: Thomas, Hurka
Structural and Biochemical Analysis of the Shikimate Dehydrogenase Family

The shikimate dehydrogenase (SDH) family consists of at least five structurally related, but functionally distinct enzyme classes. The archetypal member of the family, AroE, catalyzes the NADPH-dependent reduction of 3-dehydroshikimate to shikimate. This reaction forms the fourth step of the shikimate pathway, a metabolic route required for the biosynthesis of the aromatic amino acids. The shikimate pathway is conserved in plants, fungi, bacteria, and apicomplexan parasites, which has made AroE and the other enzymes of the pathway attractive targets for herbicides and antimicrobials. The remaining members of the SDH family, proteins known as YdiB, SdhL, RifI, and Ael1, are proposed to participate in diverse biological processes ranging from carbon assimilation to antibiotic production. Due to their different substrate preferences, these enzymes represent an ideal system for investigating mechanisms of substrate recognition, a subject that is explored in this thesis.Earlier studies have examined the structural and catalytic properties of the AroE, YdiB, and SdhL classes. The work presented here includes the first representative crystal structures of enzymes from the RifI and Ael1 groups, permitting the most in-depth analysis of substrate selectivity in the SDH family to date. In addition, the results of this thesis clarify the previously disputed catalytic mechanism employed by members of the YdiB class.Finally, we have performed the first kinetic analysis of an SDH family protein from the phylum Apicomplexa, a group that contains a number of parasites associated with human disease. High-throughput screening has identified a novel class of inhibitors active against this enzyme and AroE enzymes from plant and bacterial sources. These inhibitors may represent useful chemical scaffolds for the design of drugs targeting the shikimate pathway.

Advisor: Dinesh, Christendat
The Response of Particles in Periodic Potentials to External Forces: New Perspectives

We study the effects of an external constant and uniform force on particles in periodic potentials in the context of transport and optical phenomena. We consider two types of systems: charged carriers in a crystal subject to a constant (dc) electric field and ultracold atoms in optical lattices subject to external forces of various origins. Both systems are described by a Hamiltonian where the force is coupled to the position operator. In the context of transport phenomena, we study the motion of a wave packet prepared in one band of a periodic potential when a uniform force is suddenly applied and left constant afterwards. The semiclassical description of wave packet dynamics in periodic potentials with applied forces, slowly varying in time and space, relies on the concepts of effective mass, group velocity, and anomalous velocity. If the force is suddenly applied, these quantities do not correctly describe the dynamics, since the wave packet cannot respond instantaneously according to the properties of the lattice. We show that dynamical generalizations of the group and anomalous velocities, and of the inverse effective mass tensor, provide an appropriate description. Our approach is based on modified Bloch states that include the interband mixing due to the force; we compare our results with full numerical calculations, showing excellent agreement when Zener tunneling is negligible. We illustrate our results with one- and two-dimensional optical lattices, where the experimental detection of these dynamics is more accessible than in typical solid-state systems.In the context of optical phenomena, we consider the absorption of light by bulk semiconductors in the presence of a dc electric field including excitonic and interband coupling effects. The absorption coefficient is calculated from the time evolution of the interband polarization excited by an optical pulse. We illustrate the formalism with a numerical calculation for bulk GaAs using a 14-band k.p model, and we study the dependence of the excitonic enhancement of the absorption coefficient on the strength of the dc field and the optical polarization. We find that the polarization anisotropy described by the independent particle approximation can be modified significantly by the Coulomb interaction.

Keywords: Anomalous velocity
Effective mass
Electroabsorption
Franz-Keldysh effect
Optical lattices
Wave packet dynamics
Advisor: John, E. Sipe
State-sanctioned Violence and Mental Health: Implications for Learning and Treatment

This qualitative study examines how Canadian mental health systems may better accommodate people from the Democratic Republic of the Congo (DRC) who are living now in Canada and who may be suffering psychosocial consequences of political violence. Using an anti-racist-feminist lens, analysis of seven interviews highlights the significance of socio-political histories and conceptualisations of trauma in mental health education. Discussions focus on mental health dimensions of war and aspects of resilience in complex life-experiences which are only recently gaining representation (and transformation) in medical discourse. By correlating social and political forces with particular mental health outcomes, I focus on treatment-areas that may be discriminatory for a subset of refugees.As immigrant and refugee experiences may lack reference within traditional treatment paradigms, it becomes essential to understand specificities within which healing and social change for refugees may be relevant. A first objective looks at processes of resilience where recovery may be more meaningful, countering notions of illness as pathology within systems of deficit. Similarly, greater considerations of state-sanctioned violence, its nature and intentions, are needed to plan comprehensive mental health supports. A second objective is then to identify social indicators which may more fully articulate, express, or enable change at group and family levels. Finally, as interventions are most effective when informed by group realities, a third objective brings forward cultural, political, and social forces currently underrepresented in what we know about `treating war trauma'. In sum, this study highlights that greater attention to structural violence in mental health education may lead to better treatment outcomes. Treatments may be more effective by offering alternate pathways to care, considering broader conceptualisations of trauma, and encouraging notions of participatory, group-level initiatives. Findings critically suggest that present mental health systems may unintentionally (re)produce victims, more than enable survivors to rebuild lives after fleeing the complexity and brutality of war-affected circumstances.

Keywords: Democratic Republic of the Congo
Mental health education
Public health
Refugee war trauma
Advisor: George, S Dei