VictorJuiz/thesis huggingface dataset:
ALX4 Expression in the Normal Breast and in Breast Cancer

Aristaless-like homeobox 4 is a homeodomain transcription factor that has important functions during mouse development. A recent report demonstrated that Alx4 expression is required in periductal stromal cells in the mouse mammary gland for normal mammary morphogenesis. To test the hypothesis that ALX4 is expressed in the normal human breast, and this expression is altered in breast cancer, immunohistochemistry was performed on normal and breast cancer tissue and breast tissue microarrays. In the normal breast, ALX4 was expressed in stromal fibroblasts and luminal epithelial cells, but not in myoepithelial cells. Expression was lost in breast cancer in both cell compartments. Upon global demethylation induced by 5-aza-2’-deoxycytidine, normal and breast cancer cell lines expressed ALX4, suggesting that hypermethylation may repress expression of ALX4 during malignant transformation of the breast. These results demonstrate that ALX4 may be used as a biomarker for breast cancer, and may act as a tumour suppressor.

Keywords: ALX4
mammary gland
breast cancer
Advisor: Hamel, Paul A.
Functional Consequences of Complete GSK-3 Ablation in Mouse Embryonic Fibroblasts

Glycogen Synthase Kinase-3 (GSK-3) is a highly conserved serine/threonine kinase comprised of two mammalian homologues, GSK-3α and β, encoded by independent genes. This thesis reports the characterization of GSK-3-null primary mouse embryonic fibroblasts (MEFs) generated by gene targeting to gain insight into the physiological functions of this protein kinase. Combined inactivation of both alleles of GSK-3α and GSK-β led to elevated sensitivity to TNFα-induced apoptosis, altered organization of focal adhesion complexes, defects in cell spreading on fibronectin, decreased cell growth associated with altered cell cycle progression through the G2/M phase and increased spontaneous apoptosis. Future work will focus on unraveling the molecular mechanisms responsible for these effects and identifying the common and distinct cellular roles for GSK-3α and β, and specific variants of these isoforms.

Keywords: GSK-3
BCLAF1
Advisor: Woodgett, James
Mechanisms of Diet-induced Dyslipidemia and Insulin Resistance: Role of Chronic LXR Activation

The metabolic syndrome is a collection of pathologies including dyslipidemia, obesity and insulin resistance. A thorough understanding of the mechanisms behind metabolic syndrome development would help in the development of treatment and prevention strategies. Our lab has previously shown that cholesterol feeding exacerbates features of the metabolic syndrome in high fat-, high fructose-fed mice. The nuclear receptor Liver X Receptor (LXR), a master transcriptional regulator of cholesterol, fat and carbohydrate metabolism in the liver, is endogenously activated by oxysterols, metabolic derivatives of cholesterol. In order to determine whether cholesterol exerts its metabolic effects via LXR activation, parallel studies were conducted comparing chronic cholesterol supplementation with LXR activation in the hamster. Results showed that cholesterol feeding and LXR activation caused similar dyslipidemia, glucose intolerance and upregulation of target mRNA and proteins. These data support the hypothesis that the dyslipidemic effects of dietary cholesterol are mediated at least in part by LXR.

Keywords: LXR
Cholesterol
Dyslipidemia
Insulin resistance
Advisor: Adeli, Khosrow
Behaviour and Design of Extradosed Bridges

The purpose of this thesis is to provide insight into how different geometric parameters such as tower height, girder depth, and pier dimensions influence the structural behaviour, cost, and feasibility of an extradosed bridge. A study of 51 extradosed bridges shows the variability in proportions and use of extradosed bridges, and compares their material quantities and structural characteristics to girder and cable-stayed bridges. The strategies and factors that must be considered in the design of an extradosed bridge are discussed. Two cantilever constructed girder bridges, an extradosed bridge with stiff girder, and an extradosed bridge with stiff tower are designed for a three span bridge with central span of 140 m. The structural behaviour, materials utilisation, and costs of each bridge are compared. Providing stiffness either in the girder or in the piers of an extradosed bridge are both found to be effective stategies that lead to competitive designs.

Keywords: extradosed prestressing
bridge design
cable pretensioning
cable-stayed
cantilever construction
Advisor: Gauvreau, Douglas Paul
The Drivers and Performance of Corporate Environmental and Social Responsibility in the Canadian Mining Industry

Corporate Social Responsibility (CSR) is a movement which seeks profitable solutions to environmental and social problems facing corporations and society. In this document firm level drivers of CSR adoption are examined to develop a business case for social/environmental factor integration, built on the link between each driver and profitability. A review of CSR is followed by an examination of a set of short case studies involving the Canadian mining industry and an analysis of the environmental/social efforts of mining organizations, focusing on the industry’s environmental performance and its relationship with aboriginal peoples. It is argued that a positive link exists between firm level profitability and environmental/social performance in the Canadian mining industry. As a result, mining firms have undertaken initiatives which have led to improved environmental and social performance.

Keywords: CSR
Environment
Mining
Advisor: Desrochers, Pierre
Characterization of the Mitochondrial Fusion Protein Mgm1 Reveals Oligomerization and GTPase Activity

Mitochondrial dynamics resulting from competing fusion and fission reactions are required for normal cellular function in eukaryotes. Mgm1, a dynamin related protein, is a key component in yeast mitochondrial fusion and is evolutionarily conserved. Previous in vivo studies suggest that the GTPase domain and oligomerization are required for Mgm1 mediated mitochondrial inner membrane fusion. This work demonstrates that purified Mgm1 forms dynamic low order oligomers, and has GTPase activity and kinetic properties consistent with a mechanoenzyme and with a role in inner membrane mitochondrial fusion. Mutations of key residues in the GTPase domain show diminished GTPase activity, while a mutation in the GTPase effector domain implicated in self-assembly results in a lower propensity to form oligomers. Together these data indicate that Mgm1 mediates fusion through oligomerization and GTP binding/hydrolysis in a manner similar to other dynamin mechanoenzymes.

Keywords: mitochondrial dynamics
Mgm1
mitochondrial fusion
dynamin
Advisor: McQuibban, G. Angus
The Heterogeneous Oxidation of n-Hexane Soot by Ozone: Initial Uptake Coefficient, Mechanism, and the Effect of Surface Coatings

The heterogeneous oxidation of n-hexane soot surfaces by gas-phase ozone has been studied in a coated-wall flow tube connected to a mass spectrometer. Uptake measurements confirm earlier studies that the initial uptake is primarily non-catalytic and that the number of reactive surface sites is close to that of a full monolayer. The initial uptake kinetics exhibit an inverse dependence on ozone gas-phase concentration, as expected if the reaction proceeds via a Langmuir-Hinshelwood mechanism. Support for this reaction not being an Eley-Rideal process comes from the lack of temperature dependence of the initial uptake coefficient, and that a saturated surface coverage of adsorbed dodecane does not affect the kinetics. It is demonstrated that there is a strong similarity between the initial uptake kinetics for ozone loss on a wide variety of surfaces. This suggests that the reactions proceed through a common rate determining step, most likely involving adsorbed ozone molecules.

Advisor: Abbatt, Jonathan P. D.
Automatic Implementation of Multidisciplinary Design Optimization Architectures Using piMDO

Automatic Implementation of Multidisciplinary Design Optimization Architectures Using piMDO Christopher Marriage Masters of Applied Science Graduate Department of Aerospace Engineering University of Toronto 2008 Multidisciplinary Design Optimization (MDO) provides optimal solutions to complex, coupled, multidisciplinary problems. MDO seeks to manage the interactions between disciplinary simulations to produce an optimum, and feasible, design with a minimum of computational effort. Many MDO architectures and approaches have been developed, but usually in isolated situations with little chance for comparison. piMDO was developed to provide a unified framework for the solution of coupled op- timization problems and refinement of MDO approaches. The initial implementation of piMDO showed the benefits of a modular, object oriented, approach and laid the groundwork for future development of MDO architectures. This research furthered the development of piMDO by expanding the suite of available problems, incorporat- ing additional MDO architectures, and extending the object oriented approach to all of the required components for MDO. The end result is a modular, flexible software framework which is user friendly and intuitive to the practitioner. It allows complex problems to be quickly implemented and optimized with a variety of powerful numerical tools and MDO architectures. Importantly, it allows any of its components to be reorganized and sets the stage for future researchers to continue the development of MDO methods.

Keywords: Optimization
Aircraft Design
Multidisciplinary Design Optimization
Computing Frameworks
Advisor: Martins, Joaquim R. R. A.
Aglycone Modulation of HIV Gp120 Binding to Glycosphingolipid (GSL) Detergent-resistant Membrane (DRM) Constructs

HIV gp120 binds CD4+ cells within plasma membrane lipid rafts inducing a conformational change in gp120 that exposes its V3 loop that binds to a chemokine co-receptor, also within lipid rafts, and initiates fusion. Glycosphingolipids (GSLs) may also be bound by gp120. Lipid rafts, enriched with GSLs and cholesterol, are required for HIV entry and therefore the binding of gp120 to GSL-containing vesicles has been studied. Most of the GSL-structures were within the theoretical raft fraction on a discontinuous sucrose gradient while gp120 binding occurred outside of this fraction where a minority of structures migrated. Gb3 fatty acid content modulated binding. Gp120 bound preferentially to structures depleted of cholesterol and binding was enhanced by treating gp120 with CD4. Two water-soluble mimics of Gb3 inhibited gp120 binding to the different structures. The results demonstrate that the aglycone modulation of GSLs alters their receptor function and that the soluble mimics inhibit binding.

Keywords: HIV, Gp120, Glycosphingolipids, Lipid Rafts
Advisor: Lingwood, Clifford A.
Evaluating Alternate Anthropometric Measures as Predictors of Incident Type 2 Diabetes Mellitus (T2DM). The Insulin Resistance Atherosclerosis Study (IRAS)

The goal of this study was to compare different anthropometric measures in terms of their ability to predict T2DM and to determine whether predictive ability was modified by ethnicity. Anthropometrics were measured at baseline on 1073 non-Hispanic Whites (nHW), African Americans (AA) and Hispanics (HA), of which 146 developed T2DM after 5.2 years. Logistic regression models were used with areas under the receiver operator characteristic curve (AROC) comparing the prediction of models. Overall, there was no clear distinction between measures of overall and central obesity in terms of T2DM prediction. Waist-height ratio (AROC=0.678) was the most predictive measure, followed by BMI (AROC=0.674). Results were similar in nHW and HA, although, in AA, central adiposity measures best predicted T2DM. Measures of central and overall adiposity predicted T2DM to a similar degree, except in AA where central measures were most predictive.

Keywords: Type 2 diabetes mellitus
Obesity
Advisor: Hanley, Anthony James Gordon
Improving the Solubility of Yellow Mustard Precipitated Protein Isolate in Acidic Acqueous Solutions

The thesis objective was to investigate methods for improving the solubility of yellow mustard precipitated protein isolate (RTech Laboratories, USA) to allow for its use in protein enhanced acidic beverages along with soluble protein isolate in the pH range of 2 to 4.5. Four treatments were tested: hydrolysis with Alcalase®; cross-linking with transglutaminase; salting in with sodium chloride, sodium tripolyphosphate, and sodium hexametaphosphate; and protective colloid formation with pectin. The effectiveness of each was determined by its ability to improve nitrogen solubility (Nx6.25, AOCS-Ba11-65). The most effective treatments were hydrolysis and pectin stabilization. Pectin (1.5 w/v%) improved solubility from 6% to 29% at pH 4. Alcalase increased solubility from 20% to 70% at pH 3 after 2 h of hydrolysis (0.5AU/5g PPI, pH 8.5, 50-55degC) and eliminated the protein’s isoelectric point in the acidic pH range. Investigating the combined use of both treatments to further increase PPI solubility is recommended.

Keywords: Food Engineering
Food and Beverage Science
Protein
Advisor: Diosady, Levente L.
Multidisciplinary Cancer Conferences: Exploring Obstacles and Facilitators to Their Establishment and Function.

Multidisciplinary cancer conferences (MCCs) provide an opportunity for health professionals to discuss diagnosis and treatment options with the goal of providing optimal patient management. No prior studies have explored the experiences of adopting and implementing MCCs in Canada. Methods: Using a grounded theory approach, interviews, participant-observation, and document analysis were triangulated to explore the experiences of implementing MCCs at four hospitals in Ontario, Canada. Constant comparative analysis was used to identify themes and assimilate them into a theoretical understanding of policy, administrative/organizational, and participant contributions to implementing MCCs. Results: Thirty-seven MCCs, in three hospitals, were observed, and 48 interviews were conducted. The core conceptual category was a perceived value for time balance, which was influenced by policy and administrative factors, and themes related to MCC structure and participant interaction. Conclusions: MCC implementation in Ontario is inconsistent. Future efforts should concentrate on a systematic implementation plan involving clinicians and administrators.

Keywords: Cancer
Multidisciplinary
Qualitative
Team
Decision-making
Grounded theory
Adoption
Implementation
Advisor: Paszat, Lawrence
Wright, Frances
Synthesis and Characterization of Dye-labeled Copolymers by Reversible Addition-fragmentation Transfer (RAFT) Polymerization

Copolymers of N-(2-hydroxypropyl)methacrylamide (HPMA) and N-hydroxysuccinimide methacrylate (NMS) were synthesized by reversible addition-fragmentation transfer (RAFT) polymerization using a semi-batch method. The copolymers were prepared in a wide range of molecular weights (Mn= 4,200-14,000 g/mol) with narrow polydispersities (1.2-1.4). A new approach was developed to prepare a modified RAFT chain transfer agent, a naphthalimide-dyelabeled dithiobenzoate. It was used to prepare a naphthalimide-dye end-labeled poly(HPMA-co-NMS). The copolymer was characterized by four different methods, 1H NMR spectroscopy via end group characterization and using 3-(trimethylsilyl)propionic acid-d4 sodium salt (TSP)external standard, end group analysis by UV-Vis spectroscopy and by GPC. The results obtained from these measurements are in good agreement.

Keywords: reversible addition-fragmentation transfer polymerization
spectroscopy
Advisor: Winnik, Mitchell A.
Synthesis of Beta-(1->6) Linked N-Acetyl-D-Glucosamine Oligosaccharide Glycoconjugates as Potential Vaccine Candidates

Bacterial biofilms are surface associated colonies that are of considerable concern and interest to industry, medicine and research. They are resistant to antibiotics, their host’s defences and are able to survive under harsh conditions. Biofilm formation in many bacterial strains are dependent on the production of a polysaccharide intercellular adhesion (PIA), a beta-(1-->6)-N-acetylglucosamine polymer. Vaccines derived from biologically isolated PIA have shown efficacy against clinically isolated strains of E. coli and pathogenic strains of S. aureus in animal models. Accordingly, chemically synthesized neoglycoconjugates based on PIA glycosides will be developed to serve as lead compounds for the development of new antibiotics as well as vaccines against biofilm dependent infections. Described in this thesis is a comprehensive study of the synthesis of PIA oligosaccharides and their deacetylated equivalents, the strategy for installing a stable linker on the free reducing oligosaccharide terminus and finally the conjugation to a model carrier protein for the development of potential neoglycoprotein vaccines.

Keywords: Biofilms
Carbohydrate Vaccines
Poly N-acetylglucosamine
PIA
Advisor: Nitz, Mark
Controlling Cell Density by Micropatterning Regulates Smad Signalling and Mesendoderm Differentiation of Human Embryonic Stem Cells

Human embryonic stem cells (hESC) present a potentially unlimited supply of hematopoietic progenitors for cell-based therapies. However, current protocols for generating these progenitors typically also generate undesired cell types due to imprecise control of the hESC microenvironment and poor understanding of the signalling networks regulating mesoderm differentiation (the germ layer from which hematopoietic cells emerge). This report demonstrates that activation of the downstream effectors of Activin/Nodal and bone morphogenetic protein (BMP) signalling (Smad2 (composite of Sma (smaller) and Mad (mothers against decapentaplegic) and Smad1, respectively) are both required for mesoderm differentiation. It is further shown that microcontact printing-mediated control of hESC colony size creates local microenvironments that guide differentiation, via a Smad1-dependent mechanism, preferentially towards the mesoderm lineage. These findings demonstrate the need for precise control of the microenvironment in order to effectively guide hESC differentiation to produce specific cell types for potential therapeutic applications.

Keywords: Pluripotent Stem Cells
Mesendoderm
Hematopoiesis
Micropatterning
Advisor: Zandstra, Peter W.
Analysis of Naked in the Canonical Wnt Pathway

Wnt signalling is involved throughout development and is inappropriately activated in a variety of human cancers. In the canonical pathway, secreted Wnt proteins induce the stabilization of b-catenin. Drosophila Naked (Nkd), or Nkd1 and Nkd2 in vertebrates, is believed to antagonize canonical Wnt signalling through an interaction with Dishevelled (Dvl). Analysis of a high-throughput protein-protein interaction screen conducted in our lab led to the identification of novel Nkd1 interacting proteins, including Nkd1/2 and Axin1. Mapping of Nkd1 regions required for these novel interactions and functional studies, including transcriptional and siRNA mediated knockdown assays, were performed to examine the role of Nkd1 in canonical Wnt signalling. Previous work suggests that Nkd1 functions only through Dvl, but this work suggests that Nkd1 acts via a more complex mechanism. In addition to serving as an antagonist to regulate the canonical Wnt pathway, we propose that Nkd1 may also act positively to promote signalling.

Keywords: Naked
Wnt
Advisor: Attisano, Liliana
Access to Dental Care for Persons with Disabilities in Ontario: A Focus on Persons with Developmental Disabilities

This study was undertaken to determine if persons with disabilities encounter difficulties in accessing dental care in Ontario, to identify barriers to accessing dental care and to determine if persons with disabilities and caregivers value oral health. Community organizations providing supports for persons with disabilities were recruited to circulate a questionnaire to their members via mail or internet. Fourteen community organizations mailed out 1755 paper questionnaires. A response rate of 23.9% was calculated from original surveys returned. In total, 634 paper and internet surveys were deemed valid. Data analysis was conducted using the chi square test and logistic regression. Most (73.2%) persons with disabilities, primarily developmental disabilities, were able to access dental services in Ontario. Personal internal factors were more likely to act as barriers to dental care than external factors. The majority of caregivers and persons with disabilities believe that oral health is an important part of overall health.

Keywords: access
dentistry
special needs
disability
Canada
dental care
Advisor: Sigal, Michael
Efficient, Stable Infrared Photovoltaics based on Solution-Cast PbSe Colloidal Quantum Dots

Half of the sun’s power lies in the infrared. As a result, the optimal bandgaps for solar cells in both the single-junction and even the tandem architectures lie beyond 850 nm. However, progress in low-cost, large-area, physically-flexible solar cells has instead been made in organic and polymer materials possessing absorption onsets in the visible. Recent advances have been achieved in solution-cast infrared photovoltaics through the use of colloidal quantum dots. Here we report stable solution-processed photovoltaic devices having 3.6% power conversion efficiency in the infrared. The use of a strongly-bound bidentate linker, benzenedithiol, ensures device stability over weeks. We investigate in detail the physical mechanisms underlying the operation of this class of device. We find that diffusion of electrons and holes over hundreds of nanometers through our PbSe colloidal quantum dot solid is chiefly responsible for the high external quantum efficiencies obtained in this new class of devices.

Keywords: Nanocrystals
Infrared Photovoltaics
Advisor: Sargent, Edward H.
Near-infrared Spectroscopy as an Access Channel: Prefrontal Cortex Inhibition During an Auditory Go-no-go Task

The purpose of this thesis was to explore the potential of near-infrared spectroscopy (NIRS) as an access channel by establishing reliable signal detection to verify the existence of signal differences associated with changes in activity. This thesis focused on using NIRS to measure brain activity from the prefrontal cortex during an auditory Go-No-Go task. A singular spectrum analysis change-point detection algorithm was applied to identify transition points where the NIRS signal properties varied from previous data points in the signal, indicating a change in brain activity. With this algorithm, latency values for change-points detected ranged from 6.44 s to 9.34 s. The averaged positive predictive values over all runs were modest (from 49.41% to 67.73%), with the corresponding negative predictive values being generally higher (48.66% to 78.80%). However, positive and negative predictive values up to 97.22% and 95.14%, respectively, were achieved for individual runs. No hemispheric differences were found.

Keywords: Near-infrared Spectroscopy
access pathway
access channel
brain-computer interface
Go-No-Go Task
Prefrontal Cortex
inhibition
Change-point Detection
access technology
Advisor: Chau, Tom