VictorJuiz/thesis huggingface dataset:
The Role of GABAA Receptor-mediated Neurotransmission in Ventilatory Acclimatisation to Hypoxia
Keywords: GABAA
Chronic Hypoxia
Ventilatory
Acclimatisation

Exposure to chronic hypoxia (CH) leads to ventilatory acclimatisation to hypoxia (VAH) which is a time-dependent increase in breathing. This study examined the role of the GABAA receptor in establishing VAH. Rats were exposed to CH or control (normoxic) conditions for 10 days during which the GABAA receptor antagonist, bicuculline, was infused systemically or directly into the nucleus of the solitary tract (NTS). Acute breathing trials were then performed to measure resting ventilation and ventilatory chemoreflexes. Systemic administration of bicuculline caused reductions in breathing during acute hypoxia and acute hypercapnia in the control but not the CH animals. Continuous infusion of bicuculline in to the NTS caused a reduction in the acute hypoxic ventilatory response in animals exposed to CH but not in the control animals. The results indicate that exposure to CH alters the GABAA-mediated regulation of acute ventilatory chemoreflexes both in the NTS and elsewhere in the brain.
Applications and Orbit Scenarios for a Multistatic InSAR Formation Flying Microsatellite Mission
Keywords: microsatellites
InSAR

The Space Flight Laboratory (SFL) at the University of Toronto Institute for Aerospace Studies is currently designing CanX-4 and CanX-5, a pair of formation-flying nanosatellites that will target centimeter-level position determination and sub-meter control. Once formation flight has been demonstrated, future missions can carry payloads designed to exploit these capabilities. Earth Observation is one such application that can benefit greatly from the availability of multiple platforms with precise position determination and attitude control. This work explores multistatic interferometric synthetic aperture radar (InSAR) as a particularly promising implementation of formation flight. Several mission scenarios are considered, including three commonly proposed InSAR constellation configurations, namely the Cartwheel, the Cross-Track Pendulum, and the Car-Pe configuration, as well as three large ( kilowatt) SAR transmitters (L-, C- and X-band) and one microsatellite transmitter (X-band, 150W). Using a framework of STK and MATLAB simulation and analysis tools, each case is evaluated with respect to the available interferometric baselines, ground coverage, resolution, and utility for selected applications including digital elevation modeling, moving target detection, and superresolution imagery. The “large” X-band transmitter is found to produce the most favorable operating area and resolution, and the Car-Pe configuration provides the greatest utility and flexibility for a combination of the three selected applications.
High-thoughput Screen to Identify Small Molecule Inhibitors of the Canonical Wnt Signaling Pathway
Keywords: Wnt signaling
Small molecule screen

Wnt signaling is important in human development and disease, thus dysregulated beta-catenin constitutes an attractive target for drug intervention. The few functional inhibitors currently available target transcriptional activation, therefore, identifying novel upstream modulators would be of tremendous importance to elucidating the mechanisms involved in regulatingbeta-catenin activity. To achieve this, I developed a high-throughput screen to assess beta-catenin stability in mammalian cells using a luciferase tagged beta-catenin molecule. This assay was used to screen three chemical libraries to identify small molecule modulators of the pathway. Identified inhibitors/activators of the pathway were investigated via secondary assays. The most promising inhibitor, 21H7, significantly attenuated activated beta-catenin signaling in colon cancer cells, decreasing beta-catenin stability. The inhibitory effects of 21H7 and a structurally similar compound were shown to not only inhibit Wnt target gene expression in colon cancer cells, but also prostate cancer lines. Thus, 21H7 represents an attractive lead compound for further study.
Design and Analysis of a Tensioner for a Belt-driven Integrated Starter-generator System of Micro-hybrid Vehicles
Keywords: B-ISG
Micro-hybrid
belt drive
tensioner
automotive
integrated starter-generator
belt-driven integrated starter-generator
ISG
model
genetic algorithm
optimization
parametric analysis
hybrids
equations of motion

The thesis presents the design and analysis of a Twin Tensioner for a Belt-driven Integrated Starter-generator (B-ISG) system. The B-ISG is an emerging hybrid transmission closely resembling conventional serpentine belt drives. Models of the B-ISG system's geometric properties and dynamic and static states are derived and simulated. The objective is to reduce the magnitudes of static tension in the belt for the ISG-driving phase. A literature review of hybrid systems, serpentine belt drive modeling and automotive tensioners is included. A parametric study evaluates tensioner parameters with respect to their impact on static tensions. Design variables are selected from these for an optimization study. The optimization uses a genetic algorithm (GA) and a hybrid GA. Results of the optimization indicate the optimal system contains spans with static tensions that are significantly lower in magnitude than that of the original design. Implications of the research on future work are discussed in closing.
Modified-hyaluronan and Elastin-like Polypeptide Composite Material for Tissue Engineering of the Nucleus Pulposus
Keywords: Tissue Engineering
Intervertebral disc
Spine
Nucleus Pulposus
Hyaluronan
Elastin
Biomaterial
Biomechanics

Degenerative disc disease is a common ailment with enormous medical, psychosocial and economic ramifications. This study was designed to investigate the utility of a thiol-modified hyaluronan(TMHA) and elastin-like polypeptide(EP) composite material as a potential tissue engineering scaffold to reconstitute the nucleus pulposus in early degenerative disc disease. TMHA and EP were combined in various concentrations and cross-linked using poly(ethylene glycol)diacrylate. Resulting materials were evaluated biomechanically and biologically. Confined compression testing revealed that the addition of EP to TMHA-based gels resulted in a stiffer construct, but remained an order of magnitude less stiff than native nucleus. The in vitro cell culture experiments with human intervertebral disc cells demonstrated 70% cell viability at three weeks with apparent maintenance of phenotype. The addition of EP did not have a significant biologic effect. An in vivo pilot study demonstrated biocompatibility of the TMHA-based hydrogels; additional power is required to adequately assess treatment effect.
Performance Measurement of Water Distribution Systems (WDS). A Critical and Constructive Appraisal of the State-of-the-art
Keywords: Water Distribution Systems
Performance Measurement

Water supply and distribution infrastructures are vital for current life. They have a significant role in public health, providing safe water for drinking and human consumption as well as for essential non-potable uses such as fire fighting. These diverse objectives create challenges for everyone who must address in some way the actual performance of the system. This research critically evaluates all common objectives of conventional design approaches and evaluates the advantages and drawbacks of various performance measures. New ideas for a more realistic and comprehensive approach to the design, operation assessment of WDS are proposed. A new approach, called a Risk-based Performance Assessment, for hydraulic performance evaluation is tentatively proposed. It is based on integration of reliability, resiliency, and vulnerability as three basic operational indices in the operation of WDS. Furthermore, the Total Life-cycle Cost evaluation approach is tentatively proposed based on considering all major costs of a WDS.
ALX4 Expression in the Normal Breast and in Breast Cancer
Keywords: ALX4
mammary gland
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.
Functional Consequences of Complete GSK-3 Ablation in Mouse Embryonic Fibroblasts
Keywords: GSK-3
BCLAF1

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.
Mechanisms of Diet-induced Dyslipidemia and Insulin Resistance: Role of Chronic LXR Activation
Keywords: LXR
Cholesterol
Dyslipidemia
Insulin resistance

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.
Behaviour and Design of Extradosed Bridges
Keywords: extradosed prestressing
bridge design
cable pretensioning
cable-stayed
cantilever construction

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.
The Drivers and Performance of Corporate Environmental and Social Responsibility in the Canadian Mining Industry
Keywords: CSR
Environment
Mining

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.
Characterization of the Mitochondrial Fusion Protein Mgm1 Reveals Oligomerization and GTPase Activity
Keywords: mitochondrial dynamics
Mgm1
mitochondrial fusion
dynamin

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.
Automatic Implementation of Multidisciplinary Design Optimization Architectures Using piMDO
Keywords: Optimization
Aircraft Design
Multidisciplinary Design Optimization
Computing Frameworks

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.
Aglycone Modulation of HIV Gp120 Binding to Glycosphingolipid (GSL) Detergent-resistant Membrane (DRM) Constructs
Keywords: HIV, Gp120, Glycosphingolipids, Lipid Rafts

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.
Evaluating Alternate Anthropometric Measures as Predictors of Incident Type 2 Diabetes Mellitus (T2DM). The Insulin Resistance Atherosclerosis Study (IRAS)
Keywords: Type 2 diabetes mellitus
Obesity

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.
Improving the Solubility of Yellow Mustard Precipitated Protein Isolate in Acidic Acqueous Solutions
Keywords: Food Engineering
Food and Beverage Science
Protein

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.
Multidisciplinary Cancer Conferences: Exploring Obstacles and Facilitators to Their Establishment and Function.
Keywords: Cancer
Multidisciplinary
Qualitative
Team
Decision-making
Grounded theory
Adoption
Implementation

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.
Synthesis and Characterization of Dye-labeled Copolymers by Reversible Addition-fragmentation Transfer (RAFT) Polymerization
Keywords: reversible addition-fragmentation transfer polymerization
spectroscopy

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.
Synthesis of Beta-(1->6) Linked N-Acetyl-D-Glucosamine Oligosaccharide Glycoconjugates as Potential Vaccine Candidates
Keywords: Biofilms
Carbohydrate Vaccines
Poly N-acetylglucosamine
PIA

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.