VictorJuiz/thesis huggingface dataset:
Design of a Bioreactor to Mimic Hemodynamic Shear Stresses on Endothelial Cells in Microfluidic Systems

The mechanisms behind cardiovascular disease (CVD) initiation and progression are not fully elucidated. It is hypothesized that blood flow patterns regulate endothelial cell (EC) function to affect the progression of CVDs. A system that subjects ECs to physiologically-relevant shear stress waveforms within microfluidic devices has not yet been demonstrated, despite the advantages associated with the use of these devices. In this work, a bioreactor was designed to fulfill this need. Waveforms from regions commonly affected by CVDs including were derived. Pump motion and fluid flow profiles were validated by actuator motion tracking, particle image velocimetry, and flowmeters. While several relevant waveforms were successfully replicated, physiological waveforms could not be produced at physiological frequencies owing to actuator velocity and accuracy limitations, as well as dampening effects in the system. Overall, this work lays the foundation for designing a system that provides insight into the role of shear stress in CVD pathogenesis.

Keywords: Endothelial cell
Bioreactor
Flow loop
Cardiovascular disease
CVD
Waveform
Microfluidics
Microfluidic devices
Hemodynamics
EC
Shear stress
Shear
Pump
Actuator
Mechanical engineering
Biomedical engineering
PIV
Particle image velocimetry
Fluid dynamics
Fluid mechanics
Pressure
Model
Syringe
Peristaltic
Blood
Blood flow
Wall shear stress
Womersley number
Womersley
Purday
Physiological
Flowmeter
Sinusoid
Sinusoidal
Disturbed
Non-disturbed
Undisturbed
Oscillatory
Pulsatile
In vivo
In vitro
Advisor: Simmons, Craig A.
Santerre, J. Paul
The Health Consequences of Fructose, its Metabolite, Dihydroxyacetone and the Hepatoprotective Effects of Selected Natural Polyphenols in Rat Hhepatocytes

The introduction of high fructose corn syrup into the diet has been proposed to be the cause of many illnesses related to the metabolic syndrome. Fructose and its metabolites can be metabolized into cytotoxic reactive dicarbonyls that can cause damage to macromolecules leading to deleterious consequences. Dihydroxyacetone, a fructose metabolite, was studied in this thesis. Its ability to autoxidize and cause protein carbonylation under standard (pH 7.4, 37°C) and oxidative stress conditions (Fentons reagent) was investigated. Dihydroxyacetone was able to form significant amounts of dicarbonyls and protein carbonylation. Several selected natural polyphenols were chosen for an in vitro toxicological study involving rat hepatocytes. The chosen dietary polyphenols were rutin, gallic acid, methylgallate, ethylgallate, propylgallate and curcumin. In this thesis, the polyphenols were found to be able to significantly protect against the deleterious effects of glyoxal and methylglyoxal. In summary, these polyphenols could be candidates for future in vivo studies.

Keywords: Glyoxal
Methylglyoxal
Oxidative stress
Autoxidation
Protein carbonylation
Polyphenols
Advisor: O'Brien, Peter
Anti-GPIbα Mediated Platelet Desialylation and Activation: A Novel Fc-independent Platelet Clearance Mechanism and Potential Therapeutic and Diagnostic Target in ITP

Immune thrombocytopenia (ITP) is a common bleeding disorder caused primarily by autoantibodies against platelet GPIIbIIIa and/or the GPIb complex. Current theory suggests antibody-mediated platelet destruction occurs in the spleen via Fcγ receptors (FcγR). However, it has been demonstrated that anti-GPIbα-mediated ITP is often refractory to therapies targeting FcγR pathways. Utilizing a panel of murine monoclonal antibodies (mAbs) against murine and human GPIIbIIIa and GPIbα, it was found that anti-GPIbα induces not only platelet activation to a much greater extent than anti-GPIIbIIIa antibodies, but also significant surface expression of neuraminidase 1 and platelet desialylation. Utilizing inhibitors of platelet activation and desialylation, it was found that these two processes are not mutually exclusive, but rather exist in a positive feedback loop, leading to FcγR-independent platelet clearance in the liver likely via Ashwell-Morell receptors. Furthermore, in a murine model of ITP, sialidase inhibitor treatment rescued platelet counts in predominantly anti-GPIbα -mediated thrombocytopenia.

Keywords: Immune thrombocytopeni
Fc-independent clearance
Advisor: Ni, Heyu
Preliminary Design of Slender Reinforced Concrete Highway Bridge Pier Systems

Feasible span-to-depth ratios for many modern bridge systems have been identified and documented in literature. No such parameters have been adequately identified in terms of proportioning bridge piers. This thesis includes a study of 22 existing reinforced concrete highway bridges and their respective pier systems to determine the state-of-the-art in design. The effect of different geometric and material parameters such as concrete strength, reinforcement ratio and slenderness ratio on the structural behavior of individual piers and multiple pier systems was examined. Approximate methods, which may be used for the purposes of preliminary design are discussed and reviewed. Serviceability and ultimate limit states design aids that can be used to identify appropriate preliminary cross-sectional pier dimensions and reinforcement ratios for individual piers given various slenderness ratios were developed. The structural behavior as well as an approach to the preliminary design of multiple pier bridge systems is presented.

Keywords: columns
slender piers
pier systems
bridges
structures
second-order effects
concrete
reinforcement ratio
slenderness ratio
material nonlinearity
geometric nonlinearity
Advisor: Gauvreau, Paul
Involvement of the C-terminal Repeat (CTR) Domain in the Protein Interactions and Functions of Spt5

Transcription elongation by RNA polymerase II is regulated by an array of protein complexes. Among various elongation factors, Spt5 is conserved in the three kingdoms of life. I investigated functional interactions of its C-terminal repeats (CTR) domain with several elongation protein complexes in Saccharomyces cerevisiae. By using genetics and molecular biology methods, I established two major pathways in this thesis. The first describes how BUR kinase-mediated phosphorylation of CTR domain leads to co-transcriptional recruitment of the PAF complex to regulate histone modifications on active genes. The second describes how CTR phosphorylation facilitates recruitment of capping enzymes to enhance gene splicing. Finally, several Spt5-associated protein complexes were studied, and potential molecular mechanisms underlying these observations are proposed and discussed.

Keywords: Transcription, Histone Modification, Gene Splicing, Nucleosome, mRNA Processing, Phosphorylation, Epigenetics
Advisor: Greenblatt, Jack
A Novel Design for Fully Printed Flexible AC-driven Powder Electroluminescent Devices on Paper

ACPEL devices were fabricated onto various paper substrates. The dielectric and phosphor layers were mask printed, a PEDOT:PSS/SWCNT ink was inkjet-printed for the cathode and a translucent conductor was applied with a paintbrush for the anode resulting in a maximum luminance of 8.05 cd/m2 at 300 VAC and 60 Hz. It was found that the conductivity of the PEDOT:PSS/SWCNT ink on the various paper types was affected by the coating and paper thickness. Novel ACPEL devices were also fabricated by incorporating paper as the dielectric layer of the device. The maximum luminance achieved was 7.24 cd/m2 at 300 VAC and 60 Hz. It is shown that the dielectric constant of the paper and hence the performance of the resulting EL device may be enhanced by filling the sheet with BaTiO3 and by the surface treatment of the sheet.

Keywords: electroluminescent device
printed electronics
pulp and paper
Advisor: Ramin, Farnood
Tension Stiffening and Cracking Behaviour of GFRP Reinforced Concrete

Glass Fibre-Reinforced Polymer (GFRP) bars offer a feasible alternative in locations where steel is not the suitable reinforcement; namely locations that are sensitive to corrosion. In this study 60 specimens, 52 GFRP reinforced and 8 steel reinforced, were constructed and tested under direct tension in order to investigate the tension stiffening and cracking behaviour. The effects of different variables such as the bar type, the bar diameter, the reinforcement ratio and the concrete strength on tension stiffening and crack spacing were studied. The current code provisions for tension stiffening, namely ACI-440 and CEB-FIP were evaluated against the obtained test data. It was determined that the current code provisions significantly overestimate tension stiffening in GFRP reinforced specimens. A new tension stiffening model was, therefore, developed that provides better simulation of the test data. The CEB-FIP 1978 model for crack spacing was also modified for GFRP reinforced members.

Keywords: tension stiffening
crack spacing
GFRP
concrete
Advisor: Sheikh, Shamim A.
Evaluation and Verification of Aerosol Diluters: Accuracy and Particle Loss

The aerosol diluter characteristics of three different systems, the single-stage and the two-stage TSI 379020A rotary disk thermodiluters and Dekati FPS-4000 ejector diluter, were tested using gases and particles over a range of dilution ratios. The upstream and downstream gas and particle concentrations of the diluters were measured in real-time to compute the actual dilution ratio achieved by the three systems. Dilution ratios from approximately 15 to 100 were found to fall within the expected operating error margin of ± 10% for CO2 and CH4. Dilution ratios covering a similar range were also achieved to within ± 10% for particles with diameters from 9.3 to 200 nm. However, when engine exhaust was sampled, significant loss of particles smaller than 29.4 nm occurred during the dilution process. As the dilution ratio increased, the deviation from the expected value increased due to an increase in measurement uncertainty.

Keywords: Aerosol Diluter
Particle Loss
Advisor: Wallace, James
Evans, Greg
Epigenetic Studies of Bipolar Disorder

Bipolar disorder is a psychiatric illness characterized by recurrent fluctuations in mood and increased risk of suicide. Twin and family studies have identified the highly heritable nature of the disorder, but the limitations of the current DNA-centric paradigm underscore the need for a new perspective to gain a clearer understanding of its basis. This project investigates various facets of bipolar disorder from an epigenetic standpoint. We used mass spectrometry-based mapping of individual DNA modification differences of the brain-derived neurotrophic factor gene. Moreover, the epigenetic basis of suicidal behaviour in bipolar disorder was investigated using DNA methylation microarrays. We also used a newly-developed enrichment technique, mTAG, to interrogate chromosome-wide DNA modification profiles using tiling microarrays in post-mortem brains of bipolar disease patients and controls. Findings from these experiments highlight observable features of epigenomes of patients affected with mood disorders, and may further the understanding of the molecular origin of psychiatric diseases.

Keywords: bipolar disorder
epigenetics
suicidal behaviour
genetics
psychiatric disorder
mood disorder
Advisor: Strauss, John
Petronis, Arturas
MicroRNA Profiling in Experimental Sepsis-induced Acute Lung Injury

Introduction: Currently, there are no specific pharmacological treatments for sepsis-induced acute respiratory distress syndrome (ARDS). And mesenchymal stem cells (MSCs) have shown reparative potential in both sepsis and ARDS. Objectives: To determine the role of MSC administration in the modulation of pulmonary host-responses to sepsis via differential regulation of regulatory microRNAs (miRNAs/miRs). Methods: MicroRNA and mRNA profiling was performed to identify differential expression. Quantitative real time polymerase chain reaction (qRT-PCR), trans-endothelial electrical resistance (TEER) measurements, and luciferase activity assay were used. Results: MicroRNA expression was examined in Human Pulmonary Microvascular Endothelial Cells (HPMECs). One miRNA – miR-193b-5p, targets occludin, a tight junction protein associated with endothelial leakage. A specific regulatory relationship between miR-193b-5p and occludin was identified. The loss in endothelial integrity was rescued when miR-193b-5p inhibitor was transfected. Conclusion: miR-193b-5p is a suppressor of occludin. Studying transcriptional changes allows identification of therapeutically relevant mediators for ARDS/ALI treatment.

Keywords: microRNA
acute lung injury
experimental sepsis
mesenchymal stem cells
treatment
transcriptome
Advisor: Santos, Claudia dos
Generic Drug Pricing and Substitution in Private Drug Plans in Canada

Purpose: To estimate the willingness and ability of private plans to manage costs during the generic drug procurement reform era that began in 2006 in Canada. Two cost management aspects were assessed; the prices paid for generic drugs and the extent to which private plans have enacted measures to increase generic substitution. Methods: IMS-Brogan Pharmastat data was used to estimate the price of commonly prescribed generic drugs and generic share of prescriptions, by plan type, province and quarter from 2003 to 2012. Results: Prices did not decline unless the provincial governments mandated the reductions. Savings from this mandate was approximately $264 million in Ontario. Rates of generic substitution were unaffected by the price reductions, possibly because the rates were high beforehand. Conclusion: Private plans did not independently obtain lower generic prices. Due to already high substitution rates, there may have been limited potential for additional savings from mandatory substitution controls.

Keywords: Private insurance
Generic drug
Drug reimbursement
Drug substitution
Drug costs
Advisor: Grootendorst, Paul
Usability of Paper-based Industrial Operating Procedures

Procedures are standardized lists of instructions that designate the safe and accepted way of accomplishing a task. This study intended to develop and compare the usability of paper-based industrial operating procedures. Two procedures at a plant were redesigned with evidence-based guidelines and human factors input. 16 operators of varying experience were asked to read through and assess the new and old procedures. The new procedures were rated significantly or moderately better than their predecessors for efficiency, effectiveness, and subjective satisfaction. On average, inexperienced operators reported fewer inaccuracies, more confusion, and higher workload ratings than their experienced counterparts, regardless of procedure type or area. For satisfaction, experienced and inexperienced operators reported similar ratings across both procedure types and areas. Future studies should attempt to discern which particular change in the procedures contributed the most to increased usability, and whether operator experience significantly correlates with usability ratings.

Keywords: procedure
usability
checklist
design guidelines
Advisor: Jamieson, Greg
Association Between Electroretinogram-identified Vigabatrin Toxicity and Subsequent Visual Field Reduction

Vigabatrin (VGB) is an antiepileptic drug approved for pediatric patients with infantile spasms. VGB is associated with visual field reductions in 30-50% of adults taking the drug. The amplitude of the 30-Hz flicker electroretinogram (ERG) is recommended for screening young children on VGB treatment. To determine if standard ERG tests for VGB toxicity are correlated with visual field reductions, 22 individuals who were previously on VGB underwent visual assessment. This study also validated the use of high-resolution OCT for detecting structural changes associated with VGB toxicity. This study demonstrates that the ERG was associated with visual field loss, as measured along the temporal meridian. The retinal nerve fibre layer (RNFL) was attenuated in all children who showed a reduction in the visual fields indicating that RNFL attenuation may be a sensitive marker for VGB toxicity. We recommend using serial OCTs to monitor VGB toxicity since it is fast and non-invasive.

Keywords: vigabatrin
visual fields
Advisor: Westall, Carol
Settlement, Food Lands, and Sustainable Habitation: The Historical Development of Agricultural Policy and Urban Planning in Southern Ontario

In this thesis I recount the historical relationship between settlement and food lands in Southern Ontario. Informed by landscape and food regime theory, I use a landscape approach to interpret the history of this relationship to deepen our understanding of a pertinent, and historically specific problem of land access for sustainable farming. This thesis presents entrenched barriers to landscape renewal as institutional legacies of various layers of history. It argues that at the moment and for the last century Southern Ontario has had two different, parallel sets of determinants for land-use operating on the same landscape in the form of agricultural policy and urban planning. To the extent that they are not purposefully coordinated, not just with each other but with the social and ecological foundations of our habitation, this is at the root of the problem of land access for sustainable farming.

Keywords: Southern Ontario
Landscape
Land-use
Food
Farming
Settlement
Advisor: Friedmann, Harriet
Retinal Blood Flow in Patients with Primary Open Angle Glaucoma and Optic Disc Hemorrhage

Purpose: To investigate venous total retinal blood flow (TRBF) and retinal blood flow (RBF) in the superior and the inferior retinal hemifields in primary open angle glaucoma (POAG) patients with, and without, disc hemorrhage (DH). Methods: RBF measurements were obtained from 10 POAG with DH and 19 POAG without DH using Doppler SD-OCT (RTVue) as well as bi-directional laser Doppler flowmetry (CLBF). Results: RBF was not different between the superior and inferior hemifields for either of the two groups. Venous TRBF in the POAG with DH group was significantly lower than in the age-matched stable POAG without DH group (p=0.009). In the POAG with DH group, venous TRBF was significantly lower in the DH eye compared to contralateral eye without DH (p=0.015). Conclusions: Venous TRBF was significantly lower in the POAG with DH group compared to both the POAG without DH group and the contralateral eye of the POAG with DH group.

Keywords: Retinal Blood Flow
Glaucoma
Disc Hemorrhage
Advisor: Hudson, Christopher
Fully Quadratic Vibronic Model of Electronic Transitions through Conical Intersections

We introduce a perturbative method for studying photoinduced electronic transitions through conical intersections. Our approach uses a quadratic vibronic coupling Hamiltonian and second order cumulant approximation for the diabatic coupling to derive an analytical expression for time evolution of electronic populations at given temperatures. The formalism is an extension of a previous method called the non-equilibrium Fermi golden rule approach which used the linear vibronic coupling Hamiltonian with the same cumulant treatment for diabatic coupling. The advantage of the quadratic Hamiltonian is that it can include electronic states with different frequencies and normal modes. We explore these advantages with 2D models showing the improved accuracy of the new quadratic method over the linear method. We then apply our formalism to some real molecules, 2,6-bis(methylene) adamantyl cation, and its dimethyl derivative, with parameters obtained from electronic structure calculations followed by diabatization. The results show good agreement with quantum dynamics techniques.

Keywords: conical intersections
dynamics
Advisor: Izmaylov, Artur
Direct Synthesis of Netlists into Pre-routed FPGAs

This thesis introduces a new approach to compilation for FPGAs, which we call direct synthesis. We take a technology-mapped circuit netlist and directly map it into a pre-placed and routed FPGA overlay. Solving this problem may help to address the increasing portion of compile time that is attributed to placement and routing, and the tremendous amount of area and energy consumed by the highly flexible FPGA routing network. This thesis presents a direct synthesis algorithm and an algorithm for generating the pre-placed and routed FPGA overlays. Using the direct synthesis flow which we have designed, we can successfully map circuits less than 100 BLEs in size, after modest modi cations to the architecture of the FPGA overlay circuit. While we show that direct synthesis problem is challenging, further architectural modi cations are proposed which can allow the direct synthesis of larger circuits to succeed.

Keywords: FPGA
CAD
Advisor: Rose, Jonathan
Delineation of the Molecular and Genetic Role of Teneurin C-terminal Associated Peptide-1 (TCAP-1) in Cytoskeletal Development and Neuroprotection Against Stress

The Corticotropin Releasing Factor (CRF) peptides are an evolutionarily conserved peptide family integral to the stress response. In 2002, an investigation was undertaken into possible homologues of CRF, which led to the discovery of the Teneurin C-terminal Associated Peptide (TCAP) family located on the C-terminal end of the teneurin proteins. This peptide family is involved in neuroprotection against stress. TCAP possesses a number of biological actions independent of teneurin, however, evidence of how TCAP is processed from its proprotein had not been determined. I hypothesize that TCAP is transcribed independently and has independent functionality in promoting filopodia elongation and outgrowth. Here, I show that TCAP-1 is independently expressed as an mRNA separate from the teneurin gene. Moreover, a key step in the TCAP-1 mediated molecular mechanism of filopodia outgrowth may require an interaction between Elongation Factor-1α (EF-1α) and the actin cytoskeleton, where this mechanism is not modulated by CRF.

Keywords: Stress
Endocrinology
Advisor: Lovejoy, David
Patient-Derived Xenografts as Pre-clinical Models of Response to Chemotherapy

Ovarian high-grade serous cancer (HGSC) is the most lethal gynecologic malignancy and well-characterized models may improve patient outcomes. Patient-derived xenografts (PDXs) recapitulate disease heterogeneity; however, to be useful in predicting response to novel chemotherapeutics, they must reflect the response of the donor tissue to standard chemotherapy. The objectives of this study were: first, to evaluate the response of PDXs’ to platinum therapy and compare this response to that of the donor; and second, to determine whether treatment with chemotherapy enriches for tumourigenic cells. Eighteen samples formed tumours in the mammary fat pads of NOD-Scid-IL2Rγnull mice and were treated with Carboplatin. There was a 100% concordance between sample status and PDXs response to chemotherapy. HGS histology was confirmed for all cases. A conclusion regarding post-chemotherapy tumourigenicity could not be made due to inadequate statistical power. PDXs represent useful tools for evaluation of novel therapies and identification of patients who are platinum-resistant/sensitive.

Keywords: Xenografts
Ovarian Cancer
Chemotherapy
Models
Advisor: Neel, Benjamin
Bernardini, Marcus
Path Constraints on Movement of Objects

The present study examined 8 -10 month-old and 11 -13 month-old infants’ capabilities to infer constraints imposed by an explicit visual pathway on object movement of object. In a preferential looking paradigm, infants observed a ball rolling down a U– or V–shaped path. In the U-shaped path, infants observed a ball rolling from beginning to the end of the path (possible), and a ball rolling down from the beginning and stopping midway of the path (impossible). In the V-shaped path, infants observed a ball rolling from beginning and stopping midway (possible), and a ball rolling down the beginning to end of the path (impossible). Analyses of looking times showed a marginal effect on path, with longer looking times towards the possible V-shaped path by both age groups. Overall, infants had weak representations for constraints induced by an explicitly presented path on movement of the object.

Keywords: Path
constraints
object
motion
infants
perception
Advisor: Schmuckler, Mark