VictorJuiz/thesis huggingface dataset:
A Microfluidic Platform for the Automated Multimodal Assessment of Small Artery Structure and Function

In this thesis, I present a microfluidic platform that enables automated image-based assessment of biological structure and function. My work focuses on assessing intact resistance arteries from the mouse cerebral vascular bed with a diameter of approximately 120µm in vitro. The experimental platform consists of a microfluidic device and a world-to-chip fluidic interconnect that minimizes unwanted dead volumes and eliminates the need for any liquid-filled peripheral equipment. The integrated platform is computer controlled and capable of fully automated operation once a small blood vessel segment is loaded onto the chip. Robust operation of the platform was demonstrated through a series of case studies that assessed small artery function and changes therein induced by incubation with the drug nifedipine, a dihydropyridine calcium channel blocker. In addition artery segments were stained for L-type calcium channels, F-actin and nuclei, from which structural information about cell alignment and shape was quantified.

Keywords: Microfluidics
Resistance Artery
Automation
World to chip interconnect
Advisor: Guenther, Axel
The Problem of Translation in Modern China: A Brief Study on Lu Xun and Qian Zhongshu

This thesis aims to explore translation theory in modern China to shed light on the thought of inter-culturality through translation in the age of globalization, focussing on the works of Lu Xun and Qian Zhongshu. This paper attempts to unveil the constitution of modernization, the cultural way of crossing boundary, and the construction of imaginary otherness. The first chapter examines the methodological problems of translation in Lu Xun and Qian Zhongshu, separately, to demonstrate their contributions to Chinese modern translation theory from aesthetic viewpoints. The second chapter discusses the purpose of translation, investigating the cultural meaning of boundary crossing in translation. The third chapter examines the problems of the translatability and untranslatability from Lu Xun’s and Qian Zhongshu’s aspects, by contrasting with the concept of differences and translatability in post-structuralism theory, discussing the possibilities of mutual understanding between two cultures and languages through the imagined other in translation.

Keywords: Translation Theory
Early Modern China
Advisor: Johanna, Liu
The Accuracy of Epidemiologic Definitions of Childhood Asthma Using a Clinical Reference Standard

This study determined the sensitivity and specificity of questionnaires and administrative databases compared to a clinical reference standard for asthma. 208 schoolchildren from a population-based sample participated. They underwent a physician assessment, spirometry, methacholine challenge, exhaled nitric oxide and skin testing. Data was linked to the Ontario Asthma Surveillance Information System. “Questionnaire diagnosis” was an affirmative response to physician-diagnosed asthma. “Database diagnosis” was 2 outpatient visits or 1 hospitalization within 2 years. “Clinical diagnosis” required a physician assessment and objective findings of asthma. “Questionnaire diagnosis” of asthma was specific (92.1%) but not sensitive (75.3%) compared to the “clinical diagnosis”. “Database diagnosis” was sensitive (87.5%) but not specific (64.8%). Both sources had an excellent negative predictive value (97-98%) but poor positive predictive value (24-55%). Epidemiologic methods accurately identify those without asthma but are poor at identifying those with asthma, leading to an overestimation of asthma prevalence and dilution of risk estimates.

Keywords: Asthma
Epidemiology
Diagnosis
Pediatric
Administrative database
Questionnaire
Advisor: Dell, Sharon
Identification of Cellular Components Interacting with the Shiga-like Toxin 1 A1 Chain (SLT-1 A1)

Shiga-like toxin 1 (SLT-1) is produced by Escherichia coli strains like the pathogenic strain O157:H7. These bacterial strains are responsible for worldwide cases of food poisoning and water contamination, and the toxin is a major cause of hemorrhagic colitis and the hemolytic uremia syndrome. SLT-1 is defined as a type II ribosome-inactivating protein (RIP) and belongs to a family of plant and bacterial AB toxins. The A1 chain blocks protein synthesis in eukaryotic cells by depurinating a single adenine base in 28S rRNA. The mechanisms by which the A chain of SLT-1 interacts with the host components to route itself to the cytosol remains largely unknown. This thesis project identified a list of putative cellular proteins that interact with the SLT-1 A1 chain by the use of yeast-2-hybrid (Y2H) screens and HeLa lysate pull down/mass spectrometry analyses. Further assessment of the top 8 host interactors did not yield true interactions.

Keywords: protein toxin
shiga-like toxin 1
Advisor: Gariepy, Jean
The MET Receptor Tyrosine Kinase Is a Potential Therapeutic Target in Combination with Radiation in Head and Neck Squamous Cell Carcinoma

Radioresistance is a major cause of treatment failure and relapse in head and neck squamous cell carcinoma (HNSCC). Novel molecular targets need to be identified to increase cure rates and radiosensitivity in HNSCC. The MET receptor tyrosine kinase is highly dysregulated in cancer and plays a role in tumourigenesis, chemoresistance, and radioresistance. However, the role of MET in HNSCC radioresistance has not yet been investigated and may potentially be a radiosensitizing target. We discovered MET expression and intact ligand-induced signalling in HNSCC cell lines. Small molecule MET kinase inhibitors inhibited ligand-induced MET activation and downstream signalling. These inhibitors decreased HNSCC cell proliferation and clonogenic survival. Similarly, short-interfering RNAs targeting MET also decreased cell proliferation. The combination of radiation with the MET kinase inhibitors decreased clonogenic survival in an additive manner. Cell cycle analyses demonstrated that MET inhibitors alone or in combination with radiation induced small increases in sub-G1 cell populations.

Keywords: Radiosensitizer
Receptor Tyrosine Kinase
Radiation
MET
Radioresistance
Clonogenic Survival
Advisor: Liu, Fei-Fei
The Role of TLR2 in the Pathogenesis of Kawasaki Disease

Kawasaki disease (KD) is a childhood vasculitis with a predilection for the coronary arteries (CA). The etiology of KD is unknown; however, superantigens (SAg) have been implicated. SAg-activated T cells undergo massive proliferation followed by apoptosis; conversely, in KD these T cells may persist and target the CAs. Enhanced costimulation can rescue SAg-activated T cells from apoptosis, and Toll-like receptor 2 (TLR2) enhances costimulation. In a murine model of KD, TLR2-deficient mice are disease resistant, and evidence suggests preferential expression of TLR2 at the CA. Results from this study demonstrate that TLR2 is rapidly expressed in the heart following disease induction, and that TLR2 is expressed differentially in various arteries. The aorta, from which the CAs branch off, expressed the highest TLR2 levels. A microvascular endothelial cell line was shown to function as an APC following TLR2 stimulation, supporting the proliferation of SAg-activated T cells and their rescue from apoptosis.

Keywords: TLR2
Kawasaki Disease
Endothelial cells
Advisor: Yeung, Rae S. M.
Aggression and Competition in Two Boreal Animals

This thesis will focus on the use of agonistic behaviour in both direct and indirect competition in two arboreal species: the eastern chipmunk (Tamias striatus) and Cyphoderris monstrosa, a primitive orthopteran insect. Chipmunks are an example of indirect competitors as they are competing for finite resources for dealing with abiotic stresses to ensure their survival. Chapter 2 of this project investigates the behavioural time budget for above ground activity at a time of critical importance for overwinter survival. The chipmunks in this study displayed a focus of their time budget on eating and collecting food in preparation of winter survival while they were above ground. Chapter 3 of this research project studies the physiological differences between males of Cyphoderris monstrosa which engage in aggressive territorial contests. The data suggest that metabolic scope is correlated with RHP. Males’ ability to mobilize energy reserves may be an important factor in contest outcomes.

Keywords: aggression
Cyphoderris
chipmunk
Advisor: Mason, Andrew
Modeling Hedge Fund Performance Using Neural Network Models

Hedge fund performance is modeled from publically available data using feed-forward neural networks trained using a resilient backpropagation algorithm. The neural network’s performance is then compared with linear regression models. Additionally, a stepwise factor regression approach is introduced to reduce the number of inputs supplied to the models in order to increase precision. Three main conclusions are drawn: (1) neural networks effectively model hedge fund returns, illustrating the strong non-linear relationships between the economic risk factors and hedge fund performance, (2) while the group of 25risk factors we draw variables from are used to explain hedge fund performance, the best model performance is achieved using different subsets of the 25 risk factors, and, (3) out-of-sample model performance degrades across the time during the recent (and still on-going) financial crisis compared to less volatile time periods, indicating the models’ inability to predict severely volatile economic scenarios such as economic crises.

Keywords: Neural Networks
Hedge Funds
Advisor: Paradi, Joseph C.
The Nucleus of the Solitary Tract is Necessary for Apnea-induced Respiratory Plasticity

The respiratory system is attentive, adaptive, learns and has memory. The respiratory system remembers repeated respiratory challenges to fine tune its motor activity by modulating neuronal synaptic strength. This phenomenon, respiratory long term facilitation (LTF), functions to strengthen the ability of respiratory motor neurons to enhance contraction of breathing muscles. LTF could serve as a protective mechanism against obstructive sleep apnea, a disease characterized by the collapse of upper airways, by restoring upper airway patency. LTF can be induced through modulation of vagal afferent feedback via repeated apneas. Here, we used reverse microdialysis, electrophysiology, neuropharmacology, and histology to determine if the nucleus of the solitary tract (NTS), a brain region exclusively receiving vagal afferents, is the origin of the neural circuit responsible for apnea-induced plasticity. My work shows bilateral injection of 5% lidocaine into the NTS prevented LTF. We conclude the NTS is required for triggering apnea-induced LTF.

Keywords: respiratory plasticity
long term facilitation
Advisor: Peever, John H.
The Role of Oxidative Stress on Neural TRPC3, TRPC5, TRPC6 Expression and/or Function and Relevance to Bipolar Disorder

The etiology of bipolar disorder (BD) is multidimensional and thought to involve several factors that increase neuronal oxidative stress and disrupt intracellular calcium homeostasis. As calcium-permeable canonical transient receptor potential channels (TRPC) have been linked to bipolar pathophysiology, I sought to determine whether oxidative stress affects TRPC3/TRPC5/TRPC6 expression and/or function. Chronic (4-day) but not acute (24-hour) rotenone-induced oxidative stress dose-dependently reduced TRPC5 and TRPC6 protein levels in primary rat cortical neurons. A decrease in TRPC5 mRNA levels was only found following acute but not chronic rotenone whereas TRPC6 mRNA levels did not change significantly with either treatment. Reduced TRPC3 function was seen after chronic stress when stimulated by TRPC3/6 activator, 1-oleoyl-2-acetyl-sn-glycerol. Lithium pre-treatment attenuated the rotenone-induced reduction in TRPC3 but not TRPC6 protein levels. These results suggest TRPC subtypes are differentially regulated by oxidative stress and support a potential mechanistic link between oxidative stress and calcium dyshomeostasis in BD.

Keywords: Bipolar Disorder
Oxidative Stress
TRP Channels
Calcium
Advisor: Warsh, Jerry
Engineering the Myocardial Niche in a Microscale Self-assembling Tissue-mimetic in vitro Model

Drug- and cell-based strategies for treating heart disease, including myocardial infarction, face significant roadblocks on the path to the clinic, a primary obstacle being the lack of information-rich in vitro human model systems. Conventional model systems are hampered by at least one of three fundamental limitations which include a) the lack of an in vivo-like microenvironment specifically engineered for the input cell population, b) a relatively low-throughput assays, and c) the low-content nature of output parameters. We describe an integrated computational, design, and experimental strategy for the rational design of a microfabricated high-content screening platform which we term the Cardiac MicroWire (CMW) system. Within this system, we recapitulate the basic microenvironment found in the heart, one which integrates cardiomyocytes, non-myocytes, the extracellular matrix, and dynamic electromechanical forces. Our results highlight the CMW system’s potential as a powerful discovery tool for screening small molecules and transplantable cells toward heart regeneration therapies.

Keywords: In vitro 3D cardiac model
human pluripotent stem cell-derived cardiomyocytes
Maturation of cardiomyocytes
Microfabrication for cell-based assays
Advisor: Zandstra, Peter W.
Radisic, Milica
Achieving Low Emissions from a Biogas Fuelled SI Engine Using a Catalytic Converter

A spark ignition engine was retrofitted to operate on biogas fuel. Biogas was synthetically generated through the mixing of various pure gases. The air-fuel ratio was accurately controlled using a closed feedback system consisting of flow controllers and a wide range oxygen sensor. A natural gas catalytic converter was implemented with the use of biogas fuel. To achieve full NOx and CO reduction the engine was required to run at a slightly rich equivalence ratio. Methane emissions posed to be the hardest to reduce across the catalyst. The biogas fuel composition had no effect on the catalyst performance. The catalyst performance was only affected by exhaust temperature and equivalence ratio. The catalyst requires tight A/F ratio control for optimal performance. A Catalytic converter can be used to reach low emissions but requires the knowledge of the biogas fuel composition.

Keywords: Biogas
SI engine
Catalytic Converter
Three-way Catalyst
Natural Gas
Advisor: Wallace, James S.
Realistic Assessment of Novel Wireless Systems with Ray-tracing Based Techniques

Ray tracing based on geometric optics can be utilized for generating propagation models for arbitrary and complex environments. These methods can be employed to determine important wireless channel characteristics such as path gain and the channel impulse response which in turn can be used to deduce channel capacity. In this thesis, a fully vectorial 3-D ray-tracer is developed. The simulator is applied to study novel wireless systems such as ultra-wideband pulse propagation in complex railway tunnels and MIMO systems employing closely spaced low mutual coupling meta-material antennas. The computational complexity of the ray-tracing algorithm is reduced using optimizations and via the development of a novel hybrid method that combines the efficiency and accuracy of waveguide models with the flexibility of a ray-tracer. The resulting simulator is validated against measured results and demonstrated to show good agreement. Convergence of the solution using the ray-tracing method is also discussed.

Keywords: Ray-Tracing
Wireless Channel Modeling
Ultra-wideband Systems
MIMO
Advisor: Sarris, Costas D.
Level of Automation Effects on Situation Awareness and Functional Specificity in Automation Reliance

This thesis investigates the relationships between performance, workload, and situation awareness at varying levels of automation. The relationships observed in this study are compared to a description put forth to formalize the conventional interpretation of the trade-off between the benefits of automation during routine operation and the costs under conditions of automation failure. The original work stipulated that this “routine-failure trade-off” is likely a simplification affected by contextual factors. This work therefore aimed to i) provide empirical evidence to support or refute the trade-off and ii) to identify possible extenuating factors. The results generally supported the routine-failure trade-off, and considered in light of the functional structure of the task suggested that the relationships between goals and individual functions specific to a given task seem to affect the overall costs and benefits of automation through the mechanism of selective reliance. Further work is required to validate the findings of this study.

Keywords: Automation
Supervisory control
Level of automation
Situation awareness
Signal detection theory
Task analysis
Reliance
Trust
Human Factors
Advisor: Jamieson, Gregory Allan
Impact of Comorbid Major Depressive Disorder (MDD) on PTSD Severity in Toronto Transit Commission (TTC) Employees

Introduction: This thesis examined the impact of PTSD with Major Depressive Disorder on PTSD severity among Toronto Transit Commission employees who were exposed to a workplace traumatic event, and also the predictors of PTSD severity, mental health treatment seeking, and return to work over the six month study period. Methods: This study utilized data that was collected prospectively from the APT study participants. Information about Axis-I diagnosis and PTSD severity were collected from the SCID-I and the Modified PTSD Symptom Scale respectively. Results: PTSD without MDD (N=29) and PTSD with MDD (N=37) groups were compared. The variables: depression severity (p=0.01), female (p=0.01), non-Caucasian (p=0.01), workplace related stress (p=0.02), and lifetime trauma (p=0.01) significantly predicted PTSD severity. The BPI group significantly predicted mental health treatment seeking (p<0.01) after controlling other variables. Conclusion: This study highlights the substantial risk for experiencing greater PTSD severity after a workplace traumatic event in TTC employees.

Keywords: Psychological trauma, Posttraumatic Stress Disorder, MDD, Comorbidity, Mental health, TTC
Advisor: Links, Paul
Modelling Departure Time and Mode Choice for Commuting in the Greater Toronto and Hamilton Area (GTHA): Evaluation of Dynamic Travel Demand Management Policies

This thesis develops econometric models of departure time and travel mode choice to evaluate dynamic transportation policies. Dynamic policies affect travel attributes differently throughout the day. Both departure time and mode choice are modelled with Random Utility Maximizing (RUM) Generalized Extreme Value (GEV) discrete choice models that capture systematic and random heterogeneity. Departure time is represented by a heteroskedastic generalized extreme value model (Het-GEV) with overlapping choice sets. Studying the Greater Toronto and Hamilton Area (GTHA), models are estimated using Revealed Preference (RP) household travel data from the 2006 Transportation Tomorrow Survey (TTS). Empirical models are used to evaluate dynamic transit and road pricing policies. Results indicate that the models are capable of capturing mode and time switching behaviour in response to peak pricing policies. To alleviate demand while maintaining transit mode share, a road charge and a moderate, flat, transit fare increase throughout the morning peak are recommended.

Keywords: transportation
travel behaviour modelling
Advisor: Habib, Khandker
A Microfluidic Platform for the Investigation of Transport in Small Blood Vessels

The microvasculature has the main function of transport of dissolved gases, nutrients and waste between blood and tissue. Systematically probing transvascular transport rates in these vessels under well defined conditions is challenging. In vivo and in vitro studies are characterized, respectively, by limited optical access and control over perfusion concentrations and failure to resemble the structure and function of an intact organ. In this thesis, I present the development of a microfluidic platform for investigating molecular transport across mouse mesenteric arteries (150-300μm diameter) in a controlled physico-chemical microenvironment. Intact vessels are perfused with 4 kDa FITC-Dextran and the permeation coefficient of this molecule across the vessel wall is quantified using laser scanning confocal microscopy paired with a 2-D numerical model. Functional viability of the examined vessel, through phenylephrine and acetylcholine dose responses, is probed, and shear and phototoxic effects are reported.

Keywords: permeability
microvasculature
microfluidics
FITC-Dextran
artery-on-a-chip
Advisor: Gunther, Axel
Fluorescence Resonance Energy Transfer between a Monolayer of Quantum Dots as Donors adjacent to a Monolayer of Biorecognition Elements as Acceptors

The unique optical properties of quantum dots (QDs) have been widely used to develop bioassays based on Fluorescence Resonance Energy Transfer (FRET). The solid-phase assays using QDs as FRET donors have numerous practical advantages, including at least 10-fold enhancement in FRET efficiency, which is not immediately explained by theoretical predictions that model energy transfer processes of QDs in two-dimensional layers. Donor-acceptor separation distance, acceptor and donor concentrations were found to influence FRET efficiency in solid-phase assays. A novel immobilization strategy was implemented which made use of the high affinity of imidazole moieties to QD shells to build solid-phase QD bioassays. A 96-well polystyrene plate is presented as a platform suitable for rapid and convenient multiplexed detection. A typical microtiter plate reader was shown to be capable of discriminating different FRET pairs to picomol detection levels of target oligonucleotides. Furthermore, the QD-FRET bioassays provided for mismatch discrimination, and multiple cycles of regeneration were also demonstrated.

Keywords: quantum dots
fluorescence
hybridization
immobilization
Advisor: Krull, Ulrich Jorg
Patients’ Preferences and Trade Offs for the Treatment of Small Hepatocellular Carcinomas

Objective: The primary aim of this study was to assess patients’ preferences between radiofrequency ablation (RFA) versus hepatic resection (HR) for the treatment of small hepatocellular carcinomas (HCC). Methods: Decision analysis was performed by using probability trade-off (PTO) technique to elicit patients’ preferences and the strength of their decisions. Results: The vast majority of the study population preferred RFA over HR (70% vs. 30%, p=0.001). Their initial choice changed if 5-year survival benefit after surgery was at least 14% superior to RFA and if the 3-year disease-free survival advantage was at least 13% better than ablation. Conclusions: The results of this study suggest that fully informed cirrhotic patients would prefer RFA if diagnosed with early stage HCC even if able to undergo surgery.

Keywords: Hepatocellular Carcinoma
Radiofrequency Ablation
Hepatic Resection
Cirrhosis
Patient's Preferences
Perioperative Risks
Treatment Benefits
Probabiltity Trade-off
Advisor: Urbach, David Robert