VictorJuiz/thesis huggingface dataset:
Analysis of Signalling Network Consequent to FLT3 in AML Patients

The FMS-like tyrosine kinase 3- internal tandem duplication (FLT3/ITD) aberration is common in acute myeloid leukemia (AML) and associated with poor patient outcome. Inhibitors targeting FLT3/ITD are in development, but clinical responses are transient. This project focussed on elucidating molecular signalling consequences of FLT3/ITD inhibition, to identify rational drug combinations for future development. A Multicolour Phospho Flow Cytometry (MPFC) assay was developed to assess signalling events downstream of FLT3/ITD in primary patient samples, focusing on alterations in ERK, STAT5, Akt, and S6. STAT5 signalling appeared to be important exclusively in FLT3/ITD samples. MPFC accurately predicted the presence of FLT3/ITD, inhibitor sensitivity and the initial positive clinical response of a trial patient receiving a FLT3/ITD inhibitor. PI3K pathway upregulation was observed in a Sorafenib-resistant FLT3/ITD cell line established to study resistance mechanisms of FLT3 inhibition. Further, combination FLT3 and PI3K inhibition demonstrated synergy, suggesting potential clinical relevance to this therapeutic strategy.

Keywords: Leukemia
AML
FLT3
ITD
Flow Cytometry
Sorafenib
Resistance
TKI
Advisor: Hedley, David
Identifying Tissue Specific Distal Regulatory Sequences in the Mouse Genome

Epigenetic modifications, transcription factor (TF) availability and chromatin conformation influence how a genome is interpreted by the transcriptional machinery responsible for gene expression. Enhancers buried in non-coding regions are associated with significant differences in histone marks between different cell types. In contrast, gene promoters show more uniform modifications across cell types. In this report, enhancer identification is first carried out using an enhancer associated feature in mouse erythroid cells. Taking advantage of public domain ChIP-Seq data sets in mouse embryonic stem cells, an integrative model is then used to assess features in enhancer prediction, and subsequently locate enhancers. Significant associations with multiple TF bound loci, higher expression in the closest genes, and active enhancer marks support functionality and tissue-specificity of these enhancers. Motif enrichment analysis further determines known and novel TFs regulating the target cell type. Furthermore, the features identified can facilitate more accurate enhancer prediction in other cell types.

Keywords: Enhancers
Epigenetics
Bioinformatics
Machine learning
Histone modifications
Advisor: Mitchell, Jennifer
Vibration Suppression of Large Space Structures Using an Optimized Distribution of Control Moment Gyros

Many space vehicles have been launched with large flexible components such as booms and solar panels. These large space structures (LSSs) have the potential to make attitude control unstable due to their lightly damped vibration. These vibrations can be controlled using a collection of control moment gyros (CMGs). CMGs consist of a spinning wheel in gimbals and produce a torque when the orientation of the wheel is changed. This study investigates the optimal distribution of these CMGs on LSSs for vibration suppression. The investigation considers a beam and a plate structure with evenly placed CMGs. The optimization allocates the amount of stored angular momentum possessed by these CMGs according to a cost function dependent on how quickly vibration motions are damped and how much control effort is exerted. The optimization results are presented and their effect on the motions of the beam and plate are investigated.

Keywords: Vibration Suppression
Optimization
Advisor: Damaren, Christopher John
Rationing in Pandemics: Administrative and Private Law Challenges

Rationing of lifesaving resources in pandemics is likely to be an increasingly relevant issue. While the broad legal and ethical implications of pandemic preparedness have been explored at length, little attention has been paid to the legal issues associated with rationing. This thesis seeks to analyze the potential for administrative and private law challenges to governments’ rationing of vaccines, ventilators and antivirals. The wide variety of statutory authorities, and their associated conditions and discretionary limitations, that governments may rely on for mandating rationing protocols, makes them susceptible to administrative law challenges on the grounds of errors of jurisdiction. An analysis of the tort liability of governments, hospitals and physicians suggests that negligence suits will likely not be successful due to a lack of proximity required for a private law duty of care, the policy-making immunity of governments and a contextual standard of care.

Keywords: rationing
pandemics
private law
administrative law
torts
law
Advisor: Lemmens, Trudo
Mercury Isotope Fractionation during Aqueous Photo-reduction of Methylmercury in Presence of Different Types and Amounts of Dissolved Organic Matter

The effects of different types and amounts of dissolved organic matter (DOM) on the isotope fractionation of Hg isotopes during aqueous photo-reduction of monomethylmercury (MMHg) were investigated to assess whether mass-independent fractionation (MIF) signatures can be used to track photo-degradation of MMHg in natural waters. From experiments conducted with different amounts of reduced organic sulfur (Sred-DOM), it appears that MIF during photo-reduction may be dependent on whether MMHg is dominantly bound to Sred-DOM. Similar fractionation factors were observed for experiments where Sred-DOM was in far excess of MMHg, while significantly lower fractionation factors were observed with lower Sred-DOM. We also characterized the signature of MIF (i.e. Δ199Hg/Δ201Hg) during MMHg photo-degradation to assess if it was similar in different matrices. The experimental Δ199Hg/Δ201Hg was very similar for different matrices. However, the experimental slope is slightly but statistically different than the slope observed in freshwater fish, which preserve MMHg in nature.

Keywords: Methylmercury
Dissolved organic matter
mass-independent fractionation
Mercury Isotopes
MMHg photo-degradation
Advisor: Bergquist, Bridget
Stress-Induced Heat Generation and Strain Localization in Polycrystalline and Nanocrystalline Nickel

Commercially available polycrystalline Ni (Ni200; grain size: 32 μm) and electrodeposited nanocrystalline Ni (grain size: 57 nm), Ni-2.6%Fe (grain size: 25 nm) and Ni-8.5%Fe (grain size: 20 nm) were analyzed for the phenomena of stress-induced heat generation and strain localization during plastic deformation at room temperature (i.e. 250C). Tensile specimens according to ASTM E8 standard dimensions were tested at strain rates of 10-2/s and 10-1/s, respectively, to record the amount of heat dissipated and the change of localized strain using a high resolution infrared (IR) detector and digital image correlation (DIC) camera, respectively. Results have shown that the maximum temperatures that were recorded in nanocrystalline Ni and Ni-Fe alloys were at least 300C lower than the onset temperatures for subgrain coalescence previously measured through differential scanning calorimetry. It can be concluded that thermally activated grain growth during tensile testing of nanocrystalline Ni and Ni-Fe alloys is not likely to occur.

Keywords: stress induced
heat generation
strain localization
polycrystalline nickel
nanocrystalline nickel
digital image correlation
Advisor: Erb, Uwe
The Role of CCL5/RANTES in Regulating Cellular Metabolism in Activated T cells

Recruitment of effector T cells to sites of infection is essential for an effective adaptive immune response. The inflammatory chemokine CCL5/RANTES activates its cognate receptor, CCR5, to initiate cellular functions including chemotaxis. This thesis describes the signaling events invoked by CCL5 and its ability to regulate the energy status of activated T cells. CCL5 treatment in ex vivo activated human T cells induced the activation of AMPK and downstream substrates ACC1, PFKFB2 and GSK-3. Evidence is provided that CCL5 treatment is able to induce glucose uptake in an mTOR-dependent manner. Using 2-deoxy-D-glucose, an inhibitor of glucose uptake, and Compound C, an inhibitor of AMPK, evidence is provided that demonstrate that CCL5-mediated chemotaxis is dependent on metabolic events, since these inhibitors perturb chemotaxis in a dose-dependent manner. Collectively, these studies suggest that CCL5 may also influence the metabolic status of activated T cells by simultaneously activating the AMPK and mTOR pathways.

Keywords: Chemokines
T Lymphocytes
Cellular Metabolism
Signal Transduction
Advisor: Fish, Eleanor N.
Ohashi, Pamela S.
Zuniga-Pflucker, Juan Carlos
Regioselective Functionalization of Polyols via Organoboron Catalysis

With the increasing realization of their involvement in numerous biological processes, synthetic oligosaccharides present promising potential in drug and vaccine discovery. Selective functionalization of hydroxy groups in polyols represent a long-standing goal in chemistry since the chemical synthesis of O-glycosides often requires extensive protecting group manipulation. Organoboron catalysis is a recent strategy for regioselective activation of the equatorial hydroxy group of cis-vicinal diols. Following the initial findings that diarylborinic acid catalyzes the regioselective acylation of carbohydrate derivatives, kinetic studies were conducted to obtain better insight on the mechanism. Thereafter, the ability of diarylborinic acid to catalyze the regioselective alkylation of carbohydrates was demonstrated. Finally, investigations in the capability of diarylborinic acid to influence regiochemical outcome of glycosylation reactions were explored. Similarly, kinetic experiments were devised to shed light on the mechanism of the reaction.

Keywords: organic chemistry
organoboron
carbohydrates
alkylation
kinetic studies
glycosylation
catalysis
Advisor: Taylor, Mark S.
Online Near-infrared Spectroscopy Brain-computer Interfaces with Real-time Feedback

Near-infrared spectroscopy (NIRS) is an emerging non-invasive brain-computer interface (BCI) modality that measures changes in hemoglobin concentrations in neurocortical tissue. Previous NIRS studies have not employed real-time feedback with online classification, a combination which would allow users to alter their mental strategy on the fly. This thesis reports the results of two online studies. The first study contrasted online classification of prefrontal hemodynamics using an artificial neural network (ANN) and a hidden Markov model-based (HMM) classifier. The second study measured the accuracy of an online linear discriminant classifier. In study 1, only the ANN classifier facilitated online classification rates greater than chance (p=0.0289). In study 2, a new feedback system and experimental protocol led to improved classification rates over those of the first study (p=5.1*10^(-5)). While control over instantaneously generated feedback in online NIRS-BCIs has been demonstrated, factors such as user frustration, mental fatigue, and restrictions on ambient lighting may compromise performance.

Keywords: near-infrared spectroscopy
brain-computer interface
neurofeedback
Advisor: Chau, Tom
A Learning-based Control Architecture for Socially Assistive Robots Providing Cognitive Interventions

Due to the world’s rapidly growing elderly population, dementia is becoming increasingly prevalent. This poses considerable health, social, and economic concerns as it impacts individuals, families and healthcare systems. Current research has shown that cognitive interventions may slow the decline of or improve brain functioning in older adults. This research investigates the use of intelligent socially assistive robots to engage individuals in person-centered cognitively stimulating activities. Specifically, in this thesis, a novel learning-based control architecture is developed to enable socially assistive robots to act as social motivators during an activity. A hierarchical reinforcement learning approach is used in the architecture so that the robot can learn appropriate assistive behaviours based on activity structure and personalize an interaction based on the individual’s behaviour and user state. Experiments show that the control architecture is effective in determining the robot’s optimal assistive behaviours for a memory game interaction and a meal assistance scenario.

Keywords: Human-robot Interaction
Control Architecture
Robotics
Hierarchical Reinforcement Learning
Multi-modal Human-machine Interfaces
Cognitive Interventions
Socially Assistive Robots
Advisor: Nejat, Goldie
Relationship between Preference for Opposite-sex Odour and Morphology of the Principal Nucleus of the Bed Nucleus of the Stria Terminalis

The principal nucleus of the bed nucleus of the stria terminalis (BNSTp) is an integral component of the mouse accessory olfactory system, and plays a key role in pheromonal processing. In males, this region is not only larger and contains more neurons than in females, but the cells are also larger. The present study examined the relationship between preference for opposite-sex odour and regional volume, cell number and cell size within the BNSTp of both male and female mice. No correlations were found between olfactory preferences and any of the three morphological BNSTp parameters. However, the olfactory preference task results were not congruent with previous research. Therefore, it remains inconclusive whether relationships exist between olfactory preference behaviour and morphology of the BNSTp.

Keywords: principal nucleus of bed nucleus of stria terminalis
olfactory preferences
Advisor: Holmes, Melissa M.
Development and Characterization of Thermally Conductive Polymeric Composites for Electronic Packaging Applications

Advancements in the semiconductor industry have lead to the miniaturization of components and increased power densities, resulting in thermal management issues. Due to this shift, finding multifunctional materials with excellent thermal conductivity and electrical resistivity are becoming increasingly important. For this research thesis, thermally conductive polymer composites were developed and characterized. In the first study, a LLDPE matrix was combined with hBN and SiC to determine the effects of both filler type and filler content. Novel porous composite materials were also fabricated to align thermally conductive fillers, improving k_eff while significantly reducing the overall weight. In the second study, PPS was used as a high performance matrix material and combined with different types of hBN to investigate the effects of size, shape, and aspect ratio on the composite, as well as the effect of hybrid fillers. The composites were characterized with respect to their physical, thermal, electrical, and mechanical properties.

Keywords: polymer composites
thermal conductivity
Advisor: Naguib, Hani E.
Dawson, Francis P.
Fair Dealing and Documentaries – Is it fair?

In an attempt to strike a fair balance between rights of copyright holders and the public interest in the dissemination of intellectual works, the copyright law has established exceptions to the exclusive rights granted to creators. However, doubts concerning the applicability of these exceptions have raised discussions about whether the use of copyrighted materials in documentaries qualifies as a fair dealing or other exception to copyright, uncertainties that lead producers to use only duly authorized materials in order to avoid possible claims. This thesis analyzes the copyright exceptions set out in the Canadian law and their applicability to protected materials inserted in documentaries. This thesis suggests that the legislation should be modified in order to help producers to identify situations in which those exceptions would be applicable to protected materials included in documentaries and to avoid over protective copyright rights that may restrain the production and dissemination of documentary films.

Keywords: fair dealing
documentary
Advisor: Katz, Ariel
The Crown, Public Authorities and Class Action Lawsuits

This work considers the interplay between the Crown, public authorities and the class action device. The class action is a relatively recent legal innovation that allows for the collective redress of similarly situated victims through a single strand of litigation. Class actions are most commonly associated with the pursuit and remediation of corporate wrongdoing, however the Canadian government has been pursued to a significant extent as class action law has rolled out across the country. In stark contrast to commercial defendants, public authorities carry on their activities for the public good and on a not-for-profit basis. The best of intentions and a lack of profit do not imply that liability should be denied, rather that it should be managed as effectively as possible. This work examines and advocates for the careful use of various tools which limit the potential impact class action lawsuits pose to public service delivery.

Advisor: Morgan, Ed
Patient Views on Financial Relationships between Orthopaedic Surgeons and Orthopaedic Device Manufacturers

Revelations of kickbacks from surgical device manufacturers to surgeons raise the question whether surgeons can continue to collaborate with industry and maintain public trust. Using qualitative and quantitative methodology, this thesis explores surgical patients’ views on financial relationships between surgeons and manufacturers and patients’ recommendations for managing these conflicts of interest. A majority of patients approve of surgeon’s relationships with manufacturers that can benefit patients but disapprove of those that primarily benefit the surgeon and the manufacturer. The majority of patients do not endorse disclosure as a sole method of managing these relationships. The majority of patients trust the surgical profession to self-regulate and favour professional oversight rather than by government to ensure financial relationships between surgeons and manufacturers are appropriate. My data supports my argument that there should be professional oversight of financial relationships between surgeons and manufacturers, which may allow continued collaboration with manufacturers while maintaining public trust.

Keywords: Surgery
Bioethics
Conflicts of Interest
Advisor: McKneally, Martin
Alman, Benjamin
Becoming Chinese: The Construction of Language and Ethnicity in Modern China

This thesis explores how the standardization of language in China has been as a means to unify the empire and restructure relations between citizens and the state through processes of identification. Looking in at the case of China's minzu (ethnic groups), I argue that the current trend instituted through policies at the top-level is to eliminate linguistic and cultural diversities through the promotion of Putonghua as the lingua franca and to eventually amalgamate all minzu of the multi-minzu state into a mono-minzu, Zhonghua Minzu (citizens of the Chinese nation). Beginning with an overview of the historical practices of language standardization, I show how the ideological nature of politically influenced terminologies in the Chinese language has contributed to this restructuring of identity. With identity tied closely to language, recently enacted laws in mainland China have brought the government a step closer to achieving its ultimate goal of creating a mono-minzu state.

Keywords: Chinese
ethnicity
constitutional law
identity
language
Advisor: Wu, Yiching
Antihypertensives and Hip Fracture Risk in Community-dwelling Elderly: A Self-controlled Case Series Analysis

Antihypertensive drugs can cause hypotension in the elderly and such an effect may lead to fall injuries. This thesis examined the association between antihypertensive drugs and hip fracture risk among elderly patients during the initiation of monotherapy. This population-based self-controlled case series study used healthcare administrative databases to identify Ontario residents aged ≥ 66 years with a first prescription for a thiazide diuretic, angiotension II converting-enzyme inhibitor, angiotensin II receptor antagonist, calcium channel blocker or beta-adrenergic blocker. A cohort of newly treated hypertensive elderly was then linked to the occurrence of hip fractures from April 1, 2000 to March 31, 2009. We found that hypertensive elderly initiated on an antihypertensive drug had a 43% increased risk of having a hip fracture during the first 45 days of treatment, IRR 1.43 (95% CI 1.19-1.72). Initiating antihypertensive drugs in community-dwelling elderly should be approached with caution due to increased fracture risk.

Keywords: antihypertensives
hip fracture
Advisor: Glazier, Richard H.
Parents' Preferences for Drug Treatments in Juvenile Idiopathic Arthritis: A Discrete Choice Experiment

BACKGROUND: Parents of children with juvenile idiopathic arthritis (JIA) are often forced to make trade-offs between the effectiveness, convenience, safety, and cost of drug treatments for their child. METHODS: A discrete choice experiment was administered to parents of children with JIA to determine their preferences for drug treatments. Multinomial logit regression was used to estimate part-worth utilities and willingness-to-pay. RESULTS: Participation in daily activities was the most important attribute, followed by child reported pain. Child age, gender, years with JIA, and household income had the greatest impact on preferences. Parents’ were willing to pay $2,080 to switch from a drug representing methotrexate to etanercept (95% CI $698, $4,065). CONCLUSIONS: Parents of children with JIA have the highest maximum willingness-to-pay for drug treatments that improve daily functioning and reduce pain. Cost is a significant factor in the decisions that parents make surrounding the best treatment for a child.

Keywords: patient preference
discrete choice
health policy
juvenile idiopathic arthritis
Advisor: Ungar, Wendy Joan
Toward an Understanding of the Built Environment Influences on the Carpool Formation and Use Process: A Case Study of Employer-based Users within the Service Sector of Smart Commute’s Carpool Zone

The recent availability of geo-enabled web-based tools creates new possibilities for facilitating carpool formation. Carpool Zone is a web-based carpool formation service offered by Metrolinx, the transportation planning authority for the Greater Toronto and Hamilton Area (GTHA), Canada. The carpooling literature has yet to uncover how different built environments may facilitate or act as barriers to carpool propensity. This research explores the relationship between the built environment and carpool formation. With respect to the built environment, industrial and business parks (homogeneous land-use mix) are associated with high odds of forming carpools. The results suggest that employer transport policies are also among the more salient factors influencing carpool formation and use. Importantly, the findings indicate that firms interested in promoting carpooling will require contingencies to reduce the uncertainty of ride provision that may hamper long-term carpool adoption by employees.

Keywords: carpool
built environment
spatial analysis
GIS
Metrolinx
Smart Commute
transportation demand managment
logistic regression
workplace
transportation
Advisor: Buliung, Ron