VictorJuiz/thesis huggingface dataset:
Characterization of Diffuse Large B-cell Lymphoma of The Oral Cavity

120 oral non-Hodgkin’s lymphoma (NHL) were classified according to the World Health Organization Classification of Tumours of Haematopoietic and Lymphoid Tissues (2008). 42 of 44 cases of diffuse large B-cell lymphoma (DLBCL) were subtyped using immunohistochemical algorithms. The Hans algorithm classified 21 germinal centre B-like (GCB) (50.0%) and 21 non-GCB (50.0%) cases of DLBCL, whereas the Natkunam algorithm showed the majority of DLBCL were GCB subtype (32 cases, 76.2%). Two newly described categories of DLBCL were found to occur in the oral cavity, namely, B-cell lymphoma unclassifiable, with features intermediate between DLBCL and Burkitt lymphoma (BCLU) and Epstein-Barr virus (EBV)-positive DLBCL of the elderly. There were 5 cases of EBV-positive DLBCL of the elderly. Of the 8 cases of BCLU, 3 were double hit lymphomas.

Keywords: EBV
germinal center
high-grade B-cell lymphoma
MYC
oral lymphoma
Advisor: Leong, Iona
A Magnetoencephalography Investigation of the Role of Stuttering Anticipation on the Preparation and Execution of Speech in Adults who Stutter

Coordination of the speech neural network in developmentally stuttering adults prior to initiation of individual speech utterances has not been explored. The objectives of this study were a) to characterize sensory-motor recruitment in preparation for and execution of speech in adults who stutter (AWS) using magneto-encephalography, and b) to investigate the effect of stuttering anticipation on such sensory-motor recruitment. Brain neural oscillatory activity was recorded during a cued overt repetition task. No differences between high and low anticipation were found. However, AWS demonstrate stronger bilateral recruitment of the mouth motor cortex compared to controls in speech preparation and execution. AWS also recruit the right mouth motor cortex before the left, while controls show a preference for the left mouth motor cortex. The study was the first to find differences in motor recruitment during speech in AWS. This is proposed to reflect facilitative mechanisms adopted in a limited motor speech network.

Keywords: Neural oscillations
Speech
Stuttering
Advisor: De Nil, Luc
Investigating the Structure of MacB, an ABC Transporter Protein

Despite the need to understand membrane proteins at the molecular level, fewer than 2% of the structures in the PDB are of membrane proteins. Detergents have been the most powerful tool used in structural studies but have limitations. As a result, novel membrane mimetics have been an area of intense investigation. This thesis looks at the crystallization pipeline of an ABC transporter, L. lactis MacB. A 10-His-tagged L. lactis MacB clone was purified using Ni-NTA purification and size exclusion chromatography in n-decyl-β-D-Maltoside. The protein was characterized using a ultracentrifugation assay, size exclusion chromatography and ATPase activity assay to find optimum crystal screening conditions. Detergent screening also identified 6 other classical detergents for crystal screening. Lastly, the protein was exchanged into 10 different LPDs, DMPC/CHAPSO bicelles and monoolein based cubic phase. While no crystals were obtained, this thesis seeks to highlight some of the challenges of crystallizing a novel membrane protein.

Keywords: ABC Transporter
Drug
Exporter
MacB
Membrane Proteins
X-Ray Crystallography
Advisor: Privé, Gil
The Role of Community Exercise Programs Involving a Healthcare-recreation Partnership for People with Neurological Conditions and their Caregivers

Abstract Background: Group, task-oriented community-based exercise programs incorporating a healthcare-recreation partnership (CBEP-HRP) aim to enhance access to exercise participation for people with neurological conditions. Objectives: 1) To explore the perceived impact of a group, task-oriented CBEP-HRP on physical function, participation, and caregiver assistance and health among people with neurological conditions and their caregivers, and 2) to understand their preferences for the content and timing of education about CBEP-HRPs. Methods: A descriptive qualitative study involving in-depth interviews was conducted. A thematic analysis was performed. Results: Two themes emerged suggesting exercise participants experienced interrelated improvements in body function, activities and participation that were reinforced through repeated registration in the program, and caregivers experienced both challenges and benefits associated with the TIME™ program. Conclusions: Results provide directions for future research and program development, including incorporation of body function, activity, and participation as program outcomes and examining the need for exercise programs for caregivers.

Keywords: brain diseases
caregivers
community
exercise
qualitative
social participation
Advisor: Salbach, Nancy M.
Cameron, Jill I.
Rethinking Transfer: How Supervision and Support during Self-regulated Learning Impacts Medical Trainees’ Preparation for Future Learning in a Simulation Setting

Contemporary medical education curricula cannot cover the multitude of problems trainees will encounter in their future practice. Hence, researchers must understand how trainees adaptively transfer recently acquired knowledge and skills into subsequent learning situations (e.g. clinical context); a concept referred to as preparation for future learning (PFL). We compared the effects of instructor supervision and different educational supports during self-regulated learning (SRL) on medical trainees’ (n=45) acquisition, retention, transfer, and PFL of simulated endotracheal intubation skills. We assessed PFL abilities using a ‘double’ transfer design requiring a second learning session before testing of a new skill. Results showed that SRL-supported interventions led to better PFL than a SRL-unsupported intervention, whereas instructor supervision did not. Therefore, we recommend educators incorporate educational supports for learners’ SRL within simulation-based training environments. This thesis furthers our understanding of how educators can cultivate lifelong learners who adapt their learning flexibly in the ever-changing medical landscape.

Keywords: Medical Education
Preparation for Future Learning
Self-regulated Learning
Simulation-based Training
Advisor: Ringsted, Charlotte
Bordetella pertussis: Whole Genome Sequence Analysis and its Application to Public Health Laboratory Surveillance

Bordetella pertussis (BP) is a Gram-negative bacterium that causes respiratory infections in humans. Multi-locus sequence types (MLST), virulence factor alleles, and antimicrobial resistance markers are important molecular characteristics of BP that can provide public health officials with information on the continued efficacy of treatment guidelines, the source and spread of infections, and vaccine effectiveness. Determining these characteristics in a rapid, reproducible fashion would be an asset to public health. Short read whole genome sequencing (WGS) of 40 BP isolates and processing by the SRST2 bioinformatic package was able to identify a novel MLST genotype, reveal a significant increase of a virulence factor type compared to previous rates, and confirm the lack of BP antimicrobial resistance to macrolides. Moreover, regions of sequence similarity were also identified that can potentially interfere with the characterization of BP by WGS. This method has potential for laboratory-based public health surveillance of BP.

Advisor: Jamieson, Frances B
Farrell, David J
Development of a Noninvasive In-Vehicle Alcohol Biosensor Using Wavelength-Modulated Differential Photothermal Radiometry

Drunk driving is, in Canada, the leading cause of death on the roads. To reduce the number of drinking and driving incidences, new technologies were developed to accurately measure blood alcohol concentration (BAC) and overcome the limitations of current alcohol measuring technologies. In this research, a non-contacting, non-invasive in-vehicle alcohol biosensor is developed using laser-based Wavelength-Modulated Differential Photothermal Radiometry (WM-DPTR). After demonstrating the alcohol measuring capability of the WM-DPTR-based alcohol biosensor, a calibration method is developed for the biosensor using a combined theoretical and experimental approach. Evaluation of the calibrated biosensor shows that the proposed biosensor can achieve high accuracy and precision for the ethanol concentration range of 0-100 mg/dL and be incorporated in ignition interlocks that could be fitted as a universal accessory in vehicles in efforts to reduce the incidents of drunk driving.

Advisor: Mandelis, Andreas
Characterization and Validation of Two Zebrafish Models of Traumatic Brain Injury (TBI)

Traumatic brain injury (TBI) is a leading cause of death and morbidity in industrialized countries. The cost and time associated with pre-clinical development of TBI therapeutics is lengthy and expensive with a poor track record of successful translation to the clinic. The zebrafish is an emerging model organism with unique advantages in amenability to high-throughput automated pre-clinical drug evaluation. We developed a chemical model of TBI in zebrafish larvae as a reliable surrogate for TBI with quantifiable outcome measures for use in high-throughput drug screening. The aim is then for results to be confirmed in our adult model of TBI. We used a targeted high intensity focused ultrasound to produce the first non-penetrating brain injury model in adult zebrafish. Results indicate that the zebrafish exhibits responses to injury and intervention similar to mammalian pathophysiology after TBI and suggest the possibility of using the model to efficiently screen for potential therapeutic candidates.

Keywords: Excitotoxicity
Modelling
Neuroprotection
Secondary Injury
Traumatic Brain Injury
Zebrafish
Advisor: Baker, Andrew J
Sensitivity Analysis of Material Property Predictions in Molecular Dynamics with Interatomic Potentials under Uncertainty

Molecular Dynamics (MD) simulations complement experimental methods by offering a computationally fast and accurate framework for determining the properties of materials. However, there is uncertainty associated with MD simulations in part due to the intrinsic microstructure of the material, but also due to the interatomic potential used to describe the material. To evaluate the uncertainty associated with MD predictions, this work exploits the strong dependency of MD on the interatomic potentials. Using a methodology based on surrogate models, a sensitivity analysis of the properties of graphene and aluminium when uncertainty is introduced to the parameters of their respective potentials is presented. These surrogates are utilized to identify which parameters in the potentials greatly affect the output parameters of interest. This methodology can be used to evaluate the robustness of interatomic potentials and accelerate the solution of the inverse problem to determine the parameters of the potential from observables.

Keywords: Aluminium
Graphene
Molecular Dynamics
Surrogate Models
Advisor: Nair, Prasanth B
Attempt to Detect a Salmon Viral Pathogen from Seawater Collected in British Columbia

Wild Pacific salmon populations are subject to multiple anthropogenic stressors leading to marked declines in British Columbia. One important stressor may be disease, and disease linkages between Atlantic salmon aquaculture and wild Pacific salmon populations. Macroparasite transmission between farmed Atlantic salmon and wild Pacific salmon has been studied extensively in British Columbia. The potential for viral transmission and the abundance of viral pathogens in the marine environment has not been rigorously assessed. We collected water samples from 62 fish farm sites in B.C., where roughly half were active farms and half were inactive. Presence of the salmon viral pathogen piscine reovirus (PRV) was analyzed using quantitative PCR. PCR detection of common picorna-like virus was used to test for amplifiable material. Ultimately, the methods failed to detect PRV, most likely due to sample degradation linked to the relative instability of RNA.

Keywords: Aquaculture
Fisheries
Pacific Salmon
qPCR
Virus
Advisor: Krkosek, Martin
Short, Steven
Abrasive Slurry Jet Micro-machining of Talc Filled Polypropylene - Planar Area, Transitional Slope and Curved Edges Machining

The abrasive slurry-jet erosion of a talc-filled TPO (60% PP, 25% EP rubber and 15% talc) was measured as a function of the impact angle and the talc filler content. A ductile erosion response was observed, showing a maximum erosion rate at 45°. A superposition model was then developed to predict the cross-sectional shapes of small-scale flat-bottomed pockets and curved edges machined in TPO using abrasive slurry-jet micro-machining (ASJM). The model was based on the spatial distribution of the erosion across the jet footprint measured during a shallow "first pass" channel at a specific angle. The model predictions of planar depth and waviness were in close agreement with experimental measurements. The measured dependence of the erosion rate on the impact angle was used to develop novel machining configurations to increase the slope of bounding sidewalls. A model was then developed to predict these slopes.

Keywords: Abrasive slurry jet
Erosion
Micro-machining
Polyolefin
Polypropylene
TPO
Advisor: Spelt, Jan K
Stochastic Integer Decision Making in Operations and Finance

Two different stochastic decision models are developed for incorporating uncertainty and risk aversion into operational and financial decision making. First, a location decision model is developed for optimizing the quantity and placement of critical transformer spares over a network of industrial sites. Operational and financial sources of uncertainty are incorporated through the framework of a two-stage stochastic integer program. A conditional value-at-risk (CVaR) objective function captures risk aversion. Computational results show the risk averse model results in policies with lower loss as a result of the acquisition of more spares as a hedge against catastrophic scenarios. Second, an extension of the financial index tracking model of Cornuejols and Tutuncu (2007) is developed. To incorporate uncertainty and risk aversion, the distributionally robust stochastic programming (DRSP) framework developed in Delage and Ye (2010) is applied. Computational results show the DRSP index tracking model results in portfolios with improved tracking performance and resilience to market shocks.

Keywords: Integer
Optimization
Reliability
Spares
Stochastic
Transformer
Advisor: Kwon, Roy H
Jardine, Andrew K.S.
The Role of Neutrophils in The Invasive Behaviour of Oral Squamous Cell Carcinoma

Oral cancers are the 15th leading cause of cancer death in Canada with an overall high mortality rate (Canadian Cancer Society, 2013). A review of the current literature on neutrophils supports a pro-tumour role of neutrophils in oral squamous cell carcinomas (OSCC) but the precise mechanisms still need to be clarified. The interaction between human neutrophils and human oral cancer cell line (UMSCC47) was investigated using quantitative in vitro invasion and matrix degradation assays. Both direct and indirect co-­cultures of UMSCC47 and neutrophils increased the invasiveness of cancer cells through and increase in the number of invadopodia and matrix degradation. The results of this study show that neutrophils increase the invasiveness of OSCC through the activation of invadopodia, suggesting that the presence of neutrophils in the oral environment may modulate the clinical behaviour of OSCC.

Keywords: Cancer
Invadopodia
Invasion
Neutrophil
Oral Cancer
Advisor: Glogauer, Michael
Phosphorylation of Neuralized at Serine 73 and 74 is Required for Proper Regulation of Neuralized and Notch Signaling during Drosophila development

The Notch (N) pathway plays a crucial role in metazoan development. Neuralized (Neur), an E3 ubiquitin ligase, is responsible for ubiquitination and endocytosis of the N ligands Delta (Dl) and Serrate (Ser). While much is known about the functions of Neur, how it is regulated is less understood. I have been studying the potential role of phosphorylation in the regulation of Neuralized and Notch signaling and identified a potential aPKC phosphorylation site at amino acid S73S74. I conclude that phosphorylation at S73S74 is not required for Neur function during embryonic neurogenesis, however, overexpression of non-phosphorylatable or phosphomimetic forms of Neur at these sites disrupt sense organ development. I also show that Neur localization in non-polarized cells is unaffected, as well as the ability to bind PIPs. I hypothesize that these post-translational modifications play a role in regulating developmental signaling pathways at different stages of development.

Keywords: aPKC
Drosophila
Neuralized
Advisor: Boulianne, Gabrielle L
Effects of Androgen Receptor Overexpression on Select Sexually Dimorphic Neural Structures

There are a number of interesting sexual dimorphisms studied in the brain, each of which is affected by hormones in different ways. The purpose of this experiment was to investigate the role of overexpressed androgen receptors on the expression of three sexual dimorphisms. The first, tyrosine hydroxylase immunoreactivity in the anteroventral periventricular nucleus and the second, vasopressin immunoreactivity in the lateral septum maintained their respective sex differences; however, they were unaffected by androgen receptor (AR) overexpression. The third, the sexually dimorphic nucleus of the preoptic area, showed an effect on cell size, with an increase in females overexpressing AR. Thus, this study provides evidence that AR affects cell size, often a marker for activational effects, more than it does markers of organizational effects.

Keywords: androgen receptor
differentiation
sex difference
transgenic
Advisor: Monks, Douglas A
Estimating the Remaining GAC Removal Capacity for Geosmin and MIB

Granular activated carbon (GAC) is commonly used in drinking water treatment for the control of seasonal taste and odour events. A challenge involving this application is the difficulty in accurately estimating the remaining service life of an existing GAC bed. This study evaluates a documented method that is intended to measure the removal capacity of a GAC contactor. The method involves collecting core samples of GAC from active beds and creating “mini columns” (10 cm lab-scale GAC columns) that are challenged with geosmin and 2-methylisoborneol (MIB). For this study, the results of the mini column tests were compared to those from parallel tests using pilot-scale GAC columns that were filled with core samples from two water treatment plants. Refinements to the mini column method reported by Gillogly et al. (1999) were examined. Overall, it was determined that mini column testing is in good agreement with corresponding pilot-scale studies.

Keywords: GAC
geosmin
MIB
mini column test
T removal
Advisor: Hofmann, Ron
The Frequency and Modal System Identification of the Balloon-borne Imaging Testbed

The Balloon-borne Imaging Testbed (BIT) is a stratospheric ballooning astronomy project that was successfully launched on September 18, 2015 from Timmins, Ontario to an altitude of 36 km over the period of one night. The design of the BIT gondola must allow the on-board telescope to maintain a constant position for an extended period of time during which the structure is subjected to external forces. Oscillations created by resonances of the gondola can prove detrimental to the resulting image quality. Therefore, the development of a modal analysis method for the gondola is explored in this thesis. This method combines simulation with measurement results to identify the modes of the system. For the gondola's external frame, the four lowest natural frequencies and their corresponding mode shapes are identified. BIT represents a new generation of balloon-borne telescopes that can produce images comparable to those of space telescopes but at significantly lower costs.

Keywords: Balloon-borne Astronomy
Instrumentation
Structural Design
Structural Simulation
System Identification
Advisor: Damaren, Chris J
Investigation of Deep Eutectic Solvents and Their Derivatives for Pharmaceutical Applications

Deep eutectic solvent (DES) is a liquid typically formed by mixing two solids, such as a quaternary ammonium salt (QAS) and a hydrogen bond donor (HBD). It was found that the melting point depression can be statistically correlated with the Hansen solubility parameters of the HBD. It was also discovered that DES derivative (DESD) formed by glycolic acid and choline chloride shows a wide range of enhancement on the solubility of selected weakly basic poorly water-soluble drugs. Furthermore, a new ternary DESD based on choline chloride, glycolic acid, and oxalic acid remarkably increased the solubility of itraconazole to 5.36 mg/mL (a 53600-fold increase). Subsequently, DESD containing itraconazole was used as a topical formulation to deliver itraconazole through bovine hoof membranes. Overall, the development of the ternary DESDs has tremendously increased the solubility of itraconazole, and DESD has displayed great potential as a formulation vehicle for transungual drug delivery.

Keywords: deep eutectic solvent
Hansen solubility parameter
insoluble drugs
itraconazole
solubility
statistical modelling
Advisor: Lee, Ping I
Pang, Sandy
Using Micro-simulated Traffic Conflicts as a Surrogate Safety Assessment Technique for Evaluating Safety Performance of Transit Design Alternatives at Signalized Intersections

This study focuses on crash prediction modelling at intersection-level using micro-simulation to produce an effective surrogate safety assessment measure. The developed crash prediction model followed generalized linear model with negative binomial error structure to correlate the simulated traffic conflicts with the observed crash frequency in Toronto, Ontario, Canada. Individual crash prediction models were developed for every impact types and for transit-involved crash type. The resulting statistical performance suggested adequate predictive ability. Based on the established correlation between the simulated conflicts and observed crashes, scenarios were developed to investigate the safety impacts of transit infrastructures by making hypothetical transit infrastructure modifications in the micro-simulation networks. The findings implied that the existing transit signal priority schemes implemented in Toronto had negative contributions on safety performance and that the existing near-sided stop positioning and streetcar transit type were safer at their existing states than if they were replaced by their respective counterparts.

Keywords: Intersection
Micro-simulation
Safety
Traffic
Transit Signal Priority
Transportation
Advisor: Shalaby, Amer
Persaud, Bhagwant
Regulation of Fungal Drug Resistance and Morphogenesis by Lysine Deacetylases

Hsp90 is a molecular chaperone that governs drug resistance, morphogenesis, and virulence in the leading human fungal pathogen Candida albicans. Previous work with Saccharomyces cerevisiae and C. albicans established acetylation as a novel mechanism of post-translational control of Hsp90 in fungi and implicated lysine deacetylases (KDACs) as key regulators of resistance to the most common class of antifungals, the azoles. Here, by generating KDAC deletion mutants in azole-resistant C. albicans, we discovered high level of functional redundancy among the KDACs, and identified Hos2, Hda1, Rpd3, and Rpd31as key KDACs responsible for mediating azole resistance. Furthermore, we identified Lysine 30 and 271 as critical acetylation sites of C. albicans Hsp90, such that mutations at these residues compromised Hsp90 function. Further investigations into the circuitry through which KDACs regulates drug resistance will provide important insights into the regulatory network of C. albicans Hsp90, and suggest new targets for treating life-threatening fungal infections.

Keywords: Acetylation
Candida albicans
Deacetylases
Drug resistance
Hsp90
Morphogenesis
Advisor: Cowen, Leah E