VictorJuiz/thesis huggingface dataset:
The Discovery and Investigation of the Role of Hepatocyte Nuclear Factor 4 alpha in Controlling the Proximal Tubular Epithelial Cell Metabolism
Keywords: Ischemia Reperfusion
Metabolism
Mitochondria
Nephrology
Nuclear Receptor
Transcription Factor

Kidney transplantation is the optimal treatment for end-stage kidney disease. Normothermic ex-vivo kidney perfusion (NEVKP), a method of kidney storage prior to transplantation, results in superior graft function in porcine auto-transplantation models. We determined that key mitochondrial proteins were preserved following NEVKP. We predicted these proteins to be regulated by Hepatocyte Nuclear Factor 4-alpha (HNF4α), a transcription factor expressed in the proximal tubular epithelial cells (PTECs) of the kidney. We sought to determine the effect of HNF4α inhibition on PTEC gene expression, viability, and metabolic function. We demonstrated that inhibition of HNF4α with a pharmacological inhibitor resulted in increased cytotoxicity and an altered expression of HNF4α gene targets. HNF4A knockdown resulted in decreased oxygen consumption rate and glycolysis, measured using Seahorse, and the effects were more pronounced over time. These data suggest that inhibition of HNF4α changes the expression of metabolic proteins and influences metabolic function and cell viability.
Comparing Scope of Practice Policies in Intrauterine Device Insertion and Removal to Analyze Task Sharing Conditions in Canada, Australia, and the United Kingdom
Keywords: Family Planning
Health Policy
High Income Countries
Interprofessional Collaboration
Intrauterine Contraceptive Devices
Task Sharing

This case-based comparative policy analysis investigated task sharing in family planning by comparing scope of practice policies in intrauterine device (IUD) insertion and removal in Canada, Australia, and the United Kingdom. Informed by the “3I+N” conceptual framework and modified Donabedian model, I analyzed legislation, policy documents, and key informant interviews across regulatory bodies, professional associations, and governmental agencies involved in determining scope of practice for physicians, nurses, and midwives. Jurisdictions delegating scope of practice policymaking to specialized, centralized, and interdisciplinary authorities enabled task sharing the most in IUD services. Institutional structures surrounding legislation, funding models, and accreditation processes influenced the possibility for and impact of multidisciplinary approaches to IUD services. Uptake of task sharing policies at local levels with accompanying cultural shifts away from physician-dominated hierarchies was essential to task sharing, regardless of institutional structures. Task sharing was an important contributor to system equity, particularly in rural and remote areas.
The Effects of Pegylated Interferon-Lambda Treatment on SARS-CoV-2-specific T Cell Responses
Keywords: COVID-19
IFN
Interferon
SARS-CoV-2
T cell response
Viral immunity

Interferon lambda (IFN-λ), a type III interferon, is a key component of the innate antiviral immune response. Type III IFNs use a receptor with limited expression to epithelial cells. However, it has recently been shown that specific immune cells, including T cells, express the receptor. We recently completed a randomized clinical trial using pegylated IFN-λ (PEG-IFN-λ) to treat mild-to-moderate COVID-19 and demonstrated accelerated viral clearance with treatment. Whether IFN-λ influences virus-specific T cell responses and whether this contributes to its antiviral activity are unknown. SARS-CoV-2-specific responses in PEG-IFN-λ trial patients towards the spike, nucleocapsid, and membrane proteins were measured in this study. PEG-IFN-λ did not affect the magnitude or breadth of SARS-CoV-2-specific T cells, however we identified a delay in T cell responses in older patients. Overall, our results demonstrate that the accelerated viral clearance observed in our clinical trial was not the result of an enhancement in SARS-CoV-2-specific T cell responses.
Targeting Drug Tolerant Persisters (DTPs) in Colorectal Cancer via Anti-apoptosis Inhibition
Keywords: Apoptosis
Autophagy
Colorectal cancer
Drug tolerant persisters

Chemotherapy resistance presents a major challenge to successful therapy in colorectal cancer (CRC). Non-genetic processes can drive drug resistance, and drug tolerant persister (DTP) cells are emerging as key players. DTPs are slow-cycling cancer cells and represent a reversible state, where upon removal of treatment they resume growth yet remain sensitive to therapy. We demonstrate that patient-derived CRC tumours exposed to chemotherapy (CPT-11) and cell cultures exposed to its active metabolite (SN38) survive by entering the DTP state. This project reveals increased expression of autophagy and anti-apoptotic genes, and increased expression of the anti-apoptotic protein Bcl-xL, in SN38-induced DTPs. Annexin V/PI analysis reveals SN38 treatment in combination with an anti-apoptotic (ABT-263) and autophagy (SBI) inhibitor significantly increases cell death. Furthermore, only cultures treated with SN38, ABT-263, and SBI in combination failed to regrow following a 28-day drug holiday, suggesting the autophagy and anti-apoptotic pathways work together to promote DTP survival.
A Fast Electromigration Simulator for Integrated Circuit Power Grid Verification
Keywords: Computer methods
Electromigration
Electronic Design Automation
Very Large Scale Integration (VLSI)

Electromigration (EM) is a failure mechanism mostly present in integrated circuit power grids due to the uni-directional current flowing inside the metal lines. This phenomenon is aggravated by the high current density levels and narrow lines in these grids. It is therefore important for today’s power grid verification software to include an accurate EM checking tool. In this work, we present a complete electromigration simulator using a new equivalent RC circuit model, along with an accurate void model. This equivalent model is simple to use, and leads to a system matrix that is easy to analyze. Furthermore, this circuit model allows us to use known circuit analysis techniques to describe the stress inside the metal lines in terms of equivalent node voltages. Finally, since this system is based on circuits, there are immediate ways to speed up the method, using circuit intuition and priorliterature for circuit model order reduction.
Shared Affects: Chinese Canadian Engagement and Community Building in Subtle Asian Traits
Keywords: Chinese Canadian Studies
Community
Diaspora
Facebook
Identity
Memes

This study investigates the participation of Chinese Canadian youth in the Facebook group Subtle Asian Traits and how meaning is derived from humourous posts, such as memes, shared in the group. There are three sections to this study: a survey, a semi-structured interview, and content analysis of material shared to the group. A survey was first circulated across 19 Chinese Canadian community organizations with the goal of seeking respondents who fit the criteria of being a Chinese Canadian youth aged 18-30 in the group Subtle Asian Traits who would be open to being interviewed. Six respondents volunteered to participate in semi-structured interviews and were asked to bring between 1-10 memes they found memorable. The results of this study provide a framework for understanding digital community-building amongst Asian diasporic youth, as well as identifying key themes in contemporary Asian North American discourses online.
Weakly Supervised Perturbation Based Method for 3D Brain Tumour Segmentation
Keywords: Brain Tumour Detection
Explainable AI
Perturbation
Segmentation
Weak Supervision

Deep convolutional neural networks (CNNs) have become an essential tool in the medical imaging-based computer-aided diagnostic pipeline. However, training accurate and reliable CNNs requires large fine-grained annotated datasets. To alleviate this, weakly-supervised methods can be used to obtain local information from global labels. This work proposes using perturbations as a weakly-supervised solution to extract segmentation masks of brain tumours from a pre-trained 3D classification model. Furthermore, we propose a novel optimal perturbation method that locates the most relevant area for a given classification using a U-net architecture-based generator. We show our method can be used to extract both regions of interest and also can be used as a classification explainer.
Simulation of a Three-dimensional Lid-driven Cavity at High Reynolds Number with the Lattice Boltzmann Method
Keywords: GPU Parallelization
Lattice Boltzmann Method
Lid-Driven Cavity
Turbulent Flow

There has been recent success in combining Large Eddy Simulation (LES) with the Lattice Boltzmann Method (LBM) for simulating turbulent incompressible flow. Limitations in computational resources which can make simulation of flows at high Reynolds numbers infeasible (due to inaccuracy resulting from insufficient grid refinement) can be overcome with GPU-based parallelization of the LBM. A multi-node multi-GPU strategy for parallelization of the LES-LBM is developed for simulation on SciNet’s Mist GPU-cluster. An in-house C++ code is constructed implementing the scheme in a CUDA-aware MPI framework using up to sixteen GPUs on the cluster distributed over four nodes. Simulations of the 3D lid-driven cavity are performed up to a Reynolds number of $10^5$ using single and multiple-relaxation collision operators for comparison. Coherent structures in the generated flow fields are visualized with isosurface plots of various vortex identification criteria and ranges of energy scales are illustrated with power spectral density plots.
The Role of Dynorphin and Kappa Opioid Receptors in Chronic Pain-associated Memory Impairment in Mice
Keywords: chronic pain
long term memory
memory
neuropathic pain
pain
short term memory

The endogenous opioid peptide, dynorphin A, is upregulated throughout the central nervous system in chronic pain conditions. It also induces memory deficits when exogenously infused in the rodent hippocampus. However, whether the dynorphin/kappa-opioid receptor (KOR) system is involved in chronic pain-related memory impairment remains unknown. I used the spared nerve injury (SNI) model of chronic neuropathic pain in mice to investigate memory deficits using the 8-arm radial maze and the novel object recognition tasks. Short-term memory (STM) was impaired in SNI mice while long-term memory (LTM) was not. STM impairment correlated with increased expression of dynorphin A and KORs in the hippocampus of SNI mice. One systemic or bilateral intrahippocampal injection of nor-binaltorphimine, a KOR blocker, reversed the SNI-induced STM deficit for at least 2 weeks. These results suggest that the upregulation of dynorphin/KOR system in the hippocampus may contribute to memory deficits in chronic neuropathic pain patients.
Reassembling the Play: Navigating Dramatic Literature in Postdramatic Milieu
Keywords: Archive and repertoire
Performance
Play publication
Postradamatic theatre
Public Recordings
STO UNION

The common usage of the word “play” possesses a double meaning that encompasses objects such as books and scripts, as well as the specific live performance events they inspire or record. This paper argues that the double meaning of play reflects premodern understandings of performance, print and publication, and has implications that persist through contemporary theatre practice. This auto-ethnographic and research-based project employs the concept of performance-as-surrogation articulated by Joseph Roach, and Diana Taylor’s framework of the archive and repertoire, to propose an artistic strategy that “reassembles” the double-meaning of play. It examines the implications of such a practice and presents experiments using documents of performance by STO UNION, Public Recordings and Evan Webber and Frank Cox-O’Connell.
Pillow Placement during Robotic Bed-Making using Classical and Learning-based Methods
Keywords: AI
Bed-Making
Household Robotics
Machine Learning
Object Detection
Robotics

Bed-making is a common chore completed in various living environments to promote user comfort, hygiene, and well-being. Unfortunately, the physical and tedious nature of the act makes it challenging to complete, and thus the opportunity arises to develop robots to automate the task. However, despite the opportunity's importance and positive impact, there is very little research on developing robotic bed-making systems. The aim of this thesis is to start addressing this gap by proposing methods to accomplish pillow placement, a major part of the bed-making task. This thesis proposes a pillow placement process that uses both classical and learning-based methods. The robot was able to place pillows at desired poses fully successfully in 89\% of the runs. The results of this thesis serve as a foundation for future work, where the methods could be tested in more complex environments.
Using Passive Cooling to Improve Thermal Resilience: Evaluation of a First Nations Housing Prototype Design
Keywords: First Nations
Indigenous
Operable Windows
Overheating
Passive Cooling
Thermal Resilience

There is a need for new culturally-appropriate housing for First Nations communities. Passive cooling technologies may be well suited to this new form of housing as it can align well with the First Nations’ traditional holistic ways of knowing and may be able to address the risk of overheating, which is already apparent through the 2021 heat waves in BC and only increasing under climate change. Thermal resilience performance via passive cooling through operable windows was examined for a prototype housing design created for ʔaq’am First Nation, a community in southeastern BC. Passive cooling improved thermal resilience, although active cooling was still required to meet the BC step code thresholds for overheating hours. Future consideration is needed to improve thermal resilience practices in high performance development, and more research and discussion is required to integrate First Nations thinking into the design of mechanical systems installed in First Nations communities.
Three Dimensional Musculoaponeurotic Architecture and Innervation of the Human Flexor Digitorum Superficialis and Flexor Digitorum Profundus: Functional Implications
Keywords: architectural parameters
flexor digitorum profundus
flexor digitorum superficialis
muscle architecture
muscle modelling
muscle morphology

Stroke is a leading cause of disability in Canada. Up to 80% of stroke survivors develop post stroke spasticity that results in pain, stiffness and joint contractures that negatively impacts quality of life. Botulinum toxin injection into the target muscle is essential for effective and safe treatment of muscle spasticity. Flexor digitorum superficialis (FDS) and flexor digitorum profundus (FDP) muscles are commonly affected, however, the recommended sites of injection vary. The aim was to construct a volumetric 3D model of the contractile and connective tissue elements of the digital bellies FDS and FDP to determine their functional characteristics and optimal botulinum toxin injection sites. The musculoaponeurotic architecture of FDS and FDP, and intramuscular innervation of FDP, were defined in 3D space. This thesis elucidates the morphology, relative functional capabilities, and optimal botulinum toxin injection sites of the digital bellies of FDS and FDP.
Characterizing Topological and Topographical Resilience in Structural Networks Supporting Language in Childhood
Keywords: Development
Diffusion MRI
Language
Paediatric
White Matter Imaging

Language networks undergo robust changes through childhood. Language is first supported by an extensive network spanning both hemispheres and becomes focal and left-lateralized through development. Here, we assessed language network resilience using diffusion imaging and in silico attacks. We acquired multi-shell diffusion-weighted images of 50 typically-developing children, ages 5-18 years. Automated parcellation was combined with constrained-spherical deconvolution and anatomically-constrained tractography to estimate connectomes. We assayed network resiliency using multiple targeted attacks. Interestingly, resiliency increased with age (p < 0.05); however, spatial extent of nodes removed prior to failure decreased with age (p < 0.05). Also, left-lateralization of nodes increased with age (p < 0.05). From a wiring perspective, adolescents’ language networks are more resilient than those of children. However, critical hubs are more diffuse in younger children, and become increasingly left-lateralized and focal with age. Findings suggest that diffuse representation underlies the paediatric advantage for language outcomes following (focal) injury.
Cu-P and Cu-La-P Alloys as Hydrogen Evolution Electrocatalysts
Keywords: Electrocatalysis
Electrochemistry
Energy Conversion
Heterogeneous Materials
Materials Design
Surface Science

The recent development of anion exchange membranes has renewed interest in alkaline water electrolysis as a means of converting renewable energy to storable H2. New electrocatalysts are required to take advantage of the additional performance offered by anion exchange membrane water electrolysers. Cu-P-based alloys are interesting as hydrogen evolution electrocatalysts due to a combination of good intrinsic activity and stability. Novel Cu-La-P alloys were prepared using mechanical alloying via cryomilling and evaluated as electrocatalysts to elucidate the role of a rare earth, La, on the electrocatalytic behaviour. A thermodynamic model was used to guide alloy design, and X-ray diffraction and electron microscopy were used to characterize the morphology and phase composition. A secondary ball milling process was used to prepare nanopowders. Tafel slope and exchange current density data demonstrate spillover effects occurring on multiphase Cu3P/Cu19La5P12 surface structures. These results suggest that Cu-La-P alloys are promising catalysts for electrochemical hydrogen production.
Retention in Care for People Living with HIV in Ontario
Keywords: Canada
Care continuum
Gaps in care
HIV
Retention

Our objectives were to determine how frequently people living with HIV (PLHIV) in Ontario experience a non-retention episode, and associated individual, provider, and healthcare system factors. Using administrative, population-level data, we followed PLHIV from their first visit with an HIV-experienced provider until first non-retention episode (365 days without HIV care), death, or loss-to-follow-up. Kaplan-Meier curves, logrank tests, and Cox proportional hazards models were used to evaluate time-to-first non-retention episode. 15,242 PLHIV entered care between 2000 and 2018. The probability of non-retention at 3, 6 and 10 years was 21%, 41% and 58%, respectively. Non-retention was less likely for individuals who had previously accessed mental healthcare or public drug insurance, were an immigrant or refugee, or initiated care with an HIV-experienced or primary care provider. Many PLHIV in Ontario have not received care within recommended timeframes. Practice and policy improvements should focus on PLHIV with characteristics associated with non-retention.
Temperature Dependence of the Deuterium Concentration in SiC Codeposits
Keywords: Carbon
Codeposit
Deuterium
Fusion
Silicon Carbide
Sputtering

Silicon carbide is a low-Z material seen as a possible alternative to graphite for some plasma-facing components in magnetic confinement fusion reactors. This work focuses on measurements of deuterium content of SiC codeposits created by ion beam sputter deposition at temperatures ranging from 300 – 900 K. Various surface analysis techniques are used to analyze deposits of SiC as well as C and thermal desorption spectroscopy is used to measure deuterium content. The temperature dependence very closely followed the trends observed for plasma-created codeposits, with the D content decreasing above 400 K. The D content of such deposits was also found to be very similar to the D content of carbon deposits created in the same way. This suggests that the tritium retention associated with SiC first wall materials would be very similar to that of a graphite first wall.
Microsatellite Development, Testing and On-orbit Operation
Keywords: attitude
development
operation
optimization
satellite
spacecraft

A recent rise in the number of small spacecraft has motivated the development of the DEFIANT microsatellite platform at the Space Flight Laboratory. This thesis details the development of multiple spacecraft subsystems for the DEFIANT platform, including the guidance, navigation and control, propulsion and deployable solar panel subsystems. The testing process for spacecraft hardware is presented and used in the qualification and acceptance of several subsystems for the DEFIANT platform. Finally, developments in the on-orbit operation of the guidance, navigation and control subsystem are detailed and used in the commissioning of several spacecraft. The work outlined in this thesis was used in the design, analysis, testing, and commissioning of over 20 spacecraft for the Space Flight Laboratory, supporting its competitive advantage in the microsatellite world market.
Association of Whole-person Eigen-polygenic Risk Scores with Alzheimer’s Disease
Keywords: Alzheimer’s disease
eigen-PRS
Polygenic risk scores
WGCNA
whole-person

Late-Onset Alzheimer’s Disease (LOAD) is a heterogeneous disorder with complex etiology and high heritability. We used Pan-UK Biobank Consortium GWAS sum- mary statistics to calculate polygenic risk scores (PRSs) for 2,218 heritable traits in a sample of 2,044 elderly with clinical and post-mortem autopsy data. Weighted gene co-expression network analysis (WGCNA) was used to identify discrete correlated clusters of PRSs. Module memberships varied across different α-value SNP selection thresholds. Few modules were strongly conserved across multiple α-value thresholds. Several Eigen-PRSs (ePRSs), the first principal component of PRSs in each cluster, were derived from the modules significantly associated with LOAD-related pheno- types and improved predictive model performance over the LOAD PRS alone. The ePRS representing clusters of traits related to cholesterol levels improved variance ex- plained in a model of brain-wide beta-amyloid burden by 1.7% (likelihood ratio test p = 9.02 × 10−7). In addition to improving existing single-PRS approaches, WGCNA will aid in developing new etiological hypotheses.
Soot and Flow Field in Turbulent Swirl-stabilized Spray Flames of Jet A-1 with Downstream Air Injection in a Model Gas Turbine Combustor
Keywords: Combustion
Flame
Soot

Influence of downstream oxidation air injection in swirl-stabilized Jet A-1 spray flames was investigated in a model combustor with 94 mm X 94 mm cross-section and 188 mm length. Fuel flow rate and global equivalence ratio were held constant while the fraction of oxidation air injection was varied up to 30%. Flow field measurements were carried out using stereoscopic particle image velocimetry. Fuel spray droplet size distributions were determined through the Fraunhofer diffraction technique. Spatially-resolved soot volume fraction and mean primary particle size were measured using auto-compensating laser-induced incandescence. Measurable differences in spray and flow field characteristics were observed between flames with and without oxidation air injection. Soot was observed in wider spatial ranges in the flames with oxidation air injection compared to the flames without. The overall quantity of soot present in all configurations of flames with oxidation air injections is greater than the flames with no oxidation air injection.