VictorJuiz/thesis huggingface dataset:
Investigating the Role of the LINC Complex on Skeletal Muscle Stem and Progenitor Cell Expansion
Keywords: EDMD
LINC complex
Muscle stem cell
Regeneration

Muscle stem cells, or satellite cells (SCs), are required for skeletal muscle regeneration. Emery-Dreifuss muscular dystrophy (EDMD), a debilitating muscle disorder, is associated with LINC complex mutations, a series of nuclear envelope proteins, including Nesprins, connecting the cytoskeleton and nucleoskeleton. Despite being expressed in SCs, the LINC complex’s influence on SC fate during regeneration remains unclear. We generated transgenic mice with SC-specific LINC disruption and observed regeneration defects characterized by diminished myofibre diameter. In vitro studies suggested these defects were likely caused by inadequate SC progeny amplification and myogenic progression. EDMD patient-derived myoblasts with a Nesprin-1 mutation and primary human myoblasts with Nesprin-2 knockdown exhibited delayed proliferation and disrupted myogenic progression. LINC-disrupted EDMD myoblasts had altered cell cycle-related genes, including PAI-1, MYOD, and CCNA2, hinting toward potential proliferation-related molecular mechanisms. This study highlights the LINC complex’s role in myoblast proliferation and muscle regeneration, paving the groundwork for SC-targeting EDMD therapeutics.
Trauma Bay Re-Design: A User-Centred Approach
Keywords: Design
Design Thinking
Trauma
Trauma Bay
Trauma Bay Design
User Centred Design

Trauma bays are chaotic places due to the frequent rotation of trauma team members from different disciplines and levels of training as well as urgency in providing required treatments. The suboptimal and ad-hoc design of trauma bays has led to staff dissatisfaction and potential safety and quality concerns at Sunnybrook Health Sciences Centre (SHSC). We apply various empirical frameworks with considerations from management science and participatory design to trauma bay re-design, with emphasis on active and iterative engagement from stakeholders and the application of user-centred design principles. Through observations, focus groups, and a tabletop prototyping workshop, we identified six main themes for improvement: labelling, visibility, item location, space utilization, flow, and communication. Focusing on these themes and with the use of human factors principles, we rendered a three-dimensional model of a future state trauma bay. We continue to improve this model through virtual reality tours with stakeholders and simulation scenarios. We discuss ongoing progress on the trauma bay re-design process occurring at SHSC.
Investigating Endocannabinoid Metabolism in Cannabis Use Disorder: A PET Study Measuring Fatty Acid Amide Hydrolase During Cannabis Withdrawal
Keywords: cannabis
neuropsychopharmacology
positron emission tomography

Abstract Introduction: Fatty acid amide hydrolase (FAAH) is low during overnight abstinence from cannabis. We investigated FAAH in cannabis users at overnight abstinence (T1); after 3-to-7-days of abstinence (T2). Methods: [11C]CURB scans were conducted at T1 (n = 13) and T2 (n = 10). Measures of craving, withdrawal, mood were collected. Primary analysis utilized Repeated Measures Analysis of Covariance (ANCOVA) across whole brain in 12 regions of interest (ROIs). Results: Two participants (n = 2) had levels of cannabigerol (CBG) at T2 suggesting failure to abstain. We found no main effect of time (n = 8), (F(1,6) = 2.840, p = 0.143); pairwise comparison suggested higher FAAH at T2 across ROIs (p = 0.09 – 0.23). Craving-expectancy correlated with changes in FAAH in amygdala (n = 8; r = 0.654, p = 0.040). Discussion: These data suggest nominal increases in brain FAAH at T2 in cannabis users. Future studies may assess longer abstinence.
“If We’re Going to do Anything, We Have to Do It Ourselves” - The Case for Drug User Self-Management
Keywords: autogestion
drug poisoning crisis
drug user
drug user self-management
harm reduction
self-management

This research project looks at the (self-)management strategies of drug users amidst the hostile socio-political environment manifested through 100 years of prohibition. This thesis focuses on Vancouver, B.C., Toronto, Ontario and various Canadian regions, analysing how current measures of policy enacted to address the worsening drug poisoning crisis have not been sufficient considering the crisis' death toll. An examination of strategies of drug user (self-)management is illustrated through a study of different strategies of drug user (self-)management, examining moments of drug user self-management that illustrate that drug users are not an ambivalent, apolitical group, but rather a highly radical, organised and effective political force that has forced drug policy forward for the last 30+ years. Further, this thesis will examine and interrogate literature surrounding limitations to harm reduction implementation, problematization procedures, and the current literature on self-management. This thesis works to legitimise and celebrate the revolutionary work of drug users throughout Canada.
Experimental Characterization of Bacterial Plant Pathogen Emergence
Keywords: Arabidopsis thaliana
Bacterial virulence
Genomic island
Plant pathology
Pseudomonas syringae
Type III secreted effector

Plant pathogens pose a serious threat to worldwide crop yields and cause widespread food insecurity. Insertion of host resistance genes is a common strategy deployed to protect crops; however, this resistance can be overcome by pathogen evolution. My research aims to characterize the evolutionary trajectories that enable the bacterial plant pathogen Pseudomonas syringae to overcome host resistance barriers to cause disease. Specifically, we applied in planta experimental evolution to adapt an initially weak pathogenic strain of P. syringae to the model host Arabidopsis thaliana. We expected the emergence of P. syringae as a pathogen to depend on modulation of an immune-eliciting effector gene. We quantified bacterial growth during eleven infection cycles and performed phenotyping and sequencing of evolved lineages at the conclusion of the experiment. We found that PmaYM7930 evolved increased pathogenesis within only five infection cycles and that multiple lineages had lost a genomic island harbouring an immune-eliciting effector. These findings illustrate the speed with which novel pathogenic P. syringae strains can emerge on resistant hosts and stress the importance of development of more robust resistance engineering in crops.
Exploring the Effects of Microstructure on Electrochemical Passivation of Copper Coatings for Used Fuel Containers in Canada’s Nuclear Industry
Keywords: Cold-Sprayed
Copper
Corrosion
Electrodeposited
Microstructure
Nuclear

This thesis investigates the influence of copper microstructure on electrochemical passivation performance, for the long-term storage of nuclear waste. The increasing global demand for nuclear power necessitates safe and reliable disposal strategies. The Canada-Deuterium-Uranium (CANDU) reactors and upcoming Small-Modular-Reactors (SMRs) contribute to a significant accumulation of used fuel bundles in Canada. To address this, the Nuclear Waste Management Organization (NWMO) proposes using Deep Geological Repositories (DGRs), where copper coatings on Used Fuel Containers (UFCs) are used for corrosion prevention. Through microstructural analysis and immersion tests under corrosive conditions, the corrosion performance of electrodeposited (ED(Py)-Cu), cold-sprayed (CS-AS-Cu), and oxygen-free electronic copper sheet (OFE-Cu) were compared. The passivating layer morphology was also examined under the influence of chloride and bicarbonate ions. The findings highlight the differences in corrosion behavior and passivation between different types of copper, emphasizing the importance of microstructure in designing effective corrosion prevention strategies for long-term nuclear waste storage.
The Impact of Particle Size in Cereal and Pulse Flours on Postprandial Glycemia and Appetite in Healthy Adults
Keywords: Appetite
Cereal grains
Food Intake
Food processing
Postprandial glycemia
Pulses

The hypothesis that decreasing particle size of oat and pea flours increases postprandial glycemia and decreases appetite and food intake was tested in healthy adults. Experiment 1 examined the effects of consuming a serving of porridge prepared using 40g of coarse, whole, fine, or commercial oat flour. Experiment 2 investigated the impact of eating 45g of crackers made with 25% of coarse, whole, or fine pea flour compared to 100% wheat flour. Blood glucose, insulin, and subjective appetite were measured over 140min and energy intake was assessed at an ad libitum pizza meal. Coarse and whole flour treatments led to lower blood glucose and insulin response, but the coarser oat flours were less effective at suppressing appetite, although resulting in no differences in food intake. Larger particle sized flours can be used to develop low-glycemic value-added products with improved nutritional quality and acceptability.
Interventions to mitigate antipsychotic associated weight gain using an algorithmic measurement-based integrated clinical pathway-a retrospective chart review study
Keywords: Antipsychotics
Diabetes Mellitus
Integrated clinical pathway
metabolic syndrome
Obesity
Severe mental illness

Antipsychotics form an essential component in the treatment of several psychiatric disorders; they are, however, associated with weight gain and metabolic dysregulation resulting in significant psychological and physical challenges, leading to treatment non-adherence, poor quality of life, and increased cardiovascular morbidity. Several non-pharmacological and pharmacological interventions are available to mitigate antipsychotic-induced weight gain (AIWG). However, data on the utility of these interventions in real-world settings are limited. In this study, a retrospective chart review of patients attending the mental health and metabolism clinic that specializes in providing care for metabolic dysfunction in those with mental illness was conducted from 2016-2022. Charts of included patients were reviewed, and data pertaining to demographic, anthropometric and metabolic measures were collected and analyzed. The primary outcome measure was a change in weight at 3, 6, 9, and 12 months. A significant effect of the clinic on body weight over time was noted. The mean change in body weight was -1.54kg (SE:0.35, p<0.001), -1.79kg (SE:0.42, p<0.001), -3.5kg (SE:0.832, p<0.001) and -1.77kg (SE:0.77, p=0.35) at 3, 6, 9, and 12 months respectively. Initial evidence from our real-world clinical setting suggests that periodic monitoring and systematic administration of interventions are effective in reducing AIWG.
Determining the Role of GABA/Glycine Neurons of the Ventromedial Medulla in REM Sleep Behaviour Disorder and Cataplexy
Keywords: Cataplexy
Narcolepsy
RBD
REM Sleep
REM Sleep Behaviour Disorder

Muscle atonia loss during REM sleep underlies REM sleep behaviour disorder (RBD) while muscle atonia intrusions into wakefulness underlies cataplexy. Basic science demonstrates that ventromedial medulla (vmM) GABA/glycine neurons innervate spinal motor neurons, are selectively active during REM sleep and cataplexy in human patients and animal models, and that degeneration is associated with RBD-like behaviours. Thus, it is hypothesized that these neurons generate atonia by inhibiting motor neurons and play a role in cataplexy. To test, vmM GABA/glycine neurons in narcoleptic mice were selectively lesioned, resulting in increased twitching and muscle tone in the neck but not masseter muscles during REM sleep. Mice demonstrated reduced cataplexy during wakefulness paired with increased muscle tone during remaining cataplexic episodes without affecting waking motor performance or waking muscle tone. Furthermore, narcoleptic mice exhibited deficits in waking motor performance alongside increased twitching behaviours in the neck muscle during REM sleep compared to non-narcoleptic counterparts.
Implications of Reduced Inhibition in Schizophrenia on Human Prefrontal Microcircuit Activity and EEG
Keywords: Computational modelling
Mismatch Negativity
Parvalbumin
Prefrontal cortex
Reduced Inhibition
Schizophrenia

Reduced cortical inhibition by parvalbumin-expressing (PV) interneurons has been associated with impaired cortical processing in the prefrontal cortex (PFC) and altered EEG signals such as oddball mismatch negativity (MMN) in schizophrenia. However, establishing the link between reduced PV interneuron inhibition and reduced MMN experimentally in humans is currently not possible. To overcome these challenges, we used detailed computational models of human PFC microcircuits, and modeled schizophrenia microcircuits by integrating gene-expression data from schizophrenia patients indicating reduced PV interneuron inhibition output and NMDA input. We simulated spiking activity and EEG in microcircuits with different levels of reduced PV interneuron mechanisms and showed that a double effect of the reduction indicated by gene-expression led to a significantly reduced MMN amplitude as seen in Schizophrenia patients, whereas a single effect produced a smaller reduction in MMN that matched the magnitude seen in patients at high-risk of schizophrenia. In addition, we showed that simulated resting EEG of schizophrenia microcircuits exhibited a right shift from alpha to beta frequencies. Our study thus links the level of reduced PV interneuron inhibition to distinct EEG biomarkers that can serve to better stratify different severities of schizophrenia and improve the early detection using non-invasive brain signals.
Pathfinder: Local Obstacle Avoidance for Long-Term Autonomous Path Following
Keywords: Curvilinear Coordinates
Field Robotics
Model Predictive Control
Motion Planning
Obstacle Avoidance
Path Planning

Visual Teach and Repeat 3 (VT&R3), a generalization of stereo VT&R, achieves long-term autonomous path-following using topometric mapping and localization from a single rich sensor stream. In this thesis, we improve the capabilities of a LiDAR implementation of VT&R3 to reliably detect and avoid obstacles in changing environments. Our architecture simplifies the obstacle-perception problem to that of place-dependent change detection. We then extend the behaviour of generic sample-based motion planners to better suit the teach-and-repeat problem structure by introducing a new edge-cost metric paired with a curvilinear planning space. The resulting planner generates naturally smooth paths that avoid local obstacles while minimizing lateral path deviation to best exploit prior terrain knowledge. While we use the method with VT&R, it can be generalized to suit arbitrary path-following applications. Experimental results from online run-time analysis, unit testing, and qualitative experiments on a differential drive robot show the promise of the technique for reliable long-term autonomous operation in complex unstructured environments.
Law Reform through Deep Ecology: A Critical Review of the Canadian Environmental Protection Act, 1999
Keywords: Climate change
Human health
Right to healthy environment
Sustainable development
Well-being

The single most important piece of legislation in Canadian environmental law, the Canadian Environmental Protection Act, 1999 (CEPA) proposed its set of amendments under Bill S-5, Strengthening Environmental Protection for a Healthier Canada Act. This project is a qualitative study, using Critical Discourse Analysis (CDA) to review the amendments in Bill S-5 against the philosophy of deep ecology which argues that nature has inherent worth. Overall, Bill S-5 does not display evidence of deep ecology principles. I argue that if the Act is amended to include stricter principles inspired by deep ecology, it can enhance sustainable development. By examining the Bill’s language and the law’s sociocultural contexts, CDA provides insights into the potential implications and effects if the Act indeed displayed a case for biocentric equality. Deep ecology at times underplays the capacity of the role of humans, therefore Canadian Indigenous knowledge systems will be discussed to address this gap.
Performance Analysis, Design, and Testing of Radio Frequency Earth Observation Microsatellite Missions
Keywords: Earth Observation
Electromagnetic Compatibility
Microspace
Performance Analysis
Radio Frequency
Satellite

Modern terrestrial technologies are enabling small satellites to push the boundary of what radio frequency remote sensing payloads can achieve. Software defined radio and field programmable gate array technologies enable missions to increase the comprehensiveness of Earth observations through the flexibility inherent to these technologies. Significant engineering challenges must be overcome to fly them. This thesis presents work to enable two new missions by addressing challenges resulting from their payload systems. A new system-level performance analysis and electromagnetic compatibility testing system has been created to qualify multi-channel radio frequency payloads. Work has also been performed to facilitate spacecraft-level vibration and thermal vacuum testing, the latter of which required the design and construction of an antenna hat for safely dissipating emissions from a high power transceiver. Lastly, multiple data-handling payloads are connected using a field programmable gate array, where static timing analysis has been used to verify external interface timing requirements.
Power Grid Safety under Electromigration
Keywords: Computer Simulation
Electromigration
Power Grid Safety

Electromigration is a reliability concern that affects chip power grids carrying high current over the course of several years. Power grid safety is an important issue that can be addressed in several ways. In this work, we present two different ways of guaranteeing grid safety from electromigration. First, for safety of the chip from void nucleations due to electromigration, a set of current constraints can be generated as guidelines or constraints for chip design. The proposed procedure efficiently generates approximate constraints by projecting the system onto a smaller subspace, based on an Arnoldi scheme for model-order reduction. It then leverages several properties of the matrices at hand to efficiently perform the required computations in the reduced subspace, before projecting the results back to the original space. Second, for safety of the chip from electromigration-related voltage failures, we developed a procedure which widens some metal lines in order to prolong the lifetime of the chip. This work improves on a previous iterative method for grid fixing by the use of a faster and more accurate electromigration simulator.
Deep Learning for Long-Term Metric Visual Localization
Keywords: Autonomous Navigation
Computer Vision
Deep Learning
Long-term localization
Robotics

Visual localization is the task of estimating camera pose in a known scene, which is an essential problem in robotics and computer vision. However, long-term visual localization is still a challenge due to the environmental appearance changes caused by lighting and seasons. While experience-based localization methods bridge the appearance gap by relying on intermediate experiences, they require collecting ex- periences continuously to capture the incremental appearance changes, and cannot directly generalize to a new path. In this thesis, we tackle long-term localization using deep learning methods with- out relying on intermediate experiences. We first show that we can learn appearance- invariant sparse visual features using self-supervised learning that can be used in closed-loop path following across a full range of lighting change while preserving generalizability. We further explore deep image-to-image translation as a mean of improving long-term metric localization. We show that by transforming input images captured from different lighting conditions into a common target domain prior to feature matching substantially improves upon localization accuracy.
Biopsychosocial Characterization of Cognitive Decline and Late-Life Depression Trajectories Using Bayesian Consensus Clustering and Machine Learning
Keywords: Bayesian clustering
Biostatistics
Cognitive decline
Dementia
Depression
Machine Learning

Cognitive decline and late-life depression (LLD) often co-occur and impact elderly’s wellbeing. However, their intersection and antecedents are understudied. We analyzed 2,992 participants from the Religious Orders Study and Memory and Aging Project, integrating symptoms and diagnostic records with Bayesian consensus clustering to define latent sub-trajectories of cognitive decline and LLD. Logistic regression, elastic-net regression and XGBoost were used to build models of these trajectories including n=57 biopsychosocial predictors. Associations of subgroups with postmortem neuropathologies were assessed for 1,721 deceased participants. Three subgroups were identified for cognitive decline and two for LLD, which overlapped significantly (chi-square p=8.1x10-26). Elastic-net regression performed best overall, while XGBoost excelled at predicting moderate subgroups. High neuroticism and low physical health at baseline predicted unhealthy subgroups for both cognition and LLD. There were no neuropathologies associated with LLD trajectories. Our results suggest potential values of targeting neuroticism and physical health for healthy aging and patient screening.
Characterizing the NLRP1B Inflammasome in the Intestinal Epithelium
Keywords: Innate Immunity

The intestine is a non-sterile organ that must maintain its epithelial barrier to prevent microbial invasion into deeper tissue. Intestinal epithelial cells (IECs) are equipped with innate immune receptors, such as NOD-like receptors (NLRs), that facilitate destruction of infected cells and initiate an inflammatory response through inflammasome formation. NLRP1B, the major mouse homolog of human NLRP1, has been primarily studied in macrophages; and therefore, very little is known about this NLR in the intestinal epithelium. Here, we determine that NLRP1B is expressed higher in murine ileal organoids than in bone marrow-derived macrophages (BMDMs), however, only BMDMs are responsive to the NLRP1B activator, Val-boro-Pro. Additionally, IL-13, which is important in enteric parasite defense, induces Nlrp1b expression and this was confirmed in vivo using Tritrichomonas muris infection. Overall, our data suggests that the NLRP1B inflammasome is differentially regulated in IECs and BMDMs and could have a novel role in enteric parasite infection.
Exploring the Effect of Social Support from Sport Medicine Staff on Injured Female Athletes’ Well-Being During Rehabilitation
Keywords: Athlete well-being
Injury rehabilitation
Mattering
Social support
Sport medicine staff

This study explored female athlete experiences with sport medicine staff while they navigated injury rehabilitation, specifically exploring the ways in which social support from sport medicine staff influenced well-being during this process. Eleven injured athletes completed two semi-structured interviews and six audio diary entries. Thematic analysis of the collected data suggested that athletes perceived sport medicine staff as supportive if they made athletes feel that they mattered. Further analysis demonstrated that sport medicine staff showed athletes they mattered by providing clear information about rehabilitation, demonstrating competency in delivering treatment, and developing a personal connection with athletes. These findings provide valuable insight into how female athletes experience social support from sport medicine staff during injury rehabilitation. Additionally, it provides applied suggestions for sport medicine staff who work with injured female athletes.