VictorJuiz/thesis huggingface dataset:
The Effect of Loss of Estrogen on Trabecular Bone Score in Women at Increased Risk of Breast Cancer
Keywords: Bone mineral density
Breast cancer
DXA scan
Estrogen deficiency
Trabecular bone score

In states of estrogen deficiency bone loss is evident. We investigated two interventions that cause estrogen deprivation in the setting of breast cancer prevention: 1) prophylactic salpingo- oophorectomy, being the surgical removal of the ovaries and fallopian tubes, and 2) exemestane therapy, which prevents estrogen synthesis in the body. In the literature, bone density loss following these interventions has been studied; however, bone density does not encompass all aspects of bone strength. Our aim was to investigate bone loss after these interventions using a novel measure which assesses bone architecture termed trabecular bone score (TBS). We hypothesized that due to estrogen depletion by prophylactic salpingo-oophorectomy and exemestane, a greater loss in TBS would be observed. One year following prophylactic salpingo-oophorectomy and two years on exemestane did not cause significant loss in TBS. Based on our findings, the clinical use of TBS for detecting small changes in bone is not warranted.
Impact of PSD95 Inhibition on Rate of Stroke Recovery in a Rat Model
Keywords: Nerinetide
PSD95 Inhibition
Stroke Recovery

Stroke is one of the leading causes of death and the leading cause of neurological disability worldwide. Nerinetide, a neuroprotective PSD95 inhibitor, blocks neurotoxic signaling pathways during an acute ischemic injury, but it may affect neuroplasticity. Therefore we tested the effect of nerinetide on stroke recovery. Specifically, whether initiating treatment with nerinetide after the stroke was complete could improve the rate of functional recovery in rats. We evaluated the neurological function of rats treated with nerinetide or vehicle 4 days after middle cerebral artery occlusion, over 35 days. Nerinetide treatment restored neurological function faster than placebo, as demonstrated in the cylinder and grid-walking behavior tasks (p
Economics of Vulnerability: Infrastructures of Climate Change Adaptation in the Rupununi, Guyana
Keywords: Climate change adaptation
Guyana
Indigenous
Infrastructure
Land Use
Political Ecology

This thesis examines the recent emergence of “vulnerability to climate change” as a framework for development in rural Guyana. More specifically, I study experts’ use of the term “vulnerability” throughout the implementation of four recent water infrastructure projects on Indigenous lands in the Rupununi savannah bordering Brazil. The research draws on scholarly analyses of Guyanese postcolonial governance in conjunction with maps, semi-structured interviews, and secondary economic and climatological data. With this evidence, I demonstrate that each project approaches “vulnerability” as a justification for imposing technocratic governance through infrastructure. Examining the planning process more closely, I further find that Guyana’s push for climate change adaptation is marketized, granting decision-making power to funders and contractors over “beneficiaries”. Thus, the new infrastructures in the Rupununi reproduce many of the historical patterns of power originally responsible for the region’s present vulnerabilities. The thesis concludes by discussing alternate approaches to addressing climate change in Guyana.
Modelling and Control of a Pico-scale Hydro Turbine for Pressure Regulation
Keywords: Control
Gaussian Process Regression
Hydro turbine
Modelling
Optimal Tracking
Process Identification

Hydraulic pumping systems account for 8.6\% to 9.2\% of total global energy usage. Significant research has gone into improving pumping system efficiency. Pressure control devices, such as throttling valves, are a large source of inefficiency to any large hydraulic system. To offer an alternative to throttling valves, an inline pico-scale (
The Impact of Dance on Physical Literacy in Children: An Evaluation of the Sharing Dance Program
Keywords: Children
Dance
Physical Activity
Physical Literacy

Regular participation in physical activity (PA) provides numerous health benefits for children, yet the recommended PA guidelines are not being met. Experts have argued this may be due to the lack of physical literacy (PL) among children. The objective of this pilot study was to explore the impact of the Sharing Dance program offered by the National Ballet School of Canada (NBS) on total PL and its main components, and the effect of gender, in children (N = 70, ages 8-12). A paired samples t- test was conducted to analyze the changes in PL and its main components, and residualized regression was conducted to examine the effect of gender. Results showed a significant increase in movement competence scores from pre- to post intervention (p
Restoration of Hepatitis C Virus-specific Immune Responses following Direct Acting Antivirals Administered During Acute Hepatitis C Virus Infection
Keywords: Direct Acting Antivirals
Hepatitis C Virus
Immune Exhaustion
Immune Restoration
Protective Immunity
Reinfection

Worldwide, 71 million people are chronically infected with Hepatitis C Virus (HCV). Chronic HCV infection leads to potentially fatal outcomes including liver cirrhosis and hepatocellular carcinoma. HCV-specific immune responses play a major role in viral control and may explain why approximately 20% of infections are spontaneously cleared before chronicity is established. New well-tolerated direct-acting antivirals (DAAs) lead to a sustained virologic response in greater than 95% of patients. Generally, treatment-induced viral clearance does not protect against reinfection as prolonged antigen exposure leads to exhaustion of HCV-specific T cells. Previous studies investigated whether treatment with interferon-based therapies during acute and chronic infection or DAAs administered during chronic infection prevent or reverse this exhaustion phenotype. The objective of the present study is to investigate if treatment of acute HCV infection with DAAs further improves immune restoration, leading to responses similar to those seen in spontaneous resolvers, which may increase protection against reinfection.
Integrating Genome-scale and Pharmacokinetic Models towards Precision Medicine and the Prediction of Tetrahydrocannabinol and Ethanol Metabolism
Keywords: Ethanol
Genome Scale Model
Metabolism
Physiologically Based Pharmacokinetic Model
Precision Medicine
Tetrahydrocannabinol

Cannabis and Ethanol are two of the most frequently used recreational substances in the world and many health policies are devoted towards ensuring their safe consumption. In this thesis, the metabolism of tetrahydrocannabinol (THC) and ethanol are modelled to gain further understanding of how these compounds affect the body. First, a physiologically-based pharmacokinetic (PBPK) model was developed to characterize how individuals with different genotypes eliminate THC as well as its effect (in conjunction with ethanol) on driving. Then, a previously developed PBPK model of ethanol metabolism was combined with a whole-body genome-scale model (GEM) to better predict how genetic variations and diseases could affect ethanol metabolism and exposure to the carcinogenic metabolite, acetaldehyde. By gap-filling enzyme-specific PBPK models with general metabolic fluxes from GEMs, we can predict the impact of inter-individual variations on drug metabolism and steer the modelling field towards precision medicine and the development of a “virtual twin”.
Long-acting Opioids for Pain in Ontario: Exploring Use Patterns in an Era of Chronic Pain and Opioid Crises
Keywords: chronic pain
long-acting
medication safety
opioid
opioid misuse
pharmacokinetics

A need for rational opioid prescribing for chronic pain has emerged from the chronic pain and opioid crises in Canada. Three studies aimed to improve understanding of long-acting opioid use, particularly at shortened dosing intervals. The first was a retrospective chart review in people with chronic pain and opioid-related risk. A high proportion of those using long-acting opioids used them at shortened dosing intervals, associated with a higher dose compared with use at standard intervals. The second study evaluated the feasibility of an n-of-1 approach to examine the relationship amongst subjective opioid effects and the pharmacokinetics of long-acting opioids administered at shortened dosing intervals. It was not feasible at that time. A third, population-based cohort study, explored dispensing trends of long-acting opioids in Ontario (2013-2018). Overall, dispensing rates declined; geographic variability in rates persisted. This research has improved understanding related to use of long-acting opioids in people with chronic pain.
Characterization of Autism Spectrum Disorder-associated Protein, PTCHD1
Keywords: Autism
PTCHD1

Autism spectrum disorder(ASD) is a behaviourally-defined neurodevelopmental disorder. ASD-linked genes have not been causally associated while downstream effects are understood only in a small fraction of cases. This highlights the need for molecular characterization to establish a mechanism-based understanding of ASD. PTCHD1 has emerged as an ASD-linked gene. Despite structural similarities to transmembrane proteins mediating cholesterol fluxes, PTCHD1 remains uncharacterized. In this study, we described PTCHD1 protein interactions and evaluated consequences of ASD-related missense mutations. Using the lumenal domains, we performed unbiased screens and identified potential interacting partners, SNAPIN and SAP102, further confirmed with the full-length protein, and replicated reports of PSD95 co-localization. Additionally, consequences of PTCHD1 mutations were detailed. P32R, G303R and F549C caused aberrations in N-linked glycosylation and protein stability. They also showed an overall reduction in protein expression in stable models. These observations begin to define PTCHD1 activities and how certain mutations contribute to protein activity deficits.
Mapping Livable Geographies: Black Radical Praxis within and beyond Toronto
Keywords: activism
Black geography
Black radical traditions
creative practice
Toronto

The mid-to-late-2010s involved radical responses to gentrification, surveillance and police violence toward Black diasporic communities in Toronto. My thesis research examines these realities and conditions of Black life in the city, engaging with the following areas of inquiry: The geographies in which Black community organizing and Black art practice take place in Toronto; How Black community organizers, artists and cultural workers relate to and support one another’s work, and how their work responds to historically and contemporarily absented issues concerning Black people in Toronto. Contextualized through theoretic engagement with Black geographies, Black Canadian studies and Black radical thought, this project offers critical insight through a focus group of local Black artists, organizers and community members in Toronto who refuse notions of belonging within a state founded on Black enslavement and Indigenous dispossession. Instead, they theorize tensions and possibilities for Black radical creative practice to generate livable geographies rooted in care.
Development of a Novel Feedback System to Guide Skill Acquisition for Brain-Computer Interface Control
Keywords: Brain-Computer Interface
EEG
Instructional Feedback
Learning
Motor Imagery
Riemannian Geometry

A brain-computer interface (BCI) enables control of external devices via modulation of neural activity. Currently, BCI use is limited as many users struggle to produce neural modulations that are machine-discernible. Recent evidence suggests ineffective user-training may be partially responsible. Here, we present and evaluate a feedback interface to improve BCI user-training. The system provides feedback derived from recently proposed Riemannian geometry metrics. First, we explore the validity of these metrics for user evaluation by assessing their relation to classifier performance. Regression models showed the metrics were able to account for 45% - 59% of inter-subject variation in classification accuracy for different classifiers. Second, we evaluate whether users improve performance in feedback interpretation tasks using the proposed system over classifier feedback. Using signal detection theory, we find the proposed system significantly outperforms the classifier system in all interpretation tasks. The results suggest the system should be explored further in real BCI-training scenarios.
Investigating the Roles of UVRAG and EGFR in Skeletal Muscle Homeostasis
Keywords: aging
EGFR
mitochondrial homeostasis
sarcopenia
skeletal muscle
UVRAG

Skeletal muscle autophagy is implicated in the maintenance of skeletal muscle mass and function that is critical to sustain mobility and regulate metabolism, particularly with aging. Mice with skeletal muscle-specific deletion of ultraviolet radiation resistance-associated gene (UVRAG) displayed accelerated sarcopenia, impaired skeletal muscle function, and accumulation of epidermal growth factor receptor (EGFR) by six months of age. Constitutively active EGFR expression (EGFRL858R) in UVRAG deficient skeletal muscle led to further detrimental defects in function. Relative gene expression of markers involved in skeletal muscle and mitochondrial function that were abnormal in UVRAG deficient skeletal muscle were unchanged by concomitant EGFRL858R mutation. Rather, enhanced EGFR signaling with EGFRL858R mutation led to defects in skeletal muscle fiber type determination that further deteriorated muscle function in UVRAG-deficient mice. Overall, UVRAG and EGFR signaling together are critical in the maintenance of skeletal muscle mass and function with aging, with distinct roles in skeletal muscle homeostasis.
Role of Salinity, Genotypic Variation, Microbial Communities, and Algae on the Elimination of Benzotriazole by Duckweed Lemna minor
Keywords: algae
benzotriazole
constructed wetlands
duckweed
phytotransformation

Benzotriazole is an emerging contaminant incompletely removed by wastewater treatment plants. This work investigated several environmental factors that may influence the transformation of benzotriazole by wetland model plant duckweed Lemna minor, including salinity, variation among duckweed genotypes, microbial communities, and algae Chlorella vulgaris. Results show that high salinity (10 g/L) reduced the phytotransformation (transformation by plant) of benzotriazole. Intermediate salinity (0.8 g/L) modulated the formation of phototransformation (transformation driven by light) products aniline and 3-aminophenol. Microbial inoculation promoted the formation of a phytotransformation product, benzotriazole acetyl-alanine. Variation among duckweed genotypes in transforming benzotriazole suggests that constructed wetlands could be designed to increase benzotriazole depletion and reduce effluent toxicity by selecting appropriate duckweed genotypes. Algae also depleted benzotriazole, but it did not influence the depletion kinetics by duckweed in a symbiotic manner. Other plants and algae could potentially phytotransform benzotriazole as the proposed pathways are shared among plants and algae.
Exact and Heuristic Approaches to Batching-and-scheduling for the Composites Manufacturing Problem
Keywords: Batching
Composites Manufacturing
Constraint Programming
Heuristics
Optimization
Scheduling

The process of manufacturing composite materials is a complex problem that lacks robust and scalable solutions. This thesis aims to characterize that process and offer solutions by defining and solving a novel optimization problem, the Composites Manufacturing Problem (CMP), and its abstraction, the Two-Stage Bin Packing and Hybrid Flowshop Scheduling Problem (2BPHFSP). The CMP involves batching and scheduling jobs in a four-stage flowshop with time-varying resource requirements. The 2BPHFSP offers a simplified version of the CMP which allows us to focus on the key complexities of the CMP and deepens our understanding of the problem. By extending state-of-the-art techniques from a wide literature body, we construct solution approaches using techniques from Mixed Integer Programming, Constraint Programming, Logic-Based Benders Decomposition, heuristic algorithms, genetic algorithms, and constrained-clustering algorithms. Empirical analyses were performed for both problems on randomly generated instances based on real data from our industrial collaborator.
Investigating the Gut Microbiome, Metabolomic Signatures, and Metabolic Dysfunction in Antipsychotic Naïve Patients
Keywords: Antipsychotics
Gut Microbiome
Metabolic Dysfunction
Metabolomics
Psychotic Spectrum Disorders

Antipsychotics (APs) are the treatment cornerstone for psychotic spectrum disorders (PSDs) but have severe metabolic side-effects. Gut microbiome (GMB) and metabolomic profiling may explain these. This thesis comprises two 12-week studies. In study one, 6 AP-naïve (cases) and 6 healthy participants (HCs) completed baseline GMB and metabolic assessments, repeated at 6 and 12 weeks for cases. At baseline, alpha diversity and genera level differences were found between groups. Over the three months of AP treatment, genera changes were observed and a positive correlation between triglycerides and Actinobacteria change was noted. In study two, 24 cases and 5 HCs completed metabolomic and metabolic assessments. Cases had lower acylcarnitine levels and differences in fatty acids compared to HCs. Baseline aspartic acid was higher for cases who gained weight. The GMB and metabolome may provide biomarkers for PSDs, intrinsic metabolic abnormalities, and help predict/monitor AP induced metabolic side-effects.
Evaluation of Muscle Texture and Motor Unit Abnormalities after Experimentally Induced Sensitization using Capsaicin
Keywords: Central Sensitization
Intramuscular Electromyography
Motor Unit
Recruitment
Surface Electromyography

Central sensitization describes a state of central nervous system hyperexcitability causing pain hypersensitivity. The impact of central sensitization on muscle structure and neurophysiology is unclear. This work aimed to determine the effect of experimentally induced central sensitization on muscle structure, motor recruitment, motor unit action potential characteristics and upper limb movement. Twenty healthy participants were randomized to receive topical capsaicin – to induce central sensitization acutely – or placebo. Ultrasound images, surface electromyography(sEMG), intramuscular electromyography (iEMG), and movement data were acquired before and after treatment. Capsaicin-induced sensitization resulted in significant changes in ultrasound image texture features, motor unit recruitment pattern (sEMG) and motor unit variability (iEMG). Movement analysis revealed capsaicin-induced changes in acceleration variability, suggesting changes in anterior horn cell excitability affecting efferent output. Overall, this thesis advances understanding of central sensitization manifestation, a requisite for developing quantitative criteria to diagnose central sensitization and chronic widespread pain.
Olfactory Discrimination in Caenorhabditis elegans
Keywords: arrestin
Caenorhabditis elegans
olfaction
olfactory adaptation
olfactory discrimination

Caenorhabditis elegans (C. elegans) is an organism with only 302 neurons (in the adult hermaphrodite) and only two pairs of (bilaterally symmetrical) neurons detect attractive volatile odourants. Despite its simple neuroanatomy, C. elegans can perform olfactory discrimination between two odourants when both are detected almost exclusively by a single pair of neurons. ARR-1 (Beta-Arrestin) desensitizes the receptors detecting the two odourants in an activity-dependent manner; this allows for odourant-specific adaptation and olfactory discrimination. An arr-1 null strain of C. elegans is unable to discriminate intra-neuronally (when both odours are detected by the same pair of neurons), but is able to discriminate inter-neuronally (when odours are detected by separate pairs of neurons). This work characterizes the mechanism of intra-neuronal olfactory discrimination in C. elegans, which has been mysterious since it was first decribed by Bargmann et al in 1993.
Endocannabinoid Metabolism in Posttraumatic Stress Disorder: Preliminary Results from a Neuroimaging Study with the Novel Fatty Acid Amide Hydrolase Probe [C-11] CURB
Keywords: Endocannabinoid System
Fatty Acid Amide Hydrolase
Neuroimaging
PET imaging
Posttraumatic Stress Disorder

Background: Preclinical studies suggest that levels of Fatty Acid Amide Hydrolase (FAAH)—the catabolic enzyme for the endocannabinoid anandamide—may be elevated in the amygdala in posttraumatic stress disorder (PTSD). However, the status of FAAH in vivo in posttraumatic stress disorder remains unknown. Methods: Healthy subjects (n=29) and individuals with PTSD (n=16) completed a positron emission tomography scan following injection of the FAAH probe [C-11]CURB. Results: We find no evidence for elevated [C-11]CURB binding in PTSD. Instead, we find marginally lower [C-11]CURB binding in whole brain (-9.38%, p=0.079) and significantly lower [C-11]CURB binding in the amygdala (-14.50%, p=0.020) in PTSD subjects. [C-11]CURB binding did not correlate with PTSD symptomatology. Conclusion: Our data provide preliminary evidence contrary to preclinical literature, suggesting that FAAH may be lower in people with PTSD. These findings have implications for treatment strategies targeting this enzyme (i.e. FAAH inhibitors) in PTSD.
Development and Validation of an Automated Video-Based Analysis Tool to Identify Motor Impairment in Preterm Infants
Keywords: cerebral palsy
computer vision
general movement assessment
motor impairment
movement recognition
preterm infant

Introduction: The objective of this project was to explore automated technology as an alternative to clinical General Movements Assessment (GMA) for early identification of motor impairment (MI), including cerebral palsy (CP), in preterm infants. Methods: A systematic review evaluated gaps in current automated technologies. A 2D video-based automated tool was developed for infants
Computational Fluid Dynamics Simulation of Tubular Scaffold Re-cellularization inside Perfusion Bioreactors
Keywords: CFD
DPM
Recellularization

Humans suffer from tracheal pathologies such as malignancy, traumatic injury, and stenosis. Tissue engineering provides a viable treatment method by substituting a damaged trachea with an engineered graft that uses the recipient’s own cells to reduce the rate of transplant rejection by the recipient’s immune system. This requires a re-cellularization with cells harvested from the recipient. Bioreactors are designed to assist us in re-cellularization to distribute cells uniformly on the lumen tracheal. Currently, a lack of understanding of the bioreactor hydrodynamic and cell-seeding environment is a major obstacle for obtaining viable tracheal grafts. The complexity of cell behavior and modelling assumptions have led to significant differences between experimentally observed and computationally predicted results. In this study, we implement and compare a series of computational models of increasing complexity, incorporating previously neglected physical mechanisms, to improve the predictive ability of the models.