VictorJuiz/thesis huggingface dataset:
Role of Neutrophil Extracellular Traps in the Pathogenesis of C3 Glomerulopathy

The complement system is a component of the innate immune system and its lack in regulation leads to the development of complement-mediated diseases. Complement 3 glomerulopathy (C3G) is a spectrum of kidney diseases in which the hallmark is positive staining for C3 on the glomerular walls. There is currently no approved treatment for C3G, subsequently leading to poor prognosis for these patients. Therefore, there is a strong incentive for bridging current knowledge gaps. Neutrophils have been discovered to undergo a unique cell death, termed NETosis which has been implicated in exacerbating several diseases by disrupting physiological inflammation and coagulation. We have shown healthy neutrophils can be stimulated by complement activation to undergo NETosis in a stepwise fashion. We have demonstrated that neutrophils from C3G patients also undergo similar changes as this, suggesting that the complement activation they face in situ may play a role in the patients’ disease state.

Keywords: Cell Biology
Complement
Complement 3 Glomerulopathy
Neutrophil Extracellular Traps
Neutrophils
Renal Pathology
Advisor: Licht, Christoph
Nades, Palaniyar
Intersectoral Youth Policies and Adolescent Health System Transformation: A Multiple Case Study

Health systems are increasingly being recognized as complex adaptive systems, requiring a holistic and comprehensive, rather than reductionist, approach to change initiatives. There is compelling evidence that the health of adolescents is influenced not simply by factors that fall within the bounds of the traditional healthcare system but also by broader structural determinants of health. Intersectoral Youth Policies are initiatives that envision a coordinated, participatory, comprehensive, integrated and cross-sector approach to promoting healthy adolescent development. This study employs case studies from India, Malawi, and Ontario to examine whether Intersectoral Youth Policies can serve as mechanisms catalyzing the emergence of adolescent-responsive health systems and considers contextual factors that may contribute to this function. Findings suggest that Intersectoral Youth Policies engage key system dynamics in a manner that facilitates system change, however the pervasiveness of their impact is influenced by the approach to system tensions and by how systems are bounded.

Keywords: Adolescent
Complex Adaptive Systems
Complexity Science
Health Systems
Intersectoral
Youth
Advisor: Berta, Whitney
Experiences and Perceptions of Rural Students in an Urban Situated Regional Faith Based School

Research considering urban and rural student participation, achievement, and experiences in schools notes differences based on geography and cultural milieus. Regional faith-based schools are often populated by students from both rural and urban areas leading to convergence of cultural contexts. Regional schools located near urban centers are typically administered by urban located teachers and other staff, teaching a curriculum that is urban oriented, which has the potential to disadvantage rural students in a variety of ways. A faith-based regional school is meant to alleviate some rural/urban cultural differences by uniting all students and teachers through shared faith and doctrine. This study explores how an urban located regional faith-based school in Southern Ontario services rural students and gives these students voice to share how the school fosters either a more unified faith community through cultural exchange or entrenches a more fragmented collection of cultural communities by reinforcing rural/urban prejudices.

Keywords: cultural milieu
education
faith based
habitus
regional
rural
Advisor: Sandwell, Ruth
Design of a System with a 3D Biomimetic Stretchable Substrate for Maintenance and Study of Alveolar Epithelial Cells

Traditional in vitro alveolar epithelial cell (AEC) models lack physiological architectural cues required for regulating cell functionality. While 3D AEC organoids incorporate some characteristics of alveolar microarchitecture, they are challenging to analyze, not easily scalable, and their architecture cannot be easily controlled. Lung-on-Chips have successfully reproduced some key features of lung tissue through customized microenvironments with precise mechanical, fluidic, and structural control. However, these models lack the geometry of alveolar lumen. Thus, we developed an Alveoli-on-a-Chip that mimicked alveolar curvature and distension during respiration. We demonstrated that cells were viable and responsive to patterns of tensional forces in our chip. Additionally, through characterization of YAP localization and actin remodeling, we showed that our chip is able to recapitulate mechanosensitive response of AECs to architectural cues. We envision this technology will provide a platform to maintain iPSC derived distal epithelial cells that will be valuable for disease modeling and drug testing.

Keywords: alveoli
alveoli-on-a-chip
Lung-on-chip
microfluidic
organ-on-chip
Advisor: Waddell, Thomas K
Karoubi, Golnaz
Making Sense of the Nonsense: A Narrative Inquiry into the Experiences of Meaning-related Processes of Resiliency in Caregivers of Children with TBI

While post-injury difficulties resulting from traumatic brain injury (TBI) extend beyond the injured child, increasing attention is being paid to the ways by which individuals can promote positive adjustment following adverse life circumstances (i.e. resiliency). A principal aspect in resiliency is constructing a sense of meaning, yet little is known about how caregivers construct meaning. This study explored how six caregivers of children with a TBI experience meaning-related processes of resiliency. Using semi-structured interviews, caregivers told their stories of what it means to care for someone following a mild-severe TBI. Narratives were analyzed to reveal that caregivers construct meaning out of a desire to negotiate TBI-related adversity, specifically the uncertainty that accompanies TBI. By understanding how caregivers adjust to TBI through meaning-related processes of resiliency, caregivers can weave meaning into their lives to create a narrative about the traumatic event that goes beyond loss and hopelessness, inviting possibilities for growth.

Keywords: Adaptation
Caregivers
Resilience
Traumatic Brain Injury
Advisor: King, Gillian A
Nalder, Emily J
PGAS Communication for Heterogeneous Clusters with FPGAs

This work presents a heterogeneous communication library for generic clusters of processors and FPGAs. This library, Shoal, supports the partitioned global address space (PGAS) memory model for applications. PGAS is a shared memory model for clusters that creates a distinction between local and remote memory accesses. Through Shoal and its common application programming interface for hardware and software, applications can be more freely migrated to the optimal platform and deployed onto dynamic cluster topologies. The library is tested using a thorough suite of microbenchmarks to establish latency and throughput performance. We also show an implementation of the Jacobi method that demonstrates the ease with which applications can be moved between platforms to yield faster run times.

Keywords: API
Applied sciences
Communication
FPGAs
Heterogeneous
PGAS
Advisor: Chow, Paul
Labour and Delivery Outcomes in Pregnant Women with Cardiac Disease

Objective: This study compared and identified predictors for labour and delivery (L) outcomes in women with and without cardiac disease. Methods: A cohort study compared L outcomes (obstetric, cardiac, and perinatal complications) using adjusted odds ratios (aOR) and 95% confidence intervals (CI) and multivariable regression to identify predictors. Results: 1,189 pregnancies in women with cardiac disease were compared to 1,161 low-risk pregnancies. Outcomes were similar between groups except for higher maternal [aOR 7.19 (95%CI 1.27-134.91)] and neonatal intensive care unit admissions [1.77 (1.24-2.54)] in those with cardiac disease. Obstetric, cardiac and perinatal complications occurred in 91 (8.0%), 39 (3.3%) and 150 (14.2%) pregnancies with cardiac disease respectively. The strongest predictors were preterm birth [OR 9.80 (6.11-15.82) and operative vaginal delivery [3.75 (2.10-6.81)]. Conclusions: With multidisciplinary management, adverse L outcomes in women with cardiac disease are low. Avoiding iatrogenic prematurity and reducing instrumental delivery could further improve outcomes.

Keywords: Cardiac Disease
Delivery
Heart Disease
Labour
Outcomes
Pregnancy
Advisor: D'Souza, Rohan
Leveraging Twitter Data to Support Transit Planning and Operations

Twitter provides an unfiltered and timestamped feed of information that can be aggregated to generate valuable insights. This research creates a framework for processing a public Twitter feed to generate insights on rider satisfaction and to identify passenger–related transit incidents. Detecting these incidents in real time enables transit agencies to immediately respond to them by dispatching security, safety, or maintenance crews, and in the context of the current COVID–19 pandemic, to provide targeted cleaning measures to combat the spread of the virus. Using natural language processing, we identify eyewitness tweets about transit and then extract latent information from the tweets such as location details, sentiments, and topics. This enables agencies to respond to an incident faster and to identify spatial and temporal patterns for incidents and interests throughout the network.

Keywords: Eyewitness tweets
Incident detection
Public transit
Social media analytics
Spatial analysis
Twitter data
Advisor: Shalaby, Amer
El-Diraby, Tamer
The Effect of Loss of Estrogen on Trabecular Bone Score in Women at Increased Risk of Breast Cancer

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.

Keywords: Bone mineral density
Breast cancer
DXA scan
Estrogen deficiency
Trabecular bone score
Advisor: Cheung, Angela M
Impact of PSD95 Inhibition on Rate of Stroke Recovery in a Rat Model

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

Keywords: Nerinetide
PSD95 Inhibition
Stroke Recovery
Advisor: Tymianski, Michael
Economics of Vulnerability: Infrastructures of Climate Change Adaptation in the Rupununi, Guyana

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.

Keywords: Climate change adaptation
Guyana
Indigenous
Infrastructure
Land Use
Political Ecology
Advisor: Ekers, Michael
Modelling and Control of a Pico-scale Hydro Turbine for Pressure Regulation

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 (

Keywords: Control
Gaussian Process Regression
Hydro turbine
Modelling
Optimal Tracking
Process Identification
Advisor: Bilton, Amy
The Impact of Dance on Physical Literacy in Children: An Evaluation of the Sharing Dance Program

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

Keywords: Children
Dance
Physical Activity
Physical Literacy
Advisor: Cairney, John
Restoration of Hepatitis C Virus-specific Immune Responses following Direct Acting Antivirals Administered During Acute Hepatitis C Virus Infection

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.

Keywords: Direct Acting Antivirals
Hepatitis C Virus
Immune Exhaustion
Immune Restoration
Protective Immunity
Reinfection
Advisor: Feld, Jordan J
Integrating Genome-scale and Pharmacokinetic Models towards Precision Medicine and the Prediction of Tetrahydrocannabinol and Ethanol Metabolism

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”.

Keywords: Ethanol
Genome Scale Model
Metabolism
Physiologically Based Pharmacokinetic Model
Precision Medicine
Tetrahydrocannabinol
Advisor: Mahadevan, Radhakrishnan
Comparative Efficacy of Electronic Cigarettes versus Nicotine Patches as a Short-term Replacement for Tobacco Cigarette Smoking: A Cross-over Trial

Electronic cigarettes (e-cigarettes) have been reported to decrease craving, withdrawal, and cigarette consumption. Moreover, some research suggests smokers using an e-cigarette are as or more likely to achieve abstinence than smokers using nicotine replacement therapy. Using a novel, within-subjects, partial Latin square design, we investigated the efficacy of a second-generation nicotine e-cigarette and placebo e-cigarette against the nicotine patch in the short-term replacement of tobacco cigarette smoking. 25 participants have completed the study. Mean days of complete smoking replacement and percent cigarettes replaced was similar between the nicotine e-cigarette (1.84, 72.2%), placebo e-cigarette (1.48, 67.9%), and nicotine patch (1.52, 73.1%). Craving score was similar among products whereas withdrawal score was significantly lower with placebo e-cigarette use over nicotine e-cigarette and nicotine patch use. These findings demonstrate the efficacy of a second-generation e-cigarette, with and without nicotine, in short-term smoking replacement and presents evidence supporting its use over the nicotine patch.

Advisor: Zawertailo, Laurie
Long-acting Opioids for Pain in Ontario: Exploring Use Patterns in an Era of Chronic Pain and Opioid Crises

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.

Keywords: chronic pain
long-acting
medication safety
opioid
opioid misuse
pharmacokinetics
Advisor: Sproule, Beth A
Characterization of Autism Spectrum Disorder-associated Protein, 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.

Keywords: Autism
PTCHD1
Advisor: Hamel, Paul
Mapping Livable Geographies: Black Radical Praxis within and beyond 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.

Keywords: activism
Black geography
Black radical traditions
creative practice
Toronto
Advisor: hampton, rosalind
Predicting Fine-grained Cloud Resource Usage with Online and Offline Learning

Modern data centers have inefficiencies, leading to wasted power consumption costs. Traditional resource allocation techniques are threshold-based, which performs poorly for workloads that frequently change due to reaction time delays. This thesis attempts to address this by investigating a solution that predicts future resource usage based on previously observed usages using multiple neural network models trained on various VM datasets and explores network resource control mechanisms. Results indicate that neural networks are a strong candidate for predicting cloud workloads. Findings also showed that having more resource metrics improved prediction accuracy. This paper also showcases OnlinePred a custom online learning technique that further mitigates prediction errors, improving upon baseline prediction accuracy by up to 43.21%. OnlinePred also prevents overfitting by employing an experience buffer of both old and new data to adjust the model in real-time, improving prediction accuracy in poorly fitted models by up to 67.90%.

Advisor: Jacobsen, Hans-Arno