VictorJuiz/thesis huggingface dataset:
Building a Sparse Convolutional Neural Network Inference Accelerator on Field-programmable Gate Arrays
Keywords: Convolutional neural network
Field-programmable gate array
hardware acceleration
sparsity

High computational complexity and large memory footprint hinder the adoption of convolution neural networks (CNNs) in latency sensitive applications, such as self-driving. The presence of many zeros in CNN parameters and intermediate results -- a phenomenon known as sparsity -- presents opportunities for hardware accelerators to circumvent these problems, leading to speed-up. Prior work on accelerating CNNs using field-programmable gate arrays (FPGAs) has mostly omitted the benefits from sparsity. The few exceptions either leverage sparsity only on fully-connected layers in CNNs, or scale poorly due to complicated datapath and control logic. In this thesis, we propose a fine-grained structured weight sparsity for accelerating CNNs on FPGAs with relative ease. To leverage this sparsity for CNN acceleration on FPGAs, we design a novel processing element (PE) and an end-to-end sparse CNN inference accelerator that arranges the PEs in a systolic-array. Our results show that pruning according to the proposed structured weight sparsity pattern can reduce the amount of multiply-accumulate (MAC) operations in VGG-16 and ResNet-50 v.1.5 by 3.34 fold and 2.69 fold, respectively, while keeping the top-1 validation accuracy on ImageNet within 5\%. When implemented on an Intel Arria 10 GX1150 FPGA, our sparse CNN inference accelerator can achieve 2.26 TOP/s and 1.17 TOP/s on the MAC operations in the pruned VGG-16 and ResNet-50 v1.5, respectively. These figures translate to 2.86 fold and 1.69 fold speed-up over a baseline accelerator that is agnostic to sparsity.
Investigating the Determinants of Social Communication Differences in Neurodevelopmental Disorders
Keywords: autism spectrum disorder
neurodevelopmental disorders
social communication
structural equation modelling

Social communication differences can negatively impact long-term outcomes for children and youth with autism spectrum disorder (ASD). There is evidence to suggest that demographic factors, IQ, sensory processing, attention, language, and repetitive, restrictive behaviours contribute to social communication. However, the determinants of social communication are studied independently of each other, and there is little consideration for the interplay between them. To address this literature gap, we used structural equation modelling techniques to understand the differential contribution of these factors to social communication in a combined sample of individuals with ASD, attention deficit hyperactivity disorder, as well as typically developing individuals. We found that a combination of factors, rather than one singular factor, contributed to social communication differences. Ultimately, by understanding the factors that contribute to social communication, we hope to be able to target specific skills or behaviours and to create personalized supports for individuals with ASD.
The Experience and Perceptions of Dental Students in Treating Adults with Developmental Disabilities
Keywords: Dentistry
disability
education
oral health
qualitative
special needs

This study investigated the experience and perception of dental students with regards to treating Adults with Developmental Disabilities (AWDDs). Three groups were interviewed: experts, students who had no clinical training to treat AWDDs, and students who had completed their clinical training to treat AWDDs through a rotation at Mount Sinai Hospital (MSH) dental clinic. Motivations for working with AWDDs were described including health advocacy and social responsibility. The informal curriculum impacted the formation of student expectations. The rotation was described as a transformative learning experience. Alignment between students and experts suggested that the clinical training is adequate. The misalignment provided insight into areas for improvement. Additionally, a survey was sent out to the ten dental schools in Canada to quantify the number of clinical and didactic hours students receive in this subject matter. The survey showed a wide range of time dedicated to this subject matter across Canadian dental schools.
Uncovering a Novel Role for BIRC6 in a Dwarf Mutant Mouse
Keywords: BIRC6
Dwarfism
Inhibitor of apoptosis
Mouse model

Baculoviral inhibitor of apoptosis repeat-containing 6 (BIRC6) is a member of the inhibitor of apoptosis protein (IAP) family. The IAP family regulates apoptosis by binding caspase proteins, marking them for degradation and in turn, inhibiting apoptosis. BIRC6 is implicated in additional molecular pathways including autophagy, cell cycle regulation and DNA damage response. However, the role BIRC6 plays in normal development remains unclear. Our lab identified a mouse line with a dwarf-like phenotype in a dominant N-ethyl-N-nitrosourea (ENU) mutagenesis screen. Whole-exome sequencing (WES) identified a point mutation in Birc6 (c.9611G>A) that resulted in a p.R3204Q substitution. The association between Birc6 and dwarfism has not been previously reported; therefore, this work identifies a new model of proportional dwarfism and a novel function for BIRC6. Using CRISPR/Cas9, the Birc6R3204Q/+ dwarf phenotype was confirmed in a new mouse model and the phenotypic basis for short stature was determined to have an endocrine basis.
Investigation of Human Cerebral Organoids as an Enhanced Platform for Developmental Epilepsy Modelling
Keywords: cerebral organoids
electrophysiology
neonatal epilepsy
oxygen-glucose deprivation
power spectral density
WWOX-related epileptic encephalopathy

Approximately 1% of the world population suffers from epilepsy, a neurological disorder characterized by repeated seizures. In vitro models that capture the complexity of the human neuronal system in its early development do not exist. Cerebral organoids, derived from human iPSC lines and human embryonic stem cells, carry the potential to model developmental neurological disorders beyond the capacity of current in vitro models. To date, a detailed electrophysiological analysis of developmental epileptic phenotypes in cerebral organoids has not been performed. Here, cerebral organoids are employed to functionally characterize neonatal seizures in cerebral organoids using traditional electrophysiological methods and engineering analysis methods to reveal features of interest in an induced and genetic model of epilepsy – neonatal hypoxic-ischemic encephalopathy and WWOX-related epileptic encephalopathy, respectively. This work forms the basis of establishing benchmark features for the investigation of specific mechanisms and development of targeted therapies for developmental epileptic encephalopathies in cerebral organoids.
Perceptions of Professionalism in Dental Students
Keywords: Dental Students
Dentistry
Education
Social Pschology

This thesis explored Canadian dental students’ perceptions of professionalism and the factors associated with these perceptions. Information was collected from undergraduate dental students at the Faculty of Dentistry, University of Toronto (N = 430) using an online survey. Evaluation of professionalism was based on three outcomes: attitudes toward professionalism, moral inclusion and perceived professional roles, which were derived from the American Dental Education Association values of professionalism in dental education and existing measures in the literature. These outcomes were assessed using Likert and visual analog scale questions. Associations with environmental, institutional and student-related factors were investigated using non-parametric tests, chi-square tests and regression analysis. The survey yielded a response rate of 51.4% (n = 221). Results indicate that overall, this sample of dental students had positive perceptions of professionalism, which were negatively impacted when students viewed their future patients as consumers. These findings have implications for professionalism education in dentistry.
Relationships between Myeloperoxidase and the Cognitive and Neuroimaging Correlates of Mild Vascular Cognitive Impairment
Keywords: cardiovascular disorder
executive function
memory
mild vascular cognitive impairment
myeloperoxidase
white matter hyperintensity

Mild vascular cognitive impairment (mVCI), the most prevalent form of vascular cognitive impairment, presents with both cognitive impairment and vascular dysfunction, but the underlying disease pathophysiology is not well understood. Building upon the role of the innate immune system in cognitive and vascular disorders, this thesis explores the associations of myeloperoxidase (MPO), a neutrophil specific inflammatory protein marker, with disease markers of mVCI, specifically cognition and neural white matter damage. In n= 27 patients, elevated plasma MPO was related to decreased verbal memory (β= -2.284, p=0.035), after controlling for education and body mass index. Contrarily, elevated MPO was associated with higher periventricular white matter hyperintensity volumes (β= 0.744, p=0.028), before controlling for age and resting systolic blood pressure. The results of this study suggest that MPO may be involved in the pathophysiology of mVCI and may be facilitating its effects on cognition via affecting the neuroimaging correlates of the disease.
Development and Pharmacokinetic Evaluation of a Self-nanoemulsifying Drug Delivery System for the Oral Delivery of Cannabidiol
Keywords: bioavailability
cannabidiol
lipophilic drug
oral drug delivery
self-nanoemulsifying drug delivery systems

Cannabidiol (CBD) is a non-psychoactive cannabinoid with a notable safety profile. An oral formulation of CBD (Epidiolex®) has been approved by the FDA, and there is some evidence to suggest that CBD may alleviate symptoms of certain chronic diseases. CBD is a lipophilic compound with low oral bioavailability that undergoes significant first-pass metabolism. These characteristics limit the clinical potential of oral CBD therapies. One strategy to overcome these challenges is to develop self-nanoemulsifying drug delivery systems (SNEDDS). Here, CBD-SNEDDS were developed and optimized through in vitro assays. Two lead formulations were administered in healthy Sprague-Dawley rats via oral gavage (20 mg/kg CBD), and pharmacokinetic parameters of CBD were compared against a medium chain triglyceride oil formulation of CBD (MCT-CBD), as well as a sesame oil-based formulation similar in composition to Epidiolex (SO-CBD). The CBD-SNEDDS improved the systemic exposure to CBD compared to MCT-CBD; however, no improvement was found compared to SO-CBD.
ID1 Expression in Glioblastoma Cells Correlates with One-carbon Mediated Purine Synthesis
Keywords: Cancer Metabolism
Glioblastoma
ID1
One-Carbon metabolism
Purine synthesis

Glioblastoma is the most common primary brain tumour in adults. Inhibitor of DNA-binding-1 (ID1) is a transcriptional regulatory protein and a regulator of tumourigenesis in glioblastoma. While ID1 was shown to regulate metabolism in other cancer types, the role of ID1 in metabolic reprogramming of glioblastoma is not clear. In this thesis, we identify a correlation between ID1 expression and 1-C-mediated de novo purine synthesis in glioblastoma, and present data in support of a hypothesizes that this metabolic phenotype underlies proliferative capacity and TMZ-resistance of ID1-high glioblastoma cells. The expression of one-carbon (1-C) metabolism and purine synthesis enzymes are significantly reduced with ID1 knockout. Exogenous purine supplementation restores proliferation in ID1-deficient cells. Treatment of temozolomide-resistant glioblastoma cells (U251-TR) with AICAR sensitizes these cells to chemotherapy. Our data suggest that the metabolic phenotype observed in ID1-high treatment-resistant glioma cells is a potential therapeutic target for this cell population.
Identification of Novel Radiosensitizers in Small Cell Lung Cancer
Keywords: CRISPR screen
Epigenetics
HDAC3
Radiation
Radiosensitizers
small cell lung cancer

Small cell lung cancer (SCLC) is a lethal malignancy, marked by early metastasis into extensive-stage (ES)-SCLC. There is a critical need for improved treatments. After chemotherapy, consolidative thoracic radiotherapy improves patient survival; however, high tumor relapse in intra- and extrathoracic regions remains a challenge. One promising strategy to enhance local tumor control is the addition of radiosensitizers that also possess single agent efficacy to address extrathoracic disease. We performed a targeted CRISPR knockout screen with ionizing radiation (IR) and found several druggable, radiosensitizing candidates. HDAC3 was one top candidate identified, which we validated using genetic and pharmacological approaches. HDAC3 was found to be an essential cancer gene in which its functional loss reduced cell proliferation and, in combination with IR, effectively radiosensitizes SCLC. Our work identifies HDAC3 as a single and combination therapy target, and lays the ground for pursuing other radiosensitizing candidates with clinical translation potential for SCLC patients.
Approaches to Integrate Mental Health Services in Primary Care: A Scoping Review of System-level Barriers and Enablers to Implementation
Keywords: Collaborative Care
Health Policy
Implementation Science
Mental Health Services
Primary Care

Despite the growing prevalence of mental illness, the integration of mental health services in primary care has been a persistent challenge in Canada. Successful integration has the potential to reduce stigma, improve treatment of comorbidities, and enhance access to care. This scoping review investigated system-level barriers and enablers to implementing collaborative care models to integrate mental health services in primary care. MEDLINE, EMBASE, and PsycINFO were systematically searched in May 2020 resulting in the inclusion of 64 articles. The Consolidated Framework for Implementation Research was utilized to code and analyze implementation barriers and enablers. The main themes that emerged from the findings included: funding and reimbursement; health practitioner workforce and training; relationships with organizations and communities; and policy implementation. Results may inform the scaling up of existing promising local initiatives and pilot projects that integrate mental health services into primary care.
Impact of Anemia and SGLT-2 Inhibition on Renal Microvascular Oxygen Tension: Evidence for Renal Hypoxia Sensing
Keywords: diabetes
erythropoiesis
hemodilution
kidney
oxygen sensing
SGLT2 inhibition

Sodium glucose linked transporter 2 (SGLT2) inhibitors have been demonstrated to improve cardiovascular outcomes in patients with type 2 diabetes mellitus; by mechanisms unknown. Probability analyses have estimated that an increase in erythropoiesis may contribute to these positive outcomes. We have utilized translational animal models to investigate the impact of anemia, hyperoxia, and SGLT2 inhibitors in control and diabetic rats, to assess the impact of these treatments on renal microvascular PO2. We have demonstrated that anemia and hyperoxia alter the renal microvascular PO2 proportionally to arterial blood oxygen content. By contrast, rats with diabetes treated with the SGLT2 inhibitor dapagliflozin showed decreased renal microvascular PO2 in the renal outer medullary region, increased renal erythropoietin RNA levels, and possible evidence of enhanced erythropoiesis. This suggests that mild renal tissue hypoxia is responsible for increasing hematocrit with SGLT2 inhibition, providing insight into the potential mechanism by which SGLT2 inhibition improves cardiovascular outcomes.
Effect of Intravenous Alcohol on Resting Perfusion: Implications for the use of fMRI in the Study of the Acute Effects of Alcohol
Keywords: Alcohol
Arterial Spin Labeling
CBF
fMRI
vasodilation

Evidence suggests that alcohol’s vasodilatory properties increase resting cerebral blood perfusion, which has the potential to confound the interpretation of the BOLD signal which depends on cerebral blood flow (CBF) to index neural activity. The dynamics of alcohol’s effects on resting perfusion however are still not well understood. Participants (N=50) completed two sessions in which they received intravenous alcohol infusions calculated to achieve 80mg% BAC or saline in counterbalanced order. Arterial Spin Labeling (ASL) was used to quantify CBF at three time points (0, 40mg%, and 80mg% BAC) finding dose dependent increases in CBF related to alcohol. A subset of participants (N=29) underwent a fourth ASL scan with BAC clamped at 80mg% to investigate acute tolerance to increases in CBF, finding reductions in CBF over time during both saline and alcohol conditions despite constant BAC during the latter. Acute subjective effects were examined as moderators of CBF change, with no significant clusters emerging from these analyses.
Computational Fluid Dynamics Modeling of Cell Distributions Towards Targeted Re-endothelialization in the Lung
Keywords: cell seeding
computational fluid dynamics
lung regeneration
re-endothelialization
recellularization
tissue engineering

Complete re-endothelialization of acellular lung scaffolds remains a significant barrier for the clinical application of regenerated lungs. Current methods of delivering endothelial cells have led to insufficient coverage of the pulmonary vasculature. Understanding how reseeding parameters affect cell deposition is necessary to optimize lung re endothelialization. In this thesis, we created a computational fluid dynamics model featuring an inertial particle deposition function to quantify the deposition of cells in mouse lung vasculature for re-endothelialization. Our novel inertial algorithm demonstrated a significant reduction in cell seeding efficiency error compared to two established particle deposition algorithms when validated with experiments. With this newly presented model, cell seeding efficiency and uniformity increased with higher flow rates. Cell seeding efficiency was further improved by utilizing a surrounding parenchymal pressure. Modulating the parenchymal pressure also enabled the targeting of cell deposition locations. This work lays the foundation to computationally optimize lung regeneration towards clinical use.
Investigating the Response of Neural Precursor Cells to Chondroitin Sulfate Proteoglycan
Keywords: chondroitin sulfate proteoglycan
neural stem cells
spinal cord injury

Spinal cord injury (SCI) is a devastating condition causing lifelong disability for over one million North Americans. While human neural precursor cell transplantation (hNPC) has shown promise in early stages of the injury, the glial scar chondroitin sulfate proteoglycan (CSPG) remains a barrier to neuroregeneration in the chronic stages. Here, we aim to investigate if CSPG inhibits neuroregenerative mechanisms of hNPCs by using RNA-sequencing to explore the transcriptome of hNPCs exposed to CSPG in vitro. Our results show that hNPC global transcriptional activity is repressed and that hNPCs upregulate key genes, LINGO4 and NRTN. Gene ontology analysis reveals that upregulated genes are associated with inhibiting neurogenesis, reducing neuronal differentiation and cell migration while downregulated genes are associated with the immune response. Ultimately, we uncover key genes that could be targeted to overcome the CSPG-mediated inhibition and used to bioengineer improved hNPC therapies for chronic SCI.
Teach Me About Your Garden: Indigenous Youth Food Sovereignty in Tkaronto
Keywords: food sovereignty
Indigenous sovereignty
reciprocity
responsibility

This project aims to understand the relationship that urban Indigenous young people have with food sovereignty concepts and practices in Tkaronto. Indigenous sovereignty has been discussed at length amongst Indigenous scholars, activists, and thinkers for years. This thesis attends to Indigenous feminist discourses of sovereignty as they relate to experiences of urban Indigenous food growers in asserting self-determination. Engaging the framework of relational reciprocity presented in Robin Wall Kimmerer’s Braiding Sweetgrass, and qualitative interviews with Indigenous food growers across the city, this project seeks to build upon the tradition of Indigenous resistance and support future theorizations towards Indigenous sovereignty.
Exploring Alternative Methods of Visualizing Patient Data
Keywords: Information visualization
Patient Data visualization
Patient-generated data

Patient data visualization can help health care providers gain an overview of their patient’s condition, and assist in decision-making on next steps on management and care. This thesis explores acceptance of, and reactions to five visualizations that can be used to summarize patient data, including a Text Summary, text and frequency-based Word Cloud, a Bar Graph, a Line Graph, and a newly developed Text Graph that combines text with time-based distribution. Results from a qualitative study with medical school students and health care providers show that users can interpret patient health information from all visualizations, and can imagine using these visualizations in their medical practice. Overall, the Text Summary is the most positively received visualization, and the Text Summary and Text Graph are the most useful in extracting patient health information. This thesis provides evidence to support the idea that qualitative patient-generated information can be displayed in ways other than clinical notes.
Coping Mechanisms among Youth and Young Adults with Autism Spectrum Disorder in Competitive Employment
Keywords: Anxiety
Autism
Coping
Stress
Work

Successful integration into employment is an ongoing issue for individuals with autism spectrum disorder (ASD). A primary barrier to successful employment includes being unable to cope with the social demands of work because people with ASD are more likely to experience higher levels of stress and anxiety. The purpose of this study was to explore how youth and young adults with ASD cope with stress and anxiety in competitive employment. A phenomenological study was conducted involving in-depth interviews with twelve youth and young adults with ASD. Findings revealed three main themes: (1) salient workplace factors, (2) stress and/or anxiety inducers, and (3) coping mechanisms. The findings shed new light on the impact of stress, anxiety and coping on youth and young adults with ASD and have potential to educate employers about the issues that such employees encounter.
Annual Biogeochemical Dynamics of a Stormwater Management Pond
Keywords: Algae
Nitrogen
Phosphorus
Stormwater
Stratification
Urban ponds

Since the 1970’s stormwater ponds (SWPs) have been used to mitigate the risks of flooding and pollution posed by stormwater runoff from paved impervious surfaces. SWPs have been evaluated for their function as a nutrient and sediment sink, but few studies have investigated fine scale spatial and temporal changes in biogeochemical properties. The objective of this study was to analyze N and P dynamics in relation to other water quality indicators in a stormwater pond. Changes in total N and P fractions were examined under different water temperatures, and rain and melt event classes. Vertical gradients of N and P fractions were also compared to water column stability. This thesis shows that a SWP transforms the composition of N and P fractions in water, resulting in higher particulate exports. It also demonstrates that despite a shallow depth, stormwater ponds are capable of producing stratified water columns of variable water chemistry. .