VictorJuiz/thesis huggingface dataset:
To Know Ourselves - In Conversation on Métis Identity: Young Métis Perspectives from the Historic Georgian Bay Métis Community
Keywords: Canada
Culture
Indigenous Identity
Indigenous Studies
Indigenous Youth
Métis

Métis people as Indigenous people have encountered systematic dispossession and oppression, leading to both misrepresentation and under-representation in historic and current educational, academic, and political spheres. This legacy directly impacted young Métis people and how they understand themselves today as Indigenous people. This work aimed to uncover how Métis youth come to know themselves as being Métis, and what their definitions are regarding how they view themselves as Indigenous people. Story-based narrative inquiry was used in speaking with Métis young people from the Historic Georgian Bay Métis Community of Penetanguishene, Ontario. Personal experiences related to geo-location, seeking understanding/unknowing, relatedness/relation and responsibilities, language, challenge and journey yielded some of the first contributions in academia on how Métis youth form their Métis identities. As a result, it is critical for Métis youth to be provided spaces with these characteristics to uphold their participation in knowledge sharing in matters that effect their futurities. Les Métis, en tant qu’Autochtones, ont été systématiquement dépossédés et opprimés, ce qui a donné lieu à une fausse représentation et à une sous-représentation dans les sphères historiques et actuelles de l’éducation, de l’enseignement et de la politique. Cet héritage a eu des répercussions directes sur les jeunes Métis et sur la façon dont ils se comprennent aujourd’hui en tant qu’Autochtones. Ce travail visait à découvrir comment les jeunes Métis apprennent à se reconnaître comme Métis et quelles sont leurs définitions de la façon dont ils se perçoivent comme Métis en tant que peuple Autochtone. L’enquête narrative fondée sur l’histoire a servi à parler avec des jeunes Métis de la communauté Métis Historique de la Baie Georgienne de Penetanguishene, en Ontario. Les expériences personnelles liées à la géolocalisation, à la recherche de compréhension/méconnaissance, à la relation/relation et aux responsabilités, à la langue, aux défis et au parcours ont donné lieu à des premières contributions du milieu universitaire sur la façon dont les jeunes Métis forment leur identité Métis. Par conséquent, à l’avenir, il est essentiel que les jeunes Métis se voient offrir des espaces marqués par ces caractéristiques afin de maintenir leur participation au partage des connaissances sur les questions qui influent sur leur avenir.
Investigation of Dilation and Constriction Features of a Hypercapnic BOLD-fMRI Cerebrovascular Reactivity Challenge
Keywords: BOLD-fMRI
Cerebrovascular Reactivity
Physiology

A cerebrovascular reactivity (CVR) challenge provides the means of assessing response to a hypercapnia challenge and is used to study cerebrovascular dysfunction. This thesis uses blood oxygenated level dependent imaging during CVR to investigate individual vascular responses. We hypothesize that 1) regional vasodilation responses can be estimated using a model-free non-parametric method, 2) vasoreactivity will differ by brain region, and 3) sequential CVR estimates will be correlated. A CVR challenge was conducted in three cohorts: individuals that are pilots by occupation, patients with sleep apnea, and patients with small vessel disease. CVR was assessed in subcortical grey and white matter, and different arterial territories. Our results indicate that vasoreactivity differs by tissue type and arterial territory. We also show an association between successive CVR challenges. This work shows that distinct features of a CVR challenge can be isolated to provide additional CVR metrics to better utilize CVR in clinical and research settings.
Cardiovascular Physiology in Individuals with Obesity
Keywords: Cardiac Catheterization
Exercise
Heart Function
Hemodynamics
Obesity

Obesity is an increasingly prevalent risk factor for cardiovascular diseases including heart failure with preserved ejection fraction (HFpEF) however the hemodynamic phenotype associated with the spectrum of obesity, independent of cardiovascular disease is not fully characterized. We evaluated associations between body mass index (BMI) and cardiopulmonary hemodynamics among subjects with noncardiac dyspnea who underwent RHC during rest and exercise. We report a trend to increased pulmonary artery wedge pressures at rest and during exercise in subjects with a BMI between 30-40 kg/m2. Physiologic alterations including a depressed mixed venous oxygen saturation and an elevated arteriovenous oxygen content difference at rest were observed across studies in subjects with a BMI between 30-40 kg/m2. Together, this information suggests that obesity alone may be associated with impaired cardiac diastolic function. Both studies support the notion that obesity is associated with a hemodynamic phenotype that may predispose to HFpEF development.
Structure of the SMURF2HECT Domain with a High Affinity Ubiquitin Variant
Keywords: NEDD4
Protein Engineering
Protein Purification
SMURF
UbV
X-ray Crystallography

Therapeutic targeting of the ubiquitin (Ub) proteasome system (UPS) is currently of significant interest. The HECT domain of E3 ligases is one family of UPS enzymes that have yet to be successfully targeted, which have prominent roles in human disease including the closely related SMURF1 and SMURF2. Recent work has resulted in the engineering of a protein-based ubiquitin variant (UbV S2.4) that specifically bound and inhibited SMURF2 but not SMURF1. Here, to better understand the molecular basis of this specificity, the SMURF2HECT-S2.4 complex was solved to 2.5 Å. Structural analysis revealed several critical UbV residues responsible for SMURF2HECT binding. Additional structural modeling revealed two important residues on the binding surface of SMURF2HECT that are different from SMURF1HECT, which provide an explanation for the specificity of UbV S2.4. Taken together, these results underscore the utility of UbVs in probing structure-function relationships of UPS enzymes, which will facilitate the development of therapeutics.
Uncovering the Interactome of a Metabolism Proteome Signature in Lung Cancer
Keywords: AP-MS
BioID
Interactome
Lung Cancer
Metabolism
Proteomics

Lung cancer has the highest mortality rate of all cancers, and yet there has been limited progress towards new therapies from widespread DNA and RNA sequencing of lung tumours. Many patients lack the currently targeted driver mutations. The proteome manifests disease phenotype, so its characterization using interactome analysis may lead to identification of new actionable therapeutic targets. Proteome profiling of lung tumours identified C10, a signature comprising seven metabolism proteins that were highly correlated and upregulated in expression relative to normal lung. C10 behaves as a driver of cancer with prognostic impact, but the way in which the C10 proteins functionally interact is unknown. To investigate the function of C10, protein-protein interactions of C10 interactome proteins were analyzed using two complementary mass spectrometry-based methods. Four interactions with C10 were recapitulated and C10 was shown to be linked to serine metabolism and calcium homeostasis through an interaction at mitochondria-associated membranes.
Association of Frailty with Clinical Outcomes in Myeloproliferative Neoplasms: A Population-based Study from Ontario, Canada
Keywords: Frailty
Myeloproliferative

Impact of frailty on clinical outcomes in myeloproliferative neoplasms (MPN) is unknown. In a retrospective, population-based study, we measured association of frailty with all-cause mortality and thrombosis in MPN patients identified from Ontario Cancer Registry between 2004 to 2019 (Total=10,336: essential thrombocythemia=5,108; polycythemia vera, n=3,843; myelofibrosis, n=1,385). Baseline frailty measured using the Johns Hopkins Adjusted Clinical Groups® frailty indicator or the McIsaac’s cumulative deficit frailty index (mFI) was independently associated with increased risk of mortality after adjusting for age, sex, and comorbidities in multivariable Cox proportional hazard model in MPN. Using mFI, compared to fit patients, the HRs for all-cause mortality for prefrail and frail patients were: 1.6 (1.3-1.9), and 3.6 (2.9-4.4) in ET; 1.3 (1.1-1.5) and 2.7 (2.1-3.4) in PV, and 1.2 (1.0-1.5) and 2.0 (1.5-2.7) in MF. In multivariable Fine-Gray regression, frailty was associated with increased risk of thrombosis in MPN.
Magnetic Locking Mechanism to Enable Multiple Curvatures in a Tendon-driven Continuum Robot
Keywords: Continuum robot
Magnetic actuation
Magnetic locking mechanism
Medical robotics

Tendon-driven continuum robots have potential for surgical applications, but as each robot segment bends only with constant curvature, multiple segments are needed to achieve the dexterity required to follow surgical paths. When adding robot segments, additional on-board actuating tendons are required, enlarging the device’s diameter and rendering it unsuitable for surgery. In this work, a magnetically-actuated locking mechanism on board a tendon-driven continuum robot was developed to enable multiple curvatures in a single robot segment, thus reducing the number of segments necessary to achieve complex robot shapes and reducing the number of actuating tendons required. It is shown that one locking mechanism can be used to achieve two curvatures in a single robot segment and that two locking mechanisms can be independently actuated, demonstrating the potential to achieve three curvatures in a robot segment. This work may facilitate future miniaturization of tendon-driven continuum robots, enabling their use in surgical applications.
Predictors of Early and Long-term Readmission of Patients following Liver Transplantation
Keywords: Hepatology
Liver Transplantation
Mortality
Readmission

Background and objectives: Chronic liver disease (CLD) is on the rise, and accounts for over 2 million deaths annually. Liver transplantation (LT) is the most effective treatment for CLD but has been strongly associated with hospital readmissions and mortality outcomes. While most research focuses on predictors and reasons for readmission within the first 3 months post-LT, very few studies examine long-term readmission outcomes. The objectives of this study are: (1) to compare predictors of early (<30 day), mid-term (30-90 day), and long-term (>90 day) readmissions post-LT, (2) to assess the effects of initial readmission on survival post-LT, (3) to describe reasons for readmission post-LT within the early, mid-term, and long-term period. Methods: This is a retrospective observational study, investigating adult patients older than 18 years who underwent LT between January 1, 2010 – December 31, 2019 at Toronto General Hospital (TGH). The exclusion criteria include patients who died before LT discharge, and patients living outside of the Greater Toronto Area (GTA) at time of LT. Results: 987 patients fulfilled the inclusion criteria. Of those patients, 467 (47.3%) were readmitted at least once, with the median time from transplant discharge to initial readmission being 86 days (IQR 15-279). Of the total cohort, patients readmitted at 30 days, 90 days, and 5 years were 18.5%, 25.3%, and 55.1% respectively. Significant predictors of readmission were BMI > 30kg/m2 (HR=0.64, 95% CI= 0.42-0.98), and autoimmune/cholestatic CLD (HR=1.86, 95% CI= 1.01-3.42) at 30 days, post-LT length of stay (LOS) (HR=1.05, 95% CI= 1.02-1.08), and driving distance (HR=1.07, 95% CI= 1.01-1.14) at 30-90 days, and living donor LT (HR=1.41, 95% CI=1.06-1.89), and driving distance (HR=1.05, 95% CI=1.01-1.09) after 90 days. Readmission was significantly associated with mortality (HR=2.4, 95% CI=1.6-3.6). The main reason for readmission within the early, mid-term, and long-term period was infection, with the incidence of surgical complications (namely incisional hernias) increasing in the long-term period. Conclusion: This large single-centre study provided more information on the short-term as well as long-term predictors of readmission post-LT in a Canadian cohort. Adding to the pre-existing literature, the findings of this study show an association between readmission and mortality. Understanding the predictors of as well as reasons for readmission at specific time intervals may allow healthcare practitioners to mitigate the mortality seen post-LT.
Identification of Specific Clinical Risk Factors Associated with the Malignant Transformation of Oral Epithelial Dysplasia
Keywords: Dysplasia
Oral Cancer
Pre-cancer

Background: Factors that increase the risk of malignant transformation of oral epithelial dysplasia (OED) are not completely elucidated. Methods: A retrospective chart review was performed assessing risk factors for transformation, and cancer staging for transformed cases at Sunnybrook Health Sciences Centre in Toronto, Canada. Results: Two hundred-four patients were diagnosed with OED, and 16.7% underwent malignant transformation. Risk factors associated with transformation included: heavy tobacco smoking, excessive EtOH consumption, non-homogenous leukoplakia, size > 200 mm2, moderate or greater than moderate dysplasia, progression of dysplasia grades, and immunosuppression. Transformed cases followed for a dysplastic lesion were associated with a stage I cancer diagnosis, and cancer cases with no prior biopsy were associated with a stage IV diagnosis. Conclusions: In addition to commonly cited risk factors, immunosuppression was associated with malignant transformation, including the use of topical steroids. Analyzing risk factors can help clinicians define risk of progression in patients with OED.
The Correlation between Flowering Time and Herbivory Tolerance Depending on the Timing of Attack and Competition Intensity during Recovery
Keywords: flowering phenology
herbivory tolerance
plant ecology

Herbivory tolerance is thought to be genetically correlated with flowering time in annual plant Brassica rapa. When damage occurred, plants with late-flowering genotypes would have more time to recover before reproduction, hence be tolerant to damage. In addition, tolerance is under the influence of factors like the timing of the attack and the competition intensity during recovery. In chapter 1, I found out that late-flowering B. rapa tolerated damage better than the early-flowering ones, and tolerance was higher when the damage occurred early. In chapter 2, I mimicked different levels of post-damage competition intensity by creating different neighborhood damage levels. The results showed that when the competition was relaxed or extremely intense, the early- and late-flowering B. rapa achieved similar levels of tolerance. However, when the competition was moderate, the early-flowering ones had higher fitness after
Left Ventricular Diastolic Function in Middle-aged Endurance Athletes: Considering the Effects of Training Volume, Exercise Modality and Sex
Keywords: athletes
cardiac
endurance
function
middle-age

While middle-aged individuals are the largest and fastest growing cohort of endurance sport, the impact of chronic, intensive endurance training on resting left ventricular (LV) diastolic remodeling and the effect of exercise modality (running, cycling and triathlons) and sex is poorly understood. METHODS: Endurance (EA; n = 66, 67% male) and recreational (RA; n = 32, 59% male) athletes completed a detailed exercise history questionnaire, graded exercise to exhaustion on a treadmill and a resting transthoracic echocardiogram. RESULTS: EA displayed lower mitral A velocity, higher E/A ratios and faster time to peak strain rates compared to RA with negligible differences in diastolic function between exercise modalities. DISCUSSION: The observed LV diastolic function in EA may be a function of an increased preload and LV compliance. CONCLUSION: Chronic endurance training may have a limited influence on resting diastolic function displaying only incremental benefits with a greater training burden.
Multi-dipole Magnetic Localization for State Estimation of Ingestible Capsule Devices Bearing Dual-dipole Magnetic Mechanisms for Sampling the Gut Microbiome
Keywords: Capsule
Localization
Magnetic
Microbiome
Microrobot
Sampling

Wireless capsule endoscopes (WCEs) are a class of ingestible, robotic devices designed for imaging the digestive tract during diagnostic procedures. Sightless localization of these devices is achieved in 5DOF by embedding a single permanent magnet within the device and detecting its emitted magnetic field remotely via magnetic field sensors. The work in this thesis applies magnetic localization techniques to track two WCE-based, dual-dipole magnetic sampling capsule devices (SCDs) across ten degrees of freedom; providing full device pose and actuation state estimation in real time. A magnetic field sensing system is developed to localize the SCDs designed for obtaining targeted samples of the gut microbiome. The unique ability to determine 6DOF pose and actuation state is achieved by tracking the relative positions and orientations of the two embedded permanent magnets. The localization speed and accuracy of this system are analyzed and compared across three different SCD models.
Predicting Relapse and Long-term Renal Outcomes in Patients with Relapsing and Remitting FSGS: A Retrospective Observational Cohort Study
Keywords: ESKD
ESRD
Focal Segmental Glomerulosclerosis
FSGS
Relapse
Remission

Primary focal and segmental glomerulosclerosis (FSGS) is the leading glomerulonephritis related cause of renal failure in developed countries. Change in twenty-four-hour urinary protein excretion is the key biomarker defining remission and relapse. Predictive models for relapses and progression to renal failure are lacking. We hypothesized that two time-to-event, multivariable, survival models employing clinical variables may be utilized to predict the risk of relapse from the time of remission and predict progression to renal failure from the time of first relapse.Risk prediction models were created to (1) estimate the absolute risk of relapse among primary FSGS patients at 12, 24 and 60 months after their first remission and, (2) among patients suffering a relapse, to estimate the absolute risk of renal failure at 60 months. The model assessing relapse had poor discrimination, but reasonable calibration at 24 and 60 months. The model assessing renal failure had good discrimination with reasonable calibration.
Process Development for Double and Multiple Fortification of Salt with Ferric Pyrophosphate and Iron Absorption Enhancers
Keywords: bioavailability enhancers
double fortified salt
ferric pyrophosphate
fortification
iodine retention
multiple fortified salt

A process was developed to fortify salt using ferric pyrophosphate (FePP), to treat micronutrient deficiencies (in iron, zinc, iodine, B9, B12) causing prenatal complications. Extrusion and microencapsulation produced premixes for double (DFS) and multiple-fortified salt (MFS). Reduction in colour-masking was predicted, since FePP is off-white. FePP is significantly less bioavailable than ferrous fumarate, therefore, absorption enhancers were utilized. Formulations developed by ETH Zurich were 1:citric acid (CA), trisodium citrate (TSC); 2:CA, sodium pyrophosphate; 3: reduced levels CA, TSC; 4: disodium EDTA. 25% titanium dioxide was required to colour-mask the extrudates. Soy stearin (SS) coating at 15% w/w prevented iodine loss (from iron-iodine interaction) in fortified salts. All samples made with University of Toronto retained >50%iodine at 25, 35, 45oC after 6 months. Pilot testing of the process at JVS Foods, Jaipur confirmed the laboratory results. With 10g salt consumption/day, DFS and MFS can deliver 50-200% RDA for the added micronutrients.
Investigating Targeted Therapies for Genetic Heart Disease
Keywords: Cardiology
Genetics
Stem Cell

Hypertrophic cardiomyopathy is a phenotypically and genetically heterogeneous disease caused by MYH7 and MYBPC3 mutations. The objective of this study was to 1) create a model using patient hiPSC-cardiomyocytes from children with HCM and demonstrate rescue of phenotype via gene correction, and 2) identify differences in response to targeted and non-targeted drugs across different mutations. hiPSC-derived cardiomyocytes were generated from 4 pediatric HCM patients harbouring myosin mutations, and the mutations were corrected using CRISPR/Cas9 gene editing. The morphological, contractile, biochemical, and arrhythmogenic phenotype were compared between patient, gene-corrected, and healthy control hiPSC-CMs. We demonstrate the recapitulation of the HCM phenotype, with varying severity, in all four patient lines, which can be successfully rescued with gene correction. Targeted myosin inhibitor was effective in rescuing phenotype compared to a non-targeted drug. This provides a platform to functionally validate new variants and assess the ability of myosin-targeted drugs to rescue the HCM phenotype.
ctFS: Eliminating File Indexing with Contiguous File System on Persistent Memory
Keywords: File System
Persistent Memory

Persistent byte-addressable memory (PM) is poised to become the norm of future computer systems. PMs are significantly faster than disk storage; moreover, accesses to PMs are governed by the Memory Management Unit (MMU) just as accesses to volatile RAM (Random Access Memory) are. These unique characteristics shift bottlenecks to operations like block address lookup – for example, in write workloads, up to 45% of the overhead in ext4-DAX is due to building and searching extent trees to translate file offsets to addresses on persistent memory.We propose a novel contiguous file system - ctFS, which obsoletes the use of any indexing structures such as extent trees in the file system. Instead, ctFS represents each file as a contiguous region of virtual memory, hence a lookup from the file offset to the address is simply an offset operation.
Extending Data Flow Architectures for Convolutional Neural Networks to Object Detection and Multiple FPGAs
Keywords: Convolutional Neural Networks
Data Flow Architecture
FPGA
Hardware Acceleration
Machine Learning Acceleration
Tensorflow

This thesis augments and extends the state-of-the-art CNN inference accelerator for FPGAs, HPIPE. We first focus on the infrastructure of the accelerator, where we build an extra hardware unit to implement the Sigmoid function and automated unit tests to validate the functionality of the accelerator. We then study how to leverage the AI-optimized Stratix 10 NX FPGAs to achieve up to 7X speedup for convolution operations. Next, we extend HPIPE by integrating it with a hardware-friendly non-maximum suppression (NMS) unit to accelerate object detection and provide the highest-performing single-shot detection-based (SSD-based) object detection accelerator for FPGAs. Finally, we build an automated CAD flow to partition CNNs across multiple FPGAs that communicate via 100 Gb Ethernet. We show through a prototype system that doubling the number of FPGAs results in 2X performance improvement on three CNNs: MobileNet-V1, MobileNet-V2, and ResNet-50.