VictorJuiz/thesis huggingface dataset:
Engineering a Minimal Pseudomonas aeruginosa Bacteriophage

Phage therapy is gaining support as a treatment for diseases caused by antibiotic resistant pathogens, however many isolated therapeutic phages remain completely uncharacterised. There is a risk of these phages producing unknown gene products that could exacerbate the virulence of the disease. In this study, I describe a method using the type I-C CRISPR-Cas system that allows for the rapid screening of these unknown genes and their subsequent deletion in the Pseudomonas aeruginosa phage JBD68. I show that of the 27 genes of unknown function in the JBD68 genome, 26 are dispensable for lytic growth. With this knowledge, I produce genome reduced JBD68 phages missing upwards of 3 kbp of their genome. This corresponds to 8% of its total genome, and I show that this is likely the limit of genomic reduction from JBD68.

Keywords: Bacteriophage
CRISPR-Cas3
Phage engineering
Pseudomonas aeruginosa
Synthetic biology
Advisor: Davidson, Alan R
Immunological Humoral and Cellular Activation Profiles in the Low Dose Multi Allergen Oral Immunotherapy Trial

Low dose multi-oral immunotherapy (LOMO) may increase the safety profile of oral immunotherapy (OIT) while maintaining efficacy. Eighteen children allergic to 2-5 nuts were enrolled in LOMO (NCT03799328). Blood was collected at baseline, 6 months when the dosing target of ~30 mg protein/allergen was met, and at 18 months. Basophil activation test (BAT) was performed with allergen extracts (0.01-1000 ng/ml; FlowCAST BÜHLMANN, Switzerland). Molecular diagnosis for allergen-specific IgG4 and IgE was performed. At 18 months, BAT showed significant increase in EC50 corresponding to reduced reactivity of basophils to walnut, pistachio, cashew, and peanut relative to baseline. LOMO is effective and is accompanied by treatment-specific humoral changes and modulation of effector cell response to allergen stimulation, which reflects the desensitization process. Study results support the application of lowered maintenance dosing as a strategy to implement multi-OIT and to induce immunological changes reflective of desensitization.

Keywords: allergy
basophil
IgE
immunotherapy
oral tolerance
paediatric
Advisor: Moraes, Theo J.
Eiwegger, Thomas
Investigating Maternal, New-born, and Child Health Indicators toward the 2030 Agenda for Sustainable Development in nine sub-Saharan African Countries

This is a preliminary study that evaluates the statistical association of the SDGs on MNCH indicators in nine countries in sub-Saharan African. An Interrupted Time Series model is used to evaluate this association using six indicators from the Demographic and Health Survey. ARIMA modelling is used to forecast trends to 2030. 63% (34/54) of observations were significant, and 50% (17/34) of the indicators suggested the SDGs are associated with improving MNCH indicators. Of the MNCH indicators evaluated in this study, preliminary results of the ARIMA forecasting suggest 31% (17/54) of the observations signal progress towards the 2030 targets. Future directions suggest (1) using more recent data to evaluate the impact of COVID-19 on the indicator progress, (2) re-evaluating country progress more frequently and within income quintiles, and (3) investigating how to make the SDGs more equitable to promote progress not only in sub-Saharan Africa, but globally.

Keywords: ARIMA forecasting
global health
interrupted time series
policy evaluation
SDGs
SSA
Advisor: Essue, Beverley BE
Nauenberg, Eric EN
Microstructural Characterization of Copper Materials of Importance to the Development of Canada’s Nuclear Waste Container

The Deep Geological Repository (DGR) is a long-term solution proposed for the permanent disposal of Canada’s nuclear waste. In DGR, Used Fuel Containers (UFCs) isolate nuclear waste inside their carbon-steel cylindrical body which has a 3mm-thick copper coating on the outer surface for corrosion resistance. The thickness of the copper coating is based on a theoretical estimation of uniform corrosion attack, as opposed to “localized” corrosion attack that tends to be deeper and narrower. However, certain microstructural characteristics of copper are known to induce more localized corrosion. Therefore, the microstructure of four prototypes of copper coatings currently under consideration for UFC have been characterized using the Electron Backscatter Diffraction (EBSD) technique and compared with previous prototypes regarding those microstructural characteristics. It was shown that copper produced from pyrophosphate electrolyte is the most suitable. A similar analysis was conducted on native copper, which is a reference model for copper coatings under DGR conditions.

Advisor: Erb, Uwe
Howe, Jane
Assessing the Effects of Ischemia-Reperfusion in Multicellular Cardiovascular Tissues In Vitro

Transplanting exogenous cardiomyocytes into the infarcted myocardium is a promising strategy to prevent and potentially cure heart failure. However, many cardiomyocytes succumb to ischemia/reperfusion injury (IRI) before engraftment. Co-transplanting microvessel fragments (MVFs) can improve cardiomyocyte survival by enhancing perfusion; however, it remains unclear if MVFs can secrete factors during IRI and provide cardioprotective benefits beyond perfusion. We hypothesized that simulating aspects of IRI would impair both MVF growth and cardiomyocyte survival/function in vitro, and that co-culture would rescue cardiomyocyte survival/function. Isolated MVF cultures showed a delayed or abolished growth response to increasing durations of hypoxia, whereas cardiomyocytes demonstrated resilience unless cultured in 3D biowire constructs. Although cardiomyocyte area tended to increase on MVF-laden hydrogels, the effect was not statistically significant, and MVF conditioned media did not rescue biowire function in preliminary screens. Further investigation is necessary to conclude whether MVFs can rescue cardiomyocyte survival/function in the absence of perfusion.

Keywords: Cardiomyocytes
Heart-on-a-Chip
Hypoxia
Ischemia-Reperfusion Injury
Microvessels
Myocardial Infarction
Advisor: Vasconcelos, Sara
Development and Evaluation of Models for the Study of Enamel Remineralization

Hydroxyapatite (HAP) products have been approved as an anti-caries agent in Canada in 2015 and is currently being explored as fluoride-free alternative for the remineralization of WSL. In the first phase of our study, we performed a scoping review comparing the use of fluoride and HAP on caries prevention in vitro and in vivo. The results of our study suggest that HAP toothpaste performs equally as well as fluoride toothpaste at preventing caries in school age children. In the second phase, we used a lactic acid buffer to create artificial white spot lesions (WSL) in human extracted molars. Using this protocol, we were successfully able to induce enamel WSL and characterize them using both micro computed tomography (microCT) and optical coherence tomography (OCT). The WSL using this protocol were then compared to naturally occurring WSL. In the last phase of our study we investigated the use of amelotin (AMTN) coated HAP nanoparticles on the remineralization of artificially induced WSL. Our preliminary data suggest that 2 hours of incubation with AMTN-HAP nanoparticles significantly increased the mean mineral density and decreased the artificial WSL depth compared to controls. Collectively our early results suggest that AMTN-HAP nanoparticles are effective at remineralizing artificial WSL under the in vitro model system used. The research presented may be used to help with the development of novel therapeutic strategies for caries prevention.

Advisor: Ganss, Bernhard
Investigating the Role of Peroxisomal Biogenesis Factor 16 in Pancreatic β-cells

Peroxisome biogenesis is a complex process that involves the formation of peroxisomal membranes and import of peroxisomal proteins. Peroxisomal biogenesis factor 16 (Pex16) is a critical factor for the recruitment of membrane proteins for the formation of mature peroxisomes. However, the specific role of peroxisomes and Pex16 in pancreatic β-cells remain poorly understood. To investigate this, pancreatic beta cell (β-cell)-specific Pex16 knockout (β-Pex16 KO) mice were generated. These mice exhibited reduced protein levels of Pex16 and peroxisomal membrane protein 70 (PMP70), a peroxisomal membrane marker. Despite the reduction of Pex16 in the pancreatic islets, the β-Pex16 KO mice did not exhibit significant differences in β-cell function from wild type mice. Our findings suggest mice with Pex16 deletion in pancreatic β-cell may activate compensatory pathways to overcome functions of this peroxisome factor to maintain glucose homeostasis.

Advisor: Woo, Minna
Subgenual Anterior Cingulate Cortex (sgACC) Connectivity As Biomarker For Low-Frequency Right rTMS and The Individual Variability of rs-fc In MDD

It has been proposed that left DLPFC regions anti-correlated with right subgenual anterior cingulate cortex (sgACC) may represent optimal individualized target sites for high-frequency left rTMS (HFL). This study aimed to explore effects of left sgACC connectivity during low-frequency right rTMS (LFR), using concurrent rTMS-fMRI to directly observe rTMS effects and personalized e-field to measure stimulation over the cortex. Contrary to prior results, higher anti-correlation R-DLPFC and L-sgACC were not associated with greater clinical outcomes, suggesting strategies designed to optimize targets for HLF may not directly translate to LFR. Given individual functional connectivity (FC) predicted portions of rTMS outcomes, variability of resting state functional connectivity (rs-fc) was examined in the context of rTMS. Findings suggested that MDD patients displayed lower variability of sgACC connectivity than healthy controls; this may reflect the shared abnormality within MDD, and rTMS may normalize the lower variability of rs-fc toward healthy control.

Keywords: electrical field modelling
individual variability
Major depressive disorder
repetitive transcranial magnetic stimulation
resting-state functional MRI
treatment-resistant depression
Advisor: Hawco, Colin CH
The Consequences of Police Involvement in Mental Health Emergencies: From the Perspectives of Mental Health Professionals and Racialized Children, Youth, and Families

Current literature evaluating crisis interventions is primarily police-informed and is lacking the perspectives of service users and mental health professionals. The aim of this study is to explore the consequences of policing in mental health emergencies for racialized children, youth, and families. Focus groups were conducted for two groups of participants: 11 racialized service users and 13 mental health professionals. Four themes were developed from the service user data: Incongruity of involving police in mental health crisis response, Intersectional biases of police, Criminalization of children and youth, and Responding to mental health crisis without cops. Five themes were generated from the mental health professional data: Uncertainties around mandated reporting and crisis response, Inappropriateness of involving officers in psychiatric emergencies, Racial bias in mental health care service provision, Power imbalance between cops and clinicians, and Working around police. Both groups showcase how having police respond to mental health crises is unhelpful and unethical. Implications for researchers, policymakers, and service providers who work with racialized children, youth, and families are considered.

Keywords: Children Youth and Families
Crisis response
Mental Health
Mental Health Professionals
Policing
Racialization
Advisor: Ansloos, Jeffrey P
Structure Theory of Lie Groups via the Bruhat-Tits Building

In this paper, we will describe the Bruhat buildings of the groups SO(4) and SL(n) over p-adic fields.In order to analyze these groups, we will introduce the p-adic numbers and their associated prime ideal and integer ring. The parahoric subgroups for points in the standard apartment of SO(4) are computed, as well as the tori in SO(4) presented in [3]. The tori are compared with the parahoric subgroups. Then, the stabilizer subgroups and the points in the standard apartment fixed by the tori of both groups are determined.

Advisor: Jeffrey, Lisa
Combined Spin- and Gradient-echo Perfusion Weighted Imaging for Characterizing Vascular Architecture of Brain Tissue

Spin- and gradient-echo dynamic-susceptibility contrast (SAGE-DSC) is a magnetic resonance imaging technique that measures the passage of a contrast agent through tissue. This work proposes a simulation framework to measure SAGE-DSC given a known vessel configuration and discusses results acquired in patients diagnosed with cerebral tumours. The framework is a comprehensive model to describe signal changes due to the intrinsic properties of tissue, deoxygenated hemoglobin, and the contrast agent. With this model, perfusion curve features are extracted to describe vessel architecture, providing supplementary information about vessel structure in brain tissue. Finally, a SAGE-DSC sequence was implemented into routine clinical scans, and metric maps were generated to show differences between healthy tissue and lesions. These maps are useful in clinical settings because they display information about the blood volume and characterize tissue by vessel caliber and type. Overall, this work optimizes and extracts insightful information about tissue vasculature from DSC acquisitions.

Keywords: Cerebral tumours
Magnetic resonance imaging
Perfusion
Advisor: Uludag, Kamil
Learning the Discount Factor in Inverse Reinforcement Learning with Application to Animal Behaviour

Inverse reinforcement learning (IRL) focuses on recovering the agent's objective function through observed demonstrations, enabling us to better understand human and non-human animals' decision-making processes. However, an important aspect of decision-making---how we discount the future reward---has not been well-studied in IRL. In this thesis, we study the problem of IRL with unknown discount factor and develop its first application in animal behaviour. We investigate an existing work on IRL with unknown discount factor in detail, correcting several minor errors in the formulation and examining different mathematical characteristics of the problem. We propose an alternative algorithm for the correct gradient calculation, examine the convexity of the objective function in the optimization problem, and discuss the connections among different formulations of the objective functions seen in the literature. We then apply the framework to studying wild vervet monkeys' foraging behaviour in two different scenarios: foraging alone or in competition. We formulate and solve each scenario as an IRL problem. Our experimental results provide novel insights into vervet monkeys' cognitive decision-making process. We present several suggestions on future foraging experiment design to improve the current mathematical models.

Advisor: Beck, Christopher
Collaborative Translation and Meaning Making: Using English Language Learners’ First Language as a Resource for Language Learning and Academic Achievement in the Classroom

This MA thesis explores integrating home languages, collaborative translation, and AI-based online tools to enhance language learning and academic performance for English Language Learners (ELLs) in various subjects. The findings from this qualitative research with Arabic-speaking teachers and ELL students highlights positive impacts on vocabulary, writing, speaking, and reading. Collaborative translation boosts language transfer, metalinguistic awareness, and appears to improve speaking skills by encouraging students to freely express themselves in the target language. Translating into the first language aids comprehension, especially in math and science. Utilizing digital translation tools effectively utilizes existing linguistic knowledge, fostering better engagement and collaboration. The study underscores the transformative potential of incorporating native languages and translation tools, providing practical guidance for educators and valuable insights for diverse ELL classrooms. The goal is to bridge the linguistic gap between students' home language and English, equipping educators with powerful tools for proficiency and comprehension.

Keywords: Academic achievement
AI Tools
English language learners
First language
Language Education
Translation
Advisor: Le Pichon-Vorstman, Emmanuelle
Hēap: Listening Through Performance

This research delves into the profound interplay between the body, power, and subjugation that has come to the forefront of late twentieth-century discourse. Focused on the Iranian female body, it aims to uncover manifestations of subjugation and illuminate pathways towards conscious subjecthood. By drawing inspiration from Foucauldian concepts, the exploration led to a site-specific performance named "Hēap," an artistic endeavor to unearth the tangible experiences within Iranian society. Through an examination of power dynamics, surveillance, and spatial arrangement using Foucault's insights, the study seeks to discern signs of subjugation and pathways to empowerment. It reveals that despite historical and societal constraints, confronting and acknowledging subjugation empowers individuals to transcend limitations, fostering gradual transformation. This process holds potential for erasing the imprints of disciplinary machinery, liberating both current and future generations.

Keywords: Body
Foucault
Iran
Performance
Advisor: Eacho, Douglas
How to Restore Ravines: Ecological Restoration and the Toronto Ravine System

This paper addresses the following research question: what does ecological restoration mean to stakeholders engaged in restoring Toronto’s ravine system? Building on the International Principles and Standards for the Practice of Ecological Restoration, this proposal critically examines the relevance of two of its guiding principles. The discussion then shifts to an analysis of the Toronto Ravine Strategy and relevant literature on the Toronto ravine system. After this, a grounded theory-informed methodology is outlined, detailing interviews with 10 participants and visits to 3 sites. A section on findings follows, as well as concluding thoughts.

Keywords: Ecological Restoration
Society for Ecological Restoration
Stakeholders
Toronto Ravine Strategy
Toronto Ravines
Advisor: Yoreh, Tanhum
Intimate Monsters: On Disorder, Trans* Embodiment, and Futurity

This paper evaluates trans* use of needles for the purpose of subcutaneous injection to present a working theory of intimate technologies and how monstrosity can be utilized as a tool to build coalitions across groups of needle users. From a deeply phenomenological approach, this project presents one such body-essay that attempts to reckon with questions of assimilation, access, transition, disorder, and the medical industrial complex. Using my own experiences as a trans*, impaired, and gender-queer needle user, I interrogate how the tools and technologies we use shape how we begin to imagine the future and carry with us hopes for radically different worlds. Key themes relating to the body, how people interface with medical authorities, and embodiment carry through each section, culminating in the development of looser theory on self-actualization, one that considers that trans* individuals are not so alone in their quest for embodiment.

Keywords: Disability
Intimacy
Monstrosity
Needles
Phenomenology
Trans*
Advisor: Keilty, Patrick
Grimes, Sara
Tau PET Imaging for Atypical Parkinsonisms: A Systematic Review and Meta-analysis

Objective: To compare first- and second-generation tau PET tracer efficacy in patients with atypical parkinsonisms (APs), represented by progressive supranuclear palsy (PSP) and corticobasal degeneration (CBD). Methods: In vivo tau PET imaging data was compiled from an extensive literature search and meta-analyzed using random-effects meta-analytic models with restricted maximum likelihood estimation (REML) and subgroup analysis based on regions of interest (ROIs). Results: Second-generation tau PET tracers ([18F]PI-2620 and [18F]PM-PBB3) consistently outperformed first-generation tracers ([18F]AV-1451 and [18F]THK-5351). These tracers presented with the largest standardized mean difference (SMD) values in tracer binding, favouring patients with APs. The ROIs with the greatest differences in binding were the globus pallidus (GP) and subthalamic nucleus (STN). Conclusions: Our results provide evidence for the efficacy of second-generation tau PET tracers, particularly in the basal ganglia. These findings support and advance existing literature, ultimately contributing towards identifying a reliable diagnostic biomarker for patients with APs.

Keywords: Neuroimaging
Parkinson's disease
Parkinsonism
PET
Progressive supranuclear palsy
Tau
Advisor: Strafella, Antonio P
Model Checking and Gas Optimization of Move Smart Contracts, and Transaction Order Dependency Detection and Rectification

Blockchain technology has revolutionized various industries by providing secure transaction mechanisms in a decentralized, trustless environment. In 2014, the Ethereum blockchain platform introduced smart contracts, facilitating the deployment of a wide range of decentralized applications. However, since its inception numerous vulnerabilities have been discovered in the Ethereum Virtual Machine, many resulting in significant financial loss. Consequently, a new smart contract language, Move, has been developed, where security and verifiability are first class features. As the adoption of Move increases, it necessitates robust developer tools and adherence to best practice principles, similar to the existing infrastructure present in Ethereum. This thesis contributes to the advancement of this goal. First, it introduces VeriMove, the first model checking framework for the Move language. Experiments show that model checking is a feasible method to formally verify global properties in Move smart contracts. Second, this thesis presents the first gas optimization analysis of the Move language. Experiments show that the proposed gas optimization patterns reduce gas consumption in a typical smart contract by 7 - 56%. Lastly, this thesis proposes a novel algorithm to automatically audit the transaction order dependency vulnerability present in many popular public blockchain platforms. A prototype implementation is developed on Ethereum for the Solidity smart contract language. Experiments show that the proposed methodology can be used successfully to detect and rectify such vulnerabilities, or to certify their absence.

Keywords: Formal Verification
Gas Optimization
Model Checking
Move
Smart Contracts
Transaction Order Dependency
Advisor: Veneris, Andreas
Investigating the Relationship Between Delirium Severity and Motor Subtypes in Older Adults Presenting to the Emergency Department

Delirium is a medical emergency associated with adverse outcomes in older (> 65 years) patients and is categorized into two main motor subtypes, hyperactive and hypoactive. The objective of study one was to prospectively assess measurement differences within and between two delirium severity scales, the Confusion Assessment Method – Severity Scale (CAM-S) and Delirium Index (DI), using case vignettes of delirium motor subtypes and severity, rated by emergency department staff. We found the CAM-S and DI scales both rated hypoactive as more severe than hyperactive (Δ3%). The second study was a systematic review of studies that reported delirium subtype, severity and outcomes to investigate measurement differences between motor subtypes. The relationship between delirium subtype, severity and outcomes was largely confounded by inconsistent delirium measurement tools used between reviewed studies. This thesis identifies systematic measurement errors in delirium motor subtype severity using the CAM-S and DI, and potential implications of these differences.

Keywords: Delirium
Geriatric Emergency Medicine
Motor Subtypes
Older Adults
Severity Scales
Advisor: Lee, Jacques S