VictorJuiz/thesis huggingface dataset:
Exploring System Resilience within the North York Toronto Health Partners North York Community Access to Resources Enabling Support Program (NYCARES): A Pragmatic Case Study

Ontario Health Teams (OHTs) were implemented in 2019 as a model of health system organization to improve integration of care across Ontario. Health system integration and health system resilience are closely intertwined. North York CARES (NYCARES) is an OHT program developed to support patients with complex care needs transitioning from hospital to home. This thesis used NYCARES to study the OHT model’s integrative characteristics in practice, and its ability to respond to large scale crises, using the COVID-19 pandemic as a natural experiment. An interpretive qualitative approach was used to explore program partners’ individual and collective program experiences. The results of this thesis highlight the complexity of Ontario’s healthcare systems and the necessity of approaching healthcare programs with a Complex Adaptive Systems (CAS) lens. Further research must be done to extend the application of CAS theory to healthcare contexts, with both system integration and system resilience in mind.

Keywords: complex adaptive systems
health services research
integration
ontario health teams
resilience
Advisor: Dainty, Katie N
Effects of Theta Burst Stimulation of the Cerebellum on Tremor and Working Memory in Parkinson’s Disease

The cerebellum is involved in working memory and postural tremor. Theta burst stimulation (TBS) can modulate neural activity. We expect cerebellar intermittent TBS (iTBS) to reduce postural tremor amplitude and improve working memory in Parkinson’s disease (PD) patients. We also expect cerebellar continuous TBS (cTBS) to impair working memory in PD patients and controls. Five patients with PD and nine healthy controls received cerebellar iTBS, cTBS, and sham iTBS. After TBS, subjects performed four working memory tasks. Postural and rest tremor was measured before and after stimulation in each session. Cerebellar cTBS significantly impaired subjects’ performance only in the digit span backward task compared to sham. Tremor data was insufficient to investigate the effects of TBS on tremor as only one patient had tremor. The findings support the hypothesis that the cerebellum is involved in working memory, and this contribution may be disrupted by cerebellar cTBS but not iTBS.

Keywords: Cerebellum
Parkinson's Disease
Theta Burst Stimulation
Transcranial Magnetic Stimulation
Tremor
Working Memory
Advisor: Chen, Robert
Chemogenetic Activation of a Glutamatergic Ventrolateral Medulla Circuit Alters Breathing

Breathing is generated by complex respiratory circuits spanning many regions within the brain. The main drivers of the respiratory cycle are found within ventrolateral medulla. Inspiratory pattern is generated by a small region of the medulla known as the preBötzinger Complex (preBötC), which contains a population of glutamatergic neurons. Glutamatergic neurons can be identified through the expression of vesicular glutamate transporter 2 (VGLUT2). We investigated whether chemogenetics, which employs designer receptors exclusively activated by designer drugs (DREADDs), could be used to activate (hM3Dq) or inhibit (hM4Di) VGLUT2-expressing neurons within the preBötC to manipulate respiration. We found that unilateral excitation of VGLUT2-expressing neurons using hM3Dq increased respiratory rate, while diaphragm and genioglossus amplitudes, inspiratory duration, and expiratory duration decreased. No changes in respiration were seen when inhibiting neurons using hM4Di. Our data suggest that chemogenetics can be used to manipulate respiration through excitation of VGLUT2-expressing preBötC neurons.

Keywords: chemogenetic
control of breathing
preBötzinger Complex
respiration
Advisor: Montandon, Gaspard
Trends in Self-reported Cost Barriers to Dental Care in Ontario

Background: The affordability of dental care continues to receive attention in Canada. Since most dental care is privately financed, the use of dental care is largely influenced by insurance coverage and out-of-pocket spending. Objectives: To explore trends in self-reported cost barriers to dental care in Ontario. Methods: Secondary data analysis of five cycles (2003, 2005, 2009/10, 2013/14 and 2017/18) of the Canadian Community Health Survey, a cross-sectional survey that collects information on health status, health care utilization, and health determinants for the Canadian population. Univariate and bivariate analyses were used to determine the characteristics of Ontarians who reported cost barriers to dental care. Poisson regression was used to calculate unadjusted and adjusted prevalence ratios to determine predictors of reporting cost barriers to care. Results: Self-reported cost barriers to dental care have generally increased in Ontario but more so for those with no insurance, low income, and aged 20-39 years.

Advisor: Quiñonez, Carlos
Singhal, Sonica
Investigation On the Composite Action Of Various Connections In CLT-Glulam T-Sections

In recent years, there has been much investigation into various timber products and ways to enhance structural behaviour. This research looks into investigating more efficient and compact sections, specifically by means of considering composite action in CLT-Glulam T-sections. Pine wood was selected to be studied for its material properties alongside a combination of four different mechanical and adhesive connections. By using these material and connection properties, a finite element model was constructed and calibrated in Abaqus. The finite element model was used to predict the behaviour of different full-scale CLT-Glulam sections. The Abaqus results show that an adhesive connection with perfect composite action can reduce deflections by 50% and increase maximum span length by 30%. A mechanical connection depends on its spacing and stiffness. For the particular connection in this study, the deflection reduction and span length increase were 30% and 15%, respectively.

Keywords: Adhesive
CLT
Composite Action
Connections
Glulam
Advisor: Mercan, Oya
Investigating Ion Mobility Separation of Phosphopeptide Isomers using Tapped Ion Mobility and Mass Spectrometry

The addition of phosphorylation to serine, threonine and tyrosine residues on proteins in eukaryotic organisms is an integral mechanism of cellular signaling. However, identification of phosphopeptide isomers, i.e. phosphopeptides with identical amino acid sequences and phosphate modifications on different residues, by mass spectrometry is challenging due to the lack of separation of such species by m/z and liquid chromatography. In this work, I investigated the separation of a library of 1497 synthetic phosphopeptide isomers using trapped ion mobility spectrometry combined with Data Independent Acquisition mass spectrometry. There are some examples of complete separation of co-eluting phosphopeptide isomer pairs by ion mobility, but the majority of phosphopeptide isomer pairs are not baseline resolved. Overall the results of this study suggest that utilizing trapped ion mobility in conjunction with mass spectrometry can completely separate some pairs of phosphopeptide isomers, and may be particularly useful when implemented as a dimension in data analysis.

Keywords: Data independent acquisition
Mass spectrometry
Phosphorylation
Proteomics
Trapped ion mobility spectrometry
Advisor: Rost, Hannes
Gingras, Anne-Claude
Saccade Amplitude Encoding By Neuronal Classes in the Human Mesial Temporal Lobe

The link between single-unit-activity in the mnemonic structures of the brain and saccades during visual exploration has been subject to recent interest. Indeed, work has demonstrated directional tuning of single-units to either ipsiversive or contraversive saccades coupled with the differential activation and inhibition of narrow and broad-spiking units, respectively. However, the functional role of particular cell-types and their encoding of other saccade kinematics remains unclear. In this work, we assessed cell-class diversity in the human mesial temporal lobe (MTL) using three distinct methods to reveal a progressively greater number of functional cell types corroborated by differential baseline firing statistics. Furthermore, we identified the presence of units tuned to low-or high-amplitude saccades and demonstrate the inhomogeneity of such units across regions and cell classes. These findings comport well with the intertwinement of memory formation and exploratory viewing and break ground on the opportunity to dissect the cell-type-specific function of MTL visuomotor circuits.

Keywords: cell type
human
mesial temporal lobe
neuronal coding
saccade
single unit
Advisor: Valiante, Taufik A
Modeling the Bike Share Toronto Network

Bike Share Toronto is a docked bike share system in the City of Toronto which opened in 2011 and has since expanded to 625 stations across the city. This thesis examines the trends in bike share trips and station activity from 2017 through 2022 in order to inform a microsimulation model of the system. Each day in 2021 is then simulated with three different rebalancing strategies to evaluate the impact of such system management on the delay experienced by users. The study finds that the number and length of delays can increase dramatically without careful management and that optimizations in the rebalancing operations can improve efficiency. The goal of this model is to provide an operational tool that could be integrated into larger regional planning models.

Keywords: bike share
cycling
microsimulation
rebalancing
Toronto
Advisor: Miller, Eric J
High-school Principals’ Experiences of Building Positive Relationships with Students in Beijing, China

This qualitative study explores school principals’ experiences of building principal-student relationships (PSRs) in high schools in Beijing, China. Four aspects of relationship-building, namely, the meanings of PSR, the strategies of PSR construction, the facilitators, and the barriers of PSR-building are investigated. Many researchers have demonstrated that effective schooling is attributed to strong and positive relationships initiated by school administrators with their surroundings. In China, the national reform of education has given principals pressing missions of initiating and maintaining closer relationships with students. However, the phenomenon of PSR in Chinese schools remains unexplored. Accordingly, this research collected interview data from five Chinese high school principals who earned recognitions from principals in other schools, media news reports, and/or local educational authorities for their achievements in building and sustaining positive PSRs and identified meaningful themes through thematical analysis. Results of the analysis were organized into a conceptual framework of PSR-building in Chinese schools.

Keywords: Chinese education
Educational leadership
High school education
Principal-student relationship
Relational leadership
Advisor: Manion, Carly
Evolvability of Sexual Dimorphism in Drosophila suzukii

The evolvability of sexual dimorphism is determined, in part, by the amount of sexually antagonistic genetic variation available to selection. Here I investigate genetic constraints to the evolution of sexual dimorphism in wing-shape in the invasive spotted wing Drosophila, Drosophila suzukii. I find 8.04 times the genetic variation in trait combinations that can respond to concordant selection than can respond to antagonistic selection. I propose that patterns of stabilizing selection due to a well-adapted wing generate these patterns of genetic variation I observe. Finally, this work shows that concordant evolvability is high for this species and argue that this could allow the population to respond quickly in the future to sexually concordant selection which may make management of this species even more problematic.

Keywords: Drosophila
Evolution
Evolvability
Wings
Advisor: Sztepanacz, Jacqueline
Metal Characterization Oxidative Potential of Non-Tailpipe Vehicle Emissions

Non-tailpipe traffic emissions are an increasing health concern to communities residing in dense urban landscapes surrounded by high volumes of traffic. To understand potential negative health effects, approximately 170 non-tailpipe emission samples were collected across the City of Toronto in the form of resuspended road dust, brake dust, and tire dust. The samples were analysed using x-ray fluorescence (XRF) to detect the presence of trace metals. Trace metals associated with road dust, brake and tire wear were prominent in collected samples, including Ba, Cu, Fe, K, Ti, and Zn. Samples were analyzed for the oxidative potential (OP), a health relevant metric to quantify the toxicity of particulate matter (PM). Three in vitro assays were used: ascorbate (AA), glutathione (GSH), and dithiothreitol (DTT). Results showed OP in all three assays to be higher than ambient results. Real-time sampling of roadside PM revealed a potential need for better road dust cleaning tools.

Keywords: metal characterization
non-tailpipe
oxidative potential
particulate matter
resuspended road dust
vehicle emissions
Advisor: Evans, Greg J
The Impact of a Male Selected Chromosome on Fitness and Gene Expression in Drosophila melanogaster

Different phenotypes may optimize fitness in each sex; a unique evolutionary challenge because much of the genome is shared. To investigate the extent to which this conflict has been resolved, six populations of Drosophila melanogaster were maintained such that a pool of marked 2nd chromosomes were transmitted exclusively through males. Eliminating selection in females should cause phenotypes associated with the marked chromosome to shift closer to male specific fitness optima, assuming conflict is ongoing. Male mating success was significantly improved in males with marked chromosomes compared to those without. An Allele Specific Expression analysis identified several hundred genes with cis-regulatory differences between these two marked chromosomes. Under the hypothesis that sex-biased genes have been unable to diverge between the sexes as much as would be optimal, male-selected marked chromosomes should evolve under this experimental evolution regime to be “masculinized”. However, we detected no such pattern.

Keywords: Drosophila Melanogaster
Experimental Evolution
Intralocus Sexual Conflict
Transcriptomics
Advisor: Agrawal, Aneil F
Imaging of Non-conducting Beam Sensitive Materials using Scanning Electron Microscopy: Practical Applications of ESEM and LVSEM

Non-conducting and beam sensitive materials like polymers are utilized extensively in modern industry. With growing interest in leveraging the capabilities of these materials by optimizing their morphological and structural characteristics, scanning electron microscopy (SEM) is becoming an increasingly important tool. Despite the advancement of SEM and advent of high caliber instrumentation, numerous challenges impede the imaging and study of beam sensitive materials using SEM. This thesis focuses on Environmental SEM and Low Voltage SEM and attempts to showcase their characterization capabilities through practical examples of respirators/facemasks, and microplastics. A set of characterization protocols for evaluating the structure, chemistry, moisture retention, and wetting properties of face masks and respirators are presented in Chapter 3. Chapter 4 presents efforts undertaken for capturing and compiling SEM images to form the first open-source SEM datasets for microplastics segmentation through deep learning methods. The promising result facilitates automatic quantification and classification of microplastics.

Keywords: Low Voltage Imaging
LV SEM
Scanning Electron Microscope
Advisor: Howe, Jane
Perovic, Doug
Developmental Trajectory of the Association between Monoamine Oxidase A and Catecholamine-O-Methyltransferase Genes, and Youth Externalizing Behaviours

Youth externalizing behaviours are serious public health concerns, with significant negative outcomes. These disruptive behaviours exhibit high heritability, with putative influences from the monoamine oxidase A (MAOA) and catecholamine-O-methyltransferase (COMT) genes. Literature points to a variable effect of genes on externalizing behaviours through development. This study aimed to examine the influence of development on the association between the genetic variants regulating the MAOA and COMT genes and externalizing behaviours in youth. Results from the cross-sectional (n=278-337) sample demonstrated that both MAOA-uVNTR and COMT Val158Met exhibit a significant change in the risk variant between childhood and adolescence for males, but not in females. Conversely, there was no significant interaction effect between Val158Met and assessment time on externalizing behaviours in the larger longitudinal ABCD (n=2363) sample. While replications with longer longitudinal studies are necessary, these results underscore the importance of considering the developmental stages when analyzing genetic risk of externalizing behaviours.

Keywords: Aggression
Children and Adolescents
Development
Externalizing Behaviours
Genetics
MAOA and COMT
Advisor: Kennedy, James L. JLK
Development and Implementation of a Simple Carbon Formation Mechanism for Methane Pyrolysis in Computational Fluid Dynamics

Methane pyrolysis is a technology that can produce hydrogen with low GHG emissions. In a methane pyrolysis jet, chemical reactions occur simultaneously with mixing, and a large amount of solid carbon is produced. Our current modeling of methane pyrolysis uses complex carbon formation mechanisms, ignoring fluid dynamics. Current CFD models typically use a post-processing technique for carbon formation which is only valid for low sooting flames. There is a need for a model which can accurately model fluid dynamic mixing, gas-phase chemical reactions, and carbon formation. This work develops and implements a simple carbon formation mechanism into a CFD model of a methane pyrolysis jet. The mechanism is based on the Moss-Brooke’s reaction rates using acetylene concentrations as the precursor for nucleation and surface growth. The CFD implementation provides spatial information about the formation of carbon and other gas-phase species during methane pyrolysis, which has been overlooked in previous work.

Keywords: Carbon
Fluid
Modeling
Advisor: Thomson, Murray J.
Identification of Novel Gut Microbiome Constitutive Androstane Receptor Ligands using an Untargeted Affinity Purification-Mass Spectrometry Approach

The Constitutive Androstane Receptor (CAR) is a member of the Nuclear Receptor (NR) family of transcription factors and a key regulator of xenobiotic metabolism. Identification of high affinity CAR ligands has remained elusive. This has been exacerbated by limitations in traditional screening methods due to CAR’s constitutive activity and its potential for indirect activation in cells. This thesis describes the identification of a group of structurally related CAR ligands present in the human gut microbiome using an affinity purification-mass spectrometry-based direct-interaction screen. These ligands share a di-indoyl core and are derivatives of 3,3-diindolylmethane. Characterization of the ligands using cellular and biophysical assays revealed that they bind and stabilize the CAR ligand binding domain. They are potent agonists, and one of the compounds, 3,3-diindolylethane, has a sub micromolar effective concentration and dissociation constant, making it a promising candidate for CAR drug development.

Keywords: CAR
Constitutive Androstane Receptor (CAR)
Diindolylmethane (DIM)
Drug Discovery
Microbiome
Nuclear Receptor
Advisor: Krause, Henry
Exploration of the Structural and Mechanical Properties of Novel Disulfide and Diselenide-containing Peptide Gels

Peptide gels have gained large attraction for their biocompatibility, biodegradability, and non-immunogenicity. Within living organisms, an important component that plays a role in signalling pathways and chemical reactions are diselenides and disulfides. Herein, two novel peptide conjugates – Boc-Phe-Phe-Cys-Cys-Phe-Phe-Boc and Boc-Phe-Phe-Se-Se-Phe-Phe-Boc – and their gelation has been investigated. These conjugates have been fully characterized using mass spectrometry, one dimensional 1H nuclear magnetic resonance spectroscopy, and Fourier transform infrared spectroscopy. Successful gelation of the conjugates has been reported as well. Strong intermolecular hydrogen bonds link nearby amide and carboxyl groups, pi-pi stacking interactions for aromatic rings, and hydrogen bonding between water molecules assist in the self-assembly of the gelator molecules to form solid organogel upon dissolution in toluene or acetonitrile, or hydrogels upon dissolution in MOPS or monosodium phosphate buffer. These gels exhibit redox active properties due to the diselenide and disulfide moieties. Preliminary studies have been conducted to characterize these conjugates to support further redox and drug-loading experiments.

Keywords: diselenide
disulfide
gel
peptide
redox
Advisor: Kraatz, Heinz-Bernhard
Investigation of the Balance of Pro-inflammatory Immune Cells to T Regulatory Cells and the Role of Antigen-specific T cells in the Development of Systemic Autoimmune Rheumatic Diseases

Systemic Autoimmune Rheumatic Diseases (SARDs) are characterized by the production of anti-nuclear antibodies (ANAs). ANAs are also seen in healthy individuals and can be detected years before disease onset in SARD. However, the immunological changes that facilitate the development of SARD in non-symptomatic ANA+ (ANA+ NS) individuals remain unclear. Here we demonstrate that in ANA+ NS individuals, there are significant increases in regulatory immune subsets, whereas inflammatory subsets are increased in SARD patients. Additionally, ANA+ individuals without SARD who progress clinically have increased lymphocyte activation and increased markers of regulation compared to non-progressors. Collectively, our findings suggest that active immunoregulation prevents clinical autoimmunity in ANA+ NS individuals, which, when impaired, may result in an increasingly inflammatory environment that promotes SARD development.

Keywords: Antinuclear Antibodies
Autoimmunity
B cells
Preclinical disease
Regulatory T cells
T cells
Advisor: Wither, Joan E
Robust Feedback-based Nash Equilibrium Seeking

We consider the problem of distributed Nash equilibrium seeking over networks. Each agent desires to play a game while constraining a system output generated by a process affected by the agents' control actions as well as some unknown, exogenous disturbances. Each self-interested agent seeks to minimize their cost function within this game, while ensuring that the output obeys the given constraints. We outline the limitations of forecasting the output and the relevant external disturbances, which motivates our feedback-based approach, using measurements to lift the forecasting requirements. We then develop two algorithms: one that makes a nominal, constant approximation of the system's input-output sensitivities a priori, and another that estimates sensitivities in a model-free manner. We exploit operator-theoretic properties to show our algorithms' convergence robust to model uncertainty and unknown disturbances. We then test the developed techniques using academic and real-world examples, validating and outlining the convergence properties of our algorithm.

Keywords: Control Theory
Feedback
Game Theory
Optimization
Reinforcement Learning
Zero-Order
Advisor: Simpson-Porco, John W
Pavel, Lacra