VictorJuiz/thesis huggingface dataset:
Characterization of Sex Differences in Aortic Valve Disease in Mice
Keywords: aortic valve disease
collagen remodelling
mouse model
sex differences

Aortic valve disease has recently been shown to have sex-specific pathobiology, where female valves experience more fibrosis and less calcification than male valves despite similar levels of stenosis. To investigate whether these differences were mirrored in a mouse model, six-week old male and female Ldlr-/-;ApoB100/100 mice were fed high fat diet to induce valve disease. After four or eight months on diet, blood lipid and sex hormone levels were measured, valve function was assessed by echocardiography, and valve leaflet tissues were analyzed (immuno)histochemically and by polarized light microscopy to assess valve morphology and content. Males on high fat diet for eight months had more valvular dysfunction than females on diet, however male and female valve leaflets did not differ in size, thickness, or collagen content. However, polarized microscopy indicated more collagen remodelling in the base of the male leaflets compared to females, which could affect healthy valve mechanics. This study provides the first characterization of sex differences in a mouse model and sex-specific structural differences that relate to level of valve dysfunction.
Self-tracing Human Induced Pluripotent Stem Cell-derived Neural Stem Cells to Map Transplant Integration
Keywords: genetic engineering
neural relay
neural stem cell
spinal cord injury
tract tracing

Spinal cord injury (SCI) is a devastating condition that leaves patients with lifelong sensory, motor, and autonomic deficits. Stem cell therapies offer an attractive approach to repairing and regenerating the injured spinal cord. While previous studies have shown that human induced pluripotent stem cell-derived neural stem cells (hiPSC-NSCs) can improve locomotion, few have been able to demonstrate graft-host integration. Viral and non-viral tracing methods have been used to map neural circuits; however, only a small proportion of grafted cells are successfully traced. To overcome this challenge, we aimed to engineer NSCs to express both antero- and retrograde trans-synaptic tracers to map transplant integration. A bicistronic vector encoding WGA-mCherry and GFP-TTC was non-virally integrated into NSCs and sorted into monoclonal lines. The resultant self-tracing NSCs retained typical stem cell properties as control NSCs and differentiated into functional neurons as demonstrated by whole-cell recording. Furthermore, they successfully traced primary rat cortical neurons in vitro. To assess tracing in vivo, T-cell deficient rats with a chronic C6/7 SCI received self-tracing NSCs. Preliminary data shows that self-tracing NSCs may trace host neurons. Conventional viral tracing only traced very few interneurons sporadically. This exciting proof-of-concept shows promise as a tool to delineate synaptically integrated sensorimotor pathways involved in stem cell-mediated recovery.
Validating WDR12 as a Potential Drug Target in Triple Negative Breast Cancer
Keywords: Breast Cancer
Drug Target
Triple negative breast cancer
WD 40 repeat
WDR12

Compared to other breast cancers (BC), triple negative breast cancers (TNBCs) confer lower survival and higher disease recurrence. TNBCs lack receptors targeted by current therapies, requiring new therapeutic target identification. Recently, the ribosome biogenesis protein WDR12 was identified as a potential target from RNAi databases. WDR12 belongs to the WD40-repeat family of scaffolding proteins, which have become interesting targets due to their druggable structure. I hypothesized that TNBC cell lines would be more sensitive to WDR12 knockdown (KD) due to their increased rate of ribosome biogenesis. WDR12 depletion led to decreased proliferation in all BC cell lines that could not be attributed to apoptosis or cell cycle arrest. Interestingly, WDR12 KD decreased nucleolar size to a greater extent in TNBC, indicating a potential role for WDR12 in ribosome biogenesis. In conclusion, WDR12 may be a promising therapeutic target in TNBC, although additional confirmatory testing will be required.
Impact of an Intra-Institutional Teledermatology Service: A Mixed Methods Case Study
Keywords: dermatology
e-health
teledermatology
telemedicine

While teledermatology is proven to decrease access times to dermatologists, be clinically equivalent to in-person consults diagnostically, and have high satisfaction rates, less is known about its use in urban settings where geographical challenges to accessing dermatologists are not present. This mixed-methods evaluation of an urban, intra-institutional teledermatology initiative was guided by the Canada Health Infoway Benefits Evaluation Framework and involved a case series review of 76 teledermatology consultations, patient and provider surveys, and semi-structured interviews with health care providers. The study found that 84.2% of all consultations and 95% of inflammatory conditions (rashes) were manageable with teledermatology alone, with benefits to patients including savings in time, money, and preventing missed work. Providers were also highly satisfied with the reliability, timely responses, and quality of consults, but their administrative time increased. Further research on cost-effectiveness and the specific clinical use cases that could be optimized by institutional teledermatology is warranted.
Efficacy of Three Supplementary Irrigation Protocols in the Removal of Hard-tissue Debris from the Mesial Root Canal System of Mandibular Molars
Keywords: hard tissue debris
isthmus
micro-computed tomography
multisonic irrigation
ultrasonically activated irrigation

Removal of accumulated hard-tissue debris (AHTD) by two ultrasonically-assisted and one multisonic irrigation systems was assessed with micro-computed tomography (micro-CT). Twenty-four extracted mandibular molars having two mesial canals connected by an isthmus and converging to a single foramen were selected. After preparation of the mesial canals with WaveOne Gold instruments (Dentsply Sirona Maillefer, Ballaigues, Switzerland), anatomically matched specimens were assigned to three final irrigation protocols (n=8): intermittent-ultrasonic (IU), continuous-ultrasonic (CU) and GentleWave (GW) system (Sonendo Inc, Laguna Hills, CA). Datasets of the micro-CT scans were co-registered and the percentage reduction of AHTD was statistically compared using one-way ANOVA and post-hoc Tukey tests with 5% significance level. Mean percentage reduction of AHTD in canals and isthmuses was significantly higher for GW (96.4% and 97.9%, respectively) than for CU (80.0% and 88.9%, respectively) (P
Ultrasound-mediated MiR-495 Delivery Improves Cardiac Remodeling and Left Ventricular Function Post Myocardial Ischemia/Reperfusion Injury
Keywords: Apoptosis
Cardiac remodelling
MiR-495
Myocardial ischemia-reperfusion injury
RUNX3
UTMD

The crucial regulatory role of miRNAs has been well stablished with respect to cardiovascular diseases. RUNX3 is a post-transcriptional factor that induces apoptosis in various cells. We hypothesize that miR-495 ameliorates myocardial ischemia/reperfusion injury by targeting RUNX3. In vivo, miR-495 was delivered using ultrasound-targeted microbubble destruction post myocardial I/R in 120 rats. MiR-495 and RUNX3 expression, and cardiac function were evaluated. In vitro, neonatal rat ventricular myocytes were transfected with miR-495 in hypoxia/reoxygenation condition. MiR-495 and RUNX3 expression was measured by PCR. Apoptosis was quantified using western blotting (Bim, Bcl-2, Bax, cleaved caspase-3 protein) and fluorescence-activated cell sorting. In vivo, miR-495 delivery resulted in overexpression of miR-495, downregulation of RUNX3, and improved cardiac function. In vitro, MiR-495-transfected cells demonstrated reduction in RUNX3, Bim, Bax, and cleaved caspase-3, and up-regulation of Bcl-2. FACS showed reduction of apoptosis. Our data indicate that miR-495 improves cardiac function by decreasing RUNX3 and apoptosis.
Thermal Spray Deposition of Metals on Polymer Substrates
Keywords: Electric Wire-Arc
Glass-Transition Temperature
Mechanical Surface Treatment
Metal Deposition
Metal-to-Polymer Adhesion
Thermal Spray

Aluminum and zinc were deposited using a twin-wire arc thermal spray torch onto smooth (Ra ~0.20 µm) and rough (Ra ~ 1.60 µm) samples of polytetrafluoroethylene (PTFE/Teflon®) and ultra-high molecular weight polyethylene (UHMW PE/ HDPE). Aluminum coatings did not adhere to the HDPE samples, however coatings roughly 300 to 400 µm thick were obtained on PTFE. Zinc adhered well to both surfaces. Adhesion tests and SEM imaging were performed to determine the strength and adhesion mechanism of the coatings. Increasing surface roughness enhanced coating adhesion strength. Additionally, deposition onto polymer substrates that were heated close to their glass-transition/softening temperatures resulted in increased adhesion strengths. SEM imaging suggested that mechanical interlocking increased with the metal onto a rough surface. Heating PTFE resulted in softening, increasing Interlocking, and the PE surface, with lower softening temperature, eroded by the impact of hot aluminum particles which removed the surface roughness and prevented adhesion.
Speech-in-Noise Perception in Older Adults: Impact of Emotional Semantic Valence and Clinical Depression
Keywords: aging
Auditory neuroscience
depression
emotional valence
Speech-in-noise

Depression influences and can be influence by interpersonal interactions, which rely on speech-in-noise comprehension. The semantic emotional salience of words may influence listening abilities in noise. This study examined the effects of emotional valence and depression on speech-in-noise comprehension in older adults (OA). Participants were 28 older adults (Mage = 72.75, SD = 5.93) with current depression (n = 9), remitted depression (n = 9), or healthy controls (n = 10). In an experimental-word-in-noise task, participants heard spoken words that were neutral, positive, or negatively-valenced. It was hypothesized that older adults with depression would show a reduction in the expected positive bias observed in healthy older adults on speech comprehension. No group differences were found in speech-in-noise comprehension ability in older adults. Across groups, there were main effects of signal-to-noise ratio and valence on EWIN task accuracy. Findings partially support a positivity bias in older adults, regardless of depression status.
Exploring Refinements to the GAC Minicolumn Test and the use of Surrogates
Keywords: Cyanotoxins
GAC adsorption
Surrogates

The results of this research suggest that more than 300 bed volumes are needed to ensure pseudo-steady state of minicolumns when spiked in post-flocculation Ajax water, while stable conditions were achieved by 100 bed volumes for most compounds in pure water. Additionally, the adsorption of several micropollutants at concentrations between 25 and 150 µg/L was not affected by competitive adsorption. Finally, the QQSAR model overestimated the adsorbability of macro-molecules such as cyanotoxins, making it inaccurate for surrogate identification purposes. However, the following compounds had very similar adsorption based on their percent breakthrough during minicolumn tests in post-flocculation Ajax water: microcystin-LA and acid red 14; microcystin-LR and sucralose; microcystin-LY and orange II sodium salt; microcystin-YR, -RR, and ketoprofen; anatoxin-a and resazurin.. Minicolumn and pilot-scale tests with these compounds under different experimental conditions are needed to validate their use as surrogates for the adsoption of cyantoxins by GAC.
Identification of Subpallial Neuronal Populations Across Zebrafish Larval Stages that Express Molecular Markers for the Striatum
Keywords: Enkephalin
Evolution
GABA
Striatum
Substance P
Zebrafish

Striatal neurons within the basal ganglia play a central role in vertebrate action selection; however, their location in larval zebrafish is not well defined. We assayed for conserved striatal markers in the zebrafish subpallium using fluorescent in situ hybridization (FISH) and immunohistochemistry. Whole mount FISH revealed an inhibitory neuronal cluster rostral to the anterior commissure that expresses tac1, the gene that encodes the precursor peptide for substance P. This molecular profile is shared by mammalian striatal direct pathway neurons. A second partially overlapping population of inhibitory neurons was identified that expresses penka, the gene that encodes the precursor peptide for enkephalin. This molecular profile is shared by striatal indirect pathway neurons. Immunostaining for substance P and enkephalin confirmed the presence of these peptides in the subpallium as well as the presence of dopaminergic innervation. The tac1 and penka populations were both found to increase linearly across larval stages. Together, these findings support the existence of a striatal homologue in larval zebrafish that grows to match the development and increasing behavioural complexity of the organism.
Kinetics of Roasting of Pyrrhotite
Keywords: Fluidized bed roasting
Metallurgy
Pyrrhotite
Reaction kinetics
Tailings
Thermogravimetric analysis

Pyrrhotite tailings are generated through the beneficiation of nickel ores in Canada, and are stored in shallow lakes where it presents serious environmental risks to the local environment. This thesis investigates the possibility of converting pyrrhotite into a valuable resource through the recovery of its Ni, Fe, and S content, specifically focusing on converting FeS to iron oxide through the application of a fluidized bed roaster. Thermogravimetric analysis was performed to study the kinetics of dead roasting pyrrhotite, determining that rate decreases with increasing particle size and increases with increasing PO2, correlating to a first order reaction. Bench scale fluidized bed roasting was determined to be a sufficient means of producing a low sulfur calcine, however, roasting time was found to be sensitive to particle size. In this set-up, pyrrhotite particles reacted following the unreacted shrinking core model. Lastly, a materials and energy balance was carried out to establish the basic parameters for roasting.
Testing the Resource Allocation of Dialysis Center at Scarborough Health Network
Keywords: Dialysis staff
Healthcare
Optimization
Resource Allocation

Nursing ratios are viewed as a significant contributor to the quality of care. They vary across health care facilities due to several factors, including patient numbers and workload policies. Identifying the optimal ratio holds the potential to improve both cost efficiency and patient experience. As home to the Central East Regional Nephrology Program, one of the highest demand communities in the province for nephrological care, it was felt that there might be a benefit in applying a pre-defined model at Scarborough Health Network, General Hospital. The model, which is tested on dialysis unit at Scarborough Health Network, deals with the nurses’ quantity in each timeslot; especially when complications arise with the patients (reactions to the treatment) or machines (technical issues). This model also optimizing patient schedules. The objective is to help dialysis units schedule their patients and minimize nursing costs while having enough nurses to maintain an adequate quality of service.
Tailored Electrospun Gas Diffusion Layers for Polymer Electrolyte Membrane Fuel Cells: Design and Durability
Keywords: electrospinning
gas diffusion layer
material degradation
polymer electrolyte membrane fuel cell
renewable energy
water management

The polymer electrolyte membrane (PEM) fuel cell is a versatile alternative for the decarbonization of the transportation sector. However, high cost and limited durability of materials hinder widespread adoption. This thesis comprises two studies that aim to address both cost and durability of PEM fuel cells via the design of tailored gas diffusion layers (GDLs). First, electrospinning is presented as a platform to fabricate and design tailored GDLs with pore size gradients for the improved high current performance of PEM fuel cells. Specifically, the novel graded GDL was found to reduce ohmic resistance and improve mass transport performance. Next, the durability of electrospun GDLs was investigated via an ex situ accelerated degradation procedure. The degraded GDLs exhibited reduced hydrophobicity due to loss of surface groups and reduced electrical conductivity due to carbon degradation. This thesis offers insight into designing next generation, durable GDLs with tailored structures for PEM fuel cells.
A Framework for the Integration of Models in Structural Design and Nonlinear Analysis for Performance-based Seismic Design of Buildings
Keywords: automatic model generation
model validation
nonlinear analysis
nonlinear modelling
performance-based seismic design
steel component modelling

The increasing application of Performance-Based Seismic Design to design and retrofit buildings has been possible due to ongoing research, growing computing power, and development of numerical models to simulate cyclic structural behaviour. Performance assessment through nonlinear structural analysis can be cumbersome due to the time and expertise needed to develop a nonlinear model, running analyses, and the subsequent data post-processing, which can prevent a broader adoption of the approach by engineers. Furthermore, the volume of information on nonlinear modelling of structural components is vast and widespread. This thesis explores the formulation of a computational framework for semi-automatic conversion of an elastic structural model, developed with a commercial platform, into a nonlinear analysis model. The conversion method allows the user to focus on choosing the most suitable model for the structural components involved, from a knowledge base built of component models, while avoiding cumbersome work when defining the model.
Emotion Regulation, Motives and Personality Risk for Cannibis Use Problems in Emerging Adulthood: A Person-centred Approach
Keywords: cannabis
emerging adulthood
emotion dysregulation
motivation
personality
substance use

Legalization of cannabis in Canada and parts of the United States has created a need for additional research on factors that contribute to cannabis problems among vulnerable populations, including emerging adults (ages 18 to 29 years of age). There is substantial evidence pointing to cannabis use motives, personality, and emotion regulation difficulties as important correlates of cannabis-related problems, however, there is little research integrating these factors. This study sought to examine the combined effect of cannabis use motives, personality, and emotion dysregulation in a North American sample. Participants were 126 emerging adults (ages 19-29, 38.1 % women). Using latent profile analysis, a four-group solution was extracted. Two high risk groups were identified, suggesting that different patterns of motives for use, emotion dysregulation, and neuroticism might have greater combined risk than in isolation, and may be useful targets for future approaches to preventing or treating cannabis use problems in emerging adulthood.
Functional Moderate to Severe Tricuspid Regurgitation in Adults undergoing Transcatheter Atrial Septal Defect Closure
Keywords: Atrial septal defect
Congenital heart disease
functional tricuspid regurgitation
Interventional cardiology
long-term outcomes
survival

Background: A large proportion of patients continues to have moderate to severe tricuspid regurgitation (TR) after transcatheter atrial septal defect (ASD) closure. Objective: To determine the clinical significance of functional TR in ASD patients and identify the baseline predictors of persistent TR after ASD closure. Methods: Clinical data were collected from hard-copy and electronic records at the University Health Network (UHN), Toronto, Canada. The clinical registry was linked to Ontario population-based health administrative databases. Results: Age ≥65 years, severe TR, and right ventricular systolic pressure (RVSP) were independent baseline predictors of persistent TR. ICES analyses showed patients with baseline moderate to severe TR (n=750) were not associated with higher cardiovascular mortality compared to patients with baseline mild/no TR (n=199) after adjust for cardiovascular co-morbidities. Conclusions: Perhaps offering early ASD closure or concomitant tricuspid valve intervention may be of benefit to patients at risk for persistent TR.
Corneal Neurotization Maintains Corneal Epithelial Integrity and Restores Nerve-derived Peptides in a Rat Model of Neurotrophic Keratopathy
Keywords: Corneal innervation
Corneal neurotization
Denervation
Nerve transfer
Neurotrophic keratopathy
Rat disease model

PURPOSE: Investigate effect of corneal neurotization on epithelial integrity and restoration of nerve-derived peptides in denervated rat corneas. METHODS: Three rat corneal conditions were assessed (n=45): denervation, denervation + neurotization, normal innervation. Corneal epithelial and stromal thicknesses were evaluated using Hematoxylin and Eosin staining. Corneal ulceration and perforation were assessed under a Wood’s lamp and normal light, respectively. Immunohistochemistry and western blot were used to evaluate Substance P (SP) and calcitonin gene-related peptide (CGRP) presence. RESULTS: Where significance is p
Electromagnet Design for a Time Varying Magnetic Flux Leakage System
Keywords: Electromagnet Design
Finite Element Modeling
Magnetic Flux Leakage
Nondestructive Testing

The aim is to design and build an optimized electromagnet for a time varying magnetic flux leakage (MFL) system that can operate within a frequency range of 0 – 10 Hz. The system will be used for the inspection of fuel storage tank floors. The advantage over DC systems is that the response of each frequency component would help in estimating the remaining plate thickness at a defect location; this is usually the main concern for fuel tanks. The electromagnet is designed with finite element modeling using COMSOL Multiphysics. Experimental results are compared with simulations and are used to validate the design. A prototype MFL system that utilizes the electromagnet is tested by inspecting steel plate samples with machined defects of different depths. Simulations are then used to demonstrate the ability of AC MFL to differentiate between defects that would be difficult to characterize with DC MFL alone.
Examining an Event-related Brain Potential Index of Semantic Priming in Cannabis-using Individuals at Clinical High-risk For Psychosis
Keywords: Addiction
Cannabis
Clinical high-risk
Event-related brain potential
Neurophysiology
Psychosis

Individuals at clinical high-risk (CHR) for schizophrenia experience subthreshold symptoms of this disorder, and cannabis use further increases their risk of conversion to psychosis. To seek neurophysiological evidence that cannabis use is associated with semantic processing deficits in the CHR state, we used the N400 event-related potential (ERP) to measure semantic priming. We recorded ERPs in 15 cannabis-using and 12 non-cannabis-using help-seeking CHR individuals, and 10 cannabis-using and 15 non-cannabis-using healthy controls while they viewed related and unrelated prime-target word pairs, at a short and a long stimulus-onset asynchrony (SOA). We observed no significant differences in N400 semantic priming between the four groups, but observed a trend towards deficits at the long SOA in all CHR participants compared to all controls (p = 0.07). The results suggest that CHR individuals experience semantic priming deficits similar to those of schizophrenia patients but that cannabis use does not further impair this process.