VictorJuiz/thesis huggingface dataset:
Existence of P/Q-type Calcium Channels in Chicken Presynaptic Nerve Terminals?

Transmitter release at fast-transmitting mammalian synapses are predominately gated by CaV2.2 and CaV2.1. This was primarily determined due to pharmacological characterizations of these synapses with high fidelity neurotoxins ω-conotoxin GVIA and ω-agatoxin IVA respectively. Similar pharmacological characterizations of 'lower' vertebrates such as birds led to the assumption that CaV2.2 was the predominant and possibly the sole CaV2. The recent finding that the zebrafish CaV2.1 was also sensitive to ω-conotoxin GVIA brings into question whether avian CaV2.1 and its role in transmitter release requires re-examination. We used both biochemical western blot approaches and immunocytochemistry to characterize recently generated anti-CaV2.1 antibodies and explored CaV2.1 localization to chicken presynaptic nerve terminals. Our results identified CaV2.1 in chicken presynaptic nerve terminals. Therefore, our work furthers our understanding of avian transmitter release and illustrates its conservation throughout vertebrates.

Keywords: CaV2.1
Chicken
Exon44
Immunocytochemistry
Presynaptic
Synaptosomes
Advisor: Stanley, Elise F
An In Vivo Study of the Musculo-Aponeurotic Architecture of Human Masseter Muscle

It has been suggested that architectural changes occur in masseter muscle (MM) in conditions of facial pain. To understand pathological changes, it is necessary to elucidate normal musculo-aponeurotic architecture. Muscle architecture is characterized by parameters including fiber bundle length (FBL) and height of aponeuroses. The purpose of this study was to investigate the architecture of MM volumetrically in 24 asymptomatic participants using ultrasound, in the relaxed and maximally contracted states. Masseter consisted of superficial (SH) and deep heads (DH), each arranged in laminae. Fiber bundles extended between superior and inferior aponeuroses and/or bone. Statistically significant differences were observed in mean FBL and in the mean height of aponeuroses between the relaxed and contracted states only in superficial laminae of SH. These results suggest there is differential contraction of the laminae of MM. Future comparison with pathologic subjects can be made based on the normative database established.

Keywords: aponeuroses
architectural parameter
fiber bundle length
masseter
muscle architecture
ultrasound
Advisor: Agur, Anne M.R.
Mechanisms Contributing to Suicidal Ideation: The Relationships Between Borderline Personality Disorder Symptoms, Gender, and Emotion Dysregulation

This study examined the relationships between gender, borderline personality disorder (BPD) symptoms, emotion dysregulation, and suicidal ideation. Emotion dysregulation was examined as a potential mediator in the relationship between BPD symptoms and suicidal ideation. The moderating role of gender in these relationships was also explored. Participants were a community sample of 101 adults experiencing BPD symptomatology. Assessments were completed at baseline, 6-months, and 12-months, and included diagnostic interviews as well as questionnaires on symptomatology and suicidality. Emotion dysregulation did not mediate the BPD symptom-suicidal ideation relationship when examining the full sample. The nonacceptance of emotional responses and lack of emotional clarity dimensions of emotion dysregulation emerged as significant mediators among females only. Impulsiveness was a significant mediator among males only. The results of this study provide insight into gender differences in mechanisms contributing to suicidal ideation among individuals with BPD symptoms and highlights potential gender-specific treatment targets.

Advisor: Uliaszek, Amanda A
The Recovery of Postural Control Following a Concussion in Adults from the General Population

Following concussion, dizziness and balance deficits are commonly reported symptoms. Although evidence in the athletic population exists, limited knowledge exists regarding balance deficits and recovery timelines in adults from the general population with concussion. Currently, the Balance Error Scoring System (BESS) is widely used for assessment of balance following a concussion in athletes. Limitations associated with the BESS have encouraged work using center-of-pressure (COP) metrics during quiet standing. This thesis determined balance deficits were present acutely following concussion (on average, 5-days post-injury) in self-reported symptoms, BESS score, and COP metrics. However, objective balance deficits did not accurately reflect self-perceived symptoms of balance problems or dizziness. When examining recovery longitudinally across 3-months post-concussion, limited recovery was observed in BESS score or COP metrics. This work highlights the importance of standardizing the assessment of postural control following a concussion. Future work should include measures of dynamic balance in the concussion assessment battery.

Keywords: Balance
Brain Injury
Concussion
Mild Traumatic Brain Injury
Postural Control
Advisor: Mochizuki, George
Oral inflammatory load and salivary flow rate in morbidly obese patients: relationship with diabetes and effect of bariatric care protocol

Obesity and diabetes promote periodontal disease (PD). The bariatric care protocol, which is a very-low-calorie diet (VLCD) followed by bariatric surgery (BSx), is an effective treatment for obesity and diabetes but little is known about its effect on oral health. Study objectives are: 1) to assess PD prevalence in obese subjects using oral inflammatory load (OIL); 2) to determine the difference in OIL and salivary flow rate (SFR) between obese patients with and without diabetes; and 3) to assess the effects of VLCD, BSx and bariatric care protocol on OIL and SFR. Findings suggest that, based on OIL, PD prevalence is similar to that reported in the literature. Both VLCD and BSx improve glucose metabolism and weight but have no impact on oral parameters. However, patients with low SFR at baseline are more prone to increased OIL post-surgery, suggesting a higher risk of developing PD.

Keywords: Bariatric surgery
Obesity
Optifast
Oral health
Periodontal disease
Very low calorie diet
Advisor: Allard, Johane P
Investigating Associations Between Preoperative Patient-Reported Symptom Burden and Postoperative Outcomes Following Major Cancer Surgery: A Retrospective Cohort Study

Patient-reported outcomes (PROs) are prognostic of long-term survival in cancer patients. However, their association with postoperative outcomes following major oncologic surgery is not well characterized. A retrospective population-based cohort study of rectal cancer patients undergoing neoadjuvant radiotherapy and proctectomy was conducted. Receiver operating characteristic analysis was used to select a scoring approach for the Edmonton Symptom Assessment System to define elevated preoperative symptom burden. Multivariable regression analyses were conducted to investigate associations between preoperative symptom scores and postoperative outcomes. High preoperative symptom scores were not associated with postoperative major morbidity (OR 1.28, 95% CI 0.84-1.97). However, high preoperative symptom scores were associated with prolonged postoperative length of stay (IRR 1.23, 95% CI 1.14-1.32), 30-day hospital readmission (OR 1.74, 95% CI 1.30-2.34), and 30-day post-discharge ED visits (OR 1.34, 95% CI 1.05-1.71). PROs can contribute important information for identification of patients at risk for increased healthcare utilization in the postoperative period.

Advisor: Karanicolas, Paul J
Assessing Velocity-Dependent Features of Post-Stroke Spasticity Using Robotic Assessment Methods

Spasticity is typically assessed by examining the velocity-dependence of resistance to passive movement; however, velocity-independent features may present in tandem. This thesis examined whether velocity-dependent and velocity-independent components were distinguishable in individuals with post-stroke spasticity. A retrospective analysis was conducted in which thirty individuals with stroke (13 with spasticity, 17 without) and 98 healthy controls were recruited. Using the KINARM Robotic Exoskeleton, each participants’ upper-limb was moved through range at two speeds. Velocity-reduction angle (kinematically-detected spastic catch), between-limb final angle, and between-limb peak velocity were the primary outcomes. Individuals with spasticity displayed a velocity-reduction angle, decreased range of motion, and increased tone. While a velocity-reduction angle was detected more frequently during fast stretch, final angle and peak velocity did not differ significantly across speeds. Individuals with stroke (with and without spasticity) were also characterized based on kinematic properties. These findings suggest velocity-dependent and velocity-independent impairments are detectable in individuals post-stroke.

Keywords: Kinematics
Robotics
Spasticity
Stroke
Advisor: Mochizuki, George
THE IMPACT OF IN UTERO EXPOSURE TO GESTATIONAL DIABETES ON INSULIN RESISTANCE IN THE OFFSPRING

Background: The evolution of increased cardio-metabolic risk in offspring exposed to maternal gestational diabetes (GDM) is not well understood. Purpose: (i) To evaluate the impact of GDM exposure on insulin resistance in early childhood, and (ii) To evaluate waist-to-height ratio as a surrogate measure of cardio-metabolic risk (CMR) in children under 5 years of age. Methods: A prospective cohort of infants born to mothers with and without GDM underwent metabolic characterization between birth and 5 years of age. Results: Among non-GDM children, male gender predicted a 35.1% lower HOMA-IR (p=0.03). In GDM offspring, a 1 unit increase in maternal insulin sensitivity predicted a 17.7 % decrease in HOMA-IR (p=0.002). Waist-to-height ratio was not superior in predicting CMR. Conclusions: There are no differences in IR of children with or without GDM exposure however the determinants of IR are different. BMI-z score is the preferred measure of adiposity in this age group.

Advisor: Hamilton, Dr. Jill
An Investigation into the Viability of Using Supplementary Visual Patterns for Improved Labelling

This thesis reports on an investigation into the use of visual patterns as a means of adding identifying features in order to supplement text based labelling. Perceptual characteristics of patterns/textures were reviewed and used as the basis for a first stage experiment aimed at testing whether patterns are able to provide any improvements in performance beyond traditional text labels in a visual search and identification task. Results indicate that the addition of patterns in the background of text-based labels significantly reduced search times, and improved identification confidence, with no apparent loss of accuracy. This suggests that patterns designed in accordance with human perceptual capabilities can reduce search times and potentially reduce the possibility of errors based on label misidentifications.

Keywords: Labelling
Texture
Visual patterns
Advisor: Milgram, Paul
Bitan, Yuval
Tamoxifen Therapy in a Murine Model of Myotubular Myopathy

X-linked myotubular myopathy (XLMTM), also known as myotubular myopathy (MTM), is a fatal pediatric congenital myopathy caused by loss-of-function mutations in MTM1 that is without existing therapy. MTM1 is a phosphoinositide 3-phosphatase that antagonizes class II and III phosphatidylinositol 3-kinases (PI3Ks) to modulate levels of endosome-specific phosphoinositides. MTM1 regulates endosomal trafficking, and proper formation of the skeletal muscle triad. Using a murine model of MTM, our lab has identified tamoxifen as a novel therapeutic candidate. Using several in vitro and in vivo studies and RNA sequencing, I demonstrate the aforementioned effects of tamoxifen to be mediated primarily through estrogen receptor signaling, and the post-transcriptional regulation of dynamin-2 (DNM2), a known MTM1 modifier. The preclinical evidence presented herein identifies and uncovers the FDA approved drug tamoxifen as the first small molecule therapeutic with pre-clinical efficiency and clinical translatability for use in MTM patients.

Keywords: Medical Genetics
Myotubular Myopathy
Neuromusuclar Disease
Paediatric Neurology
Therapy
Advisor: Dowling, James
Development of a 96-well Platform for the Bulk Production of Three-Dimensional Human Skeletal Muscle Microtissues

Skeletal muscle wasting is a largely untreatable condition wherein patients lose skeletal muscle strength, stamina, and protein content. We posit that the lack of skeletal muscle wasting treatments is due to the failings of existing skeletal muscle models. To address this problem, we developed a human muscle microtissue (hMMT) platform for bulk generation of reproducible, contractile, 3D hMMTs. hMMTs recapitulated key aspects of native human skeletal muscle, including muscle-specific protein expression, drug response, and contractility. Furthermore, the hMMT platform can non-invasively assess strength, and is exceedingly simple to fabricate. To illustrate hMMT platform utility, hMMTs were used with tumour-conditioned media to model cancer-associated muscle wasting in vitro. hMMTs were also used to screen chemotherapeutics, revealing that the drug irinotecan is toxic to human myofibers. Collectively, these results underline the considerable potential of the hMMT platform as a vehicle for skeletal muscle research and drug candidate validation.

Keywords: Drug testing
Skeletal muscle
Tissue engineering
Advisor: Gilbert, Penney M
Monitoring Ice Phenology and Characteristics in Mid-latitudes using RADARSAT-2

This study investigates the use of remote sensing for monitoring ice phenology and ice characteristics (ie. ice thickness). The primary data used were RADARSAT-2 images acquired over Central Ontario between 2008 and 2017. In order to monitor ice phenology, an automated threshold method was developed to identify freeze and melt events. During the 2015/2016 and 2016/2017 ice season 12 out of 17 identified freeze events and 13 out of 17 identified melt events were successfully validated. The radar determined dates were validated using in situ data, and visible remote sensing data. Temperature models and radar backscatter were used to estimate ice thickness in Central Ontario. The results of this analysis were validated using a combination of in situ measurements and data from a Shallow Water Ice Profiler (SWIP), correlation statistics for temperature models were >0.9 and an R2 of 0.6 was observed for backscatter models.

Keywords: Central Ontario
Lake Ice Phenology
Lake Ice Thickness
RADARSAT-2
Remote Sensing
Advisor: Brown, Laura C
Dreissena Fouling Control for Water Treatment Plants and the Investigation of a New Copper-based Molluscicide

Mussel macrofouling is a major concern for water treatment plants in the Great Lakes region, with the threat typically being controlled through seasonal pre-chlorination. Treatment facilities are now re-evaluating this strategy due to the transition from zebra mussels to cold-tolerant quagga mussels, infestations at certain facilities, and stricter disinfection by-product regulations. Two problems faced when looking for alternative strategies is limited mussel monitoring data to make decisions and the lack of alternatives to chlorination. This project addressed these deficiencies through the implementation of a series of plant-specific monitoring programs to quantify mussel infestation risks to re-evaluate seasonal treatment thresholds and to identify other fouling risks. In addition, a pilot scale study was undertaken to evaluate a new copper-based molluscicide called EarthTec QZ. The research also explored interactions of EarthTec QZ with downstream organics removal during coagulation, and with chlorination decay kinetics.

Keywords: copper
dreissena
Mussel
Quagga
Water Treatment
Zebra
Advisor: Hofmann, Ron
A Role for Adseverin in the Invasion and Migration of MCF7 Breast Adenocarcinoma Cells

Adseverin (ADS) is a Ca2+--dependent, actin-capping and severing protein that is upregulated in multiple cancers. Increased Ca2+ promotes ADS-dependent severing of subcortical actin filaments, enabling modifications of cell shape, a requirement for cancer cell invasion of the matrix. Suppression of ADS expression reduces migration and proliferation of metastatic cancer cells. I hypothesized that ADS involvement in subcortical actin remodeling enables changes of cell shape, motility, and invasive potential through extracellular matrices. I examined the effects of ADS expression on cancer cells by generating a CRISPR-Cas9 knockout (KO) cell line. Morphological characteristics and invasive potential were examined. KO of ADS altered cell morphology as seen by reduced cell extension formation and degradation of collagen. Three dimensional migration, but not two dimensional migration was inhibited by KO of ADS. I conclude that ADS promotes the formation of invasive cell structure, cell migration and metastasis.

Keywords: actin microfilament
adseverin
cancer migration and metastasis
morphology
remodeling
Advisor: McCulloch, Christopher
The Role of Interleukin-1 Beta in Mediating LPS-Induced Reverse Transendothelial Migration of Intimal Dendritic Cells

Intimal dendritic-like cells (DCs) reside in regions of the aorta predisposed to atherosclerosis. LPS and interleukin-1 beta (IL-1β) injections into C57BL/6 mice result in decreased numbers of intimal DCs due to their exit into the blood via reverse transendothelial migration (RTM). This study evaluated the role of IL-1b in RTM induced by intravenous LPS injection. IL-1β mRNA expression was rapidly upregulated in the intima by LPS. Experiments using genetic approaches (Il1b-/-, Casp1-/- and Il1r1-/- mice) and function-blocking antibodies demonstrated a critical role for IL-1b production and signalling in LPS-induced RTM. Reciprocal bone marrow transplantation experiments revealed that IL-1β production and signalling only in the non- hematopoietic compartment, likely endothelium, was critical. Ex vivo studies showed that IL-1b could rescue RTM in the Il1b-/- aorta, implicating sustained intimal IL-1b signalling. These data suggest that intimal IL-1β production and signalling in endothelial cells is required for LPS- induced RTM of intimal DCs.

Keywords: Dendritic Cell
Interleukin-1 Beta
Intima
Lipopolysaccharide
Reverse Transendothelial Migration
Advisor: Cybulsky, Myron
Jongstra-Bilen, Jenny
Effect of Pressure on Soot Morphology in Laminar Diffusion Flames

The effect of pressure on soot aggregate morphology in laminar diffusion flames, specifically pertaining to primary soot particle size and soot aggregate fractal parameters, was investigated in methane-air and nitrogen-diluted ethylene flames. Soot aggregate samples were collected by thermophoretic sampling within a high-pressure combusting chamber. Soot samples were imaged via transmission electron microscopy followed by an automated imaging detection method. The experiments covered pressures from 7 to 30 bar at vertical flame heights of 3, 6, and 8 mm in methane-air flames, and 3 to 6 bar at heights of 2, 5, 10, and 15 mm in nitrogen-diluted ethylene flames. It was observed that mean primary soot particle size increased with increasing pressure for both fuel types at virtually all flame locations. The fractal dimension was found to vary with pressure for both fuel cases, suggesting that a universal soot aggregate fractal value may not be justified in high-pressure flames.

Keywords: Combustion
Flame
Fractal
Soot
Advisor: Gülder, Ömer L.
Development of TCR-engineered iNKT cells for Cancer Immunotherapy

Invariant Natural Killer T (iNKT) cells are innate T cells that respond to lipid antigens presented by the molecule CD1d. Activated iNKT cells rapidly produce copious amounts of cytokines, activate/recruit other immune cells and have been implicated in tumour rejection and tumour immuno-surveillance. Here, our goal is to exploit iNKT cell antitumour properties in adoptive cell therapy and redirect their specificity towards tumour-associated antigens (TAAs) through T cell receptor (TCR) engineering. We hypothesize that TCR-engineered iNKT cells will be more effective than conventional CD8 T cells and provide long-term immunity.

Keywords: adoptive cell therapy
cancer
Immunotherapy
iNKT cells
innate immuninty
TCR-engineering
Advisor: Mallevaey, Thierry
A Cardiac Suspension Unit for Mitigating Thoracic Pressure in Postoperative Open-Sternal Newborns: A Heat Bed and X-Ray Compatible Design

Background Newborns with heart defects require surgery where immediate chest closure may not be possible. Cardiac suspension applies chest-wall traction to mitigate complications but is limited by its unquantified tension, lack of X-ray compatibility, and aesthetic. A designed tensioner unit may resolve these challenges. Methods Design requirements are established by chart-review and surveying. Subsystems are evaluated though analytics, FEA, and experimentation. The device is assessed for rigidity, transmission, heat transfer and radiolucency. Results Patient data is presented, design requirements are established, and a cantilever design is selected. The framing achieves fixation but with slight deflection. A compensator and non-backdrivable input are developed for the wire system. Transmission friction losses are noted. EB beam modelling identifies Ultem for the cantilever design. Significance This research presents the first investigation into the cardiac suspension technique. A prototype was designed, built and tested, and is a strong step towards improving cardiac suspension.

Keywords: Cardiac Suspension
Delayed Sternal Closure
Multivariate Design
Neonates
Non-backdrivable
Tensioner
Advisor: Forte, Vito
Andrysek, Jan
Mapping Inequalities of Access to Employment and Quantifying Transport Poverty in Canadian Cities

Millions of Canadians rely on public transportation to conduct daily activities and participate in the labour force. However, many are disadvantaged because existing public transit service does not provide sufficient access to destinations. Limited transit options, compounded with socioeconomic factors like not having a private vehicle, can result in transport poverty, limiting travel to important destinations, like employment opportunities. Accordingly, the objective of this thesis is to develop accurate measures of accessibility to examine the degree to which the Canadian urban population can reach employment opportunities via public transit. These measures are used to analyze inequalities in accessibility with respect to socioeconomic status and estimate where, and to what extent, Canadians are at risk of transport poverty. This knowledge is able to inform policy aimed to increase transit ridership, reduce inequalities of transit accessibility, and limit transport-related barriers to activity participation.

Keywords: accessibility
inequalities
public transit
spatial analysis
transport poverty
urban systems
Advisor: Farber, Steven
The Role of SHP2 in Regulating Fibroblast Senescence and HER2-positive Breast Cancer

Src-homology-2 domain-containing phosphatase 2 (SHP2), encoded by the PTPN11 gene, is highly conserved across metazoans. SHP2 contains two SH2 domains, a protein-tyrosine phosphatase (PTP) domain and a C-terminal tail. SHP2 is required for full activation of the MAPK pathway by most receptor tyrosine kinases (RTKs). However, the key substrates that mediate the biological effects of SHP2 remains largely unknown. In an attempt to elucidate the mechanisms by which SHP2 activates the ERK MAPK, I discovered that SHP2 plays a key role in cell senescence. In the first part of this thesis, I summarize the experiments showing how SHP2 executes its role in senescence induction. In the second part of the thesis, I investigated the role of SHP2 in the initiation and/or maintenance of HER2+ breast cancers and presented evidence showing SHP2 might be a promising target for HER2+ breast cancer treatment.

Advisor: Neel, Benjamin