VictorJuiz/thesis huggingface dataset:
Vascular Injury Hospitalization Trends in Ontario: A Population-based Study
Keywords: vascular injury, Ontario, population-based study

A retrospective, population-based, cross-sectional time series analysis was performed utilizing Ontario&rsquo;s administrative claims database to examine vascular injury temporal trends between 1991 and 2010. The overall trend in the annual rate of vascular injury-related hospitalizations in Ontario shows a slight but statistically significant decline over the study period (p&lt;0.01). Vascular injury events were higher among young males and rural areas with low-income population. The upper limb was the most common site of injury. Transport associated vascular injuries accounted for only 22%, leaving the majority with other mechanisms of injury. However, hospital mortality was 5.5% for all vascular injury admissions with high rates among seniors with thoracic and abdomen blunt injuries. Vascular injuries were highest during June, July, and August in a regular pattern over the study period. Such findings provide a broad image with important preliminary and supplementary public health and clinical oriented implications for injury management and prevention strategies.
Corrosion of Copper in Concentrated Aqueous Chloride Under Anaerobic Conditions
Keywords: Copper
Anaerobic corrosion
Concentrated chloride

Canada’s plan for the long-term disposal of nuclear waste fuel is an approach called Adaptive Phased Management. It includes a two-vessel design for the nuclear waste containers that will be buried in the deep geological repository and kept safe for about a million years. Copper has long been considered as the outer shell of these waste containers. It shows a good resistance to corrosion and in regards to other noble metals (Pd and Pt) is less expensive. Corrosion of copper under simulated geological repository conditions is studied in this work. It was shown than thermodynamically, copper corrodes in the absence of oxygen and presence of high concentrations of chloride. However, its rate of corrosion is less than 10 nm/yr, which makes it a suitable candidate for the used fuel containers.
Novel Treatment of Colonic Dysplasia with an Oncolytic Vaccinia Virus
Keywords: oncolytic virotherapy
oncolytic virus
oncolytic vaccinia virus
vaccinia virus
vvDD
double deleted vaccinia virus
vvDD-RFP
biotherapeutic
adenoma-carcinoma sequence
adenomatous polyps
adenoma
precancerous
benign
dysplasia
colonic dysplasia
azoxymethane
dextran sodium sulfate
complex polyps
colorectal polyps
intracolonic delivery
colorectal cancer

Colonic dysplasia is a non-invasive intraepithelial neoplastic process that can eventually become cancer. Novel therapies are needed for dysplastic lesions not amenable to standard treatment. Oncolytic viruses selectively kill tumours, but the effect on dysplasia is unknown. This study determined if oncolytic vaccinia virus (vvDD) infects colonic dysplasia. After chemically inducing colonic dysplasia, mice received intraperitoneal (IP) or intracolonic (IC) vvDD expressing red fluorescent protein (vvDD-RFP) or control. RFP signal was apparent at 24h post-virus infection (pvi), peaking at 72h (IC) and 120h (IP) pvi. vvDD-RFP infected high-grade dysplasia more so than low-grade dysplasia; normal tissue was unaffected. vvDD-RFP infected larger surface areas of dysplasia when administered IC than IP. Viral titres peaked earlier and higher with IC than IP delivery. vvDD-RFP-treated mice had less polyps and dysplasia and had higher survival rates than mock-treated animals. This study suggests that oncolytic virotherapy may have a role in treating colonic dysplasia.
A Genetic and Pharmacological Response to Improve Radiation Response
Keywords: Oncology
Ionizing Radiation
Radiation Therapy
Hypoxia
AMPK
Metformin

Radiotherapy (RT) is one of two most effective treatments undertaken by 50% of cancer patients in a curative and palliative setting. However, 10-30% of patients, dependent on the tumor site, experience minimal RT response. Novel methods of improving RT response are clearly necessary. Since both radiation-activated proteins and low tumor oxygenation may negatively influence treatment response, we predicted that they represent important targets to enhance tumor radiation-sensitivity. Through this dissertation, it is demonstrated that radiation response can be enhanced through genetic disruption of adenosine mono-phosphate protein kinase (AMPK), a RT- activated protein, in-vitro, and acute pharmacological administration of metformin, a respiratory inhibitor which improves tumor oxygenation, in-vivo. Both interventions increased radiation- response under conditions of poor nutrient availability, which mimics the tumor microenvironment clinically. Therefore, genetically targeting AMPK and administration of metformin independently demonstrate clinical potential in improving radiation response as a consequence of microenvironment-mediated, contextual synthetic lethality.
Nuclear Localization of N-Ethylmaleimide Sensitive Factor
Keywords: N-Ethylmaleimide Sensitive Factor
SNARE Disassembly

N-Ethylmaleimide Sensitive Factor (NSF) was first characterized as the protein responsible for restoring vesicle trafficking to N-ethylmaleimide (NEM) treated cells. Diverse lines of evidence indicate that NSF may function in the nucleus of cells, a previously unknown site of action for the protein. In this study Chinese hamster ovary (CHO) cells were used to examine the cellular localization of NSF in fibronectin-spread cells and in cells treated with NEM and leptomycin B (LMB). We show that NSF localizes to the nuclei of several cell lines and cell types and shows variability in the level of nuclear localization during cell spreading and drug treatments. Additionally, we have identified three putative nuclear export sequences (NES) within the NSF-D2 domain. Furthermore, immunoprecipitation identified Vimentin as a likely nuclear binding partner. Thus, for the first time, we report nuclear localization of NSF and an uncharacterized interaction of NSF with Vimentin.
Murine Model of Autoimmune Hemolytic Anemia: Red Blood Cell Clearance Mechanisms and Treatment Efficacy
Keywords: autoimmunity
red blood cell
anemia
antibody

Antibodies against erythrocyte-specific antigens can cause immune red blood cell (RBC) destruction, resulting in autoimmune hemolytic anemia (AHA). Therapy for patients with AHA remains a challenge, and better knowledge of pathophysiological mechanisms is needed. In this thesis, the mechanisms of RBC clearance mediated by a panel of monoclonal anti-mouse RBC antibodies were characterized in a murine model of passive AHA, and efficacy of treatments was evaluated. It is demonstrated herein that mechanisms in addition to the classical macrophage Fcγ receptor (FcγR)- and/or complement-mediated hemolysis may be contributing to the development and/or persistence of anemia. The efficacy of intravenous immunoglobulin (IVIg) therapy varies in relation to the mechanism of anemia in mice with FcγR-mediated anemia being highly related to IVIg responsiveness. In addition, this thesis shows that monoclonal RBC-specific antibodies can ameliorate thrombocytopenia in a murine model of passive immune thrombocytopenia (ITP) analogous to the use of anti-D in ITP patients.
A Question of Change: Conceptions of Knowledge, Practices and Disability Studies
Keywords: disability studies
change
practices
metaphor
Haraway
knowledge
blindfulness

Academic fields of study are inscribed with taken-for-granted meanings, practices, and ways of articulating them. Critical disability studies is no different. How is it possible, then, to be creative and effect change when scholars are restricted by the same limitations and practices that typically do little more than reproduce more of the same? Working within sociology and equity studies, I proceed with two assumptions: meanings are intersubjectively created; and ideologies are embedded within practices. Emphasizing embodiment, reflexivity and personal narrative, I use an interpretive approach and a disability studies lens to explore the relation of conceptions of knowledge and change through the everyday practices of knowledge production. The thesis focuses on scholarly practices as sedimented ways of thinking and doing that can be shifted by reorienting in various manners in order to move from taken-for-granted conventions (that entail a standpoint) to a change in consciousness and new knowledge.
Role of Cystic Fibrosis Transmembrane Conductance Regulator and Sphingolipids in Hypoxic Pulmonary Vasoconstriction
Keywords: Hypoxic pulmonary vasoconstriction
CFTR
sphingolipids
TRPC6

Hypoxic pulmonary vasoconstriction (HPV) optimizes ventilation-perfusion matching in the lung. As cystic fibrosis patients suffer from ventilation-perfusion mismatches, we probe for a potential role for cystic fibrosis transmembrane conductance regulator (CFTR) in HPV. HPV in isolated mouse lungs is attenuated by CFTR inhibition or deficiency. In cultured human pulmonary artery smooth muscle cells (PASMC), CFTR inhibition blocks the hypoxia-induced [Ca2+ ]i increase and the caveolar translocation of transient receptor potential canonical 6 (TRPC6) channels. We also identify novel roles for sphingolipids in HPV. Ceramide production by neutral sphingomyelinase (nSMase) is required for TRPC6 translocation, and sphingosine-1-phosphste (S1P) signalling through S1P receptor 2 activates caveolae-associated TRPC6. Yet pulmonary vasoconstriction and TRPC6 translocation in response to exogenous nSMase are blocked by CFTR inhibition. CFTR function is likely required for TRPC6 trafficking or membrane stabilization, as CFTR associates with TRPC6 during hypoxia, which can be disrupted by CFTR inhibitor.
Enhancing Spatial Awareness with Multi-camera View Synthesis for Diagnostic and Manipulation Tasks
Keywords: Engineering Psychology
Human Factors

View synthesis is a technique used to generate novel views from input images captured from separate viewpoints. I have explored the use of this technique for motion parallax displays in surgical endoscopy by developing real-time interpolation software (especially for use with a three-camera endoscopic tool), and by conducting a perceptual experiment with 16 novice participants to determine the benefits of such a display in a surgical-like occluded relative-depth discrimination task. ‘Noisy-edged’ objects are proposed to aid in elimination of the relative size cue for such an investigation. Results indicate that participants performed significantly better using a motion parallax display as compared to alternate or simultaneous presentation of multiple images, and subjective rankings of display difficulty corroborate this finding. Participant interpolation control tendencies were analyzed, showing that strategies involving lengthier movement times produced higher performance. These motion parallax display benefits also pertain to similar tasks in a variety of applications.
Blood Pressure Responses to Physical and Mental Challenges in Adolescent Males and Females
Keywords: blood pressure
blood pressure reactivity
adolescence
genetics
hypertension
obesity
sex
visceral fat

Enhanced blood pressure (BP) reactivity from stressors predicts hypertension, a disease more common in men than women throughout their reproductive age. Visceral obesity and genetic predisposition are major risk factors for hypertension. Here, we investigated whether visceral fat (VF) and one of the best-established loci of hypertension, CYP17A1, contribute to the sex difference in BP reactivity. In a community-based sample of 596 adolescents, we measured beat-by-beat BP during posture and math-stress tests, quantified visceral fat with magnetic resonance imaging, and genotyped all subjects at CYP17A1. Adolescent males versus females demonstrated greater BP reactivity to physical and mental stressors. In males but not females, VF was associated with higher BP reactivity to active standing and a specific variant of CYP17A1 was associated with higher BP reactivity to math stress. VF and CYP17A1 contribute to the observed sex-differences in BP reactivity.
3D Tracking of Anti-predator Behaviour in Guppies
Keywords: 3D tracking
guppy
schooling
shoaling
anti-predator behaviour

Guppies from high- and low-predation habitats are well known for the differences in their anti-predator behaviours. However, little has been reported on the differences between social versus asocial stimulus responses. In this study, we conducted a detailed analysis of shoaling and other anti-predator behaviours of guppies from two populations, in pairs and as single fish, in three dimensions. Using custom programs in MATLAB, we quantify the behavioral responses before shoaling and during its dissipation. Our 3D reconstruction allowed us to track the inter-fish distance, velocity and orientation of both fish. Our results demonstrate a positive correlation between the relative orientation of the fish and the interfish distance, for pairs from the high-predation population. We also report that the anti-predator behaviour of guppies is comprised of the following sequence: freezing, darting/skittering, and recovery to pre-stimulus swimming behaviour. Upon repeated encounters with the stimulus, a reduced shoaling and anti-predator response was observed.
Characterizing the Role of RhoGAP19D in Drosophila Epithelial Development
Keywords: Cell Polarity
Development
Drosophila

The establishment and maintenance of epithelial polarity is dependent on polarity regulators. One such polarity regulatory is Bazooka (Baz). Baz is located around the apical circumference, serving as a cytosplasmic scaffold to assemble adherens junctions. In vitro analyses presented RhoGAP19D as a potential Baz-interacting protein. RhoGAP19D’s homologs have been linked to the actin cytoskeleton and the PAR complex through the RhoGTPase CDC42. To study RhoGAP19D’s functions, a GFP-tagged RhoGAP19D was made. This construct was expressed in the Drosophila embryonic ectoderm and follicular epithelium. It localized to the apical circumference with enrichment at Baz-puncta and actin-rich locations, but its main localization mechanism appears to be independent of Baz. Gain-of-function and loss-of-function analyses for RhoGAP19D revealed phenotypes consistent with it being an inhibitor of the PAR complex and the actin cytoskeleton. Thus, I hypothesize that RhoGAP19D regulates Drosophila epithelial polarity by inhibiting the PAR complex and the actin cytoskeleton by inhibiting CDC42.
The Role of Attachment Avoidance in Social Comparisons between Romantic Partners
Keywords: romantic relationships
social comparisons

Recent literature suggests that individuals respond more positively when outperformed by their partner (an upward comparison) than when they outperform the partner (a downward comparison). In some cases, however, individuals may respond negatively to a superior partner. In two studies, I examined attachment avoidance as a moderator of social comparison outcomes: I predicted that avoidant individuals would respond more negatively to upward than downward comparisons by distancing themselves from the partner (reducing closeness) and disengaging from the relationship (reducing commitment). In Study 1, attachment avoidance moderated comparison direction’s impact on closeness: Avoidant participants reported less closeness, especially after encountering a superior partner. Study 2 replicated Study 1’s findings and found that avoidant individuals reported less commitment after an upward comparison, but only in the organizational domain. Thus, not all individuals respond positively to upward comparisons with their partner; for avoidant individuals, upward comparisons may be harmful to their relationship.
The Effect of Enhancing Prototype Salience on the Accuracy of Categorizing Sexual Orientation from Faces
Keywords: person perception
sexual orientation

Recent literature in person perception suggests that sexual orientation and other perceptually-ambiguous group memberships could be discerned from faces with accuracy exceeding chance levels. No study to date has explored the question of how people acquire mental representations of sexual orientation, however. In Study 1, I show that the perception of sexual orientation is distinct from that of obvious group memberships. Then, I show that people can learn prototypical representations of sexual orientation to increase their sensitivity to artificially-generated stimuli (Study 2) and to actual faces (Study 3). Last, I demonstrate that this improvement is a product of participants’ attunement to the patterns of facial features in the prototypes of the two categories. Together, the results demonstrate that people can learn mental representations of sexual orientation through exposure to environmentally relevant stimuli. Furthermore, the studies provide insights about how the mind learns social categories more generally.
Fecal Microbial Composition in Relation to Diet and Body Mass Index
Keywords: Gut microbiota
Fecal Archaea
BMI
Diet
Adiposity
Microbial composition

Emerging evidence from animal and human studies has indicated a potential link between a certain pattern of gut microbiota and adiposity. In the current study, the relationship between gut microbial composition and BMI was further investigated in human with the incorporation of macronutrient consumption and quantification of methanogenic Archaea. BMI was found to be negatively associated with the amount of fecal Bacteroides/Prevotella, E. coli and total bacteria. The intake of carbohydrate and dietary fiber were negatively associated with the amount of C. coccoides, and polyunsaturated fat intake was inversely correlated with the amount of fecal C. leptum, Bacteroides/Prevotella, and total bacteria. Fecal Archaea measured by breath CH4 was positively associated with the amount of fecal E.coli but negatively associated with C. coccoides and log Firmicutes/Bacteroidetes ratio. In conclusion, our findings suggest that fecal bacterial composition is associated with BMI, diet and fecal Archaea.
The Effects of Helicobacter pylori Infection on Dendritic Cells
Keywords: H. pylori
STAT3
dendritic cells
Helicobacter pylori

Helicobacter pylori infects the human gastric mucosa and induces a chronic gastritis that does not eliminate the pathogen. H. pylori infection is the primary risk factor for gastric cancer development. The host immune system is crucial for both bacterial elimination and tumor surveillance. The interaction between H. pylori and dendritic cells (DC), key orchestrators of the host immune response, was examined. H. pylori activated the Signal Transducer and Activator of Transcription 3 (STAT3) pathway, assayed using immunoblotting, in bone marrow-derived DCs. This blunted DC maturation, determined by CD86 and MHC II expression, in an autocrine/paracrine IL-10-dependent pathway. H. pylori infection stimulated the production of cytokines including IL-10, IL-12p40, and TNF-α as determined using ELISA and multiplex analysis. DC co-culture with T cells did not drive regulatory T cell development. These results demonstrate that H. pylori blunts DC maturation, which may play an important role in promoting bacterial persistence and disease.
Genome-wide Association Study of Fat intake in Adolescence
Keywords: Fat intake
Obesity
Genome-Wide Association Study
Opioid receptor mu 1 gene

Dietary preference for fat, which increases risk for obesity, is a complex behavior regulated in part by the brain-reward system. We conducted a genome-wide association study (GWAS) to search for loci associated with relative fat intake in 598 adolescents (12-18 years) who were recruited from the French-Canadian founder population. The GWAS identified a locus in the μ-opioid receptor gene (OPRM1, rs2281617, p=5.2x10-6), which encodes a receptor expressed in the brain-reward system and which has been shown previously to modulate fat preference in animals. The minor OPRM1 allele appeared to have a “protective” effect: it was associated with lower fat intake and lower body-fat mass, In addition, OPRM1 was associated with relative fat intake in an independent sample of 490 young adults. In summary, OPRM1 may modulate dietary preference for fat and hence the risk for obesity. Further studies are required to confirm our findings.
Towards Examining FGF21 Secretion from Pancreatic Islets in a Microfluidic Device
Keywords: Diabetes
Microfluidics

Type II diabetes is characterized by impaired insulin-secretion from pancreatic β- cells. A novel endocrine factor, fibroblast growth factor 21 (FGF21) is produced by the liver and improves pancreatic β- cell function and survival. However, a state of FGF21- resistance has been described in obese mice and humans. This thesis examines (1) whether pancreatic islets temporally express FGF21 and (2) if high glucose and fat reduce transcript expression of FGF21 receptors in islets. This thesis further characterizes a novel microfluidic device that will be used to collect and assay FGF21. Our data indicate that palmitate induces maximal production of FGF21 mRNA in β- cells after 16 hours of stimulation through PPARγ. Secondly, we report that FGF21, glucose and palmitate do not cause FGF21-resistance by down-regulating receptor expression. Overall, we present a mechanism for the induction of FGF21 from islets, and describe a microfluidic device for culture and secretion studies.
NCS-1 Protein upregulation Facilitates Chronic Hypoxia-induced Respiratory Adaptation in Lymnaea stagnalis
Keywords: Hypoxia
NCS-1
Calcium binding protein

Chronic hypoxia is a consequence of many common diseases, including sleep apnea and chronic lung disease. As there is no cure for many of these diseases, managing the symptoms of these diseases, including hypoxia is of great clinical importance. Preliminary data from the Feng lab show that the calcium binding protein neuronal calcium sensor-1 (NCS-1) is upregulated in the central nervous system of the freshwater pond snail Lymnaea stagnalis following chronic hypoxia treatment. This upregulation coincides with increased aerial respiratory activity. Furthermore, knockdown of NCS-1 attenuates hypoxia-induced facilitation of aerial respiration. Since this aerial respiratory activity is controlled by a respiratory central pattern generator (rCPG), it is hypothesized that hypoxia-induced upregulation of NCS-1 may regulate rCPG activity. Using intercellular sharp electrode recording, I show that in response to chronic hypoxia treatment, there is increased bursting activity and altered action potential profile in the pacemaker neuron of the rCPG, RPeD1. Knockdown of NCS-1 partially prevents these hypoxia-induced changes. Our findings suggest that NCS-1 upregulation is necessary for chronic hypoxia-induced respiratory adaptation.
The Role of Chloroplast Localized Molecular Chaperone HSP90 in Arabidopsis thaliana Development
Keywords: HSP90
Arabidopsis
Chloroplast
co-suppression
Development
Chaperone
Heat shock protein
PsbO1
yeast two-hybrid
oxygen-evolving enhancer protein 1
chloroplast HSP90

Heat shock protein 90 (HSP90) is a molecular chaperone and it has been implicated in late stages of de novo protein folding. In Arabidopsis thaliana, there are seven HSP90 isoforms. In this project, the function of chloroplast-localized AtHSP90.5 was studied by analyzing transgenic plants overexpressing AtHSP90.5FLAG. In addition, three independent transgenic lines showing AtHSP90.5 co-suppression were identified to have an albino phenotype in photosynthetic tissues along with stunted plant growth, reduced vegetative leaf size, and malformation of thylakoid membranes. Furthermore, potential AtHSP90.5 co-chaperones and client proteins were screened via yeast two-hybrid and affinity purification coupled with mass spectrometry, and nine potential AtHSP90.5 interactors were obtained. A novel client protein of AtHSP90.5, PsbO1 (Oxygen-evolving enhancer protein 1), was identified by yeast two-hybrid. The interaction between HSP90.5 and PsbO1 was further investigated and a putative role of AtHSP90.5 in promoting PsbO1 folding and targeting to thylakoid lumen is proposed.