VictorJuiz/thesis huggingface dataset:
Microfluidic Selection of Spermatozoa Based on Total Progressive Motility and Wall-swimming Behaviour

Worldwide, 9% of couples encounter fertility problems, seeking medical assistance from assisted reproductive technologies (ARTs). Unfortunately current spermatozoa selection techniques required for ARTs have evolved little in 40 years, and depend heavily on the clinician&rsquo;s ability to manipulate and select spermatozoa for fertilization. Microfluidic devices have emerged as a potential solution to selecting viable spermatozoa for ARTs. A challenge to current microfluidic approaches is that they require extensive equipment in order to achieve the flow needed to separate the spermatozoa. In this thesis a microfluidic device was used to compare high viscosity buffers to create an environment that more closely resembles the female reproductive tract. Microfluidics was also employed to select spermatozoa using wall-swimming behaviour. The findings showed that selecting left and right wall-swimming spermatozoa will yield better DNA integrity than the traditional Percoll centrifugation technique. Both bovine and human spermatozoa were utilized throughout this thesis.

Keywords: microfluidics
sperm selection
wall-swimming
assisted reproduction
ART
methyl cellulose
hyaluronic acid
DNA integrity
Advisor: Sinton, David
Justice and Starvation in Cambodia: International Criminal Law and the Khmer Rouge Famine

Recently, an interdisciplinary discourse has emerged concerning the suitability of international criminal law as a legal response to severe famine. Despite this discourse, the topic of famine has received scant attention within actual international criminal law practice. This thesis scrutinizes this prosecutorial gap by considering whether former Khmer Rouge leaders could likely be successfully prosecuted for international crimes predicated on the catastrophic famine that occurred while the Khmer Rouge held power in Cambodia from 1975-1979. To do so, a detailed history of the Khmer Rouge period famine is developed and subsequently analyzed according to current formulations of international crimes. This analysis concludes that former Khmer Rouge leaders could likely be prosecuted for crimes against humanity, specifically those of extermination, persecution and other inhumane acts, predicated on their roles in enforcing famine conditions while in power.

Keywords: International criminal law
famine
starvation
international criminal justice
crimes against humanity
Khmer Rouge
Advisor: Brunnée, Jutta
To Do It or Not to Do It? The Role of Communal Motivation in Sexual Decision Making

In long-term romantic relationships, sexual satisfaction and sexual frequency are key to maintaining relationship satisfaction and stability. However, very little research has investigated how couples actually make decisions about whether or not to engage in sex on a day-to-day basis. Across two studies, a hypothetical scenario study and a daily experience study, we found that sexual communal strength ¬¬¬̶ the degree to which one is motivated to meet their partner’s sexual needs ¬¬¬̶ predicts decreased motivation to avoid the costs to the self of engaging in sex, as well as increased motivation to accrue benefits to the partner of engaging in sex. In turn, this predicts greater willingness to engage in sex, as well as greater sexual and relationship satisfaction for both partners. Greater sexual communal strength influences the sexual decision making process, with positive consequences for both partners in the domain of sexuality, and in relationships more generally.

Keywords: Sexuality
Communal Motivation
Advisor: Impett, Emily
The Role of Septin in Ciliogenesis

Septins are an evolutionarily conserved family of proteins that have recently been implicated in the formation of primary cilia. Work in our lab has shown that SEPT9 binds and activates a specific guanine nucleotide exchange factor for Rho, SA-RhoGEF, to promote Rho activation. Interestingly, SA-RhoGEF is localized to the basal body, raising the possibility that SEPT9-SA-RhoGEF interaction may be important in ciliogenesis. We therefore depleted SEPT9 expression in hTERT-RPE1 cells, and noticed significant shortening of the cilia upon SEPT9 depletion. We were able to rescue this phenotype by targeting either a constitutively active truncation of SA-RhoGEF, or a full length SEPT9, to the basal bodies. Our study suggests that SA-RhoGEF activity is involved in the formation of the cilia, and SEPT9 is required to interact with SA-RhoGEF at the basal body in order to achieve adequate RhoA activation.

Keywords: septin
primary cilium
ciliogenesis
Advisor: Trimble, William
Improving the Mechanical Properties of Irradiation-sterilized Bone

Bone allografts are used in orthopaedic reconstruction of defects resulting from trauma, bone cancer or infection. Gamma-irradiation sterilization is a safety measure; however it damages the tissue, specifically the organic component, and embrittles bone. This research investigated the effect of ribose pre-treatment on the mechanical properties of ribose-modified irradiated bone. The overall goal was to develop a method for improving toughness of irradiation-sterilized bone by modifying collagen with a ribose treatment prior to/during irradiation. Bulk mechanical properties and fracture properties were evaluated. Collagen characterization techniques were used to further understand the collagen alterations and suggest toughening mechanisms. We have shown it is possible to recover some of the mechanical properties of &gamma;-irradiated bone as well as collagen thermal stability and connectivity using our ribose pre-treatment. We propose that the recovery of collagen connectivity leads to functionally significant recovery of toughness, fracture toughness and strength.

Keywords: bone allograft
biomaterials
Advisor: Willett, Thomas
Grynpas, Marc
Does Location Matter? How Neighbourhoods Influence Out-of-hospital Cardiac Arrest Outcomes

Out-of-hospital cardiac arrest (OHCA) is a life-threatening emergency. Research from other disciplines has suggested that location is a strong determinant of health outcomes. Therefore, the objective of this thesis was to determine the role of neighborhoods in OHCA. We hypothesized that neighbourhood factors are associated with: survival to hospital discharge, a return of spontaneous circulation (ROSC) at emergency department (ED) arrival, and provision of bystander cardiopulmonary resuscitation (CPR). This thesis demonstrates that for the most part neighbourhood inequalities were not associated with outcomes. This thesis confirmed that, while the Utstein variables account for a large portion of patients who survive, they poorly account for patients who had a ROSC at ED arrival or received bystander CPR. Inclusion of neighbourhood factors to the Utstein variables significantly improved discrimination for survival and a ROSC at ED arrival, but not bystander CPR. Future research should determine what additional factors could predict outcomes.

Keywords: Cardiac arrest
Cardiopulmonary resuscitation
geographic information system
emergency medicine
emergency medical services
public health
Advisor: Morrison, Laurie J
The African Brain Drain and the Social Impact of Skilled Migration

The rapid rate at which educated Africans are migrating to the West has garnered much attention among scholars and has been termed ‘brain drain’. This thesis presents two arguments. First, understandings of brain drain from the African continent must be rooted in a historical context. The problems that the continent faces today have been shaped by key historical events including slavery and colonialism. Secondly, the impact of brain drain extends beyond the cost-benefit analysis related to remittances and loss of investments to the countries involved. Brain drain has significant social impacts on African immigrants in the diaspora. As such, it is important to highlight some of the triumphs and challenges that characterize the migrant experience.

Keywords: Africa
brain drain
social impact
skilled migration
slavery
colonialism
anti-colonial thought
historical context
professionals
remittances
pull-pull theory
family
education
overqualification
discrimination
identity
immigrants
mental health
corruption
poverty
political instability
unemployment
return
government
investments
debates
migrants
experience
economic impact
diaspora
Advisor: Wane, Njoki
Photoperiod Dependent Plasticity of GABA-mediated Effects on Neuronal Activity in the Pond Snail Lymnaea stagnalis

GABA is the primary inhibitory neurotransmitter in the mature mammalian CNS. Within the snail central ganglion, however, there are contradictory reports on the role of GABA, citing both inhibitory and excitatory effects. Previous work has suggested a seasonal shift in the polarity induced by GABA. My thesis work investigated whether changes in photoperiod were responsible for the seasonal shift in GABAergic polarity. Using intracellular sharp recordings from cluster F neurons within the pedal ganglia, I determined that the majority of snails exposed to either a 16h:8h or 8h:16h light:dark cycle exhibited significant hyperpolarizing inhibitory responses or depolarizing excitatory responses to GABA application, respectively. Additionally, using gramicidin-perforated patch recordings I found a shift in the reversal potential for GABA. I conclude that the seasonal shift in GABA-mediated effects results from a shift in intracellular [Cl¯] that is photoperiod dependent and is likely mediated through the relative efficacy of cation chloride co-transporters.

Keywords: GABA
L. stagnalis
KCC2
NKCC1
Hypoxia
Advisor: Buck, Leslie
Vascular Injury Hospitalization Trends in Ontario: A 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.

Keywords: vascular injury, Ontario, population-based study
Advisor: Lindsay, Thomas
Corrosion of Copper in Concentrated Aqueous Chloride Under Anaerobic Conditions

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.

Keywords: Copper
Anaerobic corrosion
Concentrated chloride
Advisor: Newman, Roger C.
Novel Treatment of Colonic Dysplasia with an Oncolytic Vaccinia Virus

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.

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
Advisor: McCart, J. Andrea
A Genetic and Pharmacological Response to Improve Radiation Response

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.

Keywords: Oncology
Ionizing Radiation
Radiation Therapy
Hypoxia
AMPK
Metformin
Advisor: Koritzinsky, Marianne
Nuclear Localization of N-Ethylmaleimide Sensitive Factor

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.

Keywords: N-Ethylmaleimide Sensitive Factor
SNARE Disassembly
Advisor: Stewart, Bryan
Murine Model of Autoimmune Hemolytic Anemia: Red Blood Cell Clearance Mechanisms and Treatment Efficacy

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.

Keywords: autoimmunity
red blood cell
anemia
antibody
Advisor: Lazarus, Alan
A Question of Change: Conceptions of Knowledge, Practices and Disability Studies

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.

Keywords: disability studies
change
practices
metaphor
Haraway
knowledge
blindfulness
Advisor: Titchkosky, Tanya
Role of Cystic Fibrosis Transmembrane Conductance Regulator and Sphingolipids in Hypoxic Pulmonary Vasoconstriction

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.

Keywords: Hypoxic pulmonary vasoconstriction
CFTR
sphingolipids
TRPC6
Advisor: Kuebler, Wolfgang
Zhang, Haibo
Enhancing Spatial Awareness with Multi-camera View Synthesis for Diagnostic and Manipulation Tasks

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.

Keywords: Engineering Psychology
Human Factors
Advisor: Milgram, Paul
Blood Pressure Responses to Physical and Mental Challenges in Adolescent Males and Females

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.

Keywords: blood pressure
blood pressure reactivity
adolescence
genetics
hypertension
obesity
sex
visceral fat
Advisor: Pausova, Zdenka
3D Tracking of Anti-predator Behaviour in Guppies

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.

Keywords: 3D tracking
guppy
schooling
shoaling
anti-predator behaviour
Advisor: Rodd, Helen
Ryu, William