VictorJuiz/thesis huggingface dataset:
Mechanisms of Action and Relative Efficacy of Glucocorticosteroid Treatment in Ameliorating Immune Thrombocytopenia Induced by Anti-platelet GPIbα Versus GPIIbIIIa Immune Responses

Immune thrombocytopenia (ITP) is an autoimmune disorder, mediated mainly by autoantibodies against platelet glycoprotein GPIIbIIIa and GPIbα resulting in enhanced platelet destruction. Decreased platelet production and cellular immunity also contribute to ITP. GPIIbIIIa and GPIbα are distinct platelet receptors. Previous studies suggested that anti-GPIbα (versus anti-GPIIbIIIa)-mediated ITP is less responsive to IVIG therapy. However, little information is available whether antibody specificities also dictate efficacy of Glucocorticosteroids (GC), which are the first-line ITP treatment. Here, I first induced ITP in mice by passive administration of anti-GPIbα or anti-GPIIbIIIa antibodies. Results suggest GCs were more effective at amelioration of anti-GPIIbIIIa-mediated thrombocytopenia. I repeated this observation in an active ITP model, in which splenocytes from wild-type platelet immunized GPIbα-/- or GPIIIa-/- mice were engrafted into wild-type mice, which developed ITP. Thus, I established new murine models of ITP for GC therapy and demonstrated that anti-GPIbα-mediated thrombocytopenia may be less responsive to GC therapy.

Keywords: Immune thrombocytopenia (ITP)
GPIIbIIIa
GPIbα
Glucocorticosteroids
Advisor: Ni, Heyu
A Continuous Flow Microwave Reactor for Organic Synthesis

Microwave reactors are important tools in chemical synthesis, as they can lead to unprecedented reductions in reaction times and improved reaction yields. In order to scale-up the technology for greater throughput and industrial application, reactor types are moving from batch to continuous flow reactors. This research designed, built, verified and modeled a continuous flow microwave reactor. The reactor could operate under high temperature/high pressure conditions, and was connected to in-line gas chromatography/mass spectrometry, for real time sample analysis. Specifically, a pressure device was developed to enable the reactor to run under high pressure conditions (< 1100 psi) without the use of a conventional back-pressure device. The reactor design was verified using two chemical reactions, and an in-line analytic apparatus was developed to assess the potential for reactor operation with in-line GC/MS. Additionally, a computational fluid dynamic model was developed to better understand the heat and mass transfer inside the reactor.

Keywords: Microwave Reactor
Organic Synthesis
Advisor: Bender, Timothy
Lawryshyn, Yuri Andrew
Organ, Mike
Consensus on Access to Mental Health Services by Children and Adolescents in Antioquia, Colombia

Few mental health studies have explored the prevalence of disorders, risk factors, and availability of services in Antioquia, especially in urban children and adolescent populations. However, access studies have never been developed. Despite growing interest in access, researchers, bureaucrats and interest groups have not come to any consensus about which specific factors may be considered in order to improve access for children and adolescents, especially in provinces with high levels of violence, displacement and inequality. This thesis aims to generate such a consensus among a diverse group of mental health stakeholders around Antioquia. Consensus suggests that predisposing, enabling, need and behaviour factors simultaneously influence access. Additionally, social capital is the resource upon which several mental health programs focus for the development and promotion of mental health services. Finally, stakeholders have identified effectiveness criteria that should be used to evaluate their efficacy as a network in order to improve their work.

Keywords: Access to mental health services
Children and adolescents
Antioquia
Colombia
Delphi study
Advisor: Berta, Whitney B.
Evaluation of an Exhaust Gas Mixing Duct for Off-road Diesel After-treatment Systems Using Numerical Methods

Due to strong motivation to reduce costs and increase performances of stationary diesel after-treatment systems, computational modeling has become a necessary step in system design and improvement. A unique mixing duct typified by significant changes in scale and strong flow curvature was evaluated for its potential to improve flow distribution across the SCR catalyst inlet face. The flow dynamics were investigated with a steady three-dimensional turbulence model and detailed chemistry was studied separately using a one-dimensional channel reactive flow model. Aqueous urea injection was modeled using Discrete Phase Modeling. The mixing duct performance relative to reactor dimensions and engine loads is discussed. The Impact of injector positions was studied using massless particle tracking. A total of three geometries were evaluated using a Uniformity Index of the ammonia-to-NOx feed ratio. It was found that a higher mixing duct height to inlet diameter ratio yielded better mixing.

Keywords: aftertreatment
Exhaust gas mixing
Advisor: Wallace, James S.
Sullivan, Pierre E.
Exacerbated Cardiac Fibrosis in Apelin-deficient Mice post Myocardial Infarction is Associated with Vimentin and MicroRNA-378

The Apelin-APJ system is transiently up-regulated in murine models of cardiac dysfunction. We have previously shown that Apelin-deficient mice subjected to aortic constriction suffer from severe fibrosis. In turn, we hypothesized that Apelin deficiency will also exaggerate the fibrosis phenotype post experimental myocardial infarction, associated with changes in fibroblast cell activity. Apelin-deficient and wildtype mice were randomly subjected to sham operation or left coronary artery ligation. Apelin deficiency worsened cardiac functionality, enhanced fibrosis-related gene expression and morphology, and enhanced vimentin intermediate filament expression, which may be involved in increasing fibroblast proliferation. MicroRNA target prediction softwares predict that apelin and vimentin 3 ’UTRs are potential targets of microRNA-378 regulation, and were confirmed with Luciferase reporter assays and western blot. Apelin up-regulation may be a useful strategy for attenuating unfavorable fibrosis through down-regulating vimentin-mediated adverse fibroblast activity. MicroRNA-378 regulation may be partly responsible for changes in apelin and vimentin expression.

Keywords: Myocardial Infarction
Apelin
Vimentin
MicroRNA
Cardiovascular disease
Cardiac Fibrosis
Advisor: Liu, Peter
Modulation of Multidrug Resistance Phosphoglycoprotein in the Mouse Placenta and Fetal Brain by the Selective Serotonin Reuptake Inhibitor Sertraline and Maternal Bacterial Infection

Multidrug resistance phosphoglycoprotein (P-gp) is expressed in the placenta and fetal blood-brain barrier (BBB) and plays a critical role in reducing fetal accumulation of xenobiotics. In other tissues, P-gp activity is inhibited by selective serotonin reuptake inhibitors (SSRIs) and by lethal doses of LPS modeling a bacterial infection. However, nothing is known with respect to the effects of SSRIs or nonlethal infection on P-gp activity in the placenta or fetal tissues. In the studies presented in this thesis, we hypothesized that (1) the SSRI sertraline and (2) a nonlethal maternal bacterial infection would decrease P-gp activity in the placenta and fetal BBB. The first study shows that sertraline affects P-gp activity at these barrier sites in a tissue-specific manner. The second study shows that nonlethal infection does not significantly affect P-gp activity at either site. However, nonlethal infection may still influence substrate biodistribution by altering hepatic elimination of these substrates.

Keywords: Reproduction
Development
Advisor: Matthews, Stephen
Canadian Mining Companies, Social Disclosure and Extra-Territorial Human Rights Obligations

The liability of companies for extra-territorial human rights violations does not solely arise from human rights statutes and traditional tort law approaches, but also from the corporate and securities law domains. Securities law requires that public companies disclose any high risk activity that the company is involved in, to the extent that it may affect the viability of the corporation, and this includes possible human rights violations. Management decisions in the field of Corporate Social Responsibility must concern the long-term viability of a company, and therefore accommodating, to the extent possible, the demands of stakeholders – be they traditional shareholders, responsible shareholders, or affected communities. This thesis will analyze the legal obligations triggering such corporate decisions, as well as the industry trends which inform them. The focus will be on Canadian public mining companies.

Keywords: securities disclosure obligations
human rights violations
Advisor: Prado, Mariana Mota
Role of Spongiotrophoblast VEGFA during Pregnancy

The role of placental VEGFA in placental development and maternal pregnancy adaptations is unknown. In this thesis, one or both copies of Vegfa was knocked out from the placental spongiotrophoblast region using a mouse Cre-loxP system. Surprisingly, in pregnancies carrying 100% conceptuses with a single deletion of Vegfa from the spongiotrophoblast layer, maternal circulating VEGFA increased by 20% accompanied by a 15% decrease in arterial pressure while no impairment in embryo growth was found. In pregnancies carrying 50% conceptuses with both copies of Vegfa deleted from spongiotrophoblast, 17% of conceptuses had been reabsorbed by late gestation suggesting a function for spongiotrophoblast VEGFA in sustaining early pregnancy. In conclusion, spongiotrophoblast VEGFA affects maternal function during pregnancy but the exact mechanism remains to be defined.

Keywords: VEGFA
spongiotrophoblast
placenta
pregnancy
cardiovascular
Advisor: Adamson, Susan Lee
Pathogenesis of Fetal and Neonatal Immune Thrombocytopenia: Role of Anti-Beta3 Integrin Antibodies in Vascular Injury and Angiogenesis

Fetal and neonatal immune thrombocytopenia (FNIT) is a severe bleeding disorder which results from fetal platelet destruction by maternal antibodies against platelet antigens, including GPIIbIIIa (αIIbβ3 integrin) and GPIbα. β3 integrin is also expressed by angiogenic endothelial cells (ECs) and is required for angiogenesis. Therefore, we investigated whether anti-β3 antibodies in FNIT cross-react with blood vessels of the fetus/neonate and contribute to pathogenesis. Antibodies to GPIbα were used as controls. To mimic human FNIT, β3 integrin- or GPIbα-deficient female mice were immunized with wild-type platelets and bred with wild-type male mice. Pups in both groups had thrombocytopenia but intracranial hemorrhage was only observed in anti-β3-mediated FNIT. Anti-β3-mediated FNIT pups had increased apoptosis in the brain and impaired vascularization of the brain and retina. In addition, anti-β3 sera inhibited proliferation and vascular-like tube formation by ECs in vitro. Therefore, anti-β3 antibodies in FNIT likely impair angiogenesis in the developing fetus/neonate.

Keywords: Fetal and neonatal immune thrombocytopenia
platelets
integrin
angiogenesis
Advisor: Ni, Heyu
Proteomics of Thyroid Carcinoma: Detection of Potential Biomarkers of Aggressive and Non-aggressive Subtypes

In search of thyroid carcinoma biomarkers, proteins secreted by thyroid cancer cell lines, papillary-derived TPC-1 and anaplastic-derived CAL62, were analyzed using liquid chromatography-tandem mass spectrometry. Of forty six high-confidence identifications, six proteins were considered for verification in thyroid cancer patients’ tissues and blood. The localization of two proteins, nucleolin and prothymosin-alpha (PTMA), was confirmed in TPC-1 and CAL62 by confocal microscopy and immunohistochemically in xenografts of TPC-1 cells and human thyroid carcinomas. Increased nuclear and cytoplasmic expression of PTMA was observed in anaplastic carcinomas compared to normal thyroid tissues, papillary and poorly differentiated carcinomas. Importantly, six proteins were detected in thyroid cancer patients’ sera, warranting future analysis to confirm their potential as blood-based thyroid cancer markers. Herein we demonstrate the ability of secretome analysis of thyroid cancer cell lines to identify proteins that may be studied for application in management of thyroid carcinomas upon future validation.

Keywords: Thyroid
Oncology
Advisor: Walfish, Paul
The Role of EphB2 Receptors in the Development of Morphine Tolerance

Recently we have begun to investigate a novel role of EphB receptors in opiate-dependant analgesia. EphB2-β-galactosidase knockins demonstrate that EphB2 is persistently expressed within a number of neural pathways involved in MOR-mediated nociception in vivo and that EphB2 colocalizes with markers of the MOR at the cellular level in the spinal cord and dorsal root ganglia. Despite demonstrating wild-type levels of sensory and motor activity, EphB2 null mice exhibit a significantly altered analgesic response to repeated (but not naive) opiate exposure compared to controls. Investigation of EphB2 null mice and wild type animals revealed no differences in MOR protein levels or affinity. Analysis of this opiate-mediated tolerance suggests that associative phenomena play a substantial role in mediating the analgesic effects observed, possibly due to defeciencies in CA1-mediated learning. Therefore, loss of EphB2 may diminish context-dependent learning and that such learning plays a substantial role in regulating morphine-dependent tolerance.

Keywords: Eph receptor
Morphine
Mu opioid receptor
Advisor: Henderson, Jeffrey T.
CREB Induces Structural Changes in LA Neurons making them more Advantageous for Inclusion into the Fear Memory Trace

The current study aimed to determine the selective advantage of lateral amygdala (LA) neurons overexpressing the transcription factor CREB that enables their preferential incorporation into the fear memory trace. I hypothesized that overexpression of CREB drives the formation of dendritic spines, potentially providing these neurons with greater connectivity to sensory inputs at the time of learning. Using viral-mediated gene transfer, CREB tagged with GFP, or GFP as a control, was overexpressed in the LA of wild-type mice. Spine number and morphology were compared in homecage mice at the time when mice are normally trained in fear conditioning. Spine density was increased in neurons with CREB vector compared to neurons with GFP vector whereas spine head diameter and length was not different. Therefore, LA neurons overexpressing CREB have increased spine number at the time of learning, potentially providing these neurons with a selective advantage for incorporation into the fear memory trace.

Keywords: Transcription factor
Dendritic spines
Fear memory
Advisor: Josselyn, Sheena
Analysis of Interactions between Cdc42 and the Protein Trafficking Machinery

Epithelial polarity is established by polarity proteins and maintained by polarized trafficking through intricate interdependent mechanisms. In the Drosophila ventral neuroectoderm (VNE), Cdc42/Par complex regulates the retromer retrieval complex to promote apical recycling and maintain epithelial polarity. I have further characterized the retromer by generating antibodies against subunits Vps35 and Vps5. In wild-type VNE, both proteins partially colocalized with early endosomes, sorting endosomes (SEs), and the Golgi network. In the VNE of dominant-negative Cdc42-expressing embryos, Vps35 becomes enriched at SEs, where apical cargo was previously shown to accumulate abnormally. This suggests that in the absence of Cdc42 function, the retromer recognizes cargo in SEs, but recycling is blocked. I have also performed a deficiency screen for genes that cooperate with Cdc42 in the VNE. I identified the ESCRT machinery, which promotes protein degradation, and the exocyst complex, which regulates vesicle secretion at the plasma membrane, as functional interactors of Cdc42.

Advisor: Tepass, Ulrich
Bad Behaviour: The Cultural Production of Addiction and the Psychologization of Everyday Life

This thesis explores the cultural production of addiction and the psychologization of everyday life. Through analyses of ubiquitous addiction literature, as well as ordinary, everyday encounters, I examine how we make meaning of addiction, thus culturally constituting the addict. I explore my situated-ness in relation to addiction, which in turn helps me to think through how I am oriented toward addiction. Through an analysis of a specific account of an intersubjective experience of addiction, I examine how experiences of addiction are made between us. This thesis also explores the relationship between substance use and harm and the role the perceived “warnings signs” of addiction play in how we recognize addiction. Using a phenomenologically informed method of social inquiry, I question what the psychologization of everyday life, or our (over) use of psychology, means for our engagement with others.

Keywords: addiction
phenomenology
disability studies
feminist
experience
intersubjectivity
cultural production
psychologization
orientation
pain
queer
interpretive sociology
Advisor: Titchkosky, Tanya
Michalko, Rod
VEGF in the Placenta and Maternal Circulation and Organs during Pregnancy in Mice

Whether vascular endothelial growth factor A (VEGF) plays an augmented role during pregnancy is unknown. In this thesis expression of VEGF in the placenta, maternal circulation and organs in mice was examined using qRT-PCR, LacZ expression, and/or ELISAs. Normal pregnancies and pregnancies with transgenic conceptuses that over-express VEGF in the placenta were examined. In normal pregnancies, VEGF120/164 levels in the ovary increased in parallel with that of the maternal circulation. In pregnancies where the placenta over-expressed VEGF, maternal circulating VEGF120/164 levels decreased and so did levels in the maternal ovary. Surprisingly, VEGF protein levels (per mg of total protein) decreased in the growing, highly vascular placenta during pregnancy. In conclusion this thesis provides evidence for an important ovarian source of maternal circulating VEGF120/164 during pregnancy.

Keywords: VEGF
placenta
Advisor: Adamson, Susan Lee
Towards Automated Recognition of Human Emotions using EEG

Emotion states greatly influence many areas in our daily lives, such as: learning, decision making and interaction with others. Therefore, the ability to detect and recognize one’s emotional states is essential in intelligence Human Machine Interaction (HMI). In this thesis, a pattern classification framework was developed to sense and communicate emo- tion changes expressed by the Central Nervous System (CNS) through the use of EEG signals. More specifically, an EEG-based subject-dependent affect recognition system was developed to quantitatively measure and categorize three affect states: Positively excited, neutral and negatively excited. Several existing feature extraction algorithms and classifiers were researched, analyzed and evaluated through a series of classification simulations using a publicly available emotion-based EEG database. Simulation results were presented followed by an interpretation discussion. The findings in this thesis can be useful for the design of affect sensitive applications such as augmented means of communication for severely disabled people that cannot directly express their emotions. Furthermore, we have shown that with significantly reduced number of channels, classification rates maintained a level that is feasible for emotion recognition. Thus current HMI paradigms to integrate consumer electronics such as smart hand-held device with commercially available EEG headsets is promising and will significantly broaden the application cases.

Keywords: Emotion Recognition
EEG
Advisor: Plataniotis, Konstantinos N.
Extracting Lipid and Carotenoids from Microalgae with Lecithin-linker Microemulsions

This study investigated the extraction of lipids and β-carotene from microalgae using microemulsions as an alternative to current solvents. Type I and type IV microemulsions composed of 4% lecithin, sorbitan monooleate, PEG-6-caprylic glycerides, and ethyl caprate were able extract lipids from lyophilized microalgae better than hexane and ethyl caprate. HPLC quantified the extracted β-carotene, with type IV microemulsions extracting the most β-carotene at 0.137±0.074% (w/w) of the total microalgae biomass after an hour. The growth recovery of the microalgae after extraction was observed over 2 weeks. Variability in the data prevented definite conclusions about the ability of algae to grow after extraction. The type IV extractions consistently showed some signs of survival. After two weeks, a pale-green colour was observed in the 15min and 1h extractions. This study showed that microemulsions can successfully extract lipids from microalgae; future work would apply microemulsion formulations to live algal cells for in-situ extraction.

Keywords: microalgae
extraction
microemulsion
lipids
Advisor: Acosta, Edgar
Impacts of Driving Patterns on Well-to-wheel Performance of Plug-in Hybrid Electric Vehicles

The well-to-wheel (WTW) environmental performance of plug-in hybrid electric vehicles (PHEVs) is sensitive to driving patterns, which vary within and across regions. This thesis develops and applies a novel approach for estimating specific regional driving patterns. The approach employs a macroscopic traffic assignment model linked with a vehicle motion model to construct driving cycles, which is done for a wide range of driving patterns. For each driving cycle, the tank-to-wheel energy use of two PHEVs and comparable non-plug-in alternatives is estimated. These estimates are then employed within a WTW analysis to investigate implications of driving patterns on the energy use and greenhouse gas emission of PHEVs, and the WTW performance of PHEVs relative to non-plug-in alternatives for various electricity generation scenarios. The results of the WTW analysis demonstrate that driving patterns and the electricity generation supply interact to substantially impact the WTW performance of PHEVs.

Keywords: light duty vehicles
plug-in hybrid electric vehicles
life cycle assessment
well-to-wheel
energy
petroleum
greenhouse gas emissions
electricity generation
driving patterns
driving conditions
driving cycles
travel demand modeling
Transportation Tomorrow Survey
Ontario
Greater Toronto Area
Emme
CALMOB6
Autonomie
GREET
Advisor: MacLean, Heather L.
Roorda, Matthew J.
Development of a Novel Pck-1: eGFP Reporter Zebrafish Line for the Discovery and Evaluation of Potential Anti-Diabetic Drugs

Overexpression of Phosphoenolpyruvate carboxykinase - cytosolic (PEPCK, encoded by Pck-1 gene) has been found to be associated with the prevalence of hyperglycemia in Type 2 Diabetes Mellitus (T2DM) patients. The Pck-1 enzyme catalyzes the rate limiting step in endogenous glucose production. The aims of this study are to develop a Pck-1:eGFP reporter zebrafish and validate it as a potential tool for the screening of novel anti-diabetic compounds. 3.6 kb zebrafish Pck-1 promoter fragment was cloned and a Pck-1:eGFP expression vector was constructed. After DNA microinjection, we generated Pck-1:eGFP reporter zebrafish with strong eGFP expression in developing liver. Validation studies confirmed that Pck-1:eGFP zebrafish embryos responded to treatment of glucose, cAMP and dexamethasone, metformin and rosiglitazone similarly to that of humans. This novel Pck-1:eGFP reporter fish line can serve as a tool for the screening and development of novel anti-diabetic drugs that may have potential in the treatment of T2DM.

Keywords: Diabetes Mellitus
gluconeogenesis
PEPCK
Pck-1
zebrafish
drug discovery
transgenics
reporter line
high throughput screening
transposon
gene regulation
novel drugs
drug screen
microinjection
deletional analysis
physiology
Advisor: Wen, Xiao-Yan