VictorJuiz/thesis huggingface dataset:
High-throughput siRNA Screen in Dendritic Cells to Discover New Genes Regulating Immunologic Tolerance

The outcome of autoantigen recognition by the immune system--self-tolerance or autoimmune disease--is largely determined by the activation state of the dendritic cells (DCs) that uptake, process, and present autoantigens to autoreactive T cells. In particular, activation of dendritic cells to an immunogenic phenotype is necessary for the full activation of naïve autoreactive T cells, and thus necessary for the initiation of autoimmune disease. A better understanding of the cellular and molecular triggers and mechanisms of DC activation could catalyze the development of novel therapies to induce self-tolerance in patients with autoimmune disease. Towards the goal of discovering new genes and pathways that regulate DC activation and immunologic self-tolerance, we (1) developed a high-throughput siRNA screen in bone marrow-derived DCs and (2) show that BMDC expression of CD80, CD86, MHC II, and IL-12/23-p40 can identify candidate genes that regulate DC activation.

Keywords: Autoimmune disease
Autoimmunity
Dendritic cell
T cell activation
Tolerance
Advisor: Mak, Tak W
Multiphysics Modelling of the Coupled Behaviour of Precision-guided Projectiles Subjected to Intense Shock Loads

Precision-guided projectiles (PGPs) are subjected to severe shock loads, often leading to the failure of the highly sophisticated embedded electronic systems (EES) responsible for guidance. It is the objective of this work to conduct a comprehensive explicit axisymmetric Lagrangian-Eulerian multiphysics finite element analysis of the entire launch process of PGPs accounting for coupling and interaction effects between the different media. The influence of these interaction and coupling effects on the local and global accelerations and pressures are studied. An extensive examination of the severity and frequency of the reflected waves and the effect of PGPs springback is conducted. The results reveal that the pressure drop at muzzle exit is the contributing factor determining the severity of exit accelerations. Moreover, the formation and interaction of shock waves has little effect on the projectile response. Finally, the interaction with barrel has a significant influence on projectile response, especially after muzzle exit.

Keywords: Acceleration history
FEM
Precision-guided projectile
Pressure history
Propellant
Wave reflection
Advisor: Meguid, Shaker A.
Insulin Signaling Promotes Ras/MAPK Cascade Activity by Inhibiting the FOXO Transcription Factor DAF-16

My research seeks to uncover novel mechanisms of cooperation between the insulin and Ras/MAPK signalling cascades. I use Caenorhabditis elegans as a model system and take advantage of a specific consequence of Ras signaling in this organism, vulva development. When hyperactivated, the C. elegans Ras homolog let-60, causes the development of ectopic vulvae, a response known as the multivulva (Muv) phenotype. I have confirmed previous results showing that a loss of function mutation in the C. elegans insulin receptor daf-2 nearly completely suppresses the Muv phenotype caused by gain of function in let-60/Ras. I have investigated which components downstream of daf-2 are critical for this response, finding that the FOXO transcription factor DAF-16 has a major role. I have also found two transcriptional targets of DAF-16/FOXO that are important for let-60/Ras suppression. This study presents a novel role for FOXO transcription factors as Ras/MAPK suppressors.

Advisor: Derry, Brent
Functional Role for Shear Responsive cis Elements and Fluid Shear Stress in Epigenetic Regulation of Endothelial Nitric Oxide Synthase

Objective of this study was to provide a biologically relevant understanding of transcriptional control of endothelial Nitric Oxide Synthase (eNOS) in endothelial cells (EC) subject to fluid shear stress in vivo. Mutation of two shear responsive cis DNA elements, the Shear-Stress Response Element (SSRE) and the Kruppel Like Factor (KLF) binding site, led to abrogation of eNOS promoter reporter expression in vivo. This was followed by aberrant hypermethylation of the proximal eNOS promoter of the insertional promoter reporter construct. Similarly, assessment of eNOS promoter methylation in vivo revealed significant discrepancy between ECs from curvatures versus straight regions of the aorta. However, exposing ECs to disturbed flow (DF) was not sufficient to induce methylation of eNOS promoter in vitro, suggesting that the aberrant methylation pattern might be established during development. In consistency with this, endothelial committed cells differentiated from mouse embryonic stem (mES) cells in absence of flow exhibited a hypermethylated promoter for eNOS. In conclusion, we report that fluid shear stress and shear responsive cis elements play critical roles in transcriptional control of eNOS both during development and in mature adult. Further, we propose that this is mediated in part through epigenetic regulation of eNOS promoter.

Keywords: DNA methylation
Endothelial cell
Endothelial nitric oxide synthase
Epigenetics
nitric oxide
Shear stress
Advisor: Marsden, Philip A
A Novel Mechanism for Gabapentin Actions: Up-regulation of δGABAA Receptors

Gabapentin is a widely used anticonvulsant and analgesic drug that also causes anxiolysis, sedation and ataxia. The mechanisms underlying these effects are poorly understood. Previously, we showed that gabapentin increases a tonic inhibitory conductance in hippocampal neurons that is generated by 5 subunit- and subunit-containing GABA

Keywords: anxiety
delta
extrasynaptic
GABAA
gabapentin
pain
Advisor: Orser, Beverley A
Environmental and Financial Performance: Aviation Biofuels

The hydrodeoxygenation (HDO) pathway produces biojet fuel that has the potential for near-term commercialization. This thesis examines the environmental and financial aspects of HDO biojet production in Western Canada using camelina, carinata and used cooking oil (UCO) waste as feedstocks. Process modeling included a rigorous HDO yield analysis based on the molecular distribution of triglycerides, isomerization modeling, and chemical and energy use estimates. The environmental impacts were estimated using the ISO 14040 Life Cycle Assessment framework and modeled in SimaPro with a focus on Greenhouse Gas emissions. Financial modeling included CAPEX and OPEX estimation, carbon price analysis, discounted cash flow modeling, sensitivity analysis and Monte Carlo simulation to test economic robustness using standard NPV and IRR indicators. The analysis found that biojet from all of the analyzed feedstocks effectively reduced emissions compared to conventional fuels, but camelina was economically viable today while carinata and UCO faced near-term economic challenges.

Keywords: Financial modeling
Hydrodeoxygenation
Life cycle assessment
Oilseeds
Process modeling
Techno-economic analysis
Advisor: Saville, Bradley A
MacLean, Heather L
A Multi-electrode Array for Impedance Spectroscopy in a Digital Microfluidic Device

Digital microfluidics (DMF) can emulate biochemical protocols on miniaturized platforms through the control of pico- to microliter sized droplets. The droplets function as isolated transport capsules and microreactors for chemical reactions to take place. To ensure system-functionality, detection methods need to be integrated. Presented in this work is a systematic procedure for the development of an interdigitated multi-electrode array (IMEA) embedded within the driving electrodes of a DMF device for in-line impedance spectroscopy. It is shown that closed-form analytical expressions based on Schwarz-Christoffel conformal transformations paired with a modification of the partial capacitance method can be used to determine the impedance of an IMEA in multi-layer structures. Experimental work is performed to develop a reliable DMF device, and to investigate different IMEA designs. Applications included conductivity detection in droplets, and the monitoring of protein films on insulated IMEA's. Further development of the integrated system is necessary for full lab-on-a-chip capability.

Keywords: Conformal Mapping
Digital Microfluidics
Impedance Spectroscopy
Multi-Electrode Array
Advisor: Sullivan, Pierre E
Examining the Nutritional Content of Prepackaged Foods and Beverages Marketed to Children in Canada

Banning the marketing of unhealthy foods and beverages to Canadian children has been suggested as a strategy to combat childhood obesity. This study aimed to characterize the prevalence of marketing to children in a large database of Canadian prepackaged foods and beverages and to examine the nutritional quality of products marketed to children. Marketing to children was largely found in subcategories with products high in sugar, fat and/or sodium, and in some subcategories, products marketed to children were of lower nutritional quality than comparable products without such marketing. A nutrient profiling model classified most children's products as "less healthy". Children's products from companies participating in the voluntary code were not healthier than comparable children's products from non-participating companies. Therefore, these findings suggest that there are limitations in the current voluntary code, as product packaging is not covered, and the products marketed to children through this strategy can be considered unhealthy.

Keywords: Canadian food supply
childhood nutrition
childhood obesity
marketing to children
nutritional quality
prepackaged foods
Advisor: L'Abbé, Mary R
Role of Rho small GTPases in the invasion of Lung Epithelial Cells by Legionella pneumophila

Legionella pneumophila is the main cause of Legionnaires' Disease, a fatal pneumonia. The filamentous form of Legionella (FLp) is capable of invading human lung epithelial cells through unique cell surface rearrangements. These unique structures curve around the bacteria, entrapping it at the host cell surface, favoring subsequent invasion. This requires cytoskeleton rearrangements mediated by bacterial activation of E-cadherin and β1-integrin receptors. We investigated the roles of the small GTPases Rac1, RhoA, and Cdc42 (actin regulators) in the attachment and internalization of FLp to lung epithelium. We found Rac1, Cdc42, RhoA, and their downstream effectors, are involved in attachment, but not in internalization of FLp. Internalization was instead dependent on a T4SS-delivered toxin. This indicates that bacterial attachment is dependent on host cell receptors activating downstream small GTPases, causing actin reorganization and bacterial entrapment, but internalization is dependent on a bacterial toxin that polymerizes actin independently of Rho small GTPases.

Keywords: Cdc42
invasion
Legionella pneumophila
lung epithelial cells
Rac1
RhoA
Advisor: Terebiznik, Mauricio
Coccolithophore Evolutionary Response to the Youngest Toba Eruption (75.0 ± 0.9 ka)

The impact of the recent super eruption, Toba, ~ 74 ka on the marine environment is unknown. For the first time it is compared to coccolithophore assemblage relative abundances, with samples taken from core SO130-289KL, located in an oxygen minimum zone in the northeast Arabian Sea. No long term evolutionary implications associated with temporally close biohorizons can be linked to the super eruption, however climatic changes associated with global cooling following the eruption have been identified indirectly through the relative abundance decrease of the species Florisphaera profunda. F. profunda relative abundance decreases are linked to an increase in primary productivity levels associated with a deepened mixed layer and are seen during the Northeast monsoon season. Northeast monsoon intensity is known to increase during cooler global periods and are here attributed to the lowered F. profunda relative abundances following the eruption.

Keywords: Arabian Sea
Coccolithophores
Florisphaera profunda
Monsoons
Super eruptions
Toba
Advisor: Bollmann, Jorg
Effect of Nuts on Markers of Cancer and Coronary Heart Disease Risk in Type 2 Diabetes: A Dose Response Study

Nuts have been shown to reduce coronary heart disease (CHD) risk and possibly cancer development. However, the mechanisms are not clear, and the small but consistent LDL-C reduction does not explain the 18-51% CHD risk reduction observed. Therefore, the effect of nuts was assessed on serum fatty acids, measures of oxidative stress, and prostate cancer (LNCaP) cell growth as part of a secondary analysis of a 12-week feeding trial (100 participants) in type 2 diabetes to explore possible mechanisms. Nuts increased serum oleic acid and monounsaturated fatty acids in the phospholipid fraction and this change related inversely to Framingham Risk Score. However, no associations were seen with markers of oxidative stress or in vitro LNCaP cell growth. It is concluded that intake of monounsaturated fat associated with the Mediterranean diet reduces CHD risk, but the beneficial effect of nuts on CHD and possible effects on cancer remain to be explained mechanistically.

Keywords: Cancer
Diabetes
Heart Disease
Monounsaturated Fat
Nuts
Oxidative Stress
Advisor: Jenkins, David JA
Meeting the Needs of Aboriginal Youth in the Ontario Justice System: Reconciling Indigenous and Non-Indigenous Ways of Knowing: An Exploratory Qualitative Study

Using a qualitative, exploratory design and drawing on interpretivist, postcolonial, and decolonizing frameworks, this study sought to comprehend the perceptions of justice system personnel and Aboriginal service users about Aboriginal-specific, community-based justice programming and to better understand the factors that influence successful referral and access to these programs within community-sentencing and probation contexts. In-depth, semi-structured interviews were conducted with 16 participants (youth court judges, crown attorneys, youth court workers, youth probation officers, service providers, and Aboriginal service users) and thematic analysis was employed to identify key themes. Results indicate that there is strong support for Aboriginal-specific, community-based programming within the youth justice community. However, barriers to matching Aboriginal service users with Aboriginal programming are numerous and include poor communication between mainstream and Aboriginal justice partners and inconsistency in Aboriginal-specific program offerings, among others. Findings are also discussed in reference to the Risk-Need-Responsivity framework.

Advisor: Peterson-Badali, Michele
Proteomic Analysis of Endothelial, Smooth Muscle, Myocytes and Fibroblasts Derived from Human Cardiac Tissue Identified Cell Type Specific Exprsession Signatures

The heart is composed of multiple constituent cell types; the primary cells being fibroblasts, cardiomyocytes, endothelial and smooth muscle cells. Here, I employed membrane isolation procedures to attain membrane enriched and depleted proteins from in vitro human fibroblasts, cardiomyocytes, coronary endothelial and coronary smooth muscle cells, obtained from human cardiac biopsy tissues. Shotgun proteomics identified a total of 2320 fibroblast, 2310 cardiomyocyte, 2209 smooth muscle and 2247 endothelial cell proteins. Statistical analysis identified 367 fibroblast-enriched, 97 cardiomyocyte-enriched, 340 endothelial-enriched and 52 smooth muscle cell-enriched proteins. I further ranked these proteins by staining in the Human Protein Atlas database. Finally, comparison of these proteins with a mouse model of dilated cardiomyopathy demonstrated that many single cell type enriched proteins were also differentially expressed in disease. Two fibroblast enriched proteins, GRB2 and PRDX1, were examined in a myocardial infarction mouse model, and demonstrated increased immunofluorescence in the fibroblast enriched, infarct- and adjacent border-zones.

Keywords: Cardiomyocyte
Endothelial Cell
Fibroblast
Heart
Mass Spectrometry
Smooth Muscle Cell
Advisor: Gramolini, Anthony O
Automatic Classification of Children's Antisocial and Prosocial Lies Using Facial Expressions

Research on the nonverbal facial expressions of children during lie-telling is extremely limited. As such, it is unknown whether the nonverbal behaviours of children telling an antisocial lie are the same or different when they tell a prosocial lie. The current study is the first to concurrently examine the facial movements of children during antisocial and prosocial lying. Through the use of the Computer Recognition Toolbox (Littlewort et al., 2011), an automated computer vision program using the Facial Action Coding System (Ekman Friesen, 1978), children's nonverbal behaviours were shown to be significantly different in terms of 8 different facial actions. Furthermore, linear support vector machine (SVM) analysis was successful in classifying children's lies with an average accuracy of 72.68%, significantly above chance levels. Implications and limitations are discussed.

Keywords: Antisocial lies
Deception
Facial Expressions
Lying
Prosocial lies
Advisor: Lee, Kang
Pragmatics, Phonological Processing, and Reading: Language Abilities in 'Unaffected' School-Aged Siblings of Children with Autism Spectrum Disorder

Siblings of children with Autism Spectrum Disorder (ASD) who do not have ASD outcomes are more likely than their peers to experience delays in language acquisition as preschoolers. However, less is known about how these siblings are faring when they are school-aged. We examined language-related abilities of 17 non-ASD siblings, aged 8-11. On average, the non-ASD siblings performed more poorly than the normative sample on measures of phonological memory and phonological awareness. In contrast, word-level reading was intact. No impairments relative to norms were found on a direct child assessment and parent-report measure of pragmatic language; however, recommendations for further research in this area are made. The two pragmatic measures demonstrated weak convergent validity; questions were raised regarding the influence of having an older child with ASD and the effects on parents' frame of reference. Comparing two direct language assessments, this sample performed more poorly in pragmatics than structural language.

Keywords: Autism Spectrum Disorder
High-risk siblings
Language development
Phonological processing
Pragmatics
Reading
Advisor: Brian, Jessica A
Effective Mitigation of Shock Loads of Embedded Electronics in Smart Ammunitions by Polymeric Encapsulation

Short duration impulse and long duration shock loads can lead to the failure of embedded electronics typically used in smart ammunitions. The objective of this work is to develop the means to protect the printed circuit board (PCB) using polymeric encapsulating materials. Three aspects of the work were considered using finite element (FE) simulations. The first is concerned with the development of a micromechanical modelling scheme of a multilayered PCB to determine its equivalent elastic properties. The second is concerned with the determination of the mechanical integrity of the embedded electronics subjected to short duration impulse. The third is concerned with the dynamic behavior of the PCB subjected to long duration shock loads. The effectiveness of different encapsulation designs to attenuate the shock loads are examined. Our results reveal the remarkable effectiveness of a novel bilayer potting approach over the commonly adopted single potting attenuation strategy.

Keywords: Bilayer potting
Embedded electronics
FEM
Polymeric encapsulation
Shock attenuation system
Advisor: Meguid, Shaker A
Resveratrol Action in the Duodenum and the Regulation of Insulin Sensitivity

Oral resveratrol improves insulin sensitivity in obese or diabetic rodents, but the underlying mechanisms remain elusive. Resveratrol's effects have been attributed, in part, to the activation of SIRT1 and/or AMPK in various tissues, although the low bioavailability of resveratrol raises questions about whether these effects are direct. We here show that intraduodenal resveratrol infusion activates duodenal SIRT1 and AMPK to enhance insulin sensitivity to lower glucose production (GP) in high-fat diet (HFD)-induced insulin resistance, while duodenal SIRT1 knockdown in chow fed-rats induces hepatic insulin resistance. The glucoregulatory role of preabsorptive resveratrol is dependent on a gut-brain neuronal network to remotely restore hypothalamic insulin sensitivity and GP regulation. Lastly, intraduodenal resveratrol infusion lowers GP and plasma glucose levels in two complementary obese and type 2 diabetic animal models. These studies highlight the therapeutic relevance of duodenal resveratrol and SIRT1/AMPK activation in improving insulin sensitivity and glucose control in obesity and diabetes.

Advisor: Lam, Tony KT
Okapi (Oka), a Novel FERM Domain Protein Essential for Drosophila Oogenesis

FERM proteins are a class of important adaptors in animal tissues. They are ubiquitous in the cytocortex, linking the plasma membrane to cytoskeletal components, and are involved in structural, transport, and signaling functions. FERM proteins interact with numerous binding partners, including the transmembrane protein Crumbs (Crb), a key regulator of cell polarity in epithelial cells. In

Keywords: Crumbs
Drosophila
Epithelia
FERM
Oogenesis
Ovary
Advisor: Tepass, Ulrich
Implementing a Manualized Group Intervention for Bereaved Siblings: An Analysis of Feasibility and Barriers

The current study, conducted in two segments, assessed the feasibility of implementing a manualized support group for siblings who had experienced the death of a brother or sister from cancer. Part 1 was carried out with a convenience sample of 10 children, aged 6 - 14 years, who attended the program. With respect to acceptability, retention rates, and treatment fidelity, positive outcomes were obtained. Results of standardized questionnaires completed by parents indicated significant improvements in overall, emotional, and social quality of life, and trend-level reductions in problem behaviours and distress symptoms. Outcomes of siblings' self-report questionnaires reflected borderline decreases in problem behaviours. Part 2 of the investigation revealed significant recruitment barriers that impeded enrolment when rigorous sampling procedures were utilized. A qualitative analysis of phone recruitment interviews with parents yielded important themes explaining families' participation declines, including impediments to enrolment, communication with surviving children, and coping with grief.

Keywords: Bereavement
Cancer
Children
Intervention
Siblings
Advisor: Barrera, Maru
Dissecting the Role of Nucleosome Assembly Protein-1 (NAP-1) in Small RNA-mediated Chromatin Modulation in Caenorhabditis elegans

Small RNA-mediated gene-silencing pathways are critical regulators of gene expression throughout development. Some of the least understood roles for these small RNA pathways are in chromatin modulation and genome organization. Chromatin-modifying factors have recently been implicated as playing key roles in small RNA-mediated pathways. This study reveals a new role for the highly conserved histone chaperone, Nucleosome Assembly Protein-1 (NAP-1), in the CSR-1 (Chromosome Segregation and RNAi-deficient) small RNA pathway in the nematode,

Keywords: C. elegans
Chromatin modulation
CSR-1 Small RNA Pathway
Nucleosome Assembly Protein-1
RNA interference
Advisor: Claycomb, Julie M