VictorJuiz/thesis huggingface dataset:
Characterizing the Immuno-genomic Landscape of High-grade Serous Ovarian Cancer Patients with Exceptional Long- and Short-term Survival

Despite poor overall survival (OS) for patients diagnosed with high-grade serous ovarian cancer (HGSOC), a subset experience long-term (LT) survival (â Ľ 10 years, vs. 1.7 years median OS). In this study, we compared clinical, genomic, and transcriptomic characteristics of 41 treatment-naive tumour specimens from HGSOC LT (n=20) and short-term (ST,

Keywords: BRCA1/BRCA2
Cancer Genomics
Ovarian Cancer
Survival
Advisor: Pugh, Trevor J
Frequency Detection for Reference-less Baud-rate Clock and Data Recovery in 28nm CMOS

This thesis presents the analysis, design, simulation, and measurements of a frequency detection method for a reference-less baud-rate clock data recovery (CDR) circuit. This CDR was designed with a continuous-time linear equalizer (CTLE) and a 1-tap decision feedback equalizer (DFE) to implement a high-speed wireline receiver in a 28nm CMOS process and packaged in a 40-pin Quad-Flat No-leads (QFN) package. The frequency detection method automatically controls an adjustable baud-rate phase detector to correct frequency error between the incoming data and the recovered clock without a separate frequency acquisition loop in the CDR. To characterize the performance of this method, PRBS-31 data ranging from 22.5Gb/s to 32Gb/s was transmitted across a Tyco 5-inch channel with -10.1dB to -14.8dB channel loss at Nyquist. The frequency detection method was measured to achieve a capture range of 34%. The entire receiver achieved a power eciency ranging from 2.9pJ/bit to 3.2pJ/bit.

Keywords: baud-rate
CDR
CTLE
DFE
frequency detectors
wireline transceivers
Advisor: Sheikholeslami, Ali
Global and CMV-specific Immune Assays to Predict Clinical Outcomes and Inform Clinical Practice in Solid Organ Transplant Recipients

Solid organ transplantation is an effective procedure for the treatment of end-stage organ failure. However, transplantation can be limited by imprecise immunosuppression and thereby, susceptibility to infections. Assays that measure immune function by quantifying release of cytokines following stimulation of immune cells have shown some predicative value for the development of infections in immunocompromised individuals. This thesis investigates the predictive value, feasibility and clinical benefit of using immune assays in the context of solid organ transplantation. We demonstrated that a newly developed global (innate and adaptive) cell-mediated immune assay called QuantiFERON-Monitor had the ability to quantify the degree of immunosuppression and predict susceptibility of transplant recipients for developing infections. Furthermore, we showed that a cytomegalovirus(CMV)-specific immune assay called QuantiFERON-CMV could predict which patients were susceptible for developing recurrent CMV infections. Finally, we demonstrated that CMV-specific cell-mediated immunity as measured by QuantiFERON-CMV was both feasible and useful in personalizing CMV prophylaxis.

Keywords: Cell-mediated Immunity
CMV
Immunosuppressive medication
Infectious Disease
Transplantation
Advisor: Humar, Atul
Kumar, Deepali
The Effect of Folic Acid Supplementation on Chemosensitivity of Human Breast Cancer Cells in an in vitro Model

In North America, blood folate levels have dramatically increased due to mandatory folic acid (FA) fortification and widespread supplement use. Breast cancer patients report highest FA containing supplement use. 5-fluorouracil (5-FU) is the cornerstone of breast cancer chemotherapy, mechanisms of action which are based in part on interruption of folate metabolism. Concerns have been raised whether increased folate status may interfere with 5-FU chemotherapy for breast cancer. This study investigated whether FA supplementation can affect chemosensitivity of human breast cancer cells to 5-FU in 3 distinct human breast cancer cell lines. FA supplementation significantly decreased 5-FU chemosensitivity in MDA-MB 231 cells, significantly increased 5-FU chemosensitivity in HCC1937 cells and induced an inverted U shape response in MCF-7 cells. Given the high FA intake in breast cancer patients, the results from this study are concerning and future studies are warranted to clarify the effect of FA supplementation on 5-FU chemosensitivity.

Keywords: 5-fluorouracil
breast cancer
chemosensitivity
folate
folic acid
Advisor: Kim, Young-In
Kotsopoulos, Joanne
The Activism of First Generation Somali Canadian Women within a Neoliberal Multicultural State

This thesis aims to explore the activism of first generation Somali Canadian Women (FGSCWA). It specifically asks 1) how do Somali women activists engage, contest and modify existing social relations within their community and mainstream society to foster anti-racist, anti-Islamaphobic feminist spaces; 2) in what ways does their activism challenge the systematic racism and Islamaphobia that is explicitly and implicitly imbedded in Canadian institutions and social relations and; 3) how has their activism and advocacy challenged the normative discourse of neoliberal multiculturalism, while simultaneously contesting gender norms and cultural dogma within the Somali community. This study combines two theoretical approaches to understand issues of citizenship, boundaries of Blackness and Muslim identity, power, representation and knowledge production in relation to Somali women activists. Working within a post-colonial and Black feminist framework, this research paper utilizes the in-depth interviews I conducted with eight Somali women activists, narrating their perspectives and lived experiences.

Keywords: Activism
Anti-Black Racism
Immigration
Intersectionality
Multiculturalism
Somali Women
Advisor: Mojab, Shahrzad
Addressing the Effects of Distractors in a Brain-computer Interface

This thesis investigated the effects of transient, visual task-irrelevant distractors on a brain-computer interface (BCI). In the first study, a motor imagery BCI was developed using electroencephalography (EEG) to measure brain signals. The performance of this system was validated in both an offline and online setting. The second study examined the effect of distractors on motor imagery-related brain patterns and on the classification accuracy of the developed BCI system. While distractors appeared to attenuate motor imagery-specific brain activity, BCI performance did not differ significantly amid distractors, indicating that the BCI system was fairly robust to distractor effects. In the third study, distractors were found to significantly increase a physiological index of cognitive load. This thesis demonstrated that it is important to address the effects of distractors in BCIs, particularly on cognitive load, to allow for the eventual translation of BCIs from the lab to the home.

Keywords: brain-computer interface
cognitive load
distractor
electroencephalography
motor imagery
Advisor: Chau, Tom
Development of a Receptor Internalization Assay for Measuring and Analysing RGS9-2 and Palmitoyl-CoA Transferase Activity in HEK Cells

Regulator of G-protein signalling 9-2 (RGS9-2) complex inhibits agonist-dependent dopamine receptor D2R activity and internalization, and plays a protective role against the development of neuro-reward circuit dysfunction. R7 binding protein (R7BP) is necessary for RGS9-2 protein stability and trafficking. Preliminary work from our group has shown the palmitoyl-CoA transferase, DHHC5, can facilitate R7BP trafficking, however this function can also enhance RGS9-2 trafficking and function. The aim of this work is to establish an in vitro assay to verify the effects of DHHC5 and R7BP on the internalization of D2R in HEK cells. We established a modified ELISA protocol that consistently showed ~20% internalization of surface D2R, which is not ideal, possibly due to the poor internalization properties of D2R in HEK cells. Future efforts, therefore, will require the development of other functional assays to examine the role of DHHC5, R7BP and RGS9- 2 as a regulator of D2R signalling and function

Keywords: D2R
DHHC5
Internalization
R7BP
RGS9-2
Advisor: Heximer, Scott P
Do Objects of Different Weights Fall at the Same Time? Learning about Gravity from Picture Books

Picture books are a primary source of knowledge for children. However, young children are rarely exposed to informational books and spend more time reading fiction. We examined how children age 4 and 5 learn that objects with different weights fall at the same rate from picture books. A realistic fiction and an informational book with identical images were designed and matched in words and reading difficulty level. A pretest and posttest were administered to 120 children. Each test contained 4 pairs of objects identical in size, where two pairs of objects had the same weight and two pairs of objects had different weight. Although generally all children improved from pretest to posttest, 5-year-olds learnt from both types of book genres, while 4-year-olds learnt only from the realistic fictional book. Finally, children reported enjoying the realistic fictional and informational genres equally.

Advisor: Ganea, Patricia A.
Anti-RBC Antibody Mediated Erythrocyte Phagocytosis and its Therapeutic Role in Immune Thrombocytopenia (ITP)

Immune thrombocytopenia (ITP) is a platelet autoimmune disorder diagnosed by an isolated low platelet count and the absence of other causes of thrombocytopenia. Rh immune globulin (anti-D) is a first line therapy for ITP which targets the RhD antigen on erythrocytes. Monoclonal antibodies are desirable alternatives to anti-D for various reasons. Here, nine erythrocyte-specific antibodies were evaluated for their ability to opsonize RBCs for phagocytosis and prevent platelet destruction in vitro using these opsonized RBCs. Only three (34-3C, TER119 and M1/69) effectively induced phagocytosis of RBCs. Antibodies that were able to opsonize RBCs for phagocytosis also inhibited platelet phagocytosis. TER119, 34-3C and M1/69 are the only antibodies tested that ameliorate ITP in a passive mouse model. These data suggest that the ability of an antibody to prevent platelet phagocytosis in vitro could be indicative of its ability to ameliorate ITP. We speculate that a future screening tool to test the therapeutic ability of monoclonal antibodies in ITP may be possible using these methods.

Keywords: Anti-D
anti- erythrocyte antibodies
Immune Thrombocytopenia
platelets
Advisor: Lazarus, Alan
Galectin-9 Regulates B Cell Receptor Signaling

B cells are an essential component of the adaptive immune system, which secrete soluble antibody against pathogen (antigen). Given that glycan-galectin lattices have been shown to regulate cell surface glycoprotein organization and signaling, one of these galectins is Galectin-9 (Gal-9); a secreted lectin with two carbohydrate recognition domains linked by a flexible peptide. Here, we show that Gal-9 is expressed at the cell surface of primary B cells, organized into discrete puncta. Gal-9 deficiency enhanced BCR microcluster formation and increased BCR signaling. Moreover, treatment of wild-type B cells with exogenous Gal-9 is sufficient to inhibit cell signaling upon BCR stimulation, suggesting that Gal-9 is a negative regulator of B cell activation. We identified CD45 and IgM as ligands for Gal-9 to which they colocalized with Gal-9 lattices. Taken together, our data suggests that Gal-9-glycan interactions at the surface of B cells plays an important role in regulating B cell signaling.

Keywords: B cell activation
BCR signaling
Galectin-9
Glycan-galectin-9 lattices
Advisor: Treanor, Bebhinn
Metabolic Engineering of Escherichia coli for Production of Adipic Acid through 2-Hexenedioate Pathway

Adipic acid is one of the most important platform chemicals in industry. Bio-based production of adipic acid is a promising alternative to the current petrochemical production routes which cause environment and energy concerns. This work describes efforts to construct a platform strain of Escherichia coli for production of adipic acid. First, we constructed an E. coli strain harbouring part of the α-aminoadipate pathway from Saccharomyces cerevisiae. Through fed-batch fermentation, the strain showed its capability of producing α-ketoadipate, a precursor of adipic acid, from its native metabolite α-ketoglutarate. Second, we constructed an E. coli strain harbouring a pathway converting α-ketoadipate to adipic acid. Through various studies, we were able to illustrate that all enzymes of the pathway are active in vivo. This work demonstrates the capability of E. coli for production of α-ketoadipate and paves the way for further studies on conversion of α-ketoadipate to adipic acid.

Keywords: 2-hexenedioate
adipic acid
alpha-ketoadipate
alpha-ketoglutarate
Escherichia coli
metabolic engineering
Advisor: Mahadevan, Radhakrishnan
Childhood Maltreatment and Parenting Alliance: Can We Get Along if You Regulate My Emotions?

This study investigated the effect of childhood maltreatment history on parenting alliance and examined whether emotion regulation mediates this link. I further examined whether emotion co-regulation could buffer individuals with childhood abuse history and their co-parenting partner against poor parenting alliance. This model was tested using mothers and fathers recruited from the community and from intervention programs addressing family violence. Consistent with my predictions, child maltreatment history was negatively associated with self-reported and partner-reported parenting alliance. However, contrary to my hypotheses emotion regulation abilities did not mediate this relationship. Furthermore, perceived partner emotion co-regulation abilities did not act as a buffer for maltreated individuals, as perceived partner co-regulation predicted better parenting alliance regardless of maltreatment severity. These findings highlight the associations between child maltreatment and subsequent co-parenting outcomes, and suggest that clinicians consider the positive influence of emotion co-regulation on co-parenting functioning for maltreated individuals and their co-parenting partners.

Keywords: childhood maltreatment
emotion co-regulation
parenting alliance
Advisor: Scott, Katreena
BRCA1 Modulation of Glucocorticoid Receptor Signal Signaling in High-grade Serous Ovarian Cancer Cells

Germline BRCA1 mutations increase a woman’s risk of developing high-grade serous ovarian cancer (HGSOC) up to 43-fold. Lifetime ovulatory events also associate with increased risk. Studies suggest the post-ovulatory pro-inflammatory milieu persists longer in BRCA1 mutation carriers compared to control women. Slowed remediation of pro-inflammatory signaling leads to increased reactive oxygen species levels that potentiate DNA damage accumulation, which may ultimately promote malignant transformation. Preliminary evidence suggests BRCA1 may modulate glucocorticoid receptor (GR) activity, a major anti-inflammatory mediator. Impairment of GR signaling by BRCA1 mutation may contribute to increased HGSOC risk. My objective was to determine if BRCA1 deficiency affects GR signaling in HGSOC cells. My results indicate BRCA1 enhances GR levels and GR transcriptional activity independent of its effect on GR levels. BRCA1 expression also correlates with diminished pro-inflammatory cytokine mRNA levels at baseline. Overall, BRCA1 has a dynamic role in modulating inflammatory signaling through GR in HGSOC cells.

Keywords: BRCA1
Breast Cancer
1
Glucocorticoids
Ovarian Cancer
Advisor: Brown, Theodore J.
The effect of Lactobacillus rhamnosus GR-1 supernatant on endotoxin-induced cytokine secretion in human myometrial cells

Prophylactic administration of probiotic Lactobacillus rhamnosus GR-1 supernatant (GR1SN) was shown to prevent lipopolysaccharide (LPS)-induced preterm birth (PTB) in mice by suppressing pro-inflammatory cytokine expression in uterine tissues in vivo. The aim of this thesis is to elucidate the effects of GR1SN in human myometrial cells in vitro, where I hypothesize it will suppress LPS-induced cytokine secretion. Here I demonstrate that PBS-based GR1SN contains protein moieties that induce endotoxin tolerance-like phenotypes in myometrial cells to suppress secretion of pro-inflammatory factors following LPS stimulus. The observed effects are unique to a GR1SN-myometrial cell interaction, and cannot be replicated using supernatant derived from non-GR-1 lactobacilli species. However, in vivo, GR1SN-PBS does not delay the onset of LPS-induced PTB in pregnant CD-1 mice under the experimental conditions used. Through this project, I have highlighted the unique capacity of protein moieties secreted by L. rhamnosus GR-1 to inhibit inflammatory signals in human myometrial cells.

Keywords: Cytokines
Lactobacillus rhamnosus GR-1
Myometrium
Preterm Birth
Probiotics
Advisor: Lye, Stephen J
The Circulating Furan Fatty Acid Metabolite CMPF Directly Enhances Hepatic FGF21 Secretion and Lipid Metabolism

Elevation of the fish oil metabolite 3-carboxy-4-methyl-5-propyl-2-furanpropanoic acid (CMPF) induces metabolic remodeling within the -cell to a preferential use of fatty acids. Although detrimental to -cell function, this energetic switch could benefit metabolic tissues like the liver, where obesity increases hepatic fat accumulation. CMPF primarily utilizes the Organic Anion Transporter (OAT) family, with OAT2 expressed in the liver. Following treatment, CMPF enters the hepatocyte. To determine a direct effect on liver function, isolated murine hepatocytes were treated for 24-hours with CMPF. CMPF significantly increased hepatic fatty acid oxidation and lipogenesis, without altering fatty acid uptake or gluconeogenesis. CMPF improved hepatic insulin signaling following lipid overload and enhanced FGF21 expression. Enhanced lipid oxidation occurred without ACC/AMPK phosphorylation, CMPF impaired enzymatic activity of isolated ACC, and direct ACC inhibition similarly increased FGF21 expression, suggesting an ACC inhibitor like effect of CMPF. These results demonstrate a potential therapeutic target to prevent hepatic steatosis.

Keywords: ACC Inhibition
CMPF
FGF21
Lipid metabolism
NAFLD
Steatosis
Advisor: Wheeler, Michael
PKCδ Regulates the Behavior of Migrating Cells in the Drosophila ovary

The border cell cluster (BCC) in the Drosophila ovary allows us to study the molecular mechanisms that regulate cell migration in vivo. Our lab previously showed that PKCδ, a member of the protein kinase C family, affects BCC motility. My goal was to determine the expression pattern and the function of PKCδ in BCCs. I generated antibodies that target PKCδ to examine BCCs with increased expression of PKCδ. PKCδ seemed to be enriched in the cortical region and some cellular protrusions, and appears to be complementary to Myosin II. An analysis of BCCs with mosaic overexpression of PKCδ revealed that rosette cells with increased PKCδ expression have a decreased tendency to reside at the leading edge of the BCC during migration. Further examination showed that PKCδ-overexpressing rosette cells extend less major protrusions than wild-type cells, and are less compact as a group than a group of wild-type cells.

Keywords: Drosophila
migration
ovary
PKCδ
Advisor: Godt, Dorothea
Engineering of Actively Targeted Block Copolymer Micelles for Delivery of Doxorubicin to Breast Cancer Cells Overexpressing HER2 and EGFR

Tumour heterogeneity remains one of the hallmark challenges in nanomedicine. Heterogeneous cell receptor expression presents a need for personalized therapeutic treatment options. In the case of human epidermal receptor 2-positive (HER2+) metastatic breast cancer (MBC), trastuzumab often results in the acquisition of trastuzumab resistance (TR). The implementation of dual-targeted nanoparticles is proposed as a strategy to overcome tumour heterogeneity and TR. A BCM delivery system was designed to deliver doxorubicin to HER2 and EGFR-overexpressing MBC cells through dual active targeting with peptides. Physico-chemical characterization of the BCM and its components was performed and in vitro cytotoxicity was evaluated in order to determine the effects of dual-targeting. Only minor targeting activity was observed during EGFR-targeting, although HER2-targeting was effective. The dual-targeted formulation was effectively able to enhance the cytotoxicity of the DOX-loaded BCMs and there is evidence that dual-targeting may provide therapeutic response to multiple cell lines with variable receptor phenotypes.

Keywords: block copolymer micelles
breast cancer
doxorubicin
EGFR
HER2
Advisor: Allen, Christine
Microfluidics for Fluid Analysis in Oil Sands and Tight Oils

Unconventional oil recovery has advanced over the decades as conventional oil supply declines. In North America, unconventional oil has been commercialized in the oil sands and shale formations. However, as oil prices collapse and emission concerns associated with hydrocarbon recovery increases, producers are seeking cost-effective methods to improve economic and environmental performance. Steam-Assisted Gravity Drainage (SAGD) and hydraulic fracturing methods are hindered by massive water demands for stimulating formations. Microfluidics, a fluid analysis tool benefiting from small sample volumes and precise quantification, has emerged as a useful platform for hydrocarbon analysis, particularly for demanding, reservoir-relevant conditions (high temperatures and pressures). In this vein, the presented work demonstrates two microfluidic applications. The first method is a tube-based viscometer with in-line mixing relevant to solvent-based recovery of oil sands. The second method is a physical model of nanopores relevant to hydraulic fracturing with the aim to show fluid interactions at the pore-scale.

Keywords: Bitumen
Hydraulic fracturing
Imbibition
Microfluidics
Oil sands
Shale oil
Advisor: Sinton, David
Development and Alpha Testing of a Fertility Decision Aid for Young Canadians Diagnosed with Breast Cancer at Risk of Infertility Following Cancer Treatment

Young women (45 years of age or younger) diagnosed with breast cancer are at risk of treatment-related infertility. Even with established fertility preservation options available in Canada, women feel as though they have limited support and access to resources. This thesis aimed to develop a Canadian decision aid to assist young women in making value-based fertility preservation decisions prior to breast cancer treatment. The development process was guided by the Ottawa Decision Support Framework and International Patient Decision Aids Standards criteria including an evaluation of existing decision support resources, initial paper prototype development and content expert review, end user engagement at a one-day meeting, development of an online decision aid, and alpha testing. The final paper and online decision aid will be pilot tested and disseminated across Canada to help young breast cancer patients make informed fertility decisions in partnership with their health care providers prior to treatment.

Keywords: Breast Cancer
Decision-Making
Decision Support Tools
Fertility
Qualitative
Young Adults
Advisor: Baxter, Nancy N
Engineering of the Plant Abscisic Acid Biosynthetic Pathway in Escherichia coli

Abscisic acid (ABA) is a phytohormone involved in many aspects of plant growth and development, including the regulation of seed development, dormancy, germination, and plant responses to environmental stress. Escherichia coli is an ideal system in which to engineer the ABA biosynthetic pathway since the early steps have been successfully reproduced in E. coli by Misawa and colleagues (1990) using the carotenoid biosynthesis gene cassette from Pantoea ananatis. In this study, Arabidopsis thaliana genes were used to build the pathway starting from the precursor zeaxanthin. The next biosynthetic enzyme, zeaxanthin epoxidase (ZEP), was successfully expressed in E. coli, leading to the effective production of violaxanthin. However, the enzyme responsible for catalyzing the subsequent step has yet to be identified. This system is now being used to identify uncharacterized genes of the pathway.

Advisor: Nambara, Eiji