VictorJuiz/thesis huggingface dataset:
Mammary Specific Lunatic Fringe Deletion Results in Tumor Development with Met Amplification, and Cooperates with Trp53 Mutation in Tumorigenesis

Mammary deletion of Lunatic Fringe (Lfng), an enzyme that regulates Notch receptor-ligand interactions, results in Basal-like tumor formation. Notch regulates mammary cell differentiation, and aberrant activity results in tumorigenesis. Lfng deficient mice develop Basal-like tumors with Met amplification. I studied Met expression in these tumors, and found it's expressed by a subset of tumor cells. Expression was associated with hypoxia, and found in epithelial-to-mesenchymal transition (EMT) regions, and near necrosis. Since Met is a transcriptional target of hypoxia-inducible factor 1, it's likely that hypoxia results in increased Met expression. Met also co-expressed with luminal cell marker Cytokeratin 8 and progenitor marker Aldehyde dehydrogenase I. Finally, I tested for cooperation between Lfng deficiency and Trp53R270H mutation in tumorigenesis. Double mutant mice showed decreased tumor-free survival suggesting a cooperative relationship. My work suggests that Met plays a role in luminal/progenitor-like cells and cooperation between Lfng deficiency and Trp53R270H results in reduced survival.

Keywords: Breast Cancer
immunofluorescence
Met
Mouse models
Notch
Transgenics
Advisor: Egan, Sean E
Coallocation of Appetitive and Aversive Memories in the Lateral Amygdala

The amygdala plays a key role in representing memories for both fear and reward. However, it is currently not understood how neurons in this structure differentially code memory traces for such strikingly different emotions. Amygdala neurons might be valence-specific, able to encode only fear or reward. Alternatively, these neurons may be equipotent â able to encode memories of any valence. We examined these two alternatives by allocating a fearful and rewarding memory to a single population of neurons in the lateral amygdala (LA). Here we show that co-allocation of these memories leads to overwriting: the fear memory formed first is erased and replaced by the reward memory formed second. These results provide evidence that LA neurons are equipotent and capable of switching the valence they encode. Together, these findings establish support for a dynamic, activity-dependent view of valence allocation in the lateral amygdala.

Keywords: Amygdala
Memory
Memory allocation
Valence
Advisor: Josselyn, Sheena
Neural Network Disturbances in Paediatric Brain Tumour Survivors

Children treated for brain tumours exhibit altered brain structure and function leading to long-term cognitive impairments. These structural and functional alterations imply there may also be perturbations in the neural networks that underlie cognitive function. We investigated neural network disturbances by examining resting-state functional connectivity in paediatric brain tumour survivors (PBTS) relative to healthy children using magnetoencephalography. Time-series were reconstructed for cortical, subcortical and cerebellar sources in the Automated Anatomical Labeling atlas and filtered into 6 frequency bandwidths. Functional connectivity among brain regions was indexed using the phase lag index. Relative to healthy children, PBTS showed significantly increased functional connectivity in the delta (2-3Hz) band and decreased functional connectivity in the low gamma (30-59Hz) and high gamma (60-100Hz) bands. Similar changes in broader patient populations suggest that increased low frequency connectivity and decreased high frequency connectivity may be an overarching neural signature of brain injury and disease.

Keywords: Brain Tumours
Cognitive Impairments
Functional Connectivity
Magnetoencephalography
Advisor: Mabbott, Donald J
Fabricating Flax/Wood Pulp Fiber Hybrid Composites For Construction of Lightweight Sandwich Panels

The growing demand for natural materials is overtaking the composite sector for various applications. However, use of natural fibers in structural applications is largely untapped. In this thesis, hybridization of flax and wood pulp fibers reinforcing Poly-lactic acid (PLA) matrix is studied to produce lightweight sandwich panels. Face and core composites were assembled using film stacking (of 30wt% fiber loading) and wet-laying (of 50wt% fiber loading) process, respectively and hot pressed to form composites. Mechanical properties were tested with varying composite weight ratios of untreated/alkali-treated flax to pulp fibers. Tensile modulus of face composites showed a positive hybrid effect via HROM and an overestimation by Halpin-Tsai. Compression strength of core composites showed an increase of 67% by replacing 10wt% pulp fiber with flax fibers. Finally, sandwich panels, constructed by hot pressing best combinations of face and core composites, showed core shearing as the primary failure mode under flexural load. The growing demand for natural materials is overtaking the composite sector for various applications. However, use of natural fibers in structural applications is largely untapped. In this thesis, hybridization of flax and wood pulp fibers reinforcing Poly-lactic acid (PLA) matrix is studied to produce lightweight sandwich panels. Face and core composites were assembled using film stacking (of 30wt% fiber loading) and wet-laying (of 50wt% fiber loading) process, respectively and hot pressed to form composites. Mechanical properties were tested with varying composite weight ratios of untreated/alkali-treated flax to pulp fibers. Tensile modulus of face composites showed a positive hybrid effect via HROM and an overestimation by Halpin-Tsai. Compression strength of core composites showed an increase of 67% by replacing 10wt% pulp fiber with flax fibers. Finally, sandwich panels, constructed by hot pressing best combinations of face and core composites, showed core shearing as the primary failure mode under flexural load.

Keywords: flax fibers
hybrid biocomposites
mechanical properties
sandwich panels
structural biocomposite
wood pulp fibers
Advisor: Yan, Ning
Caveolin1 Mediates the Midkine-Induced Angiotensin I Converting Enzyme Signaling in Human Lung Epithelial Cells

Introduction: Midkine (MK), a novel cytokine, is upregulated in acute respiratory distress syndrome (ARDS) patients. MK interacts with the cell surface receptor Notch2 to induce epithelial-mesenchymal transition (EMT) through angiotensin I converting enzyme (ACE) in lung epithelial cells. However, it remains unknown how Notch2 modulates ACE expression, since there is lack of direct interaction between these two molecules. Caveolin1 (Cav1) has been shown to regulate ACE expression. We hypothesized that Cav1 interacts with Notch2 to mediate the MK-induced ACE signaling pathway. Methods: Human lung epithelial cells were used for co-immunoprecipitation to examine Notch2 interaction with Cav1. Cells were stimulated with recombinant human midkine (rhMK) and transfected with Cav1 siRNA to determine the role of Cav1 on Notch2, ACE, and EMT. Results: Cav1 bound specifically with Notch2, but not Notch1, Notch3, or Notch4. Cav1 knockdown blocked the rhMK- induced ACE and EMT signaling in lung epithelial cells. Conclusion: Cav1 is required to mediate the MK-Notch2-ACE signaling pathway. Word count: 150

Keywords: Acute respiratory distress syndrome
Angiotensin I converting enzyme
Caveolin1
Fibrosis
Midkine
Notch2
Advisor: Zhang, Haibo
Particulate Matter Oxidative Potential as an Additional Metric of Air Pollution Exposure

Epidemiological studies have consistently demonstrated associations between particulate matter (PM) mass concentration and adverse cardio-respiratory health effects. However, PM mass concentration does not consider the PM source and constituents, and, therefore, may not adequately reflect PM toxicity. It has been proposed that PM oxidative potential (OP) may serve as a better biological index of PM toxicity. Controlled ambient particle exposures were performed to assess associations between PM OP and acute cardiovascular health responses. The PM OP was associated with cardiovascular responses and metal species indicative of traffic-related air emissions. The sensitivity of the PM OP metric to local PM sources was also evaluated using filters collected from three sites with different traffic characteristics. Spatial and temporal variations were observed in PM OP and not in PM mass concentration. These findings suggest that PM OP is a more adequate biological indicator of PM toxicity compared to that of PM mass concentration.

Keywords: Oxidative Potential
PM
Advisor: Evans, Greg J.
The Core Components of Cardiac Rehabilitation for Health Related Quality of Life in Coronary Heart Disease Patients: A Systematic Review and Meta-analysis of Randomized Controlled Trials

Background: Cardiac rehabilitation (CR) is a comprehensive program offered to patients with coronary heart disease (CHD). The aim of this study was to assess the effectiveness of providing any core component of CR on health related quality of life (HRQOL) in adult patients with CHD. Methods: We performed a systematic review, meta-analysis and meta-regression of randomized controlled trials examining the core components of CR. Identified sources were published between database inception and July 16th, 2014. Outcomes included overall, physical, emotional and social HRQOL. Outcomes were reported as standardized mean change (SMC) with 95% confidence intervals. Results: Summary effect sizes were (SMC 0.14; 95% CI 0.03 to 0.25), (SMC 0.23; 95% CI 0.08 to 0.38), (SMC 0.11; 95% CI -0.03 to 0.24) and (SMC 0.03; 95% CI -0.07 to 0.13) for overall, physical, emotional and social HRQOL respectively. Conclusion: Receiving any CR intervention was shown to improve overall and physical HRQOL.

Keywords: Cardiac Rehabilitation
Meta Analysis
Quality of Life
Systematic Review
Advisor: Krahn, Murray
Assessment of the Therapeutic Potential of a Dental Probiotic in Orthodontic Patients Affected by Gingivitis: A Randomized Control Trial

Background: As fixed orthodontic appliances pose a risk factor for plaque accumulation and gingivitis, a need for an adjunctive aid to the oral hygiene regimen exists. A probiotic complex (Lorodent) has yet to be investigated within the orthodontic context. Purpose: To investigate the efficacy of Lorodent in reducing gingivitis and selected periodontal pathogens in orthodontic patients. Research Design: This randomized controlled trial consisted of 60 patients who received either probiotic or placebo lozenges for 28 days. Gingivitis was assessed. Saliva and subgingival plaque samples were collected for evaluation of probiotic and periodontal bacteria levels over the span of 56 days. Results: Lozenge consumption compliance was >90%. The probiotic test group showed no significant change in gingival indices. There were no significant differences in the level of pathogenic bacteria between the probiotic or placebo group. Conclusions: Lorodent did not significantly reduce periodontal pathogens or gingival indices in patients undergoing orthodontic treatment.

Keywords: braces
gingivitis
Lactobacillus
orthodontics
probiotic
Streptococcus salivarius
Advisor: Gong, Siew-Ging
Tensile and Bond Behaviour of GFRP Bars under Various Load and Temperature Conditions

A study of existing research shows a need for an investigation of the tensile and bond properties of glass fiber-reinforced polymer (GFRP) bars at low and high temperatures varying between about -40oC and glass transition temperature. Study of the response of GFRP bond members at various temperatures is also essential for understanding the bond behaviour of GFRP-reinforced structural members. For this study, 55 tensile test specimens and forty cylinders reinforced with GFRP were constructed and tested under direct tension and standard pullout bond test, respectively. The influence of temperature on tensile properties and bond performance of GFRP bars is analyzed and reported. The bond strength of the GFRP bars under high temperatures was determined to be between 58% and 88% of the bond strength of the same bar at room temperature, while the tensile strength was found to be between 68% and 73% of the tensile strength at room temperature.

Advisor: Sheikh, Shamim A.
Defining Notch Functions in the Development of Innate T Cells

Innate T cells, which include PLZF+ T cells and innate memory CD8 SPs, represent a unique lineage of T cells that are pre-activated and rapidly respond to antigen. Although the role of Notch in early T cell development is well-established, its function in late T cell development, when innate T cells arise, is unclear. Here, we report that CD4-Cre-mediated intracellular Notch1 expression (ICN1) increased the non-cell autonomous development of innate memory CD8 SPs. ICN1-expression also increased the frequency of NKT2 cells and number of V6 ÎłÎ´ T cells in the thymus, which are specific PLZF-expressing innate T cell subsets suggested to drive innate memory CD8 SP development through IL-4 secretion. Collectively, my data demonstrates that Notch signaling is an important regulator of innate T cell development and emphasizes its role in late T cell development.

Keywords: IL-4
Innate memory
NKT Cells
Notch
PLZF
V6 γδ T cell
Advisor: Guidos, Cynthia J
Application of Low Consistency Refining of Pulp in Producing Multi-ply Folding Boxboards

In this study, the effect of using low consistency refined (LCR) pulp in the middle-ply furnish of folding boxboards (FBBs) is examined. LCR radiata reject pulp (LCRR) with a wide range of freeness values were blended with three commercial BCTMPs to form FBB middle-ply samples. The results indicated that increasing LC refining energy of radiata reject pulp improved the mechanical strength of samples up to the optimum freeness of about 400mL. Laboratory-made three-ply FBBs with varying LCRR contents in the middle-ply were also prepared and compared to those containing 100% commercial BCTMPs in the middle-ply. It was shown that FBBs containing 45% LCRR had better mechanical properties compared to those containing only commercial BCTMPs. Additionally, the use of HC-LC refined spruce-pine-fir (SPF) pulp as the middle-ply furnish in a three-ply FBB was investigated. It was found that sulphite pretreatment of HC-LC refined pulp had no clear effect on FBB properties. In the second part of this study, the use of HC-LC refined spruce-pine-fir (SPF) pulp as the middle ply furnish in a three ply FBB was investigated. It was found that sulphite pretreatment of HC-LC refined pulp had no clear effect on FBB properties. Instead, strength properties of three ply FBB samples were predominantly a function of the freeness.

Keywords: Folding boxboards
Low consistency refining
Reject pulp
Thermo-mechanical pulp
Advisor: Farnood, Ramin R
Mind Wandering Differences Between Younger and Older Adults: A New Neurocognitive Framework

Despite age-related executive functioning declines, older adults report mind wandering less than younger adults. This thesis behaviourally tested a new neurocognitive framework for the mechanisms behind this discrepancy. The framework focuses on age-related changes in the dorsal attention network, default mode network, and fronto-parietal control network. Younger and older adults performed the sustained attention to response task in an MRI scanner. Mind wandering was inferred from commission errors and response time (RT) patterns. RT patterns were analyzed with an ex-Gaussian model, producing three ex-Gaussian parameters (mu, sigma, tau), and by examining pre-error speeding and post-error slowing. Younger adults demonstrated greater tau values and pre-error speeding than older adults, suggesting more frequent mind wandering. Only younger adults demonstrated a positive relationship between tau and commission errors, suggesting that mind wandering drove more commission errors in younger adults. Similarly, a positive correlation between mu and sigma was only found in younger adults.

Keywords: aging
default mode network
dorsal attention network
mind wandering
response time
sustained attention to response task
Advisor: McIntosh, Anythony R.
Strother, Stephen
An evaluation of the clinical utility of the Sport Concussion Assessment Tool-3 (SCAT3) in varsity athletes

Sport-related concussion is a type of traumatic brain injury that remains challenging to identify and diagnose. The development of the Sport Concussion Assessment Tool-3 (SCAT3) provides a strong framework for evaluating concussion by amalgamating well-established assessment tools. The current study evaluated the clinical utility of the SCAT3 in identifying concussion across time by comparing varsity athletesâ post-concussion scores to pre-injury baseline scores, and also to normative data. Results suggest that the SCAT3 is sensitive to detecting concussion within 3 to 5 days and 3 weeks post-injury, with the utility being greatest using a normative approach, compared to the baseline-retest method. The symptom scale included in the SCAT3 largely contributed to the overall sensitivity of the tool, followed by the balance and cognitive measures. This study provides evidence to support the use of the SCAT3 within the first 3 weeks post-injury, however might be limited beyond this timeframe.

Keywords: Assessment
College athlete
Concussion
Sensitivity
Sport Concussion Assessment Tool-3
Sport-related concussion
Advisor: Cooper, Paul
Studies towards the Development of a DART-MS Based Assay to Study the Kinetics of PgaB, a de-N-acetylase Essential for Biofilm Formation

Bacterial biofilms are surface-attached microbial communities embedded in an extracellular matrix. The extracellular matrix of many infectious bacterial strains contains partially de-N-acetylated Î˛-(1,6)-N-acetylglucosamine polymers (dPNAG). In E. coli, the CE4 deacetylase PgaB catalyzes partial de-N-acetylation of PNAG, which is essential for biofilm formation. PgaB selectively de-N-acetylates the third position of a synthetic PNAG pentasaccharide in vitro, however, the observed catalytic efficiency is poor with a kcat/KM of 0.25 M-1s-1. We hypothesized that PgaB has higher catalytic activity with the natural PNAG polymer. Using DART-MS an assay has been developed to study the kinetics of PgaB by monitoring the release of acetate. The DART-MS based assay provided comparable kinetic information as the fluorescamine assay upon analysis of a simple reaction mixture of PgaB and PNAG oligomers, showing that DART-MS is a promising tool to monitor such reactions. However, it was not useful for a multi-enzyme reaction due to strong matrix effects.

Advisor: Nitz, Mark
Exploring Correlations between Parent Involvement and Performance and Self Efficacy Outcomes in Children with Cerebral Palsy

Little research has been done on parent involvement and outcomes in children with Cerebral Palsy. This study explored the degree to which parent involvement during and after a 12-session intervention is correlated with performance and self-efficacy outcomes in children with CP. Data for this study were collected as part of a primary study that examined a new treatment approach for children aged 7 to 12 with CP. Child outcomes measures were the Canadian Occupational Performance Measure, the Activity Scale for Kids, the Performance Quality Rating Scale, and the Self-Efficacy Probe.Â Parent involvement was measured using a both parent and therapist logs. Higher parent involvement was associated with better performance in some outcomes but this finding was reversed at post intervention to follow-up where more parent involvement was associated with poorer outcomes. These results suggest that further investigation into the associations between parent involvement and outcomes is warranted.

Keywords: Cerebral Palsy
Family Centered Care
Parent Involvement
Advisor: Cameron, Deb
Characterizing Function of Transmembrane Protein 65 in Mouse Neonatal Ventricular Cardiomycytes

The cardiomyocyte (CM) intercalated disc (ICD).is fundamental for signal propagation, cell adhesion, and transfer of molecules. Here we investigate ventricular protein Transmembrane protein 65 (Tmem65), identified among a mass spectrometry screen of membrane specific ventricular proteins from mouse neonatal and human fetal CMs. Published data has shown Tmem65 localized to the ICD and is a binding partner of Cx43, the primary ventricular gap junction protein. To verify whether decreased expression of Tmem65 orchestrates arrhythmogenic conditions by destabilizing Cx43 as well as identifying molecular mechanisms, AAV-9 containing Tmem65-BirAwas administered through the tail vein to obtain a comprehensive interactome. Additionally, cultured neonatal CMs were used to identify altered protein expression following Tmem65 knockdown. These results helped to identify Tmem65intracellular mechanisms and its functional role in CMs, providing insight into cardio-pathobiology of ICD protein interactions and underlying mechanisms of arrhythmogenic diseases.

Keywords: Cardiomyocyte
Cx43
Intercalated Disc
Ventricle
Advisor: Gramolini, Anthony O
Long-Term Risk of New-onset Diabetes in Pediatric Solid Organ Transplant Recipients

Background: Precise estimates of diabetes mellitus in transplanted children are not known. Objective: Determine the risk of diabetes in pediatric transplant recipients and compare the risk with non-transplanted children. Methods: Transplanted (n=1020) and non-transplanted children (7, 134,067) children were studied between 1991-2014 using provincial health administrative data to determine rates of diabetes. Results: Overall, the incidence rate ratio of diabetes was 7-times higher in the transplant (IRR 7.0, 95% CI:5.9, 8.3) than the non-transplant cohort. The transplant cohort had a 9-fold (HR 8.9, 95% CI:7.5, 10.5) higher hazard of diabetes than the non-transplant cohort. Risk was highest within the first year of transplant but remained elevated even after 5-10 years. Lung and multiple organ groups had a 5-fold (HR 5.4, 95% CI:3.0, 9.8) higher hazard compared to kidney transplant recipients. Conclusions: Risk of diabetes is higher in transplanted children with lung and multiple organ transplant recipients at the highest risk.

Keywords: children
diabetes
kidney
risk
transplant
Advisor: Parekh, Rulan
Dopaminergic Modulation of Excitatory Transmission in the Anterior Cingulate Cortex of Adult Mice

Bath application of dopamine (DA) (50 μM) caused a significant, rapid and reversible inhibition of evoked AMPA receptor mediated EPSCs (eEPSC). This inhibitory effect is dose-related and was absent in lower concentration of DA (5 μM). Furthermore, selective postsynaptic application of GDP-β-S (1.6 mM) in the internal solution completely abolished the inhibitory effects of DA (50 μM). We also investigated modulation of spontaneous EPSCs (sEPSCs) and TTX sensitive, miniature EPSCs (mEPSCs) by DA. Our results indicated mixed effects of enchantment and inhibition of frequency and amplitude for sEPSCs and mEPSCs. Furthermore, high doses of SCH23390 (100 μM) and sulpiride (100 μM) revealed that, inhibition of eEPSCs is mediated by postsynaptic D2-receptors (D2R). Our finding posits a pre- and postsynaptic mode of pyramidal neuron EPSC modulation in mice ACC by DA.

Keywords: ACC
AMPA
Dopamine
receptors
Whole-cell
Advisor: Zhuo, Min