VictorJuiz/thesis huggingface dataset:
Characterizing Topological and Topographical Resilience in Structural Networks Supporting Language in Childhood

Language networks undergo robust changes through childhood. Language is first supported by an extensive network spanning both hemispheres and becomes focal and left-lateralized through development. Here, we assessed language network resilience using diffusion imaging and in silico attacks. We acquired multi-shell diffusion-weighted images of 50 typically-developing children, ages 5-18 years. Automated parcellation was combined with constrained-spherical deconvolution and anatomically-constrained tractography to estimate connectomes. We assayed network resiliency using multiple targeted attacks. Interestingly, resiliency increased with age (p < 0.05); however, spatial extent of nodes removed prior to failure decreased with age (p < 0.05). Also, left-lateralization of nodes increased with age (p < 0.05). From a wiring perspective, adolescents’ language networks are more resilient than those of children. However, critical hubs are more diffuse in younger children, and become increasingly left-lateralized and focal with age. Findings suggest that diffuse representation underlies the paediatric advantage for language outcomes following (focal) injury.

Keywords: Development
Diffusion MRI
Language
Paediatric
White Matter Imaging
Advisor: Kadis, Darren S
Cu-P and Cu-La-P Alloys as Hydrogen Evolution Electrocatalysts

The recent development of anion exchange membranes has renewed interest in alkaline water electrolysis as a means of converting renewable energy to storable H2. New electrocatalysts are required to take advantage of the additional performance offered by anion exchange membrane water electrolysers. Cu-P-based alloys are interesting as hydrogen evolution electrocatalysts due to a combination of good intrinsic activity and stability. Novel Cu-La-P alloys were prepared using mechanical alloying via cryomilling and evaluated as electrocatalysts to elucidate the role of a rare earth, La, on the electrocatalytic behaviour. A thermodynamic model was used to guide alloy design, and X-ray diffraction and electron microscopy were used to characterize the morphology and phase composition. A secondary ball milling process was used to prepare nanopowders. Tafel slope and exchange current density data demonstrate spillover effects occurring on multiphase Cu3P/Cu19La5P12 surface structures. These results suggest that Cu-La-P alloys are promising catalysts for electrochemical hydrogen production.

Keywords: Electrocatalysis
Electrochemistry
Energy Conversion
Heterogeneous Materials
Materials Design
Surface Science
Advisor: Thorpe, Steven J
Retention in Care for People Living with HIV in Ontario

Our objectives were to determine how frequently people living with HIV (PLHIV) in Ontario experience a non-retention episode, and associated individual, provider, and healthcare system factors. Using administrative, population-level data, we followed PLHIV from their first visit with an HIV-experienced provider until first non-retention episode (365 days without HIV care), death, or loss-to-follow-up. Kaplan-Meier curves, logrank tests, and Cox proportional hazards models were used to evaluate time-to-first non-retention episode. 15,242 PLHIV entered care between 2000 and 2018. The probability of non-retention at 3, 6 and 10 years was 21%, 41% and 58%, respectively. Non-retention was less likely for individuals who had previously accessed mental healthcare or public drug insurance, were an immigrant or refugee, or initiated care with an HIV-experienced or primary care provider. Many PLHIV in Ontario have not received care within recommended timeframes. Practice and policy improvements should focus on PLHIV with characteristics associated with non-retention.

Keywords: Canada
Care continuum
Gaps in care
HIV
Retention
Advisor: Bayoumi, Ahmed M
Raboud, Janet M
Temperature Dependence of the Deuterium Concentration in SiC Codeposits

Silicon carbide is a low-Z material seen as a possible alternative to graphite for some plasma-facing components in magnetic confinement fusion reactors. This work focuses on measurements of deuterium content of SiC codeposits created by ion beam sputter deposition at temperatures ranging from 300 – 900 K. Various surface analysis techniques are used to analyze deposits of SiC as well as C and thermal desorption spectroscopy is used to measure deuterium content. The temperature dependence very closely followed the trends observed for plasma-created codeposits, with the D content decreasing above 400 K. The D content of such deposits was also found to be very similar to the D content of carbon deposits created in the same way. This suggests that the tritium retention associated with SiC first wall materials would be very similar to that of a graphite first wall.

Keywords: Carbon
Codeposit
Deuterium
Fusion
Silicon Carbide
Sputtering
Advisor: Davis, James W
Microsatellite Development, Testing and On-orbit Operation

A recent rise in the number of small spacecraft has motivated the development of the DEFIANT microsatellite platform at the Space Flight Laboratory. This thesis details the development of multiple spacecraft subsystems for the DEFIANT platform, including the guidance, navigation and control, propulsion and deployable solar panel subsystems. The testing process for spacecraft hardware is presented and used in the qualification and acceptance of several subsystems for the DEFIANT platform. Finally, developments in the on-orbit operation of the guidance, navigation and control subsystem are detailed and used in the commissioning of several spacecraft. The work outlined in this thesis was used in the design, analysis, testing, and commissioning of over 20 spacecraft for the Space Flight Laboratory, supporting its competitive advantage in the microsatellite world market.

Keywords: attitude
development
operation
optimization
satellite
spacecraft
Advisor: Zee, Robert E
Association of Whole-person Eigen-polygenic Risk Scores with Alzheimer’s Disease

Late-Onset Alzheimer’s Disease (LOAD) is a heterogeneous disorder with complex etiology and high heritability. We used Pan-UK Biobank Consortium GWAS sum- mary statistics to calculate polygenic risk scores (PRSs) for 2,218 heritable traits in a sample of 2,044 elderly with clinical and post-mortem autopsy data. Weighted gene co-expression network analysis (WGCNA) was used to identify discrete correlated clusters of PRSs. Module memberships varied across different α-value SNP selection thresholds. Few modules were strongly conserved across multiple α-value thresholds. Several Eigen-PRSs (ePRSs), the first principal component of PRSs in each cluster, were derived from the modules significantly associated with LOAD-related pheno- types and improved predictive model performance over the LOAD PRS alone. The ePRS representing clusters of traits related to cholesterol levels improved variance ex- plained in a model of brain-wide beta-amyloid burden by 1.7% (likelihood ratio test p = 9.02 × 10−7). In addition to improving existing single-PRS approaches, WGCNA will aid in developing new etiological hypotheses.

Keywords: Alzheimer’s disease
eigen-PRS
Polygenic risk scores
WGCNA
whole-person
Advisor: Felsky, Daniel
Sun, Lei
In Vivo Direct Reprogramming of Reactive Astrocytes into Neurons in a Rat Model of Alzheimer's Disease

Alzheimer’s disease (AD) is the most common neurodegenerative disease worldwide and remains without a cure. The buildup of amyloid-beta (Aβ) plaques and neurofibrillary tangles (NFTs) result in gliosis and inflammatory signals that contribute to and exacerbate neuronal loss and AD symptoms. As AD progresses, numerous factors can complicate treatment. Directlineage reprogramming is a technique that can restore disease-lost neurons by transiently expressing transcription factors with a viral vector. Using 14-month-old TgF344 AD rats, we unilaterally injected an AAV with a GFAP promoter and 1 of 3 transcription factors (Ascl1/Ascl1-SA6/Neurod1), to target astrocytes and promote transdifferentiation into GABAergic or glutamatergic neurons. We show that direct lineage reprogramming can beneficially affect numerous aspects of AD pathology, including Aβ load, neurodegeneration and inflammation. This study is the first to demonstrate the advantages of direct lineage reprogramming in the robust TgF344 rat model as well as investigate the off-target effects of astrocyte-to-neuron conversion.

Advisor: McLaurin, JoAnne
Soot and Flow Field in Turbulent Swirl-stabilized Spray Flames of Jet A-1 with Downstream Air Injection in a Model Gas Turbine Combustor

Influence of downstream oxidation air injection in swirl-stabilized Jet A-1 spray flames was investigated in a model combustor with 94 mm X 94 mm cross-section and 188 mm length. Fuel flow rate and global equivalence ratio were held constant while the fraction of oxidation air injection was varied up to 30%. Flow field measurements were carried out using stereoscopic particle image velocimetry. Fuel spray droplet size distributions were determined through the Fraunhofer diffraction technique. Spatially-resolved soot volume fraction and mean primary particle size were measured using auto-compensating laser-induced incandescence. Measurable differences in spray and flow field characteristics were observed between flames with and without oxidation air injection. Soot was observed in wider spatial ranges in the flames with oxidation air injection compared to the flames without. The overall quantity of soot present in all configurations of flames with oxidation air injections is greater than the flames with no oxidation air injection.

Keywords: Combustion
Flame
Soot
Advisor: Gulder, Omer L
Investigating the Role of Astrocytes in Mediating the Loss of Goal-directed Behavior Induced by a High fat, High Sugar Diet

Obesity is a growing concern in modern society, as despite weight loss attempts many people have difficulty maintaining weight loss. In animal studies, high fat, high sugar diets, like the sweetened condensed milk (SCM) diet, disrupt goal-directed behavior, impairing the ability of animals to adjust lever pressing following changes in the value of outcomes. Studies have indicated a disruption of glutamate transmission in the dorsal medial striatum (DMS), which is the region mainly involved in the acquisition and expression of goal-directed behavior. We investigated whether changes to astrocytes might explain changes in the expression of goal-directed behavior after exposing animals to the SCM diet for 6 weeks. We administered ceftriaxone, which is known to induce changes in astrocytes that improve the clearance of glutamate at synapses by restoring an astrocytic glutamate transporter, GLT-1, and by restoring physical contacts of astrocytes and synapses. We found that ceftriaxone robustly restored goal-directed behavior in animals following long-term exposure to SCM. While we did not observe changes in the expression of GLT-1 in the DMS, we observed that SCM induced changes in the morphology of astrocytes in the DMS, and that ceftriaxone mitigated these changes. These results indicate a mechanism whereby the SCM diet impairs goal-directed behavior while also altering the morphology of astrocytes in the DMS. Furthermore, these results suggest that ceftriaxone administration is sufficient to reverse the impairment of goal-directed behavior following long-term exposure to high fat, high sugar diets.

Keywords: Astrocytes
Diet
Goal-directed behavior
Neuroscience
Obesity
Striatum
Advisor: Corbit, Laura H
Oral Innate Immune System Recovery in HSCT Patients

Hematopoietic stem cell transplantation (HSCT) is a common therapy for patients with different hematopoietic disorders, both malignant and non-malignant.[35] The patient will undergo a conditioning therapy to reduce the hematopoietic cells to the point of nadir (the time of lowest white blood cell count) before transplantation. After HSCT, there will be hematologic recovery when the cells, including neutrophils, will begin to increase in number. Oral mucositis is one of the most common oral complications seen in the early stages following HSCT.[37-39] Multiple studies have reported a difference of the oral microbiome in patients who experience oral mucositis and those who do not.[40-43] The human mouth has a constant bacterial presence that is kept under control in part by a constant influx of neutrophils from surrounding periodontal tissues.[51] Neutrophils are a major component of the innate host response, and the outcome of the interaction between the oral microbiota and neutrophils is a key determinant of oral health status. The oral rinse assay enables a non-invasive assessment of neutrophil tissue delivery by measuring the level of neutrophils in oral tissues in patients recovering from HSCT.[53,54] Adult patients were screened and recruited on the bone marrow transplant floor at PMH. Oral rinse samples were obtained and analyzed by flow cytometry, as previously described.[72,73] Mucositis scoring was completed using the WHO Oral Mucositis Grading Scale.[74,75] The participant population was divided into groups based on their recovery from HSCT therapy, either experiencing mucositis (OM) or not experiencing mucositis (NM). Those participants that did not experience mucositis (NM) showed a statistically significant difference in activation levels of certain CD markers (CD14, CD18, CD66a) on oral PMNs as compared to those who did experience mucositis (OM) at the 6-month post-HSCT period. This phenomenon is still being investigated and the significance is not yet known.

Keywords: Hematopoietic Stem Cell Transplant
Neutrophils
Oral Mucositis
Advisor: Glogauer, Michael
Lipton, Jeff
Circulating Osteoprotegerin in Women with a BRCA1 Mutation

Emerging evidence implicates the dysregulation of progesterone-mediated receptor activator of nuclear factor κB (RANK)-signalling in the pathogenesis of BRCA1-associated breast cancer. Low levels of circulating osteoprotegerin (OPG), a decoy receptor of RANK-ligand, were observed among BRCA1 mutation carriers, suggesting OPG as a potential biomarker of cancer risk. This study evaluated the association between reproductive, hormonal, lifestyle, and genetic factors and OPG among BRCA1 mutation carriers using generalized linear models. Age, current smoking, and coffee consumption were significantly associated with OPG; however, overall, OPG was minimally affected by non-genetic factors. Additionally, we investigated the relationship between OPG and estimated risk of breast cancer using the CanRisk tool. OPG was weakly, albeit significantly inversely associated with estimated risk of breast cancer. These findings suggest that incorporating OPG may improve upon the current risk prediction models, stratifying women at higher risk of developing breast cancer who may be targets for anti-RANKL chemoprevention.

Keywords: BRCA1
breast cancer
osteoprotegerin
Advisor: Kotsopoulos, Joanne
Molecular Mechanisms Underlying Phosphorylation-mediated Regulation of the KRAS Oncoprotein

RAS is a small GTPase protein that cycles between GTP and GDP-loaded states to regulate vital eukaryotic cellular functions such as proliferation. Mutations in RAS account for approximately 30% of human cancers, however, it has remained ‘undruggable’ largely due to our incomplete understanding of the mechanisms governing its activity. Recently, we discovered a novel paradigm of RAS regulation in which Src-induced phosphorylation significantly impairs the entire GTPase cycle, including RAS interactions with downstream effector molecules. However, the mechanisms underlying Src-mediated regulation of RAS remain unclear. Here, using various in vitro biochemical and functional assays, the relationship between KRAS phosphorylation and RAF effector binding was analyzed. Results show that effector binding impedes phosphorylation of KRAS via Src, indicating that this modification alone is insufficient to displace RAF from KRAS, as previously expected. This valuable insight into RAS signalling may contribute to the development of novel therapeutics targeting this pathway of oncogenesis.

Keywords: Cancer
GTPase
K-RAS
Oncogene
Oncoprotein
Phosphorylation
Advisor: Ohh, Michael
Exploring Experiences with Exercise from the Perspectives of Women Living with HIV: A Qualitative Study

Introduction: Despite the benefits of exercise, experiences with exercise among women living with HIV is limited.Purpose: To explore experiences engaging in exercise among women living with HIV, specifically i) nature and extent of exercise, ii) components that characterize exercise experiences, iii) facilitators and barriers, and iv) strategies for uptake. Methods: Qualitative descriptive study involving online semi-structured interviews with women living with HIV who may or may not engage in exercise, followed by a demographic questionnaire. Thematic analysis was used. Results: Ten women characterized their exercise experiences with six intersecting components: culture, gender, HIV-related stigma, episodic nature of HIV, sense of belonging, and perceptions of exercise. Women also discussed motivators and barriers to exercise along with strategies for uptake. Conclusions: Experiences with exercise were characterized by intersecting personal and environmental contextual components. Results may help to inform tailored implementation ofexercise as a rehabilitation strategy among women living with HIV.

Keywords: AIDS
Exercise
HIV
Rehabilitation
Self-management
Women
Advisor: O'Brien, Kelly KO
Fischer-Tropsch Sustainable Aviation Fuel: An Assessment of Pioneer Plants and Canadian Supply

Aviation aims to achieve net-zero emissions by 2050, and sustainable aviation fuel (SAF) produced from biomass via gasification and Fischer-Tropsch processes could make a large contribution to this goal. This thesis assesses (1) the production costs and GHG emissions of SAF from pioneer biomass gasification and Fischer-Tropsch projects and (2) the supply, costs, and GHG abatement potential of gasification and Fischer-Tropsch SAF from forest residues in Canada. Natural gas use in the conversion process of pioneer projects could lower SAF production costs by improving yields and reducing capital expenses but significantly lowers SAF GHG reduction benefits (from 91% to up to -17%) unless process emissions are captured and permanently stored. SAF from forest residues could meet up to 27% of Canada’s projected aviation fuel demand in 2050, requiring an investment of ~15.7 billion USD in SAF facilities, and could abate up to 47% of Canada’s projected emissions from aviation in 2050.

Advisor: Saville, Bradley BAS
MacLean, Heather HLM
Phenotypic Heterogeneity in Mixed Aortic Valve Disease Patients using Machine Learning

Echocardiography is the gold standard cardiac imaging modality in valvular heart disease. Artificial Intelligence has potential to advance echocardiography by improving image acquisition, automate measurements or directly diagnose disease. While automation has been attempted in direct valvular assessment, there is accruing evidence that a “full-heart” approach could be more predictive. Mixed Aortic Valve Disease (MAVD) poses a unique challenge in automation and a method that does not involve valvular grading could have clinical benefit and eases automation. In this thesis, Machine Learning was used tos stratify MAVD patients based on non-valvular measurements. There are different adaptive changes that take place in response to MAVD and these changes do not correspond to the valvular grading. Classifications based on cardiac adaptation could be more clinically informative to guide assessment, management, and response to intervention. Broadly, our findings make automation more accessible, with implications for disease screening, test access and generalizability.

Keywords: Aortic valve
Automation
Echocardiography
Machine Learning
Risk Stratification
Valvular Heart Disease
Advisor: Wang, Bo
Establishing a Cell-based Assay to Target Hyperactive Spleen Tyrosine Kinase for High-throughput Drug Screen

Recently, five gain-of-function variants in Spleen Tyrosine Kinase (SYK) were identified in patients with immune dysregulation and systemic inflammation. SYK is a cytoplasmic, non-receptor tyrosine kinase that plays a pivotal role in multiple processes such as cytokine and chemokine production, fungal sensing, and inflammasome formation. Normally, SYK kinase activity is tightly regulated; however, patients with GOF SYK variants presented abnormal baseline phosphorylation at the activation loop (Tyr525/526) in their peripheral mononuclear cells. Patient-derived SYK mutations also exhibited hyperactivity when expressed in in vitro cell-based models and in vivo heterozygous human-equivalent knock-in mice. There are no standard treatments for GOF SYK disease; therefore, this study aims to establish a cell-based assay for high-throughput screening to select FDA-approved drugs that can diminish kinase activity and hopefully, induce clinical remission.

Advisor: Muise, Aleixo A.M.
Comparison of Pipe Loop and Pipe Section Reactor Methods for Estimating Chloramine Decay in Distribution Systems

Despite their relative stability compared to free chlorine, chloramines are known to decay in distribution systems via surface-catalyzed reactions including ferrous oxidation and microbial nitrification. As such, the prediction of in-situ chloramine demand represents an important issue for drinking water utilities. This study compared the use of continuous-flow pipe loops and batch Pipe Section Reactors (PSRs) to assess chloramine decay using materials and flow conditions typical of distribution systems in the Greater Toronto Area, Ontario. Pipe material was observed to be the greatest determinant of chloramine decay using both PSR and pipe loop methodologies. First-order decay coefficients obtained using pipe loops were statistically similar to those for PSR trials when considering harvested lined and unlined iron piping. Overall results suggest that pipe section reactors may serve as a viable and cost-effective alternative to pipe loops for estimating the impact of operational variables on disinfectant decay in distribution systems.

Keywords: Chloramine Demand
Distribution System
Drinking Water
Pipe Loop
Pipe Section Reactor
Secondary Disinfection
Advisor: Andrews, Robert C
Almuhtaram, Husein
Investigating the Effect of the Amelogenin Peptide C11 on Differentiation of Stem Cells of the Apical Papilla (SCAP) toward an Odontoblastic Phenotype: A Pilot Study in Regenerative Endodontics

Regenerative endodontic is an alternative procedure to preserve and stimulate stem cells from the apical papilla to regenerate the pulp-dentin complex using various growth factors. Objective: To investigate the effect of amelogenin C11 peptide on proliferation and differentiation of stem cells of the apical papilla toward an odontoblast cells. Materials and Methods: SCAP STRO-1 enriched, and depleted cells were cultured and treated with amelogenin C11 peptide and TGF-β1. Cell proliferation was evaluated using MTS assay. Immunohistochemistry was used to verify protein expression of three odontogenic markers DMP1, DSP and NES. Results: viable cells increased significantly (P <0.05), in SCAP STRO-1 enriched cells treated with C11 peptide in a dose dependent manner. It also showed increased expression of DSPP, DMP1, and. No expression was noted in control. Conclusion: Amelogenin C11 peptide induced SCAP proliferation and expression of (DMP1, DSP and NES) indicating potential use in regenerative endodontic.

Keywords: Amelogenin
Regenerative endodontics
Stem cells of apical papilla
Advisor: Ganss, Bernhard