VictorJuiz/thesis huggingface dataset:
Investigating the Role of Astrocytes in Mediating the Loss of Goal-directed Behavior Induced by a High fat, High Sugar Diet
Keywords: Astrocytes
Diet
Goal-directed behavior
Neuroscience
Obesity
Striatum

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.
Oral Innate Immune System Recovery in HSCT Patients
Keywords: Hematopoietic Stem Cell Transplant
Neutrophils
Oral Mucositis

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.
Circulating Osteoprotegerin in Women with a BRCA1 Mutation
Keywords: BRCA1
breast cancer
osteoprotegerin

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.
Molecular Mechanisms Underlying Phosphorylation-mediated Regulation of the KRAS Oncoprotein
Keywords: Cancer
GTPase
K-RAS
Oncogene
Oncoprotein
Phosphorylation

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.
Exploring Experiences with Exercise from the Perspectives of Women Living with HIV: A Qualitative Study
Keywords: AIDS
Exercise
HIV
Rehabilitation
Self-management
Women

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.
Phenotypic Heterogeneity in Mixed Aortic Valve Disease Patients using Machine Learning
Keywords: Aortic valve
Automation
Echocardiography
Machine Learning
Risk Stratification
Valvular Heart Disease

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.
Comparison of Pipe Loop and Pipe Section Reactor Methods for Estimating Chloramine Decay in Distribution Systems
Keywords: Chloramine Demand
Distribution System
Drinking Water
Pipe Loop
Pipe Section Reactor
Secondary Disinfection

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.
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
Keywords: Amelogenin
Regenerative endodontics
Stem cells of apical papilla

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.
Constrained, Curiosity-driven Trajectory Optimization for Learned Quadrotor Control
Keywords: optimal control
quadrotor
reinforcement learning

Quadrotors have become widely used robotic platforms in recent years, but developing controllers can be challenging for difficult-to-model scenarios such as wind or ground effect. Simultaneously, model-based reinforcement learning (MBRL) has been applied to many robot platforms due to the ability to quickly learn a dynamics model and use the model for planning and control via data-driven methods. MBRL has been augmented with probabilistic modelling in order to address model bias concerns. Recent methods have used the variance from model predictions to drive exploration during learning, inspired by curiosity. In this thesis, we show that directly applying these methods to control quadrotors via thrust and rotation rate inputs can lead to stability concerns. We propose using ideas from safety-critical control to alleviate these stability concerns. Our method applies control barrier function (CBF) constraints during planning using an augmented Lagrangian approach. The resulting algorithm restricts exploration to areas of the state space where predictive model uncertainty is within tolerable limits, so predictions are more trustworthy. However, we identify some practical issues which affect optimization feasibility. We propose additional measures to alleviate these issues to enable stable, curiosity-driven exploration for quadrotors.
5G Resource Allocation with Interference and Scarcity: Market Design for Spectrum and Beyond
Keywords: 5G
Interference
Scarcity
Spectrum

Spectrum scarcity is a growing concern that has attracted attention from researchers, industry players, and regulators on a global scale. The ability to address it is fundamentally limited by interference, which constrains its occupancy, and the lack of utilization insights available to those who determine long-term allocations for it. This thesis investigates how the advent of network slicing in 5G networks interacts with this problem of spectrum scarcity. After reviewing the problem domain, we develop a competitive resource allocation mechanism that considers interference management and pricing jointly, analyze its economic properties, and show that it improves communication performance. We also show that it can be used to improve fairness. Next, we attack the scarcity problem by developing a market for virtual resources based on a common ownership self-assessed tax. We propose a utilization-based penalty mechanism and analyze the resulting market behaviour under various scenarios.
Depression Interacts with Allostatic Load to Predict Cognitive Decline in Middle Age
Keywords: allostatic load
cognition
depression
inflammation
moderation
stress

Allostatic load (AL) indicates the cumulative impact of stress on homeostatic mechanisms. Depression and AL have been associated with cognitive deficits, but it is unclear if they do so independently.Using data from middle-aged participants in the observational Midlife in the United States study (n=704, 57.5% female, 63.8±10.6 years old in 2014), we assessed whether the effect of prior depression in 1995 on cognitive decline (via the Brief Test of Adult Cognition by Telephone) between 2004 and 2013 was moderated by AL Z-scores in 2004 (calculated from blood, urine, and electrocardiography biomarkers). A significant depression × AL interaction predicted a decline in a composite cognitive (β=-0.066, SE=0.029, p=0.024) and executive function (β=-0.068, SE=0.025, p=0.007) scores. Depression predicted a decline in composite cognition among those with AL Z-scores above -0.055. Among AL subdomains, inflammation was the strongest moderator. Here we present evidence that depression and high AL predict cognitive decline interactively.
Exogenous IL-4 and IL-10 Improve the Viability of Primary Hepatocyte Cultures
Keywords: Hepatocyte
Hepatocyte Monolayer
Immunoregulatory Cytokine
Liver
Macrophage

Most classical culture models fail to recapitulate the liver microenvironment, lacking the immune cell and factor interactions linked to regeneration in-vivo. We hypothesize that immunoregulatory cytokines IL-10, IL-4, and IL-22, secreted by hepatic macrophages and other liver cells, will maintain hepatocyte viability in primary hepatocyte monolayer culture by better mimicking the healthy in-vivo microenvironment. To assess this contribution, we determined a baseline measure of monolayer viability and function. Once established, we supplemented cells in culture with single cytokines at varying concentrations, or with a cytokine cocktail. Without cytokine supplementation, viability of hepatocyte cultures decreased significantly after 4 days, as measured via ATP secretion from metabolically active cells. We found that IL-4 supplementation at 50 ng/mL and the cytokine cocktail (IL-10, IL-4, and IL-22, 10 ng/mL each) prolonged hepatocyte viability to day 7. Optimizing these monolayer cultures using mouse livers will provide a framework for adapting this system to human liver tissue with the goal of guiding interventions that will promote human liver regeneration.
Factors Associated with End of Treatment Quality of Life, Cardiac Function and Cardiorespiratory Fitness and the Effect of Exercise in Women with Breast Cancer
Keywords: Breast Cancer
Cardiac Function
Cardiovascular Disease
Exercise
Physical Activity
Quality of Life

Women with human epidermal growth factor receptor-2 positive (HER2+) breast cancer are at increased risk of cardiovascular disease (CVD), CVD mortality, reductions in cardiorespiratory fitness and quality of life due to pre-existing CVD risk factors, cardiotoxic cancer therapies and lifestyle habits. Risk factors associated with lower cardiac function and cardiorespiratory fitness at end of treatment and strategies to mitigate this decline remain unclear. The goals of this thesis were to explore (1) pre-treatment and during treatment clinical and imaging factors that are associated with end of treatment cardiac function and cardiorespiratory fitness; (2) the effects of physical activity on cardiovascular outcomes, and quality of life during and at the end of treatment and cardiorespiratory fitness at end of treatment and; (3) the quality of evidence for cardiac rehabilitation in cancer survivors to improve cardiovascular outcomes.
Treatment Modifications in Chronic Hepatitis B
Keywords: chronic hepatitis B
HBV
hepatitis B
stopping therapy
TAF
viral hepatitis

As chronic hepatitis B continues to affect more than 250 million individuals, new treatment plans aim toward better viral suppression, safety, and functional cure. In Study I, we studied the kinetics of two new serum biomarkers, HBV RNA and HBcrAg, and their potential role as predictors for clinical applicability and treatment response after nucleosi(t)ide analog (NA) treatment withdrawal. Detectable levels of HBcrAg were associated with increased retreatment after treatment withdrawal (p<0.005, HR: 4.83), albeit with limited associations in virological and clinical relapse outcomes. In Study II we studied the efficacy and safety of switching from tenofovir disoproxil fumarate (TDF) to newer tenofovir alafenamide fumarate (TAF)-based regimens in HIV/HBV co-infected patients. TAF switch led to greater ALT normalizations in those with elevated ALT (p=0.03), and significantly halted eGFR decline compared to time on TDF (slope difference p=0.01). No significant changes in lipid profiles were observed.
Eddy Current Damping of Magnetically Actuated Neurosurgical Instruments
Keywords: Damping
Eddy Current
Magnet
Microrobotics
Neurosurgery

Magnetically actuated minimally invasive neurosurgical tools tend to oscillate for an extended period of time due to lack of avenues for energy removal from the system. After determining target damping coefficients ($4.31*10^{-9} $ Ns m$^{-1}$ for a 2% settling time less than 0.3 s and $2.01* 10^{-6} $ Ns m$^{-1}$ for critical damping), a feasibility study was conducted by approximating the damping coefficient using adapted equations from Hahn, Donoso, Mehrtash, and Sodano et al. This resulted in 0.11 Ns m$^{-1}$, 2.75*10$^{-5}$ Ns m$^{-1}$, 2.02*10$^{-4} $Ns m$^{-1}$, 0.01 Ns m$^{-1}$ respectively. An experimental study was then performed to validate the values and relationships from the feasibility study. Six measurements were taken at gap sizes (between the magnet and conductor) of $0 \mu$m, $100 \mu$m, $200 \mu$m, $300 \mu$m, $400 \mu$m, $500 \mu$m, $750 \mu$m, $1000 \mu$m, $1500 \mu$m, and $2000 \mu$m with copper conductors of thicknesses 0.005” to 0.025” in 0.005” increments. While it was determined that sufficient damping could be generated experimentally (maximum damping documented is $1.24*10^{-6}$ Ns m$^{-1}$), concrete relationships between each variable with the damping coefficient were inconclusive.
A Knowledge-based Feature Representation to Discover the Function of Non-coding Sequences
Keywords: Non-coding DNA
Orthologous Sequences
Predicting Function
Promoters
Representation Learning
Transcription Factors

Understanding how non-coding regions of DNA determine gene expression is an important challenge in genome analysis. Deep-learning approaches have aimed to “represent” DNA sequences as high-dimensional vectors, which can be used to predict gene expression. We wondered whether a high-dimensional representation using evolutionary conservation of known binding motifs could predict patterns of gene expression. By taking advantage of publicly available databases of binding motifs and by obtaining large numbers of orthologous non-coding regulatory sequences, we could group genes with similar expression patterns or functional annotations together based only on DNA sequences. Our representation could predict new function for Saccharomyces cerevisiae promoters and rediscover known regulatory function for human promoters. We used this approach to create a representation of 3’UTR sequences of S. cerevisiae using RNA binding motifs and found strong association for sub-cellular localization of mRNA. Our results suggest that global, high-dimensional views are essential to understand the cis-regulatory code.
Indigenous Resurgence in Colonial Urban Parks: Possibilities and Potential for Urban Indigenous Land-based Practices
Keywords: Indigenous futurities
Indigenous resurgence
Indigenous studies
kincentric ecologies
land-based practices
urban parks

This thesis is an exploration of colonial dispossession within cities and specifically urban parks recognizing all parks in so-called Canada exist on the traditional territories of Indigenous peoples. Within this thesis I utilize mixed methods, first conceptual analysis is used to discuss the structural-materialist emergence of urban parks as colonial spaces. Secondly, drawing from my own embodied experience earthworking with Two-Spirit Indigiqueer community in High Park, Tkaronto, I engage with land-based theoretical frameworks including land as pedagogy, kincentric ecologies, and reciprocal restoration to story ongoing Indigenous resurgence and futurities. This research considers the colonization of urban parks, and the possibilities and need for improved access for urban Indigenous peoples to engage in land-based practices. I argue, Indigenous inclusion within urban parks, at various levels, is required for the future ecological sustainability of parks and to create safe and accessible spaces for urban Indigenous peoples to enact land-based cultural practices.
Light-sheet Light-field Fluorescence Brain Imaging Enabled by Implantable Neural Probes
Keywords: computational imaging
fluorescence brain imaging
implantable neural probes
integrated optics;
light field imaging
light sheet microscopy

Deep brain fluorescence imaging for freely-behaving animals allows researchers to better understand the function of neural circuitry; however, miniature microscopes capable of high spatial resolution use implantable lenses that cause irreversible tissue damage. To reach the goal of simultaneously achieving high-resolution imaging and less invasive measurements, we developed an implantable lens-less imaging system for volumetric fluorescence brain imaging. The imaging system consists of an implantable light-sheet neural probe integrated with an image fiber bundle to realize light-sheet light-field microscopy for high-contrast, cellular resolution volumetric imaging. Our imaging system shows great promise for in vivo brain experiments and may also have clinical uses in visualizing regions of the body that are difficult to reach.