VictorJuiz/thesis huggingface dataset:
Tumour Hypoxia Induces DNA Repair Vulnerabilities Through ‘Contextual Loss-Of-Heterozygosity’

Intratumoural hypoxia leads to decreased expression in DNA damage response (DDR) and repair pathways. Given the ‘two-hit’ model for loss of gene function, we hypothesize that hypoxia-mediated down-regulation of gene expression and function, coupled with an already inactive allele contributes to an exploitable ‘contextual loss-of- heterozygosity’ phenotype. To interrogate this relationship, isogenic DLD-1 cells heterozygous and homozygous null for BRCA2, were placed under normoxic (21%) or hypoxic (0.2%) conditions for 72 hours. Hypoxia-mediated changes in DDR response and DNA repair were evaluated by cell proliferation, western blots, qPCR, immunofluorescence and clonogenic assays. Herein, we demonstrate a mechanism of ‘contextual loss-of heterozygosity’, which marries the tumour microenvironment and innate genetic alterations. The resultant increased sensitivity to DDR kinase inhibitors and PARPi highlights the therapeutic significance of this phenomenon and potential clinical utility.

Advisor: Bristow, Robert
The Identification of Novel Proteins of Interest in Pancreatic Islets and the Characterization of NIPAL1 as a Regulator of Secretion

Single-cell RNA-sequencing (scRNA-seq) has offered novel insight into individual islet cells. I hypothesize that investigation of scRNA-seq data will reveal previously uncharacterized genes related to islet function and secretion. Several recent datasets were explored in tandem with established databases. 915 candidates were investigated in silico; 28 of these progressed to transcriptional validation via qPCR; 4 progressed to translational validation via immunofluorescence studies. Through this process, magnesium influx transporter NIPAL1 was novelly identified in α-cells, Min6-K8 and α-TC6 cell lines. NIPAL1 shows partial Golgi co-localization and magnesium responsiveness. Neither overexpression nor knockdown affected Min6 insulin secretion under standard culture conditions. However, knockdown under hypo- and hypermagnesemic conditions disrupted basal secretion and decreased total insulin content. Overexpression increased total insulin content. These patterns were attributed to a magnesium-dependent increase in Min6 insulin secretion, which is regulated by NIPAL1. By extension, NIPAL1 may contribute to magnesium homeostasis important to α-cell secretion in islets.

Keywords: Diabetes
Glucagon
Insulin
Islet
Magnesium
Nipal1
Advisor: Wheeler, Michael
Nutritional Status and Dialysis Modality: Effect on Folate Status 20 Years after the Institution of a National Folic Acid Fortification Program

Canadian dialysis patients are supplemented with ≥1mg folic acid/day to prevent folate deficiency, which may not be appropriate post-fortification. Intake and blood concentrations of folate, B6 and B12 and their association with nutritional status (subjective global assessment [SGA]) and dialysis modality were evaluated in 70 subjects undergoing in-centre hemodialysis (IHD), peritoneal dialysis (PD) or home hemodialysis (HHD). Median total intakes for folate, B6, and B12 exceeded daily recommendations at 2050µg, 11.7mg, and 9.8µg, respectively. Mean folate (62.5nmol/L) and median B6 (121mg/L) concentrations were high, while B12 concentrations were within the normal range (532pmol/L). Significant differences were observed between HHD and the PD and IHD groups for median total intakes of folate, B6 and B12 (p

Keywords: Dialysis
End-stage kidney disease
Folate
Folic Acid
Fortification
Advisor: Kim, Young-in
Bargman, Joanne
Net Zero Energy Potential and Parametric Analysis for Multiunit Residential Buildings in Toronto

This research studies how multiunit residential buildings (MURB) of varying heights can achieve a net zero energy balance in Toronto. A real 38-storey MURB was created in EnergyPlus and calibrated against an existing reference model in eQuest. A series of sensitivity analyses was then conducted in EnergyPlus to study the tradeoffs involved in the net zero MURB design, and the most impactful design parameters are identified. This research produces a deep physical understanding of how key design parameters interact, identifies design practices that should be prioritized in order to reach net zero, and determines the maximum number of floors allowed for a MURB to achieve net zero with various energy efficiency measures and photovoltaic configurations, all of which provide crucial information that will help the building sector to reduce its energy use, and in turn help Canada to transition to a low-carbon economy.

Keywords: high-rise
multiunit residential buildings
MURB
net zero energy
sensitivity analysis
Toronto
Advisor: Harvey, Danny
Reducing Antibiotic Consumption in Patients with Asymptomatic Bacteriuria: a Bi-Directional Approach

Objectives: To assess safety and effectiveness of not processing midstream urine (MSU) in adults to reduce asymptomatic bacteriuria (ASB) treatment, and find a biomarker that differentiates symptomatic urinary tract infection (SUTI) from ASB in adults. Methods: From 11/2013-04/2019 MSU for surgical/medical in-patients were routinely not processed. Patients were followed up for 4 and 30 days. Primary outcome was safety; secondary outcomes were antibiotic use, lab workload, and rate/proportion of MSU submitted/processed. A systematic review was conducted to identify potential biomarkers. Results: In 912 patients, no serious adverse events (AE) and 6 (0.66%) non-serious AE occurred due to not processing MSU. Processed MSU proportion, submitted MSU rate, and lab workload decreased (P=0.002; P=0.02; 5 person-days/year). Ninety-eight patients avoided antibiotics. Urine IL-6 and IL-8 were the most promising biomarkers. Conclusion: Not processing MSU reduces ASB treatment safely and effectively. Urine IL-6 and IL-8 could possibly differentiate ASB from SUTI.

Advisor: McGeer, Allison Joan
Advances in Pit Wall Mapping and Slope Assessment using Unmanned Aerial Vehicle Technology

As mining in open pits progresses deeper, keeping slopes stable becomes more complex. Multi-bench scale instabilities can result in significant economic loss. To address this concern, systematic documentation and evaluation of the performance of benches in open pit mines is essential for pit slope assessment. This includes collecting structural and geomechanical data for rock mass characterization as well as information on the geometry and configuration of the benches. Advances in technology have made the use of unmanned aerial vehicles (UAV) for photogrammetry data collection more feasible. This thesis presents methodologies to integrate the UAV technology in open pit mine operations for collecting high quality data. The collected data was processed and useful information was extracted for design compliance audits, blast optimization studies, and slope stability analysis. This research aims to demonstrate the advantages and limitations of using this technology to collect and process field data.

Keywords: Blast optimization
Design compliance
Discrete Fracture Networks
Geotechnical data collection
Slope stability
Unmanned Aerial Vehicles
Advisor: Esmaeili, Kamran
Quantifying the Fracture Process using Surface Roughness Parameters

When a crack tip passes through a material, it produces surfaces with characteristic undulating patterns, or roughness, that can reflect the mechanics of the fracture process. These surficial features can be quantitatively described using roughness parameters. Previous studies have attempted to link roughness with fracture mechanics parameters. However, they are derived from profilometric measurements of the surface that are subjectively obtained. This work proposes to apply surface (3D) roughness parameters to fracture surfaces through the surface roughness windowing (SRW) procedure. This procedure rescales roughness to a local perspective and assembles it into a form that allows for interpretation of the roughness of local features. Its application on indirect tensile fractures revealed fracture propagation paths and the local roughness variations. Roughness parameters and an estimated critical Mode I stress intensity factor (KIC) were positively correlated similar to correlations made in literature.

Keywords: fracture mechanics
surface roughness
Advisor: Grasselli, Giovanni
Influence of Grab Bar Orientation on Balance Recovery following a Perturbation during Bathtub Exits

Grab bars are recommended to assist bathing transfers; however, little evidence on their effectiveness for fall prevention exists. The objective was to explore how grab bar orientation impacts balance recovery during transfers (exit). A low horizontal grab bar, high horizontal grab bar, and vertical grab bar were evaluated. Ten younger adults reached to grasp the grab bar following perturbations (YA RTG) and the remaining younger and older adults used it proactively (YA HIP, OA HIP). Findings showed significantly high downward and resultant loads were applied on the low horizontal grab bar. There were no significant differences in loading between the high horizontal and vertical grab bar, other than in downward forces. Grasping condition, but not age, impacted loading and balance control. The YA HIP group applied significantly higher forces and displayed greater balance control than the YA RTG group. Findings can inform clinical recommendations and standard developments on grab bars.

Keywords: Balance control
Balance recovery
Centre of mass
Grab bars
Advisor: Novak, Alison C.
Optimization of High-order Dense and Diagonal-norm Generalized Summation-by-parts Operators for Efficient Aerodynamic Computations

A general framework is developed for the symbolic construction and optimization of four primary classes of tensor-product generalized SBP (GSBP) operators. These classes encompass previously known dense and diagonal-norm GSBP operators, and extends the scope of previous work in optimizing SBP operators. Additionally, these operators are optimized in a multi-objective framework with objectives accounting for accuracy and spectral properties of the discretization. These novel operators are compared to previously optimized SBP operators and discontinuous Galerkin SBP methods for two linear test problems, where efficiency improvements are observed. Subsequently, novel non-tensor-product SBP operators are constructed on optimal cubature rules on quadrilateral elements. The non-tensor-product SBP operators use fewer nodes than equal degree tensorproduct operators. Additionally, these operators possess smaller derivative and quadrature error coefficients compared to tensor-product operators, with fewer nodes. Consequently, efficiency improvements over equal degree tensor-product SBP operators are observed for both the linear convection and the Euler equations

Keywords: computational fluid dynamics
numerical analysis
optimization
summation-by-parts
Advisor: Zingg, David W
Refined Membrane Characterization and Modeling in Forward Osmosis

This work builds upon recent FO transport models and presents an improved FO-based membrane characterization method that addresses the non-ideality of concentrated draw solutions, physical properties that are not based on the bulk draw solution, and all instances of concentration polarization. Using the FO-based characterization method of this work, consistent water permeability and structural parameter values are obtained for multiple inorganic draw solutions. When compared to additional experimental FO transport data, improvements of 18-107% were observed over the existing FO transport models. Using the transport model of this work both the water and reverse draw solute flux were found to increase with increasing crossflow velocities. Further, through experimentation, the water and reverse draw solute flux was found to decrease with decreasing temperature. Using the modeling approach developed in this work, the assessment for a potential FO application is refined by providing the means for accurate process modeling and membrane characterization.

Advisor: Papangelakis, Vladimiros G
Generative Design Optimization of Thermal Management Systems for High Output Power Electronics

Power electronic converters are becoming a critical part of the continuing electrification of transportation technology. With the increasing popularity of electric vehicles, high demands are being placed on the performance and reliability of these on-board modules. To meet these challenges, novel architectures and advanced design techniques are being utilized to address the growing issue of proper thermal management for compact power electronic devices. This thesis proposes a novel design methodology that utilizes genetic algorithms to optimize the liquid topologies of compact heat sinks for power electronic systems. By incorporating precise electrical design data into detailed thermal models, the optimization process accurately captures the heat spreading within these complex systems. The intelligence nature of this iterative program identifies ideal design characteristics to improve heat sink performance and generate optimized cooling structures, specifically tailored to target converter systems.

Keywords: CFD
Electric Vehicles
Genetic Algorithms
Optimization
Power Electronics
Thermal Modeling
Advisor: Mills, James K
Trescases, Olivier
Deciphering the Interaction between Wood Components and Preservative Chemicals: A Comparison of Analytical Techniques

The durability of preservative-treated wood is highly dependent on the interaction of wood components (cellulose, hemicellulose, lignin, and extractives) with preservative chemicals. Wood preservatives are generally comprised of metal ions, commonly copper, chromium, and arsenic, with iron as a pigment. This work establishes methods to quantify interactions between preservative chemicals and main wood components, to aid efforts in formulation development that extend the weathering performance of wood. Analytical methods for isothermal titration calorimetry (ITC) and quartz crystal microbalance with dissipation monitoring (QCMD) were developed. Iron was found to interact with organosolv softwood lignin and beechwood glucuronoxylan, whereas copper, arsenic, and chromium were found to interact with the glucuronoxylan only. Additionally, the impact of alkaline copper quaternary(ACQ)-type preservative treatment on the degradation of wood structures by UV-A light was studied using Fourier transform infrared spectroscopy (FTIR) and the distribution of copper ions visualized using time-of-flight secondary ion mass spectrometry (ToF-SIMS).

Keywords: characterization
FTIR
ITC
QCMD
ToF-SIMS
wood
Advisor: Master, Emma R
Corporate Sustainability Distinctions, Transitions and Perceptions: A Look to Canada’s Big Five Banks

Corporate sustainability (CS) is becoming increasingly mistaken for or confused with corporate social responsibility (CSR). Literature in recent years has identified this muddied area and argues for further clarity. Clarifying this confusion and understanding the fundamentals of CS can help to ensure companies implement sustainable strategies that are beneficial for current and future generations, while also ensuring resiliency and long-term success. With the creation of a theoretical framework that sets CS and CSR apart, this research emphasizes the importance of sustainability within business and explores Canada’s Big Five banks as its case study. Through the analysis of 75 past and present reports (2002-2018), as well as interviews with employees of all five companies, the ways in which sustainability and social responsibility are perceived and implemented is investigated. Findings demonstrate clear shifts beyond CSR towards greater focus on CS within Big Five operations, allowing for lessons to be learned across sectors.

Keywords: Canadian banking
corporate social responsibility
corporate sustainability
sustainability transitions
Advisor: Besco, Laurel
Distributed Trajectory Generation for Multiagent Systems

Collision-free trajectory generation is a fundamental functionality of multiagent systems. As the number of agents increases, scalable algorithms are required to efficiently compute motion plans. In this thesis we developed a multiagent trajectory generation framework based on distributed model predictive control (DMPC). First, we introduced on-demand collision avoidance to solve the planning problem completely offline. We then extended the approach to online generation of the trajectories, and presented an event-triggered replanning strategy. The framework is validated through a wide variety of simulation tests and experiments with a swarm of up to 25 quadrotors flying in an indoor environment.

Keywords: Collision Avoidance
Model Predictive Control
Motion Planning
Multiagent Systems
Advisor: Schoellig, Angela P
Production, Characterization and Application of Monolithic Biocarbon for Water Desalination

Desalination is a process of removing salts from saline solutions to produce fresh water. Currently, the challenges of desalination technology are high energy consumption and material cost. This project suggests sustainable and affordable ways to purify water via evaporation process under sunlight or capacitive deionization using monolithic biocarbon. Biocarbon was produced from woody biomass during 60 hours of slow pyrolysis. After pyrolysis, the macrostructure of wood is preserved in the produced biocarbon. The morphology, chemical composition, permeability and electro capacitance of biocarbon was measured. The effect of biocarbon amount, biocarbon particle size range, light intensity, light distance, salt concentration, and wood orientation on evaporation rate was studied. The use of monolithic biocarbon increased the evaporation rate 8 times higher from saltwater. The permeability of biocarbon and evaporation rate in axial and radial orientation was significantly different. The measured capacitance of biocarbon was 113 F/g in 1 M NH_4Cl solution.

Advisor: Jia, Charles Q
Kirk, Donald W
Characterization of Pre-retrofit Air Flow in a 1970’s Multi-unit Residential Building in Toronto, Ontario

Many multi-unit residential buildings (MURBs) constructed in the 1970s do not meet current energy standards. Air leakage through the building envelope contributes significantly to energy losses in these buildings. Retrofits such as window replacements and over-cladding can improve the air tightness of the envelope but may have unintended consequences for the ventilation of the building. Pressure distributions throughout the building may change because of reduced leakage across the exterior walls leading to increased inter-zonal air flow. Air flow tests were performed in a 1970s MURB in its pre-retrofit condition. The tests showed significant leakage across building components including the windows and balcony doors. Occupant surveys indicated odour transfer between suites despite field tests that showed adequate air change rates and low inter-zonal air transfer between suites. Air flow network modelling showed that inter-zonal air flow will likely increase between select suites after envelope air tightening retrofits are completed.

Advisor: Touchie, Marianne
Characterizing BDNF Expression and Glial Cells in the Comorbidity between Chronic Pain and Depression

Acute pain is adaptive and important for survival, but lingering pain can transition to a maladaptive state and become chronic. Chronic pain affects many people, a high proportion of those being women, who also suffer from comorbid conditions such as depression. As such, it is important to understand and study the molecular mechanisms of chronic pain and associated depression, in both males and females, in order to create new treatments and pain management methods. This thesis used a mouse model of chronic neuropathic pain and measured depressive-like behaviours and brain changes in both male and female mice. Specifically, I characterized the changes in relative BDNF expression and activation of microglia and astrocytes in various pain and affect related brain regions. Results from this thesis may be useful in directing future functional studies to manipulate BDNF, microglia and/or astrocytes to elucidate their role in the comorbidity between chronic pain and depression.

Keywords: Astrocyte
BDNF
Depression
Depression and Pain
Microglia
Neuropathic Pain
Advisor: Martin, Loren J
Motivating Students in Online Courses: Designing for Dialogue and Social Presence

This thesis is based on a case study of a 2018 Masters Level Introductory Research Methods course taught online to 32 students. The purpose of the study was to determine what motivates students to engage in online learning environments. This exploratory mixed-methods study involved 14 students volunteering to complete a survey, and six of those students agreeing to a follow up interview. Both the survey and the interview asked students to comment on aspects of the social and built environment of the course, with specific attention paid to the role of video and text-based discussions in motivating student to engage in the course. Findings suggest that text-based forums, due to built design as well as lack of visual social cues, were less effective than video-based interactions in terms of creating social presence and the type of dialogue that led to increased student perceptions of learning.

Keywords: Dialogue
Motivation
Online Learning
Social Presence
Advisor: Ryan, Sherida
Romantic Consent in Emerging Adults with Autism (ASD)

This thesis explores how emerging adults with Autism Spectrum Disorder (ASD) understand and practice consent in romantic contexts. Participants included 26 emerging adults (age 18-25) with ASD and 39 neurotypical (NT) emerging adults recruited online across Canada and the USA. Participants were presented with multiple vignettes detailing common romantic situations that emerging adults encounter and asked to decide how the main character should proceed. Thematic analysis was performed on participants’ decision making and reasoning. While overall the ASD and NT groups offered similar responses, differences did emerge: The ASD group was more likely to refer to social rules and norms, less likely to abstract the characters’ emotions, and less likely to articulate their reasoning. Gender difference also emerged: Females were sometimes more cautious and more likely to include apologies in their decisions. Implications and recommendations discussed.

Keywords: ASD
Autism
Consent
Emerging Adults
Mixed Methods
Romance
Advisor: Ferrari, Michel
HOXB4-mediated Enhanced Self-renewal of Committed Hematopoietic Progenitors

Stemness is the capacity of cells to 1) differentiate into distinct cell types and 2) self-renew. Self-renewal is the ability of a cell to produce identical daughter cells upon division and resist differentiation. Both hematopoietic and leukemic stem cells follow a hierarchy defined by varying capacities for self-renewal. Therefore, understanding the control of self-renewal is of vital importance. The Homeobox family of transcription factors, including HOXB4, plays an important role in the regulation of self-renewal. However, the specific stages in differentiation at which HOXB4 maintains self-renewal remain unknown. I identified two phenotypes of hematopoietic progenitors that sustain self-renewal in a subset of hematopoietic lineages given exogenous HOXB4. These findings provide new support to the idea that the cell sustaining self-renewal given exogenous HOXB4 is not multipotent, and contribute new specificity by finding that susceptibility to immortalization by exogenous HOXB4 is confined to specific early stages in hematopoiesis.

Keywords: hematology
hematopoiesis
HOXB4
self-renewal
stem cells
stemness
Advisor: Iscove, Norman N