VictorJuiz/thesis huggingface dataset:
Examining Variation in Somatic Mutation Rates at Chromatin Architectural Elements of Cancer Genomes

CCCTC-binding factor (CTCF) and the cohesin complex anchor chromatin loops and domains that regulate genomic interactions and transcription. These elements are also enriched for somatic mutations; however, an understanding of the underlying mutational patterns, processes, determinants, and functional implications remains elusive. It was discovered that topoisomerase II beta (TOP2B) frequently co-binds with these proteins, conceivably to relieve topological stress produced during loop formation. Here, we analyzed a dataset of CTCF, RAD21, and TOP2B binding sites experimentally derived from human liver cancer tissue. We studied the DNA-binding and genomic associations of these proteins and systematically characterized mutational patterns using a pan-cancer dataset of 2,500 whole genomes. We found that the mutation enrichment was more pronounced in sites bound by all three proteins. We identified 222 candidate drivers, 81% of which contained TOP2B binding. Subsets of these candidates correlated with gene expression changes and may represent novel non-coding drivers of cancer.

Keywords: CTCF
Mutation rates
Non-coding
RAD21
TFBS
TOP2B
Advisor: Reimand, Jüri
A Data-driven Optimized Two-stage Appointment Scheduling Model for CT Simulation and Radiation Treatments

Radiation treatment, one of the main methods to treat cancer, requires a CT simulation to view the body’s inner structure and generate treatment plans. The appointment scheduling for CT simulation and radiation treatments is a complex two-stage problem for patients of different site groups, categories, and treatment intents. The problem is formulated as a Mixed Integer Programming problem to jointly schedule both kinds of appointments and we propose two alternative objective formulations to minimize the number of patients who wait more than their wait time targets for their treatment. Using historical data analysis to estimate the parameters, the models are evaluated using daily scheduling and patient batching approaches by considering wait time statistics and the utilization of linear accelerators. A heuristic model is also developed based on the results of the patient batching approaches to generate the appointment schedule at the time of consultation. The results of different approaches are compared.

Keywords: Appointment scheduling
CT simulation
Healthcare
Operations research
Radiation treatment
Advisor: Carter, Michael W.
Attitude Control of a Flexible Solar Sail using Translating Masses

This thesis is devoted to developing attitude control of a square solar sail spacecraft made of four pre-tensioned triangular sails supported by four flexible diagonal booms each affixed with a translating mass. The control torques are created by the relative displacement of the spacecraft's center-of-mass to its center-of-pressure. A Rayleigh-Ritz method is used to discretize the equations of motion of the spacecraft. Only out-of-plane deflections of the sail membrane quadrants and support booms are considered in the present document. Modal analyses are performed to validate the model’s basic foundations against the results obtained by a finite-element method in past literature. Attitude and vibration control simulations are presented and stability results are discussed.

Keywords: Attitude Control
directional stability
eigenvalue analysis
Flexible solar sail
Rayleigh-Ritz method
translating masses
Advisor: Damaren, Christopher J.
Gendered Voices in Japanese Popular Music: A Data-driven Analysis

In this thesis, I investigate the gender ideologies, conventions, and stereotypes represented in Japanese popular music lyrics by analyzing 17,614 commercially successful songs released in Japan from 1968 to 2020 utilizing natural language processing and machine learning. In the first part, the differences in word use between the lyrics sung and written by women and those sung and written by men are examined with classification models. The dynamics between singer gender and lyricist gender and their impact on the lyrics, the differences between the lyrics written and sung by the same artists (singer-songwriters) and those written and sung by different artists, and the historical changes are also analyzed. In the second part, I explore how male characters and female characters are portrayed in popular music lyrics differently through a computational extraction of feminine and masculine personal pronouns and the words syntactically associated with them.

Keywords: computational social science
digital humanities
gender roles
gender stereotypes
Japanese popular culture
popular song lyrics
Advisor: Andritsos, Periklis
13-deoxytetrodecamycin and Thamamycin: Two Promising Tetrodecamycin Antibiotics

Antibiotic-resistant bacteria pose a serious threat to modern medicine. Methicillin-resistant Staphylococcus aureus (MRSA) is among the most alarming pathogens due to its prevalence in hospitals and the community and the emergence of multi-drug resistant isolates. 13-deoxytetrodecamycin (13-dTDM) and thamamycin (THM) are novel, related members of the tetrodecamycin antibiotic class that are bioactive against MRSA. Presently, their targets and mode of action are unknown although their structural novelty and potency against drug-resistant bacteria makes them very attractive subjects for research. The aim of this thesis was to increase the yield of 13-dTDM and THM in order to elucidate their molecular target and mode of action. Utilizing a ‘ribosome engineering’ approach, I have successfully increased the yield of THM. I also demonstrate that 13-dTDM and THM are bactericidal and do not target the lipid II cycle of cell wall biosynthesis. Lastly, preliminary data suggests possible targeting of the folate pathway by THM.

Advisor: Nodwell, Justin JN
Preventing the Development of Nitrate Tolerance and Assessing Endothelial Function.

Nitroglycerin (GTN) and other organic nitrates are widely used to treat patients with various cardiovascular diseases. However, despite beneficial effects, treatments are often limited due to the development of a phenomenon termed ‘nitrate tolerance’ and the exact contributing mechanisms remain unknown. During chronic nitrate therapy, there is rapid loss of the hypotensive effect and a greater dose is required to achieve the same response. Many hypotheses have emerged to explain the phenomenon and subsequently, to develop treatment alternatives such as combination therapies to prevent nitrate tolerance in patients. In addition, endothelial dysfunction is also commonly noted to occur along with the development of nitrate tolerance. There are many clinical tests that can assess endothelial function, such as venous occlusion plethysmography, flow mediated dilatation and quantitative coronary angiography. However, the predictive values of some clinical methods in determining endothelial dysfunction and hence, risk of cardiovascular disease remains debatable.

Keywords: Allopurinol
Endothelial
FMD
Nitrate
Tolerance
Advisor: Parker, John
A High-resolution Optical Flow-inspired 3D3C Velocimetry Method based on Sparse Representation of 3D Particle Images

We introduce a three-dimensional three-component (3D3C) particle-based velocimetry method that expands the methodology of optical flow to three dimensions. A sparse representation of intensity with kernel functions is introduced to facilitate efficient computation in 3D, and to ensure robust performance for the large displacements seen in particle images. Performance of the proposed method is evaluated in terms of accuracy and spatial resolution, using direct numerical simulation data as a ground truth. The proposed method yields lower errors than tomographic PIV and is capable of resolving finer scale features, even for large particle displacements and in the presence of tomographic reconstruction artifacts. The method is also validated on experimental images of reacting flows and shows good agreement with T-PIV results.

Keywords: Optical Flow
PIV
Velocimetry
Advisor: Yano, Masayuki MY
Steinberg, Adam AS
Cost-utility Analysis of Universal Pre-exposure Prophylaxis Coverage for Men who have Sex with Men at a High Risk of Human Immunodeficiency Virus Infection in Ontario, Canada

HIV pre-exposure prophylaxis (PrEP) was approved by Health Canada in 2016. Currently in Ontario, those under the age of 25 or aged 65 years or older can access PrEP free of charge through public drug coverage programs. This study assessed the cost-effectiveness of providing public coverage for PrEP to all high-risk Ontario MSM. A Markov cohort model was built from the perspective of the Ontario Ministry of Health and Long-Term Care (MOH) using a lifetime time horizon. Health states included HIV positive, HIV negative, and Dead. Transition probabilities, health state utilities and HIV treatment costs were sourced from published literature. Costs of HIV prevention were estimated through a micro-costing approach. HIV infection risk was estimated using the HIRI-MSM screening tool. Offering PrEP to all high-risk MSM through the Ontario MOH is dominant to current coverage circumstances due to a reduction in costly HIV infections.

Keywords: Cost-Utility Analysis
Economic Evaluation
Health Economics
HIV
MSM
PrEP
Advisor: Loutfy, Mona
Coyte, Peter
Analyzing Impact of the COVID-19 Pandemic on Traffic Congestion and Commercial Vehicle Travel Patterns within the Greater Toronto and Hamilton Area

The COVID-19 pandemic has impacted virtually all social and economic activities in our society, resulting in changing patterns of travel and traffic congestion in Canada. This thesis first analyzes traffic congestion changes throughout the first and second waves of the pandemic on detected freeway bottlenecks within the Greater Toronto Hamilton Area (GTHA), using travel speed data. Then this thesis focuses on the commercial vehicle (CV) travel patterns, specifically changes in origin and destination in the GTHA. Since the beginning of the pandemic, consumers’ shopping behaviours have changed dramatically. The impact of these changes is investigated by analyzing the origins and destinations of CVs based on GPS data collected by Geotab GO. The changes are described with figures and summary statistics. Next, CVs activities are analyzed on the worst bottleneck in the GTHA, and finally, recommendations for future research are provided.

Keywords: Bottleneck Analysis
Commercial Vehicles
COVID-19 Pandemic
E-Commerce Boom
Travel Speed
Advisor: Roorda, Matthew M
Machine Learning for Prognostic Modeling in Head and Neck Cancer using Multimodal Data

There has been significant interest recently in exploiting routinely collected clinical and medical imaging data to discover new prognostic markers in multiple cancer types. In this work, we explore the use of multi-modal machine learning (ML) for outcome prediction in head and neck cancer (HNC).We first develop a ML approach for survival prediction from multi-modal data in the presence of competing risks, based on an extension of the multi-task logistic regression framework. We then describe the results of a ML challenge to develop a prognostic model for overall survival using electronic medical records and pre-treatment imaging. Finally, we present a novel graph-based method to incorporate imaging characteristics of metastatic lymph nodes and their connectivity patterns in a prognostic ML model using Gated Graph Convolutional Networks. Our results show the potential of ML in combination with large, multi-modal datasets as a tool to guide personalized cancer care.

Keywords: Head and neck cancer
Machine learning
Medical imaging
Prognostic modeling
Advisor: Haibe-Kains, Benjamin
Factors Influencing Immune Investment in Invertebrates

Immune traits are an important facet of an organism’s biology, as the threat of infection from pathogens is universal. We nonetheless observe a large degree of variation in measured immune traits, indicative of differences in immune investment between individuals. This thesis attempts to answer two questions around how individuals navigate immune investment. One, does mating environment impact immune investment in a species of water strider and two, is the sexual dimorphism observed in a commonly cited invertebrate immune metric related to the sexual size dimorphism commonly seen across this group? While a portion of chapter 1 could not be completed due to the pandemic, I do find evidence that water striders experience changes in mating environment in the wild. In chapter 2 I find that the expansion of an existing dataset on sex bias in melanization results in no significant sex bias in this immune metric as well no relationship between melanization and sexual size dimorphism, contradicting what may be expected by theory regarding sex biased immune allocation.

Keywords: Immunity
Invertebrates
Investment
Meta analysis
Sex ratio
Sexual dimorphism
Advisor: Rowe, Locke
An Exploratory Study of the Travel Characteristics of Students who Use Mobility Aids at Ten Universities and Colleges in the Greater Toronto and Hamilton Area, Ontario, Canada

Postsecondary students are an underrepresented population in transportation research, and postsecondary students with disabilities even more so. Using survey data from ten universities and colleges in the Greater Toronto and Hamilton Area, I compare demographic, activity, and attitudinal characteristics of students who use mobility aids to other students, exploring potential differences in access and use of transport and education systems. The results indicate that many students who use mobility aids are from lower income families, receive less financial support, and travel at different times than other students. Students who use mobility aids reported greater use of modified vehicles and carpooling with household members. They were also more likely to report that commuting discouraged them from attending campus and limited their academic success. A closer look at the experiences of postsecondary students with disabilities is required. Future research should expand to include other disabilities and a longer observation period.

Keywords: Disability
Mobility
Postsecondary
Student
Travel
Advisor: Buliung, Ron
Mitra, Raktim
Visual Post-hoc Explanation of Convolutional Neural Networks Via Attribution-based Perturbation

Visual explanation algorithms are a subset of post-hoc solutions in Explainable AI that aim to open the black-box of cumbersome models utilized for image recognition tasks. These algorithms aim to determine the features in each given input data that contribute the most to the model's prediction. Producing high-resolution and class-discriminative visual explanations that accurately represent the evidence leading the model to make its predictions is a common challenge in prior visual explanation solutions. This thesis proposes a novel CNN-specific visual explanation algorithm that circumvents these limitations by extracting and aggregating semantic and spatial information from various layers of CNN. The performance, complexity, and compatibility of our proposed algorithm are analyzed through thorough comparisons with state-of-the-art methods in large-scale experiments on natural scene object recognition and visual anomaly inspection applications. Furthermore, this thesis introduces a small-scale benchmark for validating the performance of visual explanation methods on a pattern classification task.

Keywords: Artificial Intelligence
Computer Vision
Deep Learning
Explainable AI
Image Processing
Machine Learning
Advisor: Plataniotis, Konstantinos N.
Using Ice and Sediment Cores to Quantify Climate-warming Induced Inputs of Legacy Mercury to Lake Hazen, Nunavut

Mercury (Hg) is a globally dispersed contaminant that can bioaccumulate and biomagnify in food-webs. This research uses a unique combination of measurements in an ice core and a sediment core collected within the same watershed (Lake Hazen, Nunavut) to determine how the relative importance of Hg inputs from atmospheric, glacier and terrestrial sources has changed over the last century. Hg accumulation in Lake Hazen sediment began increasing dramatically in the mid- 1990s, exhibiting a decoupling from atmospheric sources (as estimated from the ice core record), due to the increased importance of remobilized terrestrial Hg inputs to Lake Hazen. Increasing glacier melt and permafrost thaw slumping have increased the delivery of catchment Hg, via glacial rivers, into Lake Hazen. These results show that climate change is likely to slow the recovery of glacierized Arctic watersheds from Hg contamination, countering the anticipated benefit from recent international efforts to reduce anthropogenic Hg emissions.

Keywords: Arctic
Climate change
Contaminants
Ice core
Methylmercury
Total Mercury
Advisor: Lehnherr, Igor
Creating and Evaluating an Audio Detection Interface to Guide Families in Musical Play and Learning with Low-cost Musical Instruments at Home

Musical play and learning are fundamental for child development, yet the opportunities are not the same for children with disabilities. Our overarching goal is to provide more opportunities for home-based musical play and learning for children who may not have access to teacher-led music programs. This thesis describes the design and evaluation of an audio detection interface which can classify low-cost, early childhood musical instruments such as a tambourine, shaker, and castanet. This interface achieves over 84% accuracy using an approximate 93 ms window length to in-lab variants across all 3 instrument families. This interface was deployed and tested with twelve families in a music application called Bootle Band. In this usability study, we observed an average accuracy of 73% [SD=6.8%] in family’s household. We found that children’s play time and responses on the Fun Toolkit Questionnaire were equivalent when the game was played with real-life instruments versus a typical touchscreen. This suggests that the performance of our audio detection interface was sufficient to support playability in real-world settings. This thesis lays the groundwork for a music education application that interacts with real-world musical instruments and is accessible to families and their children, with and without disabilities.

Keywords: Acoustic signal processing
Audio classification
Classification algorithms
Education technology
Machine learning deployment
Music information retrieval
Advisor: Biddiss, Elaine
Probing the Neural Oscillatory Patterns Associated with Incidental Learning: A MEG Study

Cortical learning is a hippocampal-independent neocortex-dependent memory consolidation process. Cortical learning could be promoted by prior knowledge. Research found hippocampal-amnesia patients, including HM, are able to acquire new semantic knowledge if it relates to prior knowledge. This study examined the underlying neural processes that are associated with cortical learning of semantic knowledge with an incidental learning paradigm and MEG. We found cortical regions in visual association areas, multi-modal areas and paralimbic areas associated with incidental learning. We also found increased alpha and gamma power in cortical regions at the end of learning, and last but not least, we found cortical regions activation power at the end of learning positively correlated with learning accuracy. This study indexed the cortical regions and neural oscillatory processes that are associated with cortical learning and provide ground for future studies to probe deeper into the neural mechanisms that support cortical learning. At the same time, our study provides new perspectives on the theories of semantic representation.

Keywords: cortical learning
incidental learning
MEG
prior knowledge
Advisor: Gilboa, Asaf
McIntosh, Randy
Interrogating the Small-cell Lung Cancer Methylome using Liquid Biopsies

Small cell lung cancer (SCLC) is one of the most aggressive types of cancers. Despite being initially responsive to treatment, most patients relapse. Currently it is not clear how such mechanisms of resistance develop, though recent evidence suggests epigenetic mechanisms may be involved. In this study the cell-free methylated DNA immunoprecipitation (cfMeDIP-seq) assay was performed on blood from SCLC patients, healthy donors, and novel circulating-tumour cell derived xenograft (CDX) models. SCLC patients appear to have a distinct methylation profile compared to healthy donors. CDX models derived from SCLC patients also appear to be highly similar, highlighting their future use for biomarker development and discovery. Finally, consensus clustering on SCLC patient methylation profiles shows three distinct methylation-defined subtypes. These subtypes appear to have differential methylation of Wnt-signalling genes, a pathway known to be dysregulated in relapsed SCLC.

Keywords: cfMeDIP-seq
DNA methylation
epigenetics
liquid biopsy
small cell lung cancer
Advisor: Lok, Benjamin
Analysis of Adenosine A2A Receptor Conformational States by Stationary Phase EPR Spectroscopy

The adenosine A2A G protein-coupled receptor (A2AR) plays an essential role in many biological functions linking extracellular signals to intracellular events. A2AR adopts various conformational states that are stabilized depending on ligand and G protein. To study A2AR’s conformational equilibria, a stationary phase pulsed electron paramagnetic resonance (EPR) spectroscopy platform was developed for characterizing the immobilized receptor on cobalt resin. This platform provides a high local A2AR concentration and comparable results to the traditional in-solution measurements. With this method, A2AR transmembrane helix (TM) 6 was found to adopt four states with a distinct outward displacement of TM6, while TM7 adopts at least three states. The partial agonist preferentially stabilizes an active intermediate state of TM6 and an inactive state of TM7. These results may stimulate further studies on more intricate aspects of A2AR’s structural dynamics, while this platform may be integrated with other advanced technologies for similar protein research topics.

Keywords: A2AR
DEER
EPR
GPCR
Advisor: Ernst, Oliver P
Territory Acknowledgment, Unacknowledgement, and Misacknowledgement: A Haunting

This thesis analyzes conversations on the practice of territory acknowledgements, particularly as they are practiced in academic spaces, arts spaces and by organizations and institutions. Themes that are drawn from these conversations and attended to include: territory acknowledgements as distinctly not “traditional protocol”, territory acknowledgements and the politics of recognition (what is their purpose?), the labour of territory acknowledgements (who is doing them, and who are they for?) and the exhausting repetition of territory acknowledgements (how often?). Territory acknowledgement (as well as unacknowledgement and misacknowledgement) is then removed from the framework of reconciliation and theorized instead as haunting. The author posits, if reconciliation is dead, is territory acknowledgement a haunting? Finally, visiting practices are introduced as alternative ways to make relationships to place not based on possession or ownership. This final chapter considers the positionality of being a visitor, an ethics of care for visiting, and offers examples of visiting practices.

Keywords: Haunting
Indigenous education
Place-based education
Reconciliation
Territory Acknowledgement
Visiting
Advisor: Tuck, Eve