VictorJuiz/thesis huggingface dataset:
Characterizing the Role of Protein Arginine Methyltransferase 5 in Colon Cancer

An epigenetic drug screen was carried out in CRC organoids which identified PRMT5 as a potential epigenetic target regulating CC-ICs. Upon analyzing a cohort of CRC patients from TCGA, PRMT5 mRNA was observed to be significantly upregulated in tumour samples compared to normal. This evidence led us to pursue further work using CC-IC enriched cell lines to understand the functional role of PRMT5. Pharmacological inhibition of PRMT5 decreased cell viability in three CC-IC enriched cell lines. In contrast, genetic knockdown of PRMT5 using shRNA increased or had no effect on cell viability. Pretreatment of CC-IC enriched spheres using PRMT5 inhibitors led to an increase in Wnt-reporter activity. No effect on CC-IC stem cell frequency was observed upon pharmacologically or genetically inhibiting PRMT5. Next, we explored the oncogenic role of PRMT5 in normal organoids. Upon overexpression of PRMT5 in normal and engineered normal organoids, no difference in proliferation was observed.

Advisor: O'Brien, Catherine A
Synthesis of Lead Sulfide Quantum Dots and their Ligands for Photon Upconversion Applications

Lead sulfide quantum dots (PbS QDs) are prime candidates for various optical applications due to their size-dependent optical properties, tunability, narrow absorption peaks, and their spin-mixing properties. Small PbS QDs have proven to be a synthetic challenge but are important candidates for use in optical upconversion which is the process by which low energy photons are combined to form a higher energy photon. We describe our attempts at optimizing the relatively new synthetic method of using thioureas as precursors to make small PbS QDs, as well as determining the mechanism of monomer formation. We also describe our synthesis and characterization of 5-(p-carboxyphenyl)tetracene, a ligand that can act as a triplet extractor from PbS QDs for use in optical upconversion.

Advisor: Wilson, Mark WB
Investigating the Role of Histone Deacetylase 1 in the Pathogenesis of Atypical Teratoid/Rhabdoid Tumours

Atypical teratoid rhabdoid tumours (AT/RTs) are devastating embryonal brain tumours that usually develop before the age of two years, with a survivability of less than one year. They are characterized by loss of the SMARCB1 gene and high expression of histone deacetylase 1 (HDAC1). Genetic inhibition of Hdac1 led to varying results between replicates, such that no conclusions can be drawn at this time. Selective pharmacological inhibition of HDAC1 decreased cell number in Group 2 cell lines, with a concomitant increase in p21 protein expression. This suggests selective pharmacological inhibition of HDAC1 culminates in cell cycle arrest, but these results differ somewhat from those found following genetic inhibition. Future experiments will focus on generating stable cell lines expressing an inducible HDAC1 shRNA construct to further elucidate the role of HDAC1 in AT/RT pathogenesis.

Keywords: Cancer
Genetics
Paediatric
Therapeutics
Advisor: Rutka, James T
HyScale: Hybrid Scaling of Dockerized Microservices Architectures

Recently, microservices architectures have garnered the attention of many organizations--providing higher levels of scalability, availability, and fault isolation. Many organizations choose to host their microservices architectures in cloud data centres to offset costs. Incidentally, data centres become over-encumbered during peak usage hours and underutilized during off-peak hours. Traditional scaling methods perform either horizontal or vertical scaling exclusively. When used in combination, however, both offer complementary benefits and compensate for each other's deficiencies. To leverage the high availability of horizontal scaling and the fine-grained resource control of vertical scaling, two novel reactive hybrid autoscaling algorithms are presented and benchmarked against Google's popular Kubernetes horizontal algorithm. Results indicated up to 1.49x speedups in response times, 10 times fewer failed requests, and 35% increase in resource efficiencies. Moreover, a novel predictive approach is also explored using neural networks and a custom online learning technique indicating prediction errors as low as 3.77%.

Keywords: autoscaling
cloud
Docker
microservices
Advisor: Jacobsen, Hans-Arno
Subway Station and Post-It Notes: The Kangnam Murder Case of 2016 and the Emergence of a New Form of Protest

This thesis examines the Kangnam Murder Case of 2016 and how its participants used a street vigil as a site of protest against misogyny in South Korea. The thesis places the case within the changing contemporary socio-economic environment and contextualizes the vigil-turned-protests with the lineage of feminist movements from the 1920s to the 2000s. The Kangnam Murder Case’s vigil used the subway station as a site of memorialization and mobilization. Examining the use of post-it notes as a form of protest in the everyday space of a subway station illustrates the complex and contradictory ways that that voice may occupy space.

Keywords: feminist movement
Space and memory
Advisor: Poole, Janet
Kilroy-Marac, Katie
Investigation of Thin Film Polymeric Contaminants by Optical and Contact-Force Microscopy

Here is investigated the presence of organic contamination on extremely flat surfaces of hexagonal boron nitride. Boron nitride has the ability to support phonon polaritons, which are strongly dependent on the material's dielectric properties. The effect of these thin films on polaritons is explored. It was found that the films were primarily comprised of poly-dimethyl siloxane type contaminants. Polymers are investigated through contact force AFM in order to understand mechanistic properties of micellular collections of polymer. Analysis through machine learning provides a promising means to mechanistic understanding of polymer clustering on surfaces.

Keywords: atomic force microscopy
infrared
phonon polaritons
polymer hydration
Advisor: Walker, Gilbert C
The Cystic Fibrosis Transmembrane Conductance Regulator as a Potential Link Between the Circadian Clock and the Myogenic Response

Cerebral autoregulation maintains relatively constant cerebral perfusion despite variations in mean arterial pressure (MAP), mainly through the myogenic response: the intrinsic ability of cerebral resistance arteries to adapt their tone to transmural pressure. I demonstrate that the myogenic responsiveness of these arteries exhibits a circadian rhythm which is anti-phasic with that of the cremaster skeletal muscle arteries. This rhythm in cerebral artery myogenic responsiveness provides a functional basis to cope with circadian oscillations in MAP. Both mRNA and protein expression of the cystic fibrosis transmembrane conductance regulator (CFTR) oscillate in a fashion that is consistent with its role as a negative regulator of the myogenic response, and circadian rhythmicity in CFTR mRNA expression persists under constant darkness. Our data suggest that rhythmic expression of CFTR may be responsible for the functional phenotype.

Advisor: Bolz, Steffen-Sebastian
Heximer, Scott
A Time-Motion Study of Multidisciplinary Bedside Rounds in Pediatric Critical Care

The objective of this study was to characterize workflow during multidisciplinary bedside rounds in a pediatric critical care unit. Time-motion data and attendance were collected through observation, and healthcare provider (HCP) perceptions were gathered through surveys. Over 65 hours of time-motion data was collected during 57 rounds. High patient acuity was related to longer encounter durations and high unit census was related to shorter encounter durations. Family interaction and a high level of multidisciplinary contribution was found to increase the encounter duration. HCP satisfaction with the current process was low; most clinicians reported often not being able to hear the discussion and not feeling free to share their opinion. The unit should determine which factors (e.g., efficiency, patient-centredness) are most valuable to the rounding process at what time, to inform the design of a system that is suited to the needs of the HCPs and the constraints of the environment.

Advisor: Trbovich, Patricia
Chignell, Mark
The Use of Activity Monitoring and Machine Learning for the Functional Classification of Heart Failure

Background: Assessing the functional status of a heart failure patient is a highly subjective task. Objective: This thesis aimed to find an accessible, objective means of assessing the New York Heart Association (NYHA) functional classification (FC) of a patient by leveraging modern machine learning techniques. Methods: We first identified relevant quantitative data and upgraded Medly, a remote patient monitoring system (RPMS), to support data collection. We then proceeded to build six different machine learning classifiers including hidden Markov model, Generalized Linear Model (GLM), random forest and neural network based classifiers. Results: The best overall classifier was found to be a boosted GLM, which achieved a classification performance (Cohen’s Kappa statistic κ=0.73, balanced accuracy=85%) comparable to human level performance (κ=0.75). Conclusions: Although the investigated classifiers are not ready for implementation into a real RPMS, they show promise for making the evaluation of NYHA FC more universally consistent and reliable.

Keywords: ambulatory monitoring
clinical decision support
heart failure
NYHA (New York Heart Association)
steps
wrist worn devices
Advisor: Cafazzo, Joseph A
Heart Rate Variability Biofeedback as an Intervention Method for Reducing PTSD Symptoms in Police Officers Exposed to Trauma

PTSD has been identified as a significant occupational hazard among first responders in Canada, associated with negative health and performance ramifications. Less is known about the accumulation of PTSD symptoms among police officers (i.e., partial PTSD [P-PTSD]) and its potential impact on performance, particularly in regards to use-of-force decisions. The current project examined levels of P-PTSD symptoms among Ontarian police officers, and its relationship with occupational performance and heart rate variability (HRV). Data was extracted from an on-going study utilizing an existing HRV biofeedback intervention to reduce lethal use-of-force decision errors. Officers’ self-reported P-PTSD symptoms did not significantly predict use-of-force decision making abilities, proxies of HRV, or significantly change from pre- to 18-months post-receiving HRV biofeedback training. While significant results were not found, this pilot study provides important insight in the potential for gathering P-PTSD symptoms from front-line police officers, as well as improving health and safety in this population.

Keywords: Autonomic Arousal
Biofeedback
Heart Rate Variability
Partial PTSD
Police
PTSD
Advisor: Andersen, Judith P
Structural and functional analysis of Golgi in Legionella-infected macrophages

Legionella pneumophila is an accidental pathogen that replicates intracellularly within the Legionella-containing vacuole (LCV). It hijacks important host regulators of early secretory pathway including Rab1. To see the consequence of the trafficking disruption, we examined the Golgi structure and function in Legionella-infected human U937 macrophages. Intriguingly, the Golgi area in infected macrophages remained similar to non-infected macrophages. Furthermore, TEM analysis also did not reveal any significant changes in the ultrastructure of the Golgi in infected cells. Drug-induced Golgi disruption had differing effects on bacterial replication in human macrophages. The glycosylation protein levels, visualized by fluorescent cis-Golgi lectin, Helix promatia agglutinin (HPA), significantly decreased over time as infection progressed, compared to control cells. This suggests that Legionella hijacks sugars which are possibly important for bacteria growth. Collectively, our results indicate that the structure of Golgi is kept intact whereas the function of Golgi is possibly impaired in Legionella-infected macrophages.

Advisor: Harrison, Rene E
Terebiznik, Mauricio
Growth and Characterization of Multicellular Spheroids in Cellulose Derived Hydrogels as an Artificial Three-Dimensional Scaffold

This thesis describes the preparation and characterization of cellulose derived hydrogels. Specifically, aldehyde-modified cellulose nanocrystals (a-CNCs) and aldehyde-modified cellulose nanofibers (a-CNFs) will chemically cross-link with gelatin, forming nanofibrillar hydrogels capable of supporting the growth and differentiation of MCF 7 cells. To begin, a microextrusion-based 3D printing method was utilized to generate anisotropic hydrogel sheets. Hydrogels exhibiting both uniform and compositional gradients were extruded, resulting in gels with gradients in structure, mechanical properties and permeability. Then, MCF 7 cells were encapsulated within a-CNC/gelatin and a-CNF/gelatin hydrogels of varying concentrations in order to determine optimum cell viability. The results of these hydrogels indicate promising contributions to tissue engineering and regenerative medicine.

Keywords: Cellulose
Hydrogels
Multicellular cancer spheroids
Advisor: Kumacheva, Eugenia
Adapting the Turkevich Method to Synthesize Colloidal Rhodium Nanocrystals

The Turkevich method has been used widely for the synthesis of gold nanocrystals. Despite its success, it has not yet been applied to the synthesis of rhodium nanocrystals, which have great potential in myriad applications due to their special optical and chemical properties. Herein, it is shown that the Turkevich method, with the appropriate modifications, can be adapted to enable access to rhodium nanocrystals. Products are generated under a wide range of experimental conditions. In most cases, quasi-spherical aggregates of ultrasmall rhodium grains are obtained. Possible means of controlling the aggregate size are proposed. The method can also yield large, anisotropic rhodium nanocrystals, although control over the geometry of this product is not achieved. Further optimizations are suggested toward obtaining monodisperse, single-crystal rhodium nanoparticles for eventual use in applications.

Keywords: nanoparticle
rhodium
transmission electron microscopy
Advisor: Walker, Gilbert C
A Machine Learning Approach to Distinguishing between Multiple Sclerosis and Cerebral Small Vessel Disease

We sought to develop an automatic diagnostic algorithm to distinguish between relapsing-remitting multiple sclerosis (RRMS) and cerebral small vessel disease (SVD) using neuroimaging and clinical features. A mixture of t-distributions and a spatial heuristic algorithm were developed for the automatic segmentation of lesions on two MRI sequences. Combined lesion probability maps of RRMS and SVD were subsequently developed using a derivation set of patients. A novel cross entropy image distance metric was used to quantify the similarity of new cases to each disease. Bayesian learning algorithms using non-informative priors were trained using neuroimaging features and clinical features. Model hyperparameters were tuned using Monte Carlo cross validation. The model consisting of both neuroimaging and clinical features misclassified one case out of 21 on the test set when distinguishing between RRMS and SVD. As the societal and monetary cost of both diseases is high, this work has real potential for clinical impact.

Keywords: Biomedical Engineering
Biostatistics
Computer Vision
Machine Learning
Medical Imaging
Neurosciences
Advisor: Aviv, Richard
Tyrrell, Pascal
Evaluation of Technology and Manufacturing Readiness Level of a Noninvasive Alcohol Biosensor Based on Wavelength-Modulated Differential Photothermal Radiometry for In-Vehicle Applications

Drunk driving remains the most prominent cause of vehicle crashes in Canada. Among all of the countermeasures, the engineering-based control can reduce recidivism by about two-thirds. This thesis work introduces the proof-of-concept and prototype development of a wavelength modulated differential photothermal radiometry (WM-DPTR) sensor that combines the advantages of all the existing blood alcohol detection technologies. It is ultrasensitive, non-invasive, non-contact, seamless with driving task, reliable, and durable with no need for recalibration and maintenance services. This research work builds on WM-DPTR sensor’s potential for application in ignition interlock devices. The measurement results from human subjects with updated compact quantum cascade laser diode and digital signal acquisition system demonstrated the capability of WM-DPTR to detect blood alcohol concentration changes with high resolution and low detection limit. WM-DPTR limitations for applications in ignition interlock devices can be tackled by further improving instrumentation and data processing techniques.

Keywords: Biological sensing and sensors
Modulation spectroscopy
Photothermal
Photothermal effects
Spectroscopy
Advisor: Mandelis, Andreas
Investigating TSPO binding in methamphetamine use disorder during early abstinence

Background: It is unclear whether chronic methamphetamine (MA) use leads to brain microgliosis in living humans. We used positron emission tomography, targeting the translocator protein (TSPO) probe [18F]FEPPA, a marker suggestive of microgliosis, to explore, during early abstinence from MA, whether (1) there are changes in brain TSPO binding, suggestive of microgliosis and (2) if TSPO expression is related to “sickness” addiction-relevant symptomology. Methods: TSPO binding was measured in 10 MA users and 25 matched controls with MRI co-registration. Results: A RM-ANOVA controlling for TSPO genotype revealed no main effect of group on FEPPA VT (F(1, 32)=0.12, p=0.73). We also found no relationship between TSPO and behaviour, such as mood, craving. Conclusion: Our findings are consistent with those of post-mortem studies showing no evidence of above-normal microgliosis in chronic MA users. We also found no relationship between TSPO and addiction-relevant behavior, but replication studies are necessary to further explore this.

Keywords: addiction
methamphetamine
microgliosis
neuroimaging
positron emission tomography
translocator protein
Advisor: Boileau, Isabelle
Kish, Stephen
Effect of Alcohol Skin Cleansing on Vaccination Local Skin Reactions: A Randomized Controlled Trial

Objective: To assess the effectiveness of skin cleansing with alcohol in reducing the incidence of delayed pain post-vaccination, and assess the feasibility of conducting a larger trial. Methods: Participants were randomized to either be cleansed at (swab) or adjacent to (control) the injection site with 70% isopropyl alcohol then let dry before vaccine administration. Parents blinded to the treatment allocation reported local reactions for 15 days post-vaccination using paper diaries and 3 telephone surveys. Results: In 6.5 months, 170 patients were recruited and received 281 vaccine injections. Eighty-one percent of diaries were returned and 94% of parents completed all 3 phone surveys. There was no difference in the incidence of reported delayed pain or any local skin reactions between both groups. Discussion: These findings are the first evidence specifically for vaccination injections demonstrating that cleansing the skin with alcohol may not be needed.

Keywords: Adverse events
Alcohol swabs
Cellulitis
Immunization
Infections
Vaccines
Advisor: Taddio, Anna
Development of the TRAISI Web Survey Builder: Designing to Reduce Bias and Respondent Burden in Household Travel Surveys

Household travel surveys (HTS) are undoubtedly the most common and amongst the largest data collection undertakings by transport agencies worldwide. Within recent years, web-based surveys have been the dominant survey mode for HTS’s. However, given the extensive detailed data collected in HTS’s, web-based HTS’s have been facing declining response rates and challenges with collecting quality data, largely due to proxy bias and poor survey designs. This study investigates methods to improve HTS data quality and reduce response burden by sharing lessons learned from the development of the TRAISI web survey builder. The study presents findings from field tests using novel features built into the platform, such as interactive maps and adaptive designs for household trip diary collection. Survey methods to reduce proxy bias, such as voluntary self and proxy reporting methods and announce-in-advance procedures, are also investigated. Overall, the study provides survey designers guidelines and recommendations for web-based HTS design.

Keywords: Household Travel Surveys
Proxy Bias
Respondent Burden
Trip Diary
Usability Testing
Web-survey
Advisor: Habib, Khandker M.N.
Miller, Eric J.
Developing Dispossession: Infrastructure, Cultural Production and Legal Discourse in Treaty 3

This thesis examines how dispossession was produced for Anishinaabeg communities of Treaty 3 through interlocking processes of legal discourse, cultural production and development. It traces the genealogical origins of infrastructure through a series of dams built across Northwestern Ontario from 1871 until 1926. In Treaty 3, the discursive foundations for infrastructure and development were laid through a series of expeditions and legal decisions that justified and facilitated settler expansion. Likewise, development involved a set of mutually constitutive and reciprocal forms of epistemic, ontological, symbolic and material violence. In this work, I argue that dispossession is structural to settler colonialism and the defining feature which ties a set of seemingly disparate histories and processes together in Treaty 3. Recognizing gaps in the literature and colonial archive, I call for the development of new practices of inquiry that allow us to provincialize and unsettle the normativity of colonial violence and narratives.

Advisor: Farish, Matt
Ekers, Michael
A (M)other Talks to White Women Teachers: A Critical Autoethnography

Using critical autoethnography, I explore relationships between White women teachers and Mothers of Colour. Looking beyond a parent involvement analysis framework, I use a decolonial prism that considers colonial constructions of White Womanhood and Motherhood as critical in the mother-teacher relationship and the marginalization of Black, Indigenous, and Brown mothers in Euro-Canadian school settings. I argue that the intersecting forces of identities formulated within empire (i.e., woman, mother, teacher) multiply their oppressive potential. The antagonism that develops between the Woman-Mother-Teacher and Mothers of Colour precludes the establishment of honest, cohesive, and supportive relations, which results in harmful consequences for students of colour, their families, and their communities.

Keywords: Anti-racist
Decolonial
Feminism
Parent engagement
White women teachers
Advisor: Dei, George S.
Gaussian Process Modeling and Supervised Dimensionality Reduction Algorithms via Stiefel Manifold Learning

Much research has gone into scaling up classical machine learning algorithms such as Gaussian Processes (GPs), but the curse of dimensionality still remains. While many supervised dimensionality reduction algorithms have been proposed in the literature, few of them can scale up to large data-sets. Furthermore, the majority of dimensionality reduction techniques are tailored for classication problems, which leaves regression tasks unexplored. The contributions of this thesis are threefold. First, we extend classical active subspace (AS) theory to a non-linear counterpart. Secondly, we introduce a scalable non linear supervised principal component analysis (SPCA) algorithm. Thirdly, we propose a novel class of supervised dimensionality reduction algorithms called smoothening analysis (SA). The SA algorithms consist of scalable linear and non-linear frequentist and Bayesian algorithms tailored (but not limited) for regression tasks that learn low dimensional Stiefel manifolds.

Keywords: Active Subspaces
Dimensionality Reduction
Gaussian Process
Machine Learning
Principal Component Analysis
Random Fourier Features
Advisor: Nair, Prasanth B.