VictorJuiz/thesis huggingface dataset:
Sequence and Structure Specificities of RNA-binding C2H2 Zinc Finger Proteins through In vivo Crosslinking and Computational Analysis

Cys2His2 Zinc Finger Proteins (C2H2ZFPs) comprise the largest yet least characterized class of human proteins and play important roles in transcriptional regulation through their ability to bind DNA via modular zinc-stabilized domains. Recent evidence of widespread RNA binding functionality has prompted a systematic capture of C2H2ZFP-RNA interactions in vivo by our lab to establish a novel RNA interactome map for human C2H2ZFPs. Through compilation and analysis of in vivo iCLIP-seq and RNA structure data, I have characterized the sequence and structural RNA-binding specificities for a comprehensive C2H2ZFP cohort. My analyses reveal C2H2ZFPs exhibit sequence specificity and preference for local nucleotide accessibility in otherwise structured RNA targets. Additionally, structural prediction of C2H2ZFP-bound RNAs identified widespread and compatible binding to short RNA hairpin structures. This investigation into C2H2ZP-RNA interactions demonstrates that RNA sequence and structure influence target specificity, providing valuable insight into the co and post-transcriptional regulatory functions of the C2H2ZFP family.

Keywords: Molecular Genetics
RNA Binding Proteins
Zinc Finger Proteins
Advisor: Greenblatt, Jack
Zhang, Zhaolei
Examining Active Learning Pedagogy and Praxis in In-service Teachers and Teacher Educators

Active learning is recognized to be superior to teacher-centered educational praxis. However, the education of teachers in active learning is hampered by its broad definition and teachers' resistances to change. First, as exemplars, this thesis will present the active learning praxis of two high school teachers. This presentation is provided as an inductive thematic analysis of the teachers' interviews. Next, using a deductive analysis, the examination of governance documents from various sources is provided. This analysis seeks to determine if these documents support active learning praxis in schools. Finally, using an inductive thematic analysis of interviews, the thesis explores the instructional behaviors of four teacher educators at OISE. These analyses are afforded through the lenses of Chi's Ontological Commitments (1994), Engeström's Activity Theory (2014), Chi and Wylie's ICAP Framework (2014), and Bloom's Taxonomy (1956). Resistances to active learning praxis are examined and suggested changes to teacher education at OISE are explored.

Keywords: Active Learing
Activity Systems
High School Science
ICAP
Ontological Commitments
Teacher Resistance to Change
Advisor: Slotta, Jim
Montemurro, David
Exploring the Connections between Linguistic Inference and Linguistic Perspective Taking

Linguistic inference and linguistic perspective taking are two aspects of cognition that both involve the ability to identify and draw on information not explicitly provided in text or speech, in turn contributing to the successful comprehension of communicated information. There are abundant scientific literature investigating linguistic inference and linguistic perspective taking separately which often use an individual differences approach to assess the links between these abilities and general aspects of cognition. However, no study to date has directly explored the possible relationship (or lack thereof) between linguistic inference and linguistic perspective taking, which would provide important evidence about the basis of these abilities. The current thesis measured individual differences in linguistic inference and linguistic perspective taking simultaneously in an integrated reading paradigm. Results showed that linguistic inference and linguistic perspective taking, as measured in the current paradigm, were not related. Interpretations and theoretical implications are discussed.

Keywords: cognition
communicative competence
experimental
inference
language
perspective taking
Advisor: Chambers, Craig
The Association Between Age and Household Food Insecurity in Canada

While there have been several studies documenting the lower risk of food insecurity among seniors, little is known about how food insecurity relates to age among Canadians under 65. This thesis aimed to i) determine how food insecurity varies by age group; and ii) characterize the association between sociodemographic characteristics and food insecurity among adolescents. Using data from the 2017-18 Canadian Community Health Survey, logistic regression analyses were conducted, adjusting for sociodemographic characteristics. Adolescents and middle-aged adults had higher odds of food insecurity than 55- to 64-year-olds, whereas seniors had lower odds. Income, homeownership and living arrangement were differently associated with food insecurity. Among adolescents, lower household income, renting, social assistance receipt, Black and Indigenous identity, single parenthood and more children were associated with moderate-severe food insecurity. Given the negative health implications of food insecurity, the elevated risk among adolescents indicates the need for policies that better protect them.

Advisor: Tarasuk, Valerie
Introducing a New Performance Metric to Quantify the Risk of Exposure to Infection Using Electronic Monitoring Systems

Healthcare-acquired infections (HAIs) are infections that were not present or incubating at the time of patient admission and are contracted during the process of care. These infections contribute to significant morbidity and mortality each year. Hand Hygiene (HH) is one of the most effective ways to prevent HAIs. The measures used to calculate and report HH performance are not able to fully benefit from the high-resolution data collected by electronic monitoring systems. This work leverages the advancement of intelligent systems to bridge the gap between HH reports and the risk of acquiring infections for patients. This thesis introduces a metric for estimating the risk of exposure to infections for patients in healthcare settings using the existing electronic monitoring systems. The proposed metric can be used to measure the risk of infection for healthcare workers who are at a high risk of infection.

Keywords: activity recognition
hand hygiene
healthcare-acquired infections
indoor localization
Advisor: Roshan Fekr, Atena
Fernie, Geoff
Knowledge Building with Low Proficiency English Language Learners: Facilitating Metalinguistic Awareness and Scientific Understanding in Parallel

Two studies were conducted to explore theoretical, pedagogical, and technological issues for advancing language/literacy and scientific understanding in parallel in knowledge building communities. Findings from the initial analysis of student change over 5-years indicated a possible cumulative gap between lexically, orthographically, and conceptually high and low achieving students. A pilot study was conducted subsequently with two Japanese children (grade 4 and 7), both having limited English language proficiency. The goal was to explore the possibility of deepening language and subject knowledge through pedagogical and technological supports. The two children wrote in English in Knowledge Forum®, technology designed to support Knowledge Building, with support from translator and specially designed dictionary. Results revealed student use of translators as a “theory-testing tool,” enabling them to experiment with Japanese and English versions of their ideas and texts. The study informed design possibilities for future work to advance linguistic and subject matter understanding in parallel.

Keywords: English Language Learner
Knowledge Building
Metalinguistic Awareness
Scientific Understanding
Advisor: Scardamalia , Marlene
Adsorption of Polycyclic Aromatic Hydrocarbons by Polyethylene Microplastics in Freshwaters

Microplastics (MPs), which are ubiquitous in the environment, have been shown to adsorb organic contaminants of concern including polycyclic aromatic hydrocarbons (PAHs). Any MPs which are not removed via drinking water treatment may enter the human body via consumption and act as vectors for PAHs. In this thesis sorption trials were conducted using both artificial and real water matrices along with two different sizes (200 µm and 1090 µm) of virgin and weathered polyethylene (PE) microspheres. This experimental design allowed direct comparison of the impacts of natural waters and weathering on sorption capacity. Of the factors examined, size and surface area, and hydrophobicity, with respect to both the polymer and PAHs were identified as most critical. Overall, results of this study provide insight into the sorption behavior of microplastics in freshwater environments and their potential to adsorb organic contaminants.

Advisor: Andrews, Robert C.
The Roles of Transcription Factors (TF)EB and E3 in the Host Defense Against Invading Bacterial Pathogens: Novel Insights into Bacterial Recognition and the Transcriptional Induction of the Anti-bacterial Response in Non-immune Cells

Upon pathogen infection, innate signaling cascades are induced to initiate the transcription of immune effectors. Transcription factors (TF) EB and E3, master regulators of lysosomal biogenesis and autophagy, were recently found to be novel regulators of innate immunity in both C. elegans and mammals. Despite TFEB and TFE3 participating in pathogen recognition and the transcriptional response to infection, little is known about their roles in the infected epithelium. In this thesis we demonstrate that TFEB and TFE3 are activated in non-immune cells upon infection with bacterial pathogens and their ligands by both mTORC1-dependent and -independent mechanisms. Additionally, we characterize a novel mechanism of bacterial recognition dependent on membrane damage, amino acid starvation, mTORC1 inactivation and TFEB nuclear import. Finally, we present data suggesting that although TFEB does not affect bacterial killing or load, it alters the host transcriptome upon infection thus promoting the transcription of cytoprotective and antimicrobial genes.

Keywords: Host-Pathogen Relationship
Infection
Innate Immunity
TFEB
Advisor: Girardin, Stephen
Neural Correlates of Visual Stimulus Encoding and Verbal Working Memory Differ between Cochlear Implant users and Normal-hearing Controls

A common concern for individuals with severe-to-profound hearing loss fitted with cochlear implants (CIs) is difficulty following conversations in noisy environments. Recent work has suggested that these difficulties are related to individual differences in verbal working memory and the degree of cross-modal reorganization of auditory areas for visual processing. However, the neural basis for these relationships is not fully understood. Here, we investigated neural correlates of visual-verbal working memory and sensory plasticity in 14 CI users and age-matched normal-hearing (NH) controls using high-density electroencephalogram (EEG). Participants completed a modified Sternberg visual working memory task where results suggested that CI users had comparable behavioral working memory performance compared to NH. However, CI users had more pronounced neural activity during visual stimulus encoding, including stronger visual-evoked activity in auditory and visual cortices, larger modulations of neural oscillations, and increased frontotemporal connectivity. In contrast, during memory retention of the characters, CI users had descriptively weaker neural oscillations and significantly lower frontal-temporal connectivity. We interpret the differences in neural correlates of visual stimulus processing in CI users through the lens of cross-modal and intra-modal plasticity.

Keywords: Cochlear Implant
Cogntion
Connectivity
Hearing Loss
Neural Oscillations
Speech Perception
Advisor: Dimitrijevic, Andrew
The Effect of Repetitive Transcranial Magnetic Stimulation on Suicidality in Patients with Treatment Resistant Depression

Objective: To investigate the effect of 10Hz repetitive transcranial magnetic stimulation (rTMS) and intermittent theta-burst stimulation (iTBS) on suicidality in patients with treatment resistant depression (TRD).Methods: Data from a three-site randomized clinical trial comparing 10Hz and iTBS rTMS applied to the left dorsolateral prefrontal cortex in patients with TRD was analyzed. The effect of 10Hz rTMS and iTBS on suicidality was compared as measured by the suicide item of the Hamilton Depression Rating Scale 17-item (HDRS-17). Results: Suicidality remitted in 71 (43.7%) of participants randomized to 10Hz stimulation and 91 (49.1%) of participants randomized to iTBS. The difference between the proportions in the two groups (X2 = 0.674, df = 1, p = 0.4117) was not significant. Conclusions: Both 10Hz and iTBS rTMS were effective in reducing suicidality in TRD. Further investigation into the effect of rTMS on suicidality is warranted.

Keywords: Brain stimulation
Depression
Repetitive transcranial magnetic stimulation
Suicidality
Advisor: Blumberger, Daniel M.
Enhancement of a HSP90 Inhibitor through Development of Thermosensitive Liposomes and in vitro Combinations

The heat shock protein 90 inhibitor, luminespib, has demonstrated potent preclinical activity against numerous cancers, yet clinical translation has been unsuccessful due to dose-limiting toxicities. Thermosensitive liposomes are proposed as a drug delivery strategy capable of delivering high concentrations of luminespib to the tumor in combination with other chemotherapeutic molecules. This work establishes that luminespib exhibits synergistic activity in lung cancer in combination with standard of care drugs, cisplatin and vinorelbine. While thermosensitive liposomes containing cisplatin or vinorelbine have previously been developed, this work presents the first liposomal formulation of luminespib. The physicochemical properties and heat-triggered release of the formulation were characterized. Cytotoxicity assays were used to determine the optimal drug ratios for treatment of luminespib in combination with cisplatin or vinorelbine in non-small cell lung cancer cells. The formulation and drug combination work presented offer the potential for resuscitation of the clinical prospects of a promising anticancer agent.

Keywords: combination chemotherapy
heat shock protein 90 inhibitors
luminespib
nanomedicine
non-small cell lung cancer
thermosensitive liposomes
Advisor: Allen, Christine
Exploring Genetic and Metabolic Factors of Neisseria gonorrhoeae using Genomic Datasets

Neisseria gonorrhoeae has evolved a suite of factors that allow it to survive in the various niches of the human host, from the genital mucosa to the bloodstream. In this thesis, I use genomic datasets to investigate the genetic factors that allow N. gonorrhoeae to persist in diﬀerent host niches. Whole genome sequences of N. gonorrhoeae isolates from Canada are used to identify genomic features associated with disseminated gonococcal infection, where I identify the porBa allele and other genes as important factors. Next, I use metatranscriptomic datasets of male and female genital tracts with gonorrhea to investigate the gene expression of the microbiota, N. gonorrhoeae and the host. Here, I identify diﬀerences in metabolic expression between N. gonorrhoeae and the microbiota of female subjects with bacterial vaginosis. These analyses contribute to a more complete understanding of the lifestyle of N. gonorrhoeae and its interactions with the host and the microbiota.

Keywords: Disseminated gonococcal infection
Gonorrhea
Metatranscriptomics
Microbiome
Neisseria gonorrhoeae
Population genomics
Advisor: Parkinson, John
Gray-Owen, Scott
Thermal Pulse Induced by Emplacement of Ramba Leucogranites in Southern Tibet

The thermal histories of Himalayan leucogranites provide critical information of the post-collisional geodynamics. The Ramba Dome is located at the intersection of the Tethyan Himalaya leucogranite belt and Yadong-Gulu Rift, hosts the youngest endmembers of Himalayan leucogranites (8 Ma, Liu et al., 2014) and provides a good opportunity to constrain the thermal history of the aureole. In the first part of this study, we focus on the carbonaceous staurolite schist at ~1.3 km from the intrusion. Our results from the phase equilibria modeling and the RSCM thermometer indicate a consistent peak metamorphic condition of 550 °C, 3.5-4 kbar. The garnet core composition yields a P-T condition 525 °C, 2.5-3 kbar, with a overstep of ~45 °C corresponds to a 5 kJ/mol (12 O) chemical affinity of garnet nucleation. The sharp dendritic zoning of the garnet core suggests that the duration of the thermal pulse was within 1.4 m.y. In the second part, we focus on the 8 Ma garnet leucogranite dykes, to test the hypothesis of rapid transportation and emplacement of the leucogranitic magma. The diffusion modeling on garnet yields a short timescale of transportation and emplacement (0.25 Ma) which indicates that the transport from the depth of garnet incorporation in leucogranite magma to the final crystallization level was fast. The rapid cooling of the Ramba Dome marked the cessation of Himalayan leucogranite magmatism, which reflects the termination of deep heat source.

Keywords: Contact aureole
Diffusion
Garnet
Himalayan leucogranites
Ramba Dome
RSCM
Advisor: Chu, Xu
A The Sustainability of Moving towards Healthy Plant-based Dietary Patterns

A synthesis of the literature on diet-related environmental impacts is needed. We therefore conducted a scoping review to assess the environmental impacts of moving towards plant-based diets. We concluded that shifting toward more plant-based diets can reduce diet-related greenhouse gas emissions (GHGE), land use, water use, energy use, and biodiversity impacts. However, there is a lack of assessment of therapeutic plant-based diet patterns and their human environmental impacts, particularly in real-life settings. Therefore, a randomized controlled trial was analyzed to determine the difference in GHGE between a more plant-based dietary pattern, the Portfolio diet, and the Dietary Approaches to Stop Hypertension (DASH). This is the first study to demonstrate how reductions in diet-related GHGE and some cardiometabolic risk factors can be achieved through well-planned therapeutic diets, using past clinical trials. Future research should analyze the many human health and environmental effects of moving towards more plant-based diets in real-life settings.

Keywords: environmental footprint
greenhouse gas emissions
plant-based diets
sustainability
sustainable diets
therapeutic diets
Advisor: Jenkins, David
A Vote of Conscience: Investigating the Early Development of Guilt and Shame in an Online Context

In the second year of life, children begin to respond to transgressions with guilt-motivated reparative behaviour or shame-motivated avoidance. Yet, questions remain regarding when and whether guilt and shame are separable, whether the way guilt and shame are measured may lead to different response patterns, and the mechanism underlying reparative responses. Here, 24 two- year-olds’ guilt and shame were assessed through a virtual experimental task, a parent-report questionnaire, and a parent interview question; we hypothesized that other-orientation (measured through children’s memory for the experimenter’s appearance) would predict their reparative behaviour. None of our measures were reliable in distinguishing guilt-specific responses from shameful behaviours and few relations were found across tasks, but admissions of guilt on the paradigm were linked to admissions of guilt on the questionnaire. Other-orientation was found to be unrelated to both guilt and shame across all measures. Implications for future research on early self-conscious emotional expressions are discussed.

Keywords: Children
Guilt
Other-Orientation
Reparation
Self-conscious Emotions
Shame
Advisor: Sommerville, Jessica
The Institutionalization of New Equity, Diversity, and Inclusion Positions and Practices in Ontario Student Affairs and Services

This study investigated the emergence of new equity, diversity, and inclusion (EDI) positions developed in student affairs and services divisions at universities in Ontario, Canada. Most Canadian universities now espouse the values of EDI, though identifying and addressing persistent systemic barriers experienced by undergraduate students from equity-deserving groups has received limited attention. Based on semi-structured interviews with seven student affairs and services staff and directors from three universities, the multiple case study analysis reveals the institutional conditions and factors contributing to staff and student agency that facilitated the development of new EDI-focused positions and practices. The results of this study highlight the importance of understanding and responding to changes in the institutional environment as a critical factor in motivating change to systemic inequities within Canadian universities.

Keywords: Equity
diversity
and inclusion
Higher education
Student affairs and services
Advisor: Childs, Ruth
A Study on Water Recovery from Industrial Effluents via Forward Osmosis

Water removal from aqueous effluents in the mining and metals processing industry poses a unique challenge due to the high concentration of dissolved ions. Forward Osmosis (FO) is a membrane technology, which employs a concentrated draw solution to osmotically draw water through a semi-permeable membrane, that can operate on high dissolved ion feeds. FO operation relies on using a draw solution of higher osmotic pressure to extract water while managing concentration polarization which limits the water flux of the membrane. This investigation evaluated how flow rates, draw salt type and membrane orientation impact FO performance on solvent extraction raffinate and mine water effluent samples under osmotic gradient equivalent scenarios for a flat-sheet commercial FO membrane. The type of feed, osmotic gradient and flow rate were found to have the largest impact on water flux while only the feed type impacted the separation efficacy of the FO membrane.

Keywords: forward osmosis
membranes
mining
water
Advisor: Papangelakis, Vladimiros
Two-phase Design for Regional Genetic Sequencing using Polygenic Risk Scores

Due to the high cost of DNA sequencing for large-scale data, I propose a two-phase design using polygenic risk scores (PRS) to inform selection of individuals in phase 1, followed by regional sequencing in a selected subsample in phase 2. Residual dependent sampling (RDS) design is implemented by regressing the phenotype of interest on the PRS and selecting individuals with extreme residuals as the phase 2 subsample. Efficient analysis can be carried out under semi-parametric modelling by the EM algorithm. A fine-mapping application in a genome-wide association study (GWAS) of triglyceride levels in 4, 504 individuals from the Northern Finland Birth Cohort of 1966 shows the proposed method can reduce sequencing costs in post-GWAS analyses while maintaining statistical performance. Simulation studies show that the proposed RDS design gives more precise estimation than simple random sampling, with adequate type one error control, while performing more similarly to the complete sample.

Advisor: Bull, Shelley B
Espin-Garcia, Osvaldo
Affective Encounters and Activist Subjectivities

In this thesis, I explore the ways in which notions of activism can be extended by a closer attention to affect from a relational-ontological perspective. Through an autoethnographic study of my own experiences with various forms of activism, I analyze the ways in which different affects emerging from processes of activism may have an impact on activist journeys and subjectivities. Analyzing the affective state of hopelessness or alienation that is often classified as activist burnout, I explore the openings it may present for transformation of self and work. Describing my own ways of addressing such “feelings out of place,” I point to the role of shifting notions of efficacy, time, and belonging in building “infrastructures of response-ability” that are dynamic and attentive to the rewards and strains of activism.

Keywords: Activism
Affect
Autoethnography
Burnout
Relational ontology
Subjectivity
Advisor: Singh, Neera