VictorJuiz/thesis huggingface dataset:
The Three I's of Diabetes Integration in Emerging Adulthood: Developing a Framework to Individualize Diabetes Care

Transition to adult diabetes care occurs during a challenging stage of life known as emerging adulthood. As emerging adults are tasked with increased responsibility for diabetes management, they are faced with competing demands in work and education. This study employed a narrative approach to elucidate the lived experiences of emerging adults with Type 1 diabetes. In-depth interviews were performed with 33 participants (18 to 24 years of age). Narrative analysis defined story typology and themes across first-hand accounts. Participants narrated life with diabetes through one of three ‘lenses’: ingrained (n=14), intrusive (n=12) and inconspicuous (n=7). Participants conveying an ingrained lens described actively integrating diabetes within their lives. Through an intrusive lens, participants described struggles trying to accept diabetes and striving for control. Participants conveying an inconspicuous lens expressed a desire to minimize attention towards diabetes to protect their normalcy. This conceptual framework presents opportunities to individualize support accordingly.

Keywords: Emerging adulthood
Health care transition
Narrative research
Self-management
Type 1 diabetes
Advisor: Advani, Andrew
Parsons, Janet A
Microrobots with Programmable Three-dimensional Magnetizations and Motions

Flexible magnetic small-scale robots use patterned magnetization to achieve fast transformation into complex three-dimensional shapes, and thereby achieve locomotion capabilities and functions. These capabilities address current challenges for microrobots such as drug delivery, object manipulation, and minimally invasive procedures. However, possible design options are limited by the existing capabilities of patterning magnetic particles in flexible materials. Here, we report a method for patterning hard magnetic microparticles in an elastomer matrix. This method, based on UV-lithography, uses controlled reorientation of magnetic particles and selective exposure to UV light to encode magnetic particles in planar materials with arbitrary orientation with a geometrical feature size as small as 100 µm. The patterned 3D magnetization profile allows higher-order and multi-axis bending, large-angle bending, and combined bending and torsion in one sheet of polymer, creating previously unachievable shape changes and micro-robotic locomotion mechanisms such as multi-arm power grasping and multi-legged crawling.

Keywords: magnetic materials
magnetization patterning
microrobots
programmable morphology
soft actuators
Advisor: Diller, Eric
Exploring nSR100/SRRM4 as a Therapeutic Target for Autism Spectrum Disorder in Mice

Misregulation of nSR100 and its target microexons are common in a large proportion of ASD patients and cause ASD-associated features in mice. This thesis explores nSR100 and its target splicing program as a potential therapeutic target using a conditional knockout allele, nSR100GT. I show that nSR100 protein is effectively depleted in the cortical regions of nSR100GT mutant mice at E17.5, E18.5, and P2 stages, which correlates with phenotypes overlapping with all core behavioral domains of ASD. I show that tamoxifen-mediated rescue in prenatal nSR100GT animals restores nSR100 protein and microexon inclusion levels comparable to those observed in wildtype mice. Collectively my thesis research shows that the nSR100GT mouse strain holds the promise for examining phenotypic effects of nSR100 reactivation in ASD-like mice at different developmental stages, and complimentary models are also to be considered for investigating the therapeutic potential of targeting nSR100 in the context of ASD.

Advisor: Blencowe, Benjamin
Cordes, Sabine
Differential Regulation of Cx43 Expression and Gap Junction Formation by Progesterone Receptor A and B in Breast Cancer Cells

Progesterone (P4) imparts distinct effects in the breast via its progesterone receptors (PRs) PRA and PRB. Since the gap junction and tumour suppressor protein Connexin 43 (Cx43) is differentially regulated by P4 via PRA/B in human myometrial cells, we sought to delineate the roles of PRA/B on Cx43 in breast cancer cells. We hypothesize that, similar to myometrial cells, the two PRs differentially affect Cx43 expression, trafficking, and gap junction intercellular communication (GJIC) in breast cancer cells. In this project, I have shown that in the luminal A cell line MCF7, PRA promotes Cx43 expression, trafficking (similarly observed in the cell line MFM223), and GJIC whereas PRB inhibits these processes. Conversely, in the basal-like cell line MDA-MB-231, P4 inhibits Cx43 expression, intracellular trafficking, and GJIC through both PRs. These data provide insight as to how PRs differentially regulate the same gene, Cx43, in contrasting in vitro models of breast cancer.

Keywords: Breast Cancer
CRISPR
Cx43
in vitro
Progesterone
Advisor: Lye, Stephen J
Soil-atmosphere Exchange of Ammonia in a Fertilized Corn Field

The dominant source of ammonia to the atmosphere today is agriculture. Urea is commonly used as fertilizer in crop production; after application, it undergoes hydrolysis and produces ammonia in soil. The exchange of ammonia between the soil and atmosphere is thought to be driven by a difference between the atmospheric concentration and the compensation point, the atmospheric amount that would be in equilibrium with the underlaying soil. The objective of this project was to characterize the soil chemical properties and temperature to calculate the emission potential ([NH4+]/[H+]) and compensation point of the soil and to measure the soil-atmosphere ammonia flux directly. Soil and air samples were collected in Ottawa, ON over the growing seasons in 2017 and 2018. Emission potentials ranged from 20 to 4432 and the corresponding compensation points were in the range of 0.1 to 47.4 ppbv. Significant NH3 fluxes were only detected shortly after fertilization application in 2017.

Advisor: Murphy, Jennifer G
Engineering Ca2+-activated Control of Ras Family GTPases

Reprogrammed cells are capable of sensing specified biomarkers for targeting disease sites. My work aims to rewire mammalian cells to use Ca2+ signaling to respond to a broad spectrum of stimuli. Previously, a Ca2+-CaM system replaced the GTP/GDP switch in Rho-GTPases such that increased intracellular Ca2+ leads to protein activation. This work applied the same strategy to a Rab and Ras GTPase, Rab5 and Ras, respectively. Ca2+-activated Rab5 (called Raber) induces cell retraction, whereas, Ca2+-activated Ras (called Raser) induces focus formation. To demonstrate rewiring potential to Ca2+ mobilizing proteins, Raber and Raser were co-expressed with either ChR2 or VEGFR2 to indirectly activate them with light and VEGF, respectively. This work demonstrates the potential for these proteins to be activated by any external stimuli via Ca2+ rewiring. In regards to cell-based therapies, Raber can enable cellular detachment, encouraging migration, whereas Raser can enable cells to form foci, accumulating at target sites.

Keywords: calcium signaling
cell-based therapies
cellular reprogramming
genetics
protein
ras
Advisor: Truong, Kevin
Examining the Relations among Autobiographical Memory Recall Types, Quality of Descriptions, and Emotional Arousal

Recalling specific or episodic (rather than generic) memories and using descriptive language in psychotherapy sessions have been shown to be two ways of enhancing clients’ emotional arousal. This study’s aim was to test the relationships among depressed clients’ types of memory recall, quality of language, and emotional arousal in psychotherapy. As predicted, correlation analyses revealed a positive relationship between clients’ quality of language and emotional arousal and a negative relationship between clients’ pre-therapy level of depression and proportion of their specific memory recalls. However, contrary to the prediction, pairwise comparisons revealed that recalls of generic memories were significantly higher in their ratings of emotional arousal than recalls of specific memories, and clients’ post-therapy levels of depression were unrelated to both their in-session levels of emotional arousal and quality of descriptions. These findings hold theoretical and clinical implications for understanding the relationships among types of memory recall, quality of language, and emotional arousal in the context of psychotherapy for depression.

Keywords: Autobiographical Memory Recall
Depression
Emotional Arousal
Psychotherapy
Quality of Descriptions
Advisor: Watson, Jeanne C
Evaluating the Clinical Utility of Long Non-coding RNAs as Prognostic Biomarkers in Cancer

Cancer patient risk stratification remains a significant challenge in the clinic. Molecular profiles of protein-coding genes have showed limited clinical utility as diagnostic or prognostic biomarkers. Long non-coding RNAs (lncRNAs) are increasingly associated with diverse cellular functions and disease mechanisms and their expression is often dysregulated in cancer. Thus, a systematic analysis of lncRNA expression in cancer is likely to lead to clinically relevant and biological insights. Here, we evaluated the expression of 5,785 lncRNAs in relation to overall patient survival across 28 cancer types and 8,454 patients. We implemented regularized survival models and cross-validation to identify the most representative lncRNA candidates. We compiled a catalogue of 166 unique lncRNAs across 22 cancer types and summarized their survival prediction performance relative to nearby protein-coding genes and previously defined prognostic features. We highlighted several high-confidence candidates with potential prognostic value and further predicted the molecular processes they may be involved in.

Keywords: Cancer
lncRNA
Prognostic
RNA
Survival
Advisor: Reimand, Juri
How Can Researchers and Research Users Initiate Integrated Knowledge Translation (IKT) Partnerships?

Integrated knowledge translation (IKT) describes researcher and research user partnerships formed with the long-term goal to increase knowledge uptake. Research shows that processes for initiating IKT partnerships are still developing and initiation remains challenging. The purpose of this thesis was to explore IKT partnership initiation to understand and provide guidance on how to optimize the process. Phase 1, a meta-narrative review of the literature guided by RAMESES reporting standards, described how IKT initiation was undertaken by others. Phase 2, semi-structured interviews guided by the COREQ checklist, explored IKT initiation processes, enablers, and barriers. Six narratives describing IKT initiation were identified from the literature: IKT, action research, stakeholder engagement, knowledge transfer, team initiation and shared mental models. Twenty-two Canadian experts in IKT were interviewed. Data from the two phases were blended to create a summary of inputs, processes, influencing factors and outputs of IKT initiation. Practice and research implications were suggested.

Keywords: Health services research
Integrated knowledge translation
Advisor: Gagliardi, Anna R
Polypyrrole-Chitosan Hydrogel Functions as a Semi-conductive Bridge Within Fibrotic Matrix and Cardiac Tissue

Myocardial infarction(MI) results in myocardial fibrosis leading to cardiac arrhythmia. We previously developed conductive biomaterial, polypyrrole-chitosan(PPY:CHI), which can prevent arrhythmias after MI. However, mechanism is unknown. I hypothesized that PPY:CHI reduces myocardial fibrotic tissue(FT) resistance to enhance myocardial conduction. To investigate electrical improvements of FT, PPY:CHI was added into Invitro and Ex-vivo FT matrix models. Three studies were performed to evaluate effect of PPY:CHI on fibrotic matrix, 1)impedance analysis using impedance spectroscopy; 2)electrical potential analysis using multi-electrode arrays(MEA), and 3)conduction velocity analysis using MEA. The research results showed 1)PPY:CHI reduced the impedance of the FT to a level like healthy myocardium; 2)PPY:CHI influenced the FT to transmit field potentials to a level like healthy myocardium; and 3)PPY:CHI influenced the FT to generate a velocity to a level like healthy myocardium. Addition of PPY:CHI to the FT models improved electrical conduction and transferred electrical potentials at a distance.

Keywords: Arrhythmia
Biomaterials
Electrophysiology
Myocardial Infarction
Tissue Engineering
Advisor: Li, Ren-Ke
Amorphous Ni-Nb-Y Alloys as Hydrogen Evolution Electrocatalysts

The recent development of anion exchange membranes (AEMs) has renewed interest in alkaline water electrolysis as a means of converting renewable energy to storable H2. New electrocatalysts are required to integrate with such AEMs in advanced electrolysers. Ni-based amorphous alloys are of interest as hydrogen evolution electrocatalysts due to high intrinsic activity. In this work, Ni-Nb-Y amorphous alloys were evaluated as electrocatalysts. A thermodynamic model of the Ni-Nb-Y system was developed guiding the ternary alloy design while X-ray diffraction and electron microscopy characterized the microstructure of mechanically alloyed powder. A novel two-step ball milling process was developed to synthesize high surface area amorphous and amorphous-nanocrystalline nanoparticles. Lower Tafel slopes and higher exchange current densities identified enhanced intrinsic activity for the amorphous Ni-Nb-Y alloys compared to crystalline Ni and Ni5Y. These results demonstrate that combining cryomilling and surfactant-assisted ball milling of Ni-based amorphous alloys yielded promising catalysts for electrochemical hydrogen production.

Advisor: Thorpe, Steven J
Kirk, Donald W
Accumulating Multimorbidity: the Role of Depression, Socioeconomic Status, and Other Factors

Multimorbidity is a significant challenge facing patients, clinicians, and the healthcare system. This study examines whether depression and socioeconomic status are associated with incident physical illness and multimorbidity, after controlling for potential sociodemographic, behavioural, and clinical confounders. This is a longitudinal retrospective cohort study. Cohorts were derived by linking adult respondents to three population health surveys to health administrative databases in Ontario and were followed for ten years. Cox proportional hazards regression was used to examine the rate at which participants developed illnesses, and Poisson regression was used to examine the number of conditions developed after ten years. In this study, depression increased the risk of accumulating multimorbidity, in terms of both time to development of conditions and number of conditions accumulated after ten years. Higher household incomes were protective against developing a second and subsequent physical illness, but not the first incident illness in a disease-free cohort.

Keywords: depression
multimorbidity
socioeconomic status
Advisor: Wodchis, Walter P
Predicting Designer Performance in Generating Reuse Concepts for Retired Wind-Turbine Blades by Measuring Individual Differences

This work examines identifying reuses for wind-turbine blades that are retired when they reach the end of their technical life. Wind-turbine blades are made from fiber-composite materials, for which effective material-based recycling technologies are extremely limited. An approach to avoid or postpone recycling is to repurpose wind-turbine blades in other applications, as they should not be reused as wind-turbine blades for safety reasons. However, identifying promising reuses for wind-turbine blades is challenging due to their specific shape properties. In addition to issues of functional fixedness, wind-turbine blades are physically much larger than everyday objects with which people typically reason. Following a series of studies where students were asked to identify wind-turbine-blade reuses, a method involving perspective-taking was developed and applied. To better understand and motivate human designers, this work also incorporates psychological concepts, including Need for Closure, Regulatory Focus Theory, and Regulatory Mode Theory.

Keywords: Component reuse
Concept generation
Functional fixedness
Regulatory mode theory
Sustainability
Wind-turbine blades
Advisor: Shu, Lily H
Prefrontal Cortex Activity during Dual Task Performance in Patients with Chronic Obstructive Pulmonary Disease

The purpose of this study was to compare changes in dorsolateral prefrontal cortex (DLPFC) oxygenated hemoglobin (ΔO2Hb), accuracy of backwards spelling, and decrements in gait velocity during single and dual tasks in patients with COPD (n=8), and healthy younger (n=20) and older adults (n=20). Participants performed: (1) backwards spelling cognitive task (CT); (2) preferred paced walk (PPW); and (3) fast paced walk (FPW). The dual tasks then paired CT with PPW and FPW. In older adults, ΔO2Hb was significantly higher in left DLPFC compared to patients with COPD and bilaterally compared to younger adults during FPW+CT versus FPW. Furthermore, older and younger adults exhibited higher decrements of velocity during FPW+CT compared to PPW+CT. CT accuracy tended to be lower in older adults. Decrements in performance during dual tasking highlight the impact of increased cognitive load and need of cognitive-motor interventions to improve cognition and physical function.

Keywords: Aging
Chronic Obstructive Pulmonary Disease
Cognition
Gait
Near-Infrared Spectroscopy
Prefrontal Cortex
Advisor: Reid, W. Darlene
A Population-based Study of Individuals with Schizophrenia and Correctional Involvement

The purpose of this study was to describe characteristics of individuals with and without schizophrenia within a Canadian correctional population. This cohort study included 46,928 individuals who were released from Ontario’s provincial correctional facilities from January 1 to December 31, 2010. Survival analysis was used to examine how schizophrenia, incarceration, comorbidity and healthcare utilization were associated with recidivism in this cohort; each of these variables showed a decrease in the risk rate of recidivism. The study results show that the schizophrenia prevalence within this cohort was 7%. Approximately 67.5% of schizophrenic individuals were reincarcerated within five years following the index incarceration, compared to 58.8% of individuals without schizophrenia. Individuals with schizophrenia were 40% (aHR: 1.39) more likely to have a reincarceration event following release than the comparative group. Descriptively, individuals with schizophrenia experienced a higher number of correctional events and higher rates of healthcare utilization throughout the observational period.

Keywords: Health Service Utilization
Ontario
Provincial Correctional Involvement
Recidivism
Schizophrenia
Advisor: Kurdyak, Paul
Predicting Formalin-fixed Paraffin-embedded (FFPE) Sequencing Artefacts from Breast Cancer Exome Sequencing Data using Machine Learning

Cancer is a lethal disease caused by the accumulation of genomic alterations. In order to investigate these diseases, cancer genome studies have largely relied on fresh frozen tissues. However, fresh frozen material is often unavailable for large-scale studies. In contrast, formalin-fixed paraffin-embedded (FFPE) tissues are abundantly available but difficult to use due to severe DNA degradation resulting in artefactual mutations. Accurate removal of these sequencing artefacts can help enable the widespread use of FFPE material for molecular analysis of cancers and other diseases. In this project, I used commercial FFPE DNA repair and library preparation kits and trained a random forest classifier to reduce the number of sequencing artefacts in FFPE breast cancer exome data. These experiments show that the classifier is able to retain the majority of true somatic variants while filtering many FFPE-induced sequencing artefacts and is suitable for application to low-quality FFPE breast cancer exomes.

Keywords: Computational biology
DNA damage
FFPE
Machine learning
Sequencing artefacts
Advisor: Stein, Lincoln D
Exploiting the Cellular Redox Control System for Activatable Photodynamic Therapy

Photodynamic therapy is a clinically-approved cancer treatment that uses a small-molecule photosensitizer, light and molecular oxygen to produce cytotoxic reactive oxygen species to promote cell death. Photodynamic therapy uses visible light for destruction of tumors, while their fluorescent properties make them useful for fluorescence-guided surgery. However, the lack of cancer cell selectivity has limited the use of current photosensitizers for cancer treatment. To overcome this, we designed activatable photosensitizers whereby in addition to light, activation depends on elements of the over-active redox system found in cancer cells. Chapter 1 provides a comprehensive overview on photodynamic therapy, photosensitizers and their applications. In chapter 2, we highlight the development and applications of an activatable photosensitizer sensitive to multiple elements of the redox system. Chapter 3 provides an overview of an activatable photosensitizer specific for protein disulfide isomerase. Finally, in chapter 4, we highlight the development and characterization of other enzyme activatable photosensitizers.

Keywords: Cancer
Glutathione
Photodynamic Therapy
Photosensitizer
Protein Disulfide Isomerase
Redox
Advisor: Beharry, Andrew
Application of the Indicator Amino Acid Oxidation Technique to Determine the Metabolic Availability of Lysine in Millet

Application of the Indicator Amino Acid Oxidation Technique to Determine the Metabolic Availability of Lysine in Millet Abrar Fakiha Masters of Science Graduate Department of Nutritional Science University of Toronto 2019 Abstract Objective 1) Determine the metabolic availability (MA) of the most limiting indispensable amino acid, lysine, in millet.2) Assess the effect of complementing millet protein with lentils Method The MA of lysine in millet was studied using the indicator amino acid oxidation (IAAO) and slope ratio methods. Five healthy males participated in 8 experiments: 4 lysine intakes from a reference protein, 3 intakes from millet and 1 complementation experiment with lentils. The MA of lysine was estimated by comparing the reference protein slope with the millet slope using the slope ratio method Results The MA of lysine from millet was 97%. Complementation with lentils decreased the IAAO response suggesting increased uptake for protein synthesis Conclusion Lysine is completely bioavailable, however still limiting in millet. Complementation with lentils in 2:1 ratio is recommended to meet the lysine and protein requirement for adults consuming a millet based diet.

Advisor: Fakiha, Abrar G
Evaluating Glutathione Peroxidase Activity as a Marker of Cognitive Impairment in Coronary Artery Disease Patients

Coronary artery disease (CAD) patients are at risk for vascular cognitive impairment (VCI), yet mechanisms remain elusive. We hypothesized that glutathione peroxidase activity (GPx), which protects from oxidative damage, would be higher in CAD patients with cognitive impairment (n=36) compared to those without (n=84), and baseline GPx and change in GPx over 6 months would be associated with changes in verbal memory. CAD patients were recruited from the Toronto Rehabilitation Institute Cardiac Rehab (TRI-CR) program. Cognitive performance and GPx activity were measured at baseline and 6-month timepoints. GPx was significantly elevated in those with cognitive impairment (F1,119=3.996, p=0.048). While a 1 nmol/min/mL increase in GPx activity was associated with a decrease in verbal memory z-scores by 0.02 standard deviations (SD) over 6 months (b=-0.02, df=184.65, p=0.004), baseline GPx did not predict change in verbal memory. This research suggests that alterations in GPx activity may be associated with cognition in CAD patients.

Keywords: biomarker
Cognitive impairment
Coronary Artery Disease
glutathione peroxidase
Advisor: Lanctot, Krista