VictorJuiz/thesis huggingface dataset:
Establishment of Zebrafish Models for Studying Mesenchymal Stromal Cell Therapy for Cardiac Disease

Bone marrow (BM)-derived mesenchymal stromal cells (MSCs) can be induced to express cardiac-specific markers by embryonic cardiomyocytes in vitro. To determine whether this phenomenon occurs in vivo, we have developed a cell transplantation system using zebrafish embryonic recipients. We were unable to isolate expandable zebrafish kidney stromal (ZKS) cells from the kidney, the human BM equivalent; hence, we analyzed the established ZKS1 cell line. We found that ZKS1 expresses stromal genes, but also expresses hematopoietic genes not normally expressed by MSCs. Furthermore, we were unable to differentiate ZKS1 cells into adipocytes, osteoblasts or cardiomyocytes in vitro. We created a transgenic ZKS1(CMV:eGFP) cell line which, after transplantation into zebrafish blastulae, was observed within the host heart, among other tissues. Finally, pT2/S2tnnt2-GM2 and pT2/S2tnnt2-DsRed transposons were generated to mark ZKS1 cardiac differentiation. The zebrafish model established here will be useful for studying the molecular mechanisms of exogenous MSC cardiac differentiation in vivo.

Keywords: Zebrafish kidney stromal cells
Transgenic transposon vectors
Cell transplantation into zebrafish embryos
Advisor: Keating, Armand
Wen, Xiao-Yan
A BH3-independent Role of the Anti-apoptotic Protein Bcl-2

The Bcl-2 family of proteins regulates apoptosis in mammalian cells through the interactions of pro-apoptotic and anti-apoptotic members at the functional region known as the BH3 groove. Some cancers manipulate the balance of Bcl-2 family members to avoid death, even in highly stressed conditions which would induce apoptosis is normal cells. A class of chemotherapeutic drugs known as BH3-mimetics are used to exploit a cancer’s dependence on anti-apoptotic proteins – Venetoclax (ABT-199) binds to the BH3 groove of the Bcl-2 anti-apoptotic protein. Our research has discovered that under certain conditions, protection offered by expression of Bcl-2 is insensitive to treatment with Venetoclax. Further exploration into the Bcl-2 protein reveals a novel anti-apoptotic role for the protein when the BH3 groove is disrupted.

Advisor: Andrews, David W
Large-scale Dynamic Traffic Assignment Modeling of Autonomous Vehicles A Case Study of Greater Toronto and Hamilton Area

With the rapid advancement of technology and people's tendency toward a driving-free lifestyle, autonomous vehicles (AVs) are expected to dominate the roads in the future. Therefore, it is crucial to quantify their transportation implications for metropolitan areas. In this project, we built a dynamic model to assess the impact of AVs on the performance of the Greater Toronto and Hamilton Area (GTHA) transportation system in both mixed traffic flow and the whole AV conditions. To this end, first, a large-scale and multi-regional network is developed for the GTHA in the AIMSUN Next® platform. Then, a generic approach is applied to model AVs in mesoscopic resolution. The results revealed that the level of aggressiveness of the AVs plays a critical role in the magnitude of their effect, where the presence of aggressive AVs improved the system performance while cautious AVs resulted in deterioration.

Keywords: Autonomous Vehicle
Dynamic Traffic Assignment
Greater Toronto and Hamilton Area GTHA
Heterogenous
Large Scale
Mesoscopic
Advisor: Abdulhai, Baher BA
Enhancing Therapeutic Efficacy of Double Negative T cells against Acute Myeloid Leukemia using Idelalisib

Double negative T cell (DNT) is a unique subset of T cells with potent anti-leukemic activity. Previously, DNT therapy has been shown to effectively target Acute Myeloid Leukemia (AML) cells in patient-derived xenograft (PDX) models. Further, a recently completed phase I/IIa clinical study demonstrated the safety, feasibility, and potential efficacy of DNTs for treatment of AML patients that relapsed after allogeneic hematopoietic stem cell transplantation. However, the persistence and durability of DNT-mediated anti-leukemic response is less well understood. In this thesis, I characterized the in vivo persistence of DNTs in PDX models. Further, I improved the efficacy and durability of DNT-mediated anti-leukemia activity with phosphoinositide 3-kinase delta (PI3K) inhibition. Mechanistically, DNTs treated with PI3K inhibitor, Idelalisib (Ide), exhibited early memory phenotype with superior viability and proliferative capacity. Further, Ide-treated DNTs were less exhausted. Collectively, the findings from this thesis support the use of Ide-treated DNTs to improve its therapeutic outcome.

Advisor: Zhang, Li LZ
Long-range Charge Transport in Linear Molecular Chains

Charge transport (CT) is the flow of charge through a medium, in this work we focus on electron CT. Due to the longer timescale of CT in longer chains, nuclear degrees of freedom must be included. In this work, we use the Landauer-B ̈uttiker probe (LBP) method to incorporate dephasing and energy exchange to the system electrons. We first present short systems of length < 1 nm to demonstrate the transition from tunneling to hopping transport mechanism. Next, we demonstrate non-trivial behaviours in high intersite tunneling energy systems. Following, we simulate longer systems up to 50 nm, showing the advantages of different transport mechanisms. We further simulate an alternating-rigidity system based on Geobacter Sulfurreducen by alternating the dephasing conditions. Finally, we apply the LBP method to study chiral-induced spin selectivity in proteins. While the results are preliminary, simulations show asymmetry of the transmission probability for different electron spin species.

Keywords: Charge Transport
Molecular Electronics
Advisor: Segal, Dvira DS
SigVM: Enabling Event-driven Execution for Truly Decentralized Smart Contracts

This paper presents SigVM, a novel blockchain virtual machine that supports an event-driven execution model, enabling developers to build truly decentralized smart contracts. Under traditional blockchain virtual machine such as Ethereum, the events have to be monitored uninterruptedly and the corresponding function in Smart Contract should be called manually by users once acquiring events. Under SigVM, contracts can emit signal events, on which other contracts can listen. Once an event is triggered, corresponding handler functions are automatically executed as signal transactions. We build an end-to-end blockchain platform SigChain and a contract language compiler SigSolid to realize the potential of SigVM. Experimental results show that our benchmark applications can be reimplemented with SigVM in an autonomous way, eliminating the dependency on unreliable mechanisms like off-chain relay servers. The development effort of reimplementing these contracts with SigVM is small, i.e., we modified on average 2.6% of the contract code.

Keywords: blockchain
programming languages
secuirty
smart contract
Advisor: Long, Fan F
Multi-modal, Multi-functional Phase-change Palladium Porphylets

Photodynamic therapy (PDT) utilizes sensitizers, such as porphyrin, and light to locally generate cytotoxic reactive oxygen species (ROS) to treat tumors. The accumulation of sensitizers in the tumor is critical for effective ROS generation. Porphyrin liposomes (porphysomes) have been demonstrated to be an effective and passive accumulation platform for PDT but cannot be used for active delivery. Porphyrin microbubbles are capable of active delivery with ultrasound for subsequent PDT but are too large and short-lived for passive delivery. In this thesis, phase-change porphyrin droplets (AKA porphylets) are investigated as an agent that can bridge porphysomes and porphyrin microbubbles. Like porphysomes, porphylets can passively accumulate in tumors due to their stability and small diameters. Like porphyrin microbubbles, porphylets can respond to ultrasound for active delivery. Such an agent can be utilized as a multi-modal, multi-functional "one-for-all" platform that is capable of therapy and delivery quantification without the need for companion diagnostic agents.

Keywords: Cancer
Droplet
Mass Spectrometry
Photodynamic Therapy
Porphyrin
Ultrasound
Advisor: Zheng, Gang
Collaborative Professional Development: The Journey of Five Core French Teachers Navigating the COVID-19 Pandemic in Ontario Public Schools

In this study, I bring forward five elementary Core French teachers’ experiences of teaching during the COVID-19 pandemic in a large school board in the Greater Toronto Area in Ontario, Canada. The study evolved from a collaborative professional development group I initiated within the school board in September of 2020. The aim was to support each other, so that we in turn could help our students. The objective of my research is to explore the extent to which the collaboration group enabled us to develop teacher agency as Core French teachers despite the challenges associated with unstable school planning. This study will look at how Core French teachers 1) planned their programs, 2) supported students, particularly those who are learning the main school language, also referred to as English Language Learners, and 3) utilized technology to support learning throughout the different stages of teaching through the pandemic.

Keywords: Collaborative Professional Development
Core French
COVID-19 Pandemic
Ontario
Public Schools
Teacher agency
Advisor: Le Pichon-Vorstman, Emmanuelle
Toward Patient-centred Care in Precision Oncology: What Matters to Patients

Aim: To explore patients’ experiences and perspectives on using precision oncology to identify domains of patient-centred care that are important in this context. Methods: Qualitative interpretive descriptive study consisting of semi-structured interviews with hereditary cancer syndromes patients who would be eligible for circulating tumour DNA (ctDNA) testing. Results: 22 patients were interviewed. Connectedness to the healthcare system was the central element to participants’ experiences of patient-centred care. It was also central to their perspectives on patient-centred delivery of ctDNA. Four domains influenced the degree participants felt connected to the system: patient-provider communication, navigation, coordination of care, and technology. ctDNA was seen as a tool to increase participants’ connectedness to the system by increasing touchpoints with providers, informing decision-making, and triggering further investigations. Conclusion: Patient-centred precision oncology should strive toward connectedness to the system (i.e., ensuring patients are in regular contact with and supported by the healthcare system (e.g., their providers)).

Keywords: Cancer screening
ctDNA
Hereditary cancer syndromes
Patient-centred care
Precision oncology
Qualitative research
Advisor: Bombard, Yvonne
Meaningful Datatypes: Ontologically-Sound Dependent Type Systems for Data Science

Data science incorporates many processes, techniques and domains to transform data into meaningful insights that inform decision-making. In practice, data science relies heavily on simplistic datatypes like strings or integers to represent common and significant complex real-world phenomena like time, mereology, and provenance. Current solutions to this problem are opaque, lack standardization, and require manual intervention to validate. To address these issues, we introduce the meaningful type safety framework (MeTS) to enforce the integrity of real-world interpretations via type-checking with dependent types. MeTS is also grounded in real-world census datasets from Statistics Canada, which also serve as the basis for a novel census data ontology and a theorem to prove the formal ontological soundness of a MeTS type environment. The MeTS framework, including its ontological foundations, challenges the status quo of data science, and introduces new avenues of research for the functional programming, data science, and knowledge modeling communities.

Keywords: data science
datatypes
dependent types
meaningful datatypes
ontology
Advisor: Sanner, Scott
Investigating the Role of 3-ketosphinganine Reductase (KDSR) in Acute Myeloid Leukemia

AML is characterized by accumulation of poorly differentiated, non-functional myeloblasts in the bone marrow and blood. Despite therapeutic advancements, AML remains a disease with poor long-term survival rates. To develop improved therapeutic strategies, this study aims to understand and target sphingolipid metabolism in AML. Sphingolipids are a heterogenous class of lipids that share an 18-carbon amino alcohol backbone. Bioactive sphingolipids regulate leukemic cell survival, apoptosis, chemoresistance, and differentiation. In this study, we show that early sphingolipid synthesis enzyme, 3-ketosphinganine reductase (KDSR), is essential for AML pathogenesis. KDSR is overexpressed in primary AML patient samples compared to healthy controls. Knockdown of KDSR impairs proliferation, viability, and self-renewal properties in AML cell lines. Using liquid-chromatography mass-spectrometry, we show that lack of KDSR activity induces a significant change in the cellular lipidome. Altogether, our findings suggest that KDSR promotes AML pathogenesis by regulating lipid homeostasis, thereby proposing KDSR as a novel target in AML.

Keywords: Acute Myeloid Leukemia
Lipidome
Lipidomics
Metabolism
Sphingolipids
Advisor: Schimmer, Aaron
Measurement and Characterization of Neighbourhood Scale Air Quality in the Vicinity of an Urban Rail Yard in Toronto, Ontario

This study explores potential neighbourhood scale air quality impacts of an urban rail yard in Toronto, Ontario. Measurements of NO, NO2, NOx, O3, PM10, PM2.5, BC and UFP were completed at two urban background stations near the rail yard. Two mobile monitoring campaigns measuring BC and UFP were also carried out on the surrounding road network. Fixed station measurements approximately 150 m from the nearest tracks exhibited statistically significant evidence of elevated indicator pollutant concentrations during downwind conditions. On-road mobile measurements exhibited strong influences from on-road traffic compared to other neighbourhood sources such as the rail yard. Paired analysis between the two fixed stations to estimate maximum potential rail yard pollutant enhancements demonstrated measurable impacts when contributions from confounding local sources were typically minimized, such as during downwind conditions and overnight hours. Future research could benefit from collaboration with rail operators for collection of detailed rail yard activity data.

Keywords: Air Quality
Emissions
Measurement
Pollution
Rail
Rail Yard
Advisor: Hatzopoulou, Marianne
Sex Differences in Stroke Dysbiosis in Rodent Models of Focal Cortical Ischemia

Stroke is a devastating neurological disease that differentially affects males and females across the lifespan. Interestingly, clinical, and preclinical research findings indicate that stroke induced changes in gut microbiota composition, termed stroke dysbiosis, plays an important role in stroke outcomes. Given that there are also sex differences in gut microbiota composition throughout the lifespan, there has been little study of sex differences in stroke dysbiosis. In this study, we utilized rodent models of focal cortical ischemia to study sex differences in stroke dysbiosis. Using 16s rRNA sequencing approaches, we observed that the trajectory of stroke dysbiosis differs between males and females over time, however this was not associated with a concomitant increase in biomarkers of increased intestinal permeability. Furthermore, we assessed whether probiotic interventions may improve functional outcomes following stroke injury. Interestingly, we observed functional recovery following probiotic treatment in a sensorimotor model of focal cortical ischemia. This highlights the potential use of probiotics as an adjunct therapeutic for ischemic stroke.

Keywords: Focal cortical ischemia
Gut-microbiota-brain-axis
Rodent models
Sex differences
Stroke
Advisor: Faiz, Maryam
Soil Nitrogen Mineralization and Nitrous Oxide Dynamics in an Extensive Agro-Green Roof System

Understanding microbially mediated nutrient cycling processes, including soil nitrogen (N) dynamics is key to maximizing the potential for extensive green roofs to support crop production. In this thesis, I used three substrate treatments (Organic, FLL, and FLL+) and four cropping treatments (bush-bean and Sedum spp. planted in monoculture and together in polyculture) and a no plant control. Measuring various plant parameters, soil N mineralization rates (n=48), and soil nitrous-oxide (N2O) (n=36) across extensive green roof modules, I found that both crop and vegetation productivity, as well as N mineralization rates were significantly affected across substrate treatments, however no significance was detected for soil N2O production across all experimental treatments. Overall, findings from this study show that FLL substrates demonstrate ability to support crop production, and that substrate type is key to maintaining soil nutrient fluxes for crop growth on extensive green roofs.

Keywords: extensive green roof
nitrogen mineralization
nitrous oxide
rooftop agriculture
Advisor: MacIvor, Scott
Isaac, Marney
Regulating and Supporting Ecosystem Services Provided by Urban Greenspace and Restored Meadows along a Hydro Corridor in Toronto

The Meadoway project, led by the Toronto and Region Conservation Authority (TRCA), aims to restore 200 ha of meadow habitats along the Gatineau Hydro Corridor across Scarborough, Ontario. The hydro corridor’s transition from turf grass to deep-rooted native meadow plants is hypothesized to enhance regulating and supporting services. To evaluate this hypothesis, in-situ infiltration, penetrometer tests, and soil sampling were conducted on two pre-restored turf lands and two restored meadows in 2020. Soil samples were analyzed for bulk density, porosity, pore structure, total carbon, total nitrogen, and available phosphorus. Water balance analysis was conducted by simulating artificial rainfall events upon undisturbed vegetated soil samples accompanied by saturated hydraulic conductivity measurements. The meadow restoration altered soil structure and enhanced its runoff reduction and available water capacity, and decreased soil available phosphorus. The Meadoway can potentially enhance multiple ecosystem services including flood and erosion control, and soil quality and nutrient cycling regulation.

Keywords: ecosystem restoration
ecosystem service
green infrastructure
soil nutrient analysis
urban ecosystem
water balance analysis
Advisor: Drake, Jennifer
Testing Pyrrhotite Trace Element Chemistry as A Vector Towards the Mineralization in The Sullivan Deposit, B.C.

Mineral exploration methods are expensive and time-consuming, especially more recently because most near surface deposits have been found. To overcome these challenges, new strategies must be developed. Here we test whether trace element chemistry of pyrrhotite changes systematically with distance from mineralization at the Sullivan deposit, B.C. If so, this will be an additional tool to search for new ore bodies, especially in areas too deep for current techniques. Forty samples of the hangingwall, footwall and host horizon were collected from six drill holes proximal and distal to the Sullivan deposit. These were then analyzed using reflected light microscopy, electron microprobe, and LA-ICPMS (laser ablation, inductively coupled plasma mass spectrometry). Three hundred ninety LA-ICPMS analyses were used to build machine learning classifiers (cluster analysis and random forests) to identify whether an unknown pyrrhotite sample was from the mineralized horizon and if so whether it was from near the mineralization.

Keywords: Economic Geology
Geology
Pyrrhotite
SEDEX
Trace elements
Advisor: Gregory, Daniel DG
Exploring Autophagy-related Genetic Interactions in Renca cells via genome-wide CRISPR Screens

Previous CRISPR-Cas9 TNFα killing screens performed in Renca cancer cells identified Atg5 and Atg16l1 as top resistance genes in Atg12Δ cells, indicating a positive genetic interaction between Atg12 and Atg5/16l1, where Atg12Δ-Atg5Δ and Atg12Δ-Atg16l1Δ cells have improved cell fitness and survival under TNFα pressure compared to single-mutant cells (e.g., Atg12Δ). However, knowledge of genetic pathways responsible for mediating differential sensitivity to TNFα between single- and double-mutants is currently unknown. Here, I performed a pooled genome-wide TNFα killing screen in Renca Atg5Δ-Atg12Δ cells to determine genetic pathways that protect double-mutant cells (Atg5Δ-Atg12Δ) against TNFα-mediated cytotoxicity. CRISPR screening identified several non-canonical pro-survival TNFα signaling factors in Atg5Δ-Atg12Δ cells and revealed differential TNFα signaling pathways between Atg12Δ and Atg5Δ-Atg12Δ cells.

Keywords: autophagy
CRISPR-Cas9 screen
genetic interaction
TNFa signaling
Advisor: Moffat, Jason
Brain Alterations in Obese Children and Adolescents with Obstructive Sleep Apnea: an MRI Study

Obstructive sleep apnea (OSA) is a breathing disorder associated with obesity, characterized by recurrent episodes of apnea and/or hypopnea during sleep. Both obesity and OSA independently lead to systemic derangements; when combined, they may cause significant brain structure alterations, particularly in childhood. This study investigated cortical thickness alterations in obese youths with no, mild, and moderate/severe OSA. We hypothesized that OSA is associated with global and regional alterations (with sex differences), and that it causes a deviation from the typical trajectory of age-related cortical thickness decrease reported in lean subjects. Overall, there were no differences in global and regional cortical thickness between groups or sexes. However, the trajectory of the expected age-related cortical thickness decrease was significantly altered: absent in mild OSA, it presented a significant increase in moderate/severe OSA, involving several areas of the cortex. Therefore, cortical alterations caused by OSA in obese youths appear significantly associated with age.

Keywords: Adolescence
Childhood
Cortical thickness
MRI
Obesity
Obstructive sleep apnea
Advisor: Kassner, Andrea
Deep Brain Stimulation as a Treatment for Depressive-like Behaviour in Rodents: Role of the 5-HT1A and 5-HT1B Serotonin Receptors in a Modified Chronic Social Defeat Stress Model

Despite the prevalence and pervasiveness of major depression disorder (MDD), ~30% of patients demonstrate resistance to all forms of conventional treatment. An alternative therapy, deep brain stimulation (DBS), has consistently reversed a depressive-like phenotype (DLP) in rodents when targeted to the ventromedial prefrontal cortex (vmPFC). While the underlying mechanisms remain elusive, the antidepressant-like response of DBS has demonstrated dependence on the serotonergic system. This thesis examined the validity of a modified chronic social defeat stress (CSDS) model and the potential mediatory role of the serotonin receptors, 5-HT1A and 5-HT1B, in a DBS response. This model reliably induced DLP in mice, which chronic vmPFC DBS reversed. The antidepressant-like effects of DBS were sustained following 5-HT1A antagonism but abolished with 5-HT1B antagonism. These findings demonstrate the face and construct validity of a modified CSDS model and suggest that the modulation of the 5-HT1B receptor may be intrinsic to DBS for the treatment of depression.

Keywords: Animal models of depression
Deep Brain Stimulation
Depression
Neuroscience
Serotonin
Treatment Resistant Depression
Advisor: Hamani, Clement