VictorJuiz/thesis huggingface dataset:
Ex Vivo Perfusion Decellularization and Recellularization of Rat Hindlimbs for Vascular Composite Allotransplantation

Traumatic injuries, tumor resections, and large burns significantly impact patient quality of life and cause functional deficits due to volumetric soft tissue loss and musculoskeletal damage. Vascular composite allotransplantation (VCA) is an emerging surgical reconstructive avenue in transferring multiple, complex tissues as a composite subunit from donors to recipients. Although promising, significant side effects due to long-term immunosuppression regimens significantly impede the clinical implication of VCA. Tissue engineered composite tissues developed using decellularization and recellularization represent a solution. Herein, we established an ex vivo perfusion decellularized composite rat hindlimb and demonstrated cell clearance while maintaining tissue structure. We subsequently recellularized the vascular and muscle compartments simultaneously, demonstrating cell engraftment, survival, and evidence of a regenerated neo-endothelium and nascent myotube muscle formation. We furthered our ex vivo perfusion bioreactor design by incorporating electrical stimulation to advance towards re-functionalization. Altogether, our findings substantiate a proof-of-concept tissue engineered small animal model for VCA.

Keywords: Decellularization
Recellularization
Regenerative Medicine
Tissue Engineering
VCA
Advisor: Haykal, Siba
The Role of PDGFRα+ Mesenchymal Niche Cells in Intestinal Stem Cell Homeostasis and Tumorigenesis

Colorectal cancer is the world’s third most common and second deadliest cancer. Intestinal tumors are characterized by mutations of Apc, leading to Wnt signaling overactivation in intestinal stem cells (ISCs). Tightly associated with ISCs, mesenchymal niche cells (MNCs) and their signaling interactions with epithelium are poorly understood. Aiming to uncover the identity of MNCs, single-cell RNA sequencing studies have implicated cells expressing the Platelet-derived growth factor receptor α (PDGFRα), which is involved in cell recruitment, proliferation, and differentiation. My project focuses on PDGFRα+ MNC signaling and epithelial cross-talk in adult intestinal stem cell homeostasis and tumorigenesis. My work has revealed that tumor-associated MNCs have differences from homeostatic MNCs in their ability to stimulate stem cell growth. Lastly, PDGFRα signaling might be critical during adult homeostasis since gene deletion possibly confers a competitive disadvantage. Altogether, my work demonstrates the involvement of PDGFRα+ M.N.C. signaling in intestinal tumorigenesis and homeostasis.

Keywords: Disease
Homeostasis
Intestinal cancer
Mesenchymal niche cells
Stem cells
Stromal cells
Advisor: Kim, Tae-hee
Design and Simulation of Microfluidic Chip for Detection of Bacteria

Bacterial infections and associated diseases are of high importance to be addressed in a timely yet efficient manner. In recent years, increasing antimicrobial resistance statistics around the world and a very slow rate of improvement of bacterial diseases in low-resource environments necessitates practical ways to address the issue with a reliable technique.Microfluidics merged with diffraction sensing pose a great potential for point-of-care diagnostics, specifically for capturing and concentrating the bacteria from its host such as drinking water. This study proposed an efficient technique for bacteria concentration and trapping using microfluidics. We studied the behavior of fluid and particles then adjusted corresponding parameters. While several designs were explored, we focused on periodic structures of dimensions compatible with the diffraction-based detection method invented in our group. Doubled Herringbone showed outstanding results, Reversed Herringbone and Simple Herringbone designs performed reliably (capturing bacteria with 72.3%, 54.5%, and 51.8% efficiency respectively).

Keywords: Bacteria
Diffraction Sensing
Point-of-Care
Pre-concentration
Advisor: Goh, Cynthia
Mapping Toxin-Host Interactions: A Novel Application of TurboID to AB Bacterial Toxins

Toxins are proteins secreted by bacteria that target host cells and impair cellular function. Significant knowledge gaps remain as to how existing and emerging toxins exploit host factors or processes. In this thesis, I present the first application of enzyme-catalyzed proximity labelling with TurboID to class AB bacterial toxins, introducing a new tool to uncover host-toxin interactions. Fusions of TurboID to the active domain of TcdB, and the related toxin TcsL, biotinylated proximal proteins at the plasma membrane, including members of Rho GTPase signaling cascades and the actin cytoskeletal network. I also present the first application of TurboID paired with mass spectrometry to identify cell surface receptors with recombinant fusions of a prey protein and the biotinylating enzyme. Using this novel approach, I present supporting evidence for the role of LRP1 as a receptor for TcdB.

Keywords: Clostridial toxins
Diphtheria
protein engineering
TcdB
toxin
Advisor: Melnyk, Roman
COVID-19 as a glitch in time: Park-use in a Pandemic and the ‘Revolving Door of Emergencies’ in Toronto’s St. James Town

This project uses park restrictions implemented during the COVID-19 lockdowns in Toronto as an entry point to examine the relationship between park use and housing conditions, focusing specifically on St. James Town, the most densely populated neighbourhood in Canada. Drawing upon interviews, as well as analysis of municipal policies and archival documents, I find that closures of outdoor spaces in St. James Town went beyond the standard COVID park restrictions implemented in the rest of the city, limiting available outdoor spaces for residents for three years. COVID park restrictions represented both a physical and temporal displacement for residents who experienced the lockdowns as a multi-scaled process of infrastructural abandonment. The targeting of green spaces, together with an increase in building maintenance issues and feeling of abandonment by decision makers made people feel like they had to leave the neighbourhood to access to social supports and an increased quality of life.

Keywords: COVID-19
displacement
gentrification
housing
policy
public space
Advisor: Vinodrai, Tara
Identification of Novel Protein Abundance Fold Changes in Rett Syndrome in Neural Progenitor Cells and Neurons

Rett Syndrome (RTT) is a neurological disorder primarily caused by mutations in MECP2 (methyl-CpG-binding protein 2), a global modulator of transcription and translation. RTT has been well-studied at the RNA level, but despite the known effects of MECP2 on translation, RTT has been poorly studied at the protein level. To address this, I performed whole cell and membrane-enriched tandem mass tag-labeled mass spectrometry on neural precursor cells (NPCs) and neurons derived from a RTT patient induced pluripotent stem cell line. I quantified over 5000 proteins and found over 250 misregulated in RTT NPCs and neurons, many of which were not previously detected in RTT including CRABP1, a retinoic acid shuttling protein and marker of cell fate. The analysis of both whole cell and membrane-enriched neurons also identified a potential mislocalization phenotype not previously described in RTT. Overall, this work provides novel targets for RTT research and therapeutic development.

Keywords: iPSC
proteomics
Rett Syndrome
Advisor: Ellis, James
Attitude Determination and Control Hardware Testing and System Level Testing for Maritime Monitoring MicroSatellite

This thesis presents the hardware testing for the Attitude Determination and Control System (ADCS) and the contributions to the automation of system level testing of NorSat-4, a maritime monitoring microsatellite mission. Due to the success of the previous NorSat missions, Space Flight Laboratory has been asked to design and build NorSat-4, a new microsatellite with the goal to monitor Norwegian maritime resources through an Automatic Identification System (AIS) and to demonstrate the capabilities of a Low Light Imager (LLI) and Nanocrypto Unit (NCU). The first focus of the thesis is the hardware testing and analysis required for an accurate attitude determination and control system. The second focus of this thesis is the development of automated testing software for effective testing of the two new payloads.

Advisor: Zee, Robert
Health and Wellness Impacts of Being on the Land for Indigenous Peoples in North America

Indigenous people globally face disparate chronic health outcomes when compared to non-Indigenous counterparts. In Canada, First Nations people experience higher rates of obesity and associated conditions. The causes behind this are multifactorial and include colonialism alongside various social determinants of health. Being on the land (traditional lifestyle) can have numerous benefits, including an attenuating effect on obesity associated conditions. This thesis explored being on the land in two prongs. Chapter 2 is a systematic review conducted to explore the diverse health experiences related to traditional physical activities for Indigenous youth worldwide. Overall, the literature described numerous emotional, mental and spiritual benefits of traditional physical activity, including familial and communal relationships. This research shows the importance of including traditional physical activity in future programs. Chapter 3 examined the association between selected morphometry measures and body burdens of persistent organic pollutants (POPs) and toxic metals in seven communities of Eeyou Istchee. Results indicated a negative association between cadmium with various obesity measures in both males and females. Null associations were found between POPs and morphometry.

Keywords: Environmental Contaminants
Environmental Health
Indigenous Health
Land-based activities
Obesogens
Traditional activities
Advisor: Tsuji, Leonard JS
Zuk, Aleksandra M
Defining the Roles of the Iroquois Homeobox Factors in Murine Nephrogenesis

Nephron deficiency is a leading cause of end-stage kidney disease in children, yet the underlying signaling mechanisms are largely undefined. The Iroquois (Irx) transcription factors, well- established in tissue patterning and specification, are expressed within the developing nephron, with suggested roles in nephron differentiation. Here, I show that Irx1 and separately Irx3/5 have distinct roles in controlling nephron number when deleted from the Six2+ nephrogenic lineage. Six2-Cre; Irx1loxP/- and Six2-Cre; Irx3/5loxP/loxP kidneys exhibited a 34.4% and 59.5% reduction in nephron number compared to control kidneys at E18.5, respectively. Compound deletion of Irx2 with Six2-Cre; Irx1loxP/- kidneys did not change nephron number. Six2-Cre; Irx3/5loxP/loxP kidneys were found to manifest nephron deficiency at E15.5, displaying reductions in nephron progenitors and intermediate structures. Bulk RNA-sequencing and in-silico screening was leveraged in E15.5 Six2-Cre; Irx3/5loxP/loxP kidneys to determine the primary molecular effects through which Irx3/5 control nephron number and select candidate genes for downstream analysis.

Advisor: Rosenblum, Norman D.
Intercept Estimation of Semi-parametric Joint Models in the Context of Longitudinal Data Subject to Irregular Observations

Longitudinal data is often subject to irregular visiting times. While there are established methods developed to deal with certain irregular visiting patterns, not much is known regarding modelling scenarios where the current value of the outcome influences the visit intensity at that time. One model that allows for such dependence provided there is conditional independence given a random effect is the Sun multiplicative model, which is one of the few semi-parametric joint models that is suitable for count data. We extend this model by additionally estimating the intercept term which was formerly treated as a nuisance parameter. This technique enables us to assess prognosis by examining the evolution of the outcome variable over time, rather than just the relative effects of model covariates. This extended estimator exhibits desirable large-sample properties such as consistency and asymptotic normality. We evaluate finite-sample performance with a simulation study, which shows that the proposed method outperforms standard approaches in terms of bias and standard error under a range of scenarios. Moreover, the proposed model is more computationally efficient than the standard method for different specifications of the intercept term. Furthermore, we present an application to a study of tumour recurrence for a longitudinal cohort of bladder cancer patients characterized by informative visits. We recommend that unless the intercept term fluctuates extensively through time, applying our proposed method results in improved model estimates and reduced computational complexity compared to the standard Sun model estimation, and permits the additional estimation of the mean outcome trajectories.

Advisor: Pullenayegum, Eleanor
The Dream Job Academy: University Students’ Experiences of an Arts-Based Career Exploration Group

University students struggle with making career decisions. Given the important roles that identity and unconscious/intuitive thinking play in decision-making in today’s world of work, career guidance should help students gain self-understanding and access unconscious/intuitive insights. Emerging research suggests that arts-based methods may be an effective career guidance approach. The present study sought to empirically investigate the question, “What is the impact of an arts-based intervention on university students’ career decision-making?” Eight participants of an existing arts-based career exploration group at the University of Toronto were interviewed. Using reflexive thematic analysis (Braun & Clark, 2006), three themes were developed: (1) A Weight Has Been Lifted, (2) New Questions, New Insights, and (3) Thinking in 3D. Results support the ability of arts-based methods to promote self-understanding and highlight the importance of appropriate scaffolding and the group format in delivering arts-based career interventions. The psychosocial implications of the intervention are also discussed.

Advisor: Chen, Charles P.
Exploring the Association Between Organizational Justice and Work Outcomes in Chronic Pain Patients: A Systematic Review and Feasibility Study

Chronic pain often interferes with employment retention and work productivity is often overshadowed by mental and physical health concerns. Personal factors and pain perceptions or beliefs may influence employment outcomes, but few studies have examined the association between work-related psychosocial factors and work outcomes in individuals with chronic pain. A systematic review found evidence that perceived support, workload, and work-related fear avoidance beliefs showed a low to moderate association with employment status, return to work, and productivity. A feasibility study to explore the association between organizational justice and work outcomes was hampered by challenges in recruitment and failed to meet three out of the four feasibility criteria. Alterations to the recruitment methods such as including additional sites and improving advertising material may help with future research. The association between the work environment and work behaviors within the chronic pain population remains under investigated.

Advisor: Furlan, Andrea
Assessment of Depression in Kidney-Pancreas Transplant Recipients: PROMIS Depression Item Bank with Computer Adaptive Testing

Kidney-pancreas transplant recipients (KPTRs) experience physical and psychological symptoms, despite improvements in survival and quality-of-life. Routine assessment of depressive symptoms using patient-reported outcome measures may identify KPTRs requiring clinical assessment and support. Validity and reliability of the PROMIS Depression Computer Adaptive Test (PROMIS-D CAT) was assessed. A cross-sectional, single-center convenience sample of KPTRs completed PROMIS-D CAT and additional legacy measures. PROMIS-D CAT demonstrated excellent validity and reliability. PROMIS-D CAT also had excellent discrimination in identifying KPTRs with potentially significant depressive symptoms. Results provide supporting evidence for the validity and reliability of PROMIS-D CAT to characterize depressive symptom severity among KPTRs.

Keywords: Depression
Kidney-Pancreas Transplant
PROMIS CAT
Psychosocial
Validation
Advisor: Mucsi, Istvan
Investigation of Material-Process-Structure-Property Relationships for Lignocellulosic Nanofibril Reinforced Polylactic Acid Composites

This study explores polylactic acid (PLA)-based composites reinforced with lignocellulosic nanofibrils (LCNF) processed by spray drying (SD), freeze drying (FD), solvent exchange (SE), and solution transfer (ST) via polyethylene glycol (PEG). The LCNF ranged from near-spherical in the SD LCNF to fibrillar in SE LCNF. SE and FD LCNF agglomerated significantly which inhibits their ability to improve crystallization kinetics and tensile properties. SD LCNF, by its dispersed nature, facilitates high nucleation density, leading to crystallization-induced tensile enhancement. ST LCNF self-assembled into core-shell structures with PEG localizing at the LCNF/PLA interface, reducing agglomeration, yielding significant rheological modification, and greatly enhancing toughness. LCNFs processed by these methods impart differing morphologies that give rise to varying degrees of dispersion and agglomeration, which impacts downstream structures that form after processing and give rise to observed properties. Such material-process-structure-property relationships are foundational in the intelligent design of novel bio-based and biodegradable packaging materials.

Keywords: Biodegradable
Biopolymer
Cellulose
LCNF
Packaging
PLA
Advisor: Lee, Patrick C
Yan, Ning
UWB Radar Tool Tracking in Minimally Invasive Procedures

Minimally invasive surgeries result in less trauma, less bleeding and faster recovery compared to traditional open surgeries. Tracking systems are used to detect and localize surgical tools during the procedure. In catheterization procedures, electromagnetic or impedance based systems are used. These systems have limitations such as requiring device customization, patches in contact with the patient, and require an external source for tracking. In laparoscopic procedures, optical based systems are used. Complications arise when there are adverse lighting conditions, or the tools are occluded by tissue, smoke, or blood spatters. To address this issue, a radar-based tracking solution was proposed, motivated by its ability to detect and localize objects through occlusions. In this thesis, the efficacy of the Walabot ultrawideband radar for tracking of an ablation catheter and laparoscopic forceps was investigated. Three experiments were conducted to test the localization and position tracking of the tool tips and the detection of tool poses. Results from the experiment show that a single sensor could localize and track the position of the catheter with 5cm of spatial accuracy, and pose detection is infeasible. We also discuss the existing limitations of the proposed radar-based procedure and suggest some approaches to overcome these limitations.

Advisor: Adve, Raviraj S
Tavallaei, Ali
Reciprocal Stimulation of HMGB1 and TGF-β in Pulmonary Fibroblasts – Implications for Pulmonary Arterial Hypertension

A characteristic hallmark of pulmonary arterial hypertension (PAH) involves vascular remodeling and cellular dysfunction of the pulmonary vasculature. In addition to endothelial dysfunction, the outer adventitial layer of pulmonary vessels is a key site for immune cell activation and inflammatory initiation. The danger signal high mobility group box-1 (HMGB1) and the cytokine transforming growth factor beta (TGF-β) have long been recognized as critical mediators of PAH. With this in mind, we aimed to assess the relationship between HMGB1 and TGF-β signaling with respect to disease-related phenotypes in resident pulmonary artery adventitial fibroblasts (PAAF). We demonstrate that extracellular HMGB1 induces the secretion of TGF-β from PAAF in vitro, and inversely, TGF-β promotes intracellular protein expression of HMGB1, potentially via SMAD3 signaling. Our results introduce a mechanistic positive-feedback loop between HMGB1 and TGF-β on PAAF, progressively driving inflammation and vascular remodeling in PAH.

Keywords: Fibroblasts
HMGB1
Inflammation
Pulmonary Arterial Hypertension
TGF-β
Vascular Remodeling
Advisor: Goldenberg, Neil M
Development of a Robotic System for Femoral Artery Puncture and Access

Femoral access is used to complete endovascular procedures and is the recommended treatment for conditions such as stroke and cardiovascular diseases. These treatments are very time-sensitive and should ideally be performed within 3 hours to minimize long-term adverse effects. In addition to being time-sensitive, the procedures are highly complex and currently can only be performed by well-trained medical professionals. These factors are most significant in rural areas or underserved communities, where there is a shortage of healthcare professionals and the evacuation time to a hospital is the longest. If these procedures are to be performed in these areas, a device capable of completing the entire procedure with minimal human intervention is required. This thesis aims to accomplish this by developing a robotic system capable of US-guided needle puncture into the femoral artery, followed by the advancement of a guidewire.

Keywords: Endovascular
Femoral Artery
Robot
Robotics
Surgery
Ultrasound
Advisor: Sun, Yu
The Guidance Signal Building Algorithm: A Method to Guide Neural Abstractive Summarization

The pervasiveness of large language models has been met with polarizing perspectives from the public. Calls for regulation from prominent institutions have increased the necessity to control the output of these models or perhaps align their learning, understanding, and generative capabilities with the values current societies deem important. The Guidance Signal Building algorithm builds a "guidance" feature using the XSum dataset as input. The guidance feature uses Text Rank and Parts of Speech Tagging to locate and store keywords from the document feature. The keywords are concatenated to the source document and summary features for the T5 transformer model. T5 is fine-tuned on the task of text summarization. After training, concatenation of the keywords did not prove to be an effective method of guidance. The training process illuminates recommendations for potentially adjustments to causal language modeling and masked language modeling by adding a guidance objective.

Keywords: Natural Language Processing
Semantic Spaces
Transfer Learning
Transformers
Word Embeddings
Advisor: Andritsos, Periklis
Maharaj, Tegan