VictorJuiz/thesis huggingface dataset:
Adapting Muscle Endogenous Repair (MEndR) Assay for Academic and Industry Adoption

Skeletal muscle is an essential tissue and in healthy individuals it can self-repair through the activity of muscle stem cells (MuSCs). In age and disease, MuSC endogenous repair proficiency is lost, and therapeutics that target and restore functionality are of interest. However, in vivo validation of drugs with potential to stimulate muscle endogenous repair proves to be a bottleneck in drug discovery and to address this problem we developed a MuSC mediated skeletal muscle endogenous repair (MEndR) phenotypic culture assay that predicts gold-standard in vivo assay outcomes. Roadblocks exist that prevent scale-up, and assay adoption. My thesis addresses two issues: phenotypic data analysis and the use of cells with access and scale-up limitations. My thesis offers a semi-automated pipeline to analyze MuSC-derived myotubes from confocal images with the power to stratify MuSC drug treatment response. I also identify immortalized myoblast cell lines with which to engineer the muscle templates.

Keywords: Endogenous repair
Muscle stem cell
Skeletal muscle
Tissue engineering
Advisor: Gilbert, Penney M
A Hardware Accelerator for Fully Homomorphic Encryption based Machine Learning Applications

Fully homomorphic encryption (FHE) is a lattice-based cryptography scheme that enables mathematical operations to be performed on encrypted data without first having to decrypt the data, allowing for the implementation of secure machine learning (ML). As performing ML applications with FHE-encrypted data using current processors can take significant computation time, DARPA has created the DPRIVE challenge for the design of an FHE hardware accelerator. In this thesis, we design and verify through a cycle-accurate Verilog model both residue number system (RNS) and large arithmetic word size (LAWS) implementations of a hardware accelerator capable of realizing the DPRIVE performance specifications for 1024-point logistic regression using the Cheon-Kim-Kim-Song (CKKS) mathematical foundation. We show that the two implementations achieve comparable execution time performance, and that the estimated CMOS ASIC implementation area of the LAWS design requires only 68% of the core area of the equivalent RNS design in an equivalent technology node.

Keywords: ASIC
Fully Homomorphic Encryption
Machine Learning
Advisor: Gulak, Glenn
Development of Xylitol-based Formulations as Novel Alternatives for Surgical Site Preparation Agents

Xylitol has numerous applications. We hypothesize that when used as a surgical site preparation agent, xylitol will significantly reduce the bacterial load on a given area of skin. We developed a protocol to test the ability of xylitol to inhibit the growth of, and eradicate, Staphylococcus aureus. Preclinical studies revealed that planktonic growth was inhibited by the supplementation of 40% (w/v) xylitol, with a noted 2-log fold reduction in planktonic cell survival. Biofilm growth was inhibited when cultivated in xylitol concentrations above 30% (w/v). Biofilms were eradicated when exposed to 40% xylitol, or to 40% xylitol/10% isopropyl alcohol. In clinical studies, baseline bacterial counts were inadequate. Therefore, xylitol could not be assessed as a surgical site preparation agent. Our preclinical findings suggest that 40% xylitol, or 40% xylitol/ 10% IPA can significantly reduce the growth, biofilm formation and eradicate mature biofilms of S. aureus.

Keywords: surgical site infections
surgical site preparation
xylitol
Advisor: Azarpazhooh, Amir
Lam, David K
Impact of Exogenous Hydrogen Sulfide on Short-term Synaptic Plasticity in the Anoxia-tolerant Western Painted Turtle

The western painted turtle has evolved mechanisms that allow for survival during months of severe hypoxia without neuronal damage. This is achieved by suppressing metabolism and excitatory neuronal activity. What remains unclear, however, is what happens at the synaptic level and what signalling molecules regulate synaptic activity during hypoxia. Hydrogen sulfide (H2S), a gasotransmitter, participates in neuroprotective pathways and is found to accumulate in the neuronal tissue during low O2 conditions. I hypothesize that H2S modulates synaptic transmission during hypoxia in the turtle brain. Using cortical tissue, I demonstrated that exogenous H2S application: 1) causes mitochondrial membrane depolarization similar to severe hypoxia; 2) and when combined with hypoxia does not affect synaptic transmission and short-term plasticity and 3) does not impact the membrane potential of pyramidal neurons as severe hypoxia is known to do. These findings indicate that synaptic transmission and short-term plasticity are maintained during hypoxic conditions.

Keywords: Electrophysiology
Hydrogen sulfide
Rhodamine
Short-term synaptic plasticity
Synaptic transmission
Western painted turtle
Advisor: Buck, Leslie
Developing a DNA Origami-based Nanoscale Ruler for Accurate Quantification of Proximity Probe Resolution

The spatial organization of transmembrane proteins helps to regulate intracellular signal transmission which contributes to biological processes and diseases. Bottom-up proximity-based methods of studying protein-protein interactions, such as proximity ligation assay (PLA), offer the ability to study protein proximity in a high-throughput manner. However, although probe designs evolve, the theoretically stated spatial resolution does not reflect these modifications. This thesis proposes the generation of a DNA origami-based nanoscale molecular ruler to rapidly quantify PLA probe interactions at defined separation distances. Successful generation of the DNA nanogrid enabled us to validate the distance dependency of PLA through the interactions of anchored oligonucleotides, where an exponential decay in PLA signal was observed. Current efforts attempt to adapt this ruler to evaluate whole-probe resolution by improving target-specific PLA probe binding. By permitting rapid and accurate quantification of probe resolution, this nanoscale ruler will assist in making more biologically relevant hypotheses about protein-protein interactions.

Advisor: Chou, Leo Y. T.
Neutrophil Development and Function in a Murine Model of Severe Acute Malnutrition

Severe malnutrition is associated with life-threatening complications and underlies morbidity and mortality in children under five. Immune dysregulations, especially of innate immunity, underlies these adverse outcomes. I used a lipopolysaccharide (LPS)-challenged protein restriction mouse model to investigate the impact of malnutrition and acute inflammation on neutrophil biology, the first responders of innate immunity that remain understudied in malnutrition. Following LPS, the malnourished mice were more susceptible to disease and mortality. Neutrophils (Ly6G+ cells) were expanded in the lungs of malnourished mice. However, neutrophil-mediated ROS production was reduced. Gene expression of transcription factors was also reduced in the bone marrow of these mice. These transcription factors control the gain of neutrophil effector functions throughout development. Therefore, this evidence points to changes in the neutrophil-intrinsic program driving increased susceptibility of the malnourished mice to mortality following acute inflammation. Overall, this study provides a novel understanding of neutrophil responses in malnutrition and inflammation.

Keywords: Acute Inflammation
Anti-Microbial Functions
Cellular Differentiation
Malnutrition
Mouse Model
Neutrophils
Advisor: Bandsma, Robert
Farooqui, Amber
Design and Manufacturing of an Encapsulation for a High-temperature Ultrasonic Transducer

This thesis describes the design and manufacturing of an encapsulation for a high-temperature ultrasonic transducer to operate in the temperature range of 25℃ to 650℃. The internal transducer components are a lithium niobate piezoelectric crystal, a porous zirconia attenuative backing layer, a stainless steel matching layer, and annealed silver foils as the ultrasonic coupling agents. An encapsulation design was proposed to comply with the specifications set by an industrial partner. This design was then modeled in the COMSOL Multiphysics® finite element package to analyze its mechanical and ultrasonic behavior. After design refinements, a prototype transducer was developed and tested in the temperature range of 25℃ to 650℃. Ultrasonic echo signal produced by the prototype had a Signal-to-Noise ratio (SNR) of ~31 dB and half-power (-3 dB) bandwidth of ~70%.

Keywords: Design
Nondestructive testing
Transducer
Ultrasound
Advisor: Sinclair, Anthony
Characterization of Abscisic Acid Transport in Arabidopsis thaliana and Brassica napus

The phytohormone abscisic acid (ABA) plays an important role in regulating numerous plant processes such as seed maturation, seed dormancy, and stress responses. These regulations require the long-distance movement of ABA in plants, which has been documented and requires a proper network of ABA transporters. Positron Emission Tomography (PET) in planta allows a real-time and non-destructive method for studying the movement of small molecules using a radiotracer. We show that 3’-F-ABA displayed similar bioactivity as ABA via ABA-responsive β-glucuronidase (GUS) reporter expression in Arabidopsis thaliana. In addition, the destructive phytochemical analysis of Brassica napus plants co-applied 3’-F-ABA and deuterium-labeled ABA (d6-ABA) showed a similar distribution pattern. Arabidopsis transporter mutants (abcg25, abcg40, ait1) showed delayed GUS expression in shoots which suggests that ABCG25, ABCG40, and AIT1 are required for the quick transport of ABA from root to shoot. Lastly, several ABA analogs were found to be candidates for ABA transport inhibitors.

Keywords: Abscisic Acid
Abscisic Acid Transport
Arabidopsis thaliana
Brassica napus
Positron emission tomography
Advisor: Nambara, Eiji
Developing a DNA Origami Based In Vitro Antigen Presentation Platform

DNA Origami is a novel tool with the capacity to generate arbitrary shapes at the nanoscale. A powerful application of this technique has been to interrogate the nanoscale dynamics governing immune cell triggering. B cells are a major component of the adaptive immune system, whose primary roles are to directly participate in immune responses through antibody production, and by augmenting T cell responses. However, the exact requirements of nanoscale antigen organization driving B cell triggering remain poorly characterized. We sought to address this gap, by harnessing the programmability of DNA origami to establish an in vitro reconstitution platform for antigen presentation on a supported lipid bilayer (SLB) system. In a cellular context, we found that BCR microclusters were efficiently generated, and that their production was correlated with antigen concentration. Future work will be aimed at further developing this platform to refine the precision of its antigen presentation capabilities.

Keywords: B cell receptors
B cells
DNA Nanotechnology
DNA Origami
Immunology
Advisor: Chou, Leo Y.T.
The Use of Primary Care Electronic Medical Record Data in the Prediction and Identification of Health Service Use

Primary health care (PHC) services play an essential role in reducing health system burden, including within emergency departments (ED) and hospitals. The longitudinal nature and population-based approach of primary care contributes to electronic medical record (EMR) data which is a rich source of information on patients and health service use. A review of theliterature on using primary care EMR data to predict ED visits, hospitalizations, and mortality was conducted. Thirty-one studies were included, and several common elements were identified to contribute value to the prediction of health service use. Next, case-finding algorithms to identify hospitalizations and ED visits were developed and validated within PHC. The best performing algorithms for hospitalizations demonstrated good agreeance with reference standards (ICC = 0.71-0.78) and excellent agreeance for ED visits (ICC = 0.87-0.92). This research provides a foundation for advancing the use of primary care EMR data to predict health service use and outcomes.

Keywords: electronic medical record
emergency department
health prevention
hospitalization
predictive analytics
primary health care
Advisor: Pinto, Andrew D
Benchmarking the Robustness of Deep Learning Segmentation Models to Out-of-distribution and Corrupted Data in MR Neuroimaging

A principal challenge in the large-scale deployment of deep neural networks (DNNs) in neuroimage analysis is the potential for shifts in signal-to-noise ratio, contrast, resolution, and presence of artifacts (i.e., distribution shifts) from site to site due to variances in scanners and acquisition protocols. Currently, there are no benchmarking frameworks to assess the robustness of DNN-based models to distribution shifts in MRI, and accessible multi-site benchmarking datasets are still scarce or task-specific. To address these limitations, we develop a platform providing modules for generating benchmarking datasets using transforms that model distribution shifts in MRI and newly derived benchmarking metrics. We apply our methodology to hippocampus, ventricle, and white matter hyperintensity segmentation in several large studies, demonstrating that modern DNNs are highly susceptible to distribution shifts in MRI and that data augmentation strategies and architectural design considerations (e.g., U-Nets vs. transformer-based models) have significant implications for robustness to particular transforms.

Keywords: Benchmarking
Corruptions and artifacts
Generalizable deep learning
MRI
Out-of-distribution data
Segmentation
Advisor: Goubran, Maged
Climate Risk Modeling and Quarterly Sales Forecasting for North American Retail Companies

This thesis introduces a method for quantifying the impact of extreme weather on retail companies. The method uses four machine learning models to label extreme weather during a given time period, and then uses a Seasonal Autoregressive Integrated Moving Average model (SARIMA) to predict a company's quarterly sales revenue and sales momentum. In our study of six retail companies located in Canada and the United States, this method demonstrated up to a 40.98% improvement in sales revenue forecasting compared to a general model that did not consider climate risk, and up to an 18.75% improvement in predicting sales momentum. This approach can predict a company's sales before it releases its quarterly report by using existing weather information, greatly improving investors' understanding of a company's climate risk exposure and helping them better predict its financial situation while effectively hedging climate risk in their investment portfolios.

Advisor: Lawryshyn, Yuri
Monitoring and Controlling Respiratory Effort in Acute Hypoxemic Respiratory Failure

Ventilation and sedation are used to manage acute hypoxemic respiratory failure (AHRF), but their individual and interactive effects on respiratory effort (|∆Pes|) and lung-distending pressure (∆PL,dyn) are unknown. This is a secondary analysis of a trial of a lung- and diaphragm-protection strategy in patients with AHRF, where ventilator settings and sedation were systematically manipulated to optimize |∆Pes| and ∆PL,dyn. The study showed that propofol attenuates |∆Pes| and ∆PL,dyn. Sedation with fentanyl was associated with lower respiratory drive, but not with lower respiratory effort. Increasing inspiratory pressure also attenuated |∆Pes|, but not ∆PL,dyn. The effect of inspiratory pressure varied according to the propofol dose: increasing inspiratory pressure resulted in higher ∆PL,dyn in patients receiving higher propofol dose. Patients on VV-ECMO had lower |∆Pes| and required lower propofol dose to control respiratory effort. This study highlights the complex interactions between interventions to modulate respiratory effort and provides insights on optimal management strategies.

Keywords: Acute hypoxemic respiratory failure
Lung and diaphragm protective ventilation
Respiratory effort
Ventilator induced diaphragm dysfunction
Ventilator induced lung injury
VV-ECMO
Advisor: Goligher, Ewan C
Ferguson, Niall D
The Effects of Radiotherapy on Tumour Microvasculature: Insights from Optical Coherence Angiography and Dynamic Contrast-Enhanced Magnetic Resonance Imaging Towards Adaptive Radiation Medicine

The efficacy of hypofractionated radiotherapy (RTx) protocols may potentially be improved as its mechanism of action remains unknown. It has been hypothesized that microvascular damage assumes an increasingly important role as the dose levels increase. We investigate this pre-clinically in human pancreatic cancer xenografts grown in a murine dorsal skinfold window chamber model. A pipeline enabling longitudinal monitoring of both micro- (via optical coherence tomography angiography (OCTA)) and macro- (via dynamic contrast enhanced magnetic resonance imaging (DCE-MRI)) vascular responses to irradiation was developed. We studied responses to single fraction irradiation (10, 20 and 30 Gy). New metrics describing the microvascular heterogeneity were longitudinally extracted from OCTA and appear to be promising predictive biomarkers for tumour response. High Spearman correlations up to ~0.8 (p<10^-4) between OCTA and DCE-MRI derived metrics were obtained, towards bridging the resolution gap. Insights from the developed experimental pipeline may improve our understanding of hypofractionated RTx radiobiology, towards adaptive radiation medicine. L'efficacité des protocoles de radiothérapie hypofractionnée (RTx) peut potentiellement être améliorée car son mécanisme d'action reste inconnu. Il a été postulé que les dommages microvasculaires jouent un rôle de plus en plus important à mesure que les niveaux de dose augmentent. Nous étudions cela de manière préclinique dans des xénogreffes de cancer du pancréas humain cultivées dans un modèle murin de chambre à fenêtre de pli cutané dorsal. Une méthodologie permettant la surveillance longitudinale des réponses micro- (via l'angiographie par tomographie à cohérence optique (OCTA)) et macro- (via l'imagerie par résonance magnétique à contraste dynamique (DCE-IRM)) à l'irradiation a été développé. Nous avons étudié les réponses à une irradiation à fraction unique (10, 20 et 30 Gy). De nouvelles mesures décrivant l'hétérogénéité microvasculaire ont été extraites longitudinalement de l'OCTA et semblent être des biomarqueurs prédictifs prometteurs pour la réponse tumorale. Des corrélations de Spearman élevées jusqu'à ~0,8 (p <10^-4) entre les mesures dérivées de l'OCTA et du DCE-IRM ont été obtenues, en vue de combler l'écart de résolution. Les résultats obtenus à partir de la nouvelle méthodologie expérimentale développée peuvent améliorer notre compréhension de la radiobiologie RTx hypofractionnée, vers une médecine radiologique adaptative.

Keywords: Imaging
Microvasculature
Pre-clinical
Radiotherapy
Translational
Tumours
Advisor: Vitkin, Alex I.
Efficient Generation of Pancreatic Progenitor Cells from Induced Pluripotent Stem Cells Derived from a Non-Invasive and Accessible Tissue Source – The Plucked Hair Follicle

The development of induced pluripotent stem cell technology has revolutionized regenerative medicine by providing innovative approaches for disease modeling, drug testing, and cell replacement therapies. Patient-specific, stem cell-based therapies offer the advantage of reducing the risk of adverse reactions due to immune rejection. However, the manufacturing of autologous therapies is still expensive and complex, making them commercially unviable. The use of hair follicle-derived induced pluripotent stem cells (HF-iPS), which can be obtained non-invasively and transported via regular mail, makes them an ideal starting material for an autologous biobank. In this study, cryopreserved HF-iPS lines were generated using integration-free vectors from a diverse group of participants, and their therapeutic potential was confirmed through direct differentiation towards the pancreatic cell lineage.

Keywords: Autologous Cell Therapy
Cell Banking
Hair Follicles
Induced Pluripotent Stem Cells
Regenerative Medicine
Stem Cells
Advisor: Rogers, Ian IR
Tactile Sensing for Monitoring Tissue Interaction Forces on Miniaturized Intraventricular Neurosurgery Robotic Tools

Researchers have developed miniaturized neurosurgical robots for use in RMIS pediatric intraventricular surgeries, but there is a risk of tissue trauma due to loss of sensory information during the procedures. The aim of this thesis is to improve surgical experience through haptic feedback, achieved by incorporating tactile and force information through the development of tactile sensors. These sensors were made using screen printing techniques and subjected to tests that simulate tool-tissue interaction forces to evaluate their performance. A resistive tactile sensor has been created for the end-effector tip to measure contact forces, while an ultra-thin capacitive tactile sensor has been developed for the inner gripper to optimize grasping. This research has the potential to lead to the fabrication of low-cost, sensitive, disposable, and biocompatible tactile sensors. This will contribute to the development of minimally invasive surgical tools and improve the safety and quality of RMIS pediatric neuroendoscopic surgeries.

Keywords: Capacitive sensor
Minimally Invasive Surgery
Neurosurgery
Piezoresistive sensor
Surgical Tool
Tactile Sensing
Advisor: Naguib, Hani E.
Diller, Eric
The Impact of Online Learning on Language Development in French Immersion.

This study investigated the impact of online learning during the pandemic on language and reading development among French Immersion (FI) students. The in-person cohort consisted of 72 students, 51 students in grade 1 (M= 80.32 months, 28 males) and 21 students in grade 2 (M= 92.86 months, 9 males). The online cohort consisted of 65 students, 18 students in grade 1 (M= 82.56 months, 18 males) and 47 students in grade 2 (M= 91.93 months, 15 males). ANCOVAs were carried out to assess the effect of cohort and grade on vocabulary knowledge, word reading accuracy, word reading fluency and phonological awareness in English and French, with guardian education as a covariate. Students in the in-person cohort performed significantly better on French vocabulary than students online. Grade 2 students significantly outperformed grade 1 students in word reading. This study shows that online learning negatively impacted bilingual children’s L2 vocabulary development.

Keywords: Bilingualism
French Immersion
Online learning
Pandemic
Second language learning
Advisor: Chen, Xi
Branched GDGTs in Modern Soils in NW Canada and Late Pleistocene Loess Deposits in Eastern Beringia

Branched glycerol dialkyl glycerol tetraethers (brGDGTs) have been applied as a biomarker for past terrestrial temperatures; however, despite their abundance in soils globally, avenues for applying this biomarker to high-latitude regions have been little explored. This thesis uses i) modern soils from northwestern Canada (Whitehorse to Tuktoyaktuk) to test the applicability of existing globally calibrated brGDGT proxies and uses ii) late Pleistocene loess from the Klondike Goldfield region to apply said proxies. Local calibrations of brGDGT proxies in the eastern Beringian region are found to be very similar to their corresponding global calibrations, removing the need for local calibrations altogether. Reconstructions of late Pleistocene temperatures using brGDGTs uncover a temperature depression of 10°C during MIS 2 (presumably including the Last Glacial Maximum) compared to modern—a depression found by other studies. This research supports the use of globally calibrated brGDGT proxies in high-latitude regions.

Keywords: Acidobacteria
Beringia
Calibration
GDGT
MIS 2
Pleistocene
Advisor: Porter, Trevor J