VictorJuiz/thesis huggingface dataset:
The Effects of Radiotherapy on Tumour Microvasculature: Insights from Optical Coherence Angiography and Dynamic Contrast-Enhanced Magnetic Resonance Imaging Towards Adaptive Radiation Medicine
Keywords: Imaging
Microvasculature
Pre-clinical
Radiotherapy
Translational
Tumours

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.
Efficient Generation of Pancreatic Progenitor Cells from Induced Pluripotent Stem Cells Derived from a Non-Invasive and Accessible Tissue Source – The Plucked Hair Follicle
Keywords: Autologous Cell Therapy
Cell Banking
Hair Follicles
Induced Pluripotent Stem Cells
Regenerative Medicine
Stem Cells

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.
Tactile Sensing for Monitoring Tissue Interaction Forces on Miniaturized Intraventricular Neurosurgery Robotic Tools
Keywords: Capacitive sensor
Minimally Invasive Surgery
Neurosurgery
Piezoresistive sensor
Surgical Tool
Tactile Sensing

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.
The Impact of Online Learning on Language Development in French Immersion.
Keywords: Bilingualism
French Immersion
Online learning
Pandemic
Second language learning

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.
Branched GDGTs in Modern Soils in NW Canada and Late Pleistocene Loess Deposits in Eastern Beringia
Keywords: Acidobacteria
Beringia
Calibration
GDGT
MIS 2
Pleistocene

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.
Development of Nanomaterial-Modified Electrochemical Sensors for the Analysis of Nucleic Acids
Keywords: Bioelectrochemistry
Chemical Neuroscience
Electrochemistry

Research in the quest for advanced and innovative diagnostic tools has driven the healthcare and pharmaceutical industry to explore new frontiers in biosensing technologies, with electrochemical sensors showing great promise in detecting biomarkers for DNA damage and oxidative stress. This thesis focuses on the detection of Guanine (G), Inosine (INO), and 8-hydroxyguanine (8-OH-G), biomolecules relevant to understanding the onset and progression of neurodegenerative diseases like Alzheimer’s. The working electrode surface has been modified in various ways, including the creation of multi-walled carbon nanotube iron oxide nanoparticles (MWCNT-Fe3O4 NPs) and glassy carbon electrode 4-thiophenol-gold nanoparticles (GCE-Ph-S-AuNPs), to develop an electrochemical platform for decentralized point-of-care testing. These modifications, along with nanotechnology, enable simultaneous detection of G, INO, and 8-OH-G with high accuracy. This thesis demonstrates the potential of microfabrication for developing simple point-of-care devices that allow timely and accurate diagnoses of neurodegenerative diseases, leading to improved patient outcomes and quality of life.
Software for Embedded and Formation Flying Systems to Support Growing Operational Complexities of Constellation Missions
Keywords: Embedded Systems
Flight Software
GNC
Satellite Constellations
Satellite Formation Flying
Satellite Operations Software

The last decade has seen numerous small satellite constellation missions being flown owing to their rising popularity for terrestrial and deep-space applications. This can be partly attributed to rapid technological advancements in distributed satellite systems increasing mission capabilities and attracting commercial, academic, and government institutions to establish a wide-reaching space presence. This thesis presents the development of two major software systems at the Space Flight Laboratory (SFL), with the overarching objective of supporting the growing computational and operational complexities of large-scale constellation missions. The design of the first software application, the OBC-400 Automated Testing Software (OATIS), will be presented in addition to how it fits into the space heritage accumulation plan for the SFL next-generation On-Board Computer. This on-orbit technology demonstration powered by OATIS will take the first step in incorporating advanced hardware into all future SFL missions, with its debut in the Commercial Constellation Mission designed and built by SFL, set to launch in the fall of 2023. The design of the second software application, the Constellation Formation Operations Planning Software (C-FOPS), will be presented in addition to the underlying formation control algorithms implemented within it. This software aims to reduce ground-based operations complexity related to prominent constellations of formation flying spacecraft. This software automates an end-to-end pipeline for formation maintenance operations planning for all currently on-orbit and future satellite clusters in the larger Commercial Constellation Mission. This thesis builds on foundational knowledge in orbital dynamics, formation flying, and the characteristics of embedded systems in satellites, implementing practical software solutions to enhance ground-based and on-orbit mission capabilities. OATIS and C-FOPS are designed for use in the majority of future SFL missions, with their debut being the ninth installment of the Commercial Constellation Mission set to launch in the fall of 2023.
Studies to Characterize the Neuroprotective Targets of Lipoxin B4
Keywords: ctnna1
glutamate
ht22
knockdown
lipoxin
xtt

Recent discoveries have shown that lipoxin A4 (LXA4) and lipoxin B4 (LXB4) in astrocyte conditioned media that conferred neuroprotection in vivo and in vitro. LXB4 is of interest, as it shows higher potency and protection against glutamatergic stressors compared to LXA4. However, LXB4 binding targets and its downstream mechanisms are unclear. I hypothesized that LXB4 binds to distinct receptors from LXA4 to elicit its unique neuroprotective activities. I established an in vitro screening model of neuronal degeneration to evaluate LXB4 analog bioactivities, which were used as probes to investigate LXB4 binding partners through pulldown studies and receptor binding assays. In follow up work I discovered that LXB4 binds to Ctnna1 and Spt6, and that physical interaction of both targets are linked to its neuroprotection. Together, these findings reveal undiscovered LXB4 binding targets linked to neuroprotection, allowing future studies to investigate the downstream signaling involved in this activity.
Functionalized DNA Tetrahedron for Concomitant Delivery of Doxorubicin and Paclitaxel to HER2+ Breast Cancer Cells
Keywords: Breast Cancer
Chemotherapy
DNA Nanotechnology
Drug delivery

Breast cancer is the most common cancer among women. Current chemotherapeutics present low solubility and selectivity, requiring toxic excipients in formulations and causing several dose-limiting side effects. Here, we describe the modification of a DNA tetrahedron (TDN), where alkyl chains were placed at the nanostructure's core, for encapsulation of the hydrophobic drug paclitaxel (PTX). In addition, a HER2+ aptamer was attached to the outside of the DNA nanostructure in an attempt to increase its target ability. The functionalized TDN can be loaded with PTX and doxorubicin (DOX), through base-pair interaction, for concomitant delivery into MCF7 cells. Therefore, results indicate that the drug carrier system described in this thesis increases cancer cell morbidity with a lower applied drug concentration, reducing side effects for breast cancer patients. This system presents approaches amenable to the delivery of other clinically relevant hydrophobic drugs or drug combinations.
Role of Dapagliflozin in Attenuating Right Ventricular Remodelling: Transverse Aortic Constriction Model
Keywords: biventricular disease
dapagliflozin
heart failure
right ventricle remodelling
sodium glucose co transporter 2
sodium glucose co transporter 2 inhibitor

Heart Failure (HF) might be better considered a biventricular disease whereby left ventricular (LV) dysfunction leads to right ventricular (RV) dysfunction and vice versa. Structurally, the two chambers not only share a common septum and a pericardial space, but also share myocyte bundles that cross between the ventricles. Dapagliflozin is a sodium glucose linked co-transporter 2 (SGLT2) inhibitor that has recently been shown to improve heart function in the setting of diabetes. However, the effect of dapagliflozin on HF in a non-diabetic setting is unknown. Currently, dysfunction of the RV does not have a treatment strategy that has displayed a reduction in mortality. Therefore, we hypothesized that by reducing excess fluid volume, dapagliflozin will reduce RV chamber dilatation and wall tension, thereby leading to a reduction in RV hypertrophy and improved function. We utilized transverse aortic constriction (TAC) to induce pressure overload and administered one of three treatments: vehicle, dapagliflozin or perindopril, an angiotensin-converting enzyme inhibitor. At end study, measurement for biochemistry, echocardiography and cardiac catheterization took place. Overall, our results demonstrate a neutral impact by dapagliflozin, on a pressure overload induced model of TAC.
Neuropathology of Late Life Depression: Clinical Predictors of Amyloid and Tau Neuropathology in Non-demented Older Adults with Depression
Keywords: Alzheimer's disease
amyloid
late-life depression
neuropathology
tau

Previous studies regarding the relationship between late-life depression and Alzheimer’s amyloid and tau neuropathology have reported conflicting findings. This study is a cross-sectional post-mortem study of non-demented older adults in the 2005-2020 National Alzheimer’s Coordinating Center database (n=395; 94 Thal [spread of amyloid pathology beyond the neocortex], 393 Braak [spread of tau pathology], 394 CERAD [density of amyloid neuritic plaques]). Those who had recent depression (within previous 2 years) were more likely to have higher Thal phase compared to those without a history of depression (OR=13.3, p=0.019). Depression was not associated with CERAD or Braak scores. Sex or apolipoprotein-E did not moderate their associations. The relationship between late-life depression and Alzheimer’s neuropathology may be explained by spread of amyloid pathology beyond the neocortex to involve subcortical regions implicated in regulation of mood and motivated behaviour, which may be therapeutic targets for the prevention of Alzheimer’s dementia in this population.
Comparative Study of Anomaly Detection in Financial Journal Entries using Machine Learning and Deep Learning Methods
Keywords: Anomaly Detection
Computer-assisted Audit Tools and Techniques (CAATs)
Deep Learning
Intelligent Systems In Accounting
Journal Entry
Machine Learning

In this thesis, we compare the deep neural network's ability to detect anomalous journal entries in large-scale accounting data with the use of state-of-the-art classification methods. We train and test methods including logistic regression (LGR), support vector machine (SVM), random forest (RF) and deep neural networks (DNNs), on a real-world dataset, which contains 2.2 million journal entries. We show that a lightweight DNN out-performs LGR and SVM by a significant margin in terms of area under the receiver operating characteristic curve. Though RF has a close performance to DNN, DNN still performs slightly better and its updating friendly structure also makes it more suitable for long-term use in a production environment. In addition, we compute the permutation feature importance to improve our DNN's interpretability. We also present a strategy to properly optimize the precision-recall trade-off according to different needs in real-world scenarios.
Sustained Metabolic Benefits of Intermittent Fasting
Keywords: Calorie restriction
Dieting
Intermittent fasting
Metabolic health
Post-dietary
Weight regain

The prevalence of obesity and metabolic disorders are significantly increased. Diet interventions have been widely practiced to counteract obesity and metabolic disorders due to its flexibility, customizability and independence of pharmacological agents. While calorie restriction (CR) is a commonly practiced diet, it has been shown to be difficult to adhere to from a long-term perspective due to its stringent dietary restrictions. Additionally, body weight regain and subsequent metabolic deterioration have been reported as adverse effects after withdrawal of the intervention (post-dietary effects). Periodic energy restriction regimens such as intermittent fasting (IF) has gained interest due to its flexibility and has been extensively studied both in preclinical and clinical settings. While we and others have previously demonstrated that IF alleviates metabolic syndromes and counteract obesity, the IF post-dietary effects of IF remain unclear. My study aims to specifically investigate the sustainability and potential drivers of IF mediated post-dietary benefits.
Non-destructive Method for Measuring In-situ Stress of Concrete
Keywords: Concrete
In-Situ
Non-Destructive

Current conventional methods of determining in-situ stresses within concrete involves the destruction of the structural components to some degree in order to obtain measurable data. In theory, if changes in mechanical properties of concrete can be imposed in a non-destructive way, the resulting displacements can be measured to determine in-situ stresses. There is limited knowledge about the behavior of concrete under sub-zero temperatures, particularly in the cryogenic range where the concrete experiences a significant change in its elastic modulus. This thesis investigates the feasibility of using liquid nitrogen as a non-destructive method of inducing changes in concrete’s elastic modulus and measuring the resulting thermal displacement from which the in-situ stresses can be inferred. By analyzing a detailed model simulating this condition, results suggest that calibration charts may be produced which map in-situ stresses as a function of the measured displacement over time.
Body Adiposity and Brain Structure in the Mouse: A Potential Role of Neuroinflammation
Keywords: MRI
neuroinflammation
obesity
systemic inflammation

Human cross-sectional studies suggest that obesity adversely impacts the brain. These studies, however, do not establish causality nor enhance understanding of cellular changes. Here I placed 8-week-old male and female mice on high-fat diet (HFD, or normal diet [ND]) for 12 weeks and performed longitudinal in vivo T1-weighted magnetic resonance imaging of the brain and ex vivo immunohistochemistry. HFD (vs. ND) males and females showed higher increases in body adiposity, and they showed lower age-related increases in the whole-brain, corpus callosum and hippocampus volumes, and higher age-related decreases in the cerebral cortex volume. Only HFD (vs. ND) males showed higher age-related increases in normalized T1-weighted signal intensity in the hippocampus. HFD-induced increases in adiposity interfere with the natural growth of the brain and alter brain microstructure. Some of these effects are sex specific.
Trade, Trust, and Testamentary Practice in Late-Medieval London: Commerce and Continuity in the Romeyn–Burford Family, 1280–1330
Keywords: Family Strategy
Medieval London
Medieval Wills
Merchants
Roesia Burford
Trade and Commerce

This thesis provides the most detailed study to date of a merchant family active in thirteenth- and fourteenth-century London. In two parts, it charts the commercial life cycle of a family of prominent London pepperers over a fifty-year period, from 1280 and 1330. Part one analyzes the family’s economic activities, trade relationships, and its means of ensuring the generational continuity of commerce and the transmission of land and capital. It concludes with a case study of the continuation of merchant commerce by a widow, Roesia Burford. Part two probes the extensive testamentary evidence connected to the family, illuminating the trust-based relationships between testators and executors and reconstructing the executors' activities in detail. The resulting portrait of the family’s activity over multiple generations contributes to the historiography of London’s mercantile milieux and provides novel insight into the relationship between commerce, family strategy, and testamentary practice.
Characterization of Novel Anti-VEGFR Antibodies to Develop Agonists Targeting Mesoderm Differentiation
Keywords: Agonist
endothelial cells
Phage display antibodies
Protein engineering

Novel antibodies against VEGF receptors were produced and characterized to develop agonists for targeted mesoderm differentiation. A major drawback underlying mesoderm differentiation is the inefficient production of hemogenic endothelial cells (HECs) affecting self-renewal and differentiation abilities. HECs are found in the vasculature of the embryo and are a promising source of cells for revascularization of damaged tissues. Therefore, these cells required optimization for application in endogenous tissue repair. This work aimed to generate anti-VEGFR antibodies to replace natural growth factor VEGF by mimicking its agonistic activity as a more stable, specific, and cost-effective alternative for the use in the differentiation pathways of endothelial cells. As a result, 16730 Diabody was identified as a specific agonist of VEGFR-2. The signaling assays unequivocally demonstrated its ability to agonize VEGFR-2 as potently as VEGF. This study demonstrates the benefit of engineered synthetic antibodies as agonists to receptor tyrosine kinase towards becoming therapeutic tools.