VictorJuiz/thesis huggingface dataset:
Modeling Congenital Heart Disease in Mice and Assessing its Effects on Fetal Brain Development
Keywords: Brain
Congenital heart disease
Imaging
Immunohistochemistry
Mouse
Neurodevelopment

In congenital heart disease (CHD), defined as structural defects of the heart that arise in-utero, neurocognitive deficits are common and are associated with brain dysmaturation in the perinatal period. Clinical studies involving CHD cohorts have shown an association between fetal brain abnormalities and hypoxemia, which is thought to result from altered cardiovascular physiology due to CHD. However, despite this association, it is not known whether the cardiac lesion in CHD causes cerebral hypoxia. Furthermore, given that factors such as shared genetic defects in heart and brain development and underlying placental disease may independently contribute to brain abnormalities, the extent to which hypoxemia/decreased substrate delivery is responsible for fetal brain dysmaturation in CHD is unknown. In this thesis, I examine whether fetal brain abnormalities can be directly caused by altered hemodynamics due to CHD. To investigate this question, I developed a surgically-induced, cardiac-specific mouse model of a CHD known as hypoplastic left heart syndrome (HLHS), which is clinically associated with hypoxemia and brain abnormalities. Next, I interrogated brain development in HLHS fetal mice using high-resolution magnetic resonance imaging (MRI) and immunohistochemistry. At a structural level, HLHS mice had volumetric reductions in compartments responsible for neurogenesis and white matter development, as observed clinically, and the size of these brain structures was partly determined by the size of the cardiac vessels. Furthermore, HLHS mice had volume loss in midbrain structures, which has not been previously observed. At a cellular level, HLHS mice had increased cerebral hypoxia and a decreased number of mature neurons globally. Given these results, I make the case that during development, altered cardiovascular physiology due to a severe cardiac lesion can directly cause brain dysmaturation at a structural and cellular level, independent of genetic factors. Furthermore, given that HLHS mice show evidence of cerebral hypoxia, therapies aimed at improving cerebral substrate delivery should be explored for improving neurological outcomes in the CHD population.
Rational Design of CO(2) Electroreduction Catalysts and their Chemical Micro-environments in Gas Diffusion Electrode Systems
Keywords: CO2
electrocatalysis
electrochemistry
electrolyzer
gas diffusion electrode
industrial decarbonization

A growing abundance of renewable low-carbon electricity coupled with CO2 capture and utilization are two critical components of global net-zero emissions plans. The electrochemical conversion of CO2 and CO into value-added chemicals and fuels is a promising strategy to electrify hard-to-decarbonize sectors of industry. Electrolyzers employing gas diffusion electrodes (GDEs) offer a means to elevate operational reaction rates to scalable regimes. In this thesis, I use experiment and atomistic simulations to investigate CO2 electroreduction property-performance relationships at multiple length-scales along the cross-section of a gas diffusion electrode. I begin with describing the need for industrial decarbonization, the role of CO2 electroreduction in hard-to-decarbonize chemicals manufacturing and renewable fuels production, and fundamental background information of the reaction from theoretical and experimental perspectives. I then conduct an experimental investigation into the effect of gas diffusion layer properties on electrochemical performance, finding a 100x increase in C2H4:CO ratio by tuning surface morphology to extend the residence time of locally-produced CO in the catalyst layer. I also experimentally explore catalyst:ionomer intefaces in the catalyst layer of the GDE, leading to a record ethylene partial current density of 1.3 A/cm2. I concluded from both experimental studies that *CO coverage on the catalyst surface, as a result of \ch{CO2} and CO concentrations in the local chemical environment of catalyst sites, was an important variable influencing selective chemical production. I applied this insight -- through two studies involving computational atomistic simulations -- to guide catalyst material design. I studied how low *CO coverage reaction environments favor methane selectivity on CuAu catalyst materials, leading to an experimental selectivity of 56% at a production rate of 112 mA/cm2. Conversely, I found that high *CO coverage regimes favor pathways to acetate production in the electrochemical CO reduction reaction, leading to an experimental selectivity of 91% at a production rate of 113 mA/cm2. I conclude with a reflection on future priorities to advance the technological readiness of CO2 electrolyzers. Broadly, the studies herein enable scientists and engineers to better understand the interplay between reaction chemistry and reactor design in gas diffusion electrode systems for CO2 and CO electroreduction.
A Social Cognitive Career Theory Approach to Understanding the Academic and Career Experience of Practical and Baccalaureate Nursing Students
Keywords: career
confidence
nursing
performance
SCCT
student

Background: There is a current and predicted nursing shortage. Recruitment and retention of nursing students are two of many factors that impact a nursing shortage. Understanding the profile of first semester nursing students and their academic and career development experiences may enhance the recruitment and retention of nursing students, which will help to ease the nursing shortage. In Ontario, the term nursing student includes two subcategories: practical nursing (PN) and Bachelor of Science in Nursing (BScN) students. Methods: Using a case study research design with a mixed methods methodology, the Social Cognitive Career Theory (SCCT) interest, choice, and performance models guided the exploration of first semester PN and BScN students. Sixty-nine students (32 PN; 37 BScN) completed a comprehensive survey questionnaire, 14 of whom also participated in interviews. The two programs were situated in the same geographical location. Factor analysis and multiple regression were used to assess the ability of the SCCT model variables (past performance, self-efficacy, outcome expectations and goals) to predict student performance as measured by first semester grades. Results: The main part of the study identified the similarities between PN and BScN students and highlighted the differences which were not captured with the use of the inclusive term nursing student. The main differences identified among the two groups included career choice factors, academic confidence, and career confidence. In addition, the SCCT model variables explained 48% of the variance for PN students and 40% of the variance for BScN students. Of all the independent variables, anatomy and physiology confidence and career confidence were statistically significant for PN students and for BScN students it was only anatomy and physiology confidence. Conclusions: Identifying the similarities and differences of PN and BScN student career development is important information for effective career counseling, recruiting, marketing, curriculum development, teaching, and policy development as they relate to the retention of nursing students, especially in times of nursing shortages. This study reinforces the importance of assessing not only the students’ academic performance as they move through the first semester of a nursing program, but also the students’ career confidence.
Optimizing Neuroimaging of Patients with Suspected Acute Stroke
Keywords: health services research
ischemic stroke
meta-analysis
neuroimaging
thrombolytic therapy

In patients with suspected acute stroke, prompt neuroimaging is required to determine eligibility for revascularization treatment, and earlier revascularization increases its benefit for patients of any age and any type of stroke severity; yet little is known about the frequency, predictors, and outcomes of timely neuroimaging. The objectives of this thesis were to (1) describe the characteristics of patients with suspected acute ischemic who do and do not receive timely neuroimaging; (2) assess the potential benefits of screening for suspected acute ischemic stroke with computed tomography perfusion (CTP) neuroimaging, within a meta-analysis of experimental and observational studies; and (3) assess outcomes of patients with suspected acute ischemic stroke who do and do not receive timely neuroimaging. In the retrospective cohort study of the time to neuroimaging in Ontario patients with suspected acute ischemic stroke, we found that 27.3% of patients with stroke-like symptoms who presented within the four-hour intravenous (IV) thrombolytic treatment window received timely neuroimaging. Neuroimaging delays were significantly influenced by several patient and hospital factors including a less severe stroke, longer time from symptom onset to presentation, female sex, and presentation to a rural hospital. The meta-analysis of outcomes among patients with acute ischemic stroke who were screened using perfusion computed tomography (CTP) imaging demonstrated that mortality, morbidity and symptomatic intracranial hemorrhage (SICH) rates appear favourable for patients selected with CTP imaging to receive IV thrombolytic treatment more than three hours after symptom onset. Finally, in our second retrospective cohort study we found that timely neuroimaging was associated with higher use of intravenous thrombolysis, no difference in the risk of hemorrhage or mortality, and a greater likelihood of disability at discharge. Overall, these results reaffirm the importance of multi-level efforts to optimize timely neuroimaging among patients who present with suspected acute stroke. Specific contributions of this work to the understanding of management, clinical decision-making and directions for future research in acute stroke neuroimaging and care are discussed.
Photodynamic Therapy During In Vivo Lung Perfusion for Treatment of Lung Metastases
Keywords: Dosimetry
Lung Injury
Lung Perfusion
Oncology
Optical Properties
Photodynamic Therapy

Isolated lung metastases in sarcoma and colorectal cancer patients are inadequately treated with current standard therapies. In Vivo Lung Perfusion, a novel platform, could overcome limitations to photodynamic therapy treatment volumes by using low cellular perfusate, removing blood, and thus theoretically allowing greater light penetration. Development of personalized photodynamic therapy protocols requires in silico light propagation simulations based on optical properties and maximal permissible photodynamic threshold doses of lung tissue. This approach aims to maximize the effective treatment dose to the lung while avoiding toxicity to healthy lung tissue. Based on this rationale, the overall objective of this thesis is to create a whole-lung perfusion assisted PDT protocol for the treatment of lung metastases demonstrating adequate safety and feasibility to guide clinical translation. To achieve this goal, the first aim is to quantify key biophysical properties necessary for PDT; specifically, the optical properties for blood and low-cellular perfusion and the photodynamic threshold dose for 5-ALA and Chlorin e6. This will demonstrate the difference in light penetration for low cellular perfusate vs. blood. The second aim of this work is to develop a 72-hr porcine In Vivo Lung Perfusion survival model to allow assessment of acute and delayed lung toxicity. This model is validated using an accelerated titration dose-escalation study of delivery of oxaliplatin chemotherapy. The final aim of this work involves combining the previous aims to develop a full treatment protocol. Firstly, a light delivery system is created that can homogenously deliver light to the entire lung, and using Monte Carlo simulation software, can be used to simulate personalized treatment plans. The safety and feasibility of a full treatment protocol of whole-lung perfusion-assisted photodynamic therapy is then demonstrated, examining the maximally tolerated doses of 5-ALA and Chlorin e6 photosensitizers. Overall, the protocols and knowledge from this work will provide the basis for Phase 1 clinical trials assessing the safety of whole-lung perfusion assisted PDT.
Tracking the Continuity of the Leviticus Laws of Genital Fluids in the Dead Sea Scrolls and Rabbinic Literature
Keywords: Dead Sea Scrolls
Hebrew Bible
Rabbinic Literature
Second Temple Literature

This comparative study explores Leviticus’ rules on the impurity caused by genital fluxes as attested in the Dead Sea Scrolls and rabbinic literature to shed light on the state of halakhah in the pre-rabbinic stage. Using the five impurity categories of genital fluxes outlined in Lev 15 and 12, this study demonstrates the Dead Sea Scrolls' relevance as a textual product of the Second Temple period for tracking the antiquity of some rabbinic halakhic rulings. As a starting point, an analysis of the biblical exposition of each impurity category is undertaken, noting hermeneutical, textual, and text-critical difficulties in the text but selectively limiting the detailed examination to problems that have implications in the attestation of these rules in the Dead Sea Scrolls or other Second Temple period texts in comparison with their attestation in the rabbinic literature. The study pays particular attention to variant readings found in ancient translations (the LXX and the Targumim) and the Samaritan Pentateuch, and to cases of word choices in the DSS and other Second Temple period texts. It contends that these variants and word-choices are hermeneutically pertinent to our understanding of the state of halakhah in the Second Temple period when verified by their conformity with a particular position on a halakhic issue for which rabbinic opinions diverge. The investigation leads to the conclusion that difficulties in the biblical text are responsible for many divergences or innovations in later attestations of the biblical rules, and that many rabbinic rulings can be linked to the innovations or polemical texts in the Dead Sea Scrolls or to variant readings in ancient translations or versions of the Hebrew Bible. This study stands out from other comparative approaches to the DSS and rabbinic texts which tend to have broader perspectives by narrowing down the scope of the investigation to one type of impurity to demonstrate from that standpoint how a textual, text-critical, and hermeneutical analysis of the Dead Sea Scrolls texts can yield valuable pieces of evidence on the state of halakha in the Second Temple period, and thus shed light on the trajectory of halakhic development.
Self-Centering, Shear-Controlling Rocking-Isolation Podium System for Enhanced Resilience of Tall Buildings
Keywords: base mechanism
higher-mode effects
rocking
seismic resilience
self-centering
tall buildings

The seismic performance of tall buildings has become a major consideration for the sustainable and resilient development of urban centers in earthquake-prone regions. One of the most critical design challenges using current prescriptive code-based design methods is to properly account for the contribution of higher modes of vibrations to the overall dynamic response of these structures, especially for reinforced concrete shear wall structures that are commonly used in tall building developments. It has been widely acknowledged that the actual seismic demands in these systems can be much larger than predicted when using simplified design equations. These higher-mode effects are primarily attributed to the amplified dynamic response of tall buildings at higher frequency modes that are not controlled by the designated plastic-hinging mechanism at the base. This amplified dynamic response can cause unexpectedly higher structural and non-structural damage, making these tall buildings more susceptible to service disruptions and extensive repairs following a major earthquake.Working towards more sustainable and resilient cities, the overarching objective of this thesis is to develop and validate a novel base system that can mitigate higher-mode effects and enhance the overall seismic performance of tall buildings. The proposed system is a dual base-mechanism system that enables independent control of the shear force and overturning moment demands at the base of tall buildings to mitigate higher-mode effects, while eliminating residual deformations and high-stress concentrations within the structure that otherwise would need to be designed for. A schematic overview of the proposed system is first presented, followed by the detailed design and numerical validation of a practical implementation of the system based on a benchmark 42-story tall building. Extensive shake table tests are performed on a scaled specimen with and without the proposed system, which experimentally demonstrated the enhanced seismic performance of the specimen with the proposed system. To better understand the influence of the proposed system on the overall seismic behaviour of tall buildings, a generalized parametric study was conducted. Based on these numerical and experimental studies, a comprehensive performance-based design methodology was developed and validated to assist engineers in the detailing of proposed system and the capacity design of the structures above.
Developing Efficient Electrocatalysts for Oxygen Evolution at High Current Densities
Keywords: CO2 reduction
Green hydrogen
Machine Learning
Material discovery
Metal oxides
Quantum-annealing

The energy efficiency of water electrolyzers is limited by the sluggish kinetics incurred by oxygen evolution reaction (OER) catalysts. Iridium oxide is a widely used OER catalyst that is both electrochemically active and stable, however, it proves uneconomic for large-scale application due to the scarcity and high cost of Iridium. Therefore, finding affordable alternatives is critical for scaling up water electrolysis. In this work, I devise material design strategies to develop Iridium-free catalysts that combine both activity and stability. I use advanced electrochemical characterization, electron microscopy, and synchrotron X-ray absorption to investigate the multimodal correlation between atomic structure, physical properties, and electrochemical performance.First, I develop a cryogenic ball-milling technique to synthesize Ni-Co-Se catalysts for alkaline OER. During OER, the electrocatalyst is anodized and Se is fully leched out of the structure forming a disordered -NiCoOOH. The resulting electrocatalyst demonstrates an exceptional performance maintaining an overpotential of 279 mV at 0.5 A.cm-2 for 500 hours. I find that introducing structural disordering in the pre-catalyst promotes the evolution of highly active and stable structures. Next, I use quantum-inspired search to accelerate the discovery of active OER catalysts in acid. I build surrogate models based on band structure to screen the theoretical overpotential for a vast space of rutile mixed-metal oxides. Then, I identify candidates with superior performance and validate the predictions experimentally. As a result, I show that the best candidate Ru0.58Cr0.25Mn0.08Sb0.07Ox demonstrate eight times improvement in mass activity compared to RuO2. Finally, I use crystal graph convolutional neural networks and computational descriptors to optimize the acidic stability of OER catalysts. I find that incorporating Ti increases the metal-oxygen covalency and Pourbaix dissociation energy of RuO2 resulting in improved electrochemical stability. The best candidate Ru0.6Cr0.2Ti0.2O2 demonstrate OER for 200 hours at 0.1 A.cm-2. I reveal that the formation of a metastable structure consisting of a strong Ti-O network and a hydrous Cr-O passivation layer slowed the dissolution of Ru by 20 times. The findings in this thesis demonstrate the role of machine learning and advanced characterization in guiding catalyst design paving the way for commercializing water electrolysis at scale.
In vivo Screening Reveals Epigenetic Regulation of Mammary Epithelial Lineage Integrity and Tumorigenesis
Keywords: Breast Cancer
CRISPR screening
Epigenetics
Mammary gland biology

Systematic investigation of the scores of genes mutated in cancer to discern disease drivers from inconsequential bystanders is a prerequisite for precision medicine but remains challenging. Here, I developed a somatic CRISPR/Cas9 mutagenesis screen to study 215 genes that are recurrently mutated in ~2-10% of human breast cancers but lacked thorough study. Screen results revealed epigenetic regulation as a major tumor suppressive mechanism. I identified components of the COMPASS-like and PR-DUB complexes, including KDM6A, ASXL1/2, BAP1 and KMT2C, function as epigenetic tumor suppressor genes (EpiDrivers) that cooperate with PIK3CAH1047R to transform mouse and human breast epithelial cells. Mechanistically, I found that activation of PIK3CAH1047R and concomitant loss of EpiDrivers triggered an alveolar-like lineage conversion of basal mammary epithelial cells and accelerated formation of luminal-like tumors. Mutations in EpiDrivers are found in ~39% of human breast cancers and casein expression can be seen in ~50% of ductal-carcinoma-in-situ, suggesting that lineage infidelity and alveologenic mimicry may significantly contribute to early steps of breast cancer etiology.
Detecting and Monitoring Wildlife Parasites: Determining the Current Extent and Future Impact of the Winter Tick (
Keywords: cervid
citizen science
climate change
disease ecology
integrated data
parasite

The causes and consequences of species’ distributional change has long been of interest in ecology, but it is of ever-pressing importance given increasingly rapid changes to both climate and land. Escalation of established and novel parasite populations in space and time within northern ecosystems has led to growing concern for the health of potential wildlife hosts, but the initial detection, monitoring, and trajectory of wildlife parasites in remote subarctic and Arctic regions is challenging to study and difficult to predict. In this thesis I examine the distribution of the winter tick,