VictorJuiz/thesis huggingface dataset:
Development of Nanomaterial-Modified Electrochemical Sensors for the Analysis of Nucleic Acids

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.

Keywords: Bioelectrochemistry
Chemical Neuroscience
Electrochemistry
Advisor: Kerman, Kagan KK
Software for Embedded and Formation Flying Systems to Support Growing Operational Complexities of Constellation Missions

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.

Keywords: Embedded Systems
Flight Software
GNC
Satellite Constellations
Satellite Formation Flying
Satellite Operations Software
Advisor: Zee, Robert E
Studies to Characterize the Neuroprotective Targets of Lipoxin B4

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.

Keywords: ctnna1
glutamate
ht22
knockdown
lipoxin
xtt
Advisor: Sivak, Jeremy J
Functionalized DNA Tetrahedron for Concomitant Delivery of Doxorubicin and Paclitaxel to HER2+ Breast Cancer Cells

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.

Keywords: Breast Cancer
Chemotherapy
DNA Nanotechnology
Drug delivery
Advisor: Magalhaes, Marco A
Carneiro, Karina M
Role of Dapagliflozin in Attenuating Right Ventricular Remodelling: Transverse Aortic Constriction Model

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.

Keywords: biventricular disease
dapagliflozin
heart failure
right ventricle remodelling
sodium glucose co transporter 2
sodium glucose co transporter 2 inhibitor
Advisor: Connelly, Kim A
Statistical Issues in Epigenome-Wide Association Studies

Two statistical issues in epigenome-wide association studies were explored. Correlated CpGs leading to conservative Bonferroni correction, as well as confounded CpG-quantitative trait associations as a result of within-probe SNPs. First, empirical permutation-based significance thresholds were less stringent than the Bonferroni-corrected and thus should be used to account for correlated CpGs. Second, in the presence of within-probe SNPs, a joint test of CpG and SNP-specific CpG effects on quantitative traits was a powerful alternative to the traditional marginal CpG test, where quantitative traits were modelled by CpGs only. As such, the traditional marginal CpG test and the joint test should be used in conjunction in epigenome-wide association studies, for CpGs without and with within-probe SNPs, respectively.

Advisor: Paterson, Andrew D
Neuropathology of Late Life Depression: Clinical Predictors of Amyloid and Tau Neuropathology in Non-demented Older Adults with Depression

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.

Keywords: Alzheimer's disease
amyloid
late-life depression
neuropathology
tau
Advisor: Lanctôt, Krista L
Comparative Study of Anomaly Detection in Financial Journal Entries using Machine Learning and Deep Learning Methods

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.

Keywords: Anomaly Detection
Computer-assisted Audit Tools and Techniques (CAATs)
Deep Learning
Intelligent Systems In Accounting
Journal Entry
Machine Learning
Advisor: Lawryshyn, Yuri A.
Plataniotis, Konstantinos N.
Sustained Metabolic Benefits of Intermittent Fasting

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.

Keywords: Calorie restriction
Dieting
Intermittent fasting
Metabolic health
Post-dietary
Weight regain
Advisor: Sung, Hoon-Ki HKS
Non-destructive Method for Measuring In-situ Stress of Concrete

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.

Keywords: Concrete
In-Situ
Non-Destructive
Advisor: Bentz, Evan C
Kwon, Oh-Sung
Body Adiposity and Brain Structure in the Mouse: A Potential Role of Neuroinflammation

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.

Keywords: MRI
neuroinflammation
obesity
systemic inflammation
Advisor: Pausova, Zdenka
Pharmacoepigenetics of Schizophrenia

Schizophrenia is a severe psychiatric disorder primarily involving symptoms of psychosis. Antipsychotic administration is primarily relied upon by clinicians to treat and manage symptoms of schizophrenia. Pharmacogenetic studies have already uncovered DNA sequence variants that influence antipsychotic treatment response. However, several lines of evidence also suggest that antipsychotics alter epigenetic modifications such as DNA methylation. Our objectives was to investigate the effect of antipsychotic dosage on genome-wide methylation and explore differences in genome-wide methylation between various antipsychotics. From a well-characterized sample of 137 schizophrenia patients prescribed antipsychotics we measured DNA methylation in leukocytes. Results showed that there is no genome-wide significant association between DNA methylation in leukocytes and antipsychotic dosage, although paired sample analyses between antipsychotic cohorts and non-psychiatric controls revealed differentially methylated positions and regions. The present study encourages further research on antipsychotic induced methylation patterns and its potential clinical translatability to predict antipsychotic treatment response and/or side-effects.

Advisor: De Luca, Vincenzo VDL
Trade, Trust, and Testamentary Practice in Late-Medieval London: Commerce and Continuity in the Romeyn–Burford Family, 1280–1330

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.

Keywords: Family Strategy
Medieval London
Medieval Wills
Merchants
Roesia Burford
Trade and Commerce
Advisor: Ghosh, Shami
Characterization of Novel Anti-VEGFR Antibodies to Develop Agonists Targeting Mesoderm Differentiation

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.

Keywords: Agonist
endothelial cells
Phage display antibodies
Protein engineering
Advisor: Sidhu, Sachdev
The Determinants of Effective Information Sharing in the Health Capital Planning Process

The objective of this paper is to examine the determinants of effective information sharing in the health capital planning process, particularly the Ontario-Canada process. We conducted a scoping review which included 40 studies, and we interviewed 17 sector experts from Ontario to outline the determinants of most critical information sharing in the Health Capital Planning process. Due to the nature of capital planning which requires the involvement of numerous partners, we focused our study on inter-organization information sharing. Our study provides an inter-organization information-sharing framework for health capital projects. Our framework demonstrates that inter-organization information sharing is only effective if organizations also show effective interpersonal and intra-organization information sharing. We concluded that in order for organizations to successfully collaborate on developing an infrastructure project, they must ensure an effective flow of information from within and between the organizations involved. We found that the determinants of effective inter-organization information sharing in the health capital planning process are: human resources and expertise; incentives and rewards; clear and standardized information; record retention; reducing complex bureaucracies; organizational characteristics; networks; negotiation abilities; alignment of goals; quality; and early planning. The findings of this paper can guide organizations and system planners to improve their inter-organization information sharing, which could promote stronger accountability and more efficient use of resources in the health capital planning process.

Advisor: Brown , Adalsteinn
The Role of the Drop out Protein Kinase during Drosophila embryogenesis

Animal embryos are initially transcriptionally silent, and early developmental processes are driven by proteins and mRNAs loaded into the egg by the mother. Eventually, these maternal factors are degraded, and the zygotic genome becomes expressed during a stage known as the maternal-to-zygotic transition (MZT). During the MZT, maternal mRNAs are degraded in two phases: early, which occurs prior to zygotic genome activation, and late, which occurs after. Prior work from the Smibert, Lipshitz, and Hughes labs has implicated the RNA-binding protein Pumilio (PUM) in a late decay pathway. Additional unpublished data from our lab and Arno Müller led us to propose that PUM’s function in mRNA decay is temporally regulated by the protein kinase Drop out (DOP) via phosphorylation of PUM. Here, I describe my efforts to assess whether PUM’s interaction with its degradation target smaug mRNA is temporal, and to characterize DOP’s role in this pathway.

Keywords: Biochemistry
Drosophila
Embryogenesis
Maternal-to-Zygotic Transition
Molecular Biology
Post-transcriptional regulation
Advisor: Smibert, Craig A
Mechanisms Involved in Colonic Folate Absorption and Metabolism in Humans and the Impact of Folic Acid Supplementation

The colon may play a significant role in the absorption of dietary and bacterially synthesized folate; however, the exact mechanisms involved in colonic folate absorption and the impact of folic acid supplementation are unclear. A 16-week open-labelled randomized clinical trial was conducted where healthy adults recruited from a colonoscopy waiting list received daily a multivitamin plus a 400 μg folic acid supplement (n =12) or no supplement (n=12). At colonoscopy, tissue biopsies were collected from various sections of the colon. mRNA and protein expression of the folate influx transporter, reduced folate carrier (RFC), was markedly higher compared to proton-coupled folate transporter in colon biopsies samples, suggesting RFC may play a dominant role in colonic folate absorption. Folic acid supplementation of 400 μg did not appear to affect the regulation of various folate influx and efflux transporters. These findings may help to inform future revisions of dietary and supplemental folate intake recommendations.

Keywords: Absorption
Colon
Folate
Folic acid
Metabolism
Transport
Advisor: O'Connor, Deborah L
Effects of Synthetic Glucocorticoids on Human Hippocampal Neuronal Gene Expression, In Vitro

While antenatal synthetic glucocorticoid (sGC) treatment greatly reduces preterm infant mortality, there have been reported lifetime risks of adverse neurodevelopmental outcomes. Human neural stem cells (hNSCs) present an opportunity to study the effects of sGCs in a human model where access to primary tissue is a major obstacle. We hypothesize that sGC exposure of hippocampal neurons derived from hNSCs will result in long-term changes in gene expression. hNSCs were expanded in vitro, differentiated into neurons, and characterized by immunocytochemistry. Responses were recorded after exposing neurons to doses (1-1000nM) of sGC (n=6/treatment) for 24h. Neuronal gene expression of Nr3c1, Ube3a, Bdnf, Mecp2, Tet3, CRH, Fkbp5, and Dnmt3A was assessed by qPCR. There was a significant dose-dependent increase in Fkbp5 expression. No other significant changes to gene expression were detected. This is one of the first studies in a human hippocampal neuronal model elucidating the effects of sGCs on critical neurodevelopmental genes.

Keywords: dexamethasone
FKBP5
gene expression
neural stem cells
neurons
synthetic glucocorticoids
Advisor: Matthews, Stephen