VictorJuiz/thesis huggingface dataset:
Fluoroanthranilate Based Biosynthetic Labelling and Characterization of Proteins - A Study of the Dimeric Enzyme Fluoroacetate Dehalogenase and the Membrane Protein A2A

Fluorine NMR is commonly used to study biological systems, largely due to the extreme sensitivity of the fluorine chemical shift to changes in the local environment. Approaching fluorine NMR studies through fluorinated analogs of tryptophan is desirable as it is commonly found along polar-apolar interfaces and within the active sites of proteins. Fluorinated analogs are commonly introduced into proteins via biosynthesis. Generation of a labelled tryptophan can be accomplished with the addition of fluoro-indole or fluoro-tryptophan to cell cultures. Here we demonstrate the potential of fluoroanthranilate based labelling of tryptophan analogs in two different expression systems - E. coli (fluoroacetate dehalogenase) and Pichia pastoris (adenosine A2A receptor). FAcD and A2AR serve as model proteins for a large subset of alpha/ beta hydrolases and over 700 Class A receptors respectively. Both possess few tryptophan residues and 19F labelling of these can provide great insight into conformational dynamics and key motifs.

Advisor: Prosser, Robert Scott
A Systematic Investigation of Anti-phage Defense in Pseudomonas aeruginosa

Phages are obligate parasites that kill bacteria through their lytic life cycle. This constant selective pressure causes coevolution, which has been described as an “evolutionary arms race”. To evade phage predation, bacteria have evolved “defense systems”. To counter these bacterial mechanisms, phages contain reciprocal “anti-defense systems”. With the growing rise of antibiotic resistance, finding alternative ways to treat pathogenic bacterial infections is becoming more pressing. Phage therapy is one such alternative. Pseudomonas aeruginosa is a multidrug-resistant, opportunistic pathogen. I aimed to study the intracellular defense/anti- defense interactions of P. aeruginosa strains/phages, in vivo, as a greater knowledge of these interactions will hopefully allow for more successful phage therapy. I conducted a screen to assess the ability of a large collection of phages to replicate on diverse P. aeruginosa strains. In cases where a phage did not replicate on a strain, I determined whether the phage in question was able to adsorb to the strain. If adsorption did occur, it was likely that phage replication was being blocked by anti-phage defense systems operating within the cell. Since these types of systems are of greatest current interest, we conducted further studies on these phage/host combinations. In the hope of finding phage genes involved in anti-defense, I expressed several phage moron genes within P. aeruginosa strains being infected by phages that could adsorb but not replicate. I identified one phage protein, gene product 15 from Pseudomonas phage JBD26, the expression of which decreased phage resistance.

Keywords: aeruginosa
anti-defense
Bacteriophage
defense
Phage
Pseudomonas
Advisor: Davidson, Alan R.
Identifying Divergent Selection in Structured Populations of Daucus carota

Determining causes of trait divergence between populations is a historically difficult task, as both selection and drift can instigate significant evolutionary change. Qst-Fst has been the most popular method for distinguishing between selection and drift but has numerous limitations making it unideal for most experimental designs. Recently, a new method analogous to Qst-Fst has been developed called Qpc. Qpc seeks to remedy certain limitations of Qst-Fst and provide a more accessible framework for testing trait divergence. In this paper, we apply Qpc to a comparatively small set of Daucus carota populations to test its applicability and efficacy, as well as identify drivers of evolution in D. carota. We affirm Qpc’s ability to identify selection by identifying adaptively divergent traits in D. carota and provide comparisons of Qpc to previous methodology.

Advisor: Stinchcombe, John
The Effects of Acute Olanzapine Exposure on Central Leptin Mediated Regulation of Energy Homeostasis and Food Intake

Second-generation antipsychotic (SGAs) use is associated with severe metabolic side-effects which may be due to disrupted actions of leptin in the brain. We investigated the ability of olanzapine, a widely used SGA, to impair hypothalamic-leptin-mediated regulation of energy homeostasis and food intake. Healthy, male, Sprague Dawley rats received an acute intracerebroventricular (ICV) infusion of leptin or vehicle along with an acute peripheral injection of olanzapine or vehicle at the beginning of 12-h light and dark cycles. Changes in metabolic parameters were recorded using indirect calorimetry cages over 24 hours. Glucose tolerance was assessed using IPGTTs. Treatment with leptin and olanzapine, alone or in combination, reduced respiratory exchange ratio (RER) in light and dark cycles. ICV-leptin reduced dark-cycle food intake regardless of olanzapine treatment. Furthermore, treatment with olanzapine resulted in disturbed glucose tolerance. Olanzapine-induced dysglycemia appeared to be independent of hypothalamic leptin action, and ICV-leptin did not alleviate olanzapine-induced glucose intolerance.

Advisor: Hahn, Margaret
Exploration and Analysis of Self-supervision in Semi-supervised Framework for Mixed-type Wafer Map Defect Recognition and Classification

Wafer map defect detection algorithms are deployed to improve semiconductor manufacturing relative to production yield, detection accuracy, and time-cost. Due to the increasing complexity of wafer and integrated circuit designs, complex defects have higher probabilities. As a result, existing developments, which solely focused on single-type defects, and leveraged large-scale datasets, are not suitable for mixed-type defect detection. The objective of this thesis is to develop and apply a semi-supervised framework with self-supervised contrastive learning at small amounts of labeled data for mixed-type defect detection. The performance and scalability of the proposed method is evaluated and compared to supervised baseline methods. With label fractions of 1% and 10%, the proposed framework demonstrated high scalability for defect detection. The proposed method obtained validation and test exact match ratio scores of 0.7063 and 0.7071 for mixed-type defect classification based on pretraining and finetuning with 10% of the labeled data and 90% unlabeled data.

Advisor: Behdinan, Kamran
Investigating the Temporal Dynamics of SMX Assembly and Disassembly throughout the Cell Cycle

Genome instability is a hallmark of cancer. The accurate removal of replication and recombination intermediates is essential for maintaining genome stability. Structure-selective endonucleases, such as the SMX complex, are required to resolve such structures. SMX is composed of three structure-selective endonucleases called SLX1-SLX4, MUS81-EME1, and XPF-ERCC1. Human SLX4 provides the scaffold for assembling these proteins into a tri- nuclease complex. SMX is formed predominately in prometaphase, however, it is still unclear how this complex disassembles in humans. The goal of my thesis was to determine when and how the SMX complex disassembles in human cells. My work showed that the assembly of SMX peaks in early mitosis and then declines in late mitosis. This suggests that the SMX complex does not have an “on” and “off” switch for assembly and disassembly. Future experiments are required to understand the molecular mechanism that triggers SMX disassembly.

Keywords: Cell cycle
Homologous recombination
SLX4
Advisor: Wyatt, Haley
Multivariate Associations between White Matter and the Cognitions in Schizophrenia

Deficits in “the cognitions” are important contributors to functional outcomes in schizophrenia. An unanswered question of considerable import is if neurocognitive and social cognitive deficits arise from overlapping or distinct white matter impairments. By applying dimensional multivariate statistical analyses to the Social Processes Initiative in the Neurobiology of the Schizophrenia(s) (SPINS) dataset, the present thesis establishes that white matter circuitry is related to both neurocognition and social cognition. In particular, the uncinate fasciculus and the rostral body of the corpus callosum may assume a “privileged role” subserving both. Further, we found that participant-wise estimates of white matter microstructure, weighted by cognitive performance, do not reveal novel biotypes, but are largely consistent with participants’ categorical diagnosis, and predictive of functional outcome. In tandem, our results underscore the promise of white matter and cognitive assessment to identify biomarkers of functioning, with potential prognostic and therapeutic relevance.

Keywords: Canonical correlation analysis
Cognition
Multivariate statistics
Schizophrenia
Tractography
White matter
Advisor: Voineskos, Aristotle N
Cryogenic Characterization and Modelling of FinFET Technology

This thesis investigates the performance of commercial 5nm and 7nm FinFET technology from room temperature down to cryogenic temperatures for quantum computing and other low-temperature applications. DC characteristics and high-frequency figures of merits show significant improvement in all devices at cryogenic temperaturecompared to room temperature, with 5nm devices performing better than 7nm devices. Furthermore, all measured devices exhibit quantum dot (QD) behaviour when biased in the subthreshold region up to 35K, suggesting the potential of commercial FinFET technologies for monolithic quantum processors where the semiconductor qubits are integrated with the control electronics on the same die. A novel compact analytical model is developed to capture the effect of bias and temperature on the QD characteristics, required to develop a complete simulation environment for designing monolithic quantum processors.

Keywords: characterization
coulomb blockade
cryogenic
finfet
modelling
quantum computing
Advisor: Voinigescu, Sorin P
Bacteriopheophorbide Nanoemulsions as Photodynamic Therapy Agents

Bacteriochlorins exhibit ideal photosensitizer properties: they have near-infrared excitation wavelengths, large molar extinction coefficients, and intersystem crossing quantum yields approaching unity. By loading bacteriochlorins into a nanoparticle, it may be possible to extend the circulation kinetics of this otherwise potent agent, allowing for cell-targeted photodynamic therapy. Nanoemulsions were first evaluated in solution and found to be colloidally stable. The droplets also behaved as off-on probes, becoming fluorescent and photoactive upon particle disruption. Cellular studies revealed that cells rapidly uptake the nanoemulsion, and treated cells are very sensitive to subsequent photodynamic therapy. Confocal imaging showed that the nanoemulsion is diffused throughout the cytosol. Unfortunately, in vivo experiments revealed no improvement in circulation kinetics, with droplets clearing very rapidly from circulation. Although this work was unable to improve the circulation kinetics of bacteriopheophorbide, it marks an important step in the development of bacteriochlorin-based nanomedicines, especially with respect to nanoemulsions.

Keywords: Nanoemulsion
Photodynamic therapy
Advisor: Zheng, Gang
Contextualizing the Science, Technology, Engineering and Mathematics Gender Gap in European and sub-Saharan African Universities

The STEM gender-equality paradox, which occurs when there are greater gender disparities in STEM education within countries that are considered more gender equal, has raised many questions about factors causing the disparities in tertiary enrollment. This study aims to understand how different contextual factors effect enrollment and self-perception of women in tertiary STEM programs across the European and Sub-Saharan African contexts. This study uses an explanatory sequential mixed-methods approach with a feminist and gender role theory theoretical framework. An online survey (NS=188) and interviews (NI=11) were used to investigate the role of sociocultural, student self-perception and economic factors on tertiary STEM enrollment. Men and women identified different factors on their pursuit of tertiary education where men indicated financial motives whereas women expressed personal preferences for STEM. Sociocultural factors were found as a discouraging force against STEM education for women. Power, and maintaining institutional patriarchy, are concluded as the key cause for the STEM gender gap. Ignorance and normalized misogyny must be reduced across the studied contexts to improve gender equity in STEM.

Advisor: Manion, Caroline
Intracellular Complement: Activation and Expression in Human Skeletal Muscle Myotubes Under Pro-inflammatory Cytokine Stress

The complement system was known to be mainly liver-derived and being effective in the serum, however, a concept of intracellular complement has emerged, where local production of complement has nonconical roles in various cell types. We have discovered a novel production of complement C3 in skeletal muscle myotubes, and we hypothesized that it can be stimulated under pro-inflammatory cytokines stress. This study utilizes human myotubes differentiated in serum-free conditions to study skeletal muscle C3. Our results show that pro-inflammatory cytokines, tumour necrosis factor-alpha, interleukin 6, and interleukin 1 beta increase both the expression and activation of C3 in myotubes. Moreover, pro-inflammatory cytokine stress induces intracellular C3 deposition which can activate membrane attack complex. In addition, the proteolytic activity of Cathepsin L might be important for intracellular C3 activation in myotubes. This study will help us further elucidate the new phenomenon of intracellularly functional complement in the context of muscle inflammation.

Keywords: Complement C3
Human Skeletal Myotubes
IL-1β
IL-6
Inflammation
TNF-α
Advisor: Licht, Christoph
Electrophysiological Correlates of Subjective Cognitive Demand in Cochlear Implant Users during Listening in Noise

There is a weak relationship between clinical and self-reported speech perception outcomes in CI listeners, potentially due to differences in clinical and real-world listening environments. Therefore, the objectives of this thesis were to 1) quantify neural speech tracking in CI listeners to naturalistic audiovisual stimuli in various levels of background noise using temporal response functions (TRFs), and 2) assess speech tracking and alpha power as objective measures of cognitive demand compared to subjective self-reports. Neural tracking of a dialogue-based television show and alpha power were measured for fifteen adult CI listeners, and correlated to their self-reported demand ratings. Late TRF components significantly changes as an effect of background noise, along with non-significant parametric changes in early components. Change in auditory alpha power and demand ratings were significantly correlated as well. These results indicate that meaningful information about the CI listening experience can be extracted from neural responses using “ecological” stimuli.

Keywords: attention
cochlear implants
EEG
speech perception
speech tracking
temporal response functions
Advisor: Dimitrijevic, Andrew
A Study of Observability-aware Trajectory Optimization

Ideally, robots should move in ways that maximize knowledge gained about the state of both their internal system and external operating environment. Recently, observability-based metrics have been proposed to find trajectories that enable rapid and accurate estimation. A system is observable, roughly, if relevant states and parameters can be recovered from measurements over finite time. Degree of observability has been applied as a metric to optimize motion to produce more observable trajectories that yield better estimation accuracy. The viability of methods for observability-aware trajectory optimization are not yet well understood in the literature. In this thesis, we compare two state-of-the-art methods for trajectory optimization and seek to add important theoretical clarifications and valuable discussion about their effectiveness. For evaluation, we examine the representative task of sensor-to-sensor extrinsic self-calibration using a realistic physics simulator. We also study the sensitivity of these algorithms to changes in information content of exteroceptive sensor measurements.

Keywords: observability
robotics
self-calibration
sensor fusion
state estimation
trajectory optimization
Advisor: Kelly, Jonathan S
Expression Level of KRAB Domains as a Confounding Variable in Measurement of Repressive Ability

KRAB domains are repressive effector domains commonly associated with C2H2 zinc finger transcription factors. These domains are found throughout all tetrapods and even lobe-finned fish and have been associated with the binding and repression of transposable elements. The goal of my master’s thesis was to characterize the repressive capabilities of this domain, however, upon closer analysis, I discovered a confounding variable in the form of the domain’s steady-state expression levels. I first designed both a panel of scores and a series of benchmarks to analyze poly-bin sequencing results from a flow-activated cell sorting based MPRA. I then discovered a major correlation between confounding expression levels and the presence and absence of flanking sequences on KRAB domains. Finally, I discuss an improved library construct that includes flanking sequences, a faster recruitment mechanism, and the ability to monitor the overall expression levels of the KRAB domains.

Advisor: Hughes, Timothy R
Twin Pregnancy and Severe Maternal Mental Illness: A Canadian Population-based Cohort Study

Objective: To quantity the short- and long-term risks of severe maternal mental illness arising after a twin vs. singleton birth. Methods: This propensity-score weighted population-based retrospective cohort study comprised primiparous Canadian women aged 15-50 years. We compared 15,024 twin livebirths to 796,804 singletons livebirths, from 2003-2019. The primary composite outcome was a psychiatric emergency department visit, hospitalization, self-harm or suicide event – both in the first year postpartum, and from 1 year postpartum up to 17 years post-delivery. Results: In the first year postpartum, after weighting, the rate of composite outcome events was 10.5 vs. 8.7 per 1000 person-years among twin and singleton births respectively (HR 1.21, 95% CI 1.07-1.47). Starting from 1 year postpartum, the corresponding rates were 5.9 vs. 6.1 per 1000 person-years (HR 0.96, 95% CI 0.89-1.04). Conclusions: Women with a twin birth may experience more severe adverse mental health within 1-year postpartum, but not in the long-term.

Keywords: Health services research
Maternal mental health
Postpartum mental illness
Pregnancy
Twin pregnancy
Advisor: Vigod, Simone N
Role of Saturated Fatty Acids in the Development of Insulin Resistance via NOD1 Activation In vivo

Obesity is associated with elevated free fatty acids (FFA), chronic low-grade inflammation and insulin resistance (IR). We hypothesize that FFA can act as damage associated molecular patterns (DAMPs) to activate innate immune receptors such as nucleotide oligomerization domain (NOD) 1 receptor inducing IR and type 2 diabetes (T2D). We here show that i.v. infusion of ethylpalmitate (EtP), which is broken down into palmitate and ethanol in circulation, can induce whole body IR in WT mice, which was assessed using the hyperinsulinemic-euglycemic clamp. Furthermore, NOD1 KO mice were protected from EtP induced whole-body and peripheral IR. We used GSK583, a pharmacological inhibitor of RIPK2, which is downstream of NOD1. We found that GSK583 treatment protected against EtP induced whole body and hepatic IR. This data suggests NOD1 as a potential therapeutic target for IR and T2D.

Keywords: Diabetes
in vivo
Insulin resistance
NOD1
Palmitate
Saturated fatty acids
Advisor: Giacca, Adria
Instructional Components and their Combinations for Teaching Empathy to Mental Health Practitioners and Trainees: Pairwise and Network Meta-analyses

The current study investigated the most effective instructional components (didactic, rehearsal, reflection, observation, feedback, mindfulness), instructional component combinations, and program characteristics for teaching empathy to mental health practitioners. Thirty-seven studies were included (N = 1591). Data were pooled using random-effects pairwise and network meta-analyses. Overall, empathy interventions demonstrated a medium to large effect (d = .76, 95% CI = .57, .95). Pairwise analyses showed that didactic (d = .87 vs. d = .43, p = .03) and rehearsal components (d = .88 vs. d = .50, p = .05) were more effective, on average, than those that did not use these respective approaches. None of the program characteristics significantly impacted intervention effectiveness. Network analyses revealed didactic, rehearsal, and observation components were included among the most effective intervention combinations compared to other intervention combinations.

Keywords: counselling
empathy
intervention
meta-analysis
network meta-analysis
therapy
Advisor: Jenkins, Jennifer
Investigating the Relationships between Menstrual Cycle, Progesterone, and Concussion in Female Athletes

Sport related concussion is a traumatic brain injury induced by biomechanical forces. Progesterone, a female sex hormone, is thought to be neuroprotective and may have implications in concussion. The current study examined how changes in hormone levels may affect menstrual functioning and outcomes after concussion in university athletes. The influence of progesterone was examined in relation to variation in the menstrual cycle and the severity of symptoms post-concussion. Specifically, our findings suggest that there may be changes in menstrual cycle patterns and neuroendocrine disturbances occurring after concussion in female athletes. Additionally, progesterone may have a neuroprotective effect as its increased concentration is associated with decreases in symptom severity acutely after concussion. Findings from this study are informative for future research aiming to explore the influence of female sex hormones in the field of concussion and brain injury.

Keywords: Concussion
Female Athletes
Menstrual Cycle
Progesterone
Advisor: Mainwaring, Lynda
Empathizing with Victims or Culprits: The Roles of Political Orientation and Competitive Worldview in Empathy

Victim-blaming and exonerating perpetrators can often be seen in society. This present research aims to understand these phenomena through the lens of empathy for victims and culprits. As victims and culprits espouse qualities that conservatives and liberals may value differently, political orientation may influence who an individual empathizes more with. I propose a model in which political conservatism predicts lower empathy for victims and higher empathy for culprits, as a function of competitive worldview. Study 1 tests this model in a correlational design, finding support for competitive worldview as a mediator of political orientation and empathy. Study 2 builds on these findings by examining the causal effect of inducing competitive views on the relationship between political orientation and empathy, further demonstrating the proposed model. Despite potential limitations, these studies provide initial evidence for the association of political orientation, competitive worldview, and empathy. Planned future studies and research ideas are discussed.

Keywords: competitive worldview
culprits
empathy
political orientation
victims
Advisor: Lee, Spike W. S.