VictorJuiz/thesis huggingface dataset:
Screening for Suppressors of Nemaline Myopathy in Zebrafish and Mouse Models of the Disease

Nemaline myopathy is a rare neuromuscular disorder that affects 1 in 50,000 live births, with prevalence as high as 1 in 20,000 in certain populations. 13 genes have been linked to nemaline myopathy, all of which are associated with the thin filament of the muscle sarcomere. Of the 13 associated genes, mutations in nebulin accounts for up to 50% of all cases. Currently, the disease is poorly understood and there are no available therapeutics for patients. To address this issue, I performed a chemical screen and a genetic screen using a nebulin deficient zebrafish and murine model of the disease, respectively. Following the completion of both screens, I concluded that finding chemical or genetic suppressors of nemaline myopathy is challenging and therefore a novel approach should be taken for therapy development. Preliminary results suggest the novel approach of “domain skipping” provides an exciting avenue for the treatment of nemaline myopathy.

Keywords: Drug screening
Mouse
Muscle
Nebulin
Nemaline myopathy
Zebrafish
Advisor: Dowling, James J
Pamidronate Does not Affect Cortical Porosity in Transgenic Mice Overexpressing Osteoblastic Gαs

G-protein coupled receptors are involved in many signal transduction pathways. The Gαs protein becomes activated following ligand binding, to stimulate downstream adenylyl cyclase. Previously, Zhang et al. generated a transgenic murine model with osteoblastic Gαs overexpression, which led to increased bone mass. µCT showed a marked increase in closed cortical porosity, which histologically showed intracortical pores lined with osteoclasts. Pamidronate is clinically used for excessive bone loss. It inhibits farnesyl pyrophosphate, an enzyme involved in synthesis of regulatory proteins, leading to osteoclastic apoptosis. Our objective was to use pamidronate to ameliorate intracortical porosity. Low dose pamidronate led to increased trabecular bone mass in wild-type mice only. High dose pamidronate led to increased trabecular bone mass in both wild-type and Gs-Tg mice. Cortical porosity was not affected at both dosages. There is evidence to suggest that pamidronate unsuccessful in affecting intracortical porosity due to lack of penetration into the intracortical space.

Keywords: bone
g-protein
musculoskeletal
pamidronate
Advisor: Mitchell, Jane
Grynpas, Marc D
Pharmacological and Behavioral Modulation of Impulsivity in the Touchscreen-based Mouse 5-choice Serial Reaction Time Test

This work characterized the performance of mice on a new touchscreen version of the 5-choice serial reaction time test (5CSRTT). We investigated whether task-parameter and pharmacological manipulations that influence impulsivity in the older rat 5CSRTT exerted similar influences in the mouse 5CSRTT. Using premature responding as a measure of impulsive actions, we found that increasing the inter-trial interval from 5 to 9s reliably increased impulsivity. The psychostimulant cocaine increased premature responding but had a weaker effect in mice than in rats. The α2-adrenoceptor antagonist yohimbine, which heightens impulsivity in rats, reduced impulsivity in mice. The serotonin 5HT2C receptor agonist lorcaserin, noradrenaline re-uptake inhibitor atomoxetine, and selective serotonin re-uptake inhibitor citalopram decreased premature responding. These results indicate that the touchscreen version of the 5CSRTT can reliably measure impulsivity, and that there is some correspondence between the effects of pharmacological and behavioral manipulations on the 5CSRTT in rats and mice.

Keywords: 5 choice serial reaction time test
impulsivity
inhibitory control
pharmacology
serotonin
touchscreen
Advisor: Fletcher, Paul J
Inferring Temporal Delays in Brain Interactions from Neural Population Activity

The brain is a network of billions of neurons and even at rest, it exhibits complex patterns in activity such as synchrony. This is largely dependent on the temporal latencies in brain region interactions which represent an important aspect of healthy cognitive function, and play a role in neurological disorders such as epilepsy. An effective method of studying the variables involved in shaping these brain dynamics is through computational simulation of biophysical network models, such as the Wilson-Cowan and Kuramoto models. In this thesis, a computational pipeline is developed for inferring the macro-structure of temporal delays in brain region interactions, directly from neural time series data. This pipeline has great potential to be used as a tool to understand white matter and its relationship to brain dynamics.

Keywords: Conduction Delays
Connectivity
Simulations
Synchrony
White Matter
Advisor: Lefebvre, Jérémie
Clinician Wellbeing and Resilience: The Impact of Working in Complex Care Rehabilitation

Introduction: This study explored the experiences of working in complex rehabilitation, the impact this had on clinician wellness, and resilience strategies utilized in practice. Methods: A qualitative descriptive approach was used to understand clinician’s experiences working in complex care, at a large Toronto-based complex rehabilitation hospital. In-person interviews were conducted with fourteen therapists and nurses, and analyzed using inductive qualitative content analysis strategies. Results: Clinicians perceived most patients to be ‘complex’; however reflected both positive and negative effects of working with complex stroke patients. Clinicians faced tensions in the balance between care provision and maintaining personal wellness, and often discussed the importance of putting up ‘barriers’ for self-preservation. Collaborative working relationships and support provided by the interprofessional team were critical in managing practice pressures. Conclusion: This study identified positive and negative long standing impacts of working in a complex care environment and how they impact the clinician’s ability to thrive in the workplace.

Keywords: Complex care
Qualitative
Rehabilitation
Resilience
Wellbeing
Advisor: Nelson, Michelle
Exploring Voltage-gated Sodium Channel NaV1.6 as an Interacting Partner with G Protein-coupled Receptors

G protein-coupled receptors (GPCRs) comprise the largest family of drug targets in the current pharmaceutical landscape. Typically, they are known to signal through G proteins or β-arrestins. Several GPCRs have been implicated in homo/heterodimerization or interactions with other partners resulting in altered signaling modalities. Our lab has established a role for voltage-gated sodium channel (Nav) 1.6 as a modulator of dopamine D2 receptor (D2R) signaling mediated by β-arrestin2. The 242 amino acid C-terminus segment of Nav 1.6 is sufficient to interact with D2R, and specifically the first 50 amino acids of the C-tail are shown here to be important for the interaction. Using a dual approach of the TANGO assay and bioluminescence resonance energy transfer (BRET), the generalizability of Nav 1.6 as an interacting partner with several other GPCRs was assayed.

Keywords: GPCR
Voltage-gated sodium channels
Advisor: Beaulieu, Jean Martin
Mechanical Properties of Cemented Paste Backfill under Low Confining Stress

Cemented paste backfill (CPB) plays an increasingly important role in the mining industry due to rapid delivery rate, tight-filling characteristics, relatively insignificant water management issues during filling, and generally uniform as-placed mechanical properties. The most common basis for assessing backfill strength is Unconfined Compressive Strength (UCS), and some of the most commonly used design methods have UCS as a fundamental design parameter. However, actual CPB properties and behavior under the range of confining stresses relevant to these design methods has been studied very little. This work uses UCS tests and a novel direct tensile test method and compares test results with strengths obtained from direct shear tests. A form of punching shear was also investigated, but the results were found unsatisfactory for design purposes. For materials with UCS up to about 1 MPa, the UCS and tensile strengths are consistent with the Mohr-Coulomb failure envelope obtained from direct shear tests.

Keywords: cemented paste backfill
CPB
dog bone
mining
punching shear
Tensile
Advisor: Grabinsky, Murray
Visual Localization for UAVs in Outdoor GPS-denied Environments

Vision-based navigation techniques are commonly used for autonomous flight in outdoor GPS-denied environments. We adapt Visual Teach and Repeat (VT), a vision-based autonomous route-following system, to use on multirotor UAVs. Since multirotors are underactuated, there are no guarantees that the camera viewpoint will be the same at matching positions along the teach and repeat paths, which causes visual localization to be challenging. The first part of this thesis demonstrates that by using a 3-axis gimballed camera with an appropriate active pointing strategy, we can improve the visual localization performance and robustness within the VT framework. The second part of this thesis presents a method to estimate the global pose of a UAV by using an information-theoretic approach to register real images with rendered georeferenced images from 3D Google Earth. We show that this method is capable of accurately estimating the 6DoF pose with a position accuracy on par with GPS.

Keywords: Field Robotics
Unmanned Aerial Vehicles
Visual Localization
Advisor: Schoellig, Angela
A Novel Converter Topology and Mixed-signal Controller for Pulsed Power Applications

The work presented in this thesis introduces a novel converter topology and associated controller for pulsed power systems. The presented work offers a flexible solution to the challenges of pulsed power charging by managing long pulse duration and high pulsing frequency while avoiding the limitations of linear solutions. The proposed converter is flexible, allows universal conversion ratios, high frequency operation and its viability is verified through an application specific design. The operating modes and control methods of the proposed topology for operation as a pulsed power supply are analyzed. Also presented is an application specific implementation for use in pulsed battery charging systems. The prototype can operate as both a constant and pulsed power supply, achieve a maximum pulsing frequency of 50 kHz while providing output currents up to 30A, while also offering over voltage protection and battery maintenance modes. The practical challenges and limitations of the solutions are discussed.

Keywords: Batteries
Power Electronics
Pulsed Power
Advisor: Prodic, Aleksandar
Identifying Potential Factors Regulating the Fear Extinction Switch in Mice

Anatomical, synaptic and behavioural data suggest that prefrontal cortex (PFC)-amygdala synaptic strengthening coincides with changes in behaviour dependent on this circuit, such as fear extinction, in early life. Still, very little is known about how circuit maturation affects the maturation of behaviour, or which factors may interfere with this ontogeny. This thesis investigates the effects of three early life stress paradigms (maternal separation, limited bedding and unpredictable postnatal stress), three bedding materials (1/8” corncob, 1/4” corncob and 1/4” cellulose), and three different strains of mice (C57BLK/6J, C57BLK/6Tac, and 129S1/SvlmJ x C57BLK/6J or hybrids) on the fear extinction switch in mice. Although we failed to see any meaningful effects with the ELS studies, we report altered fear extinction trajectories across bedding materials and strains of mice. In fact, unlike cellulose bedding, corncob results in a clear extinction switch in mice between postnatal day (P) 16 and P30. We also found that C57BLK/6Tac and hybrid (JAX) mice likely transition to the adult extinction system by P21, while C57BLK/6J mice demonstrate the switch by P25. Taken together, our experiments identify important variables to consider when designing follow-up models of stress or enrichment when investigating the extinction switch in mice.

Keywords: amygdala
circuit maturation
early life stress
extinction
fear conditioning
prefrontal cortex
Advisor: Arruda-Carvalho, Maithe
The Role of Adenomatous Polyposis Coli in Slit2/Robo1 Signaling and Actin Remodeling

A hallmark of many pathogenic diseases is localized inflammation and influx of leukocytes. The neuronal guidance cue, Slit2, acting through receptor, Robo1, constitute a signaling pathway which has inhibitory effects on leukocyte chemotaxis and adhesion by regulating Rho family GTPase activity. To further elucidate the Slit2/Robo1 signaling pathway, a BioID assay was performed and the protein adenomatous polyposis coli (APC) was found to differentially associate with Robo1 in the presence/absence of Slit2. APC regulates Rho family GTPase activity and in cellular functions such as migration, adhesion, and spreading. We found that APC knockdown inhibited monocyte chemotaxis and adhesion on endothelial cells to the same extent as control monocytes exposed to Slit2. Additionally, APC overexpression in COS-7 cells reversed inhibitory effects of Slit2 on cell spreading. suggesting that APC functions downstream of Slit2/Robo1 signaling, and may promote a vital first step in Slit2/Robo1-induced modulation of actin remodeling.

Keywords: Actin
APC
Monocyte
Robo
Signaling
Slit
Advisor: Robinson, Lisa
Geometric and Dynamical Properties of the Cremona Group

The Cremona group of birational transformations of P2C acts naturally by isometries on an infinite dimensional hyperbolic space. We construct this space, first introduced by Manin, and then describe the action which allows us to classify the elements of this group as elliptic, parabolic or hyperbolic. We then discuss the notion of dynamical degrees and how Cremona transformations can also be classified according to the growth rate of the norms of iterates of the induced maps on cohomology. The two classifications correspond, with the one from algebraic geometry being slightly finer than that arising from hyperbolic geometry.

Advisor: Tiozzo, Giulio
Deep Learning Aided Runtime Opcode Based Malware Detection

Thousands of new malware codes are developed every day. Signature-based methods, which are employed by common malware detectors, are susceptible to code obfuscation and novel malware. In this paper, we present an alternative method for malware detection which makes use of assembly opcode sequences or frequencies obtained during runtime. First, for sequential opcode data, we utilize natural language processing and deep learning techniques to facilitate the extraction of deeper behavioral features. Due to these features, this method can be impervious to code obfuscation and effective against novel malware. Finally, these features are fed to various machine learning algorithms for classification. The experiments on 26027 samples that were conducted demonstrated high MCC (Matthew Correlation Coe ficient) scores are achievable with this approach. Secondly, for the frequency dataset, we conduct another experiment that indicates the runtime opcode approach can achieve %70 accuracy for 16 malware labels on 59424 samples. ii

Keywords: Deep Learning
Malware Detection
Runtime Opcodes
Advisor: Hatzinakos, Dimitrios
Lawryshyn, Yuri
Beep, Aim, Repeat: Influence of Use-dependent and Advance Preparation Processes during Sequential Movements

Sequential goal-directed actions can be influenced by both recent motor history, and the characteristics of planned movements. That is, the current movement can be biased toward the direction of a preceding target and/or an upcoming target through the activation of movement planning mechanisms associated with repeated motor sequences: use-dependent and advance preparation processes, respectively. Although the two motor planning processes have been studied independently, how these processes interact with one another is not well understood. The present studies were thus designed to differentiate the characteristics of use-dependent and advance preparation processes during the repetition of movement sequences. Participants completed a sequential aiming task, where the factors such as orientation of the targets, availability of vision, type of movements, and presentation of trials were manipulated. Although the studies did not clearly indicate the individual contribution of use-dependent and advance preparation processes, there was some evidence suggesting co-activation of the two processes.

Advisor: Welsh, Timothy
An Investigation of Cross-frequency Interactions in a Gas Turbine Combustor at Flight-relevant Conditions

This thesis presents the analysis of experimental thermoacoustic data obtained from experiments on an optically accessible aeronautical gas turbine combustor operating at elevated pressures to mimic flight-relevant conditions. High-speed optical diagnostics, including chemiluminescence of several species, laser Mie scattering and stereoscopic particle image velocimetry, were used to characterize the heat release rate, fuel spray and velocity fields respectively. Simultaneous dynamic pressure measurements also were obtained. Spectral analysis and mode isolation via spectral proper orthogonal decomposition indicated potential cross-frequency interactions between the fundamental acoustic frequency and its first harmonic observed in the heat release, velocity and fuel spray oscillations. Synchronization analysis was conducted using three different metrics for comparison. The analysis revealed that the cross-frequency interactions are related to the intermittency detected in the pressure fluctuations, where the pressure exhibited bursts of oscillations dominated by the fundamental frequency interspersed with incoherent intervals.

Keywords: Combustion
Cross-frequency interactions
Experimental
Gas turbines
Modal decompositions
Thermoacoustics
Advisor: Steinberg, Adam M
Comparing Apples to Apples: Measuring Mental Representations with Linked and Complete Markov Chain Monte Carlo

Previously, research exploring mental representations of categories has faced two challenges: 1) Preselection of stimuli by the experimenter limited full exploration of the mental representation. 2) No task was applicable across age ranges to assess a developmental trend. Here, we utilized a novel methodology in the categorization literature, Markov chain Monte Carlo (MCMC) with people. Stimuli were directly sampled from the participant’s mental representations through a series of two-alternative forced-choice questions. In our first experiment, we replicated Sanborn, Griffiths, and Shiffrin’s (2010) findings on fruit categories where participants completed full Markov chains. In our second experiment, chains were completed by linking multiple participants to reduce the number of questions asked to each person. Stimuli produced were reflective of our intuitive representation regardless of the number of participants in a chain and were similar between Experiment 1 and 2. Our results highlighted MCMC’s potential to explore the developmental trend in categorization.

Keywords: Categorization
Experimental design
Markov chain Monte Carlo
Mental representation
Advisor: Buchsbaum, Daphna
An Autoethnography: A Research into my Educational Journey of Self Discovery and Coming to Know through the Lens of African Indigenous Knowledge

This is an autoethnographic study that examines the personal, professional and scholarly aspects of my learning, unlearning and relearning, with the goal to find my African Indigenous cultural roots. Beginning this study as a colonized African woman, I achieved this goal by considering critically the ongoing challenges of how colonization, through western education inflicts spiritual and mental injury upon African/Black people through imposing its alien systems; while systematically endeavouring to annihilate and extinguish any traces of Indigenous education, knowledge and collective ancestral memory. Working with a theoretical framework of African Indigenous Knowledge, I articulate some of the knowledge gained from this autoethnographic research, which was by way of undergoing the most challenging process of decolonizing the self. Through the result of this process, I found my spiritual core – my centre - within my African Indigenous cultural roots, which now grounds/intertwines my personal, professional and scholarly practice, thus creating a holistic being.

Keywords: African Ancestors
African Cultural Worldview
African Culture
Spirituality Science
African History (African OurStory)
African Indigenous Knowledge Systems
Africans/Blacks
Advisor: Lopez, Ann
Wane, Njoki
Extending Rare Variant Association Tests in Affected Siblings to Account for Background Genetic Risk

Complex diseases are thought to be caused by both common and rare variants. Family studies are typically used to detect inherited rare variants associated with disease while population-based studies are used to identify common variants. Population-based studies have led to the development of individual-level genetic risk scores (GRS), aggregates of putative common susceptibility variants derived from genome-wide association studies. Currently, rare variant tests of affected sibling pairs (ASPs) do not include the background disease risk from common variants. We demonstrate how to extend existing rare variant ASP tests to include GRS of common variants and report simulations that evaluate: (1) validity of the methods and (2) relative efficacy of considering risk from common variants when testing for rare variant association in family settings. We apply the methods to whole-exome sequence data of sisters ascertained on early-onset breast cancer and incorporate a recently reported breast cancer GRS.

Advisor: Bull, Shelley B
Peer Coaches’ Perceptions: Can Coaches Support Teachers in Enacting Transformative Classroom Practice?

The need for educational practices to be responsive to Ontario’s diverse student population is urgent. As such, many Ontario school districts look to peer coaches, to initiate school reform aimed at inclusive pedagogy. This study explored peer coaches’ perspectives on how their relationship with educators can transform classroom practices. Open-ended interviews and a focus group session were conducted. Two main themes emerged. First, when teachers worked with peer coaches to develop an inquiry question linked to a teaching challenge, the coaches tended to embrace a “learning by doing” stance encouraging teachers to explore various strategies to become more inclusive while addressing gaps in student achievement. Second, it appears that a peer coach’s open stance and willingness to co-construct the goals of this type of teacher learning provide a strong foundation for growth and change. This qualitative thesis contributes to our understanding of the role of peer coaches in supporting inclusive teaching practices.

Keywords: Equity
Inclusive Education
Instructional Coaching
Peer Coach
School Reform Intiative
Transformative Classroom Practices
Advisor: Gagne, Antionette
Biological Effects of Ultrafast Burst-Mode Laser Ablation of Chondral Tissues

Tissue grafting can correct damaged joint cartilage and become permanently incorporated into the body, delaying invasive joint replacement surgery for patients with osteoarthritis. Ultrafast burst-mode lasers may allow for minimally invasive procedures yielding precise custom-cut osteochondral tissue with minimal collateral damage. Study of the outcomes of laser machining parameters on cartilage tissue with a femtosecond laser system determined suitable ablation settings and were compared to mechanical removal methods. A preliminary investigation studied long term effects of laser ablation. With appropriate settings, minimal collateral tissue damage immediately following ablation was achieved; ablation outcomes were comparable to or better than mechanical removal methods. Following in vitro culturing, large regions of cellular death and matrix degeneration around the laser ablated area emerged. This work highlights potential benefits and the next steps required to develop a femtosecond burst-mode laser as an orthopedic surgical tool.

Advisor: Akens, Margarete