VictorJuiz/thesis huggingface dataset:
Mammalian Cardiovascular Patterning as Determined by Hemodynamic Forces and Blood Vessel Genetics

Cardiovascular development is a process that involves the timing of multiple molecular events, and numerous subtle three-dimensional conformational changes. Traditional developmental biology techniques have provided large quantities of information as to how these complex organ systems develop. However, the major drawback of the majority of current developmental biological imaging is that they are two-dimensional in nature. It is now well recognized that circulation of blood is required for normal patterning and remodeling of blood vessels. Normal blood vessel formation is dependent upon a complex network of signaling pathways, and genetic mutations in these pathways leads to impaired vascular development, heart failure, and lethality. As such, it is not surprising that mutant mice with aberrant cardiovascular patterning are so common, since normal development requires proper coordination between three systems: the heart, the blood, and the vasculature. This thesis describes the implementation of a three-dimensional imaging technique, optical projection tomography (OPT), in conjunction with a computer-based registration algorithm to statistically analyze developmental differences in groups of wild-type mouse embryos. Embryos that differ by only a few hours' gestational time are shown to have developmental differences in blood vessel formation and heart development progression that can be discerned. This thesis describes how we analyzed mouse models of cardiovascular perturbation by OPT to detect morphological differences in embryonic development in both qualitative and quantitative ways. Both a blood vessel specific mutation and a cardiac specific mutation were analyzed, providing evidence that developmental defects of these types can be quantified. Finally, we describe the implementation of OPT imaging to identify statistically significant phenotypes from three different mouse models of cardiovascular perturbation across a range of developmental time points. Image registration methods, combined with intensity- and deformation-based analyses are described and utilized to fully characterize myosin light chain 2a (Mlc2a), delta-like ligand 4 (Dll4), and Endoglin (Eng) mutant mouse embryos. We show that Eng mutant embryos are statistically similar to the Mlc2a phenotype, confirming that these mouse mutants suffer from a primary cardiac developmental defect. Thus, a loss of hemodynamic force caused by defective pumping of the heart is the primary developmental defect affecting these mice.

Keywords: Cardiovascular Development
Developmental Biology
Dll4
Endoglin
Mlc2a
Optical Projection Tomography
Advisor: Henkelman, Mark
Understanding the Role of Potassium and its Transport Systems in Streptococcus mutans

Streptococcus mutans is a cariogenic bacterium found in the human dental plaque biofilm. Amongst its various attributes, the ability to metabolize a variety of dietary sugars to produce acid, resistance to pH stress by activating an acid tolerance response, ability to produce sticky glucan polymers and the ability to naturally take up genetic material are important properties of S. mutans. One way bacteria withstand external environmental stress is by accumulating intracellular potassium. In the genome of S. mutans, four putative potassium transport systems were identified, namely, the Trk1 (trkB/trk/pacL) system, Trk2 (trkA/trkH) system, GlnQHMP, and Kch (SMU_1848). The hypothesis of this study was that S. mutans transports potassium using specific transport systems, and relies on K+ homeostasis for regulation of its multiple physiological and virulence attributes. To investigate the role of these systems, strains with deletions of each system were constructed. The most profound effects on the growth, pH tolerance, genetic transformation and biofilm formation were observed when the Trk2 system was absent compared to wild type UA159 and trk1-, glnQHMP- or kch deficient strains. Furthermore, deletion of the Trk2 transport system resulted in reduced intracellular potassium accumulation. To confirm the role of Trk2 as a potassium uptake system, this system was cloned, expressed and functionally characterized in the Escherichia coli TK2420 mutant strain lacking constitutive potassium uptake systems. Collectively, this study identified Trk2 as the key potassium transport system in S. mutans, and demonstrated its importance and the role of potassium homeostasis with regard to biofilm formation, stress tolerance, growth and genetic transformation. This work constitutes the first characterization of the Trk systems in oral streptococci.

Keywords: biofilm
potassium
Streptococcus mutans
transformation
Advisor: Cvitkovitch, Dennis G
Senadheera, Dilani B
"Acts of Resistance": Reclaiming Native Womanhood in Canadian Aboriginal Theatre.

This study investigates the representation of Aboriginal womanhood in Aboriginal women’s theatre in Canada. Using five core case studies to explore Indigenous women’s self-representation, I demonstrate how Native theatre engages in acts of resistance that promote the decolonization of Aboriginal womanhood. Drawing on concepts of Aboriginal storytelling, I attempt to weave the connections between the personal story and the collective history to demonstrate how these plays use theatrical presence to rebuke historical and contemporary absences of Native women. Each play does this by taking aim at political policies, stereotypes in popular culture, and sexual violence, which all sustain negative constructions of Native womanhood. Chapter one establishes the context(s) in which these plays exist and explores a history of legislation and policies that contributes to the negative representations of Aboriginal women. Chapters two and three demonstrate how Native women's theatre confronts stereotypes of Aboriginality and deconstructs them as a form of personal and collective healing. Chapter two explores how culture jamming and humour are used to disrupt the re-circulation of stereotypes in order to challenge the cultural currency stereotypes maintain in film, television, and other medias. In chapter three I explore the connection between the stereotypes and sexualized violence. I identify strategies used to represent violence, specifically around concepts of “presence” and “absence.” The function of violence in these plays is not one of (re)victimization, but one that evokes concepts of testimony, witnessing, and storytelling. It will also deal with the problematic perceived trajectory of healing and identity formation through violence in some of the plays. Chapter four looks to the relationship between identity and community and signals how a return to “home” and community can help rebuild positive Indigenous identities and becomes the final act of resistance. Chapter five examines the relationship between storytelling (in the theatre), history, and witnessing trauma. It proposes that Native storytelling, especially in the theatre, is an act of survivance that challenges historical absences. Finally, in chapter six, I look forward to the transnational applications of my research and gesture to Indigenous eco-theatre as one avenue that promotes the decolonization of Indigenous peoples globally.

Keywords: Culture jamming
Native theatre in Canada
Representations of Aboriginal women
Storytelling
Survivance
Theatrical violence
Advisor: Barton, Bruce
Separating Within-trial Activities in the Stop Signal Task Using fMRI

Functional magnetic resonance imaging (fMRI) approaches tend to focus on a particular process of interest, and model neural activity as a single phase of activity on a given trial. This thesis presents new methods for separating rapidly unfolding within-trial activities in a stop signal task using fMRI. Current models of inhibitory control address processes that are engaged after the presentation of go- and stop-signals. The first study presented here separated warning- from response-phase activities in healthy adults (A. Chevrier, Cheyne, Graham, Schachar, 2015). This work revealed activities in posterior networks that signal the need for top-down control followed by fronto-posterior activities involved in implementing top-down control. Both of these phases contained activities that influenced inhibitory control. Reinforcement learning models treat errors as a unitary phase of activity. The second study presented here separated error detection from post-error slowing on failed stop trials (A. Chevrier Schachar, 2010). Error detection deactivated structures that are richly innervated by midbrain dopamine neurons (dorsal striatum and ventral anterior cingulate cortex (ACC)), followed by deactivations during post-error adjustment in structures that modulate the ascending dopamine response (ventral striatum and caudal orbitofrontal cortex), which encode error magnitude. The third study involved the separation of error detection and post-error slowing in adolescents with and without attention deficit hyperactivity disorder (ADHD) (Chevrier, Bhaijiwala, Cheyne, Graham Schachar, manuscript in preparation). A recent study of these data from our laboratory (Bhaijiwala, Chevrier, Schachar, 2014) showed that previous evidence of ADHD subjects under-activating inhibition networks, is instead the result of deactivating these networks during preparation, when healthy controls were pre-activating. This suggests that inhibitory control deficits in ADHD result from dysfunctional reinforcement, which tunes appropriate networks in an inappropriate way. Consistent with this hypothesis, we found that ADHD subjects failed to fully deactivate dopamine targets on error detection, and inappropriately activated the reciprocal pathway on post-error slowing. Dysfunctional reinforcement would explain the lack of potency of behavioral interventions that are based on the known properties of normal reinforcement. Further, the effects of dysfunction in moment-to-moment reinforcement would accumulate over experience, suggesting a mechanism for the delayed maturation of function and cortical thickness observed in ADHD.

Advisor: Cheyne, Douglas
Schachar, Russell J.
Development of a Lead-free Piezoelectric (K,Na)NbO3 Thin Film Deposited on Nickel-based Electrodes

It is desirable to replace noble metals used as electrode materials for piezoelectric thin film with base metals. This will reduce the piezoelectric thin film fabrication cost. A nickel−based layer in conjunction with other protective layers is proposed as a bottom electrode for lead−free piezoelectric KNN thin film. The obtained results do not indicate the oxidation of the nickel−based bottom electrode after the deposition of KNN at 600 °C for 10 hours in the presence of oxygen and/or after annealing the sample at 400 °C for an hour in air. The fabricated KNN thin film was fully characterized in this work. The effective piezoelectric coefficients d33 and d31 were estimated to be 37 pm/V and 17.2 pm/V, respectively, at 100 kV/cm. The piezoelectric properties of the fabricated KNN/Ni/Ti/SiO2/Si are affected by the crystal orientation of the KNN layer, which was preferentially oriented in the (110) direction. Optimization of the deposition parameters of the fabricated KNN/Ni/Ti/SiO2/Si film is expected to further enhance the piezoelectric properties. Two novel systems utilizing the developed KNN piezoelectric thin film are proposed and their performance simulated based on the achieved KNN thin film parameters. The first is a precision automated nanomanipulation system using an AFM as a sensor and piezo−actuated manipulators. Real−time feedback of the particle being manipulated can be achieved using the proposed system. The length of the manipulators needs to be at least 2 mm to be incorporated with a commercial AFM system. To fabricate the required manipulators, a three−step electrochemical etching technique was developed. Tungsten tips combining well−defined conical shape, a length as large as 2 mm, and sharpness with a radius of curvature of around 20 nm were fabricated using the proposed technique. By depositing the KNN thin film on the fabricated manipulator, nanomanipulators with out−of−plane actuation can be produced. Ultrasonic piezoelectric fan array, the second system, is proposed for GPU cooling applications. The developed KNN thin film is proposed as the piezo layer in the piezo fan structure. The novel solution can offer large air flow rate and low power consumption. Since the operating frequency is beyond the human audible frequencies, non−audible noise fans are expected by using the proposed ultrasonic piezo fan system. Moreover, fabrication of these ultrasonic piezo fans can be part of the GPU fabrication process itself.

Keywords: Micro actuator
Nanomanipulation
Piezoelectric
Piezoelectric fan
Thin film
Tungsten nano-tips
Advisor: Ben Mrad, Ridha
Motivational Interviewing, Therapist Fidelity and Treatment Outcomes Among Adolescents with Concurrent Disorders

Addressing motivational issues has been considered an important target in treatment among adolescents with concurrent disorders (CD). The client-centered, collaborative and non-confrontational approach of MI, make it a particularly useful approach with adolescents. MI has been shown to be effective at increasing commitment to change and enhance treatment engagement among adolescents. To date, there have been limited studies to examine the effectiveness of MI as a pre-treatment intervention among adolescents with CDs. The purpose of the study was to address this need for research and to understand which specific MI interventions are essential for facilitating client change among adolescent CDs. The current study was a pilot sub-project from a larger study examining the feasibility and effectiveness of a single MI session as a pre-treatment intervention among adolescents with CDs. Thirty-two adolescent males and females attended a brief MI intervention session prior to participating in a group treatment program. The goals of this study were to: (1) examine the efficacy of a brief MI intervention among adolescents with CDs; (2) develop a better understanding of the important elements of the intervention that influence outcomes, specifically examining treatment effects at the level of therapist behaviours. The results were consistent with the hypothesis that following the MI session, adolescents would report greater motivation, specifically taking greater steps and actions to changing their alcohol use. Contrary to our predictions, no significant changes emerged in readiness to change alcohol use, drug use or problems following the brief MI intervention. The relationship between MI fidelity and treatment engagement (i.e., number of DBT sessions attended) was significant. Specifically, the greater the percent of MI adherent statements made by the practitioner, the greater the treatment engagement by the adolescent (i.e., attendance in group treatment). Although other MI fidelity dimensions such as percent complex reflections, percent open questions, reflection-to-question ratio and Global Spirit were not significantly associated with treatment engagement individually, the combined use of these MI fidelity dimensions had a significant effect at increasing adolescent treatment engagement. These results add to the literature which has suggested the strength of the intervention lies in the integration of the skills and MI spirit and that the 'whole is greater than the sum of its parts.' The findings from the current pilot study demonstrate the effectiveness of MI as a pre-treatment intervention for adolescents with CDs and provide essential information for therapist training and supervision. Future studies could examine the efficacy of brief MI interventions using a randomized control study design.

Keywords: Adolescent
Concurrent Disorders
Motivational Interviewing
Advisor: Goldstein, Abby L
The Family Study: Assessment of the Incidence, Etiology, Circumstances and Familial Risk for Sudden Cardiac Death and Aborted Sudden Cardiac Death in Young Individuals

Background: Recent reviews have highlighted our lack of information on the incidence etiology and circumstances of sudden death (SD) in the young, particularly the distribution of underlying disorders, preventable triggers, and identifiable familial predisposition to fatal arrhythmias. Methods: This study had 3 parts: (1) the development and (2) implementation of a novel, comprehensive methodology to capture all SDs and aborted SDs (both cardiac and non-cardiac) in a defined geographic area, (3) followed by a feasibility study with a case control design. We utilized a prospectively collected, population-based registry of all out-of-hospital cardiac arrests (OHCAs) in the Greater Toronto Area, to identify patients from 2009-2012. The retrospective study included cases that were OHCAs ages 2-45, treated or untreated, died or survived and we reviewed all available data for each case and adjudicated an etiology. In the feasibility study, included cases were presumed cardiac, treated OHCAs ages 18-65. Two relatives per patient were interviewed regarding symptoms prior to the arrest, cardiac history, and family history of sudden cardiac death (SCD). Two sets of control patients were administered the same questionnaire as cases. Results: We identified 656 SCDs ages 2-45 over a 4 year period, with an overall annual incidence rate of 3.97 per 100,000 persons. We report a high autopsy rate, with a shift towards ischemic heart disease as the predominant underlying etiology in adults ages 35-45, from structural heart disease and sudden unexplained deaths in children. Adults experienced their SCDs more frequently at home and at rest than did children, and most reported new symptoms in the day preceding their event. Our feasibility studies demonstrated that it is viable to obtain a reliable family history of SCD and major cardiac risk factors from both cases and controls using a self-developed survey. Conclusions: By using a validated comprehensive population based registry of consecutive cases to identify all eligible patients, in combination with a novel classification methodology, large sample size, and multiple sources of data, we were able to better describe the nature and scope of the problem of sudden cardiac death within a young, urban Canadian population.

Keywords: Epidimiology
Family History
Incidence
Sudden Cardiac Death
Sudden Death
Young Individuals
Advisor: Dorian, Paul
International Structure, Cooperation, and Sovereign Debt Crises: The Brazilian Debt Restructurings of 1898, 1931, and 1983

In this dissertation, I offer three main contributions to the literature on sovereign debt. First, I make the case for a structurally-oriented perspective on debt crises. The social institutions that comprise the finance and production structures of the international economy act as conduits for the transmission of crises from developed countries to the periphery of the system, as they increase the relative scarcity of capital through mechanisms such as capital and trade flows. I argue that defaults and moratoria are thus better understood as reactions to the relative scarcity of capital at the international level and not as opportunistic strategies adopted by utility-maximizing politicians who want to avoid the costs associated with repayment. Second, I reevaluate the relationship between debtors and creditors and how they cooperate. I argue that they cooperate by means of positive-sum debt restructuring processes whose results fall within a continuum between full repayment and full repudiation. In other words, cooperation is based on a compromise and not on the enforcement of the original terms of debt contracts by creditor countries or the creditors themselves. Finally, I offer a deeper and more nuanced analysis of the role that the structural power of creditors and creditor countries play in the sovereign debt market, and I argue that they shape the social arrangements that regulate their relationship with debtor countries. I support my claims with qualitative historical studies of three past cases of Brazilian moratoria and debt renegotiations - the Funding Loans of 1898 and 1931, and the Financing Program for 1983.

Keywords: Brazil
Debt Crises
International Political Economy
International Relations
Sovereign Debt
Advisor: Bernstein, Steven
Design of Novel Endoscopic Suction Grasping and Superelastic Surgical Clips Based on a Novel Model of Thin Collagenous Tissue

Current endoscopic manipulation and sealing techniques are ineffective at large puncture repair, fistula closure, and anastomosis in tubular organs. For manipulation, the working channel of the endoscope is unavoidably small and thus so are the conventional graspers which can be passed through them. Small grasping jaws cannot distribute force widely enough to apply large forces without tearing tissue, thereby limiting the applied pulling force. Additionally, the surface of tubular organs is smooth, concave, and lubricated, making conventional grasping difficult or requiring hooked jaws that further damage the tissue. Endoscopic tissue sealing is currently accomplished by mechanical clips which protrude into the lumen from the organ wall when deployed and become a possible obstruction when placing several clips to seal larger openings or when performing an anastomosis. To address these clinical needs, a novel suction grasper and a superelastic, self-closing surgical clip were developed, characterized, and optimized. Additionally, to properly design the grasper and clip, a novel model of the esophageal wall that can be used for puncture and bearing force, in addition to the traditional stress-strain behaviour, was developed and validated. The tissue model was constructed using a bottom-up approach and validated against ex-vivo testing. The bottom-up approach was accomplished by examining the concentrations of each of structural components of tissue (collagen, elastin, muscle) and arranging them according to histological findings. For the superelastic, self-closing clip, the metallurgy of nitinol was reviewed and used to devise a single-step manufacturing process which would optimize the strain limit and closing force of the material. Next, the optimal diameter of clip and wire were set taking the opening force, material elastic limit, and bearing force on the tissue into account. Lastly, grasping force from suction was characterized for hole size, number, and distribution and suction force was compared against puncture force. Histology was performed to assess for tissue damage from suction grasping during clip application in vivo.

Keywords: Endoscopic
Medical Devices
Nitinol
Surgery
Advisor: Drake, James
Goldenburg, Andrew