VictorJuiz/thesis huggingface dataset:
The Role of C-Type Natriuretic Peptide Signaling in Aortic Valve Disease

Calcific aortic valve disease (CAVD) is a cell-mediated pathology without effective pharmacotherapy whose early pathogenesis is drastically understudied. C-type natriuretic peptide (CNP) is expressed 3x more on the disease-protected ventricular side than the disease-prone aortic side of the valve, and inhibits valvular interstitial cell myofibrogenesis and osteogenesis in vitro. Importantly, CNPâ s functional significance to CAVD in vivo has not been studied. In this thesis, a mildly atherogenic dietary mouse model of CAVD was characterized. Diet-induced proteoglycan synthesis identified in these mouse valves was versican-rich, occurred along with increased SOX9 expression, and developed before myofibrogenesis, calcification, or deficits in valvular function. Subsequently, mice with a loss-of-function mutation of the CNP receptor Npr2 were employed to test whether CNP/NPR2 were protective against CAVD in vivo. Npr2+/- mice developed cardiac dysfunction, hypertrophy, and fibrosis. Npr2 deficiency produced impaired valve function, which was exacerbated by long-term hypercholesterolemia. A portion of Npr2+/- mice had bicuspid aortic valves (BAVs, ~10%) with the most severe deficits in valvular function, and worst cusp thickening, fibrosis, and calcification. Lastly, NPR2-deficient mice developed ascending aortic dilatations characterized by elastin fragmentation and loss of medial collagen and smooth muscle cells; dilatation was accelerated in those mutants with BAVs. Abnormal hemodynamics likely contribute to aggravated CAVD and aortic dilatation in BAVs. However, there is a lack of tools to quantify complex hemodynamics in small animals where genetic/metabolic contributions to disease can be controlled. Echocardiographic particle image velocimetry (echoPIV) without exogenous contrast particles was employed with high-framerate ECG-gated Kilohertz Visualization (EKV) to track erythrocyte movement in the mouse ventricle and aortic root. EKV+echoPIV identified strong ventricular vortices during diastolic filling that transitioned to high-velocity systolic outflow. In the aortic root, that systolic aortic jet with recirculatory flow in the sinuses was apparent; oscillatory flow occurred once valve leaflets apposed. In summary, this thesis sheds light on the early pathogenesis of CAVD, identifies a novel therapeutic signaling axis in vivo, and presents a novel imaging technique for quantifying hemodynamics in small animal models of cardiovascular disease.

Keywords: aortic valve disease
C-type natriuretic peptide
echocardiographic particle image velocimetry
heart valve
natriuretic peptide receptor 2
proteoglycan
Advisor: Simmons, Craig A
Modelling Air Bubble Entrapment and Transport in Sprayed Liquid Films

A parallel, three-dimensional multiphase fluid flow solver was employed to model the physics of droplet coalescence, bubble entrapment, bubble impact, and Marangoni convection in a sprayed liquid layer. The results are relevant to understanding the formation of common defects in paint films such as non-uniform thickness, bubble entrapment and surface patterns. Coalescence of unequal sized droplets eventually results in the smaller droplet being drawn into the larger droplet. Droplets sprayed on a solid surface do not form a uniform film but agglomerate in large liquid masses. Air bubbles are entrapped under impacting droplets because of increased pressure in the air film between the droplets and the solid surface. The substrate orientation and liquid-solid contact angle influence the number of bubbles remaining in a liquid film. Once liquid motion stops, buoyancy forces drive the bubbles towards the substrate for a downward facing substrate. Depending on the bubble approach velocity and substrate properties the bubbles may either attach to the surface or bounce off. In evaporating liquid films, surface tension gradients create Marangoni flows that transport bubbles along with them and may force them to the free liquid surface where they break through and escape. Marangoni convection flows can also deform the surface of paint films and create orange peel defects.

Keywords: Bubble Entrapment
Bubble Impact
Droplet Coalescence
Marangoni Flow
Spray Paint Film
VOF Numerical Modelling
Advisor: Mostaghimi, Javad
Chandra, Sanjeev
A Variable Gain Direct Digital Readout System for Capacitive Inertial Sensors

High fidelity interface circuits for capacitive accelerometers make use of feedback for signal detection but these feedback systems are limited by the sense capacitance and sensitivity of the accelerometers. This problem is addressed by a variable gain delta sigma based interface circuit that time multiplexes the accelerometer sense capacitance between the feedforward gain stage and feedback digital to analog (DAC) stage. Interfaced with a commercial accelerometer with sensitivity of 4.5 fF/g, the circuit achieves 40.6 dB SNDR in the x-direction and 42.5 dB SNDR in the y-direction due to limitations of the available testing equipment. With proper equipment, the system has the potential to achieve 53.0 and 54.9 dB SNDR in the x and y direction respectively while significantly reducing harmonics associated with the non-linear variable sense capacitors. Other interface circuits using the same sensor at comparable power would achieve linearity below 40 dB due to the limitation of the feedback structure.

Keywords: accelerometers
charge balanced
flexible
interface circuits
ratiometric
readout circuits
Advisor: Johns, David Andrew
A Systems-Level Investigation of the Metabolism of Dehalococcoides mccartyi and the Associated Microbial Community

Dehalococcoides mccartyi are a group of strictly anaerobic bacteria important for the detoxification of man-made chloro-organic solvents, most of which are ubiquitous, persistent, and often carcinogenic ground water pollutants. These bacteria exclusively conserve energy for growth from a pollutant detoxification reaction through a novel metabolic process termed organohalide respiration. However, this energy harnessing process is not well elucidated at the level of D. mccartyi metabolism. Also, the underlying reasons behind their robust and rapid growth in mixed consortia as compared to their slow and inefficient growth in pure isolates are unknown. To obtain better insight on D. mccartyi physiology and metabolism, a detailed pangenome-scale constraint-based mathematical model of metabolism was developed. The model highlighted the energy-starved nature of these bacteria, which probably is linked to their slow growth in isolates. The model also provided a useful framework for subsequent analysis and visualization of high-throughput transcriptomic data of D. mccartyi. Apart from confirming expression of the majority genes of these bacteria, this analysis helped review the annotations of metabolic genes. Revised annotations of two such metabolic genes — NADP+-isocitrate dehydrogenase and phosphomannose isomerase — were then experimentally verified. Finally, growth experiments were performed with a D. mccartyi-containing anaerobic mixed enrichment culture to explore the effects of exogenous vitamin omission from the growth medium on D. mccartyi and the associated microbial community. The experiments showed how nutritional requirements of these bacteria changed the composition and dynamics of their associated microbial community. Overall, a systems-level approach was used in this research to obtain a fundamental and critical understanding of the metabolism and physiology of D. mccartyi in isolates, as well as in microbial communities they naturally inhabit. The results presented in this thesis, therefore, will help design effective strategies for future bioremediation efforts by D. mccartyi.
Malignant Europeanization: Schengen, Irregular Migration Governance, and Insecurity on Europe's Peripheries

This thesis examines the relationship between open borders and free mobility in Europe, the Schengen regime, and security around Europe’s peripheries. Schengen is a constitutive element of the European project. Its maintenance depends on what the EU refers to as “compensatory measures” for addressing uncontrolled migration. I ask two questions: What is the relationship between the European project and changes in irregular migration systems? How do Schengen’s compensatory measures meet the EU’s stated foreign policy goals of fostering a ring of stable democracies in its near-abroad? My causal argument is that Schengen’s compensatory measures cause changes in irregular migration systems, which result in insecurity around Europe’s peripheries. I argue these dynamics are evidence of Malignant Europeanization, which I define as insecurity and regressive practices and norms resulting from Europe’s regional integration. I situate this project in the Europeanization literature, which analyzes relationships between European integration and changes in practices, institutions, and norms. Europeanization’s main indicators are reform toward democratic governance, rule of law, rights protections, and liberal market economies: benign Europeanization. In contrast, I identify eight indicators for Malignant Europeanization: migrant insecurity; increased transnational crime; security sector corruption; emboldened militarized non-state actors; domestic political contestation; entrenched authoritarianism and democratic backsliding; burden-shifting and regional tensions; and international norm degeneration. Findings are based on comparative case studies across four irregular migration systems: the Western Mediterranean, Central Mediterranean, Western Balkans, and Central and Eastern Europe. Evidence is derived from three years of fieldwork. Variation depends on domestic characteristics in transit states and external incentive structures. In the absence of membership incentives Europe lacks leverage to foster benign Europeanization. Findings problematize the framing of Europe as a progressive global influence. They also raise significant questions about the effectiveness of European foreign policy goals of fostering a ring of stable democracies around its near abroad.

Keywords: Europeanization
Migration
Refugee Regime
Regionalism
Security
Advisor: Bernstein, Steven
THE IMPACT OF UNIVERSITY COSTS AND STUDENT DEBT IN ONTARIO AND QUEBEC: A COMPARATIVE STUDY

For the past three decades, Canada has adopted post-secondary education policies that have reduced per student funding for universities and increased tuition fees and student debt levels. This thesis used mixed methods to investigate the impact of this neoliberal policy matrix on university students in Canada’s two largest provinces, Ontario and Quebec. The research includes the findings of a survey of 1,982 university students and 10 follow-up interviews. Ontario and Quebec provide the basis for a natural experiment as Ontario has the lowest per-student government funding and highest student debt in Canada, whereas Quebec has among the highest government funding and lowest student debt (Canadian Association of University Business Officers, 2015; CFS, 2015; MacDonald Shaker, 2013). The survey results show that median tuition fees were double for Ontario ($8,000) versus Quebec respondents ($3,000) and that median student debt was significantly higher in Ontario ($20,000) than Quebec ($12,000). The research investigated five potential impacts of university costs and student debt that are identified in the literature and found that a significantly larger proportion of Ontario than Quebec students reported: • that cost is a barrier to accessing the program, university and career of their choice, • that their university values them for the revenue they provide rather than as individuals, • and that they have higher levels of mental distress. The third finding on mental distress is concerning. In Ontario 46.0% scored above the diagnostic cut off using the Mental Health Index-5 versus 28.7% in Quebec. The results also show that approximately one quarter of Ontario respondents and one fifth of Quebec respondents report that cost is a barrier to achieving good grades or continuing and completing their studies. The policies that have led to students paying for a large portion of their own university education through debt were proposed by the neoliberal economist, Milton Friedman, in the early 1960s. The findings of this research project indicate a need to review this neoliberal policy matrix because of the detrimental effects on students.

Keywords: Neoliberalism
Ontario
Quebec
Survey
Tuition Fees
University
Advisor: Quarter, Jack
Falenchuk, Olesya
Ontario's Retirement Homes and Long-Term Care Homes: Policy Implications for Care Services, Funding and Governance Regimes

Abstract Purpose: The Province of Ontario is experiencing substantial growth in the seniors’ population requiring care, with capacity, cost and regulatory pressures across all settings. This study compares long-term care homes (LTCHs) and retirement homes (RHs), significant residential care alternatives for seniors in Ontario, regarding pricing, levels of care and availability of services, in the context of different government funding and regulatory oversight. Attention is given to the way owners of homes shape their services in response to prevailing policy instruments and other environmental factors. Methods: The research uses an explanatory sequential mixed methods design, with a first phase involving the analysis of quantitative data regarding LTCHs and RHs, and a second phase involving qualitative (interview) data from key informants. The first phase informs the interview questions for the second phase, with integration occurring after Phase 2. Results: Substantial overlaps exist in the characteristics of the two resident populations (LTCHs and RHs), which are most evident among the population of seniors requiring high levels of care and support. However, the two sectors are funded and regulated differently, which affect how services are delivered. Most care costs in LTCHs are publicly funded, while residents in RHs generally cover these expenses personally. Equity of access issues arise from shortages of beds in LTCHs and limited government funding for care services in RHs. LTCH owner strategies are affected by excess demand for beds and by regulatory instruments that limit profit for care and accommodation. With RHs, more flexible owner strategies are evident for care levels, pricing and location. However, without public funding, availability and affordability of RHs to the resident suffer and owner strategies focus on areas of higher income, population density or community infrastructure. The two sectors are also regulated differently in respect of care standards, security and enforcement. Conclusions: Policy instruments influence the features of residential care service offerings by shaping how the owners of seniors’ residential care offer services, with important consequences regarding access to those services. Policy instruments play an important part in determining the availability and affordability of seniors’ residential care, and consistency of governance.

Keywords: funding
governance
long-term care homes
ontario
policy instruments
retirement homes
Advisor: Deber, Raisa
An Exploratory Mixed-Methods Evaluation of Acceptance and Commitment Therapy for Outpatient Group Treatment of Adolescents

Acceptance and commitment therapy (ACT) is a transdiagnostic therapeutic approach that has proven effective for a wide range of psychiatric disorders with adults. There is some evidence suggesting the effectiveness of group-based ACT with adolescents, but the research is limited. This dissertation aims to expand on previous research of group-based ACT with adolescents experiencing heterogeneous anxiety and/or depressive psychiatric disorders in a community hospital outpatient setting. The research consists of two studies using a mixed-methods approach to examine the utility and participants’ experience of group-based ACT. The first study utilized a quantitative methodology to explore treatment effects on symptom amelioration and the therapeutic processes underlying ACT. Seventy-two adolescents participated in this preliminary investigation, and completed outcome and ACT-related process measures at pre, post and three-month follow-up (3MFU) intervals. Repeated measures ANOVAs and pairwise comparisons revealed significant reductions in anxiety and depression symptoms from pre to post, and further significant reductions in symptoms post to 3MFU. There were significant changes in the therapeutic processes of acceptance/defusion, mindfulness and committed action. An investigation of mechanisms of change revealed that change in particular ACT process measures was related to reductions in anxiety and depression symptoms. The second study utilized a qualitative approach to explore adolescents’ experience and better understand the utility of group-based ACT to corroborate and potentially expand on Study 1 results. A subset of 10 adolescents from Study 1 participated in semi-structured interviews at post and 3MFU. Interpretative phenomenological analysis revealed themes of usefulness of treatment, improvements attributed to ACT, non-ACT factors, barriers to treatment use, and treatment within a group context. All participants reported ACT to be a beneficial treatment for emotional difficulties and behavioural functioning, with a few indicating that other factors, in addition to ACT, contributed to improvements. Overall this mixed-methods evaluation provides support for the utility of group-based ACT as a transdiagnostic treatment approach with adolescents. Firm conclusions could not be drawn, however, due to the exploratory nature of this investigation and lack of control or comparison group. Future research is warranted comparing ACT group treatment to control and existing treatments with a similar population across multiple contexts.

Keywords: acceptance and commitment therapy
adolescents
anxiety
community hospital outpatient clinic
depression
group-based treatment
Advisor: Willows, Dale
Numerical characterization of high-frequency flow fluctuations in intracranial aneurysms

Rupture of intracranial aneurysms (IAs), saccular outpouching of blood vessels, can lead to death or permanent disability in majority of the patients. Hemodynamic forces are thought to play a key role in the process, but, currently, can only be estimated through computational fluid dynamic (CFD) simulations of patient's cerebrovasculature. IA flows have conventionally been considered laminar and stable; however, recent studies highlighted the presence of high-frequency flow fluctuations consistent with clinical evidence — a discrepancy attributed to conventional use of low-order CFD. The goal of this doctoral thesis was to investigate the nature and characteristic of these flow fluctuations, and its prevalence in IAs. Towards that goal, we performed the first mesh, time, and solver refinement study to investigate the isolated impact of each modelling choice (Chapter 2). With 320-fold increase in mesh size, 25-fold increase in time-steps, and considering both a low-order solver and a high-order solver, we found that solver choice had a relatively higher impact on hemodynamics compared to other modelling assumptions. Finding of these flow fluctuations also meant rethinking the conventional assumption of Newtonian rheology for blood. As a first step, we performed a controlled numerical experiment on an idealized stenotic vessel for Re=500-1000, which suggested that shear-thinning non-Newtonian rheology caused a delay of 10% in the critical Reynolds number (Chapter 3). We later investigated the practical impact of these findings on IA hemodynamics (Chapter 4). These findings suggested that assumption of shear- thinning rheology had a negligible impact, particularly when compared to effects of low-order solvers. Due to limitations of current hemodynamic metrics in quantifying flow fluctuations, we proposed a frequency-based (Chapter 5). Using this tool and aforementioned findings, we performed high-resolution simulations of 19 IAs to characterize and investigate the prevalence of flow fluctuations (Chapter 6). Through proper orthogonal decomposition, we showed that, depending on the patient, a wide range of spectra exists, some with high concentration of energy in higher modes. We also found that approximately half of IA aneurysms are ‘turbulent-like and 30% can have cycle-to-cycle fluctuations. Further investigation is needed to establish the clinical impact of these flow fluctuations in IA rupture.

Keywords: cardiovascular flows
Computational Fluid Dynamics (CFD)
Hemodynamics
Intracranial Aneurysms
shear-thinning rheology
Advisor: Steinman, David A.
Education Hubs in the Making: Policy Rationales and International Relations

Since the late 1990s, several governments worldwide have launched initiatives to transform their countries into education hubs in order to attract large numbers of foreign students, scholars, education providers, research institutes, and multinational companies. While many observers consider these initiatives as entrepreneurial projects typical of cross-border education, a proper analysis demands a closer examination of the multiple realities of education hub development and their implementation challenges. This thesis investigates the development of Malaysia, Singapore, and Hong Kong as education hubs. The research examines national initiatives as well as those that are specific to an economic zone (EduCity Iskandar) and a discipline (Islamic finance education hub). What are the rationales driving the development of theses education hubs? What patterns of engagement are evident as these societies forge regional and international ties through higher education? Through policy document analysis and interviews with 36 policymakers and 42 context informants, this study has identified four key rationales: 1) economic benefits, 2) talent development, 3) educational capacity, and 4) soft power. Each rationale generates specific policy objectives and implementation strategies. While Malaysia is keen to generate revenue through student fees and improve its quality of education by injecting competition, Singapore is eager to commercialize research innovations and develop talent in all forms (local, foreign, and diaspora). In contrast, Hong Kong remains skeptical of the economic benefits of an education industry and instead emphasizes talent development while cultivating local institutions. All three societies also aim to exert influence regionally and internationally though ties based on cultural heritage or networks with leading experts (i.e., soft power). These efforts meld a realist approach to international relations with neoliberalism and social constructivism. Nevertheless, serious contextual factors such as the prevailing political climate, deepening ethnic divisions, and the lack of academic freedom present challenges to the development of education hubs.

Advisor: Hayhoe, Ruth