Investigating the Role of cAMP-Signaling in the Regulation of Vascular Endothelial Cell Adaptive Responses to Fluid Shear Stress

The circulating blood exerts a force on the vascular endothelium, termed fluid shear stress (FSS), which directly impacts numerous vascular endothelial cell (VEC) functions. For example, high rates of linear and undisturbed (i.e. laminar) blood flow maintains a protective and quiescent VEC phenotype. Meanwhile, deviations in blood flow, which can occur at vascular branchpoints and large curvatures, create areas of low, and/or oscillatory FSS, and promote a pro-inflammatory, pro-thrombotic and hyperpermeable phenotype. Indeed, it is known that these areas are prone to the development of atherosclerotic lesions. Herein, we show that cyclic nucleotide phosphodiesterase (PDE) 4D (PDE4D) activity is increased by FSS in human arterial endothelial cells (HAECs) and that this activation regulates the activity of cAMP-effector protein, Exchange Protein-activated by cAMP-1 (EPAC1), in these cells. Importantly, we also show that these events directly and critically impact HAEC responses to FSS, especially when FSS levels are low. Both morphological events induced by FSS, as measured by changes in cell alignment and elongation in the direction of FSS, and the expression of critical FSS-regulated genes, including Krüppel-like factor 2 (KLF2), endothelial nitric oxide synthase (eNOS) and thrombomodlin (TM), are mediated by EPAC1/PDE4D signaling. At a mechanistic level, we show that EPAC1/PDE4D acts through the vascular endothelial-cadherin (VECAD)/ platelet-cell adhesion molecule-1 (PECAM1)/vascular endothelial growth factor receptor 2 (VEGFR2) mechanosensor to activate downstream signaling though Akt. Given the critical role of PDE4D in mediating these effects, we also investigated the impact of various patterns of FSS on the expression of individual PDE genes in HAECs. Notably, PDE2A was significantly upregulated in response to high, laminar FSS, while PDE3A was upregulated under low, oscillatory FSS conditions only. These data may provide novel therapeutic targets to limit FSS-dependent endothelial cell dysfunction (ECD) and atherosclerotic development.

THE TRANSPORT OF HEAT BY FLOWING GROUNDWATER IN A DISCRETE FRACTURE

In typical theoretical or experimental studies of heat migration in discrete fractures, conduction and thermal dispersion are commonly neglected from the fracture heat transport equation, assuming heat conduction into the matrix is predominant. In this study analytical and numerical models are used to investigate the significance of conduction and thermal dispersion in the plane of the fracture for a point and line sources geometries. The analytical models account for advective, conductive and dispersive heat transport in both the longitudinal and transverse directions in the fracture. The heat transport in the fracture is coupled with a matrix equation in which heat is conducted in the direction perpendicular to the fracture. In the numerical model, the governing heat transport processes are the same as the analytical models; however, the matrix conduction is considered in both longitudinal and transverse directions. Firstly, we demonstrate that longitudinal conduction and dispersion are critical processes that affect heat transport in fractured rock environments, especially for small apertures (eg. 100 μm or less), high flow rate conditions (eg. velocity greater than 50 m/day) and early time (eg. less than 10 days). Secondly, transverse thermal dispersion in the fracture plane is also observed to be an important transport process leading to retardation of the migrating heat front particularly at late time (eg. after 40 days of hot water injection). Solutions which neglect dispersion in the transverse direction underestimate the locations of heat fronts at late time. Finally, this study also suggests that the geometry of the heat sources has significant effects on the heat transport in the system. For example, the effects of dispersion in the fracture are observed to decrease when the width of the heat source expands.

Medical Curriculum Change at Queen's-affiliated Medical Colleges: 1881 – 1910

This study explores the curriculum at Queen’s-affiliated medical colleges, specifically The Royal College of Physicians and Surgeons, Kingston, the Kingston Women’s Medical College, and Queen’s Medical College, from 1881 to 1910, using the textbooks prescribed by these institutions as primary sources. The central question encompasses what factors primarily motivated the curriculum at Queen’s-affiliated medical colleges to change. Within the historiographical scholarship on Queen’s College, this question has not yet been addressed and, to my knowledge, this is the first medical education history to specifically address textbooks as part of a medical school curriculum. During this period, these institutions experienced reorganizational shifts, such as the reunification of Queen’s Medical College with The Royal College of Physicians and Surgeons, Kingston, as well as the introduction and subsequent exclusion of female students. Within this context, this study examines how the forces of scientific innovation and co-education impacted the curriculum during the period under study, as measured by textbook change, specifically in the courses of obstetrics and gynaecology, the theory and practice of medicine, and surgery. To what degree was curriculum in these courses responsive to scientific inventions and discoveries, changing therapeutic practices, and possible gender biases? From 1881 to 1910, innovations such as x-ray and anaesthesia became commonplace within medical practice. Some technologies gained acceptance in the curriculum, while others fell out of favour. This study tracks these scientific discoveries through the textbooks used at Queen’s-affiliated medical colleges in order to demonstrate how the evolving nature of medicine was represented in the curriculum. To address how gender influenced the curriculum, textbooks from the Kingston Women’s Medical College and The Royal College of Physicians and Surgeons, Kingston, were compared. For two out of the three examined courses, it was found that sections of textbooks discussing various topics at the Kingston Women’s Medical College contained significantly more detail than their corresponding sections within The Royal College’s textbooks. It was speculated that the instructors preferred to teach their female students through textbooks, rather than lectures.

Interpersonal Emotion Dynamics in Mother-Daughter Dyads during Adolescence

Thesis (Ph.D, Psychology) -- Queen's University, 2016-05-16 14:38:20.622

Performing Pedagogies and Exploring Embodied Knowledge

Performing Pedagogies was a week-long performance and exhibition series I organized that took place in Kingston, Ontario between March 15th - March 20th 2016. The motivation for this project came from a desire to explore performative modes of experiencing critical, embodied knowledge. The series featured five performances, a long distance collaboration between thirty-one Queen’s undergraduate students and a Vancouver artist-run free school (The School for Eventual Vacancy), a subsequent exhibition, a panel discussion, and a radical performance pedagogy workshop led by co-artistic director of the international performance art troupe, La Pocha Nostra. Artists featured included Golboo Amani, Basil AlZeri, Caitlin Chaisson, Justin Langlois, Saul Garcia-Lopez, Francisco-Fernando Granados, and Andrew Rabyniuk. By curating examples of performance art that variously incorporated embodied pedagogical interventions, I examined the processes of performance as pedagogy. Performing Pedagogies explored interventions into contemporary contours of neoliberal education paradigms through embodied encounters—fostering conversations about the meanings and limitations of knowledge dissemination and education today and posing questions about possibilities for radical pedagogies, embodied knowledge, and counter curricula.

The Modelling of Photovoltaic, Solar Thermal, and Photovoltaic/Thermal Domestic Hot Water Systems

Solar heating of potable water has traditionally been accomplished through the use of solar thermal (ST) collectors. With the recent increases in availability and lower cost of photovoltaic (PV) panels, the potential of coupling PV solar arrays to electrically heated domestic hot water (DHW) tanks has been considered. Additionally, innovations in the SDHW industry have led to the creation of photovoltaic/thermal (PV/T) collectors, which heat water using both electrical and thermal energy. The current work compared the performance and cost-effectiveness of a traditional solar thermal (ST) DHW system to PV-solar-electric DHW systems and a PV/T DHW system. To accomplish this, a detailed TRNSYS model of the solar hot water systems was created and annual simulations were performed for 250 L/day and 325 L/day loads in Toronto, Vancouver, Montreal, Halifax, and Calgary. It was shown that when considering thermal performance, PV-DHW systems were not competitive when compared to ST-DHW and PVT-DHW systems. As an example, for Toronto the simulated annual solar fractions of PV-DHW systems were approximately 30%, while the ST-DHW and PVT-DHW systems achieved 65% and 71% respectively. With current manufacturing and system costs, the PV-DHW system was the most cost-effective system for domestic purposes. The capital cost of the PV-DHW systems were approximately $1,923-$2,178 depending on the system configuration, and the ST-DHW and PVT system were estimated to have a capital cost of $2,288 and $2,373 respectively. Although the capital cost of the PVT-DHW system was higher than the other systems, a Present Worth analysis for a 20-year period showed that for a 250 L/day load in Toronto the Present Worth of the PV/T system was approximately $4,597, with PV-DHW systems costing approximately $7,683-$7,816 and the ST-DHW system costing $5,238.

Performing Pedagogies and Exploring Embodied Knowledge as Curatorial Investigation

Performing Pedagogies was a week-long performance and exhibition series I organized that took place in Kingston, Ontario between March 15th - March 20th 2016. The motivation for this project came from a desire to explore performative modes of experiencing critical, embodied knowledge. The series featured five performances, a long distance collaboration between thirty-one Queen’s undergraduate students and a Vancouver artist-run free school (The School for Eventual Vacancy), a subsequent exhibition, a panel discussion, and a radical performance pedagogy workshop led by co-artistic director of the international performance art troupe, La Pocha Nostra. Artists featured included Golboo Amani, Basil AlZeri, Caitlin Chaisson, Justin Langlois, Saul Garcia-Lopez, Francisco-Fernando Granados, and Andrew Rabyniuk. By curating examples of performance art that variously incorporated embodied pedagogical interventions, I examined the processes of performance as pedagogy. Performing Pedagogies explored interventions into contemporary contours of neoliberal education paradigms through embodied encounters—fostering conversations about the meanings and limitations of knowledge dissemination and education today and posing questions about possibilities for radical pedagogies, embodied knowledge, and counter curricula.

A Cloud-based Framework for Security Analysis of Browser Extensions

In today's internet world, web browsers are an integral part of our day-to-day activities. Therefore, web browser security is a serious concern for all of us. Browsers can be breached in different ways. Because of the over privileged access, extensions are responsible for many security issues. Browser vendors try to keep safe extensions in their official extension galleries. However, their security control measures are not always effective and adequate. The distribution of unsafe extensions through different social engineering techniques is also a very common practice. Therefore, before installation, users should thoroughly analyze the security of browser extensions. Extensions are not only available for desktop browsers, but many mobile browsers, for example, Firefox for Android and UC browser for Android, are also furnished with extension features. Mobile devices have various resource constraints in terms of computational capabilities, power, network bandwidth, etc. Hence, conventional extension security analysis techniques cannot be efficiently used by end users to examine mobile browser extension security issues. To overcome the inadequacies of the existing approaches, we propose CLOUBEX, a CLOUd-based security analysis framework for both desktop and mobile Browser EXtensions. This framework uses a client-server architecture model. In this framework, compute-intensive security analysis tasks are generally executed in a high-speed computing server hosted in a cloud environment. CLOUBEX is also enriched with a number of essential features, such as client-side analysis, requirements-driven analysis, high performance, and dynamic decision making. At present, the Firefox extension ecosystem is most susceptible to different security attacks. Hence, the framework is implemented for the security analysis of the Firefox desktop and Firefox for Android mobile browser extensions. A static taint analysis is used to identify malicious information flows in the Firefox extensions. In CLOUBEX, there are three analysis modes. A dynamic decision making algorithm assists us to select the best option based on some important parameters, such as the processing speed of a client device and network connection speed. Using the best analysis mode, performance and power consumption are improved significantly. In the future, this framework can be leveraged for the security analysis of other desktop and mobile browser extensions, too.

Terahertz Response of Excitons in Nanorod Heterostructures

Quantum-confined systems are one of the most promising ways to enable us to control a material's interactions with light. Nanorods in particular offer the right dimensions for exploring and manipulating the terahertz region of the spectrum. In this thesis, we model excitons confined inside a nanorod using the envelope function approximation. A region-matching transfer matrix method allows us to simulate excitonic states inside arbitrary heterostructures grown along the length of the rod. We apply the method to colloidal CdSe rods 70 nm in length and under 10 nm in diameter, capped with ligands of DDPA and pyridine. We extend past studies on these types of rods by taking into account their dielectric permittivity mismatch. Compared to previous calculations and experimentally measured terahertz absorption, we predict a higher energy main 1S$z$ to 2P$z$ transition peak. This indicates that the rods are likely larger in diameter than previously thought. We also investigate a nanorod with GaAs/Al$_{0.3}$Ga$_{0.7}$As coupled double dots. The excitonic transitions were found to be manipulable by varying the strength of an applied electric field. We employ quasi-static state population distributions to simulate the effects of exciton relaxation from optically active states to dim ground states. A critical value of the applied field, corresponding to the exciton binding energy of ~18 meV, was found to dramatically alter the terahertz absorption due to state mixing. Above this critical field, more nuanced shifts in transition energies were observed, and gain from radiative relaxation to the ground state is predicted.

Countermanding in rats as a practical model for investigation of adaptive control of behaviour, lifespan changes in behavioural control and neurotransmitter function

The countermanding paradigm was designed to investigate the ability to cancel a prepotent response when a stop signal is presented and allows estimation of the stop signal response time (SSRT), an otherwise unobservable behaviour. Humans exhibit adaptive control of behaviour in the countermanding task, proactively lengthening response time (RT) in expectation of stopping and reactively lengthening RT following stop trials or errors. Human performance changes throughout the lifespan, with longer RT, SSRT and greater emphasis on post-error slowing reported for older compared to younger adults. Inhibition in the task has generally been improved by drugs that increase extracellular norepinephrine. The current thesis examined a novel choice response countermanding task in rats to explore whether rodent countermanding performance is a suitable model for the study of adaptive control of behaviour, lifespan changes in behavioural control and the role of neurotransmitters in these behaviours. Rats reactively adjusted RT in the countermanding task, shortening RT after consecutive correct go trials and lengthening RT following non-cancelled, but not cancelled stop trials, in sessions with a 10 s, but not a 1 s post-error timeout interval. Rats proactively lengthened RT in countermanding task sessions compared to go trial-only sessions. Together, these findings suggest that rats strategically lengthened RT in the countermanding task to improve accuracy and avoid longer, unrewarded timeout intervals. Next, rats exhibited longer RT and relatively conserved post-error slowing, but no significant change in SSRT when tested at 12, compared to 7 months of age, suggesting that rats exhibit changes in countermanding task performance with aging similar to those observed in humans. Finally, acute administration of yohimbine (1.25, 2.5 mg/kg) and d-amphetamine (0.25, 0.5 mg/kg), which putatively increase extracellular norepinephrine and dopamine respectively, resulted in RT shortening, baseline-dependent effects on SSRT, and attenuated adaptive RT adjustments in rats in the case of d-amphetamine. These findings suggest that dopamine and norepinephrine encouraged motivated, reward-seeking behaviour and supported inhibitory control in an inverted-U-like fashion. Taken together, these observations validate the rat countermanding task for further study of the neural correlates and neurotransmitters mediating adaptive control of behaviour and lifespan changes in behavioural control.

Surveillance Studies and the Surveilled Subject

Surveillance studies has been somewhat inattentive to the perspective of the surveilled subject. It is the functioning of the surveillance apparatus, not the relatively inconsequential subject, which has tended to frame the focus of surveillance inquiries; leaving understandings of surveilled subjects’ experiences relatively limited. This research addresses this gap in the literature, exploring ways in which surveillance studies might understand the surveilled subject with greater consistency. Participants (N=47) shared their encounters with and perceptions of surveillance in a specific (Pearson International Airport) and general (everyday life) context through semi-structured interviews. The findings suggest that surveilled subjects’ encounters can be understood with some consistency – characterized by consistent criteria across subjects and contexts, and through a consistent theoretical framework across subjects in a specific context. However, consistency should not be confused with uniformity; encounters with surveillance must also be recognized for the extent to which they are nuanced and situated. For example, as this study also highlights, participants’ perceptions of encounters with surveillance at Pearson International Airport were differentially distributed in relation to identity characteristics (particularly minority status).

BEYOND WORDS: HOW LEARNING TO READ AND MENTAL HEALTH ARE RELATED FOR STRUGGLING READERS

The overarching purpose of this research program was to describe how intervening for academic deficits may be accompanied by changes in mental health. This multi-dimensional, multi-perspective, and iterative research program was developed to report on two distinct but related studies that addressed the same issue: in what ways does the mental health of students change as they transition from being struggling readers to more able readers? To describe the changes, these studies used a number of qualitative research methodologies—focus groups, individual interviews, and ethnographic case studies. Themes that emerged from the focus group and interview data in the first study were used to create a model that guided observations and interview questions in the second study. The first study described what parents, classroom teachers, and two reading instructors of nine previously struggling readers reported as the outcomes of becoming a more proficient reader. Data from this study indicated three broad domains in which change, as perceived by participants, occurred―cognitive/learning, behavioural/social, and psychological/emotional. Within these three domains, six dimensions were identified as having changed as reading improved: (a) academic achievement, (b) attitude, (c) attention, (d) behaviour, (e) mental health, and (f) empowerment. These domains, dimensions, and 15 constituent elements were used to create the model to guide the subsequent study. The purpose of the second study was to validate and refine this model by using an ethnographic case study approach to explore the ways in which the model accounted for the changes in reading and mental health seen in three boys over the months they participated in the intervention. By investigating the relationship between learning to read and mental health, this research aimed to enhance our understanding of how gains in reading may also improve the mental health of struggling readers. The model was found to be robust and a convenient conceptual framework to further our understanding of this relationship. Importantly, gains made in the cognitive/learning domain through an effective reading intervention, offered in a supportive learning environment, were shown to be accompanied by concomitant gains in both the behavioural/social and psychological/emotional domains—all of which enhance student thriving.

RELIGIOUS SCULPTURE OF THE CHILOÉ ARCHIPELAGO, FROM THE 17TH TO THE 21ST CENTURY

Despite its central role in religious life of the region, the sculptural tradition of the Southern Chilean Chiloé Archipelago, ranging from the 17th century to the present day, has been vastly understudied. Isidoro Vázquez de Acuña’s 1994 volume Santeria de Chiloe: ensayo y catastro remains the only catalogue of Chilote sculpture. Though the author includes photographs of a vast array of works, he does not attempt to place the sculptures within a chronology, or consider their place within the greater Latin American context. My thesis will place this group of works within a chronological and geographical context that reaches from the 16th century to the present day, connected to the artistic traditions of regions as far afield as Paraguay and Lima. I will first consider the works brought to the Archipelago by religious orders – the Jesuits and Franciscans – as well as influences on artistic style and religious culture throughout the 17th, 18th and 19th centuries. I will focus in particular on three works generally considered to be from the 17th and 18th centuries – the Virgin of Loreto at Achao, the Saint Michael at Castro, and the Jesus Nazareno of Caguach – using visual analysis and sifting through generations of primary and secondary sources to determine from where and when these sculptures came. With this investigation as a foundation, I will consider how they inspired vernacular sculptural expression and trace ‘family trees’ of vernacular works based on these precedents. Vernacular artistic traditions are often viewed as derivative and lacking in skill, but Chilote sculptors in fact engaged with a variety of outside influences and experimented with different sculptural styles. I will conclude by considering which aspects of these styles Chilote artists chose to incorporate into their own work, alter or exclude, artistic decisions that shed light on the Archipelago’s religious and cultural fabric.

Lost in Translation? Russian Media Portrayals and Laypersons’ Interpretations of Angelina Jolie’s Breast Cancer Discourse

In May 2013, Angelina Jolie revealed that because she had a family history of breast and ovarian cancer and carried a rare BRCA gene mutation, she had undergone a preventive double mastectomy. Media coverage has been extensive around the world, including in Russia, not an English-language country, where all global news is inevitably filtered by translation. After examining the reactions of Russian mass media and members of the public to Jolie’s disclosure, I consider what transformations have occurred with Jolie’s message in the process of cross-cultural transfer. I explore the mass media portrayal of Jolie’s announcement, laypersons’ immediate and prolonged reactions, and the reflections of patients involved directly in the field of hereditary breast cancer. To my knowledge, this multifaceted and bilingual project is the first conceptualization of Jolie’s story as it has been translated in a different sociocultural environment. I start with examination of offline and online publications that appeared in Russia within two months after Jolie’s announcement. In this part of my analysis, I conceptualize the representation of Jolie’s case in Russian mass media and grasp what sociocultural waves were generated by this case among general lay audiences. Another part of my study contains the results of qualitative in-depth interviews. Eight women with a family history of hereditary breast cancer were recruited to participate in the research. The findings represent Jolie’s case through the eyes of Russian women with the same gene mutation as Jolie. Consolidating my findings, I argue that Jolie’s announcement was misinterpreted and misrepresented by Russian mass media, as well as misunderstood by a considerable part of the media audience. Jolie’s perspective on hereditary breast cancer mostly remained unheard among members of the Russian public. I make suggestions about the reasons for such a phenomenon, and demonstrate how Jolie’s case is implicated in politics, economics, and the culture of contemporary Russia.

Investigating the potential magnetic origin of wind variability in OB stars

In this thesis, the origin of large-scale structures in hot star winds, believed to be responsible for the presence of discrete absorption components (DACs) in the absorption troughs of ultraviolet resonance lines, is constrained using both observations and numerical simulations. These structures are understood as arising from bright regions on the stellar surface, although their physical cause remains unknown. First, we use high quality circular spectropolarimetric observations of 13 well-studied OB stars to evaluate the potential role of dipolar magnetic fields in producing DACs. We perform longitudinal field measurements and place limits on the field strength using Bayesian inference, assuming that it is dipolar. No magnetic field was detected within this sample. The derived constraints statistically refute any significant dynamical influence from a magnetic dipole on the wind for all of these stars, ruling out such fields as a cause for DACs. Second, we perform numerical simulations using bright spots constrained by broadband optical photometric observations. We calculate hydrodynamical wind models using three sets of spot sizes and strengths. Co-rotating interaction regions are yielded in each model, and radiative transfer shows that the properties of the variations in the UV resonance lines synthesized from these models are consistent with those found in observed UV spectra, establishing the first consistent link between UV spectroscopic line profile variability and photometric variations and thus supporting the bright spot paradigm (BSP). Finally, we develop and apply a phenomenological model to quantify the measurable effects co-rotating bright spots would have on broadband optical photometry and on the profiles of photopheric lines in optical spectra. This model can be used to evaluate the existence of these spots, and, in the event of their detection, characterize them. Furthermore, a tentative spot evolution model is presented. A preliminary analysis of its output, compared to the observed photometric variations of xi Persei, suggests the possible existence of “active longitudes” on the surface of this star. Future work will expand the range of observational diagnostics that can be interpreted within the BSP, and link phenomenology (bright spots) to physical processes (magnetic spots or non-radial pulsations).