VictorJuiz/thesis huggingface dataset:
The role of Diencephalon/Mesencephalon Homeobox 1 (Dmbx1) in Zebrafish Visual System Development

Visual system development is highly conserved across all vertebrates. The retina receives visual inputs and transfers the sensory information to the brain for processing. In zebrafish, the largest synaptic target of the retinal projections is the optic tectum, which acts as a relay center that organizes visuomotor activities. My research has revealed that the transcriptional regulator Diencephalon/mesencephalon homeobox 1 (dmbx1), of which there are two paralogs represented in the zebrafish genome, plays a pivotal role in coordinating neurogenesis in these functionally integrated regions. During the course of my doctoral research, I have characterized the functions of dmbx1 paralogs in zebrafish retinal and tectal development and showed that they are required for sustaining growth in the retina and the optic tectum. Functional deficiency of the dmbx1 genes caused a severe cell cycle defect in progenitor cells, resulting in reduced tissue growth and delayed differentiation within those structures. Further analysis revealed that progenitor cells require dmbx1 to reduce the level of cyclinD1 expression, in order to promote cell cycle exit. In addition, I discovered that misexpression of both dmbx1 genes could duplicate wnt3a expression and lead to enhanced proliferation at the tectal midline. This suggested that the two transcription factors could regulate different cellular mechanisms with the presence of canonical Wnt signaling. Overall, this research demonstrates that dmbx1 is involved in the timing of retinal and tectal neurogenesis, and provides novel insight into the transcriptional regulation of visual system development in vertebrates.

Keywords: zebrafish visual system
cell cycle
dmbx1
Advisor: Tropepe, Vincent
The Atomic Capital of the World: Technoscience, Suburbanization, and the Remaking of Pittsburgh during the Cold War

Using metropolitan Pittsburgh as an example, this dissertation traces the relationship between suburbanization, the remaking of urban space, technoscience, and the Cold War. It argues that producing spaces for technoscience was a central part of the remaking and suburbanization of metropolitan Pittsburgh. An elite regional alliance enrolled scientists and engineers in their efforts to transform the region from a center of manufacturing to a place focused on rationalizing, administering, and financing production that took place elsewhere. In doing so they created a technological landscape that cast the region’s transformation as part of an inevitable search for progress and as a widely deployable symbol of capitalist rebirth. To enroll scientists and engineers in their efforts they created spaces – research centers, residential suburbs, and urban renewal projects among others – that helped reproduce scientists and engineers’ privilege and authority. Metropolitan Pittsburgh became a key site where technoscience took place, but it was also remade through technoscience. This points to the need for a broader understanding of the processes that reproduce scientists and engineers and their authority and the spaces where technoscience takes place.

Keywords: Technoscience
Suburbs
Pittsburgh
Cold War
Nuclear industry
Urban renewal
Scientists and engineers
Advisor: Lewis, Robert
Securitizing the Coast of Somalia: Political Geographies of Piracy

This dissertation is an organizational ethnography about the process of securitizing piracy off the coast of Somalia. Rather than assume an apolitical shift towards a security-development counter piracy framework, this research explores the relationship between the actors, motives, and contexts underlying efforts to securitize Somali piracy. It seeks to draw out commonly held assumptions about the causal link between security, development and piracy in Somalia. In an effort to disrupt these assumptions, it offers an alternative understanding that highlights the political geographies and economic motivations for securitizing piracy. Through an exploration of the discourse and practices of a United Nations’ messaging campaign it demonstrates the centrality of manufactured narratives, identity constructions, and gendered practices in efforts to securitize piracy. It also explores how securitizing piracy became institutionalized within participating sectors and enabled securitizing actors to rework the spatial and temporal geographies of combating piracy to gain institutional advantage. This dissertation argues that the process of securitizing piracy is a geopolitical project that reflects a wider, emerging trend of employing security-development technologies as disciplinary strategies for the prevention and containment of particular actions and bodies. It reveals that securitizing actors, including the development sector, are complicit in (re)working territorial sovereignties and producing markets of security and development. As these markets are produced in Somalia, it demonstrates the specific local manifestations of broader global patterns of racialized incarceration and criminalization in contemporary millennial capitalist crisis/expansion at work in numerous other locations around the world.

Keywords: Security
Development
Gender
Political Economy
Somalia
Piracy
United Nations
Containment
Political Geography
Geopolitics
Advisor: Silvey, Rachel
A Public Health Ethics Analysis of Consent as a Least Restrictive Alternative for Newborn Screening in Ontario

Background: Public health ethics (PHE) is a theoretical lens used to analyze public health initiatives. PHE strives to find a balance between achieving population health goals and promoting individual liberty. To reach this balance PHE scholars encourage the use of least restrictive alternatives. However, least restrictive approaches are often taken for granted as presumed goods and their ability to protect individual liberty and the common good is often assumed. I examine this presumption through an examination of informed consent – implied and express – for newborn screening (NBS) in Ontario. Methods: I conducted an exploratory qualitative case study to understand how 57 individuals involved in the lobbying, development, and implementation of expanded NBS in Ontario perceive consent policy for NBS. Semi-structured interviews were audio-recorded and transcribed. Data transformation was descriptive, analytic, interpretive, and applied. Findings: Participants described their attitudes towards informed consent for NBS. PHE principles of least restrictive alternatives, effectiveness, autonomy, and social justice were key themes within implied consent data. Participants appreciated implied consent’s capacity to achieve high screening uptake, yet doubted its ability to generate informed decisions. Regarding express consent, participants introduced a host of concerns – interpreted as harm-causing – perceived to threaten NBS’s public health goals and individual autonomy. I applied the practice of consent to a PHE framework as a mechanism through which to consider consent policy for NBS in a way that moves towards achieving a balance between fulfilling public health goals and respecting individual rights and freedoms. Conclusion: What participants in advisory capacities (and those to whom they turn for input) think about consent for NBS arguably influences their recommendations to the government. Challenging informed consent as a presumed good and submitting the practice of consent to the same ethical scrutiny as the NBS program itself legitimates the concerns of those wary of consent, illuminates the perceived benefits and risks of consent, and creates an opportunity to mitigate risks before implementing or adjusting consent policy. Treating the practice of consent as an intervention in theory could work to ensure that the ideals reflected in the concept of consent are realized in NBS practice.

Keywords: public health ethics
newborn screening
qualitative research
case study
Advisor: Uphsur, Ross E.G.
Verifiable Fictions: Didactic Narrative in the Antirealist American Novel

This study examines the revival of didactic narrative in exemplary antirealist American novels of the last forty years. In chapters on Don DeLillo, William H. Gass, William Gaddis, and Richard Powers, I trace the ways in which these writers deploy antirealist literary practices of ontological destabilization, metafictional digression, and deliberate textual difficulty as ways of revisiting the proposition, rejected by many among their cohort, that fiction may have pedagogical value. These novelists attempt to reconcile their commitment to formal innovation with the belief that fiction offers cognitive gains, beholden though it is to humanistic values of the sort that avant-garde principles ostensibly repudiate. As such, these novelists grapple with an ambivalent conception of the novel as both a self-enclosed aesthetic object and a culturally promiscuous text that samples from--and speaks back to--a range of nonfictional discourses. In reading these works, I consider the epistemological potency of literature within a tradition of antirealist experimentation that has typically disavowed any affiliations with the didactic, and in particular its pejorative connotations with rigid, authoritarian moralizing. Drawing upon Jacques Rancière's model of the ignorant schoolmaster, I argue that these novelists reject the mantle of encyclopedic mastery, deploying instead a "pedagogy of failure" that encourages an autodidactic mode of verification among readers. In exploring scenes of failed instruction, these novels reconfigure postmodern authorship in terms of a reluctant teacher addressing an audience of recalcitrant students. These works thus acclimatize readers to a mode of attention that encourages a continual revision of one's beliefs and attitudes in the wake of failure and misunderstanding. In so doing, these authors attempt--with varying success--to avoid the self-imposed cultural marginalization that comes with adhering to antirealism's more ludic, oppositional strictures.

Keywords: American Literature
Antirealist Fiction
Didactic Literature
Literary Cognitivism
Advisor: Henderson, Greig
Development and characterization of microfluidic platforms for endothelial cell biology

Endothelial cells (ECs) line all blood contacting surfaces within the body and are exposed to hemodynamic shear stresses in vivo. To investigate EC biology in vitro, researchers have primarily used either conventional static systems such as well plates, or flow systems, such as parallel plate flow chambers. These macroscale platforms, although convenient, use large quantities of reagents and/or are not physiologically relevant. Recently, microfluidics has emerged as an alternative approach to study vascular biology. To demonstrate the usefulness of microfluidics in studying EC biology, four microfabricated platforms were developed and characterized. We demonstrated for the first time that primary cells, specifically multiple EC types, could be cultured and analyzed on a digital microfluidic platform. ECs patterned on a device using a fluorocarbon liftoff technique displayed both appropriate morphologies and functions. Second, a membrane microfluidic device was developed to mimic key components of the vascular microenvironment. Complex interactions between shear stress and tumour necrosis factor-α stimulation on monocyte adhesion to ECs and preferential transmigration of monocytes in response to a chemoattractant were investigated. This platform was subsequently advanced to incorporate a mural cell-laden three-dimensional gelatin methacrylate hydrogel beneath a confluent EC monolayer to more fully mimic the vascular/valvular environment. The presence of ECs suppressed valvular interstitial cell pathological differentiation to α-smooth muscle actin-expressing myofibroblasts, an effect that was enhanced when the endothelium was exposed to flow-induced shear stress. Lastly, EC phenotypes under static and flow conditions were analyzed in simple, straight, rectangular microfluidic channels to better characterize EC behaviour in microchannels. Interestingly, ECs were observed to align perpendicular to the direction of flow in microchannels of widths between 300 – 20000 µm. Vascular ECs align parallel to flow in vivo, and have never been reported to align perpendicular to flow in vitro. A comparison of EC phenotype between microchannel and macroscale culture showed differences in the arrangement of cell-cell junctions suggesting a possible role for junctional proteins in mediating perpendicular versus parallel alignment to flow. Overall, the work presented in this thesis demonstrates the utility of microfluidic platforms for EC biology and opens a discussion on potential new mechanisms of endothelial mechanotransduction.

Keywords: endothelial cells
shear stress
Advisor: Simmons, Craig
Wheeler, Aaron
In Search of an Imprint of Magnetization in the Balloon-borne Observations of the Polarized Dust Emission from Molecular Clouds

The observation of the polarization of thermal emission from dust grains is a key method in the study of the role of the magnetic fields in the star formation process. This dissertation introduces BLASTPol, a submillimeter telescope for polarization designed for mapping dust polarization in scales ranging from pre-stellar cores to sections of molecular clouds and the Histogram of Relative Orientations (HRO), a new statistical tool for the analysis of the polarization maps. The observations of BLASTPol were possible thanks to a novel light-weight carbon fiber sunshield structure and the detailed thermal modeling of the balloon-borne platform. The carbon fiber structure is based on the construction technique developed for the Spider gondola which integrates detailed Finite Element Analysis with the use of composite materials and adhesive joints. The thermal model uses 3D Computer Assisted Design allowing unprecedented control of the sun avoidance limits and detailed modeling of the gondola components. BLASTPol made observations of the Lupus I and Vela C molecular clouds, the Carina Nebula, and the Puppis Cloud Complex in two balloon-borne flights over Antarctica in 2010 and 2012. The construction of polarization maps from the BLASTPol10 observations was affected by multiple pathologies in the data. However, the preliminary maps indicate the need of a statistical tool which allows relating these observations to magnetohydrodynamics (MHD) simulations motivating the development of HRO. Most of the problems in the BLASTPol10 data were successfully addressed in BLASTPol12 and the construction of polarization maps of the observed regions is currently in progress. The HRO is a statistical tool which assesses the relative orientation between the magnetic field and the density structures. This tool was characterized by using simulated molecular clouds with different magnetization indicating that: 1. There is an imprint of the magnetization level in the relative orientation of the projected magnetic field with respect to the column density structure. 2. This imprint of magnetization can be used to complement the current estimates of magnetic field strength provided by the Chandrasekhar-Fermi method. HRO establishes a direct link with MHD simulations providing a common tool for the analysis of polarization maps from BLASTPol.

Keywords: ISM: magnetic fields, ISM: clouds, polarization, submillimeter
Advisor: Netterfield, Calvin Barth
Rebuilding St. Kunibert: Artistic Integration, Patronage, and Institutional Identities in Thirteenth-Century Cologne

This dissertation examines the architecture and art of the early-thirteenth-century collegiate church of St. Kunibert in Cologne. Rebuilt completely from circa 1210 to 1247, St. Kunibert retains most of its original architectural fabric and an array of monumental images and liturgical furnishings from the time of the rebuilding. The latter include stained glass windows, frescoes, altars, a pavement, and reliquaries, all preserved in situ in the choir in the east end. One of medieval Cologne’s preeminent religious houses, St. Kunibert provides a unique opportunity to investigate both the different modalities and the significance of artistic integration in the medieval church. Taking a synthetic approach to the building and its corpus of imagery, this study probes the relationship between high clerical artistic patronage and institutional identity in Cologne in the early thirteenth century. Part I examines the extended historical background of the rebuilding project, beginning with the foundation of the church by St. Kunibert (ca. 590–663?). This examination of the institution and the predecessor churches up to the rebuilding is followed in Part II by a detailed rereading of the chronology, design, and sources of the architectural fabric of the thirteenth-century church. The concluding chapter of Part II then situates the canonical community’s architectural patronage within the institutional and ecclesiastical political context of the contemporary Church of Cologne. Part III analyzes the community’s visual construction of institutional identity through integrative readings of groups of images, objects, and furnishings in the space of the clerical choir. These final three chapters address numerous overarching topics and issues, including the staging of the past; art and the liturgy; the cult of saints and relics; pictorial narrative; materiality and spolia; and individual artistic patronage among the canons and elite members of the urban laity. But one of several renovatio projects in Cologne at this time, the enterprise at St. Kunibert illuminates art and architecture’s central role as active, integrated agents in the formation of identity among high medieval religious communities.

Keywords: Art and identity
Artistic patronage
Germany
Cologne
Church of St. Kunibert
Architecture
Stained glass
Wall painting
Reliquaries
Advisor: Cohen, Adam S
Orthodontic tooth movement is associated with orofacial mechanical and thermal hypersensitivities and face sensorimotor cortex neuroplasticity

This study addressed the General Hypothesis that orthodontic tooth movement (OTM) is associated with neuroplasticity of the rat’s primary face motor cortex (face-M1) and somatosensory cortex (face-S1) motor representations and with mechanical and thermal hypersensitivities in the orofacial region. Objective 1 was to develop an OTM rat model, and design and manufacture a cephalostat for standardized radiographic measurements of the amount and the rate of OTM. A constant force of 10 ± 4 cN applied for 28 days produced a uniform rate of OTM of the right three maxillary molars and maxillary incisors of 1.75 ± 0.23 mm. The well-defined force parameters correlated with clinical observations of OTM in humans. Objective 2 was to use intracortical microstimulation (ICMS) and electromyographic (EMG) recordings to test if neuroplastic changes occur in the ICMS-defined motor representations of anterior digastric (LAD, RAD), masseter (LMa, RMa), buccinator (LBu, RBu), and genioglossus (GG) muscles within the rat’s face-M1 and face-S1 during OTM; the analyses to include any alterations in the number of ICMS sites representing these muscles and in the onset latencies of ICMS-evoked responses in the muscles. OTM resulted in significant changes in LAD, RAD, and GG motor representations in face-M1 and face-S1 at days 1, 7, and 28; there were no significant difference in the onset latency for these muscles across the groups, and between face-M1 and face S1 within each group. Objective 3 was to test if orofacial mechanical and thermal hypersensitivities occur in rats during OTM. The mechanical and thermal sensitivities at ipsilateral and contralateral orofacial sites were significantly increased in the early postoperative period (1 – 5 days), with peaks reached on day 1, and then returned to preoperative levels until postoperative day 28. These findings suggest that the cortical neuroplastic changes are unlikely related to maintained OTM-induced pain, although pain may have contributed to the changes in the early postoperative period. Thus, this new OTM rat model was successfully used for neurophysiological and behavioural studies that revealed the relevance of cortical neuroplasticity to orthodontic therapy and concepts of orofacial growth and development.

Keywords: orthodontic
orthodontic tooth movement
pain
orthodontic tooth movement pain
neuroplasticity
orthodontic tooth movement neuroplasticity
sensorimotor cortex
sensorimotor cortex neuroplasticity
tooth
tooth movement neuroplasticity
Advisor: Sessle, Barry
Developing a Framework to Evaluate Collaborative Mental Health Services in Primary Care Systems in Latin America

Mental health, including substance and concurrent disorders, is a major public health challenge worldwide. Approaches to collaborative mental health care (CMHC) are being implemented in Latin America to strengthen the accessibility and delivery of mental health services in primary health care settings. However, there are no well-defined frameworks to evaluate CMHC. Objective: To develop a feasible and meaningful evaluation framework to support the ongoing improvement and performance measurement of services and systems in Latin America regarding CMHC. Methods: Three public health networks were selected in Mexico, Nicaragua and Chile. The study included: (1) a critical review of the literature focused on relevant health services research approaches, theory and evaluation models; (2) an environmental scan at each of the three research sites, comprising document reviews, key informant interviews with decision makers, focus groups with front line clinicians, and a survey for other key stakeholders, to better understand the local context and evaluation needs, as well as to identify some implementation challenges and opportunities; (3) a Delphi group with experts to identify the main areas of consensus, as well as disagreements about the importance and feasibility of evaluation dimensions; and (4) a final consultation in the three sites aimed at discussing preliminary results and refining the evaluation framework. Quantitative and qualitative data were integrated in the analysis. Results: A comprehensive evaluation framework for CMHC in Latin America was developed. It includes 5 levels, 28 dimensions and 40 domains, as well as examples of indicators and an implementation plan. A knowledge exchange strategy was developed aimed at reaching the research sites as well as the academic community and other stakeholders. Conclusion: The evaluation framework represents an important effort to foster accountability and quality regarding CMHC in Latin America. Recommendations to build upon current capacity and to successfully address the existing implementation challenges are further discussed.

Keywords: Collaborative Mental Health Care
Latin America
Addiction
Health Services Evaluation
Primary Care
Mixed Methods
Advisor: Rush, Brian