VictorJuiz/thesis huggingface dataset:
Methods to Evaluate and Increase the RF Safety of Cardiovascular Interventional Devices During MRI

Percutaneous revascularization could benet greatly from MRI guidance and device tracking, but MRI guidance is currently contraindicated due to RF safety concerns. The success rate of such procedures could be improved by devices designed to exploit the unique features of MRI. Unfortunately such devices require long linear conductive structures, which present a significant risk to the patient in the form of RF heating. A priori safety prediction is impractical in vivo and thus, safety is typically investigated in vitro and extrapolated. A method of remotely predicting safety in situ during an exam would be very beneficial for ensuring safety in patients. A method of increasing the safety of revascularization devices would also be necessary to allow their employment in many clinical scenarios. Techniques are developed and presented in this thesis to enable safe, remote quantification of induced RF current and heating in vivo. Also presented is a technique of increasing the safety of revascularization guidewires without altering mechanical properties. The first technique is a method of analyzing phase artifacts introduced into MRI images by RF current flowing on linear conductive structures. The technique ts a theoretical representation of the phase artifact to an acquired image to quantify the current that induced the artifact. The measured current is then used to predict power deposition and heating. The technique is developed theoretically, and demonstrated with an in vitro feasibility study. Extensions to this phase-based technique are also presented. Sources of unwanted phase artifacts in vivo are discussed and it is demonstrated that a custom imaging sequence is capable of eliminating said artifacts. A feasibility study is presented wherein heating is accurately predicted in several pig experiments, using the custom sequence for current characterization. A novel application of floating RF traps, towards suppressing induced current on guidewires, is also presented. Theory of trap function is developed and veried through modelling and in-vitro experimentation. It is demonstrated that traps can feasibly increase the RF safety of guidewires, without altering the guidewire mechanical properties. Finally, future studies and extensions of the presented techniques towards robust clinical implementation are proposed and discussed.

Keywords: Conductive
Current
MRI
RF Heating
Advisor: Wright, Graham A
Role of Ion Channels and Activation State in Regulation of Podosomes, Migration and Invasion, and Phagocytosis in Microglia

Microglia are resident immune cells and professional phagocytes of the CNS. They rapidly respond to injury and disease and can assume a spectrum of activation states with pro-inflammatory (M1) or anti-inflammatory (M2) being at the extreme ends. It is important to understand how microglial activation states affect their migration and phagocytosis, crucial functions after injury. However, the mechanisms that regulate these phenotypes are not well characterized. As well, the cytokine profile after injury or disease is changing yet little is known about the molecular and functional consequences. We hypothesized that the microglial phenotype is different in each activation state, with ion channels regulating specific microglia functions. Rat microglia cultures were stimulated with IFN-γ plus TNF-α ("I + T"; M1 activation), interleukin-4 (M2a/alternative activation), and interleukin-10 (M2c/acquired deactivation). I report that IL-4- and IL-10-treated cells differentially express podosomes but migrate and invade much better. Further, based on enrichment of KCa2.3/SK3 Ca2+-activated potassium channels in microglial podosomes, we predicted that it regulates migration and invasion. Surprisingly, of three KCa2.3 inhibitors (apamin, tamapin, NS8593), only NS8593 abrogated the increased migration and invasion of IL-4 and IL-10-treated microglia. This discrepancy was explained by the observed block of TRPM7 currents by NS8593. We conclude that TRPM7 (not KCa2.3) contributes to the enhanced ability of microglia to migrate and invade under anti-inflammatory states. Next, we assessed: (i) gene expression changes reflecting microglial activation and inflammatory states, and receptors and enzymes related to phagocytosis and ROS production; (ii) myelin phagocytosis and production of ROS; and (iii) expression and contributions of several ion channels that are considered potential targets for regulating microglial behavior. M1 stimulation increased pro-inflammatory genes, phagocytosis, and ROS. M2a stimulation increased anti-inflammatory genes and ROS production. Myelin phagocytosis enhanced the M1 profile and dampened the M2a profile, and both phagocytosis and ROS production were dependent on NOX enzymes, Kir2.1 and CRAC channels. Importantly, microglia showed some capacity for re-polarization between M1 and M2a states, based on gene expression changes, myelin phagocytosis, and ROS production. Together, these results characterize two major reactive phenotypes observed after injury, and elucidate regulatory roles of ion channels for specific microglia functions.

Keywords: Activation states
Ion channels
Microglia
Migration
Neuroinflammation
Phagocytosis
Advisor: SCHLICHTER, LYANNE C
The Seat of the Soul: Blood and Spirituality in Late Medieval English Literary Culture

My dissertation uncovers the ways that medieval literature both shares a physiological vocabulary with medieval English medicine and extends it. I argue that medieval romances, devotional prose tracts, and dramatic works all use a specifically physiological language to represent transformative miracles. At the same time that these texts use this vocabulary, however, they also do what medicine cannot: medieval literature, I argue, complicates and extends its physiological background in order to represent religious identities, mark religious difference, and explain the inextricability of physical and spiritual life. To establish an intellectual context for my analysis, I examine the earliest known academic medical treatise written in English: the Liber Uricrisiarum (c. 1379) by Dominican friar, Henry Daniel. Danielâ s treatise serves not as a singular source for the medical ideas discussed here but rather as a contemporary intertext that shares a physiological language with literature and that intersects with medieval literary culture in its distinctly vernacular style. The succeeding chapters focus on the role of blood in providing physical form and conferring religious identity in the anonymous King of Tars, Julian of Norwichâ s Revelation of Love, and the N-Town Nativity play. These works collectively demonstrate a desire on the part of late medieval writers to negotiate the shifting relationship between the body, religion, and the English language. Ultimately, I reconceptualize our understanding of late medieval intellectual culture, showing that medical works have relevance beyond a strictly professional or curative context and that literary works, in their physiological and symbolic representations of blood, combine medical and theological discourses in greater detail than scholarship has acknowledged previously.

Advisor: Conklin Akbari, Suzanne
Slums as Urban Constellations: Tales from Toba Tek Nagar, Mumbai

Three hegemonic phenomena dictate the fate of slums in contemporary Mumbai, India. First, the teleological statement: “Mumbai is to be Slum Free.” This ubiquitous proclamation denounces the possibility that the practices through which slum-residents build urban habitats can help rethink urban planning, and in doing so, relegates slums to the realm of “non-planning.” Second, the dominance of neoliberal slum policies, which reify localities built by residents over years into lands with a “developmental value” and alienate residents from their memories, desires, and the sociality embedded in the built environment. And third, the utilitarian impulse of urban development, which uses planning as instrumental means to achieve specific ends. This instrumentality can be traced back to colonialism, during which the ideologies of industrious reason and utilitarianism played a key role in the capitalist transformation of colonized lands. This relationship between means and ends, normalized today, legitimizes the will and the power to “improve” the world of “others” in the names of planning, development, and progress. This dissertation is a response to these three hegemonic phenomena. It uses the concepts of mimesis, excess, and aesthetics to present ethnographic stories about four objects—idle time, films, toilets, and waste, located in the quasi-fictitious Muslim-dominated slum of Toba Tek Nagar. These stories explore four interrelated themes: Chapter One highlights how everyday storytelling, while idling in public spaces, is significant to confronting urban violence and slum planning; Chapter Two describes how rundown video-theaters and locally produced crime-shows become spatial and virtual mediums for residents to construct imaginary worlds in a melancholic context; Chapter Three explores the subject-positions and practices through which residents navigate the world of neoliberal developmental programs in order to build community toilets in their localities; and Chapter Four documents how the ongoing modernization of Mumbai’s waste-management system encloses and divides the common spaces of waste collection and recycling, and its varied impacts on waste pickers. Each story provides a thick description of the daily life and politics that constitute these objects, and contextualizes them within Mumbai’s history. The conclusion draws on the ethnographic insights to conceptualize planning as a form of “commoning.”

Advisor: Goonewardena, Kanishka
Rankin, Katharine
'Adjusting to Powerlessness' in Occupied Jerusalem: Theodore "Teddy" Kollek, the Palestinians, and the Organizing Principles of Israeli Municipal Policy, 1967-1987

This dissertation examines the art of government on the part of the Israeli Municipality in Jerusalem by tracking its rationalization and implementation from the beginning of the occupation in June 1967 until the breakout of the first Palestinian intifada in December 1987. I argue that local policymakers assumed a uniqueness to the history and sociality of Jerusalem and posited a primordial set of political and cultural traditions among Palestinian residents. These preconceptions encouraged them to develop a particular structure for local government and concomitant blueprint for social/administrative relations. Architects of these policies were Mayor Theodore “Teddy” Kollek and an allied group of municipal functionaries who variously identified their policies as “national-pluralist,” “bi-cultural,” and “mosaic” oriented. They believed that an approach towards consolidating political power in Jerusalem that catered to ancient urban forms and norms would stabilize the occupation over time and cultivate cordial social relations between Jews and Arabs. While concern over international scrutiny towards the Israeli occupation was a factor behind the conceptualization of an administrative model emphasizing accommodation, cultural exchange, and “liberalizing” trends, my dissertation will stress how Kollek’s vision was considered in itself to be an ethnographically sound and humane strategy toward the civic incorporation of Palestinian residents and the procurement of consent to Israeli domination. My dissertation examines the colonial taxonomy informing Kollek’s vision as well as its materialization through a network of institutions and the ways in which it impacted forms of Palestinian engagement with the post-1967 political reality. At the same time, I illustrate that Kollek’s code for administrative and social conduct was anticipated prior to the Israeli conquest of East Jerusalem. Therefore I begin my analysis during the era of military rule over Palestinians citizens of Israel (1948-1966/68). I outline the conditions that prompted a gradual (albeit incomplete) shift in state discourse and policy regarding Palestinian citizens by the mid-1950s, where they went from being strictly objects of military control (enemy population) to subjects of sociological observance and civilian oversight (minorities). I argue that Kollek drew on projects and institutions that emerged as a result of this shift to craft an art of government in Jerusalem that complemented settler-colonial objectives and the liberal dispositions of the mayor and his allies.

Keywords: Jerusalem
Jerusalem Municipality
Palestinians
settler-colonialism
Advisor: Reilly, James A
Film Aesthetics in the Ukrainian Novel of the 1920s: The Novel as Experiment

The primary goal of Ukrainian modernist and avant-garde writers was the construction of a new Ukrainian novel. In search of revolutionary models of representation and storytelling, these writers turned to cinema for themes, compositional principles, and narrative devices. This study focuses on the aesthetics of cinema as a vehicle for modernizing narrative modes, structure, and characterization in Ukrainian experimental novels of the 1920s. The adoption of the dispassionate camera-eye narration reconfigured the traditional role of the novelistic narrator and contributed to vivid, lively narration. The literary emulation of film techniques such as montage revolutionized narrative structure and composition through rejection of linear storytelling and adoption of a fragmented, discontinuous style of narration. Cinematic aesthetics also affected character development, contributing to external, predominantly visual, characterization. Chapter 1 examines the fascination with cinema among Ukrainian writers during the 1920s artistic revolution, focusing on film aesthetics and early application of cinematic devices in Ukrainian prose and poetry. Following chapters analyze the two most representative novels to absorb aesthetics of cinema. Chapter 2 analyzes the memoir-novel Maister korablia (Master of the ship; 1928) by Iurii Ianovs’kyi. The novel chronicles the history of film production in a 1920s Ukrainian film studio, the specifics of which are reflected in the novel’s collage composition, creating an effect of collective production. The incorporation of camera-eye narration produces a sense of immediacy and narrative authenticity, while montage construction shapes the sequence of the narrator’s fragmented memories. Chapter 3 explores the dramatically different effect of the application of cinematic devices in Leonid Skrypnyk’s Intelihent (The intellectual; 1927–28), presenting the “screened novel” as a new, utilitarian literary form. At once an exaggerated Bildungsroman and a study of the life of a specimen of the bourgeois intelligentsia, this novel incorporates fiction, cinema and non-fiction. The employment of camera-eye narration emphasizes the mechanical, puppet-like qualities of the bourgeois characters, while the montage construction and juxtaposition of cinematic narration with the narrator’s commentary directed to the audience generate irony and satire. Conclusions assess the legacy of these innovative yet understudied intermedial experiments both in Ukraine and in the broader European context.

Keywords: Avant-garde prose
Camera-eye narration
Iurii Ianovs'kyi
Leonid Skrypnyk
Literary montage
Ukrainian experimental novel
Advisor: Koznarsky, Taras
Caltubin - A Novel Regulator of Neuronal Microtubule Assembly in Mammals

Microtubules constitute a major component of the neuronal cytoskeleton, and tight regulation of microtubule dynamics is critical in establishing and maintaining proper cellular structure and function. As such, microtubule regulation is central to neuronal differentiation, as well as recovery from neuronal injury. Previously, our lab identified a protein in Lymnaea stagnalis (pond snail) called caltubin that is required for neurite outgrowth and regeneration in snails, and that is sufficient to increase neurite outgrowth and limit retraction of lesioned neurites when introduced into mammalian central neurons by plasmid transfection (Nejatbakhsh et al. 2011). Mechanistically, it was established that caltubin contains 4 putative EF-hand calcium binding domains and associates with tubulin. In this thesis project, a cell penetrating version of caltubin was created for more efficient delivery of caltubin into cells in vitro, with the added capability of being able to efficiently deliver caltubin in vivo. Functionally, this protein promoted neurite outgrowth and short term regeneration in mammalian central neurons in culture, while increasing the stability of microtubules. Mechanistically, it was determined that caltubin (1) promotes the assembly of microtubules directly, and (2) interferes with the function of tubulin tyrosine ligase â an enzyme that catalyzes the retyrosination of tubulin â and thus may also indirectly affect tyrosination-sensitive mechanisms of microtubule regulation. Furthermore, it was determined that calcium: (1) binds to caltubin, (2) changes its conformation, (3) increases its binding to tubulin, and (4) enhances its effect on neurite outgrowth. Finally, specific caltubin-tubulin binding domains have been identified, as well as the caltubin functional domain that promotes neurite outgrowth. Taken together, it has been established that caltubin functions as an effective and regulatable enhancer of microtubule assembly and thus could potentially have therapeutic value as a neuroprotectant or enhancer of neuronal regeneration.

Keywords: caltubin
microtubule
neuron
regeneration
tubulin tyrosine ligase
Advisor: Feng, Zhong-Ping
Forms of Mediation: Chaucer, Spenser and English Literary History

This dissertation argues that Spenser represents his relation to Chaucer as an unresolved dialectic between the desire for an intimate, immediate connection with him, and the recognition of the obstacles and enabling qualifications to it. Spenser’s version of English literary history is the product of a double vision which balances a linear genealogy of direct influence with a more circumlocutory sequence of indirect mediation. From one perspective, Spenser’s Chaucer is partner in an exclusive bond and uninterrupted dialogue: he is the friendly “maister” providing first-hand tutelage in his poetic craft; the fecund source promising a stream of inspired drops straight from his learned head; the Father of English poetry offering a privileged inheritance to his lineal descendant; the “well of English vndefyled” infusing his famous soul directly into Spenser’s body. But from the other, Chaucer is only one figure in a far less exclusive and far more polyvocal past: he is the Old Poet whose lessons are transmitted only after being refracted by his successor Lydgate and his contemporary Gower; the canonized literary sovereign whose learned head has been reconstructed by the politicized ideas of his Tudor readers; the adaptable model whose verse can be shaped by the intervening hermeneutic of Ovidian complaint; the printed auctor whose influence comes through the unauthorized and idiosyncratic texts of his sixteenth-century editors. The diverse components of this double vision mean that Spenser’s engagement with Chaucer extends well beyond Chaucer alone: the recursus to the Chaucerian fontes leads Spenser to swim in extra-Chaucerian waters. And in doing so, the New Poet fashions an English poetic tradition that is more capacious and erratic than scholarship has previously acknowledged. Chaucer and Spenser are at the center of English literary history, but their connection is also guided by people usually kept at the periphery of it.

Advisor: Galbraith, David
Examining the Role of Autophagy Proteins in Host Defenses

Autophagy is an evolutionarily conserved catabolic pathway required for maintaining cellular homeostasis and responding to microbial infections. The autophagy related genes (ATG) play a key role in the autophagy pathway, which culminates in the delivery of cargo to lysosomes for degradation. How autophagy is regulated is not clear. Salmonella enterica serovar Typhimurium is a Gram-negative pathogen that can be targeted to the autophagy pathway, which involves engulfment of bacteria in membranes decorated with the ATG8 family member LC3. This targeting requires a ubiquitin signal on bacteria and adaptor proteins, such as p62 and NDP52, that can simultaneously bind both ubiquitin- and LC3. In my studies, I showed that these two adaptors are recruited to bacteria with similar kinetics but independently of each other. Depletion of either adaptor leads to impairment of antibacterial autophagy, yet simultaneous depletion of both adaptors does not have a synergistic effect. Importantly, the two adaptors do not colocalize, but rather form non-overlapping microdomains surrounding the bacterium. Hence, p62 and NDP52 act cooperatively to drive efficient antibacterial autophagy by targeting the protein complexes they coordinate to distinct microdomains associated with bacteria. My studies also examined the role of an IRGQ, a newly identified LC3B-binding protein, IRGQ is a member of the Immunity Related GTPases (IRG) family for which very little is known in humans. I showed that IRGQ localizes to a perinuclear region and was required for autophagy of S. Typhimurium and protein aggregates. These findings identify a new role for IRGQ in the autophagy pathway in humans. In addition to autophagy, a subset of the ATGs are also involved in a poorly understood process that involves delivery of the LC3 to phagosomes, termed LC3-associated phagocytosis (LAP). Previous studies have suggested that LAP accelerates phagosome fusion with the lysosome, though this has become controversial in the field. Here, I examined the role of ATG proteins in phagosome maturation using mouse embryonic fibroblasts and bone marrow macrophages. In both cell types, the essential autophagy gene Atg5 had no impact on the maturation of phagosomes, as judged by LAMP1 acquisition, acidification, or generation of a degradative phagosome. These findings suggest that the LAP pathway is not universally required for phagosome maturation. Instead, LAP functions are subject to variation due to factors that are not fully understood.

Keywords: autophagy
host-pathogen interactions
Salmonella
ubiquitin
Advisor: Brumell, John H