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

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.
Role of Ion Channels and Activation State in Regulation of Podosomes, Migration and Invasion, and Phagocytosis in Microglia
Keywords: Activation states
Ion channels
Microglia
Migration
Neuroinflammation
Phagocytosis

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.
'Adjusting to Powerlessness' in Occupied Jerusalem: Theodore "Teddy" Kollek, the Palestinians, and the Organizing Principles of Israeli Municipal Policy, 1967-1987
Keywords: Jerusalem
Jerusalem Municipality
Palestinians
settler-colonialism

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.
Film Aesthetics in the Ukrainian Novel of the 1920s: The Novel as Experiment
Keywords: Avant-garde prose
Camera-eye narration
Iurii Ianovs'kyi
Leonid Skrypnyk
Literary montage
Ukrainian experimental novel

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.
Caltubin - A Novel Regulator of Neuronal Microtubule Assembly in Mammals
Keywords: caltubin
microtubule
neuron
regeneration
tubulin tyrosine ligase

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.
Examining the Role of Autophagy Proteins in Host Defenses
Keywords: autophagy
host-pathogen interactions
Salmonella
ubiquitin

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.
Sac1 is required for Pigment Cell Morphogenesis and Function in the Drosophila Eye
Keywords: cell adhesion
Drosophila melanogaster
ER homeostasis
eye development and pigmentation
membrane trafficking and regulation
phosphoinositides

Phosphatidylinositol (PI) phosphates (PIPs) are membrane lipids that regulate an array of cellular processes by recruiting effector proteins to specific membranes, as well as orchestrating membrane function and identity. Phosphatidylinositol 4-phosphase (PI4P) is one of the most abundant cellular PIPs. PI4P is produced by PI 4-kinases (PI4Ks) and kept in check by a sole, highly conserved phosphatase called Sac1. Studies in yeast and cultured mammalian cells have implicated Sac1 in a variety of cellular processes, including membrane trafficking, cytoskeletal dynamics, sphingolipid production and lipid homeostasis. However, because Sac1 is essential in multicellular organisms, it has been difficult to determine its contribution to development and homeostasis in vivo. To this end, I used a temperature-sensitive allele of sac1 (sac1[ts]) in Drosophila melanogaster to study the role of Sac1. Using this allele, I discovered that Sac1 is required for proper Drosophila eye formation and function, as well as for normal oogenesis. In the developing pupal retina, Sac1 is essential for patterning and specification of retinal cell precursors. Within these cells, Sac1 is important for microtubule (MT) stability and organization, transmembrane protein distribution and degradation, as well as endoplasmic reticulum (ER) homeostasis. Moreover, Sac1 loss leads to increased intracellular PI4P and decreased plasma membrane (PM) PI 4,5-bisphosphate [PI(4,5)P2]. The elevated pool of PI4P in sac1[ts] mutants is likely produced by the type II PI4K (PI4KII), since deletion of PI4KII can suppress Sac1 loss of function phenotypes, including defects in retinal cell patterning and eye formation. This indicates that Sac1 and PI4KII regulate a pool of PI4P that is required for Drosophila eye development. Proper regulation of PI4P by Sac1 and PI4KII is also required for eye pigmentation in adult flies. PI4KIIÎ or sac1[ts] mutants exhibit reduced pigment levels and fewer pigment granules (PGs) per ommatidium. Thus, PG biogenesis is highly sensitive to alterations in PI4P. Together, my results highlight the importance of Sac1 during development and provide a sensitized model for future studies.
A Tale of Two Tails: Characterization of R-type and F-type Pyocins of Pseudomonas aeruginosa
Keywords: antibiotic resistance
bacteriocin
novel therapeutics
Pseudomonas aeruginosa
Pyocin
tailocin and phage-tail-like-bacteriocin

Pseudomonas aeruginosa causes a broad spectrum of infections with high mortality rates. There is significant interest in development of alternative therapeutics due to the rise in multidrug-resistant infections. One such alternative is the use of protein-based antimicrobials called pyocins, which are produced by P. aeruginosa to kill related strains. This study focuses on R-type and F-type pyocins. R-type pyocins are evolutionarily related to contractile bacteriophage tails and F-type pyocins to non-contractile tails. Most previous work has focused on R-type pyocins, under-emphasizing F-type pyocins. In this study both pyocins are characterized, with a specific focus on F-type pyocins and their potential to be developed as a therapeutic. To understand their diversity and bactericidal activity, I characterized R-type and F-type pyocins of 32 P. aeruginosa strains. I found R-type pyocin gene clusters in 24 genomes and F-type in 23. R-type pyocins could be categorized into previously known groups (R1, R2 and R5). I confirmed that the O-specific antigen could act as a receptor or shield for R-type pyocins. I categorized the F-type pyocin clusters into seven groups, F1, F2 and F4-F8 (only F1 and F2 were previously known). The differences between these groups lay in the 3â end of the gene clusters that constituted of nine, six or five genes, referred herein as the â putative specificity regionâ . I showed that every F-type pyocin possesses bactericidal activity. The putative specificity region determines killing spectrum of each group of F-type pyocin and this specificity can be genetically engineered to target resistant strains. O-specific antigen could also act as a receptor or shield for F-type pyocins, however F-type pyocins can kill strains that R-type pyocins cannot. Finally, I developed a platform to rapidly clone F-type pyocin clusters into E. coli plasmids and demonstrated that functional F-type pyocins could be produced in a safe and cost-effective manner.
Policing in Unsettled Times: An Analysis of Culture in the Police Organization
Keywords: Organizations
Police Culture
Policing
Sociology of Culture

This dissertation examines how actors within a public sector institution - a police organization - use culture to make sense of a shifting occupational landscape. Interviews with 100 police officers and field notes from 50 ride-along hours were collected over the course of 18 months in the police service of a medium-sized city. Rather than conceive "police culture" as an ideal-type of values and attitudes, this project engages with concepts from sociological literature on culture and organizations to re-conceptualize police culture as a "resource" officers deploy to navigate what can be risky work in a contentious organization. First, contrasting traditional cultural depictions of police officers as unremittingly mission-oriented and indivisible, findings reveal the fragility of officer solidarity and unwillingness to engage with risky situations. Expanding surveillance outside the reach of law enforcement (e.g. cellphone videos, social media, etc.) contribute to uncertainty as officers carry out their duties. Second, police engage with a combination of myths and generational scripts in ways that both defend and challenge the status quo in their organization. "Old-school" scripts sustain the prominence of paramilitarism, camaraderie and athleticism. And while "new-generation" scripts are mainly deployed ceremonially to signal legitimacy to external policing constituents, some officers also use them to express the importance of education, the banality of military mindsets, and the need for equitable practices to be implemented on a more routine basis. Finally, results show that police rely on jointly established understandings about their local community to both perform and justify their organization's non-conformity with certain industry standards. Overall, insofar as change in policing is the objective in the current era of wavering public confidence and fiscal crisis, this study suggests that mere top-down policy reform is insufficient: organizational policy and actual practices are only loosely-linked and those charged with implementing a new course of action (i.e. senior officers) are often the staunchest supporters of non-change. Without a disruption to the lock-step hierarchical structure of the police organization, institutional reform is likely only to emerge generationally, as the most promising energy for transformative change rests among cohorts entering the occupation at a particularly unsettled time.