Digital Commons Network^™

Investigation Of 89zr-Siderophores As Molecular Imaging Agents For Positron Emission Tomography Imaging Of Bacterial Infections, Nora C. M. Goscinski

Arts & Sciences Electronic Theses and Dissertations

Siderophores are small molecules synthesized by bacteria to harvest Fe³⁺ from their environment. In infection scenarios, their production can increase infection virulence by increasing the ability of bacteria to obtain Fe³⁺ and therefore grow more rapidly. The selective uptake of siderophores in vivo in multi-bacteria environments indicates that this class of molecules has a potential use as selective imaging agents. In this work, DFO-NCS and a library of trihydroxamate siderophores were evaluated as vehicles to deliver ⁸⁹Zr selectively to bacteria for Positron Emission Tomography (PET) imaging of bacterial infections.

Productive work with radiometals involves thorough knowledge of …

Ion Selectivity And Allostery In The Nak Channel, Joshua B. Brettmann

Arts & Sciences Electronic Theses and Dissertations

Ion channels require proper ion selectivity and regulated gating in order to perform their cellular functions. Bacterial ion channels serve as excellent model systems to study structure/function relationships concerning the fundamental processes of ion selectivity and gating. NaK, a non-selective cation channel from Bacillus cereus, has the conserved pore structure of K+ channels. However, its non-canonical selectivity filter structure leads to non-selectivity between Na+ and K+. Full selectivity is restored with two mutations that lead to the restoration of a Kcsa-like selectivity filter structure. Many mutations can be made to the selectivity filter of NaK without loss of protein stability …

Collective Action Dynamics In Urban Neighborhoods: A Study Of Urban Community Gardens, Nishesh Chalise

Arts & Sciences Electronic Theses and Dissertations

Lessons from various policies and programs both in the United States and international development have led to a knowledge base concluding that an engaged community is a critical component for developing a thriving community. This is based on a premise that even in the modernized world community still has a role to play along with government and the market in their own development. Community’s role is further highlighted in areas such as low-income urban neighborhoods where both the government and the market may not be able to fulfill all the needs.

Research has followed by trying to understand why people …

Identifying The Origin Of Galactic Cosmic Rays With The Supertiger Instrument, Ryan Patrick Murphy

Arts & Sciences Electronic Theses and Dissertations

The SuperTIGER (Trans-Iron Galactic Element Recorder) experiment was launched on a long-duration balloon flight from Williams Field, Antarctica, on December 8, 2012. The instrument measured the relative elemental abundances of galactic cosmic rays (GCR) in the charge (Z) range Z>10 with excellent charge resolution, displaying well resolved individual element peaks for 10 ≤ Z ≤ 40. During its record-breaking 55-day flight, SuperTIGER collected ~4.15 x10^6 Iron nuclei, ~ 7.5 times as many as detected by its predecessor, TIGER, with charge resolution at iron of < 0.18 cu. SuperTIGER measures charge (Z) and energy (E) using a combination of three scintillator and two Cherenkov detectors, and employs a scintillating fiber hodoscope for event trajectory determination. The SuperTIGER data have been analyzed to correct for instrument effects and remove events that underwent nuclear interactions within the instrument. The data include more than 600 events in the charge range 30 < Z ≤ 40. SuperTIGER is the first experiment to resolve elemental abundances in this charge range with single-element resolution and high statistics. The relative abundances of the galactic cosmic ray source have been derived using atmospheric and interstellar propagations of the measured relative elemental abundances. The SuperTIGER measured abundances are generally consistent with previous experimental results from TIGER and ACE-CRIS, with improved statistical precision. The SuperTIGER results confirm the earlier results from TIGER, supporting a model of cosmic-ray origin in OB associations, with preferential acceleration of refractory elements over volatile elements ordered by atomic mass (A).

The Role Of Trauma And Mental Health Problems In The Perpetration Of Intimate Partner Violence In Post-Genocide Rwanda, Sarah Myers Tlapek

Arts & Sciences Electronic Theses and Dissertations

Exposure to political violence or war is associated with intimate partner violence (IPV) in post-conflict settings (Clark et al., 2010; Gupta, Reed, Kelly, Stein, & Williams, 2012), and civilians and veterans who develop posttraumatic stress disorder (PTSD) after exposure to combat or violence are more likely to perpetrate violence against an intimate partner (Taft, Watkins, Stafford, Street, & Monson, 2011). Rwandan health professionals estimate that after the 1994 genocide more than one-quarter of the country’s population now suffers from PTSD (Munyandamutsa, Nkubamugisha, Gex-Fabry, & Eytan, 2012). Although the majority of Rwandan women (56%) have experienced IPV in their lifetime (National …

Human Immunodeficiency Virus Type 1 Envelope Protein Interaction With Host Cell Coreceptor C-X-C Chemokine Receptor Type 4, Jie Zhang

Arts & Sciences Electronic Theses and Dissertations

Human Immunodeficiency Virus Type 1 (HIV-1) envelope protein is the sole determinant for viral entry and tropism. The ability of HIV-1 to infect susceptible host cells depends on the ability of its envelope protein to engage host cell receptor CD4 and coreceptor C-C Chemokine Receptor Type 5 (CCR5) and/or C-X-C Chemokine Receptor Type 4 (CXCR4). Most naturally occurring infections start with a single CCR5-tropic virion. In approximately 50% of HIV-1 Clade B infected patients, the viral population spontaneous develops the ability to utilize CXCR4 at a late disease stage, and this coreceptor shift corresponds to a poor prognosis for the …

Structural Evolution, Chemical Order, And Crystallization Of Metallic Liquids And Glasses, Mark Johnson

Arts & Sciences Electronic Theses and Dissertations

Over the last 60 years, bulk metallic glasses have emerged as a new class of materials with highly desirable material properties. Their high strength, high elasticity, and corrosion resistance are attractive properties for viable commercial products. At its core, material properties are directly related to the underlying microstructure. By understanding the structural and chemical order in the liquid and undercooled liquid and their relationship to thermophysical properties such as viscosity, a greater understanding of bulk metallic glass formation can be achieved. In this dissertation, electrostatic levitation techniques are used to study the liquid in a containerless environment using a combination …

Solid-State Nmr Study Of The Tertiary Structure Of The Peptidoglycan Of Enterococcus Faecalis And The Structures Of Phorbol Diacetate And Bryostatin Bound To Protein Kinase Cδ C1b Domain, Hao Yang

Arts & Sciences Electronic Theses and Dissertations

Solid-state NMR was used to study the structures of phorbol diacetate and bryostatin bound to protein kinase Cδ C1b domain in lipid bilayers. The interaction of protein kinase C (PKC) with native physiological ligands drives fundamental cellular signal transductions, and aberrant PKC signaling is associated with cancer, cardiovascular disease, neurological disorders, stroke, pain, etc. Bryostatin modulates PKC and exhibits remarkable potential in treating cancer, Alzheimer's disease, and HIV/AIDS. However, the structural information and dynamics of this modulation, which are crucial for better understanding of PKC-ligand interactions in the membrane microenvironment to drive the development of new drugs, remain elusive. REDOR …

Humans Integrate Monetary And Liquid Incentives To Motivate Cognitive Task Performance, Debbie Yee

Arts & Sciences Electronic Theses and Dissertations

It is unequivocal that a wide variety of incentives can motivate behavior. However, few studies have explicitly examined whether and how different incentives are integrated in terms of their motivational influence. The current study examines the combined effects of monetary and liquid incentives on cognitive processing, and whether appetitive and aversive incentives have distinct influences. We introduce a novel task paradigm, in which participants perform cued task-switching for monetary rewards that vary parametrically across trials, with liquid incentives serving as post-trial performance feedback. Critically, the symbolic meaning of the liquid was held constant (indicating successful reward attainment), while liquid valence …

Science And Nature In The Medieval Ecological Imagination, Jessica Rezunyk

Arts & Sciences Electronic Theses and Dissertations

This dissertation explores the intersections between nature and culture in medieval literature and art with particular focus on Geoffrey Chaucer’s House of Fame, the thirteenth-century French Bible Moralisée (Vienna, Österreichische Nationalbibliothek Codex Vindobonensis 2554), and William Langland’s Piers Plowman. Current academic paradigms tend to place the study of nature firmly within the sciences and the study of culture firmly within the humanities, creating a gap between the fields that effectively isolates their respective methodologies and vocabularies from one another. This dissertation seeks to bridge that gap between the sciences and the humanities by approaching medieval literature through the lens of …

The Mechanism And Regulation Of Mammalian Photoreceptor Dark Adaptation, Yunlu Xue

Arts & Sciences Electronic Theses and Dissertations

The visual perception of vertebrates begins in rod and cone photoreceptors. Both photoreceptors require visual pigments to detect light. At the first step of light detection, a chromophore molecule (i.e. 11-cis retinal), which is conjugated to the visual pigment in photoreceptor outer segment, absorbs a photon. Photoisomerization of the chromophore activates the visual pigment, triggers the phototransduction cascade, and produces electrical signals. After photoisomerization, the chromophore is ultimately converted to all-trans retinol, which must be recycled to regenerate the visual pigment. This visual pigment regeneration process is called the visual cycle. It is the rate-limiting step of the photoreceptor dark …

Investigating The Complexity Of Impact Crater Ejecta, Michael Raymond Zanetti

Arts & Sciences Electronic Theses and Dissertations

The formation of an impact crater ejecta blanket can be viewed as a form of organized chaos. Material that is ejected from a crater is heavily brecciated, but falls back to the surface along ballistic trajectories, generally preserving an inverted sense of the original stratigraphy. As the ejecta re-impacts the area surrounding the crater it forms a thick blanket of ejected material and reworked target surface that gradually thins away from the crater rim. Within the crater, crater modification processes, such as wall terrace formation and impact melt drainage, transform the crater in expectable ways.

The approach adopted in this …

Lysosomal Rnaset2 Is Required For Metabolic Stress-Mediated Ros Generation And Cell Death, George Caputa

Arts & Sciences Electronic Theses and Dissertations

Ectopic lipid deposition in non-adipose tissues is a hallmark of metabolic diseases, such as obesity and diabetes, and associated with cell dysfunction, cell death, and organ dysfunction. However, the molecular mechanisms linking excess free fatty acid to cell death are poorly understood. In order to identify genes critical for lipotoxicity, our lab performed a genetic screen in Chinese hamster ovary cells and isolated mutants that were resistant to lipotoxic death. In one of the lines, mutant 2B1, an allele encoding RNASET2, a ribonuclease of the T2 family, was disrupted by proviral insertion. We found that RNASET2 is induced during lipotoxicity …

Functional Consequences Of Cantu Syndrome Associated Mutations In The Atp Sensitive Potassium Channel, Paige Cooper

Arts & Sciences Electronic Theses and Dissertations

ATP-sensitive potassium (KATP) channels are composed of inward-rectifying potassium channel pore-forming subunits (Kir6.1 and Kir6.2, encoded by KCNJ8 and KCNJ11, respectively) and regulatory sulfonylurea receptor subunits (SUR1 and SUR2, encoded by ABCC8 and ABCC9, respectively). These channels couple metabolism to excitability in multiple tissues. Mutations in ABCC9 have been linked to Cantú syndrome (CS), a multi-organ disease characterized by congenital hypertrichosis, distinct facial features, osteochondrodysplasia, and cardiac defects. Additionally, two ABCC9 mutation-negative patients, exhibiting clinical hallmarks of CS, have been identified as having KCNJ8 mutations. This body of work is focused on determining the functional consequences and molecular mechanisms of …

Characterizing The Role Of Sialylated Milk Glycans And The Infant Gut Microbiota In Growth And Metabolism, Mark Richard Charbonneau

Arts & Sciences Electronic Theses and Dissertations

Undernutrition is a pressing and pervasive global health problem. The pathogenesis of this disease remains unclear, but epidemiologic studies indicate that it is not due to food insecurity alone. Moreover, current therapeutic interventions have limited efficacy in preventing or ameliorating the long-term sequelae of undernutrition, including stunting and cognitive deficits. Recent culture-independent studies have demonstrated that the normal postnatal pattern of gut microbiota development is disrupted in children with undernutrition, leading to the proposal that perturbations in gut microbiota development impairs healthy growth of the host. Human breast milk contains a diverse repertoire of free and conjugated human milk oligosaccharides …

The Identification Of Alkaloid Pathway Genes From Non-Model Plant Species In The Amaryllidaceae, Matthew B. Kilgore

Arts & Sciences Electronic Theses and Dissertations

Secondary metabolites are often restricted in their distribution to different groups of organisms. For this reason, attempts to study these often useful and interesting products of metabolism require an ability to work in a diversity of non-model species. Methods for gene discovery with low investment and high efficiency are needed to effectively identify the biosynthetic genes in these diverse pathways. During this work, a workflow for efficiently identifying biosynthetic genes was developed and applied to Amaryllidaceae alkaloid biosynthesis. Genes discovered during this work include a norbelladine 4’-O-methyltransferase, a cytochrome P450 capable of phenol-phenol coupling 4’-O-methylnorbelladine to noroxomaritidine, and a short-chain …

Implications Of A Fully Nonlocal Implementation Of The Dispersive Optical Model, Mohammadhossein Mahzoon

Arts & Sciences Electronic Theses and Dissertations

A fully nonlocal treatment for the dispersive optical model (DOM) is implemented for both the real and imaginary part of the self-energy inspired by ab initio theoretical calculations

of this quantity. By means of the dispersion relation between the real and imaginary part of the optical potential a link between the energy domain of nuclear

reactions and nuclear structure is

established. The relevant scattering data for neutrons and protons on $^{40}$Ca are described with the same quality as was accomplished with previous local versions of the DOM.

The solution of the Dyson equation at positive and negative energies

is generated …

Endogenous Protection In Subarachnoid Hemorrhage, Eric Milner

Arts & Sciences Electronic Theses and Dissertations

Vasospasm-induced delayed cerebral ischemia (DCI) remains a major source of morbidity in patients with aneurysmal subarachnoid hemorrhage (SAH). Moreover, cognitive dysfunction is the primary driver of poor long-term outcome in SAH survivors; modeling such deficits preclinically is thus key for mechanistic and translational investigation. We hypothesized that activating innate neurovascular protective mechanisms by conditioning may represent a novel therapeutic approach against SAH-induced DCI, short-term, neurological deficits, and long-term neurocognitive deficits; and, secondarily, that the neurovascular protection it provides is mediated by endothelial nitric oxide synthase (eNOS) and hypoxia-inducible factor 1α (HIF-1α).

In Experiment 1, wild-type C57BL/6 mice were subjected to …

Transcriptional Regulation Of The Endoplasmic Reticulum In Dedicated Secretory Cells, Benjamin David Moore

Arts & Sciences Electronic Theses and Dissertations

Differentiating cells express subsets of genes to build the cellular machinery necessary to perform their specific function as they acquire their mature fate. These subsets of genes are regulated by networks of transcription factors as cells progress through their developmental program. In secretory tissue, highly-specialized cells establish a complex secretory apparatus and scale up their cellular architecture to facilitate the production and secretion of large amounts of protein. Here, we identify a network of transcription factors responsible for the development of this cellular machinery in these professional secretory cells, and develop new tools to better study the molecular networks that …

Behavioral And Fmri-Based Characterization Of Cognitive Processes Supporting Learning And Retrieval Of Memory For Words In Young Adults, Binyam Nardos

Arts & Sciences Electronic Theses and Dissertations

A novel word is rarely defined explicitly during the first encounter. With repeated exposure, a decontextualized meaning of the word is integrated into semantic memory. With the overarching goal of characterizing the functional neuroanatomy of semantic processing in young adults, we employed a contextual word learning paradigm, creating novel synonyms for common animal/artifact nouns that, along with additional real words, served as stimuli for the lexical-decision based functional MRI (fMRI) experiment. Young adults (n=28) were given two types of word learning training administered in multiple sessions spread out over three days. The first type of training provided perceptual form-only training …

Molecular Mechanisms Of Axon Growth And Regeneration, Dana Watt

Arts & Sciences Electronic Theses and Dissertations

Neurons are cells with unique and extremely polarized morphologies. The axon allows communication between the cell soma and the distantly located synaptic terminal and can extend up to one meter in humans. This exceptional cellular structure therefore has specialized biological processes dedicated to its growth, maintenance and regeneration. The structure that carries out axon elongation during development and regeneration is the growth cone, which features a cytoskeletal structure that is both highly dynamic yet consistent in overall organization. The growth cone coordinates a leading edge of dynamic actin with the microtubules of the growing axon, enabling directed outgrowth while maintaining …

Flap Endonuclease 1 Promotes Telomere Replication And Stability By Distinct Mechanisms On The Leading And Lagging Strands, Daniel Cole Teasley

Arts & Sciences Electronic Theses and Dissertations

High fidelity DNA replication is essential for genomic stability and cell survival; this fact is underscored by the redundancy present in DNA replication and repair pathways. The complexity of these pathways is most evident at challenging DNA templates, such as those with repetitive sequence and transcribed loci. Among these challenging templates are telomeres, which are terminal, highly repetitive sequences that maintain genomic stability by preventing aberrant end-to-end chromosome fusions. In the absence of accurate, complete telomere replication, genomic instability results, ultimately leading to cell death or transformation. Here, we describe two unique roles in telomere stability for the DNA replication …

Manipulating Electron Transfer Reactions From Micro- To Preparative Scale, Matthew Duane Graaf

Arts & Sciences Electronic Theses and Dissertations

The utilization of electron transfer reactions has allowed the transformation of a variety of substrates from polymer surfaces to highly functionalized organic molecules. The intricacies of these electron transfer reactions have been utilized to develop a new platform for building and studying addressable molecular libraries as they interact with biological targets. As a low cost, reusable alternative to other methods of these studying binding interactions, microelectrode arrays are beginning to gain traction with the scientific community as we continually push the limits of their potential. Additionally, the electron transfer techniques used to build the molecular libraries can be expanded to …

Dissection Of Affective Catecholamine Circuits Using Traditional And Wireless Optogenetics, Jordan Gary Mccall

Arts & Sciences Electronic Theses and Dissertations

Parsing the complexity of the mammalian brain has challenged neuroscientists for thousands of years. In the early 21st century, advances in materials science and neuroscience have enabled unprecedented control of neural circuitry. In particular, cell-type selective manipulations, such as those with optogenetics and chemogenetics, routinely provide answers to previously intractable neurobiological questions in the intact, behaving animal.

In this two-part dissertation, I first introduce new minimally invasive, wireless technology to perturb neural activity in the ventral tegmental area dopaminergic system of freely moving animals. I report a series of novel devices for studying and perturbing intact neural systems through optogenetics, …

Social Networking Website Use And Eating Pathology: Relations, Moderators, And Motivation To Improve, Michelle S. St. Paul

Arts & Sciences Electronic Theses and Dissertations

Social networking website (SNW) use has been found to be associated with decreased body image or esteem and increased eating disorder (ED) symptoms. In turn, SNW use may also be associated with decreased motivation to improve body image (BI) and reduced self-efficacy in one’s ability to do so. However, the impact of SNW use on motivation or self-efficacy to improve BI has not yet been studied. Also, particular moderators of the relationships between SNW and eating pathology have not yet been evaluated. This study aimed to: 1) replicate past literature by examining the relation between SNW use and eating pathology, …

Genetic Factors That Contribute To The Pathogenesis Of Amyotrophic Lateral Sclerosis, Janet Elizabeth Cady

Arts & Sciences Electronic Theses and Dissertations

Amyotrophic lateral sclerosis (ALS) is fatal neurodegenerative disease for which there is no cure. The only treatment available extends survival by only a matter of months. There are over 20 genes that are known to cause ALS. Over half of the ALS cases with a family history of disease (FALS) can be explained by mutations in known ALS genes with hexanucleotide repeat expansions in C9ORF72 accounting for 40% of families. However roughly 90% of cases have no family history of disease (sporadic ALS or SALS) and a much smaller proportion (10%) of these cases can be explained by mutations in …

From Tibetan Refugees To Transmigrants: Negotiating Cultural Continuity And Economic Mobility Through Migration, Namgyal Choedup

Arts & Sciences Electronic Theses and Dissertations

ABSTRACT OF THE DISSERTATION

This dissertation research, funded by International Dissertation Research Fellowship from Social Science Research Council, investigates how a group of people, who continues to valorize their “statelessness”, critically and actively engages with the powers and policies of host nation-states and international geopolitics to negotiate their individual and collective goals of socio-economic mobility and cultural continuity. Through the study of lived experiences of three generations of Tibetan exiles living as “stateless” people in India, the study investigates historical and contemporary expressions of nation-state, homeland, cultural and ethnic identity within the Tibetan exile communities in India with reference to …

Adaptive Mechanisms Of Niche Remodeling In Streptococcus Pyogenes, Elyse Paluscio

Arts & Sciences Electronic Theses and Dissertations

The Gram-positive bacterium Streptococcus pyogenes is a remarkably successful pathogen, capable of infecting numerous tissue sites within its human host. The ability of S. pyogenes to invade these different niches is, in part, due to the species’ ability to monitor various physical and chemical signals in its environment and alter its transcriptional profile in response to these differential conditions. As a member of the lactic acid bacteria, S. pyogenes has a simple fermentative metabolism and relies exclusively on a combination of homo-lactic and mixed acid fermentation as a means of generating energy in the cell. As a consequence of its …

Screening Protein Ligand Interactions Using Microelectrode Arrays, Sakshi Uppal

Arts & Sciences Electronic Theses and Dissertations

G proteins comprising of α subunit and βγ dimer are signaling proteins that play essential

roles in various pathological conditions. Direct modulation of these G proteins (specifically Gα subunit) using small chemical probes to elucidate their acute function is of great value. YM-254890 is a small molecule which is the first selective inhibitor of a class of G proteins, Gαq. However, despite its biological importance, this molecule is not available to researchers. In addition, the complex core structure of this cyclic depsipeptide has thwarted efforts to obtain a series of analogs by total synthesis. Moeller lab sought to overcome this …

Emotion Regulation Goals Influence Strategy Use And Outcomes, Lameese Eldesouky

Arts & Sciences Electronic Theses and Dissertations

Functionalist theories of emotion posit that people regulate their emotions in ways that help them accomplish their goals, suggesting that goals may be important for strategy selection. Two studies were conducted to examine reappraisal and suppression use when pursuing emotional and instrumental goals, and to assess the utility of those strategies in achieving distinct goals. Both studies found a stronger link between emotional goals and reappraisal than between emotional goals and suppression, but found no preference between strategies when pursuing an instrumental goal. Study 1 found that reappraisal had higher utility than suppression in achieving emotional goals, but not instrumental …