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From The Coils Of The Anaconda, Restriction Of Constitutional Amendment By Popular Initiative In Montana Association Of Counties V. State, Ryan Douglas

Montana Law Review

This note examines the ways in which Montana Association of Counties concerns Montana law, elections, and history. While it is now nearly futile to suggest any regulation of campaign speech based on the speaker's corporate identity, it is possible to limit the influence of outsiders on the political process and fundamental text of the state. Part II discusses the historical development of the statutory initiative and referendum regime that existed under the 1889 Constitution and tracks its transition to the constitutional amendment by popular initiative process that emerged as part of Montana's 1972 Constitution. Part III describes the factual background, …

Piezoelectric Energy Harvesting Via Frequency Up-Conversion Technology, Amin Abedini

Dissertations

Ambient energy harvesting has attracted significant attention over the last years for applications such as wireless sensors, implantable devices, health monitoring systems, and wearable devices. The methods of vibration-to-electric energy conversion can be included in the following categories: electromagnetic, electrostatic, and piezoelectric. Among various techniques of vibration-based energy harvesting, piezoelectric transduction method has received the most attention due to the large power density of the piezoelectric material and its simple architectures. In contrast to electromagnetic energy harvesting, the output voltage of a piezoelectric energy harvester is high, which can charge a storage component such as a battery. Compared to electrostatic …

Oxidative Phosphorylation: A Critical Feature And Novel Therapeutic Target In Melanoma Brain Metastases, Grant Fischer

Dissertations and Theses (Open Access)

We recently showed via RNA-sequencing (RNA-seq) analysis of clinical samples that melanoma brain metastases (MBMs) have higher expression of oxidative phosphorylation (OXPHOS) genes (including PPARGC1A or PGC1α) than patient-matched extracranial metastases (ECMs). Thus, the central hypothesis of this dissertation is that OXPHOS plays a critical role in the pathogenesis of MBMs.

RNA-seq analysis identified increased expression of OXPHOS genes in intracranial (ICr) vs. subcutaneous (SQ) xenografts of 4 different human melanoma cell lines. Increased OXPHOS in the ICr xenografts was confirmed by direct metabolite analysis and [U-¹³C]-glucose tracing analysis. Together, these studies indicate that the brain TME …

The Influence Of The Pep-Pts And Other Metabolic Systems On The Master Virulence Regulator Atxa And To Xin Gene Expression In Bacillus Anthracis, Naomi Bier-Reizes

Dissertations and Theses (Open Access)

AtxA, the master virulence gene regulator in Bacillus anthracis, is a PRD-containing virulence regulator (PCVR) as indicated by the crystal structure, post-translational modifications, and activity of the protein. PCVRs are transcriptional regulators, named for the regulatory domains subject to phosphorylation by the phosphoenolpyruvate phosphotransferase system (PEP-PTS), termed PTS Regulatory Domains (PRD), and for their impact on virulence gene expression. Generally, the phosphorylation of a PCVR regulates protein activity and multimerization. AtxA is phosphorylated at two histidine residues - one in each of its two PRDs. Phosphorylation at position 199 allows for AtxA to positively affect expression of virulence genes, whereas …

Dhhc5 Regulates Beta-Adrenergic Signaling In The Heart Through Palmitoylation Of G Alpha Proteins, Jie Chen

Dissertations and Theses (Open Access)

S-palmitoylation is a reversible posttranslational modification that plays an important role in regulating protein localization, trafficking, and stability. Recent studies have shown that some proteins undergo extremely rapid palmitoylation/depalmitoylation cycles after cellular stimulation supporting a direct signaling role for this posttranslational modification. The work in this dissertation investigated whether β-adrenergic stimulation led to stimulus-dependent palmitoylation of downstream signaling proteins in immortalized and primary cell models. I found that β-adrenergic stimulation led to rapidly increased Gαs and Gαi palmitoylation only in primary cardiomyocytes. The kinetics of palmitoylation was temporally consistent with the downstream production of cAMP and contractile responses. I identified …

Obscurin Mediates Ankyrin Complex Formation In The Heart, Janani Subramaniam

Dissertations and Theses (Open Access)

Distinctly organized domains of receptors, ion channels, transporters, signaling molecules, cell adhesion molecules, and contractile proteins are crucial to cardiac function. Interactions between adaptor proteins such as ankyrins and cytoskeletal proteins such as obscurin play a pivotal role in organizing these functional domains in cardiomyocytes. Therefore, dysfunction of both ankyrin as well as obscurin lead to a host of cardiovascular diseases such as arrhythmias and cardiomyopathies. Alternative splicing of ankyrin yields numerous isoforms that interact with obscurin at various sub-cellular domains. And while some of these obscurin-ankyrin complexes have been studied, many others have not been characterized. Further, previous studies …

Tracking Treatment Response And Resistance To Parp Inhibition (Talazoparib) In Hereditary Pancreatic Cancer., Jennifer Goldstein

Dissertations and Theses (Open Access)

polyADP ribose polymerase (PARP) inhibitors are a class of drugs that block the PARP enzymes, involved in the repair of singe-stranded DNA breaks through the base excision repair pathway. PARP inhibition leads to replication-associated double stranded DNA breaks, which are repaired by homologous recombination (HR). In tumors with HR defects (i.e. BRCA mutants), there is a shift to error-prone DNA repair and subsequent genomic instability and cell death.

In 2014, Olaparib became the first FDA-approved PARP inhibitor for the treatment of BRCA-mutant ovarian cancer. In the phase III POLO (Pancreas cancer OLaparib Ongoing) trial presented at the American Society …

Bilirubin Nanoparticle As An Anti-Inflammatory Therapy For Graft Versus Host Disease, Sumedha Pareek

Dissertations and Theses (Open Access)

Graft versus host disease (GvHD) caused by alloreactive donor lymphocytes is a fatal complication of hematopoietic stem cell transplant (HSCT). Myeloablative conditioning regimen, consisting of chemotherapy and/or radiation, given prior to HSCT can cause tissue damage. This non-specific tissue damage triggers cross-presentation of alloantigens to the donor immune cells, causing recruitment of leukocytes and production of inflammatory cytokines. Targeting this inflammation without affecting the anti-leukemia effects of HSCT, continues to be one of the biggest challenge in finding a therapy for GvHD. Bilirubin is a tetrapyrrole pigment, found in the blood, with natural anti-oxidative and anti-inflammatory properties. Using mouse models …

Role Of Nudt21 Mediated Alternative Polyadenylation And Hyaluronan In The Development Of Pulmonary Hypertension, Scott Dale Collum

Dissertations and Theses (Open Access)

Pulmonary hypertension (PH) is a progressive disease with serious effects on quality of life and life expectancy of patients. PH is a complex disease that likely develops due to multiple influences, and no curative treatments exist for this disease. It has been shown that alternative polyadenylation (APA) due to depletion of Nudix Hydrolase 21(NUDT21) is involved in several disease states including the chronic lung disease idiopathic pulmonary fibrosis (IPF). Additionally, hyaluronan, an extracellular matrix glycosaminoglycan has been associated with PH. The role and mechanism of NUDT21 and hyaluronan have not yet been described in this disease. My results reveal that …

Investigations Of The Structure-Function Relationship In Kainate Receptors Using FöRster Resonance Energy Transfer, Douglas Litwin

Dissertations and Theses (Open Access)

Kainate receptors belong to the family of ion channels known as the ionotropic glutamate receptors. Ionotropic glutamate receptors mediate the majority of excitatory synaptic transmission, modulate the release of presynaptic glutamate, and facilitate dendrite formation. Kainate receptors are unique among the ionotropic glutamate receptors in being modulated by sodium ions. They have also been implicated in the development of higher learning and epilepsy. In recent years a wealth of structural data has become available for the AMPA and NMDA classes; however, the structural characterization of kainate receptors has been limited. The work in this dissertation utilizes luminescence resonance energy transfer …

Modeling Cancer Using Li-Fraumeni Syndrome Patient-Derived Induced Pluripotent Stem Cells, Ruoji Zhou

Dissertations and Theses (Open Access)

Li-Fraumeni syndrome (LFS) is an autosomal dominant disease caused by germline mutations in the gene TP53, which predispose individuals to a wide range of malignancies, including osteosarcoma and breast cancer. In the previous study, our group developed a novel disease model platform by reprograming LFS patients' fibroblasts to induced pluripotent stem cells (iPSCs), and further differentiate these iPSCs into mesenchymal stem cells (MSCs) then to osteoblasts (OBs), the cells from which osteosarcomas originate. Interestingly, LFS iPSC-derived osteoblasts recapitulated the osteosarcoma phenotype, creating “a bone tumor in a dish”. This “tumor in a dish” platform proved that LFS is an …

Deubiquitinating Enzymes Promote Cancer Progression And Metastasis Via Regulating Protein Stability, Zhenna Xiao

Dissertations and Theses (Open Access)

Deubiquitinating enzymes (DUBs, also called deubiquitinases) are enzymes that remove monoubiquitin or polyubiquitin chains from target proteins. DUBs have critical roles in cell homeostasis and signal transduction, as they regulate protein degradation, subcellular localization, and protein-protein interaction. Deregulation of DUBs contributes substantially to tumor formation and progression, and therefore targeting DUBs may be a promising cancer therapy strategy. My dissertation focuses on identifying the DUBs of EZH2 and SNAI1, two proteins critical for cancer progression and metastasis, and establishing these DUBs as promising anti-cancer targets.

EZH2, the catalytic component of the PRC2 complex, silences gene transcription by histone methylation. High …

P53r245w Mutation Elicits Metastatic Phenotype In Pten Deficient Prostate Cancer, Ky Pham

Dissertations and Theses (Open Access)

Trp53 mutations are the most frequent genetic alterations in prostate cancer and are associated with more aggressive disease and worse overall survival. The majority of Trp53 mutations in prostate cancer are missense mutations, resulting in amino acid substitutions with profound effect. In addition to the loss of wild type function, missense mutations in Trp53 result in a gain-of-function (GOF) phenotype. This GOF phenotype confers biologic advantages to the tumor cells, enabling them to metastasize and invade distant organs. In this study, we generated mice carrying a conditional prostate-specific p53R245W mutant and Pten deletion to access the role of this common …

Fasting Reduces Intestinal Radiotoxicity Enabling Dose-Escalated Radiotherapy For Pancreatic Cancer, Marimar De La Cruz Bonilla

Dissertations and Theses (Open Access)

Surgical resection is the only potentially curative treatment for pancreatic cancer, but only 15-20% of patients have resectable tumors. In unresectable cases, stereotactic body radiotherapy (SBRT) may be used to give tumor-directed radiotherapy (RT). Unfortunately, this can cause severe gastrointestinal (GI) toxicity due to proximity of the pancreatic head to the duodenum. Protecting the intestine from the toxic side-effects of radiation may enable dose-escalation that could achieve more effective local control of disease. We and others have previously shown that a fast of 24 hours protects mice from lethal doses of the DNA-damaging agent etoposide. In this study, we demonstrate …

Investigating The Role Of Cd109 In Pancreatic Ductal Adenocarcinoma, Mennatallah Shaheen

Dissertations and Theses (Open Access)

Pancreatic Ductal Adenocarcinoma (PDAC) is the 3rd leading cause of cancer death in the US. We performed loss of function genomic screening on a cohort of four patient derived PDAC cell populations and our data shows a cell surface receptor CD109 to be a common vulnerability, the biologic role of which in PDAC is yet unstudied and largely unknown. We hypothesized that CD109 expression provides PDAC cells with a survival advantage, and promotes cancer progression through activation of downstream signaling. We believe therefore that targeting CD109 could improve PDAC patients’ survival. Here we report that CD109 plays a role in …

Gcn5 Loss Impacts Myc-Driven Cancer In Mice And Human Cells, Aimee Farria

Dissertations and Theses (Open Access)

GCN5 is the catalytic subunit in the acetyltransferase module of SAGA and ATAC, multiprotein complexes involved in the modification of histone and nonhistone proteins. GCN5 is most recognized as a co-activator of gene transcription. The SAGA complex is recruited to chromatin by transcription factors such as MYC and E2F1 where GCN5 acetylates H3K9 leading to a more open and accessible chromatin structure. Previous research has demonstrated that GCN5 also acetylates MYC, a protein that amplifies the expression of cancer-promoting genes and is frequently dysregulated in cancer, increasing its stability. Our lab has found there is a significant overlap in the …

Executive Compensation In The Charitable Sector: Beyond The Tax Cuts And Jobs Act, Lauren Rogal

Vanderbilt Law School Faculty Publications

The Tax Cuts and Jobs Act of 2017 (“TCJA”) reformed charity executive compensation for the first time in decades, introducing an across-the-board excise tax on compensation over $1 million.1 Its enactment represents a significant step toward securing accountability for the use of the charitable tax exemption under Section 501(c)(3) of the Internal Revenue Code. These organizations receive preferential tax treatment to subsidize their provision of socially beneficial outputs that would otherwise be undersupplied. Overcompensation of charity executives subverts this purpose by diverting those subsidies for private gain and undermining public confidence in the charitable sector.

With the enactment of the …

Creation, Destruction, And The Tension Between: A Cautionary Note On Individuation In Tristan Egolf, W. G. Sebald, And Niall Williams, Nicholas Kanaar

Masters Theses

The modern individual faces a psychological disconnect between his conscious mind and unconscious due primarily to the outward attachments that dictate false tenets of ontological worth. This thesis investigates the benchmark of creation and destruction and narrows in on its utility in the individual’s pursuit for individuation. The creation and destruction paradox is used to penetrate liminal space where personal transformation occurs, and it is used within those spaces to strip away old, ego-centric ideals in the service of new ones. C. G. Jung’s “archetypes of transformation” are the main tools of the psyche for assisting the conscious mind to …

Microfluidic Particle Separation Via Elasto-Inertial Focusing In Straight Rectangular Microchannels, Di Li

All Dissertations

Label-free separation of target particles or cells in a continuous flow is a crucial process in many commercial and industrial applications. Among the various particle and cell separation techniques, microfluidic separator based on elasto-inertial forces in the flow of non-Newtonian fluids has received increasing attention in the past decade. However, current studies have been mainly focused upon the use of viscoelastic forces to manipulate particles and cells. Little work has been done to obtain a fundamental understanding on how the fluid rheological properties, such as viscoelasticity and shear thinning, affect the motion of particles. This dissertation is aimed to address …

Melt-Spinning And Properties Of Soy-Filled Polyethylene, Polypropylene, And Poly-(Lactic Acid) Fibers, Ozgun Guzdemir

All Dissertations

No abstract provided.

Creativity And Information Systems: A Theoretical And Empirical Investigation Of Creativity In Is, Jackie Patrick London

All Dissertations

Be productive. Since the industrial revolution, managers have had an almost singular focus on equipping employees with productivity tools in productivity-supportive environments. Information technologies—systems designed to increase productivity—entered the marketplace in the 1980's and were initially credited with the subsequent boom. Eventually, innovation was shown to be the primary spark, and the managerial focus shifted. Increasingly, the imperative is: be creative. This dissertation investigates how a technology environment designed to be fast and mechanistic influences the slow and organic act of creativity. Creativity—the production of novel and useful solutions—can be an elusive subject and has a varied history within Information …

Performance Of Latent Dirichlet Allocation With Different Topic And Document Structures, Haotian Feng

All Dissertations

Topic modeling has been used widely to extract the structures (topics) in a collection (corpus) of documents. One popular method is the Latent Dirichlet Allocation (LDA). LDA assumes a Bayesian generative model with multinomial distributions of topics and vocabularies within the topics. The LDA model result (i.e., the number and types of topics in the corpus) depends on tuning parameters. Several methods, ad hoc or heuristic, have been proposed and analyzed for selecting these parameters. But all these methods have been developed using one or more real corpora. Unfortunately, with real corpora, the true number and types of topics are …

Self-Repair And Self-Cleaning Of The Lepidopteran Proboscis, Suellen Floyd Pometto

All Dissertations

The proboscis of butterflies and moths is a key innovation contributing to the high diversity of the order Lepidoptera. In addition to taking nectar from angiosperm sources, many species take up fluids from overripe or sound fruit, plant sap, animal dung, and moist soil. The proboscis is assembled after eclosion of the adult from the pupa by linking together two elongate galeae to form one tube with a single food canal. How do lepidopterans maintain the integrity and function of the proboscis while foraging from various substrates?

The research questions included whether lepidopteran species are capable of total self-repair, how …

The Job Demands-Resources Model: Understanding The Impact Of Job Characteristics On Healthcare Leaders, Nastassia Marie Savage

All Dissertations

The job demands-resources (JD-R) model is one of the most popular in occupational health psychology but it often overlooks a key group: leaders. This study applies this framework to leaders in healthcare, considering how challenge and hindrance demands and resources via their unit's perceptions of teamwork impact the affective states of the leader. This study also considers meaningful work, rather than engagement, as the motivational process as it is highly relevant in healthcare. Many JD-R models also include how the motivational and health impairment processes influence performance; this study considers the leader's rating of their unit's performance, accounting for the …

The Below-Ground Competitive Ability And Allelopathic Potential Of Palmer Amaranth (Amaranthus Palmeri) In Soybean, Dwayne D. Joseph

All Dissertations

Palmer amaranth (Amaranthus palmeri S. Watson) has quickly become one of the most economically important weeds in South Carolina soybean production. Its ability to rapidly accumulate root and shoot biomass allows it to effectively compete with crops for light, nutrients and water. To better understand the below-ground competition dynamics between soybean and Palmer amaranth, greenhouse and field experiments were conducted. In 2016 and 2017, field studies were initiated with a split-plot 3x2x2 factorial treatment design. Treatments factors consisted of: neighbor (Palmer amaranth, soybean, none), divider (with and without) and irrigation (irrigated and non-irrigated). The response variables measured were soil …

Targeted Edta Chelation Therapy With Albumin Nanoparticles To Reverse Arterial Calcification And Restore Vascular Health In Chronic Kidney Disease, Saketh Ram Karamched

All Dissertations

Cardiovascular diseases (CVDs) are the leading cause of death globally. An estimated 17.9 million people died from CVDs in 2016, with ~840,000 of them in the United States alone. Traditional risk factors, such as smoking, hypertension, and diabetes, are well discussed. In recent years, chronic kidney disease (CKD) has emerged as a risk factor of equal importance. Patients with mild-to-moderate CKD are much more likely to develop and die from CVDs than progress to end-stage renal failure. Vascular calcification (VC), typical in aging, several genetic and metabolic disorders, is now recognized as a strong and independent predictor of cardiovascular events …

Discovery And Engineering Of An Endophytic Pseudomonas Strain From Taxus Chinensis For Efficient Production Of Zeaxanthin Diglucoside, Ozkan Fidan, Jixun Zhan

Biological Engineering Faculty Publications

Background

Endophytic microorganisms are a rich source of bioactive natural products. They are considered as promising biofertilizers and biocontrol agents due to their growth-promoting interactions with the host plants and their bioactive secondary metabolites that can help manage plant pathogens. Identification of new endophytes may lead to the discovery of novel molecules or provide new strains for production of valuable compounds.

Results

In this study, we isolated an endophytic bacterium from the leaves of Taxus chinensis, which was identified as Pseudomonas sp. 102515 based on the 16S rRNA gene sequence and physiological characteristics. Analysis of its secondary metabolites revealed …

Dynamics Of Land Use, Environment, And Social Organization In The Sasanian Landscape Of Eastern Iraq—Western Iran, Mitra Panahipour

Graduate Theses and Dissertations

Understanding human-environment interactions has been one of the main challenges in archaeological studies over recent years. Past research on the Near Eastern territorial empires in general, and the Sasanian Empire in particular, primarily emphasized the dominant role of human on landscape transformation. In addition, politically centralized schemes such as agricultural intensification and expansion of water supply systems have been at the center of most of the discussions and remained the main hypothesis of the Sasanian land use practices.

This dissertation investigates population’s diverse responses to environmental variability during the Sasanian period (224-651 CE) across a landscape in eastern Iraq—western Iran. …

On The Path To A Resilient Urban Food System In A Rural State: A Mixed-Method Needs Assessment Of Urban Producers And County Extension Agents In Arkansas, Catherine Elizabeth Dobbins

Graduate Theses and Dissertations

This project utilized a mixed-method needs assessment approach to urban agriculture in Arkansas, a predominately-rural state. Chapter II was a qualitative study, using semi-structured, in-depth interviews, that investigated the perceptions, needs, and experiences of Arkansas urban farmers and their interactions with the University of Arkansas Division of Agriculture Cooperative Extension Service (CES). Interviews were conducted with 16 urban farmers in Northwest and Central Arkansas. The interview data revealed individualized needs based on the size, years in operation, and mission of each urban farmer interviewed. General needs were determined, such as market pricing, co-ops, and access to appropriate equipment, but generally …

A Csra-Binding, Trans-Acting Srna Of Coxiella Burnetii Is Necessary For Optimal Intracellular Growth And Vacuole Formation During Early Infection Of Host Cells, Shaun Wachter, Matteo Bonazzi,, Kyle Shifflett, Abraham Moses, Rahul Raghavan, Michael F. Minnick

Biology Faculty Publications and Presentations

Coxiella burnetii is an obligate intracellular gammaproteobacterium and zoonotic agent of Q fever. We previously identified 15 small non-coding RNAs (sRNAs) of C. burnetii. One of them, CbsR12 (Coxiella b urnetii small RNA 12), is highly transcribed during axenic growth and becomes more prominent during infection of cultured mammalian cells. Secondary structure predictions of CbsR12 revealed four putative CsrA-binding sites in stem loops with consensus AGGA/ANGGA motifs. We subsequently determined that CbsR12 binds to recombinant C. burnetii CsrA-2, but not CsrA-1, proteins in vitro. Moreover, through a combination of in vitro and cell …