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Selectivity Targeting Polo-Like Kinase 1 (Plk1) Using Novel Inhibitors Of The Polo-Box Domain, Merissa Lynnea Baxter

Theses and Dissertations

Polo-like Kinse 1 (PLK1) is a serine/threonine protein kinase that is expressed in dividing cells. It is a widely studied protein that plays an important role in regulating mitotic progression. PLK1 is over-expressed in several tumor types, and studies have shown that down-regulating PLK1 expression inhibits cancer cell proliferation, validating PLK1 as an oncotarget. Efforts to target this protein therapeutically has led to the development of several ATP-based inhibitors, although these are not exclusively specific. Because other PLK family members are tumor suppressors, it is important that PLK1 inhibitors selectively bind to PLK1 and not the other PLKs, particularly PLK3. …

A Mechanical Approach To The Characterization Of Material Failure Of Atherosclerotic Lesions, Lindsey A. Davis

Theses and Dissertations

Failure of atherosclerotic plaques can lead to potentially life threatening clinical events such as myocardial infarction (MI), stroke, or transient ischemic attack (TIA). The most frequently described plaque failure mechanism is tensile rupture of the fibrous cap; however, often during angioplasty another plaque failure mechanism occurs in which the atherosclerotic plaque separates from the internal elastic lamina (IEL). This study aims assess the material strength of atherosclerotic lesions using mechanical concepts.

To assess likelihood of plaque dissection at the vessel wall, adhesion strength was assessed in both mouse and human specimens using plaque delamination experiments. Measuring plaque adhesion in transgenic …

Citrate Coated Silver Nanoparticles With Modulatory Effects On Aflatoxin Biosynthesis In Aspergillus Parasiticus, Chandrani Mitra

Theses and Dissertations

The manufacture and usage of silver nanoparticles has drastically increased in recent years (Fabrega et al. 2011a). Hence, the levels of nanoparticles released into the environment through various routes have measurably increased and therefore are concern to the environment and to public health (Panyala, Peña-Méndez and Havel 2008). Previous studies have shown that silver nanoparticles are toxic to various organisms such as bacteria (Kim et al. 2007), fungi (Kim et al. 2008), aquatic plants (He, DorantesAranda and Waite 2012a), arthropods (Khan et al. 2015), and mammalian cells (Asharani, Hande and Valiyaveettil 2009) etc. Most of the toxicity studies are carried …

Exploring Pharmacological And Behavioral Mechanisms Involved In Alcohol Dependence During Adolescence, Rabha Mousa Younis

Theses and Dissertations

Alcoholism is a serious illness that is marked by uncontrollable drinking and physical dependence to alcohol. Long-term alcoholism has been linked to many health concerns such as cirrhosis of the liver and cardiovascular disease. Alcohol is one of the most commonly used drugs among adolescent populations. Given that adolescence is a unique developmental stage during which alcohol has long-term effects on future drug-taking behavior; it is essential to understand how early exposure to alcohol during adolescence may affect the abuse liability of the drug later in life. Indeed, most alcohol users start during adolescence suggesting that exposure to alcohol during …

Genomic Comparisons And Genome Architecture Of Divergent Trypanosoma Species, Katie Bradwell

Theses and Dissertations

Virulent Trypanosoma cruzi, and the non-pathogenic Trypanosoma conorhini and Trypanosoma rangeli are protozoan parasites with divergent lifestyles. T. cruzi and T. rangeli are endemic to Latin America, whereas T. conorhini is tropicopolitan. Reduviid bug vectors spread these parasites to mammalian hosts, within which T. rangeli and T. conorhini replicate extracellularly, while T. cruzi has intracellular stages. Firstly, this work compares the genomes of these parasites to understand their differing phenotypes. Secondly, genome architecture of T. cruzi is examined to address the effect of a complex hybridization history, polycistronic transcription, and genome plasticity on this organism, and study its highly …

Pathways Linking Sleep Timing To Obesity In Midlife Women, Dana R. Schreiber

Theses and Dissertations

Midlife women are vulnerable to developing obesity. Both sleep timing and negative emotion are risk factors, yet limited research has explored their role on weight outcomes in this population. The current investigation explored the association of sleep timing (i.e., mean sleep time, sleep time variability) and obesity (i.e., BMI, waist circumference) in midlife women, considering emotional pathways (i.e., depressive symptoms, anger) that might mediate this association. PROCESS parallel mediation models assessed direct and indirect pathways. In follow-up analyses, sleep duration was explored as an indirect pathway linking sleep timing to obesity. Results demonstrated that sleep timing does not directly predict …

Tumor-Specific Cell Death Induction By Noxa Overexpression For Head And Neck Squamous Cell Carcinoma (Hnscc) Treatment, Nicolas T. Maxim Mr.

Theses and Dissertations

The primary focus of this research is the mechanisms of cell death in head and neck squamous cell carcinoma (HNSCC) treatment. These cancers typically originate in squamous cells that line the moist mucosal surfaces of head and neck. HNSCC is commonly treated with a platinum based agent, cisplatin. While the drug does offer strong antitumor effects, its prolonged use often results in tumor-acquired resistance, which limits treatment effectiveness. We have shown that cisplatin treatment induces the expression of a pro-apoptotic BCL-2 family member Noxa, which then initiates caspase- dependent apoptosis through its binding and sequestration of pro-survival protein MCL-1 for …

If She Isn’T Working Miracles, What Is She Doing On The Battlefield?, Alex Matzke

Theses and Dissertations

The images included in my thesis work reflect my experience growing up with military propaganda—pictures of cheerful white women in pearls as part of my rural middle American landscape. I do not name the oppressor because I am not here to pick at the thorns, but to get to the root of the oppression. These are some of the servicewomen I’ve met. Their stories parallel but cannot encompass the private experiences of all service women. I am grateful for their generosity; without them there would be no pictures.

The battle for equality is much older than Rosie the Riveter but …

Pharmacological Inhibition Of Cyclophilin Ameliorates Experimental Allergic Encephalomyelitis, Zi L. Huang

Theses and Dissertations

A subset of cyclophilins have been implicated in mechanisms of neuroinflammation and neurodegeneration that contributes to the pathogenesis of Multiple Sclerosis. Mitochondrial dysfunction leading to mitochondrial permeability transition plays a pivotal role in axonal damage and disease progression in Multiple Sclerosis. Cyclophilin D (CypD) is a crucial regulatory component of the mitochondrial permeability transition pore and it was demonstrated that the cyclophilin D knockout animals showed reduced experimental allergic encephalomyelitis (EAE) clinical disease severity and axonal injury. We investigated the effect of N-methyl-4-isoleucine-cyclosporin (NIM811), a non-immunosuppressive and non-selective cyclophilin inhibitor, on the course and severity of EAE. EAE mice treated …

Obesity And Asthma: Adiponectin Receptor 1 (Adipo R1) And Adiponectin Receptor 2 (Adipo R2) Are Expressed By Normal Human Bronchial Epithelial (Nhbe) Cells At Air-Liquid Interface (Ali) And Expression Changes With Il-13 Stimulation, Jennifer L. Bradley

Theses and Dissertations

Obesity is recognized as an important risk factor for the development of many chronic diseases such as hypertension, Type 2 diabetes mellitus (T2DM) cardiovascular disease, cancer, renal disease, neurologic dysfunction, metabolic syndrome and asthma (3, 4). Circulating serum adiponectin levels in obese asthmatics have been reported to be low. Therefore, we aimed to investigate the role of adiponectin in a mucus hypersecretion model and hypothesized that adiponectin would decrease IL-13 induced MUC5AC expression from differentiated NHBE cells and that increasing concentrations of IL-13 would cause a decrease in Adipo R1 and Adipo R2 expression. MUC5AC expression with exposure to adiponectin …

In Pursuit Of Women Scientists: Using Science Plays To Promote Women Entering Stem Disciplines, Danielle Hartman

Theses and Dissertations

Higher education currently seeks to increase female enrollment in STEM. Women face many challenges attempting to breach this male dominated arena with misconceptions, gender stereotypes, and few female role models. With the recent trend in higher education to encourage more women to enter the STEM disciplines and K-12 schools cutting funding for arts programs, theatre may be losing its value in the education system. The value of interdisciplinary studies is beginning to be forgotten during the grade school years as school boards battle budget cuts, but we can remind society of it through science plays. Theatre artists use other disciplines …

Understanding The Activity Of Model Catalyst Surfaces: Ultrahigh Vacuum And Atmospheric Pressure Studies, Kangmin Xie

Theses and Dissertations

Heterogeneous Catalysis plays an extremely important role in the world. Metal particles supported on oxide supports are the most widely employed heterogeneous catalysts. In order to provide insight into the development of new catalytic materials, a fundamental understanding of surface reactions is required. Vapor-deposited metal clusters on single-crystal surfaces are well-defined systems that can be used to understand the structure-relationships in commercial catalysts. The pressure gap between fundamental surface analysis under ultra-high vacuum (UHV, P~10-10 Torr) conditions and kinetic evaluation of catalysts under realistic pressures has been bridged by constructing a micro-reactor interfaced with UHV chamber: pre- and post-reaction surfaces …

Utilization Of Satellite-Derived Salinity To Study Indian Ocean Climate Variability, Joseph Matthew D’Addezio

Theses and Dissertations

For several decades, researchers have explored Indian Ocean climate variability primarily using numerical models because of a lack of observations. Remote sensing technology has helped overcome this scarcity of observational data, but satellite-derived salinity has only been recently made available by the ESA’s Soil Moisture and Ocean Salinity (SMOS, operating since November 2009-present) and NASA’s Aquarius SAC-D (operated during June 2011-June 2015) satellites. Along with the Lagrangian in situ Argo floats array, these new datasets may be used to validate widely used numerical models, such as the HYbrid Coordinate Ocean Model (HYCOM), and also potentially observe new salinity phenomena that …

Assessing Individual Transit Vulnerability To Nuisance Flooding In The Charleston, Sc Area, Sumathee Selvaraj

Theses and Dissertations

Minor coastal flooding, also known as nuisance flooding, is projected to be more frequent due to relative sea level rise. Nuisance flood events in Charleston have resulted in various social impacts caused by road closures, traffic disruptions, and economic losses. This thesis presents research conducted to understand the dimensions of individual transit vulnerability to nuisance flooding and how transit vulnerability will be affected by increased extents of nuisance flooding driven by rising sea levels and heavy rainfall. Mixed methods were used to conduct this research in Berkley, Charleston, and Dorchester Counties, South Carolina. An electronic, in-person survey was administered at …

Stimuli Responsive Nanoparticle For Cancer Targeted Therapy, Huacheng He

Theses and Dissertations

Nanoparticle is the particle with a size in the range from several nanometers to hundreds of nanometers. It has been extensively used for cancer diagnosis and therapy. However, it is still a great challenge to fabricate nanoparticles with spatiotemporally controllable delivery of anticancer drugs to tumors and with high therapeutic efficacy. This thesis mainly focuses on the development of stimuli responsive nanoparticles for cancer targeted therapy. These nanoparticles either response to internal stimuli such as pH and redox potential or external stimuli like temperature and light could effectively target tumors and control the release of anticancer drugs there to improve …

Mass Spectrometry-Based Protein Profiling And Investigations Of Tgf-Ss1-Induced Epithelial-Mesenchymal Transition Signatures In Namru Murine Mammary Gland Epithelial Cells, Matsepo Ramaboli

Theses and Dissertations

Breast cancer is the second-most common cancer and the second-leading cause of cancer-related deaths in women. Despite advances in cancer early detection, prevention and treatment, breast cancer is still a major health challenge due to low survival caused by breast cancer metastasis. This warrants critical attention and intervention. From the proteomic standpoint, a protein-based multiplex system that provides large array of informative signals for cancer identification and prognosis is still limited. In this dissertation work, we developed two mass spectrometry-based strategies involving chemical biology tools for rapid protein fingerprinting of breast cancer cell lines, and for probing the O-linked N-acetylglucosamine …

Biodegradable Hybrid Tissue Engineering Scaffolds For Reconstruction Of Large Bone Defects, Danial Barati

Theses and Dissertations

Complex skeletal injuries and large bone fractures are still a significant clinical problem in US. Approximately 1.5 million Americans (veterans, their families, and civilians) every year suffer from bone loss due to traumatic skeletal injuries, infection, and resection of primary tumors that require extensive grafting to bridge the gap. The US bone graft market is over $2.2 billion a year. Due to insufficient mechanical stability, lack of vascularity, and inadequate resorption of the graft, patients with traumatic large skeletal injuries undergo multiple costly operations followed by extensive recovery steps to maintain proper bone alignment and length. Current strategies for repairing …

The Role Of Nuclear Factor-Erythroid-2-Related Factor 2 In Sensitivity To Thymidylate Synthase Inhibitors In Colon Cancer Cells, Sarah Ashley Clinton

Theses and Dissertations

Nuclear factor-erythroid-2-related factor 2 (NRF2), a member of the cap ‘n’ collar family of bZIP transcription factors, confers protection against oxidative and electrophilic stress. NRF2 is of great interest in cancer research, due to its role in response to chemotherapy. The class of drugs targeting thymidylate synthase (TYMS) has been useful in the treatment of colorectal cancer, among other cancers. It has long been known that inhibition of TYMS leads to depletion of thymidine levels and the onset of programmed cell death, deriving from the enzyme’s function as the sole de novo source of thymidine for DNA replication and repair. …

Renewable Bio-Based Intermediates, Monomers And Polymeric Materials From Plant Oils, Liang Yuan

Theses and Dissertations

In the dissertation work, new chemical intermediates, monomers and thermoplastic polymers were derived from renewable soybean oil. Elastomers were further developed using monomers and polymers from soybean oil. The properties of these polymeric materials were characterized and discussed.

In Chapter 1, the overall background and recent development polymers from renewable biomass, especially plant oils, is introduced. Major research objectives of my doctoral research were described.

The first section of the dissertation, on the preparation of renewable intermediates, novel monomers and homopolymers, is provided in Chapter 2 and Chapter 3. In Chapter 2, amidation of soybean oil with amino alcohols was …

Screening For Pathogenic Escherichia Coli In The Chattahoochee River, Columbus, Georgia, Micah A. Staples

Theses and Dissertations

Escherichia coli testing is frequently used to indicate the possible presence of harmful pathogens, but E. coli itself can be pathogenic. Serotype 0157:H7, enterohemorrhagic E. coli, is likely the most medically important pathogenic strain of E. coli in the United States. In this study, we surveyed for 0157:H7 and three strains of another pathogenic subtype: enterotoxigenic E. coli. We isolated E. coli colonies from samples taken from the Chattahoochee River in Columbus, Georgia at two different locations, above and below wastewater outputs. We used PCR to test for the individual subtypes and then used a nested PCR protocol …

The Loss Of Methanol Utilization In Methylobacteria, Justin T. Skariah

Theses and Dissertations

Methylobacteria primary uses Cl substrates as a carbon and energy source. This experiment was performed to see if Methylobacteria would lose the ability to use Cl compound methanol after prolonged exposure to multi-carbon substrates. To determine this, the bacteria was grown on MR2A3 (multi-carbon substrates) and MOM (single-carbon substrates) for multiple generations and tested for loss of function on a series of generations. These tests include streaking plates of MOM and R2A with bacteria from MR2A3 then getting a bacterial colony count and also toothpick transfers of the colonies to verify findings. After 20 generations there were no significant decrease …

An Analysis Of The Impact Of The Csu Peer Leader Program On Student Performance In 2014-2015, Harrison E. Sharitt

Theses and Dissertations

In efforts to retain students and increase student performance, Columbus State implemented a Peer Leader program. With access to archival data on the CSU Peer Leader Program, the goal of this project was to determine if the program at CSU had a significant impact on students’ course performance. The impact of the program was assessed by performing multiple regression analyses and ANOVA. Preliminary results showed that Columbus State’s Peer Leader program had a small, but statistically significant, positive impact on students’ final course grades.

Barriers To Career Advancement: Asian Americans In The U.S. Aerospace Industry, Rahul Dixit

Theses and Dissertations

This qualitative study explored the lack of Historically Underrepresented Population (HUP) inclusion in management and leadership roles. Specifically, why Asian Americans (AA) do not reach executive levels in southern California aerospace and defense companies (SCDCs). The AA members of HUP are among the highest educated and display model-behavior characteristics, yet, somehow do not thrive in management assignments. The U.S. defense industry has operated in a single-customer market, and that customer (the U.S. Government) is imposing social change agendas, to establish a leadership that is reflective of the company’s diversity. Exacerbating the underrepresentation of AAs is a shrinking domestic defense appropriations …

Themes In Therapy With Emerging Adults : A Qualitative Study, Brian Louie

Theses and Dissertations

The path to adulthood has traditionally been marked by demographic transitions, such as graduating from college, attaining employment, becoming married, and having a child. Previous models of development have conceptualized adolescence as a time of identity exploration and consolidation. However, in the US, as well as many other countries, the timeline for attaining the aforementioned markers has been delayed. Additionally, a significant portion of individuals between the ages of 18 to 29, across several counties, report not seeing themselves fully as adults, and ascribing internal changes, such as taking responsibility for one’s actions, as more indicative of adulthood status. Emerging …

A Comparative Analysis Of Middle Level Teacher Preparation And Certification In California, Rodas Paula Hart

Theses and Dissertations

The young adolescent learner is in a unique and distinctive phase of development, and as such requires a developmentally responsive educational program delivered by specially prepared middle level educators. The purpose of this qualitative mixed methods study was to compare current California policies for middle school teacher licensure and preparation programs with the most recent research on young adolescent development. A second purpose of this study was to investigate the design and implementation of middle school specific teacher preparation programs in California in relation to the most recent research on young adolescent development. The findings of this study indicate that …

Themes In Therapy With Emerging Adults: A Qualitative Study, Brian Louie

Theses and Dissertations

The path to adulthood has traditionally been marked by demographic transitions, such as graduating from college, attaining employment, becoming married, and having a child. Previous models of development have conceptualized adolescence as a time of identity exploration and consolidation. However, in the US, as well as many other countries, the timeline for attaining the aforementioned markers has been delayed. Additionally, a significant portion of individuals between the ages of 18 to 29, across several counties, report not seeing themselves fully as adults, and ascribing internal changes, such as taking responsibility for one’s actions, as more indicative of adulthood status. Emerging …

Promoting Resilience In Latino/A Youth: An Examination Of Resilience Research And Its Implications For The Developmental Outcomes Of U.S.-Born Latino/A Youth, Darlene R. Moreno

Theses and Dissertations

Resilience research has done much to shift attention away from a deficit perspective in mental health theory and practice to a more strength-based approach. Despite often being cited as one of the populations most at risk for negative developmental outcomes, some Latino/a youth demonstrate resilience in the face of adversity. To further expand knowledge and understanding of resilience and protective processes among U.S.-born Latino/a youth, the current study sought to integrate existing findings related to protective factors identified in research associated with parenting as well as other areas of development with those being generated in the field of resilience with …

The Major Supporting Mechanisms For Successful Single Working Mothers, Toia Thompson Mengesha

Theses and Dissertations

Single mothers are commonly characterized as low-income welfare recipients. In 2010, close to 30% of single mother households were below the poverty line (U.S. Census Bureau, 2010a) conversely leaving 70% of single mothers above the poverty line. Being a married working mother is challenging and comes with the need of several supports. With the growing divorce rate and the introduction of women choosing to become single mothers, the numbers of single working mothers are growing rapidly. In order to be a successful single mother certain factors need to be accounted for. This study focused on single mothers who are in …

The Fragmentation Of Self And Others: The Role Of The Default Mode Network In Post-Traumatic Stress Disorder, Aldrich Chan

Theses and Dissertations

In Post-Traumatic Stress Disorder (PTSD), social and emotional dysfunction has been interpreted as a secondary consequence of the broad impact of amygdala and fear circuitry dysregulation. However, research in social neuroscience has uncovered a number of neural systems involved in attachment and emotional regulation that may be impacted by trauma. One example is the Default Mode Network (DMN), which is implicated in human beings’ sense of self and ability to connect with others. This qualitative study explored the impact of physical and emotional traumata on the structures and functions of the DMN. The goal was to determine if dysregulation of …

Driving Employee Engagement Through Greater Purpose, Mark R. Gasta

Theses and Dissertations

A significant challenge for growing businesses is maintaining the culture that made them successful. An organization’s culture is manifested through rewards systems, values, rituals, stories, and celebrations. Vail Resorts’ mission is simple: to create the experience of a lifetime for their employees so they can, in turn, provide exceptional experiences for their guests. Vail Resorts faces a challenge: how to grow without becoming disconnected from the heart and soul of skiing and disenfranchising those that have joined the industry for the same purpose-driven reasons upon which the company was founded. This case study explored the specific actions taken by Vail …