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Stromal Derived Growth Factor Alpha (Sdf-1Α) Induces The Differentiation Of Bone Marrow Progenitor Cells (Bmcs) Into Pericytes By Regulating Platelet Derived Growth Factor B (Pdgf-B) Transcription, Randala Hamdan

Dissertations and Theses (Open Access)

We previously demonstrated that bone marrow cells (BMCs) migrate to TC71 and A4573 Ewing’s sarcoma tumors where they can differentiate into endothelial cells (ECs) and pericytes and, participate in the tumor vascular development. This process of neo-vascularization, known as vasculogenesis, is essential for Ewing’s sarcoma growth with the soluble vascular endothelial growth factor, VEGF₁₆₅, being the chemotactic factor for BMC migration to the tumor site. Inhibiting VEGF₁₆₅ in TC71 tumors (TC/siVEGF_7-1) inhibited BMC infiltration to the tumor site and tumor growth. Introducing the stromal-derived growth factor (SDF-1α) into the TC/siVEGF_7-1 tumors partially restored vasculogenesis …

The Role And Mechanism Of The Homeobox Gene Dlx4 In Transforming Growth Factor-B Resistance In Cancer, Bon Q. Trinh

Dissertations and Theses (Open Access)

Transforming growth factor-b (TGF-b) is a cytokine that plays essential roles in regulating embryonic development and tissue homeostasis. In normal cells, TGF-b exerts an anti-proliferative effect. TGF-b inhibits cell growth by controlling a cytostatic program that includes activation of the cyclin-dependent kinase inhibitors p15^Ink4B and p21^WAF1/Cip1 and repression of c-myc. In contrast to normal cells, many tumors are resistant to the anti-proliferative effect of TGF-b. In several types of tumors, particularly those of gastrointestinal origin, resistance to the anti-proliferative effect of TGF-b has been attributed to TGF-b receptor or Smad mutations. However, these mutations are absent from many …

The Effects Of Curcumin On Body Composition Of Patients With Advanced Pancreatic Cancer, Henrique A. Parsons Md

Dissertations and Theses (Open Access)

Cachexia is very common among patients with advanced pancreatic cancer and is a marker of poor prognosis. Weight loss in cachexia is due to both adipose and muscle compartments, and sarcopenia (severe muscle depletion) is associated with worse outcomes. Curcumin has shown a myriad of biological effects, including anti-cancer and anti-inflammatory. The ability of curcumin to attenuate cachexia and muscle loss has been tested in animal models, with conflicting results so far. The hypothesis of this study was that patients with advanced pancreatic cancer treated with curcumin for two months have less fat and muscle loss as compared to matched …

Cell Cycle Regulatory Roles Of Estrogen Receptor Alpha (Erα) In Breast Cancer Cells, Sonia Javanmoghaddam

Dissertations and Theses (Open Access)

Previous studies have shown that Estrogen Receptor alpha (ERα) is an important indicator for diagnosis, prognosis and treatment of breast cancers. However, the question remains as to the role of ERα in the cell in the presence versus absence of 17-β estradiol  In this dissertation the role of ERα in both its unliganded and liganded state, with respect to the cell cycle will be explored.  The cell line models used in this project are ER-positive MCF-7 cells with and without siRNA to ERα and ER-positive MDA-MB-231 cells that have been engineered to express ERα. Cells were synchronized and the cell …

Physician Perceptions Of Risk Regarding Mood Disorders And Pharmacological Management During Pregnancy: What Is Current Practice?, Laura G. Hendon

Dissertations and Theses (Open Access)

Mood disorders are the most common form of mental illness and one of the leading causes of morbidity worldwide.  Major depressive disorder and bipolar disorder have a lifetime prevalence of 16.2% and 4.4%, respectively.  Women comprise a substantial proportion of this population, and an estimated 500,000 pregnancies each year involve women with a psychiatric condition.  Management with psychotropic medications is considered standard of care for most patients with mood disorders.  However, many of these medications are known human teratogens.  Because pregnant women with mood disorders face a high risk of relapse if unmanaged, the obstetrician faces a unique challenge in …

Cell Polarity Regulates Organ Growth Through The Hippo Pathway, Chiao-Lin Chen

Dissertations and Theses (Open Access)

Defects in apical-basal cell polarity and abnormal expression of cell polarity determinants are linked to human cancer. Loss of polarity is highly correlated with malignancy. In Drosophila, perturbation of apical-basal polarity, including overexpressing the apical determinant Crumbs, can lead to uncontrolled tissue growth. Cells mutant for the basolateral determinant scribble overproliferate and can form neoplastic tumors. Interestingly, scribble mutant clones that arise in wild-type tissues are eliminated and therefore do not manifest their tumorigenic potential. However, the mechanisms by which cell polarity coordinates with growth control pathways in developing organs to achieve appropriate organ size remain obscure.

To investigate …

Gene Discovery In Nonsyndromic Cleft Lip With Or Without Cleft Palate, Brett T. Chiquet

Dissertations and Theses (Open Access)

Nonsyndromic cleft lip with or without cleft palate (NSCLP), a common, complex orofacial birth defect that affects approximately 4,000 newborns each year in the United States, is caused by both genetic and environmental factors. Orofacial clefts affect the mouth and nose, causing severe deformity of the face, which require medical, dental and speech therapies. Despite having substantial genetic liability, less than 25% of the genetic contribute to NSCLP has been identified. The studies described in this thesis were performed to identify genes that contribute to NSCLP and to demonstrate the role of these genes in normal craniofacial development. Using genome …

A Novel Function For Aurora B Kinase In The Regulation Of P53 By Phosphorylation, Chris P. Gully

Dissertations and Theses (Open Access)

The mitotic kinase Aurora B plays a pivotal role in mitosis and cytokinesis and governs the spindle assembly checkpoint which ensures correct chromosome segregation and normal progression through mitosis.  Aurora B is overexpressed in breast and other cancers and may be an important molecular target for chemotherapy.  Tumor suppressor p53 is the guardian of the genome and an important negative regulator of the cell cycle. Previously, it was unknown whether Aurora B and p53 had mutual regulation during the cell cycle.  A small molecule specific inhibitor of Aurora B, AZD1152, gave us an indication that Aurora B negatively impacted p53 …

Patient Characteristics And Outcomes Of Gastrointestinal Stromal Tumor Patients Undergoing Imatinib Plasma Level Testing, Laura Nolden

Dissertations and Theses (Open Access)

Although gastrointestinal stromal tumor (GIST) is effectively treated with imatinib, there are a number of clinical challenges in the optimal treatment of these patients. The plasma steady-state trough level of imatinib has been proposed to correlate with clinical outcome. Plasma imatinib level may be affected by a number of patient characteristics. Additionally, the ideal plasma trough concentration of imatinib is likely to vary based on the KIT genotype (genotype determines imatinib binding affinity) of the individual patient. Patients’ genotype or plasma imatinib level may influence the type and duration of response that is appreciable by clinical evaluation.

The objectives of …

Regulation Of Set1-Mediated Methylation Of Dam1, John A. Latham

Dissertations and Theses (Open Access)

Eukaryotic genomes exist within a dynamic structure named chromatin in which DNA is wrapped around an octamer of histones forming the nucleosome. Histones are modified by a range of posttranslational modifications including methylation, phosphorylation, and ubiquitination, which are integral to a range of DNA-templated processes including transcriptional regulation. A hallmark for transcriptional activity is methylation of histone H3 on lysine (K) 4 within active gene promoters. In S. cerevisiae, H3K4 methylation is mediated by Set1 within the COMPASS complex. Methylation requires prior ubiquitination of histone H2BK123 by the E2-E3 ligases Rad6 and Bre1, as well as the Paf1 transcriptional …

The Role Of Il-6 In Adenosine-Mediated Pulmonary Fibrosis, Mesias Pedroza

Dissertations and Theses (Open Access)

Adenosine is a purinergic signaling molecule that regulates various aspects of inflammation and has been implicated in the pathogenesis of chronic lung diseases. Previous studies have demonstrated that adenosine up-regulates IL-6 production through the engagement of the A_2B adenosine receptor in various cell types, including alveolar macrophages. IL-6 is elevated in mouse models and humans with chronic lung disease, suggesting a potential role in disease progression. Furthermore, chronic elevation of adenosine in the lungs of adenosine deaminase deficient (Ada^-/-) mice leads to the development of pulmonary inflammation, alveolar destruction, and fibrosis, in conjunction with IL-6 elevation. …

The Role Of Cyclin E In Pkc Iota-Driven Early Ovarian Tumorigenesis, Angela Nanos-Webb

Dissertations and Theses (Open Access)

Among the gynecologic malignancies, epithelial ovarian tumors are the leading cause of death. For the past few decades, the only treatment has involved surgical resection of the tumor and/or general chemotherapies. In an attempt to improve treatment options, we have shown that several oncogenes that are overexpressed in ovarian cancer, PI3K, PKCiota, and cyclin E, all of which have been shown to lead to a poor prognosis and decreased survival, converge into a single pathway that could potentially be targeted therapeutically.

Because of the ability of either PKCiota or cyclin E overexpression to independently induce anchorage-independent growth, a hallmark of …

Prevalence Of Premature Ovarian Failure In Women With Tuberous Sclerosis, Emily Gabitzsch

Dissertations and Theses (Open Access)

Tuberous Sclerosis Complex (TSC) is an autosomal dominant tumor suppressor disorder characterized by hamartomas, or benign growths, in various organ systems. Inactivating mutations in either the TSC1 or the TSC2 gene cause most cases of TSC. Recently, the use of ovarian specific conditional knock-out mouse models has demonstrated a crucial role of the TSC genes in ovarian function. Mice with complete deletion of Tsc1 or Tsc2 showed accelerated ovarian follicle activation and subsequent premature follicular depletion, consistent with the human condition premature ovarian failure (POF). POF is defined in women as the cessation of menses before the age of 40 …

Expression And Regulation Of Human Cytochrome P450 4f Isoforms In Tissue Samples And Under Tnf-Alpha Challenges, Jordan C. Bell

Dissertations and Theses (Open Access)

CYP4F (Cytochrome P4504F) enzymes metabolize endogenous molecules including leukotrienes, prostaglandins and arachidonic acid. The involvement of these endogenous compounds in inflammation has led to the hypothesis that changes in the inflamed tissue environment may affect the expression of CYP4Fs during the pro-inflammatory state, which in turn may modulate inflammatory conditions during the anti-inflammatory state. We demonstrated that inflamed tissues have different levels of CYP4F isoform expression profiles in a number of human samples when compared to the average population. The CYP4F isoform expression levels change with the degree of inflammation present in tissue. Further investigation in cell culture studies revealed …

The Association Between Cancer-Related-Fatigue, Response To Fatigue Treatment, And Cytokines And Their Receptors, In Patients With Advanced Cancer, Sriram Yennu

Dissertations and Theses (Open Access)

Background: Inflammation is implicated in the development of cancer related fatigue (CRF). However there is limited literature on the mediators of inflammation (namely), cytokines and their receptors, associated with clinically significant fatigue and response to treatment.

Methods: We reviewed 37 advanced cancer patients with fatigue (≥4/10), who participated in two Randomized Controlled Trials, of anti-inflammatory agents (Thalidomide and Dexamethasone) for CRF. Responders showed improvement in FACIT-F subscale at the end of study (Day 15). Baseline patient characteristics and symptoms were assessed by FACIT-F, ESAS; serum cytokines [IL-1β and receptor antagonist (IL-1RA), IL-6, IL-6R, TNF-α and sTNF-R1 and R2, IL-8, …

Immune Modulation Of The Mycobacterium Tuberculosis Granulomatous Response, Kerry J. Welsh

Dissertations and Theses (Open Access)

Tuberculosis (TB) remains a major public health burden. The immunocompetant host responds to Mycobacterium tuberculosis (MTB) infection by the formation of granulomas, which initially prevent uncontrolled bacterial proliferation and dissemination. However, increasing evidence suggests that granuloma formation promotes persistence of the organism by physically separating infected cells from effector lymphocytes and by inducing a state of non-replicating persistence in the bacilli, making them resistant to the action of antibiotics. Additionally, immune-mediated tissue destruction likely facilitates disease transmission. The granulomatous response is in part due to mycobacterial glycolipid antigens. Therefore, studies were first undertaken to determine the innate mechanisms of mycobacterial …

Molecular Mechanisms Underlying The Transcriptional Regulation Of T Helper 17 And Regulatory T Cells, Gustavo Javier Martinez

Dissertations and Theses (Open Access)

CD4⁺ T helper (Th) lymphocytes are vital for integrating immune responses by orchestrating the function of other immune cell types. Naïve Th cells can differentiate into different effector subsets that are characterized by their cytokine profile and immune regulatory functions. These subsets include Th1, Th2, Th17, natural and inducible regulatory T cells (nTreg and iTreg respectively), among others. We focused our investigation on two Th lineages, Th17 and regulatory T cells, with opposing functions in the immune system. These subsets have been suggested to be reciprocally regulated since they both require TGF-b for their development. We investigated the role …

Examination Of Qualitative Methodology Usefulness In Assessing Management Effectiveness Of Protected Areas: A Case Study Of Mexico, Carla Mora-Trejos

All Theses

Parks and Protected Areas (PAs) are an important approach for conservation of cultural and natural diversity worldwide (Bruner 2001; McNeely 1994; Rao & Geisler 1990). Their long term success depends on effective management in relation to the goals set forth for the PA. Measuring this can be complex and challenging and has been done in a variety of ways in order to better get at the answer of how to measure management effectiveness. The purpose of this research was to develop and test qualitative methodology designed to explore management effectiveness using all six elements from the WCPA framework (Hockings et …

Wounded Planet, Wounded People: The Possibility Of Ecological Trauma, Lauren Woolbright

All Theses

In recognizing that the human relationship to the nonhuman natural world has been characterized primarily by trauma, we might notice that humans abuse landscapes and deplete resources, harming the very ecosystems that support us, moving on when they no longer can or using technology in order to remain. This might be seen as a double trauma in which the human traumatizes ecosystems, which are then traumatic to the human. Our unwillingness as a culture to consider the nonhuman natural world as a valuable subject capable of experiencing trauma prevents us from understanding the repercussions of our actions. Spivak's theory offers …

Evaluation Of Manganese Control In The Source Water And Microfiltration Plant Of A South Carolina Water Utility, Daniel Lewis

All Theses

Although present in most water supplies, manganese is a difficult-to-treat nuisance contaminant in drinking water. The US Environmental Protection Agency (EPA) has set a Secondary Maximum Contaminant Level (SMCL) of 0.05 mg/L but experts have recommended a goal of 0.02 mg/L or less to avoid chronic issues with the metal. This work is a report on manganese control for the Startex-Jackson-Wellford-Duncan (SJWD) Water District, a water utility in northwestern SC. Fourteen locations were sampled from June 2010 through October 2011. Manganese, iron, dissolved organic carbon, dissolved oxygen, and other relevant parameters were measured.
The lake-fed Middle Tyger River is the …

The Materiality Of The Self: A Multimodal, Communicative Approach To Identity, Sachi Sekimoto

Communication ETDs

The purpose of this dissertation is to propose a multimodal approach as an alternative way of theorizing and researching identity. The multimodal approach utilizes four modes of interaction--multidirectional interpellation, spatiality, temporality, and corporealit--to explore the processes of interaction and engagement between an individual and his/her social worlds. The multimodal approach focuses on the materiality of lived experience and the process of interaction and engagement between an individual and his/her social worlds through which his or her identity materializes. I apply the multimodal approach to analyze two autobiographical texts in which the authors deal with Asian identity in different cultural and …

The Leadership Experience Of Female Chief Admissions Officers: A Phenomenological Research Study, Krista Timney

All Dissertations

College admissions is a highly-competitive, business-oriented, and collaborative profession where women continue to be underrepresented in leadership positions. A study is needed of the barriers that have the potential to hinder the advancement of women in this unique and challenging field, as well as the opportunities and approaches to leadership that may lead to their success. The southeast region of the U.S. was chosen for this study because it is an area where women have been successful in advancing into leadership roles in admissions. The primary research question was: How do female chief admissions officers describe their lived leadership experiences? …

Biodiesel Production Using Chemical And Enzymatic Catalysts And Improvement Of Cold Flow Properties Using Additives, Hem Joshi

All Dissertations

Biodiesel production was carried out from soybean, canola and cottonseed oils along with poultry fat using catalytic potassium hydroxide. Further, the physical properties of biodiesel were studied with addition of ethyl levulinate (ethyl 4-oxopentanoate), short-chain alcohols (ethanol, isopropanol and butanol), and commercial cold flow improver (CFI) additives. The effects of adding ethyl levulinate, short-chain alcohols, and commercial additives were determined by studying their influence on the acid value (AV), cloud point (CP), pour point (PP), cold filter plugging point (CFPP), induction period (IP), kinematic viscosity (KV) and the flash point (FP). The results showed improved low temperature properties of the …

Particle Beam Glow Discharge Spectroscopy As A Tool For Speciation And Metallomics Analysis, Charles Quarles Jr

All Dissertations

Metallomics is a growing field of interdisciplinary research that investigates metals in biological and environmental systems. One of the major problems in detecting metals in biological systems is the instrumentation required to analyze these complex biological samples. Typically, an inductively coupled plasma-optical emission spectrometer or -mass spectrometer (ICP - OES or - MS) is used for elemental analysis and an electrospray ionization-mass spectrometer (ESI-MS) is used for molecular information. In almost all cases, the sample introduction matrix is different for each instrument, which can affect the physiological conditions of the sample and change its properties. Particle beam/hollow cathode-optical emission spectroscopy …

Information Seeking Behavior: The Effects Of Relationalism On The Selection Of Information Sources, Chris Zimmer

All Dissertations

In a world where 'Google' is a verb, this research asks the question 'what influences an individual's decision to select one information source over another?' Previous works have discussed relational versus nonrelational information sources (Rulke, Zaheer, & Anderson, 2000). Other research focuses on the information quality (O'Reilly, 1982), source accessibility (Culnan, 1984, 1985), or source richness (Daft, Lengel, & Trevino, 1987; Daft & Macintosh, 1981) but all these prior works do not address the social aspects of information sources.
This research defines and develops the construct of relationalism which is reflective of the social aspects of information sources. An important …

Understanding Black Student Perceptions Of Targeted Student Support Services On A Predominantly White College Campus, Kendra Stewart

All Dissertations

Black students' perceptions of their experiences on predominantly White campuses have been marred by a sense of isolation and alienation from the overall campus community. Black students do not feel they have sufficient access to important resources to satisfactorily navigate an unfamiliar campus environment. Support services for Black students, such as ethnically-themed student organizations or mentoring programs, have been implemented to react to and address such perceptions. A review of literature focused on Black student challenges on predominantly White campuses implicated the need for such support services, but there is a need in higher education to have a more detailed …

Regulation Of Trypanosoma Brucei Hexokinase 1 And 2 On Multiple Levels: Transcript Abundance, Protein Expression And Enzyme Activity, Heidi Dodson

All Dissertations

Trypanosoma brucei, a unicellular eukaryotic parasite, is the causative agent of African sleeping sickness in sub-Saharan Africa. The parasite encounters two main environments as it progresses through its life cycle: the tsetse fly and the mammalian
bloodstream. Nutrient availability is distinct in the two environments, requiring the parasite to utilize diverse metabolic pathways to efficiently produce ATP for survival. Bloodstream form parasites (BSF), residing in a glucose rich environment, rely solely on
glycolysis for energy, while procyclic form (PF) parasites metabolize readily available proline and threonine in addition to glucose.
T. brucei expresses two hexokinases, the first enzyme in the …

Automated, Parallel Optimization Algorithms For Stochastic Functions, Dheeraj Chahal

All Dissertations

The optimization algorithms for stochastic functions are desired specifically for real-world and simulation applications where results are obtained from sampling, and contain experimental error or random noise. We have developed a series of stochastic optimization algorithms based on the well-known classical down hill simplex algorithm. Our parallel implementation of these optimization algorithms, using a framework called MW, is based on a master-worker architecture where each worker runs a massively parallel program. This parallel implementation allows the sampling to proceed independently on many processors as demonstrated by scaling up to more than 100 vertices and 300 cores.
This framework is highly …

Targeting A-Form Nucleic Acids: A Neomycin Based Approach, Nicholas Shaw

All Dissertations

This manuscript reflects our most recent advancements in the recognition of nucleic acids. Chapter one focuses on previously established methods in nucleic acid recognition. Nucleic acid targeting by small molecules affords a unique way to potentially inhibit biological functions, which is different from targeting enzyme and protein bio-macromolecules. We seek to further develop an aminoglycoside approach to targeting nucleic acids. Since aminoglycosides were first introduced, over 60 years ago, as treatment for tuberculosis, natural product discovery and demands for therapeutically more effective aminoglycosides, with lowered toxicity, have dominated the landscape of aminoglycoside research. More recently, our group has established neomycin …

Ecosystem Responses To Fuel Reduction Treatments In Stands Killed By Southern Pine Beetle, Aaron Stottlemyer

All Dissertations

Heavy fuel loads were created by multiple southern pine beetle (Dendroctonus frontalis Ehrh.) outbreaks throughout the southern Piedmont between 1999 and 2002. Prescribed burning and mechanical mastication are proposed to reduce fuel loading in beetle-killed pine (Pinus L. spp.) stands in the upper South Carolina Piedmont, but their ecological impacts are unknown. Prescribed burning reduced fuelbed continuity by consuming litter (Oi) and fine (1- and 10-hr timelag size classes) woody fuels immediately after the treatment. Duff (Oe + Oa) layer thickness also decreased and mineral soil was exposed in some areas. Mastication resulted in a thick, continuous layer of shredded …