Digital Commons Network^™

Clinical Impact Of Couch To P And Rails On Imrt And Arc Therapy, Kiley B. Pulliam

Dissertations and Theses (Open Access)

Purpose: To evaluate the clinical impact of the Varian Exact Couch on dose and volume coverage to targets and critical structures and tumor control probability (TCP) for 6-MV IMRT and Arc Therapy.

Methods: Five clinical prostate patients were planned with both, 6-MV 8-field IMRT and 6-MV 2-field RapidArc using the Eclipse treatment planning system (TPS). These plans neglected treatment couch attenuation, as is standard clinical practice. Dose distributions were then recalculated in Eclipse with the inclusion of the Varian Exact Couch (imaging couch top) and the rails in varying configurations. The changes in dose and coverage were evaluated using the …

Enforced Expression Of Tbx1 In Fetal Thymic Epithelial Cells Antagonizes Thymus Organogenesis, Kim T. Cardenas

Dissertations and Theses (Open Access)

Enforced expression of Tbx1 in fetal thymic epithelial cells antagonizes

thymus organogenesis

Kim T. Cardenas

The thymus and parathyroid glands originate from organ-specific domains of 3rd pharyngeal pouch (PP) endoderm. At embryonic day 11.5 (E11.5), the ventral thymus and dorsal parathyroid domains can be identified by Foxn1 and Gcm2 expression respectively. Neural crest cells, (NCCs) play a role in regulating patterning of 3rd PP endoderm. In addition, pharyngeal endoderm influences fate determination via secretion of Sonic hedgehog (Shh), a morphogen required for Gcm2 expression and generation of the parathyroid domain. Gcm2 is a downstream target of the transcription factor Tbx1, …

The Mechanism Of Tumorigenesis In The Immortalized Human Pancreatic Cell Lines: Cell Culture Models Of Human Pancreatic Cancer, Zhe Chang

Dissertations and Theses (Open Access)

The mechanism of tumorigenesis in the immortalized human pancreatic cell lines: cell culture models of human pancreatic cancer

Pancreatic ductal adenocarcinoma (PDAC) is the most lethal cancer in the world. The most common genetic lesions identified in PDAC include activation of K-ras (90%) and Her2 (70%), loss of p16 (95%) and p14 (40%), inactivation p53 (50-75%) and Smad4 (55%). However, the role of these signature gene alterations in PDAC is still not well understood, especially, how these genetic lesions individually or in combination contribute mechanistically to human pancreatic oncogenesis is still elusive. Moreover, a cell culture transformation model with sequential …

Gene By Bmi Interactions Influencing C-Reactive Protein Levels In European-Americans, Sarah Tudor

Dissertations and Theses (Open Access)

C-Reactive Protein (CRP) is a biomarker indicating tissue damage, inflammation, and infection. High-sensitivity CRP (hsCRP) is an emerging biomarker often used to estimate an individual’s risk for future coronary heart disease (CHD). hsCRP levels falling below 1.00 mg/l indicate a low risk for developing CHD, levels ranging between 1.00 mg/l and 3.00 mg/l indicate an elevated risk, and levels exceeding 3.00 mg/l indicate high risk. Multiple Genome-Wide Association Studies (GWAS) have identified a number of genetic polymorphisms which influence CRP levels. SNPs implicated in such studies have been found in or near genes of interest including: CRP, APOE, APOC, IL-6, …

Ldoc1, A Novel Biomarker Of Prognosis In Chronic Lymphocytic Leukemia, Hatice Duzkale

Dissertations and Theses (Open Access)

In chronic lymphocytic leukemia (CLL), one of the best predictors of outcome is the somatic mutation status of the immunoglobulin heavy chain variable region (IGHV) genes. Patients whose CLL cells have unmutated IGHV genes have a median survival of 8 years; those with mutated IGHV genes have a median survival of 25 years. To identify new prognostic biomarkers and molecular targets for therapy in untreated CLL patients, we reanalyzed the raw data from four published gene expression profiling microarray studies. Of 88 candidate biomarkers associated with IGHV somatic mutation status, we identified LDOC1 (Leucine Zipper, Down-regulated in Cancer 1), as …

Sumo-Specific Protease 1 Controls Lymphoid Development Through Regulation Of Sumoylation/Acetylation Switch In Stat5, Thang Van Nguyen

Dissertations and Theses (Open Access)

SUMOylation has emerged as an important regulatory mechanism for protein function. SUMO-specific proteases (SENPs) are essential for removing SUMO from conjugated proteins in many different systems, but the physiological functions of SENPs are poorly understood. STAT5 (Signal Transducer and Activator of Transcription 5) plays a critical role in the development of lymphoid cells. However, it is not known whether STAT5 is regulated by the SUMOylation pathway. Here, we showed that SUMOylated STAT5 is accumulated in SENP1^-/- lymphoid precursors. SENP1 deficiency results in severe defects in early T and B cell development, similar to that observed in mice harboring a …

Downregulation Of Pax2 Suppresses Ovarian Cancer Cell Growth, Huijuan Song

Dissertations and Theses (Open Access)

PAX2 is one of nine PAX genes regulating tissue development and cellular differentiation in embryos. PAX2 promotes cell proliferation, oncogenic transformation, cell-lineage specification, migration, and survival. Unattenuated PAX2 has been found in several cancer types. We therefore sought to elucidate the role of PAX2 in ovarian carcinomas. We found that PAX2 was expressed in low-grade serous, clear cell, endometrioid and mucinous cell ovarian carcinomas, which are relatively chemoresistant compared to high grade serous ovarian carcinomas. Four ovarian cancer cell lines, RMUGL (mucinous), TOV21G (clear cell), MDAH-2774 (endometrioid) and IGROV1 (endometrioid), which express high-levels of PAX2, were used to study the …

Crosstalk Between R1175 Methylation And Y1173 Phosphorylation Negatively Modulates Egfr-Mediated Erk Activation, Jung-Mao Hsu

Dissertations and Theses (Open Access)

Post-translational protein modifications are critical regulators of protein functions as they expand the signaling potentials of the modified proteins, leading to diverse physiological consequences. Currently, increasing evidence suggests that protein methylation is as important as other post-translational modifications in the regulation of various biological processes. This drives us to ask whether methylation is involved in the EGFR (epidermal growth factor receptor) signaling, a biological process extensively regulated by multiple post-translational modifications including phosphorylation, glycosylation and ubiquitination. We found that EGFR R1175 is methylated by a protein arginine methyltransferase named PRMT5. During EGFR activation, PRMT5-mediated R1175 methylation specifically enhances EGF-induced EGFR …

Dissecting The Interaction Between P53 And Trim24, Aundrietta D. Duncan

Dissertations and Theses (Open Access)

Dissecting the Interaction of p53 and TRIM24

Aundrietta DeVan Duncan

Supervisory Professor, Michelle Barton, Ph.D.

p53, the “guardian of the genome”, plays an important role in multiple biological processes including cell cycle, angiogenesis, DNA repair and apoptosis. Because it is mutated in over 50% of cancers, p53 has been widely studied in established cancer cell lines. However, little is known about the function of p53 in a normal cell. We focused on characterizing p53 in normal cells and during differentiation. Our lab recently identified a novel binding partner of p53, Tripartite Motif 24 protein (TRIM24). TRIM24 is a member of …

Dual Energy Computed To Mography For Proton Therapy Treatment Planning, Ming Yang

Dissertations and Theses (Open Access)

Proton radiation therapy is gaining popularity because of the unique characteristics of its dose distribution, e.g., high dose-gradient at the distal end of the percentage-depth-dose curve (known as the Bragg peak). The high dose-gradient offers the possibility of delivering high dose to the target while still sparing critical organs distal to the target. However, the high dose-gradient is a double-edged sword: a small shift of the highly conformal high-dose area can cause the target to be substantially under-dosed or the critical organs to be substantially over-dosed. Because of that, large margins are required in treatment planning to ensure adequate dose …

Stat3 Controls The Neutrophil Migratory Response To Cxcr2 And Its Ligand Mip-2 (Cxcl2), Hoainam Nguyen-Jackson

Dissertations and Theses (Open Access)

Among the first white blood cells to respond to bacterial and fungal infections, neutrophils are produced in the bone marrow, released into circulating blood, and recruited to inflamed tissue. The cytokine granulocyte colony-stimulating factor (G��CSF) is used clinically to induce neutrophil mobilization from the marrow. This process was previously demonstrated to require the STAT3 transcription factor (signal transducer and activator of transcription 3), the principal signaling molecule activated upon G-CSF-binding of its receptor, but the mechanism was unknown. The chemokines KC (Cxcl1) and MIP-2 (Cxcl2), and their shared receptor CXCR2 (l8rb), also stimulate neutrophil mobilization, in contrast to SDF-1 (Cxcl12), …

Upregulation Of Reactive Oxygen Species During The Retrovirus Life Cycle And Their Roles In A Mutant Of Moloney Murine Leukemia Virus, Ts1-Mediated Neurodegeneration, Soo Jin Kim

Dissertations and Theses (Open Access)

Viral invasion of the central nervous system (CNS) and development of neurological symptoms is a characteristic of many retroviruses. The mechanism by which retrovirus infection causes neurological dysfunction has yet to be fully elucidated. Given the complexity of the retrovirus-mediated neuropathogenesis, studies using small animal models are extremely valuable. Our laboratory has used a mutant moloney murine leukemia retrovirus, ts1-mediated neurodegneration. We hypothesize that astrocytes play an important role in ts1-induced neurodegeneration since they are retroviral reservoirs and supporting cells for neurons. It has been shown that ts1 is able to infect astrocytes in vivo and in …

A Cell Biological Determination Of Integrator Subunit Localization, Sarah B. May

Dissertations and Theses (Open Access)

Uridine-rich small nuclear (U snRNAs), with the exception of the U6 snRNA, are RNA polymerase II (RNAPII) transcripts. The mechanism of 3’ cleavage of snRNAs has been unknown until recently. This area was greatly advanced when 12 of the Integrator complex subunits (IntS) were purified in 2005 through their interaction with the C-terminal domain (CTD) of the large subunit (RpbI) of RNAPII. Subsequently, our lab performed a genome-wide RNAi screen that identified two more members of the complex that we have termed IntS13 and IntS14. We have determined that IntS9 and 11 mediate the 3’ cleavage of snRNAs, but the …

Study Of Rest As A Negative Regulator Of P16ink4a, Monica B. Gireud

Dissertations and Theses (Open Access)

STUDY OF REST AS A NEGATIVE REGULATOR OF P16^INK4A

Monica Gireud, B.S.

Thesis Advisor: Vidya Gopalakrishnan, Ph.D.

The RE1 Silencing Transcription Factor (REST) is a negative regulator of neuronal differentiation. It is expressed ubiquitously in early embryos, but downregulated in neural progenitors concomitant with onset of neuronal differentiation in these cells. REST has been widely studied as a negative regulator of neuronal differentiation genes. Our recent work identified a novel role for REST in control of cell proliferation. However, the underlying molecular mechanism(s) are not known and is a focus of the current thesis project. Here, we provide evidence …

Aberrations Of A Putative Tumor Suppressor Gene Sel1l In Pancreatic Ductal Adenocarcinoma, Qian Liu

Dissertations and Theses (Open Access)

Introduction: Pancreatic cancer is the fourth leading cause of cancer-related death among males and females in the United States. Sel-1-like (SEL1L) is a putative tumor suppressor gene that is downregulated in a significant proportion of human pancreatic ductal adenocarcinoma (PDAC). It was hypothesized that SEL1L expression could be down-modulated by somatic mutation, loss of heterozygosity (LOH), CpG island hypermethylation and/or aberrantly expressed microRNAs (miRNAs).

Material and methods: In 42 PDAC tumors, the SEL1L coding region was amplified using reverse transcription polymerase chain reaction (RT-PCR), and analyzed by agarose gel electrophoresis and sequenced to search for mutations. Using fluorescent …

Prediction Of Dna Methylation Based On Genomic Architecture And Applications Of Positional Weight Matrices, Juan Gallegos

Dissertations and Theses (Open Access)

Gene silencing due to epigenetic mechanisms shows evidence of significant contributions to cancer development. We hypothesis that the genetic architecture based on retrotransposon elements surrounding the transcription start site, plays an important role in the suppression and promotion of DNA methylation. In our investigation we found a high rate of SINE and LINEs retrotransposon elements near the transcription start site of unmethylated genes when compared to methylated genes. The presence of these elements were positively associated with promoter methylation, contrary to logical expectations, due to the malicious effects of retrotransposon elements which insert themselves randomly into the genome causing possible …

The Development And Implementation Of An Anthropomorphic Head Phantom For The Assessment Of Proton Therapy Treatment Procedures, Paige A. Summers

Dissertations and Theses (Open Access)

Proton therapy has become an increasingly more common method of radiation therapy, with the dose sparing to distal tissue making it an appealing option, particularly for treatment of brain tumors. This study sought to develop a head phantom for the Radiological Physics Center (RPC), the first to be used for credentialing of institutions wishing to participate in clinical trials involving brain tumor treatment of proton therapy. It was hypothesized that a head phantom could be created for the evaluation of proton therapy treatment procedures (treatment simulation, planning, and delivery) to assure agreement between the measured dose and calculated dose within …

Mechanisms Of Adenovirus-Mediated Autophagy, Erin White

Dissertations and Theses (Open Access)

A patient diagnosed with a glioma, generally, has an average of 14 months year to live after implementation of conventional therapies such as surgery, chemotherapy, and radiation. Glioblastomas are highly lethal because of their aggressive nature and resistance to conventional therapies and apoptosis. Thus other avenues of cell death urgently need to be explored. Autophagy, which is also known as programmed cell death type II, has recently been identified as an alternative mechanism to kill apoptosis- resistant cancer cells. Traditionally, researchers have studied how cells undergo autophagy during viral infection as an immune response mechanism, but recently researchers have discovered …

Mechanisms Of Adenovirus-Mediated Autophagy, Erin White

Dissertations and Theses (Open Access)

A patient diagnosed with a glioma, generally, has an average of 14 months year to live after implementation of conventional therapies such as surgery, chemotherapy, and radiation. Glioblastomas are highly lethal because of their aggressive nature and resistance to conventional therapies and apoptosis. Thus other avenues of cell death urgently need to be explored. Autophagy, which is also known as programmed cell death type II, has recently been identified as an alternative mechanism to kill apoptosis- resistant cancer cells. Traditionally, researchers have studied how cells undergo autophagy during viral infection as an immune response mechanism, but recently researchers have discovered …

Tp53 As A Biomarker In Head And Neck Squamous Cell Carcinoma, Thomas J. Ow Md

Dissertations and Theses (Open Access)

Currently, there are no molecular biomarkers that guide treatment decisions for patients with head and neck squamous cell carcinoma (HNSCC). Several retrospective studies have evaluated TP53 in HNSCC, and results have suggested that specific mutations are associated with poor outcome. However, there exists heterogeneity among these studies in the site and stage of disease of the patients reviewed, the treatments rendered, and methods of evaluating TP53 mutation. Thus, it remains unclear as to which patients and in which clinical settings TP53 mutation is most useful in predicting treatment failure.

In the current study, we reviewed the records of a cohort …

Positional Control Over Nanoparticle Deposition Into Nanoholes, Moshood K. Morakinyo, Shankar B. Rananavare

Chemistry Faculty Publications and Presentations

Controlled deposition of metal nanoparticles (NPs) into lithographic patterned nanoholes has been a major challenge. Electrostatic attraction was employed in directing gold NPs of precise size into e-beam lithographically patterned holes. Citrate stabilized gold NPs with a net negative surface charge were deposited on a positively charged well-bottom surface generated by adsorption of long-chain amino-terminated organosilane N-(2-aminoethyl)-11-aminoundecyltrimethoxy- silane (AATMS). Scanning electron microscopy (SEM) results indicate that deposition of NPs into patterned holes is a function of deposition time and NPs concentration. Other factors affecting NP fill fraction are thickness of silane and resist layer and spacing between the nanoholes.

Analysis Of The Conformational Behavior And Stability Of The Sap And Tsap Isomers Of Lanthanide(Iii) Nb-Dota-Type Chelates, Gyula Tircso, Benjamin Charles Webber, Benjamin E. Kucera, Victor G. Young, Mark Woods

Chemistry Faculty Publications and Presentations

Controlling the water exchange kinetics of macrocyclic Gd(3+) chelates, a key parameter in the design of improved magnetic resonance imaging (MRI) contrast media, may be facilitated by selecting the coordination geometry of the chelate. The water exchange kinetics of the mono- capped twisted square antiprism (TSAP) being much closer to optimal than those of the mono capped square antiprism (SAP) render the TSAP isomer more desirable for high relaxivity applications. Two systems have been developed that allow for selection of the TSAP coordination geometry in 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA)-type Gd(3+) chelates, both based upon the macrocycle nitrobenzyl cyclen. In this paper …

An Analysis Of Non-Traditional Intervention Programs For At-Risk Youth, Christine Moore

All Theses

ABSTRACT
Through content analysis, this thesis analyzes relevant wilderness therapy programs and residential treatment centers specifically designed for at-risk youth. More specifically, this study is an applied analysis. The results provide primary care-givers with a guide for assessing programs before their adolescent continues down the path to juvenile incarceration. The study analyzed 20 wilderness therapy programs and 19 residential treatment centers through a series of exploratory questions derived from empirical research concerning the effective and ethically sound treatment of at-risk youth.
The five research questions are as follows:
1) What aspects of the program promote and include family involvement?
2) …

Factors Influencing Reproductive Success Of Near-Shore Seabirds In Cape Romain National Wildlife Refuge, South Carolina, Gillian Brooks

All Theses

Little is known about the reproductive success of Least Terns (Sternula antillarum) and Black Skimmers (Rynchops niger) along the coast of South Carolina. It appears reproductive success of both species may be limited by a variety of ecological stressors. To provide baseline measurements of reproductive success of Least Terns and Black Skimmers in South Carolina, and to assess factors which may influence nest success of both species, 257 Least Tern and 347 Black Skimmer nests were monitored at four colony sites within Cape Romain National Wildlife Refuge, 2009-2010. Nest success was highly variable among colony sites and years for both …

Social And Spatial Relationships Driving Landowner Attitudes Towards Aquatic Conservation, Samuel Chambers

All Theses

Because of a gap between the science and practice of conservation planning, it has been suggested that there is a need for better understanding of the social systems within which conservation projects are embedded. Given that more than half of the land in the United States is privately owned and that private land covers the majority of the mapped endangered species habitat, understanding attitudes of private landowners towards biodiversity conservation may help to bridge the science-practice gap. Aquatic biodiversity is particularly imperiled throughout the world; in the United States headwater streams and small, isolated wetlands receive little protection through regulations …

Multivalued Subsets Under Information Theory, Indraneel Dabhade

All Theses

In the fields of finance, engineering and varied sciences, Data Mining/ Machine Learning has held an eminent position in predictive analysis. Complex algorithms and adaptive decision models have contributed towards streamlining directed research as well as improve on the accuracies in forecasting. Researchers in the fields of mathematics and computer science have made significant contributions towards the development of this field. Classification based modeling, which holds a significant position amongst the different rule-based algorithms, is one of the most widely used decision making tools. The decision tree has a place of profound significance in classification-based modeling. A number of heuristics …

An Investigation Of The Effectiveness Of Gestures To Enhance Concept Retention In Chemistry Instruction, Jeffrey Lamb

All Theses

The emergence of embodied cognition as a theory of learning has placed new emphasis on the interdependent relationship between what the mind perceives and what the body experiences. Movement and objects in the physical environment take on significant roles in the process of learning within this view and the role of gesturing in cognition has become increasingly interesting. Significant research suggests that the physical process of gesturing is connected to how the mind processes information. Gesturing during the recall of information is a universally known phenomena and one that seems to aid in the process of recall. More recent findings …

Biomarkers In The Lower Huron Shale (Upper Devonain) As Indicators Of Organic Matter Source, Depositional Environment, And Thermal Maturity, John Kroon

All Theses

The Lower Huron Shale (Upper Devonian) is considered the largest shale gas reservoir in the Big Sandy Field in Kentucky and West Virginia. The potential for gas shales, such as the Lower Huron, to produce natural gas is a function of type, amount, and thermal maturation of their organic matter. Twenty-one Lower Huron Shale samples from eight wells located in eastern Kentucky and southern West Virginia were analyzed for biomarker content to interpret biological source of organic matter, depositional environment conditions, and thermal maturity. The following biomarkers were identified: n-alkanes (C15 to C31), pristane (Pr), phytane (Ph), steranes (αααR, (αααS, …

A Design Framework For Sustainable Infrastructure, Jacqualyn Blizzard

All Theses

Aristotle theorized, 'The whole is more than the sum of its parts.' Design engineers often overlook this simple philosophy. We employ a reductionist approach when designing the built environment: engineering solutions for the individual parts rather than the system as a whole, creating and exacerbating problems in the process. A whole system, interdisciplinary approach that considers the interrelatedness of global issues is increasingly recognized as essential to finding truly sustainable engineering solutions (NSB, 2007). However, both the precise nature of this whole systems approach, and the best ways to incorporate it in engineering education remain undefined. To address this gap …

Predicting The Thermal Performance For The Multi-Objective Vehicle Underhood Packing Optimization Problem, Ravi Teja Katragadda

All Theses

The ever increasing demands towards improvement in vehicle performance and passenger comfort have led the automotive manufacturers to further enhance the design in the early stages of the vehicle development process. Though, these design changes enhance the overall vehicle performance to an extent, the placement of these components under the car hood also plays a vital role in increasing the vehicle performance. The study of the placement of these components in an automobile underhood forms a 3-Dimensional packaging problem. In the past, a study on the automobile underhood packaging problem was conducted and a multi objective optimization routine with three …