Digital Commons Network^™

Repression Of Phlpp By Mir-190 Contributes To Arsenic-Induced Akt Activation And Carcinogenesis, Kevin John Beezhold

Graduate Theses, Dissertations, and Problem Reports (ETD)

Arsenic is a well-studied human carcinogen. The mechanism by which arsenic induces cancer, however, is not fully understood. It is known that as a general stress inducer, arsenic can activate kinases, such as mitogen-activated protein kinases, leading to over activation of transcription factors. These transcription factors, including AP-1, NF-kB and Myc, are known to regulate the expression of early response genes, and likely to regulate miRNAs. The expression of miRNAs is often altered in cancer and other proliferative disorders. It is highly probable that miRNAs whose expressions are altered by arsenic will play a significant role in carcinogenesis. To test …

Restoration Of Forested Ecosystems On The Monongahela National Forest, West Virginia, Melissa A. Thomas-Van Gundy

Graduate Theses, Dissertations, and Problem Reports (ETD)

The focus of resource management on National Forests is slowly changing to restoration of ecosystems and habitats. In West Virginia, the revised Land and Resource Management Plan for the Monongahela National Forest (MNF) guides resource management on the MNF. The MNF revised Forest Plan restructured management areas and goals toward restoration of red spruce dominated forests and oak and oak-pine forests in two separate management prescriptions that cover approximately 48% of the MNF. Incorporating ecosystem restoration in forest management may be guided by goals and objectives based on known previous conditions and the range of natural variability of those conditions. …

Vascular Consequences Of Metabolic Syndrome Related Shifts In Cyclooxygenase Mediated Arachidonic Acid Metabolism, Adam G. Goodwill

Graduate Theses, Dissertations, and Problem Reports (ETD)

The metabolic syndrome is a multi-faceted disease state in which the initial pathology of obesity leads to the development of a cadre of comorbidities including, but not limited to, atherogenic dyslipidemia, a prothrombotic state, a proinflammatory state, a pro-oxidant state, hypertension and type II diabetes mellitus. The prevalence of obesity is drastically increasing both nationally and globally, indicating that understanding obesity related disease is more relevant now then ever before. The metabolic syndrome has been demonstrated to result in numerous deleterious consequences for afflicted individuals, not the least of which is peripheral vascular disease. While the study of peripheral vascular …

Iris Recognition: Robust Processing, Synthesis, Performance Evaluation And Applications, Jinyu Zuo

Graduate Theses, Dissertations, and Problem Reports (ETD)

The popularity of iris biometric has grown considerably over the past few years. It has resulted in the development of a large number of new iris processing and encoding algorithms. In this dissertation, we will discuss the following aspects of the iris recognition problem: iris image acquisition, iris quality, iris segmentation, iris encoding, performance enhancement and two novel applications.;The specific claimed novelties of this dissertation include: (1) a method to generate a large scale realistic database of iris images; (2) a crosspectral iris matching method for comparison of images in color range against images in Near-Infrared (NIR) range; (3) a …

Exploration Of Stream Habitat Spatial Modeling; Using Geographically Weighted Regression, Ordinary Least Squares Regression, And Natural Neighbor Interpolation To Model Depth, Flow, And Benthic Substrate In Streams, Kenneth R. Sheehan

Graduate Theses, Dissertations, and Problem Reports (ETD)

Assessment and modeling of stream habitat are integral to understanding streams and the biota within them. In the past several decades, assessment sophistication of ecologic systems increased due to analysis power afforded by gains in computing capability. Spatial data analysis methodology grew alongside computing power and incorporated spatial qualities of ecological data, thereby providing new insights. New methods like geographically weighted regression (GWR) and more established methods like interpolation are now being used in ecological studies to guide assessments and management decisions. However, their accuracy and utility for analysis of stream habitat data have not been fully explored. To clarify …

Effects Of Delay Order And D-Amphetamine On Delay Discounting In Rats, Shana R. Bailey

Graduate Theses, Dissertations, and Problem Reports (ETD)

Impulsive choice is defined as choice for a smaller, more immediate reinforcer over a larger, more delayed reinforcer, whereas self-controlled choice is defined as choice for a larger, more delayed reinforcer over a smaller, more immediate reinforcer. Determinants of impulsive and self-controlled choices may be studied by employing delay-discounting procedures. When using a discrete-trials delay-discounting procedure, a difference in delay discounting as a function of order of presentation of delays to larger-reinforcer delivery was reported by one previous study, whereas another study reported no differences. In both studies, subjects had a history of exposure to both ascending and descending order …

Creating Reporter Systems Within Drosophila Melanogaster, Ashley Elizabeth Banks

Graduate Theses, Dissertations, and Problem Reports (ETD)

The objective of these projects was to generate two fluorescently based systems within Drosophila melanogaster for the advancement of molecular research. The first project was aimed to create fluorescent phosphomimetic constructs of m8, a regulator in eye formation. The second project was to create a fluorescent visual marker for heterochromatic gene silencing in Drosophila. Proper formation of the eye requires that only one cell from a group of equipotent cells assumes a neural fate (the R8 cell). The cells surrounding the R8 cell are prevented from assuming this outcome through a process known as lateral inhibition. Lateral inhibition uses the …

Educators' Perceptions Of Preparation And Practice For Teaching Algebra I To Students With Mathematical Learning Disabilities, Sararose Devore Lynch

Graduate Theses, Dissertations, and Problem Reports (ETD)

The purpose of this mixed methods study was to describe the current state of Algebra I instruction for students with mathematical learning disabilities (MLD) in West Virginia and teachers. preparation for this practice, as perceived by teachers. Further, this study examined the extent teachers. instructional practices for teaching students with MLD Algebra I aligned with best practices recommended in the research literature. Fifty-seven educators from West Virginia who taught Algebra I to students with Mathematical Learning Disabilities completed the Survey of Instructional Practices Implemented by Algebra I General and Special Educators When Educating Students with a MLD. In addition, a …

Accounting Methods To Effectively Measure The Performance Of Public Universities' Academic Units And Increase Allocation Efficiency: The Role Of Research Grants, Madeleine Arivett

Honors Capstones

No abstract provided.

Avian Assemblages And Red-Eyed Vireo Nest Survival Within Mineland Forest, Jeremy Mizel

Graduate Theses, Dissertations, and Problem Reports (ETD)

Since the passage of the Surface Mining Control and Reclamation Act (SMCRA) in 1977, mined lands have generally been reclaimed to an environment characterized by severely compacted minesoils, a growth medium comprised largely of unweathered materials, and a predominance of aggressive groundcovers that inhibit native species colonization. Under these conditions, succession is arrested. Within landscapes that are fragmented by traditionally reclaimed surface mines, forest patches are smaller and forest cover on the landscape scale is reduced. As a result, forest songbirds that require large, continuous blocks of forest are negatively affected.;Some pre-SMCRA abandoned minelands contain areas of uncompacted minesoils on …

Can Changes In Sr Protein Acetylation Affect Alternative Splicing?, Heather E. Knupp

Graduate Theses, Dissertations, and Problem Reports (ETD)

Cellular phenotype and function is determined by the cellular proteome. Within the cellular proteome there are processes that have a potential to significantly alter the composition of the proteome. One such process is called alternative splicing. Splicing is the removal of introns from a pre-mRNA sequence and the remaining pre-mRNA sequences, called exons, are combined. Alternative splicing modifies the intron-exon combination, and can form novel products from the different arrangement of the coding sequences. This process, due to the high potential for new, possibly unwanted products, is highly regulated and can occur in a tissue and developmental-specific fashion. The misreguation …

Hydroclimatic Variability In North-Central Mongolia As Inferred From Tree Rings, Caroline Leland

Graduate Theses, Dissertations, and Problem Reports (ETD)

The influence of increasing temperatures on hydrologic regimes across Mongolia is difficult to evaluate from a spatial perspective, particularly at fine resolutions. Therefore, networks of tree-ring chronologies are a valuable means of assessing regional and local variability in hydroclimate while placing recent moisture trends in a historical context. Tree-ring data are particularly useful in Mongolia, where instrumental records are spatially and temporally limited. Here, I present two chapters that are essentially related and complement one another. The first chapter seeks to identify tree-growth anomaly regions (i.e. inferred hydroclimatic regions) across north-central Mongolia based on a network of 21 tree-ring chronologies. …

Distributed Monte Carlo Simulation, Aruna Sri Bommagani

Graduate Theses, Dissertations, and Problem Reports (ETD)

Monte Carlo simulation is an effective way to analyze models of sophisticated problems, but often suffers from high computational complexity. Distributed computing is an effective technology that can be used for compute-intensive applications, such as Monte Carlo simulation. The goal of this thesis is to combine the concepts of Monte Carlo simulation and distributed computing in an effort to develop an efficient system capable of rapidly executing computationally-demanding simulations.;When distributed computing is used to support the simulations of multiple users, a scheduling algorithm is required to allocate resources among the users' jobs. In this thesis, a scheduling algorithm is developed …

Relationships Among The Personal Fable, Drug Use And Parental Monitoring In Adolescents And Young Adults, Xin Liu

Graduate Theses, Dissertations, and Problem Reports (ETD)

Relationships among the personal fable, drug use and parental monitoring in adolescents and young adults were tested in this study. Participants were 56 students, with 25 from a small, suburban area in southern Michigan, and 32 from West Virginia University (87.5 % female, 94.6% Caucasian). Participants completed questionnaires about demographics, the personal fable, parental monitoring and drug use in an online survey. Results showed that there was a negative correlation between parental monitoring and youth drug use, but no correlation between the personal fable and drug use. There was some evidence that the personal fable had a moderated effect on …

Critical Review Of Inundation Mapping Procedures For Floodplain Management, Richard M. Wise

Graduate Theses, Dissertations, and Problem Reports (ETD)

Inundation mapping is a major component of floodplain management, providing critical information as to the consequences of potential failures of flood control structures, such as dams. To develop inundation maps, a dam and river system are modeled with engineering computer programs, and a simulation of the dam failure is performed to generate data for the flood. This output data is input into other programs to develop inundation maps. Inundation maps have traditionally been produced in a paper format, but recent advances in computer modeling have provided the capability for virtual inundation maps. Thus, these mapping methods need to be investigated …

Model Development And Incorporation Of Gis Tools For Floodplain Management, Andrew P. Darnell

Graduate Theses, Dissertations, and Problem Reports (ETD)

Floodplain management consists of efforts to reduce flood damage to critical infrastructure and to protect the life and health of individuals from flooding. A major component of this effort is the monitoring of flood control structures such as dams because the potential failure of these structures may have catastrophic consequences. In order to prepare for these threats, engineers utilize inundation maps that model the flood resulting from high river stages. To create the maps, the structure and river systems are modeled using engineering software programs, and hydrologic events are used to simulate the conditions leading to the failure of the …

Validation Of The Resilience Competencies Scale (Rcs) For Applications Among American Indian Youth, Melanie Hockenberry

Graduate Theses, Dissertations, and Problem Reports (ETD)

Historical trauma, poverty, educational inequalities, and discrimination are among the many factors contributing to current problems, such as substance abuse, experienced by some American Indian youth today. Much of the literature on American Indian adolescents has been problem-focused; but it is also important to identify factors that are associated with resilient outcomes, such as personal, social, and ecological factors highlighted in models of resilience. As a step toward conducting such studies, it is necessary to have measures that are valid, reliable, and culturally-applicable for American Indian adolescents. Therefore, a mixed methods study (focus groups; survey) was conducted to examine the …

Differentiating Faking-Good Parents From Non-Faking Parents On The Child Abuse Potential Inventory, Amanda H. Costello

Graduate Theses, Dissertations, and Problem Reports (ETD)

Parental fitness evaluations remain common during child abuse investigations, as evidenced by the 19% of victims of maltreatment receiving an evaluation in 2007 in the United States (U.S. Department of Health and Human Services, 2009). A "best practice" approach to parental fitness evaluations consists of using a comprehensive assessment including clinical interviews, risk assessment measures, and behavioral observation (Budd, 2001; 2005). The Child Abuse Potential Inventory (CAP; Milner, 1986) is one risk assessment measure that is often used during evaluations. Unfortunately, abuse risk at pre- and post-treatment as measured by the CAP may be confounded by faking-good responding from the …

Bioelectrical Impedance Analysis Methods For Prediction Of Brook Trout Salvelinus Fontinalis Percent Dry Weight, Andrew William Hafs

Graduate Theses, Dissertations, and Problem Reports (ETD)

Reliable fish condition estimates are valued by fisheries ecologists and managers. Fish condition is used as an indicator of ecosystem health or to assess the population status for a species of interest. In aquaculture, proximate composition estimates are often wanted because of their relationship to fillet quality. Past researchers have used bioelectrical impedance analysis (BIA) to provide nonlethal mass based estimates of proximate composition for fish. Percent dry weight (PDW) of a fish is highly correlated to proximate composition values and energy density, therefore reliable predictions of PDW would eliminate the need for costly and laboratory analyses lethal to the …

Characterization Of M-Cadherin's Role In Regulating Apoptosis And Myogenic Differentiation Of Myoblasts By Interacting With Key Components Of Canonical Wnt Signaling, Yan Wang

Graduate Theses, Dissertations, and Problem Reports (ETD)

Activation, proliferation, and differentiation of satellite cells are the basic means for adult muscle regeneration. Apoptosis is concurrent to differentiation of satellite cells and dysregulated apoptosis contributes to the occurrence and progression of certain muscular dystrophies. This study investigated the role of M-cadherin-mediated signaling in regulating apoptosis versus survival of myoblasts during the process of myogenic differentiation. Inhibition of M-cadherin expression by RNAi (RNA interference) in confluent C2C12 myoblasts sensitized the cells to mitochondria-associated intrinsic apoptosis induced by either cell confluence or serum starvation. Manipulation of M-cadherin signaling regulated the Glycogen Synthase Kinase-3beta (GSK-3beta) activity via phosphoinositide-3 kinase (PI3K)/Akt pathway. …

Identification Of Factors Involved In Dna Methylation Of Cpg-Island-Promoters, Yan Zhang

Dissertations and Theses (Open Access)

Repression of many tumor suppressor genes (TSGs) in cancer is mediated by aberrantly increased DNA methylation levels at promoter CpG islands (CGI). About one-fourth of empirically defined human promoters are surrounded by or contain clustered repetitive elements. It was previously observed that a sharp transition of methylation occurs between highly methylated repetitive elements (SINE or LINE) and unmethylated CGI-promoters (e.g. P16, VHL, CDH and RIL) in normal tissues. The functions that lead to increased CGI methylation in cancer remain poorly understood. We propose that CGI-promoters contain cis-elements for triggering de novo DNA methylation. In the first part of our project, …

Annexin A5-Conjugated Polymeric Micelles For Dual Spect And Optical Detection Of Apoptosis, Rui Zhang

Dissertations and Theses (Open Access)

Apoptosis, a form of programmed cell death, is critical to homoeostasis, normal development, and physiology. Dysregulation of apoptosis can lead to the accumulation of unwanted cells, such as occurs in cancer, and the removal of needed cells or disorders of normal tissues, such as heart, neurodegenerative, and autoimmune diseases. Noninvasive detection of apoptosis may play an important role in the evaluation of disease states and response to therapeutic intervention for a variety of diseases. It is desirable to have an imaging method to accurately detect and monitor this process in patients. In this study, we developed annexin A5-conjugated polymeric micellar …

Function Of Znf668 In Cancer Development, Ruozhen Hu

Dissertations and Theses (Open Access)

Human cancer develops as a result of accumulation of mutations in oncogenes and tumor suppressor genes. Zinc finger protein 668 (ZNF668) has recently been identified and validated as one of the highly mutated genes in breast cancer, but its function is entirely unknown. Here, we report two major functions of ZNF668 in cancer development.

(1) ZNF668 functions as a tumor suppressor by regulating p53 protein stability and function. We demonstrate that ZNF668 is a nucleolar protein that physically interacts with both MDM2 and p53. By binding to MDM2, ZNF668 regulates MDM2 autoubiquitination and prevents MDM2-mediated p53 ubiquitination and degradation; ZNF668 …

Improving The Accuracy Of Radiation Pneumonitis Dose Response Models, Yevgeniy Vinogradskiy

Dissertations and Theses (Open Access)

The prognosis for lung cancer patients remains poor. Five year survival rates have been reported to be 15%. Studies have shown that dose escalation to the tumor can lead to better local control and subsequently better overall survival. However, dose to lung tumor is limited by normal tissue toxicity. The most prevalent thoracic toxicity is radiation pneumonitis. In order to determine a safe dose that can be delivered to the healthy lung, researchers have turned to mathematical models predicting the rate of radiation pneumonitis. However, these models rely on simple metrics based on the dose-volume histogram and are not yet …

Contribution Of Ectodomain Mutations In Epidermal Growth Factor Receptor To Signaling In Glioblastoma Multiforme, Marta L. Rojas

Dissertations and Theses (Open Access)

CONTRIBUTION OF ECTODOMAIN MUTATIONS IN EPIDERMAL GROWTH FACTOR RECEPTOR TO SIGNALING IN GLIOBLASTOMA MULTIFORME

Publication No._________

Marta Rojas, M.S.

Supervisory Professor: Oliver Bögler, Ph.D.

The Cancer Genome Atlas (TCGA) has conducted a comprehensive analysis of a large tumor cohort and has cataloged genetic alterations involving primary sequence variations and copy number aberrations of genes involved in key signaling pathways in glioblastoma (GBM). This dataset revealed missense ectodomain point mutations in epidermal growth factor receptor (EGFR), but the biological and clinical significance of these mutations is not well defined in the context of gliomas.

In our study, we focused on understanding …

Dual Targeting Of Tumor Angiogenesis And Chemotherapy By Endostatin- Cytosine Deaminase-Uracil Phosphoribosyltransferase, Chun-Te Chen

Dissertations and Theses (Open Access)

Antiangiogenesis is a promising anti-tumor strategy through inhibition tumor vascularformation to suppress tumor growth. Targeting specific VEGF/R has been showntherapeutic benefits in many cancer types and become a first approvedantiangiogenic modalities by Food and Drug Administration (FDA) in United States.However, interruption of homeostasis in normal tissues that is likely due to theinhibition of VEGF/R signaling pathway induces unfavorable side effects. Moreover,cytostatic nature of antiangiogenic drugs frequently causes less tumor cell specifickilling activity, and cancer cells escaped from cell death induced by these drugseven gain more malignant phenotypes, resulting in tumor invasion and metastasis.To overcome these issues, we developed a novel …

Glycogen Synthase Kinase 3 Is Required For Optimal Akt Activation, Debora S. Bruno

Dissertations and Theses (Open Access)

The phosphatidylinositol 3-kinase (PI3K) pathway, through its major effector node AKT, is critical for the promotion of cell growth, division, motility and apoptosis evasion. This signaling axis is therefore commonly targeted in the form of mutations and amplifications in a myriad of malignancies. Glycogen synthase kinase 3 (GSK3) was first discovered as the kinase responsible for phosphorylating and inhibiting the activity of glycogen synthase, ultimately antagonizing the storage of glucose as glycogen. Its activity counteracts the effects of insulin in glucose metabolism and AKT has long been recognized as one of the key molecules capable of phosphorylating GSK3 and inhibiting …

Applications Of Ephb4 Receptor Specific Peptides In Targeted Cancer Imaging And Therapy, Miao Huang

Dissertations and Theses (Open Access)

EphB4 receptors, a member of the largest family of receptor tyrosine kinases, are found over-expressed in a variety of tumors cells including glioma cells as well as angiogenic blood vessels. Noninvasive imaging of EphB4 could potentially increase early detection rates, monitor response to therapy directed against EphB4, and improve patient outcomes. Targeted delivery of EphB4 receptor specific peptide conjugated hollow gold nanoshells (HAuNS) into tumors has great potential in cancer imaging and photothermal therapy. In this study, we developed an EphB4 specific peptide named TNYL-RAW and labeled with radioisotope ⁶⁴Cu and Cy5.5 dye. We also conjugate this specific peptide …

Modelling Β2ar Regulation, Sharat J. Vayttaden

Dissertations and Theses (Open Access)

The β2 adrenergic receptor (β2AR) regulates smooth muscle relaxation in the vasculature and airways. Long- and Short-acting β-agonists (LABAs/SABAs) are widely used in treatment of chronic obstructive pulmonary disorder (COPD) and asthma. Despite their widespread clinical use we do not understand well the dominant β2AR regulatory pathways that are stimulated during therapy and bring about tachyphylaxis, which is the loss of drug effects. Thus, an understanding of how the β2AR responds to various β-agonists is crucial to their rational use. Towards that end we have developed deterministic models that explore the mechanism of drug- induced β2AR regulation. These mathematical models …

The Role Of Tak1 In Pancreatic Cancer Development, Qianghua Xia

Dissertations and Theses (Open Access)

Pancreatic cancer is the fourth leading cause of cancer-related mortality in the United States and the fifth leading cause of cancer-related mortality worldwide. Pancreatic cancer is a big challenge in large due to the lack of early symptoms. In addition, drug resistance is a major obstacle to the success of chemotherapy in pancreatic cancer. The underlying mechanism of drug resistance in human pancreatic cancers is not well understood. Better understanding of the mechanism of molecular pathways in human pancreatic cancers can help to identify the novel therapeutic target candidates, and develop the new preventive and clinic strategies to improve patient …