Digital Commons Network^™

Recurrent Mutations Of T-Cell Receptor And Co-Stimulatory Signaling Proteins In Peripheral T-Cell Lymphomas, Joseph Rohr

Theses & Dissertations

Peripheral T-cell lymphomas (PTCLs) comprise a heterogeneous group of mature T-cell neoplasms with a poor prognosis. Recently, mutations in TET2 and other epigenetic modifiers as well as RHOA have been identified in these diseases, particularly in angioimmunoblastic T-cell lymphoma (AITL). CD28 is the major co-stimulatory receptor in T-cells which, upon binding ligand, induces sustained T-cell proliferation and cytokine production when combined with T-cell receptor stimulation, through many signaling molecules including VAV1. This thesis identifies recurrent mutations in CD28 in PTCLs, as well as mutations in VAV1. Two residues of CD28 – D124 and T195 – were recurrently mutated in 11.3% …

Interrogating Raf-1 Kinase Inhibitor Protein (Rkip) As A Novel Therapeutic Target For Modulating Inflammatory Responses, Kyle T. Wright

Doctoral Dissertations

The studies presented here were designed to test if Raf-1 kinase inhibitor protein (RKIP) plays a functionally significant role in immunity, and to interrogate its possibility of providing a novel therapeutic target for modulating inflammatory responses. Based on previous studies from other laboratories that attributed negative regulatory functions to RKIP in the context of MAPK and NF-κB signaling in cell lines, we tested the hypothesis that its function was to suppress the production of pro-inflammatory cytokines, proliferation, and cell survival. However, after extensive investigation, our data clearly demonstrate that RKIP is actually necessary for the production of certain cytokines, namely …

Students Perceptions Of Individuals With Intellectual And Developmental Disabilities And The Impact Of Inclusion, Marissa Visse

Honors Theses

The objective of this study is to determine if inclusion of people identified with intellectual and developmental disabilities (IDD) has an impact on their typically developing peers as well as determining the perceptions that college students at EKU have of people with IDD. A survey was conducted online through Surveymonkey.com and was sent out to EKU students through email. There were 82 respondents to the survey. The survey consisted of questions on age, gender, and status at EKU of each participant and asked them questions about the perceptions they have of those with IDD and if they have been involved …

Rescuing Victims Of Human Trafficking: Strategies And Solutions, Andrew J. Pullins

Honors Theses

The purpose of this thesis is to research and investigate how victims of human trafficking are removed from exploitative situations. There are three main methods of removal, which are raids, purchases, and escapes. Each method has its own unique characteristics, advantages and disadvantages. The research was conducted in the form of a literature review. The findings of this research indicate that there is no one “right” way to rescue a victim of human trafficking. Each rescue must be carefully researched and planned before being executed, or the consequences can be severe.

Evaluation Of Thiol Raman Activities And Pka Values Using Internally Referenced Raman-Based Ph Titration, Nuwanthi Savindrika Suwandaratne

Theses and Dissertations

Thiols are one of the most important classes of chemicals used broadly in organic synthesis, biological chemistry, and nanosciences. Thiol pKa values are key indicators of thiol reactivity and functionality. This study is an internally-referenced Raman-based pH titration method that enables reliable quantification of thiol pKa values for both mono- and di-thiols in water. The degree of thiol ionization is monitored directly using the peak intensity of the S-H stretching feature relative to an internal reference peak as a function of solution pH. The thiol pKa values and Raman activity relative to its internal reference were then determined by curveitting …

Restriction Enzyme Generated Next-Generation Sequencing Libraries And Genetic Risk Modifiers Of Brca1 Mutation Carriers, Bradley Downs

Theses & Dissertations

Next-generation sequencing (NGS) is a high throughput technique used to sequence large amounts of DNA in a short amount of time. However, a limitation to NGS is that the generated data is in a single consensus sequence without distinguishing between variants on homologous chromosomes. Separating or phasing the variants from the maternal and paternal chromosomes can provide information about the genetic origin of disease and information about how DNA nucleotide alterations interact in cis. This dissertation explores a new technical method of using restriction enzymes during NGS library preparation and its ability to increase the amount of phasing information that …

Molecular Mechanisms Of Necrotic Cell Death In Ischemic Renal Injury, Yuan Ying

Theses & Dissertations

Acute kidney injury is a common clinical syndrome particularly in hospitalized patients. Necrotic cell death, as one type of major cell death after ischemic reperfusion injury, is partially responsible for the rapid decline in GFR. p53 is a novel apoptosis and necrosis inducer and is found to be activated after ischemic renal injury. Although previous studies suggest that p53 could be an important mediator of kidney dysfunction, no studies have examined its role in necrotic cell death and the cross talk between p53 and other necrotic cell inducers such as PARP-1 and CypD. Thus, in this study our first goal …

Block Copolymer Based Magnetic Nanoclusters For Cancer-Theranostics: Synthesis, Characterization And In Vitro Evaluation, Hemant M. Vishwasrao

Theses & Dissertations

“There is plenty of room at the bottom”. In this visionary lecture in 1959 Prof. Richard Feynman spoke of the interesting ramifications of working with matter at the atomic scale. Since then, scientists have worked relentlessly towards realizing his vision. The influence of nanobiotechnology on material science and polymer chemistry has given rise to a new field called ‘theranostics’, combining drug delivery and diagnostics within the same nanostructures, thereby enabling simultaneous diagnosis, targeted drug delivery and continued therapy monitoring. Iron oxide nanoparticles (MNPs) are one such class of MRI contrast agents that can be converted into theranostic nanomedicines for cancer …

Molecular Mechanisms Regulating Myc And Pgc1Β Expression In Colon Cancer, Jamie L. Mccall

Theses & Dissertations

Identification and characterization of pathways specific to tumor cell survival, but absent in normal tissues, provide opportunities to develop effective cancer therapies with reduced toxicity to the patient. Kinase suppressor of Ras 1 (KSR1) is required for the survival of colorectal cancer (CRC) cells, but dispensable in normal cells. Using KSR1 as a reference standard, we identified EPH (erythropoietin-producing hepatocellular carcinoma) receptor (EPHB4) as a KSR1 functional analog.

We show here that, like KSR1, EPHB4 is aberrantly overexpressed in human CRC cells and selectively required for their survival. Both KSR1 and EPHB4 support tumor cell survival by promoting the expression …

Genetic Predisposition And M1 Macrophage Polarization Created By Elastin-Derived Peptides Drive Abdominal Aortic Aneurysm Formation, Matthew A. Dale

Theses & Dissertations

Abdominal aortic aneurysm (AAA) is a dynamic vascular disease characterized by inflammatory cell invasion and extracellular matrix (ECM) degradation. Evidence has demonstrated a profound influence of genetic background on AAA formation. The work presented herein discusses two studies: the first demonstrates how genetic components can enhance the susceptibility to AAA formation and the second demonstrates how ECM degradation enhances AAA progression by influencing inflammatory cell phenotypes. An understanding of the pathways involved in AAA pathogenesis can help not only to identify potential patients at risk of AAA development, a heritable disease in which the incriminating component has yet to be …

Using Homeland Security Exercise Evaluation Program To Execute A Mass Prophylaxis Exercise In A Rural Community., Brian K. Smith

Theses & Dissertations

This project explores the execution of point of distribution exercises in a rural community. Harrison County Iowa is a rural county with a population over 15,000 located approximately 45 minutes north of the Omaha metro area. The project explored the existing point of distribution plans and inventory for the Harrison County Home and Public Health Department. Prior to this project, many staff at Harrison County Home and Public Health Department had no experience with table top or full scale exercises. The mass prophylaxis point of distribution plan had not been updated, and staff had not received training on the point …

The Role Of Dna Methyltransferases In Normal And Malignant Hematopoiesis, Staci Haney

Theses & Dissertations

DNA methylation is an epigenetic modification that regulates gene transcription. The addition of a methyl group to cytosine is catalyzed by a family of enzymes known as DNA methyltransferases (Dnmts). The three catalytically active Dnmts in humans and mice are Dnmt1, Dnmt3a, and Dnmt3b. DNA methylation is clinically relevant, as aberrations in the methylation landscape are a hallmark of nearly all human cancers. Cancer methylomes are typically characterized by genome wide hypomethylation and regional specific hypermethylation, both of which have been linked to alterations in gene expression. In order to understand the contribution of epimutations to the development of hematological …

Color Stability, Physical Properties And Antifungal Effects Of Zro2 And Tio2 Nanoparticle Additions To Pigmented Polydimethylsiloxanes, Mazen Alkahtany

Theses & Dissertations

Introduction: Color changes, physical degradation and fungal infections are potential challenges to the longevity of polydimethylsiloxane (PDMS) elastomers. The purpose of this study was to evaluate potential improvements in color change, physical properties and anti fungal properties of PDMS loaded with TiO2 and ZrO2 nanoparticles.

Methods: 1% weight of 40 nm or 200 nm diameter TiO2 or ZrO2 nanoparticles were mixed into PDMS with 2% functional intrinsic yellow pigment and polymerized. Control materials contained 13% weight 200 nm silica. Samples were exposed to either 3000 hours of UVB radiation (200 μW/cm2) or darkness. Color parameters L*a*b* and ΔE*, ultimate tensile …

Physical Activity Levels And Related Factors In Midwestern Rural Hispanic Or Latino Adults, Alison K. Clevette

Theses & Dissertations

The purpose of this dissertation was to examine physical activity levels and specific intrapersonal, interpersonal and community physical environment factors that influence physical activity in Midwestern rural Hispanic or Latino adults. Instruments used in the study included: Self-Efficacy for Exercise Behaviors Survey, Social Support for Exercise Survey, Short Acculturation Scale for Hispanics (SASH), and Neighborhood Environment Walkability Scale (NEWS). Physical activity was measured by 7-Day Physical Activity Recall and ActiGraph^® accelerometer data. In the study of 54 participants, it was found that there was a very low level of physical activity. For example, 97% of the time was spent …

The Role Of Oncogenic Kras In Initiation, Progression And Maintenance Of Pancreatic Cancer, Nirakar Rajbhandari

Theses & Dissertations

Pancreatic cancer is a lethal disease that is almost invariably associated with a KRAS gene mutation. Due to a very high frequency of gain-of-function mutations within the KRAS gene, and its proven role in initiation of pancreatic cancer in animal models, mutant KRAS is considered a rational therapeutic target. To determine the potential role of oncogenic KRAS in pancreatic tumor maintenance in vivo, we generated a mouse model with a Doxycycline regulated expression of oncogenic KRAS (KRAS^G12D) in pancreas. Using this reversible model, we demonstrated that the expression of oncogenic KRAS in a Cdkn2a deficient background was …

Role Of Cell Type And Genetic Alterations In Driving Breast Cancer Pathogenesis, Divya Bhagirath

Theses & Dissertations

Breast cancer is the second most leading cause of death among women in the United States. Several environmental and genetic factors contribute to the pathogenesis of the disease. It is classified into different subtypes based on expression of certain markers as well as that of set of genes that define the disease progression and associated mortality. Identification of various subtypes namely: Luminal-like (Luminal-A, Luminal-B), ErbB2 over-expressing, Basal-like and Claudin low types, showed an association of survival outcomes with that of the corresponding gene expression signatures, thus paving a way for therapeutic intervention. It further emphasizes the importance of nature of …

Role Of Akt2 In Cell Survival, Establishment And/Or Maintenance Of Colorectal Cancer Metastasis, Ekta Agarwal

Theses & Dissertations

There is extensive evidence for the role of aberrant cell survival signaling mechanisms in cancer progression and metastasis. Akt acts as a key signaling node that bridges oncogenic receptors to many essential pro-survival cellular functions, and is perhaps the most commonly activated signaling pathway in human cancer. Akt has three isoforms, Akt1, 2 and 3. Variable phenotypic differences are observed following the genetic inactivation and/or removal of the Akt isoforms, which suggests that the isoforms have distinct non-redundant functional characteristics despite sharing a high level of structural homology and similar mechanisms of activation.

The major goal of the work presented …

Role Of Stemloop D In Terminally Deleted Coxsackievirus B3 Replication, Lee K. Jaramillo

Theses & Dissertations

Coxsackievirus B3 (CVB3) is an enterovirus with no known form of latency. However, assays designed to detect enteroviral RNA have shown that CVB3 RNA can persist for weeks beyond the acute infection both naturally and experimentally. Our previous work with coxsackievirus revealed an inhibited version of enteroviral replication where the progeny virus, termed terminally deleted (TD) virus, was missing a maximum of 49 nucleotides from the beginning of the 5’ non-translated region (NTR). The largest terminally deleted virus, TD50, effaced stem a, stemloop b, and stemloop c from the secondary structure, the cloverleaf. We hypothesized that further deletion beyond those …

Inflammation- And Cancer-Associated Neurolymphatic Remodeling And Cachexia In Pancreatic Ductal Adenocarcinoma, Darci M. Fink

Theses & Dissertations

This work addresses two understudied elements of inflammation and malignancy—namely, (1) neurolymphatic remodeling during transitions in microenvironmental inflammatory status and (2) the systemic paraneoplastic inflammatory syndrome cancer-associated cachexia in the context of pancreatic adenocarcinoma (PDAC). Lymphatic vessels undergo dramatic phenotypic changes in initial inflammation, wound recovery, and recurrent inflammation. We identified complementary novel neuroremodeling behaviors under these conditions and hypothesized that both nerve and lymphatic remodeling were directed by a tissue remodeling factor with overlapping functions. We found that nerve growth factor (NGF) influenced not only nerves but also lymphatics. NGF stimulated lymphangiogenesis, inhibited lymphatic vessel regression during wound recovery, …

The Role Of Ada3 Overexpression In Proliferation Through Enhancing Myc Expression, Nicolas I. Griffin

Theses & Dissertations

Breast cancer is a heterogeneous disease that is the second leading cause of cancer related deaths in women. Cancer is defined as abnormally heightened proliferation. In order for gene transcription and eventual translation to occur to drive the cell cycle to generate more cells, DNA must be uncoiled from nucleosomes by histone acetylation complexes. One of the key evolutionarily conserved components of these HAT complexes is alteration/deficiency in activation 3 (ADA3). In addition to the role in histone acetylation, this protein also functions as a coactivator for nuclear hormone receptors. Recent findings indicated that nuclear Ada3 correlates with ER+ breast …

Role Of Ecdysoneless In Erbb2/Her2 Mediated Breast Oncogenesis, Shalis A. Ammons

Theses & Dissertations

Breast cancer is the second leading cause of cancer related deaths in women in the United States. The human Epidermal Growth Factor 2 (ErbB2) gene amplification and/or receptor overexpression subtype of breast cancer accounts for 25% of all breast cancers. A crucial regulator of the ErbB2 signaling pathway is the heat shock protein 90 (Hsp90) and its interacting protein complex. One such complex is the R2TP/Prefoldin-like complex that is composed of four proteins, RUVBL1, RUVBL2, PIH1D1, and RPAP3 and seven prefoldin-like proteins. This complex has been shown to be involved in telomere elongation, ribosome biogenesis, protein stability; etc. We and …

Exploitation Of The Ligand-Binding Properties Of The Mannose 6-Phosphate/Insulin-Like Growth Factor Ii (Igf-Ii) Receptor To Inhibit Igf-Ii-Dependent Growth Of Cancer Cells, Megan Zavorka Thomas

Theses & Dissertations

The mannose 6-phosphate/insulin-like growth factor II receptor (M6P/IGF2R) is a multifunctional, type I transmembrane receptor that is a member of the P-type lectin family. A large, extracytoplasmic (EC) region of the M6P/IGF2R binds various ligands, allowing the receptor to regulate multiple biological functions, including the role as a tumor suppressor. Two major classes of ligands, M6P-glycosylated (i.e. any proteins that bear M6P due to post-translational modification in the trans-Golgi network (TGN)) and non-glycosylated (i.e., the mitogen insulin-like growth factor II (IGF-II)), bind within distinct regions of the EC of the receptor and are trafficked to the lysosome. The M6P/IGF2R as …

Utilization Of Dissection Videos In Graduate-Level Gross Anatomy Education: An Analysis Of Student Confidence, Utilization, And Scoring Outcomes, Jessica Gamerl

Theses & Dissertations

The use of videos in anatomy education has become a potential tool for learning by students. It is currently unclear if using videos that show how to perform a dissection can have an impact on student practical scores. This thesis attempted to address that question as well as address how videos can impact student confidence levels and how students might implement videos into their study strategies. A set of high definition videos was made following the specific steps of a dissector guide and provided to students prior to their third and fourth lab practicals. A series of three surveys was …

Secretory Mucin Muc5ac In Gastrointestinal Malignancies, Shiv Ram Krishn

Theses & Dissertations

Secretory mucin MUC5AC is an extensively glycosylated high molecular weight protein that forms a polymeric gel layer over the epithelial layers under physiological conditions, to protect these surfaces from myriad of insults. MUC5AC is known to be implicated in various malignancies including pancreatic cancer and colorectal cancer. MUC5AC is overexpressed in pancreatic cancer compared to no expression in normal pancreas. However, its functional implications and associated mechanistic basis in pancreatic cancer remains obscure. Therefore, we investigated the role of MUC5AC in onset and progression of pancreatic cancer. Our study showed that MUC5AC expression is elevated during pancreatic cancer progression while …

The Role Of Cbl Family Of E3 Ubiquitin Ligases In Intestinal Epithelial Homeostasis, Neha Zutshi

Theses & Dissertations

All adult organs are endowed with a small pool of resident stem cells that must be maintained throughout life to provide for cell turnover during homeostasis and tissue repair following any injury. The unique ability to self-renew as well as to differentiate into functional cells of organs in which they reside makes stem cells essential for the maintenance of organ systems. It is now becoming increasingly evident that aberrant activity of stem cells contributes to diseases such as cancer or tissue/organ atrophy. Thus, it is critical to better understand the mechanisms that regulate adult stem cells. Ligand-activated receptor tyrosine kinases …

Novel Regulatory Mechanisms And Functions Of Muc4 In Pancreatic Cancer, Suhasini Joshi

Theses & Dissertations

Mucins are high molecular weight glycoproteins and have critical functions in protecting epithelial cells from a myriad of cellular stress. However, mucins are expressed aberrantly under cancer conditions that allow tumors to progress and metastasize. Among many mucins, Mucin 4 (MUC4) serves as one of the top-differentially expressed proteins in pancreatic cancer (PC), however, the precise mechanism responsible for its aberrant expression is still not clear. The evolving view of cancer as an energetic and growing ecosystem underlines an intricate interplay between cancer and its microenvironment. In spite of being recognized as one of the most critical oncogenic proteins in …

Human Papillomavirus And Its Impact On Vulnerable Populations, Harpriya Kaur

Theses & Dissertations

Human papillomavirus (HPV) is the most common sexually transmitted infection. The infection is higher in certain racial/ethnic groups and those who are immunocompromised including pregnant women. Because immune system is suppressed during pregnancy, women are at higher risk of various types of infection including HPV, a known risk factor for pregnancy complications. However, its role in adverse pregnancy outcomes is unclear. Another high risk population is Northern Plain American Indian. In the Northern Plains region, American Indian women have significantly higher rate of HPV infection than white counterparts and are infected with different types of HPVs than the general population. …

Expression And Function Of Inflammation-Associated Micrornas In Traumatic Brain Injury, Emily Harrison

Theses & Dissertations

MicroRNAs (miRNAs) are important regulators of gene expression. Many neurological diseases, including traumatic brain injury alter expression of miRNAs in the brain. However, the function of these molecules in the context of TBI is largely unknown. Here we report multiple potential roles for miRNAs in TBI, some of which extend beyond the traditional model of post-transcriptional regulation, highlighting that these RNA molecules may have broader implications for the neurobiology of disease. We found that miR-155 plays an essential role in interferon expression after CCI and that miR-155 contributes to TBI induced anxiety, potentially through regulation of interferons. Expression of miR-155 …

Analyzing The Influence Oxygen Deprivation Has On The Capability Of Listeria Monocytogenes To Induce Listeriosis In Gerbils, Jillian Leigh Harris

Theses and Dissertations

Listeria monocytogenes is food-borne pathogen that causes listeriosis in individuals with a compromised immune system and pregnant women. This pathogen can survive in anaerobic conditions present in specially packaged foods as well as the gastrointestinal tract. The purpose of this study is to evaluate virulence of L. monocytogenes F2365 in anaerobic conditions. Another goal of this study is to establish gerbils as the ideal animal model since descrepancies exist in current models. Gerbils were orally infected with one of four doses: 1) phosphate buffered saline, 2) 5X106CFU aerobic dose, 3) 5X108CFU aerobic dose, and 4) 5X106CFU anaerobic dose. Results indicate …

Use Of The Heat Stress Score To Predict Preparedness To Run In An Outdoor, Warm Weather Race, Rachel K. Katch

Master's Theses

No abstract provided.