Characterization Of Erbb4 Expression In Osteosarcoma, Nupur Lala

Dissertations and Theses (Open Access)

ERBB4 (Her-4) is a member of the ERBB family of Class I receptor tyrosine kinases. ERBB4 is unique within the ERBB family for alternate splicing in its juxtamembrane and cytoplasmic regions, which produces four juxtamembrane isoforms and two cytoplasmic isoforms. The cleavable juxtamembrane isoforms, Jm-a and Jm-d, can undergo proteolytic cleavage and produce an 80-kDa cytoplasmic fragment referred to as “p80,” which has been demonstrated to enhance cellular survival and malignant behavior in many solid tumors [44]. ERBB4 was almost exclusively 80 kDa in size and localized to the nucleus in primary tumors and metastases in studies characterizing ERBB4 expression …

Regulation Of The Oxidative Stress Response By Arid1a, Suet Yan Kwan

Dissertations and Theses (Open Access)

SWI/SNF is mutated in about 20% of all human cancers; in particular ARID1A is the most frequently mutated SWI/SNF subunit. ARID1A is a tumor suppressor gene, inactivating mutations in ARID1A are most frequently found in ovarian and endometrial cancers, specifically uterine corpus endometrioid carcinomas (UCEC), ovarian clear cell carcinomas (OCCC) and ovarian endometrioid carcinomas (OEC). The functional roles of ARID1A are not completely understood and there are limited therapeutic strategies that specifically target ARID1A-mutant cancers. Given that ARID1A expression is lost in cancer, ARID1A mutations cannot be targeted directly and novel therapeutic strategies are required to target ARID1A-mutant …

In Vivo Functional Significance Of Ccat2 Long Non-Coding Rna In Myelodysplastic Syndrome, Maitri Y. Shah

Dissertations and Theses (Open Access)

Long non-coding RNAs form the largest part of the mammalian non-coding transcriptome and control gene expression at various levels including chromatin modification, transcriptional and post-transcriptional processing. Although the underlying molecular mechanisms are not yet entirely understood, lncRNAs are implicated in initiation and progression of several cancers. CCAT2 is a lncRNA that spans the highly conserved 8q24 region associated with increased risk for various cancers. CCAT2 has been shown to play an important role in inducing chromosomal instability and supporting cell proliferation and cell cycle arrest. However, a causal role of CCAT2 in initiation of tumorigenesis and the importance of G/T …

Role Of Stat3 In Human Nk Cell Functions, Prasad V. Phatarpekar

Dissertations and Theses (Open Access)

Natural Killer (NK) cells are cytotoxic lymphocytes, which play a critical role in the immune response against malignant cells and microbial infections. NK cells are equipped with activating receptors, which upon detecting ligands expressed on stressed cells induce cytolytic activity of NK cells. Stimulation of NK cell proliferation and priming of NK cytolytic capability are accomplished by cytokines, which mediate their signals mainly through JAK-STAT signaling pathway. Previously, we found that K562 cells genetically modified to express membrane bound IL-21 (mbIL-21), which predominantly activates STAT3, induce robust expansion and activation of human NK cells. Further investigations revealed role of STAT3 …

Mobilization Of Adipose Stromal Cells In Obesity And Cancer By Sparc And Its Proteolytic Isoforms, Chieh Tseng

Dissertations and Theses (Open Access)

Obesity increases cancer risk and progression as shown by epidemiologic studies. However, the underlying pathophysiology remained unclear. Adipose stromal cells (ASC) are adipose tissue-derived mesenchymal progenitors, abundant in white adipose tissue (WAT). In this study, we show that the ASC pool is expanded in obesity and is associated with promoted tumor growth. Next, by using a chimeric GFP-RFP bone marrow transplant model, we observed higher tumor infiltrating cells with ASC phenotype in obese mice compared to lean. Consistently, systemic circulating ASC frequency is six fold higher in tumor-bearing obese mice compared to lean. The tumor infiltrating cells with ASC phenotype …

The Tumor Suppressor Notch Inhibits Head And Neck Squamous Cell Carcinoma (Hnscc) Tumor Growth And Progression By Modulating Proto-Oncogenes Axl And Ctnnal1 (Α-Catulin), Shhyam Moorthy, Shhyam Moorthy

Dissertations and Theses (Open Access)

Background: Head and Neck Squamous Cell Carcinoma (HNSCC) is the sixth most common malignancy worldwide, with roughly 300,000 cancer related deaths occurring globally each year. The survival of patients with HNSCC has not changed significantly over the past decade, leading investigators to search for promising molecular targets. To identify new treatment targets and biomarkers that could better guide therapy, we previously characterized the genomic alterations from primary HNSCC patient samples. We were among the first to discover that NOTCH1 is one of the most frequently mutated genes in this cancer type. The spectrum of inactivating NOTCH1 mutations in HNSCC suggested …

Voxel-Level Absorbed Dose Calculations With A Deterministic Grid-Based Boltzmann Solver For Nuclear Medicine And The Clinical Value Of Voxel-Level Calculations, Justin Mikell

Dissertations and Theses (Open Access)

Voxel-level absorbed dose (VLAD) is rarely calculated for nuclear medicine (NM) procedures involving unsealed sources or 90Y microspheres (YM). The current standard of practice for absorbed dose calculations in NM utilizes MIRD S-values, which 1) assume a uniform distribution in organs, 2) do not use patient specific geometry, and 3) lack a tumor model. VLADs overcome these limitations. One reason VLADs are not routinely performed is the difficulty in obtaining accurate absorbed doses in a clinically acceptable time. The deterministic grid-based Boltzmann solver (GBBS) was recently applied to radiation oncology where it was reported as fast and accurate for both …

Normal Glycolytic Enzyme Activity Is Critical For Hypoxia Inducible Factor-1a Activity And Provides Novel Targets For Inhibiting Tumor Growth, Geoffrey Grandjean Phd

Dissertations and Theses (Open Access)

Normal Glycolytic Enzyme Activity is Critical for Hypoxia Inducible Factor-1α Activity and Provides Novel Targets for Inhibiting Tumor Growth

By Geoffrey Grandjean

Advisory Professor: Garth Powis, D. Phil

Unique to proliferating cancer cells is the observation that their increased need for energy is provided by a high rate of glycolysis followed by lactic acid fermentation in a process known as the Warburg Effect, a process many times less efficient than oxidative phosphorylation employed by normal cells to satisfy a similar energy demand ^[1]. This high rate of glycolysis occurs regardless of the concentration of oxygen in the cell and …

Redirecting T Cells With Chimeric Antigen Receptors To Target Cd123+ Leukemia, Radhika Thokala

Dissertations and Theses (Open Access)

ABSTRAC

REDIRECTING T CELLS WITH CHIMERIC ANTIGEN RECEPTORS TO TARGET CD123+ LEUKEMIA

Radhika Thokala, Ph.D*

Advisory Professor: Dean Anthony Lee, M.D, Ph.D

CD123 or interleukin receptor alpha (IL-3Rα) is expressed on hematological malignancies such as acute myeloid leukemia (AML) and some acute lymphoblastic leukemia (ALL). Significantly, CD123 is over-expressed on leukemic stem cells (LSCs) compared to normal hematopoietic stem cells and thus targeting this tumor- associated antigen (TAA) provides the potential to prevent relapse. The prototyical chimeric antigen receptor (CAR) is fashioned by …

Molecular Regulation Of Vascular Calcification In Murine Models Of Atherosclerosis, Shanshan Gao

Dissertations and Theses (Open Access)

Background: Calcification occurs often in the atherosclerotic lesions of patients with coronary heart disease and animals with hypercholesterolemia, such as apolipoprotein-E deficient (ApoE-/-) mice. However, the mechanism(s) underlying the development of calcification in atherosclerosis remains unclear. ApoE acts as a lipid transporter, but also has been recognized as a potential regulator of osteogenesis. Little information is available as to whether ApoE has any direct impact on osteogenesis and calcification in vascular smooth muscle cells (VSMC). Several signal transduction pathways play a role in regulation of calcification, including the Wnt/β-catenin system and potentially GTAP, an ubiquitin-conjugating enzyme responsible for protein …

Effects Of Pharmacological And Genetic Disruption Of Chemokine Receptor Cxcr4 In B-Cell Acute Lymphoblastic Leukemia, Shubhchintan Randhawa

Dissertations and Theses (Open Access)

The CXCR4 chemokine receptor plays a pivotal role in homing and retention of B-cell Acute Lymphoblastic Leukemia cells to bone marrow niches. The bone marrow stromal cells (BMSCs) constitutively secrete the CXCR4 ligand CXCL12, thus attracting leukemia cells and protecting them from cytotoxic drugs, a mechanism that might be responsible for minimal residual disease after conventional chemotherapy against B-ALL. Indeed, in this study we observed that B-ALL cells that had migrated beneath the BMSCs were highly resistant to chemotherapeutic drugs. Inhibition of CXCR4 to disrupt this interaction presents itself as an attractive target to overcome bone marrow derived drug resistance …

Defining The Molecular Networks Necessary For Thymus Fate And Organogenesis, Kaitlin A. Reeh

Dissertations and Theses (Open Access)

The thymus and parathyroid (PT) glands originate from endodermal progenitors in the bilateral third pharyngeal pouches (3^rd pps). By E11.5 during mouse development, cells committed to the thymus lineage express Foxn1 whereas PT-fated cells express Gcm2. While these transcription factors are required for organ-specific differentiation, the exact molecular mechanisms that specify endodermal progenitors to either the thymus or parathyroid lineage are not well defined. Tbx1 is initially expressed throughout the 3^rd pp endoderm, as it is required for segmentation of the pharyngeal apparatus, but is downregulated in the thymus-fated domain by E10.5. Despite the widely held notion …

Evaluating Long-Term Land Cover Changes For Malheur Lake, Oregon Using Envi And Arcgis, Ryan Joseph Woods

Theses and Dissertations

Land cover change over time can be a useful indicator of variations in a watershed, such as the patterns of drought in an area. I present a case study using remotely sensed images from Landsat satellites for over a 30-year period to generate classifications representing land cover categories, which I use to quantify land cover change in the watershed areas that contribute to Malheur, Mud, and Harney Lakes. I selected images, about every 4 to 6 years from late June to late July, in an attempt to capture the peak vegetation growth and to avoid cloud cover. Complete coverage of …

New Genres In The Art Classroom: Shifting Ideas And Identities, Alyssa Grant Ridge

Theses and Dissertations

Secondary art education programs primarily offer courses in traditional mediums like drawing, painting, sculpture, and ceramics. In addition to valuing these traditional art forms, art education research supports integrating new technologies and media in the classroom. However, the possibilities of creating an exclusively contemporary, new genres curriculum have yet to be explored. This study examines the affordances and limitations of a high school-level new genre curriculum and describes how students reacted to these new genres and how their perceptions of art, student-peer relationships, and artist identities changed over time. By introducing students to new genres, the author found students expanded …

Diversification And Speciation Across Sundaland And The Philippines: The Effects Of 30 Million Years Of Eustatic Flux, Luke J. Welton

Theses and Dissertations

I highlight two squamate lineages endemic to Southeast Asia, the Asian water monitors (Varanus salvator Complex) and the Angle-headed lizards (Agamidae: Gonocephalus), and elucidate their systematic affinities and historical biogeography. My results represent novel phylogenetic inferences, with biogeographic histories and diversification events corresponding to major climatic fluctuations over the past 30 million years. Additionally, I solidify the taxonomy and systematics of the Varanus salvator Complex, and enumerate more than a dozen Gonocephalus lineages as candidate species in need of taxonomic scrutiny. Lastly, I investigate contemporary and historical patterns of dispersal throughout Sundaland, and between Sundaland and the Philippines.

Non-Suitable Habitat A Cause For Declining Bobolink Populations In Northern Utah, Bethany Q. Unger

Undergraduate Honors Capstone Projects

Bobolink, Dolichonyx oryxivories, populations are declining in Utah. I characterized the habitat conditions of known bobolink nesting sites in Utah and compared these conditions to those for nest sites in Wisconsin where bobolinks are abundant. My habitat assessment included identifying vegetation species, vegetation cover, pH, temperature, and precipitation at each site location. Vegetation cover different between Utah and Wisconsin nest sites. Precipitation varied for both locations with no correlation between water availability and bobolink presence. One possible driver for the reduction in bobolinks throughout Utah is the drastic increase in temperature. Other possible external factors include livestock grazing, edge distance, …

Consumer Assessment Of New Creative Products Across China And The United States, Eva Teruzzi

Creative Studies Graduate Student Master's Theses

This cross-cultural research investigates how consumers assess creativity in new products and if their assessment impacts desire to own. Implicit and explicit scale-based measures were tested in China and the U.S. in online consumer samples and were positively correlated. Novelty, affect and importance dimensions of creative products were tested through Horn and Salvendy’s (2006, 2009) Product Creativity Measurement (PCM) scale. Findings point to a different role of novelty in determining desirability of creative new products across-cultures.In fact, novelty and affect are key to explain desire to own in China, while affect and importance are the drivers in the U.S. Affect, …

Management And Impacts Of Wild Hogs (Sus Scrofa) In South Carolina, Susan Sullivan

All Theses

Wild hogs (Sus scrofa) are an invasive species that can damage native ecosystems, negatively impact native wildlife, and potentially act as disease reservoirs in the U.S. To better understand how natural resource professionals in South Carolina approach wild hog management, I conducted a web-based survey of natural resource professionals focused on aspects of wild hog impacts and management. Generally, there was agreement among natural resource professionals regarding the approaches used to control wild hog populations and their subsequent effectiveness. The majority of respondents indicated high priority impacts needing to be addressed in wild hog management were agricultural damage …

Weeds, Nitrogen, And Yield: Measuring The Effectiveness Of An Organic No-Till System, David Robb

All Theses

Previous research in the mid-Atlantic and midwestern USA has identified advantages and drawbacks of "organic no-till" vegetable production, but few studies have been conducted in the warmer southeastern region. The purpose of this study was to examine the effects of tillage [no-till (NT) vs. conventional tillage (CT) of a cereal rye/crimson clover cover crop] and three nitrogen fertilization rates on organic tomato (Solanum lycopersicum L.) and summer squash (Cucurbita pepo L.) yield, weed suppression, and soil N dynamics in two years in a soil series in Clemson, SC. Squash yields were similar between tillage treatments in both years. NT tomato …

Single Particle And Biological Cell Detection By A Radio Frequency Interferometer, Zheng Wang

All Theses

This thesis presents a series of studies on single particle and biological cell detection and differentiation by a radio frequency (RF) interferometer system. Several techniques, such as dielectrophoresis (DEP), time domain method and 3D focusing have been illustrated and investigated to demonstrate the capacity of interrogating the electric property of single particle or biological cell by the RF interferometer. Silica particles and live yeast cells are trapped at the sensing area by DEP force and detected by the RF sensor. Solutions of particle mixtures (~4 μm silica and ~10 μm polystyrene) and cell mixtures (viable and non-viable yeast cells, normal …

Tracking Anisotropic Optical Tracers To Study Biophysical Processes And Cytotoxicity, Khanh Van Nguyen

All Dissertations

We use anisotropic optical tracers (also called magnetically modulated optical nanoprobes – MagMOONs or MOONs for non-magnetic nanoprobes in this dissertation) to study biophysical processes such as enzyme-catalyzed cleavage through tissue, intracellular transport of these tracers and cytotoxicity based on this transport. The anisotropic optical properties cause these tracers to blink when rotating. This blinking is distinguishable from the background and can be tracked on a single-particle level in the absence of tissue, or for an ensemble average of tracers blinking through tissue. An alginate gel containing these tracers in the form of a thin film can be used as …

The Detection And Characterization Of Some Viruses Infecting Blackberry And Cherry In South Carolina, Bindu Poudel

All Dissertations

Three separate virus research projects were conducted. Blackberry yellow vein disease (BYVD), a disorder caused by virus complexes, has become a major threat to blackberry production in the United States, especially in the southeastern part of the country where blackberries are grown for the fresh market. More than 30 viruses have been found to be associated with the disease. Most of these induce no symptoms when infecting the plant alone. However, when more than a single virus is present in the host visible symptoms are displayed. The incidence of 6 different viruses (Blackberry yellow vein-associated virus, Blackberry virus Y, Blackberry …

Examining The Space-Time Constraints Concept On Tourist Behavior For Visitors To The South Carolina Coastal Area Of The United States, Sanghoon Kang

All Dissertations

This dissertation explored three themes with regard to the spatial aspects of tourist behavior, conducting three independent analyses. For these analyses, this dissertation research adapted Shoval's (2012) definition of the space-time constraints concept developed by Hagerstrand (1970): the purpose of trip (i.e., authority constraints), the length of visit (i.e., capability constraints), and the composition of travel party (i.e., coupling constraints). The purposes of the three analyses were to examine the relationships 1) between the space-time constraints and the spatial patterns of travel; 2) between ICT use (i.e., smartphones) and the spatial patterns of travel, space-time constraints, tourists' unplanned destination visits, …

Nematicidal Activity Of Extracts From Phytolacca Americana On Five Plant-Pathogenic Nematode Species Of Economic Importance, Saleh Ahmed

All Dissertations

Plant-parasitic nematodes cause significant losses to plant agriculture annually. The limited availability and high cost of synthetic nematicides, along with the environmental risks associated with their use, have created a renewed interest in the search for alternative management tactics. One such alternative tactic is the use of plant extracts. The focus of this research is the evaluation of the nematicidal activity of water extracts from Pokeweed (Phytolacca americana). In vitro and greenhouse tests were performed to evaluate the effects of the extracts on five species of plant-pathogenic nematodes of economic importance: Aphelenchoides fragariae, Ditylenchus dispsaci, Meloidogyne incognita, Pratylenchus penetrans, and …

Leisure, Obesity And Weight Loss: An Exploration Of Leisure, The Public Health Ecological Model Of Obesity And Identity Theory, Weber Player

All Dissertations

Obesity is a global health crisis with complex causal relationships. From the mid 1990s to 2010, obesity related research in the clinical and social sciences has exploded. This expansion has resulted in a proliferation of obesity-related articles published in top-tier journals and the creation of new journals solely devoted to obesity research. In contrast within leisure scholarship, a review of leisure journals reveals that published research on the relationship of leisure, obesity and weight loss is minimal. However, numerous leisure scholarship/theory principles are relevant to obesity prevention and treatment. Similarly, public health officials have developed numerous systems-oriented multilevel framework models …

Effects Of Semi-Rigid Plastic Tray Geometry On Thermal Processing And Quality Factors In Retorted Foods, Curtis Stowe

All Dissertations

This research studied the effect of packaging geometry changes on heat penetration and quality attributes of a food system processed in a rotary retort vessel. Studies were conducted to determine the effect of package geometry in a rotary retort on heat penetration, analytical, and physical properties of a model food system processed at optimum conditions. Additionally, heat mapping for each shape was used to determine the heating profiles during retorting. Retort-able trays were filled with a tomato based food simulate and thermally processed in a water immersion, automated batch retort system (ABRS) using rotational speeds of 6 RPM and 11 …

Robust Model Development For Evaluation Of Existing Structures, Saurabh Prabhu

All Dissertations

In the context of scientific computing, validation aims to determine the worthiness of a model in supporting critical decision making. This determination must occur given the imperfections in the mathematical representation resulting from the unavoidable idealizations of physics phenomena. Uncertainty in parameter values furthers the validation problems due to the inevitable lack of information about material properties, boundary conditions, loads, etc. which must be taken into account in making predictions about structural response. The determination of worthiness then becomes assessing whether an unavoidably imperfect mathematical model, subjected to poorly known input parameters, can predict sufficiently well in its intended purpose. …

Electrospray Deposition Of Chalcogenide Glass Films For Gradient Refractive Index And Quantum Dot Incorporation, Spencer Novak

All Dissertations

Chalcogenide glasses (ChGs) are well-known for their optical properties, making them ideal candidates for emerging applications of mid-infrared microphotonic devices, such as lab-on-a-chip chemical sensing devices, which currently demand additional flexibility in processing and materials available to realize new device designs. Solution-derived processing of ChG films, initially developed in the 1980s by Chern and Lauks, has consisted mainly of spin-coating and offers unique advantages over the more traditional physical vapor deposition techniques. In the present effort, the nanoparticles of interest are luminescent quantum dots (QDs), which can be used as an on-chip source of light for a planar chemical sensing …

Optimization Of Pyrochlore Catalysts For The Dry Reforming Of Methane, Felipe Polo Garzon

All Dissertations

The conversion of methane into syngas (a mixture of CO and H2), which can be further converted into a variety of chemicals and particularly liquid fuels, is of growing importance given recent increases in methane production world-wide. Furthermore, since using CO2 as the co-feed offers many environmental advantages, dry reforming of methane (DRM, CH4 + CO2 ⇌ 2CO + 2H2) has received renewed attention. In recent years, experimentalists have shown that the Rh-substituted lanthanum zirconate pyrochlore (LRhZ) material is catalytically active for DRM, exhibits long-term thermal stability and resists deactivation; however, previous to this doctoral work, a detailed understanding of …

Development And Validation Of A Novel In Vitro Model For The Assessment Of Heterocellular Interactions Mediated By Connexin43, Emily Ongstad

All Dissertations

The injury border zone (IBZ), a region of transitional tissue between intact myocardium and the ischemic area, is often the site of lethal reentrant arrhythmia generation in post-myocardial infarction (MI) patients. Disruption to normal connexin43 (Cx43) localization at the intercalated disc (ID), separation of myocytes by activated fibroblasts and deposited scar tissue are thought to be factors that render the IBZ a pro-arrhythmic substrate, though there is a current need to better understand these changes so directed therapies can be developed. There are no clinically available therapies focused on the mechanistic changes in the IBZ. Additionally, generation of new compounds …