Digital Commons Network^™

The Role And Mechanism Of The Homeobox Gene Hoxa9 In The Growth Of Epithelial Ovarian Cancer, Song Yi Ko

Dissertations and Theses (Open Access)

Epithelial ovarian cancer (EOC) is the fifth leading cause of cancer death among women in the United States. The high lethality of EOCs stems from rapid peritoneal involvement. EOCs frequently colonize peritoneal surfaces that overlie connective and adipose tissues. However, the mechanisms that enable ovarian cancer cells to readily adapt to the peritoneal environment are poorly understood. HOXA9, a homeobox gene that is normally expressed in the developing female reproductive tract, is aberrantly expressed in EOCs and controls the morphologic features of these tumors. The differentiation pattern of a tumor is an important determinant of its clinical behavior and …

Therapeutic Efficacy Of P53 Restoration In Mdm2-Overexpressing Tumors, Qin Li

Dissertations and Theses (Open Access)

The TP53 tumor suppressor is the most mutated gene in human cancers. Recent studies using genetically modified mouse models have shown that restoring the expression of wild-type p53 has led to tumor growth suppression in various types of tumors lacking p53. Other mechanisms, e.g. upregulation of Mdm2 levels, exist in tumors to inactivate the p53 pathway. Mdm2, an E3 ubiquitin-ligase that targets p53 for proteasomal degradation, is present at high levels in many tumors with wild-type p53. In this study, we probed the effects of restoring p53 activity in Mdm2-overexpressing tumors genetically using animal models. Here we demonstrated high levels …

Radiogenic Second Cancer Risk Differences In Female Hodgkin Lymphoma Patients Treated With Proton Versus Photon Radiotherapies, Kenneth L. Homann

Dissertations and Theses (Open Access)

Hodgkin Lymphoma (HL) is the most common cancer diagnosis of young adults in the United States. Advances in curative treatments for HL, including the use of photon radiation therapy (RT) techniques, have increased 10 year survival rates to approximately 90% among young patients. These RT treatments, however, contribute to an increased incidence of radiogenic second cancer (RSC) formation to the healthy tissue surrounding the tumor volume relative to the general population. These RSCs are the leading cause of death among long-term HL survivors. Proton therapy has been shown to reduce the therapeutic dose, and therefore, the risk of developing a …

Mtorc1 Signaling In Memory Formation And Dysfunction, Natalia S. Rozas De O'Laughlin

Dissertations and Theses (Open Access)

The mechanistic Target of Rapamycin Complex 1 (mTORC1) pathway integrates cellular availability of growth factors, energy and amino acids to regulate protein synthesis and autophagy. The mTORC1 pathway has also been shown to be required for memory consolidation, and its dysregulation is associated with many neurological disorders. MTORC1 is negatively regulated by the tuberous sclerosis complex (TSC1/2). When ATP and growth factors are available, TSC1/2 is inhibited and mTORC1 activity can be restored. In a complementary regulatory pathway, amino acids signal to mTORC1 through the Rag GTPases and Ragulator complex, which modulate the translocation of mTORC1 from the cytoplasm to …

Characterization Of The Role(S) Of Env Protein Of Human Endogenous Retrovirus-K In Multiple Human Cancers, Ming Li

Dissertations and Theses (Open Access)

Human endogenous retroviruses (HERVs) are remnants from ancient retroviral infections, and most of them are inactive in normal tissues. One family of HERV, HERV-K, is found to be associated with multiple human cancers including breast cancer, pancreatic cancer and melanoma, but the causal relationship between HERV-K and cancer is still unclear. Increased expression of HERV-K in melanoma cells correlates with malignant transformation, while a serological response to HERV-K in breast cancer or melanoma patients correlates with survival probability. However, the mechanism behind these observations remains obscure. Our laboratory reported that anti-HERV-K envelope (Env) protein antibodies show antitumor potential in targeting …

The Staphylococcus Pseudintermedius Adhesin Spsd Contains A Central Fibronectin-Binding Domain, Andrea S. Bordt

Dissertations and Theses (Open Access)

Staphylococcus pseudintermedius is a Gram-positive bacterium significant because of its ability to cause costly and difficult to treat veterinary infections worldwide. It exhibits several similarities to Staphylococcus aureus, however, very little is known about its surface adhesins. Surface adhesins in S. aureus are significant contributors to pathogenesis. S. pseudintermedius encodes the surface protein SpsD, which contains characteristics of the microbial surface components recognizing adhesive matrix molecules family and confers attachment of the heterologous host Lactococcus lactis to fibronectin. This work has identified a centrally-located fibronectin binding domain in SpsD which binds the 30 kDa N-terminal domain of fibronectin with …

Investigating Apoptosis Pathway In Chronic Lymphocytic Leukemia: Stromal Influence And Therapeutic Activation, Viralkumar M. Patel

Dissertations and Theses (Open Access)

Chronic lymphocytic leukemia (CLL) is a B-cell malignancy. High levels of Bcl-2 and IAP family proteins are responsible for apoptotic-resistance and accumulation of mature CLL lymphocytes in bone-marrow, lymph nodes and peripheral blood. Besides pro-survival proteins, supporting stromal cells as well as soluble factors in the microenvironment of bone-marrow and lymph nodes provide survival advantage to CLL leukemic cells.

Though the stromal – leukemia cell interactions has been studied extensively, in-depth-knowledge on the regulation of apoptotic pathway proteins in the context of microenvironment is still limited. To address this, the first part of our study focused on comprehensive analysis of …

Characterizing The Effect Of Dasatinib On Anti-Tumor Immune Response And Exploring The Potential Of Combining Targeted Therapy And Immunotherapy In A C-Kit Mutant Mastocytoma Model, Yan Yang

Dissertations and Theses (Open Access)

Targeted therapy and immunotherapy eradicate malignant cells through different mechanisms, and the strengths and weaknesses of these two approaches are potentially complementary. Therefore, the combination of molecular targeted drugs with immune- based therapies is considered an attractive approach for improving the therapeutic efficacy of cancer treatment. The mutation and amplification of the c-KIT proto- oncogene are associated with multiple different cancer types, and multiple c-KIT inhibitors have been tested clinically. In spite of some encouraging results using these agents, most patients with c-KIT mutant cancers still relapse due to drug resistance. This also demonstrates the inherent limitation of molecular targeted …

C-Jun N-Terminal Kinases Regulate Adenovirus-Mediated Autophagy And Antigen Presentation, Sarah R. Klein

Dissertations and Theses (Open Access)

Targeted immunotherapy with recombinant, oncolytic adenoviruses is under investigation for the treatment of cancer. Evidence indicates adenoviruses induce autophagy that is required for oncolysis, but the molecular regulation of autophagy in infected cells remains under investigation. Our data suggested the canonical pathway regulating starvation-induced autophagy was not implemented in adenovirus-induced autophagy; however, adenovirus infection triggered phosphorylation of c-Jun N-terminal kinases (JNK) that was essential for autophagy. Adenoviral replication within the host cell elicited JNK pathway activation leading to B cell lymphoma-2 (Bcl-2) phosphorylation. JNK-dependent Bcl-2 phosphorylation stimulated the dissociation of Bcl-2/beclin 1 heterodimers, enabling beclin 1 to initiate autophagy. Moreover, …

Basis For Targeting Met Activation Mediated Resistance To Pi3k Inhibition In Breast Cancer, Ana M. Gonzalez-Angulo

Dissertations and Theses (Open Access)

The identification of resistance mechanisms to emerging therapies, such as those targeting the PI3K pathway and the MET receptor, has the potential to benefit a significant number of patients with breast cancer. In this study we hypothesized that concurrent aberrations in PI3K and MET will render breast cancers resistant to therapies targeting each pathway, and that combination therapy targeting the PI3K and MET pathway will optimize therapy-effect by preventing the acquisition of resistance.

We analyzed cMET and phospho-cMET levels in 257 breast cancer samples and found that high levels of both the proteins were seen in all breast cancer subtypes, …

Characterization Of The Rna Binding And Rna Degrading Subunits Of The Eukaryotic Exosome, Borislava Tsanova

Dissertations and Theses (Open Access)

The exosome is an essential complex of ten proteins involved in the processing and degradation of many RNAs in the cell. These include various stable RNAs, mRNAs, and aberrant transcripts both in the nucleus and in the cytoplasm.

In this work I characterize the three members of the exosome “cap”, the RNA binding proteins Rrp4, Rrp40, and Csl4. I determine that in spite of their structural similarity, they each have a unique essential role. Second, I determine that two of the cap proteins Rrp4 and Rrp40 have a role in bridging subunits of the PH ring of the exosome. The …

Neural Correlates Of Audiovisual Speech Perception In Aphasia And Healthy Aging, Sarah H. Baum

Dissertations and Theses (Open Access)

Understanding speech in face-to-face conversation utilizes the integration of multiple pieces of information, most importantly the auditory vocal sounds and visual lip movements. Prior studies of the neural underpinnings of audiovisual integration in the brain have provided converging evidence to suggest that neurons within the left superior temporal sulcus (STS) provide a critical neural hub for the integration of auditory and visual information in speech. While most studies of audiovisual processing focus on neural mechanisms within healthy, young adults, we currently know very little about how changes to the brain can affect audiovisual integration in speech. To examine this further, …

Regulation Of The Myostatin Protein In Overload-Induced Hypertrophied Rat Skeletal Muscle, Paige Abriel Affleck

Theses and Dissertations

Myostatin (GDF-8) is the chief chalone in skeletal muscle and negatively controls adult skeletal muscle growth. The role of myostatin during overload-induced hypertrophy of adult muscle is unclear. We tested the hypothesis that overloaded adult rodent skeletal muscle would result in reduced myostatin protein levels. Overload-induced hypertrophy was accomplished by unilateral tenotomy of the gastrocnemius tendon in male adult Sprague-Dawley rats followed by a two-week period of compensatory overload of the plantaris and soleus muscles. Western blot analysis was performed to evaluate changes in active, latent and precursor myostatin protein levels. Significant hypertrophy was noted in the plantaris (494 ± …

Shaping Swarms Through Coordinated Mediation, Shin-Young Jung

Theses and Dissertations

A swarm is a group of uninformed individuals that exhibit collective behaviors. Without any information about the external world, a swarm has limited ability to achieve complex goals. Prior work on human-swarm interaction methods allow a human to influence these uninformed individuals through either leadership or predation as informed agents that directly interact with humans. These methods of influence have two main limitations: (1) although leaders sustain influence over nominal agents for a long period of time, they tend to cause all collective structures to turn in to flocks (negating the benefit of other swarm formations) and (2) predators tend …

Association Between In Utero Arsenic Exposure, Placental Gene Expression, And Infant Birth Weight: A Us Birth Cohort Study, Dennis Liang Fei, Devin C. Koestler, Zhigang Li, Camilla Giambelli, Avencia Sanchez-Mejias, Julie Gosse, Carmen J. Marsit, Margaret R. Karagas, David J. Robbins

Dartmouth Scholarship

Epidemiologic studies and animal models suggest that in utero arsenic exposure affects fetal health, with a negative association between maternal arsenic ingestion and infant birth weight often observed. However, the molecular mechanisms for this association remain elusive. In the present study, we aimed to increase our understanding of the impact of low-dose arsenic exposure on fetal health by identifying possible arsenic-associated fetal tissue biomarkers in a cohort of pregnant women exposed to arsenic at low levels.

Methods: Arsenic concentrations were determined from the urine samples of a cohort of 133 pregnant women from New Hampshire. Placental tissue samples collected from …

Characterization Of The Hydrogeology And Stress State In The Vicinity Of The Homestake Mine, Lead, Sd, Johnathan Ebenhack

All Theses

Underground workings in fractured rock are common worldwide. They have applications in numerous areas and fields of study. These include mining operations, civil engineering projects like tunnels and underground facilities, and research projects that require underground laboratories such as the physics research being conducted by Sanford Laboratory at the former Homestake mine and Fermi Laboratory near Chicago (Bahcall et al. 2001, Elsworth 2009, Sadoulet et al. 2006, bge science@DUSEL, fnal.gov). These excavations can reach several kilometers in depth including the 3.9 km deep TauTona mine in South Africa, the 3 km deep LaRonde mine in Quebec and the 2.4 km …

Sequential Autotrophic-Heterotrophic Culture Of Scenedesmus Spp. For Lipid Production, Jazmine Taylor

All Theses

Algae are fascinating organisms that are receiving growing attention for their versatility on many fronts of research areas. Immense amounts of research is being conducted to find solutions to challenges in energy and climate change. A large portion of research is focused on algae as a potential solution to both of these issues. The focus of this research is to look at algae closer to home as a local, economical resource to aid in solving both of these problems. The algal genus Scenedesmus was tested for growth in a bi-phased scheme: photoautotrophically for carbon sequestration then heterotrophically on glycerol for …

Twelve Mile Creek Channel Morphology, Substrate Composition, And The Macroinvertebrate Community Changes Resulting From Multiple Dam Removals, Patricia Whitener

All Theses

Dam removal is gaining global attention as a potential restoration tool for impacted rivers. As the practice of dam removal increases, physical, chemical and biological monitoring before and after dam removal is essential to our understanding of the ecological consequences of this type of disturbance. Under the Lake Hartwell Restoration and Compensation Determination Plan, two dams (>9 m height) were removed from the Twelve Mile Creek watershed (170 km2) in Pickens county, South Carolina. To assess the short term impacts of dam removal on the Twelve Mile Creek ecosystem we conducted biomonitoring of macroinvertebrate species and surveys of river …

Scratch Damage Evolution On Metals In Total Joint Replacements, Caleb Eljach

All Theses

The goal of total joint replacement (TJR) is to replace nonfunctioning joint components and relieve pain, improve quality of life, and to improve joint function. Although TJR is a successful procedure, more than 54,000 knee revisions occur each year due to factors, such as wear, loosening, infection, fracture, instability, and patient related factors (Ranawat, 2010). TJRs consist of components typically composed of polyethylene and a metallic counterface (Navarro, 2008). The sliding contact that occurs between the metal and polyethylene components has been well studied and is shown to produce both surface damage and wear of the implant components (Barbour, 1997; …

Development Of Liriodendron Est-Ssr Markers And Genetic Composition Of Two Liriodendron Tulipifera L. Orchards, Xinfu Zhang

All Theses

Liriodendron tulipifera L., commonly known as yellow-poplar, is a fast-growing hardwood tree species with great ecological and economic value and is native to eastern North America. Liriodendron occupies an important phylogenetic position as a basal angiosperm and has been used in studies of the evolution of flowering plants. Genomic resources, such as Expressed Sequence Taq (EST) databases and Bacterial Artificial Chromosome (BAC) libraries, have been developed for this species. However, no genetic map is available for Liriodendron, and very few molecular markers have been developed. In this study, a total of 119 informative genomic SSR markers suitable were identified for …

Improvements In The Process Of Biohydrogen Production By Thermotoga Neapolitana, Louis Hill

All Theses

The production of biological hydrogen is an important process for the future of sustainability and alternative energies. Thermotoga neapolitana is a hyperthermophilic bacterium that produces H ₂ , CO₂ and acetate via fermentation. The goal of the research was to investigate the sustainable production of H₂ gas using waste agricultural feedstocks, recycled water and a simplified N₂ sparging method technique. A limited sparging method was developed which includes 1 minute of N₂ gas sparging of the reactor headspace and 90 minutes of idle reaction time for cysteine-HCl to react with dissolved oxygen prior to inoculation. This …

Macroscopic Investigation Of Ionic- And Nano-Silver Toxicity To Soil Nitrification Process, Abdurrahman Masrahi

All Theses

The worldwide production of engineered nanoparticles (ENPs) has grown rapidly in our era because of the popular applications in industrial and consumer markets. Especially silver (Ag) NP is one of mostly common ENPs in our consumer products due to its unique antimicrobial property. However, release of AgNPs into environment through wastewater treatment plants poses a question that what impact AgNPs have on microbially mediated processes in environment (e.g., nutrient and trace element cycles). In the last decades, numerous toxicological studies of AgNPs on bacteria have been conducted in pure culture systems, and several different antimicrobial mechanisms of AgNPs have been …

The Effect Of Cell Culture Environment On Expression Of Cd44+, Ki67, And Foxo3a And Its Implications On The Role Of Foxo3a In Triple Negative Breast Cancer, Erin Vegter

All Theses

Triple negative breast cancer (TNBC) is a highly aggressive cancer, which is known for a high rate of metastasis and poor prognosis. TNBC cells are hypothesized to undergo the cellular processes epithelial-to-mesenchymal transition (EMT) and mesenchymal-to-epithelial transition (MET). The known prognostic markers CD44+ and Ki67 as well as the transcription factor and proposed tumor suppressor FoxO3a are thought to be indicators of EMT and MET activity in cancer cells. In order to better understand these processes an effective cell culture technique to mimic the tumor environment needs to be established. The purpose of this study was to determine if changing …

A Study Of The Frothing Capacity Of Whole Milk- 1. A Market Survey Of Conventional And Organic Milks, 2. The Effect Of Clean In Place (Cip) Cleaning Solutions, Sara Stancil

All Theses

Gourmet coffee drink consumption is on the rise (NCAUSA 2013). With most of these coffee drinks including milk and/or milk foam, an emphasis on producing quality foam is of high importance. Recent complaints have been received on the failure of milk to foam to expectations of the coffee house (Randolph & Associates 2013). Identifying the source of this failure could enable the milk industry to provide higher foam quality milk to meet the growing needs of coffee houses.

A two-part study on the frothing capacity of milk was carried out to investigate potential variations in the market place and to …

Bite Detection And Differentiation Using Templates Of Wrist Motion, Soheila Eskandari

All Theses

We introduce a new algorithm of bite detection during an eating activity based on template matching. The algorithm uses a template to model the motion of the wrist over a 6-second window centered on the time when a person takes a bite. We also determine if different types of bites (for example food vs. drink, or using different types of utensils) have different wrist motion templates. This method is implemented on 22,383 bites and 5 different types of templates are built. We then describe a method to recognize different types of bites using the set of templates. The obtained accuracy …

The Effects Of Different Size Gold Nanoparticles On Mechanical Properties Of Vascular Smooth Muscle Cells Under Mechanical Stretching, Tri Kieu

All Theses

The field of nanotechnology research has seen a large growth in the past few decades due to the great potential of novel nano-size material for useful applications such as drug delivery and medical imaging. Also, they are a promising platform for the detection of terrible diseases such as cancer and atherosclerosis. Although these materials hold great promise, there is very limited understanding about the biological effects of these nanoparticles on normal healthy cells, such as vascular smooth muscle cells (VSMCs). The VSMCs are unique cells due to the two distinct phenotype characteristics it can express: a contractile and a synthetic …

The Fabrication And Study Of Silver Nanoparticle Structures, Aubrie Pfirman

All Theses

Nanotechnology and the synthesis of nanoparticle systems are attractive in part because of interesting, tunable optical and electrical properties that are not observed with bulk material. Silver nanoparticles (Ag NPs) interact with visible light more efficiently than any other system due to the excitation of plasmon resonances, which are the collective oscillations of the free electron density. These collective oscillations produce an enhanced local electromagnetic (EM) field: this field is responsible for highly-utilized phenomena such as surface enhanced Raman scattering (SERS), enhanced fluorescence, surface enhanced infrared absorption (SEIRA), and many others. Many experiments have been conducted to optimize and tailor …

Rapid Riparian Buffer Width And Quality Analysis Using Lidar In South Carolina, Emre Akturk

All Theses

The importance of protecting water quality and aquatic resources are increasing because of harmful human impacts within and around waterways. Establishing or restoring functional riparian areas protect water quality and are a good mechanism to conserve aquatic systems, plants, and wildlife. Laser-based remote sensing technology offers a high resolution approach to both characterize and document changes in riparian buffer zones (RBZs). The objectives of this study were to build a model to calculate riparian buffer width on both sides of a stream using a LiDAR-derived slope variable, to classify riparian buffers and determine their quality, and to evaluate the appropriateness …

Studies Of Molecular Mechanisms Of Cranberry Mediated Healthspan Promotion In Caenorhabditis Elegans, Sujay Guha

All Dissertations

Extensive studies have demonstrated the potent ability of many nutraceuticals to alleviate the symptoms of aging and stress. We found that cranberry extract (CBE) supplementation at an optimum concentration could prolong Caenorhabditis elegans (C. elegans) lifespan in a manner of daf-16 and osr-1 dependence. Considering that aging is a progressive degeneration of physiological functions, it is intriguing to know whether CBE consumption may delay the age-related degenerative changes in animals. Thus, we examined the effect of CBE consumption on healthspan in C. elegans populations with different ages and age-related disorders. Our results suggest that long-term CBE supplementation leads to a …

Synthesis And Characterization Of Polymer Layers For Control Of Fluid Transport, Fehime Vatansever

All Dissertations

The level of wetting of fiber surface with liquids is an important characteristic of fibrous materials. It is related to fiber surface energy and the structure of the material. Surface energy can be changed by surface modification via the grafting methodologies that have been reported for introducing new and stable functionality to fibrous substrates without changing bulk properties.

Present work is dedicated to synthesis and characterization of macromolecular layers grafted to fiber surface in order to achieve directional liquid transport for the modified fabric. Modification technique used here is based on formation of stable polymer layer on fabric surface using …