Chemotherapy-Induced Pdl-1 Expression In Cancer-Associated Fibroblasts Promotes Chemoresistance In Nsclc, Gayathri Heenatigala Palliyage

Graduate Theses, Dissertations, and Problem Reports (ETD)

A cure for cancer is out of reach for most patients due to chemoresistance. Cancer-associated fibroblasts (CAFs), one of the most abundant types of stromal cells in the tumor microenvironment, are known to provide functional and structural support for tumor progression. These cells also play a role in cancer chemoresistance, but a detailed understanding of the process, particularly in chemoresistant lung cancer, is lacking. In this study, we investigated programmed death-ligand 1 (PDL-1) as a potential biomarker for CAF-induced chemoresistance and evaluated its role and underlying mechanisms of chemoresistance in non-small cell lung cancer (NSCLC). We demonstrated that chemotherapy-stimulated CAFs …

Targeting Hiv-1 Reservoirs In T Cell Subsets, Min Li, Marietta M Budai, Min Chen, Jin Wang

Faculty, Staff and Students Publications

The HIV-1 reservoirs harbor the latent proviruses that are integrated into the host genome. It is a challenging task to eradicate the proviruses in order to achieve an HIV cure. We have described a strategy for the clearance of HIV-1 infection through selective elimination of host cells harboring replication-competent HIV (SECH), by inhibition of autophagy and promotion of apoptosis during viral re-activation. HIV-1 can infect various CD4+ T cell subsets, but it is not known whether the SECH approach is equally effective in targeting HIV-1 reservoirs in these different subsets in vivo. In a humanized mouse model, we found …

Learning Representations For Novelty And Anomaly Detection, Ranya Almohsen

Graduate Theses, Dissertations, and Problem Reports (ETD)

The problem of novelty or anomaly detection refers to the ability to automatically

identify data samples that differ from a notion of normality. Techniques

that address this problem are necessary in many applications, like in medical

diagnosis, autonomous driving, fraud detection, or cyber-attack detection, just to

mention a few. The problem is inherently challenging because of the openness of

the space of distributions that characterize novelty or outlier data points. This is

often matched with the inability to adequately represent such distributions due

to the lack of representative data.

In this dissertation we address the challenge above by making several …

Response Of Running Buffalo Clover (Trifolium Stoloniferum Muhl Ex. A. Eaton) To Herbaceous Competition And Transplanting In Monongahela National Forest, Ruben E. Sabella

Graduate Theses, Dissertations, and Problem Reports (ETD)

Running buffalo clover (RBC) is a rare perennial plant that grows throughout the American Midwest and the Appalachian Mountains. It requires disturbed forests to establish and proliferate. It has been suggested that, in the past, these conditions were created by buffalo; now logging operations maintain RBC populations. However, forest managers have been looking for ways to create suitable habitat for RBC that do not involve harvesting practices. This could help create new populations in areas that cannot be logged. Once established, competing vegetation might influence RBC abundance and flowering. This study seeks to quantify this influence by measuring the vegetation …

A Program Evaluation Of The West Virginia University Health Science Center Interprofessional Education First-Year Curriculum, Kathryn Lynn Smalley

Graduate Theses, Dissertations, and Problem Reports (ETD)

Background: The Interprofessional Education (IPE) First-Year Program was started at the West Virginia University Health Sciences Center in 2013 with the goal of providing participants introductory knowledge of the IPE Core Competencies as defined by the Interprofessional Education Collaborative (IPEC). This program transfers 16 different disciplines out of their isolated educational silos and allows them to learn about, for, and with one another. Participants are introduced to foundational knowledge through several didactic sessions over the course of an academic year. Although the program has been increasingly incorporated by many health sciences disciplines since its inception, it has never officially …

Burkholderia Collagen-Like Protein 8, Bucl8, Is An Outer-Membrane Component Of A Novel Efflux Pump And Immunogenic Vaccine Candidate, Megan Elizabeth Grund

Graduate Theses, Dissertations, and Problem Reports (ETD)

Burkholderia spp. are Gram‐negative intrinsically resistant bacteria that are responsible for environmental and nosocomial infections of clinical and biodefense concern. Our laboratory previously identified in silico Burkholderia collagen-like protein 8 (Bucl8) in the BSL-3 pathogens Burkholderia pseudomallei and Burkholderia mallei (Figure 1). The protein sequence of Bucl8 contains tandem outer-membrane efflux protein domains (OEP) typical of efflux systems and a unique collagen-like domain (CL) consisting of a repeating sequence of Glycine-Alanine-Serine (GAS). Because efflux pumps are often a mechanism of pathogenicity and antibiotic resistance, we investigated Bucl8 further. Here, we determined that the locus of bucl8 contains genes …

Evaluating The Degradation Relationship Between Latent Print Impressions And Touch Dna Under Varying Environmental Conditions, Katrina M. Rupert B.S.

Graduate Theses, Dissertations, and Problem Reports (ETD)

Latent prints have been processed as a source of touch DNA evidence in the hopes of attaining partial or even full DNA profiles. However, the relationship between the latent quality and the DNA quality has not yet been fully explored, resulting in gaps in understanding how the two are connected. A common source of touch DNA is from latent print evidence, which is typically processed and photographed at a scene, and subsequently processed for DNA in the laboratory. However, there is skepticism in the forensic community around touch DNA as laboratory procedures are often manipulated beyond standard operating procedures to …

Development Of A Model Sustainability Management Plan For The City Of Morgantown, West Virginia, Caitlyn Elizabeth Lewis

Graduate Theses, Dissertations, and Problem Reports (ETD)

This report has been prepared to demonstrate the research for a model planning document with a focus on sustainability in Morgantown, WV. It discusses the role of three categories in the context of sustainability and proposes a design solution for selected areas of concern throughout the City of Morgantown in order to demonstrate opportunities for a sustainable approach toward resolution for city officials.

The City of Morgantown, West Virginia, is a college town along the Monongahela River with a backstory of industrialism that is echoed by many other places in Appalachia. However, distinctively, in Morgantown 25,000 college students populate the …

Stability Properties Of A System Of Receptors In The Presence Of Attractive Domains, Basim Mohammed Al-Maliki

Graduate Theses, Dissertations, and Problem Reports (ETD)

I use mathematical modeling to understand aspects of molecular processes in living cells. Specifically, we look at the first few steps in cell signaling. Signal initiation requires that receptors located on the cell membrane bind together to form dimers. Microscopic imaging of receptors on the cell membrane revealed that receptors tend to accumulate in small areas (clusters). Studies also show that the membrane has a complex landscape consisting of domains and barriers of various origin.

Here we study the way receptor dimerization is influenced by domains on the cell membrane. Our underlying hypothesis is that the physical and chemical properties …

Enabling Technologies For Chemical Synthesis: I. Selective Microwave Heating; Ii. Synthesis And Regioselective Cyclotrimerizations Of Tethered 1,6-Diynes, Amir Tavakoli

Graduate Theses, Dissertations, and Problem Reports (ETD)

Reaction discoveries, method developments, and technology advancements lie at the heart of synthetic organic chemistry. These innovations are essential for creating and manipulating complex molecules, which are the building blocks of many important chemical compounds, including pharmaceuticals, materials, and agrochemicals. Here, we first describe new methods to prepare neopentylene-tethered (NPT) 1,6-diynes which are valuable substrates for reaction discovery and target-oriented synthesis, especially in benzannulation strategies toward illudalane natural products. NPT 1,6-diynes have been employed as coupling partners in cyclotrimerization reactions for the synthesis of highly substituted benzene rings which present a persistent challenge in chemical synthesis and are underrepresented scaffolds …

Enantioselective Dearomatization Facilitated By Non-Covalent Interactions Of N-Heterocyclic Carbene Catalysts And Pyridinium Salts, Jack A. Patterson

Graduate Theses, Dissertations, and Problem Reports (ETD)

Dihydropyridines are a practical organic scaffold commonly used for their pharmaceutical properties. Nucleophilic dearomatization of pyridines has proven to be a useful method in obtaining dihydropyridines. By using N-heterocyclic carbene (NHC) organocatalysts, dihydropyridines can be synthesized with high regioselectivity of the 1,4 regioisomer over the 1,2- regioisomer but often with low enantioselectivity. By incorporating non-covalent interaction contact points, we hypothesize that enantioselectivity can be enhanced. By synthesizing numerous NHCs, each proposed to exhibit a different type of non-covalent interaction (i.e., hydrogen bonding or ion pairing), an understanding of the secondary interactions within this reaction system can be studied and …

Businesses Supposedly Held The Key To The Ada, But They Dropped The Ball: Can Marketing Be The Shot In The Arm America Needs To Bring The Spirit Of The Ada Back To Life?, Elizabeth T. Gratz

Graduate Theses, Dissertations, and Problem Reports (ETD)

This research investigates the historical and current focus of the field of marketing on the disability community and considers whether marketers can positively impact attitudes toward the group through their firm media content. My first essay uses the Rocky Road to Policy Pavers model to discuss the importance of this large and underserved consumer group, and highlights several opportunities for the marketing community to reduce existing barriers to disabled consumers in the marketplace. One way that marketers can reduce stigma and improve attitudes toward the disability community is by strategically portraying individuals with disabilities in their firm media content. My …

Elucidation Of The Role Of Agouti-Signaling Protein Throughout Folliculogenesis And Early Embryonic Development In Cattle, Heather L. Chaney

Graduate Theses, Dissertations, and Problem Reports (ETD)

The oocyte expresses certain genes during folliculogenesis to regulate the acquisition of oocyte competence. Oocyte competence, which refers to the presence of imperative molecular factors in the oocyte that are critical for high oocyte quality, is directly related to the ability of the oocyte to result in a successful pregnancy following fertilization. Over the past few decades, the development and optimization of assisted reproductive technologies, particularly in vitrofertilization, have enabled the beef and dairy industries to advance cattle genetics and productivity. However, only approximately 40% of bovine embryos will develop to the blastocyst stage in vitro. In addition, bovine embryos …

Exploring The Usage Of Acid Mine Drainage Sludge As A Soil Amendment For Reclaimed Mine Lands, Brady Watters

Graduate Theses, Dissertations, and Problem Reports (ETD)

Acid mine drainage (AMD) is a form of water pollution generated when water and oxygen come into contact with sulfide minerals, forming metal ions, sulfuric acid, and sulphates in solution. AMD is characterized by its toxic metals content and low pH, both of which are an environmental concern. The treatment of AMD separates the contaminants into a high-water content sludge. This sludge is a pure waste product under current evaluation for alternative uses as well as improvements to storage and treatment processes. This thesis focused on analyzing the potential for AMD sludge to be used in recently reclaimed lands as …

Gender Inclusivity In Italian: Can Gender Neutrality Be Reached In A Gendered Language? Difficulties, Proposals And Public Perception Of The Phenomenon, Gaia Prunotto

Graduate Theses, Dissertations, and Problem Reports (ETD)

Italian is a gendered language in which reference to grammatical gender has been constant and inevitable. As language reflects and shapes society, grammatical gender reinforces binary views of social gender and the invizibilization of non-binary identities. Movements for social justice have inspired gender-fair linguistic innovations, such as the feminization of job titles and gender-neutral markers, to promote gender equity and challenge hierarchies of power and dominance in society. This research aimed to explore gender-neutral forms in the Italian grammatical system and public perceptions of these innovations through two studies with two groups of participants.

The first group of participants (n=27) …

Survival Of Listeria Monocytogenes On Organic Honeycrisp And Fuji Apples During Storage At 5, 12 And 22.5◦C, Connor S. Freed

Graduate Theses, Dissertations, and Problem Reports (ETD)

This study aimed to evaluate and model the survival of Listeria monocytogenes on organic HoneyCrisp (HC) and Fuji (FJ) apples during storage at various temperatures. Fresh organic HC and FJ apples (without wax coating) obtained from a local wholesale market were inoculated with a 2-strain mix of L. monocytogenes followed by storage at 5.0 (22.9% RH), 12.0 (37.0% RH), and 22.5oC (50.4% RH) for 60, 35, 7 days, respectively, and periodically (day-0 to 60) analyzing microbial populations. Surviving L. monocytogenes were spread-plated on Modified-Oxford agar after 10 or 100-fold serial dilution. Data were analyzed using the mixed-model procedure of SAS …

Mechanisms Of Pulmonary Inflammation And Lung Function Decline After Ultrafine Carbon Black And Ozone Inhalation Co-Exposure, Nairrita Majumder

Graduate Theses, Dissertations, and Problem Reports (ETD)

Air pollution is a mixture of particulate matter, gaseous substances, and other contaminant, yet most of the studies have addressed single exposure outcomes. The effect of environmental toxicants in lung adverse outcomes can be evaluated by studying the co-exposure scenario. The impact of co-exposures is not well addressed in susceptible populations like patients suffering from acute lung injury, asthma, and fibrosis. Without such knowledge it would be difficult to establish a safe exposure limit for mitigating environmental burden in patients and public. The main goal of this study was to understand the effect of ultrafine particle and ozone co-exposure in …

Specialized Metabolism In Retina, Retinal Pigmented Epithelium, And Testis, Siyan Zhu

Graduate Theses, Dissertations, and Problem Reports (ETD)

The retina and its neighboring retinal pigmented epithelium (RPE) are high energy-demanding and metabolically active tissues with specialized and complementary metabolism. They are metabolically interdependent and impact each other’s viability. Interestingly, many of the metabolic features in the retina and RPE are shared with the testis. For example, testis is also energy costly due to continuous sperm differentiation and it has similar metabolic inter-dependence between different testis cells. Both the retina and testis are vulnerable to mitochondrial metabolic impairments.

We conducted three research projects to understand 1) the nutrient utilization and communication in retina and RPE; 2) The profiling of …

Effects Of Invasive Species On Ohio River Zooplankton, Samuel John Johnston

Graduate Theses, Dissertations, and Problem Reports (ETD)

Invasive species have the potential to dramatically change both aquatic and terrestrial ecosystems with rates of introduction only expected to increase across the Globe. In the Mississippi River basin filter feeding silver (Hypophthalmichthys molitrix) and bighead carp (Hypophthalmichthys nobilis) collectively known as invasive carp were introduced into aquaculture ponds where they subsequently escaped and spread to interconnected basins. Invasive carp have not yet completely established throughout the entire Ohio River. Managers recognize three distinct phases of carp invasion: establishment front, invasion front and presence front. In the Illinois River invasive carp are very well established and …

Il-27 Negatively Impacts Immunity Developed Following Bcg Administration, Shelby D. Bradford

Graduate Theses, Dissertations, and Problem Reports (ETD)

Mycobacterium tuberculosis (Mtb) is the causative agent of tuberculosis (TB), a predominantly respiratory pathogen responsible for over ten million infections and one million deaths last year. Despite it being a primary objective of the World Health Organization (WHO) for several decades to irradicate TB, progress toward this objective has fallen short of the 2020 target to end TB by 2035. Meeting this goal will require advancements in diagnostic tools, education, healthcare access, and treatments and preventatives. Regarding prevention, the primary tool for this strategy is through vaccination. Currently, the only licensed vaccine for protection against TB is the century old …

An Assessment Of The Forensic Aspects Of Genetic Genealogy, Sarah Hester

Graduate Theses, Dissertations, and Problem Reports (ETD)

Forensic genetic genealogy has grown in both popularity and controversy in recent years. The genetic information comes from large numbers of single nucleotide polymorphism (SNP) markers. Polymorphism variations can be traced through familial lineage, determining how closely individuals are related to each other based on the similarities and differences in SNPs within their DNA. Polymorphisms account for approximately 85% of human variation. Genealogy and ancestry determination companies trace the lineage of a person back through multiple generations using polymorphisms. As more individuals submit their DNA for analysis the genealogical profile databases continue to grow in size. Law enforcement uses genealogical …

The Investigation Of Novel Bovine Oocyte-Specific Long Non-Coding Rnas And Their Roles In Oocyte Maturation And Early Embryonic Development, Jaelyn Zoe Current

Graduate Theses, Dissertations, and Problem Reports (ETD)

Early embryonic loss is a significant factor in livestock species' infertility, resulting in an economic deficit. In cattle, the in vivo fertilization rate is ~90%, with an average calving rate of about 55%, indicating an embryonic-fetal mortality rate of roughly 35%. Further, 70-80% of total embryonic loss in cattle occurs during the first three weeks after insemination, particularly between days 7-16. Growing evidence indicates that the oocyte plays an active role in regulating critical aspects of the reproductive process required for successful fertilization, embryo development, and pregnancy. However, defining oocyte quality remains enigmatic. Recently, many have abandoned the notion that …

Beneficial Impacts Of Nod-Like Receptor X1(Nlrx1) Agonism In Lipopolysaccharide-Induced Inflammation, Mena Mansy

Graduate Theses, Dissertations, and Problem Reports (ETD)

Introduction: The regulation of inflammation at the cellular and molecular level is a crucial aspect of homeostasis that is often overlooked, and most treatment options are limited to antibiotics and symptom management drugs. The development of novel molecular-targeted therapy options downstream of pathogen recognition receptors will fulfill the unmet need for therapy to effectively regulate excessive inflammation. NLRX1 is a unique NOD-like receptor that is anti-inflammatory in nature; it has been shown to negatively regulate the NF-kB pathway and has been involved in the pathology of a plethora of inflammatory disorders. This makes NLRX1 an emerging therapeutic molecular target for …

Selective Recovery Of Rare Earth Elements From Acid Mine Drainage Treatment Byproduct, Zeynep Cicek

Graduate Theses, Dissertations, and Problem Reports (ETD)

Rare earth elements (REEs) are critical in emerging clean energy, advanced technologies, and military defense applications due to their unique physical, chemical, optical, and luminescent properties. Given the potential supply chain restrictions imposed by one country's dominance in the global REE market and the consistently growing demand for REEs, developing the US domestic REE supply chain is imperative. Thus, alternative sources are crucial to supply the demand and prevent interruption in manufacturing products that consume REEs. Concurrently, acid mine drainage (AMD) is a long-standing and widespread global challenge the mining industry encounters. AMD is generated in large volumes and continuously …

Expansion On The Use Of The Novel Compound, Elp-004, Using A Mycobacterium Tuberculosis Experimentation Model, Kendyl Marie Berry

Graduate Theses, Dissertations, and Problem Reports (ETD)

Osteoarticular tuberculosis (OAT) is a bone degenerative disease that results in bone erosion, joint effusion, joint swelling, and sometimes, nerve compression. OAT occurs from the hematogenous dissemination of Mycobacterium tuberculosis (Mtb) bacilli spreading from the primary site of infection to the bones and joints; the primary site of infection tends to be the lungs as pulmonary tuberculosis infections are the most common. OAT can occur as the result of an active or latent infection. Latent infections result in OAT when bacilli are able to escape granulomas. The incidence of OAT is not as high as pulmonary infections, making up about …

Optimal Path Planning For Aerial Robots Using Genetic Algorithm, Anna Puigvert I Juan

Graduate Theses, Dissertations, and Problem Reports (ETD)

This thesis presents a path optimization solution for a robot in two different constrained 3-dimensional (3D) environments. The robot is required to travel from its current position to a goal position following minimum cost paths (optimal paths). The first environment has 3D obstacles that interfere with the robot’s path. The path cost for this environment accounts for the minimum distance traveled by the robot from the start to the goal position while avoiding obstacles. The second environment is the atmosphere of Venus, specifically a flyable region of this atmosphere with characteristics similar to Earth’s. This environment has strong westward winds …

Synthesis And Pharmacology Of Illudalic Acid And Analogous Chemical Structures, Robert Gaston Jr

Graduate Theses, Dissertations, and Problem Reports (ETD)

Natural products are the foundation of modern medicine and an inspiration for chemical innovation. Developing new synthetic strategies to complex natural products drives synthetic innovation and promotes pharmacological exploration. As bioactive secondary metabolites of fungi, illudalic acid and associated analogs have unrealized medicinal potential due to synthetic limitations. Illudalic acid is notably the first selective covalent inhibitor of the LAR-PTPs, a class of enzymes linked to many human illnesses, including stimulant addiction. The chemistry herein focuses on optimizing synthetic routes to illudalic acid and associated analogs toward exploring their pharmaceutical potential. We report a second-generation synthesis of illudinine (55% overall …

Clinical And Economic Burden Of Inflammatory Chronic Conditions Among Adults In The United States: Evidence From Three Nationally Representative Surveys, Mohammad Ikram

Graduate Theses, Dissertations, and Problem Reports (ETD)

A significant proportion of adults in the United States (US) suffer from various inflammatory chronic conditions (ICCs). They include a wide range of diseases such as diabetes, rheumatoid arthritis, asthma, and chronic obstructive pulmonary diseases. ICCs are not curable, and their management typically involves medications such as NSAIDs and corticosteroids. Recently, a whole health approach that places patients’ well-being at the center is increasingly being used for better management of ICCs. The whole health approach uses an integrated approach that includes multimodal management with complementary and alternative medicines (CAM) and prescription drugs. However, the use of CAM and prescription drugs …

Computational Mechanisms Of Face Perception, Jinge Wang

Graduate Theses, Dissertations, and Problem Reports (ETD)

The intertwined history of artificial intelligence and neuroscience has significantly impacted their development, with AI arising from and evolving alongside neuroscience. The remarkable performance of deep learning has inspired neuroscientists to investigate and utilize artificial neural networks as computational models to address biological issues. Studying the brain and its operational mechanisms can greatly enhance our understanding of neural networks, which has crucial implications for developing efficient AI algorithms. Many of the advanced perceptual and cognitive skills of biological systems are now possible to achieve through artificial intelligence systems, which is transforming our knowledge of brain function. Thus, the need for …

Drought Effects On Biofuel Feedstock Production By Populus Trichocarpa, Marvin Jacob Wright

Graduate Theses, Dissertations, and Problem Reports (ETD)

As the world population continues to increase, so does the need for sustainable sources of fuel. Biofuels are of particular interest and could be an economically feasible fuel source given the right conditions. Populus trichocarpa, is a rapidly growing plantation species that, in addition to having a fully sequenced genome available for study, displays a wide range of phenotypic traits among genotypes. By analyzing these differences in both plantation and more controlled greenhouse settings, we aimed to discover which genotypes performed the best under drought conditions, and which physiological mechanisms granted them that high performance. In the field, differences in …