Digital Commons Network^™

Orientia Tsutsugamushi Secretes Two Ankyrin Repeat-Containing Effectors Via A Type 1 Secretion System To Inhibit Host Nf-Κb Function, Sean M. Evans

Theses and Dissertations

Scrub typhus is a potentially fatal infection that threatens one billion persons in the Asia-Pacific region and is caused by the obligate intracellular bacterium, Orientia tsutsugamushi. How this organism facilitates its intracellular survival and pathogenesis is poorly understood. Intracellular bacterial pathogens utilize the Type 1 (T1SS) or Type 4 secretion system (T4SS) to translocate ankyrin repeat-containing proteins (Anks) into the host cell to modulate host cell processes. The O. tsutsugamushi genome encodes one of the largest known bacterial Ank libraries as well as Type 1 and Type 4 secretion systems (T1SS and T4SS), which are expressed during infection. In …

Characterization Of The Immune Stimulating Properties Of Type Iii Secretion System Needle Protein Bscf From Bordetella Pertussis: Towards The Development Of A New Acellular Pertussis Vaccine, Travis Douglas Alvine

Theses and Dissertations

Despite widespread vaccination, Bordetella pertussis, the causative agent of whooping cough, is still a threat to global health. One cause of pertussis reemergence observed in many countries is ineffective immunity generated by the current acellular pertussis (aP) vaccines. Interestingly, recent studies have shown that TLR stimulating agents can enhance aP vaccine induced immunity. Type III secretion (T3S) system needle proteins from many gram-negative bacteria have been shown to be strong TLR agonists that induce NF-B/AP-1 signaling and promote inflammatory cytokine release from innate cells in vitro. In this study, we investigated the immune modulating properties of BscF, a purified T3S …

Nitrosative Stress Sensing In Porphyromonas Gingivalis: Structure And Function Of The Heme Binding Transcriptional Regulator Hcpr, Benjamin R. Belvin

Theses and Dissertations

Porphyromonas gingivalis, a Gram negative anaerobe implicated in the progression of periodontal disease, is capable of surviving and causing infection despite high levels of reactive nitrogen species found in the oral cavity due to its efficient nitrosative stress response. HcpR is an important sensor-regulator that plays a vital step in the initiation of the nitrosative stress response in many Gram negative anaerobic bacteria. We employ a combination of X-ray crystallography, SAXS, resonance Raman spectroscopy, UV-Vis spectroscopy, and molecular biology techniques to better understand this key regulator. Knockout of the hcpR gene in W83 P. gingivalis results in the inability of …

Promotional Effect Of Molten Carbonates On Proton Conductivity And Oxygen Reduction Reaction – An Experimental And Computational Study, Xiaolei Xiong

Theses and Dissertations

Recent research of Solid oxide fuel cells (SOFCs) is aimed to lower the operating temperature to an intermediate temperature (IT) range of 500 to 700^oC, while maintaining a proper performance. This Ph.D. research project investigates the promotional effects of alkaline carbonate eutectics on the proton conductivity of proton conducting electrolytes and cathodic ORR reactivity in SOFCs by both experimental and computational methods. The ionic conductivity of the MC-BZY composite above 500^oC increases with the higher loading of MC. The sample exhibited nearly a factor of two higher conductivity in H₂-containing atmosphere than in air. …

Best Practice For Screening Adult Patients With Psoriasis For Polyautoimmunity: Celiac Disease, Rheumatoid Arthritis And Crohn’S Disease, Susan Danielle Ashbaugh

Theses and Dissertations

The purpose of this quality improvement project was to determine if screening primary care patients with psoriasis will improve early detection of celiac disease (CD), rheumatoid arthritis, and Crohn’s disease (CrD). The aim of this project is to assess the utility of early screening in patients with psoriasis in order to facilitate earlier diagnosis of CD, RA and CrD, which would consequently initiate earlier treatment and improve long-term patient outcomes. Genetic and population-based studies suggest that individuals with psoriasis have a greater risk of also having CrD, CD or RA, than do individuals without psoriasis. The literature also suggests that …

Depressive Symptoms Association With Health Outcomes And Treatment In Older Americans With Diabetes, Lashonda Jovon Williams

Theses and Dissertations

Introduction: Diabetes remains the 7th leading cause of death in the United States. Diabetes is a major public health concern of its own, but when you add the comorbidity of depression, diabetes outcomes are amplified. This dissertation examines how depressive symptomatology and treatment for depression are associated with selfreported health (SRH) and diabetes control.

Methods: Chi-square and logistic regression were used to analyze data from the Health and Retirement Study (2012). We assessed the associations between SRH and diabetes control with depressive symptomatology data.

Results: In our sample (n=4374), 19% of respondents reported high depressive symptomatology and …

Recipients’ Perspectives Regarding Expanded Carrier Screening Of Gamete Donors, Erika Kristy Jackson

Theses and Dissertations

Purpose: This study explored the perspectives of intended parents regarding genetic carrier screening of a gamete donor. The main goal of this study was to determine how much genetic carrier screening information a recipient would prefer to receive about potential donors. The study also aimed to identify factors that potentially influence a recipient’s choice of donor based on genetic screening results. Methods: An online questionnaire was developed to assess intended parents’ preferences regarding expanded carrier screening (ECS) of their donors. Participants were recruited from various online support groups and were eligible if they had previously utilized or were currently utilizing …

A Quality Improvement Project To Reduce The Incidence Of Clostridium Difficile Infection Through Implementation Of Evidence-Based Terminal Clean Procedures, Tamara Cook

Theses and Dissertations

Hospital-acquired infections (HAIs) are a huge economic burden and threat to patient health and outcomes. Clostridium difficile is the most common HAI. Effective hand hygiene and proper environmental cleaning procedures are significant to preventing the spread of C. difficile infections. The research question used to guide this project is: Does the use of a monitoring system for post C. difficile isolation terminal clean procedure reduce the rate of hospital-acquired C. difficile in the acute care population? A thorough organizational assessment was performed and directed this project to identify causes that may contribute to the recurrences of C. difficile infections. The …

Impact Of Corporate Social Responsibility On Financial Performance In The Pharmaceutical Industry, Stephen A. Adamu

Theses and Dissertations

Many studies have examined the association between corporate social responsibility (CSR) and corporate financial performance, but scholars argue that the exact relationship between CSR and corporate financial performance remains unclear. This quantitative study examines the impact of CSR on corporate financial performance in the pharmaceutical industry. The study addresses the research question: What is the financial performance in the pharmaceutical industry among companies that have embraced CSR? The alternative hypothesis predicted positive correlations between financial performance and CSR. The related null hypotheses predicted that there would be no correlations between any of 8 dimensions of CSR and corporate financial performance. …

Type 2 Immune Responses In The Context Of Helminth Infection, Asthma, Dendritic Cells, And Myeloid Derived Suppressor Cell Function, Sheela Ruby Damle

Theses and Dissertations

Type 2 (T_H2) immune responses evolved to respond to helminth parasite infections by the production of T_H2 cytokines, which stimulate anti-helminth immunity. Macrophage migration inhibitor factor (MIF) is a pleiotropic cytokine, which is produced by many cell types. We demonstrate that mice deficient in MIF have enhanced clearance of a helminth parasite. MIF deficiency in CD4⁺ T cells was found to be the most important for mediating parasite clearance. We mimicked MIF deficiency by administering an inhibitor of the MIF tautomerase activity, sulforaphane, and this also increased parasite clearance (Section I).

T_H2 immune …

Designing Effective Messages To Promote Future Zika Vaccine Uptake, Jeanine Guidry

Theses and Dissertations

The Zika virus is associated with the devastating birth defect microcephaly, and while a vaccine was not yet available in early-2017, several were under development. It is imperative to identify effective communication strategies to promote uptake of a new vaccine, particularly among women of reproductive age. Moreover, though the Zika outbreak has received much social media attention, little is known about these conversations on Instagram. The purpose of this dissertation, therefore, was to understand current Zika-focused communication on Instagram and to inform effective communication strategies to promote future Zika vaccine uptake intent.

The study aims were: (1) explore Zika conversations …

Discovery And Characterization Of Cytomegalovirus Inhibitors Using Reporter-Based Antiviral Assays, Amine Ourahmane

Theses and Dissertations

ABSTRACT

DISCOVERY AND CHARACTERIZATION OF CYTOMEGALOVIRUS INHIBITORS

USING REPORTER-BASED ANTIVIRAL ASSAYS

By Amine Ourahmane, MS

A thesis submitted in partial fulfillment of the requirements for the degree of Master of Science at Virginia Commonwealth University.

Virginia Commonwealth University, August 2017

Major Director: Michael McVoy, Ph.D.

Professor, Department of Pediatrics and Microbiology and Immunology

Human cytomegalovirus (HCMV), a member of the herpesvirus family, causes significant disease in immunocompromised patients and is the major infectious cause of birth defects when acquired congenitally. Current HCMV antivirals are suboptimal due to modest potency, significant toxicities, and emergence of resistance. Because HCMV does not infect …

Depressive Symptoms Among College Students: An Exploration Of Fundamental Cause Theory, Peter A. Carrico

Theses and Dissertations

Fundamental Cause Theory suggests that socioeconomic and demographic factors are causal to various illnesses, including depression. However, no known previously existing research has used Fundamental Cause Theory to create a model of depression among college students. To do this, the present study conducted a stepwise binomial logistic regression to examine how socioeconomic status and the sociodemographic variables of Gender, Race, and Sexual Orientation, and others predict depressive symptoms in a large sample of undergraduates when controlling for stressful life events and social support (N = 2,915). Results support the hypothesis that socioeconomic disparities in depressive symptoms are the result …

A Systems Biology Approach For Predicting Essential Genes And Deciphering Their Dynamics Under Stress In Streptococcus Sanguinis, Fadi El-Rami

Theses and Dissertations

Infectious diseases are the top leading cause of death worldwide. Identifying essential genes, genes indispensable for survival, has been proven indispensable in defining new therapeutic targets against pathogens, major elements of the minimal set genome to be harnessed in synthetic biology, and determinants of evolutionary relationships of phylogenetically distant species. Thus, essentiality studies promise valuable revenues that can decipher much of biological complexities.

Taking advantage of the available microbial sequences and the essentiality studies conducted in various microbial models, we proposed a framework for the prediction of essential genes based on our experimentally verified knowledge of the pathways involved in …

Health Aid In Africa: Placement, Service Utilization, And Benefit, Carrie Dolan

Theses and Dissertations

While the health sector has attracted significant foreign aid, evidence on the effectiveness of this support is mixed. This dissertation examines the allocation of health aid within the context of placement, service utilization, and benefit. The first paper examined the sub-national allocation of Chinese development aid projects across Africa. I determined how political preferencing of Chinese aid specifically, allocating aid to the birth region of the current political leader differs across sectors such as health, education, and transportation. I find some evidence that aid, more broadly defined, is subject to political preferencing in recipient countries, which could potentially limit its …

Paleodemographic And Biochemical Analysis Of Urbanization, Famine, And Mortality, Brittany S. Walter

Theses and Dissertations

Urbanization is a transitional period often associated with deteriorating population health and increased mortality, as the rapid increase of population density in urban centers facilitates the transmission of infectious diseases, unsanitary living conditions, and precarious food supplies. Research on the transition to an urban environment in the past offers a temporal depth to our understanding of the consequences of urbanization that cannot be accomplished through examination of contemporary populations. This project integrates paleodemographic (hazard analysis) and biochemical (stable isotope analysis) approaches to examine the health and diet of inhabitants in late medieval England (c. 1120-1539 CE), specifically the relationship between …

Analysis Of Food Exposures In Foodborne Disease Outbreaks, Alecia T. Alianell

Theses and Dissertations

Foodborne illness remains a serious public health problem in the United States in general as well as South Carolina in particular. Obtaining good food ingestion histories as well as possible risky environmental exposures is one of the earliest, most important tasks to complete in any foodborne outbreak investigations. Because time is of the essence in investigations, we have evaluated a rarely used biostatistical method, Random Forests, to data obtained from DHEC. Random Forests has the potential to facilitate more rapid identification of foods or environmental exposures that may be associated with outbreaks. We also examined previous cases of salmonellosis using …

Tuberculosis Screening In New Healthcare Employees: A Comparison Of Quantiferon®-Tb Gold In-Tube Test And Tuberculin Skin Test, Mary C. Giovannetti

Theses and Dissertations

Background: Streamlining onboarding processes for new hires to maximize efficiency and reduce costs while meeting regulatory requirements is a constant challenge for healthcare systems’ Employee Health staff. Health screening is a required step and includes obtaining a detailed health history, tuberculosis screening, drug screens, immunizations, fit for duty examinations, obtaining medical records, clarification of disability accommodations, pre-work screens, and other tests which are time consuming and result in delays in hire dates. Faced with a high volume of potential new employee hires a major southeast healthcare system was concerned about delays in new hire start dates. The two-step tuberculin skin …

Mast Cell Activation By Diverse Stimuli Can Be Suppressed By Steroid Therapy And Targeting The Fyn-Stat5b Cascade, Anuya Paranjape

Theses and Dissertations

Mast cells are critical effectors of allergic disease that can be activated by numerous stimuli. We have examined mast cell control by the inflammatory cytokine, IL-33, as well as IgG. In the first study reported here, we found that the synthetic glucocorticoid, dexamethasone, potently and rapidly suppressed IL-33-induced cytokine production from murine bone marrow–derived and peritoneal mast cells, as well as human mast cells. Dexamethasone also antagonized IL-33-mediated enhancement of IgE-induced cytokine production and migration. Although dexamethasone had no effect on IL-33-induced phosphorylation of MAP kinases or NFκB p65 subunit, it antagonized AP-1 and NFκB-mediated transcriptional activity. Finally, intraperitoneal administration …

Comparing The Structural Components Variance Estimator And U-Statistics Variance Estimator When Assessing The Difference Between Correlated Aucs With Finite Samples, Anna L. Bosse

Theses and Dissertations

Introduction: The structural components variance estimator proposed by DeLong et al. (1988) is a popular approach used when comparing two correlated AUCs. However, this variance estimator is biased and could be problematic with small sample sizes.

Methods: A U-statistics based variance estimator approach is presented and compared with the structural components variance estimator through a large-scale simulation study under different finite-sample size configurations.

Results: The U-statistics variance estimator was unbiased for the true variance of the difference between correlated AUCs regardless of the sample size and had lower RMSE than the structural components variance estimator, providing better type 1 error …

Role Of Mir-155 And Mir-146a In Mast Cell Function, Amina Abdul Qayum

Theses and Dissertations

Mast cells are resident immune cells abundantly found in the tissue at the host-environment interface, where they play a critical role in inflammatory allergic responses. Mast cell responses may be regulated by the cytokine milieu at the site of inflammation. Recent studies have revealed microRNAs to be important in altering cytokine signaling in immune cells. Here, we demonstrate for the first time that IL-10 and IL-33 induce miR-155 and miR-146a, respectively, to alter mast cell functions. We report that IL-10 enhanced IgE induced activation of mast cells. IL-10 effects are dependent on Stat3 activation, which elicits miR-155 expression, resulting in …

Role Of The Pediatric Dental Provider In Human Papillomavirus (Hpv) Education, Meredith L. Dugoni

Theses and Dissertations

Purpose: This study investigates knowledge about HPV and examines if pediatric dental providers should include HPV education for guardians of patients 10-18 years.

Methods: Legal guardians of 10-18 year-old patients of the Virginia Commonwealth University Pediatric Dental Clinic were enrolled in this prospective cohort study. Participants completed a baseline survey, were provided HPV education, completed an initial follow-up survey, and then completed a 6-month follow-up survey.

Results: A total of 54 participants completed the baseline and initial follow-up surveys and 17 completed the 6-month follow-up survey. The average number of correct responses was 3.4 of 6 knowledge questions, which significantly …

The Role Of The Nucleosome Remodeling Factor Nurf In Inhibiting T And Natural Killer Cell Mediated Antitumor Immunity By Suppressing Tumor Antigenicity And Natural Cytotoxicity Receptor Co-Ligands, Kimberly Mayes

Theses and Dissertations

Tumor immunoediting is a dynamic process in which the immune response attacks tumor cells by detecting danger signals and tumor antigens. In order to survive, tumor cells develop mechanisms to avoid detection or destruction by the immune system. To counteract this, several strategies are being developed to enhance the antitumor immune response, including the depletion of immunosuppressive cells, enhancing the activation of antitumor immune cells and increasing tumor cell immunogenicity. These therapies have seen limited success individually, however, and it is likely that combination therapy with novel targets will be necessary to see reproducible beneficial responses. Epigenetic modifications are attractive …

Functional Study Of Cmya5, A Candidate Gene For Schizophrenia, Anting Hsiung

Theses and Dissertations

CMYA5 is a candidate gene for schizophrenia because of the association of variant rs10043986 (Pro4063Leu). Studies of CMYA5 and its gene product, myospryn, in brain and neuronal cells have not been previously reported. We examined the neuronal expression of myospryn and its binding partner, desmin intermediate filament (IF), and investigated the difference in binding and colocalization of the two alleles of myospryn to IFs. Myospryn and desmin are expressed in brain regions. Using yeast two-hybrid and surface plasmon resonance, the T allele (Leu) is found to have higher binding affinity to desmin than the C allele (Pro). Myospryn localizes to …

A Targeted Approach To Increasing The African American Blood Donor Pool, Arnethea L. Sutton

Theses and Dissertations

A continuous need for blood products, specifically for those who require frequent transfusions, such as individuals with sickle cell disease, warrants the need for targeted interventions to increase blood donations from underrepresented populations. One population in particular, African Americans, only account for 1% of blood donors in the United States. Literature indicates numerous reasons why this population is underrepresented amongst donors, including fear, lack of knowledge about the blood donation, and specific to this population, lack of trust in the medical community. This study involves the development, implementation, and assessment of a targeted educational approach, incorporating the Theory of Planned …

Mechanistic Insights Into Neutrophil Turnover During Gram-Negative Pneumonic Sepsis, Christopher Jondle

Theses and Dissertations

Sepsis is one of the oldest and most elusive syndromes in medicine. It is characterized by a systemic inflammatory response leading to acute organ dysfunction. In the United States alone there are over 750,000 cases of sepsis each year, with a mortality rate between 20-50%. Sepsis is the second leading cause of death in the ICU and the tenth leading cause of death overall in the United States. Over half of all ICU resources are consumed in the treatment of sepsis. There are currently no effective therapies available against sepsis, all attempts to develop an effective therapy have failed. Respiratory …

Multilevel And Multisectoral Processes Of Implementing Nutritionsensitive Ideology And Programming In Ethiopia’S Development Landscape, Andrea Marie Warren

Theses and Dissertations

This research sought to understand the ways in which ideas and discourses in international development are adapted in a country context. Our particular focus was on how ideas at the international and national level become reality at the subnational and community levels. We primarily examined the sensitization of Ethiopia’s Productive Safety Net Program to nutrition across sectors and down levels of government as a way to understand how the global momentum around nutrition, particularly multisectoral or nutrition-sensitive initiatives, can be translated into action.

The first manuscript delves further into the operational realities of implementing multisectoral nutrition-sensitive programming among the neglected …

Network Interdiction Models And Algorithms For Information Security, Apurba Kumer Nandi

Theses and Dissertations

Major cyber attacks against the cyber networks of organizations has become a common phenomenon nowadays. Cyber attacks are carried out both through the spread of malware and also through multi-stage attacks known as hacking. A cyber network can be represented directly as a simple directed or undirected network (graph) of nodes and arcs. It can also be represented by a transformed network such as the attack graph which uses information about network topology, attacker profile, and existing vulnerabilities to represent all the potential attack paths from readily accesible vulnerabilities to valuable target nodes. Then, interdicting or hardening a subset of …

Antigenic And Genetic Evolution Of Emerging Avian Origin Influenza A Viruses, Yifei Xu

Theses and Dissertations

Periodic introductions of influenza A viruses (IAVs) from wild birds contribute to emergence of novel strains that infect domestic poultry, lower mammals, and humans, but the mechanisms of emergence are unclear. The objectives of this dissertation research are to infer the genesis of two emerging IAVs, low pathogenic avian influenza (LPAI) H10N8 and highly pathogenic avian influenza (HPAI) H7N8 viruses, and to characterize the antigenic diversity and genetic evolution of contemporary H7 avian influenza viruses (AIVs) from North America. First, AIVs that are genetically close to the human H10N8 isolate were recovered at the live poultry market (LPM) visited by …

The Effects Of Sub-Lethal Chlorine Induced Oxidative Stress On Biofilm Formation And Thermal Resistance Of Salmonella, Janak Dhakal

Theses and Dissertations

The effect of sub-lethal chlorine stress on various strains/serotypes of Salmonella on biofilm formation and thermal resistance was studied. The effect of oxidative stress (induced by 150 ppm of chlorine in TSB) on Salmonella biofilm formation on polystyrene and stainless steel surfaces at three temperatures (4°C, 30°C, and room temperature) in nutrient rich (full strength TSB) and nutrient limited conditions (1/10th TSB) was evaluated. On polystyrene surface, chlorine stressed S. Heidelberg (strain ID 72), S. Newport (strain ID 107) and S. Typhimurium (ATCC 14028) formed stronger (P < 0.05) biofilms at 30°C. On stainless steel, the chlorine stressed S. Heidelberg (ATCC 8326) and S. Enteritidis (ATCC 4931) at room temperature formed stronger (P < 0.05) biofilms as compared to the non-stressed control cells. The thermal resistance of short-term (1h) and long-term (27d) chlorine stressed Salmonella Heidelberg and S. Typhimurium were compared with the non-stressed controls at three different temperatures (55°C, 58°C and 61°C) and two growth phases (logarithmic and stationary). The short-term stressed log phase cells (both serotypes) were found to be more sensitive (P< 0.05) to thermal inactivation in TSB. Upon long-term sub-lethal chlorine exposure, Salmonella developed a rugose morphotype on tryptic soy agar at 37°C. The rugose morphotype provided significant thermal protection (P< 0.05) against heat stress as compared to smooth morphotype. In chicken broth, at 55°C, short-term chlorine stressed stationary phase S. Typhimurium displayed a higher D55 value compared to non-stressed cells. The findings from this research reveal that some Salmonella strains have the potential to form stronger biofilms and exhibit higher thermal tolerance upon exposure to sub-lethal chlorine concentration.