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A Weighted Gene Co-Expression Network Analysis For Streptococcus Sanguinis Microarray Experiments, Erik C. Dvergsten

Theses and Dissertations

Streptococcus sanguinis is a gram-positive, non-motile bacterium native to human mouths. It is the primary cause of endocarditis and is also responsible for tooth decay. Two-component systems (TCSs) are commonly found in bacteria. In response to environmental signals, TCSs may regulate the expression of virulence factor genes.

Gene co-expression networks are exploratory tools used to analyze system-level gene functionality. A gene co-expression network consists of gene expression profiles represented as nodes and gene connections, which occur if two genes are significantly co-expressed. An adjacency function transforms the similarity matrix containing co-expression similarities into the adjacency matrix containing connection strengths. Gene …

Probing Allosteric, Partial Inhibition Of Thrombin Using Novel Anticoagulants, Stephen S. Verespy Iii

Theses and Dissertations

Thrombin is the key protease that regulates hemostasis; the delicate balance between procoagulation and anticoagulation of blood. In clotting disorders, like deep vein thrombosis or pulmonary embolism, procoagulation is up-regulated, but propagation of clotting can be inhibited with drugs targeting the proteases involved, like thrombin. Such drugs however, have serious side effects (e.g., excessive bleeding) and some require monitoring during the course of treatment. The reason for these side effects is the mechanism by which the drugs’ act. The two major mechanisms are direct orthosteric and indirect allosteric inhibition, which will completely abolish the protease’s activity. Herein we sought an …

High Affinity Block Of Icl,Swell By Thiol-Reactive Small Molecules, Sung H. Park

Theses and Dissertations

Ebselen (Ebs) is considered as a glutathione peroxidase (GPx) mimetic and primarily thought to function by scavenging intracellular reactive oxygen species (ROS). Previous to our work, Deng et al. (2010a) demonstrated complete block of I_Cl,swell with 15 microM Ebs following endothelin-1 (ET-1) induced activation of the current in cardiomyocytes. This block was presumed to take effect mainly via the quenching of ROS. Nonetheless, our work with DI TNC1 astrocytes strongly emphasizes that Ebs might function by an alternative mechanism based on its kinetic profile in blocking I_Cl,swell. Our experiments showed that 45 nM Ebs can fully block …

Evaluating The Pennebaker Paradigm With Bereaved Emerging Adults: Applications Of Text Analysis, Elizabeth A. Collison

Theses and Dissertations

Bereavement is an important research area as it can result in grief reactions that lead to serious psychological and health consequences, particularly for the at-risk group of emerging adults (Arnett, 2000; Balk, Walker, & Baker, 2010; Fisher, Murray, & Frazer, 1985; Stroebe, Schut, & Stroebe, 2007). Expressive writing is a well-researched intervention for trauma and adjustment, yet research repeatedly has revealed null results with the classic Pennebaker paradigm as a bereavement intervention (Stroebe et al., 2002; Stroebe, Schut, & Stroebe, 2006). It may be premature, however, to conclude expressive writing is ineffective for the bereaved due to limitations in extant …

Investigating The Mechanism Of The Compartmentalized Cbp (Creb-Binding Protein) Ubiquitin Ligase Activities, Oluwatoyin E. Akande

Theses and Dissertations

CBP (CREB Binding Protein) is global transcriptional co-activator and histone acetyltransferase. CBP is involved in the modulation of the transcription of many genes via histone acetylation at the promoter regions of the target genes. Also, non-histone proteins and transcription factors can be acetylated by CBP to promote their transcriptional activation. In addition to its transcription co-activator role, CBP is involved in many other pathological and physiological cellular processes such as cell growth and differentiation, cell transformation and development, response to stress, cell cycle regulation and apoptosis.

CBP and its paralogue p300, play double-edged roles in the regulation of p53, a …

Involvement Of Signal Peptidase I In Streptococcus Sanguinis Biofilm Formation, Jessica Aynapudi

Theses and Dissertations

Biofilm accounts for 65%-80% of microbial infections in humans. Considerable evidence links biofilm formation to oral disease and consequently systemic infections. Eradication of biofilm-associated infections is important. Streptococcus sanguinis, a Gram-positive bacterium, is one of the most abundant species in oral biofilm. It contributes to biofilm development in oral cavities and is one of the recognized causes of infective endocarditis. To study and identify biofilm genes in S. sanguinis, biofilm formation of 51 mutants was compared with the wild type SK36 strain using crystal violet (CV) staining in a microtiter plate. Confocal laser scanning microscopy (CLSM) and image analysis was …

Upper Thermal Limits Differ Among Component Species In A Host-Parasitoid-Hyperparasitoid System, Kanchan A. Joshi

Theses and Dissertations

Among the predicted impacts associated with global climate change, warming is of special interest because the rates of physiological processes are temperature-dependent. Insects and other ectotherms are likely to be affected due to their limited ability to control body temperature. In this study, I measured the tolerance to extreme high temperatures, i.e., critical thermal maximum (CT_max), of component species in a tri-trophic system, including an herbivore (Manduca sexta), a primary larval parasitoid (Cotesia congregata) and a hyperparasitoid (genus Silochalcis). For wild insects, the parasitoid had the lowest CT_max, the hyperparasitoid had …

Plant Functional Trait And Hyperspectral Reflectance Responses To Comp B Exposure: Efficacy Of Plants As Landmine Detectors, Paul V. Manley Ii

Theses and Dissertations

At least 110 million landmines have been planted since the 1970s in about 70 nations, many of which remain in place today. Some risk of detection may be mitigated using currently available remote sensing techniques when vegetation is present. My study focused on using plants as phytosensors to detect buried explosives. I exposed three species representing different functional types (Cyperus esculentus (sedge), Ulmus alata (tree), Vitis labrusca (vine)) to 500 mg kg^-1 of Composition B (Comp B; 60/40 mixture of hexahydro-1,3,5-trinitro-1,3,5-triazine (RDX) and 2,4,6-trinitrotoluene (TNT)), a commonly used explosive mixture, and measured functional traits and reflectance over …

Celecoxib Enhances Sorafenib/Sildenafil Lethality In Cancer Cells And Reverts Platinum Chemotherapy Resistance, Timothy A. Webb

Theses and Dissertations

The present studies sought to determine whether the lethality of the drug combination [sorafenib + sildenafil] could be enhanced by the anti-inflammatory agent celecoxib, using ovarian cancer and other tumor cell lines as models. Also, in a dose dependent fashion celecoxib enhanced [sorafenib + sildenafil] lethality in multiple ovarian cancer cell lines. In a dose dependent fashion celecoxib enhanced the ability of [sorafenib + sildenafil] to reduce expression of multiple chaperone proteins in parallel with lower levels of the drug efflux pumps ABCB1 and ABCG2. Over-expression of GRP78 and HSP27 maintained pump expression in the presence of drugs. Cell killing …

Introducing Novel Combinatorial Targeted Therapies In Multiple Types Of Cancer, Mehrad Tavallai

Theses and Dissertations

The cancers of liver, colon and breast are amongst the top five most prevalent and most fatal worldwide. As the Raf/MEK/ERK pathway is frequently deregulated in hepatocellular carcinoma (HCC), sorafenib, a Raf kinase inhibitor, became the first systemic therapy approved for the treatment of patients with HCC. However, sorafenib only produced modest effects with low response rates in the clinic. Similarly, regorafenib, which was approved for the treatment of metastatic colorectal cancer (CRC), has had a poor response rate in the clinic. Since phosphodiesterase type 5 has been reported to be overexpressed in HCC and CRC, we hypothesized that sildenafil, …

Drug And Vaccine Development For Neisseria Gonorrhoeaea, Devin R. Cash

Theses and Dissertations

Neisseria gonorrhoeae, the causative agent of the STI gonorrhea, is not preventable by vaccination and is rapidly developing resistance to antibiotics. One important strategy for gonococcal survival in the host is iron acquisition in the face of nutritional immunity. To overcome iron limitation, the gonococcus expresses TonB dependent transporters (TdTs), outer membrane proteins that facilitate nutrient acquisition. Of the TdTs, the transferrin (Tf), lactoferrin (Lf), and hemoglobin (Hb) receptors hijack iron directly from host proteins, and studies have already shown that the Tf receptor is essential for the initiation of human infection. Given that the TdTs are virulence factors, …

Characterization Of Fibrin Matrix Incorporated Electrospun Polycaprolactone Scaffold, Cho Yi Wong

Theses and Dissertations

Specific objective: Guided tissue regeneration (GTR) aims to regenerate the lost attachment apparatus caused by periodontal disease through the use of a barrier membrane. For the GTR procedures to be successful, barrier membranes are required to be present at the surgical site for an extended period of time (weeks to months). Synthetic membranes have the advantage of prolonged presence in a wound site; however, they do not actively contribute to wound healing. Biologic membranes are recognized by the host tissue and participate in wound healing but have the disadvantage of early resorption. Therefore, the goal of this study is …

Vital Pulp Therapy Survivability Based On Radiographic Depth Of Caries, Aaron T. Schmick

Theses and Dissertations

Purpose: The purpose of this retrospective chart review was to determine if the survival of two methods of vital pulp therapy (VPT) were influenced by the pre-operative radiographic depth and location of caries. Methods: Electronic patient records (axiUm®) that contained the procedure codes D3120, Indirect Pulp Therapy (IPT), or D3220, Therapeutic Pulpotomy (TP), were queried. Qualifying charts’ pre-operative and post-operative radiographs were viewed in MiPACS® by two raters. Visit records were queried again to identify any other treatment failures. Results: A total of 568 primary molars met the eligibility criteria. There was a difference in survival depending upon the treatment …

Considerations In The Provision Of Mental Health Services Toward Arabs, Dalia Khoury

Theses and Dissertations

Existing evidence suggests that disparities exist in the use of mental health services by Arabs in the U.S. While there are likely many factors that contribute, lack of cultural competence of mental health providers is one potentially important barrier for mental health service use among racial/ethnic minorities, including Arabs. The primary purpose of this study was to identify and examine factors related to the development and existence of cultural competence toward Arabs. Variables measuring demographics, professional characteristics, familiarity with Arabs, prior experience and knowledge of Arabs, and readiness for change were tested with a randomly selected sample of mental health …

A Mapping System As A Method In Experiential Culture Learning And Engagement, Faisal Mohammad

Theses and Dissertations

From my observation as a new resident in Education City, I recognize a need for cultural awareness and communication amongst those studying and working in this particular area. With this project I propose a different experience, a new way to use experiential learning as a mechanism to change people’s predetermined opinions about one another and disrupt personal biases in order to foster cultural awareness and friendship.

A mapping system or wayfinding strategy to navigate a new city is the beginning of a visitor’s experience in a new place. This new experience is one way for users to identify locations through …

Gender And Sexual Health: Applying Gender Role Theory To Men And Women’S Intention To Engage In Sexual Health Information Seeking Behaviors, Ariella R. Tabaac

Theses and Dissertations

The purpose of the present study is to examine the pathways between gender and behavioral intention to engage in sexual HISB through application of the Theory of Planned Behavior (TPB). It was found that feminine and masculine gender role stress differentially influence perceived behavioral control and behavioral attitudes, and that intention to engage in HISB was higher among women than men. Attitudes and PBC significantly predicted behavioral intention in this model. Further, women in the sample were more likely to search for sexual health information, with online sources being the most frequently reported resource. Additionally, past HISB was a significant …

A Longitudinal Study Of The Motivations For The Non-Medical Use Of Prescription Drugs In A National Sample Of Young Adults, Tess K. Drazdowski

Theses and Dissertations

Young adults are most at-risk for the non-medical use of prescription drugs (NMUPD) and many of its associated negative consequences. Understanding this population’s motivations for use can help to inform efforts to reduce NMUPD. Past research has been limited in scope, consisting primarily of cross-sectional work with college students focusing on prescription stimulants. The current study researched how motivations for NMUPD changed over young adulthood using three waves of data from a longitudinal, nationally representative sample of 14,990 19 to 24 year olds in the Monitoring the Future study cohorts collected between 1976 to 2013. Prescription stimulants, central nervous system …

Serum Vitamin D, Pth, And Calcium Levels In Patients With And Without Early Childhood Caries, Susan A. Meinerz, Harmeet Chiang, Peter C. Moon, Lorin M. Bachmann, Tegwyn Brickhouse, Al M. Best, Tiffany Williams

Theses and Dissertations

Purpose: The purpose was to determine differences in serum vitamin D, parathyroid hormone (PTH), and calcium levels between patients with early childhood caries (ECC) and patients without dental decay.

Materials and Methods: Serum vitamin D, PTH, and calcium levels were obtained from 30 children without dental decay who acted as controls and 60 children with ECC. A questionnaire was filled out by the parent/guardian of each participant consisting of questions regarding medical and dental history, exposure to sources of vitamin D and demographic information.

Results: The difference in the vitamin D levels of the participants was most …

Social Determinants Of Participation In A Home Visitation Fluoride Varnish Program, James E. Puryear, Tegwyn Brickhouse, Caroline Carrico

Theses and Dissertations

Purpose: The purpose of this study is to examine the social determinants of CHIP (Child Health Investment Partnership) of Roanoke Valley children who participated in the preventive oral health program compared to those who did not.

Methods: This is a retrospective cohort study of children (n=2,425) enrolled in CHIP of Roanoke Valley from September 2008-September 2014. Bivariate analysis and multivariable logistic regression models were used to compare age, gender, race, locality, parents’ education level, age at enrollment, and length of enrollment for oral health program participants versus those who did not participate.

Results: Children who were Hispanic …

Post-Tbi Hippocampal Neurogenesis In Different Tbi Models, Kaushal S. Patel

Theses and Dissertations

Traumatic brain injury (TBI) leads to short-term and long-term consequences that can cause many different life-long disorders. Studies of TBI have generally focused on the acute stage; however, it is now becoming important to investigate chronic responses following TBI as clinical reports of dementia and cognitive impairments have been linked to a history of TBI. Recent data have established that cognitive function is associated with hippocampal neurogenesis. Chronic injury induced changes in the brain may affect this endogenous process. Chronic responses following TBI include cell death pathways and inflammatory responses that are persistent in the brain for months to years …

Analysis Of Radiographic Changes Associated With The Periradicular Diagnosis Of Symptomatic Apical Periodontitis, Preeti Batra

Theses and Dissertations

Symptomatic apical periodontitis (SAP) is indicative of inflammation of the periodontal ligament. It may or may not be accompanied by radiographic changes and may occur with vital or necrotic pulpal diagnosis. Purpose of this study was to analyze clinical and radiographic presentations of SAP in a retrospective electronic dental chart and digital radiograph review utilizing the endodontic diagnostic template note of predoctoral dental school patients presenting with SAP. The aim was to determine prevalence of periapical radiolucencies (PARLs) in SAP, association of SAP to pulpal diagnosis, and define associated radiographic changes. Most prevalent pulpal diagnosis with SAP was symptomatic irreversible …

Design And Structure-Activity Relationship Of Small Molecule C-Terminal Binding Protein (Ctbp) Inhibitors And Investigation Of The Scope Of Palladium Multi-Walled Carbon Nanotubes (Pd-Mwcnt) Catalyst In C–H Activation Reactions, Sudha Korwar

Theses and Dissertations

C-terminal binding proteins (CtBPs) are transcriptional co-repressors involved in developmental processes, and also implicated in a number of breast, ovarian, colon cancers, and resistance against cancer chemotherapy. CtBP is a validated novel potential anti-cancer target. In this project we sought to develop potent and selective small-molecule inhibitors of CtBP. Using a combination of classical medicinal chemistry and modern computational approaches, we designed a potent inhibitor HIPP (hydroxyimino-3-phenylpropanoic acid) that showed an IC₅₀ of 0.24 μM against recombinant CtBP. Further elucidation of the structure-activity relationship (SAR) of HIPP led to the design of more potent inhibitors 3-Cl HIPP (CtBP IC …

The Study Of The Regulon Of Oxyr In Escherichia Coli And Porphyromonas Gingivalis, Christopher K. Pham

Theses and Dissertations

The facultative anaerobe, Escherichia coli and the obligate anaerobe, Porphyromonas gingivalis are two bacteria that reside in our body. Although they reside in separate environments, they are both subject to hydrogen peroxide stress and have mechanisms to regulate the stress. OxyR is the primary transcriptional regulator/sensor of oxidative stress response caused by hydrogen peroxide. OxyR in P. gingivalis is not well-characterized compared to OxyR in E. coli. We sought to characterize and compare the two forms of OxyR in order to gain a better understanding of the protein. We determined the oligomeric state of both proteins: primarily a tetramer for …

Investigating The Molecular Etiologies Of Sporadic Als (Sals) Using Rna-Sequencing, David G. Brohawn

Theses and Dissertations

ALS is an often lethal disease involving degeneration of motor neurons in the brain and spinal cord. Current treatments only extend life by several months, and novel therapies are needed. We combined RNA-Sequencing, systems biology analyses, and molecular biology assays to elucidate sporadic ALS group-specific differences in postmortem cervical spinal sections (7 sALS and 8 control samples) that may be relevant to disease pathology. >55 million 2X150 RNA-sequencing reads per sample were generated and processed.

In Chapter 2, we used bioinformatics tools to identify nuclear differentially expressed genes (DEGs) between our two groups. Further, we used Weighted Gene Co-Expression Network …

"They Believe That Because They Are Women, It Should Be Easier For Them." Subtle And Overt Sexism Toward Women In Stem From Social Media Commentary, Katherine Hall

Theses and Dissertations

This study implemented a social media based content analysis to examine the subjective experiences and the current public perceptions of sexism in STEM fields. Participants included men and women who a) identified as either in STEM or not identified as in STEM and b) commented through Facebook on HuffPost Women articles about women in STEM. The analysis indicated that sexism remains an issue for women in STEM careers. Women in STEM identified several gender-based challenges that they have experienced; some participants discussed how they handled those challenges. Men both in and not in STEM were less likely to acknowledge and …

Identification Of Size And Shape Changes In Orofacial Development And Disease, Allyson E. Kennedy

Theses and Dissertations

Among the most prevalent and devastating types of human birth defects are those affecting the mouth and face, such as orofacial clefts. Children with malformed orofacial structures undergo multiple surgeries throughout their lifetime and struggle with facial disfigurements, speech, hearing, and eating problems. Therefore, facilitating new research in cranio- and orofacial development is paramount to prevention and treatment of these types of birth defects in humans. Xenopus laevis has emerged as a new tool for dissecting the mechanisms governing facial development. Thus, molecular analyses accompanied by quantitative assessment of morphological changes during orofacial development of this species could be very …

The Microbiome In Light Of Host Evolution, Alexander M. Waldrop Jr.

Theses and Dissertations

Recent advances in sequencing technologies have provided an unprecedented window in the unseen biological world. Accompanying this revolution is a growing appreciation for the ubiquity and diversity of beneficial interactions between animals and the microbes they carry. Given the symbiotic roles of microbes in host nutrition, immunity, behavior, development, and nearly every other facet of host biology, it is becoming increasingly clear that any understanding of hosts and their evolution would be incomplete without also considering the microbial dimension. Yet despite the growing body of evidence that many of these partnerships are rooted deep in evolutionary time, the majority of …

Genome Wide Epigenetic Analyses Of Araptus Attenuatus, A Bark Beetle, Chitra Seshadri

Theses and Dissertations

Phylogeographic studies have relied on surveying neutral genetic variation in natural populations as a way of gaining better insights into the evolutionary processes shaping present day population demography. Recent emphasis on understanding putative adaptive variation have brought to light the role of epigenetic variation in influencing phenotypes and the mechanisms underlying local adaptation. While much is known about how methylation acts at specific loci to influence known phenotypes, there is little information on the spatial genetic structure of genome-wide patterns of methylation and the extent to which it can extend our understanding of both neutral and putatively adaptive processes. This …

A Neural Circuit Of Appetite Control In C. Elegans, Kristen C. Davis

Theses and Dissertations

Feeding behavior and its associated neural circuitry is complex and intricate in mammalian systems, however, a simple model organism, such as C. elegans provides a more basic approach to understand factors and molecules involved. The fruit-dwelling nematode provides a unique set of resources; it only consists of 959 cells, 302 of which are neurons. In addition, each neuron’s connectivity and position within the worm is known and consistent between animals. Conservation of neurotransmitters and biochemical processes add to this impressive list. These resources provide an excellent background to address feeding behavior and the neural structures governing it.

Feeding behavior in …

Courageous Solstice: Reconstructing Fairy Tales For A Black Youth Aesthetic, Tanya Boucicaut

Theses and Dissertations

This thesis interrogates the historical, philosophical, and existential implications of the Black Arts Movement and its major artists on the recurring themes of social injustice, Western hegemony, and the fight for aesthetic authenticity to reimagine fairy tales for the youth Black Aesthetic. As a personal reflection and foundational document for a larger project, this work weaves these implications through the practical application of the varied stages of program development for youth artists. This project also is a handbook that encompasses scholarly research, reflective analysis and anecdotal journal evidence. The subsequent chapters explore the theological and theatre pedagogical educational influences that …