Digital Commons Network^™

Carbon Cycling Along The James River Continuum, Timothy B. Jones

Theses and Dissertations

Fluvial systems act as conduits for terrestrial carbon transport to coastal oceans. However, riverine systems not only transport allochthonous carbon, they transform and store carbon in many different ways. The different mechanisms of transformation and storage need to be considered for fluvial systems in order to accurately account for modifications to the carbon pool when developing carbon budgets. Of interest was to investigate the carbon dynamics in the James River, in Virginia, from headwaters to the tidal fresh estuary to gain a better understanding of carbon dynamics along the continuum. Sites along the river continuum were sampled for dissolved organic …

Touched With All The Radiance That A Sudden Sun Discloses, Marie Fornaro

Theses and Dissertations

The thread running through my work is a constant impulse to rend and repair; to make, unmake, and remake. This repetitive and circular approach allows me to confront the cyclical nature of gendered oppression. What does it mean to make something beautiful and then to dismantle it? How do we reckon with the pieces that remain? By deconstructing the beautiful and lovingly crafted objects that I spend hours making, I recenter “craft” as a verb rather than a noun, forcing myself and my audience to resist the comforting illusion of certainty.

I contextualize my piecework and quilting in a long …

Trauma Related Drinking To Cope: A Phenotypic And Molecular Genetic Investigation Of The Self-Medication Model, Sage E. Hawn

Theses and Dissertations

Posttraumatic stress disorder (PTSD) and alcohol use problems (AUP) commonly co-occur, have shared latent genetic risk, and are associated with many negative public health outcomes. Via a self-medication framework, trauma-related drinking to cope (TRD), an unexplored construct to date, may help explain why these two disorders co-occur, thus serving as an essential target for treatment and prevention efforts. The present study aimed to create a novel measure of TRD and examine its psychometric properties, investigate its indirect influences on the association between PTSD and AUP, as well as explore its potential shared molecular genetic risk with PTSD in a genetically-informative …

The Anaplasma Phagocytophilum Adhesin Asp14 Directs Pdi-Mediated Disulfide Reduction To Promote Infection, Ryan S. Green

Theses and Dissertations

Obligate intracellular pathogens must invade host cells to survive and pose a global health risk. As such, internalization is a critical life stage and represents an excellent therapeutic target. Oxidoreductase exploitation is a thematic invasion strategy among obligate intracellular pathogens. Delineating the mechanisms and proteins mediating this exploitation could identify novel therapeutic targets for many important pathogens. Anaplasma phagocytophilum infects neutrophils by an incompletely defined mechanism, resulting in the emerging potentially fatal disease, human granulocytic anaplasmosis. The bacterial adhesin, Asp14, contributes to invasion by virtue of its C-terminus engaging an unknown receptor. Yeast two-hybrid analysis identified protein disulfide isomerase (PDI) …

Regorafenib Enhances Lethality Of Sildenafil And Curcumin In Colorectal Cancer Cells, Kervin Benjamin Owusu

Theses and Dissertations

In the United States, more than 130,000 people will be diagnosed with colorectal cancer (CRC) each year and an estimated 50,000 people will die from the disease. Standard of care (SOC) therapies for CRC combine multiple cytotoxic chemotherapeutic drugs. These combinations have varying degrees of effectiveness and can often result in significant patient morbidity. For second recurrence patients, the multi-kinase inhibitor, regorafenib, is an approved agent, but is often poorly tolerated at current doses. In the current study, we propose to develop therapeutic regime of combining agents with modest toxicity profiles: curcumin and sildenafil with regorafenib. Using clinically achievable enterohepatic …

Pharmacologic Profiling Of Novel Compounds Via Fluorometric Analyses Of Monoamine Transporter Responses, Ashkhan Hojati

Theses and Dissertations

In humans and other organisms, monoaminergic systems are crucial in neuronal function and behavior. The monoamine transporters (MATs), which can be found on the presynaptic plasma membrane of neurons in the central nervous system (CNS), are crucial in the regulation of neurotransmitter concentration in the synaptic cleft. As the duration and concentration of neurotransmitters in the cleft affect further downstream signaling responses, these proteins are important targets for both understanding neuronal physiology and compounds of interest. Multiple theories exist proponing the contribution of MATs to a variety of mental and neurological disorders, including depression. This theory establishes that depression is …

Examining Biobehavioral Variables And Predictors Associated With Type 2 Diabetes Self- Management, Karin A. Emery

Theses and Dissertations

Type 2 diabetes mellitus self-management is a challenging process that brings forward a variety of emotional responses. The purpose of this work was to explore relationships between diabetes distress, self-efficacy and resilience and outcomes of glycosylated hemoglobin, quality of life and health status. A cross sectional descriptive design was used for this pilot study of 78 individuals enrolled from an Endocrine clinic in the Midwest United States and a Primary Care clinic in the southeast United States.

Data were analyzed using descriptive statistics to characterize the sample and model variables. Spearman’s correlation was completed to identify relationships among variables. A …

Inhibition Of Cancer Stem Cells By Glycosaminoglycan Mimetics, Connor P. O'Hara

Theses and Dissertations

Connor O’Hara July 29, 2019

Inhibition of Cancer Stem Cells by Glycosaminoglycan Mimetics

In the United States cancer is the second leading cause of death, with colorectal cancer (CRC) being the third deadliest cancer and expected to cause over 51,000 fatalities in 2019 alone.¹ The current standard of care for CRC depends largely on the staging, location, and presence of metastasis.² As the tumor grows and invades nearby lymph tissue and blood vessels, CRC has the opportunity to invade not only nearby tissue but also metastasize into the liver and lung (most commonly).³ The 5-year survival rate …

Factors Influencing Parental Care And Home Range Size Of A Monomorphic Species, The Red-Headed Woodpecker (Melanerpes Erythrocephalus), L. Abigail Walter

Theses and Dissertations

Parental care in animals can be costly and is shared between both parents in many bird species. Not surprisingly, most studies of how parental care is shared between the sexes are in sexually dimorphic species, and much less in known about sexually monomorphic species where sex cannot be determined in the field. This has prevented a full understanding of parental care behaviors – which are intrinsically linked to fitness – in species such as the Red-headed Woodpecker (Melanerpes erythrocephalus) that is experiencing population declines throughout much of its range. In this study we assessed whether Redheaded Woodpecker brooding time, nestling …

Role Of Glial Ccr5 In Mediating Hiv-1 Tat And Opiate Neurotoxicity And Behavioral Phenotype, Sarah Kim

Theses and Dissertations

Human immunodeficiency virus type 1 (HIV-1) persists in certain CNS cell populations, despite peripheral control of the infection with modern antiretroviral therapy. Infected and/or activated cells release viral proteins, such as trans-activator of transcription (Tat) and various pro-inflammatory factors such as CCL5, creating a positive loop of neuro-inflammation. This serves as the basis for the resulting sublethal and lethal neuropathology that manifests as a spectrum of HIV-mediated CNS impairments, known as HIV-associated neurocognitive disorders (HAND). Opiates, which exist as an interlinked epidemic with HIV-1 infections, exacerbate these neurological effects through direct and indirect mechanisms that disrupt both glial and neuronal …

Structural Determinants Of High Potency Mdpv Inhibition Of The Dopamine Transporter, Tyler Steele

Theses and Dissertations

Monoamine transporters (MATs) are a unique group of neurotransmitter transporters that include the dopamine, serotonin, and norepinephrine transporters (DAT, SERT, and NET, respectively). MATs are a target for a number of licit and illicit compounds. The significance of this work lies in the fact that these transporters share affinity for certain ligands to varying degrees, but the structural features within the transporters that govern the observed selectivity for these ligands has not been completely determined. One such ligand is methylenedioxypyrovalerone (MDPV), which was frequently found in “bath salts” preparations that were available in convenience stores and were sold with “not …

The Role Of Psychosocial And Health Behavioral Factors In Pregnancy Induced Hypertension, Sylvia Sreeparna Rozario

Theses and Dissertations

Background: Pregnancy induced hypertension (PIH) is the leading cause of maternal mortality and a major contributor to preterm birth and neonatal mortality. Literature suggests that several modifiable psychosocial and health behavioral factors may play significant roles in the development of PIH. However, interrelationships among these factors and their collective impact on PIH are not well understood.

Objectives: This study aims to: 1) Examine the relationship between pre-pregnancy physical activity and risk of PIH, 2) Determine the association between prepregnancy depression and PIH and the role of race/ethnicity in this association, 3) Evaluate the association between intimate partner violence (IPV) in …

Conceptualization Of Body Image And Eating Disorders Among South Asian American Women: A Qualitative Investigation, Neha J. Goel

Theses and Dissertations

Though it is known that eating disorders (EDs) affect individuals of all racial/ethnic backgrounds (Cheng, Perko, Fuller-Marashi, Gau, & Stice, 2019), people of color tend to be overlooked in the ED literature. South Asian Americans, a specific subset of individuals traditionally categorized within the larger umbrella group of “Asians,” have been notoriously neglected in both the broader mental health literature, and in the ED literature (Inman, Devdas, Spektor, & Pendse, 2014; Iyer & Haslam, 2003, 2006). Currently, very little information exists on the etiology and presentation of EDs amongst South Asian communities. Even less is known about culturally-specific barriers to …

An Enzymology And Inhibition Study Of A Camp-Dependent Protein Kinase Linked To Acth-Independent Cushing's Syndrome, Nicole Luzi

Theses and Dissertations

Cyclic-AMP dependent protein kinase (PKA) is a key intracellular signal transduction kinase that is modulated by G_s- and G_i-coupled GPCRs. Under normal physiological conditions, PKA exists as an inactive holoenzyme made up of two catalytic subunits and two regulatory subunits. Upon cAMP binding to the regulatory subunits, the catalytic subunits (PKACa) are released to perform various downstream phosphorylation events. However, aberrant PKA activation can cause various diseases including Cushing’s Syndrome, which is an endocrine disorder caused by the overproduction of cortisol by the hypothalamus-pituitary-adrenal hormone system. This disorder can be caused by pituitary adenomas that release …

Using Lipidomics To Characterize The Inflammatory Mechanisms In Sepsis And Pre-Eclampsia, Daniel Stephenson

Theses and Dissertations

Lipidomics, a rapidly developing field of study, focuses on the classification and quantitation of lipid species. Lipidomics has emerged in the forefront of scientific research due to the key roles that lipids play in metabolism, cancer, and disease. Using mass spectrometry as a tool for analysis, understanding the role eicosanoids and sphingolipids play has advanced rapidly. Being able to observe these small molecules in vivo has led to better understanding of several lipid-driven mechanisms and identification of eicosanoid and sphingolipid biomarkers in neurodegenerative disease, cancer, sepsis, wound healing, and pre-eclampsia. In the studies herein, we developed targeted mass spectrometric methods …

Spatial And Temporal Distributions Of Larval Clupeid Fishes In A Tidal Freshwater Marsh Complex, Philip Reid Anderson

Theses and Dissertations

Tidal freshwater wetlands provide valuable ecosystem services such as nutrient cycling, coastal flood control, and reproductive habitat for early life stages of economically and ecologically important fishes. The nutrient rich environments that tidal freshwater wetlands occur in support high levels of primary productivity of phytoplankton and vegetation that provide essential reproductive habitat for anadromous clupeid fishes (Alosa spp., Brevoortia tyrannus) in Chesapeake Bay tributaries. Seasonal retention of clupeid eggs and larvae within tidal freshwater habitats may enhance early growth, survival, and year class strength. The primary goal of the present study was to characterize the relative importance of …

Adaptation And Validation Of The Situation Awareness Global Assessment Technique For Student Registered Nurse Anesthetists, Deniz Dishman

Theses and Dissertations

Anesthesia is a health care specialty fraught with high workload demands, stressful work environments, increased production pressure, work areas with many distractions, an increasing use of advanced technology, and the constant need to prioritize work actions. Effective clinical judgment in this dynamic environment necessitates that the provider demonstrate the ability to project what may occur secondary to actual or potential condition changes. These key elements operationalize situation awareness (SA).

High level SA is an important characteristic for the successful development of student registered nurse anesthetists (SRNAs). With Endsley’s “Theory of Situation Awareness” as the foundation, the goal of this study …

Development Of Bivalent Ligands Targeting The Putative Mu Opioid Receptor And Chemokine Receptor Cxcr4 Heterodimer, Bethany A. Reinecke

Theses and Dissertations

Human immunodeficiency virus (HIV) and opioid abuse have been described as synergistic epidemics. Pharmacologically, it has been found that opioids have the capacity to enhance HIV infection and replication. Research has shown that activation of the mu-opioid receptor (MOR) elevates the expression of the HIV-1 entry co-receptor CXCR4 on T-lymphocytes in the peripheral nervous system, thus allowing for enhanced viral entry and invasion. Although the exact mechanism for opioid modulation of CXCR4 expression and subsequent exacerbation of HIV is unknown, several hypotheses exist. One hypothesis is that MOR and CXCR4 are functionally interacting through the formation of a heterodimer. This …

Glial Cell Mechanisms Regulate Alcohol Sedation In Drosophila Melanogaster, Kristen M. Lee

Theses and Dissertations

Approximately 16 million people in America are diagnosed with Alcohol Use Disorder (AUD) but no efficacious medical treatments exist. Alcohol-related behaviors can be studied in model organisms, and changes in these behaviors can be correlated with either (i) a risk for alcohol dependence or (ii) a symptom/feature of AUD itself. Although AUD is a disease of the central nervous system, a majority of research has focused on the neuronal underpinnings, leaving glial contributions largely undescribed. We used Drosophila melanogaster (fruit fly) to identify genes whose expression in glia regulates alcohol sedation. Mammals and Drosophila have conserved behavioral responses to alcohol …

Evaluating Predixcan’S Ability To Predict Differential Expression Between Alcoholics And Non-Alcoholics, John E. Drake Jr

Theses and Dissertations

PrediXcan is a recent software for the imputation of gene expression from genotype data alone. Using an overlapping set of transcriptome datasets from postmortem brain tissues of donors with alcohol use disorder and neurotypical controls, which were generated by two different platforms (e.g., Arraystar and Affymetrix), and an additional unrelated transcriptome dataset from lung tissue, we sought to evaluate PrediXcan’s ability to impute gene expression and identify differentially expressed genes. From the Arraystar platform, 1.3% of matched genes between the measured and imputed expression had a Pearson correlation ≥ 0.5. Our attempt to replicate this finding using the expression data …

Bantaba: Designing The Sacred Circle, Tashiara Scott

Theses and Dissertations

MOTIVATION In Richmond, there are 1.21 times as many African Americans as any other ethnic group. Yet 63.4% of African Americans live in poverty (Richmond, VA). African Americans face greater exposure to stress due to low socioeconomic status and poverty. In these communities, “discrimination and deprivation undermine individuals’ ability to accumulate the social and material resources to mitigate the effects of stress” (Brondolo, 2018). In this city’s African American community, where stress levels are high and consequential health concerns are prevalent, dance can be a remedy for managing stress and improving health (Hanna, 2006).

DESIGN PROBLEM How can an intentionally …

Upper Thermal Limits Vary Among And Within Native Bee Species In Relation To Season, Voltinism, And Nest Type, Kálmán K. Csigi Xiv

Theses and Dissertations

Native bees are only recently gaining attention for the extent to which they aid in pollination and ecosystem services. These services are threatened by predictions of warming temperatures if bees are not able to respond. Voltinism - the number of generations produced annually- can strongly influence thermal conditions experienced by both developing and adult bees based on emergence strategies for each voltinism type. Differences in experienced thermal conditions brought on by climate change could therefore affect upper thermal limits (UTL) in bees. This study observes UTLs across a foraging season within and among native bee species vi to elucidate the …

Facilitative And Competitive Tradeoffs Between Morella Cerifera Seedlings And Coastal Grasses, Michael N. Sinclair

Theses and Dissertations

Morella cerifera is a rapidly expanding native shrub on the Virginia barrier islands which displaces other native coastal species and may interrupt normal sediment dynamics. Barrier islands are considered stressful environments with low nutrients, high solar load, and frequent drought and salt exposure; facilitation often dominates in stressful environments according to the Stress Gradient Hypothesis. The objective of this project was to understand the importance of species interactions with grasses on the growth and physiology of M. cerifera at the seedling life stage through both field and lab experiments. Grasses provided ~1.3°C insulation to shrubs during winter freeze events and …

Determination Of Optimal Parameter Estimates For Medical Interventions In Human Metabolism And Inflammation, Marcella Torres

Theses and Dissertations

In this work we have developed three ordinary differential equation models of biological systems: body mass change in response to exercise, immune system response to a general inflammatory stimulus, and the immune system response in atherosclerosis. The purpose of developing such computational tools is to test hypotheses about the underlying biological processes that drive system outcomes as well as possible real medical interventions. Therefore, we focus our analysis on understanding key interactions between model parameters and outcomes to deepen our understanding of these complex processes as a means to developing effective treatments in obesity, sarcopenia, and inflammatory diseases.

We develop …

Expansion Of The Genetic Code To Include Acylated Lysine Derivatives And Photocaged Histidine, William D. Kinney

Theses and Dissertations

The genetic code of all known organisms is comprised of the 20 proteinogenic amino acids that serve as building blocks on a peptide chain to form a vast array of proteins. Proteins are responsible for virtually every biological process in all organisms; however, the 20 amino acids contain a limited number of functional groups that often leaves much to be desired. The lack of diversity addresses the need to increase the genetic repertoire of living cells to include a variety of amino acids with novel structural, chemical, and physical properties not found in the common 20 amino acids. In order …

(And I Can't Stress This Enough) In My Mouth: Extradiegetic Affect As Material, C. Klockner

Theses and Dissertations

(and i can’t stress this enough) in my mouth: Extradiegetic Affect as Material is a non-linear exploration into the structures of feeling that exist in relation to cinema in its role as a technology for generating subjectivity. In the development of this research, a proposal of cinema’s likeness to the ecological circulation of microplastics is drawn in order to illustrate cinema’s materiality and nearly invisible ubiquity. The notion of extradiegetic affect is outlined as a post-cinematic condition in which lived experience becomes secondary to cinematic representation and which, simultaneously, becomes directly shaped by engaging with these representations.

Biometal-Induced Structural Consequences Of Α-Synuclein – The Parkinson’S Disease Protein, Dinendra L. Abeyawardhane

Theses and Dissertations

The pre-synaptic protein α-Synuclein (αS) is often linked to the pathology of Parkinson’s disease (PD), an age-related neurodegenerative disorder. Lewy bodies, the cytopathological hallmarks of PD, are found to be rich in aggregates of misfolded αS protein. Metal dyshomeostasis has also been linked to PD due to the accumulation of iron in the substantia nigra pars compacta, and diminished copper levels reported in this same region. Metal dyshomeostasis in the brain coupled with oxidative stress can enhance the aggregation of αS. Recently, it was confirmed that mammalian αS is universally acetylated at the N-terminus, a common post-translational modification in …

The Development Of Intrinsically Cell-Permeable Peptide Libraries Using Mrna Display, Nicolas A. Abrigo

Theses and Dissertations

Peptides are emerging as promising therapeutics due to their inhibitory affinity towards protein-protein interactions (PPI). However, peptides have been limited mainly by their poor bio-stability and lack of cell permeability. Efforts to generate drug-like peptides have led to the development of macrocyclic peptides, which exhibit improved stability. Yet, most macrocyclic peptides still require the assistance of a cell penetrating peptide (CPP) for cellular entry.

High throughput technologies have been exceptional tools for the discovery of peptides to interrupt PPIs. This work details the recent advancements we have made to improve our high throughput technique, mRNA display, to yield more therapeutically …

Research On The Law Of Garlic Price Based On Big Data, Feng Guo, Pingzeng Liu, Chao Zhang, Weijie Chen, Wei Han, Wanming Ren, Yong Zheng, Jianrui Ding

Computer Science Student Research

In view of the frequent fluctuation of garlic price under the market economy and the current situation of garlic price, the fluctuation of garlic price in the circulation link of garlic industry chain is analyzed, and the application mode of multidisciplinary in the agricultural industry is discussed. On the basis of the big data platform of garlic industry chain, this paper constructs a Garch model to analyze the fluctuation law of garlic price in the circulation link and provides the garlic industry service from the angle of price fluctuation combined with the economic analysis. The research shows that the average …

High-Resolution Trophic Models Reveal Structure And Function Of A Northeast Pacific Ecosystem, Szymon Surma, Villy Christensen, Rajeev Kumar, Cameron H. Ainsworth, Tony J. Pitcher

Marine Science Faculty Publications

This paper examines the structure and dynamics of the marine ecosystem surrounding Haida Gwaii (an archipelago in the southeastern Gulf of Alaska). Based on previous research, a set of improved mass-balanced models was constructed in Ecopath with Ecosim (EwE) to represent ecosystem states existing circa 1900, 1950, and currently. These models feature increased taxonomic and ecological resolution relative to their predecessors across trophic levels and size classes from zooplankton to whales. A more detailed representation of Pacific herring (Clupea pallasii), including its age structure, predators, and prey, was introduced to permit modeling of the ecosystem role of herring …