Digital Commons Network^™

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 …

Physiological Approach To Characterize Drowsiness In Simulated Flight Operations During Window Of Circadian Low, Bijay Guragain

Theses and Dissertations

Drowsiness is a psycho-physiological transition from awake towards falling sleep and its detection is crucial in aviation industries. It is a common cause for pilot’s error due to unpredictable work hours, longer flight periods, circadian disruption, and insufficient sleep. The pilots’ are prone towards higher level of drowsiness during window of circadian low (2:00 am- 6:00 am). Airplanes require complex operations and lack of alertness increases accidents. Aviation accidents are much disastrous and early drowsiness detection helps to reduce such accidents. This thesis studied physiological signals during drowsiness from 18 commercially-rated pilots in flight simulator. The major aim of the …

Per- And Polyfluoroalkyl Substances In The Soil Environment: Sorption, Bioaccumulation And Biotransformation, Bosen Jin

Theses and Dissertations

Per- and polyfluoroalkyl substances (PFASs) are man-made chemicals, widely used in both industries and daily lives, such as in non-stick cookware, waterproof clothing, and painting materials. Researchers have investigated PFASs for about two decades, but most of the studies focus on perfluoroalkyl substances with very limited information available on polyfluoroalkyl substances. In this research, we investigated the sorption/desorption mechanisms perfluorooctanoic acid (PFOA) and its two cationic and zwitterionic precursor compounds, perfluorooctanesulfonamido ammonium salt (PFOSAmS) and perfluorooctaneamido betaine (PFOAB) in a group of soil. We also studied the bioaccumulation and bioconcentration of these chemicals along with perfluorooctane sulfonate (PFOS) and its …

Thermal Performance Analysis Of The Liquid Cooling And Ventilation Garment (Lcvg) With Respect To Tubing Geometry, Kayla Marie Daniels

Theses and Dissertations

The technology of a liquid-cooled garment allows astronauts to complete extravehicular activities while maintaining a degree of thermal comfort. The garment has gone largely unchanged despite advancements in technology, materials, and knowledge. This research examines possible advancements in thermal efficiency with an alternate tubing geometry through heat transfer rate calculations. A semi-circle cross-section was selected and compared against the current circular cross-section tubing. Each tubing cross-section was 3-D printed and integrated into forearm sleeves. For comparison, the assembly of each sleeve resembled the current Liquid Cooling and Ventilation Garment used with the Extravehicular Mobility Unit. Subjects wore the forearm sleeves …

Measuring Friendship Maintenance In Gay Men, Eliah Reding

Theses and Dissertations

This dissertation examines the existing friendship maintenance literature to develop a psychometrically sound scale for the measurement of friendship maintenance among gay men. Existing friendship maintenance research does not adequately capture the uniqueness of gay male friendship. Utilizing DeVellis’s (2016) steps of scale development, this dissertation constructs a new scale, the GayFABS, to assess the unique aspects of friendship maintenance in gay men. Unique in this dissertation is the use of a focus group to establish content validity rather than the traditional approach of expert review. An exploratory factor analysis is conducted to structure the scale and its component subscales. …

The Reliability Of Indirect Assessments Of Standing Forward Head Posture In Asymptomatic Adults, Bailey Strand

Theses and Dissertations

Background: Measurement reliability has important decision-making implications for physical therapists and researchers when assessing individuals. Given that physical therapists often visually assess forward head posture (FHP) to guide treatment, the aims of this study were to quantify: (a) the reliability of indirect (visual) assessments of standing FHP in asymptomatic adults, and (b) the magnitude of the biological (postural) and technical errors involved.

Methods: A reliability analysis of two indirect assessments (visual assessments of real and 3D body scanned people) of FHP was undertaken. The sample comprised 10 physical therapists and 50 asymptomatic participants. Participants were scanned using the Vitus Smart …

Influences Of Nesting Behaviors In Common Eiders (Somateria Mollissima Sedentaria) In The Western Hudson Bay, Tanner John Stechmann

Theses and Dissertations

Reproductive decisions of birds are shaped by minimizing predation while meeting physiological needs of parents and offspring. As a result, birds must make decisions about investment in offspring that allows them to maximize their overall fitness. This often drives nesting behaviors and can provide insights into reproductive success. Common eiders (Somateria mollissima) are thought to have high nest attendance (time spent tending the nest) and use substantial energetic resources during breeding. However, the specific behaviors at the nest of these birds are not well studied, with even less known about the Hudson Bay common eider (S. m. sedentaria). The objectives …

Development Of Dna-Based Biosensors And Antibacterial Additive, Yuqian Xing

Theses and Dissertations

In the first project, an ultrasensitive assay has been developed for the detection and determination of Hg2+(aq) based on single-particle inductively coupled plasma-mass spectrometry (spICP-MS). In the presence of Hg2+(aq), AuNPs modified with a segment of single-stranded DNA can aggregate due to the formation of well-known thymine (T)-Hg2+-T complex. The spICP-MS can sensitively and quantitatively measure the degree of aggregation by the overall decrease in number of detected AuNPs or NP aggregates. Compared with most other Hg assays that use the same principle of aggregation-dispersion with DNA modified AuNPs, this spICP-MS-based method achieved a much lower detection limit of 0.031 …

Associations Between Parental Alcoholism And Adult Internalized And Externalized Indicators Of Maladjustment, Stephanie Brezinski

Theses and Dissertations

Associations between parental alcoholism and internalized and externalized indicators of maladjustment in adult children of alcoholics were examined. College students (N = 2,531) and respondents from the general population (N = 703) provided self-reports of various internalized and externalized indicators of maladjustment. Several hypotheses were tested: (1) CAST scores will be positively associated with symptom severity; (2) Combined maternal and paternal alcoholism will be associated with the most severe maladjustment compared to ACAs from a single parent and/or non-ACAs; (3) Male ACAs will exhibit relatively more externalized symptoms than internalized symptoms and female ACAs will exhibit relatively more internalized symptoms …

Photography Methods To Understand Rural Resilience And Environmental Literacy: The Example Of Fracking In The Bakken, Bruce Evan Farnsworth

Theses and Dissertations

This dissertation examines the social and environmental impacts of fracking through deep ethnographic interviews and observations with farmers and ranchers living and leasing on the Bakken and Three Forks shale oil formations of western North Dakota, currently the second largest oil-producing region in the United States. This study investigates how photographic methods such as photo elicitation, repeat photography, and aerial photographs/maps elicit local knowledge and testify to the resilience of ranchers and farmers challenged by oil development and the alteration of their environment. Motivated by heritage, political marginalization and the pervasive loss of ruralness, the participants express several roles, among …

Chromatin Associated Small Rna Show Evidence Of Processing After Promoter Proximal Rna Polymerase Ii Pausing, Nii Koney-Kwaku Koney

Theses and Dissertations

Paused Pol II has been implicated in the generation of short non-coding RNAs, such as transcription start site RNAs (TSSa RNAs) and transcription initiation RNAs (tiRNAs), which are found within or around the 5’ ends of gene promoters. The generation of these RNAs (which I termed “processed RNAs”) is known to occur in the nucleus; however, whether their biogenesis is co-transcriptional or post-transcriptional is unknown. These RNAs have been proposed to be remnants of 5’ to 3’ processing and protected by paused Pol II. Processed RNAs may represent a novel class of small RNAs derived from promoter-proximal transcription termination.

I …

Temporal Trends In The Standing Broad Jump Test Performance Of United States Children And Adolescents, Bridget Kate Pinoniemi

Theses and Dissertations

Muscular fitness is a very important indicator of health. Using a systematic review strategy, the aim of this study was to estimate the temporal trends in broad jump performance of United States youth. Broad jump data on apparently healthy United States youth (aged 10–17 years) were located through a systematic electronic database search and by pearling reference lists, topical systematic reviews and personal libraries. Sample-weighted temporal trends (expressed as percent and standardized trends) were estimated for separate age-sex groups using best-fitting regression models relating the year of testing to mean jump performance. Mean trends standardized to the year 1985 were …

Characterizing The Contribution Of Groudwater In The Water Budgets Of Wetlands Using Gis Groundwater Modeling And The Field Measurement Of Water Quality, Brianna Fuller Speldrich

Theses and Dissertations

Wetlands provide many benefits to society, including flood attenuation, groundwater recharge, water quality improvement, and habitat for wildlife. Because their structure and function are sensitive to changes in hydrology, characterizing the water budgets of wetlands is crucial to effective management and conservation. The groundwater component of a budget, which often controls resiliency and water quality, is particularly difficult to estimate and can be costly, time-consuming, and invasive. This study used a GIS approach using a digital elevation model (DEM) and the elevations of lakes, wetlands, streams, and hydric soils to produce a water-table surface raster for a portion of the …

Therapeutic Targeting Of Relaxin Signaling In Ischemic Heart Disease, Siva Teja Vk Devarakonda

Theses and Dissertations

Ischemic heart disease is characterized by reduced perfusion of oxygenated blood to the myocardium, potentially resulting in infarction upon occlusion of coronary arteries. While prompt reperfusion and advances in in-hospital care have led to a decline in short term mortality, sustained damage to the ventricle, along with reperfusion injury, can lead to progressive deterioration in cardiac function. Limiting the extent of this initial ischemia-reperfusion injury and combating the course of adverse remodeling remains the scope of several preclinical studies geared towards improving cardiac health after MI. To this, relaxin-2 – the peptide hormone that regulates maternal hemodynamic function during pregnancy …

Glycosaminoglycan Mimetics For The Treatment Of Cancer And Lung Inflammation, Shravan Morla

Theses and Dissertations

Glycosaminoglycans (GAGs) are linear polysaccharides whose disaccharide building blocks consist of an amino sugar and either uronic acid or galactose. They are expressed on virtually all mammalian cells, usually covalently attached to proteins, forming proteoglycans. GAGs are highly negatively charged due to an abundance of sulfate and carboxylic acid groups, and are structurally very diverse, with differences arising from chain length, the type of monomeric units, the linkages between each monomeric unit, the position of sulfate groups, and the degree of sulfation. GAGs are known to interact with a multitude of proteins, impacting diverse physiological and pathological processes. In addition, …

Designing Biomimetic Implant Surfaces To Promote Osseointegration Under Osteoporotic Conditions By Revitalizing Mechanisms Coupling Bone Resorption To Formation, Ethan M. Lotz

Theses and Dissertations

In cases of compromised bone remodeling like osteoporosis, insufficient osseointegration occurs and results in implant failure. Implant retention relies on proper secondary fixation, which is developed during bone remodeling. This process is disrupted in metastatic bone diseases like osteoporosis. Osteoporosis is characterized low bone mass and bone strength resulting from either accelerated osteoclast-mediated bone resorption or impaired osteoblast-mediated bone formation. These two processes are not independent phenomena. In fact, osteoporosis can be viewed as a breakdown of the cellular communication connecting bone resorption to bone formation. Because bone remodeling occurs at temporally generated specific anatomical sites and at different times, …