Digital Commons Network^™

Development Of Dexamethsone Sodium Phosphate Loaded Nanoparticles For Treating Corneal Allograft Rejection, Vineet R. Kulkarni

Theses and Dissertations

Corneas are the most commonly transplanted tissue worldwide, with approximately 80,000 transplantations performed in the United States in 2018 alone. Corneal transplantation is used to restore the vision due to opaque corneas in various diseases such as fungal keratitis, keratoconus, Fuchs’s dystrophy, corneal ulceration, traumatic injury, abrasions or scarring, inflammation, and infection. Corneal transplant surgery could involve replacing the entire cornea (penetrating keratoplasty) or selective replacement of the corneal layers (e.g. Descemet’s membrane endothelial keratoplasty and deep anterior lamellar keratoplasty). Immunologic graft rejection is one of the main causes of graft failure in these corneal transplantations. The 2-year rejection rate …

Reaction Profiling Of Extracellular Protein Phosphorylation Through A Microfluidic Reactor Coupled With Raman Spectroscopy, Abigail Casey

Theses and Dissertations

Diseases and disorders in the human body are considered abnormalities of proper cellular function. Understanding the signal transduction mechanisms that cause these abnormalities is crucial to developing earlier detection methods, better treatment options and effective cures. While current diagnostic procedures are powerful tools in diagnosing diseases, they are ineffective in informing physicians on the real-time behavior of the signal transduction mechanisms associated with diseases and disorders. Currently, disease progression is monitored over time through routine patient visits and testing by one or more of the above techniques. By developing an approach that can monitor structural and conformational changes of proteins …

Dendrimer-Based Therapeutic Delivery Vehicle For The Treatment Of Ocular Diseases, Remy C. Cooper

Theses and Dissertations

The treatment of ocular diseases poses a significant challenge to drug delivery design, due to the eye’s complex anatomy, with a semi-permeable blood-ocular barrier and associated immune privilege. To address some of the delivery challenges, polycationic dendrimers are explored as vehicle for the treatment of posterior chamber disease. Dendrimers are a class of polymeric nanoparticles that are highly branched, multivalent and monodisperse, whose three-dimensional globular architecture has given them the nickname of “synthetic proteins”. Dendrimers are synthesized by reacting monomers in a step-wise fashion to produce generationally and radially increasing structures, with core, interior and surface chains that are highly …

Characterization Of The Gonococcal Calprotectin Zn-Acquisition System, Tdfh, And The Efficacy Of Metal Starvation For Treating Gonococcal Disease, Michael T. Kammerman

Theses and Dissertations

Abstract

Characterization of the Gonococcal Calprotectin Zn-Acquisition System, TdfH, and the Efficacy of Metal Starvation for Treating Gonococcal Disease.

By Michael T. Kammerman, B.S.

A dissertation submitted in partial fulfillment of the requirements for the degree of Doctor of Philosophy at Virginia Commonwealth University

Virginia Commonwealth University, 2020

Major Director: Cynthia Nau Cornelissen, Ph.D.

Professor, Department of Microbiology and Immunology

Neisseria gonorrhoeae, the bacterial agent that is responsible for the human disease gonorrhea, has had a steady increase in the number of infections per year. In 2018 the WHO estimated over 87 million infections occurred world-wide, and the CDC …

Surrogate Memories In Animation And Sound, Jared Duesterhaus

Theses and Dissertations

A document in support of my exploration into memory in relation to the mediums of animation, sound, and theater. A reflection on remembering as a creative act.

It’S Funny Because It’S True: The Transmission Of Explicit And Implicit Racism In Internet Memes, Tabitha Fairchild

Theses and Dissertations

Video games are traditionally seen as the domain of heteronormative white males. The purpose of this study is to explore how racism is transmitted and reproduced within digital communities, and how humor is being used to frame racist discourse in virtual spaces. Digitally, internet memes are widely used rhetorical vehicles, reaching large and broad audiences. The roles these artifacts play in the reproduction and transmission of racist ideology is often obfuscated by the perception that internet memes are "just jokes." This study analyzes internet memes collected from 16 months of communication between members of Discord servers that self-identify as communities …

Investigation Into The Reaction Profile Of A Bioinspired Nickel Complex, Denver Heitger

Theses and Dissertations

Metal complexes that can activate natural oxidants like H₂O₂ and O₂ have become a key research topic in many labs in hope of mimicking nature, by generating a bioinspired complex that can perform unique chemistry through green processes. To prepare the perfect catalyst, this has lead scientists to explore numerous avenues, including the use of both natural and artificial oxidants, to tease apart the reaction pathway taking place. A ligand system dear to the Lucas Lab (13-DOB) has been metalated with nickel, a cheap and earth abundant transition metal. Our bioinspired metal-(di)oxygen adducts can be formed …

The Quantified Elf, Umico Niwa

Theses and Dissertations

The Quantified Elf is an ongoing collection of scientific, medical, archaeological articles and excerpts from my personal journal. It is a way by which I explore the various ways Western notions of personhood subsume human life into constructs of sexuality and gender, overlooking the various other modes of unbridled existence: plant, microbial. fungal, animal, celestial bodies. The speculative medical papers propose novel forms of body modification to combat gender dysphoria.

A Story About A Girl With Snakes For Hair, Kate M. Turner

Theses and Dissertations

My work is autobiographical. I use various art making processes to create a visual archive of my life. By abstracting these memories and experiences, I can examine how culture works surrounding issues of identity. This is my story.

The Impact Of Aging And Mechanical Injury On Alveolar Epithelial And Macrophage Responses In Acute Lung Injury And Inflammation, Michael S. Valentine

Theses and Dissertations

Patients with severe lung pathologies, such as Acute Respiratory Distress Syndrome (ARDS), often require mechanical ventilation as a clinical intervention; however, this procedure frequently exacerbates the original pulmonary issue and produces an exaggerated inflammatory response that potentially leads to sepsis, multisystem organ failure, and mortality. This acute lung injury (ALI) condition has been termed Ventilator-Induced Lung Injury (VILI). Alveolar overdistension, cyclic atelectasis, and biotrauma are the primary injury mechanisms in VILI that lead to the loss of alveolar barrier integrity and pulmonary inflammation. Stress and strains during mechanical ventilation are believed to initiate alveolar epithelial mechanotransduction signaling mechanisms that contribute …

Epigenetic Regulation Of Drug Metabolizing Enzymes In Normal Aging, Mohamad M. Kronfol

Theses and Dissertations

Geriatric populations are at a higher risk for adverse drug reactions (ADRs). This may be partly due to changes in drug metabolism in old age, but the underlying mechanisms are poorly understood. Prior research in humans and mice has shown age-associated changes to the expression of several genes involved in drug metabolism. Furthermore, studies of human blood showed that epigenetic regulation of genes encoding drug metabolizing enzymes change with age. However, it is unknown if genes in the liver are similarly affected. Therefore, we hypothesize that genes encoding drug metabolizing enzymes may show differential epigenetic regulation in the liver with …

Signaling Mechanism Responsible For 5-Ht2a Receptor Tolerance To Psychedelic Induced Head-Twitch Behavior In Mice, Audrey R. Mcmurtrie

Theses and Dissertations

In recent years, there has been a growing interest in psychedelic compounds stemming from their promising use as therapeutic agents and research tools that can be used to treat and study several neuropsychiatric disorders. Psychedelics have proven useful in a broad range of these diseases - they serve as models for psychosis in schizophrenia but have also had promising results in treating major depressive disorder, anxiety, and other common disorders. Decreased stigmatization surrounding psychedelics has further increased their use in research and clinical settings. In light of these trends and the promising nature of their use, a thorough understanding of …

Language-Supportive Strategies And Their Associations With Child Language Outcomes During Instructional Time, Erin S. Wallace

Theses and Dissertations

In this dissertation, I conducted a correlational study that examined the frequency of educator-delivered language-supportive strategies during instructional time in public Kindergarten classrooms. Additionally, I explored the association between educators’ use of language-supportive strategies and child language outcomes. To index child language, I assessed a sample of 96 children from 10 different classrooms on standardized measures of expressive and receptive language. I recruited 10 educators to participate in the present study and assessed their use of language-supportive strategies during instructional time in the classroom through transcription and coding of audio recordings. The educators completed demographic forms for themselves as well …

Novel Bayesian Techniques For Dose Response Data, Faten Alamri

Theses and Dissertations

All forms of life are being exposed to different levels of harmful chemicals that can cause various and serious side effects. Toxicological experiments enable researchers to test these chemicals on animal to determine their major effects. Although optimal and acceptable dose levels have been investigated, researchers continue to strive to minimize side effects and the chemical dosages. Dose-response models and other benchmark approaches play a role in determining the acceptable exposure levels of hazardous chemicals. Parametric techniques, used to determine the tolerable dosages, utilizing ANOVA and non-linear regression models are well represented in the literature. We determined the benchmark dose …

Novel Duel Mtor Inhibitors/Ampk Activators Improve Therapeutic Efficacy Of Doxorubicin And Ameliorate Its Associated Cardiotoxicity In Mice, Sahak Eric Hovsepian

Theses and Dissertations

Triple-negative breast cancer (TNBC) is a particularly aggressive subset of breast cancer that has a molecular expression profile which lacks the estrogen receptor (ER), progesterone receptor (ER), and human epidermal growth factor receptor type 2 (HER2). No targeted treatment options currently exist for TNBC, unlike other types of breast cancer, and therefore survival rates are far lower for these patients. The current treatment for TNBC is systemic anthracycline chemotherapy, typically doxorubicin (DOX), which has great clinical efficacy in increasing survival. However, DOX induces a dose-dependent progressive cardiomyopathy, which can present years and up to decades after the last treatment. This …

Effects Of Gestational Ozone Exposure On Privileged Placental And Brain Barrier Integrity, Alexander I. Hamm

Theses and Dissertations

Ambient outdoor ozone, a common of component of photochemical smog and urban air pollution, is linked to various neurological and vascular pathologies. Its immediate reaction with lung surfactant after inhalation results in complete reactivity of the gas, with no active ozone passing into circulation. This indicates the presence of secondary and tertiary mediators in ozone-related systemic pathologies after pulmonary insult. In vasculature, ozone exposure is associated with an acute hypertensive phenotype apparent at least 24 hours after dose, such as experienced on a hot summer afternoon in a large metropolitan area like Los Angeles or Mexico City. However, the effects …

Mef2-Bound Genes May Influence Ethanol Sedation In Drosophila Melanogaster, Katlyn M. Myers

Theses and Dissertations

Alcohol Use Disorder (AUD) is a global health issue that affects millions of people every year. This disorder has serious negative mental and physical consequences. Currently, treatment options for this disorder are largely limited to psychological therapy, with very few medications available to treat it. Being able to identify the environmental and genetic components that influence AUD can help improve diagnosis and treatment options. Previous studies in humans have shown a link between initial sensitivity and risk for alcohol abuse. Our laboratory uses Drosophila melanogaster as a model to study the genetic and environmental components of alcohol-related behaviors. Previous lab …

An Identification Of Tgf-B'S Role In Ischemic Cholangiopathy, Courtney Chmielewski

Theses and Dissertations

Organ transplants are a necessary intervention for many diseases that result in end stage organ failure. The donation pool cannot match the demands of the transplant list, so expanding the pool to include donation after cardiac death (DCD) is desired. However, there are increased odds of graft failure and ischemic cholangiopathy leading to inferior outcomes when DCD livers are used. Ischemic cholangiopathy consists of multiple diffuse strictures and fibrosis of the bile ducts leading to a loss of epithelialization and fibrosis. The cellular mechanism is proposed to be epithelial-to-mesenchymal transition (EMT). TGF-�� is seen as a key initiator of EMT, …

Modeling Gardnerella Host-Pathogen Interaction: Characterization Of Vaginolysin And The Opacity Phenotype, Erin M. Garcia

Theses and Dissertations

Bacterial vaginosis (BV) describes a dysbiotic state of the vaginal mucosa, during which the dominance by beneficial lactobacilli species is lost, the vaginal pH increases, and the flora comprising the vaginal microbiome becomes more diverse. Bacterial taxa associated with this dysbiotic state interact to form a dense polymicrobial biofilm on the surface of the vaginal epithelium. This shift in the vaginal microflora is clinically important, even when symptoms are not noted, as women with BV are at increased risk for acquisition of other sexually transmitted infections, including HIV, and are more than two times as likely to experience preterm birth. …

Evidence Of Local Adaptation To Climate In An Invasive Ectotherm: A Study On The Eurasian Gypsy Moth (Lymantria Dispar) In North America, Phillip M. Gibbs

Theses and Dissertations

Invasive species exist in nearly every ecosystem both terrestrial and aquatic. Improving our understanding of the mechanisms that shape the ability of these organisms to physiologically cope with their surroundings will be crucial to preparing for future impacts of climate change. The Gypsy Moth (Lymantria dispar) has been expanding its range across North America over the last 100+ years since its arrival in Medford, Massachusetts. This study quantifies upper thermal limits (UTL) across 8 different populations of L. dispar in North America and seeks to determine if signals of local adaptation to climate across a latitudinal gradient may …

Towards A Greener Route To Blockbuster Statin Drugs: Harnessing The Power Of Biocatalysis And Integrating Cross-Coupling Catalysis In The Synthesis Of Rosuvastatin, Chanaka M. Amarasekarage

Theses and Dissertations

As global and political awareness about green and sustainable practices sharpens in the face of dramatic climate change and environmentally detrimental practices, one attractive approach is to harness the catalytic potential of enzymes. Thus influenced, our efforts focused on the development of an innovative chemoenzymatic route to widely prescribed Blockbuster statin drugs, specifically rosuvastatin. In this work, we engineered novel deoxyribose phosphate aldolase (DERA) variants via rationally designed site-directed mutagenesis to accept non-natural, less polar substrate, acrolein, along with acetaldehyde. Several of new mutants displayed elevated tolerance towards aldehydes and showed effective incorporation of acrolein into the unprecedented enzymatically-derived chiral …

Ceramide Synthase 2 Interacts With Ceramide Synthases 5 And 6 At The Mrna And Protein Levels, Dorothy Yen

Theses and Dissertations

Ceramides and sphingolipids make up major portions of the plasma membrane and therefore are crucial for cell proliferation, survival, and death. With dysregulation comes numerous pathophysiological conditions, such as Alzheimer's, Huntington's Disease, Creutzfeldt-Jakob, cardiovascular disease, and many cancers. However, the regulation of the enzymes responsible for catalyzing the formation of ceramides is still not well understood. In this experiment, three isoforms were of focus: CerS2, CerS5, and CerS6. Through mRNA, protein, and immunofluorescence analysis, it can be concluded that these isoforms do indeed interact within the human cell in order to upregulate their activity. It was also found that cells …

Beneficiation Of Coal Using Supercritical Water And Carbon Dioxide Extraction, Matthew Decuir Virginia Commonwealth University Cl

Theses and Dissertations

This work explores the use of carbon dioxide, water, and their mixtures as solvent for the pre-combustion beneficiation of raw coal without using any toxic mineral acids in the temperature range of 200-400℃. The fluid polarity, ionic constant, and supercritical point can be adjusted by H₂O/CO₂ ratio and temperature. Adding carbon dioxide to hydrothermal fluid also increases the ionization by forming carbonic acid. Extractions with supercritical fluids have several benefits including enhanced mass transport, ease of separation and recycle, wide range of extractive capability and tunability, better inherent safety, and in the case of carbon dioxide and …

Bee Diversity Of Three Appalachian Shale Barren Sites, Olivia C. Latham

Theses and Dissertations

Insect pollination is vital to ecosystem function. However, climate change, habitat loss, pesticides, and a variety of other anthropogenic sources are contributing to a decline in pollinator diversity. Fragile small ecosystems with a high composition of specialized plant species that rely on specific pollinators such as Appalachian shale barrens, are especially at risk of losing biodiversity. This study combines the use of active sweep net sampling of endemic shale barren forbs and passive trap methods over the course of a bloom season (April-August) in three barren sites to identify bee community populations and visitation relationships between pollinator species and endemic …

Sphingolipids In Cancer Health Disparities And As Prospective Targets For Cancer Therapy, April E. Boyd

Theses and Dissertations

Lung cancer is the deadliest cancer both in the United States and worldwide. Non-small cell lung cancer (NSCLC) accounts for approximately 85% of all lung cancers. However, lung cancer disparities are not shared equally across racial groups, with large differences between African American and Caucasian populations. Advances in research have revealed roles of lipid mediators in cancer biology and disease progression, but sphingolipid alterations in tissues should be explored further. To address this, using mass spectrometry (MS), extensive sphingolipidomic characterization of NSCLC tumors and adjacent uninvolved tissues from African American and Caucasian patients were performed. This study revealed that NSCLC …

Recovery From Visual Dysfunction Following Mild Traumatic Brain Injury Is Associated With Adaptive Reorganization Of Retinal Inputs To Lateral Geniculate Nucleus In The Mouse Model Utilizing Central Fluid Percussion Injury., Vishal C. Patel

Theses and Dissertations

Traumatic brain injury (TBI) is a leading cause of morbidity and mortality nationwide. Prevalence of mild TBI (mTBI) vastly outnumbers more severe forms however the associated morbidity has only recently gained public attention. Visual dysfunction is a significant component of mTBI associated morbidity with recovery of function linked with improvement in global outcomes. Examination of sensory and motor pathways in other brain injury paradigms support that recovery is largely dependent on adaptive plasticity of remaining connections. Current examinations of visual function recovery following mTBI is limited to identifying evidence for recovery and objective evidence for adaptive plasticity is limited. Therefore, …

Integration Of Multi-Omic Platforms To Understand The Regulation Of Genes In Human Disease, Eva Lancaster

Theses and Dissertations

Epigenetic mechanisms have been hypothesized to modify gene expression (GE) in response to both genetic variation and environmental exposures, ultimately contributing to the development of complex traits. Epigenome-wide association studies (EWAS) aim to test the theory that marks of DNA methylation (DNAm) have downstream consequences that result in the development of complex diseases. Although these methods have been successful in identifying DNAm patterns in complex traits, specific molecular mechanisms involved in the etiology of complex diseases remain unidentified. This knowledge gap does not originate from a lack of DNAm-trait associations, but rather stems from study design issues that affect the …

Multi-Label Classification Models For Heterogeneous Data: An Ensemble-Based Approach., Jose Maria Moyano Murillo

Theses and Dissertations

In recent years, the multi-label classification gained attention of the scientific community given its ability to solve real-world problems where each instance of the dataset may be associated with several class labels simultaneously, such as multimedia categorization or medical problems.

The first objective of this dissertation is to perform a thorough review of the state-of-the-art ensembles of multi-label classifiers (EMLCs). Its aim is twofold: 1) study state-of-the-art ensembles of multi-label classifiers and categorize them proposing a novel taxonomy; and 2) perform an experimental study to give some tips and guidelines to select the method that perform the best according to …

Lpa Receptors Modulate Gene Expression During Oligodendrocyte Differentiation, Samantha A. Spencer

Theses and Dissertations

LPA, produced by the lysoPLD activity of ATX, binds its cognate receptors and regulates the development of multiple brain cells, including oligodendrocytes (OLGs). OLGs progress through a lineage from precursor (OPC) to early OLG to immature OLG, until finally the cells mature and enwrap axons to enable saltatory conduction and provide trophic support. The studies in this dissertation characterized the receptors LPA4 and LPA6 as inhibitors of OPC differentiation. Western blot analysis of MS patient lesion tissue found a negative correlation between ATX levels and levels of LPA4 and LPA6. A previously created homology model for LPA4 was used to …

The Analysis Of Neural Heterogeneity Through Mathematical And Statistical Methods, Kyle Wendling

Theses and Dissertations

Diversity of intrinsic neural attributes and network connections is known to exist in many areas of the brain and is thought to significantly affect neural coding. Recent theoretical and experimental work has argued that in uncoupled networks, coding is most accurate at intermediate levels of heterogeneity. I explore this phenomenon through two distinct approaches: a theoretical mathematical modeling approach and a data-driven statistical modeling approach.

Through the mathematical approach, I examine firing rate heterogeneity in a feedforward network of stochastic neural oscillators utilizing a high-dimensional model. The firing rate heterogeneity stems from two sources: intrinsic (different individual cells) and network …