Digital Commons Network^™

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 …

Role Of Free Fatty Acid Receptors In The Regulation Of Brain-Derived Neurotrophic Factor Levels In The Enteric Glial And Endocrine Cells, Reem M. Alkahtani

Theses and Dissertations

Recent deorphanization of several G-protein-coupled receptors (GPRs) as endogenous receptors for free fatty acids (FFAs) has increased our understanding of these nutrients as signaling molecules and the integral role of gut microbiota in the regulation of host defense mechanisms, energy metabolism, gastrointestinal motility and secretion. There are five distinct FFA receptors (FFRAs: FFAR1, FFAR2, FFAR3, FFAR4 and GPR84) that differ in molecular structure, ligand specificity, expression pattern, and functional properties. FFARs are grouped according to the chain length of FFAs that activate each FFAR.

Enteric glial cells and enteroendocrine cells play a pivotal role in the secretion of gliotransmitters and …

Resolution Of Inflammation Rescues Axon Initial Segment Disruption, Nicholas M. George

Theses and Dissertations

Axonal domains are required for proper neuron function. These domains are unstable and degenerate concurrent with the inflammation in multiple sclerosis (MS) and the inflammatory disease models experimental autoimmune encephalomyelitis (EAE) and lipopolysaccharide (LPS) induced inflammation. Previous studies from our laboratory have shown that the axon initial segment (AIS) is maintained independently of the presence of myelin, but that AIS disruption is seen in MS as well as EAE and LPS-mediated inflammation. AIS loss can be interrupted in the early stage of EAE using the anti-inflammatory drug Didox. However, the potential for Didox directed repair of the AIS in later …

Behavioral Phenotyping Of Vmat1 Knockout Mice: Relevance To Neuropsychiatric Disorders, Kevin A. Webster Ph.D.

Theses and Dissertations

Schizophrenia is a debilitating mental disorder that causes a large economic burden and is prevalent across all cultures and countries around the world. Although both environmental factors and genetics are known to play an important role in the etiology of schizophrenia, the exact role of genetics and its interaction with environmental factors in an individual’s predisposition to develop schizophrenia is poorly understood. Schizophrenia is characterized by symptoms that include positive symptoms (e.g. delusions, hallucinations, disorganized thinking and speech), negative symptoms (e.g. avolition, anhedonia, depressive-like behavior), and cognitive dysfunctions (e.g. executive functioning deficits in learning and memory, attention, and vigilance). Genomic …

Fabrication Of Multifunctional Nanostructured Porous Materials, Ahmed A. Farghaly

Theses and Dissertations

Nanostructured porous materials generally, and nanoporous noble metals specifically, have received considerable attention due to their superior chemical and physical properties over nanoparticles and bulk counterparts. This dissertation work aims to develop well-established strategies for the preparation of multifunctional nanostructured porous materials based on the combination of inorganic-chemistry, organic-chemistry and electrochemistry. The preparation strategies involved one or more of the following processes: sol-gel synthesis, co-electrodeposition, metal ions reduction, electropolymerization and dealloying or chemical etching. The study did not stop at the preparation limits but extended to investigate the reaction mechanism behind the formation of these multifunctional nanoporous structures in order …

Loneliness, Cynical Hostility, And Cognitive Decline In Americans Above Age 50, Sarah C. Griffin

Theses and Dissertations

Background. Research identifies isolation (being alone) as a risk factor for cognitive decline— yet it is possible that subjective dimensions of isolation are more critical. Potential risk factors are loneliness (the distress stemming from feeling alone) and cynical hostility (an attitude of distrust and cynicism). The present study examined the relationship between these factors and cognitive functioning and decline.

Methods. Data came from the Health and Retirement Study, a nationally representative longitudinal study of US adults over 50. Loneliness was measured using the Hughes Loneliness Scale; cynical hostility was measured using items from the Cook-Medley Hostility Inventory. Cognitive functioning was …

Influence Of Historic Landscapes And Contemporary Species Management On Chesapeake Bay Bald Eagles And Osprey, Catherine B. Viverette

Theses and Dissertations

Influence of historic landscapes and contemporary species management on Chesapeake Bay Bald Eagles and Osprey

Catherine B. Viverette

Co-distributed species with well documented demographic histories can provide good models for testing alternative hypotheses about the impact of evolutionary history, contemporary landscapes, and species management on current distribution and population structure. The Osprey (Pandion haliaetus) and Bald Eagle (Haliaeetus leucocephalus) have been extensively studied, managed and monitored across their North American breeding range, particularly in the Chesapeake Bay. We used a combination of ecological niche modelling, diet reconstruction, and population genetic modeling to understand the role of …

Causes And Consequences Of Peer Victimization Among Adolescents With Autism, Sarah T. Doyle

Theses and Dissertations

A significant, yet understudied issue that demands attention is the experience of peer victimization among adolescents with autism spectrum disorders (ASDs). Research indicates that youth with disabilities, including those with ASDs, are victimized more frequently as compared to their typically developing peers. However, little is known about the peer victimization experience for adolescents with ASDs beyond its frequency of occurrence. This study examined relations between peer victimization and individual, peer, and parent factors and outcomes including internalizing and externalizing symptoms among adolescents with ASDs. No significant indirect effects were found for peer victimization on relations between individual social-cognitive and emotion …

Interactions Of The Naphthalene Radical Cation With Polar And Unsaturated Molecules In The Gas Phase, Sean P. Platt

Theses and Dissertations

Characterizing the interactions of solvent molecules with ions is fundamental in understanding the thermodynamics of solution chemistry. These interactions are difficult to observe directly in solution because the number of solvent molecules far exceed that of ions. This lend the gas phase to be the ideal medium in the study ion-solvent interactions on a molecular level. Ionized polycyclic aromatic hydrocarbon (PAH) molecules can readily form hydrogen bonds with neutral solvent molecules in aqueous and interstellar medium. Previous research has been done for stepwise solvation of small molecules such as benzene⁺, pyridine, and phenylacetylene. The similarity in these results …

Narrative And The Reconfiguration Of The Humanist Subject In Robbe-Grillet, Ballard, And Ligotti, Zachary L. Acosta-Lewis

Theses and Dissertations

This thesis examines the utility of the novels, short stories, critical writing, and generically indistinct work of Alain Robbe-Grillet, J.G. Ballard, and Thomas Ligotti in developing a critique of the contemporary manifestations of liberal humanist social, economic, and political subjectivities. To this end, the concurrence of formal fragmentation and sublime aesthetics in early Gothic fiction models the manner in which narrative structures can appropriate structural tropes of dominant institutions, critically reflecting ideological fracture. Read according to the assemblative approach outlined by Deleuze and Guattari, these authors serve as a productive and incisive response to the hegemony of capitalist territorialization with …

The Entertainment Is Terrorism: The Subversive Politics Of Doing Anything At All, Joe Woods

Theses and Dissertations

When the body is observed through a certain combination of technologies, there can be subversive politics to doing anything at all. The nature of media and biopolitics has permitted for a set of systems aimed at total control of the human body; a power which can permeate all facets of life. This thesis is a collection of essays which argues that speculative fiction contains multitudes of approaches to biopolitical discourse, permitting the reader of the text to approach politics from their own set of experiences, but not allowing the political to be ignored. These chapters contain three separate but interrelated …

A Two Host Species Stage-Structured Model Of West Nile Virus Transmission, Taylor A. Beebe

Theses and Dissertations

We develop and evaluate a novel host-vector model of West Nile virus (WNV) transmission that incorporates multiple avian host species and host stage-structure (juvenile and adult stages), with both species-specific and stage-specific biting rates of vectors on hosts. We use this model to explore WNV transmission dynamics that occur between vectors and multiple structured host populations as a result of heterogeneous biting rates. Our analysis shows that increased exposure of juvenile hosts results in earlier, more intense WNV transmission when compared to the effects of differential host species exposure, regardless of other parameter values. We also find that, in addition …

Sulfated Dehydropolymer Of Caffeic Acid For Repair Of Lung Damage And Emphysema, Tien M. Truong

Theses and Dissertations

The complex pathobiologic mechanisms of emphysema are not fully understood, leaving this deadly disease without effective pharmacotherapy for a cure. This project hypothesized that the sulfated dehydropolymer of caffeic acid (CDSO3) exhibits Fe²⁺ chelation-based hypoxia inducible factor-1a (HIF-1a) up-regulatory protective activities against in vitro emphysematous cell death and for in vivo reversal of emphysema induced with SU5416, a vascular endothelial growth factor blocker.

Using in vitro chromogenic competitive inhibition assays, CDSO3 was shown to chelate Fe²⁺ (IC₅₀ of 23 µM), but not Fe³⁺ ions. The trypan blue exclusion and lactate

dehydrogenase assays were then employed to …

Examining Genetic And Environmental Influences On Alcohol Use And Externalizing Behaviors In African American Adolescents, Neeru Goyal

Theses and Dissertations

The aim of this thesis is to expand our understanding of the etiology of alcohol misuse and related disorders in African Americans using genetically informative study designs. Specifically, we take advantage of the candidate-gene approach and polygenic score analysis to extend the literature specific to African American populations. Chapter 2 explores gene x environment (GxE) interactions through the candidate gene approach to explore the relationship between two genes chosen on their potential relevance to stress response and adolescent alcohol use and misuse, among African American youth living in highly impoverished neighborhoods, as moderated by stressful life events. Chapter 3 implements …

I Reach Toward The Ground I Reach Toward Space, Kristen A. Sanders

Theses and Dissertations

Imagine one million and six hundred thousand years ago — a prehistoric character points. There in the moistened soil, the hominid Homo habilis draws a line, inscribing with her finger the first mark. At the core of my work is a meditation on this very scene as the otherwise unknowable origins of image making. And at the center of this discovery is a prehistoric woman — a previously invisible character within human evolution. My work aims to insert these characters into the origins of tool use, image making, and other supposed markers of humanness while also examining historical representations of …

Sweaty Mother Slow Groove, Devin Kylie Harclerode

Theses and Dissertations

Sweaty Mother Slow Groove is an engagement in magical thinking that proposes a displacement of swamp methodologies into the virtual realm, existing during the fourth wave. In doing so the cyborg and goddess are united in a re-routing of essentialism and the neo-liberal domination of technology. The metaphorical swamp is the possibility of a mushy danger zone that harnesses the absorption of an unwanted space: a disintegration of the binary and the soft-coded awareness of the body as a process, not a site.

The Curiosity Of Con, Petrified Breath, And An Accident Known As Blue., Steven Randall

Theses and Dissertations

My thesis installation emerged from an interest in visualizing breath. The resulting work came to exist at the intersection between art, biology, and performance.

The unicorn tapestries were used as a generative point of departure to explore the preservation and transformation of images through time, by time, and with time. Reproductions of the six tapestries were each etched into paper and then submerged into solutions of Phenol Red dye, Ferric Ferrocyanide (also known as Prussian Blue), and various forms of sodium chloride. Exhaled breath was used to encrust these images of the tapestries into physical objects which gradually crystallized and …

Design Thinking For The Development Of Formal Operations: A Team-Based Middle School Design Curriculum, Stephanie K. O'Dell

Theses and Dissertations

In this thesis, I propose a team-based design curriculum that aligns with the cognitive development of middle school age students. The ability to think abstractly develops at a specific time in development, according to widely accepted cognitive theory. The middle school years are the launching pad of abstract thinking. At this age, students are also primed for learning through social activity. The design process often includes abstract problem solving challenges, and working within a team structure. These ideas build a foundation for a research question—could a team-based design curriculum in middle school strengthen students’ natural cognitive development by providing opportunities …

Telomere Length In Women With Breast Cancer: A Longitudinal Study Of Their Relationship To Chemotherapy And Acquired Psychoneurological Symptoms, Areej Alhareeri

Theses and Dissertations

Breast Cancer (BC) is one of the most commonly diagnosed malignancies in females. The 5-year survival rate for women with early stage BC is about 90%. However, the quality of life (QOL) for many of these women may be adversely affected due to treatment/cancer–related side effects, including a constellation of symptoms (anxiety, depression, pain, fatigue, sleep disturbance and depression), that are collectively termed psychoneurological symptoms (PNS). To gain insight into the contributory role of telomere length (TL) in the development and persistence of PNS, we have longitudinally studied 72 women (ages 23-71) with early stage BC (I-IIIA) at 5 time …

Momentum Clinic For Teen And Young Adult Cancer Patients, Merian O'Neil

Theses and Dissertations

This study explores the needs of teen and young adult cancer patients undergoing long-term chemotherapy treatments and the design of an outpatient clinic that accommodates this population’s unique needs. Most teens endure long-term treatments in a pediatric facility targeted primarily for children, while others are treated in adult facilities. Teens have different privacy and social needs than children, and while they are not adults, they are involved in their own treatment decisions, unlike children. The target age group for this study is teens and young adults, ages thirteen to twenty-two. A common theme emerged from research and interviews conducted in …

Novel Small Airway Model Using Electrospun Decellularized Lung Extracellular Matrix, Bethany M. Young

Theses and Dissertations

Chronic respiratory diseases affects many people worldwide with little known about the mechanisms diving the pathology, making it difficult to find a cure. Improving the understanding of smooth muscle and extracellular matrix (ECM) interaction is key to developing a remedy to this leading cause of death. With currently no relevant or controllable in vivo or in vitro model to investigate diseased and normal interactions of small airway components, the development of a physiologically relevant in vitro model with comparable cell attachment, signaling, and organization is necessary to develop new treatments for airway disease. The goal of this study is to …

Quantitative Analysis Of 5-Chloro-2-Methoxy-N-[2-(4-Sulfamoylphenyl)Ethyl]Benzamide (Glyburide Analogue, Ga) In Mouse Plasma And Whole Blood Using A Micro-Extraction And Liquid Chromatography-Tandem Mass Spectrometry, Ankit Zalavadia

Theses and Dissertations

Pharmacokinetic evaluation of 5-chloro-2-methoxy-N-[2-(4- sulfamoylphenyl)ethyl]benzamide in mouse plasma demanded for a suitable bioanalytical method. No reported bioanalytical method exists to-date that can quantify concentration of this compound in any biological matrix. The purpose of this study was 1) to develop and validate a new bioanalytical method using a micro-extraction and LC-MS/MS to quantify the target analyte in mouse plasma and 2) to partially validate the method in whole blood. A bioanalytical method was developed and validated in both matrices for a linear concentration range of 2-1000 ng/ml. For both matrices, the reverse predicted concentration of calibration standards (-8.95% to 12.16% …

Conditional Cardiac-Specific Akap13 Knockout Induces Sex Dependent Biventricular Dilated Cardiomyopathy With Sarcomeric And Mitochondrial Defects, Kimberlyn M. Baig-Ward

Theses and Dissertations

Heart disease is a complex and heterogeneous disease. Notably, studies have demonstrated gender differences in the expression and types of cardiovascular disease, such as dilated cardiomyopathy (DCM), a major underlying cause of heart failure. Previously we showed that loss of A-Kinase Anchoring Protein 13 (Akap13), a unique proto-oncogene and estrogen receptor modulator, resulted in enlarged embryonic hearts, defective cardiac sarcomere formation, and embryonic lethality in mice. Data have also shown cAMP-dependent Protein Kinase A (PKA) to be involved in DCM pathophysiology. Given the established role of AKAP13 in cell signaling, its ability to bind and modulate ligand-activated nuclear hormone …

Response Adaptive Randomization Using Surrogate And Primary Endpoints, Hui Wang

Theses and Dissertations

In recent years, adaptive designs in clinical trials have been attractive due to their efficiency and flexibility. Response adaptive randomization procedures in phase II or III clinical trials are proposed to appeal ethical concerns by skewing the probability of patient assignments based on the responses obtained thus far, so that more patients will be assigned to a superior treatment group. General response-adaptive randomizations usually assume that the primary endpoint can be obtained quickly after the treatment. However, in real clinical trials, the primary outcome is delayed, making it unusable for adaptation. Therefore, we utilize surrogate and primary endpoints simultaneously to …