Digital Commons Network^™

Determination Of Local Elastic Modulus Of Soft Biomaterial Samples Using Afm Force Mapping, Faieza Saad Ejweada Bodowara

Theses and Dissertations

Conventional methods of mechanical testing cannot measure properties of soft materials at the nanoscale. In fields such as tissue engineering, it is important to distinguish the bulk elastic modulus from the surface elastic modulus and to characterize the spatial distribution of material with non-uniform stiffness. One of the important new methods of testing is the force mapping using the atomic force microscope. The existing force mapping approaches often suffer from omitting important effects that might result in artifacts. The most important effects include taking into account sample’s adhesion and viscoelasticity and considering more realistic probe shapes. In this work, we …

Examining Two Structural Equation Models To Determine The Effect Of Parental Practices And Familial Cultural Values On Mexican Adolescents’ Sexual Health, Efren A. Velazquez

Theses and Dissertations

Sexual behavior is a normative part of adolescence and it is important to understand how familial factors influence Latina/o adolescents’ sexual health. The current study examined two structural equation models (SEM) and the associations between familial cultural values (i.e., familismo and filial piety), maternal and paternal monitoring (i.e., disclosure and solicitation) and Latina/o adolescent’s sexual behavior (i.e., intentions to have sex, sexual behavior, sexual responsibility). A hypothesized SEM examined whether paternal/maternal monitoring mediated the relation between familial cultural values and adolescents’ sexual health, while an alternative SEM examined whether familial cultural values mediated the association between paternal/maternal monitoring and adolescents’ …

Gender Beyond Binary, Sidra Zubairi

Theses and Dissertations

Transgender individuals challenge the binary definition of gender accepted in Pakistani society and as a result, Pakistan’s transgender community is highly marginalized. Pakistani society regards transgender individuals as “abnormal,” because their physical appearance and behavior fail to conform with conventional expectations. Based on contextual research and interviews conducted with transgender individuals in Pakistan, my thesis explores the obstacles transgender individuals face in the course of everyday survival. My research responds to the physical realities of being transgender in Pakistani society and analyzes cultural norms associated with gender, which trigger harassment. By designing transformable apparel for these individuals, informed by primary …

Anxious?: Re-Designing Women’S Jewelry To Help Manage Symptoms Of Anxiety Disorders, Nourbanu Feras Hijazi

Theses and Dissertations

Anxiety is a common and often stigmatized condition. Destigmatizing mental disorders can positively impact people’s interaction and communication with others and can prompt conversations in which people share their experiences with mental health, leading to improved societal understanding and perception.

My design solution tackles behavioral symptoms of anxiety, specifically two conditions that fall under obsessive-compulsive behavior: Dermatillomania and Trichotillomania. By redesigning women’s jewelry to specialized accessories, my intention is for these objects to help destigmatize these conditions and relieve symptoms of maladaptive behaviors and hurtful impulses. By redirecting these irresistible urges to an external artifact, the objects are designed to …

Impaired Cardiorespiratory Fitness Following Thoracic Radiotherapy, Justin M. Canada

Theses and Dissertations

Cancer (CA) is the second leading cause of death in the United States preceded only by cardiovascular disease (CVD). Over the past 30 years, the 5-year survival rate for all cancers combined has increased by more than 20%. This improved survival rate is due to early diagnosis and advances in treatment involving a multimodality treatment approach that includes radiotherapy [RT] with about half of all CA patients receiving some type of RT sometime during the course of their treatment. Cardiotoxicity is one of the most important adverse reactions of RT and leads to a meaningful risk of CVD-related morbidity and …

Utilizing Voltage-Gated Calcium Channels To Assess The Activity Of Cathinone Derivatives At Human Monoamine Transporters, Brian A. Ruiz

Theses and Dissertations

Cathinones are psychostimulant compounds heavily implicated as drugs of abuse. They exert their physiological actions at the monoamine transporters, which are responsible for maintaining synaptic neurotransmitter homeostasis. Monoamine transporters produce currents during transport and have been shown to depolarize cell membranes and activate voltage-gated calcium channels in mammalian expression systems. This phenomenon is harnessed in an assay which measures these induced calcium transients, allowing for quantification of pharmacodynamic effects of compounds at monoamine transporters. It is unknown if this electrical coupling occurs in neurons, but the implications if it does are significant. In the current work, fluorescent resonance energy transfer …

Impact Of Phosphoinositides On Regulation Of K-Atp By Atp And Hydrogen Sulfide, Tyler Hendon

Theses and Dissertations

Hydrogen sulfide (H2S) reduces ischemia reperfusion (IR) injury by stimulating adenosine triphosphate (ATP) sensitive potassium channels (KATP) [1-5]. Demonstrating H2S stimulation is unique to KATP, as other inwardly rectifying potassium (Kir) channels demonstrate inhibition or are unaffected [6]. We recently showed that H2S inhibits Kir2 and Kir3 by decreasing channel sensitivity to phosphatidylinositol 4,5-bisphosphate (PI(4,5)P2 or PIP2) [6]. Here, we test the hypothesis that H2S regulation of Kir6.2, a pore-forming subunit of the KATP channel, is also dependent on PIP2. Using whole-cell patch-clamp we show that H2S increases the activity of Kir6.2 channels expressed in HEK-293 cells. To study the …

Aerobic Exercise Exposure Targeting Anxiety Sensitivity: Effects On Associated Health Behaviors In Young Adults, Autumn Lanoye

Theses and Dissertations

Anxiety sensitivity (AS) is associated with health behaviors such as low rates of physical activity, overeating, alcohol use, and poor sleep; however, interventions targeting AS via exercise-based interoceptive exposure have not assessed these as outcomes. In addition, previous studies are limited by brief follow-up periods. This study aimed to replicate previous aerobic exercise interoceptive exposures with an extended (6-week) follow-up and measurement of health behaviors.

Participants were 44 sedentary young adults with elevated AS randomized to intervention (6 20-minute sessions of moderate-intensity treadmill walking) or assessment-only control. Assessments took place at baseline, week 2 (post-treatment), week 4, and week 8 …

Periodontal Therapy Improves Oral And Gut Microbiota And Reduces Systemic Inflammation And Endotoxemia In Patients With Cirrhosis, Payam Matin

Theses and Dissertations

Objectives: The aim of this pilot study was to compare the changes in oral and gut microbiota, endotoxemia, and systemic and local inflammatory markers following oral interventions in subjects with and without cirrhosis.

Methods: Study subjects displaying gingivitis or mild/moderate periodontitis were placed into two groups: with cirrhosis (n= 24) and without cirrhosis (n=21). Each subject received nonsurgical periodontal therapy. Serum, stool and saliva samples were collected prior to and 30 days post-therapy and analyzed for stool/saliva microbiome, MELD score, endotoxin and IL-6 levels.

Results: There was no difference in age, gender and the periodontal disease status between groups. At …

Oncogene Induced Dna Replication In Lung Injury Repair And Carcinogenesis, Shilpa Singh

Theses and Dissertations

Deregulation of genome duplication is a common theme in cancer cells. Although multitude of pathways has been discovered and implicated in the ability of oncogenes or loss of function tumor suppressors to induce oncogenesis, most of the pathways ultimately converge in deregulated genome duplication or uncoupling of DNA replication and segregation in cancer cells. It is important to determine how known oncogenes deregulate genome duplication, and if prevention of deregulated genome duplication could be a feasible target to thwart uncontrolled proliferation of cancer cells. Conventional paradigm ascribes the cell proliferative function of the human oncoprotein mouse double minute2 (MDM2) primarily …

Accuracy Of A Smartphone-Based Orthodontic Treatment Monitoring Application, Heather Moylan

Theses and Dissertations

Objectives: Dental Monitoring® (“DM,” Dental Monitoring, Paris, France), is a cloud-based software that allows orthodontists to track patients’ treatment remotely. The purpose of this study was to investigate the accuracy of the software in making linear measurements.

Methods: Patients took intraoral photographs using the DM application, immediately followed by impressions for plaster models. Intercanine and intermolar width and arch depth measurements were made by DM and compared to measurements made on the plaster models. Data was analyzed using two one-sided t-tests for equivalence with equivalence bounds of

+/-0.5mm. Significance level was set at 0.05.

Results: Thirty sets of measurements were …

Metalloglycomics: Investigating The Interactions Of Metal Complexes With Heparan Mimetics, Wyatt Johnson

Theses and Dissertations

Proteoglycans containing Heparan Sulfate (HS), a sulfated glycosaminoglycan (GAG), play a major role in the cell signaling process, interacting with many different proteins. HS is over expressed on the surface of many cancer cells. Enzymatic cleavage of HS-GAGs by heparanase causes release of angiogenic growth factors leading to tumor cell migration. Heparanase is also over-expressed in tumors with significant correlation between metastatic potential and heparanase activity. Proteoglycans and their associated enzymes are thus significant drug targets of high biological relevance.

A functional consequence of strong PPC-HS binding has been shown in proof-of-concept studies confirming inhibition of the model pentasaccharide, Fondaparinux, …

Orientia Tsutsugamushi Modulates Endoplasmic Reticulum Stress To Benefit Its Intracellular Growth And Targets Nlrc5 To Inhibit Major Histocompatibility Complex I Expression, Kyle G. Rodino

Theses and Dissertations

Scrub typhus, caused by the obligate intracellular bacterium Orientia tsutsugamushi, afflicts one million people annually. Despite being a global health threat, little is known about O. tsutsugamushi pathogenesis. Here, we demonstrate that O. tsutsugamushi modulates the ER and ER-associated processes as mechanisms of nutritional virulence and immune evasion. To obtain amino acids to fuel replication, O. tsutsugamushi simultaneously induces ER stress and the unfolded protein response (UPR) while inhibiting ER-associated degradation (ERAD) during early infection time points. During exponential growth, the bacterium releases the ER bottleneck, resulting in generation of ERAD-derived amino acids that it parasitized for replication. …

Prevalence And Factors Of Sibling-Recurrent Dental Treatment Under General Anesthesia, Brandy N. Edmonds

Theses and Dissertations

Objective/Aims: Assess the prevalence of sibling recurrent dental general anesthesia (DGA) at VCU Pediatric Dentistry. Assess factors that contribute to sibling recurrent dental general anesthesia. Methods: The guardian of patients with siblings were provided a questionnaire to assess the prevalence and factors associated with recurrent DGA. Results: A total of 40 families with a child presenting for GA and at least one sibling were included in the study. Of these, 45% had sibling-recurrent GA treatment (20% in one sibling; 25% in 2 or more siblings). Additionally, 13% of the children currently presenting for GA had already been treated under GA, …

Using The Frog Epidermis To Uncover Desmosome Function And Regulation In The Developing Embryo, Navaneetha Krishnan Bharathan

Theses and Dissertations

The desmosome is one of the major cell adhesion junctions found in the epithelia, heart, and hair follicle. Described as a “rivet” that hold cells together, it provides these tissues with the integrity to withstand the tremendous forces they face in everyday life. Defects in this junction can lead to devastating diseases where patients are susceptible to skin infections and cardiovascular defects. Limited treatments exist for diseases of the desmosome, and strategies do not target all symptoms. Therefore, delineating the function and regulation of desmosomes is of paramount importance for the development of prevention and treatment strategies. The Xenopus laevis …

Anxiety In Menopause: A Qualitative Inquiry, Eleanor Bremer

Theses and Dissertations

Background: Anxiety is one of the mood symptoms experienced by menopausal women; however, anxiety symptoms during menopause have received little attention in the literature despite the potential impact on quality of life. Many of the tools used to evaluate and measure anxiety associated with menopause assume that menopausal anxiety shares similar criteria as anxiety disorders and this may not be entirely true. There are very few studies that have assessed anxiety in the context of menopause leaving the concept of menopausal anxiety not well defined and raising the question: Is menopausal anxiety a unique and distinctly different syndrome? The purpose …

Directing Mesenchymal Stem Cells For Periodontal Regeneration, Charles Stoianovici

Theses and Dissertations

Background: Directing autogenous Mesenchymal Stem Cell (MSC) to defect sites has a great promise in bone regeneration. We designed a MSC specific, bone affinity peptide (E7HA7) by conjugating E7 with a polyglutamate hydroxyapatite (HA) binding motif. We sought to characterize the in-vivo releasing pattern and bioactivity of E7HA7. Methods: HA discs were coated with fluorescent labeled peptides E7HA7, E7HA2 or E7 were subcutaneously implanted in Sprague Dawley rats. In an ectopic bone formation model was used to test the in-vivo bioactivity of E7HA7 conjugated to DBM. Results: E7HA7 showed slower peptide release from scaffolds in comparison to other groups, being …

The Cognitive And Functional Impact Of Open Heart Surgery: A Pilot Study Including Three Common Procedures (Coronary Artery Bypass Graft, Heart Valve Replacement, And Left Ventricular Assist Device), Robert Fix

Theses and Dissertations

This study investigated the impact of open heart surgery (Coronary Artery Bypass Graft, Heart Valve Replacement, or Left Ventricular Assist Device placement) on cognition, functional performance, and mood in the three months following surgery. The Montreal Cognitive Assessment (MoCA), Kettle Test (KT), Physical Self Maintenance Scale (PSMS), and Hospital Anxiety and Depression Scale (HD) measured global cognition, functional cognition, functional performance, and mood states, respectively.

Thirteen male participants (ages 38 – 75) completed assessments at four time points -- when they were scheduled for surgery, within one week prior to surgery, before hospital discharge after surgery, and three months after …

Metabolic Engineering Of Serratia Marcescens, Qiang Yan

Theses and Dissertations

The potential value of the chitin biomass (e.g. food waste) is recently considered being ignored by landfill. Chitin can be a potential cheap carbon source for converting into value-added chemicals by microorganisms. Serratia marcescens is a chitinolytic bacterium that harbors endogenous chitinase systems. With goals of characterzing S. marcescens chitinolytic capabilities and applying S. marcescens to chemical production from chitin, my dissertation main content includes five chapters: 1) Chapter 1 highlights background information of chitin source, S. marcescens and potential metabolic engineering targets using chitin as a substrate; 2) Chapter 2 demonstrates that ChiR is a key regulator in regulating …

The Progress On Mapping Ubiquitin Signaling Using Photocrosslinking Mono And Di-Ubiquitin Probes And Other Ubiquitin Moieties, Courtney N. Braxton

Theses and Dissertations

Ubiquitin (Ub) is a small, 76 amino acid, and post-translational modification (PTM) protein in eukaryotes. Modification of a substrate protein via the covalent attachment of the C-terminal glycine of Ub to the ε-amino group of lysine residues in a substrate is termed ubiquitination. Unlike, other PTM proteins, Ub can form polyUb chains at one or more of its seven lysine residues. (K6, K11, K27, K29, K33, K48, and K68). The consequence of these different polymerization sites is altered biological response with different polyUb linkages conferring different fates to target proteins. Unfortunately, the study of these chains have been limited by …

A Familiar House, William Lenard

Theses and Dissertations

The landscapes of my home in Connecticut are important to me. When I was young, I went to the woods for seclusion and comfort. While I wandered through the woods, I discovered a passion for storytelling. Now that I no longer live in New England, I miss the familiar landscapes of home. As a way to portray my sentiment, I write poetic narratives and create objects to illustrate natural landscapes.

I combine my interests of classic Americana art and literature with brutalist architecture and modern furniture to create immersive installations. I work with concrete and hardwood to materially bridge the …

Heparan Sulfate, A New Target For Platinum In Metastatic Tnbc, Samantha J. Katner

Theses and Dissertations

Abstract

Heparan Sulfate, A New Target for Platinum in Metastatic TNBC

Author: Samantha J. Katner, Ph.D.

A dissertation submitted in partial fulfillment of the requirements for the degree of Doctor of Philosophy

Virginia Commonwealth University, 2018

Advisor: Dr. Nicholas Farrell, Professor, Chemistry Department

Heparan sulfate proteoglycans (HSPGs), composed of the linear polysaccharide heparan sulfate (HS) conjugated to a protein core, are located on the cell surface and extracellular matrix. The HS chains display varying degrees of sulfation, which constitutes the molecular recognition motif for many HS-protein interactions. HSPGs, associated growth factors, and heparanase promote tumor progression by facilitating invasion, angiogenesis, …

Graphene As A Solid-State Ligand For Palladium Catalyzed Cross-Coupling Reactions, Yuan Yang

Theses and Dissertations

Palladium-catalyzed carbon-carbon cross-coupling reactions have emerged a broadly useful, selective and widely applicable method to synthesize pharmaceutical active ingredients. As currently practiced in the pharmaceutical industry, homogeneous Pd catalysts are typically used in cross-coupling reactions. The rational development of heterogeneous catalysts for cross-coupling reactions is critical for overcoming the major drawbacks of homogeneous catalysis including difficulties in the separation, purification, and quality control process in drug production. In order to apply heterogeneous catalysis to flow reactors that may overcome this limitation, the catalyst must be strongly bound to a support, highly stable with respect to leaching, and highly active. While …

Placental Eicosanoids And Sphingolipids In Preeclampsia, Daniel T. Reep

Theses and Dissertations

Placental dysfunction is implicated in the pathogenesis of preeclampsia. Chemical signals between the placenta and maternal circulation are a suspect cause of endothelial dysfunction and maternal hypertension. This study examined select lipid mediators of inflammation produced by the placenta. Patients were recruited from Virginia Commonwealth University’s pregnancy clinics and placentas were collected at delivery. Forty-eight-hour explant cultures of villous placental tissue were used to model lipid production. Electrospray ionization mass spectrometry was used to quantify concentrations of free lipids in the culture media. Bicinchoninic acid assays were performed to quantify protein in each culture for normalization of lipid data. After …

Role Of C121a In Mglur2 Homodimeric Expression And Function, Jong M. Shin

Theses and Dissertations

The group II metabotropic glutamate receptors are known for their involvement in various psychiatric disorders. The mGluR2 in particular is linked with etiology of schizophrenia especially in the context of crosstalk with 5-HT2A. Thus, the mGluR2 has attracted attentions for its potential therapeutic applications. Despite numerous physiological evidences on the actions of mGluR2, its mechanism is still unclear to this day. It is partially due to the lack of understanding in characteristics of mGluR2 homodimer which is its functionally active form. Therefore, the characterization of dimeric interaction serves as a foundation to advanced understanding of the role of mGluR2. On …

Novel Insights Into The Contribution Of Cellular Senescence To Cancer Therapy: Reversibility, Dormancy And Senolysis., Tareq Saleh

Theses and Dissertations

Cellular senescence a specialized form of growth arrest that contributes to the pathogenesis of several aging-related disorders including cancer. While by definition tumor cells are considered immortalized, they can undergo senescence when exposed to conventional and targeted cancer therapy. Therapy-Induced Senescence (TIS) represents a fundamental response to therapy and impacts its outcomes. However, TIS has been considered a positive therapeutic goal since senescent tumor cells are expected to enter a state of permanent growth abrogation. In this work we examined the hypothesis that a subpopulation of senescent cells can re-acquire proliferative potential after a state of senescent dormancy, indicating that …

Trna Profiling Of Mesenchymal Stem Cell Exosome, Khin Mimi San

Theses and Dissertations

Background: Exosomes have great potential in regenerative medicine through the

transfer of their bioactive cargos, such as RNA. tRF RNA and tiRNA are tRNAderived

non-coding RNA. Here, we sought to identify the tRF/tiRNA profile in human

mesenchymal stem cell (hMSC) exosomes. Methods: Bone marrow hMSCs were

cultured with/without osteogenic differentiation medium and exosomes were

harvested. RNA was extracted from: 1) control cells (Cell-NT); 2) control exosomes

(EXO-NT); 3) differentiated cells (Cell-OM); 4) exosomes produced by differentiated

cells (EXO-OM). RNA was sequenced to profile the small RNA with a focus on

tRF/tiRNA. Results: tRF/tiRNA was highly enriched in hMSC exosomes. Less …

Regulation Of Prostaglandin D2 And Angiogenesis-Related Factors From Human Skin Mast Cells By Interleukin-6 And Resveratrol, Cody Cody Mchale

Theses and Dissertations

Mast cells are classically recognized as the effector cells of Immunoglobulin E (IgE)-mediated hypersensitivity reactions (i.e. allergic reactions). Mast cells also play an important role in the innate immune response to parasitic helminth infection. Allergic disease including allergic rhinitis, asthma, atopic dermatitis, and anaphylaxis, is a major health concern in the United States with greater than 60 million Americans suffering from allergy and asthma. In addition, mast cells have more recently been implicated in non-allergic disease including various human cancers, which will affect approximately 39.6% of U.S. men and women. Therefore, understanding the immunological and molecular mechanisms that regulate mast …

Advancing Understanding Of Dynamic Mechanisms In Onset To Event Models: Discrete Time Survival Mediation With A Time Variant Mediator, Heather Lasky Mcdaniel

Theses and Dissertations

Integrating discrete time survival and mediation analytic approaches, discretetime survival mediation models (DTSM) help researchers elucidate the impact of predictors on the timing of event occurrence. Though application of this model has been gainful in various applied developmental and intervention research contexts, empirical work has yet to consider how DTSM models operate with a mediator that has a varying effect over time. The importance of examining this situation has important impacts for application of the model, given more complex statistical models are required, and subsequent interpretation of model parameters differ from the basic DTSM model. The overarching purpose of this …

Selective Deposition Of Platinum By Strong Electrostatic Adsorption Onto Cobalt- And Iron-Based Catalysts For Fischer-Tropsch Synthesis, Fahad A. Almalki

Theses and Dissertations

Cobalt and iron based catalysts are commercially predominant for Fischer-Tropsch synthesis, Co-based catalysts for their stability, activity, and inactivity for the water gas shift reaction and Fe-based catalysts for their cheap cost, high light-olefins and alcohols selectivity, and tolerance to H2/CO ratio. These catalysts are structure sensitive with lower activity at nanoparticle sizes smaller than 6-8 nm. Co-based catalysts exhibit high activity, low CH4 selectivity, and high C5+ selectivity, while Fe-based catalysts are more selective to low-molecular-weight hydrocarbons such as olefins and alcohols. The reducibility of cobalt and iron is another important factor which may be key for improving their …