Digital Commons Network^™

Analysis Of The Gtp Cyclohydrolase I/Tetrahydrobiopterin Pathway In Glioblastoma Biology, Anh Tran

All ETDs from UAB

Glioblastomas (GBMs) are the most common primary malignant brain tumors in adults and one of the most aggressive cancers with high rates of recurrence and therapeutic resistance. In GBMs, subpopulations of highly tumorigenic cells called brain tumor initiating cells (BTICs) have the unique capacity to promote tumor maintenance, therapeutic resistance, and angiogenesis. Depending on the level, differentiation state, and tumor stage, reactive nitrogen and oxygen species inhibit or increase cancer growth and BTIC maintenance. GTP cyclohydrolase 1 (GCH1) is the rate limiting enzyme in a pathway that can regulate reactive species production but has not been thoroughly investigated in GBM. …

Strap Promotes Stemness And Tumorigenesis In Colon Cancer, Trung Vu

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Emerging data suggest that Serine-Threonine Kinase Receptor-Associated Protein (STRAP), a scaffold protein, is upregulated in several human cancers. Here, we report a novel oncogenic function of STRAP, maintaining the colorectal cancer stem cell subpopulations in a heterogeneous mixture and drug resistance by suppressing the formation of polycomb repressive complex 2 (PRC2) and epigenetically activating Notch signals in human colorectal cancer. Our data show that depletion of STRAP by shRNA sensitizes the colorectal tumor cells to drug-induced apoptosis. STRAP knockdown also contributes to the reduced stem-like phenotype of cells, indicated by reduced expression of CSC signatures and Notch signaling regulators in …

Global Analysis Of Rpl12 Epistasis Within The Yor1-Δf Biogenesis Network, Mert Icyuz

All ETDs from UAB

In frame deletion of the phenylalanine residue at position 508 of the cystic fibrosis transmembrane conductance regulator (CFTR-ΔF508) results in protein misfolding and degradation, which reduces expression and function at the plasma membrane. The resulting loss of chloride and bicarbonate transport is the molecular basis of cystic fibrosis (CF). The F508-analogous mutation in the yeast oligomycin resistance 1 gene, yor1-ΔF670, has the same molecular consequences, but the phenotypic consequence is reduced resistance to growth inhibition by oligomycin. Comprehensive, systematic and quantitative analysis Yor1-ΔF gene modifiers has been demonstrated as a powerful way to further characterize known and to discover novel …

Prenatal And Postnatal Factors Regulate Food Intake And Body Composition, Minsung Kang

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This research sought to identify the effects of prenatal and postnatal factors on systemic metabolism and the regulation of food intake, weight, and body composition. It was found that the manipulation of maternal diets influenced the systemic metabolism of offspring. The offspring of dams fed an isocaloric, low protein diet were significantly smaller and consumed less food than offspring from dams fed a control diet. In the case of the offspring from dams fed a western diet, they were significantly heavier and consumed more food than offspring from dams fed a control diet. In addition, the offspring showed altered glucose …

A Qualitative Study Of The Philanthropic Behavior Of Generation X And Crowdfunding, Donna R. Lowe

Theses and Dissertations

This applied dissertation was designed to explore the connection between social triggers, virtual validation, and philanthropic behaviours of the Generation X population. Current literature largely ignores the Generation X population and no research has yet been conducted that directly links the successful funding of crowdfunding campaigns to both virtual validation and social triggers in the Generation X population.

To explore the connection between social triggers, virtual validation, and philanthropic behaviours of the Generation X population, the writer reviewed the application of retrieving psychological motivations based on non-conscious responses by way of belongingness theory, social comparison theory, and Maslow’s Hierarchy of …

Out Of America, William Ervin King

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OUT OF AMERICA WILLIAM ‘BO’ KING ENGLISH ABSTRACT Out of America is a creative nonfiction novella that tells the story of my life as an expatriate minor, living away from the United States where I was born. The story covers a number of themes including divorce, kidnapping, race, anti-American sentiment, death, rebirth, and figuring out my place in the middle of all of it. I wanted to write this piece to finally give voice to myself and my history. The story begins with my family’s flight from the United States. This came after legal recourse had been denied following allegations …

Evaluating Fty720 As An Anticancer Agent In Models Of Ovarian Cancer, Kelly Marie Kreitzburg

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Despite satisfactory initial responses to frontline therapies that combine tumor debulking with platinum and taxane-based chemotherapies, ovarian cancer remains the principle cause of gynecological malignancies. Drug resistance at relapse contributes to poor outcomes for women diagnosed with advanced disease and underscores the need for novel therapeutic strategies. Compelling data have implicated bioactive sphingolipids and their metabolism in the development and progression of ovarian cancer. Aberrations in sphingolipid metabolism that limit levels of the tumor suppressor lipid ceramide contribute to chemotherapy resistance. This dissertation presents work investigating the anticancer efficacy of the immunomodulatory drug FTY720. The sphingosine analog FTY720 has shown …

An Investigation Of Sla Class Ii As A Xenoantigen, Joseph Ladowski

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Xenotransplantation, using genetically-modified pigs as organ donors, is a potential solution to the growing transplant organ shortage. Avoiding antibody-mediated rejection (AMR) is the remaining hurdle to widespread application. The development of a triple glycan knockout pig reduced antibody binding to clinically acceptable levels, allowing for the screening of the history of antibodies to the major histocompatibility complex (MHC). In allotransplantation, the MHC is a group of proteins divided into two classes and anti-MHC antibodies possess the ability to cause both acute and chronic AMR. The pig MHC, the swine leukocyte antigen (SLA), is a hypothesized target of antibodies. This dissertation …

Genetic Influences On Rheumatoid Arthritis In Global Populations, Vincent Albert Laufer

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Rheumatoid arthritis (RA) is a complex disease having numerous genetic and environmental risk factors the interplay of which produces RA pathobiology. While the sheer number of genetic and environmental risk factors complicates understanding of disease biology, understanding has progressed far enough for insight into the most likely mechanisms for the development of the disease. Modern studies of the genetics of RA are massively parallel, enabling researchers to systematically interrogate variants throughout the human genome for associations in genome-wide association studies or GWAS. Such studies have been carried out in European and Asian cohorts many times, and the most recent RA …

The Mechanism Of Tobacco-Induced Decrements In Mucociliary Clearance, Vivian Lin

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Chronic obstructive pulmonary disease (COPD), characterized by progressive loss of lung function including mucus obstruction and airway remodeling, is primarily caused by cigarette smoking. This pulmonary phenotype resembles that of cystic fibrosis (CF), which results from genetic mutations in the cystic fibrosis transmembrane conductance regulator (CFTR), an ion channel important in maintaining airway surface hydration and mucus clearance. Cigarette smoke exposure has been found to induce acquired CFTR dysfunction, leading to airway dehydration, abnormal mucin production, and impaired mucus transport. Smoke exposure also induces mucus hypersecretion and ciliary dysfunction; together, these changes result in defective mucus clearance and subsequent muco-obstruction. …

Cortical-Subcortical Functional Connectivity Of Autism Spectrum Disorders, Jose Omar Maximo

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Autism Spectrum Disorder (ASD) is characterized by impairments in social communication and the presence of repetitive behaviors and restricted interests. Studies examining functional brain networks have risen exponentially over the last decade and have characterized ASD as a disorder of altered brain network connectivity and organization. These studies typically rely on blood oxygen level-dependent (BOLD) signal correlations between two or more regions in the cerebral cortex and make inferences about brain connectivity. However, brain connectivity differences might span subcortical regions such as the thalamus and basal ganglia as well; and only a few studies have examined cortico-subcortical connectivity in ASD. …

Inception Of A Cellulose Nitrate-Layered Silicate Nanocomposite Coating: Study Of The Formulation Procedure, Degree Of Dispersion, Coating Properties, And Uv Stability, Precious Mitchell

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Cellulose nitrate lacquer is a coating system that is used in the conservation of silver art pieces in museums. This coating degrades prematurely in the presence of extensive light exposure, which is prominent in display cases, thus comprising the surface of the art piece. When facing this fact, it is imperative to create a new polymer coating system with an in-crease in barrier properties so that the life expectancy of the coating increases. The synthesis of a cellulose nitrate-layered silicate nanocomposite coating stands to enhance the barrier properties of cellulose nitrate through proper dispersion of layered silicates. A proper formulation …

Neighborhood Disorder And Risky Sexual Behaviors In Adolescents, Catheryn Orihuela

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This present study addresses the effect of neighborhood decay and a need for security on early sexual initiation, use of contraception, number of sexual partners, teen pregnancy and sexually transmitted infection (STI). As part of a larger investigation of adolescent health (Healthy Passages) the sample included 1,253 youth who were recruited from 5th grade classrooms in public schools in Birmingham, Alabama and followed throughout adolescence [1]. At baseline (Mage=11 years), trained observers completed assessments of neighborhood decay and security; geocoded census tract data yielded a composite measure of concentrated poverty; and youth and parents reported on their demographics and family …

Examining The Role Of Injustice Perception In A Multiethnic Sample Of Individuals With Chronic Low Back Pain, Terence Matthew Penn

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Chronic low back pain (CLBP) is among the most disabling, costly, and painful conditions worldwide. In the United States, there is consistent evidence that the burden of chronic pain and associated disability disproportionately affect non-Hispanic Blacks (“Blacks”) compared to non-Hispanic Whites (“Whites”), with Blacks reporting greater pain frequency, severity, and disability. Moreover, emerging evidence suggests that perceptions of injustice related to personal pain or injury is a crucial risk factor for poor outcomes in chronic pain, including persistent musculoskeletal pain disorders. Although racial differences have been reported for multiple chronic pain conditions, relatively minimal attention has been given to potential …

T Cell Immunity Directed Against Novel Anti-Sense Cryptic Epitopes And Its Impact On Hiv Viral Evolution, Binghao Jason Peng

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After nearly four decades of scientific research, a global solution in eradicating the human immunodeficiency virus - 1 (HIV-1) pandemic has still yet to be discovered. The advent of antiretroviral therapies (ART) has significantly decreased the diseases burden for those infected with the virus; however, the access to ART is often limited to those with the financial abilities to afford it. For this reason, finding a way to vaccinate against HIV-1 successfully remains a sought-after pragmatic solution to this worldwide health issue. HIV immunological studies have taught us that increasing the breadth of response to the virus holds significant potential …

Mucus Adhesion As A Therapeutic Target In Cystic Fibrosis, Courtney Fernandez Petty

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Cystic fibrosis (CF) is a genetic disease resulting from mutations of the cystic fibrosis transmembrane conductance regulator (CFTR) gene. CFTR is an ion channel responsible for proper movement of chloride and bicarbonate ions across the apical cell surface. Defective CFTR results in an absence of bicarbonate transport, which functions in part to chelate Ca2+, a divalent cation found in abundance in mucin granules in normal conditions; this yields a hyperviscous and adhesive mucus on the respiratory and gastrointestinal tracts of patients with CF. Bronchial mucins are glycosylated proteins with neutral and negative sugars modified by negatively charged sialic and neuraminic …

Transcriptional Changes Underpinning Poor Prognosis And Chemoresistance In Pancreatic Cancer, Ryne Ramaker

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With a 5-year survival rate of 7% and only marginal improvements in recent dec-ades, pancreatic adenocarcinoma (PDAC) survival statistics present a disheartening chal-lenge. A majority of the high mortality rate associated with PDAC is due to late-stage diagnosis and limited efficacy of the current chemotherapeutic arsenal. This work is largely focused on the ~20% of tumors detected prior to metastasis for which curative surgical resection can be combined with chemotherapy and radiation therapy, increasing the 5 year survival rate to ~25%. Although a subset of these patients who undergo surgi-cal resection experience sustained remission, a majority of patients still relapse …

The Effect Of Novel Antibiotic Compounds On Endodontic Biofilms, Steven Rhodes

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Purpose: To investigate the effects of three novel experimental antibiotics on monospecies (Enterococcus faecalis) and polymicrobial (mixed) endodontic biofilms. Materials and Methods: Biofilms containing pure Enterococcus faecalis, as well as biofilms derived from mixed bacterial samples aspirated from inside the pulp spaces of necrotic human teeth, were grown onto slices of human dental in vitro. Biofilm formation capability was verified with SEM. The treatment groups consisted of 3 novel experimental antibiotics. 8.25% sodium hypochlorite and sterile saline were used as the controls. The biofilms were investigated with live/dead fluorochrome staining and confocal laser scanning microscopy. Results: The full strength sodium …

Modeling And Analysis Of Iot Systems Using Shannon's Channel Model, Anthony G. Winchester

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The Internet of Things (IoT) is a ubiquitous technology that can mark the evolution of modern world. Since the internet has become a common household resource like the land line was in the past, it is time to take technology to the next level. With the manipulation of signals, we now have the use of wireless devices that are connected to various devices (both wireless and wired). The idea is to not only engineer devices that connect to the web, but also make them smart using processors embedded in devices coupled with internet to provide an intelligent system. Our research …

Assessing The Comparative Effect Of Tocilizumab On Risk Of Cardiovascular Disease Among Rheumatoid Arthritis Patients Using Claims Data: A Direct Comparison Among Biologic Disease-Modifying Antirheumatic Drugs, Fenglong Xie

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ASSESSING THE COMPARATIVE EFFECT OF TOCILIZUMAB ON RISK OF CARDIOVASCULAR DISEASE AMONG RHEUMATOID ARTHRITIS PATIENTS USING CLAIMS DATA: A DIRECT COMPARISON AMONG BIOLOGIC DISEASEMODIFYING ANTIRHEUMATIC DRUGS FENGLONG XIE PhD-EPID ABSTRACT Tocilizumab is a humanized monoclonal anti-body against the interleukin-6 receptor and is effective in the treatment of rheumatoid arthritis (RA) [1]. Multiple studies have observed unfavorable changes in the lipid profile of tocilizumab-treated RA patients. Few studies have compared the cardiovascular disease (CVD) risk associated with tocilizumab to other biologic disease-modifying antirheumatic drugs (bDMARDS). Due to limitations in existing studies, the real-world association of tocilizumab with CVD risk remains uncertain. …

Novel Anti-Cancer Therapy Development Using Omics Guided Rational Cell Process Engineering, Ningning Xu

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Cancer is one of the leading causes of mortality globally, and multiple anti-cancer therapies have been developed and applied over last few decades. Antibody-based cancer therapies have been on one of the most exciting and promising therapeutic strategies. Monoclonal antibodies (mAbs) can control the progression of cancers via targeted binding to the specific antigen of tumors to trigger an immune response, target and block the signaling pathway involved in cancer progression, or deliver cytotoxic agents into tumors. Two chimeric/humanized monoclonal antibodies (anti-HER2 mAb and anti-CD 20 mAb) with higher efficacy were successfully expressed in engineered Chinese Hamster Ovary Cells (CHO). …

Shaped Stimuli-Responsive Layer-By-Layer Hydrogels For Targeted Drug Delivery, Bing Xue

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The development of polymeric delivery systems help overcome the intrinsic drawbacks of systemically-delivered therapeutic drugs, such as poor solubility and stability, multidrug resistance, inefficient accumulation in the diseased sites and unexpected toxicity to normal tissues. Polymeric vehicles possessing stimuli-sensitivity can prevent premature drug leakage and enable controlled cargo release. The modification with bioactive ligands aids to the accumulation of carriers in the targeted tissues to locally increase the concentration of therapeutics and decrease off-target toxicity. The manipulation of physical characteristics (e.g. size, shape) is also essential in the design of drug delivery systems since these properties play pivotal roles in …

Effects Of Dietary R,S-1,3 Butanediol Diacetoacetate On Components Of Energy Balance, Rachel A H Davis

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Ketogenic diet (KD) has been used to attenuate the decline in energy expenditure occurring from calorie restriction-induced weight loss, but long-term adherence can be difficult due to the strict nature of the diet. The growing body of evidence supporting KD-treatment of neurologic and metabolic diseases, as well as obesity, has prompted interest in the ability to increase circulating ketones via exogenous delivery. Ketone esters (KE) can raise blood ketone concentrations similarly to fasting and appear to reduce food intake acutely, but studies assessing effects on energy balance are limited and provide a potentially promising direction for weight control. Previous investigations …

Macrodomain Mystery: Investigating The Structure-Function Link In Novel Tylonycteris Hku4 And Rousettus Hku9 Coronavirus Proteins, Robert Glenn Hammond

All ETDs from UAB

Since 2003, two severely human pathogenic viruses have emerged as a formidable health threat with no effective treatment to date. These viruses belong to the coronavirus (CoV) family. Upon infection, this viral family uses host cell machinery to translate nonstructural proteins (nsps) which are used to facilitate the viral life cycle. The first major human viral threat, the severe acute respiratory syndrome (SARS) virus, contains a multidomain region within its nsp3 called the SARS Unique Domain (SUD). This region contains macrodomains, which are implicated in viral replication. Macrodomains bind monomeric and polymeric ADP-ribose, a biomolecule involved in many cellular processes. …

Elucidating The Role Of Hedgehog Signaling In Modulating Macrophage Function In Breast Cancer, Ann Hanna

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In the tumor microenvironment, breast cancer cells participate in crosstalk with the surrounding stroma. This tumoral-stromal interaction forms a balance that dictates tumor suppressing or tumor promoting response mechanisms. Macrophages in the tumor microenvironment are plastic and can mediate several functions depending on their activation states. Tumor associated macrophages co-exist as two major phenotypes: anti-tumorigenic and immune-eliciting classically activated M1 as well as tumor-promoting and immune-suppressive alternatively activated M2 macrophages. Alternatively activated macrophages are specifically associated with more aggressive stages and poor clinical outcomes in breast cancer patients as they suppress the tumoricidal properties of the immune system, thus facilitating …

Applications Of Next-Generation Sequencing And Functional Genomics In Translational Medicine, Andrew Hardigan

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The development of next-generation sequencing (NGS) technologies has led to unparalleled advances in our understanding of the genetic basis of disease, evolution, and genetic and genomic regulation. Building on the advances made in the Human Genome Project and more recent efforts such as the Encylopedia of DNA Elements (ENCODE) and the Roadmap Epigenomics Project, whole-genome and whole-exome sequencing (WGS/WES) and a wide variety of NGS-enabled functional assays are bridging the gap between scientific discovery and clinical medicine. This trend towards genomically informed “bench-to-bedside” translational medicine is driven in large part by the sharply decreasing costs for NGS in both clinical …

A Qualitative Descriptive Study Exploring The Adaptation Of Families Of Children With Multiple Sclerosis From The Perspective Of Family Caregivers, Yolanda Carol Harris

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Two to 5% of the US population of individuals afflicted with multiple sclerosis (N = 400,000) are diagnosed prior to the age of 18 with pediatric onset multiple sclerosis (POMS). Most children and teens with POMS have a relapsing remitting course of the disease with unpredictable relapse onset causing cognitive and physical disability. This can result in school absences, hospital and outpatient visits, poor academic performance and interruption in normal social activities. In turn, these individuals may develop an inability to provide self-care, which could lead to poor quality of life. POMS can affect the individual diagnosed but may also …

Evaluation Of The Factors Influencing Feed Intake And Satiety Of The Variegated Sea Urchin, Lytechinus Variegatus, Marlee Hayes

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Feed intake is the primary determinant of nutrient and energy acquisition for most metazoans. Satiety regulates feed intake and may have cascading effects on nutrient acquisition and health. Satiety of many higher organisms involves complex processes and a variety of signaling molecules that are responsive to many factors associated with nutrient intake. However, the ability to sate is observed in many simpler animals with less complex physiological processes. Sea urchins, with relatively simple digestive and nervous systems, provide an ideal model for the study of fundamental drivers of feed intake. Understanding the process of satiety in this primitive deuterostome can …

Diginol: A Joule-Heated Binary-Partitioned Nitinol Actuator, Martin Dawson Holland

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New and innovative robotic designs are always needed in both research and commercial fields. To that end, new and innovative actuators are needed as well. In this paper, a digitally controlled Nitinol actuator, Diginol, is proposed. Diginol is a Nitinol actuator that uses Joule heating to individually activate partitions of a length of Nitinol. The lengths of the partitions follow a base-2 pattern, minimizing the number of partitions required for a given number of actuation lengths. Activating separate partitions instead of the entire length of Nitinol circumvents the need to account for the hysteresis and nonlinearities inherent in the transformation …

Epigenetic Regulation Of Stem Cell Fate Determination And Tumorigenesis, Kushani Shah

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It is unclear how H3K4 methylation, an epigenetic modification associated with gene activation, regulates stem cell fate determination and tumorigenesis. DPY30 is one of the core subunits of the SET1/MLL complex in mammals responsible for H3K4me. DPY30 enhances the H3K4me activity of the SET1/MLL complex. Here, I sought to define role of DPY30 and H3K4me3 in postnatal neurogenesis and hematopoietic malignancies. Using a conditional knockout model, I found that Dpy30 deficiency halts the development of postnatal hippocampus, the subventricular zone, and cerebellum. Deficiency in cerebellum is most likely the cause of uncoordinated ataxia-like movements in these mice. By deleting Dpy30 …