Digital Commons Network^™

A Dual-Action, Armed Replicating Adenovirus For The Treatment Of Bone Metastases Of Breast Cancer, James Joseph Cody V

All ETDs from UAB

Most patients with advanced breast cancer develop osteolytic bone metastases, which have numerous complications. Because current therapies are not curative, new treatments are needed. Conditionally replicating adenoviruses (CRAds) are anti-cancer agents designed to infect and lyse tumor cells. For increased efficacy, CRAds have been armed with therapeutic transgenes. Osteoprotegerin (OPG), an inhibitor of osteoclastic bone resorption, represents a promising candidate with which to arm a CRAd intended to treat osteolytic bone metastases. We hypothesize that a CRAd armed with OPG will inhibit breast cancer bone metastasis and reduce tumor burden in the bone by directly lysing tumor cells and by …

Relationship Between The Neural Correlates Of Symbolic Numerical Magnitude Processing And Individual Differences In Children’S Arithmetic Competence, Stephanie Bugden

Digitized Theses

The aim of the present thesis was to bridge the gap between neuroscience and education by

exploring the cognitive and neural functions of numerical magnitude processing in 3rd and 4th gradechildren. First,thedevelopmentofthebehaviouralnumericalratioeffectwasexplored

over three testing sessions, as well as its relationship to individual differences in math achievement. Second,duringthethirdtestingsession,theneuralcorrelatesoftheratioeffect wererelatedtomathperformance. Thelongitudinalresultsrevealthattheratioeffectdecreased over time indicating children develop a precise representation of numerical magnitude with age, and this developmental trajectory is negatively correlated with math achievement scores. A significant effect of ratio was found in the prefrontal cortex and the intraparietal sulcus which was positively correlated with math achievement scores. These findings suggest …

The Role Of Community-Based Programs In Addressing Health Disparities As It Relates To Breast And Cervical Cancer In African American Women: A Systematic Review Of Studies, Rashaan Anderson

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In an effort to extrapolate the detail intricacies of how community-based programs impact public health a systematic review of the literature was performed. This research will examine ways in which community based programs reduce health disparities in breast and cervical cancer in African American women. The primary mechanism used to identify appropriate citations for systematic review and inclusion was performed using the PubMed, CINAHL, MEDLINE, EMBASE, CancerLit and PsychINFO online databases. Key-word searches to be included for were the terms community, community based participatory research, community-based organizations, community coalitions, non for profit organizations, action plan, action research, grassroots organizations, community …

Mesenchymal Stem Cell Interaction With Nanostructured Biomaterials For Orthopaedic Applications, William Charles Clem

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Orthopaedic implants fail when bone loss around the anchoring region of the prosthesis causes the components to loosen. A revision surgery is needed to replace worn components, and bone grafting is often required to fill the void caused by osteolysis. A solution for the problem of osteolysis may be the improvement of wear resistance at the articulating surfaces by substituting materials with greater hardness. This dissertation describes two strategies for increasing the surface hardness of titanium alloy (Ti-6Al-4V) implants, without increasing surface roughness or compromising osseointegration. The first strategy utilizes microwave plasma to induce titanium nitride formation by nitrogen diffusion. …

Internav2.0: Minimally Invasive Robot-Assisted Tumour Ablative Therapies, Shiva Mohan

Digitized Theses

Canadian Surgical Technologies & Advanced Robotics has undertaken a major initiative in the field of lung cancer treatment. A platform is being developed for tumour ablative therapies using minimally invasive robotic sys­ tems. As a proof-of-concept for the platform, a system has been built for Brachytherapy as a treatment for lung cancer. This system uses a navigational software, InterNAVl.O, to consolidate ultrasound imaging and electromagnetic positioning.

Early work on InterNAVl.O looked to develop a research tool to handle imaging information obtained through ultrasound imaging. It was not de­ signed as a navigation and control environment for clinical use. The objective …

Human Papillomavirus: Segregation And Replication, Luan D. Dao

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Human papillomavirus are small DNA tumor viruses. The viral genome is a small circular double stranded DNA that replicates autonomously as an extrachromosomal plasmid. Occasionally infections by the high risk HPV viruses can lead to DNA integration and progression to cancer. How the HPV DNA is maintained and becomes established in the dividing host cells is not well understood. Additionally, as a double-stranded DNA virus it is likely that double-stranded DNA breaks in the viral genome, either from replication or random damage, will trigger a DNA repair response from the host cell. Such responses have been alternatively reported to be …

Occupational Stressors, Job Satisfaction, And Back Pain In Firefighters, Mantana Damrongsak

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Occupational back pain is a significant health and safety problem in many industrialized countries for persons who are required to perform work-related forceful movement and lifting. Firefighters, an occupational group at high risk for back injury, perform many job tasks under hazardous work conditions. One-third of firefighters retire due to job-related health and safety problems and 49.4% of this group retire as a result of back pain, the leading cause of early retirements in firefighters. Most studies have examined factors influencing back problems among other workers, especially nurses and hospital workers, but few studies have investigated factors that influence back …

Metabolism Of Neutrophil-Deprived Chlorinated Isoflavones, Tracy Lyn D'Alessandro

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Despite medical advances in both drug therapy and surgical techniques, Americans mostly die from heart disease. Many belong to the low- and middle-class families who do not have sufficient access to medical care due to its high costs. An alternative is the development of healthier lifestyles such as diet which may play a positive role in chronic disease management. Epidemiological and migratory studies suggest that soy plays a pivotal role in the decreased incidence of heart disease in East Asian countries, such as China, Japan, and Korea. The role of soy in cardiovascular disease progression has been the subject of …

Analysis Of Hiv-1 Variable Loop 3-Specific Neutralizing Antibody Responses By Hiv-2/Hiv-1 Envelope Chimeras, Katie L. Davis

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Defining the epitope specificities of the neutralizing antibody response to the HIV-1 envelope protein (Env) during natural human infection and in response to vaccination by HIV-1 immunogens could provide insight into the mechanisms of virus immune containment and facilitate vaccine design. Transplantation of discrete HIV-1 neutralizing epitopes into HIV-2 Env scaffolds may provide a sensitive, biologically functional context in which to quantify specific antibody reactivities in complex sera. Here we describe the development of a novel HIV-2 proviral scaffold (pHIV-2KR.X7) into which we have substituted the env V3 region of several laboratory and primary HIV-1 strains to yield a panel …

Multiracial Tobacco, Alcohol, And Drug Use: An Investigation Of The Function Of Racial Identity In A Longitudinal Sample From Youth To Young Adulthood, Julia Katrina Crumly

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The purpose of the research is threefold. The first purpose is to determine if multiracial individuals are at a higher risk for alcohol, tobacco, and drug use. The second purpose is to determine the relationship between racial identity and risk behaviors. The third purpose is to determine how the change/no change of racial identity longitudinally contributes to one’s risk to engage in risk behaviors. A national representative longitudinal data set was obtained and analyzed for the purpose of this study. Results of the study reveal that there are differences in multiracial groups for risk behaviors, minority identification is not necessarily …

Strengthening And Rehabilitation Of Steel Bridge Girders Using Cfrp Laminates, Ahmed Sabri Abd-El-Meguid

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hile traditional retrofitting methods for steel bridge girders could be time consuming and uneconomical, an alternative repair method is suggested using Carbon Fiber Reinforced Polymers (CFRP) laminate strips, providing engineers with a competitive solution that will increase the life-cycle of repaired bridges. This study investigated its feasibility as an option to strengthen and rehabilitate steel bridges. The main advantages of using CFRP laminates are their light weight and durability, which results in ease of handling and maintenance. The dissertation conducted experimental and analytical work to evaluate the effectiveness of strengthening steel beams by the use of novel CFRP laminate strips …

Perception Of Motion-In-Depth: Induced Motion Effects On Monocular And Binocular Cues, John Eric Gampher

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Three cues are available to the visual system to determine motion: image displacement across the retina (retinal slip), eye movements, and configuration changes within a scene (Becklen and Wallach, 1985). Any one may lead to the false perception of motion. Induced motion is the illusory movement of one object (or objects) as a result of other movement in the visual field. A wide variety of displays have been used to study induced motion, leading to apparently different classes of induced motion. Current theories of induced motion can be categorized based on local motion, global motion, eye movement suppression, and cognitive …

Impact Of An Electronic Medical Record On Adherence To Current Diabetes Guidelines In A Family Medicine Center, Thomas Macandrew English

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OBJECTIVE: Extensive research shows that diabetic care often falls below recommended guidelines. Many believe that Electronic Medical Records (EMR) have the ability to improve quality of care. The primary goal of this study is to evaluate the changes in diabetic care and outcomes pre and post EMR implementation. RESEARCH DESIGN AND METHODS: The study took place at the UAB Huntsville Family Medicine Center. A retrospective chart review was conducted in order to determine the impact of an EMR on diabetes care. This is a natural experiment that uses a pre post model in order to determine impact. Generalized Estimating Equations …

The Effects Of Maternal Prenatal Insults On The Bmi Growth Trajectory Of Children Between The Ages Of 5-12 Years, Anthony Goudie

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The level of childhood obesity in the United States is at epidemic proportions. Most population studies looking at the factors contributing to childhood obesity focus on obesity as a dichotomous outcome. The purpose of this study is to test for the effects of maternal prenatal insult behaviors on the growth trajectory of a sample of children 5-12 years of age in the United States. This is the first known study to use a latent growth curve model and a cohort-concurrent analytical design to test the association between maternal prenatal insult behaviors and the annual longitudinal increase in body mass index …

Validation Of Two Qualitative Occupational Expose Assessment Models For Particulates And Vapors, Leshan J. Elliott

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o ensure industrial workers are not overexposed to hazardous chemicals, it is necessary to evaluate the magnitude of occupational exposures. Small and medium sized companies usually do not employ industrial hygienists or other professionals trained in occupational exposure evaluations. Thus, traditional quantitative air sampling methods are usually not feasible due to resource and budgetary limitations. Qualitative exposure assessment models have gained in popularity because they are simple, inexpensive, and less time consuming than quantitative methods. Models are available which predict exposure concentrations or categorize exposures as acceptable or unacceptable. Unfortunately, most models have not been validated or previous studies have …

Determinants Of Growth Hormone Receptor Downregulation, Luqin Deng

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Growth hormone (GH), a 22 kD polypeptide primarily produced in the anterior pituitary gland, is a key regulator of postnatal growth and affects carbohydrate, protein and lipid metabolism. Growth hormone receptor (GHR) is a single membrane-spanning type Ⅰ glycoprotein of the cytokine receptor family and is initially synthesized as a precursor and undergoes carbohydrate processing during transport through the Golgi. It has no intrinsic kinase activity. One molecule of GH binding to predimerized GHR on the cell surface induces the receptor conformational change activating the cytoplasmic domainassociated tyrosine kinase, Janus Kinase 2 (JAK2), which phosphorylates GHR, followed by the activation …

Quasi-Static And Multi-Site High Velocity Impact Response Of Composite Structures, Lawshya J. Deka

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Understanding of low and high velocity transverse impact of laminated fiber reinforced composites is of interest in military, aerospace, marine and civilian structures. Recent advances in the field of numerical simulation provide a means of predicting the performance characteristics of layered materials for impact protection. The overall objective of this work is to investigate the behavior of laminated composites which include both thermoplastic and thermoset systems subjected to quasi-static, low and high velocity impact; both from an experimental and numerical modeling view point. To analyze this problem, a series of quasi-static, low and high velocity impact tests have been performed …

Effects Of Aerobic Exercise On The Asthmatic Lung, Matthew M. Hewitt

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Asthma is identified by the clinical symptoms of wheezing, chest tightness, dyspnea and cough, and by the presence of airway hyperresponsiveness (AHR) to inhaled stimuli. We have reported previously that repeated bouts of moderate intensity aerobic exercise attenuate airway inflammatory responses in a mouse model of atopic asthma. Because the effects of exercise on physiological responses are dependent upon several variables, including total exercise duration, the hypothesis of the current work was that differing amounts of moderate intensity aerobic exercise exert dissimilar effects on AHR and airway inflammation. The aims to test this hypothesis included: 1) determine the effect of …

The Role Of Melanopsin Containing Retinal Ganglion Cells In The Pupillary Responses Of Human And Non-Human Primates, David H. Mcdougal

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Historically, the characteristics of the light-evoked neural signals driving the human pupillary light reflex (PLR) have been poorly understood. It was assumed that these light signals originated exclusively from rod and cone photoreceptors, although the measured spectral sensitivity and response dynamics of the PLR were difficult to reconcile with the known properties of rods and cones. Recently, a novel photoreceptive cell class has been discovered in the mammalian retina. These unique retinal ganglion cells not only receive rod and cone inputs, but also express the photopigment melanopsin, and exhibit intrinsic photoresponses independent of rod and cone inputs. These intrinsically photosensitive …

Mechanism Of The Cross Talk Between Growth Hormone Receptor And Epidermal Growth Factor Receptor, Xin Li

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EGF receptor (EGFR) is a receptor tyrosine kinase, mediating cell growth from ectodermal and mesodermal origin. The overexpression and aberrant function of EGFR are involved in a wide range of human carcinomas. Growth hormone receptor (GHR) coexists with EGFR in various cell types and implicated in malignant tumor behavior. Previously in our lab, we found that via ERK activation GH can threonine phosphorylate EGFR and reduce EGF-induced EGFR downregulation. GH also synergizes with EGF in activating ERK. In this project, using reconstitution, we studied the mutation of the ERK phosphorylation consensus residue on EGFR, 669T. CHO-GHR cells, which lack EGFR …

Lipomatous Tissue: Variation In Treatment Procedures, Comorbidities, And Outcomes, Theresa L. Keel

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Benign lipomas are the most common soft tissue tumors. They exhibit great variation in severity and are associated with significant comorbidity. Advanced understanding of genetic and morphological aspects of benign lesions has revealed unexpected similarities to malignant lesions, but little work has addressed variation among benign lesions. There is a need for better understanding of the effects of variation in lipomas on comorbidity, treatment, and outcomes. Improved knowledge of the effects will clarify the extent of the health and economic burden that severe forms of benign lipomas present to patients and society and may add to understanding of malignant lesions. …

Function Of Human Retinol Dehydrogenase 12 (Rdh12) In Retinoid Metabolism, Seung-Ah Lee

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Retinol dehydrogenase 12 (RDH12) is a member of the microsomal short-chain dehydrogenase/reductase superfamily of proteins that is highly expressed in photorecep-tor cells. Mutations in RDH12 are associated with severe early-onset autosomal recessive retinal dystrophy, leading to legal blindness. Disease-associated RDH12 variants exhibit lower protein levels when expressed in eukaryotic cells. However, the physiological role of RDH12 remains unclear. As established previously, RDH12 recognizes both retinoids and lipid peroxidation products (medium-chain aldehydes) as substrates and exhibits the highest catalytic efficiency for all-trans-retinaldehyde. As the main goal of this dissertation, we characterized the catalytic properties of RDH12 and its naturally occurring mutants …

Biogenesis, Trafficing, And Function Of Wild-Type And Mutant Cystic Fibrosis Transmembrane Conductance Regulator (Cftr), Asta Jurkuvenaite

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Cystic fibrosis (CF) is a genetic disease resulting from mutations in the cystic fibrosis transmembrane conductance regulator (CFTR), a cAMP-activated chloride channel that functions at the apical surface of epithelial cells and plays a critical role in mucociliary clearance. The most common mutation in the CFTR gene involves a deletion of phenylalanine at position 508 in the protein (ΔF508 CFTR). ΔF508 CFTR is recognized as misfolded in the endoplasmic reticulum (ER) and is degraded. In vitro manipulations such as culturing cells at 27°C can “rescue” ΔF508 CFTR to the plasma membrane (rΔF508 CFTR), but no pharmacological agent has produced comparable …

Changes In Hippocampal Excitability During Withdrawal From Chronic Nicotine, Rachel E. Penton

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seeking behavior following chronic drug use lasts for many months or even years. Short-term withdrawal experiments have suggested that the neuroadaptations thought to underlie learning and memory may also contribute to addictive behavior. However, there is little information about the physiological mechanisms that participate in craving and relapse following long-term withdrawal. Here I show in hippocampal slices from rats treated with nicotine for 1 week that there is a change in the excitability of CA1 pyramidal cells that persists for up to 9 months following the cessation of drug treatment. The expression of this enhanced excitability is dependent on different …

Processing And Characterization Of Long Fiber Thermoplastics, Krishnan Balaji Thattai Parthasarathy

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Thermoplastic composites have found increasing use in transportation, military, and aerospace applications. Specifically, long fiber thermoplastics (LFT) have become well established as medium performance, high volume, and low cost materials due to high level of productivity in processing. The mechanical properties of LFT components are defined by the fiber / matrix system and also, to a large extent, by the process-induced flow orientation and fiber lengths. The orientations and fiber length are influenced significantly by the flow characteristics, processing method, and parameters. This work focuses on the rheological characterization of LFT processed via the extrusion-compression molding technique. The squeeze flow …

Roles Of Extracellular Atp And Zinc In Pancreatic Ss-Cell Physiology, Clintoria Richards-Williams

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Insulin secretory defects within pancreatic beta-cells (β-cells) of islets of Langerhans play a role in the pathogenesis of diabetes mellitus. Furthermore, it is also well established that ATP and zinc are co-secreted with insulin in response to elevated extracellular glucose. Despite this knowledge, the physiological roles of extracellular secreted ATP and zinc within islets are ill-defined. We hypothesized that secreted ATP and zinc are autocrine purinergic signaling molecules that activate P2X purinergic receptor (P2XR) channels expressed by β-cells to enhance glucose-stimulated insulin secretion (GSIS). To test this postulate, ELISA, luciferin/luciferase-based bioluminescence and zinquin-based fluorescence assays were utilized to examine insulin, …

Characterizing Semantic Memory In Mild Cognitive Impairment, Kelli L. Netson

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Episodic memory is clearly impaired in mild cognitive impairment (MCI), although recent studies have revealed deficits in other cognitive domains such as attention, executive function, and semantic memory. Studies of semantic memory in MCI have been limited by inconsistent use of diagnostic criteria and variability in the measures used. The purpose of this study was to examine semantic memory in a sample of individuals diagnosed with amnestic MCI using Mayo criteria. Performance of individuals with consensus-diagnosed MCI (n=12) was compared to that of normal controls (n=15) on a battery of semantic memory tasks. MANOVA results indicated that the MCI group …

Wavelet-Based Regression And Classification For Longitudinal Diffusion Tensor Imaging Data, William R. Prucka

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Diffusion tensor imaging (DTI) is a magnetic resonance imaging (MRI) technique capable of in vivo characterization of the spatial and angular dependence of free water diffusion in tissue. By studying intra- and extra-cellular water mobility, inference can be made about the surrounding medium. The non-uniform angular dependence of diffusion, known as anisotropy, is evident in fibrous tissues, which exhibit greater diffusion parallel versus perpendicular to the fiber orientation. DTI’s sensitivity to anisotropy makes it an effective tool for measuring the integrity of fibrous myelinated white matter tracts in the brain. For demyelinating diseases such as multiple sclerosis (MS), DTI has …

The Role Of Tgfß Signaling In Skeletal Development, Hwa-Seon Seo

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skeletal element is essential for body movement along with the joints, muscles, tendons and ligaments. They also protect internal organs and serve as a reservoir for hematopoietic stem cells and minerals. To accomplish these multiple tasks, the size and shape of the skeletal elements need to be carefully designed during development of the embryo. Skeletal formation in vertebrae is a complex developmental processes controlled by dynamic and well-balanced interactions between a number of molecular signals. Intensive efforts in the past several decades have made substantial progress in understanding molecular and cellular mechanisms of skeletal development. Despite the fact that TGFß …

Adenovirus As A Platform For Assembly And Targeted Delivery Of Gold Nanoparticles To Tumor Cells, Vaibhav Saini

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Novel combinatorial strategies need to be explored to achieve tumor eradication. In this regard, viral vector based gene therapy and nanotechnology offer unique possibilities for cancer therapy. As an example, multifunctional adenoviral (Ad) vectors capable of targeting, imaging, and successful cancer gene therapy have been advanced into multiple clinical trials. Similarly, novel multifunctional gold nanoparticles (AuNPs) have been utilized for drug delivery, targeting, imaging, and hyperthermia tumor therapy. Therefore, to accrue the benefits of both gene therapy and nanotechnology for cancer therapy, we proposed to combine Ad vectors and AuNPs in a single multifunctional nanodevice. Towards this goal, herein, we …