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Bioactive Glass Scaffolds For The Regeneration Of Load-Bearing Bone, Xin Liu

Doctoral Dissertations

"Biocompatible scaffolds that replicate the structure and function of bone would be ideal bone substitutes for structural bone loss, provided they have the requisite mechanical properties for reliable long-term loading. In this dissertation, strong porous scaffolds of silicate 13-93 bioactive glass, created with two different microstructures, were evaluated to determine their mechanical properties and their capacity to regenerate bone in a rat calvarial defect model. Scaffolds with an oriented microstructure of columnar pores were prepared by unidirectional freezing of camphene-based suspensions, followed by thermal annealing and sintering. By optimizing the freezing conditions, annealing time, and sintering temperature, constructs (porosity = …

Evaluation Of Single Electron Transfer Reduction Products Of 3-Oxoindoles As Antibacterial Agents, Debasish Bandyopadhyay, Irani Biswas, Subrata Laskar, Bidyut Basak

School of Integrative Biological & Chemical Sciences (Formerly Dept. of Chemistry)

Objective: The objective of the present study is to assess the antibacterial properties of six indole derivatives viz, 3-(Naphth-1-y - methyl) –indole (II), 3-(1-Naphthylcarbonyl – indole (III), 3,3' –diformyl-2,2' –bis indole (IV), 1,4- (3,3' –di indolyl) – 1,4-dioxobutane (V), 3-benzoyl indole (VI) and 1,1 – bis – (3-indolyl)- ethane (VII) synthesized by single electron transfer reduction of 3-formylindole (I) against two Gram +ve and two Gram –ve bacteria which usually cause human infections.

Methods: Synthesis of 3-formyl indole from which the indole derivatives were prepared were further characterized by IR and NMR analysis. The six synthesized compounds were screened for …

Photothermal Desorption Of Toluene From Single Walled Carbon Nanotube And Activated Carbon Sorbents, Evan Lee Floyd

All ETDs from UAB

Millions of workers are occupationally exposed to volatile organic compounds (VOC) annually, requiring exposure assessments through air sampling. Reducing time to knowledge while maintaining adequate sensitivity and affordability is a constant struggle. Sorbent sampling is the preferred technique for VOC exposure assessments. Chemical desorption of sorbents is the most common desorption technique, but sensitivity is limited due to the small injection fraction. Thermal desorption has excellent sensitivity, but provides only one analysis per sample and is cost prohibitive. The goal of this dissertation was to develop a desorption technique that bridges the sensitivity gap between chemical desorption (0.1%) and thermal …

The Development Of An In Vitro Surrogate Assay For Screening Protective Antibodies Against Pneumococcal Surface Protein A (Pspa), Kristopher Ruben Genschmer

All ETDs from UAB

PCV13 is the current pneumococcal protein conjugated vaccine made up of the 13 most clinically relevant capsular polysaccharides. While protective, it is limited to a small portion of the overall serotypes of Streptococcus pneumoniae. The possibility of "serotype replacement" by serotypes not covered by the vaccine and the high cost of producing this conjugated polysaccharide vaccine stress the need for a protein based vaccine, one that is more broad in its protection. Pneumococcal surface protein A (PspA) has been shown to be both immunogenic and protective in mice and is a promising protein vaccine candidate. However, there are no current …

Predictors Of Physical Activity In Child And Adolescent Survivors Of Cancer, Margaux Barnes Gilliam

All ETDs from UAB

Childhood cancer survivors are at increased risk for future health problems. As such, physical activity (PA) has been targeted as a health promotion priority in child and adolescent cancer survivors. Despite research suggesting PA has protective health benefits, a large proportion of survivors do not meet PA recommendations. Development of effective interventions to increase PA in pediatric cancer survivors requires an understanding of the processes that determine survivor PA. Research on the determinants of PA in child and adolescent survivors is sparse, with most research focusing on late adolescent, young adult, and adult survivors of childhood cancer. The following papers …

Experience-Dependent Synaptic Integration Of Adult-Generated Dentate Granule Cells, Jessica Hotard Chancey

All ETDs from UAB

The dentate gyrus (DG) contains neural stem cells that continually generate new neurons throughout life. The contribution of adult neurogenesis to hippocampal function is not well understood, but ablation or silencing of adult-generated neurons in the DG disrupts learning and memory, and neurogenesis is altered in many pathologies associated with impaired cognition including Alzheimer's Disease, epilepsy, and schizophrenia. Neurogenesis in the DG is a stepwise process in which neural stem cells leave the cell cycle and undergo an approximately two month long maturation process to form fully functional dentate granule cells (GCs) that are indistinguishable from those formed during development. …

Targeting Ovarian Cancer Through Epigallocatechin Gallate And Sulforaphane Combinational Treatment, Huaping Chen

All ETDs from UAB

The cellular development of resistance to chemotherapy contributes to the high mortality noted in patients affected by ovarian cancer. Novel compounds that can enhance efficacy of conventional chemotherapy or target both drug-sensitive and -resistant ovarian cancers directly are highly desired. Previous epidemiological studies indicate that consumption of green tea and cruciferous vegetables is inversely associated with occurrence of ovarian cancer. Therefore, revealing the effects and mechanisms of major components of green tea (epigallocatechin gallate, EGCG) and cruciferous vegetables (sulforaphane, SFN) on ovarian cancer cells will provide necessary knowledge for developing potential novel treatments for the disease. Since drug resistance generation …

Cortical Thickness In Amnestic Mild Cognitive Impairment And Its Relationships With Neuropsychological Functioning And Financial Capacity, Jacquelynn Nicosia Copeland

All ETDs from UAB

Diagnostic criteria for amnestic mild cognitive impairment (aMCI) include subjective memory complaint, objective memory impairment, preserved general cognitive function, intact functional abilities, and absence of dementia diagnosis (Petersen, 2004). However, there is evidence to suggest that some aMCI patients show declines in complex instrumental activities of daily living. Under the conceptual model proposed in this study, neuropathological changes occurring in the brain of aMCI and Alzheimer's disease (AD) patients underlie specific forms of neurocognitive dysfunction, which in turn drive decline in everyday functional skills such as financial capacity. The current study examined the relationships between structural brain changes in aMCI, …

The Molecular Basis Of Male Sex Determination During Temperature-Dependent Sex Determination, Kayla Bieser

All ETDs from UAB

The red-eared slider turtle (Trachemys scripta) possesses temperature-dependent sex determination (TSD) in which the incubation temperature of the developing embryo determines gonadal sex. Although a number of mammalian gene homologues have been identified in the sex determination/differentiation cascade of reptiles with TSD, the exact trigger(s) is not well understood. As such, this dissertation research addresses the mRNA expression profiles of putative sex-determining/differentiation genes (Dmrt1, Sox9, Amh, Lhx9, and Foxl2) with an emphasis on the male cascade in embryonic gonads of T. scripta. Additionally, this research addresses the influence of exogenous estrogen and aromatase inhibitors on gene expression. Lastly, this dissertation …

Tuberculosis Verrucosa Cutis In A Patient With Keloid Over Ear Lobule, Muhammad Sohail Halim, Sadaf Qadeer Ahmed, Montasir Junaid, Muhammad Rizwan Bashir

Section of Otolaryngology, Head & Neck Surgery

Tuberculosis (TB) is a global health problem with predominance in resource-poor countries. Extrapulmonary TB constitutes approximately 10% of the cases and can present as different forms depending on the route of entry. Cutaneous TB is a small subset of the extrapulmonary TB. Cutaneous TB can either be of primary origin or secondary origin or it can be a part of a systemic infection. TB verrucosa cutis (TBVC) is the exogenous reinfection of TB in a previously sensitised patient. Routine cultures do not have a high yield in TBVC due to the paucibacillary nature of the organism. Here we are presenting …

Neural Substrates That Mediate Learning-Related Changes In The Emotional Response To A Threat, Joshua Richard Shumen

All ETDs from UAB

Recognizing cues that predict a threat allows one to react more effectively under threatening conditions, attenuating or potentiating the response to the threat depending on the circumstances. This is demonstrated during Pavlovian fear conditioning when the unconditioned response (UCR) to a predictable unconditioned stimulus (UCS) is diminished compared to the UCR of an unpredictable UCS (Dunsmoor, Bandettini, & Knight, 2008; Wood, Ver Hoef, & Knight, 2012). In the current study skin conductance, electromyography (orbicularis oculi), UCS expectancy, and blood oxygen level dependent (BOLD) functional magnetic resonance imaging (fMRI) were assessed during a Pavlovian temporal fear conditioning paradigm. Right-handed volunteers were …

Ultrasound And Microbubbles: A Role In Cancer, Anna Sorace

All ETDs from UAB

Successful cancer treatment relies on the sensitivity to monitor cancer response to therapy and the ability to efficiently deliver drugs to the tumor. Cancer research has continuously improved patient outcomes over the last decades; however, it is still the second leading cause of death in the United States. It is essential to improve methods to progress all areas of cancer treatment, including monitoring and drug delivery. Ultrasound (US) is a popular clinical imaging modality due to its low levels of radiation, portability, and cost effective imaging. These advantageous characteristics have allowed for novel research advancements in the US field including …

The Role Of O-Glcnacylation In Synaptic Function, Erica Wynette Taylor

All ETDs from UAB

O-GlcNAcylation is a dynamic protein posttranslational modification that adds the monosaccharide ß-N-acetylglucosamine (GlcNAc) to specific serine and threonine residues on nucleocytoplasmic proteins. The hippocampus is a part of brain that has been shown to play a crucial role in learning and memory. Hippocampal neurons have high expression of O-GlcNAc transferase and O-GlcNAcase, which catalyze the addition and removal of GlcNAc from proteins respectively. Moreover, synaptic plasticity which is the strengthening or weakening of synaptic function on short- and long-term time scales is believed to be a cellular correlate of learning and memory. Several forms of synaptic plasticity have been characterized …

Role Of Kca3.1, A Calcium-Activated Potassium Channel, In Cell Migration In The Adult Brain, Kathryn L. Turner

All ETDs from UAB

A limited amount of migration occurs in the adult brain, including migration of neuroblasts during adult neurogenesis and pathological migration of primary brain tumors. Ion channels are commonly utilized during migration to allow shape and volume changes required for cell movement, and we specifically examine the role of KCa3.1 in the adult brain. These channels are well-suited to facilitate movement because they respond to common migration signals, i.e. intracellular Ca2+ changes, and efflux K+, allowing the outflow of water and cell volume regulation. Our findings suggest that KCa3.1 is highly expressed in migratory cells, adult neuroblasts and glioma cells, but …

The Effects Of Nicotine On The Human Adult Visual Pathway And Processing, Stefanie B. Varghese

All ETDs from UAB

Nicotine, the primary addictive component found in tobacco/cigarettes, can bind to nicotinic acetylcholine receptors (nAChR), which are found throughout the central nervous system including the retina of the eye. Previous studies have shown nAChR expression in the retina of non-human and human (Hutchins & Hollyfield, 1985; Liu et al., 2009). By use of electrophysiologic measures, i.e. electroretinograms (ERGs), early reports indicated that nicotine and/or cigarette smoking affects vision and visual processing in different species (Jurklies, Kaelin-Lang, & Niemeyer, 1996; Jünemann & Damaske, 1968). Because previous human studies have used only cigarette smokers, there are questions about what role nicotine, itself, …

The Impact Of Fine Sensor Spacing On Complex Tissue Impedance Spectra Measurements In Rabbit Ventricular Epicardium, Charlotte Mae Kent Waits

All ETDs from UAB

Our research group recently developed an instrumentation and signal processing approach that overcomes many of the obstacles associated with using small sensors to complete complex composite impedance (uCI) measurements, whose amplitude and phase depend upon the tissue's resistive and capacitive properties. The goal of this study was to test the feasibility of using smaller electrodes with finer separations than sizes traditionally employed in cardiac electrophysiologic studies with whole hearts to resolve uCI spectra in terms of magnitude (|uCI|) and phase (

The Role Of Pneumococcal Choline-Binding Protein A (Pcpa) In The Mechanism Of Virulence And Protective Immunity, Melissa Marie Walker

All ETDs from UAB

pcpA is under control of the Mn 2-dependent repressor PsaR. In the high manganese environment of mucosal sites pcpA gene expression is repressed and at the low manganese environment of the lung and blood derepression of pcpA gene expressionis observed. Previous data has shown that immunization of mice with rPcpA elicits protection against pneumonia and sepsis but had no effect on nasal colonization. We and others have shown that pcpA expression significantly enhances adherence of pneumococci to lung epithelial cell lines and although it is a virulence factor for pneumonia in mice there is no biologically relevant role for PcpA …

Anti-Group B Streptococci Monoclonal Antibodies Protect Against Invasive Aspergillosis, Rebekah Wharton

All ETDs from UAB

Aspergillus fumigatus is a ubiquitous saprophytic fungus which can potentially cause life-threatening infections in immunocompromised individuals. Although a serious threat, current treatments are largely ineffective at reducing morbidity and mortality. To this end, we have characterized a monoclonal antibody generated against Group B Streptococci, type Ib, which also recognizes Aspergillus fumigatus conidia and hyphae. We show that this antibody appears to bind a similar epitope on both pathogens and provides a significant degree of protection in a murine model of invasive aspergillosis via a mechanism that appears to be dependent on complement. The studies we performed using this antibody should …

Genetic And Biochemical Characterizations Of The Capsular Glycosyltransferases In Streptococcus Pneumoniae Serotype 2, David Boyd Anthony James

All ETDs from UAB

The principle objective of this dissertation is to develop a thorough understanding of the genetics and biochemistry of capsule synthesis. Specifically, it involves the identification and characterization of the capsular glycosyltransferases in Streptococcus pneumoniae serotype 2, with investigations into their regulation. S. pneumoniae (the pneumococcus) is a significant human pathogen that has the ability to persist as a commensal and then transition to a virulent state, the latter of which is a major contributor to global morbidity and mortality. The capsular polysaccharide (CPS) of S. pneumoniae is a protective surface structure that plays an integral role in this disease process. …

Marcks Is A Regulator Of Growth, Radiation Sensitivity And Is A Novel Prognostic Factor For Glioblastoma Multiforme, John Jarboe

All ETDs from UAB

Glioblastoma multiforme (GBM) is the most common and deadly primary brain malignancy necessitating improved understanding of GBM biology. In this study, we explore the role of Myristoylated Alanine Rich C-Kinase Substrate (MARCKS) in the context of GBM. We have discovered that the MARCKS protein regulates GBM growth as well as response to radiation therapy through its effects on proliferation, senescence, and DNA repair based on our studies in cell culture and in patient-derived xenograft tumors implanted in mice. Importantly, our analysis of clinical patient data demonstrates that MARCKS is an independent predictor for outcome in GBM patients. Indeed, high MARCKS …

The Effect Of An Intensive Oral Hygiene Regimen On Gingival Inflammation During Pregnancy: Clinical And Laboratory Analysis, Maninder Kaur

All ETDs from UAB

Background: Recent evidence suggests that systemic inflammation as host immune response to oral microbial challenge may well underlie the observed association between periodontal disease and preterm birth/low birth weight (PTB/LBW). The aim of this pilot study was to evaluate the effect of vigorous oral hygiene regimen on gingival inflammation and gingival crevicular fluid (GCF)/serum biomarkers (TNF-&alpha, IL-1&beta and IL-6) during pregnancy and its impact on pregnancy outcome. Methods: 120 participants with pregnancy between 16-24 weeks gestation and with gingival index (GI) scores &ge 2 at &ge 50 % of tooth sites were recruited from the available pool of patients at …

The Role Of Histone Deacetylase Inhibitors In Ameliorating Memory Dysfunction Of An Alzheimer's Disease Mouse Model, Mark Kilgore

All ETDs from UAB

Alzheimer's disease (AD) is a neurodegenerative disorder characterized by amyloid beta plaques and neurofibrillary tangles, along with cognitive impairments that progress to dementia and eventually death. The development of drug treatments that rescue memory deficits could be a promising therapy given in the early stages of AD. In the following studies, we tested the potential for systemic treatment with histone deacetylase (HDAC) inhibitors to ameliorate cognitive deficits in a mouse model of AD. Using the APPSwe/PS1dE9 mouse model of AD, we showed that giving HDAC inhibitors systemically for 3 weeks reversed contextual memory deficits, stably maintained memories over a 2-week …

Cyclic Gmp Phosphodiesterase As A Novel Target For Colorectal Cancer Chemoprevention, Nan Li

All ETDs from UAB

Nonsteroidal anti-inflammatory drugs (NSAIDs) display promising antineoplastic activity for colorectal and other cancers, but toxicity from cyclooxygenase (COX) inhibition limits their long-term use for chemoprevention. However, many investigators have concluded that COX-independent mechanisms are responsible for their antineoplastic activity. We previously reported that cyclic guanosine monophosphate phosphodiesterase (cGMP PDE) is a non-COX target of sulindac sulfide (SS). However, the specific isozyme families involved have not been well studied. Here we demonstrate that SS inhibits the growth of colon tumor cells through a novel mechanism involving inhibition of two cGMP degrading isozymes, PDE5 and PDE10, to activate cGMP-dependent protein kinase (PKG). …

Surveying The Serum Proteome For Biomarkers Of Early-Stage Pancreatic Cancer, Michael Robert Ludwig

All ETDs from UAB

SURVEYING THE SERUM PROTEOME FOR BIOMARKERS OF EARLY STAGE PANCREATIC CANCER MICHAEL ROBERT LUDWIG MICROBIOLOGY ABSTRACT Pancreatic ductal adenocarcinoma (PDAC) is a uniformly fatal disease due to its refractory nature to conventional therapies at the time of initial diagnosis. In order to in-crease the curative potential of surgical resection, early detection of organ-confined neoplasia is needed. Currently, no effective diagnostic tools are available to detect early-stage pancreatic ductal lesions termed pancreatic intraepithelial neoplasia (PanIN) or lo-cally invasive, organ-confined disease. One way to identify biomarkers that may be use-ful for the early detection of PDAC is through the study of the …

Volumetric Contrast-Enhanced Ultrasound Imaging Of Vascular Perfusion In Renal Tissue, Marshall Joseph Mahoney

All ETDs from UAB

This research examines the ability of volumetric contrast-enhanced ultrasound (VCEUS) imaging to quantify kidney blood flow, with the potential to monitor changes in renal perfusion following acute kidney injury (AKI). Ultrasound (US) imaging of microbubble contrast agents allows for increased imaging isolation of the vasculature, creating a non-toxic approach to visualizing blood flow. VCEUS utilizes a series of planar ultrasound acquisitions that can be collected in real time to survey the vascularity of a volumetric region-of-interest. Through post-processing methods it is possible to quantify perfusion parameters such as peak intensity (IPK), time-to-peak intensity (TPK), wash-in rate (WIR), and area-under-curve (AUC). …

Perception Of Attractiveness: A Comparison Of Two-Dimensional Versus Three-Dimensional Images, Aksana Marshall

All ETDs from UAB

Introduction: The aims of this study were (1) to evaluate whether there is a difference in perception of facial attractiveness when viewing two-dimensional (2D) versus three-dimensional images (3D) within each population studied (Caucasian, African American, and Chinese), (2) to evaluate whether panels of raters with different levels of orthodontic education would give similar facial attractiveness scores, and (3) to identify the soft tissue features that influence facial attractiveness when viewing 2D and 3D images. Materials and methods: A total of 60 3D images from three populations selected for this study were acquired using a 3dMDfaceTM system (Atlanta, GA) and were …

Temp, Callie Gartrell Mauldin

All ETDs from UAB

Temp is a collection of short stories about four young women living in New York City. Each woman struggles with her own identity while tethered to a family past that informs her current situation. Through failures and flirtations with disaster, Hannah, Anna, Liz, and Rachel learn how to accept themselves and the lives they've been dealt. The stories, ultimately, explore loss and acceptance through connections and relationships with others.

Characterizing The Roles Of Il-11 And Cd68 In Breast Cancer Bone Metastasis, Erin Mills Mccoy

All ETDs from UAB

The molecular mechanisms regulating the preferential metastasis of breast cancer to bone have not been fully elucidated, but it is hypothesized that local conditions in the bone create an environment conducive to colonization by breast cancer cells and that the breast cancer cells interact directly with cells in the bone. In this dissertation, two goals were pursued: (1) to explore breast cancer secreted interleukin (IL)-11's role on osteoclast function and (2) investigate the expression and potential role of CD68 in breast cancer adhesion to bone. Higher rates of bone metastasis occur in human breast cancer tumors expressing IL-11, a cytokine …

The Effects Of Extremes Of Ph On The Growth And Transcriptomic Profiles Of Three Haloarchaea, Aida Moran-Reyna

All ETDs from UAB

The Archaea represent a fascinating domain of life where each species comprises a hybrid of bacterial and eukaryal features. Unfortunately, there have been few investigations of the Archaea and many fundamental questions remain regarding their biochemistry, genetics, and genomics. One reason for this is that few archaea are amenable to detailed experimental analysis; however, a few halophilic archaea (haloarchaea) can be easily manipulated in the laboratory and contain a sequenced genome, allowing for bioinformatics studies, such as recording changes in the transcriptomes. Haloarchaea are found wherever seawater is concentrated above 2 M NaCl and contain a similarly high concentration of …

Understanding The Relation Between Routines And Problem Behaviors In Children With Clinical Diagnoses, Mark Ryan Pennick

All ETDs from UAB

The current study investigated the impact of routines on problem behaviors in children with the clinical diagnoses of either PDD, ADHD, or depression/anxiety. Previous research has identified negative relations between externalizing behaviors and routines as well as a link between using routines and having positive parenting. The study extends these findings to children with these various diagnoses and also to internalizing symptoms. In our sample negative relations were found between routines, as measured by the Child Routines Inventory (CRI), and both internalizing and externalizing symptoms when all groups were examined together. Additionally routines were found to moderate the relation between …