Digital Commons Network^™

Molecular Influences Of Racial Disparities In Pancreatic Neuroendocrine Tumors, Brendon Herring

All ETDs from UAB

Pancreatic Neuroendocrine Tumors (PNETs) are highly heterogeneous neoplasms arising from the hormone-secreting cells of the endocrine pancreas. PNETs are broadly categorized as functional and non-functional based on the presence of symptoms associated with hormone secretion, which occurs in approximately 30% of cases. While functional tumors are all considered for resection because of these symptoms and their associated sequelae, non-functional tumors > 2cm are currently resected based on increased risk of developing metastatic disease. However, this criterion is based on data from predominantly White patients. Recent studies have shown that Black patients have much higher rates of lymph node metastatic disease at …

Optimization Of Progranulin Gene Therapy, A Potential Treatment For Frontotemporal Dementia, Shreya Natesh Kashyap

All ETDs from UAB

Heterozygous loss of function mutations in the progranulin gene cause frontotemporal dementia, characterized by deficits in social behavior, language comprehension and motor function. Almost every frontotemporal dementia-related progranulin mutation is loss of function and results in progranulin haploinsufficiency. For this reason, progranulin replacement is a conceptually straightforward therapeutic strategy for patients with frontotemporal dementia caused by progranulin mutations. Here, we outline progranulin biology, progranulin deficient mouse models of frontotemporal dementia and preclinical interventions centered around increasing brain progranulin levels. We have demonstrated that blocking the progranulin C-terminus, which harbors the sortilin binding site, improves the cross-correctional capacity of neurotropic progranulin …

The Long Non-Coding Rna Neat1 Mediates Astrocyte Gene Expression And Hippocampus-Dependent Memory In Aging And Alzheimer's Disease, Ashleigh Burns Irwin

All ETDs from UAB

Dysregulation of long non-coding RNAs (lncRNAs) is increasingly associated with cognitive dysfunction and neurodegenerative disorders such as Alzheimer’s disease (AD). The highly evolutionarily conserved lncRNA Nuclear-Enriched Abundant Transcript 1 (NEAT1) is expressed not only in a tissue- and temporally-specific manner, but also celltype specific manner. Despite the predominance of NEAT1 in glial populations, and the significant role astrocytes play in memory, relatively little is known about Neat1 regulation of astrocyte transcriptomics during age-related memory. Here, we report a crucial role of the lncRNA Neat1 in astrocyte dysfunction and memory deficits associated with both normal aging and AD. Expression of Neat1 …

The Effects Of Alzheimer's Disease-Associated Variants And Ligands On The Structure And Function Of Trem2, Hunter Byron Dean

All ETDs from UAB

Alzheimer’s disease (AD) is a devastating, complex form of dementia. Contributions from genetics make up almost 70% of a person’s risk of developing AD, but the mechanisms by which this occurs are not well understood. Attempts to tease apart the risk contributions from individual genes have identified lipid processing and activation of innate immunity as convergent pathways for many of the known genetic risk factors. One of the strongest known risk factors, TREM2, codes for a transmembrane receptor that activates a protective immune response when it detects bound lipids. Variants in TREM2 that control AD risk have been identified, but …

Reduction Of Sphingomyelinases Associated With Progranulin Deficiency And Frontotemporal Dementia, Nicholas R. Boyle

All ETDs from UAB

Frontotemporal dementia (FTD) is a leading cause of early-onset dementia and has a significant socioeconomic burden due to difficulties in diagnosis and delay to diagnosis. FTD is a clinically, pathologically, and genetically heterogeneous disorder. The pathological changes associated with FTD are termed frontotemporal lobar degeneration (FTLD). Protein aggregates are always present in FTLD, with >90% of cases presenting with either TDP-43 or tau pathology. Most cases of FTD are sporadic, but familial cases account for up to 25% of FTD. All familial FTD is inherited in an autosomal dominant fashion with most cases being caused by mutations in tau (MAPT), …

Investigation Into The Structure And Function Of Tyrosyl-Dna Phosphodiesterase I'S N-Terminal Domain, Evan J. Brettrager

All ETDs from UAB

Tyrosyl-DNA phosphodiesterase I (Tdp1) is a eukaryotic DNA repair enzyme that removes adducts from DNA ends via hydrolysis of a phosphodiester bond. These adducts consist of damaged nucleotides or trapped protein-DNA complexes. Tdp1 hydrolyzes the phosphodiester bond utilizing two catalytic histidines and forming a Tdp1-DNA covalent intermediate. Mutations of these catalytic histidines have been shown to increase the stability of the Tdp1-DNA covalent intermediate and cause Topoisomerase I dependent toxicity in cells. We use these toxic Tdp1 mutant enzymes to study the function of Tdp1’s N-terminal domain (NTD). Full-length Tdp1 has proven difficult to purify due to degradation of the …

The Global And Local Correspondence Between Unicritical And Maximally Critical Laminations And The Realization Of Laminations To Julia Sets, Brittany Burdette

All ETDs from UAB

In this thesis, we first discuss the concept of laminations which was initially introduced by Thurston [1] as a way to understand quadratic polynomials and their parameter space. Laminations are a combinatorial way to model Julia sets. We go into detail explaining the introductory definitions in hopes it makes the following chapters easier to follow. In the next chapter, we go into detail discussing unicritical laminations and laminations with a single critical moment (SCM). We show there is a one - to - one correspondence between globally unicritical laminations and single critical moment laminations. The goal in this correspondence is …

Effects Of Mindfulness-Based Intervention On Mental Health Outcomes In Youth Who Are Underserved, Melanie Grace Albright

All ETDs from UAB

olescence, a period of rapid brain maturation and development coincides with the development of mental health disorders. Many teens in the United States with diagnosable mental health conditions lack mental health treatment due to limited access and provider availability, particularly affecting adolescents who are underserved. School-based interventions, including those centered around mindfulness-based stress reduction (MBSR) have shown promise in their effectiveness among adolescents. This study examines the impact of an in-school MBSR-based program, MindUP, on mental health outcomes, including depressive symptomology, anxiety symptomology, and perceived stress, in adolescents who are underserved. Additionally, focus group discussions were conducted with students participating …

Epigenetic Aberrations In Systemic Sclerosis And Systemic Lupus Erythematosus, Peter C. Allen

All ETDs from UAB

Autoimmune diseases are a classification of more than eighty diseases where the immune system recognizes a self-antigen and mistakenly attacks the body’s own tissue, inducing inflammation a nd p otentially l eading t o d amage. Autoimmune diseases disproportionately affect women and develop at any age depending on the disease. The prevalence of some autoimmune diseases is increased in minority populations. Despite this, research into higher-risk populations is lacking. This highlights the need to contribute research into understanding autoimmune disease pathogenesis in diverse studies to understand why disease is more severe in these populations. We analyzed transcriptomes and methylomes of …

Social Vulnerability And Racial Disparities In Overall Survival Among Endometrial Cancer Patients, Alfonsus Adrian Hadikusumo Harsono

All ETDs from UAB

Introduction. Social vulnerability (SV) refers to potential negative effects on communities caused by external stresses on human health. The CDC/ATSDR Social Vulnerability Index (SVI) scores communities on 15 social indicators in 4 themes: (1) socioeconomic status (SES), (2) household composition and disability, (3) minority status and language, and (4) housing type and transportation. An overall score ranging from 0 (least vulnerable) to 1 (most vulnerable) is calculated to estimate vulnerability. We investigated whether SV as measured by the SVI can explain why black endometrial cancer (EC) patients survive less well than do white EC patients. Methods. We studied the survival …

Failure Modes Of Different Zirconia Crown Heights And Materials On Titanium Base Abutments, Aikaterini Anastasaki

All ETDs from UAB

Statement of the Problem: The existing scientific literature lacks comprehensive information regarding the influence of zirconia crown height on debonding and fracture occurrences between zirconia crowns and titanium base abutments. Additionally, there is a lack of comparative studies evaluating different zirconia materials as restorative options for screw-retained restorations. Purpose: The purpose of this study was to assess the failure modes of the zirconia crown/titanium implant abutment complex by investigating the impact of increasing zirconia crown heights and different zirconia materials. Materials and Methods: The experimental design encompassed six groups, each consisting of 10 specimens. Group 1 included 10 non-anatomical crowns …

Pharmacologic Proteasome Activators Ameliorate Alzheimer's-Like Pathology In Ad Fly Models, Mehar Bano

All ETDs from UAB

The proteasome is a large multi-subunit protease responsible for the degradation and removal of oxidized, misfolded, and polyubiquitinated proteins. The proteasome plays a critical role in nervous system processes. This includes the maintenance of cellular homeostasis in neurons (1). It also includes synaptic efficacy and plasticity as well as protein turnover, presynaptic vesicle transport, and neuronal protesostasis. Proteasome function is impaired as a consequence of aging, which is aggravated by conditions like Alzheimer's Disease and Related-Dementias (AD, ADRD) (2). According to earlier work from our lab the proteasome is critical to how quickly AD progresses. In Drosophila, human cells, and …

Increasing Patient Safety By Reducing Falls Among In-Hospital Community-Dwelling Patients 65 Years Old Or Older By Using A Shift Change Fall Safety Checklist, Janice Isaac Brooks

All ETDs from UAB

This manuscript is designed to promote and improve healthcare safety, quality, efficiency, and lower medical costs for hospitals and patients. Falls, fall injuries, and their devastating consequences are rising, yet falls are preventable even among senior patients. Search Engines and Key Terms SciWheel was used to save the literature and eliminate duplications. Key terms were used in the Boolean strings: elderly fall prevention, senior fall safety, in-hospital fall prevention, falls in the aging, and fall prevention tools. The CINAHL Plus yielded 58. PubMed search yielded 121. And Google Scholar yielded 32. The total of all three searches was 211. Thirteen …

Transmission Competence Of B. Burgdorferi Infected Ixodes Ticks And Development Of An Ospc-Based Lyme Disease Vaccine, Samanta Kamalika

Theses and Dissertations (ETD)

Introduction. Lyme disease, otherwise called Lyme borreliosis, is a vector-borne infectious disease caused by the spirochete Borrelia burgdorferi (Bb). Studying the increase in overall Lyme disease incidence requires understanding the role of the vector Ixodes scapularis (I. scapularis) as the agent that carries the spirochete which is important to limit the occurrence of Lyme disease. Once we understand the vector-pathogen response, it also becomes important to determine the remedies for Lyme disease. Lyme disease can be treated with antibiotics if detected early, but the major obstacle lies in the early detection process. Therefore, it is important to investigate alternative preventive …

Physiologically-Based Pharmacokinetic (Pbpk) Modeling For The Preclinical Development Of Spectinamide Antibiotics, Keyur R. Parmar

Theses and Dissertations (ETD)

Despite being an ancient disease caused by Mycobacterium tuberculosis (Mtb) and after decades of research, tuberculosis (TB) still affects millions of people every year worldwide. In 2018, the World Health Organization (WHO) reported that 10 million people developed tuberculosis and 1.5 million died of the disease. With the increase in the multidrug-resistant (MDR) and extensively drug-resistant (XDR) cases, the treatment for TB with the standard first and second-line therapy is becoming increasingly difficult. Therefore, there is an urgent need to find new anti-TB drugs as combination partners of existing and experimental classes of antimicrobial agents to shorten and simplify the …

Taking Corrigibility Seriously, Dora Klein

Faculty Articles

This article argues that the Supreme Court's creation of a category of "irreparably corrupt" juveniles is not only an epistemological mistake but also a tactical mistake which has undermined the Court's express desire that only in the "rarest" of cases will juveniles be sentenced to life in prison without the possibility of parole.

Medical Emergency Preparedness Among Undergraduate Students, Savannah L. Finigan

Honors Theses

Knowing how to respond to a medical emergency is a valuable life skill that college students ought to have the opportunity to attain in order to save lives. This study aims to understand how prepared and confident local students are to respond to a medical emergency. Participants consisted of undergraduate students who had no healthcare or nursing school experience. A survey was distributed that asked students to rank and describe their own confidence to respond to medical emergencies. The survey also questioned how much former training or experience they had with medical emergencies. The results of the survey show that …

Originalism And The Meaning Of "Twenty Dollars", Michael L. Smith

Faculty Articles

Originalism claims to provide answers, or at least assistance, for those hoping to interpret a Constitution filled with wide-ranging, morally loaded terminology. Originalists claim that looking to the original public meaning of the Constitution will constrain interpreters, maintain consistency and predictability in judicial decisions, and is faithful to ideals like democratic legitimacy. This essay responds with the inevitable, tough question: whether originalism can tell interpreters what the Seventh Amendment's reference to "twenty dollars" means--both as a matter of original meaning and for interpreters today.

While this appears to be an easy question, I demonstrate that rather than telling modern legal …

Rates, Presentation, & Effects Of Public Autism Stigma, Monica Abdul-Chani

All ETDs from UAB

Limited availability of resources regarding developmental issues, health literacy, linguistic-sensitivity (i.e., use of linguistically appropriate resources and measures), structural barriers (i.e., appointment length, transportation), and cultural values and beliefs are commonly-cited barriers in identifying Latine autistic children. Stigma may also play a role, as it is negatively related to both knowledge/awareness within ASD and to acculturation in other disorders (i.e., HIV). Stigma can have detrimental, pervasive effects on daily living for those stigmatized and their families. Limited research examined the rate, presentation, and effect of ASD stigma within the Latine community, and all available studies explored stigma as reported by …

Quantitative Analysis Of The Impact Of Automatically Generated Normal Tissue Contours On Knowledge-Based Planning Model Quality, Samuel Christopher Baker Arnold

All ETDs from UAB

While radiotherapy has become one of the primary standards of treatment for cancer in areas such as the brain, treatment plans are limited by the time it takes physicians to contour CT images used for dose distribution calculations. Automation of the contouring process can not only improve the rate of plan formation but establish an improved standard of care. With the development and implementation of knowledge-based planning (KBP) in radiation oncology, information derived from treatment plans provide machine learning models with years of experience to assess and create future treatment plans. Since KBP model quality rely on contouring from training …

Regulatory Elements Of Polyphosphate Biosynthesis, Marvin Qortez Bowlin

All ETDs from UAB

Polyphosphate (polyP) is an ancient, conserved, inorganic biomolecule. Biological systems have adapted many functions for this high-energy molecule, ranging from immune regulation in mammals to gene regulation in prokaryotes. Of particular interest is its use in bacterial stress responses. Bacteria use polyP to resist hazardous environmental elements like toxic molecules or nutrient starvation. In many bacterial species, polyP is synthesized by polyphosphate kinases (PPKs). PPK – discovered in Escherica coli (E. coli) – hydrolyzes adenosine-5’-triphosphate (ATP) to synthesize polyP. Species that use PPK develop multiple pathogenic defects when PPK activity is impaired, including, among others, antibiotic susceptibility. There is no …

Towards Minimally Invasive Genetically Targeted Control Of Neural Activity Using X-Rays, Kelli Cannon

All ETDs from UAB

X-genetics aims to replace visible light stimulation in optogenetics with X-radiation, offering improved bone penetration, minimal scattering, and enhanced targeting capabilities. This eliminates the need for surgical optic fiber implantation, reducing invasiveness and minimizing off-target effects. Discovering a receptor protein sensitive to X-rays or their byproducts is pivotal for advancing X-genetics.Two genetically encoded X-ray receptors (GEXRs) were investigated for X-genetics application: rhodopsin, historically associated with X-ray responses, and LITE-1, an unexpected candidate. Rhodopsin, when expressed in human embryonic kidney (HEK293) cells, demonstrated robust cAMP decreases upon visible light stimulation but remained unresponsive to moderate and high-dose X-rays, suggesting it may …

Enhancing Racial Identity And Promoting Academic Enablers In Black Adolescent Males Through Film Viewing, Carlos Napoleon Espinoza

All ETDs from UAB

Among Black adolescent males, classroom discrimination is associated with lower academic performance, academic self-concept, and value placed on education. Although efforts aimed at eliminating racism and discrimination should be made, it is important to identify interventions that may mitigate the effects of discrimination on academic outcomes of Black adolescent males. Previously identified protective factors include positive racial socialization, positive racial identity, and Black role models. Thus, this project attempted to integrate these protective factors into a unified intervention approach in which Black role models deliver positive racial socialization messages to enhance positive racial identity and academic enablers through films. Preexisting …

Effects Of Light Curing Bonding Agent With Dual Cure Cement On The Retention Of Zirconia And Lithium Disilicate Crowns: An In-Vitro Study., Mariam Issa

All ETDs from UAB

Objective: To measure and compare the bond strength of zirconia and lithium disilicate crowns bonded to human teeth (enamel and dentin) using universal adhesive with resin cement and different light curing protocols.Methods: Sixty extracted sound non carious human teeth (second premolars) were stored in formalternate solution (FormalternateTM, Concentrate, 500 mL, Canada) and the roots were notched and mounted into acrylic resin (Yates Motloid, USA). Flat surface preparation was done on the occlusal surface of the samples using model trimmer. The surface area of the specimens was measured with digital light microscopy. Samples were randomly divided into six groups of 10 …

The Relative Impact Of Transformational Leadership On The Academic Optimism Of High Poverty Urban Elementary Schools In Alabama, Cheritta Latrice Hayes

All ETDs from UAB

THE RELATIVE IMPACT OF TRANSFORMATIONAL LEADERSHIP ON THE ACADEMIC OPTIMISM OF URBAN ELEMENTARY SCHOOLS IN ALABAMA In an era of accountability, educational leaders seek and implement reform efforts to help promote school improvement and student achievement on a regular basis (Marzano et al., 2014). When considering school improvement, a possible strategy to increase student achievement could be the relationship between the school leadership style and the characteristics of the organization that are within the control of the school leader. The purpose of this study was to examine the relative impact of transformational leadership on the academic optimism of schools. Elementary …

Synthesis And Characterization Of High Entropy Borides Under High-Pressure And High-Temperature Environments, Seth David Iwan

All ETDs from UAB

The high-entropy materials containing five or more constituent elements are of current interest because of enhancement in physical, mechanical, and thermal properties that are not achievable by simple elements or binary alloys. In this thesis, high pressure and high temperature synthesis studies have been carried out on High-Entropy Borides(HEB) like (Hf0.2, Mo0.2, Nb0.2, Ta0.2, Zr0.2)B2 , (Hf0.2, Mo0.2, Nb0.2, Ta0.2, Ti0.2)B2, and (Hf0.2, Ti0.2, Zr0.2, Ta0.2, Mo0.2)B2, at the Advanced Photon Source(APS) High Pressure Collaborative Access Team (HPCAT) Facility. These High Entropy materials are synthesized under high pressure and high temperature starting from a precursor powder composed of desired transition …

Transdiagnostic Symptom Clusters Among Idiopathic Pain And Fatigue Disorders, Chloe Lisette Jones

All ETDs from UAB

Background: There are no established etiologies, biomarkers, or approved treatments for myalgicencephalomyelitis/chronic fatigue syndrome (ME/CFS). It is thought that the ME/CFS criteria may be diagnosing individuals within a spectrum of different disease states, or even different diseases. There likely exist shared mechanisms across idiopathic pain and fatigue disorders, and diverse mechanisms underneath each individual diagnosis. The need to compare ME/CFS to similar, overlapping, and distinct disorders is a critical element in progressing our understanding of idiopathic pain and fatigue. Methods: A total of 2,731 comprehensive medical history and symptom reports were collected from respondents across the globe with a variety …

The Critical Period Of Long-Term Plasticity In Adult-Born Granule Cells Is Mediated By T-Type Calcium Channels, William Michael Kennedy

All ETDs from UAB

Neurogenesis occurs in the dentate gyrus of adult rodents leading to a heterogeneous population of dentate granule cells (GCs) in the granule cell layer. Adult-born granule cells (abGCs) exhibit a transient period of elevated synaptic plasticity that contributes to their role in dentate gyrus function. Various mechanisms have been proposed to underlie the critical period of plasticity, including minimal GABAergic synaptic inhibition, robust NMDAR2B currents, and high intrinsic excitability conferred by T-type Ca2+ channels. In this collection of work, we investigate the critical period for long-term potentiation (LTP) in 4–6-week-old abGCs. We conclude that GABAergic inhibition regulates LTP in 4-week-old …

Characterizing The Role Of Mapk Phosphatases In Age-Dependent Macrophage Dysfucntion And Increased Suceptiblity To Pneumonia In A Tnf-Dependent Manner, Katherine Lauren Kruckow

All ETDs from UAB

Lower respiratory infections are the primary cause of infectious death among the elderly. One reason for this is ‘inflamm-aging,’ a chronic low-grade inflammatory state that develops with advanced age. Pertinently, our group has shown increases in TNF levels to be responsible for age-dependent macrophage dysfunction (ADMD) and, in turn, enhanced susceptibility to Streptococcus pneumoniae, the leading cause of community-acquired pneumonia. The underlying molecular mechanisms responsible, however, remain unclear. Following adoptive transfer of alveolar macrophages (AM) from aged (18+ months) or young (3-6 month) mice into young mice, followed by infection with S. pneumoniae, we found that aged AM were sufficient …

Molecular Imaging To Evaluate Tumor Heterogeneity And Guide Treatment Of Breast Cancer, Yun Lu

All ETDs from UAB

Molecular imaging plays an important role in predicting and evaluating treatment response and revealing the underlying biological mechanisms in the cancer field. Especially, PET imaging serves as a valuable tool for comprehending the tumor microenvironment (TME), allowing us to track tumor metabolism, proliferation, receptor expression, and immune infiltration. In this comprehensive study, three distinct aspects of cancer research were explored using molecular imaging techniques.The first study aimed to evaluate the accuracy of the fluorescence ubiquitination cell cycle indicator (FUCCI) system with fluorescence in vivo imaging compared to 3'-Deoxy-3'-[18F]fluorothymidine ([18F]-FLT) positron emission tomography (PET)/computed tomography (CT) in assessing cancer cell proliferation. …