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Impact Of Achromobacter Xylosoxidans Infection On The Cf Lung In Single-Species And Polymicrobial Infection With Pseudomonas Aeruginosa, Caitlin E. Billiot Jan 2025

Impact Of Achromobacter Xylosoxidans Infection On The Cf Lung In Single-Species And Polymicrobial Infection With Pseudomonas Aeruginosa, Caitlin E. Billiot

All ETDs from UAB

Achromobacter xylosoxidans is a Gram-negative bacillus that acts as an opportun- istic pathogen in those with cystic fibrosis (CF). Infection with A. xylosoxidans in these populations is associated with decreased lung function. Thus, this raises the question of the role of A. xylosoxidans in CF disease progression. CF is a polymicrobial disease and A. xylosoxidans is oftentimes isolated alongside Pseudomonas aeruginosa, a major CF colonizer. In the context of CF disease, it is important to understand the implications of polymicrobial infection as altered infection dynamics are observed when multiple microbes colonize together. In the first half of this work, we …

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Development Of Momordica Saponin-Based Vaccine Adjuvants, Hyunjung Kim Jan 2025

Development Of Momordica Saponin-Based Vaccine Adjuvants, Hyunjung Kim

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Vaccine adjuvants are indispensable substances that help induce a fast, potent, and durable immune response when administered with vaccine antigens. Among the FDA-approved vaccine adjuvants for human use, three of the most recently approved ones contain saponin adjuvant QS-21. To address QS-21’s inherent drawbacks, we investigated the adjuvant activity of a series of saponin-based semisynthetic vaccine adjuvants, including VSA-1 and VSA-2, prepared from natural Momordica saponins I and II in one-step. The natural saponins precursors are isolated from the widely available and inexpensive seeds of Momordica cochinchinensis SPRENG. In general, VSA adjuvants can enhance both humoral and cellular immune responses …

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Black/African American Community Health Workers In Hhs Region 4 And Covid-19 Vaccination: Position Perspective And Power, Cecily A. Gray Jan 2025

Black/African American Community Health Workers In Hhs Region 4 And Covid-19 Vaccination: Position Perspective And Power, Cecily A. Gray

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COVID-19 is caused by the novel and easily transmissible SARS-C0V-2 virus. SARS-C0V-2 was first reported in the Chinese Providence of Hubei in December 2019 and in the United States in January 2020. After nearly 120,000 confirmed global cases and 4,200 deaths in 114 countries, the WHO declared COVID-19 a worldwide pandemic in March of 2020. By fall of 2020, COVI9-19 had become the third leading cause of death in the United States. When compared to other groups, Black/African Americans were disproportionately impacted by the COVID-19 pandemic due to ongoing racial inequities/disparities including chronic illness. Black/African Americans who are more likely …

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Characterizing The Molecular Complexities Of Iga1 By Serum Proteomics In The Context Of Iga Nephropathy, Mary A. Cunningham Jan 2025

Characterizing The Molecular Complexities Of Iga1 By Serum Proteomics In The Context Of Iga Nephropathy, Mary A. Cunningham

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Immunoglobulin A1 (IgA1) is the second most abundantly produced immunoglobulin in circulation per day and plays a key role in human immunity. Two molecular complexities of IgA1 make accurately studying the protein challenging. The first is that IgA1 exists in three main molecular forms in the serum of humans: monomeric (mIgA1, 80-90% of serum IgA1), polymeric (pIgA1, 10-20% of serum IgA1), and IgA1-containing immune complexes (IgA1-IC, <0.5% of serum IgA1). The second complexity is that the hinge-region of IgA1 is extensively O-glycosylated and exhibits a high level of variation in its O-glycans, particularly in the degree of sialylation. In context of the autoimmune disease IgA nephropathy (IgAN), patients have elevated levels of IgA1 that has reduced levels of galactose (Gal) in the IgA1 hinge-region (Gal-deficient IgA1). This Gal-deficient IgA1 forms immune complexes with IgG autoantibodies (IgA1-IC), deposits in the glomeruli, and induces kidney injury. While it is established that these large IgA1-IC (>700 kDa) formed in the circulation are pathogenic, there remains a gap in knowledge about other blood proteins that may be associating with IgA1 in complexes. It is also necessary to understand the native …

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Neural Mechanisms Of Proactive And Reactive Cognitive Control In Humans, Anas Khan Jan 2025

Neural Mechanisms Of Proactive And Reactive Cognitive Control In Humans, Anas Khan

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Cognitive control enables flexible, goal-directed behavior by dynamically adjusting our actions in response to changing task demands. This dissertation investigates the neural mechanisms underlying proactive and reactive cognitive control, particularly focusing on the dorsolateral prefrontal cortex (dlPFC) and the dorsal anterior cingulate cortex (dACC) during tasks that require response inhibition and conflict processing. Using intracranial electroencephalography (iEEG) recordings from human participants, this research examines the distinct roles of oscillatory activity in these regions in both short-term reactive adjustments and long-term proactive control strategies. Chapter 2 explores the role of low-frequency oscillations in the mid-rostral dlPFC during motor inhibition, revealing that …

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A Mixed Methods Approach To Understanding What Knowledge Alabama K-12 In-Service Educators Hold In Regard To School-Based Trauma-Informed Practices, Katherine Busch Jan 2025

A Mixed Methods Approach To Understanding What Knowledge Alabama K-12 In-Service Educators Hold In Regard To School-Based Trauma-Informed Practices, Katherine Busch

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Childhood trauma is prevalent in epidemic proportions, with data showing 40%-90% of individuals experiencing one or more childhood traumatic events that permanently changes neurobiology and stress response. These stress responses can manifest in behaviors that lead to problems in schools, including behavior issues, special education referrals, suspensions or expulsions, and decreased academic achievement. In adulthood, these traumatic stressors increase the odds of engaging in risky behaviors and developing chronic health conditions. Schools can be places of healing, promoting resilience and utilizing trauma-informed practices to help children and educators. Emerging studies show promise in the benefits of school-based trauma-informed practices, but …

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Development Of A Lifestyle Wellness Assessment For Obesity Treatment-Seeking Adults, Katie M. Ellison Jan 2025

Development Of A Lifestyle Wellness Assessment For Obesity Treatment-Seeking Adults, Katie M. Ellison

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Obesity is strongly associated with, and effective at, preventing and managing cardiometabolic disease but proponents of Health at Every Size® approaches challenge the importance of weight loss for improving health. While some patients want to lose weight, there is evidence that others desire to focus on improving broader aspects of health and wellness such as metabolic, fitness, and psychosocial health. Clinicians may benefit from a comprehensive understanding of the multifactorial benefits of obesity treatments to effectively capture overall patient wellness. However, existing wellness assessments are often either not comprehensive, unreliable, or subject to time, space, or cost constraints in clinical …

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A Biomechanical Comparison Of Varying Peg Angles On Glenoid Implant Stability For Anatomic Total Shoulder Arthroplasty, Erica Nicole Schilling Jan 2025

A Biomechanical Comparison Of Varying Peg Angles On Glenoid Implant Stability For Anatomic Total Shoulder Arthroplasty, Erica Nicole Schilling

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Anatomic total shoulder arthroplasty (ATSA) is a surgical procedure in which both the humeral head and the glenoid cavity are replaced with implants resembling the natural anatomy of the shoulder. Several complications may occur after an ATSA, but the most common is glenoid loosening, which makes up about 37.7% of these complications. The overall structure of a glenoid implant is a concave oval plate commonly manufactured from ultra-high molecular weight polyethylene (UHMWPE) with various stabilizing structures, including pegs, protruding from the back of the implant. For this study, the focus was on Catalyst OrthoScience’s pegged glenoid implants and how the …

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Where The Black Women At? Exploring The Narratives & Experiences Of Black Women In Higher Education Leadership, Jasmine P. Jean Jan 2025

Where The Black Women At? Exploring The Narratives & Experiences Of Black Women In Higher Education Leadership, Jasmine P. Jean

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WHERE THE BLACK WOMEN AT? EXPLORING THE NARRATIVES & EXPERIENCES OF BLACK WOMEN IN HIGHER EDUCATION LEADERSHIP JASMINE P. PARKER JEAN HIGHER EDUCATION ADMINISTRATION ABSTRACT This thesis explores the experiences of Black Women in mid- and senior-level leadership roles in higher education, with a focus on the unique challenges they face due to the intersection of race and gender. Black Women remain significantly underrepresented in leadership positions across the academic landscape, despite earning higher education degrees at high rates. The study seeks to amplify the voices of Black Women leaders, providing insight into the barriers they encounter, the strategies they …

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Molecular Mechanism Of Congenital Cataract Caused By G91 Deletion In Cryβa1, Akosua Konadu Boateng Jan 2025

Molecular Mechanism Of Congenital Cataract Caused By G91 Deletion In Cryβa1, Akosua Konadu Boateng

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The Deletion of Glycine 91 is a mutational hotspot in the CRYβA1 gene (mutant named βA3ΔG91), which causes autosomal dominant congenital nuclear cataracts in several ethnically diverse populations worldwide. Previous in-vitro studies of recombinant βA3ΔG91 protein revealed that this mutation results in defective protein folding, reduced solubility, and oligomerization with other crystallins. While βA3/A1-crystallin is primarily known as a structural protein in the lens, it also plays a role in autophagy regulation in the retinal pigment epithelium (RPE) by controlling endolysosomal acidification through the V-ATPase proton pump. This study employs a novel βA3ΔG91 knock-in mouse model to investigate the pathogenic …

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Transcriptomic Transformations And Epigenetic Elements: The Heart Of The Matter Across Diverse Cardiac Pathophysiologies, Sayan Bakshi Jan 2025

Transcriptomic Transformations And Epigenetic Elements: The Heart Of The Matter Across Diverse Cardiac Pathophysiologies, Sayan Bakshi

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Cardiovascular disease (CVD) comprises a complex array of disorders affecting the heart and blood vessels, representing the leading cause of mortality worldwide. This multifaceted nature of CVD has prompted extensive research into its molecular underpinnings and etiological diversity. Despite significant advances, the majority of CVD management strategies are guideline-based symptomatic treatment. This necessitates extensive research studies on therapeutic interventions aimed at disease prevention or cure. In this dissertation, we have employed next-generation sequencing (NGS) techniques to elucidate the cardiac transcriptional and epigenetic landscape across various conditions, including ischemic heart failure (IHF), Cardiogenic shock (CS), and diabetic heart failure (DHF). Our …

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Keep Your Head Up King, Your Crown Is Slippin': An Anti-Deficit Critical Phenomenological Analysis Of Black Male Stem Educators' Experiences, Desmond R. Parker Jan 2025

Keep Your Head Up King, Your Crown Is Slippin': An Anti-Deficit Critical Phenomenological Analysis Of Black Male Stem Educators' Experiences, Desmond R. Parker

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Black males comprise approximately 3% to 5% of the overall K-12 teaching workforce. The science, technology, engineering, and mathematics (STEM) fields are overrepresented in this shortage. This research project aimed to shed light on the experiences of Black male STEM educators to better understand what garnered their interests in STEM, and what ultimately led them to step into the STEM classroom. This study used a critical anti-deficit framework and hermeneutic phenomenological philosophy to understand the experiences of 10 Black male STEM educators in Alabama ranging from three to 30 years of teaching experience. Research data were collected through two semi-structured …

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Processing, Testing, And Characterization Of A Novel Continuous Fiber Thermoplastic Composite Filament For Extrusion Based Additive Manufacturing, Yongzhe Yan Jan 2025

Processing, Testing, And Characterization Of A Novel Continuous Fiber Thermoplastic Composite Filament For Extrusion Based Additive Manufacturing, Yongzhe Yan

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Polycaprolactone (PCL) is a thermoplastic polymer with a low melting point (60°C) and is recognized for its biodegradability and biocompatibility, both of which makes PCL suitable for 3D printing components in biomedical applications. However, its mechanical properties are relatively low and insufficient for some applications such as bone engineering and scaffold design. This study aims to overcome these limitations in mechanical properties by introducing high-performance polymer fibers and by using the fused deposition modeling (FDM) process to print continuous fiber-reinforced PCL composites. This research work focuses on development, testing, and characterization of continuous fiber reinforced PCL composite filaments for extrusion …

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Targeting Streptococcus Mutans Diadenylate Cyclase For The Prevention Of Dental Caries, Edwin Miguel Rojas Jan 2025

Targeting Streptococcus Mutans Diadenylate Cyclase For The Prevention Of Dental Caries, Edwin Miguel Rojas

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Streptococcus mutans (S. mutans) is the primary etiological agent involved in the initiation and progression of dental caries. S. mutans forms robust biofilms on the tooth surface, and current preventative treatments, such as oral rinses, eliminate both pathogenic and commensal oral species. Therefore, there is an urgent need for therapeutics which selectively inhibit S. mutans biofilms while keeping the oral microbiome intact. The diadenylate cyclase (DAC) enzyme in S. mutans plays a key role in biofilm formation. DAC converts adenosine triphosphate (ATP) into cyclic di-AMP (c-di-AMP), a secondary messenger involved in several cellular pathways. Increased levels of c-di-AMP have shown …

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Characterization Of Dhdds Rp59 Knock-In Mouse Models Of Retinitis Pigmentosa, Mai Ngoc Nguyen Jan 2025

Characterization Of Dhdds Rp59 Knock-In Mouse Models Of Retinitis Pigmentosa, Mai Ngoc Nguyen

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Cis-prenyltransferase (CPT), a prenyl chain elongation enzyme made up of two copies of dehydrodolichyl diphosphate synthase (DHDDS) and two copies of Nogo-B Receptor (NgBR), condenses metabolites from the mevalonate pathway to create dolichol, a sugar carrier required for glycosylation in all cells of the body. However, certain missense mutations in DHDDS cause non-syndromic retinitis pigmentosa (RP59). Three missense mutations, K42E, T206A, and R98W have been found in RP59 patients that present the cardinal phenotypes of RP – diminished ERG responses, attenuated retinal vessels, bone spicule-like pigmentation, and retinal thinning due to photoreceptor loss. However, no global changes in glycosylation are …

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Theory-Based Nutrition Education To Improve Food Security In Postsecondary Students, Tara Kelly Jan 2025

Theory-Based Nutrition Education To Improve Food Security In Postsecondary Students, Tara Kelly

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The high prevalence of food insecurity among college students is a public health concern that requires well designed interventions to address. College students experiencing food insecurity are more likely to practice diet-related behaviors that contribute to poor health, yet this population lacks the necessary knowledge and skills to make adequate behavior changes. The purpose of this present dissertation is to (1) assess preliminary data collected to inform the development of a theory-based nutrition education intervention; then (2) evaluate the feasibility of this novel intervention design and (3) its effectiveness at improving college students’ food security and factors that may impact …

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Evaluations Of Hand-Arm Vibration (Hav) Exposure And Related Vascular And Musculoskeletal Heath Effects Among Groundskeeping Workers In Southeastern U.S., Nathan Chen Jan 2025

Evaluations Of Hand-Arm Vibration (Hav) Exposure And Related Vascular And Musculoskeletal Heath Effects Among Groundskeeping Workers In Southeastern U.S., Nathan Chen

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Long-term, excessive exposure to hand-arm vibration (HAV) may induce vascular, neurological, and musculoskeletal disorders, collectively known as hand-arm vibration syndrome (HAVS). However, concerns arise when adopting the currently available guidelines and standards to protect workers who regularly use vibrating tools due to the lack of standardized exposure assessment methods for HAV and reliable health indicators for HAVS. The existing exposure-response relationship addressed in ISO 5349-1 was developed based on epidemiological studies predominantly performed in temperate zones. Thus, this dissertation aimed to evaluate the HAV exposure levels and vascular and muscular health effects from vibration exposure among groundskeepers in the southeastern …

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Voltage-Gated Sodium Channel Nav1.7 Subtype: A Promising Therapeutic Target For Metastatic Medullary Thyroid Cancer, Piyasuda Pukkanasut Jan 2025

Voltage-Gated Sodium Channel Nav1.7 Subtype: A Promising Therapeutic Target For Metastatic Medullary Thyroid Cancer, Piyasuda Pukkanasut

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Medullary thyroid carcinoma (MTC), a rare neuroendocrine tumor, presents considerable clinical challenges due to its tendency to metastasize to organs such as the liver, bones, and brain, resulting in poor patient outcomes. Voltage-gated sodium channels (VGSCs) have emerged as potential therapeutic targets in various malignancies due to their crucial role in promoting cancer cell progression, migration, invasion, and metastasis. This dissertation investigates the specific contributions of the VGSC NaV1.7 subtype in MTC, evaluating its potential as a therapeutic target and elucidating its mechanistic involvement in MTC. Initially, we assessed VGSC subtypes expression in MTC cells. The screening revealed an overexpression …

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New Frontiers In Synthesis Of High-Entropy Materials Enabled By Microwave-Induced Plasma, Bria Christina Storr Jan 2025

New Frontiers In Synthesis Of High-Entropy Materials Enabled By Microwave-Induced Plasma, Bria Christina Storr

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This dissertation presents the novel approach for synthesizing high entropy borides (HEBs) and high entropy alloys (HEAs) using microwave-induced plasma as a rapid and efficient processing tool. High entropy materials (HEMs) have peaked interested in recent years due to their unique properties and practical applications such as thermal stability, and corrosion and wear resistance. HEMs are designed by combining multiple principal elements in near-equimolar ratios, enhancing stability, and offering a broad spectrum of tailored mechanical properties. The inclusion of multiple transition metals within these structures increases hardness and oxidation resistance, and the flexibility in element selection enables precise tuning for …

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Development Of Cardiac Tissue Chip Platforms For In Vitro Modeling Of Myocardial Fibrosis, Caleb Graham Jan 2025

Development Of Cardiac Tissue Chip Platforms For In Vitro Modeling Of Myocardial Fibrosis, Caleb Graham

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Myocardial fibrosis often accompanies cardiovascular disease of varying etiologies. Initial reparative myocardial remodeling following insult, characterized by fibroblast-to-myofibroblast transdifferentiation and myofibroblast-mediated collagen deposition, can become a chronic, maladaptive process if injurious stimuli are not removed and inflammation persists, and the resultant fibrosis worsens cardiac function through myocardial stiffening and arrhythmogenic disruption of cardiomyocyte coupling. There are no FDA-approved therapies targeting myocardial fibrosis, in large part due to the complexity of the disease process. In vitro models can serve as useful complements to in vivo studies as they allow for significantly greater control over experimental variables. Cardiac tissue chips (CTCs) are …

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Voices From Rural Classrooms: African American Girls’ Middle School Experiences And Engagement With Science, Malysa Chandler Jan 2025

Voices From Rural Classrooms: African American Girls’ Middle School Experiences And Engagement With Science, Malysa Chandler

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Although the number of women pursuing science careers has increased, there is still a very low representation of African American women in science-related professions. In effort to ignite the interest of African American women in science-related careers, a shift will need to take place in the pedagogical practices of middle school teachers that will increase African American girls’ engagement in science. This shift in pedagogical practices will require the conjoining efforts of informal science programs that operate under the same pedagogical practices. The purpose of this qualitative study was to explore the middle years science experiences of African American girls …

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The Unknown Turning Point: How Operation Pedestal Secured Allied Dominance In Europe, Brian Zachary Williamson Jan 2025

The Unknown Turning Point: How Operation Pedestal Secured Allied Dominance In Europe, Brian Zachary Williamson

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Operation Pedestal was a World War II convoy operation in the Mediterranean that successfully resupplied the island of Malta in late 1942. The convoy fought through constant Axis air raids and submarine attacks, which resulted in high British losses. The operation was overshadowed by the Allied invasion of North Africa during Operation Torch, which was launched soon after. Malta’s role throughout the war in the Mediterranean made it vital for the British to hold and the Pedestal convoy’s successful effort to keep the island from capitulation should make the operation be considered as a turning point. The few military historians …

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The Dopaminergic Cell-Intrinsic Clock And Bidirectional Relationships Of Circadian Disruption And Synucleinopathy, Ananya Swaroop Jan 2025

The Dopaminergic Cell-Intrinsic Clock And Bidirectional Relationships Of Circadian Disruption And Synucleinopathy, Ananya Swaroop

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Circadian rhythms are crucial endogenous cycles with period of ~24 hours that evolved to adapt to light – dark driven changes in environmental conditions. At a molecular level, circadian rhythms are generated by the actions of clock genes that form a transcriptional- translational feedback loop and regulate the rhythmic expression of downstream clock-controlled genes. Cumulatively, the actions of these molecular clocks regulate rhythmicity of physiological and behavioral processes and are extensively characterized within the central circadian pacemaker, the suprachiasmatic nucleus (SCN). Like SCN neurons, dopaminergic neurons of the SN are intrinsically pacemaking, though it is unknown if this intrinsic firing …

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Understanding The Insecticidal Toxin Xpta2: A Shift In Toxin Complex Biology, Cole Lorenza Martin Jan 2025

Understanding The Insecticidal Toxin Xpta2: A Shift In Toxin Complex Biology, Cole Lorenza Martin

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Pore forming toxins (PFTs) belonging to the ABC toxin complex (Tc) family are responsible for targeting and translocating toxins into target cells. ABC toxins consist of three separate subunits, each subunit providing a vital role in the cytotoxic mechanism of the Tc. The A subunit or TcA is the largest subunit of the complex and contains the binding domains and the translocation channel that perforates the membrane. The B subunit or TcB functions as a gated linker that forms a cocoon with the TcC which houses the toxic peptide and subsequently gets translocated through the TcB and TcA into the …

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Role Of Ring-Box E3 Ligases In Runx2 And Sp7 Protein Turnover During Osteoblast Differentiation, Abeera Sikandar Jan 2025

Role Of Ring-Box E3 Ligases In Runx2 And Sp7 Protein Turnover During Osteoblast Differentiation, Abeera Sikandar

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The bone matrix synthesis by osteoblast during skeletogenesis is regulated by several transcription factors and signaling pathways. Runx2 and Sp7 are master regulators of osteoblast differentiation and bone formation. Deletion of both genes in mice results in the complete failure of ossification. In humans, Sp7 and Runx2 genes mutations cause osteogenesis imperfecta and cleidocranial dysplasia, respectively. The progression of osteoblast differentiation requires a coordinated and temporal expression of Runx2 and Sp7 genes. Posttranslational modifications regulate the cellular levels and function of Runx2 and Sp7 proteins. Ubiquitination controls protein turnover through targeted degradation. The multi-subunit SCF-complex is the largest class of …

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Mitigating The Impacts Of Future Climate Change On Urban Infrastructure In Alabama Through Updating Precipitation Intensity-Duration-Frequency (Idf) Curves, Kofi Ntow Opare Jan 2025

Mitigating The Impacts Of Future Climate Change On Urban Infrastructure In Alabama Through Updating Precipitation Intensity-Duration-Frequency (Idf) Curves, Kofi Ntow Opare

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Climate change is set to profoundly impact urban infrastructure, causing increased flooding and storm damage, necessitating the reevaluation and adaptation of design methodologies to account for increasing precipitation extremes. This dissertation aims to enhance the resilience of urban infrastructure in Alabama by updating Precipitation Intensity-Duration-Frequency (IDF) curves, which are crucial for designing stormwater management systems, drainage networks, and flood control structures. Traditional IDF curves, derived from historical rainfall data, operate under the assumption of stationarity, an assumption increasingly invalidated by climate change. This research employs the Generalized Extreme Value (GEV) distribution and compares the efficacy of L-moments and Generalized Maximum …

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Gendered Sexual Behaviors: Unintended Pregnancies, And Sexually-Transmitted Infections, Deirdre Ferguson Jan 2025

Gendered Sexual Behaviors: Unintended Pregnancies, And Sexually-Transmitted Infections, Deirdre Ferguson

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Education is the most effective way to address unintended pregnancies and sexually-transmitted infections (STIs). Education through preventative counseling has been negatively correlated with unintended pregnancies. Although research has shed light on the risks posing challenges to the prevention of unintended pregnancies, the consequential costs of these pregnancies continue to mount, both individually and societally. Birth control counseling corresponds with reducing the behavior of nonuse of contraceptives significantly. Education is thus associated with combatting inaccurate information passed along via primary social groups. To gain insight into the prevention of unintended pregnancies and STIs, data was gathered using a mixed-method approach incorporating …

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St6gal1 Is Upregulated In Pancreatic Cancer Cells By Pro-Inflammatory Cytokines, Austin David Silva Jan 2025

St6gal1 Is Upregulated In Pancreatic Cancer Cells By Pro-Inflammatory Cytokines, Austin David Silva

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The sialyltransferase ST6GAL1 is overexpressed in several cancers, including pancreatic ductal adenocarcinoma (PDAC). ST6GAL1 adds an α2-6-linked sialic acid to N-glycosylated membrane proteins, modifying their structure and function. Despite extensive research on how ST6GAL1 affects cell phenotype, the mechanisms regulating its expression remain largely unexplored. In this study, we investigated how two pro-inflammatory cytokines, IL-1β and IL-6, prevalent in the PDAC tumor microenvironment, regulate ST6GAL1 expression. We used the Suit-2 PDAC cell line and its metastatic subclones, S2-013 and S2-LM7AA, to monitor cytokine activity. Treatment with IL-1β or IL-6 increased ST6GAL1 protein and mRNA expression across all cell models. Specifically, …

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Mechanistic Insights Of Translational Readthrough To Suppress Nonsense Mutations, Kari Thrasher Jan 2025

Mechanistic Insights Of Translational Readthrough To Suppress Nonsense Mutations, Kari Thrasher

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A nonsense mutation is a point mutation in DNA that gives rise to a premature termination codon (PTC) in the open reading frame of the transcribed mRNA. Translation of this PTC-containing transcript terminates prematurely, leading to the creation of truncated non-functional protein. Translational readthrough is one therapeutic option being explored to suppress nonsense mutations that cause disease. Here, we further elucidate amino acid incorporation and the functional consequences of readthrough of nonsense mutations that cause cystic fibrosis. Additionally, we reveal the molecular mechanisms activated by a recently described small molecule readthrough agent, SRI- 41315. Finally, we discuss the various therapeutic …

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Production And Radiochemistry Of Theranostic Radioscandium Nuclides, Shelbie Jaylene Cingoranelli Jan 2025

Production And Radiochemistry Of Theranostic Radioscandium Nuclides, Shelbie Jaylene Cingoranelli

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In nuclear medicine, theranostics utilizes radionuclide pairs for diagnosis and therapy. Radioscandium isotopes (43Sc, 44Sc, and 47Sc) offer a promising alternative to the 68Ga/177Lu theranostic pair due to their identical radiolabeling conditions, complexes and in vivo pharmacokinetics. 43Sc (t1/2=3.89h, β+=88%) and 44Sc (t1/2 =3.97h. β+=94.3%) are suitable for Positron Emission Tomography (PET) imaging whereas 47Sc (t1/2=3.3d. Eβ-ave=162keV) is suitable for targeted radiotherapy and Single Photon Emission Computed Tomography (SPECT). These isotopes require production routes that lead to high radionuclidic purity and radiochemistry development for incorporation into radiopharmaceuticals. This study explores the production, purification, and application of these isotopes. The proton …

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