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2020

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T Cells In Synucleinopathies, Gregory Paul Williams Jan 2020

T Cells In Synucleinopathies, Gregory Paul Williams

All ETDs from UAB

Synucleinopathies, which include Parkinson disease (PD), dementia with Lewy Bodies (DLB), and multiple system atrophy (MSA), are a collection of neurodegenerative diseases that are in major part defined by the presence of alpha-synuclein (α-syn) rich protein aggregates in the brain. Increasing evidence has highlighted a neuroinflammatory phenotype also associated with these synucleinopathies. This neuroinflammatory phenotype includes the activation of central nervous system (CNS) microglia, increased pro-inflammatory cytokines, and the infiltration of peripheral T cells into the CNS. We sought to further explore the T cell responses associated with PD and MSA. Using two preclinical mouse models of PD and MSA, …

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Co-Factors In Fgf Signaling, Christopher Yanucil Jan 2020

Co-Factors In Fgf Signaling, Christopher Yanucil

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The fibroblast growth factor (FGF) family consists of a group of proteins whose diverse biological functions are mediated by receptor tyrosine kinases, termed FGF receptors (FGFR) 1-4. While paracrine FGFs require heparin sulfate as a co-factor for FGFR bind-ing and signaling, it has been assumed that endocrine FGFs, such as FGF23, do not bind heparin but instead require klotho, a family of transmembrane proteins, as a co-receptor on specific target cells. FGF23 acts as bone-derived hormone that targets tubular epitheli-al cells in the kidney via FGFR1 and α-klotho to reduce renal phosphate uptake. In chron-ic kidney disease (CKD), the kidney …

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Network-Based Analytics For Discovering Gene Modules And Biomarkers In Complex Diseases, Zongliang Yue Jan 2020

Network-Based Analytics For Discovering Gene Modules And Biomarkers In Complex Diseases, Zongliang Yue

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With rapidly increasing novel discoveries of associations between genomic data and complex disease phenotypes, the translation of those associations into knowledge and the identification of critical molecular mechanisms are essential to guild clinical decisions such as the diagnosis of symptomatic individuals, the prediction of disease risk, reproductive genetic counseling, and determining pharmacogenetic profiles for treatment. To decipher the genome of complex diseases, gene-centric analyses focus on detecting molecular mechanisms lead by driver genetics variants, abnormally expressed genes and high-abundance proteins through gene module construction. Additionally, the gene module construction approaches implement systems biology analysis to reveal the causative co-expressed gene …

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Development Of Natural Language Processing Algorithm For Dental Charting, Yi-Fan Zhang Jan 2020

Development Of Natural Language Processing Algorithm For Dental Charting, Yi-Fan Zhang

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Purpose: The purpose was to develop a natural language processing algorithm, which will input data from oral examination transcripts to a structured database. Methods: Four case vignettes were produced for primary, mixed, and permanent dentition patients with varying degree of soft tissue pathology, caries, existing restorations and occlusion relationships. After calibration, dental students were instructed to perform simulated oral examinations based on the case vignettes, using natural language as they would to an assistant who was charting the case. The investigator transcribed the audio recordings of the simulated oral exams. Twenty simulated oral examinations were collected to develop a natural …

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Dietary Nitrate And The Oral Microbiome In Obesity, Health And Exercise, Christian E. Behrens Jan 2020

Dietary Nitrate And The Oral Microbiome In Obesity, Health And Exercise, Christian E. Behrens

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Obesity ranks among the top growing health concerns worldwide. The prevalence of obesity at all life stages continues to rise with nearly 40% of adults and 35% of children/adolescents being affected. Equally troublesome is the increased risk for a number of comorbidities associated with obesity including cardiovascular disease, stroke, type 2 diabetes mellitus, and certain types of cancer. The successful treatment of obesity, particularly long-term, continues to prove challenging and is often met with limited success. This highlights the importance of continued investigation into alternative strategies that may reduce the incidence and severity of obesity and associated pathophysiologies. Regular physical …

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Parents’ Personal Characteristics In Explaining Perceptions Of Infant Temperament, Logan Boe Jan 2020

Parents’ Personal Characteristics In Explaining Perceptions Of Infant Temperament, Logan Boe

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Although a popular topic in developmental psychology research, straightforward ways to interpret measurements of infant temperament (IT) are lacking. Notably, parental personal characteristics, such as psychological distress and regulatory abilities, and resources available to parents may influence parents’ IT reports. The aims of the current project were to: 1) determine if parental characteristics mediate the association between IT and household income; 2) determine if personal resources available to parents (social support, coping, partner satisfaction) moderate the relationships between parental characteristics and IT; and 3) determine which parental characteristics predict differences between mothers’ and fathers’ IT reports. Prenatally, 201 mothers and …

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Measuring Student Attitudes Toward Offenders: The Potential Mediating Role Of Familial Incarceration, Susan Faith Boyd Jan 2020

Measuring Student Attitudes Toward Offenders: The Potential Mediating Role Of Familial Incarceration, Susan Faith Boyd

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Each year hundreds of thousands of ex-offenders are released from U.S. jails and prisons to return to their communities. After release, ex-offenders’ families can play a critical role in helping their loved ones re-adjust to life outside of prison as well as meet the terms of their release; however, the severe financial, emotional, and social hardships associated with reentry have great potential to strengthen or weaken ex-offenders’ family support networks. The current study sought to explore how attitudes toward offenders differ between offenders’ family members and individuals who have never experienced familial incarceration. Adaptations of The Attitudes Toward Prisoners Scale …

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Symbolic Annihilation, The Politics Of (Mis)Representation, And The Stress And Health Of Millennial Black Women, Chenoia Nicole Bryant Jan 2020

Symbolic Annihilation, The Politics Of (Mis)Representation, And The Stress And Health Of Millennial Black Women, Chenoia Nicole Bryant

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The (mis)representation of Black populations in media has been extensively explored and critiqued by several scholars. From their introduction into media through radio to their visi-bility in television and news, the tropes of Black womanhood have carried over from colo-nialist perspectives to present day. Considering race and gender as cultural structures con-straining Black women through the assignment of stereotypical scripts, it is important to consider how, when and where Black women’s agency enters. Negative racialized and gendered stereotypes are informed by culture at large, but Black women’s agency impacts the interpretation of these (mis)representations, offering space for both conformity and …

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Cognitive Factors And Treatment Adherence In Individuals With Cystic Fibrosis, Benjamin Edwin Burgess Jan 2020

Cognitive Factors And Treatment Adherence In Individuals With Cystic Fibrosis, Benjamin Edwin Burgess

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Cystic fibrosis (CF) is a life-threatening chronic illness which requires adherence to a many complex and time-consuming treatments. Adherence is suboptimal in this population. Thus, it is important to consider predictors of treatment adherence. Research has evaluated a number of cognitive factors that are related to adherence in groups with chronic illnesses, including those with CF. The present study considers three factors (health locus of control (HLC), perceived social support, and perceived disease severity) in order to address important gaps in the literature evaluating their relationships with treatment adherence. For each of these factors, the current research is limited by …

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Epigenetic Regulation In Cancer And Development, Theodore Busby Jan 2020

Epigenetic Regulation In Cancer And Development, Theodore Busby

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Feedback loops between cellular cues and changes in gene expression mediate the interactions between a multitude of regulatory events that promote development and cancer. Vesicular trafficking is an important process in carrying out signaling events by transporting receptors and ligands to and from the cell surface. GBF1 and BIG1 are large guanine-exchange factors (GEFs) that activate GTPase mediated shuttling of cargo through the Golgi apparatus. This dissertation demonstrates that GBF1 localizes to the cytoplasmic membrane in glioblastoma multiform cells to maintain cell shape and promote migration. Reports have shown that BIG1translocates to the nucleus is hepatocyte carcinoma cell lines in …

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Understanding Adolescent Sexual Health Through Exploration Of Their Perceptions, Behaviors, And Beliefs, Jessica L. Corcoran Jan 2020

Understanding Adolescent Sexual Health Through Exploration Of Their Perceptions, Behaviors, And Beliefs, Jessica L. Corcoran

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Adolescents in the United States disproportionately experience adverse sexual health outcomes compared to adolescents in other developed countries. The purpose of this dissertation is to provide an in-depth examination of adolescent sexual health through the generation of three manuscripts. The first manuscript will provide an integrative review of adolescents’ perceptions of sexual health education programs. The second manuscript will illuminate the five-year trends in adolescent chlamydia rates by region, race, and sex. The third manuscript will provide a qualitative analysis from interviews with African American adolescent females in the southern U.S. Manuscript one reviewed studies from 2008 to 2019. The …

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Enhancer Rnas As Regulators Of Gene Expression And Neuronal Function, Nancy Verena Nicole Carullo Jan 2020

Enhancer Rnas As Regulators Of Gene Expression And Neuronal Function, Nancy Verena Nicole Carullo

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Genomic enhancers are cis-regulatory elements in the DNA that exhibit spatial and temporal control over intricate gene expression programs shaping fate and function of heterogeneous cell populations in the developing and adult brain. In addition to their role in cellular development and maintenance, enhancer activity drives transcriptional changes in response to stimulation. Active enhancers are subject to bidirectional transcription that yields non-coding enhancer RNAs (eR-NAs). However, the functional role of eRNAs in transcriptional regulation remains controversial. Therefore, we used primary neuronal cultures to investigate en-hancers and eRNAs in the rat genome. We identified and verified enhancer-gene pairs, characterized their response …

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Disparities In End-Of-Life Care In Children Dying Of Cancer In Alabama: A Cross Sectional Study, Elizabeth Statham Davis Jan 2020

Disparities In End-Of-Life Care In Children Dying Of Cancer In Alabama: A Cross Sectional Study, Elizabeth Statham Davis

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Regional studies show that children dying of cancer receive medically intense end-of-life care but there is limited information about end-of-life care in the Deep South and limited information about hospice and palliative care involvement at EOL. We conducted a retrospective electronic medical record review of children (0-x years) that died of cancer between 2010-20199 who received cancer directed therapy at Children’s of Alabama. We collected patient clinical and sociodemographics factors, including sex, race, and area deprivation index, cancer diagnosis and treatment, palliative care and hospice involvement, location of death, and medical care in the last 30d of life, including chemotherapy …

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Obesity-Induced Immune Dysfunction: Implications For Anti- Tumor Immunity And Immunotherapeutic Efficacy, Justin Tyler Gibson Jan 2020

Obesity-Induced Immune Dysfunction: Implications For Anti- Tumor Immunity And Immunotherapeutic Efficacy, Justin Tyler Gibson

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In the US, nearly 40% of adults have obesity. Further, obesity is known toincrease the risk for development, recurrence, and mortality associated with multiple types of cancer. However, despite such high prevalence, the impact of excess body weight on anti-tumor immunity and response to immunotherapeutics remains poorly and incompletely understood. In order to address these deficiencies, we have utilized multiple approaches to study obesity-associated perturbations in the immunogenetic, soluble protein, and cellular profiles of mice bearing mammary tumors and treatment naive human subjects with clear cell renal cell carcinoma (ccRCC). In a pre-clinical murine model of breast cancer, we find …

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Denervation Supersensitivity Of Βeta-Adrenergic Receptors In A Prodromal Model Of Alzheimer's Disease, The Tgf344-Ad Rat, Anthoni Goodman Jan 2020

Denervation Supersensitivity Of Βeta-Adrenergic Receptors In A Prodromal Model Of Alzheimer's Disease, The Tgf344-Ad Rat, Anthoni Goodman

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The central noradrenergic (NA) system is critical for maintenance of attention, behavioral flexibility, spatial navigation, and learning and memory, those cognitive functions lost first in early Alzheimer’s disease (AD). In fact, the locus coeruleus (LC), the major source of norepinephrine (NE) in brain, is the first site of pathological tau accumulation in human AD associated with axon loss throughout forebrain, including hippocampus. The dentate gyrus (DG) is heavily innervated by LC-NA axons, where released norepinephrine (NE) acts on β adrenergic receptors (ARs) at excitatory synapses from entorhinal cortex (EC) to facilitate long-term synaptic plasticity and memory formation. These synapses show …

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Il-17 Producing Cd4 T Cells In Spontaneous Germinal Center And Autoantibody Formation In Murine Lupus, Huixian Hong Jan 2020

Il-17 Producing Cd4 T Cells In Spontaneous Germinal Center And Autoantibody Formation In Murine Lupus, Huixian Hong

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IL-23 promotes autoimmune disease, including Th17 CD4 T-cell development and autoantibody (autoAb) production. Here, we show that a deficiency of the p19 component of IL-23 in the autoimmune BXD2 (BXD2-p19−/−) mouse leads to a shift of the follicular T-helper cell program from Tfh-IL-17 to Tfh-IFN-ɣ. Although the germinal center (GC) size and the number of GC B cells remained the same, BXD2-p19−/− mice exhibited a lower class-switch recombination (CSR) in the GC B cells, leading to lower serum levels of IgG2b. Single-cell transcriptomics analysis of GC B cells revealed that while Ifngr1, Il21r and Il4r genes exhibited a synchronized expression …

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Examining The Role Of Neighborhood Quality On The Association Of Mammography Adherence Among Racial/Ethnic Groups, Roman Johnson Jan 2020

Examining The Role Of Neighborhood Quality On The Association Of Mammography Adherence Among Racial/Ethnic Groups, Roman Johnson

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Although several racial/ethnic minority women groups (e.g., Latina, Black, Asian-American, and Native-American women) have lower breast cancer incidence than white women, they are more likely to die from breast cancer. One possible explanation for this discrepancy is racial/ethnic differences in mammography use. Mammography has been shown to contribute to the discovery of tumor proliferation earlier which translates to less breast cancer complications like greater risk of breast cancer-related mortality. Previous studies on racial/ethnic differences in mammography adherence (e.g., annual and biannual mammography adherence) have been inconclusive, and they generally overlook important contextual factors, namely neighborhood quality and geographic location (e.g., …

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Is Ambition Consequential? Exploring The Association Between Depressive Symptomatology And The Educational Expectation Trajectories And Achievements Of Immigrant Youth, Fabrice Stanley Julien Jan 2020

Is Ambition Consequential? Exploring The Association Between Depressive Symptomatology And The Educational Expectation Trajectories And Achievements Of Immigrant Youth, Fabrice Stanley Julien

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Concerning mental health outcomes, immigrant youth are a particularly vulnerable population. The lack of health care access contributes to aggrandized and unmet mental health needs. This research explores how the social positions of immigrant families influence stress exposure and contribute to a worsening of well-being. Past research points to the societal stressors experienced by these young people, as significant predictors of their well-being. But what occurs when the source of stress originates within the home? Specifically, this study examines how stress, educational expectations and academic achievement influence the depressive symptomatology of immigrant youth. Education is a widely recognized predictor of …

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Pharmacodynamic Responses And Efficacies Associated With Lrrk2 Inhibition, Kaela Kelly Jan 2020

Pharmacodynamic Responses And Efficacies Associated With Lrrk2 Inhibition, Kaela Kelly

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Parkinson’s disease (PD) is an age-related, progressive, movement disorder pathologically characterized by the loss of dopaminergic neurons in the substantia nigra pars compacta (SNpc) and the presence of proteinaceous aggregates, termed Lewy bodies, that are largely comprised of αSynuclein (αSyn). Missense mutations in the leucine-rich repeat kinase (LRRK2) gene are the most common genetic cause of PD and lead to gain-of-function increases in kinase activity. The G2019S-LRRK2 mutation is the most frequent mutation and elevates kinase activity by ~2-3 fold. Genetic and biochemical evidence suggest elevated LRRK2 kinase activity plays a pathogenic role in the development of PD, implicating LRRK2 …

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The Effect Of Gi Patients' Health Literacy Levels On Gi Patients' Health Outcomes, Dae Hyun Kim Jan 2020

The Effect Of Gi Patients' Health Literacy Levels On Gi Patients' Health Outcomes, Dae Hyun Kim

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The paper in this dissertation provide empirical evidence on the effect of GI patients’ health literacy levels on GI patients’ health outcomes. The findings of this study contribute to existing body of literature on health literacy and health outcomes. Furthermore, the findings also offer both theoretical and practical implications to physicians, healthcare administrators, and policymakers. Overall, the results of this study show that GI patients’ health literacy levels are negatively associated with GI patients’ health outcomes (hospital length of stay, readmission, and complication). However, partial support was shown for different types of GI surgeries accentuating the negative association between GI …

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Incorporating Spatial Structure Into Bayesian Variable Selection Using Spike-And-Slab Priors With Application To Imaging Data, Justin Leach Jan 2020

Incorporating Spatial Structure Into Bayesian Variable Selection Using Spike-And-Slab Priors With Application To Imaging Data, Justin Leach

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Many applications in neuroscience, psychology, medicine, and public health require collecting and analyzing imaging data. While fine resolution images may appear continuous to the naked eye, they are in fact made up of measurements at discrete locations, either pixels in 2D or voxels in 3D. These data may be treated as the scientific outcomes of interest, or as predictors of outcomes of interest. Here, the concern is with the latter situation, which involves converting images into formats amenable to a linear modeling framework; i.e., each subject’s image is converted into a vector, and used to model the subject’s (scalar) outcome …

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A Preliminary Analysis On The Effects Of Acute Beetroot Juice Intake On Glycemic And Blood Pressure Control In Type 2 Diabetes, Braxton Linder Jan 2020

A Preliminary Analysis On The Effects Of Acute Beetroot Juice Intake On Glycemic And Blood Pressure Control In Type 2 Diabetes, Braxton Linder

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Cardiometabolic diseases are becoming increasingly prevalent in modern society due to low activity lifestyles and poor nutrition. Inorganic dietary nitrate (diNO3) has shown to potentially improve cardiometabolic health in a number of different populations but remains to be corroborated in humans with type 2 diabetes (T2D). This preliminary analysis aimed to determine the effects of consuming an acute, concentrated dose of diNO3 containing beetroot juice (BRJ) on hemodynamic and glycemic responses in humans with T2D while controlling for pharmacological influences. Three participants with a clinical diagnosis of T2D were recruited into this study. Pulsewave Velocity (PWV) was used to assess …

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The Retention Of Zirconia Crowns Luted With Resin And Rmgi Cements And The Effect Of Salivary Contamination, Stephen Liu Jan 2020

The Retention Of Zirconia Crowns Luted With Resin And Rmgi Cements And The Effect Of Salivary Contamination, Stephen Liu

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Purpose: To measure retention of zirconia crowns bonded with resin and RMGI cements and the effect of salivary contamination following 10,000 cycles of thermocycling. Materials and Methods: 64 extracted human mandibular premolars were divided into eight groups (n = 8/group). The specimens in each group were prepared for Katana HT zirconia (eight groups) and one of four luting cements (one for each group): 3M ESPE RelyX Luting Plus RMGI, 3M ESPE Rely X Unicem 2 self-adhesive, Kuraray Panavia SA Universal self-adhesive, and 3M ESPE RelyX Ultimate dual cure resin cement with Scotchbond Universal. The roots of the selected teeth were …

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Nonsyndromic Hypodontia Of Maxillary Lateral Incisors, Its Genetics And Its Association With Other Dental Anomalies, Giana Lupinetti Jan 2020

Nonsyndromic Hypodontia Of Maxillary Lateral Incisors, Its Genetics And Its Association With Other Dental Anomalies, Giana Lupinetti

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NONSYNDROMIC HYPODONTIA OF MAXILLARY LATERAL INCISORS, ITS GENETICS, AND ITS ASSOCIATION WITH OTHER DENTAL ANOMALIES GIANA LUPINETTIDEPARTMENT OF ORTHODONTICS ABSTRACT Congenital absence of maxillary lateral incisors presents a difficult situation for clini-cians for restorative and orthodontic purposes. Further, missing lateral incisor agenesis (MLIA) has been associated with other dental anomalies and cancer. 1 Few studies have targeted MLIA as a specific subtype of hypodontia. WNT10A is a candidate gene for MLIA. 2 The hypothesis was that genetic mutations in WNT10A affect maxillary lateral tooth development and can contribute to other dental anomalies. The first aim was to evaluate patients with …

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Protective Host Responses During Acute And Chronic Lung Exposure To Aspergillus Fumigatus, Joseph Mackel Jan 2020

Protective Host Responses During Acute And Chronic Lung Exposure To Aspergillus Fumigatus, Joseph Mackel

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Aspergillus fumigatus is an environmental airborne fungus that acts as both an opportunistic pathogen and an allergen. In immunocompromised hosts, A. fumigatus can germinate in the lung, cause tissue damage and pneumonia, and disseminate to other organs, causing a disease termed invasive aspergillosis (IA). In severe asthma, sensitization to fungi such as A. fumigatus is associated with more severe disease. Determination of host and fungal factors that drive immunoprotection versus immunopathogenesis in both of these settings will ultimately enable therapeutic modulation of immune responses to improve disease outcomes. In this body of work, we build on recent findings that implicate …

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Gp44, A Minor Protein With A Major Role In Bacteriophage 80Α Infection, Keith Allen Manning Jan 2020

Gp44, A Minor Protein With A Major Role In Bacteriophage 80Α Infection, Keith Allen Manning

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Bacteriophage 80α is a temperate double-stranded DNA phage that infects Staphylococcus aureus and is capable of mobilizing a variety of mobile genetic elements named S. aureus Pathogenicity Islands. The capsid of the mature virion is composed of subunits of the capsid protein, portal protein, and a minor capsid protein gp44 as well as packaged phage genomic DNA. The loss of the gp44 protein completely eliminates the phage titer of 80α but does not eliminate the transduction of the pathogenicity islands. In this dissertation, I show that the minor capsid protein is primarily active in a post-ejection role. Without gp44 the …

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Life-Space And Cognitive Function By Cardiovascular Disease Risk: A Cross-Sectional Analysis From The Regards Study, Emiri Matsuda Jan 2020

Life-Space And Cognitive Function By Cardiovascular Disease Risk: A Cross-Sectional Analysis From The Regards Study, Emiri Matsuda

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Performance on mobility assessments has been extensively linked to processing speed and executive function among older adults. However, less is known about the relationship between cognitive function and functional mobility as part of day to day life. African American individuals are at higher risk of cardiovascular complications, functional mobility, and cognitive decline compared to Whites. In addition, cardiovas-cular disease risk factors and neuropathology have been linked to impairment in several domains of cognitive function, including processing speed. The current study examined the cross-sectional association between life-space and cognitive function, specifically performance on the Digit Symbol Substitution Test (DSST), a measure …

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The Role Of The Β-Catenin Signaling Pathway In Modulating The Nucleolar Proteome Of Triple Negative Breast Cancer, Shannon E. Meier Jan 2020

The Role Of The Β-Catenin Signaling Pathway In Modulating The Nucleolar Proteome Of Triple Negative Breast Cancer, Shannon E. Meier

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Previously, abnormal nucleoli were noted as indicators of cancerous lesions andused as a pathologic readout of neoplasia. Nucleolar hypertrophy and increased nucleolar number have been correlated with increased breast cancer (BC) mortality rates. Although various functions of the nucleolus have been investigated, it remains widely understudied in the context of cancer. The nucleolus was initially thought to be solely the site of ribosome biogenesis. However, over half of the proteins found in the nucleolus are associated with other biological functions. It is evident that the nucleolus plays major roles in stress response, DNA repair, and critical cellular aspects that influence …

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Evaluation Of The Effectivenss Of Rotc Army Cadet Exercise Training For The Army Combat Fitness Test, Jake Mintz Jan 2020

Evaluation Of The Effectivenss Of Rotc Army Cadet Exercise Training For The Army Combat Fitness Test, Jake Mintz

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The purpose of the study is to evaluate the effectiveness of ROTC Army cadet exercise training for the Army Combat Fitness Test (ACFT). A secondary purpose was to evaluate the effectiveness and perception of a remote training program. The cadets performed an 8-week training program that consisted of similar movements to the movements seen on the ACFT. Following 8 weeks, the cadets retested the ACFT. Performance measures were in-creased in the scores and scoring variable of the 3-repetition deadlift and 2-mile run (p < .005). The overall testing score also improved significantly. These results imply that an 8-week training program focusing on movements similar to those tested by the ACFT could improve ACFT score.

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Advancing Single Cell And Crispr/Dcas9 Technologies For The Study Of Reward Learning And Addiction, Corey Grant Duke Jan 2020

Advancing Single Cell And Crispr/Dcas9 Technologies For The Study Of Reward Learning And Addiction, Corey Grant Duke

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Drug addiction is a chronic relapsing condition inflicting tremendous harm to individuals and society with ineffective treatment options available to most people. Drugs of abuse elevate dopamine levels in a brain region known as the nucleus accumbens (NAc), and activate gene programs considered essential for producing lasting synaptic and cell state changes which underlie the generation of addictive behavior. These gene expression changes remain poorly understood due to a complex heterogenous cellular architecture, and the rapidly fluctuating nature of the transcriptional processes themselves which make investigation difficult. Recent technical advances increase access to both profiling and manipulating these transcriptional changes …

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