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Tau-Dependent Regulation Of Network Hyperexcitability By Alzheimer’S Disease Risk Gene Bin1, Yuliya Voskobiynyk Jan 2020

Tau-Dependent Regulation Of Network Hyperexcitability By Alzheimer’S Disease Risk Gene Bin1, Yuliya Voskobiynyk

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Alzheimer’s disease (AD) is the leading neurodegenerative disorder that affects an astonishing 5.8 million Americans, a number projected to reach 14 million by the year 2050. While only about 1% of all AD cases are caused by mutations in APP, PSEN1, and PSEN2, the cause of sporadic AD remains unknown. Variations in several risk genes have been proposed to contribute to the development of sporadic AD cases. Since, currently, there are no disease-modifying therapies for families affected by AD and multiple anti-amyloid-beta therapies failed in clinical trials, determining how these risk genes contribute to the development of AD is crucial …

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Gene–Environment Interaction In Parkinson Disease: The Gut Microbiome, Zachary D. Wallen Jan 2020

Gene–Environment Interaction In Parkinson Disease: The Gut Microbiome, Zachary D. Wallen

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GENE–ENVIRONMENT INTERACTION IN PARKINSON DISEASE: THE GUT MICROBIOME ZACHARY D. WALLEN GENETICS, GENOMICS, AND BIOINFORMATICS ABSTRACTParkinson disease (PD) is a progressive neurodegenerative disease with no cure. Majority of cases are idiopathic, and the cause is unknown. Studies have been conducted in human and animals to identify PD risk factors, resulting in a list of genetic and environmental factors that modestly increases risk of PD. Still, no individual risk factor fully explains the cause of PD, and neither has the combination of these factors. Additional avenues of research are being investigated to find potential triggers of PD, and factors that might …

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The Mir-23a Cluster Controls An Epigenetic Axis In Osteoblast Development During Bone Formation, Benjamin J. Wildman Jan 2020

The Mir-23a Cluster Controls An Epigenetic Axis In Osteoblast Development During Bone Formation, Benjamin J. Wildman

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Differentiation of pre-osteoblasts is critical to controlling in-vivo development and growth of bone. Recent studies highlight the importance of epigenetic regulation in directing osteoblast commitment and function. Here we show that the microRNA-23a cluster (miR-23a, 27a, and 24-2) controls bone mass in-vivo through a previously unknown epigenetic mechanism. MiR-23a cluster knockdown increased the intensity of Alkaline Phosphatase staining in MC3T3-E1 cells. Additionally, it upregulated mRNA expression of osteogenic marker genes such as Runx2 and Osteocalcin. Micro-CT analysis of 2-month and 6-month femurs showed that trabecular bone volume and trabecular number significantly increased in miR-23aClZIP mice as compared to controls. Histological …

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Race, Type Ii Diabetes Mellitus And Vertebral Fragility Fractures: A Cross-Sectional Analysis From Nhanes, Yuchen At Xiao Jan 2020

Race, Type Ii Diabetes Mellitus And Vertebral Fragility Fractures: A Cross-Sectional Analysis From Nhanes, Yuchen At Xiao

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IntroductionThis study examined the association between race and bone health, and if T2DM modifies this association in a diverse sample of adults. Methods We conducted a cross-sectional study using the 2013-2014 National Health and Nutrition Examine Survey (NHANES) data. Bone health outcomes included lumbar spine BMD (lowered BMD based on T-scores <-1), and vertebral deformities, assessed via vertebral fracture assessment (VFA), including presence, number of deformities, and severity ratio of deformities. T2DM status and other demographic, lifestyle, and health characteristics were self-reported via questionnaire data. To assess if T2DM modifies the association between race and bone health outcomes, we conducted stratified analyses using logistic regression for dichotomous outcomes, Poison regression for count outcomes, and linear regression for continuous outcomes. Results Non-Hispanic (NH) Blacks have significantly less odds of being lowered BMD and osteoporosis comparing to NH-Whites in the crude model and significantly less odds of having vertebral deformities comparing to NH-White in both crude and adjusted model for non-diabetic participants. Such differences are not observed in diabetic groups. Participants in Other race group have significantly more odds of being lowered BMD comparing to NH-Whites in the adjusted model for both diabetic and non-diabetic groups. And have significantly more odds of having vertebral deformities in the diabetic group, crude and adjusted, yet the differences are not significant in non-diabetic groups. Similar results were seen in the number of deformities and total bone loss ratio. The potential modification effect of T2DM was not significant in these models. Conclusions In our national evaluation, bone health differs not only by race and ethnic group but also by T2DM status. The protective vertebral fragility effects observed among NH-Blacks was no longer present among those with diabetes. Likewise, among participants in other racial and ethnic groups, T2DM seemed to magnify the association of worse vertebral fragility. Such trends indicate a potential modifying effect of participants’ T2DM status and should be noted clinically, yet more studies are required for more precise results.

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Circadian Control Of Blood Pressure And Renal Electrolyte Excretion, Dingguo Zhang Jan 2020

Circadian Control Of Blood Pressure And Renal Electrolyte Excretion, Dingguo Zhang

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Many physiological processes, including blood pressure (BP) regulation, follow specific rhythms tied to a 24-h cycle. This is largely because circadian genes operate in virtually every cell type in the body. In healthy individuals, BP during nighttime is 10-20% lower compared to daytime, a phenomenon known as “nocturnal dipping”. It is acknowledged that the dipping of BP is essential in maintaining normal cardiovascular and renal function. However, it remains unclear as to what factors contribute to nocturnal dipping. The purpose of this dissertation is to elucidate mechanisms underlying the circadian rhythm of BP. Bmal1 is one of the core circadian …

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Toward The Mechanism Underlying Latanoprost- And Benzalkonium Chloride-Induced Meibomian Gland Dysfunction In Patients Treated For Glaucoma, Jillian Ziemanski Jan 2020

Toward The Mechanism Underlying Latanoprost- And Benzalkonium Chloride-Induced Meibomian Gland Dysfunction In Patients Treated For Glaucoma, Jillian Ziemanski

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Once thought to be no more than a vexing eye condition, ocular surface disease (OSD) is now being viewed as a differentiating factor between sight and no sight. In the setting of glaucoma, OSD can interfere with treatment success, potentially allowing the visually devastating pathology of glaucoma to plow onward with little restraint. Compounding the clinical challenge is the growing awareness that glaucoma-associated OSD appears to be iatrogenically induced by topical ophthalmic medications. Daily, topical instillation of preserved prostaglandin analogs (PGAs), the most common first-line treatment for glaucoma, has been linked to a variety of OSD subtypes, including meibomian gland …

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A Modified Standard American Diet (Msad) Induces Physiological Parameters Associated The With Metabolic Syndrome In C57bl/6j Mice, Sophie Bru Chehade Jan 2020

A Modified Standard American Diet (Msad) Induces Physiological Parameters Associated The With Metabolic Syndrome In C57bl/6j Mice, Sophie Bru Chehade

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Obesity manifests physiologically in multiple organ systems of the body, typically increasing the risk of developing cardiometabolic disorders. Researchers have questioned the causative role that western dietary patterns have on disease pathogenesis and have speculated that quality and quantity of dietary fats and/or carbohydrates have a predictive role in the development of these disorders. Standard reference diets such as the AIN-93 rodent diet have historically been used to promote optimal animal model health and reduce variation of results across experiments. These diets have been invaluable to murine research; however, their translational value in studying human nutrition-related pathologies is limited. Early …

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Lim Transcriptional Complexes That Impact Endocrine Pancreas Development And Function, Maigen Bethea Jan 2020

Lim Transcriptional Complexes That Impact Endocrine Pancreas Development And Function, Maigen Bethea

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The Ldb1:Isl1 LIM transcriptional complex is critical for endocrine pancreas development as well as b-cell terminal differentiation. These complexes have been shown to interact with various proteins to elicit transcriptional regulation in other tissues, yet few interactors have been identified in b-cells. Therefore, the objective of this dissertation was to identify interactors of Ldb1 and Isl1 and assess their contributions to endocrine pancreas development and function. Using a reversible crosslink immunoprecipitation (ReCLIP) and mass spectrometry (MS) strategy to isolate endogenous Ldb1 and/or Isl1 interacting protiens, SSBP3, Rnf20, and Rnf40 (E3 ubiquitin ligases) coregulators were identified. SSBP3 was found to interact …

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Distinct Tissue Specific Functions Of Bone Marrow Regulatory T Cells, And Their Therapeudic Applications In Myeloid Neoplasms, Virginia Camacho Jan 2020

Distinct Tissue Specific Functions Of Bone Marrow Regulatory T Cells, And Their Therapeudic Applications In Myeloid Neoplasms, Virginia Camacho

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In the bone marrow, Regulatory T cells (Tregs) constitute nearly 30% of CD4+ T cells, a significantly higher ratio than other tissues. Although a few of the mechanisms by which Tregs regulate normal hematopoiesis have been elucidated, our understanding of this process during leukemogenesis is ex-tremely limited. In this work, we define how Tregs maintain and support the bone marrow microenvironment. We propose that the role of Tregs extends be-yond their canonical immuno-suppressive function and that these cells are re-quired to maintain healthy hematopoiesis. We have defined tissue-specific roles for Tregs in the bone marrow including the maintenance of hematopoietic …

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Impact Of Diet And Meal Timing On Time-Of-Day Dependent Hippocampal Function, Jennifer Davis Jan 2020

Impact Of Diet And Meal Timing On Time-Of-Day Dependent Hippocampal Function, Jennifer Davis

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Circadian rhythms are biological processes that cycle every ~24 hours and have allowed life to adapt for optimal function across the day. These rhythms are present in all tissues in the body and are coordinated to the light/dark cycle by the suprachiasmatic nucleus (SCN) in the hypothalamus. Along with active-rest cycles, cognitive performance fluctuates across the course of the day, peaking during the active phase. In addition to the light cycle, food and meal timing can provide signaling cues to extra-SCN tissues. Food access only during the inactive phase results in weight gain and memory impairment. High fat diet protocols …

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Structural Studies Of Rna Synthesis Machinery In Vesicular Stomatitis Virus, Joseph Ryan Gould Jan 2020

Structural Studies Of Rna Synthesis Machinery In Vesicular Stomatitis Virus, Joseph Ryan Gould

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Vesicular stomatitis virus (VSV) is a member of the order Mononegavirales, which is comprised of viruses with genomes of non-segmented negative sense RNA. Many fundamental insights into the molecular biology of mononegaviruses were first made in VSV, such as the unique viral RNA synthesis template comprised of the nucleocapsid (N) protein and genomic RNA and the distinctive large (L) protein which contributes all enzymatic activities of RNA synthesis and transcript maturation. The L protein performs its enzymatic functions in concert with the phosphoprotein (P), a flexible, charged, and phosphorylated cofactor. The goal of the research presented in this dissertation was …

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Mechanisms Of Virtual Reality To Improve Walking And Reaching Behavior In Individuals With Chronic Low Back Pain, Rebecca Hennessy Jan 2020

Mechanisms Of Virtual Reality To Improve Walking And Reaching Behavior In Individuals With Chronic Low Back Pain, Rebecca Hennessy

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Chronic low back pain (cLBP), low back pain persisting longer than three to six months, is a prevalent condition that can greatly interfere with movement quality. Specifically, cLBP can result in slower walking speeds and negatively affect reaching movements. Virtual reality (VR) encompasses a variety of technologies which may potentially improve therapeutic interventions for individuals with cLBP by presenting users with fun, distracting, and engaging challenges that align with their rehabilitative goals. While VR systems have become more accessible to everyday users, there is limited research which specifically examines VR mechanisms to improve walking and reaching quality. This dissertation presents …

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Parent Reactions To Sexual And Gender Identity Disclosure Events In The Deep South, Allison Claire Estep Jan 2020

Parent Reactions To Sexual And Gender Identity Disclosure Events In The Deep South, Allison Claire Estep

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Disclosure of sexuality by coming out is a central part of the process of self-identification for LGBT youth (Denes & Afifi, 2014). Parents’ initial response to their child’s coming out is linked to parent-child relationship satisfaction and if the child will later feel the need to come out for a second time or to clarify their sexual identity (Denes et al. 2014). Parental acceptance of LGBT youth’s disclosure has been linked to higher self-esteem and lower rates of suicidal tendencies, depression, and substance abuse (Needham & Austin, 2010; Ryan, Russell, Huebner, Diaz, & Sanchez, 2010). Current research regarding parent reactions …

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The Benefits Of Automation In Forensic Toxicology: A Lean Six Sigma And Cost-Analysis Approach, Sarah Guertin Jan 2020

The Benefits Of Automation In Forensic Toxicology: A Lean Six Sigma And Cost-Analysis Approach, Sarah Guertin

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Reducing backlogs, improving case turnaround times, and streamlining methodologies are major focus points for forensic toxicology laboratories. In order to reduce expenses and save time, some laboratories have implemented protocols that limit their scope of testing for driving under the influence (DUI) cases. However, this approach will not only provide less information toward DUI investigations but also limit the data available to fully capture the drugged-driving problem in the United States and inhibit offenders from receiving rehabilitation. This research project explored the impact of incorporating fully automated methods into the forensic toxicology laboratory as a solution to saving money and …

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Stimuli-Responsive Polymeric Particles: Ph-Sensitive Multilayer Capsules And Biodegradable Polylactic Acid Microsponges, Nirzari Gupta Jan 2020

Stimuli-Responsive Polymeric Particles: Ph-Sensitive Multilayer Capsules And Biodegradable Polylactic Acid Microsponges, Nirzari Gupta

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The behavior of stimuli-responsive polymers is often inspired by the desire to mimic nature. Over the years, the development of polymeric systems, which respond to the environment by changing their physical and/or chemical properties, has been increased in biomedical and environmental applications. The demand for fresh water is also growing dramatically. This long-term development in the global water situation is closely connected to the growth of the world population and global climate change. In recent years, the use of nanomaterials in water remediation has increased considerably. In addition, shape and stimuli-responsiveness to size and surface chemistry of micro-engineered delivery carriers …

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Disease Specific Dysregulation Of Stat1 And Stat5 Activation In Mature Cd4+ And Cd8+ T Cells Influences Enhanced Kinetic Responses And Inflammation In Patients With Treatment-Naïve Relapsing Remitting Multiple Sclerosis (Rrms), Brandon Jay Pope Jan 2020

Disease Specific Dysregulation Of Stat1 And Stat5 Activation In Mature Cd4+ And Cd8+ T Cells Influences Enhanced Kinetic Responses And Inflammation In Patients With Treatment-Naïve Relapsing Remitting Multiple Sclerosis (Rrms), Brandon Jay Pope

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Autoimmunity is propagated through the lack of effective mechanisms of central and peripheral tolerance. In relapsing remitting multiple sclerosis (RRMS), dysregulated adaptive immune cells have been shown to contribute to disease morbidity through the influence of immune-modulating cytokines in the peripheral blood. Interleukin-2 (IL-2) is a cytokine with several key functions in regulating homeostatic mechanisms within the human immune system. Interferon gamma (IFNγ) is a type II interferon that is needed for an effective response to intracellular bacteria infection through the actions of Th1 cells. IL-2 and IFNγ signaling occurs primarily through signal transducer and activator of transcription (STAT) activation. …

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Noninvasive Neuromodulation Using A Benchtop Approach To Mri-Guided Focused Ultrasound Blood Brain Barrier Opening, Megan Rich Jan 2020

Noninvasive Neuromodulation Using A Benchtop Approach To Mri-Guided Focused Ultrasound Blood Brain Barrier Opening, Megan Rich

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Fundamental neuroscience research has provided a deeper understanding of the genes, molecules and cellular circuitry involved in neurological disorders, however translating discovery into clinical application remains a major challenge. This bench to bedside gap is in part due to the discrepancy in techniques used in the laboratory vs. the clinic for targeting the mechanisms that underlie disease. Ideally this discrepancy would be resolved not only by implementing novel clinical techniques to provide more precise targeting of disease foci, but also by using the same techniques in the clinic that are used at the lab bench to provide a direct bench …

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The Reproductive Ecology Of The Diamondback Terrapin (Malaclemys Terrapin Pileata) In Coastal Alabama: Implications For Conservation Amid Global Climate Change, Catherine Audrey Sirgo Jan 2020

The Reproductive Ecology Of The Diamondback Terrapin (Malaclemys Terrapin Pileata) In Coastal Alabama: Implications For Conservation Amid Global Climate Change, Catherine Audrey Sirgo

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The diamondback terrapin is the only emydid turtle within the United States that exclusively resides in salt marsh habitats. Over the past century, the species has seen dramatic declines in numbers due to being exploited for terrapin soup as well as other threats, including crab trap induced mortality, nest depredation, and habitat alteration or loss. In addition to these well-known historic threats, global climate change has become a growing concern due its potential threats on the terrapin and its habitat. The goal of this study was to assess the reproductive ecology of the Mississippi diamondback terrapins that reside within the …

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Epitranscriptomic Regulation Of Fibroblast Activation In Diseased Heart, Zainab Gbongbo Suleiman Jan 2020

Epitranscriptomic Regulation Of Fibroblast Activation In Diseased Heart, Zainab Gbongbo Suleiman

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Background: Transforming growth factor β (TGFβ) is a chemokine released during cardiac hypertrophy and remodeling. Evidence has shown that it plays a significant role in fibroblast differentiation/activation to myofibroblasts , which ultimately leads to adverse cardiac remodeling. It is previously suggested that m6A methylation plays important role in cardiac pathology in both ischemic and hypertrophic heart failure [1, 2], however, its role in fibroblast activation/differentiation is largely unknown. Therefore, in this study we investigated the relationship between m6A methylation and fibroblast activation using proinflammatory/profibrotic factor, TGFβ. Methods: Fibroblasts were isolated from neonatal rat heart and activated with TGFβ for 48 …

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Exploring The Roles Of Long Non-Coding Rnas In Glioblastoma Tumor Recurrence And Therapy Resistance, Christian Tyler Stackhouse Jan 2020

Exploring The Roles Of Long Non-Coding Rnas In Glioblastoma Tumor Recurrence And Therapy Resistance, Christian Tyler Stackhouse

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ABSTRACT Glioblastoma (GBM) is the most common and devastating primary CNS brain tumor with a median survival time of around 14 months. Most patients succumb to re-current disease which is often more malignant than the primary tumor and is frequently therapy resistant. There have not been significant advances in the treatment of GBM despite decades of research. This is partly due to the lack of accurate preclinical models and of the focus on primary rather than recurrent tumors. We created a 350 gene custom GBM-specific panel which contains 16 molecular signatures including molecular sub-typing signatures. We have demonstrated concordance of …

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Functionalized Aromatic Organic Scintillators As Tools For Non-Invasive Optogenetics, David French Jan 2020

Functionalized Aromatic Organic Scintillators As Tools For Non-Invasive Optogenetics, David French

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Optogenetics is a growing discipline of neuroscience that attempts to control brain circuits using light. Current techniques involving surgically implanted light-emittingdiodes are highly invasive. This limitation could be avoided by the use of a tissuepenetrative light source, such as x-rays, and a locally applied down-converting material. This work describes the design, optimization, and proof-of-concept application of organic aromatic-based scintillators as non-invasive tools for optogenetics. The first chapter describes the synthesis of 2-anthryl methacrylate-co-methyl methacrylate copolymers and an evaluation of their use as x-ray induced scintillators (radioluminescence). The 2-anthryl methacrylate monomer and the copolymers all exhibited radioluminescence in the solid state. …

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The Impact Of The Edtpa: An Inside Look From The Perspectives Of Teacher Candidates And Novice Teachers, Hannah Stephens Kennedy Jan 2020

The Impact Of The Edtpa: An Inside Look From The Perspectives Of Teacher Candidates And Novice Teachers, Hannah Stephens Kennedy

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The purpose of the qualitative research study was to examine the perspectives and experiences of teacher candidates and novice teachers regarding the edTPA assessment for teacher certification at a public university in the southeast. Aside from understanding their perspectives, the researcher hoped to gain an understanding of the impact on teaching practices and real-life experiences in the classroom. Research questions served as the framework for this study, including the following: (1) How do participants describe their perspectives and experiences as teacher candidates in the process of completing edTPA? (2) How do teacher candidates describe how edTPA influences their perspectives on …

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Facial Recognition With Image Signaling: Efficacy Of Two Factor Authentication Utilizing A Single Image Input Mechanism On A Smartphone, Jaret Langston Jan 2020

Facial Recognition With Image Signaling: Efficacy Of Two Factor Authentication Utilizing A Single Image Input Mechanism On A Smartphone, Jaret Langston

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Society generates 2.8 quintillion bytes of new data every day. Much of this data is sensitive information that should be protected from unauthorized access. Sensitive information is defined as information that, if compromised or misused, could adversely affect the privacy of the individual or organization. There are many types of information that fit this definition and places it is found, but for this discussion we will focus on: • Personally Identifiable Information (PII) (e.g., birth date, social security number, driver’s license number, passport number). • Medical information (e.g., insurance policy numbers, prescriptions, history). • Consumer information (e.g., credit card, banking, …

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Cd8 T-Cell Responses To A Diverse Virus: Adaptation And Cross-Reactivity In Hiv Vaccination, Sushma Boppana Jan 2020

Cd8 T-Cell Responses To A Diverse Virus: Adaptation And Cross-Reactivity In Hiv Vaccination, Sushma Boppana

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In the four decades since human immunodeficiency virus (HIV) was discovered, significant progress has been made in treating HIV infection and in understanding the viral and immune dynamics underlying disease pathogenesis. However, in spite of scientific advances, HIV remains a significant global health issue, and an effective preventative vaccine has yet to be created. Many groups have demonstrated the importance of CD8 T cells in viral control during natural HIV infection and believe that CD8 T cells could contribute to vaccine efficacy by alleviating disease course in individuals who became infected despite vaccination. One major obstacle to inducing potent CD8 …

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‘Is The Dress Made To Excite Me?’: Analyzing Gender Narratives As Social Protest In Mae West’S The Drag And Joe Orton’S What The Butler Saw, Toby Camp Jan 2020

‘Is The Dress Made To Excite Me?’: Analyzing Gender Narratives As Social Protest In Mae West’S The Drag And Joe Orton’S What The Butler Saw, Toby Camp

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The Drag, the second play Mae West ever wrote and produced, debuted in 1927; What the Butler Saw, Joe Orton’s final play debuted in 1969, two years after its author’s death. These comedies are very similar when considered through the lens of Judith Butler’s gender performance theory, most notably from her books Gender Trouble (1990) and Bodies that Matter (1993). In the latter book, she notes that “Drag is subversive to the extent that it reflects on the imitative structure by which the hegemonic gender is itself produced and disputes heterosexuality’s claim on naturalness and originality” (85). Accordingly, since gender …

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Self-Awareness Of Functional Deficits In Older Adults With Mild Cognitive Impairment, Kayla Ann Steward Jan 2020

Self-Awareness Of Functional Deficits In Older Adults With Mild Cognitive Impairment, Kayla Ann Steward

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Performance of instrumental activities of daily living (IADLs) can become compromised in older adults with mild cognitive impairment (MCI). Poor self-awareness of deficits, also known as anosognosia, occurs in a substantial minority of those with MCI and varies in extent depending on the domain examined. This dissertation attempts to explain the inter- and intra-patient variability in anosognosia by examining (1) differences in objective IADL performance and self-awareness of functional difficulties between those with amnestic single- (-ASD) and multi-domain (-AMD) MCI, and by examining (2) the neuropsychological and (3) neuroanatomical correlates of anosognosia for IADLs in older adults across a broad …

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Use Of Lc-Qtof-Ms For Determining The Presence Of Illicit Substances In Urine, Rebecca Howell Jan 2020

Use Of Lc-Qtof-Ms For Determining The Presence Of Illicit Substances In Urine, Rebecca Howell

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Confirmation testing for drug screens has most commonly been conducted using gas chromatography-mass spectrometry (GC-MS), but the use of liquid chromatography-mass spectrometry (LC-MS) methods has been gaining popularity in recent years. This can be attributed to several advantages that LC-MS has over GC-MS including the ability to detect non-volatile, thermolabile and polar compounds. Additionally, most compounds can be analyzed without any previous derivatization steps, meaning that sample prepara-tion is simpler, cheaper and faster. The method used for this study consisted of using a nano-LC-electrospray ionization (ESI) system in conjunction with a hybrid Quadrupole OrthogonalTime-of-Flight mass spectrometer (QTOF-MS), which yields high …

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Novel Mechanisms Of Nitric Oxide Activation In The Kidney, Randee Sedaka Jan 2020

Novel Mechanisms Of Nitric Oxide Activation In The Kidney, Randee Sedaka

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Globally, adult sodium consumption has far exceeded daily intake recommendations, leading to one in ten cardiovascular deaths. Given the rise in hypertension prevalence, uncontrolled hypertension with antihypertensive medication use, and significant associations between high salt intake and high blood pressure, there is a need to better understand the mechanisms involved in hypertension. Nitric oxide synthase 1 (NOS1) is a well-established regulator of fluid and electrolyte balance in the renal collecting duct (CD) with highest activity in the inner medulla (IM). We previously reported that high salt (HS) intake stimulates CD endothelin B receptor (ETBR)/NOS1-dependent generation of NO, thereby inhibiting the …

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Diurnal Dysfunction In Control Of Sodium Excretion In Diet-Induced Obesity, Reham Soliman Jan 2020

Diurnal Dysfunction In Control Of Sodium Excretion In Diet-Induced Obesity, Reham Soliman

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The renal endothelin system plays a key role in sodium excretion, particularly under high salt (HS) diet. HS stimulates renal endothelin-1 (ET-1), which binds and activates the endothelin receptor B (ETB) to excrete the excess salt. Loss of ETB receptor is linked to the development of hypertension under HS. Central clock genes are important in maintaining rhythmic patterns of sodium excretion and ET-1 is identified as a target for clock genes, including Period and Bmal1. ET-1 excretion follows a diurnal rhythm along with sodium excretion. Sexual dimorphism is evident in the diurnal regulation of endothelin-mediated natriuresis and its downstream targets. …

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Mitochondrial Priming Of Tumor Initiating Cells Involves Repression Of Mitochondrial Fission Activity Towards Redox Regulation Of The Cell Cycle Regulator Cyclin E, Brian Spurlock Jan 2020

Mitochondrial Priming Of Tumor Initiating Cells Involves Repression Of Mitochondrial Fission Activity Towards Redox Regulation Of The Cell Cycle Regulator Cyclin E, Brian Spurlock

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Mitochondrial dynamics primarily refers to the opposing fission or fusion events between individual mitochondria, which maintains steady-state mitochondrial morphology in cells. Fission and fusion activities maintain the energetics of normal and neoplastic stem cells. We developed the novel approach mito-SinCe2 to study the bidirectional relationship between mitochondrial dynamics and energetics. Application of this method led to the hypothesis that mitochondria-dependent ovarian tumor initiating cells interconvert between 3 states with distinct mitochondrial energetics/dynamics relationships. Cells in one state, characterized by high mitochondrial ROS and low fission activity, appear to be primed for self-renewal by mitochondria. We call these cells mitochondria-primed stem …

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