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Diet, Physical Activity, And Healthy Aging In People Living With Hiv, Josh Newson Muhammad Jan 2018

Diet, Physical Activity, And Healthy Aging In People Living With Hiv, Josh Newson Muhammad

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As life expectancy for people living with HIV (PLWH) has increased, healthy aging in this community has become an emerging public health concern. Although the benefits of adopting healthy diets and regular physical activity are well-documented, implementing strategies for lifestyle modifications among older PLWH remains a challenge. The complex milieu of social, physiological and economic burdens encountered by PLWH exposes this population to increased risk for adverse health outcomes, especially from preventable metabolic diseases. The interaction of diet, physical activity and social determinants of health in persons who are HIV positive is an understudied area. The aim of this dissertation …

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Neuropeptide Y Cells Regulate Anxiety Behavior, Katelynn Corder Jan 2018

Neuropeptide Y Cells Regulate Anxiety Behavior, Katelynn Corder

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Dysregulation of the GABAergic system has long been implicated in anxiety disorders. Classic anxiolytic drugs, such as benzodiazepines, increase GABAergic transmission by modulating GABA¬A receptors, relieving anxiety symptoms. However, these treatments are not always effective and are often accompanied by negative side effects. Glutamate decarboxylase (GAD) is the enzyme responsible for producing GABA. Recent studies have shown that when the isoform GAD67 is reduced in specific brain regions or GABAergic subtypes, differential anxiety effects were found. These studies suggest that targeting specific GABAergic cell subtypes may provide a more effective treatment for anxiety disorders. Neuropeptide Y (NPY) is an abundant …

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Post-Transcriptional Regulation Of Myeloid Cell Leukemia 1 In Cancers, Jia Cui Jan 2018

Post-Transcriptional Regulation Of Myeloid Cell Leukemia 1 In Cancers, Jia Cui

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Apoptosis, a highly regulated process of programmed cell death, is essential for maintaining normal tissue homeostasis. Myeloid cell leukemia 1 (MCL1), an anti-apoptotic BCL-2 family protein, lies at the center of apoptosis regulation. Overexpression of MCL1 has been identified as a key contributor to tumorigenesis and further enables resistance to anti-cancer chemotherapies and radiation. Due to the critical roles of MCL1 in cancer, it is essential to understand the regulatory mechanisms of MCL1 expression in cells. Previous studies have detailed how MCL1 expression is controlled by multiple mechanisms. However, characterization of the post-transcriptional regulation of MCL1 mRNA has been poorly …

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Psychological Well-Being And Smoking Cessation, Christopher Thorne Jan 2018

Psychological Well-Being And Smoking Cessation, Christopher Thorne

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Introduction: The substantial death toll from smoking combined with the low success rates of current treatment approaches warrants further investigation into mechanisms that promote cessation. While the role of negative affect has been studied extensively in relationship to smoking cessation, the role of psychological well-being (PWB; e.g., life satisfaction, optimism, positive affect, purpose in life, resilience) has received little attention. Treatment outcomes might improve with a better understanding of PWB’s role in smoking cessation. Methods: Relationships between smoking and PWB were examined in three studies. First, using panel data from the biennial, longitudinal Health and Retirement Study, I developed separate …

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Immune Modulation Of Pain And Recovery Via Diet, Stacie Totsch Jan 2018

Immune Modulation Of Pain And Recovery Via Diet, Stacie Totsch

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Chronic pain is the most common disability in the United States. Additionally, one out of three adults in America are obese and obesity and pain are often comorbid. Obesity is an inflammatory state due to the release of pro-inflammatory mediators from adipose tissue. Generally, obesity is a result of a poor-quality diet. Specific dietary components and patterns are independent activators of the immune system and can exacerbate the obesity-induced inflammatory state. It is known that immune system activation is a critical aspect in the development and progression of many chronic pain conditions. To address a general lack of preclinical investigations …

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Novel Insights Into Neurofibromin Function And Human Neurofibromatosis Type 1 Mutations Using Genetically Engineered Mouse Models, Ashley Nicole Turner Jan 2018

Novel Insights Into Neurofibromin Function And Human Neurofibromatosis Type 1 Mutations Using Genetically Engineered Mouse Models, Ashley Nicole Turner

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Loss of NF1 in different developmental and cellular contexts leads to unique physiological outcomes due to loss of neurofibromin function, including embryonic lethality, sporadic cancers, and the genetic disorder NF1. Neurofibromin acts as a tumor suppressor by modulation of RAS signaling, with other functions of this multi-domain protein being less clear. Even within the monogenic disorder of NF1, the clinical heterogeneity and mutational spectrum are immense, revealing the complexity underlying this disorder. There is a huge urgency and need for NF1 therapeutic treatments, and the same urgency to develop in vivo models to better understand NF1 that can be utilized …

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Endothelialization Of Microchannels In A Three Dimensional Breast Cancer Tumor Surrogate Model, Derek Van Vessem Jan 2018

Endothelialization Of Microchannels In A Three Dimensional Breast Cancer Tumor Surrogate Model, Derek Van Vessem

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Drug discovery and testing commonly employs two dimensional (2D) human cell line monolayers for lead compound identification before becoming a candidate therapy to be studied in animal models. Culturing cells in 2D produces a homogenous disbursement of nutrients and anticancer-therapeutics resulting in a response specific to 2D that does not necessarily translate to a three dimensional (3D) response. This method unfortunately distorts the in vivo human drug response. The lack of physiologic dimensionality in 2D cell monolayers distort cellular responses relative to 3D systems that can be attributed to minimal drug approvals. Oncology drugs are the least successful with only …

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Cardiovascular Disease Risk Among Breast Cancer Survivors, Jacqueline B. Vo Jan 2018

Cardiovascular Disease Risk Among Breast Cancer Survivors, Jacqueline B. Vo

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Background: There are nearly 3.5 million breast cancer survivors in the U.S., and approximately 10% are diagnosed prior to age 45 and considered “young.” The overall five-year survival rate for breast cancer survivors is approaching 90%. Living longer, many breast cancer survivors are at risk for developing cardiovascular disease due to cancer treatment, such as anthracyclines and/or trastuzumab. This study’s purpose was to examine cardiovascular disease risk, measured using excess heart age, among young breast cancer survivors. Methods: A retrospective, two-year longitudinal design was used to review electronic medical records of breast cancer survivors diagnosed between 30 and 44 years …

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Social Factors, Public Policies, And Infant Mortality, Lauren Wallace Jan 2018

Social Factors, Public Policies, And Infant Mortality, Lauren Wallace

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Despite consistent and substantial investments, the United States’ infant mortality rate (IMR) has not decreased significantly in the 21st century and disparities between racial and ethnic groups have increased. This study investigates the impact of social and health factors, and public policies on IMR at the state level. The research aims were to: 1) evaluate which state-level social factors and public policies were associated with state IMRs using principal component (PC) analysis; and 2) evaluate whether states cluster on their PC scores and IMRs using cluster analysis. The data used were six composite index scores based on social factor and …

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Assessment Of A Peer Mentoring Program At Lawson State Community College, Teneasha Washington Jan 2018

Assessment Of A Peer Mentoring Program At Lawson State Community College, Teneasha Washington

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ABSTRACT Colleges and universities have begun implementing mentoring programs to offset rising attrition rates; however, the literature on the benefits of these programs is limited particularly among community colleges with peer mentoring programs serving minority students. Further limiting our understanding of post-secondary peer mentoring programs is the lack of research on mentor’s as well as mentee’s perspectives on the mentoring experience. As mentors and mentees serve in a variety of capacities within the mentoring program, it is often difficult to identify outcomes that can be assessed within the mentoring program. Although the success of peer mentoring programs is directly affected …

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The Computational Discovery Of Genetic Determinants Of Gene Regulatory Variation In Human Liver, Benjamin Todd Weaver Jan 2018

The Computational Discovery Of Genetic Determinants Of Gene Regulatory Variation In Human Liver, Benjamin Todd Weaver

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From its foundations, modern genetic science has focused on understanding the causal connections between genotypes and phenotypes. The emergence of tools and techniques for microarray-based genomic science has enabled hundreds of genome-wide association studies (GWAS) to rapidly uncover thousands of previously unknown links between genetic variants and complex phenotypes, including human diseases (Li et al., 2011b). The output of genomic association research has yielded significant insights into basic biology and disease, including the identification of disease DNA variants that are possibly targetable by pharmaceuticals and gene therapeutics. Despite evident successes of the GWAS paradigm, opinion is divided on the overall …

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Nf-Κb And Methyl-Lysine Signaling In The Epigenetic Regulation Of Memory, William Mitchell Webb Jan 2018

Nf-Κb And Methyl-Lysine Signaling In The Epigenetic Regulation Of Memory, William Mitchell Webb

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Epigenetic mechanisms such as DNA methylation and histone methylation are critical regulators of gene transcription during memory consolidation and retrieval. However, the means by which these mechanisms are themselves initiated and directed to specific gene regions, and the extent to which these marks coordinate control of gene expression, remain poorly understood. In this dissertation, we explore the role of methyl-lysine signaling in the epigenetic regulation of gene expression in two contexts. First, we investigated the role of histone H3 lysine 4 tri-methylation (H3K4me3) and DNA 5-hydroxymethylation (5hmC) during memory retrieval, finding that these marks increased globally and at CpG-enriched coding …

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Identification Of Molecular Regulators Of Morphogenesis During Early Development Of Xenopus, Ivan Popov Jan 2018

Identification Of Molecular Regulators Of Morphogenesis During Early Development Of Xenopus, Ivan Popov

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During embryonic development of all animal species, dramatic changes in morphology occur to transform a single-celled zygote into a well-organized adult body that contains different organs positioned in stereotypical ways for the species. The processes that shape tissues and organs are called morphogenesis, and gastrulation is the first morphogenetic process in embryogenesis. During gastrulation, three germ layers are specified and a set of regionally specific cell movements act in concert to position these germ layers for proper establishment of future body plan of the developing animal. Although factors regulating cell lineage specification have been studied extensively, the molecular machinery controlling …

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Calcium Signaling And Regulation Of Ecdysteroid Molting Hormone Production In Y-Organs Of The Blue Crab (Callinectes Sapidus), Megan Elizabeth Roegner Jan 2018

Calcium Signaling And Regulation Of Ecdysteroid Molting Hormone Production In Y-Organs Of The Blue Crab (Callinectes Sapidus), Megan Elizabeth Roegner

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In the blue crab (Callinectes sapidus), molting, and subsequent incremental growth, is triggered by the release of molting hormones, or ecdysteroids, from paired endocrine glands termed Y-organs. The method that triggers the increase in ecdysteroid release before molting is not fully resolved, but previous evidence suggests a calcium (Ca2+) signal may be involved. The goal of this research is to better understand the role Ca2+ signaling plays in blue crab molt hormone production. The first part of my dissertation focused on the Ca2+ regulatory protein sarco/endoplasmic reticulum Ca2+ ATPase (SERCA), which removes Ca2+ to the ER after a Ca2+ influx. …

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Combinatorial Withaferin A And Sulforaphane And Their Potential Roles In Breast Cancer Prevention And Therapy, Kendra Jeanine Royston Jan 2018

Combinatorial Withaferin A And Sulforaphane And Their Potential Roles In Breast Cancer Prevention And Therapy, Kendra Jeanine Royston

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Cancer is a leading cause of death worldwide and is a devastating disease. Breast cancer is of particular interest because it is a major cause of cancer-related fatality in women in the United States. To date, more than 40,000 women are expected to die due to breast cancer and more than 200,000 will be diagnosed every year. Despite numerous advancements in the field, breast cancer remedies can be harsh and while life may be prolonged, the quality of life may decrease. This being said, preventive measures and less harsh treatment options are needed to help eliminate breast cancer as a …

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Effects Of Stored Red Blood Cells On The Components Of The Lung-Capillary Membrane, Kaitlyn S. Ryan Jan 2018

Effects Of Stored Red Blood Cells On The Components Of The Lung-Capillary Membrane, Kaitlyn S. Ryan

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Trauma is the leading cause of death for Americans between the ages of 1 and 44. Implementation of massive transfusion protocols has improved early mortality due to traumatic hemorrhage; however, long-term complication rates associated with hemorrhagic shock remain high due to the development of multiple organ failure. In particular, resuscitation with large volumes of stored red blood cells (RBC) introduces high concentrations of free heme, which contributes to the development of acute lung injury (ALI) after trauma. Angiopoietin-2 (Agpt-2) is a mediator of trauma-related lung injury, but the effect of RBC storage-derived free heme on Agpt-2 regulation is unknown. The …

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Molecular Characterization Of The Rare Cftr Mutation P67l As A Model For Genotype-Specific Drug Development And Personalized Medicine In Cystic Fibrosis, Carleen Mae Pomperada Sabusap Jan 2018

Molecular Characterization Of The Rare Cftr Mutation P67l As A Model For Genotype-Specific Drug Development And Personalized Medicine In Cystic Fibrosis, Carleen Mae Pomperada Sabusap

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The traditional CFTR functional defect subcategories (i.e. protein misfolding, gating, conductance, etc.) are sometimes inadequate for determining patients most likely to benefit from emerging modulator treatment. We employ the P67L variant as emblematic of ways a thorough biochemical analysis of a rare CF defect can guide new therapeutic approaches, help predict drug response, and facilitate clinical precision. Historically, P67L has been designated a class IV conductance abnormality (i.e., malformed ion pore). In contrast, our studies demonstrate P67L disrupts CFTR protein maturation, prompts misfolding, causes gating defects, and exhibits wild-type like conductance. We show that P67L CFTR is robustly rescued by …

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Endothelin-1 And The Diurnal Regulation Of Sodium Excretion, Jermaine Gajrae Johnston Jan 2018

Endothelin-1 And The Diurnal Regulation Of Sodium Excretion, Jermaine Gajrae Johnston

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Healthy individuals typically have a diurnal rhythm in sodium (Na+) excretion, with levels higher during the daytime and lower at nighttime. While the mechanism behind this rhythm is not yet fully understood, molecular clock genes such as Bmal1 may contribute to the diurnal variation in urinary Na+ excretion (UNaV). Endothelin-1 (ET-1) is a peptide that aids in the regulation of Na+ balance through activation of the endothelin B (ETB) receptor. Although the ETB receptor has been shown to play an important role in promoting natriuresis, whether this varies according to time of day is unknown. This dissertation examines the role …

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Simulation Of Correlated Variables, Mixture Distributions, And Repeated Measures And Comparison Of Pharmacogenetic Prediction With Machine Learning Methods, Allison Cynthia Fialkowski Jan 2018

Simulation Of Correlated Variables, Mixture Distributions, And Repeated Measures And Comparison Of Pharmacogenetic Prediction With Machine Learning Methods, Allison Cynthia Fialkowski

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Pharmacogenetics aims to improve individualized medicine by combining genetic information with clinical data when assigning drug treatments. Different diseases are often associated with different factors, each with its own distributional characteristics. For rare or complex diseases, these characteristics may not be well understood and standard analysis methods may not be appropriate. In psychiatric disorders, for example, multiple drug treatments need to be compared across small sample sizes with heterogeneous patient populations, making implementation of standard methods difficult. Simulating data that mirrors clinical data is important because it allows investigators to determine which method is best suited for data from their …

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African American Caregivers’ Decision To Use Hospice Services For A Loved One: A Grounded Theory Study, Paula M. Gordon Jan 2018

African American Caregivers’ Decision To Use Hospice Services For A Loved One: A Grounded Theory Study, Paula M. Gordon

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This qualitative grounded theory study explored the process of decision making for African American family caregivers in the southeastern United States, as they make hospice decisions for their loved ones, Although hospice use in the United States has grown over the last decade, a disparity continues to exist between African American and Caucasian populations. African Americans represent a small percentage of hospice users in the United States, despite research that has found that patients who use hospice experience improved symptom control, fewer unmet needs, and better end of life care. Research has identified many reasons for this disparity; however, little …

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Risk Factors Associated With Multiple Myeloma, Stephen Gragg Jan 2018

Risk Factors Associated With Multiple Myeloma, Stephen Gragg

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Multiple myeloma (MM) is a hematologic malignancy in which clonal plasma cells accumulate in the bone marrow, leading to the formation of lytic bone lesions, hypercalcemia, anemia, renal insufficiency, and immunosuppression. It develops from a pre-malignant condition known as monoclonal gammopathy of undetermined significance (MGUS), which is prevalent in up to 3% of White populations over the age of 50 years, and twice that in Black populations. Although much progress has been made toward understanding the large scale genomic aberrations that facilitate the formation of MGUS clones and the various copy-number variations and mutations that trigger the development of MM, …

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Trichomonas Vaginalis Virus (Tvv) And Its Role In Trichomoniasis Infection, Keonte Graves Jan 2018

Trichomonas Vaginalis Virus (Tvv) And Its Role In Trichomoniasis Infection, Keonte Graves

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Background: Trichomonas vaginalis virus (TVV) is a non-segmented, 4.5-5.5 kbp, double-stranded RNA (dsRNA) virus infecting T. vaginalis (TV). The objectives of this study were to examine TVV prevalence in U.S. TV isolates and associations with patient demographics, clinical outcomes, and metronidazole (MTZ) resistance. Methods: Archived TV isolates from the enrollment visit of 355 women participating in a TV treatment trial in Birmingham, AL were thawed and grown in culture. Total RNA was extracted using Trizol reagent. Contaminating single-stranded RNA was precipitated using 4.0M LiCl and centrifugation. Samples were analyzed by gel electrophoresis to visualize a 4.5kbp band representative of TVV. …

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Role Of Diminished Pulsatility From Continous Flow Ventricular Assist Devices On Small Vessel Endothelial Dysfunction, Thomas Haglund Jan 2018

Role Of Diminished Pulsatility From Continous Flow Ventricular Assist Devices On Small Vessel Endothelial Dysfunction, Thomas Haglund

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Ventricular assist devices (VADs) are standard therapy for patients with advanced heart failure that is refractory to medical therapy. VADs can be categorized as pulsatile flow VADs (PF-VADs) and continuous flow VADs (CF-VADs). Both PF-VADs and CF-VADs are similarly effective in providing hemodynamic benefit and improving the quality of life and functional capacity of patients. CF-VADs are preferred over the PF-VADs due to advantages such as compact size, reliability, energy efficiency, installation and operation. However, CF-VAD support results in non-physiological diminished arterial pressure and flow pulsatility. Using the endothelial cell culture model (ECCM), we previously established that diminished pulsatility resulted …

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Mechanisms Of Leucine-Rich Repeat Kinase 2 And Alphα-Synuclein In Pathogenesis Of Parkinson Disease, Hisham Abdelmotilib Jan 2018

Mechanisms Of Leucine-Rich Repeat Kinase 2 And Alphα-Synuclein In Pathogenesis Of Parkinson Disease, Hisham Abdelmotilib

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Two pathological hallmarks define Parkinson disease (PD) including dopaminergic neurodegeneration in substantia nigra pars compacta (SNpc) and accumulation of α-synuclein insoluble inclusions, called Lewy pathology, in surviving neurons. LRRK2 (encoding Leucine-rich repeat kinase 2) and SNCA (encoding α-synuclein (α-syn)) are two major genes linked to PD. Pathogenic mutations in these two genes cause autosomal dominant (AD) PD. Additionally, genetic variations in LRRK2 and SNCA are associated with increased risk of sporadic PD. Cellular and animal studies using preformed α-syn fibrils (PFF) demonstrate that the fibrils can be internalized by neurons and act as seeds that can recruit and corrupt endogenously …

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Prohealing Multifunctional Endothelium Nanomatrix Coated Stents, Grant Alexander Jan 2018

Prohealing Multifunctional Endothelium Nanomatrix Coated Stents, Grant Alexander

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Cardiovascular disease is currently the number one cause of death in the United States, and indeed, worldwide. Stents are the most commonly implanted devices used to treat cardiovascular disease. Bare metal stent use remains limited by relatively high rates of in-stent restenosis, a re-narrowing of the artery after stent deployment. Restenosis within stents is a result of neointimal proliferation of smooth muscle cells and the accom-panying extracellular matrix deposition in response to vessel injury. To address this, drug-eluting stents have been developed to reduce restenosis; however, difficulties with late stent thrombosis, inflammation, and poor re-endothelialization remained. Thus, alt-hough numerous approaches …

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Effects Of Novel Inhibitors Against Wnt/Β-Catenin Signaling In Ovarian And Triple-Negative Breast Cancers, Abhishek Gangrade Jan 2018

Effects Of Novel Inhibitors Against Wnt/Β-Catenin Signaling In Ovarian And Triple-Negative Breast Cancers, Abhishek Gangrade

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Ovarian and triple-negative breast cancers (TNBC) are aggressive due to their dependence on Wnt/β-catenin signaling. Niclosamide, a strong inhibitor of Wnt/β-catenin signaling, is an efficacious cytotoxic agent for various cancers in vitro, including ovarian and breast cancers. However, it has cross-reactivity with mTOR, STAT3, and Notch pathways. A limitation of using the agent in animal studies involves its poor water solubility and bioavailability. This study investigates novel compounds based on the structure of niclosamide to improve specificity for the Wnt/β-catenin signaling pathway. The investigation evaluates three questions: 1) whether WNT974 inhibits Wnt/β-catenin signaling in ovarian cancer; 2) whether novel analogs …

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Effects Of Proanthocyanidins In Combination With Resveratrol And Sulforaphane Respectively On Human Breast Cancer Cells, Yifeng Gao Jan 2018

Effects Of Proanthocyanidins In Combination With Resveratrol And Sulforaphane Respectively On Human Breast Cancer Cells, Yifeng Gao

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Breast cancer is the second most common cancer and the second leading cause of death from cancer among women in the United States. Cancer prevention and therapy through use of phytochemicals that have epigenetic properties has gained considerable popularity during the past few decades. Such dietary components include but are not limited to grape seed proanthocyanidins (GSPs), resveratrol (Res) and sulforaphane (SFN). Here we report for the first time that GSPs and Res in combination dose- and time-dependently inhibited cell viability and posttreatment colony forming ability synergistically in MDA-MB-231 and MCF-7 human breast cancer cells, while GSPs and SFN in …

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Examining The Relationship Between Teacher Beliefs, Prekindergartener’S Self-Regulation And Classroom Quality: Informing Professional Development Programs, Cailin Jane Kerch Jan 2018

Examining The Relationship Between Teacher Beliefs, Prekindergartener’S Self-Regulation And Classroom Quality: Informing Professional Development Programs, Cailin Jane Kerch

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The purpose of this convergent parallel, mixed methods study was to examine and explore the relationship between subjective teacher beliefs, classroom quality, and pre-kindergartener’s self-regulatory abilities within a publicly funded pre-kindergarten program. Teacher subjective beliefs (beliefs of classroom management, classroom practice, and beliefs of children) were studied operantly using Q-Methodology, in addition to, audio-recorded focus groups to explore the lived experience of teachers within the sample (n = 20). Classroom quality was measured using the Classroom Assessment Scoring System (CLASS) and pre-kindergartener’s self-regulatory abilities were studied using pre/post proxy items from the Devereux Early Childhood Assessment for Preschoolers, Second Edition …

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The Effects Of Glucose And Amino Acid Restriction On Protein Turnover And Micro-Rna Composition In The Muscle Of Rainbow Trout, Mary Neslund Latimer Jan 2018

The Effects Of Glucose And Amino Acid Restriction On Protein Turnover And Micro-Rna Composition In The Muscle Of Rainbow Trout, Mary Neslund Latimer

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Changes in nutritional status, through glucose and amino acid restriction, have the ability to augment both the protein turnover and micro-RNA (miR) composition in the skeletal muscle of rainbow trout in vitro and in vivo. In vitro, the restriction of glucose in the media for a period of 24h was able to reduce protein synthesis by 41.2% compared to control conditions. In addition, 48h of glucose restriction affected the expression of both mstn2a and igfbp5, genes involved in muscle growth dynamics and synthesis. The restriction of amino acids, specifically the amino acid methionine, in vitro was able to reduce the …

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Mechanisms And Treatment Of Halogen Inhalation-Induced Pulmonary And Systemic Injuries In Pregnant Mice, James Lambert Jan 2018

Mechanisms And Treatment Of Halogen Inhalation-Induced Pulmonary And Systemic Injuries In Pregnant Mice, James Lambert

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Toxic chemicals may pose an increased threat to vulnerable populations such as pregnant women and their unborn fetuses. The halogen bromine has numerous industrial utilities that include flame retardant, pharmaceutical, insecticide, and bleaching additive production. At room temperature, bromine is a volatile liquid. When the gas is inhaled, bromine causes exposure-dependent acute and chronic pulmonary and systemic injuries that range from mild eye and airway irritation to severe damage to the cardiopulmonary system and other organs, which can lead to death. If exposure is survived, patients still may develop reactive airway disease syndrome and pulmonary fibrosis as well as restrictive …

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