Digital Commons Network^™

Comprehensive Analysis Of Chromosome 14q32 Deletions In Chronic Lymphocytic Leukemia, Rachel A. Harris

Theses & Dissertations

Chronic lymphocytic leukemia (CLL) is a genetically heterogeneous disease characterized in part by a combination of conventional cytogenetic and fluorescence in situ hybridization (FISH) analyses. Previous studies have investigated the occurrence of many cytogenetic abnormalities in CLL. However, few have focused on the frequency and variation of deletions within chromosome 14 (14q32), including genes associated with the IGH gene region and the possible related prognostic implications. We performed a comprehensive analysis and examined the frequency of abnormalities, specifically, deletions of the 14q32 region, categorized the size variation of these deletions using microarray, and assessed the effect on time-to-first-treatment (TTFT) and …

A Multicenter Mixed-Effects Model For Inference And Prediction Of 72-H Return Visits To The Emergency Department For Adult Patients With Trauma-Related Diagnoses, Ehsan Yaghmaei, Louis Ehwerhemuepha, William Feaster, David Gibbs, Cyril Rakovski

Mathematics, Physics, and Computer Science Faculty Articles and Research

Objective

Emergency department (ED) return visits within 72 h may be a sign of poor quality of care and entail unnecessary use of healthcare resources. In this study, we compare the performance of two leading statistical and machine learning classification algorithms, and we use the best performing approach to identify novel risk factors of ED return visits.

Methods

We analyzed 3.2 million ED encounters with at least one diagnosis under “injury, poisoning and certain other consequences of external causes” and “external causes of morbidity.” These encounters included patients 18 years or older from across 128 emergency room facilities in the …

Therapeutic Trem2 Activation Ameliorates Amyloid-Beta Deposition And Improves Cognition In The 5xfad Model Of Amyloid Deposition, Brittani R. Price, Tiffany L. Sudduth, Erica M. Weekman, Sherika Johnson, Danielle Hawthorne, Abigail E. Woolums, Donna M. Wilcock

Sanders-Brown Center on Aging Faculty Publications

BACKGROUND: Triggering receptor expressed on myeloid cell-2 (TREM2) is a lipid and lipoprotein binding receptor expressed by cells of myeloid origin. Homozygous TREM2 mutations cause early onset progressive presenile dementia while heterozygous, point mutations triple the risk of Alzheimer's disease (AD). Although human genetic findings support the notion that loss of TREM2 function exacerbates neurodegeneration, it is not clear whether activation of TREM2 in a disease state would result in therapeutic benefits. To determine the viability of TREM2 activation as a therapeutic strategy, we sought to characterize an agonistic Trem2 antibody (AL002a) and test its efficacy and mechanism of action …

Ligand-Installed Polymeric Nanocarriers For Combination Chemotherapy, Xinyuan Xi

Theses & Dissertations

Combination chemotherapy remains the mainstay of cancer treatment because such strategy targets different cell signaling pathways to decrease the likelihood of developing protective mechanisms by cancer cells, thereby delaying the onset of recurrence and prolonging the survival. The co-delivery of binary drug combination via a single nanocarrier provides benefits in reducing dose-limiting toxicities, improving the pharmacokinetic properties of the cargo, spatial-temporal synchronization of drug exposure, and synergistic therapeutic effects. Rational design of such regimen is crucial for maximizing the therapeutic effects since only certain drug ratios exposed to the target might be synergistic while other ratios exert additive or even …

Effect Of Nanofiller Coating And Loading On Facial Elastomer Physical Properties, Rahmi K. Aulia

Theses & Dissertations

Current materials used for facial prostheses are far from being desirable, and improved properties with “skin-like” feel are needed. This study evaluates property changes induced by sequential additions of uncoated and hydrophobic-coated nano-SiO₂ to polydimethylsiloxane (PDMS) and compares them with those measured for conventional submicron SiO₂-filled materials. Each filler type was sequentially added to vinyl-terminated PDMS at 0%, 0.5%, 5%, 10%, and 15% by weight. Tensile, tear, Durometer hardness, translucency and viscoelastic properties were evaluated, with hardness and translucency also evaluated following 3000 hours of outdoor weathering. Results demonstrated that 15% coated nano-SiO₂-filled PDMS materials …

Development Of Cxcr4-Inhibiting Rna Delivery Vectors For The Treatment Of Metastatic Pancreatic Cancer, Yu Hang

Theses & Dissertations

Pancreatic ductal adenocarcinoma (PDAC) is a growing medical problem associated with extensive metastasis and high mortality. Late diagnosis and complexity of the tumor microenvironment (TME) with severe hypoxia, desmoplasia, and hypovascular nature contributes to poor effectiveness of conventional chemotherapies. RNA interference (RNAi) holds great potential in the treatment of multiple genetic and acquired diseases, including PDAC. CXCR4/CXCL12 chemokine axis plays a pivotal role in PDAC TME remodeling to promote tumor proliferation, angiogenesis, metastasis, and chemoresistance. This project developed polymeric AMD3100 (PAMD) derivatives as dual-function vectors capable of simultaneously delivering small RNAs and blocking CXCR4/CXCL12 signaling.

Administration route plays pivotal role …

Glycan-Dependent Adherence And Skin Colonization Of Staphylococcus Epidermidis Mediated By The Surface Protein Aap., Paroma Roy

Theses & Dissertations

Skin-dwelling coagulase-negative staphylococci (CoNS), a group of bacteria that includes Staphylococcus epidermidis, has been implicated to promote skin immunity and antimicrobial defense and prohibit colonization of skin by pathogens like S. aureus. As a skin inhabitant, S. epidermidis lives in tight association with corneocytes, the cells that constitute the uppermost layer of the skin epidermis. Yet the molecular mechanism responsible for adhesion of S. epidermidis to corneocytes remains poorly understood. Our study indicated that Accumulation-associated protein (Aap), a cell-wall anchored, fibrillar adhesin mediates bacterial-host interaction, demonstrated by significantly higher corneocyte binding by Aap-positive 1457 mutants as compared to …

Exercise And Nrf2 In Chronic Heart Failure, Ahmed Wafi

Theses & Dissertations

Increased activation of the sympathetic nervous system (SNS) plays an essential role in the pathogenesis of cardiovascular diseases such as chronic heart failure (CHF) and hypertension. Oxidative stress in key brain regions that are involved in maintenance and regulation of sympathetic vasomotor tone has been implicated in mediating this sympathoexcitation. One particular mechanism of oxidative stress-mediated increases in SNS is a reduction of antioxidant enzymes in rostral ventrolateral medulla (RVLM) neurons. Nuclear factor erythroid 2 related factor 2 (Nrf2) is a master regulator of cellular redox homeostasis that impacts the expression of antioxidant gene expression. Recent studies have demonstrated that …

Genomic And Transcriptomic Alterations In Metabolic Regulators And Implications For Anti-Tumoral Immune Response, Ryan J. King

Theses & Dissertations

Metabolic and immune alterations are ubiquitous hallmarks of cancer that are established during the foundational mutations and are further selected upon to generate highly aggressive tumors. Recent evidence suggests that cancer cells employ an altered metabolism to induce immune evasion. To further discover the relationship between metabolism and immunity in cancer, this thesis aimed to discover potential candidates of interest by first examining the mucin family for differences, as they exert a wide range of activities in cancer, including altered metabolism and immune alterations. Unique differences lead to further profiling in pancreatic and esophageal cancer. In pancreatic cancer, CD73 was …

Cooperativity Of Ccne1 And Foxm1 In High-Grade Serous Ovarian Cancer, Lucy Elge

Theses & Dissertations

High-grade serous ovarian cancer (HGSC) ranks as the fifth leading cause of female cancer related deaths. A greater understanding of the molecular mechanisms underlying HGSC will elucidate better detection methods and identify potential treatment targets.

Forkhead Box M1 (FOXM1) is a key player in HGSC, as data from The Cancer Genome Atlas (TCGA) revealed that its activation is the second most frequent molecular alteration in HGSC. Similarly, cyclin E1 (CCNE1) is also important in HGSC, as the gene is amplified in 20% of HGSC cases. Both genes and proteins have been studied extensively, but the potential interaction between the two …

Exosomes Secreted Under Hypoxia Enhance Stemness In Ewing’S Sarcoma And Transform Microenvironment Cells, Matthew J. Kling

Theses & Dissertations

Intercellular communication between tumor cells and stroma within the hypoxic microenvironment promote aggressiveness and poor patient prognoses in ways that remain unclear. Here we show that hypoxic Ewing’s sarcoma (EWS) cells release exosomes that promote sphere formation, a stem-like phenotype, in EWS cells by enhancing survival and a cancer-associated phenotype in fibroblasts (CAFs). Given that hypoxia enriches for stem-like cells, we exposed EWS cells to hypoxia and hypoxic EWS-derived exosomes and assessed the stem cell phenotype. Hypoxia and hypoxic EWS-derived exosomewere found to enhance TIC formation in vitro and in vivo by reprogramming EWS cells. Analysis of the hypoxic exosomal …

Highly Swelling Ph-Responsive Microgels For Dual Mode Near Infra-Red Fluorescence Reporting And Imaging, Mingning Zhu, Dongdong Lu, Qing Lian, Shanglin Wu, Wenkai Wang, L. Andrew Lyon, Weiguang Wan, Paulo Bártolo, Mark Dickinson, Brian R. Saunders

Engineering Faculty Articles and Research

Near infra-red (NIR) fluorescence is a desirable property for probe particles because such deeply penetrating light enables remote reporting of the local environment in complex surroundings and imaging. Here, two NIR non-radiative energy transfer (NRET) fluorophores (Cy5 and Cy5.5) are coupled to preformed pH-responsive poly(ethylacrylate-methacrylic acid-divinylbenzene) microgel particles (PEA-MAA-5/5.5 MGs) to obtain new NIR fluorescent probes that are cytocompatible and swell strongly. NIR ratiometric photoluminescence (PL) intensity analysis enables reporting of pH-triggered PEA-MAA-5/5.5 MG particle swelling ratios over a very wide range (from 1–90). The dispersions have greatly improved colloidal stability compared to a reference temperature-responsive NIR MG based on …

Parameters Autumn: 2020, Usawc Parameters

The US Army War College Quarterly: Parameters

No abstract provided.

Perceptions Of High School Principals On The Utilization Of Block Scheduling In Arkansas Schools, Deborah Ann Knowles

Student Theses and Dissertations

This qualitative study highlighted the perceptions of high school principals on the utilization of block scheduling in Arkansas public high schools. While block scheduling is not the prevalent model of scheduling in the state, many schools continue to experience success using this schedule. By interviewing principals, this study uncovered the factors needed in order to make utilizing this schedule effective. This study examines both the benefits and disadvantages of block scheduling and adds to the existing body of knowledge concerning block schedules. As new standards are adopted and new measures of accountability are implemented in the upcoming years, block scheduling …

Cerulean Warbler Habitat Selection, Breeding Biology, Survival, And Space Use In The Ozark Region, Jacob Louis Wessels

Student Theses and Dissertations

For many declining migratory birds, gaps in information on their ecology can impede conservation efforts. Cerulean Warblers (Setophaga cerulea; hereinafter ceruleans) are one such rapidly declining species and have regional ecological variation, so more comprehensive information may benefit their effective conservation. We studied ceruleans in the Ozark region of Arkansas to increase the scientific knowledge of this species in an understudied region that likely supports a ‘natural population’ of ceruleans. We assessed habitat selection, breeding biology, survival, and space use of ceruleans. Consistent with other regions, ceruleans at our study sites selected areas with large trees across spatial scales. Males …

Antioxidant Characterization Of Peanut Hairy Root Extracts Enriched With Prenylated Stilbenoids, Patrick Roberto

Student Theses and Dissertations

Peanut (Arachis hypogaea) is a prolific producer of prenylated stilbenoids that may confer health benefits in humans by their antioxidant activity. Therefore, the objective of this study was to use peanut hairy roots as a bioproduction system of extracts enriched with prenylated stilbenoids and evaluate their antioxidant activity in vitro. The 2,2-diphenyl-1-picrylhydrazyl (DPPH) assay suggested that the whole extract and pure prenylated stilbenoids exhibit antioxidant activity. High-performance liquid chromatography combined with DPPH identified arachidin-1, arachidin-3, and arachidin-5 as the principle antioxidants in the extract. The DPPH assay revealed that the arachidin portion of the extract contains greater antioxidant capacity than …

The Similar Other Bias: Does Perceived Similarity Impact Judgements Of Goal Commitment?, Brandon J. Higdon

Student Theses and Dissertations

Research investigating our perceptions of others’ goal commitment has found that three variables predict these perceptions: satisfaction, investment, and alternatives. The extent to which feelings of similarity to those we are judging impacts our perceptions of their goal commitment and ability has thus far gone unexplored. The present study sought to investigate the possible moderating role of perceived similarity in judgements of others’ commitment to their goals. Participants read a vignette describing a student musician who was described as either high in goal commitment or low in goal commitment and as similar or dissimilar to the participant. Participants then completed …

Nonnative Insect Invasions In Natural Ecosystems: Impacts, Policy, And Evaluation Of Drivers Using Underutilized Biocontrol Datasets, Ashley N. Schulz

Student Theses and Dissertations

The fundamental goal in invasion ecology is to understand what drives the success of nonnative species. To assess mechanisms of invasion, invasion ecologists traditionally study populations of nonnative species that have already established and spread within an environment. A less common method is to use data from classical biocontrol agents, which are also nonnative and have variable impacts with respect to efficacy and non-target effects. Further elucidation of mechanisms of invasion can help researchers develop better methods for detection, prevention, and control of nonnative species. To make progress in the battle against nonnative species, focus should be placed on both …

Drosophila Model To Study Muscle Atrophy, Aaron Aghai

Master of Science in Integrative Biology Theses

Muscle atrophy (MA) is a phenomenon of muscle mass loss due to accelerated protein degradation in muscle fibers. Some pathological conditions, such as chronic inflammation or cancer, induce accelerated MA, which complicates medical treatment, hampers recovery of fragile patients, and ultimately can be the cause of a patient’s death. To gain better control over MA, more information is required about the whole spectrum of genetic factors that can influence MA.

Drosophila provides an excellent platform for genetic screening, although it has somewhat limited utility for MA research since insect muscles lack the level of plasticity found in mammalian muscles. We …

Epidemiology Of Brain Tumors In The United Arab Emirates: A National Registry Cross-Sectional Study, Sarah Khan, Mona El Kouatly Kambris, Eman T. Alshamsi

All Works

© 2020 The Author(s). Background: Cancer is the third leading cause of death in the United Arab Emirates (UAE); brain cancer ranks 10th among the cancers, with 2.9% of the primary cancers originating from the nervous system. The epidemiology of brain cancers has not been explored. The unique population dynamics of UAE make it a fertile ground for analyzing the epidemiology of brain cancer. In this study, we aim to look at the frequency patterns and distribution of malignant primary brain tumors in the UAE. Methods: A cross sectional study was carried out using data obtained from the Tawam Hospital …

Dual Tasking Impairments Are Associated With Striatal Pathology In Huntington’S Disease, Johnny Lo, Alvaro Reyes, Timothy S. Pulverenti, Timothy J. Rankin, Danielle M. Bartlett, Pauline Zaenker, Grant Rowe, Kirk Feindel, Govinda Poudel, Nellie Georgiou‐Karistianis, Mel R. Ziman, Travis M. Cruickshank

Publications and Research

Background: Recent findings suggest that individuals with Huntington’s disease (HD) have an impaired capacity to execute cognitive and motor tasks simultaneously, or dual task, which gradually worsens as the disease advances.The onset and neuropathological changes mediating impairments in dual tasking in individuals with HD are unclear. The reliability of dual tasking assessments for individuals with HD is also unclear.

Objectives: To evaluate differences in dual tasking performance between individuals with HD (presymptomatic and prodromal) and matched controls, to investigate associations between striatal volume and dual tasking performance, and to determine the reliability of dual tasking assessments.

Methods: Twenty individuals with …

Compassion Fatigue Among U.S. Military Rns Post Overseas Deployment, Dawn Marie Goldstein

Dissertations

Describe the meaning of compassion fatigue (CF) as experienced by the U.S. military registered nurse (RN) post-deployment from Iraq and Afghanistan. Background: CF is characterized by deep emotional and physical exhaustion, and may resemble posttraumatic stress disorder (PTSD). Often this causes a shift in confidence and clouds RN perceptions. Symptoms include difficulty concentrating, intrusive imagery, hopelessness, exhaustion, and irritability leading to profound alterations in one's view of the world, patients, family, and friends. Outcomes include depersonalizing patients, poor coping mechanisms, lowered standards, clinical errors, and blurring boundaries, all can contribute to a toxic work environment and RNs leaving the profession.

Development Of An Lc-Esi-Ms/Ms Method For Determination Of A Novel Pyrrolomycin (Mp-1) And Application To Pre-Clinical Adme Studies, Wafaa N. Aldhafiri

Theses & Dissertations

A rapid, selective, and sensitive liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS) method was developed and validated for quantitation of a novel Pyrrolomycin (MP-1) in mouse plasma. MP-1 was extracted from plasma utilizing a structural analog (PL-3) as the internal standard (IS). Analyte separation was achieved using a Waters Acquity UPLC®BEH C18 column (1.7 µm, 100 x 2.1 mm) protected with Acquity UPLC C18 guard column. Mobile phase consisted of 0.1% acetic acid in water (10%) and methanol (90%) at a total flow rate of 0.25 mL/min. The mass spectrometer was operated at unit resolution in the multiple reaction …

From Development To Therapy: A Panoramic Approach To Further Our Understanding Of Cancer, Brittany Poelaert

Theses & Dissertations

Solid tumors, such as pancreatic cancer, often result in dismally low survival outcomes for patients due to insufficient understanding of disease development and progression. Pancreatic cancer is the fourth leading cause of cancer-related deaths in the United States and although oncogenic drivers (such as KRAS mutation or loss of tumor suppressor p53) and stages of disease development have been studied, further understanding of pancreatic cancer development is greatly needed. Studies from our laboratory have identified novel and varied functions of amyloid precursor-like protein 2 (APLP2) in the development and progression of pancreatic cancer. These functions include promoting cancer cell migration, …

Sintesis Tetrapeptida Antioksidan Tkps Dengan Metode Fasa Padat, Nety Kurniaty, Predi Mubarok

Chimica et Natura Acta

Senyawa tetrapeptida antioksidan threonin-lysin-prolin-serin (TKPS) merupakan salah satu derivat hasil isolasi dari jamur Tolypocladium inflatum dan telah berhasil disintesis menggunakan metode solid-phase peptide synthesis (SPPS). Penelitian ini bertujuan untuk menyintesis senyawa tetrapeptida TKPS dengan metode SPPS dan mengetahui aktivitas antioksidan senyawa tetrapeptida hasil sintesis dengan uji DPPH. Tetrapeptida TKPS disintesis menggunakan strategi SPPS pada resin 2-klorotritilklorida sebagai padatan penyangga, strategi gugus pelindung Fmoc, dan penggunaan reagen kopling HBTU/HOBt. Padatan TKPS berhasil dimurnikan menghasilkan TKPS sebanyak 111,4 mg. Setelah dimurnikan, TKPS dikarakterisasi dengan HR-TOF-MS yang memberikan nilai m/z [M+H]+ 431,2588 yang sesuai untuk TKPS. Uji aktivitas antioksidan dilakukan pada TKPS dengan …

Respons Dua Mutan Tomat Terhadap Cekaman Kekeringan, Ayu Ratna Ningrum, Anne Nuraini, Erni Suminar, Syariful Mubarok

Jurnal Kultivasi

Kondisi cekaman kekeringan pada tanaman tomat dapat menyebabkan pertumbuhan dan produksi tanaman tomat menurun. Salah satu upaya yang dapat dilakukan untuk mengatasi masalah tersebut adalah dengan perakitan varietas tanaman baru yang tahan terhadap cekaman kekeringan. Beberapa hasil mutasi gen IAA pada tomat mutan Micro-Tom mampu menghasilkan tanaman yang toleran terhadap kondisi stress secara abiotik, yaitu pada galur iaa9-3 dan iaa9-5. Penelitian ini dilakukan untuk mengetahui respons pertumbuhan vegetatif pada iaa9-3 dan iaa9-5 dalam kondisi cekaman kekeringan dengan metode in vitro. Penelitian dilaksanakan di Laboratorium Kultur Jaringan dan Teknologi Benih Fakultas Pertanian Universitas Padjadjaran pada bulan September sampai Desember 2019. Rancangan …

Aligned Fingolimod-Releasing Electrospun Fibers Increase Dorsal Root Ganglia Neurite Extension And Decrease Schwann Cell Expression Of Promyelinating Factors, Devan L. Puhl, Jessica L. Funnell, Anthony R. D'Amato, Jonathan Bao, Dmitri V. Zagorevski, Yelena Pressman, Daniel Morone, Agnes E. Haggerty, Martin Oudega, Ryan J. Gilbert

Chemical and Biochemical Engineering Faculty Research & Creative Works

Researchers are investigating the use of biomaterials with aligned guidance cues, like those provided by aligned electro spun fibers, to facilitate axonal growth across critical-length peripheral nerve defects. To enhance the regenerative outcomes further, these aligned fibers can be designed to provide local, sustained release of therapeutics. The drug fingolimod improved peripheral nerve regeneration in preclinical rodent models by stimulating a pro-regenerative Schwann cell phenotype and axonal growth. However, the systemic delivery of fingolimod for nerve repair can lead to adverse effects, so it is necessary to develop a means of providing sustained delivery of fingolimod local to the injury. …

Sars-Cov-2 (Covid-19) Structural And Evolutionary Dynamicome Insights Into Functional Evolution And Human Genomics, Ruchir Gupta, Jacob Charron, Cynthia L. Stenger, Jared Painter

University Faculty Publications and Creative Works

The pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has challenged the speed at which laboratories can discover the viral composition and study health outcomes. The small ~30-kb ssRNA genome of coronaviruses makes them adept at cross-species spread while enabling a robust understanding of all of the proteins the viral genome encodes. We have employed protein modeling, molecular dynamics simulations, evolutionary mapping, and 3D printing to gain a full proteome- and dynamicome-level understanding of SARS-CoV-2. We established the Viral Integrated Structural Evolution Dynamic Database (VIStEDD at RRID:SCR_018793) to facilitate future discoveries and educational use. Here, we highlight the …

Gut Microbiota Features Associated With Campylobacter Burden And Postnatal Linear Growth Deficits In A Peruvian Birth Cohort, Saba Rouhani, Nicholas W Griffin, Pablo Peñataro Yori, Maribel Paredes Olortegui, Mery Siguas Salas, Dixner Rengifo Trigoso, Lawrence H Moulton, Eric R Houpt, Michael J Barratt, Margaret N Kosek, Jeffrey I Gordon

2020-Current year OA Pubs

BACKGROUND: Campylobacter infection is associated with impaired growth of children, even in the absence of symptoms. To examine the underlying mechanisms, we evaluated associations between Campylobacter infection, linear growth, and fecal microbial community features in a prospective birth cohort of 271 children with a high burden of diarrhea and stunting in the Amazonian lowlands of Peru.

METHODS: Campylobacter was identified using a broadly reactive, genus-specific enzyme-linked immunosorbent assay. 16S rRNA-based analyses were used to identify bacterial taxa in fecal samples at ages 6, 12, 18, and 24 months (N = 928). Associations between infection, growth, and gut microbial community composition …

Ultrasonic Vocalizations As A Potential Indicator Of A Negative Affective State In Forelimb-Amputated Rats, Carey Daniel Womack

Electronic Theses and Dissertations Archive

Most amputees experience phantom limb pain (PLP) post-amputation, the mechanisms of which are not fully understood. Rat amputees may serve as a practical model for studying PLP, as rats process pain similarly to primates. Ultrasonic vocalizations (USVs) of acclimated, formalin-injected rats and acclimated, forelimb-amputated rats were recorded to investigate the potential for measuring USVs as an indicator of a negative affective state. Subcutaneous injections of 10% formalin in the hindpaw elicited increased USV emission, primarily in the 22 kHz-AFR. Unoperated rats and forelimb-amputated rats were monitored for seven weeks following acclimation and surgery. Amputees emitted a greater quantity of 22 …