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Development And Applications Of Capillary Vibrating Sharp-Edge Spray Ionization Coupled With Atmospheric Pressure Chemical Ionization (Cvssi-Apci), Madison Elizabeth Pursell

Graduate Theses, Dissertations, and Problem Reports (ETD)

Mass spectrometry (MS) is a technique that is used in fields in which both complex and non-complex mixtures are analyzed. The state-of-the-art ion sources that are utilized for MS are being demonstrated to be functional for direct infusion of samples as well as for use with online separations. However, ion sources, such as electrospray ionization (ESI) and atmospheric pressure chemical ionization (APCI) can encounter problems such as ion suppression and an inability to ionize based on size and/or polarity, respectively. Further these sources are bulky and require gas flow, heat sources, and additional high voltage power supplies for optimal performance. …

Conformational Investigation Of Biopolymers Through Molecular Dynamics (Md) Simulations And In-Droplet Hdx-Ms Utilizing Cvssi, Samira Hajian Foroushani

Graduate Theses, Dissertations, and Problem Reports (ETD)

Over the last two decades, mass spectrometry (MS) has received significant interest in biological study platforms, especially in the areas of proteomics and metabolomics. With the development of soft ionization methods like electrospray ionization (ESI), mass spectrometry has emerged as a potent method for directly characterizing proteins in their native state. The recent invention of capillary vibrating sharp-edge spray ionization has opened new avenues for the study of biopolymer native structure including the usage of droplet charge tuning and in-droplet hydrogen-deuterium exchange (HDX) labeling. With this new technique comes the opportunity to study biopolymer ion structure preservation with molecular dynamics …

Advanced Techniques In Time Series Forecasting: From Deterministic Models To Deep Learning, Xue Bai

Graduate Theses, Dissertations, and Problem Reports (ETD)

This dissertation discusses three instances of temporal prediction, applied to population dynamics and deep learning.

In population modeling, dynamic processes are frequently represented by systems of differential equations, allowing for the analysis of various phenomena. The first application explores modeling cloned hematopoiesis in chronic myeloid leukemia (CML) via a nonlinear system of differential equations. By tracking the evolution of different cell compartments, including cycling and quiescent stem cells, progenitor cells, differentiated cells, and terminally differentiated cells, the model captures the transition from normal hematopoiesis to the chronic and accelerated-acute phases of CML. Three distinct non-zero steady states are identified, representing …

Syntheses Of Indoles And Natural Indole Alkaloids From 2-Nitrostyrene Derivatives, S M Ashikur Rahman

Graduate Theses, Dissertations, and Problem Reports (ETD)

A short and flexible synthesis of 2,3-disubstituted indoles employing a Barluenga-type palladium-catalyzed cross-coupling of p-tosylhydrazones with 2-nitroarylhalides followed by a palladium-catalyzed, carbon monoxide-mediated reductive cyclization was developed. Significantly better overall yields were obtained performing the two-step reaction sequence in a one-pot reaction. Secondly, in order to facilitate biological studies of ergotryptamine, a recently isolated ergot alkaloid, it was selected as a target for synthesis. In an attempt to synthesize ergotryptamine, a palladium catalyzed Kosugi-Migita-Stille cross coupling, a Mizoroki-Heck reaction, and a carbon monoxide-mediated palladium-catalyzed reductive cyclization were utilized as the key steps. Using a similar synthetic approach, synthesis of …

Biocompatible And Multifunctional Trityl Spin Probes For Electron Paramagnetic Resonance Spectroscopy, Teresa D. Gluth

Graduate Theses, Dissertations, and Problem Reports (ETD)

The primary objective of my thesis was to develop and utilize a biocompatible multifunctional trityl spin probe for concurrent measurement of pO₂, pH_e, and [P_i] in vivo by electron paramagnetic resonance (EPR) spectroscopy (Chapter 2). My first goal was to synthesize the proposed probe we are terming HOPE71. Secondly, HOPE71 was characterized by X-band and L-band EPR spectroscopy. Next, the biocompatibility of HOPE71 was assessed through an albumin binding test, cytotoxicity assays, and in vivo intravenous tolerance. Then, the use of HOPE71 to measure the target parameters was demonstrated in a breast cancer …

Harnessing Acoustic Streaming For Bioanalysis In Microfluidics, Xiaojun Li

Graduate Theses, Dissertations, and Problem Reports (ETD)

In the past few decades, microfluidic technology has been developed rapidly in both fabrication methods and multifunctionality integrations, making it a powerful tool for a wider variety of biological applications. The device fabrication method has expanded from conventional polymer-based micro devices to 3D-printed micro devices, and allows multiple functions such as electric, optic, magnetic and acoustic to be integrated on a single platform. This dissertation focuses on method development of acoustic streaming-based microfluidics in bioanalysis such as immunoassay, enzyme kinetics and DNA fragmentation analysis. In this dissertation, a micromixer was developed based on acoustic streaming generated from sharp-edge structure vibration …

Assessment Of Heat Stress For Outdoor Work Conditions In Saudi Arabia, Jamal Alanazi

Graduate Theses, Dissertations, and Problem Reports (ETD)

Outdoor workers have an increased risk of heat stress in Saudi Arabia since it is one of the hottest places in the Middle East. Recently, the government decided to limit outdoor work hours during the months of June, July, and August every year, and banned working under the direct sunlight from 12:00 to 03:00 p.m., although outdoor workers in the petroleum, natural gas, or emergency maintenance work industries are exempt from this prohibition. Traditionally, the efforts by safety and health professionals to mitigate work-related heat injury has been directed toward the assessment of environmental heat stress (e.g., wet-bulb globe temperature), …

The Role Of Genotype In Saccharomyces Cerevisiae Resistance To 4-Methylcyclohexanemethanol, Michael C. Ayers

Graduate Theses, Dissertations, and Problem Reports (ETD)

The chemical 4-methylcyclohexanemethanol (MCHM) spilled in the Elk River near Charleston, WV in January 2014, impacting the drinking water of 300,000 residents. Initial studies on MCHM following the spill attempted to characterize its toxicological effects in animals, but largely ignored characterization of its effects on cellular pathways and metabolism. In this study, I used this chemical as a novel stressor for the model eukaryote S. cerevisiae to explore the relationship of genotype and stress phenotypes. Initial exploration characterized the stress phenotype of MCHM in yeast through growth assays, cell cycle analysis, and transcriptomic data. MCHM exposure caused cells to arrest …

Protein/Peptide Characterization Using Mass Spectrometry And Molecular Dynamics Simulations, Ahmad Kiani Karanji

Graduate Theses, Dissertations, and Problem Reports (ETD)

Mass spectrometry (MS) based-techniques and molecular dynamics (MD) simulations have been used to characterize protein/peptide structure as well as their interactions with lipid vesicles and detergents. Chapter 1 introduces an introduction to the concepts and tools that were used in this work. In Chapter 2, the dominant gas-phase conformer of [M+3H]3+ ions of the model peptide Acetyl-PSSSSKSSSSKSSSSKSSSSK are examined with ion mobility spectrometry (IMS), gas-phase hydrogen deuterium exchange (HDX), and mass spectrometry (MS) techniques. This section furthers the development of a protein structural prediction tool by providing information about gas-phase ion conformers of two model peptides having different solution conformational …

Syntheses Of Azepinoindole Alkaloids Cimitrypazepine, Fargesine And Hyrtioreticulins C & D, Ganesh Ghimire

Graduate Theses, Dissertations, and Problem Reports (ETD)

The Watanabe-Cenini-Söderberg reductive N-heterocyclization has emerged as a powerful tool for the synthesis of a variety of functionalized indoles. Söderberg’s elaboration of this methodology has been utilized as a late-stage cyclization protocol for the synthesis of azepinoindole alkaloids, a class of natural products characterized by an azepane skeleton fused with an indole ring. Short syntheses of the naturally occurring azepino[5,4,3-cd]indole alkaloids, cimitrypazepine, fargesine, and the diastereomeric hyrtioreticulins C & D have been completed starting from commercially available tetra-substituted benzene derivatives. The key azepinoindole core in each case was assembled via an intramolecular Mizoroki-Heck reaction followed by a …

Investigating The Role Of Mechanical Properties In Biological Systems, Nicole Shamitko-Klingensmith

Graduate Theses, Dissertations, and Problem Reports (ETD)

There is considerable interest in measuring, with nanoscale spatial resolution, the physical and material properties of biological membranes and whole cells because of their role in the physiology of living systems. The atomic force microscope (AFM) has proven to be particularly well-suited for biological studies because samples can be maintained in near physiological conditions to preserve sample integrity (such as in a buffer solution at a physiologically relevant pH or temperature), and the imaging process is relatively nondestructive. In this work, the mechanical properties of supported lipid bilayers and neurons were examined using AFM-based techniques. Specifically, tapping mode AFM-based techniques …

Microfluidic Impedance-Metric Biosensor For Monitoring Carbon Nanotube-Induced Epithelial Permeability, Zhouchun Huang

Graduate Theses, Dissertations, and Problem Reports (ETD)

Carbon nanomaterials, including carbon nanotubes (CNTs) gain increasing interest in commercial and biomedical applications. Adverse health effects of engineered CNTs may result from either direct exposure during production, inadvertent exposure during use of by-products, and/or release of these materials into the environment. Recent studies have shown that CNTs can induce cytotoxicity, apoptosis, DNA damage, and tumor formation in animals, suggesting their potential toxicity in humans. To address the current needs in developing in vitro cell assays for assessment of the adverse health effects of CNTs in lung respiratory, we have developed a microfluidic impedance-metric biosensor for investigation of multi-walled CNTs …

Surfaces Modulate Β-Amyloid Peptide Aggregation Associated With Alzheimer's Disease., Elizabeth Anne Yates

Graduate Theses, Dissertations, and Problem Reports (ETD)

A hallmark of Alzheimer's disease, a late onset neurodegenerative disease, is the presence of neuritic amyloid plaques deposited within the brain composed of β-amyloid (Aβ) peptide aggregates. Aβ can aggregate into a variety of polymorphic aggregate structures under different chemical environments, specifically affected by the presence of differing surfaces. There are several point mutations clustered around the central hydrophobic core of Aβ (E22G Arctic mutation, E22K Italian mutation, D23N Iowa mutation, and A21G Flemish mutation). These mutations are associated with hereditary diseases ranging from almost pure cerebral amyloid angiopathy to typical Alzheimer's disease pathology with both plaques and tangles. To …

Pharmacological Characterization Of An Optimized Sigma Receptor Ligand, Michael Seminerio

Graduate Theses, Dissertations, and Problem Reports (ETD)

Methamphetamine is an addictive psychostimulant drug with an increasing prevalence of abuse worldwide. Recent evidence has linked methamphetamine exposure to a wide array of neurological complications some of which lead to neurodegenerative changes in the brain and hyperthermia. Currently, there are no FDA approved pharmacologic agents to treat the effects of methamphetamine. Recent evidence has suggested methamphetamine may, in part, produce some of its effects through sigma receptors making them a potential target for pharmacological intervention. While our lab has shown a number of selective sigma receptor ligands can provide neuroprotection against the neurotoxic and behavioral effects of methamphetamine, limitations …

The Relationship Between Temperament And Facets Of Creativity, Clark Daniel Pinson

Graduate Theses, Dissertations, and Problem Reports (ETD)

The purported association between mental illness and creativity has been most heavily researched in individuals diagnosed with a bipolar disorder. The bipolar disorders have been conceptualized as a spectrum of disorders that range from problematic and labile affect to different types of temperament. Temperament has classically been defined as elements of personality that are heritable, stable, based on emotion, and uninfluenced by socio-cultural learning. Contemporary literature suggested that at least some aspects of creativity may be enhanced by an affective range that has been best characterized by the milder part of the bipolar spectrum of disorders. The primary inquiry of …

Assessment Of Pulmonary Fibrogenic Potential Of Multi Walled Carbon Nanotubes In Vitro., Anurag Mishra

Graduate Theses, Dissertations, and Problem Reports (ETD)

Multi-walled carbon nanotubes (MWCNT) have many applications due to their unique mechanical and electrical properties. However, these fiber shaped materials have been shown to possess unusual fibrogenic activity in vivo and are currently the focus of intense toxicological investigations. To date very few detailed mechanistic studies on the fibrogenic activity of CNT have been reported. The aim of this series of studies is to determine fibrogenic potential of well dispersed MWCNT in human lung cell culture models and develop a novel platform for understanding the cellular mechanisms of MWCNT-induced lung fibrosis. Dispersion of large agglomerates of MWCNT in suspension to …

Computational Hybrid Systems For Identifying Prognostic Gene Markers Of Lung Cancer, Ying-Wooi Wan

Graduate Theses, Dissertations, and Problem Reports (ETD)

Lung cancer is the most fatal cancer around the world. Current lung cancer prognosis and treatment is based on tumor stage population statistics and could not reliably assess the risk for developing recurrence in individual patients. Biomarkers enable treatment options to be tailored to individual patients based on their tumor molecular characteristics. To date, there is no clinically applied molecular prognostic model for lung cancer. Statistics and feature selection methods identify gene candidates by ranking the association between gene expression and disease outcome, but do not account for the interactions among genes. Computational network methods could model interactions, but have …

The Use Of The Palladium-Catalyzed Glycosylation For The Synthesis Of C- And O-Linked Glycosylated Natural Products, Xiaomei Yu

Graduate Theses, Dissertations, and Problem Reports (ETD)

The carbohydrate portions of natural products play a crucial role in their pharmacological properties. These properties can vary from improved water solubility, improved membrane transport properties, improved tissue targeting, as well as improved target binding. Herein we describe our efforts to use de novo synthesis to help elucidate the various roles carbohydrates play in biologically active glycosylated natural products.;The O'Doherty group has developed a method that uses asymmetric synthesis for the de novo synthesis of carbohydrates. In contrast to traditional carbohydrate methods, this de novo approach builds the desired functionality and stereochemistry within each sugar. This methodology relies on a …

Asymmetric Synthesis Of Sl0101, Cyclitol And Jadomycin, Mingde Shan

Graduate Theses, Dissertations, and Problem Reports (ETD)

The carbohydrate portion of natural products plays a crucial role in biology, such as target binding, solubility, tissue targeting, and membrane transportation. The O'Doherty group has developed a de novo methodology to build the desired functionality and stereochemistry within each sugar, in contrast to the traditional approach using known carbohydrates as starting materials. This methodology relies on a highly diastereoselective palladium(0)-catalyzed glycosylation reaction to control the stereochemistry at the anomeric center and post-glycosylation transformation to introduce the corresponding functionality in the sugar moiety.;Continuing our investigations on the utility of this strategy, we turned our attention to the syntheses of the …

Development Of Volunteer-Driven Indices Of Biological Integrity For Wetlands In West Virginia, Walter Emil Veselka Iv

Graduate Theses, Dissertations, and Problem Reports (ETD)

Wetland indices of biological integrity (IBIs) are used to satisfy the water resources monitoring requirements of the Clean Water Act (CWA). However, debate still exists on what classification systems and taxa to base these IBIs upon. Our cumulative research, representing indices of biological integrity designed for regional HGM subclasses, designated HGM management classes and Cowardin et al. (1979) classes for West Virginia. The indices were derived from metrics calculated from anuran, avian, macroinvertebrate, and vegetation communities; each representing increasing levels of resources associated with gathering the necessary data. For example, avian and anuran data used to derive floodplain wetland IBI …

Bioinformatic Study Of Gamma-Secretase And Its Substrates, Fei Nan

Graduate Theses, Dissertations, and Problem Reports (ETD)

gamma-Secretase is an enzymatic complex critical to amyloid formation and other important pathophysiological processes. Non-specific gamma-secretase inhibitors are not ideal for intervention of familial Alzheimer's disease. The four essential include Presenilin (PS1 or PS-2), APH-1, Pen-2, nicastrin (Nct). Also gamma-secretase cleaves a variety of substrates (over 30). But different sites are cleaved even in a single substrate and no consensus sequence for cleavage by gamma-secretase is identified. We hypothesize that consensus compositional sequence (or functional domain) in components of gamma-secretase and/or its substrates should exist during gamma-secretase regulation and specific gamma-secretase inhibitor based on such consensus sequence (or functional domain) …

Rates Of Swim Bladder Parasite Infection And Pit Tag Retention In Upstream Migrant American Eels Of The Upper Potomac River Drainage, Jennifer L. Zimmerman

Graduate Theses, Dissertations, and Problem Reports (ETD)

This thesis involved two components: identification of the parasite Anguillicola crassus in American eels, Anguilla rostrata and PIT tag retention in eels in a laboratory setting. The recent spread of the swim bladder nematode parasite, Anguillicola crassus, in American eels has caused concern among biologists and fishery managers. A total of 244 yellow-phase American eels were collected at the Millville Dam eel ladder on the Shenandoah River, WV. Swim bladders were removed and examined for the presence of the nematode parasite. The number of parasites in each eel was recorded, and prevalence, intensity, and mean intensity were calculated. A swim …

De Novo Asymmetric Synthesis Of Mannopeptimycin-E, Novobiocin And Methymycin Analogues, Sanjeeva Rao Guppi

Graduate Theses, Dissertations, and Problem Reports (ETD)

The carbohydrate portion of the natural products plays a crucial role in biology, such as target binding, solubility, tissue targeting, and membrane transportation. The O'Doherty group use a de novo methodology to build the desired functionality and stereochemistry within each sugar, in contrast to the traditional approach using known sugar isomers as starting materials. Recently, we have developed a practical and highly diastereoselective palladium catalyzed glycosylation reaction to control the stereochemistry at the anomeric center. Continuing, our investigations on the utility of this strategy, we turned our attention to the syntheses of the bioactive carbohydrate-based natural product analogues. The targets …

De Novo Asymmetric Syntheses Of Unnatural Manno-Trisaccharides, Homo-Adenosine, Digitoxin And Landomycin A., Maoquan Zhou

Graduate Theses, Dissertations, and Problem Reports (ETD)

De novo asymmetric synthesis is a strategy that uses asymmetric catalysis to construct chiral molecules from achiral starting materials. De novo approach to carbohydrate builds saccharides from commercially available achiral starting material which will enable the medicinal chemist to install a much broader range of carbohydrates on natural products and in a SAR-amenable fashion. The palladium-catalyzed glycosylation reaction stereoselectively converts 2-substituted 6-tert-butoxycarboxy-2H-pyran-3(6H)-ones into 2-substituted 6-alkoxy-2H-pyran-3(6H)-ones. By using this reaction, a divergent library of the natural and unnatural 1,4-manno-trisaccharides as well as branched 1,4- and 1,6-linked trisacchardes were synthesized. The 1,4-α-manno-disaccharides were achieved in eight total steps starting from achiral acylfuran. …

Gene Expression Profiling In Prepubertal And Adult Male Mice Using Cdna And Oligonucleotide Microarrays, Lisa Marie Tomascik-Cheeseman

Graduate Theses, Dissertations, and Problem Reports (ETD)

Variations in gene expression are the basis of differences in cell and tissue function, response to DNA damaging agents, susceptibility to genetic disease, and cellular differentiation. The purpose of this dissertation research was to characterize variation in basal gene expression among adult mouse tissues for selected stress response, DNA repair and damage control genes and to utilize variation in temporal gene expression patterns to identify candidate genes associated with germ cell differentiation from mitosis through meiosis in the prepubertal mouse testis. To accomplish these goals, high throughput analyses of gene expression were performed using custom cDNA and random oligonucleotide microarrays. …

Dark Wilderness A Phenomenological Exploration Of The Idea Of Cave Wilderness, Patricia E. Seiser

Graduate Theses, Dissertations, and Problem Reports (ETD)

It has been almost forty years since the passage of the 1964 Wilderness Act and the establishment of the National Wilderness Preservation System. Forty years later, we still have not seen a wilderness that is not a surface environment. There exist neither subterranean nor marine wilderness areas. Efforts on behalf of cave wilderness have focused on the 1964 Wilderness Act legal definition of wilderness. Perhaps what is required is a different concept for the establishment of cave wilderness. This study explored the idea of cave wilderness from a human dimension perspective, via focus groups, using stakeholders from two cave regions …

Design And Implementation Of Web-Based Gis For Forest Fragmentation Analysis, Fei Wang

Graduate Theses, Dissertations, and Problem Reports (ETD)

The advantages and limitations of current web GIS software for forest fragmentation information and analysis functionality were investigated using Landsat Thematic Mapper data of 1987 to 1999 for a test site in northern West Virginia. ESRI's ArcIMS technology was used to build a Web-based forest fragmentation analysis system to query, represent, and analyze the status of forest fragmentation using landscape metrics. Both ArcIMS HTML and Java fragmentation analysis tools were constructed. The web GIS was evaluated with respect to accessibility, navigation, interactive cartographic functionality, and spatial analysis functionality. The current ArcIMS approach was found to offer only limited support for …

Factors Influencing Habitat Selection And Activity Of Ground Beetles (Coleoptera: Carabidae) In Central Appalachia. Part I. The Influence Of Soil And Soil Surface Characteristics On Habitat Selection By Carabidae. Part Ii. Precipitation And Temperature Fluctuations: Effects On Carabidae Activity. Part Iii. The Effects Of Two Microbial Insecticides For Gypsy Moth Control On Carabidae Populations., Terry R. Carrington

Graduate Theses, Dissertations, and Problem Reports (ETD)

A study was conducted in the George Washington National Forest in Virginia and the Monongahela National Forest in West Virginia. Carabid samples were collected over four years and compared to soil characteristics, surface characteristics and meteorological conditions to determine what role these factors play in carabid habitat selection. Opportunity also existed to compare carabid populations before and after the application of microbial insecticides on the sampling sites. This study was conducted as as part of a larger project investigating non-target impacts from gypsy moth, Lymantria dispar (L.)(Lepidoptera: Lymantriidae), insecticide applications and the interaction of Entomophaga maimaiga Humber, Shimazu, and Soper …

Effects Of Nicotine On Content Of Corticotropin Releasing Factor (Crf) In Rat Amygdala, Hypothalamus And Brain Stem, Sibonisiwe Ntini Masilela

Graduate Theses, Dissertations, and Problem Reports (ETD)

Effects of 1.0 mg/kg and 0.4 mg/kg intraperitoneal nicotine on hypothalamic and extra hypothalamic levels of corticotropin releasing factor (CRF) were examined in 104 rats. CRF, a 41-amino acid peptide involved in responses to stress, fear and anxiety, influences the same neurotransmitter systems as nicotine, a psychoactive component of tobacco. Radioimmunoassays revealed that in macro-dissected hypothalami, 15 minutes treatment with 1.0 mg/kg nicotine significantly increased CRF content compared to no treatment. The 1.0 mg/kg dose did not elicit effects in macro-dissected amygdala and brain stem. With 0.4 mg/kg nicotine, no significant effects were observed in micro-dissected hypothalamic paraventricular nucleus, amygdaloid …

A Study Of The Biology Of Phyllocoptes Fructiphilus Keifer, And Its Ability To Transmit Rose Rosette Disease To Multiflora Rose, Rosa Multiflora Thunb., Abdullah Kassar

Graduate Theses, Dissertations, and Problem Reports (ETD)

The eriophyid mite Phyllocoptes fructiphilus is the vector of rose rosette disease (RRD). The mite occurs naturally on several wild roses and on multiflora rose. P. rosarum is a related eriophyid mite found on multiflora and other rose plants. A successful mass rearing program was developed and a rearing arena designed to allow observation of individual mites. Biological studies were conducted of both mites including life history, sex ratio, hibernation site, effect of temperature on egg laying and rate of development, and host range. Effect of relative humidity on P. rosarum was studied. Transmission trials were conducted both in the …