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Mass Spectrometric Analysis Of Environmental Contaminants, Protein Structure And Expression, Ian E. Atkinson
Mass Spectrometric Analysis Of Environmental Contaminants, Protein Structure And Expression, Ian E. Atkinson
ETD Archive
There are a wide array of sciences at our disposal to further our understanding of the roles of toxins in the environment and their effects on living organisms. Of these disciplines, the field of mass spectrometry offers a powerful analytical means to identify compounds in varying and complex sample media. The presence of altered expressions of biomolecules upon exposure to toxins, the effects that these toxins may have on biomolecule structure and the identity of toxins in the sample all can be determined by mass spectrometry. In this study mass spectrometric analysis has been applied to environmental toxicological problems. First, …
Role Of Transcription Factor Mef2a In Development Of Coronary Artery Disease (Cad) And Myocardial Infarction (Mi), Maniragava Sai Bhagavatula
Role Of Transcription Factor Mef2a In Development Of Coronary Artery Disease (Cad) And Myocardial Infarction (Mi), Maniragava Sai Bhagavatula
ETD Archive
Coronary artery disease (CAD) and myocardial infarction (MI) are the leading cause of death in developed countries. Genetic factors play an important role in the pathogenesis of CAD and MI. The revolutionary advances in molecular genetics have provided new insights into the genetic pathways involved in this disease. Recently, our laboratory used linkage analysis to map the first disease-causing gene for CAD and MI to chromosome 15q26 in a large family and subsequently mutation analysis identified a 7-amio acid deletion in MEF2A, a gene encoding a transcription factor. Later we identified three novel mutations N263S, P279L, G283D in four other …
New Insights Into Molecular Mechanisms Of Fludarabine, Alina D. Bulgar
New Insights Into Molecular Mechanisms Of Fludarabine, Alina D. Bulgar
ETD Archive
Nucleotide analogs (e.g. fludarabine) are antimetabolites used in the treatment of a wide variety of hematological malignancies and solid tumors. Upon being metabolized to their active triphosphate form, these agents are incorporated into DNA. Among other molecular targets, their incorporation may lead to activation of base excision repair (BER) pathway. The molecular mechanism of BER recognition and repair of the incorporated fludarabine has not yet been elucidated. The main focus of this research was to study the involvement of BER pathway in the response to fludarabine induced DNA damage. Also, the possibility of enhancing antineoplastic activity of fludarabine by inhibition …
Factor Va Directs Catalysis By Factor Xa During Prothrombin Activation, Michael Anthony Bukys
Factor Va Directs Catalysis By Factor Xa During Prothrombin Activation, Michael Anthony Bukys
ETD Archive
Hemostasis occurs through the controlled activation and inactivation of clotting factors resulting in the arrest of bleeding without blockage to the vasculature, while thrombosis is the undesired formation of vascular blood clots, which adversely affects millions of people annually. Clotting factors circulate in blood as inactive zymogens, which are proteolytically activated in response to vascular injury, assembled into enzymatic complexes and in turn activate additional coagulation factors culminating in the production of thrombin from the enzymatic complex prothrombinase. The prothrombinase complex is composed of the activated enzymatic component factor Xa (fXa) complexed to the activated cofactor portion factor Va (fVa) …
Phylogeography Of Smallmouth Bass (Micropterus Dolomieu) And Comparative Myology Of The Black Bass (Micropterus, Centrarchidae), William Calvin Borden
Phylogeography Of Smallmouth Bass (Micropterus Dolomieu) And Comparative Myology Of The Black Bass (Micropterus, Centrarchidae), William Calvin Borden
ETD Archive
Biogeographic patterns were investigated within a single species and among its congenerics. Smallmouth bass (Micropterus dolomieu) were characterized by portions of the cytochrome b gene and the control region although bass in Lake Erie were also evaluated using eight nDNA microsatellites. Overall, little population structure was observed among sites in Lake Erie which was surprising given that most male smallmouth bass exhibit nest site fidelity. But, these lake bass were divergent from bass residing in nearby tributaries indicating that lacustrine bass are reproductively isolated from riverine bass even though both groups may spawn in the same rivers. Adjacent riverine populations …
Quadrupole Magnetic Field-Flow Fractionation;A Novel Technique For The Characterization Of Magnetic Particles, Francesca Carpino
Quadrupole Magnetic Field-Flow Fractionation;A Novel Technique For The Characterization Of Magnetic Particles, Francesca Carpino
ETD Archive
In the last few decades, the development and use of nanotechnology has become of increasing importance. Magnetic nanoparticles, because of their unique properties, have been employed in many different areas of application. They are generally made of a core of magnetic material coated with some other material to stabilize them and to help disperse them in suspension. The unique feature of magnetic nanoparticles is their response to a magnetic field. They are generally superparamagnetic, in which case they become magnetized only in a magnetic field and lose their magnetization when the field is removed. It is this feature that makes …
A Case In Kinase 2 Inhibitor Is A Potent Anti-Cancer Drug Candidate, Alieta Ciocea
A Case In Kinase 2 Inhibitor Is A Potent Anti-Cancer Drug Candidate, Alieta Ciocea
ETD Archive
Cancer is so widespread and lethal that it can be considered the biggest health problem of our century. Cancer drug development is a real challenge. Efforts outlined in this work were directed towards showing solid evidence that casein kinase 2 inhibitors can be used as a starting point for the development of potential cancer therapy. We first studied the effect of a specific CK2 inhibitor, DMAT, in a malignant megakaryoblastic leukemia cell line (MEG-01). Treated cells grew at a significantly lower rate than non-treated cells. Apoptosis was induced by DMAT in MEG-01 cells, dose and time dependent. When stimulated with …
Hydrogenase Inhibition By O2: Density Functional Theory/Molecular Mechanics Investigation, Daniela Dogaru
Hydrogenase Inhibition By O2: Density Functional Theory/Molecular Mechanics Investigation, Daniela Dogaru
ETD Archive
[Fe-Fe]-hydrogenases are enzymes that reversibly catalyze the reduction of protons to molecular hydrogen, which occurs in anaerobic media. In living systems, [Fe-Fe]-hydrogenases shift the reversible reaction towards H2 formation. The [Fe-Fe]-hydrogenase H-cluster is the active site, which contains two iron atoms (Fep-Fed, i.e., proximal and distal iron). Because most experimental and theoretical investigations confirm that the structure of di-iron air inhibited species is FepII-FedII-O-O-H-, O2 has to be prevented from binding to Fed in all di-iron subcluster oxidation states in order to retain a catalytically active enzyme. By understanding the catalytic processes of metalloenzymes, researches are enabled to produce an …
Technologies For Proteomic And Genomic Biomarker Analysis, Yiding Liu
Technologies For Proteomic And Genomic Biomarker Analysis, Yiding Liu
ETD Archive
In the first part of this dissertation, we systematically validated the application of molecular weight cut-off ultrafiltration in separation and enrichment of low-molecular-weight peptides from human serum. Under optimized conditions, both free-phase and bound LMW peptides could be separated and enriched. The method proved to be highly efficient and reproducible coupled with MALDI-TOF MS proteomic pattern analysis. Three marker peaks were found to be eligible for distinguishing normal and ovarian cancer samples. A novel organic solvent precipitation method coupled with enzymatic deglycosylation was also developed for biomarker detection from human serum. This method allowed us to generate reproducible free-phase peptide …
Development Of Oligonucleotide Microarray For High Throughput Dna Methylation Analysis, Xiaopeng Li
Development Of Oligonucleotide Microarray For High Throughput Dna Methylation Analysis, Xiaopeng Li
ETD Archive
DNA methylation is a key event regulating gene expression. DNA methylation analysis plays a pivotal role in unlocking association of epigenetic events with cancer. However, simultaneous evaluation of the methylation status of multiple genes is still a technical challenge. Microarray is a promising approach for high-throughput analysis of the methylation status at numerous CpG sites within multiple genes of interest. In this dissertation study, we conducted a systematic study to examine the use of microarray methods for methylation analysis. First, a robust universal microarray was established with more flexible in design and content, and potential cost saving over commercial arrays. …
Inhibition Of The Nf-Kb Signaling Pathway And Its Effects On Apoptosis And Cancer, Joseph A. Lupica
Inhibition Of The Nf-Kb Signaling Pathway And Its Effects On Apoptosis And Cancer, Joseph A. Lupica
ETD Archive
The Rel/NF-kB family of inducible transcription factors are evolutionarily conserved structurally and functionally, from insects to humans. They are ubiquitously expressed in a number of mature cell types, playing a pivotal role regulating cell growth, differentiation and apoptosis. Under normal circumstances, the proliferation of new cells is tightly regulated, as is the programmed lifespan of most cells, occasionally however cells loose their responsiveness to growth control mechanisms, resulting in a tumor or neoplasm. Sustained or chronic inflammation has been linked to a number of pathological conditions that destroy tissue and facilitate neoplastic growth. NF-kB in part mediates the opposing signals …
A Theoretical Study For The Reactivation Of O2 Inhibited [Fe-Fe]-Hydrogenase, Stefan Motiu
A Theoretical Study For The Reactivation Of O2 Inhibited [Fe-Fe]-Hydrogenase, Stefan Motiu
ETD Archive
The current investigation presents a reactivation pathway of the exogenously inhibited H-cluster (viz., by O2, or OH-, which metabolizes to H2O), for both vacuum and aqueous enzyme phase. The H-cluster is the catalytic site of [Fe-Fe]-hydrogenase, with the latter extracted from Desulfovibrio desulfuricans (Dd) bacteria. It consists of proximal iron, Fep, and distal Fed subunit, [Fep-Fed], which is bridged by di(thiomethyl)amine (DTMA) ligand, and a proximal cubane subunit, [Fe4-S4]2+p. [Fep-Fed] is coordinated by two cyanides (CN-), two terminal carbonyls (COt), and a bridging carbonyl (COb)*. An Fe atom from [Fe4-S4]2+p connects Fep through a cysteinyl sulfur (of Cys382). Density functional …
High Temperature Volatility And Oxidation Measurements Of Titanium And Silicon Containing Ceramic Materials, Quynhgiao N. Nguyen
High Temperature Volatility And Oxidation Measurements Of Titanium And Silicon Containing Ceramic Materials, Quynhgiao N. Nguyen
ETD Archive
Titanium (Ti) and silicon (Si) containing materials are of high interest to the aerospace industry due to its high temperature catability, strength, and ligh weight. A continuous exterior oxide layer is desirable to reduce the oxidation rate of these two materials. At high temperatures, water vapor plays a key role in the volatility of materials including oxide surfaces. This study first evaluated several hot-pressed Ti and Si-containing compositions at high temperatures as a function of oxidation environments to determine the volatile hydoxy! species using the transpiration method. The water content ranged from 0-76 mole and the oxygen content range was …
Modeling The Human Prothrombinase Complex Components, Tivadar Orban
Modeling The Human Prothrombinase Complex Components, Tivadar Orban
ETD Archive
Thrombin generation is the culminating stage of the blood coagulation process. Thrombin is obtained from prothrombin (the substrate) in a reaction catalyzed by the prothrombinase complex (the enzyme). The prothrombinase complex is composed of factor Xa (the enzyme), factor Va (the cofactor) associated in the presence of calcium ions on a negatively charged cell membrane. Factor Xa, alone, can activate prothrombin to thrombin however, the rate of conversion is not physiologically relevant for survival. Incorporation of factor Va into prothrombinase accelerates the rate of prothrombinase activity by 300,000-fold, and provides the physiological pathway of thrombin generation. The long-term goal of …
Mass Spectrometry-Based High Throughput Approach For Identification Of Molecular Modification Of Oxidative Process In Respiratory Diseases, Wei Song
ETD Archive
Eosinophil peroxidase (EPO) and myeloperoxidase (MPO) have been implicated in generating reactive species and promoting oxidative modifications in numerous diseases. The detection and identification of potential pathways has been proven extremely challenge due to evanescence nature of these reactive species. An alternative approach to study the involvement of oxidative modification is to detect and quantify the stable molecular fingerprints, like oxidized tyrosine species, in biological matrices. Previously reported analytical methods for quantifying oxidized amino acids have typically been limited by: low sensitivity, specificity and the failure of detection potential oxidation products generated during sample handling. Using GC/MS in combination with …
Synthesis And Characterization Of Acylphosphine Oxide Photoinitiators, Hany F. Sobhi
Synthesis And Characterization Of Acylphosphine Oxide Photoinitiators, Hany F. Sobhi
ETD Archive
Recently, polymerization science has assumed an increasing relevance in many applications, including orthopedic and dental biomaterials. Current technologies are based on the use of photochemically reactive systems, which are suited to absorb light to produce primary radical species capable of initiating polymerization. Acylphosphine oxides and acylphosphonates are known to be very effective photoinitiators for various unsaturated polymeric systems. The high reactivity observed was ascribed to the phosphinyl and phosphinoyl radicals generated. Because of the poor qualities of other initiators, we examined new routes to synthesize acylphosphine oxide initiators to achieve compatibility with aqueous media and improved performance. The preparation and …
Multiple Logs Analysis For Detecting Zero-Day Backdoor Trojans, Sinchai Caravut
Multiple Logs Analysis For Detecting Zero-Day Backdoor Trojans, Sinchai Caravut
ETD Archive
Trojan horses commonly known as "Trojans" are the computer threats that have been recently causing trouble on the internet because of their new propagation techniques. Social engineering has become a popular strategy to deceive people to run the attacker's malicious programs. Trojans use this technique to propagate themselves from a computer or a network to others, thus making them hard to prevent. The only way to keep computers and networks safe from them is by detecting them as soon as possible. Because of their quiet behavior, it's hard to detect by only IDS (Intrusion Detection System) log analysis therefore, multiple …
The Effect Of Wetland Size And Surrounding Land Use On Wetland Quality Along An Urbanization Gradient In The Rocky River Watershed, Marilyn S. Gunsch
The Effect Of Wetland Size And Surrounding Land Use On Wetland Quality Along An Urbanization Gradient In The Rocky River Watershed, Marilyn S. Gunsch
ETD Archive
An intensive floristic evaluation of 17 Cleveland Metroparks (CMP) wetlands in the Rocky River Watershed (RRW) was undertaken to determine whether wetland size or anthropogenic disturbance in the surrounding landscape is a better predictor of wetland quality in this protected parkland. Wetland study sites were selected in three reservations, Hinckley, Mill Stream Run, and Rocky River. My research adds valuable information to the CMP wetland database and will contribute to its wetland management policies. Wetland quality was determined using the following floristic indices: species richness, non-native species, wetland species, mean coefficient of conservatism (C of C), floristic quality assessment index …
A Diatom Phosphorus Inference Model For 30 Freshwater Lakes In Ne Ohio And Nw Pennsylvania, Kyle C. Scotese
A Diatom Phosphorus Inference Model For 30 Freshwater Lakes In Ne Ohio And Nw Pennsylvania, Kyle C. Scotese
ETD Archive
Nutrient enrichment in the form of anthropogenic phosphorous and nitrogen inputs has occurred in lakes worldwide. In the absence of historical water chemistry data, the extent to which this disturbance has impacted lakes in the Erie/Ontario drift and lake plain and Western Allegheny Plateau ecoregions remains to be determined. The objective of this study was to develop a diatom calibration set through analysis of surface sediments and water chemistry from 30 lakes spanning a phosphorous and nitrogen gradient in the glaciated regions of northeast Ohio and northwest Pennsylvania with an additional lake in New York. No current training set exists …
Study Of 3'-Untranslated Region Of Inducible Nitric Oxide Synthase And Identification Of Other Targets Of Gaitpathway, Sirisha Vadlamani
Study Of 3'-Untranslated Region Of Inducible Nitric Oxide Synthase And Identification Of Other Targets Of Gaitpathway, Sirisha Vadlamani
ETD Archive
Macrophages and other leukocytes play a vital role during inflammation. IFN-Îđ which is secreted by Th1 cells activates monocyte-macrophages and this activation leads to induction as well as suppression of certain genes expressed during inflammation. This suppression of genes may be potentially vital for resolution of inflammation. Upon IFN-Îđ stimulation, a Gamma-activated inhibitor of translation complex (GAIT) is formed, which binds to 3'-UTR of target mRNAs thereby silencing their translation. VEGF-A and ceruloplasmin are two proteins whose translation is suppressed by this pathway. The GAIT complex proteins have been identified as ribosomal protein L13a, glutamyl-prolyl tRNA synthatase (EPRS), NS-1 associated …