Open Access. Powered by Scholars. Published by Universities.®

Physical Sciences and Mathematics Commons™

Open Access. Powered by Scholars. Published by Universities.®

Chemistry

ETD Archive

Theses/Dissertations

2008

Articles 1 - 16 of 16

Full-Text Articles in Physical Sciences and Mathematics

Mass Spectrometric Analysis Of Environmental Contaminants, Protein Structure And Expression, Ian E. Atkinson Jan 2008

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, …

Go to article

Role Of Transcription Factor Mef2a In Development Of Coronary Artery Disease (Cad) And Myocardial Infarction (Mi), Maniragava Sai Bhagavatula Jan 2008

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 …

Go to article

New Insights Into Molecular Mechanisms Of Fludarabine, Alina D. Bulgar Jan 2008

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 …

Go to article

Factor Va Directs Catalysis By Factor Xa During Prothrombin Activation, Michael Anthony Bukys Jan 2008

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) …

Go to article

Quadrupole Magnetic Field-Flow Fractionation;A Novel Technique For The Characterization Of Magnetic Particles, Francesca Carpino Jan 2008

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 …

Go to article

A Case In Kinase 2 Inhibitor Is A Potent Anti-Cancer Drug Candidate, Alieta Ciocea Jan 2008

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 …

Go to article

Hydrogenase Inhibition By O2: Density Functional Theory/Molecular Mechanics Investigation, Daniela Dogaru Jan 2008

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 …

Go to article

Technologies For Proteomic And Genomic Biomarker Analysis, Yiding Liu Jan 2008

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 …

Go to article

Development Of Oligonucleotide Microarray For High Throughput Dna Methylation Analysis, Xiaopeng Li Jan 2008

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. …

Go to article

Inhibition Of The Nf-Kb Signaling Pathway And Its Effects On Apoptosis And Cancer, Joseph A. Lupica Jan 2008

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 …

Go to article

A Theoretical Study For The Reactivation Of O2 Inhibited [Fe-Fe]-Hydrogenase, Stefan Motiu Jan 2008

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 …

Go to article

High Temperature Volatility And Oxidation Measurements Of Titanium And Silicon Containing Ceramic Materials, Quynhgiao N. Nguyen Jan 2008

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 …

Go to article

Modeling The Human Prothrombinase Complex Components, Tivadar Orban Jan 2008

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 …

Go to article

Mass Spectrometry-Based High Throughput Approach For Identification Of Molecular Modification Of Oxidative Process In Respiratory Diseases, Wei Song Jan 2008

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 …

Go to article

Synthesis And Characterization Of Acylphosphine Oxide Photoinitiators, Hany F. Sobhi Jan 2008

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 …

Go to article

Study Of 3'-Untranslated Region Of Inducible Nitric Oxide Synthase And Identification Of Other Targets Of Gaitpathway, Sirisha Vadlamani Jan 2008

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 …

Go to article