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Articles 61 - 90 of 101
Full-Text Articles in Physical Sciences and Mathematics
Thermal Analysis As An Important Research Tool For Colleges And Universities, Jeffrey Allen Fruscella
Thermal Analysis As An Important Research Tool For Colleges And Universities, Jeffrey Allen Fruscella
ETD Archive
Three experiments were performed to demonstrate that thermal analysis is an important tool for use in colleges and universities for conducting scientific research. The first experiment used thermogravimetry, differential scanning calorimetry and thermal mechanical analysis to compare polymer resins from two ResinKits®, one from 1994 and the other from 2010. Analysis was done to determine if resins from the 1994 kit were viable standards. The experiments showed significant thermal differences between select resins and it was concluded that resins form the 1994 ResinKit® are no longer acceptable as standards.The second experiment used thermogravimetry and differential scanning calorimetry to determine the …
Factors Affecting Heme Transfer From "Gapdh": A Possible Heme Carrier Protein, Rajesh Vempati
Factors Affecting Heme Transfer From "Gapdh": A Possible Heme Carrier Protein, Rajesh Vempati
ETD Archive
The aim of my research is to understand the mechanism of heme transfer by carrier proteins into heme proteins. The mechanism of heme insertion into proteins is poorly understood. Previous experiments reported from our lab identified GAPDH as a possible heme carrier protein involved in heme transfer (Ritu Chakravarti et al PNAS). This work focuses on 2 aspects of heme transfer. a.) Rate of transfer of heme from GAPDH to apomyoglobin. We examined the rate of transfer of native proto-heme and the analogue meso-heme. The results showed that the rate of heme transfer was twice as fast for meso-heme compared …
Novel Thermal Analytical Techniques To Characterize Drugs And Drug Delivery, Lakshmi Swetha Kaza
Novel Thermal Analytical Techniques To Characterize Drugs And Drug Delivery, Lakshmi Swetha Kaza
ETD Archive
This thesis encompasses three significant projects. The study includes the characterization and evaluation of the properties of a commercial contraceptive transdermal patch, Ortho Evra® by Dielectric Analysis and Differential Scanning Calorimetry (DSC). This study helps in monitoring the mobility of the drug and transport properties by Isothermal and Scanning Dielectric Analysis as a function of temperature and frequency. The drugs in this product are norelgestromin and ethinyl estradiol. DSC was used to detect any crystalline character of the drugs by their fusion properties. Having no melting endotherm and detecting a glass transition temperature suggested that the drugs in the patches …
Introduction To Pharmaceutical Thermal Analysis: A Teaching Tool, Shravan Singh Thakur
Introduction To Pharmaceutical Thermal Analysis: A Teaching Tool, Shravan Singh Thakur
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Significant Thermal Analysis-physical chemical data needs to be acquired by the new analyst whether an entry level chemist or a new function for the experienced pharmaceutical scientist. This teaching tool describes the introductory use of Differential Scanning Calorimetry (DSC), Thermogravimetric Analysis (TGA) and Thermomechanical Analysis (TMA) for characterizing pharmaceuticals. Optimum Experimental conditions for DSC, TGA and TMA will focus on collecting the best results and interpretations. Does the sample contain volatiles? Evaporation creates endothermic peaks, 2 water or solvent can lower the glass transition temperature (Tg) by up to 100°C and affect the crystallization temperature on cooling. The decomposition temperature …
Design, Synthesis And Characterization Of Oriented Glyco-Affinity Macroligands For Glyco-Capturing, Glycomics And Glycoproteomics Applications, Srinivas Chalagalla
Design, Synthesis And Characterization Of Oriented Glyco-Affinity Macroligands For Glyco-Capturing, Glycomics And Glycoproteomics Applications, Srinivas Chalagalla
ETD Archive
Cell surface carbohydrates existing as parts of glycoproteins, glycolipids, and other conjugates present the first information about cell to the outside world and are intimately involved in various biological events such as intercellular communication, and molecular and cellular targeting. However, mechanisms of most processes at the molecular level are still unclear. Therefore, it is very important to develop carbohydrate-specific binding molecules for rapid, efficient, sensitive purification and accurate analysis of complex carbohydrate structures as well as their functions. Furthermore, carbohydrate-specific binding molecules can be expected to be used in medical diagnostic applications for carbohydrate biomarkers. In this thesis study, oriented …
Dna Mutation/Methylation Screening Method For Colon Cancer Screening, Wei Meng
Dna Mutation/Methylation Screening Method For Colon Cancer Screening, Wei Meng
ETD Archive
Cancer is a result of unregulated cell growth. For all types of cancer currently studied, the transition from a healthy cell to a malignant tumor cell is a step-by-step process which requires mutation in at least several oncogenes and tumor suppressor genes together. Another cancer early event is DNA methylation. Cancer-related DNA methylation focuses on promoter hypermethylation of the certain genes. The DNA mutation and methylation profile can serve as biomarkers for diagnosing early stage of cancer. Colorectal cancer is the third most common cancer type in the United States and has been well studied. The essential mechanism of cancer …
Molecular Basis Of The Role Of Kindlin 2 In Cell Adhesion, Hettiarachchige Dhanuja Deepamalee Perera
Molecular Basis Of The Role Of Kindlin 2 In Cell Adhesion, Hettiarachchige Dhanuja Deepamalee Perera
ETD Archive
Kindlins are a novel family of cytoskeleton proteins that plays an important role in the activation of heterodimeric integrin transmembrane receptors. These receptors play a vital role in cell adhesion, cell migration and other cellular processes. The Kindlin protein family consists of three homologous proteins, Kindlin 1, 2 and 3 with differential tissue distribution and varying expression levels in human. Mutations of Kindlin 1 protein are clinically linked to Kindler Syndrome. Kindlin 2 knockdown studies have shown embryonic lethality in mouse, but no diseases have been clinically testified. Kindlin 3 mutations are associated with bleeding disorders, e.g. LADIII. Talin is …
Human Prostate Cancer Cell Apoptosis Induced By Interferon-Y And Double-Stranded Rna And Studies On The Biological Roles Of Transmembrane And Coiled-Coil Domains 1, Haiyan Tan
ETD Archive
No abstract provided.
Study Of Drug Delivery Behavior Through Biomembranes Using Thermal And Bioanalytical Techniques, Hareesha Reddy Venumuddala
Study Of Drug Delivery Behavior Through Biomembranes Using Thermal And Bioanalytical Techniques, Hareesha Reddy Venumuddala
ETD Archive
This Master of Science thesis encompasses two projects in chemical pharmaceuticals. The first is a study of excipients and the added new information collected beyond Thermal Gravimetric Analysis and Differential Scanning Calorimetry from Dielectric Analysis. These new properties enhance our global knowledge of excipients by thermal analytical methods. Excipients, the inactive ingredients in formulated drugs, aid different functions of the active pharmacy ingredient, the drugs. Low temperature transitions, by DEA including melting of frozen solvents, e.g. water, are more definitive than observed by low temperature DSC. Millions of dollars are expended annually on pharmaceutical testing to qualify excipients for fully …
Disintegration Of Tablets And Capsules Measured By Isothermal Thermal Mechanical Analysis And Macrophotography, Visweswararao Badipatla
Disintegration Of Tablets And Capsules Measured By Isothermal Thermal Mechanical Analysis And Macrophotography, Visweswararao Badipatla
ETD Archive
The current United States Pharmacopoeia (USP) test for tablet and encapsulated drug disintegration does not specify the initial disintegration time and provides limited information on the disintegration process itself. An isothermal Thermal Mechanical Analysis (IsoTMA) method is presented to measure the rate and initial time of drug disintegration, that is, the mechanical collapse of the gelatin capsule or the solid tablet. This method monitors changes in the dimensions of the formulated drugs during their disintegration in a liquid. Dimensional changes can be followed as a function of time, temperature, applied stress and pH. Some of the drugs studied were Olanzapine®, …
Nos-Based Biopolymers: Towards Novel Thromboresistant No-Release Materials, Charbel Abou Diwan
Nos-Based Biopolymers: Towards Novel Thromboresistant No-Release Materials, Charbel Abou Diwan
ETD Archive
Nitric Oxide releasing biopolymers have the potential to prolong vascular graft and stent potency without adverse systemic vasodilation. It was reported in literature that eNOS-overexpressing endothelial cell seeding of synthetic small diameter vascular grafts decreased human platelet aggregation by 46 and bovine aortic smooth muscle cell proliferation by 67.2 in vitro. We hypothesized that incorporating the enzyme nitric oxide synthase (NOS) in biocompatible polymeric matrix will provide a source of NO that utilizes endogenous compounds to maintain an unlimited supply of NO. To test this hypothesis, we have incorporated the enzyme nitric oxide synthase into a polyethyleneimine film using a …
Cofactor Control Of A Vital Enzymatic Reaction;The Effect Of Factor Va On Thrombin Formation During Blood Coagulation, Jamila Hirbawi
Cofactor Control Of A Vital Enzymatic Reaction;The Effect Of Factor Va On Thrombin Formation During Blood Coagulation, Jamila Hirbawi
ETD Archive
The LONG-TERM goal of our research is to study and analyze the structure and function of the factor V molecule in order to understand its regulatory effects on the natural process of hemostasis and its role in the life-threatening development of deep venous thrombosis. The SHORT-TERM goal of our research is to identify the amino acid residue(s) of factor V that interact with prothrombin during the assembly and function of the prothrombinase complex in order to fully understand its particular role in maintaining the integrity of the blood coagulation cascade. The final goal of the coagulation cascade is the formation …
Hemoprotein-Mediated Activation Of Nitroalkanes, Ling Li
Hemoprotein-Mediated Activation Of Nitroalkanes, Ling Li
ETD Archive
Chemicals and drugs are known to be metabolized mostly by Cytochrome P450 xenobiotic metabolizing enzymes. However, the detailed mechanism of nitro-compounds metabolism is still unclear. The activation of nitro-xenobiotics by heme-P450 enzymes is a potential explanation for the origin of nitro-compound carcinogenesis. Investigating the interaction of simple nitro-compounds with redox activity of heme enzymes is therefore critical to explore the mechanism and products of activation. In this study, multiple analytical methods and instrumentations are employed and graphic and simulation software such as Origin┬« and Digisim┬« are utilized to quantitatively derive parameters from experimental raw data. This study shows that myoglobin, …
Structural Investigation Of The Complex Of Filamin A Repeat 21 With Integrin Αiib And Β3 Cytoplasmic Tails – A Potential “Transmission” To Regulate Cell Migration, Jianmin Liu
ETD Archive
Cell functions in multi-cellular organisms are strongly depend on the dynamic cooperation between cell adhesion and cytoskeleton reorganization. Integrins, the major cell adhesion receptors, bind to extracellular matrix (ECM) and soluble ligands on the cell surface and link to the actin cytoskeleton inside the cell membrane. In this manner, integrins integrate cell adhesion and cytoskeleton reorganization by acting as a mechanical force transducer and a biochemical signaling hub (Zamir and Geiger 2001). Consequently, integrins are vital for development, immune responses, leukocyte traffic and hemostasis, and a variety of other cellular and physiological processes. Integrins are also are the focal point …
Hemeproteins Bathed In Ionic Liquids;Examining The Role Of Water And Protons In Redox Behavior And Catalytic Function, John Joseph Moran
Hemeproteins Bathed In Ionic Liquids;Examining The Role Of Water And Protons In Redox Behavior And Catalytic Function, John Joseph Moran
ETD Archive
We investigate the changing behaviors of myoglobin and nitric oxide synthase (NOS) in the near-absence of bulk water and/or protons by using ionic liquid butyl methyl imidazolium tetrafluoroborate as a non-aqueous milieu. Through direct charge transfer and metalloprotein-mediated catalytic reduction of oxygen and nitric oxide, we shed light on diverging aspects on how the two hemeproteins face the scarcity of water and/or protons in bulk. Isotopic effect investigations using D2O further elucidates kinetic aspects of proton transfer. Finally, in the case of NOS oxygenase, pterin cofactor binding and NOS-mediated catalytic oxidation of L-arginine in ionic liquids interrogates proton and water …
Development Of Quantitative Bioanalytical Methods For The Measurement Of Pharmaceutical Compounds Via Hplc-Uv And Hplc-Ms/Ms, Melissa A. Mcculloch
Development Of Quantitative Bioanalytical Methods For The Measurement Of Pharmaceutical Compounds Via Hplc-Uv And Hplc-Ms/Ms, Melissa A. Mcculloch
ETD Archive
Research in pharmaceutical treatments for illnesses and disease processes has rapidly grown in the past decade. The field is fueled by advances in our understanding of the molecular mechanics of the human body, coupled with the development of sophisticated scientific instruments which can efficiently generate massive amounts of important data. This has led to an ever-growing need for the development of quantitative bioanalytical methods to measure pharmaceutical compounds. In this work, the theory behind the analytical processes and instruments that make these investigations possible is discussed. Further, the development of two high performance liquid chromatographic (HPLC) methods with both ultra …
Fabricating New Miniaturized Biosensors For The Detection Of Dna Damage And Dna Mismatches, N. Indika Perera
Fabricating New Miniaturized Biosensors For The Detection Of Dna Damage And Dna Mismatches, N. Indika Perera
ETD Archive
A large number of genetic diseases and genetic disorders are simply caused by base alterations in the genome. Therefore, developing efficient and cost effective techniques for routine detection of these alterations is of great importance. Different methods involving gel electrophoresis and Polymerase Chain Reaction have been widely employed, but majority of these methods are costly, time consuming, and lack throughput, creating a fundamental gap between the current state-of-the-art and desired characteristics of low-cost, high-speed, simplicity, versatility, and potential for miniaturization. In this study, we attempt to bridge this gap by developing new sensing platforms to detect DNA base mismatches and …
New Generation Of Electrochemical Sensors For Nitric Oxide;Ruthenium/Carbon-Based Nanostructures And Colloids As Electrocatalytic Platforms, W. Pubudu M. Peiris
New Generation Of Electrochemical Sensors For Nitric Oxide;Ruthenium/Carbon-Based Nanostructures And Colloids As Electrocatalytic Platforms, W. Pubudu M. Peiris
ETD Archive
Nitric oxide (NO) is an important intercellular messenger that acts in many tissues to regulate a diverse range of physiological and pathological processes. The physiologically implications of NO function are far from being completely understood. The multifaceted reactivity of NO prompted the need for accurate determination of the concentration of this molecule. However, it is difficult to detect nitric oxide, particularly in biological media and near live cells due to its short half-life, a result of its reactivity and the low levels of NO produced in vivo. As a result, the accurate and reliable detection of NO under varying experimental …
Nitric Oxide Synthase In Confined Environments;Detection And Quantification Of Nitric Oxide Released From Cells And Modified Liposomes Using A Sensitive Metal Catalyst-Pedot Modified Carbon Fiber Electrode, P. A. Reshani H. Perera
Nitric Oxide Synthase In Confined Environments;Detection And Quantification Of Nitric Oxide Released From Cells And Modified Liposomes Using A Sensitive Metal Catalyst-Pedot Modified Carbon Fiber Electrode, P. A. Reshani H. Perera
ETD Archive
Nitric oxide (NO) is a freely diffusible, gaseous free radical, associated with many physiological and pathological processes that include neuronal signaling, immune response, and inflammatory response. NO is produced from L-arginine in an NADPH-dependent reaction catalyzed by a family of nitric oxide synthase (NOS) enzymes. A deficiency in NO plays a role in hypertension, hyperglycaemia, and arteriosclerosis, among other pathological states. Conversely, increased NO levels contribute to arthritis, septic shock, and hypotention. Therefore, measuring and quantifying NO production in biological systems and matrices may be vital in elucidating physiological and pathological processes. The goal of this work is to develop …
Development Of A Novel Gradient Chromatofocusing Tandem Mass Spectometry Technique For The Determination Of Cationic Compounds In Biofluids;Identification Of Caspace 3 Cleavage Sites Of Nhe-1 By High Performance Liquid Chromatography- Mass Spectrometry, Jianhua Tang
ETD Archive
In Part I, work was done to develop a novel gradient chromatofocusing liquid chromatography-tandem mass spectrometry (MS/MS) technique for the determination of ionic compounds in biological matrix. The analysis of ionic compounds poses a great challenge to current LC-MS techniques, due to the fact that there is little or no retention. These ionic compounds are eluted at almost the same time as biological matrix, which is normally directed to waste prior to connecting to the mass spectrometer. A review of current LC-MS techniques for ionic compounds is given in Chapter 1. They all have advantages and disadvantages. To retain and …
Plasma Biomarkers For Age-Related Macular Degeneration, Jiaqian Ni
Plasma Biomarkers For Age-Related Macular Degeneration, Jiaqian Ni
ETD Archive
No abstract provided.
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) …
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. …