Digital Commons Network^™

Incorporation Of The Actin-Myosin Biomolecular Motor System Into A Microfluidic Device, Rebecca Marie Ragland

Theses, Dissertations and Capstones

Recently, the field of bionanotechnology has sought to develop a device containing a biomolecular motor nano-cargo transport system. Among many applications, a device of this sort could be used to sort, purify, or detect specific molecules. In this work, an attempt was made to incorporate the actin-myosin biomolecular motor system into a microfluidic device constructed out of polydimethylsiloxane (PDMS) and glass. Methods for cleaning and functionalizing the glass surface of the device were optimized. After performing actin-myosin motility assays in a variety of PDMS/glass devices, it was determined that the oxygen permeability of PDMS limited the quality of motility that …

Monitoring The Health Of Glen Helen Nature Preserve: Spring 2012 Sediment And Water, Audrey E. Mcgowin Ph.D., Triet Minh Truong, David Kammler Ph.D., Joe Solch

Chemistry Student Publications

This poster presents the results for environmental testing in Glen Helen by the Special Topics in Analytical Chemistry course at Wright State University under the direction of Professor Audrey McGowin in Spring 2012. Water quality data are presented for the Yellow Spring in Yellow Springs, Ohio for April and May of 2012. Other test sites range from locations along Yellow Springs Creek to the covered bridge near Little Miami River.

This poster was created by Triet M. Truong.

Detailed Comparison Of The Pnicogen Bond With Chalcogen, Halogen And Hydrogen Bonds, Steve Scheiner

Chemistry and Biochemistry Faculty Publications

The characteristics of the pnicogen bond are explored using a variety of quantum chemical techniques. In particular, this interaction is compared with its halogen and chalcogen bond cousins, as well as with the more common H-bond. In general, these bonds are all of comparable strength. More specifically, they are strengthened by the presence of an electronegative substituent on the electron-acceptor atom, and each gains strength as one moves down the appropriate column of the periodic table, for example, from N to P to As. These noncovalent bonds owe their stability to a mixture in nearly equal parts of electrostatic attraction …

Transmetallation Of A Lithium Porphyrin With Iron(Ii), Kidus Debesai

The Corinthian

Synthesis and characterization of the iron(III) derivative of the 2,3,7,8,12,13,17,18-octabromo-meso-tetrakis(N-methylpyridium-4-yl)porphyrin was accomplished via metal metathesis of the lithium porphyrin and iron(II) ion. Preliminary molecular orbital analysis of the iron(II) and iron(III) derivatives demonstrate that the iron(III) porphyrin exists at a lower energy state.

First Steps In Growth Of A Polypeptide Toward Β-Sheet Structure, U. Adhikari, Steve Scheiner

Chemistry and Biochemistry Faculty Publications

The full conformational energy surface is examined for a molecule in which a dipeptide is attached to the same spacer group as another peptide chain, so as to model the seminal steps of β-sheet formation. This surface is compared with the geometrical preferences of the isolated dipeptide to extract the perturbations induced by interactions with the second peptide strand. These interpeptide interactions remove any tendency of the dipeptide to form a C5 ring structure, one of its two normally stable geometries. A C7 structure, the preferred conformation of the isolated dipeptide, remains as the global minimum in the full molecule. …

Extrapolation To The Complete Basis Set Limit For Binding Energies Of Noncovalent Interactions, Steve Scheiner

Chemistry and Biochemistry Faculty Publications

A means of extrapolating from double and triple-valence basis sets to a complete basis set is examined in the context of the pnicogen bonds in the BH2P⋯NH3 complexes, with B = CH3, H, NH2, CF3, OH, Cl, F, and NO2. Binding energies converge smoothly, and the trends for the various substituents B are unaffected by the basis set size, extrapolation, or level of inclusion of electron correlation, including MP2 and CCSD(T). The approach appears to be successful also for H-bonded systems, in particular the water dimer. In the event that full extrapolation within the context of CCSD(T) is not feasible, …

Plasma Spectroscopic Techniques Applied To Biological And Environmental Matrices, Morgan Steele Schmidt

Electronic Theses and Dissertations

The purpose of this research was to apply the use of direct ablation plasma spectroscopic techniques, including spark-induced breakdown spectroscopy (SIBS) and laser-induced breakdown spectroscopy (LIBS), to a variety of environmental matrices. These were applied to two different analytical problems. SIBS instrumentation was adapted in order to develop a fieldable monitor for the measurement of carbon in soil. SIBS spectra in the 200 nm to 400 nm region of several soils were collected, and the neutral carbon line (247.85 nm) was compared to total carbon concentration determined by standard dry combustion analysis. Additionally, Fe and Si were evaluated in a …

Sensitivity Of Noncovalent Bonds To Intermolecular Separation: Hydrogen, Halogen, Chalcogen, And Pnicogen Bonds, Steve Scheiner

Chemistry and Biochemistry Faculty Publications

It is well known that noncovalent bonds are weakened when stretched from their equilibrium intermolecular separation. Quantum chemical calculations are used to examine and compare the sensitivity to stretches of hydrogen, halogen, chalcogen, and pnicogen bonds. NH3 was taken as the universal electron donor, paired with HOH and FH in H-bonds, as well as with FPH2, FSH, and FCl. Even though the binding energies span a wide range, stretching the intermolecular separation by 1 Å cuts this quantity by the same proportion, roughly in half, for each system. Taking the sum of van der Waals radii as an arbitrary cutoff, …

Silica As A Matrix For Encapsulating Proteins:Surface Effects On Protein Structure Assessed By Circular Dichroism Spectroscopy, Daryl K. Eggers, P. J. Calabretta, M. C. Chancellor, C. Torres, G. R. Abel Jr., C. Neihaus, N. J. Birtwhistle, N. M. Khouderchah, G. H. Zemede

Faculty Publications, Chemistry

The encapsulation of biomolecules in solid materials that retain the native properties of the molecule is a desired feature for the development of biosensors and biocatalysts. In the current study, protein entrapment in silica-based materials is explored using the sol-gel technique. This work surveys the effects of silica confinement on the structure of several model polypeptides, including apomyoglobin, copper-zinc superoxide dismutase, polyglutamine, polylysine, and type I antifreeze protein. Changes in the secondary structure of each protein following encapsulation are monitored by circular dichroism spectroscopy. In many cases, silica confinement reduces the fraction of properly-folded protein relative to solution, but addition …

Redox Proteomics In Selected Neurodegenerative Disorders: From Its Infancy To Future Applications, Allan Butterfield, Marzia Perluigi, Tanea Reed, Tasneem Muharib, Christopher P. Hughes, Rena A.S. Robinson, Rukhsana Sultana

Chemistry Faculty and Staff Scholarship

Several studies demonstrated that oxidative damage is a characteristic feature of many neurodegenerative diseases. The accumulation of oxidatively modified proteins may disrupt cellular functions by affecting protein expression, protein turnover, cell signaling, and induction of apoptosis and necrosis, suggesting that protein oxidation could have both physiological and pathological significance. For nearly two decades, our laboratory focused particular attention on studying oxidative damage of proteins and how their chemical modifications induced by reactive oxygen species/reactive nitrogen species correlate with pathology, biochemical alterations, and clinical presentations of Alzheimer's disease. This comprehensive article outlines basic knowledge of oxidative modification of proteins and lipids, …

Dynamic Light Scattering And Microelectrophoresis: Main Prospects And Limitations, Vuk Uskoković

Pharmacy Faculty Articles and Research

Microelectrophoresis based on the dynamic light scattering (DLS) effect has been a major tool for assessing and controlling the conditions for stability of colloidal systems. However, both the DLS methods for characterization of the hydrodynamic size of dispersed submicron particles and the theory behind the electrokinetic phenomena are associated with fundamental and practical approximations that limit their sensitivity and information output. Some of these fundamental limitations, including the spherical approximation of DLS measurements and an inability of microelectrophoretic analyses of colloidal systems to detect discrete charges and differ between differently charged particle surfaces due to rotational diffusion and particle orientation …

Preferred Configurations Of Peptide-Peptide Interactions, U. Adhikari, Steve Scheiner

Chemistry and Biochemistry Faculty Publications

The natural and fundamental proclivities of interaction between a pair of peptide units are examined using high-level ab initio calculations. The NH···O H-bonded structure is found to be the most stable configuration of the N-methylacetamide (NMA) model dimer, but only slightly more so than a stacked arrangement. The H-bonded geometry is destabilized by only a small amount if the NH group is lifted out of the plane of the proton-accepting amide. This out-of-plane motion is facilitated by a stabilizing charge transfer from the CO π bond to the NH σ* antibonding orbital. The parallel and antiparallel stacked dimers are nearly …

Evaluation Of Dft Methods To Study Reactions Of Benzene With Oh Radical, Steve Scheiner

Chemistry and Biochemistry Faculty Publications

Several density functional theory” (DFT) methods are applied to two different reaction channels involving OH• + C6H6, and the results compared with high-level ab initio calculations. The OH• adds directly to one C atom in the first channel, first forming an encounter complex with the OH• poised above the aromatic plane. B3LYP, BH&HLYP, and MPW1K compute an accurate estimate of the overall exothermicity, whereas M05-2X, PBE0, and PBEPBE overestimate this quantity to some degree. With the exceptions of PBEPBE and PBE0, the other methods produce an acceptable barrier to addition. All approaches except BH&HLYP correctly predict an exothermic H• abstraction, …

Structural Polymorphism In Tau Filaments: An Implication For Neurodegenerative Diseases, Ayisha Siddiqua

Electronic Theses and Dissertations

Tau filaments are the pathological hallmark of >20 neurodegenerative diseases including Alzheimer's disease, Pick's disease, and progressive supranuclear palsy. In the adult human brain, six isoforms of tau are expressed that differ by presence or absence of the second of the four semiconserved repeats. As a consequence, half of the tau isoforms have three repeats (3R tau), whereas the other half has four repeats (4R tau).

Site-directed spin labeling of recombinant tau in conjunction with electron paramagnetic resonance spectroscopy was used to obtain structural insights into tau filaments. The studies showed that the filaments of 4R tau and 3R tau …

Β-Casein–Phospholipid Monolayers As Model Systems To Understand Lipid–Protein Interactions In The Milk Fat Globule Membrane, Sophie Gallier, Derek E. Gragson, Rafael Jiménez-Flores, David W. Everett

Chemistry and Biochemistry

Phospholipid–protein monolayer films were studied as model systems to mimic the structure of the native bovine milk fat globule membrane (MFGM) and to understand lipid–protein interactions at the surface of the globule. Phospholipids extracted from bovine raw milk, raw cream, processed milk and buttermilk powder were spread onto the air–water interface of a Langmuir trough, β-casein was then added to the sub-phase, and Langmuir–Blodgett films were studied by epifluorescence microscopy and atomic force microscopy. In all films, β-casein was responsible for clustering of the sphingomyelin- and cholesterol-rich microdomains into larger platforms. This suggests that the same phenomenon may happen at …

Kinetic Models Of The Prebiotic Replication Of Dsrna Under Thermal Cycling Conditions, Pauline Schwartz, Dante M. Lepore, Carl Barratt

Chemistry and Chemical Engineering Faculty Publications

We present computational models for the replication of double stranded RNA (dsRNA) or related macromolecules under thermal cycling conditions that would reflect prebiotic (i.e. non-enzymatic) environments. Two models of the replication of dsRNA are represented as multi-step chemical systems. The objective of this investigation was to better understand the kinetic features of such chemical systems. It is shown that thermal cycling in a chemical system is advantageous (relative to a fixed temperature) if there are two competing reactions, one favored at high temperature and one favored at low temperature. For the prebiotic replication of dsRNA, a high temperature favors formation …

Contributions Of Various Noncovalent Bonds To The Interaction Between An Amide And S-Containing Molecules, U. Adhikari, Steve Scheiner

Chemistry and Biochemistry Faculty Publications

N-Methylacetamide, a model of the peptide unit in proteins, is allowed to interact with CH3SH, CH3SCH3, and CH3SSCH3 as models of S-containing amino acid residues. All of the minima are located on the ab initio potential energy surface of each heterodimer. Analysis of the forces holding each complex together identifies a variety of different attractive forces, including SH⋅⋅⋅O, NH⋅⋅⋅S, CH⋅⋅⋅O, CH⋅⋅⋅S, SH⋅⋅⋅π, and CH⋅⋅⋅π H-bonds. Other contributing noncovalent bonds involve charge transfer into σ* and π* antibonds. Whereas some of the H-bonds are strong enough that they represent the sole attractive force in several dimers, albeit not usually in the …

Structure And Reversible Pyran Formation In Molybdenum Pyranopterin Dithiolene Models Of The Molybdenum Cofactor, Benjamin R. Williams, Yichun Fu, Glen P. A. Yap, Sharon J. Nieter Burgmayer

Chemistry Faculty Research and Scholarship

The syntheses and X-ray structures of two molybdenum pyranopterin dithiolene complexes in biologically relevant Mo(+4) and Mo(+5) states are reported. Crystallography reveals these complexes possess a pyran ring formed through a spontaneous cyclization reaction of a dithiolene side-chain hydroxyl group at a C=N bond of the pterin. NMR data on the Mo(+4) complex suggests a reversible pyran ring cyclization occurs in solution. These results provide experimental evidence that the pyranopterin dithiolene ligand in molybdenum and tungsten enzymes could participate in catalysis through dynamic processes modulated by the protein.

Linus Pauling: Scientist Of The 20th Century, Laura Ward

Natural Sciences Student Research Presentations

This poster describes the contributions scientist Linus Pauling made to the fields of chemistry and molecular biology, including his hybridization theory.

Development Of An Electrospary Ionization Source And Vacuum Interface For Guided Ion Beam Tandem Mass Spectrometry Experiments: Structural And Energetic Effects In The Molecular Recognition Of Amino Acids By 18-Crown-6, Yu Chen

Wayne State University Dissertations

Absolute 18-crown-6 (18C6) binding affinities of the side chains of AAs in peptides and proteins were determined in a step by step fashion using guided ion beam tandem mass spectrometry techniques. Firstly, 18C6 binding affinities of several peptidomimetic bases (B) that serve as mimics of the side chains of Lys, Arg, and His and n-terminal amino group have been examined to provide initial estimates of the 18C6 binding affinities of the side chains of AAs. The Bs were extended to natural occurring AAs and further extended to acetylated AAs (AcAA) to determine the binding affinities of the side chains of …

Design And Synthesis Of Antithrombotic Liposomal Protein Conjugate, Hailong Zhang

ETD Archive

Recent advances in the molecular bases of haemostasis have highlighted that endothelial thrombomodulin (TM) plays a critical role in local haemostasis by binding thrombin and subsequently converting protein C to its active form (APC). In addition, the binding of thrombin to TM drastically alters the thrombin's procoagulant activities to anticoagulant activities. The lipid bilayer in which it resides serves as an essential 'cofactor', locally concentrating and coordinating the appropriate alignment of reacting cofactors and substrates for protein C activation. On the other hand, liposomes have been extensively studied as cell membrane model as well as carrier for delivering certain vaccines, …

Development Of A ‘Clickable’ Non-Natural Nucleotide To Visualize The Replication Of Non-Instructional Dna Lesions, Edward A. Motea, Irene Lee, Anthony J. Berdis

Chemistry Faculty Publications

The misreplication of damaged DNA is an important biological process that produces numerous adverse effects on human health. This report describes the synthesis and characterization of a non-natural nucleotide, designated 3-ethynyl-5-nitroindolyl-2′-deoxyriboside triphosphate (3-Eth-5-NITP), as a novel chemical reagent that can probe and quantify the misreplication of damaged DNA. We demonstrate that this non-natural nucleotide is efficiently inserted opposite an abasic site, a commonly formed and potentially mutagenic non-instructional DNA lesion. The strategic placement of the ethynyl moiety allows the incorporated nucleoside triphosphate to be selectively tagged with an azide-containing fluorophore using ‘click’ chemistry. This reaction provides a facile way to …

Ua94/6/10 Student / Alumni Personal Papers Wku Carl Ellis, Wku Archives

WKU Archives Collection Inventories

Scientific notebooks used by Carl Ellis during his years at WKU.

Ellagic Acid-Mediated Ck2 Inhibition;A Natural, Multifunctional Strategy To Trigger Cervical Cancer Cell Death In Vitro And In Vivo, Hanan F. Mohammad

ETD Archive

Targeting CK2 for cancer therapy has proven effective in inhibiting tumor growth in several histology's. The main goal of this study was to acquire pre-clinical data on a naturally occurring CK2-inhibitor (ellagic acid) in support of a human clinical trial. In vitro analysis included testing the spectrum of ellagic acid anti-cancer activity, defining the mode of growth inhibition in cancer cells and its impact on biochemical and molecular pathways. In vivo studies included determination of ellagic acid inhibitory effect in animal tumor models and toxicity analysis. We found that CK2 inhibition mediated by ellagic acid, was effective in inhibiting the …

Proteomic Approaches To Elucidate Molecular Mechanisms Of Metal Accumulation In Plants With Focus On Arsenic, Chamari Hasintha Walliwalagedara Kiribandage

ETD Archive

No abstract provided.

Rnase L Manipulates Macrophages In Innate Immunity And Tumor Growth, Xin Yi

ETD Archive

RNase L is one of the key enzymes in the 2-5A system of interferon (IFN) action against viral infection and cellular proliferation. Tissue distribution analysis has revealed that RNase L is highly expressed in the spleen, thymus, lung, testis, intestine and most of immune cells such as T, B cells and macrophages. However, the physiological role of RNase L in the immune system is largely unknown. My thesis thus focused on studying the possible physiological role of RNase L in macrophages. By using bone marrow-derived macrophages (BMMs) from RNase L+/+and -/- mice, we demonstrated that RNase L is involved in …

Purification And Characterization Of Blood Aspirin Hydrolases, Gang Zhou

ETD Archive

Aspirin prophylaxis suppresses major adverse cardiovascular events, but its turnover in blood is rapid, which limits its inhibitory effects on platelet cyclooxygenase and thrombosis. Inter-individual variability of platelet responses to aspirin clinically presents as treatment failure, and this increasing clinical phenomenon is frequently named aspirin "resistance". However, the molecular mechanisms behind this are unclear. Blood aspirin hydrolases are believed to control aspirin survival in vivo, but the identity of the circulating enzyme(s) that hydrolyzes aspirin remains unknown. In this thesis, blood aspirin hydrolases were identified and characterized. The relationship between blood aspirin hydrolases and aspirin efficacy was investigated. RP-HPLC analysis …

Boronic Acid Macroligands For Glycomics Applications, Poornima Pinnamaneni

ETD Archive

Cell surface carbohydrates existing as glycoproteins and glycolipids represent the first information about the cell with the outside world and are closely involved in various biological processes such as cell communication, and the molecular recognition and cell targeting. However, the mechanisms of most of the processes at the molecular level are still unclear. It is therefore very important to develop specific carbohydrate-binding molecules for a fast, efficient, sensitive and accurate analysis of complex carbohydrates structures and functions, known as glycomics. In addition, certain carbohydrate-binding molecules can be used in medical applications such as biomarkers for diseases diagnosis and targeted drug …

Methylation Markers In Hepatocellular Carcinoma, Avinash Gavicharla

ETD Archive

Hepatocellular Carcinoma is one of the major causes for mortality in the world and is usually asymptomatic until late stage decreasing the survival rate. There is an increase of incidence every year and current diagnostic and prognostic bio markers like AFP have their limitations in the wider context. Therefore, it is important to develop novel biomarkers. The aim of the Research is to understand the cytosine methylation and investigate the role of the p16 and SLIT-2 genes as biomarkers in Hepatocellular Carcinoma. The methylation profiles of the genes were assessed on bisulfite modified DNA samples with the aid of Real …

The Structural Requirements Of Histone Deacetylase (Hdac) Inhibitors: Suberoylanilide Hydroxamic Acid (Saha) Analogues Modified At C3, C6, And C7 Positions Enhance Selectivity, Sun Ea Choi

Wayne State University Dissertations

Histone deacetylase (HDAC) proteins are targets for drug design towards the treatment of cancers since overexpression of HDAC is linked to cancer. Several HDAC inhibitors, including the FDA approved drug suberoylanilide hydroxamic acid (SAHA, Vorinostat), have cleared clinical trials and emerged as anti-cancer drugs. However, SAHA inhibits all of the 11 metal ion-dependent HDAC proteins. Therefore, we synthesized several libraries of small molecule HDAC inhibitors based on SAHA to help understand the structural requirements of inhibitory potency and isoform selectivity.

In previous work, SAHA analogues functionalized at the C2 position (C2-SAHA analogues) near the metal binding hydroxamic acid displayed decreased …