Physical Sciences and Mathematics Commons^™

A Comparison Of Boltzmann And Gibbs Definitions Of Microcanonical Entropy For Small Systems, Randall B. Shirts

Faculty Publications

Two different definitions of entropy, S= klnW, in the microcanonical ensemble have been competing for over 100 years. The Boltzmann/Planck definition is that W is the number of states accessible to the system at its energy E (also called the surface entropy). The Gibbs/Hertz definition is that W is the number of states of the system up to the energy E (also called the volume entropy). These two definitions agree for large systems but differ by terms of order N^-1 for small systems, where N is the number of particles in the system. For three analytical …

Microfluidic Devices With Integrated Sample Preparation For Improved Analysis Of Protein Biomarkers, Pamela Nsang Nge

Theses and Dissertations

Biomarkers present a non-invasive means of detecting cancer because they can be obtained from body fluids. They can also be used for prognosis and assessing response to treatment. To limit interferences it is essential to pretreat biological samples before analysis. Sample preparation methods include extraction of analyte from an unsuitable matrix, purification, concentration or dilution and labeling. The many advantages offered by microfluidics include portability, speed, automation and integration. Because of the difficulties encountered in integrating this step in microfluidic devices most sample preparation methods are often carried out off-chip. In the fabrication of micro-total analysis systems it is important …

Towards A Unification Of Supercomputing, Molecular Dynamics Simulation And Experimental Neutron And X-Ray Scattering Techniques, Benjamin Lindner

Doctoral Dissertations

Molecular dynamics simulation has become an essential tool for scientific discovery and investigation. The ability to evaluate every atomic coordinate for each time instant sets it apart from other methodologies, which can only access experimental observables as an outcome of the atomic coordinates. Here, the utility of molecular dynamics is illustrated by investigating the structure and dynamics of fundamental models of cellulose fibers. For that, a highly parallel code has been developed to compute static and dynamical scattering functions efficiently on modern supercomputing architectures. Using state of the art supercomputing facilities, molecular dynamics code and parallelization strategies, this work also …

Anti-Germinants As A New Strategy To Prevent Clostridium Difficile Infections, Amber Janece Howerton

UNLV Theses, Dissertations, Professional Papers, and Capstones

Clostridium difficileinfections (CDI) have emerged as a leading cause of hospital-associated complications. CDI is the major cause of antibiotic-related cases of diarrhea and nearly all cases of pseudomembranous colitis. The infective form of C. difficileis the spore, a dormant and hardy structure that forms under stress. Germination of C. difficile spores into toxin producing bacteria in the GI tract of susceptible patients is the first step in CDI establishment. Patient susceptibility occurs with a disruption of the natural gut microbiota by broad-spectrum antibiotics. Antibiotic treatments usually resolve CDI but refractory cases are on the rise. Of great concern is the …

Secondary Structure, A Missing Component Of Sequence- Based Minimotif Definitions, David P. Sargeant, Michael R. Gryk, Mark W. Maciejewsk, Vishal Thapar, Vamsi Kundeti, Sanguthevar Rajasekaran, Pedro Romero, Keith Dunker, Shun-Cheng Li, Tomonori Kaneko, Martin Schiller

Life Sciences Faculty Research

Minimotifs are short contiguous segments of proteins that have a known biological function. The hundreds of thousands of minimotifs discovered thus far are an important part of the theoretical understanding of the specificity of protein-protein interactions, posttranslational modifications, and signal transduction that occur in cells. However, a longstanding problem is that the different abstractions of the sequence definitions do not accurately capture the specificity, despite decades of effort by many labs. We present evidence that structure is an essential component of minimotif specificity, yet is not used in minimotif definitions. Our analysis of several known minimotifs as case studies, analysis …

Part 1. Design And Synthesis Of Cysteine/Cystine Prodrugs And Bioisosteres Including Symmetrical And Unsymmetrical Disulfides Designed To Increase Cystine Levels In The Cns In Order To Drive The Cystine/Glutamate Antiporter: A Novel Treatment For Schizophrenia And Drug Addiction. Part 2. Design And Synthesis Of Subtype Selective Ester Bioisosteres Of Bzr Ligands For Gabaa/Benzodiazepine Receptors To Enhance Metabolic Stability, Edward Merle Johnson Ii

Theses and Dissertations

Part 1. Schizophrenia is a debilitating disorder that affects almost 1% of the world's population; pharmacotherapy expenditures for this disorder exceed $10 billion dollars even though existing medications exhibit a poor safety/efficacy profile. It is estimated that 75% of patients discontinue drug treatment, in part due to poor safety/efficacy. The current data set demonstrates that cysteine prodrug NAC reverse the behavioral and neurochemical effects of PCP used to model schizophrenia.

As a result cysteine prodrugs represent a highly novel approach to treating schizophrenia; indeed, these compounds may ultimately be more effective than existing medications because these drugs target the pathology …

Investigation Of The Quaternary Structure Of An Abc Transporter In Living Cells Using Spectrally Resolved Resonance Energy Transfer, Deo R. Singh

Theses and Dissertations

Förster resonance energy transfer (FRET) has become an important tool to study proteins inside living cells. It has been used to explore membrane protein folding and dynamics, determine stoichiometry and geometry of protein complexes, and measure the distance between two molecules. In this dissertation, we use a method based on FRET and optical micro-spectroscopy (OptiMiS) technology, developed in our lab, to probe the structure of dynamic (as opposed to static) protein complexes in living cells. We use this method to determine the association stoichiometry and quaternary structure of an ABC transporter in living cells. Specifically, the transporter we investigate originates …

Nanoroughened Surfaces For Efficient Capture Of Circulating Tumor Cells Without Using Capture Antibodies, Weiqiang Chen, Shinuo Weng, Feng Zhang, Steven Allen, Xiang Li, Liwei Bao, Raymond H. W. Lam, Jill A. Macoska, Sofia D. Merajver, Jianping Fu

Weiqiang Chen

Circulating tumor cells (CTCs) detached from both primary and metastatic lesions represent a potential alternative to invasive biopsies as a source of tumor tissue for the detection, characterization and monitoring of cancers. Here we report a simple yet effective strategy for capturing CTCs without using capture antibodies. Our method uniquely utilized the differential adhesion preference of cancer cells to nanorough surfaces when compared to normal blood cells and thus did not depend on their physical size or surface protein expression, a significant advantage as compared to other existing CTC capture techniques.

Microfabrication, Characterization, And Application Of Carbon Nanotube Templated Thin Layer Chromatography Plates, And Functionalization Of Porous Graphitic Carbon, David S. Jensen

Theses and Dissertations

This dissertation contains the following sections. Chapter 1 contains a detailed description of the theory of thin layer chromatography (TLC). Chapter 2 describes the benefits and practical considerations of elevated temperatures in liquid chromatography (LC). The porous graphitic carbon (PGC) I modified as part of my work is often used in elevated temperature LC. Chapter 3 shows a thermodynamic analysis of chromatographic retention at elevated temperature, and Chapter 4 contains a closer look at the van 't Hoff equation in LC and how it can be used in retention modeling. In Chapter 5, I describe a new procedure for microfabricating …

Deposition And Characterization Of Hydrophobic Coatings, Vipul Gupta

Theses and Dissertations

Hydrophobic coatings find application in various sectors of the economy including to electronics, textiles, optical devices, and in scientific and commercial equipment. These different applications demand that different hydrophobic coatings posses a range of properties that may include smoothness or roughness, thicknesses on the order of a monolayer or a micron, robustness or the ability to dissolve quickly, transparency or opacity, water resistance or water permeability, electrical conductivity, oleophobicity, etc. However, whatever the final/desired properties, deposition via dry-deposition processes offers significant advantages, including greater reproducibility, increased environmental friendliness, and cost effectiveness on an industrial scale. Herein I explore the chemical …

Proposed Coherent Trapping Of A Population Of Electrons In A C60 Molecule Induced By Laser Excitation, Thomas George, G.P. Zhang

Chemistry & Biochemistry Faculty Works

This Letter demonstrates the possibility of generating coherent population trapping in C60. Similar to a three-level Λ system, C60 has a forbidden transition between the highest occupied molecular orbital (HOMO) (|a⟩) and the lowest unoccupied molecular orbital (LUMO) (|c⟩), but a dipole-allowed transition between HOMO and LUMO+1 (|b⟩) and between |b⟩ and |c⟩. We employ two cw laser fields, one coupling and one probe. The strong coupling field is switched on first to resonantly excite the transition between |b⟩ and |c⟩. After a delay, the probe is switched on; the coherent interaction between the coupling and probe fields traps the …

Proposed Coherent Trapping Of A Population Of Electrons In A C60 Molecule Induced By Laser Excitation, Thomas F. George, G.P. Zhang

Thomas George

Mechanism Of Action Studies On A New Class Of Anticancer Nucleosides, Megan E. Browning

Theses and Dissertations

We have completed mechanism of action studies on a new class of anticancer nucleosides typified by a novel nucleoside discovered in our lab, MAP-870. In order to study the mechanism of MAP-870, several experiments were completed on a colorectal adenocarcinoma cell line, HT-29, including trypan blue cell count, sulforhodamine B assays, flow cytometry of cell cycle, propidium iodide incorporation, and phosphatidylserine externalization, Caspase-Glo3/7 assays, DNA fragmentation gel, cyclophilin A release gel, PAMPA, and confocal imaging. Sulforhodamine B assays show that MAP-870 does indeed cause growth inhibition and cell death in the model tested. PAMPA assays show that MAP-870 does not …

New Multidetector Solution Could Lead To Safer Alternatives To Faulty Silicone Breast Implants, Judit D. Puskas, Geof Wyatt

Chemical, Biomolecular, and Corrosion Engineering Faculty Research

The article discusses the effort of the University of Akron's Department of Chemical and Biomolecular Engineering to pursue research which aims to reduce or eliminate capsular contracture associated with breast implants. It notes that the new multidetector nanotechnology developed by researchers can be better alternative to silicone gel-filled breast implants. It mentions that the new technology can also help in early diagnosis and imaging of breast cancer.

Differential Effects Of The Hydrophobic Surfactant Proteins On The Formation Of Inverse Bicontinuous Cubic Phases, Mariya Chavarha, Ryan W. Loney, Kamlesh Kumar, Shankar B. Rananavare, Stephen B. Hall

Chemistry Faculty Publications and Presentations

Prior studies have shown that the biological mixture of the two hydrophobic surfactant proteins, SP-B and SP-C, produces faster adsorption of the surfactant lipids to an air/water interface, and that they induce 1-palmitoyl-2-oleoyl phosphatidylethanolamine (POPE) to form inverse bicontinuous cubic phases. SP-B has a much greater effect than SP-C on adsorption. If the two proteins induce formation of the bicontinuous structures and faster adsorption by similar mechanisms, then they should also have differential ability to form the cubic phases. To test this hypothesis, we measured small angle X-ray scattering on the individual proteins combined with POPE. SP-B replicated the doserelated …

Comparison Of Phenolic Compounds And Antioxidant Capacities Of Traditional Sorghum Beers With Other Alcoholic Beverages, Fatouma Abdoul-Latif, Romaric G. Bayili, Louis C. Obame, Mamoudou H. Dicko Prof.

Pr. Mamoudou H. DICKO, PhD

Thirty samples of sorghum beers “dolo” were selected from traditionally fermented household manufacturers from Burkina Faso. Dolo samples were screened for their total phenolic content, proanthocyanidins and putative antioxidant capacities, and were compared with industrial beers and wines. Total phenols were measured using the Folin-Ciocalteu method. Proanthocyanidins content were determined by the method of HCl-butanol hydrolysis. Antioxidant activities were evaluated both with 2,2-diphenyl-1-picrylhydrazyl (DPPH) assay and by the trolox equivalent antioxidant capacity (TEAC) using 2,2’-azinobis(3-ethyl-benzothiazoline-6-sulfonic acid radical) (ABTS•+). The average contents of total phenols and proanthocyanidins were 506 μg GAE/ml of dolo and 45 μg APE/ml of dolo, respectively. An …

36 Degrees Step Size Of Proton-Driven C-Ring Rotation In Fof1-Atp Synthase, Monika Düser, Nawid Zarrabi, Daniel Cipriano, Stefan Ernst, Gary Glick, Stanley Dunn, Michael Börsch

Stanley D Dunn

Synthesis of adenosine triphosphate ATP, the 'biological energy currency', is accomplished by F(o)F(1)-ATP synthase. In the plasma membrane of Escherichia coli, proton-driven rotation of a ring of 10 c subunits in the F(o) motor powers catalysis in the F(1) motor. Although F(1) uses 120 degrees stepping during ATP synthesis, models of F(o) predict either an incremental rotation of c subunits in 36 degrees steps or larger step sizes comprising several fast substeps. Using single-molecule fluorescence resonance energy transfer, we provide the first experimental determination of a 36 degrees sequential stepping mode of the c-ring during ATP synthesis.

Bicatalytic Allylation–Cross-Metathesis Reactions As Γ-Carbonyl Cation Equivalents, Jake R. Henkie, Sugadar Dhaliwal, James R. Green

Chemistry and Biochemistry Publications

The products corresponding to the reactions of arenes and γ-carbonyl cations may be obtained by a one-pot, bicatalytic process involving InCl₃-catalyzed arene allylation and cross metathesis with electron-deficient alkenes. The process is successful with electronically neutral and electron-rich arenes, and modestly Lewis basic donor groups are tolerated with an increase in InCl₃ loading from 10 mol% to 15 mol%, and in one case, 20 mol%.

A Molecular Dynamics (Md) And Quantum Mechanics/Molecular Mechanics (Qm/Mm) Study On Ornithine Cyclodeaminase (Ocd): A Tale Of Two Iminiums, Bogdan F. Ion, Eric Andre Bushnell, Phil De Luna, James Gauld

Chemistry and Biochemistry Publications

Ornithine cyclodeaminase (OCD) is an NAD⁺-dependent deaminase that is found in bacterial species such as Pseudomonas putida. Importantly, it catalyzes the direct conversion of the amino acid L-ornithine to L-proline. Using molecular dynamics (MD) and a hybrid quantum mechanics/molecular mechanics (QM/MM) method in the ONIOM formalism, the catalytic mechanism of OCD has been examined. The rate limiting step is calculated to be the initial step in the overall mechanism: hydride transfer from the L-ornithine’s C_α–H group to the NAD⁺cofactor with concomitant formation of a C_α=NH₂⁺ Schiff base with a barrier …

Libraries At The University Of Massachusetts Amherst: Seeking An International Perspective, Maxine G. Schmidt

Maxine G Schmidt

Presentation delivered to librarians in China, Japan and South Korea as part of my sabbatical research on the use of libraries by Asian students in their home countries.

Re-Introduction Of Transmembrane Serine Residues Reduce The Minimum Pore Diameter Of Channelrhodopsin-2, Robert Dempski, Ryan Richards

Robert E. Dempski

Channelrhodopsin-2 (ChR2) is a microbial-type rhodopsin found in the green algae Chlamydomonas reinhardtii. Under physiological conditions, ChR2 is an inwardly rectifying cation channel that permeates a wide range of mono- and divalent cations. Although this protein shares a high sequence homology with other microbial-type rhodopsins, which are ion pumps, ChR2 is an ion channel. A sequence alignment of ChR2 with bacteriorhodopsin, a proton pump, reveals that ChR2 lacks specific motifs and residues, such as serine and threonine, known to contribute to non-covalent interactions within transmembrane domains. We hypothesized that reintroduction of the eight transmembrane serine residues present in bacteriorhodopsin, but …

Structural Insights Into Neuronal K+ Channel-Calmodulin Complexes, Karen Mruk, Shivender Shandilya, Robert Blaustein, Celia Schiffer, William Kobertz

Celia A. Schiffer

Calmodulin (CaM) is a ubiquitous intracellular calcium sensor that directly binds to and modulates a wide variety of ion channels. Despite the large repository of high-resolution structures of CaM bound to peptide fragments derived from ion channels, there is no structural information about CaM bound to a fully folded ion channel at the plasma membrane. To determine the location of CaM docked to a functioning KCNQ K(+) channel, we developed an intracellular tethered blocker approach to measure distances between CaM residues and the ion-conducting pathway. Combining these distance restraints with structural bioinformatics, we generated an archetypal quaternary structural model of …

Exploring The Role Of A Conserved Class A Residue In The Ω-Loop Of Kpc-2 Β-Lactamase: A Mechanism For Ceftazidime Hydrolysis

Chemistry Faculty Publications

Gram-negative bacteria harboring KPC-2, a class A β-lactamase, are resistant to all β-lactam antibiotics and pose a major public health threat. Arg-164 is a conserved residue in all class A β-lactamases and is located in the solvent-exposed Ω-loop of KPC-2. To probe the role of this amino acid in KPC-2, we performed site-saturation mutagenesis. When compared with wild type, 11 of 19 variants at position Arg-164 in KPC-2 conferred increased resistance to the oxyimino-cephalosporin, ceftazidime (minimum inhibitory concentration; 32→128 mg/liter) when expressed in Escherichia coli. Using the R164S variant of KPC-2 as a representative β-lactamase for more detailed analysis, we …

Achieving High Accuracy Prediction Of Minimotifs, Tian Mi, Sanguthevar Rajasekaran, Jerlin Camilus Merlin, Michael R. Gryk, Martin Schiller

Life Sciences Faculty Research

The low complexity of minimotif patterns results in a high false-positive prediction rate, hampering protein function prediction. A multi-filter algorithm, trained and tested on a linear regression model, support vector machine model, and neural network model, using a large dataset of verified minimotifs, vastly improves minimotif prediction accuracy while generating few false positives. An optimal threshold for the best accuracy reaches an overall accuracy above 90%, while a stringent threshold for the best specificity generates less than 1% false positives or even no false positives and still produces more than 90% true positives for the linear regression and neural network …

Toxicity Assessment And Analgesic Activity Investigation Of Aqueous Acetone Extracts Of Sida Acuta Burn F. And Sida Cordifolia L. (Malvaceae), Medicinal Plants Of Burkina Faso, Kiessoum Konate, Adama Hilou, Raïssa Rr Aworet-Samseny, Alain Souza, Nicolas Barro, Mamoudou H. Dicko Prof., Jacques Datté, Bertrand M’Batchi

Pr. Mamoudou H. DICKO, PhD

Background Sida acuta Burn f. and Sida cordifolia L. (Malvaceae) are traditionally used in Burkina Faso to treat several ailments, mainly pains, including abdominal infections and associated diseases. Despite the extensive use of these plants in traditional health care, literature provides little information regarding their toxicity and the pharmacology. This work was therefore designed to investigate the toxicological effects of aqueous acetone extracts of Sida acuta Burn f. and Sida cordifolia L. Furthermore, their analgesic capacity was assessed, in order to assess the efficiency of the traditional use of these two medicinal plants from Burkina Faso. Method For acute toxicity …

Breast Tumour Initiating Cell Fate Is Regulated By Microenvironmental Cues From An Extracellular Matrix, Sharmistha Saha, Pang-Kuo Lo, Xinrui Duan, Hexin Chen, Qian Wang

Faculty Publications

Cancer stem cells, also known as tumour-initiating cells (TICs), are identified as highly tumorigenic population within tumours and hypothesized to be main regulators in tumour growth, metastasis and relapse. Evidence also suggests that a tumour microenvironment plays a critical role in the development and progression of cancer, by constantly modulating cell–matrix interactions. Scientists have tried to characterize and identify the TIC population but the actual combination of extracellular components in deciphering the fate of TICs has not been explored. The basic unanswered question is the phenotypic stability of this TIC population in a tissue extracellular matrix setting. The in vivo …

Gas Phase Characterization Of Supramolecules Using Cross-Sectional Areas By Fticr And Sustained Off-Resonance Irradiation Collision Induced Dissociation Techniques In A Fourier Transform Ion Cyclotron Resonance Mass Spectrometer, Fan Yang

Theses and Dissertations

In my dissertation, I use a Fourier Transform Ion Cyclotron Resonance Mass Spectrometer (FTICR-MS) to investigate supramolecules. Cross-sectional areas by Fourier transform ICR (CRAFTI), a novel technique for measurements of collision cross sections by FTICR, is demonstrated for the first time. The CRAFTI method measures the total "dephasing cross section" for removal of the ions from the coherent packet in the FTICR cell, including contributions not only from momentum transfer but also from reactive collisions including those leading to collisional dissociation. Experimental CRAFTI collision cross sections correlate linearly with theoretically computed results and with results obtained using ion mobility measurements. …

Flow Valve Diagnostics For Label-Free, Quantitative Biomarker Detection: Device Fabrication, Surface Modification, And Testing, Danielle Scarlet Mansfield

Theses and Dissertations

Diseases are often diagnosed by detection of disease-specific biomarkers in fluid samples. However, many state-of-the-art detection methods require a lab with complex machinery, trained operators, and/or lengthy analysis time. In contrast, point-of-care (POC) devices are brought to the patient's location, they are easy to use, and results are obtained almost immediately. Many current POC devices are too difficult to be used without a skilled assistant, and although many are able to detect analytes above a threshold value, they give little or no quantitative information. This work presents the development of polymer-based microfluidic devices capable of sensing and quantifying biomarkers in …

Synthesis And Biological Evaluation Of Various Derivatives Of A Broad-Spectrum Anticancer Nucleoside, Jadd R. Shelton

Theses and Dissertations

Recently the Peterson lab discovered a promising anticancer adenosine derivative-- 2´,3´-bis-O-tert-butyldimethylsilyl-5´-deoxy-5´-[N-(methylcarbamoyl)amino]-N6-(N-phenylcarbamoyl)adenosine. This compound showed selective toxicity against human colon cancer cells in vitro with LC50's = 6--10 µM. It was hypothesized that the lead compound exerted its cytotoxic effects by interacting with a protein kinase. A systematic Structure Activity Relationship (SAR) was undertaken in an attempt to increase the kinase-binding affinity of the lead compound. Many regions of the lead compound were examined: the N6-phenyl urea moiety, the 5´-N-methyl urea group, the 2´,3´-bis-O-TBS groups, the nucleobase, and the ribose sugar. Results of these studies produced some promising new derivatives. In …

Quantification And In Vitro Analysis Of Nanolipoproteins (Nlps) Containing Adjuvants, Purna Venkataraman, Craig Blanchette, Nicholas O. Fischer

STAR Program Research Presentations

Nanolipoprotein particles (NLPs) self-assemble into nanoscale structures that can be used as vaccines or drug delivery agents. Due to the nature of the NLPs, a variety of immune stimulating compounds or adjuvants can be readily incorporated into NLPs: a characteristic difficult to engineer into most other nanoscale platforms. In light of this, a method for quantifying the amount adjuvant actually incorporated into NLPs is a question of high importance. Through the use of reverse phase High-Performance Liquid Chromatography (HPLC) and an Evaporative Light Scattering Detector (ELSD), standard curves can be constructed by analyzing mixtures of NLP components of known concentration, …