Science.gov

Sample records for dynamic combinatorial chemistry

  1. UNC Center for Dynamic Combinatorial Chemistry

    DTIC Science & Technology

    2014-04-09

    Waters). 9) “Developing small molecules for anion binding using dynamic combinatorial chemistry”, Oct. 26, 2010, group meeting (J. Beaver /Waters...combinatorial chemistry-update”, Jan. 10, 2011, group meeting (J. Beaver /Waters). 12) “Developmen of DCC assay for protein-protein interaction inhibitors...dynamic combinatorial chemistry-update”, Aug. 4, 2011, DCC intergroup meeting (J. Beaver /Gagné/Waters). 15) “Development various peptides for G

  2. Dithioacetal Exchange: A New Reversible Reaction for Dynamic Combinatorial Chemistry.

    PubMed

    Orrillo, A Gastón; Escalante, Andrea M; Furlan, Ricardo L E

    2016-05-10

    Reversibility of dithioacetal bond formation is reported under acidic mild conditions. Its utility for dynamic combinatorial chemistry was explored by combining it with orthogonal disulfide exchange. In such a setup, thiols are positioned at the intersection of both chemistries, constituting a connecting node between temporally separated networks.

  3. Introducing Dynamic Combinatorial Chemistry: Probing the Substrate Selectivity of Acetylcholinesterase

    ERIC Educational Resources Information Center

    Angelin, Marcus; Larsson, Rikard; Vongvilai, Pornrapee; Ramstrom, Olof

    2010-01-01

    In this laboratory experiment, college students are introduced to dynamic combinatorial chemistry (DCC) and apply it to determine the substrate selectivity of acetylcholinesterase (AChE). Initially, the students construct a chemical library of dynamically interchanging thioesters and thiols. Then, AChE is added and allowed to select and hydrolyze…

  4. Protein-Directed Dynamic Combinatorial Chemistry: A Guide to Protein Ligand and Inhibitor Discovery.

    PubMed

    Huang, Renjie; Leung, Ivanhoe K H

    2016-07-16

    Protein-directed dynamic combinatorial chemistry is an emerging technique for efficient discovery of novel chemical structures for binding to a target protein. Typically, this method relies on a library of small molecules that react reversibly with each other to generate a combinatorial library. The components in the combinatorial library are at equilibrium with each other under thermodynamic control. When a protein is added to the equilibrium mixture, and if the protein interacts with any components of the combinatorial library, the position of the equilibrium will shift and those components that interact with the protein will be amplified, which can then be identified by a suitable biophysical technique. Such information is useful as a starting point to guide further organic synthesis of novel protein ligands and enzyme inhibitors. This review uses literature examples to discuss the practicalities of applying this method to inhibitor discovery, in particular, the set-up of the combinatorial library, the reversible reactions that may be employed, and the choice of detection methods to screen protein ligands from a mixture of reversibly forming molecules.

  5. Identification of inhibitors for vascular endothelial growth factor receptor by using dynamic combinatorial chemistry.

    PubMed

    Yang, Zhao; Fang, Zheng; He, Wei; Wang, Zhixiang; Gan, Haifeng; Tian, Qitao; Guo, Kai

    2016-04-01

    The novel analysis method consisting of size-exclusion chromatography (SEC) and HRMS analysis was firstly applied in the discovery of potential inhibitors towards cancer drug targets. With vascular endothelial growth factor receptor (VEGFR-2) as a target, dynamic combinatorial libraries (DCLs) were prepared by reacting aldehydes with amines. Four sensitive binders targeted VEGFR-2 were directly isolated from the library. Antitumor activity test in vitro and inhibition experiments toward angiogenesis were also carried out.

  6. From Dynamic Combinatorial Chemistry to in Vivo Evaluation of Reversible and Irreversible Myeloperoxidase Inhibitors.

    PubMed

    Soubhye, Jalal; Gelbcke, Michel; Van Antwerpen, Pierre; Dufrasne, François; Boufadi, Mokhtaria Yasmina; Nève, Jean; Furtmüller, Paul G; Obinger, Christian; Zouaoui Boudjeltia, Karim; Meyer, Franck

    2017-02-09

    The implementation of dynamic combinatorial libraries allowed the determination of highly active reversible and irreversible inhibitors of myeloperoxidase (MPO) at the nanomolar level. Docking experiments highlighted the interaction between the most active ligands and MPO, and further kinetic studies defined the mode of inhibition of these compounds. Finally, in vivo evaluation showed that one dose of irreversible inhibitors is able to suppress the activity of MPO after inducing inflammation.

  7. Mass spectrometry in combinatorial chemistry.

    PubMed

    Enjalbal, C; Martinez, J; Aubagnac, J L

    2000-01-01

    In the fast expanding field of combinatorial chemistry, profiling libraries has always been a matter of concern--as illustrated by the buoyant literature over the past seven years. Spectroscopic methods, including especially mass spectrometry and to a lesser extent IR and NMR, have been applied at different levels of combinatorial library synthesis: in the rehearsal phase to optimize the chemistry prior to library generation, to confirm library composition, and to characterize after screening each structure that exhibits positive response. Most of the efforts have been concentrated on library composition assessment. The difficulties of such analyses have evolved from the infancy of the combinatorial concept, where large mixtures were prepared, to the recent parallel syntheses of collections of discrete compounds. Whereas the complexity of the analyses has diminished, an increased degree of automation was simultaneously required to achieve efficient library component identification and quantification. In this respect, mass spectrometry has been found to be the method of choice, providing rapid, sensitive, and informative analyses, especially when coupled to chromatographic separation. Fully automated workstations able to cope with several hundreds of compounds per day have been designed. After a brief introduction to describe the combinatorial approach, library characterization will be discussed in detail, considering first the solution-based methodologies and secondly the support-bound material analyses.

  8. Dynamic combinatorial/covalent chemistry: a tool to read, generate and modulate the bioactivity of compounds and compound mixtures.

    PubMed

    Herrmann, Andreas

    2014-03-21

    Reversible covalent bond formation under thermodynamic control adds reactivity to self-assembled supramolecular systems, and is therefore an ideal tool to assess complexity of chemical and biological systems. Dynamic combinatorial/covalent chemistry (DCC) has been used to read structural information by selectively assembling receptors with the optimum molecular fit around a given template from a mixture of reversibly reacting building blocks. This technique allows access to efficient sensing devices and the generation of new biomolecules, such as small molecule receptor binders for drug discovery, but also larger biomimetic polymers and macromolecules with particular three-dimensional structural architectures. Adding a kinetic factor to a thermodynamically controlled equilibrium results in dynamic resolution and in self-sorting and self-replicating systems, all of which are of major importance in biological systems. Furthermore, the temporary modification of bioactive compounds by reversible combinatorial/covalent derivatisation allows control of their release and facilitates their transport across amphiphilic self-assembled systems such as artificial membranes or cell walls. The goal of this review is to give a conceptual overview of how the impact of DCC on supramolecular assemblies at different levels can allow us to understand, predict and modulate the complexity of biological systems.

  9. Similarity searching in large combinatorial chemistry spaces

    NASA Astrophysics Data System (ADS)

    Rarey, Matthias; Stahl, Martin

    2001-06-01

    We present a novel algorithm, called Ftrees-FS, for similarity searching in large chemistry spaces based on dynamic programming. Given a query compound, the algorithm generates sets of compounds from a given chemistry space that are similar to the query. The similarity search is based on the feature tree similarity measure representing molecules by tree structures. This descriptor allows handling combinatorial chemistry spaces as a whole instead of looking at subsets of enumerated compounds. Within few minutes of computing time, the algorithm is able to find the most similar compound in very large spaces as well as sets of compounds at an arbitrary similarity level. In addition, the diversity among the generated compounds can be controlled. A set of 17 000 fragments of known drugs, generated by the RECAP procedure from the World Drug Index, was used as the search chemistry space. These fragments can be combined to more than 1018 compounds of reasonable size. For validation, known antagonists/inhibitors of several targets including dopamine D4, histamine H1, and COX2 are used as queries. Comparison of the compounds created by Ftrees-FS to other known actives demonstrates the ability of the method to jump between structurally unrelated molecule classes.

  10. Dynamic combinatorial self-replicating systems.

    PubMed

    Moulin, Emilie; Giuseppone, Nicolas

    2012-01-01

    Thanks to their intrinsic network topologies, dynamic combinatorial libraries (DCLs) represent new tools for investigating fundamental aspects related to self-organization and adaptation processes. Very recently the first examples integrating self-replication features within DCLs have pushed even further the idea of implementing dynamic combinatorial chemistry (DCC) towards minimal systems capable of self-construction and/or evolution. Indeed, feedback loop processes - in particular in the form of autocatalytic reactions - are keystones to build dynamic supersystems which could possibly approach the roots of "Darwinian" evolvability at mesoscale. This topic of current interest also shows significant potentialities beyond its fundamental character, because truly smart and autonomous materials for the future will have to respond to changes of their environment by selecting and by exponentially amplifying their fittest constituents.

  11. Integrating virtual screening and combinatorial chemistry for accelerated drug discovery.

    PubMed

    López-Vallejo, Fabian; Caulfield, Thomas; Martínez-Mayorga, Karina; Giulianotti, Marc A; Nefzi, Adel; Houghten, Richard A; Medina-Franco, Jose L

    2011-07-01

    Virtual screening is increasingly being used in drug discovery programs with a growing number of successful applications. Experimental methodologies developed to speed up the drug discovery processes include high-throughput screening and combinatorial chemistry. The complementarities between computational and experimental screenings have been recognized and reviewed in the literature. Computational methods have also been used in the combinatorial chemistry field, in particular in library design. However, the integration of computational and combinatorial chemistry screenings has been attempted only recently. Combinatorial libraries (experimental or virtual) represent a notable source of chemically related compounds. Advances in combinatorial chemistry and deconvolution strategies, have enabled the rapid exploration of novel and dense regions in the chemical space. The present review is focused on the integration of virtual and experimental screening of combinatorial libraries. Applications of virtual screening to discover novel anticancer agents and our ongoing efforts towards the integration of virtual screening and combinatorial chemistry are also discussed.

  12. Dynamic mixtures and combinatorial libraries: imines as probes for molecular evolution at the interface between chemistry and biology.

    PubMed

    Herrmann, Andreas

    2009-08-21

    In analogy to evolution in biological processes, "molecular evolution", based on the reversible formation of imines, has successfully been explored for drug discovery, receptor design and as a controlled-release vehicle. Multicomponent systems composed of amines and carbonyl compounds generate structural diversity by reversible reaction of the different components to form equilibrated dynamic mixtures or combinatorial libraries (DCLs). Under thermodynamic control and in the presence of an external factor which influences the equilibrium, these systems evolve by selective adaptation to the changing external conditions. This concept allows the casting of biologically or catalytically active substrates and the molding of receptors from DCLs which are composed of smaller non-active amine and carbonyl moieties. Similarly, if the amine or carbonyl compounds are the biologically active compounds of interest, the corresponding dynamic mixtures are found to be efficient delivery systems, allowing their controlled release over time.

  13. DNA-Encoded Dynamic Combinatorial Chemical Libraries.

    PubMed

    Reddavide, Francesco V; Lin, Weilin; Lehnert, Sarah; Zhang, Yixin

    2015-06-26

    Dynamic combinatorial chemistry (DCC) explores the thermodynamic equilibrium of reversible reactions. Its application in the discovery of protein binders is largely limited by difficulties in the analysis of complex reaction mixtures. DNA-encoded chemical library (DECL) technology allows the selection of binders from a mixture of up to billions of different compounds; however, experimental results often show low a signal-to-noise ratio and poor correlation between enrichment factor and binding affinity. Herein we describe the design and application of DNA-encoded dynamic combinatorial chemical libraries (EDCCLs). Our experiments have shown that the EDCCL approach can be used not only to convert monovalent binders into high-affinity bivalent binders, but also to cause remarkably enhanced enrichment of potent bivalent binders by driving their in situ synthesis. We also demonstrate the application of EDCCLs in DNA-templated chemical reactions.

  14. Generalized topological spaces in evolutionary theory and combinatorial chemistry.

    PubMed

    Stadler, Bärbel M R; Stadler, Peter F

    2002-01-01

    The search spaces in combinatorial chemistry as well as the sequence spaces underlying (molecular) evolution are conventionally thought of as graphs. Recombination, however, implies a nongraphical structure of the combinatorial search spaces. These structures, and their implications for search process itself, are heretofore not well understood in general. In this contribution we review a very general formalism from point set topology and discuss its application to combinatorial search spaces, fitness landscapes, evolutionary trajectories, and artificial chemistries.

  15. Method and apparatus for combinatorial chemistry

    DOEpatents

    Foote, Robert S [Oak Ridge, TN

    2012-06-05

    A method and apparatus are provided for performing light-directed reactions in spatially addressable channels within a plurality of channels. One aspect of the invention employs photoactivatable reagents in solutions disposed into spatially addressable flow streams to control the parallel synthesis of molecules immobilized within the channels. The reagents may be photoactivated within a subset of channels at the site of immobilized substrate molecules or at a light-addressable site upstream from the substrate molecules. The method and apparatus of the invention find particularly utility in the synthesis of biopolymer arrays, e.g., oligonucleotides, peptides and carbohydrates, and in the combinatorial synthesis of small molecule arrays for drug discovery.

  16. Method and apparatus for combinatorial chemistry

    DOEpatents

    Foote, Robert S.

    2007-02-20

    A method and apparatus are provided for performing light-directed reactions in spatially addressable channels within a plurality of channels. One aspect of the invention employs photoactivatable reagents in solutions disposed into spatially addressable flow streams to control the parallel synthesis of molecules immobilized within the channels. The reagents may be photoactivated within a subset of channels at the site of immobilized substrate molecules or at a light-addressable site upstream from the substrate molecules. The method and apparatus of the invention find particularly utility in the synthesis of biopolymer arrays, e.g., oligonucleotides, peptides and carbohydrates, and in the combinatorial synthesis of small molecule arrays for drug discovery.

  17. Method and apparatus for combinatorial chemistry

    SciTech Connect

    Foote, Robert S.

    2009-06-23

    A method and apparatus are provided for performing light-directed reactions in spatially addressable channels within a plurality of channels. One aspect of the invention employs photoactivatable reagents in solutions disposed into spatially addressable flow streams to control the parallel synthesis of molecules immobilized within the channels. The reagents may be photoactivated within a subset of channels at the site of immobilized substrate molecules or at a light-addressable site upstream from the substrate molecules. The method and apparatus of the invention find particularly utility in the synthesis of biopolymer arrays, e.g., oligonucleotides, peptides and carbohydrates, and in the combinatorial synthesis of small molecule arrays for drug discovery.

  18. Natural products and combinatorial chemistry: back to the future.

    PubMed

    Ortholand, Jean-Yves; Ganesan, A

    2004-06-01

    The introduction of high-throughput synthesis and combinatorial chemistry has precipitated a global decline in the screening of natural products by the pharmaceutical industry. Some companies terminated their natural products program, despite the unproven success of the new technologies. This was a premature decision, as natural products have a long history of providing important medicinal agents. Furthermore, they occupy a complementary region of chemical space compared with the typical synthetic compound library. For these reasons, the interest in natural products has been rekindled. Various approaches have evolved that combine the power of natural products and organic chemistry, ranging from the combinatorial total synthesis of analogues to the exploration of natural product scaffolds and the design of completely unnatural molecules that resemble natural products in their molecular characteristics.

  19. Automated Combinatorial Chemistry in the Organic Chemistry Majors Laboratory

    ERIC Educational Resources Information Center

    Nichols, Christopher J.; Hanne, Larry F.

    2010-01-01

    A multidisciplinary experiment has been developed in which students each synthesize a combinatorial library of 48 hydrazones with the aid of a liquid-handling robot. Each product is then subjected to a Kirby-Bauer disk diffusion assay to assess its antibacterial activity. Students gain experience working with automation and at the…

  20. Discovery of New Luminescent Oxides by Combinatorial Solid State Chemistry

    NASA Astrophysics Data System (ADS)

    McFarland, Eric

    1998-03-01

    Combinatorial synthesis and screening of extraordinarily large numbers of different organic compounds has been widely applied in the pharmaceutical industry for drug discovery. Combinatorial chemistry is particularly well suited for ternary and higher order inorganic materials discovery where efforts to predict basic properties have been unsuccessful. New compounds for ultraviolet excited phosphors are important for flat panel displays and for lighting applications. Utilizing automated thin film synthesis and parallel screening techniques, combinatorial libraries with up to 25,000 compositions have been investigated for photoluminescence. Screening of the libraries identified Y_0.845Al_0.070La_0.060Eu_0.025VO4 as a new red phosphor which, when synthesized in bulk, has an intrinsic quantum efficiency under 254 nm excitation of 0.83 ± 0.06 (A COMBINATORIAL APPROACH TO THE DISCOVERY AND OPTIMIZATION OF LUMINESCENT MATERIALS, Earl Danielson, Josh Golden, Eric W. McFarland, Casper M. Reaves, W. Henry Weinberg, and Xin Di Wu, Nature), Vol. 389, (1997). In addition, the first one-dimensional (1-D) luminescent inorganic oxide, Sr_2CeO_4, has been discovered using combinatorial solid state chemistry. The elemental ratios from a diverse discovery library led to the synthesis of a bulk sample of single phase Sr_2CeO4 that was structurally characterized by Rietveld refinement of the powder X-ray data to possess a new structure type for a luminescent oxide built up from 1-D chains of edge sharing CeO6 octahedra, with two terminal O atoms per Ce center isolated from one another by Sr^2+ cations. The cerate shows broad excitation and emission maxima at 310 and 485 nm. The lifetime of the excited state, epr data, crystallographic structure, and magnetic susceptibility all suggest that the mechanism of luminescence originates from a ligand to metal Ce^4+ charge transfer. We speculate that the relatively electron rich terminal O atoms bonded to Ce^4+ in Sr_2CeO_4, which give rise

  1. Sponge derived bromotyrosines: structural diversity through natural combinatorial chemistry.

    PubMed

    Niemann, Hendrik; Marmann, Andreas; Lin, Wenhan; Proksch, Peter

    2015-01-01

    Sponge derived bromotyrosines are a multifaceted class of marine bioactive compounds that are important for the chemical defense of sponges but also for drug discovery programs as well as for technical applications in the field of antifouling constituents. These compounds, which are mainly accumulated by Verongid sponges, exhibit a diverse range of bioactivities including antibiotic, cytotoxic and antifouling effects. In spite of the simple biogenetic building blocks, which consist only of brominated tyrosine and tyramine units, an impressive diversity of different compounds is obtained through different linkages between these precursors and through structural modifications of the side chains and/or aromatic rings resembling strategies that are known from combinatorial chemistry. As examples for bioactive, structurally divergent bromotyrosines psammaplin A, Aplysina alkaloids featuring aerothionin, aeroplysinin-1 and the dienone, and the bastadins, including the synthetically derived hemibastadin congeners, have been selected for this review. Whereas all of these natural products are believed to be involved in the chemical defense of sponges, some of them may also be of particular relevance to drug discovery due to their interaction with specific molecular targets in eukaryotic cells. These targets involve important enzymes and receptors, such as histone deacetylases (HDAC) and DNA methyltransferases (DNMT), which are inhibited by psammaplin A, as well as ryanodine receptors that are targeted by bastadine type compounds. The hemibastadins such as the synthetically derived dibromohemibastadin are of particular interest due to their antifouling activity. For the latter, a phenoloxidase which catalyzes the bioglue formation needed for firm attachment of fouling organisms to a given substrate was identified as a molecular target. The Aplysina alkaloids finally provide a vivid example for dynamic wound induced bioconversions of natural products that generate highly

  2. Dynamic combinatorial libraries of artificial repeat proteins.

    PubMed

    Eisenberg, Margarita; Shumacher, Inbal; Cohen-Luria, Rivka; Ashkenasy, Gonen

    2013-06-15

    Repeat proteins are found in almost all cellular systems, where they are involved in diverse molecular recognition processes. Recent studies have suggested that de novo designed repeat proteins may serve as universal binders, and might potentially be used as practical alternative to antibodies. We describe here a novel chemical methodology for producing small libraries of repeat proteins, and screening in parallel the ligand binding of library members. The first stage of this research involved the total synthesis of a consensus-based three-repeat tetratricopeptide (TPR) protein (~14 kDa), via sequential attachment of the respective peptides. Despite the effectiveness of the synthesis and ligation steps, this method was found to be too demanding for the production of proteins containing variable number of repeats. Additionally, the analysis of binding of the individual proteins was time consuming. Therefore, we designed and prepared novel dynamic combinatorial libraries (DCLs), and show that their equilibration can facilitate the formation of TPR proteins containing up to eight repeating units. Interestingly, equilibration of the library building blocks in the presence of the biologically relevant ligands, Hsp90 and Hsp70, induced their oligomerization into forming more of the proteins with large recognition surfaces. We suggest that this work presents a novel simple and rapid tool for the simultaneous screening of protein mixtures with variable binding surfaces, and for identifying new binders for ligands of interest.

  3. Dynamic chemistry of anion recognition

    SciTech Connect

    Custelcean, Radu

    2012-01-01

    In the past 40 years, anion recognition by synthetic receptors has grown into a rich and vibrant research topic, developing into a distinct branch of Supramolecular Chemistry. Traditional anion receptors comprise organic scaffolds functionalized with complementary binding groups that are assembled by multistep organic synthesis. Recently, a new approach to anion receptors has emerged, in which the host is dynamically self-assembled in the presence of the anionic guest, via reversible bond formation between functional building units. While coordination bonds were initially employed for the self-assembly of the anion hosts, more recent studies demonstrated that reversible covalent bonds can serve the same purpose. In both cases, due to their labile connections, the molecular constituents have the ability to assemble, dissociate, and recombine continuously, thereby creating a dynamic combinatorial library (DCL) of receptors. The anionic guests, through specific molecular recognition, may then amplify (express) the formation of a particular structure among all possible combinations (real or virtual) by shifting the equilibria involved towards the most optimal receptor. This approach is not limited to solution self-assembly, but is equally applicable to crystallization, where the fittest anion-binding crystal may be selected. Finally, the pros and cons of employing dynamic combinatorial chemistry (DCC) vs molecular design for developing anion receptors, and the implications of both approaches to selective anion separations, will be discussed.

  4. Photoelectrochemical Hydrogen Production Using New Combinatorial Chemistry Derived Materials

    SciTech Connect

    Jaramillo, Thomas F.; Baeck, Sung-Hyeon; Kleiman-Shwarsctein, Alan; Stucky, Galen D.; McFarland, Eric W.

    2004-10-25

    Solar photoelectrochemical water-splitting has long been viewed as one of the “holy grails” of chemistry because of its potential impact as a clean, renewable method of fuel production. Several known photocatalytic semiconductors can be used; however, the fundamental mechanisms of the process remain poorly understood and no known material has the required properties for cost effective hydrogen production. In order to investigate morphological and compositional variations in metal oxides as they relate to opto-electrochemical properties, we have employed a combinatorial methodology using automated, high-throughput, electrochemical synthesis and screening together with conventional solid-state methods. This report discusses a number of novel, high-throughput instruments developed during this project for the expeditious discovery of improved materials for photoelectrochemical hydrogen production. Also described within this report are results from a variety of materials (primarily tungsten oxide, zinc oxide, molybdenum oxide, copper oxide and titanium dioxide) whose properties were modified and improved by either layering, inter-mixing, or doping with one or more transition metals. Furthermore, the morphologies of certain materials were also modified through the use of structure directing agents (SDA) during synthesis to create mesostructures (features 2-50 nm) that increased surface area and improved rates of hydrogen production.

  5. Advances in microwave-assisted combinatorial chemistry without polymer-supported reagents.

    PubMed

    Martínez-Palou, Rafael

    2006-08-01

    Combinatorial methodologies have dramatically changed the chemical research and discovery process, offering an unlimited source of new molecule entities to be screened for activity. The application of microwave irradiation in Combinatorial Chemistry and high-throughput synthesis has become increasingly popular. By taking advantage of this energy source, compound libraries for lead generation can be assembled in a fraction of time required by conventional thermal heating. This review focuses on the advances in developing synthetic methodologies in microwave without polymer-supported reagents suitable for combinatorial chemistry, including the advances in microwave-assisted fluorous synthesis technology.

  6. Application of computer assisted combinatorial chemistry in antivirial, antimalarial and anticancer agents design

    NASA Astrophysics Data System (ADS)

    Burello, E.; Bologa, C.; Frecer, V.; Miertus, S.

    Combinatorial chemistry and technologies have been developed to a stage where synthetic schemes are available for generation of a large variety of organic molecules. The innovative concept of combinatorial design assumes that screening of a large and diverse library of compounds will increase the probability of finding an active analogue among the compounds tested. Since the rate at which libraries are screened for activity currently constitutes a limitation to the use of combinatorial technologies, it is important to be selective about the number of compounds to be synthesized. Early experience with combinatorial chemistry indicated that chemical diversity alone did not result in a significant increase in the number of generated lead compounds. Emphasis has therefore been increasingly put on the use of computer assisted combinatorial chemical techniques. Computational methods are valuable in the design of virtual libraries of molecular models. Selection strategies based on computed physicochemical properties of the models or of a target compound are introduced to reduce the time and costs of library synthesis and screening. In addition, computational structure-based library focusing methods can be used to perform in silico screening of the activity of compounds against a target receptor by docking the ligands into the receptor model. Three case studies are discussed dealing with the design of targeted combinatorial libraries of inhibitors of HIV-1 protease, P. falciparum plasmepsin and human urokinase as potential antivirial, antimalarial and anticancer drugs. These illustrate library focusing strategies.

  7. Discovery of bioactive molecules from CuAAC click-chemistry-based combinatorial libraries.

    PubMed

    Wang, Xueshun; Huang, Boshi; Liu, Xinyong; Zhan, Peng

    2016-01-01

    The rapid assembly and in situ screening of focused combinatorial fragment libraries using CuAAC click chemistry is a highly robust and efficient strategy for establishing SAR and for discovering bioactive molecules. This review outlines the current status of this methodology in drug discovery application. The inherent limitations, challenges and prospects are critically discussed.

  8. Carbonic anhydrase II-induced selection of inhibitors from a dynamic combinatorial library of Schiff's bases.

    PubMed

    Nasr, Gihane; Petit, Eddy; Supuran, Claudiu T; Winum, Jean-Yves; Barboiu, Mihail

    2009-11-01

    A dynamic combinatorial library (DCL) has been generated under thermodynamic control by using the aminocarbonyl/imine interconversion as reversible chemistry, combined with non-covalent binding within the active site of the metalloenzyme human carbonic anhydrase II (hCA II, EC 4.2.1.1). The high affinity of hCA II isozyme towards some sulfonamide inhibitors obtained here was used to select from the dynamic library specific inhibitors of this isoform. These results point out to the possibility of identifying sulfonamide amplified compounds presenting potent inhibition and high yield of formation in the presence of the isoform(s) towards which the inhibitors were designed.

  9. A new combinatorial method for synthesizing, screening, and discovering antifouling surface chemistries.

    PubMed

    Imbrogno, Joseph; Williams, Matthew D; Belfort, Georges

    2015-02-04

    A set of diverse monomers were synthesized using combinatorial chemistry and tested using our unique high-throughput screening platform. The versatility of our platform is exemplified by possible applications in reducing biological fouling on ship hulls, filtration membranes, and surgical instruments, to name a few. To demonstrate its efficacy, the novel monomers were graft-polymerized onto light sensitive poly(ether sulfone) (PES) membranes via atmospheric-pressure plasma polymerization. A diverse library was synthesized by reacting a common vinyl ester linker with a library of maleimides containing various different functional groups. This allowed us to produce a library of many different surfaces and graft them all using the same linker chemistry. The modified surfaces were then tested and screened for the best antiprotein adsorption (nonfouling) properties. Membranes, functionalized with carboxylic acid, zwitterionic, and ester groups, had the lowest protein adhesion compared with that of an unmodified control PES membrane after a static fouling test. After dynamic fouling, these same functionalities as well as a hydroxyl group exhibited the highest permeability. These monomers performed better than our best previously synthesized amide monomers as well as our best poly(ethylene glycol) monomers, which are known to have very high protein resistance. Hansen solubility parameters qualitatively predicted which monomers performed best, indicating favorable interactions with water molecules.

  10. Combinatorial computational chemistry approach for materials design: applications in deNOx catalysis, Fischer-Tropsch synthesis, lanthanoid complex, and lithium ion secondary battery.

    PubMed

    Koyama, Michihisa; Tsuboi, Hideyuki; Endou, Akira; Takaba, Hiromitsu; Kubo, Momoji; Del Carpio, Carlos A; Miyamoto, Akira

    2007-02-01

    Computational chemistry can provide fundamental knowledge regarding various aspects of materials. While its impact in scientific research is greatly increasing, its contributions to industrially important issues are far from satisfactory. In order to realize industrial innovation by computational chemistry, a new concept "combinatorial computational chemistry" has been proposed by introducing the concept of combinatorial chemistry to computational chemistry. This combinatorial computational chemistry approach enables theoretical high-throughput screening for materials design. In this manuscript, we review the successful applications of combinatorial computational chemistry to deNO(x) catalysts, Fischer-Tropsch catalysts, lanthanoid complex catalysts, and cathodes of the lithium ion secondary battery.

  11. Transfer RNA modifications: Nature’s combinatorial chemistry playground

    PubMed Central

    Jackman, Jane E.; Alfonzo, Juan D.

    2012-01-01

    Following synthesis, tRNAs are peppered by numerous chemical modifications which may differentially affect a tRNA’s structure and function. Although modifications affecting the business ends of a tRNA are predictably important for cell viability, a majority of modifications play more subtle structural roles that can affect tRNA stability and folding. The current trend is that modifications act in concert and it is in the context of the specific sequence of a given tRNA that they impart their differing effects. Recent developments in the modification field have highlighted the diversity of modifications in tRNA. From these the combinatorial nature of modifications in explaining previously described phenotypes derived from their absence has emerged as a growing theme. PMID:23139145

  12. DNA functionalization by dynamic chemistry

    PubMed Central

    Kanlidere, Zeynep; Jochim, Oleg; Cal, Marta

    2016-01-01

    Summary Dynamic combinatorial chemistry (DCC) is an attractive method to efficiently generate libraries of molecules from simpler building blocks by reversible reactions under thermodynamic control. Here we focus on the chemical modification of DNA oligonucleotides with acyclic diol linkers and demonstrate their potential for the deoxyribonucleic acid functionalization and generation of libraries of reversibly interconverting building blocks. The syntheses of phosphoramidite building blocks derived from D-threoninol are presented in two variants with protected amino or thiol groups. The threoninol building blocks were successfully incorporated via automated solid-phase synthesis into 13mer oligonucleotides. The amino group containing phosphoramidite was used together with complementary single-strand DNA templates that influenced the Watson–Crick base-pairing equilibrium in the mixture with a set of aldehyde modified nucleobases. A significant fraction of all possible base-pair mismatches was obtained, whereas, the highest selectivity (over 80%) was found for the guanine aldehyde templated by the complementary cytosine containing DNA. The elevated occurrence of mismatches can be explained by increased backbone plasticity derived from the linear threoninol building block as a cyclic deoxyribose analogue. PMID:27829920

  13. Mass spectrometry and combinatorial chemistry: new approaches for direct support-bound compound identification.

    PubMed

    Enjalbal, C; Maux, D; Martinez, J; Combarieu, R; Aubagnac, J L

    2001-06-01

    Mass spectrometry is a powerful analytical tool allowing rapid and sensitive structural elucidation of a wide range of molecules issued from solution-, solid- and liquid-phase syntheses. Therefore, mass spectrometry has become the most widely used tool to probe combinatorial libraries. A significant portion of the reported combinatorial data are being produced using solid phase organic synthesis. In contrast to indirect strategies where the tethered structures were released from the support into solution to undergo standard mass spectrometric analyses, static - secondary ion mass spectrometry (S-SIMS) has enabled the identification of support-bound molecules without any chemical treatment of the resin bead. Such non-destructive characterization was applied at the bead level and facilitated the step-by-step monitoring of solid-phase peptide syntheses. Side-reactions were also detected. The relevance of S-SIMS in the rehearsal phase of combinatorial chemistry is demonstrated by comparison with infrared and nuclear magnetic resonance (NMR) spectroscopies, the two other techniques investigated in that field. An alternative to solid-phase synthesis consists of assembling molecules on a soluble polymer. This methodology is termed liquid-phase synthesis. Compound characterization is facilitated since the derivatized support is soluble in spectroscopic solvents used in NMR or in electrospray ionization mass spectrometry. The advantages and drawbacks of this approach will be discussed in terms of the direct monitoring of supported reactions during chemistry optimization and rehearsal library validation.

  14. Synthesis of Chemiluminescent Esters: A Combinatorial Synthesis Experiment for Organic Chemistry Students

    ERIC Educational Resources Information Center

    Duarte, Robert; Nielson, Janne T.; Dragojlovic, Veljko

    2004-01-01

    A group of techniques aimed at synthesizing a large number of structurally diverse compounds is called combinatorial synthesis. Synthesis of chemiluminescence esters using parallel combinatorial synthesis and mix-and-split combinatorial synthesis is experimented.

  15. WORKSHOP ON NEW DEVELOPMENTS IN CHEMICAL SEPARATIONS FROM COMBINATORIAL CHEMISTRY AND RELATED SYNTHETIC STRATEGIES

    SciTech Connect

    Weber, Stephen G.

    1998-08-22

    The power of combinatorial chemistry and related high throughput synthetic strategies is currently being pursued as a fruitful way to develop molecules and materials with new properties. The strategy is motivated, for example in the pharmaceutical industry, by the difficulty of designing molecules to bind to specific sites on target biomolecules. By synthesizing a variety of similar structures, and then finding the one that has the most potent activity, new so-called lead structures will be found rapidly. Existing lead structures can be optimized. This relatively new approach has many implications for separation science. The most obvious is the call for more separations power: higher resolution, lower concentrations, higher speed. This pressure butresses the traditional directions of research into the development of more useful separations. The advent of chip-based, electroosmotically pumped systems1 will certainly accelerate progress in this traditional direction. The progress in combinatorial chemistry and related synthetic strategies gives rise to two other, broadly significant possibilities for large changes in separation science. One possibility results from the unique requirements of the synthesis of a huge number of products simultaneously. Can syntheses and separations be designed to work together to create strategies that lead to mixtures containing only desired products but without side products? The other possibility results from the need for molecular selectivity in separations. Can combinatorial syntheses and related strategies be used in the development of better separations media? A workshop in two parts was held. In one half-day session, pedagogical presentations educated across the barriers of discipline and scale. In the second half-day session, the participants broke into small groups to flesh out new ideas. A panel summarized the breakout discussions.

  16. Constitutional dynamic chemistry: bridge from supramolecular chemistry to adaptive chemistry.

    PubMed

    Lehn, Jean-Marie

    2012-01-01

    Supramolecular chemistry aims at implementing highly complex chemical systems from molecular components held together by non-covalent intermolecular forces and effecting molecular recognition, catalysis and transport processes. A further step consists in the investigation of chemical systems undergoing self-organization, i.e. systems capable of spontaneously generating well-defined functional supramolecular architectures by self-assembly from their components, thus behaving as programmed chemical systems. Supramolecular chemistry is intrinsically a dynamic chemistry in view of the lability of the interactions connecting the molecular components of a supramolecular entity and the resulting ability of supramolecular species to exchange their constituents. The same holds for molecular chemistry when the molecular entity contains covalent bonds that may form and break reversibility, so as to allow a continuous change in constitution by reorganization and exchange of building blocks. These features define a Constitutional Dynamic Chemistry (CDC) on both the molecular and supramolecular levels.CDC introduces a paradigm shift with respect to constitutionally static chemistry. The latter relies on design for the generation of a target entity, whereas CDC takes advantage of dynamic diversity to allow variation and selection. The implementation of selection in chemistry introduces a fundamental change in outlook. Whereas self-organization by design strives to achieve full control over the output molecular or supramolecular entity by explicit programming, self-organization with selection operates on dynamic constitutional diversity in response to either internal or external factors to achieve adaptation.The merging of the features: -information and programmability, -dynamics and reversibility, -constitution and structural diversity, points to the emergence of adaptive and evolutive chemistry, towards a chemistry of complex matter.

  17. Dynamic imine chemistry.

    PubMed

    Belowich, Matthew E; Stoddart, J Fraser

    2012-03-21

    Formation of an imine--from an amine and an aldehyde--is a reversible reaction which operates under thermodynamic control such that the formation of kinetically competitive intermediates are, in the fullness of time, replaced by the thermodynamically most stable product(s). For this fundamental reason, the imine bond has emerged as an extraordinarily diverse and useful one in the hands of synthetic chemists. Imine bond formation is one of a handful of reactions which define a discipline known as dynamic covalent chemistry (DCC), which is now employed widely in the construction of exotic molecules and extended structures on account of the inherent 'proof-reading' and 'error-checking' associated with these reversible reactions. While both supramolecular chemistry and DCC operate under the regime of reversibility, DCC has the added advantage of constructing robust molecules on account of the formation of covalent bonds rather than fragile supermolecules resulting from noncovalent bonding interactions. On the other hand, these products tend to require more time to form--sometimes days or even months--but their formation can often be catalysed. In this manner, highly symmetrical molecules and extended structures can be prepared from relatively simple precursors. When DCC is utilised in conjunction with template-directed protocols--which rely on the use of noncovalent bonding interactions between molecular building blocks in order to preorganise them into certain relative geometries as a prelude to the formation of covalent bonds under equilibrium control--an additional level of control of structure and topology arises which offers a disarmingly simple way of constructing mechanically-interlocked molecules, such as rotaxanes, catenanes, Borromean rings, and Solomon knots. This tutorial review focuses on the use of dynamic imine bonds in the construction of compounds and products formed with and without the aid of additional templates. While synthesis under thermodynamic

  18. Integrating medicinal chemistry, organic/combinatorial chemistry, and computational chemistry for the discovery of selective estrogen receptor modulators with Forecaster, a novel platform for drug discovery.

    PubMed

    Therrien, Eric; Englebienne, Pablo; Arrowsmith, Andrew G; Mendoza-Sanchez, Rodrigo; Corbeil, Christopher R; Weill, Nathanael; Campagna-Slater, Valérie; Moitessier, Nicolas

    2012-01-23

    As part of a large medicinal chemistry program, we wish to develop novel selective estrogen receptor modulators (SERMs) as potential breast cancer treatments using a combination of experimental and computational approaches. However, one of the remaining difficulties nowadays is to fully integrate computational (i.e., virtual, theoretical) and medicinal (i.e., experimental, intuitive) chemistry to take advantage of the full potential of both. For this purpose, we have developed a Web-based platform, Forecaster, and a number of programs (e.g., Prepare, React, Select) with the aim of combining computational chemistry and medicinal chemistry expertise to facilitate drug discovery and development and more specifically to integrate synthesis into computer-aided drug design. In our quest for potent SERMs, this platform was used to build virtual combinatorial libraries, filter and extract a highly diverse library from the NCI database, and dock them to the estrogen receptor (ER), with all of these steps being fully automated by computational chemists for use by medicinal chemists. As a result, virtual screening of a diverse library seeded with active compounds followed by a search for analogs yielded an enrichment factor of 129, with 98% of the seeded active compounds recovered, while the screening of a designed virtual combinatorial library including known actives yielded an area under the receiver operating characteristic (AU-ROC) of 0.78. The lead optimization proved less successful, further demonstrating the challenge to simulate structure activity relationship studies.

  19. Selective host molecules obtained by dynamic adaptive chemistry.

    PubMed

    Matache, Mihaela; Bogdan, Elena; Hădade, Niculina D

    2014-02-17

    Up till 20 years ago, in order to endow molecules with function there were two mainstream lines of thought. One was to rationally design the positioning of chemical functionalities within candidate molecules, followed by an iterative synthesis-optimization process. The second was the use of a "brutal force" approach of combinatorial chemistry coupled with advanced screening for function. Although both methods provided important results, "rational design" often resulted in time-consuming efforts of modeling and synthesis only to find that the candidate molecule was not performing the designed job. "Combinatorial chemistry" suffered from a fundamental limitation related to the focusing of the libraries employed, often using lead compounds that limit its scope. Dynamic constitutional chemistry has developed as a combination of the two approaches above. Through the rational use of reversible chemical bonds together with a large plethora of precursor libraries, one is now able to build functional structures, ranging from quite simple molecules up to large polymeric structures. Thus, by introduction of the dynamic component within the molecular recognition processes, a new perspective of deciphering the world of the molecular events has aroused together with a new field of chemistry. Since its birth dynamic constitutional chemistry has continuously gained attention, in particular due to its ability to easily create from scratch outstanding molecular structures as well as the addition of adaptive features. The fundamental concepts defining the dynamic constitutional chemistry have been continuously extended to currently place it at the intersection between the supramolecular chemistry and newly defined adaptive chemistry, a pivotal feature towards evolutive chemistry.

  20. Combinatorial and automated synthesis of phosphodiester galactosyl cluster on solid support by click chemistry assisted by microwaves.

    PubMed

    Pourceau, Gwladys; Meyer, Albert; Vasseur, Jean-Jacques; Morvan, François

    2008-08-01

    Small libraries of di-, tri-, and tetragalactosyl clusters were efficiently synthesized using combinatorial methodology, on solid support, by click chemistry assisted by microwaves, starting from different poly alkyne DNA-based scaffolds and two galactosyl azide derivatives. The scaffold was synthesized by standard DNA solid-supported phosphoramidite chemistry using a novel alkyne phosphoramidite and an alkyne solid support. The proportion of each glycocluster in a library was modulated using different molar ratios of both galactose azides.

  1. Salt-induced adaptation of a dynamic combinatorial library of pseudopeptidic macrocycles: unraveling the electrostatic effects in mixed aqueous media.

    PubMed

    Atcher, Joan; Moure, Alejandra; Bujons, Jordi; Alfonso, Ignacio

    2015-04-27

    Dynamic combinatorial libraries are powerful systems for studying adaptive behaviors and relationships, as models of more complex molecular networks. With this aim, we set up a chemically diverse dynamic library of pseudopeptidic macrocycles containing amino-acid side chains with differently charged residues (negative, positive, and neutral). The responsive ability of this complex library upon the increase of the ionic strength has been thoroughly studied. The families of the macrocyclic members concentrating charges of the same sign showed a large increase in its proportion as the ionic strength increases, whereas those with residues of opposite charges showed the reverse behavior. This observation suggested an electrostatic shielding effect of the salt within the library of macrocycles. The top-down deconvolution of the library allowed us to obtain the fundamental thermodynamic information connecting the library members (exchange equilibrium constants), as well as to parameterize the adaptation to the external stimulus. We also visualized the physicochemical driving forces for the process by structural analysis using NMR spectroscopy and molecular modeling. This knowledge permitted the full understanding of the whole dynamic library and also the de novo design of dynamic chemical systems with tailored co-adaptive relationships, containing competing or cooperating species. This study highlights the utility of dynamic combinatorial libraries in the emerging field of systems chemistry.

  2. Fuzzy electron density fragments in macromolecular quantum chemistry, combinatorial quantum chemistry, functional group analysis, and shape-activity relations.

    PubMed

    Mezey, Paul G

    2014-09-16

    example, in medicinal drug design, and (g) tools for combinatorial quantum chemistry approaches using fuzzy fragment databanks and rapid construction of a large number of approximate electron densities for large sets of related molecules, relevant in theoretical molecular and nanostructure design.

  3. A combinatorial chemistry method for fast screening of perovskite-based NO oxidation catalyst.

    PubMed

    Yoon, Dal Young; Lim, Eunho; Kim, Young Jin; Cho, Byong K; Nam, In-Sik; Choung, Jin Woo; Yoo, Seungbeom

    2014-11-10

    A fast parallel screening method based on combinatorial chemistry (combichem) has been developed and applied in the screening tests of perovskite-based oxide (PBO) catalysts for NO oxidation to hit a promising PBO formulation for the oxidation of NO to NO2. This new method involves three consecutive steps: oxidation of NO to NO2 over a PBO catalyst, adsorption of NOx onto the PBO and K2O/Al2O3, and colorimetric assay of the NOx adsorbed thereon. The combichem experimental data have been used for determining the oxidation activity of NO over PBO catalysts as well as three critical parameters, such as the adsorption efficiency of K2O/Al2O3 for NO2 (α) and NO (β), and the time-average fraction of NO included in the NOx feed stream (ξ). The results demonstrated that the amounts of NO2 produced over PBO catalysts by the combichem method under transient conditions correlate well with those from a conventional packed-bed reactor under steady-state conditions. Among the PBO formulations examined, La0.5Ag0.5MnO3 has been identified as the best chemical formulation for oxidation of NO to NO2 by the present combichem method and also confirmed by the conventional packed-bed reactor tests. The superior efficiency of the combichem method for high-throughput catalyst screening test validated in this study is particularly suitable for saving the time and resources required in developing a new formulation of PBO catalyst whose chemical composition may have an enormous number of possible variations.

  4. Heuristic Implementation of Dynamic Programming for Matrix Permutation Problems in Combinatorial Data Analysis

    ERIC Educational Resources Information Center

    Brusco, Michael J.; Kohn, Hans-Friedrich; Stahl, Stephanie

    2008-01-01

    Dynamic programming methods for matrix permutation problems in combinatorial data analysis can produce globally-optimal solutions for matrices up to size 30x30, but are computationally infeasible for larger matrices because of enormous computer memory requirements. Branch-and-bound methods also guarantee globally-optimal solutions, but computation…

  5. Olefin Metathesis in Peptidomimetics, Dynamic Combinatorial Chemistry, and Molecular Imprinting

    DTIC Science & Technology

    2006-08-01

    inhibitor against an enzyme found in bacteria .26 Scheme 2-3. Retrosynthethic analysis of 2-6...potential HIV protease inhibitors by grafting pharmacophoric groups on a azasugar scaffold (Figure 1-4),46 but a rather lengthy synthetic scheme starting...macrocyclic lactams is shown in Scheme 2- 2, in which Pei et al. discovered that 15-17 membered rings provided the best inhibitor properties against an

  6. Estimating equilibrium constants for aggregation from the product distribution of a dynamic combinatorial library.

    PubMed

    Hunt, Rosemary A R; Ludlow, R Frederick; Otto, Sijbren

    2009-11-19

    Multicomponent chemical systems that exhibit a network of covalent and intermolecular interactions may produce interesting and often unexpected chemical or physical behavior. The formation of aggregates is a well-recognized example and presents a particular analytical challenge. We now report the development of a numerical fitting method capable of estimating equilibrium constants for the formation of aggregates from the product distribution of a dynamic combinatorial library containing self-recognizing library members.

  7. Combinatorial optimization using dynamical phase transitions in driven-dissipative systems

    NASA Astrophysics Data System (ADS)

    Leleu, Timothée; Yamamoto, Yoshihisa; Utsunomiya, Shoko; Aihara, Kazuyuki

    2017-02-01

    The dynamics of driven-dissipative systems is shown to be well-fitted for achieving efficient combinatorial optimization. The proposed method can be applied to solve any combinatorial optimization problem that is equivalent to minimizing an Ising Hamiltonian. Moreover, the dynamics considered can be implemented using various physical systems as it is based on generic dynamics—the normal form of the supercritical pitchfork bifurcation. The computational principle of the proposed method relies on an hybrid analog-digital representation of the binary Ising spins by considering the gradient descent of a Lyapunov function that is the sum of an analog Ising Hamiltonian and archetypal single or double-well potentials. By gradually changing the shape of the latter potentials from a single to double well shape, it can be shown that the first nonzero steady states to become stable are associated with global minima of the Ising Hamiltonian, under the approximation that all analog spins have the same amplitude. In the more general case, the heterogeneity in amplitude between analog spins induces the stabilization of local minima, which reduces the quality of solutions to combinatorial optimization problems. However, we show that the heterogeneity in amplitude can be reduced by setting the parameters of the driving signal near a regime, called the dynamic phase transition, where the analog spins' DC components map more accurately the global minima of the Ising Hamiltonian which, in turn, increases the quality of solutions found. Last, we discuss the possibility of a physical implementation of the proposed method using networks of degenerate optical parametric oscillators.

  8. Chemistry in dynamically evolving clouds

    NASA Technical Reports Server (NTRS)

    Tarafdar, S. P.; Prasad, S. S.; Huntress, W. T., Jr.; Villere, K. R.; Black, D. C.

    1985-01-01

    A unified model of chemical and dynamical evolution of isolated, initially diffuse and quiescent interstellar clouds is presented. The model uses a semiempirically derived dependence of the observed cloud temperatures on the visual extinction and density. Even low-mass, low-density, diffuse clouds can collapse in this model, because the inward pressure gradient force assists gravitational contraction. In contrast, previous isothermal collapse models required the low-mass diffuse clouds to be unrealistically cold before gravitational contraction could start. Theoretically predicted dependences of the column densities of various atoms and molecules, such as C and CO, on visual extinction in diffuse clouds are in accord with observations. Similarly, the predicted dependences of the fractional abundances of various chemical species (e.g., CO, H2CO, HCN, HCO(+)) on the total hydrogen density in the core of the dense clouds also agree with observations reported to date in the literature. Compared with previous models of interstellar chemistry, the present model has the potential to explain the wide spectrum of chemical and physical properties of both diffuse and dense clouds with a common formalism employing only a few simple initial conditions.

  9. Synthesis of new water-soluble metal-binding polymers: Combinatorial chemistry approach. 1997 mid-year progress report

    SciTech Connect

    Smith, B.F.

    1997-06-01

    'The first objective of this research is to develop rapid discovery and optimization approaches to new water-soluble chelating polymers. A byproduct of the development approach will be the new, selective, and efficient metal-binding agents. The second objective is to evaluate the concept of using water and organic soluble polymers as new solid supports for combinatorial synthesis. The technology under development, Polymer Filtration (PF), is a technique to selectively remove or recover hazardous and valuable metal ions and radionuclides from various dilute aqueous streams. Not only can this technology be used to remediate contaminated soils and solid surfaces and treat aqueous wastes, it can also be incorporated into facilities as a pollution prevention and waste minimization technology. Polymer Filtration uses water-soluble metal-binding polymers to sequester metal ions in dilute solution. The water-soluble polymers have a sufficiently large molecular size that they can be separated and concentrated using commercial ultrafiltration technology. Water, small organic molecules, and unbound metals pass freely through the ultrafiltration membrane while concentrating the metal-binding polymer. The polymers can then be reused by changing the solution conditions to release the metal ions. The metal-ions are recovered in concentrated form for recycle or disposal using a diafiltration process. The water-soluble polymer can be recycled for further aqueous-stream processing. To advance Polymer Filtration technology to the selectivity levels required for DOE needs. fixture directions in Polymer Filtration must include rapid development, testing, and characterization of new metal-binding polymers. The development of new chelating molecules can be equated to the process of new drugs or new materials discovery. Thus, the authors want to build upon and adapt the combinatorial chemistry approaches developed for rapid molecule generation for the drug industry to the rapid

  10. A hybrid approach using chaotic dynamics and global search algorithms for combinatorial optimization problems

    NASA Astrophysics Data System (ADS)

    Igeta, Hideki; Hasegawa, Mikio

    Chaotic dynamics have been effectively applied to improve various heuristic algorithms for combinatorial optimization problems in many studies. Currently, the most used chaotic optimization scheme is to drive heuristic solution search algorithms applicable to large-scale problems by chaotic neurodynamics including the tabu effect of the tabu search. Alternatively, meta-heuristic algorithms are used for combinatorial optimization by combining a neighboring solution search algorithm, such as tabu, gradient, or other search method, with a global search algorithm, such as genetic algorithms (GA), ant colony optimization (ACO), or others. In these hybrid approaches, the ACO has effectively optimized the solution of many benchmark problems in the quadratic assignment problem library. In this paper, we propose a novel hybrid method that combines the effective chaotic search algorithm that has better performance than the tabu search and global search algorithms such as ACO and GA. Our results show that the proposed chaotic hybrid algorithm has better performance than the conventional chaotic search and conventional hybrid algorithms. In addition, we show that chaotic search algorithm combined with ACO has better performance than when combined with GA.

  11. Combinatorial Spacetimes

    NASA Astrophysics Data System (ADS)

    Hillman, David

    1995-11-01

    Combinatorial spacetimes are a class of dynamical systems in which finite pieces of spacetime contain finite amounts of information. Most of the guiding principles for designing these systems are drawn from general relativity: the systems are deterministic; spacetime may be foliated into Cauchy surfaces; the law of evolution is local (there is a light-cone structure); and the geometry evolves locally (curvature may be present; big bangs are possible). However, the systems differ from general relativity in that spacetime is a combinatorial object, constructed by piecing together copies of finitely many types of allowed neighborhoods in a prescribed manner. Hence at least initially there is no metric, no concept of continuity or diffeomorphism. The role of diffeomorphism, however, is played by something called a "local equivalence map.". Here I attempt to begin to lay the mathematical foundations for the study of these systems. (Examples of such systems already exist in the literature. The most obvious is reversible cellular automata, which are flat combinatorial spacetimes. Other related systems are structurally dynamic cellular automata, L systems and parallel graph grammars.) In the 1+1-dimensional oriented case, sets of spaces may be described equivalently by matrices of nonnegative integers, directed graphs, or symmetric tensors; local equivalences between space sets are generated by simple matrix transformations. These equivalence maps turn out to be closely related to the flow equivalence maps between subshifts of finite type studied in symbolic dynamics. Also, the symmetric tensor algebra generated by equivalence transformations turns out to be isomorphic to the abstract tensor algebra generated by commutative cocommutative bialgebras. In higher dimensions I attempt to follow the same basic model, which is to define the class of n-dimensional space set descriptions and then generate local equivalences between these descriptions using elementary

  12. Dynamic Mechanical and Nanofibrous Topological Combinatory Cues Designed for Periodontal Ligament Engineering.

    PubMed

    Kim, Joong-Hyun; Kang, Min Sil; Eltohamy, Mohamed; Kim, Tae-Hyun; Kim, Hae-Won

    2016-01-01

    Complete reconstruction of damaged periodontal pockets, particularly regeneration of periodontal ligament (PDL) has been a significant challenge in dentistry. Tissue engineering approach utilizing PDL stem cells and scaffolding matrices offers great opportunity to this, and applying physical and mechanical cues mimicking native tissue conditions are of special importance. Here we approach to regenerate periodontal tissues by engineering PDL cells supported on a nanofibrous scaffold under a mechanical-stressed condition. PDL stem cells isolated from rats were seeded on an electrospun polycaprolactone/gelatin directionally-oriented nanofiber membrane and dynamic mechanical stress was applied to the cell/nanofiber construct, providing nanotopological and mechanical combined cues. Cells recognized the nanofiber orientation, aligning in parallel, and the mechanical stress increased the cell alignment. Importantly, the cells cultured on the oriented nanofiber combined with the mechanical stress produced significantly stimulated PDL specific markers, including periostin and tenascin with simultaneous down-regulation of osteogenesis, demonstrating the roles of topological and mechanical cues in altering phenotypic change in PDL cells. Tissue compatibility of the tissue-engineered constructs was confirmed in rat subcutaneous sites. Furthermore, in vivo regeneration of PDL and alveolar bone tissues was examined under the rat premaxillary periodontal defect models. The cell/nanofiber constructs engineered under mechanical stress showed sound integration into tissue defects and the regenerated bone volume and area were significantly improved. This study provides an effective tissue engineering approach for periodontal regeneration-culturing PDL stem cells with combinatory cues of oriented nanotopology and dynamic mechanical stretch.

  13. Dynamic Mechanical and Nanofibrous Topological Combinatory Cues Designed for Periodontal Ligament Engineering

    PubMed Central

    Kim, Joong-Hyun; Kang, Min Sil; Eltohamy, Mohamed; Kim, Tae-Hyun; Kim, Hae-Won

    2016-01-01

    Complete reconstruction of damaged periodontal pockets, particularly regeneration of periodontal ligament (PDL) has been a significant challenge in dentistry. Tissue engineering approach utilizing PDL stem cells and scaffolding matrices offers great opportunity to this, and applying physical and mechanical cues mimicking native tissue conditions are of special importance. Here we approach to regenerate periodontal tissues by engineering PDL cells supported on a nanofibrous scaffold under a mechanical-stressed condition. PDL stem cells isolated from rats were seeded on an electrospun polycaprolactone/gelatin directionally-oriented nanofiber membrane and dynamic mechanical stress was applied to the cell/nanofiber construct, providing nanotopological and mechanical combined cues. Cells recognized the nanofiber orientation, aligning in parallel, and the mechanical stress increased the cell alignment. Importantly, the cells cultured on the oriented nanofiber combined with the mechanical stress produced significantly stimulated PDL specific markers, including periostin and tenascin with simultaneous down-regulation of osteogenesis, demonstrating the roles of topological and mechanical cues in altering phenotypic change in PDL cells. Tissue compatibility of the tissue-engineered constructs was confirmed in rat subcutaneous sites. Furthermore, in vivo regeneration of PDL and alveolar bone tissues was examined under the rat premaxillary periodontal defect models. The cell/nanofiber constructs engineered under mechanical stress showed sound integration into tissue defects and the regenerated bone volume and area were significantly improved. This study provides an effective tissue engineering approach for periodontal regeneration—culturing PDL stem cells with combinatory cues of oriented nanotopology and dynamic mechanical stretch. PMID:26989897

  14. Dynamic combinatorial interactions of RUNX1 and cooperating partners regulates megakaryocytic differentiation in cell line models.

    PubMed

    Pencovich, Niv; Jaschek, Ram; Tanay, Amos; Groner, Yoram

    2011-01-06

    Specific interactions of transcription factors (TFs) with their targets are crucial for specifying gene expression programs during cell differentiation. How specificity is maintained despite limited selectivity of individual TF-DNA interactions is not fully understood. RUNX1 TF is among the most frequently mutated genes in human leukemia and an important regulator of megakaryopoiesis. We used megakaryocytic cell lines to characterize the network of RUNX1 targets and cooperating TFs in differentiating megakaryocytes and demonstrated how dynamic partnerships between RUNX1 and cooperating TFs facilitated regulatory plasticity and specificity during this process. After differentiation onset, RUNX1 directly activated a large number of genes through interaction with preexisting and de novo binding sites. Recruitment of RUNX1 to de novo occupied sites occurred at H3K4me1-marked preprogrammed enhancers. A significant number of these de novo bound sites lacked RUNX motif but were occupied by AP-1 TFs. Reciprocally, AP-1 TFs were up-regulated by RUNX1 after 12-O-tetradecanoylphorbol-13-acetate induction and recruited to RUNX1-occupied sites lacking AP-1 motifs. At other differentiation stages, additional combinatorial interactions occurred between RUNX1 and its coregulators, GATA1 and ETS. The findings suggest that in differentiating megakaryocytic cell lines, RUNX1 cooperates with GATA1, AP-1, and ETS to orchestrate cell-specific transcription programs through dynamic TF partnerships.

  15. Photodissociation dynamics and atmospheric chemistry

    NASA Astrophysics Data System (ADS)

    Wayne, R. P.

    1993-07-01

    The paper uses data from the literature to explore photodissociation dynamics of molecules possessing three, four, and five atoms, as represented by O3 and CO2, NH3 and C2H2, and CH4, respectively. The results yield many details, even in regard to the disposal of energy into rotation, which have applications to atmospheric problems. For instance, experiments probing the translational energies of the O and the vibrational and rotational distributions in the CO suggest that a spin-forbidden channel operates as it does in ozone photolysis. The data for both O3 and CO2 suggest a relationship between the structure of the parent molecule and the dynamics of dissociation.

  16. A dynamic multiarmed bandit-gene expression programming hyper-heuristic for combinatorial optimization problems.

    PubMed

    Sabar, Nasser R; Ayob, Masri; Kendall, Graham; Qu, Rong

    2015-02-01

    Hyper-heuristics are search methodologies that aim to provide high-quality solutions across a wide variety of problem domains, rather than developing tailor-made methodologies for each problem instance/domain. A traditional hyper-heuristic framework has two levels, namely, the high level strategy (heuristic selection mechanism and the acceptance criterion) and low level heuristics (a set of problem specific heuristics). Due to the different landscape structures of different problem instances, the high level strategy plays an important role in the design of a hyper-heuristic framework. In this paper, we propose a new high level strategy for a hyper-heuristic framework. The proposed high-level strategy utilizes a dynamic multiarmed bandit-extreme value-based reward as an online heuristic selection mechanism to select the appropriate heuristic to be applied at each iteration. In addition, we propose a gene expression programming framework to automatically generate the acceptance criterion for each problem instance, instead of using human-designed criteria. Two well-known, and very different, combinatorial optimization problems, one static (exam timetabling) and one dynamic (dynamic vehicle routing) are used to demonstrate the generality of the proposed framework. Compared with state-of-the-art hyper-heuristics and other bespoke methods, empirical results demonstrate that the proposed framework is able to generalize well across both domains. We obtain competitive, if not better results, when compared to the best known results obtained from other methods that have been presented in the scientific literature. We also compare our approach against the recently released hyper-heuristic competition test suite. We again demonstrate the generality of our approach when we compare against other methods that have utilized the same six benchmark datasets from this test suite.

  17. Overview on the current status on virtual high-throughput screening and combinatorial chemistry approaches in multi-target anticancer drug discovery; Part II.

    PubMed

    Geromichalos, George D; Alifieris, Constantinos E; Geromichalou, Elena G; Trafalis, Dimitrios T

    2016-01-01

    Conventional drug design embraces the "one gene, one drug, one disease" philosophy. Nowadays, new generation of anticancer drugs, able to inhibit more than one pathway, is believed to play a major role in contemporary anticancer drug research. In this way, polypharmacology, focusing on multi-target drugs, has emerged as a new paradigm in drug discovery. A number of recent successful drugs have in part or in whole emerged from a structure-based research approach. Many advances including crystallography and informatics are behind these successes. In this part II we will review the role and methodology of ligand-, structure- and fragment-based computer-aided drug design computer aided drug desing (CADD), virtual high throughput screening (vHTS), de novo drug design, fragment-based design and structure-based molecular docking, homology modeling, combinatorial chemistry and library design, pharmacophore model chemistry and informatics in modern drug discovery.

  18. Combinatorial Solid-Phase Synthesis of Aromatic Oligoamides: A Research-Based Laboratory Module for Undergraduate Organic Chemistry

    ERIC Educational Resources Information Center

    Fuller, Amelia A.

    2016-01-01

    A five-week, research-based experiment suitable for second-semester introductory organic laboratory students is described. Each student designs, prepares, and analyzes a combinatorial array of six aromatic oligoamides. Molecules are prepared on solid phase via a six-step synthetic sequence, and purities and identities are determined by analysis of…

  19. A review of mesospheric dynamics and chemistry

    SciTech Connect

    Viereck, R.A. )

    1991-01-01

    Advances made in understanding the chemistry and dynamics of the atmosphere in the approximate altitude range of 50 to 90 km are addressed. Attention is given to mesospheric structure and seasonal variations, gravity waves and gravity wave saturation, the effects of gravity waves on thermal, momentum and constituent fluxes, and the effect of gravity waves on airglow emissions. A review of research on tides and planetary waves and their effects on the mesosphere are presented as well as discussions on ozone hydroxyl, water vapor, and noctilucent cloud research. 217 refs.

  20. Dynamic expression of combinatorial replication-dependent histone variant genes during mouse spermatogenesis.

    PubMed

    Sun, Rongfang; Qi, Huayu

    2014-01-01

    Nucleosomes are basic chromatin structural units that are formed by DNA sequences wrapping around histones. Global chromatin states in different cell types are specified by combinatorial effects of post-translational modifications of histones and the expression of histone variants. During mouse spermatogenesis, spermatogonial stem cells (SSCs) self-renew while undergo differentiation, events that occur in the company of constant re-modeling of chromatin structures. Previous studies have shown that testes contain highly expressed or specific histone variants to facilitate these epigenetic modifications. However, mechanisms of regulating the epigenetic changes and the specific histone compositions of spermatogenic cells are not fully understood. Using real time quantitative RT-PCR, we examined the dynamic expression of replication-dependent histone genes in post-natal mouse testes. It was found that distinct sets of histone genes are expressed in various spermatogenic cells at different stages during spermatogenesis. While gonocyte-enriched testes from mice at 2-dpp (days post partum) express pre-dominantly thirteen histone variant genes, SSC-stage testes at 9-dpp highly express a different set of eight histone genes. During differentiation stage when testes are occupied mostly by spermatocytes and spermatids, another twenty-two histone genes are expressed much higher than the rest, including previously known testis-specific hist1h1t, hist1h2ba and hist1h4c. In addition, histone genes that are pre-dominantly expressed in gonocytes and SSCs are also highly expressed in embryonic stem cells. Several of them were changed when embryoid bodies were formed from ES cells, suggesting their roles in regulating pluripotency of the cells. Further more, differentially expressed histone genes are specifically localized in either SSCs or spermatocytes and spermatids, as demonstrated by in situ hybridization using gene specific probes. Taken together, results presented here

  1. Dynamic covalent chemistry of bisimines at the solid/liquid interface monitored by scanning tunnelling microscopy

    NASA Astrophysics Data System (ADS)

    Ciesielski, Artur; El Garah, Mohamed; Haar, Sébastien; Kovaříček, Petr; Lehn, Jean-Marie; Samorì, Paolo

    2014-11-01

    Dynamic covalent chemistry relies on the formation of reversible covalent bonds under thermodynamic control to generate dynamic combinatorial libraries. It provides access to numerous types of complex functional architectures, and thereby targets several technologically relevant applications, such as in drug discovery, (bio)sensing and dynamic materials. In liquid media it was proved that by taking advantage of the reversible nature of the bond formation it is possible to combine the error-correction capacity of supramolecular chemistry with the robustness of covalent bonding to generate adaptive systems. Here we show that double imine formation between 4-(hexadecyloxy)benzaldehyde and different α,ω-diamines as well as reversible bistransimination reactions can be achieved at the solid/liquid interface, as monitored on the submolecular scale by in situ scanning tunnelling microscopy imaging. Our modular approach enables the structurally controlled reversible incorporation of various molecular components to form sophisticated covalent architectures, which opens up perspectives towards responsive multicomponent two-dimensional materials and devices.

  2. Development of the first potent and selective inhibitor of the zinc endopeptidase neurolysin using a systematic approach based on combinatorial chemistry of phosphinic peptides.

    PubMed

    Jirácek, J; Yiotakis, A; Vincent, B; Checler, F; Dive, V

    1996-08-09

    A new systematic approach, based on combinatorial chemistry of phosphinic peptides, is proposed for rapid development of highly potent and selective inhibitors of zinc metalloproteases. This strategy first evaluates the effects on the inhibitory potency and selectivity of the following parameters: 1) size of the phosphinic peptides, 2) position of the phosphinic bond in the sequence, and 3) the state (free or blocked) of the peptide extremities. After this selection step, the influence of the inhibitor sequence is analyzed in order to determine the identity of the residues that optimized both the potency and the selectivity. We demonstrate the efficiency of this novel approach in rapid identification of the first potent inhibitor of the mammalian zinc endopeptidase neurolysin(24-16), able to discriminate between this enzyme and the related zinc endopeptidase thimet oligopeptidase(24-15). The most potent and selective inhibitor developed in this study, Pro-LPhePsi(PO2CH2)Gly-Pro, displays a Ki value of 4 nM for 24-16 and is 2000 times less potent on 24-15. The specific recognition of such a free phosphinic tetrapeptide by 24-16, as well as the unique specificity of the 24-16 S2 and S2' subsites for proline, unveiled by this study, are discussed in terms of their possible significance for the function of this enzyme and its related zinc endopeptidase activities.

  3. Combinatorial Origami

    NASA Astrophysics Data System (ADS)

    Dieleman, Peter; Waitukaitis, Scott; van Hecke, Martin

    To design rigidly foldable quadrilateral meshes one generally needs to solve a complicated set of constraints. Here we present a systematic, combinatorial approach to create rigidly foldable quadrilateral meshes with a limited number of different vertices. The number of discrete, 1 degree-of-freedom folding branches for some of these meshes scales exponentially with the number of vertices on the edge, whilst other meshes generated this way only have two discrete folding branches, regardless of mesh size. We show how these two different behaviours both emerge from the two folding branches present in a single generic 4-vertex. Furthermore, we model generic 4-vertices as a spherical linkage and exploit a previously overlooked symmetry to create non-developable origami patterns using the same combinatorial framework.

  4. Chemogenomics: a discipline at the crossroad of high throughput technologies, biomarker research, combinatorial chemistry, genomics, cheminformatics, bioinformatics and artificial intelligence.

    PubMed

    Maréchal, Eric

    2008-09-01

    Chemogenomics is the study of the interaction of functional biological systems with exogenous small molecules, or in broader sense the study of the intersection of biological and chemical spaces. Chemogenomics requires expertises in biology, chemistry and computational sciences (bioinformatics, cheminformatics, large scale statistics and machine learning methods) but it is more than the simple apposition of each of these disciplines. Biological entities interacting with small molecules can be isolated proteins or more elaborate systems, from single cells to complete organisms. The biological space is therefore analyzed at various postgenomic levels (genomic, transcriptomic, proteomic or any phenotypic level). The space of small molecules is partially real, corresponding to commercial and academic collections of compounds, and partially virtual, corresponding to the chemical space possibly synthesizable. Synthetic chemistry has developed novel strategies allowing a physical exploration of this universe of possibilities. A major challenge of cheminformatics is to charter the virtual space of small molecules using realistic biological constraints (bioavailability, druggability, structural biological information). Chemogenomics is a descendent of conventional pharmaceutical approaches, since it involves the screening of chemolibraries for their effect on biological targets, and benefits from the advances in the corresponding enabling technologies and the introduction of new biological markers. Screening was originally motivated by the rigorous discovery of new drugs, neglecting and throwing away any molecule that would fail to meet the standards required for a therapeutic treatment. It is now the basis for the discovery of small molecules that might or might not be directly used as drugs, but which have an immense potential for basic research, as probes to explore an increasing number of biological phenomena. Concerns about the environmental impact of chemical industry

  5. Scent Transmutation: A New Way to Teach on Chemical Equilibrium, Distillation, and Dynamic Combinatorial Chemistry

    ERIC Educational Resources Information Center

    Ji, Qing; El-Hamdi, Nadia S.; Miljanic´, Ognjen S?.

    2014-01-01

    Esters are volatile and pleasantly smelling compounds, commonly used as food additives. Using Ti(OBu)[subscript 4]-catalyzed acyl exchange, we demonstrate a scent transmutation experiment, in which two fragrant esters swap their acyl and alkoxy substituents and are, during the course of a reactive distillation, quantitatively converted into two…

  6. Dynamics and Chemistry of Planet Construction

    NASA Astrophysics Data System (ADS)

    Taylor, G. J.

    2010-03-01

    Sophisticated calculations of how planetesimals assembled into the terrestrial planets can be tested by using models of the chemistry of the solar nebula. Jade Bond (previously at University of Arizona and now at the Planetary Science Institute, Tucson, AZ), Dante Lauretta (University of Arizona) and Dave O'Brien (Planetary Sciences Institute) combined planetary accretion simulations done by O'Brien, Alessandro Morbidelli (Observatoire de Nice, France), and Hal Levison (Southwest Research Institute, Boulder) with calculations of the solar nebula chemistry as a function of time and distance from the Sun to determine the overall chemical composition of the planets formed in the simulations. They then compared the simulated planets with the compositions of Earth and Mars. The simulated planets have chemical compositions similar to real planets, indicating that the accretion calculations are reasonable. Questions remain about the accretion of water and other highly volatile compounds, including C and N, which are essential for life.

  7. Organoactinide chemistry: synthesis, structure, and solution dynamics

    SciTech Connect

    Brennan, J.G.

    1985-12-01

    This thesis considers three aspects of organoactinide chemistry. In chapter one, a bidentate phosphine ligand was used to kinetically stabilize complexes of the type Cp/sub 2/MX/sub 2/. Ligand redistribution processes are present throughout the synthetic work, as has often been observed in uranium cyclopentadienyl chemistry. The effects of covalent M-L bonding on the solution and solid state properties of U(III) coordination complexes are considered. In particular, the nature of the more subtle interaction between the metal and the neutral ligand are examined. Using relative basicity data obtained in solution, and solid state structural data (and supplemented by gas phase photoelectron measurements), it is demonstrated that the more electron rich U(III) centers engage in significant U ..-->.. L ..pi..-donation. Trivalent uranium is shown to be capable of acting either as a one- or two-electron reducing agent toward a wide variety of unsaturated organic and inorganic molecules, generating molecular classes unobtainable via traditional synthetic approaches, as well as offering an alternative synthetic approach to molecules accessible via metathesis reactions. Ligand redistribution processes are again observed, but given the information concerning ligand lability, this reactivity pattern is applied to the synthesis of pure materials inaccessible from redox chemistry. 214 refs., 33 figs., 10 tabs.

  8. Dynamic covalent chemistry approaches toward macrocycles, molecular cages, and polymers.

    PubMed

    Jin, Yinghua; Wang, Qi; Taynton, Philip; Zhang, Wei

    2014-05-20

    The current research in the field of dynamic covalent chemistry includes the study of dynamic covalent reactions, catalysts, and their applications. Unlike noncovalent interactions utilized in supramolecular chemistry, the formation/breakage of covalent bonding has slower kinetics and usually requires the aid of a catalyst. Catalytic systems that enable efficient thermodynamic equilibrium are thus essential. In this Account, we describe the development of efficient catalysts for alkyne metathesis, and discuss the application of dynamic covalent reactions (mainly imine, olefin, and alkyne metathesis) in the development of organic functional materials. Alkyne metathesis is an emerging dynamic covalent reaction that offers robust and linear acetylene linkages. By introducing a podand motif into the catalyst ligand design, we have developed a series of highly active and robust alkyne metathesis catalysts, which, for the first time, enabled the one-step covalent assembly of ethynylene-linked functional molecular cages. Imine chemistry and olefin metathesis are among the most well-established reversible reactions, and have also been our main synthetic tools. Various shape-persistent macrocycles and covalent organic polyhedrons have been efficiently constructed in one-step through dynamic imine chemistry and olefin metathesis. The geometrical features and solubilizing groups of the building blocks as well as the reaction kinetics have significant effect on the outcome of a covalent assembly process. More recently, we explored the orthogonality of imine and olefin metatheses, and successfully synthesized heterosequenced macrocycles and molecular cages through one-pot orthogonal dynamic covalent chemistry. In addition to discrete molecular architectures, functional polymeric materials can also be accessed through dynamic covalent reactions. Defect-free solution-processable conjugated polyaryleneethynylenes and polydiacetylenes have been prepared through alkyne metathesis

  9. Combinatorial Optimization Algorithms for Dynamic Multiple Fault Diagnosis in Automotive and Aerospace Applications

    NASA Astrophysics Data System (ADS)

    Kodali, Anuradha

    In this thesis, we develop dynamic multiple fault diagnosis (DMFD) algorithms to diagnose faults that are sporadic and coupled. Firstly, we formulate a coupled factorial hidden Markov model-based (CFHMM) framework to diagnose dependent faults occurring over time (dynamic case). Here, we implement a mixed memory Markov coupling model to determine the most likely sequence of (dependent) fault states, the one that best explains the observed test outcomes over time. An iterative Gauss-Seidel coordinate ascent optimization method is proposed for solving the problem. A soft Viterbi algorithm is also implemented within the framework for decoding dependent fault states over time. We demonstrate the algorithm on simulated and real-world systems with coupled faults; the results show that this approach improves the correct isolation rate as compared to the formulation where independent fault states are assumed. Secondly, we formulate a generalization of set-covering, termed dynamic set-covering (DSC), which involves a series of coupled set-covering problems over time. The objective of the DSC problem is to infer the most probable time sequence of a parsimonious set of failure sources that explains the observed test outcomes over time. The DSC problem is NP-hard and intractable due to the fault-test dependency matrix that couples the failed tests and faults via the constraint matrix, and the temporal dependence of failure sources over time. Here, the DSC problem is motivated from the viewpoint of a dynamic multiple fault diagnosis problem, but it has wide applications in operations research, for e.g., facility location problem. Thus, we also formulated the DSC problem in the context of a dynamically evolving facility location problem. Here, a facility can be opened, closed, or can be temporarily unavailable at any time for a given requirement of demand points. These activities are associated with costs or penalties, viz., phase-in or phase-out for the opening or closing of a

  10. Designing a new Diels-Alderase: a combinatorial, semirational approach including dynamic optimization.

    PubMed

    Linder, Mats; Johansson, Adam Johannes; Olsson, Tjelvar S G; Liebeschuetz, John; Brinck, Tore

    2011-08-22

    A computationally inexpensive design strategy involving 'semirational' screening for enzymatic catalysis is presented. The protocol is based on well-established computational methods and represents a holistic approach to the catalytic process. The model reaction studied here is the Diels-Alder, for which a successful computational design has recently been published (Siegel, J. B. et al. Science 2010, 329, 309-313). While it is a leap forward in the field of computational design, the focus on designing only a small fraction of the active site gives little control over dynamics. Our approach explicitly incorporates mutagenesis and the analysis of binding events and transition states, and a promising enzyme-substrate candidate is generated with relatively little effort. We estimate catalytic rate accelerations of up to 10⁵.

  11. Acceleration of the chemistry solver for modeling DI engine combustion using dynamic adaptive chemistry (DAC) schemes

    NASA Astrophysics Data System (ADS)

    Shi, Yu; Liang, Long; Ge, Hai-Wen; Reitz, Rolf D.

    2010-03-01

    Acceleration of the chemistry solver for engine combustion is of much interest due to the fact that in practical engine simulations extensive computational time is spent solving the fuel oxidation and emission formation chemistry. A dynamic adaptive chemistry (DAC) scheme based on a directed relation graph error propagation (DRGEP) method has been applied to study homogeneous charge compression ignition (HCCI) engine combustion with detailed chemistry (over 500 species) previously using an R-value-based breadth-first search (RBFS) algorithm, which significantly reduced computational times (by as much as 30-fold). The present paper extends the use of this on-the-fly kinetic mechanism reduction scheme to model combustion in direct-injection (DI) engines. It was found that the DAC scheme becomes less efficient when applied to DI engine simulations using a kinetic mechanism of relatively small size and the accuracy of the original DAC scheme decreases for conventional non-premixed combustion engine. The present study also focuses on determination of search-initiating species, involvement of the NOx chemistry, selection of a proper error tolerance, as well as treatment of the interaction of chemical heat release and the fuel spray. Both the DAC schemes were integrated into the ERC KIVA-3v2 code, and simulations were conducted to compare the two schemes. In general, the present DAC scheme has better efficiency and similar accuracy compared to the previous DAC scheme. The efficiency depends on the size of the chemical kinetics mechanism used and the engine operating conditions. For cases using a small n-heptane kinetic mechanism of 34 species, 30% of the computational time is saved, and 50% for a larger n-heptane kinetic mechanism of 61 species. The paper also demonstrates that by combining the present DAC scheme with an adaptive multi-grid chemistry (AMC) solver, it is feasible to simulate a direct-injection engine using a detailed n-heptane mechanism with 543 species

  12. Complex Dynamics in Nonequilibrium Economics and Chemistry

    NASA Astrophysics Data System (ADS)

    Wen, Kehong

    Complex dynamics provides a new approach in dealing with economic complexity. We study interactively the empirical and theoretical aspects of business cycles. The way of exploring complexity is similar to that in the study of an oscillatory chemical system (BZ system)--a model for modeling complex behavior. We contribute in simulating qualitatively the complex periodic patterns observed from the controlled BZ experiments to narrow the gap between modeling and experiment. The gap between theory and reality is much wider in economics, which involves studies of human expectations and decisions, the essential difference from natural sciences. Our empirical and theoretical studies make substantial progress in closing this gap. With the help from the new development in nonequilibrium physics, i.e., the complex spectral theory, we advance our technique in detecting characteristic time scales from empirical economic data. We obtain correlation resonances, which give oscillating modes with decays for correlation decomposition, from different time series including S&P 500, M2, crude oil spot prices, and GNP. The time scales found are strikingly compatible with business experiences and other studies in business cycles. They reveal the non-Markovian nature of coherent markets. The resonances enhance the evidence of economic chaos obtained by using other tests. The evolving multi-humped distributions produced by the moving-time -window technique reveal the nonequilibrium nature of economic behavior. They reproduce the American economic history of booms and busts. The studies seem to provide a way out of the debate on chaos versus noise and unify the cyclical and stochastic approaches in explaining business fluctuations. Based on these findings and new expectation formulation, we construct a business cycle model which gives qualitatively compatible patterns to those found empirically. The soft-bouncing oscillator model provides a better alternative than the harmonic oscillator

  13. Forcing of stratospheric chemistry and dynamics during the Dalton Minimum

    NASA Astrophysics Data System (ADS)

    Anet, J. G.; Muthers, S.; Rozanov, E.; Raible, C. C.; Peter, T.; Stenke, A.; Shapiro, A. I.; Beer, J.; Steinhilber, F.; Brönnimann, S.; Arfeuille, F.; Brugnara, Y.; Schmutz, W.

    2013-11-01

    The response of atmospheric chemistry and dynamics to volcanic eruptions and to a decrease in solar activity during the Dalton Minimum is investigated with the fully coupled atmosphere-ocean chemistry general circulation model SOCOL-MPIOM (modeling tools for studies of SOlar Climate Ozone Links-Max Planck Institute Ocean Model) covering the time period 1780 to 1840 AD. We carried out several sensitivity ensemble experiments to separate the effects of (i) reduced solar ultra-violet (UV) irradiance, (ii) reduced solar visible and near infrared irradiance, (iii) enhanced galactic cosmic ray intensity as well as less intensive solar energetic proton events and auroral electron precipitation, and (iv) volcanic aerosols. The introduced changes of UV irradiance and volcanic aerosols significantly influence stratospheric dynamics in the early 19th century, whereas changes in the visible part of the spectrum and energetic particles have smaller effects. A reduction of UV irradiance by 15%, which represents the presently discussed highest estimate of UV irradiance change caused by solar activity changes, causes global ozone decrease below the stratopause reaching as much as 8% in the midlatitudes at 5 hPa and a significant stratospheric cooling of up to 2 °C in the mid-stratosphere and to 6 °C in the lower mesosphere. Changes in energetic particle precipitation lead only to minor changes in the yearly averaged temperature fields in the stratosphere. Volcanic aerosols heat the tropical lower stratosphere, allowing more water vapour to enter the tropical stratosphere, which, via HOx reactions, decreases upper stratospheric and mesospheric ozone by roughly 4%. Conversely, heterogeneous chemistry on aerosols reduces stratospheric NOx, leading to a 12% ozone increase in the tropics, whereas a decrease in ozone of up to 5% is found over Antarctica in boreal winter. The linear superposition of the different contributions is not equivalent to the response obtained in a simulation

  14. Interactions between dynamics and chemistry by COMMA modeling

    NASA Astrophysics Data System (ADS)

    Berger, U.; Koerner, U.; Sonnemann, G.

    Much of our current knowledge of the chemistry and circulation of the middle atmosphere derives from the spacecraft instruments since the the late 1970s (LIMS, SAGE II, ATMOS) and in particular the 1990s (HALOE, MLS, MAS, ILAS POAM III). In parallel , knowledge of the global circulation has continued to advance thanks to rapid developments in theoretical studies performed using numerical general circulation models (GCMs). This paper will focus on the upper atmosphere at polar latitudes because this region is of special importance for climate studies where trace gases like carbon dioxide, water vapor, ozone, etc. are key ingredients in determing the thermal structure of the summer high latitude mesopause region. Both processes, chemistry as well as dynamical induced transports, and their numerical description define the quality criterions of Middle Atmosphere GCMs. Due to comparisons of modeled and observed trace gas distributions (time scale season down to hours) we will discuss recent advance in numerical modeling of the MLT region.

  15. Ionic Liquids: Radiation Chemistry, Solvation Dynamics and Reactivity Patterns

    SciTech Connect

    Wishart, J.F.

    2011-06-12

    Ionic liquids (ILs) are a rapidly expanding family of condensed-phase media with important applications in energy production, nuclear fuel and waste processing, improving the efficiency and safety of industrial chemical processes, and pollution prevention. ILs generally have low volatilities and are combustion-resistant, highly conductive, recyclable and capable of dissolving a wide variety of materials. They are finding new uses in chemical synthesis, catalysis, separations chemistry, electrochemistry and other areas. Ionic liquids have dramatically different properties compared to conventional molecular solvents, and they provide a new and unusual environment to test our theoretical understanding of primary radiation chemistry, charge transfer and other reactions. We are interested in how IL properties influence physical and dynamical processes that determine the stability and lifetimes of reactive intermediates and thereby affect the courses of reactions and product distributions. We study these issues by characterization of primary radiolysis products and measurements of their yields and reactivity, quantification of electron solvation dynamics and scavenging of electrons in different states of solvation. From this knowledge we wish to learn how to predict radiolytic mechanisms and control them or mitigate their effects on the properties of materials used in nuclear fuel processing, for example, and to apply IL radiation chemistry to answer questions about general chemical reactivity in ionic liquids that will aid in the development of applications listed above. Very early in our radiolysis studies it became evident that the slow solvation dynamics of the excess electron in ILs (which vary over a wide viscosity range) increase the importance of pre-solvated electron reactivity and consequently alter product distributions and subsequent chemistry. This difference from conventional solvents has profound effects on predicting and controlling radiolytic yields

  16. Forcing of stratospheric chemistry and dynamics during the Dalton Minimum

    NASA Astrophysics Data System (ADS)

    Anet, J. G.; Muthers, S.; Rozanov, E.; Raible, C. C.; Peter, T.; Stenke, A.; Shapiro, A. I.; Beer, J.; Steinhilber, F.; Brönnimann, S.; Arfeuille, F.; Brugnara, Y.; Schmutz, W.

    2013-06-01

    especially UV and volcanic eruptions dominate the changes in the ozone, temperature and dynamics while the NOx field is dominated by the EPP. Visible radiation changes have only very minor effects on both stratospheric dynamics and chemistry.

  17. Combinatorial methods in sol-gel technology

    NASA Astrophysics Data System (ADS)

    Rantala, Juha T.; Kololuoma, Terho K.; Kivimaki, L.

    2000-05-01

    Sol-gel processing consists several variable parameters during materials synthesis and post processing steps. The sol-gel synthesis is rather sensitive for the parameters such as pH, temperature, type of catalyst, reaction time etc. However, this sensitivity can be taken as an advantage when developing and studying new materials and their properties. Furthermore, since the sol-gel technology mainly describes the fabrication of solid state materials from a liquid phase by applying metal alkoxides or metal salts as precursors, the post processing such as sintering has critical effects on the final form and properties of the solid material. Combinatorial chemistry and methods are valuable tools to estimate the effects of different variables and to build-up combinatorial libraries for the sol-gel technique. This paper generally describes potentials and the usage motivation of combinatorial chemistry in the sol-gel technology by taking into account some major steps in the synthesis and processing which are valuable for the estimation of the final product properties. Different kind of post processing steps in the combinatorial manner are studied in details. As an example the post processing of sol-gel derived semiconductor oxides and photosensitivity of hybrid sol-gel glasses are presented. The combinatorial treatment and measurement methods for these materials are explained.

  18. Future Arctic ozone recovery: the importance of chemistry and dynamics

    NASA Astrophysics Data System (ADS)

    Bednarz, Ewa; Maycock, Amanda; Abraham, Luke; Braesicke, Peter; Dessens, Olivier; Pyle, John

    2016-04-01

    Future trends in Arctic springtime total column ozone, and its chemical and dynamical drivers, are assessed using a 7 member ensemble from the Met Office Unified Model with United Kingdom Chemistry and Aerosols (UM-UKCA) simulating the period 1960-2100. The Arctic mean March total column ozone increases throughout the 21st century at a rate of ~11.5 DU/decade, and is projected to return to the 1980 level in the late 2030s. However, the integrations show that even past 2060 springtime Arctic ozone can episodically drop by ~50-100 DU below the long-term mean to near present day values. Consistent with the global decline in inorganic chlorine over the century, the estimated mean halogen induced chemical ozone loss in the Arctic lower atmosphere in spring decreases by around a factor of two between 1981-2000 and 2061-2080. However, in the presence of a cold and strong polar vortex elevated halogen losses well above the long-term mean continue to occur in the simulations into the second part of the century. The ensemble shows a radiatively-driven cooling trend modelled in the Arctic winter mid- and upper stratosphere, but there is less consistency across the seven ensemble members in the lower stratosphere. This is partly due to an increase in downwelling over the Arctic polar cap in winter, which increases transport of ozone into the polar region as well as drives adiabatic warming that partly offsets the radiatively-driven stratospheric cooling. However, individual years characterised by significantly suppressed downwelling, reduced transport and low temperatures continue into the future. We conclude that despite the future long-term recovery of Arctic ozone, the large interannual dynamical variability is expected to continue thereby facilitating episodic reductions in springtime ozone columns. Whilst our results suggest that the relative role of dynamical processes for determining Arctic springtime ozone will increase in the future, halogen chemistry will remain a

  19. Combinatorial enzyme technology for the conversion of agricultural fibers to functional properties

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The concept of combinatorial chemistry has received little attention in agriculture and food research, although its applications in this area were described more than fifteen years ago (1, 2). More recently, interest in the use of combinatorial chemistry in agrochemical discovery has been revitalize...

  20. Dynamics and Chemistry of Marine Stratocumulus (DYCOMS) Experiment.

    NASA Astrophysics Data System (ADS)

    Lenschow, D. H.; Paluch, I. R.; Bandy, A. R.; Pearson, R., Jr.; Kawa, S. R.; Weaver, C. J.; Huebert, B. J.; Kay, J. G.; Thornton, D. C.; Driedger, A. R., III

    1988-09-01

    A combined atmospheric chemistry-meteorology experiment, the Dynamics and Chemistry of the Marine Stratocumulus (DYCOMS), was carried out during the summer of 1985 over the eastern Pacific Ocean using the NCAR Electra aircraft. The objectives were to 1) study the budgets of several trace reactive species in a relatively pristine, steady-state, horizontally homogeneous, well-mixed boundary layer capped by a strong inversion and 2) study the formation. maintenance and dissipation of marine stratocumulus that persists off the California coast (as well as similar regions elsewhere) in summer. We obtained both mean and turbulence measurements of meteorological variables within and above the cloud-capped boundary layer that is typical of this region. Ozone was used successfully as a tracer for estimating entrainment rate. We found, however, that horizontal variability was large enough for ozone that a correction needs to be included in the ozone budget for the horizontal displacement due to turns even though the airplane was allowed to drift with the wind. The time rate-of-change term was significant in both the ozone and radon budgets; as a result, a considerably longer time interval than the two hours used between sets of flight legs would be desirable to improve the measurement accuracy of this tern.

  1. Ionic Liquids: Radiation Chemistry, Solvation Dynamics and Reactivity Patterns

    SciTech Connect

    Wishart,J.F.

    2008-09-29

    Ionic liquids (ILs) are a rapidly expanding family of condensed-phase media with important applications in energy production, nuclear fuel and waste processing, improving the efficiency and safety of industrial chemical processes, and pollution prevention. ILs are generally nonvolatile, noncombustible, highly conductive, recyclable and capable of dissolving a wide variety of materials. They are finding new uses in chemical synthesis, catalysis, separations chemistry, electrochemistry and other areas. Ionic liquids have dramatically different properties compared to conventional molecular solvents, and they provide a new and unusual environment to test our theoretical understanding of charge transfer and other reactions. We are interested in how IL properties influence physical and dynamical processes that determine the stability and lifetimes of reactive intermediates and thereby affect the courses of chemical reactions and product distributions. Successful use of ionic liquids in radiation-filled environments, where their safety advantages could be significant, requires an understanding of ionic liquid radiation chemistry. For example, characterizing the primary steps of IL radiolysis will reveal radiolytic degradation pathways and suggest ways to prevent them or mitigate their effects on the properties of the material. An understanding of ionic liquid radiation chemistry will also facilitate pulse radiolysis studies of general chemical reactivity in ILs, which will aid in the development of applications listed above. Very early in our radiolysis studies it became evident that slow solvation dynamics of the excess electron in ILs (which vary over a wide viscosity range) increases the importance of pre-solvated electron reactivity and consequently alters product distributions. Parallel studies of IL solvation phenomena using coumarin-153 dynamic Stokes shifts and polarization anisotropy decay rates are done to compare with electron solvation studies and to evaluate

  2. IONIC LIQUIDS: RADIATION CHEMISTRY, SOLVATION DYNAMICS AND REACTIVITY PATTERNS.

    SciTech Connect

    WISHART,J.F.

    2007-10-01

    energy production, nuclear fuel and waste processing, improving the efficiency and safety of industrial chemical processes, and pollution prevention. ILs are generally nonvolatile, noncombustible, highly conductive, recyclable and capable of dissolving a wide variety of materials. They are finding new uses in chemical synthesis, catalysis, separations chemistry, electrochemistry and other areas. Ionic liquids have dramatically different properties compared to conventional molecular solvents, and they provide a new and unusual environment to test our theoretical understanding of charge transfer and other reactions. We are interested in how IL properties influence physical and dynamical processes that determine the stability and lifetimes of reactive intermediates and thereby affect the courses of chemical reactions and product distributions. Successful use of ionic liquids in radiation-filled environments, where their safety advantages could be significant, requires an understanding of ionic liquid radiation chemistry. For example, characterizing the primary steps of IL radiolysis will reveal radiolytic degradation pathways and suggest ways to prevent them or mitigate their effects on the properties of the material. An understanding of ionic liquid radiation chemistry will also facilitate pulse radiolysis studies of general chemical reactivity in ILs, which will aid in the development of applications listed above. Very early in our radiolysis studies it became evident that slow solvation dynamics of the excess electron in ILs (which vary over a wide viscosity range) increases the importance of pre-solvated electron reactivity and consequently alters product distributions. Parallel studies of IL solvation phenomena using coumarin-153 dynamic Stokes shifts and polarization anisotropy decay rates are done to compare with electron solvation studies and to evaluate the influence of ILs on charge transport processes. Methods. Picosecond pulse radiolysis studies at BNL

  3. Neural Meta-Memes Framework for Combinatorial Optimization

    NASA Astrophysics Data System (ADS)

    Song, Li Qin; Lim, Meng Hiot; Ong, Yew Soon

    In this paper, we present a Neural Meta-Memes Framework (NMMF) for combinatorial optimization. NMMF is a framework which models basic optimization algorithms as memes and manages them dynamically when solving combinatorial problems. NMMF encompasses neural networks which serve as the overall planner/coordinator to balance the workload between memes. We show the efficacy of the proposed NMMF through empirical study on a class of combinatorial problem, the quadratic assignment problem (QAP).

  4. Vesper - Venus Chemistry and Dynamics Orbiter - A NASA Discovery Mission Proposal: Submillimeter Investigation of Atmospheric Chemistry and Dynamics

    NASA Technical Reports Server (NTRS)

    Chin, Gordon

    2011-01-01

    Vesper conducts a focused investigation of the chemistry and dynamics of the middle atmosphere of our sister planet- from the base of the global cloud cover to the lower thermosphere. The middle atmosphere controls the stability of the Venus climate system. Vesper determines what processes maintain the atmospheric chemical stability, cause observed variability of chemical composition, control the escape of water, and drive the extreme super-rotation. The Vesper science investigation provides a unique perspective on the Earth environment due to the similarities in the middle atmosphere processes of both Venus and the Earth. Understanding key distinctions and similarities between Venus and Earth will increase our knowledge of how terrestrial planets evolve along different paths from nearly identical initial conditions.

  5. Future Arctic ozone recovery: the importance of chemistry and dynamics

    NASA Astrophysics Data System (ADS)

    Bednarz, Ewa M.; Maycock, Amanda C.; Abraham, N. Luke; Braesicke, Peter; Dessens, Olivier; Pyle, John A.

    2016-09-01

    Future trends in Arctic springtime total column ozone, and its chemical and dynamical drivers, are assessed using a seven-member ensemble from the Met Office Unified Model with United Kingdom Chemistry and Aerosols (UM-UKCA) simulating the period 1960-2100. The Arctic mean March total column ozone increases throughout the 21st century at a rate of ˜ 11.5 DU decade-1, and is projected to return to the 1980 level in the late 2030s. However, the integrations show that even past 2060 springtime Arctic ozone can episodically drop by ˜ 50-100 DU below the corresponding long-term ensemble mean for that period, reaching values characteristic of the near-present-day average level. Consistent with the global decline in inorganic chlorine (Cly) over the century, the estimated mean halogen-induced chemical ozone loss in the Arctic lower atmosphere in spring decreases by around a factor of 2 between the periods 2001-2020 and 2061-2080. However, in the presence of a cold and strong polar vortex, elevated halogen-induced ozone losses well above the corresponding long-term mean continue to occur in the simulations into the second part of the century. The ensemble shows a significant cooling trend in the Arctic winter mid- and upper stratosphere, but there is less confidence in the projected temperature trends in the lower stratosphere (100-50 hPa). This is partly due to an increase in downwelling over the Arctic polar cap in winter, which increases transport of ozone into the polar region as well as drives adiabatic warming that partly offsets the radiatively driven stratospheric cooling. However, individual winters characterised by significantly suppressed downwelling, reduced transport and anomalously low temperatures continue to occur in the future. We conclude that, despite the projected long-term recovery of Arctic ozone, the large interannual dynamical variability is expected to continue in the future, thereby facilitating episodic reductions in springtime ozone columns

  6. Muonium chemistry and spin dynamics in sulphur, modelling interstitial hydrogen.

    PubMed

    Cox, S F J; Lord, J S; McKenzie, I; Adjizian, J-J; Heggie, M I; Jayasooriya, U A; Grinter, R; Reid, I D

    2011-08-10

    The nature of the elusive muonium centre in sulphur is re-examined in the light of new data on its level-crossing resonance and spin-lattice relaxation. The aim is to provide a model for the solid-state chemistry of interstitial hydrogen in this element, which is as yet unknown, as well as to solve one of the longest standing puzzles in μSR spectroscopy, namely the surprisingly strong depolarization of muons mimicking ion-implanted protons in this innocuous non-magnetic material. The paramagnetic muonium (and by inference hydrogen) centre is confirmed to have the character of a molecular radical, but with huge anisotropy at cryogenic temperatures and a striking shift of the resonance at ordinary temperatures, the hyperfine parameters appearing to collapse and vanish towards the melting point. New density-functional supercell calculations identify a number of possible structures for the defect centre, including a novel form of bond-centred muonium in a closed-ring S(8)Mu complex. Simulations of the spin dynamics and fits to the spectra suggest a dynamical equilibrium or chemical exchange between several configurations, with occupancy of the bond-centre site falling from unity at low cryogenic temperatures to zero near the melting point.

  7. Design of a Dynamic Undergraduate Green Chemistry Course

    ERIC Educational Resources Information Center

    Kennedy, Sarah A.

    2016-01-01

    The green chemistry course taught at Westminster College (PA) incorporates nontraditional teaching techniques and texts to educate future chemists about the importance of using green chemistry principles. The course is designed to introduce green chemistry concepts and demonstrate their inherent necessity by discussing historical missteps by the…

  8. Nonparametric Combinatorial Sequence Models

    NASA Astrophysics Data System (ADS)

    Wauthier, Fabian L.; Jordan, Michael I.; Jojic, Nebojsa

    This work considers biological sequences that exhibit combinatorial structures in their composition: groups of positions of the aligned sequences are "linked" and covary as one unit across sequences. If multiple such groups exist, complex interactions can emerge between them. Sequences of this kind arise frequently in biology but methodologies for analyzing them are still being developed. This paper presents a nonparametric prior on sequences which allows combinatorial structures to emerge and which induces a posterior distribution over factorized sequence representations. We carry out experiments on three sequence datasets which indicate that combinatorial structures are indeed present and that combinatorial sequence models can more succinctly describe them than simpler mixture models. We conclude with an application to MHC binding prediction which highlights the utility of the posterior distribution induced by the prior. By integrating out the posterior our method compares favorably to leading binding predictors.

  9. Reactive Molecular Dynamics Studies of Thermal Induced Chemistry in TATB

    NASA Astrophysics Data System (ADS)

    Germann, Timothy; Quenneville, Jason

    2007-03-01

    Equilibrium molecular dynamics (MD) simulation of high explosives can provide important information on their thermal decomposition by helping to characterize processes with timescales that are much longer than those attainable with non-equilibrium MD shock studies. A reactive force field is used with MD to probe the chemisty induced by intense heating (`cook-off') of 1,3,5-triamino-2,4,6-trinitrobenzene (TATB). The force field (ReaxFF) was developed by van Duin, Goddard and coworkers [1] at CalTech and has already shown promise in predicting the chemistry in small samples of RDX under either shock compression or intense heat. Large-system simulations are desired for TATB because of the high degree of carbon clustering expected in this material. We will show results of 800-particle simulations at several temperatures, and detail current capabilities for large-scale (10^4 -- 10^5 atoms) systems carried out with the massively parallel GRASP MD software developed at Sandia National Lab. Finally, we will compare the reaction timescales with those of RDX and HMX. [1] A. C. T. Van Duin, et al, J. Phys. Chem. A, 1005, 9396 (2001).

  10. Molecular Dynamics Simulations of Thermal Induced Chemistry in TATB

    NASA Astrophysics Data System (ADS)

    Quenneville, Jason; Germann, Timothy

    2006-03-01

    Equilibrium molecular dynamics (MD) simulation of high explosives can provide important information on their thermal decomposition by helping to characterize processes with timescales that are much longer than those attainable with non-equilibrium MD shock studies. A reactive force field is used with MD to probe the chemisty induced by intense heating (`cook-off') of 1,3,5-triamino-2,4,6-trinitrobenzene (TATB). The force field (ReaxFF) was developed by van Duin, Goddard and coworkers^ at CalTech and has already shown promise in predicting the chemistry in small samples of RDX under either shock compression or intense heat. Large-system simulations are desired for TATB because of the high degree of carbon clustering expected in this material. We will show results of 100,000-particle simulations at several temperatures, carried out with the massively parallel GRASP MD software developed at Sandia National Lab. Finally, we will compare the reactions and reaction timescales with those of RDX and HMX. ^ A. C. T. Van Duin, et al, J. Phys. Chem. A, 1005, 9396 (2001).

  11. Crossing the Boundaries within Computational Chemistry: From Molecular Dynamics to Cheminformatics and back.

    PubMed

    Riniker, Sereina

    2014-09-01

    The research in the group for computational chemistry at the ETH Zurich focuses on the development of methods and software for classical molecular dynamics simulations and cheminformatics, and their application to biological and chemical questions. Here, important advances and challenges in these subfields of computational chemistry are reviewed and potential opportunities for cross-fertilization are outlined.

  12. Combinatorial synthesis of anti-HIV agents--a review.

    PubMed

    Sriram, Dharmarajan; Yogeeswari, Perumal; Nagappa, Ananantha Naik

    2005-08-01

    Combinatorial chemistry has been well recognized as an important tool of drug discovery. An ongoing hand is to integrate the combinatorial approach with fundamentals of medicinal chemistry and rational drug design. The last five years has seen an explosion in the exploration and adoption of combinatorial techniques. Indeed, it is difficult to identify any other topic in chemistry that has ever caught the imagination of chemists with such fervor and with the continuous development of high throughput screening methods. There is a growing need for the synthesis of a large number of molecules. Compound libraries designed to produce specific inhibitors of therapeutic target proteins have generated significant interest in drug discovery research. Combinatorial chemistry provides the opportunity to generate large libraries of compounds for biological testing. A literature search revealed that many lead compounds have indeed been discovered from libraries and this review presents a survey of combinatorial synthesis of HIV-1 reverse transcriptase inhibitors, protease inhibitors, HIV-1 function inhibitors such as adsorption inhibitors, CCR5 antagonists and HIV-1 Tat-tar inhibitors that can be developed as potential anti-HIV drugs.

  13. Fast combinatorial optimization with parallel digital computers.

    PubMed

    Kakeya, H; Okabe, Y

    2000-01-01

    This paper presents an algorithm which realizes fast search for the solutions of combinatorial optimization problems with parallel digital computers.With the standard weight matrices designed for combinatorial optimization, many iterations are required before convergence to a quasioptimal solution even when many digital processors can be used in parallel. By removing the components of the eingenvectors with eminent negative eigenvalues of the weight matrix, the proposed algorithm avoids oscillation and realizes energy reduction under synchronous discrete dynamics, which enables parallel digital computers to obtain quasi-optimal solutions with much less time than the conventional algorithm.

  14. Street Canyon Atmospheric Composition: Coupling Dynamics and Chemistry

    NASA Astrophysics Data System (ADS)

    Bright, V.; Bloss, W. J.; Cai, X.

    2010-12-01

    Atmospheric composition within the urban environment, particularly within street canyons (formed by a road running between two rows of buildings), has a direct effect on the air quality of an environment in which a large majority of people live and work. The composition of air within a street canyon is determined by the composition of background air mixed in from above, advection of air into and out of the canyon, vehicle exhaust and other emissions from within the street, together with the mixing and chemical processing of pollutants within the canyon. This occurs on a timescale of a few seconds to minutes and as a result, within-canyon atmospheric processes can have a significant effect on atmospheric composition on such timescales. This paper outlines a modelling study of street canyon atmospheric composition, integrating the combined effects of emissions, dynamics and chemistry. This work builds upon an existing dynamical model of canyon atmospheric motion (Large Eddy Simulation (LES) model) by adding a detailed chemical reaction scheme. Previous studies have considered basic NOx-O3 cycles with only a small number of chemical reactions included. Initially, a zero-dimensional box model was used to develop and assess the accuracy of a suitable reduced chemical scheme to be included within the LES. The reduced chemical scheme, based upon a subset of the Master Chemical Mechanism (MCM), includes 51 chemical species and 136 reactions. Vehicle emissions taken from the UK National Atmospheric Emissions Inventory (NAEI) were subsequently added to the box model. These elements were then combined with the canyon dynamics simulated by the Large Eddy Simulation (LES) model. Results demonstrate that the enhanced model is a suitable tool to be used to further investigate the combined effects of mixing and chemical processing upon air quality within the street canyon. Subsequently, a number of key questions relating to urban atmospheric composition are addressed using the

  15. Combinatorial auction design

    PubMed Central

    Porter, David; Rassenti, Stephen; Roopnarine, Anil; Smith, Vernon

    2003-01-01

    Combinatorial auctions allow for more expressive bidding in which participants can submit package bids with logical constraints that limit allowable outcomes. This type of auction can be useful when participants' values are complementary or when participants have production and financial constraints. However, combinatorial auctions are currently rare in practice. The main problems confronted in implementing these auctions are that they have computational uncertainty (i.e., there is no guarantee that the winning bids for such an auction can be found in a “reasonable” amount of time when the number of bidders and items becomes larger) and that the auction is cognitively complex and can lead participants to pursue perverse bidding strategies. This article describes a type of combinatorial auction that, during laboratory testing, eliminated these problems and produced extremely efficient outcomes. PMID:12893875

  16. Physical Chemistry of Reaction Dynamics in Ionic Liquid

    SciTech Connect

    Maroncelli, Mark

    2016-10-02

    Work completed over the past year mainly involves finishing studies related to solvation dynamics in ionic liquids, amplifying and extending our initial PFG-NMR work on solute diffusion, and learning how to probe rotational dynamics in ionic liquids.

  17. Combinatorial Auctions without Money

    DTIC Science & Technology

    2014-05-01

    society itself (and then “reduce” its total happiness ) to ensure truthfulness. CAs without money would avoid this paradox, automatically guarantee...Combinatorial Auctions without Money ∗ Dimitris Fotakis National Technical Univ. of Athens Greece fotakis@cs.ntua.gr Piotr Krysta University of...absence of money , very little can be done to enforce truthfulness. However, in certain applications, money is unavailable, morally unacceptable or might

  18. Dynamic sulfur chemistry as a key tool in the design of self-healing polymers

    NASA Astrophysics Data System (ADS)

    Martin, Roberto; Rekondo, Alaitz; Ruiz de Luzuriaga, Alaitz; Casuso, Pablo; Dupin, Damien; Cabañero, Germán; Grande, Hans J.; Odriozola, Ibon

    2016-08-01

    The rich variety of reversible or dynamic covalent chemistries based on sulfur offers a unique opportunity for the design of self-healing polymer networks. The reversibility of such chemical bonds can be used to create soft systems which can self-mend at ambient conditions. Here we focus on the mechanism of three different dynamic sulfur chemistries which have been used for the development of self-healing elastomers and hydrogels: thiolate/nanoparticle exchange, aromatic disulfide exchange and gold(I)-thiolate/disulfide exchange.

  19. Chemistry in interstellar space. [environment characteristics influencing reaction dynamics

    NASA Technical Reports Server (NTRS)

    Donn, B.

    1973-01-01

    The particular characteristics of chemistry in interstellar space are determined by the unique environmental conditions involved. Interstellar matter is present at extremely low densities. Large deviations from thermodynamic equilibrium are, therefore, to be expected. A relatively intense ultraviolet radiation is present in many regions. The temperatures are in the range from 5 to 200 K. Data concerning the inhibiting effect of small activation energies in interstellar clouds are presented in a table. A summary of measured activation energies or barrier heights for exothermic exchange reactions is also provided. Problems of molecule formation are discussed, taking into account gas phase reactions and surface catalyzed processes.

  20. Beyond Problem-Based Learning: Using Dynamic PBL in Chemistry

    ERIC Educational Resources Information Center

    Overton, Tina L.; Randles, Christopher A.

    2015-01-01

    This paper describes the development and implementation of a novel pedagogy, dynamic problem-based learning. The pedagogy utilises real-world problems that evolve throughout the problem-based learning activity and provide students with choice and different data sets. This new dynamic problem-based learning approach was utilised to teach…

  1. Dynamics of the Chemistry of Electronically Excited Atoms in Defined Quantum States.

    DTIC Science & Technology

    1978-05-01

    laser development . In essence, this research concerns itself with the elucidation of the role of electronic energy in affecting the chemistry or photochemistry of excited halogen atoms and molecules. While much is known about the dynamics of chemical and physical processes which are carried out on the lowest potential energy hypersurface correlating with reactants and products in their electronic ground state, relatively little is known about the dynamics of such phenomena as energy transfer and chemical reactivity on higher-lying potential

  2. Combinatorial Mechanical Metamaterials

    NASA Astrophysics Data System (ADS)

    van Hecke, Martin

    The structure of most mechanical metamaterials is periodic so that their design space is that of the unit cell. Here we introduce a combinatorial strategy to create a vast number of distinct mechanical metamaterials, each with a unique spatial texture and response. These are aperiodic stackings of anisotropic building blocks, and their functionality rests on both the block design and their stacking configuration which is governed by a tiling problem. We realize such metamaterials by 3D printing, and show that they act as soft machines, capable of pattern recognition and pattern analysis.

  3. Interplay between chemistry and dynamics in embedded protostellar disks

    NASA Astrophysics Data System (ADS)

    Brinch, C.; Jørgensen, J. K.

    2013-11-01

    Context. A fundamental part of the study of star formation is to place young stellar objects in an evolutionary sequence. Establishing a robust evolutionary classification scheme allows us not only to understand how the Sun was born but also to predict what kind of main sequence star a given protostar will become. Traditionally, low-mass young stellar objects are classified according to the shape of their spectral energy distributions. Such methods are, however, prone to misclassification due to degeneracy and do not constrain the temporal evolution. More recently, young stellar objects have been classified based on envelope, disk, and stellar masses determined from resolved images of their continuum and line emission at submillimeter wavelengths. Aims: Through detailed modeling of two Class I sources, we aim at determining accurate velocity profiles and explore the role of freeze-out chemistry in such objects. Methods: We present new Submillimeter Array observations of the continuum and HCO+ line emission at 1.1 mm toward two protostars, IRS 63 and IRS 43 in the Ophiuchus star forming region. The sources were modeled in detail using dust radiation transfer to fit the SED and continuum images and line radiation transfer to produce synthetic position-velocity diagrams. We used a χ2 search algorithm to find the best model fit to the data and to estimate the errors in the model variables. Results: Our best fit models present disk, envelope, and stellar masses, as well as the HCO+ abundance and inclination of both sources. We also identify a ring structure with a radius of about 200 AU in IRS 63. Conclusions: We find that freeze-out chemistry is important in IRS 63 but not for IRS 43. We show that the velocity field in IRS 43 is consistent with Keplerian rotation. Owing to molecular depletion, it is not possible to draw a similar conclusion for IRS 63. We identify a ring-shaped structure in IRS 63 on the same spatial scale as the disk outer radius. No such structure

  4. Cryptographic Combinatorial Securities Exchanges

    NASA Astrophysics Data System (ADS)

    Thorpe, Christopher; Parkes, David C.

    We present a useful new mechanism that facilitates the atomic exchange of many large baskets of securities in a combinatorial exchange. Cryptography prevents information about the securities in the baskets from being exploited, enhancing trust. Our exchange offers institutions who wish to trade large positions a new alternative to existing methods of block trading: they can reduce transaction costs by taking advantage of other institutions’ available liquidity, while third party liquidity providers guarantee execution—preserving their desired portfolio composition at all times. In our exchange, institutions submit encrypted orders which are crossed, leaving a “remainder”. The exchange proves facts about the portfolio risk of this remainder to third party liquidity providers without revealing the securities in the remainder, the knowledge of which could also be exploited. The third parties learn either (depending on the setting) the portfolio risk parameters of the remainder itself, or how their own portfolio risk would change if they were to incorporate the remainder into a portfolio they submit. In one setting, these third parties submit bids on the commission, and the winner supplies necessary liquidity for the entire exchange to clear. This guaranteed clearing, coupled with external price discovery from the primary markets for the securities, sidesteps difficult combinatorial optimization problems. This latter method of proving how taking on the remainder would change risk parameters of one’s own portfolio, without revealing the remainder’s contents or its own risk parameters, is a useful protocol of independent interest.

  5. Aqueous vanadium ion dynamics relevant to bioinorganic chemistry: A review.

    PubMed

    Kustin, Kenneth

    2015-06-01

    Aqueous solutions of the four highest vanadium oxidation states exhibit four diverse colors, which only hint at the diverse reactions that these ions can undergo. Cationic vanadium ions form complexes with ligands; anionic vanadium ions form complexes with ligands and self-react to form isopolyanions. All vanadium species undergo oxidation-reduction reactions. With a few exceptions, elucidation of the dynamics of these reactions awaited the development of fast reaction techniques before the kinetics of elementary ligation, condensation, reduction, and oxidation of the aqueous vanadium ions could be investigated. As the biological roles played by endogenous and therapeutic vanadium expand, it is appropriate to bring the results of the diverse kinetics studies under one umbrella. To achieve this goal this review presents a systematic examination of elementary aqueous vanadium ion dynamics.

  6. JACOB: a dynamic database for computational chemistry benchmarking.

    PubMed

    Yang, Jack; Waller, Mark P

    2012-12-21

    JACOB (just a collection of benchmarks) is a database that contains four diverse benchmark studies, which in-turn included 72 data sets, with a total of 122,356 individual results. The database is constructed upon a dynamic web framework that allows users to retrieve data from the database via predefined categories. Additional flexibility is made available via user-defined text-based queries. Requested sets of results are then automatically presented as bar graphs, with parameters of the graphs being controllable via the URL. JACOB is currently available at www.wallerlab.org/jacob.

  7. Dynamical mean-field theory for quantum chemistry.

    PubMed

    Lin, Nan; Marianetti, C A; Millis, Andrew J; Reichman, David R

    2011-03-04

    The dynamical mean-field concept of approximating an unsolvable many-body problem in terms of the solution of an auxiliary quantum impurity problem, introduced to study bulk materials with a continuous energy spectrum, is here extended to molecules, i.e., finite systems with a discrete energy spectrum. The application to small clusters of hydrogen atoms yields ground state energies which are competitive with leading quantum chemical approaches at intermediate and large interatomic distances as well as good approximations to the excitation spectrum.

  8. Combinatorial optimization games

    SciTech Connect

    Deng, X.; Ibaraki, Toshihide; Nagamochi, Hiroshi

    1997-06-01

    We introduce a general integer programming formulation for a class of combinatorial optimization games, which immediately allows us to improve the algorithmic result for finding amputations in the core (an important solution concept in cooperative game theory) of the network flow game on simple networks by Kalai and Zemel. An interesting result is a general theorem that the core for this class of games is nonempty if and only if a related linear program has an integer optimal solution. We study the properties for this mathematical condition to hold for several interesting problems, and apply them to resolve algorithmic and complexity issues for their cores along the line as put forward in: decide whether the core is empty; if the core is empty, find an imputation in the core; given an imputation x, test whether x is in the core. We also explore the properties of totally balanced games in this succinct formulation of cooperative games.

  9. Biophysical chemistry.

    PubMed

    Häussinger, Daniel; Pfohl, Thomas

    2010-01-01

    Biophysical chemistry at the Department of Chemistry, University of Basel, covers the NMR analysis of protein-protein interaction using paramagnetic tags and sophisticated microscopy techniques investigating the dynamics of biological matter.

  10. Chemistry Notes

    ERIC Educational Resources Information Center

    School Science Review, 1972

    1972-01-01

    Thirteen ideas are presented that may be of use to chemistry teachers. Topics covered include vitamin C, industrial chemistry, electrical conductivity, electrolysis, alkali metals, vibration modes infra-red, dynamic equilibrium, and some new demonstrations in gaseous combinations. (PS)

  11. Determination of Quantum Chemistry Based Force Fields for Molecular Dynamics Simulations of Aromatic Polymers

    NASA Technical Reports Server (NTRS)

    Jaffe, Richard; Langhoff, Stephen R. (Technical Monitor)

    1995-01-01

    Ab initio quantum chemistry calculations for model molecules can be used to parameterize force fields for molecular dynamics simulations of polymers. Emphasis in our research group is on using quantum chemistry-based force fields for molecular dynamics simulations of organic polymers in the melt and glassy states, but the methodology is applicable to simulations of small molecules, multicomponent systems and solutions. Special attention is paid to deriving reliable descriptions of the non-bonded and electrostatic interactions. Several procedures have been developed for deriving and calibrating these parameters. Our force fields for aromatic polyimide simulations will be described. In this application, the intermolecular interactions are the critical factor in determining many properties of the polymer (including its color).

  12. Extended Lagrangian Born-Oppenheimer molecular dynamics simulations of the shock-induced chemistry of phenylacetylene

    SciTech Connect

    Cawkwell, M. J. Niklasson, Anders M. N.; Dattelbaum, Dana M.

    2015-02-14

    The initial chemical events that occur during the shock compression of liquid phenylacetylene have been investigated using self-consistent tight binding molecular dynamics simulations. The extended Lagrangian Born-Oppenheimer molecular dynamics formalism enabled us to compute microcanonical trajectories with precise conservation of the total energy. Our simulations revealed that the first density-increasing step under shock compression arises from the polymerization of phenylacetylene molecules at the acetylene moiety. The application of electronic structure-based molecular dynamics with long-term conservation of the total energy enabled us to identify electronic signatures of reactivity via monitoring changes in the HOMO-LUMO gap, and to capture directly adiabatic shock heating, transient non-equilibrium states, and changes in temperature arising from exothermic chemistry in classical molecular dynamics trajectories.

  13. Spatial and temporal dynamics of stream chemistry in a forested watershed impacted by atmospheric deposition

    NASA Astrophysics Data System (ADS)

    Piatek, K. B.; Christopher, S. F.; Mitchell, M. J.

    2008-09-01

    We analyzed spatial and temporal dynamics of solute chemistry in a forest watershed impacted by atmospheric deposition in the Adirondack Mountains of New York State, USA. Spatial dynamics of solute chemistry and natural abundance isotopes of nitrate (15N and 18O) were examined in 6 locations and the watershed outlet in 2001 and 2002. Temporal dynamics were examined during 5 discharge periods: winter, snowmelt, spring, summer, and fall, which were based on discharge levels at the outlet. Solute concentrations were statistically significantly different (p≤0.05) among stream sampling locations and discharge periods, with no interaction effects. Groundwater sources located in upper watershed controlled stream chemistry at higher elevations with highest pH, Ca2+, sum of base cations, Si, NO3-, total N, and SO42- and lowest Al concentrations. Two low elevation wetlands had a substantial influence over stream chemistry at those locations contributing lowest NO3-, total N, and highest DOC and DON. Snowmelt exhibited among the lowest pH, sum of base cations, and SO42-, and highest NO3-, total N, DON, and total Al; snowmelt appeared to dilute groundwater, and flush stored soil-derived solutes. Summer discharge, composed mainly of groundwater, exhibited the lowest flow, among the highest Mg2+, Ca2+, and lowest DON, DOC, and total Al concentrations. Isotopic analysis together with patterns of NH4+ versus NO3- dynamics indicated that NO3- was microbial, generated in fall and accumulated in winter in upper watershed soils, and flushed to stream during high discharge events. Highest discharge in snowmelt 2001, a summer drought in 2002, and fall storms following the drought were further evaluated for their specific effects on stream chemistry. Snowmelt 2001 had the lowest pH and highest NO3-, base flow during summer drought had the lowest total Al, and storms in fall 2002 had highest SO42- of all periods, but all other solute concentrations were comparable to other discharge

  14. Quantum combinatorial model of gene expression

    PubMed Central

    Grover, Monendra; Grover, Ritu; Singh, Rakesh; Kumar, Rajesh; Kumar, Sundeep

    2013-01-01

    We propose that the DNA within the chromatin behaves as a dynamic combinatorial library capable of forming novel structures by reversible processes. We also hypothesize that states within the library may be linked via quantum tunneling. RNA polymerase then could scan these states and the system decoheres to the “appropriate” state. Two ways of sustaining quantum coherence at relevant time scales could be possible, first, screening: the quantum system can be kept isolated from its decohering environment, second, the existence of decoherence free subspaces .We discuss the role of superconductivity in context of avoiding decoherence in context of our hypothesis. PMID:23422839

  15. Study of the diurnal variability of atmospheric chemistry with respect to boundary layer dynamics during DOMINO

    NASA Astrophysics Data System (ADS)

    van Stratum, B. J. H.; Vilà-Guerau de Arellano, J.; Ouwersloot, H. G.; van den Dries, K.; van Laar, T. W.; Martinez, M.; Lelieveld, J.; Diesch, J.-M.; Drewnick, F.; Fischer, H.; Hosaynali Beygi, Z.; Harder, H.; Regelin, E.; Sinha, V.; Adame, J. A.; Sörgel, M.; Sander, R.; Bozem, H.; Song, W.; Williams, J.; Yassaa, N.

    2012-03-01

    We study the interactions between atmospheric boundary layer (ABL) dynamics and atmospheric chemistry using a mixed-layer model (MXLCH) coupled to chemical reaction schemes. Guided by both atmospheric and chemical measurements obtained during the DOMINO campaign (2008), numerical experiments are performed to study the role of ABL dynamics and the accuracy of chemical schemes with different complexity: MOZART-4 and a reduced mechanism of this chemical system. Both schemes produce satisfactory results, indicating that the reduced scheme is capable of reproducing the O3-NOx-VOC-HOx diurnal cycle during conditions characterised by a low NOx regime and small O3 tendencies (less than 1 ppb per hour). By focussing on the budget equations of chemical species in the mixed-layer model, we show that for species like O3, NO and NO2, the influence of entrainment and boundary layer growth is of the same order as chemical production/loss. This indicates that an accurate representation of ABL processes is crucial in understanding the daily cycle of chemical species. By comparing the time scales of chemical reactive species with the mixing time scale of turbulence, we propose a classification based on the Damköhler number to further determine the importance of dynamics on chemistry during field campaigns. Our findings advocate an integrated approach, simultaneously solving the ABL dynamics and chemical reactions, in order to obtain a better understanding of chemical pathways and processes and the interpretation of the results obtained during measurement campaigns.

  16. Amplification without instability: applying fluid dynamical insights in chemistry and biology

    NASA Astrophysics Data System (ADS)

    McCoy, Jonathan H.

    2013-11-01

    While amplification of small perturbations often arises from instability, transient amplification is possible locally even in asymptotically stable systems. That is, knowledge of a system's stability properties can mislead one's intuition for its transient behaviors. This insight, which has an interesting history in fluid dynamics, has more recently been rediscovered in ecology. Surprisingly, many nonlinear fluid dynamical and ecological systems share linear features associated with transient amplification of noise. This paper aims to establish that these features are widespread in many other disciplines concerned with noisy systems, especially chemistry, cell biology and molecular biology. Here, using classic nonlinear systems and the graphical language of network science, we explore how the noise amplification problem can be reframed in terms of activatory and inhibitory interactions between dynamical variables. The interaction patterns considered here are found in a great variety of systems, ranging from autocatalytic reactions and activator-inhibitor systems to influential models of nerve conduction, glycolysis, cell signaling and circadian rhythms.

  17. Trends in Mesospheric Dynamics and Chemistry: Simulations With a Model of the Entire Atmosphere

    NASA Astrophysics Data System (ADS)

    Brasseur, G. P.

    2005-05-01

    The cooling resulting from infrared CO2 radiative transfer is a major contribution to the energy budget of the middle atmosphere and thermosphere. The rapid increase of the atmospheric CO2 concentration resulting from anthropogenic emissions is therefore expected to lead, in general, to a substantial cooling in this height range. This can potentially be counteracted by heating due to absorption of near infrared radiation by CO2. Changes in ozone as a consequence of increasing methane and water vapor may also have an impact on the energy budget as dynamical changes caused by increased tropospheric temperatures. By means of numerical simulations with a general circulation and chemistry model of the entire atmosphere we will address the following questions: 1.) Can state-of-the-art atmospheric modeling explain the mesospheric temperature trends observed during the last decades? 2.)Which part of the temperature changes resulting from an increase of atmospheric CO2 is caused by local changes in the radiative budget and which part is influenced by remote dynamical effects? The model used is the newly developed Hamburg Model of the Neutral and Ionized Atmosphere (HAMMONIA) that resolves the atmosphere from the Earth's surface up to about 250 km altitude, and is based on the 3-D dynamics from the ECHAM5 general circulation model and the chemistry scheme from MOZART-3. Results from different time slice experiment representative of years 1970 and 2000, and for a doubling of CO2 will be presented.

  18. Experimental Design for Combinatorial and High Throughput Materials Development

    NASA Astrophysics Data System (ADS)

    Cawse, James N.

    2002-12-01

    In the past decade, combinatorial and high throughput experimental methods have revolutionized the pharmaceutical industry, allowing researchers to conduct more experiments in a week than was previously possible in a year. Now high throughput experimentation is rapidly spreading from its origins in the pharmaceutical world to larger industrial research establishments such as GE and DuPont, and even to smaller companies and universities. Consequently, researchers need to know the kinds of problems, desired outcomes, and appropriate patterns for these new strategies. Editor James Cawse's far-reaching study identifies and applies, with specific examples, these important new principles and techniques. Experimental Design for Combinatorial and High Throughput Materials Development progresses from methods that are now standard, such as gradient arrays, to mathematical developments that are breaking new ground. The former will be particularly useful to researchers entering the field, while the latter should inspire and challenge advanced practitioners. The book's contents are contributed by leading researchers in their respective fields. Chapters include: -High Throughput Synthetic Approaches for the Investigation of Inorganic Phase Space -Combinatorial Mapping of Polymer Blends Phase Behavior -Split-Plot Designs -Artificial Neural Networks in Catalyst Development -The Monte Carlo Approach to Library Design and Redesign This book also contains over 200 useful charts and drawings. Industrial chemists, chemical engineers, materials scientists, and physicists working in combinatorial and high throughput chemistry will find James Cawse's study to be an invaluable resource.

  19. Invention as a combinatorial process: evidence from US patents.

    PubMed

    Youn, Hyejin; Strumsky, Deborah; Bettencourt, Luis M A; Lobo, José

    2015-05-06

    Invention has been commonly conceptualized as a search over a space of combinatorial possibilities. Despite the existence of a rich literature, spanning a variety of disciplines, elaborating on the recombinant nature of invention, we lack a formal and quantitative characterization of the combinatorial process underpinning inventive activity. Here, we use US patent records dating from 1790 to 2010 to formally characterize invention as a combinatorial process. To do this, we treat patented inventions as carriers of technologies and avail ourselves of the elaborate system of technology codes used by the United States Patent and Trademark Office to classify the technologies responsible for an invention's novelty. We find that the combinatorial inventive process exhibits an invariant rate of 'exploitation' (refinements of existing combinations of technologies) and 'exploration' (the development of new technological combinations). This combinatorial dynamic contrasts sharply with the creation of new technological capabilities-the building blocks to be combined-that has significantly slowed down. We also find that, notwithstanding the very reduced rate at which new technologies are introduced, the generation of novel technological combinations engenders a practically infinite space of technological configurations.

  20. Invention as a combinatorial process: evidence from US patents

    PubMed Central

    Youn, Hyejin; Strumsky, Deborah; Bettencourt, Luis M. A.; Lobo, José

    2015-01-01

    Invention has been commonly conceptualized as a search over a space of combinatorial possibilities. Despite the existence of a rich literature, spanning a variety of disciplines, elaborating on the recombinant nature of invention, we lack a formal and quantitative characterization of the combinatorial process underpinning inventive activity. Here, we use US patent records dating from 1790 to 2010 to formally characterize invention as a combinatorial process. To do this, we treat patented inventions as carriers of technologies and avail ourselves of the elaborate system of technology codes used by the United States Patent and Trademark Office to classify the technologies responsible for an invention's novelty. We find that the combinatorial inventive process exhibits an invariant rate of ‘exploitation’ (refinements of existing combinations of technologies) and ‘exploration’ (the development of new technological combinations). This combinatorial dynamic contrasts sharply with the creation of new technological capabilities—the building blocks to be combined—that has significantly slowed down. We also find that, notwithstanding the very reduced rate at which new technologies are introduced, the generation of novel technological combinations engenders a practically infinite space of technological configurations. PMID:25904530

  1. Measuring and Specifying Combinatorial Coverage of Test Input Configurations.

    PubMed

    Kuhn, D Richard; Kacker, Raghu N; Lei, Yu

    2016-12-01

    A key issue in testing is how many tests are needed for a required level of coverage or fault detection. Estimates are often based on error rates in initial testing, or on code coverage. For example, tests may be run until a desired level of statement or branch coverage is achieved. Combinatorial methods present an opportunity for a different approach to estimating required test set size, using characteristics of the test set. This paper describes methods for estimating the coverage of, and ability to detect, t-way interaction faults of a test set based on a covering array. We also develop a connection between (static) combinatorial coverage and (dynamic) code coverage, such that if a specific condition is satisfied, 100% branch coverage is assured. Using these results, we propose practical recommendations for using combinatorial coverage in specifying test requirements.

  2. Triazolinediones enable ultrafast and reversible click chemistry for the design of dynamic polymer systems

    NASA Astrophysics Data System (ADS)

    Billiet, Stijn; de Bruycker, Kevin; Driessen, Frank; Goossens, Hannelore; van Speybroeck, Veronique; Winne, Johan M.; Du Prez, Filip E.

    2014-09-01

    With its focus on synthetic reactions that are highly specific and reliable, ‘click’ chemistry has become a valuable tool for many scientific research areas and applications. Combining the modular, covalently bonded nature of click-chemistry linkages with an ability to reverse these linkages and reuse the constituent reactants in another click reaction, however, is a feature that is not found in most click reactions. Here we show that triazolinedione compounds can be used in click-chemistry applications. We present examples of simple and ultrafast macromolecular functionalization, polymer-polymer linking and polymer crosslinking under ambient conditions without the need for a catalyst. Moreover, when triazolinediones are combined with indole reaction partners, the reverse reaction can also be induced at elevated temperatures, and the triazolinedione reacted with a different reaction partner, reversibly or irreversibly dependent on its exact nature. We have used this ‘transclick’ reaction to introduce thermoreversible links into polyurethane and polymethacrylate materials, which allows dynamic polymer-network healing, reshaping and recycling.

  3. Interactions between snow chemistry, mercury inputs and microbial population dynamics in an Arctic snowpack.

    PubMed

    Larose, Catherine; Prestat, Emmanuel; Cecillon, Sébastien; Berger, Sibel; Malandain, Cédric; Lyon, Delina; Ferrari, Christophe; Schneider, Dominique; Dommergue, Aurélien; Vogel, Timothy M

    2013-01-01

    We investigated the interactions between snowpack chemistry, mercury (Hg) contamination and microbial community structure and function in Arctic snow. Snowpack chemistry (inorganic and organic ions) including mercury (Hg) speciation was studied in samples collected during a two-month field study in a high Arctic site, Svalbard, Norway (79 °N). Shifts in microbial community structure were determined by using a 16S rRNA gene phylogenetic microarray. We linked snowpack and meltwater chemistry to changes in microbial community structure by using co-inertia analyses (CIA) and explored changes in community function due to Hg contamination by q-PCR quantification of Hg-resistance genes in metagenomic samples. Based on the CIA, chemical and microbial data were linked (p = 0.006) with bioavailable Hg (BioHg) and methylmercury (MeHg) contributing significantly to the ordination of samples. Mercury was shown to influence community function with increases in merA gene copy numbers at low BioHg levels. Our results show that snowpacks can be considered as dynamic habitats with microbial and chemical components responding rapidly to environmental changes.

  4. Molecular dynamics for irradiation driven chemistry: application to the FEBID process*

    NASA Astrophysics Data System (ADS)

    Sushko, Gennady B.; Solov'yov, Ilia A.; Solov'yov, Andrey V.

    2016-10-01

    A new molecular dynamics (MD) approach for computer simulations of irradiation driven chemical transformations of complex molecular systems is suggested. The approach is based on the fact that irradiation induced quantum transformations can often be treated as random, fast and local processes involving small molecules or molecular fragments. We advocate that the quantum transformations, such as molecular bond breaks, creation and annihilation of dangling bonds, electronic charge redistributions, changes in molecular topologies, etc., could be incorporated locally into the molecular force fields that describe the classical MD of complex molecular systems under irradiation. The proposed irradiation driven molecular dynamics (IDMD) methodology is designed for the molecular level description of the irradiation driven chemistry. The IDMD approach is implemented into the MBN Explorer software package capable to operate with a large library of classical potentials, many-body force fields and their combinations. IDMD opens a broad range of possibilities for modelling of irradiation driven modifications and chemistry of complex molecular systems ranging from radiotherapy cancer treatments to the modern technologies such as focused electron beam deposition (FEBID). As an example, the new methodology is applied for studying the irradiation driven chemistry caused by FEBID of tungsten hexacarbonyl W(CO)6 precursor molecules on a hydroxylated SiO2 surface. It is demonstrated that knowing the interaction parameters for the fragments of the molecular system arising in the course of irradiation one can reproduce reasonably well experimental observations and make predictions about the morphology and molecular composition of nanostructures that emerge on the surface during the FEBID process.

  5. Effects of Aircraft Wake Dynamics on Measured and Simulated NO(x) and HO(x) Wake Chemistry. Appendix B

    NASA Technical Reports Server (NTRS)

    Lewellen, D. C.; Lewellen, W. S.

    2001-01-01

    High-resolution numerical large-eddy simulations of the near wake of a B757 including simplified NOx and HOx chemistry were performed to explore the effects of dynamics on chemistry in wakes of ages from a few seconds to several minutes. Dilution plays an important basic role in the NOx-O3 chemistry in the wake, while a more interesting interaction between the chemistry and dynamics occurs for the HOx species. These simulation results are compared with published measurements of OH and HO2 within a B757 wake under cruise conditions in the upper troposphere taken during the Subsonic Aircraft Contrail and Cloud Effects Special Study (SUCCESS) mission in May 1996. The simulation provides a much finer grained representation of the chemistry and dynamics of the early wake than is possible from the 1 s data samples taken in situ. The comparison suggests that the previously reported discrepancy of up to a factor of 20 - 50 between the SUCCESS measurements of the [HO2]/[OH] ratio and that predicted by simplified theoretical computations is due to the combined effects of large mixing rates around the wake plume edges and averaging over volumes containing large species fluctuations. The results demonstrate the feasibility of using three-dimensional unsteady large-eddy simulations with coupled chemistry to study such phenomena.

  6. Combinatorial synthesis of ceramic materials

    DOEpatents

    Lauf, Robert J [Oak Ridge, TN; Walls, Claudia A [Oak Ridge, TN; Boatner, Lynn A [Oak Ridge, TN

    2010-02-23

    A combinatorial library includes a gelcast substrate defining a plurality of cavities in at least one surface thereof; and a plurality of gelcast test materials in the cavities, at least two of the test materials differing from the substrate in at least one compositional characteristic, the two test materials differing from each other in at least one compositional characteristic.

  7. Combinatorial synthesis of ceramic materials

    DOEpatents

    Lauf, Robert J.; Walls, Claudia A.; Boatner, Lynn A.

    2006-11-14

    A combinatorial library includes a gelcast substrate defining a plurality of cavities in at least one surface thereof; and a plurality of gelcast test materials in the cavities, at least two of the test materials differing from the substrate in at least one compositional characteristic, the two test materials differing from each other in at least one compositional characteristic.

  8. Microfluidic platform for combinatorial synthesis in picolitre droplets.

    PubMed

    Theberge, Ashleigh B; Mayot, Estelle; El Harrak, Abdeslam; Kleinschmidt, Felix; Huck, Wilhelm T S; Griffiths, Andrew D

    2012-04-07

    This paper presents a droplet-based microfluidic platform for miniaturized combinatorial synthesis. As a proof of concept, a library of small molecules for early stage drug screening was produced. We present an efficient strategy for producing a 7 × 3 library of potential thrombin inhibitors that can be utilized for other combinatorial synthesis applications. Picolitre droplets containing the first type of reagent (reagents A(1), A(2), …, A(m)) were formed individually in identical microfluidic chips and then stored off chip with the aid of stabilizing surfactants. These droplets were then mixed to form a library of droplets containing reagents A(1-m), each individually compartmentalized, which was reinjected into a second microfluidic chip and combinatorially fused with picolitre droplets containing the second reagent (reagents B(1), B(2), …, B(n)) that were formed on chip. The concept was demonstrated with a three-component Ugi-type reaction involving an amine (reagents A(1-3)), an aldehyde (reagents B(1-7)), and an isocyanide (held constant), to synthesize a library of small molecules with potential thrombin inhibitory activity. Our technique produced 10(6) droplets of each reaction at a rate of 2.3 kHz. Each droplet had a reaction volume of 3.1 pL, at least six orders of magnitude lower than conventional techniques. The droplets can then be divided into aliquots for different downstream screening applications. In addition to medicinal chemistry applications, this combinatorial droplet-based approach holds great potential for other applications that involve sampling large areas of chemical parameter space with minimal reagent consumption; such an approach could be beneficial when optimizing reaction conditions or performing combinatorial reactions aimed at producing novel materials.

  9. Combinatorial biosynthesis of RiPPs: Docking with marine life

    PubMed Central

    Sardar, Debosmita; Schmidt, Eric W.

    2016-01-01

    Ribosomally synthesized natural products are found in all forms of life. Their biosynthesis uses simple ribosomally synthesized peptides as starting materials that are transformed into complex structures via posttranslational modifications, enriched with elaborate chemical scaffolds that make them desirable as pharmacological tools. In addition, these natural products often exhibit combinatorial biosynthesis, making them attractive targets for engineering. An increasing knowledge of their biosynthetic machinery has provided key insights into their fascinating chemistry. Marine organisms have been a rich source of this class of natural products and here we review the lessons learned from marine life that enables exploitation of their potential for combinatorial engineering, opening up new routes for peptide-based drug discovery. PMID:26709871

  10. Why is combinatorial communication rare in the natural world, and why is language an exception to this trend?

    PubMed Central

    Scott-Phillips, Thomas C.; Blythe, Richard A.

    2013-01-01

    In a combinatorial communication system, some signals consist of the combinations of other signals. Such systems are more efficient than equivalent, non-combinatorial systems, yet despite this they are rare in nature. Why? Previous explanations have focused on the adaptive limits of combinatorial communication, or on its purported cognitive difficulties, but neither of these explains the full distribution of combinatorial communication in the natural world. Here, we present a nonlinear dynamical model of the emergence of combinatorial communication that, unlike previous models, considers how initially non-communicative behaviour evolves to take on a communicative function. We derive three basic principles about the emergence of combinatorial communication. We hence show that the interdependence of signals and responses places significant constraints on the historical pathways by which combinatorial signals might emerge, to the extent that anything other than the most simple form of combinatorial communication is extremely unlikely. We also argue that these constraints can be bypassed if individuals have the socio-cognitive capacity to engage in ostensive communication. Humans, but probably no other species, have this ability. This may explain why language, which is massively combinatorial, is such an extreme exception to nature's general trend for non-combinatorial communication. PMID:24047871

  11. Why is combinatorial communication rare in the natural world, and why is language an exception to this trend?

    PubMed

    Scott-Phillips, Thomas C; Blythe, Richard A

    2013-11-06

    In a combinatorial communication system, some signals consist of the combinations of other signals. Such systems are more efficient than equivalent, non-combinatorial systems, yet despite this they are rare in nature. Why? Previous explanations have focused on the adaptive limits of combinatorial communication, or on its purported cognitive difficulties, but neither of these explains the full distribution of combinatorial communication in the natural world. Here, we present a nonlinear dynamical model of the emergence of combinatorial communication that, unlike previous models, considers how initially non-communicative behaviour evolves to take on a communicative function. We derive three basic principles about the emergence of combinatorial communication. We hence show that the interdependence of signals and responses places significant constraints on the historical pathways by which combinatorial signals might emerge, to the extent that anything other than the most simple form of combinatorial communication is extremely unlikely. We also argue that these constraints can be bypassed if individuals have the socio-cognitive capacity to engage in ostensive communication. Humans, but probably no other species, have this ability. This may explain why language, which is massively combinatorial, is such an extreme exception to nature's general trend for non-combinatorial communication.

  12. Label-free in situ imaging of oil body dynamics and chemistry in germination

    PubMed Central

    Waschatko, Gustav; Billecke, Nils; Schwendy, Sascha; Jaurich, Henriette; Bonn, Mischa; Vilgis, Thomas A.

    2016-01-01

    Plant oleosomes are uniquely emulsified lipid reservoirs that serve as the primary energy source during seed germination. These oil bodies undergo significant changes regarding their size, composition and structure during normal seedling development; however, a detailed characterization of these oil body dynamics, which critically affect oil body extractability and nutritional value, has remained challenging because of a limited ability to monitor oil body location and composition during germination in situ. Here, we demonstrate via in situ, label-free imaging that oil bodies are highly dynamic intracellular organelles that are morphologically and biochemically remodelled extensively during germination. Label-free, coherent Raman microscopy (CRM) combined with bulk biochemical measurements revealed the temporal and spatial regulation of oil bodies in native soya bean cotyledons during the first eight days of germination. Oil bodies undergo a cycle of growth and shrinkage that is paralleled by lipid and protein compositional changes. Specifically, the total protein concentration associated with oil bodies increases in the first phase of germination and subsequently decreases. Lipids contained within the oil bodies change in saturation and chain length during germination. Our results show that CRM is a well-suited platform to monitor in situ lipid dynamics and local chemistry and that oil bodies are actively remodelled during germination. This underscores the dynamic role of lipid reservoirs in plant development. PMID:27798279

  13. Spatial and temporal dynamics of stream chemistry in a forested watershed

    NASA Astrophysics Data System (ADS)

    Piatek, K. B.; Christopher, S. F.; Mitchell, M. J.

    2009-03-01

    Spatial dynamics of solute chemistry and natural abundance isotopes of nitrate (15N and 18O) were examined in seven locations and at the watershed outlet in 2001 and 2002 in a forest watershed in the Adirondack Mountains of New York State, USA. Temporal dynamics were examined during five discharge periods: winter, snowmelt, spring, summer, and fall, based on discharge levels at the watershed outlet. Solute concentrations were variable across space and time with significant (p≤0.05) interaction effects. Year*period was significant for pH, NH4+, NO3-, total N, DOC, and total Al suggesting that inter-annual variability in discharge levels was more important for these solutes than intra-annual variability. Period*sampling point was significant for pH, Mg2+, Ca2+, sum of base cations, Si, and total Al suggesting that the differences in concentration of these solutes among sampling points were moderated by discharge levels. In general, groundwater sources located in upper watershed controlled stream chemistry at higher elevations with highest pH, Ca2+, sum of base cations, Si, and SO42- concentrations, with higher values in summer, and dilution effects during snowmelt. Two low elevation wetlands had a substantial influence over stream chemistry at those locations contributing lowest NO3- and highest DOC. Snowmelt exhibited among the lowest pH, sum of base cations, and SO42-, and highest NO3-, total N, and total Al; snowmelt appeared to dilute groundwater, and flush stored soil-derived solutes. Summer discharge, composed mainly of groundwater, exhibited the lowest flow, among the highest Mg2+, Ca2+, and lowest DON, DOC, and total Al concentrations. Isotopic analysis indicated that NO3- was microbial with primary source in upper watershed soil, from where it was flushed to stream under high discharge-conditions, or drained to groundwater which became its secondary source when discharge was low. Watershed outlet did not exhibit specific solute levels found at source

  14. Spatial and temporal dynamics of stream chemistry in a northern forest watershed.

    NASA Astrophysics Data System (ADS)

    Piatek, K. B.; Christopher, S. F.; Mitchell, M. J.

    2009-05-01

    Spatial dynamics of solute chemistry and natural abundance isotopes of nitrate (15N and 18O) were examined in six locations and at the watershed outlet in 2001 and 2002 in a forest watershed in the Adirondack Mountains of New York State, U.S.A. Temporal dynamics were examined during five discharge periods: winter, snowmelt, spring, summer, and fall, based on discharge levels at the watershed outlet. Solute concentrations were variable across space and time with significant (pÜ0.05) interaction effects. Year*period was significant for pH, NO3-, total N, DOC, and total Al suggesting that inter-annual variability in discharge levels was more important for these solutes than intra-annual variability. Period*sampling point was significant for pH, Mg2+, Ca2+, sum of base cations, Si, and total Al suggesting that the differences in concentration of these solutes among sampling points were moderated by discharge levels. In general, groundwater sources located in upper watershed controlled stream chemistry at higher elevations with highest pH, Ca2+, sum of base cations, Si, SO42- concentrations, with higher values in summer, and dilution effects during snowmelt. Two low elevation wetlands had a substantial influence over stream chemistry at those locations contributing lowest NO3- and highest DOC. Snowmelt exhibited among the lowest pH, sum of base cations, and SO42-, and highest NO3-, total N, and total Al; snowmelt appeared to dilute groundwater, and flush stored soil-derived solutes. Summer discharge, composed mainly of groundwater, exhibited the lowest flow, among the highest Mg2+, Ca2+, and lowest DON, DOC, and total Al concentrations. Isotopic analysis indicated that NO3- was microbial with primary source in upper watershed soil, from where it was flushed to stream under high discharge-conditions, or drained to groundwater which became its secondary source when discharge was less. Watershed outlet did not exhibit specific solute levels found at source-areas, but

  15. Combinatorial microfluidic droplet engineering for biomimetic material synthesis

    PubMed Central

    Bawazer, Lukmaan A.; McNally, Ciara S.; Empson, Christopher J.; Marchant, William J.; Comyn, Tim P.; Niu, Xize; Cho, Soongwon; McPherson, Michael J.; Binks, Bernard P.; deMello, Andrew; Meldrum, Fiona C.

    2016-01-01

    Although droplet-based systems are used in a wide range of technologies, opportunities for systematically customizing their interface chemistries remain relatively unexplored. This article describes a new microfluidic strategy for rapidly tailoring emulsion droplet compositions and properties. The approach uses a simple platform for screening arrays of droplet-based microfluidic devices and couples this with combinatorial selection of the droplet compositions. Through the application of genetic algorithms over multiple screening rounds, droplets with target properties can be rapidly generated. The potential of this method is demonstrated by creating droplets with enhanced stability, where this is achieved by selecting carrier fluid chemistries that promote titanium dioxide formation at the droplet interfaces. The interface is a mixture of amorphous and crystalline phases, and the resulting composite droplets are biocompatible, supporting in vitro protein expression in their interiors. This general strategy will find widespread application in advancing emulsion properties for use in chemistry, biology, materials, and medicine. PMID:27730209

  16. Combining research in physical chemistry and chemical education: Part A. The femtosecond molecular dynamics of small gas-phase anion clusters. Part B. Surveying student beliefs about chemistry and the development of physical chemistry learning tutorials

    NASA Astrophysics Data System (ADS)

    Barbera, Jack

    2007-12-01

    This dissertation combines work in the areas of experimental physical chemistry and chemical education. In the area of physical chemistry, femtosecond pump-probe spectroscopy is used to interrogate the time-dependence for energy redistribution, solvent reorientation, and dissociation dynamics in small gas-phase anion clusters. The chemical education research addressed in this manuscript include the development and validation of a survey to measure students' beliefs about chemistry and the learning of chemistry and the development and testing of learning tutorials for use in undergraduate physical chemistry courses in thermodynamics and kinetics. In the first part of this dissertation, the Cu(CD3OD) dynamics are investigated using a combination of femtosecond pump-probe experiments and ab initio calculations. Dissociation of this complex into Cu and CD3OD occurs on two distinct time scales: 3 and 30 ps, which arise, respectively, from the coupling of intermolecular solvent rotations and excited methyl rotor rotation into the Cu-O dissociation component upon electron photodetachment of the precursor anion. In the second part of this dissertation, the time-resolved recombination of photodissociated IBr-(CO2)n (n = 5 - 10) cluster anions is investigated. Upon excitation to the A' 2pi 1/2 state of the chromophore, the bare anion results in I- and Br products, upon solvation with CO2, the IBr- chromophore regains near-IR absorption after recombination and vibrational relaxation on the ground electronic state. The recombination times vary with the number of solvent molecules from 12 ps for n = 5 to 900 ps for n = 10. Extensive electronic structure and non-adiabatic molecular dynamic simulations provide a framework to understand this behavior. In the third part of this dissertation, the modification and validation of the Colorado Learning Attitudes about Science Survey (CLASS) for use in chemistry is presented in detail. The CLASS survey is designed to measure student

  17. Proton enhanced dynamic battery chemistry for aprotic lithium–oxygen batteries

    DOE PAGES

    Zhu, Yun Guang; Liu, Qi; Rong, Yangchun; ...

    2017-02-06

    Water is generally considered to be deteriorating to the performance of aprotic Li-air batteries, while it is challenged by the disparate effects observed recently. This has provoked a range of discussion on the role of water and its impact on the battery operation. In this work, a distinct battery chemistry that prevails in water-contaminated aprotic Li-O2 batteries was discovered. Both lithium ions and protons were found to be involved in the oxygen reduction (ORR) and evolution reactions (OER), and LiOOH and LiOH were identified as predominant materials in the discharge product. As a new lithium compound, the crystallographic and spectroscopicmore » characteristics of LiOOH∙H2O were scrutinized both experimentally and theoretically. The structure of LiOOH∙H2O was found to be closely related to that of LiOH∙H2O implying a fast conversion kinetics between the two phases. Intriguingly, LiOOH∙H2O exhibits superior dynamic property towards the reaction with I3-, which renders considerably lower overpotential during the charging process. We anticipate that the new battery chemistry unveiled in this mechanistic study would provide important insights to the understanding of nominally aprotic Li-O2 batteries and help to tackle the critical issues confronted.« less

  18. Size distribution dynamics reveal particle-phase chemistry in organic aerosol formation.

    PubMed

    Shiraiwa, Manabu; Yee, Lindsay D; Schilling, Katherine A; Loza, Christine L; Craven, Jill S; Zuend, Andreas; Ziemann, Paul J; Seinfeld, John H

    2013-07-16

    Organic aerosols are ubiquitous in the atmosphere and play a central role in climate, air quality, and public health. The aerosol size distribution is key in determining its optical properties and cloud condensation nucleus activity. The dominant portion of organic aerosol is formed through gas-phase oxidation of volatile organic compounds, so-called secondary organic aerosols (SOAs). Typical experimental measurements of SOA formation include total SOA mass and atomic oxygen-to-carbon ratio. These measurements, alone, are generally insufficient to reveal the extent to which condensed-phase reactions occur in conjunction with the multigeneration gas-phase photooxidation. Combining laboratory chamber experiments and kinetic gas-particle modeling for the dodecane SOA system, here we show that the presence of particle-phase chemistry is reflected in the evolution of the SOA size distribution as well as its mass concentration. Particle-phase reactions are predicted to occur mainly at the particle surface, and the reaction products contribute more than half of the SOA mass. Chamber photooxidation with a midexperiment aldehyde injection confirms that heterogeneous reaction of aldehydes with organic hydroperoxides forming peroxyhemiacetals can lead to a large increase in SOA mass. Although experiments need to be conducted with other SOA precursor hydrocarbons, current results demonstrate coupling between particle-phase chemistry and size distribution dynamics in the formation of SOAs, thereby opening up an avenue for analysis of the SOA formation process.

  19. An integrated microfluidic device for two-dimensional combinatorial dilution†

    PubMed Central

    Jang, Yun-Ho; Hancock, Matthew J.; Kim, Sang Bok; Selimović, Šeila; Sim, Woo Young; Bae, Hojae; Khademhosseini, Ali

    2012-01-01

    High-throughput preparation of multi-component solutions is an integral process in biology, chemistry and materials science for screening, diagnostics and analysis. Compact microfluidic systems enable such processing with low reagent volumes and rapid testing. Here we present a microfluidic device that incorporates two gradient generators, a tree-like generator and a new microfluidic active injection system, interfaced by intermediate solution reservoirs to generate diluted combinations of input solutions within an 8 × 8 or 10 × 10 array of isolated test chambers. Three input solutions were fed into the device, two to the tree-like gradient generator and one to pre-fill the test chamber array. The relative concentrations of these three input solutions in the test chambers completely characterized device behaviour and were controlled by the number of injection cycles and the flow rate. Device behaviour was modelled by computational fluid dynamics simulations and an approximate analytic formula. The device may be used for two-dimensional (2D) combinatorial dilution by adding two solutions in different relative concentrations to each of its three inputs. By appropriate choice of the two-component input solutions, test chamber concentrations that span any triangle in 2D concentration space may be obtained. In particular, explicit inputs are given for a coarse screening of a large region in concentration space followed by a more refined screening of a smaller region, including alternate inputs that span the same concentration region but with different distributions. The ability to probe arbitrary subspaces of concentration space and to control the distribution of discrete test points within those subspaces makes the device of potential benefit for high-throughput cell biology studies and drug screening. PMID:21837312

  20. Upper atmosphere research satellite program. [to study the chemistry energetics, and dynamics

    NASA Technical Reports Server (NTRS)

    Huntress, W. T., Jr.

    1978-01-01

    A satellite program to conduct research on the chemistry, energetics, and dynamics of the upper atmosphere was developed. The scientific goals of the Upper Atmospheric Research Program, the program requirements, and the approach toward meeting those requirements are outlined. An initial series of two overlapping spacecraft missions is described. Both spacecraft are launched and recovered by the STS, one in the winter of 1983 at a 56 deg inclination, and the other a year later at a 70 deg inclination. The duration of each mission is 18 months, and each carries instruments to make global measurements of the temperature, winds, composition, irradation, and radiance in the stratosphere, mesosphere, and lower thermosphere between the tropopause and 120 km altitude. The program requires a dedicated ground-based data system and a science team organization that leads to a strong interaction between the experiments and theory. The program includes supportive observations from other platforms such as rockets, balloons, and the Spacelab.

  1. Partial Overhaul and Initial Parallel Optimization of KINETICS, a Coupled Dynamics and Chemistry Atmosphere Model

    NASA Technical Reports Server (NTRS)

    Nguyen, Howard; Willacy, Karen; Allen, Mark

    2012-01-01

    KINETICS is a coupled dynamics and chemistry atmosphere model that is data intensive and computationally demanding. The potential performance gain from using a supercomputer motivates the adaptation from a serial version to a parallelized one. Although the initial parallelization had been done, bottlenecks caused by an abundance of communication calls between processors led to an unfavorable drop in performance. Before starting on the parallel optimization process, a partial overhaul was required because a large emphasis was placed on streamlining the code for user convenience and revising the program to accommodate the new supercomputers at Caltech and JPL. After the first round of optimizations, the partial runtime was reduced by a factor of 23; however, performance gains are dependent on the size of the data, the number of processors requested, and the computer used.

  2. PINCA: A scalable parallel program for compressible gas dynamics with nonequilibrium chemistry

    NASA Astrophysics Data System (ADS)

    Wong, C. C.; Blottner, F. G.; Payne, J. L.; Soetrisno, M.; Imlay, S. T.

    1995-04-01

    This report documents an exploratory research work, funded by the Laboratory Directed Research and Development (LDRD) office at Sandia National Laboratories, to develop an advanced, general purpose, robust compressible flow solver for handling large, complex, chemically reacting gas dynamics problems. The deliverable of this project, a computer program called PINCA (Parallel INtegrated Computer Analysis) will run on massively parallel computers such as the Intel/Gamma and Intel/Paragon. With the development of this parallel compressible flow solver, engineers will be better able to address large three-dimensional scientific arid engineering problems involving multi-component gas mixtures with finite rate chemistry. These problems occur in high temperature industrial processes, combustion, and hypersonic: reentry of space-crafts.

  3. Stem cells and combinatorial science.

    PubMed

    Fang, Yue Qin; Wong, Wan Qing; Yap, Yan Wen; Orner, Brendan P

    2007-09-01

    Stem cell-based technologies have the potential to help cure a number of cell degenerative diseases. Combinatorial and high throughput screening techniques could provide tools to control and manipulate the self-renewal and differentiation of stem cells. This review chronicles historic and recent progress in the stem cell field involving both pluripotent and multipotent cells, and it highlights relevant cellular signal transduction pathways. This review further describes screens using libraries of soluble, small-molecule ligands, and arrays of molecules immobilized onto surfaces while proposing future trends in similar studies. It is hoped that by reviewing both the stem cell and the relevant high throughput screening literature, this paper can act as a resource to the combinatorial science community.

  4. Combinatorial 3D Mechanical Metamaterials

    NASA Astrophysics Data System (ADS)

    Coulais, Corentin; Teomy, Eial; de Reus, Koen; Shokef, Yair; van Hecke, Martin

    2015-03-01

    We present a class of elastic structures which exhibit 3D-folding motion. Our structures consist of cubic lattices of anisotropic unit cells that can be tiled in a complex combinatorial fashion. We design and 3d-print this complex ordered mechanism, in which we combine elastic hinges and defects to tailor the mechanics of the material. Finally, we use this large design space to encode smart functionalities such as surface patterning and multistability.

  5. Urban street canyons: Coupling dynamics, chemistry and within-canyon chemical processing of emissions

    NASA Astrophysics Data System (ADS)

    Bright, Vivien Bianca; Bloss, William James; Cai, Xiaoming

    2013-04-01

    Street canyons, formed by rows of buildings in urban environments, are associated with high levels of atmospheric pollutants emitted primarily from vehicles, and substantial human exposure. The street canyon forms a semi-enclosed environment, within which emissions may be entrained in a re-circulatory system; chemical processing of emitted compounds alters the composition of the air vented to the overlying boundary layer, compared with the primary emissions. As the prevailing atmospheric chemistry is highly non-linear, and the canyon mixing and predominant chemical reaction timescales are comparable, the combined impacts of dynamics and chemistry must be considered to quantify these effects. Here we report a model study of the coupled impacts of dynamical and chemical processing upon the atmospheric composition in a street canyon environment, to assess the impacts upon air pollutant levels within the canyon, and to quantify the extent to which within-canyon chemical processing alters the composition of canyon outflow, in comparison to the primary emissions within the canyon. A new model for the simulation of street canyon atmospheric chemical processing has been developed, by integrating an existing Large-Eddy Simulation (LES) dynamical model of canyon atmospheric motion with a detailed chemical reaction mechanism, a Reduced Chemical Scheme (RCS) comprising 51 chemical species and 136 reactions, based upon a subset of the Master Chemical Mechanism (MCM). The combined LES-RCS model is used to investigate the combined effects of mixing and chemical processing upon air quality within an idealised street canyon. The effect of the combination of dynamical (segregation) and chemical effects is determined by comparing the outputs of the full LES-RCS canyon model with those obtained when representing the canyon as a zero-dimensional box model (i.e. assuming mixing is complete and instantaneous). The LES-RCS approach predicts lower (canyon-averaged) levels of NOx, OH and HO

  6. Implementation of a Research-Based Lab Module in a High School Chemistry Curriculum: A Study of Classroom Dynamics

    ERIC Educational Resources Information Center

    Pilarz, Matthew

    2013-01-01

    For this study, a research-based lab module was implemented in two high school chemistry classes for the purpose of examining classroom dynamics throughout the process of students completing the module. A research-based lab module developed for use in undergraduate laboratories by the Center for Authentic Science Practice in Education (CASPiE) was…

  7. Comparative molecular surface analysis (CoMSA) for virtual combinatorial library screening of styrylquinoline HIV-1 blocking agents.

    PubMed

    Niedbala, Halina; Polanski, Jaroslaw; Gieleciak, Rafal; Musiol, Robert; Tabak, Dominik; Podeszwa, Barbara; Bak, Andrzej; Palka, Anna; Mouscadet, Jean-Francois; Gasteiger, Johann; Le Bret, Marc

    2006-12-01

    We used comparative molecular surface analysis to design molecules for the synthesis as part of the search for new HIV-1 integrase inhibitors. We analyzed the virtual combinatorial library (VCL) constituted from various moieties of styrylquinoline and styrylquinazoline inhibitors. Since imines can be applied in a strategy of dynamic combinatorial chemistry (DCC), we also tested similar compounds in which the -C=N- or -N=C- linker connected the heteroaromatic and aromatic moieties. We then used principal component analysis (PCA) or self-organizing maps (SOM), namely, the Kohonen neural networks to obtain a clustering plot analyzing the diversity of the VCL formed. Previously synthesized compounds of known activity, used as molecular probes, were projected onto this plot, which provided a set of promising virtual drugs. Moreover, we further modified the above mentioned VCL to include the single bond linker -C-N- or -N-C-. This allowed increasing compound stability but expanded also the diversity between the available molecular probes and virtual targets. The application of the CoMSA with SOM indicated important differences between such compounds and active molecular probes. We synthesized such compounds to verify the computational predictions.

  8. Spatial and Temporal Dynamics of Carbonate Chemistry in the Northwestern Hawaiian Islands

    NASA Astrophysics Data System (ADS)

    Coughlin, C.; Winn, C. D.; Kahng, S.

    2014-12-01

    The rapid increase in atmospheric and surface ocean CO2 concentrations has the potential to drastically alter the metabolic processes particularly in nearshore ecosystems. However, much of what is known about carbonate chemistry is based on observations and analysis of surface waters of the open ocean where spatial and temporal variability is far less dynamic than in nearshore coral reef ecosystems. Carbon system dynamics data from four consecutive years has been examined in the coastal and nearshore waters of the Papahānaumokuākea Marine National Monument in the Northwest Hawaiian Islands. This data has been collected for the purpose of improving our understanding of the carbon system dynamics in this unique and pristine environment. The data collected includes continuous CTD data and discrete bottle samples, as well as continuous underway measurements. In addition to standard hydrographic profile data, water column alkalinity and pH have been measured on discrete water samples, and continuous underway measurements of pCO2 and pH have been obtained. This data is used to investigate the impact of NWHI coral reef ecosystems on the carbon system in and surrounding the archipelago. The data demonstrates that a significant "island mass effect" with respect to the oceanographic carbon system exists around the islands within the archipelago. In addition, spatial and temporal variability of several oceanographic features that exhibit a radial, latitudinal, or longitudinal gradient in the nearshore waters of the NWHI islands, islets, and atolls will be described. Finally, a shallow pH maximum coincident with the shallow oxygen maximum is observed, which suggests an open ocean feature substantially influenced by turbulence surrounding the islands within the monument. The data analysis and coral reef ecosystem monitoring will aid in developing a long-term plan to assist in the sustainability of Papahānaumokuākea Marine National Monument.

  9. Strain-Induced Reactivity in the Dynamic Covalent Chemistry of Macrocyclic Imines.

    PubMed

    Ratjen, Lars; Vantomme, Ghislaine; Lehn, Jean-Marie

    2015-07-06

    The displacement of molecular structures from their thermodynamically most stable state by imposition of various types of electronic and conformational constraints generates highly strained entities that tend to release the accumulated strain energy by undergoing either structural changes or chemical reactions. The latter case amounts to strain-induced reactivity (SIR) that may enforce specific chemical transformations. A particular case concerns dynamic covalent chemistry which may present SIR, whereby reversible reactions are activated by coupling to a high-energy state. We herewith describe such a dynamic covalent chemical (DCC) system involving the reversible imine formation reaction. It is based on the formation of strained macrocyclic bis-imine metal complexes in which the macrocyclic ligand is in a high energy form enforced by the coordination of the metal cation. Subsequent demetallation generates a highly strained free macrocycle that releases its accumulated strain energy by hydrolysis and reassembly into a resting state. Specifically, the metal-templated condensation of a dialdehyde with a linear diamine leads to a bis-imine [1+1]-macrocyclic complex in which the macrocyclic ligand is in a coordination-enforced strained conformation. Removal of the metal cation by a competing ligand yields a highly reactive [1+1]-macrocycle, which then undergoes hydrolysis to transient non-cyclic aminoaldehyde species, which then recondense to a strain-free [2+2]-macrocyclic resting state. The process can be monitored by (1) H NMR spectroscopy. Energy differences between different conformational states have been evaluated by Hartree-Fock (HF) computations. One may note that the stabilisation of high-energy molecular forms by metal ion coordination followed by removal of the latter, offers a general procedure for producing out-of-equilibrium molecular states, the fate of which may then be examined, in particular when coupled to dynamic covalent chemical processes.

  10. Statistical Mechanics of Combinatorial Auctions

    NASA Astrophysics Data System (ADS)

    Galla, Tobias; Leone, Michele; Marsili, Matteo; Sellitto, Mauro; Weigt, Martin; Zecchina, Riccardo

    2006-09-01

    Combinatorial auctions are formulated as frustrated lattice gases on sparse random graphs, allowing the determination of the optimal revenue by methods of statistical physics. Transitions between computationally easy and hard regimes are found and interpreted in terms of the geometric structure of the space of solutions. We introduce an iterative algorithm to solve intermediate and large instances, and discuss competing states of optimal revenue and maximal number of satisfied bidders. The algorithm can be generalized to the hard phase and to more sophisticated auction protocols.

  11. Effect of water chemistry upsets on the dynamics of corrective reagent dosing systems at thermal power stations

    NASA Astrophysics Data System (ADS)

    Voronov, V. N.; Yegoshina, O. V.; Bolshakova, N. A.; Yarovoi, V. O.; Latt, Aie Min

    2016-12-01

    Typical disturbances in the dynamics of a corrective reagent dosing system under unsteady-state conditions during the unsatisfactory operation of a chemical control system with some water chemistry upsets at thermal and nuclear power stations are considered. An experimental setup representing a physical model for the water chemistry control system is described. The two disturbances, which are most frequently encountered in water chemistry control practice, such as a breakdown or shutdown of temperature compensation during pH measurement and an increase in the heat-transfer fluid flow rate, have been modeled in the process of study. The study of the effect produced by the response characteristics of chemical control analyzers on the operation of a reagent dosing system under unsteady-state conditions is important for the operative control of a water chemistry regime state. The effect of temperature compensation during pH measurement on the dynamics of an ammonia-dosing system in the manual and automatic cycle chemistry control modes has been studied. It has been demonstrated that the reading settling time of a pH meter in the manual ammonia- dosing mode grows with a breakdown in temperature compensation and a simultaneous increase in the temperature of a heat-transfer fluid sample. To improve the efficiency of water chemistry control, some systems for the quality control of a heat-transfer fluid by a chemical parameter with the obligatory compensation of a disturbance in its flow rate have been proposed for use. Experimental results will possibly differ from industrial data due to a great length of sampling lines. For this reason, corrective reagent dosing systems must be adapted to the conditions of a certain power-generating unit in the process of their implementation.

  12. Making the Earth: Combining dynamics and chemistry in the Solar System

    NASA Astrophysics Data System (ADS)

    Bond, Jade C.; Lauretta, Dante S.; O'Brien, David P.

    2010-02-01

    No terrestrial planet formation simulation completed to date has considered the detailed chemical composition of the planets produced. While many have considered possible water contents and late veneer compositions, none have examined the bulk elemental abundances of the planets produced as an important check of formation models. Here we report on the first study of this type. Bulk elemental abundances based on disk equilibrium studies have been determined for the simulated terrestrial planets of O'Brien et al. [O'Brien, D.P., Morbidelli, A., Levison, H.F., 2006. Icarus 184, 39-58]. These abundances are in excellent agreement with observed planetary values, indicating that the models of O'Brien et al. [O'Brien, D.P., Morbidelli, A., Levison, H.F., 2006. Icarus 184, 39-58] are successfully producing planets comparable to those of the Solar System in terms of both their dynamical and chemical properties. Significant amounts of water are accreted in the present simulations, implying that the terrestrial planets form "wet" and do not need significant water delivery from other sources. Under the assumption of equilibrium controlled chemistry, the biogenic species N and C still need to be delivered to the Earth as they are not accreted in significant proportions during the formation process. Negligible solar photospheric pollution is produced by the planetary formation process. Assuming similar levels of pollution in other planetary systems, this in turn implies that the high metallicity trend observed in extrasolar planetary systems is in fact primordial.

  13. Active upper-atmosphere chemistry and dynamics from polar circulation reversal on Titan.

    PubMed

    Teanby, Nicholas A; Irwin, Patrick G J; Nixon, Conor A; de Kok, Remco; Vinatier, Sandrine; Coustenis, Athena; Sefton-Nash, Elliot; Calcutt, Simon B; Flasar, F Michael

    2012-11-29

    Saturn's moon Titan has a nitrogen atmosphere comparable to Earth's, with a surface pressure of 1.4 bar. Numerical models reproduce the tropospheric conditions very well but have trouble explaining the observed middle-atmosphere temperatures, composition and winds. The top of the middle-atmosphere circulation has been thought to lie at an altitude of 450 to 500 kilometres, where there is a layer of haze that appears to be separated from the main haze deck. This 'detached' haze was previously explained as being due to the co-location of peak haze production and the limit of dynamical transport by the circulation's upper branch. Here we report a build-up of trace gases over the south pole approximately two years after observing the 2009 post-equinox circulation reversal, from which we conclude that middle-atmosphere circulation must extend to an altitude of at least 600 kilometres. The primary drivers of this circulation are summer-hemisphere heating of haze by absorption of solar radiation and winter-hemisphere cooling due to infrared emission by haze and trace gases; our results therefore imply that these effects are important well into the thermosphere (altitudes higher than 500 kilometres). This requires both active upper-atmosphere chemistry, consistent with the detection of high-complexity molecules and ions at altitudes greater than 950 kilometres, and an alternative explanation for the detached haze, such as a transition in haze particle growth from monomers to fractal structures.

  14. Smart macrocyclic molecules: induced fit and ultrafast self-sorting inclusion behavior through dynamic covalent chemistry.

    PubMed

    Han, Ji-Min; Pan, Jin-Long; Lei, Ting; Liu, Chenjiang; Pei, Jian

    2010-12-10

    A family of macrocycles with oligo(ethylene glycol) chains, 4O, 5O, and 6O, was developed to construct a series of new incorporated macrocycles through dynamic covalent chemistry. These flexible macrocycles exhibited excellent "self-sorting" abilities with diamine compounds, which depended on the "induced-fit" rule. For instance, the host macrocycles underwent conformational modulation to accommodate the diamine guests, affording [1+1] intramolecular addition compounds regardless of the flexibility of the diamine. These macrocycles folded themselves to fit various diamines with different chain length through modulation of the flexible polyether chain, and afforded intramolecular condensation products. However, if the chain of the diamine was too long and rigid, oligomers or polymers were obtained from the mixture of the macromolecule and the diamine. All results demonstrated that inclusion compounds involving conformationally suitable aromatic diamines were thermodynamically favorable candidates in the mixture due to the restriction of the macrocycle size. Furthermore, kinetic and thermodynamic studies of self-sorting behaviors of both mixed 4O-5O and 4O-6O systems were investigated in detail. Finally, theoretical calculations were also employed to further understand such self-sorting behavior, and indicated that the large enthalpy change of H(2)NArArNH(2)@4O is the driving force for the sorting behavior. Our system may provide a model to further understand the principle of biomolecules with high specificity due only to their conformational self-adjusting ability.

  15. Active Upper-atmosphere Chemistry and Dynamics from Polar Circulation Reversal on Titan

    NASA Technical Reports Server (NTRS)

    Teanby, Nicholas A.; Irwin, Patrick Gerard Joseph; Nixon, Conor A.; DeKok, Remco; Vinatier, Sandrine; Coustenis, Athena; Sefton-Nash, Elliot; Calcutt, Simon B.; Flasar, Michael F.

    2012-01-01

    Saturn's moon Titan has a nitrogen atmosphere comparable to Earth's, with a surface pressure of 1.4 bar. Numerical models reproduce the tropospheric conditions very well but have trouble explaining the observed middle-atmosphere temperatures, composition and winds. The top of the middle-atmosphere circulation has been thought to lie at an altitude of 450 to 500 kilometres, where there is a layer of haze that appears to be separated from the main haze deck. This 'detached' haze was previously explained as being due to the colocation of peak haze production and the limit of dynamical transport by the circulation's upper branch. Herewe report a build-up of trace gases over the south pole approximately two years after observing the 2009 post-equinox circulation reversal, from which we conclude that middle-atmosphere circulation must extend to an altitude of at least 600 kilometres. The primary drivers of this circulation are summer-hemisphere heating of haze by absorption of solar radiation and winter-hemisphere cooling due to infrared emission by haze and trace gases; our results therefore imply that these effects are important well into the thermosphere (altitudes higher than 500 kilometres). This requires both active upper-atmosphere chemistry, consistent with the detection of high-complexity molecules and ions at altitudes greater than 950 kilometres, and an alternative explanation for the detached haze, such as a transition in haze particle growth from monomers to fractal structures.

  16. Light Weight UAVs for Unravelling the Nexus Between Chemistry, Physics and Dynamics

    NASA Astrophysics Data System (ADS)

    Ramanathan, V.

    2015-12-01

    New discoveries in atmospheric sciences involve unravelling the interactions and feedback processes between chemitsry, physics and dynamics. One of the most complex of such problems is the role of aerosol-clouds-climate interactions in climate change. During the last 7 years we have designed field experiments with light weight UAVs that are flown in stacked as well as formation flying patterns to map out the three dimensional structure of the atmosphere. Such formation and stacked formation flights have enabled us to measure simulatneously aerosol chemistry, cloud micro physics, cloud albedo, divergence of radiative heating of the atmosphere and more recently the vertical structure of turbulent fluxes of water avpor and momentum. These first-such measurments have provided new insights into the role of aerosols in cloud albedo; vertical distribution of black and brown carbon heating; role of absorbing aerosols in the melting of Himalayan glaciers; role of mixing state of aerosols in aerosol forcing and recently the link between absorbing aerosols and turbulent fluxes. All of the instruments had to be miniaturized to fit into the UAVs with maximum of 6 kg of payload. The most impprtant aspects of our studies are that the instruments and their intergration with the UAvs were all developed by post doctoral candidates and students. Thus the light weight UAVs are ideal platforms for making pioneerign studies by students and young scientists.

  17. Ozone budgets from the Dynamics and Chemistry of Marine Stratocumulus experiment

    NASA Technical Reports Server (NTRS)

    Kawa, S. R.; Pearson, R., Jr.

    1989-01-01

    Measurements from the Dynamics and Chemistry of marine Stratocumulus experiment have been used to study components of the regional ozone budget. The surface destruction rate is determined by eddy correlation of ozone and vertical velocity measured by a low-flying aircraft. Significant variability is found in the measured surface resistance; it is partially correlated with friction velocity but appears to have other controlling influences as well. The mean resistance is 4190 s/m which is higher (slower destruction) than most previous estimates for seawater. Flux and mean measurements throughout the marine boundary layer are used to estimate the net rate of in situ photochemical production/destruction of ozone. Averaged over the flights, ozone concentration is found to be near steady state, and a net of photochemical destruction of 0.02-0.07 ng/cu m per sec is diagnosed. This is an important confirmation of photochemical model results for the remote marine boundary layer. Ozone vertical distributions above the boundary layer show a strongly layered structure with very sharp gradients. These distributions are possibly related to the stratospheric ozone source.

  18. NON-EQUILIBRIUM CHEMISTRY OF DYNAMICALLY EVOLVING PRESTELLAR CORES. II. IONIZATION AND MAGNETIC FIELD

    SciTech Connect

    Tassis, Konstantinos; Willacy, Karen; Yorke, Harold W.; Turner, Neal J.

    2012-07-20

    We study the effect that non-equilibrium chemistry in dynamical models of collapsing molecular cloud cores has on measurements of the magnetic field in these cores, the degree of ionization, and the mean molecular weight of ions. We find that OH and CN, usually used in Zeeman observations of the line-of-sight magnetic field, have an abundance that decreases toward the center of the core much faster than the density increases. As a result, Zeeman observations tend to sample the outer layers of the core and consistently underestimate the core magnetic field. The degree of ionization follows a complicated dependence on the number density at central densities up to 10{sup 5} cm{sup -3} for magnetic models and 10{sup 6} cm{sup -3} in non-magnetic models. At higher central densities, the scaling approaches a power law with a slope of -0.6 and a normalization which depends on the cosmic-ray ionization rate {zeta} and the temperature T as ({zeta}T){sup 1/2}. The mean molecular weight of ions is systematically lower than the usually assumed value of 20-30, and, at high densities, approaches a value of 3 due to the asymptotic dominance of the H{sup +}{sub 3} ion. This significantly lower value implies that ambipolar diffusion operates faster.

  19. Dynamic adaptive chemistry with operator splitting schemes for reactive flow simulations

    NASA Astrophysics Data System (ADS)

    Ren, Zhuyin; Xu, Chao; Lu, Tianfeng; Singer, Michael A.

    2014-04-01

    A numerical technique that uses dynamic adaptive chemistry (DAC) with operator splitting schemes to solve the equations governing reactive flows is developed and demonstrated. Strang-based splitting schemes are used to separate the governing equations into transport fractional substeps and chemical reaction fractional substeps. The DAC method expedites the numerical integration of reaction fractional substeps by using locally valid skeletal mechanisms that are obtained using the directed relation graph (DRG) reduction method to eliminate unimportant species and reactions from the full mechanism. Second-order temporal accuracy of the Strang-based splitting schemes with DAC is demonstrated on one-dimensional, unsteady, freely-propagating, premixed methane/air laminar flames with detailed chemical kinetics and realistic transport. The use of DAC dramatically reduces the CPU time required to perform the simulation, and there is minimal impact on solution accuracy. It is shown that with DAC the starting species and resulting skeletal mechanisms strongly depend on the local composition in the flames. In addition, the number of retained species may be significant only near the flame front region where chemical reactions are significant. For the one-dimensional methane/air flame considered, speed-up factors of three and five are achieved over the entire simulation for GRI-Mech 3.0 and USC-Mech II, respectively. Greater speed-up factors are expected for larger chemical kinetics mechanisms.

  20. Crystallization of macromolecular complexes: combinatorial complex crystallization

    NASA Astrophysics Data System (ADS)

    Stura, Enrico A.; Graille, Marc; Charbonnier, Jean-Baptiste

    2001-11-01

    antigens. We find that such binding involves only the well conserved framework region of the variable domain of the antibody heavy chain (VH) and does not affect the conformation of the hypervariable loops that define the antigen recognition site. Thus this domain could be used to complex to Fab or Fv fragments derived from a wide variety of antibodies. While protein A complexes with the VH domain, protein L recognizes the VL region of immunoglobulins. Our recent study of the interaction between an Fab and a domain of protein L shows that the situation is very similar. Indeed this domain binds to the VL framework region outside the antigen binding site. Since individual domains from each of these three multi-domain proteins bind to well separated and independent locations on immunoglobulins, they can be combined to search for a suitable crystalline lattice. This allows us to propose a combinatorial method as a rational way to exploit antibody complexation for the crystallographic structure determination of proteins that are otherwise difficult to crystallize. The overall method has strong parallels with other combinatorial methods used elsewhere in biology and chemistry, and we propose that together with stoichiometry variation screening (SVS), it may further enhance the probability of crystallization.

  1. Reversible control of pore size and surface chemistry of mesoporous silica through dynamic covalent chemistry: philicity mediated catalysis.

    PubMed

    Singh, Dheeraj Kumar; Pavan Kumar, B V V S; Eswaramoorthy, M

    2015-08-28

    Here, we report the synthesis of adaptive hybrid mesoporous silica having the ability to reconfigure its pore properties such as pore size and philicity in response to the external environment. Decyl chains were reversibly appended to the pore walls of silica through imine motifs as dynamic covalent modules to switch the pore size and philicity in response to pH. This switching of pore properties was used to gate the access of reactants to the gold nanoparticles immobilized inside the nanopores, thus enabling us to turn-on/turn-off the catalytic reaction. The use of such dynamic covalent modules to govern pore properties would enable the realization of intelligent hybrids capable of controlling many such chemical processes in response to stimuli.

  2. Reversible control of pore size and surface chemistry of mesoporous silica through dynamic covalent chemistry: philicity mediated catalysis

    NASA Astrophysics Data System (ADS)

    Singh, Dheeraj Kumar; Pavan Kumar, B. V. V. S.; Eswaramoorthy, M.

    2015-08-01

    Here, we report the synthesis of adaptive hybrid mesoporous silica having the ability to reconfigure its pore properties such as pore size and philicity in response to the external environment. Decyl chains were reversibly appended to the pore walls of silica through imine motifs as dynamic covalent modules to switch the pore size and philicity in response to pH. This switching of pore properties was used to gate the access of reactants to the gold nanoparticles immobilized inside the nanopores, thus enabling us to turn-on/turn-off the catalytic reaction. The use of such dynamic covalent modules to govern pore properties would enable the realization of intelligent hybrids capable of controlling many such chemical processes in response to stimuli.Here, we report the synthesis of adaptive hybrid mesoporous silica having the ability to reconfigure its pore properties such as pore size and philicity in response to the external environment. Decyl chains were reversibly appended to the pore walls of silica through imine motifs as dynamic covalent modules to switch the pore size and philicity in response to pH. This switching of pore properties was used to gate the access of reactants to the gold nanoparticles immobilized inside the nanopores, thus enabling us to turn-on/turn-off the catalytic reaction. The use of such dynamic covalent modules to govern pore properties would enable the realization of intelligent hybrids capable of controlling many such chemical processes in response to stimuli. Electronic supplementary information (ESI) available. See DOI: 10.1039/c5nr02959g

  3. Size distribution dynamics reveal particle-phase chemistry in organic aerosol formation

    NASA Astrophysics Data System (ADS)

    Shiraiwa, M.; Yee, L. D.; Schilling, K.; Loza, C. L.; Craven, J. S.; Zuend, A.; Ziemann, P. J.; Seinfeld, J.

    2013-12-01

    Organic aerosols are ubiquitous in the atmosphere and play a central role in climate, air quality and public health. The aerosol size distribution is key in determining its optical properties and cloud condensation nucleus activity. The dominant portion of organic aerosol is formed through gas-phase oxidation of volatile organic compounds, so-called secondary organic aerosol (SOA). Typical experimental measurements of SOA formation include total SOA mass and atomic oxygen-to-carbon ratio. These measurements, alone, are generally insufficient to reveal the extent to which condensed-phase reactions occur in conjunction with the multi-generation gas-phase photooxidation. Combining laboratory chamber experiments and kinetic gas-particle modeling for the dodecane SOA system, here we show that the presence of particle-phase chemistry is reflected in the evolution of the SOA size distribution as well as its mass concentration. Particle-phase reactions are predicted to occur mainly at the particle surface and the reaction products contribute more than half of the SOA mass. Chamber photooxidation with a mid-experiment aldehyde injection confirms that heterogeneous reaction of aldehydes with organic hydroperoxides forming peroxyhemiacetals can lead to a large increase in SOA mass. The results of the current work have a number of implications for SOA models. While the dynamics of an aerosol size distribution reflects the mechanism of growth, we demonstrate here that it provides a key constraint in interpreting laboratory and ambient SOA formation. This work, although carried out specifically for the long chain alkane, dodecane, is expected to be widely applicable to other major classes of SOA precursors. SOA consists of a myriad of organic compounds containing various functional groups, which can generally undergo heterogeneous/multiphase reactions forming low-volatility products such as oligomers and other high molecular mass compounds. If particle-phase chemistry is indeed

  4. Reconstructing pedigrees: a combinatorial perspective.

    PubMed

    Steel, Mike; Hein, Jotun

    2006-06-07

    A pedigree is a directed graph that displays the relationship between individuals according to their parentage. We derive a combinatorial result that shows how any pedigree-up to individuals who have no extant (present-day) ancestors-can be reconstructed from (sex-labelled) pedigrees that describe the ancestry of single extant individuals and pairs of extant individuals. Furthermore, this reconstruction can be done in polynomial time. We also provide an example to show that the corresponding reconstruction result does not hold for pedigrees that are not sex-labelled. We then show how any pedigree can also be reconstructed from two functions that just describe certain circuits in the pedigree. Finally, we obtain an enumeration result for pedigrees that is relevant to the question of how many segregating sites are needed to reconstruct pedigrees.

  5. Mapping the Materials Genome through Combinatorial Informatics

    NASA Astrophysics Data System (ADS)

    Rajan, Krishna

    2012-02-01

    The recently announced White House Materials Genome Initiative provides an exciting challenge to the materials science community. To meet that challenge one needs to address a critical question, namely what is the materials genome? Some guide on how to the answer this question can be gained by recognizing that a ``gene'' is a carrier of information. In the biological sciences, discovering how to manipulate these genes has generated exciting discoveries in fundamental molecular biology as well as significant advances in biotechnology. Scaling that up to molecular, cellular length scales and beyond, has spawned from genomics, fields such as proteomics, metabolomics and essentially systems biology. The ``omics'' approach requires that one needs to discover and track these ``carriers of information'' and then correlate that information to predict behavior. A similar challenge lies in materials science, where there is a diverse array of modalities of materials ``discovery'' ranging from new materials chemistries and molecular arrangements with novel properties, to the development and design of new micro- and mesoscale structures. Hence to meaningfully adapt the spirit of ``genomics'' style research in materials science, we need to first identify and map the ``genes'' across different materials science applications On the experimental side, combinatorial experiments have opened a new approach to generate data in a high throughput manner, but without a clear way to link that to models, the full value of that data is not realized. Hence along with experimental and computational materials science, we need to add a ``third leg'' to our toolkit to make the ``Materials Genome'' a reality, the science of Materials Informatics. In this presentation we provide an overview of how information science coupled to materials science can in fact achieve the goal of mapping the ``Materials Genome''.

  6. Seasonal dynamics of water and air chemistry in an indoor chlorinated swimming pool.

    PubMed

    Zare Afifi, Mehrnaz; Blatchley, Ernest R

    2015-01-01

    Although swimming is known to be beneficial in terms of cardiovascular health, as well as for some forms of rehabilitation, swimming is also known to present risks to human health, largely in the form of exposure to microbial pathogens and disinfection byproducts (DBPs). Relatively little information is available in the literature to characterize the seasonal dynamics of air and water chemistry in indoor chlorinated swimming pools. To address this issue, water samples were collected five days per week from an indoor chlorinated swimming pool facility at a high school during the academic year and once per week during summer over a fourteen-month period. The samples were analyzed for free and combined chlorine, urea, volatile DBPs, pH, temperature and total alkalinity. Membrane Introduction Mass Spectrometry (MIMS) was used to identify and measure the concentrations of eleven aqueous-phase volatile DBPs. Variability in the concentrations of these DBPs was observed. Factors that influenced variability included bather loading and mixing by swimmers. These compounds have the ability to adversely affect water and air quality and human health. A large fraction of the existing literature regarding swimming pool air quality has focused on trichloramine (NCl₃). For this work, gas-phase NCl₃ was analyzed by an air sparging-DPD/KI method. The results showed that gas-phase NCl₃ concentration is influenced by bather loading and liquid-phase NCl₃ concentration. Urea is the dominant organic-N compound in human urine and sweat, and is known to be an important precursor for producing NCl₃ in swimming pools. Results of daily measurements of urea indicated a link between bather load and urea concentration in the pool.

  7. Reconstructing monsoon dynamics on the Tibetan Plateau using ostracod shell chemistry

    NASA Astrophysics Data System (ADS)

    Boerner, N.; De Baere, B.; Yang, Q.; Francois, R. H. G. M.; Jochum, K. P.; Frenzel, P.; Schwalb, A.

    2014-12-01

    Ostracod shells have widely been used as source material for geochemical analysis of stable isotope and trace element composition in paleolimnological reconstruction of lake hydrochemistry and climate as they provide insight into past water balance and solute evolution of lakes. During five fieldtrips to the Tibetan Plateau, taking place between 2008 and 2012, we collected live and sub-recent ostracods from 333 sites. Hydrochemical parameters, such as temperature, electrical conductivity, pH as well as major and minor ion concentrations were measured at each site and show high variability between sites. Adult intact individuals from the most common ostracod taxa were selected and their shell chemistry analyzed. The trace elemental data for the living ostracods compared to the hydrological data provides a calibration dataset for further hydrological and thus climatological reconstruction. Mg/Ca, Sr/Ca and Ba/Ca ratios in ostracod shells provide information about past water temperature and salinity resulting from changes in precipitation vs. evaporation ratios and monsoon activity. Furthermore, Mn/Ca, Fe/Ca and U/Ca ratios are being explored as redox indicators to reconstruct oxygenation cycles. To reconstruct the monsoon dynamics on the Tibetan Plateau, sediment cores from different lakes on an east-west transect were taken: two long sediment cores from lakes Nam Co and Tangra Yumco, covering the past 20,000 years, and a short core from Lake Taro Co. The lakes feature an alkaline environment but show significant differences in their electrical conductivity ranging from 0.99 mS/cm (Taro Co) and 1.8 mS/cm (Nam Co) to 12 mS/cm (Tangra Yumco). The chemical composition of valves of the most common ostracod species in these lakes, Leucocytherella sinensis, was analyzed using laser ablation ICP-MS. The reconstruction provides a more extensive insight in past precipitation - evaporation balance and lake level change and provides clues about the interaction between the

  8. Chemistry and dynamics: a post-processing tool towards a real coupling

    NASA Astrophysics Data System (ADS)

    Valdivia, V.; Godard, B.; Hennebelle, P.; Gerin, M.; Lesaffre, P.

    2016-12-01

    Chemistry plays a key role in the comparison between observations and theoretical predictions, but its treatment in numerical simulations is a real challenge. In particular the full treatment of the chemistry requires to solve simultaneously hundreds to thousands of reactions, constraining the time-steps to be as small as the smallest one. Fortunately, several species reach the chemical equilibrium much faster than others, and careful choices allow to describe the chemical state in a simpler manner. Here we present a hybrid approach to treat the chemistry of the interstellar medium.

  9. Towards a Comprehensive Dynamic-chemistry Assimilation for Eos-Chem: Plans and Status in NASA's Data Assimilation Office

    NASA Technical Reports Server (NTRS)

    Pawson, Steven; Lin, Shian-Jiann; Rood, Richard B.; Stajner, Ivanka; Nebuda, Sharon; Nielsen, J. Eric; Douglass, Anne R.

    2000-01-01

    In order to support the EOS-Chem project, a comprehensive assimilation package for the coupled chemical-dynamical system is being developed by the Data Assimilation Office at NASA GSFC. This involves development of a coupled chemistry/meteorology model and of data assimilation techniques for trace species and meteorology. The model is being developed using the flux-form semi-Lagrangian dynamical core of Lin and Rood, the physical parameterizations from the NCAR Community Climate Model, and atmospheric chemistry modules from the Atmospheric Chemistry and Dynamics branch at NASA GSFC. To date the following results have been obtained: (i) multi-annual simulations with the dynamics-radiation model show the credibility of the package for atmospheric simulations; (ii) initial simulations including a limited number of middle atmospheric trace gases reveal the realistic nature of transport mechanisms, although there is still a need for some improvements. Samples of these results will be shown. A meteorological assimilation system is currently being constructed using the model; this will form the basis for the proposed meteorological/chemical assimilation package. The latter part of the presentation will focus on areas targeted for development in the near and far terms, with the objective of Providing a comprehensive assimilation package for the EOS-Chem science experiment. The first stage will target ozone assimilation. The plans also encompass a reanalysis (ReSTS) for the 1991-1995 period, which includes the Mt. Pinatubo eruption and the time when a large number of UARS observations were available. One of the most challenging aspects of future developments will be to couple theoretical advances in tracer assimilation with the practical considerations of a real environment and eventually a near-real-time assimilation system.

  10. Parallel and Distributed Computing Combinatorial Algorithms

    DTIC Science & Technology

    1993-10-01

    FUPNDKC %2,•, PARALLEL AND DISTRIBUTED COMPUTING COMBINATORIAL ALGORITHMS 6. AUTHOR(S) 2304/DS F49620-92-J-0125 DR. LEIGHTON 7 PERFORMING ORGANIZATION NAME...on several problems involving parallel and distributed computing and combinatorial optimization. This research is reported in the numerous papers that...network decom- position. In Proceedings of the Eleventh Annual ACM Symposium on Principles of Distributed Computing , August 1992. [15] B. Awerbuch, B

  11. The DACCIWA Project: Dynamics-Aerosol-Chemistry-Cloud interactions in West Africa

    NASA Astrophysics Data System (ADS)

    Knippertz, Peter

    2014-05-01

    Massive economic and population growth and urbanisation are expected to lead to a tripling of anthropogenic emissions from southern West Africa (SWA) between 2000 and 2030, the impacts of which on human health, ecosystems, food security and the regional climate are largely unknown. An assessment of these impacts is complicated by (a) a superposition with effects of global climate change, (b) the strong dependence of SWA on the sensitive West African monsoon, (c) incomplete scientific understanding of interactions between emissions, clouds, radiation, precipitation and regional circulations and (d) by a lack of observations to advance our understanding and improve predictions. The purpose of this contribution is to introduce the research consortium DACCIWA (Dynamics-Aerosol-Chemistry-Cloud interactions in West Africa), which comprises 16 partners in six European and West African countries. The interdisciplinary DACCIWA team will build on the scientific and logistical foundations established by the African Monsoon Multidisciplinary Analysis (AMMA) project and collaborate closely with operational centres. DACCIWA will receive funding of about M8.75€ from the European Commission as part of Framework Programme 7 from 2015 until 2018. The DACCIWA project will conduct extensive fieldwork in SWA to collect high-quality observations, spanning the entire process chain from surface-based natural and anthropogenic emissions to impacts on health, ecosystems and climate. This will include a major field campaign in summer 2015 with three research aircrafts and two ground-based supersites. Combining the resulting benchmark dataset with a wide range of modelling activities will allow us: (a) to assess all relevant physical and chemical processes, (b) to improve the monitoring of climate and compositional parameters from space, (c) to determine health impacts from air pollution, and (d) to develop the next generation of weather and climate models capable of representing coupled

  12. Combinatorial explosion in model gene networks

    NASA Astrophysics Data System (ADS)

    Edwards, R.; Glass, L.

    2000-09-01

    The explosive growth in knowledge of the genome of humans and other organisms leaves open the question of how the functioning of genes in interacting networks is coordinated for orderly activity. One approach to this problem is to study mathematical properties of abstract network models that capture the logical structures of gene networks. The principal issue is to understand how particular patterns of activity can result from particular network structures, and what types of behavior are possible. We study idealized models in which the logical structure of the network is explicitly represented by Boolean functions that can be represented by directed graphs on n-cubes, but which are continuous in time and described by differential equations, rather than being updated synchronously via a discrete clock. The equations are piecewise linear, which allows significant analysis and facilitates rapid integration along trajectories. We first give a combinatorial solution to the question of how many distinct logical structures exist for n-dimensional networks, showing that the number increases very rapidly with n. We then outline analytic methods that can be used to establish the existence, stability and periods of periodic orbits corresponding to particular cycles on the n-cube. We use these methods to confirm the existence of limit cycles discovered in a sample of a million randomly generated structures of networks of 4 genes. Even with only 4 genes, at least several hundred different patterns of stable periodic behavior are possible, many of them surprisingly complex. We discuss ways of further classifying these periodic behaviors, showing that small mutations (reversal of one or a few edges on the n-cube) need not destroy the stability of a limit cycle. Although these networks are very simple as models of gene networks, their mathematical transparency reveals relationships between structure and behavior, they suggest that the possibilities for orderly dynamics in such

  13. Combinatorial Methodology for Screening Selectivity in Polymeric Pervaporation Membranes.

    PubMed

    Godbole, Rutvik V; Ma, Lan; Doerfert, Michael D; Williams, Porsche; Hedden, Ronald C

    2015-11-09

    Combinatorial methodology is described for rapid screening of selectivity in polymeric pervaporation membrane materials for alcohol-water separations. The screening technique is demonstrated for ethanol-water separation using a model polyacrylate system. The materials studied are cross-linked random copolymers of a hydrophobic comonomer (n-butyl acrylate, B) and a hydrophilic comonomer (2-hydroxyethyl acrylate, H). A matrix of materials is prepared that has orthogonal variations in two key variables, H:B ratio and cross-linker concentration. For mixtures of ethanol and water, equilibrium selectivities and distribution coefficients are obtained by combining swelling measurements with high-throughput HPLC analysis. Based on the screening results, two copolymers are selected for further study as pervaporation membranes to quantify permeability selectivity and the flux of ethanol. The screening methodology described has good potential to accelerate the search for new membrane materials, as it is adaptable to a broad range of polymer chemistries.

  14. Applications of dynamic nuclear polarization to the study of reactions and reagents in organic and biomolecular chemistry.

    PubMed

    Hilty, Christian; Bowen, Sean

    2010-08-07

    Nuclear Magnetic Resonance (NMR) is an important spectroscopic tool for the identification and structural characterization of molecules in chemistry and biochemistry. The most significant limitation of NMR compared to other spectroscopies is its relatively low sensitivity, which thus often requires long measurement times or large amounts of sample. A way of increasing sensitivity of single scan NMR spectra by several orders of magnitude is through hyperpolarization of nuclear spins. Dynamic nuclear polarization allows hyperpolarization of most spins in small molecules encountered in chemistry and biochemistry. NMR spectra of small amounts of samples from natural source, or from chemical synthesis can readily be acquired. Perhaps more interestingly, the availability of the entire hyperpolarized NMR signal in one single scan allows the measurement of transient processes in real time, if applied together with a stopped-flow technique. Through observation of chemical shift, different reactant and product species can be distinguished, and kinetics and mechanisms, for example in enzyme catalyzed reactions, can be elucidated. Real-time hyperpolarization-enhanced NMR is uniquely amenable to correlating atomic positions not only through space, but also over time between reactant and product species. Such correlations carry mechanistic information about a reaction, and can prove reaction pathways. Applications of this technique are emerging in different areas of chemistry concerned with rapid reactions, including not only enzymatic processes, but also chemical catalysis and protein folding.

  15. Defining the radiation chemistry during liquid cell electron microscopy to enable visualization of nanomaterial growth and degradation dynamics.

    PubMed

    Woehl, T J; Abellan, P

    2017-02-01

    We present a critical review of methods for defining the chemical environment during liquid cell electron microscopy investigation of electron beam induced nanomaterial growth and degradation. We draw from the radiation chemistry and liquid cell electron microscopy literature to present solution chemistry and electron beam-based methods for selecting the radiolysis products formed and their relative amount during electron irradiation of liquid media in a transmission electron microscope. We outline various methods for establishing net oxidizing or net reducing reaction environments and propose solvents with minimal overall production of radicals under the electron beam. Exemplary liquid cell electron microscopy experiments in the fields of nanoparticle nucleation, growth, and degradation along with recommendations for best practices and experimental parameters are reported. We expect this review will provide researchers with a useful toolkit for designing general chemistry and materials science liquid cell electron microscopy experiments by 'directing' the effect of the electron beam to understand fundamental mechanisms of dynamic nanoscale processes as well as minimizing radiation damage to samples.

  16. Exploring Interactive and Dynamic Simulations Using a Computer Algebra System in an Advanced Placement Chemistry Course

    ERIC Educational Resources Information Center

    Matsumoto, Paul S.

    2014-01-01

    The article describes the use of Mathematica, a computer algebra system (CAS), in a high school chemistry course. Mathematica was used to generate a graph, where a slider controls the value of parameter(s) in the equation; thus, students can visualize the effect of the parameter(s) on the behavior of the system. Also, Mathematica can show the…

  17. Do High School Chemistry Examinations Inhibit Deeper Level Understanding of Dynamic Reversible Chemical Reactions?

    ERIC Educational Resources Information Center

    Wheeldon, R.; Atkinson, R.; Dawes, A.; Levinson, R.

    2012-01-01

    Background and purpose: Chemistry examinations can favour the deployment of algorithmic procedures like Le Chatelier's Principle (LCP) rather than reasoning using chemical principles. This study investigated the explanatory resources which high school students use to answer equilibrium problems and whether the marks given for examination answers…

  18. Dynamic Vertical Profiles of Peat Porewater Chemistry in a Northern Peatland

    SciTech Connect

    Griffiths, Natalie A.; Sebestyen, Stephen D.

    2016-10-14

    We measured pH, cations, nutrients, and total organic carbon (TOC) over 3 years to examine weekly to monthly variability in porewater chemistry depth profiles (0–3.0 m) in an ombrotrophic bog in Minnesota, USA. We also compared temporal variation at one location to spatial variation in depth profiles at 16 locations across the bog. Most solutes exhibited large gradients with depth. pH increased by two units and calcium concentrations increased over 20 fold with depth, and may reflect peatland development from minerotrophic to ombrotrophic conditions. Ammonium concentrations increased almost 20 fold and TOC concentrations decreased by half with depth, and these patterns likely reflect mineralization of peat or decomposition of TOC. There was also considerable temporal variation in the porewater chemistry depth profiles. Ammonium, soluble reactive phosphorus, and potassium showed greater temporal variation in near-surface porewater, while pH, calcium, and TOC varied more at depth. This variation demonstrates that deep peat porewater chemistry is not static. Lastly, temporal variation in solute chemistry depth profiles was greater than spatial variation in several instances, especially in shallow porewaters. In conclusion, characterizing both temporal and spatial variability is necessary to ensure representative sampling in peatlands, especially when calculating solute pools and fluxes and parameterizing process-based models.

  19. Virtual Laboratory in the Role of Dynamic Visualisation for Better Understanding of Chemistry in Primary School

    ERIC Educational Resources Information Center

    Herga, Nataša Rizman; Cagran, Branka; Dinevski, Dejan

    2016-01-01

    Understanding chemistry includes the ability to think on three levels: the macroscopic level, the symbolic level, and the level of particles--sub-microscopic level. Pupils have the most difficulty when trying to understand the sub-microscopic level because it is outside their range of experience. A virtual laboratory enables a simultaneous…

  20. Dynamic Vertical Profiles of Peat Porewater Chemistry in a Northern Peatland

    DOE PAGES

    Griffiths, Natalie A.; Sebestyen, Stephen D.

    2016-10-14

    We measured pH, cations, nutrients, and total organic carbon (TOC) over 3 years to examine weekly to monthly variability in porewater chemistry depth profiles (0–3.0 m) in an ombrotrophic bog in Minnesota, USA. We also compared temporal variation at one location to spatial variation in depth profiles at 16 locations across the bog. Most solutes exhibited large gradients with depth. pH increased by two units and calcium concentrations increased over 20 fold with depth, and may reflect peatland development from minerotrophic to ombrotrophic conditions. Ammonium concentrations increased almost 20 fold and TOC concentrations decreased by half with depth, and thesemore » patterns likely reflect mineralization of peat or decomposition of TOC. There was also considerable temporal variation in the porewater chemistry depth profiles. Ammonium, soluble reactive phosphorus, and potassium showed greater temporal variation in near-surface porewater, while pH, calcium, and TOC varied more at depth. This variation demonstrates that deep peat porewater chemistry is not static. Lastly, temporal variation in solute chemistry depth profiles was greater than spatial variation in several instances, especially in shallow porewaters. In conclusion, characterizing both temporal and spatial variability is necessary to ensure representative sampling in peatlands, especially when calculating solute pools and fluxes and parameterizing process-based models.« less

  1. Probing Student Teachers' Subject Content Knowledge in Chemistry: Case Studies Using Dynamic Computer Models

    ERIC Educational Resources Information Center

    Toplis, Rob

    2008-01-01

    This paper reports case study research into the knowledge and understanding of chemistry for six secondary science student teachers. It combines innovative student-generated computer animations, using "ChemSense" software, with interviews to probe understanding of four common chemical processes used in the secondary school curriculum. Findings…

  2. Automated quantum chemistry based molecular dynamics simulations of electron ionization induced fragmentations of the nucleobases Uracil, Thymine, Cytosine, and Guanine.

    PubMed

    Grimme, Stefan; Bauer, Christopher Alexander

    2015-01-01

    The gas-phase decomposition pathways of electron ionization (EI)-induced radical cations of the nucleobases uracil, thymine, cytosine, and guanine are investigated by means of mixed quantum-classical molecular dynamics. No preconceived fragmentation channels are used in the calculations. The results compare well to a plethora of experimental and theoretical data for these important biomolecules. With our combined stochastic and dynamic approach, one can access in an unbiased way the energetically available decomposition mechanisms. Additionally, we are able to separate the EI mass spectra of different tautomers of cytosine and guanine. Our method (previously termed quantum chemistry electron ionization mass spectra) reproduces free nucleobase experimental mass spectra well and provides detailed mechanistic in-sight into high-energy unimolecular decomposition processes.

  3. Fabrication of combinatorial polymer scaffold libraries.

    PubMed

    Simon, Carl G; Stephens, Jean S; Dorsey, Shauna M; Becker, Matthew L

    2007-07-01

    We have designed a novel combinatorial research platform to help accelerate tissue engineering research. Combinatorial methods combine many samples into a single specimen to enable accelerated experimentation and discovery. The platform for fabricating combinatorial polymer scaffold libraries can be used to rapidly identify scaffold formulations that maximize tissue formation. Many approaches for screening cell-biomaterial interactions utilize a two-dimensional format such as a film or surface to present test substrates to cells. However, cells in vivo exist in a three-dimensional milieu of extracellular matrix and cells in vitro behave more naturally when cultured in a three-dimensional environment than when cultured on a two-dimensional surface. Thus, we have designed a method for fabricating combinatorial biomaterial libraries where the materials are presented to cells in the form of three-dimensional, porous, salt-leached, polymer scaffolds. Many scaffold variations and compositions can be screened in a single experiment so that optimal scaffold formulations for tissue formation can be rapidly identified. In summary, we have developed a platform technology for fabricating combinatorial polymer scaffold libraries that can be used to screen cell response to materials in a three-dimensional, scaffold format.

  4. Fabrication of combinatorial polymer scaffold libraries

    NASA Astrophysics Data System (ADS)

    Simon, Carl G.; Stephens, Jean S.; Dorsey, Shauna M.; Becker, Matthew L.

    2007-07-01

    We have designed a novel combinatorial research platform to help accelerate tissue engineering research. Combinatorial methods combine many samples into a single specimen to enable accelerated experimentation and discovery. The platform for fabricating combinatorial polymer scaffold libraries can be used to rapidly identify scaffold formulations that maximize tissue formation. Many approaches for screening cell-biomaterial interactions utilize a two-dimensional format such as a film or surface to present test substrates to cells. However, cells in vivo exist in a three-dimensional milieu of extracellular matrix and cells in vitro behave more naturally when cultured in a three-dimensional environment than when cultured on a two-dimensional surface. Thus, we have designed a method for fabricating combinatorial biomaterial libraries where the materials are presented to cells in the form of three-dimensional, porous, salt-leached, polymer scaffolds. Many scaffold variations and compositions can be screened in a single experiment so that optimal scaffold formulations for tissue formation can be rapidly identified. In summary, we have developed a platform technology for fabricating combinatorial polymer scaffold libraries that can be used to screen cell response to materials in a three-dimensional, scaffold format.

  5. Proton enhanced dynamic battery chemistry for aprotic lithium-oxygen batteries.

    PubMed

    Zhu, Yun Guang; Liu, Qi; Rong, Yangchun; Chen, Haomin; Yang, Jing; Jia, Chuankun; Yu, Li-Juan; Karton, Amir; Ren, Yang; Xu, Xiaoxiong; Adams, Stefan; Wang, Qing

    2017-02-06

    Water contamination is generally considered to be detrimental to the performance of aprotic lithium-air batteries, whereas this view is challenged by recent contrasting observations. This has provoked a range of discussions on the role of water and its impact on batteries. In this work, a distinct battery chemistry that prevails in water-contaminated aprotic lithium-oxygen batteries is revealed. Both lithium ions and protons are found to be involved in the oxygen reduction and evolution reactions, and lithium hydroperoxide and lithium hydroxide are identified as predominant discharge products. The crystallographic and spectroscopic characteristics of lithium hydroperoxide monohydrate are scrutinized both experimentally and theoretically. Intriguingly, the reaction of lithium hydroperoxide with triiodide exhibits a faster kinetics, which enables a considerably lower overpotential during the charging process. The battery chemistry unveiled in this mechanistic study could provide important insights into the understanding of nominally aprotic lithium-oxygen batteries and help to tackle the critical issues confronted.

  6. Proton enhanced dynamic battery chemistry for aprotic lithium-oxygen batteries

    NASA Astrophysics Data System (ADS)

    Zhu, Yun Guang; Liu, Qi; Rong, Yangchun; Chen, Haomin; Yang, Jing; Jia, Chuankun; Yu, Li-Juan; Karton, Amir; Ren, Yang; Xu, Xiaoxiong; Adams, Stefan; Wang, Qing

    2017-02-01

    Water contamination is generally considered to be detrimental to the performance of aprotic lithium-air batteries, whereas this view is challenged by recent contrasting observations. This has provoked a range of discussions on the role of water and its impact on batteries. In this work, a distinct battery chemistry that prevails in water-contaminated aprotic lithium-oxygen batteries is revealed. Both lithium ions and protons are found to be involved in the oxygen reduction and evolution reactions, and lithium hydroperoxide and lithium hydroxide are identified as predominant discharge products. The crystallographic and spectroscopic characteristics of lithium hydroperoxide monohydrate are scrutinized both experimentally and theoretically. Intriguingly, the reaction of lithium hydroperoxide with triiodide exhibits a faster kinetics, which enables a considerably lower overpotential during the charging process. The battery chemistry unveiled in this mechanistic study could provide important insights into the understanding of nominally aprotic lithium-oxygen batteries and help to tackle the critical issues confronted.

  7. Proton enhanced dynamic battery chemistry for aprotic lithium–oxygen batteries

    PubMed Central

    Zhu, Yun Guang; Liu, Qi; Rong, Yangchun; Chen, Haomin; Yang, Jing; Jia, Chuankun; Yu, Li-Juan; Karton, Amir; Ren, Yang; Xu, Xiaoxiong; Adams, Stefan; Wang, Qing

    2017-01-01

    Water contamination is generally considered to be detrimental to the performance of aprotic lithium–air batteries, whereas this view is challenged by recent contrasting observations. This has provoked a range of discussions on the role of water and its impact on batteries. In this work, a distinct battery chemistry that prevails in water-contaminated aprotic lithium–oxygen batteries is revealed. Both lithium ions and protons are found to be involved in the oxygen reduction and evolution reactions, and lithium hydroperoxide and lithium hydroxide are identified as predominant discharge products. The crystallographic and spectroscopic characteristics of lithium hydroperoxide monohydrate are scrutinized both experimentally and theoretically. Intriguingly, the reaction of lithium hydroperoxide with triiodide exhibits a faster kinetics, which enables a considerably lower overpotential during the charging process. The battery chemistry unveiled in this mechanistic study could provide important insights into the understanding of nominally aprotic lithium–oxygen batteries and help to tackle the critical issues confronted. PMID:28165008

  8. Combinatorial gene regulation by modulation of relative pulse timing

    PubMed Central

    Lin, Yihan; Sohn, Chang Ho; Dalal, Chiraj K.; Cai, Long; Elowitz, Michael B.

    2015-01-01

    Studies of individual living cells have revealed that many transcription factors activate in dynamic, and often stochastic, pulses within the same cell. However, it has remained unclear whether cells might modulate the relative timing of these pulses to control gene expression. Here, using quantitative single-cell time-lapse imaging of Saccharomyces cerevisiae, we show that the pulsatile transcription factors Msn2 and Mig1 combinatorially regulate their target genes through modulation of their relative pulse timing. The activator Msn2 and repressor Mig1 pulsed in either a temporally overlapping or non-overlapping manner during their transient response to different inputs, with only the non-overlapping dynamics efficiently activating target gene expression. Similarly, under constant environmental conditions, where Msn2 and Mig1 exhibit sporadic pulsing, glucose concentration modulated the temporal overlap between pulses of the two factors. Together, these results reveal a time-based mode of combinatorial gene regulation. Regulation through relative signal timing is common in engineering and neurobiology, and these results suggest that it could also function broadly within the signaling and regulatory systems of the cell. PMID:26466562

  9. A Synthesis of Fluid Dynamics and Quantum Chemistry for the Design of Nanoelectronics

    NASA Technical Reports Server (NTRS)

    MacDougall, Preston J.

    1998-01-01

    In 1959, during a famous lecture entitled "There's Plenty of Room at the Bottom", Richard Feynman focused on the startling technical possibilities that would exist at the limit of miniaturization, that being atomically precise devices with dimensions in the nanometer range. A nanometer is both a convenient unit of length for medium to large sized molecules, and the root of the name of the new interdisciplinary field of "nanotechnology". Essentially, "nanoelectronics" denotes the goal of shrinking electronic devices, such as diodes and transistors, as well as integrated circuits of such devices that can perform logical operations, down to dimensions in the range of 100 nanometers. The thirty-year hiatus in the development of nanotechnology can figuratively be seen as a period of waiting for the bottom-up and atomically precise construction skills of synthetic chemistry to meet the top-down reductionist aspirations of device physics. The sub-nanometer domain of nineteenth-century classical chemistry has steadily grown, and state-of-the-art supramolecular chemistry can achieve atomic precision in non-repeating molecular assemblies of the size desired for nanotechnology. For nanoelectronics in particular, a basic understanding of the electron transport properties of molecules must also be developed. Quantum chemistry provides powerful computational methods that can accurately predict the properties of small to medium sized molecules on a desktop workstation, and those of large molecules if one has access to a supercomputer. Of the many properties of a molecule that quantum chemistry routinely predicts, the ability to carry a current is one that had not even been considered until recently. "Currently", there is a controversy over just how to define this key property. Reminiscent of the situation in high-Tc superconductivity, much of the difficulty arises from the different models that are used to simplify the complex electronic structure of real materials. A model

  10. Quantum control implemented as combinatorial optimization.

    PubMed

    Strohecker, Traci; Rabitz, Herschel

    2010-01-15

    Optimal control theory provides a general means for designing controls to manipulate quantum phenomena. Traditional implementation requires solving coupled nonlinear equations to obtain the optimal control solution, whereas this work introduces a combinatorial quantum control (CQC) algorithm to avoid this complexity. The CQC technique uses a predetermined toolkit of small time step propagators in conjunction with combinatorial optimization to identify a proper sequence for the toolkit members. Results indicate that the CQC technique exhibits invariance of search effort to the number of system states and very favorable scaling upon comparison to a standard gradient algorithm, taking into consideration that CQC is easily parallelizable.

  11. Estimating meme fitness in adaptive memetic algorithms for combinatorial problems.

    PubMed

    Smith, J E

    2012-01-01

    Among the most promising and active research areas in heuristic optimisation is the field of adaptive memetic algorithms (AMAs). These gain much of their reported robustness by adapting the probability with which each of a set of local improvement operators is applied, according to an estimate of their current value to the search process. This paper addresses the issue of how the current value should be estimated. Assuming the estimate occurs over several applications of a meme, we consider whether the extreme or mean improvements should be used, and whether this aggregation should be global, or local to some part of the solution space. To investigate these issues, we use the well-established COMA framework that coevolves the specification of a population of memes (representing different local search algorithms) alongside a population of candidate solutions to the problem at hand. Two very different memetic algorithms are considered: the first using adaptive operator pursuit to adjust the probabilities of applying a fixed set of memes, and a second which applies genetic operators to dynamically adapt and create memes and their functional definitions. For the latter, especially on combinatorial problems, credit assignment mechanisms based on historical records, or on notions of landscape locality, will have limited application, and it is necessary to estimate the value of a meme via some form of sampling. The results on a set of binary encoded combinatorial problems show that both methods are very effective, and that for some problems it is necessary to use thousands of variables in order to tease apart the differences between different reward schemes. However, for both memetic algorithms, a significant pattern emerges that reward based on mean improvement is better than that based on extreme improvement. This contradicts recent findings from adapting the parameters of operators involved in global evolutionary search. The results also show that local reward schemes

  12. Hypergraph-Based Combinatorial Optimization of Matrix-Vector Multiplication

    ERIC Educational Resources Information Center

    Wolf, Michael Maclean

    2009-01-01

    Combinatorial scientific computing plays an important enabling role in computational science, particularly in high performance scientific computing. In this thesis, we will describe our work on optimizing matrix-vector multiplication using combinatorial techniques. Our research has focused on two different problems in combinatorial scientific…

  13. Extended Lagrangian quantum molecular dynamics simulations of shock-induced chemistry in hydrocarbons

    SciTech Connect

    Sanville, Edward J; Bock, Nicolas; Challacombe, William M; Cawkwell, Marc J; Niklasson, Anders M N; Dattelbaum, Dana M; Sheffield, Stephen; Sewell, Thomas D

    2010-01-01

    A set of interatomic potentials for hydrocarbons that are based upon the self-consistent charge transfer tight-binding approximation to density functional theory have been developed and implemented into the quantum molecular dynamics code ''LATTE''. The interatomic potentials exhibit an outstanding level of transferability and have been applied in molecular dynamics simulations of tert-butylacetylene under thermodynamic conditions that correspond to its single-shock Hugoniot. We have achieved precise conservation of the total energy during microcanonical molecular dynamics trajectories under incomplete convergence via the extended Lagrangian Born-Oppenheimer molecular dynamics formalism. In good agreement with the results of a series of flyer-plate impact experiments, our SCC-TB molecular dynamics simulations show that tert-butylactylene molecules polymerize at shock pressures around 6.1 GPa.

  14. Dynamic Covalent Polymer Networks: from Old Chemistry to Modern Day Innovations.

    PubMed

    Zou, Weike; Dong, Jiante; Luo, Yingwu; Zhao, Qian; Xie, Tao

    2017-04-01

    Dynamic covalent polymer networks have long been recognized. With the initial focus on the unintended impact of dynamic covalent linkages on the viscoelasticity of commercial rubbers, efforts in modern times have transitioned into designing dynamic covalent polymer networks with unique adaptive properties. Whereas self-healing and thermoset reprocessing have been the primary motivations for studying dynamic covalent polymer networks, the recent discovery of the vitrimeric rheological behavior and solid-state plasticity for this type of material have opened up new opportunities in material innovations. This, coupled with the revelation of the dynamic characteristics of commercially relevant polymer building blocks such as esters and urethanes, suggests a promising future for this class of materials.

  15. A combinatorial code for pattern formation in Drosophila oogenesis

    PubMed Central

    Yakoby, N.; Bristow, C.A.; Gong, D.; Schafer, X.; Lembong, J.; Zartman, J.J.; Halfon, M.S.; Schüpbach, T.; Shvartsman, S.Y.

    2010-01-01

    Summary Two-dimensional patterning of the follicular epithelium in Drosophila oogenesis is required for the formation of three-dimensional eggshell structures. Our analysis of a large number of published gene expression patterns in the follicle cells suggested that they follow a simple combinatorial code, based on six spatial building blocks and the operations of union, difference, intersection, and addition. The building blocks are related to the distribution of the inductive signals, provided by the highly conserved EGFR and DPP pathways. We demonstrated the validity of the code by testing it against a set of newly identified expression patterns, obtained in a large-scale transcriptional profiling experiment. Using the proposed code, we distinguished 36 distinct patterns for 81 genes expressed in the follicular epithelium and characterized their joint dynamics over four stages of oogenesis. This work provides the first systematic analysis of the diversity and dynamics of two-dimensional gene expression patterns in a developing tissue. PMID:19000837

  16. Scanning SQUID microscopy of local superconductivity in inhomogeneous combinatorial ceramics.

    PubMed

    Iranmanesh, Mitra; Stir, Manuela; Kirtley, John R; Hulliger, Jürg

    2014-11-24

    Although combinatorial solid-state chemistry promises to be an efficient way to search for new superconducting compounds, the problem of determining which compositions are strongly diamagnetic in a mixed-phase sample is challenging. By means of reactions in a system of randomly mixed starting components (Ca, Sr, Ba, La, Y, Pb, Bi, Tl, and Cu oxides), samples were produced that showed an onset of diamagnetic response above 115 K in bulk measurements. Imaging of this diamagnetic response in ceramic samples by scanning SQUID microscopy (SSM) revealed local superconducting areas with sizes down to as small as the spatial resolution of a few micrometers. In addition, locally formed superconducting matter was extracted from mixed-phase samples by magnetic separation. The analysis of single grains (d<80 μm) by X-ray diffraction, elemental analysis, and bulk SQUID measurements allowed Tl2Ca3Ba2Cu4O12, TlCaBaSrCu2O(7-δ), BaPb(0.5)Bi(0.25)Tl(0.25)O(3-δ), TlBa2Ca2Cu3O9, Tl2Ba2CaCu2O8, and YBa2Cu3O7 phases to be identified. SSM, in combination with other diagnostic techniques, is therefore shown to be a useful instrument to analyze inhomogeneous reaction products in the solid-state chemistry of materials showing magnetic properties.

  17. More Combinatorial Proofs via Flagpole Arrangements

    ERIC Educational Resources Information Center

    DeTemple, Duane; Reynolds, H. David, II

    2006-01-01

    Combinatorial identities are proved by counting the number of arrangements of a flagpole and guy wires on a row of blocks that satisfy a set of conditions. An identity is proved by first deriving and then equating two expressions that each count the number of permissible arrangements. Identities for binomial coefficients and recursion relations…

  18. Quantum Resonance Approach to Combinatorial Optimization

    NASA Technical Reports Server (NTRS)

    Zak, Michail

    1997-01-01

    It is shown that quantum resonance can be used for combinatorial optimization. The advantage of the approach is in independence of the computing time upon the dimensionality of the problem. As an example, the solution to a constraint satisfaction problem of exponential complexity is demonstrated.

  19. Incorporating modeling and simulations in undergraduate biophysical chemistry course to promote understanding of structure-dynamics-function relationships in proteins.

    PubMed

    Hati, Sanchita; Bhattacharyya, Sudeep

    2016-01-01

    A project-based biophysical chemistry laboratory course, which is offered to the biochemistry and molecular biology majors in their senior year, is described. In this course, the classroom study of the structure-function of biomolecules is integrated with the discovery-guided laboratory study of these molecules using computer modeling and simulations. In particular, modern computational tools are employed to elucidate the relationship between structure, dynamics, and function in proteins. Computer-based laboratory protocols that we introduced in three modules allow students to visualize the secondary, super-secondary, and tertiary structures of proteins, analyze non-covalent interactions in protein-ligand complexes, develop three-dimensional structural models (homology model) for new protein sequences and evaluate their structural qualities, and study proteins' intrinsic dynamics to understand their functions. In the fourth module, students are assigned to an authentic research problem, where they apply their laboratory skills (acquired in modules 1-3) to answer conceptual biophysical questions. Through this process, students gain in-depth understanding of protein dynamics-the missing link between structure and function. Additionally, the requirement of term papers sharpens students' writing and communication skills. Finally, these projects result in new findings that are communicated in peer-reviewed journals.

  20. Comparison of Chain Conformation of Poly(vinyl alcohol) in Solutions and Melts from Quantum Chemistry Based Molecular Dynamics Simulations

    NASA Technical Reports Server (NTRS)

    Jaffe, Richard; Han, Jie; Matsuda, Tsunetoshi; Yoon, Do; Langhoff, Stephen R. (Technical Monitor)

    1997-01-01

    Confirmations of 2,4-dihydroxypentane (DHP), a model molecule for poly(vinyl alcohol), have been studied by quantum chemistry (QC) calculations and molecular dynamics (MD) simulations. QC calculations at the 6-311G MP2 level show the meso tt conformer to be lowest in energy followed by the racemic tg, due to intramolecular hydrogen bond between the hydroxy groups. The Dreiding force field has been modified to reproduce the QC conformer energies for DHP. MD simulations using this force field have been carried out for DHP molecules in the gas phase, melt, and CHCl3 and water solutions. Extensive intramolecular hydrogen bonding is observed for the gas phase and CHCl3 solution, but not for the melt or aqueous solution, Such a condensed phase effect due to intermolecular interactions results in a drastic change in chain conformations, in agreement with experiments.

  1. The Interaction Between Dynamics and Chemistry of Ozone in the Set-up Phase of the Northern Hemisphere Polar Vortex

    NASA Technical Reports Server (NTRS)

    Kawa, S. R.; Bevilacqua, R.; Margitan, J. J.; Douglass, A. R.; Schoeberl, M. R.; Hoppel, K.; Sen, B.; Bhartia, P. K. (Technical Monitor)

    2001-01-01

    The morphology and evolution of the stratospheric ozone (O3) distribution at high latitudes in the Northern Hemisphere (NH) are examined for the late summer and fall seasons of 1999. This time period sets the O3 initial condition for the SOLVE/THESEO field mission performed during winter 1999-2000. In situ and satellite data are used along with a three-dimensional model of chemistry and transport (CTM) to determine the key processes that control the distribution of O3 in the lower-to-middle stratosphere. O3 in the vortex at the beginning of the winter season is found to be nearly constant from 500 to above 800 K with a value at 3 ppmv +/- approx. 10%. Values outside the vortex are up to a factor of 2 higher and increase significantly with potential temperature. The seasonal time series of data from POAM shows that relatively low O3 mixing ratios, which characterize the vortex in late fall, are already present at high latitudes at the end of summer before the vortex circulation sets up. Analysis of the CTM output shows that the minimum O3 and increase in variance in late summer are the result of: 1) stirring of polar concentric O3 gradients by nascent wave-driven transport, and 2) an acceleration of net photochemical loss with decreasing solar illumination. The segregation of low O3 mixing ratios into the vortex as the circulation strengthens through the fall suggests a possible feedback role between O3 chemistry and the vortex formation dynamics. Trajectory calculations from O3 sample points early in the fall, however, show only a weak correlation between initial O3 mixing ratio and potential vorticity later in the season consistent with order-of-magnitude calculations for the relative importance of O3 in the fall radiative balance at high latitudes. The possible connection between O3 chemistry and the dynamics of vortex formation does suggest that these feedbacks and sensitivities need to be better understood in order to make confident predictions of the recovery

  2. Coral reef metabolism and carbon chemistry dynamics of a coral reef flat

    NASA Astrophysics Data System (ADS)

    Albright, Rebecca; Benthuysen, Jessica; Cantin, Neal; Caldeira, Ken; Anthony, Ken

    2015-05-01

    Global carbon emissions continue to acidify the oceans, motivating growing concern for the ability of coral reefs to maintain net positive calcification rates. Efforts to develop robust relationships between coral reef calcification and carbonate parameters such as aragonite saturation state (Ωarag) aim to facilitate meaningful predictions of how reef calcification will change in the face of ocean acidification. Here we investigate natural trends in carbonate chemistry of a coral reef flat over diel cycles and relate these trends to benthic carbon fluxes by quantifying net community calcification and net community production. We find that, despite an apparent dependence of calcification on Ωarag seen in a simple pairwise relationship, if the dependence of net calcification on net photosynthesis is accounted for, knowing Ωarag does not add substantial explanatory value. This suggests that, over short time scales, the control of Ωarag on net calcification is weak relative to factors governing net photosynthesis.

  3. Some aspects of metallic ion chemistry and dynamics in the mesosphere and thermosphere

    NASA Technical Reports Server (NTRS)

    Mathews, J. D.

    1987-01-01

    The relationship between the formation of sporadic layers of metallic ion and the dumping of these ions into the upper mesosphere is discussed in terms of the tidal wind, classical (i.e., windshear) and other more complex, perhaps highly nonlinear layer formation mechanisms, and a possible circulation mechanism for these ions. Optical, incoherent scatter radar, rocket, and satellite derived evidence for various layer formation mechanisms and for the metallic ion circulation system is reviewed. The results of simple one dimensional numerical model calculations of sporadic E and intermediate layer formation are presented along with suggestions for more advanced models of intense or blanketing sporadic E. The flux of metallic ions dumped by the tidal wind system into the mesosphere is estimated and compared with estimates of total particle flux of meteoric origin. Possible effects of the metallic ion flux and of meteoric dust on D region ion chemistry are discussed.

  4. Do high school chemistry examinations inhibit deeper level understanding of dynamic reversible chemical reactions?

    NASA Astrophysics Data System (ADS)

    Wheeldon, R.; Atkinson, R.; Dawes, A.; Levinson, R.

    2012-07-01

    Background and purpose : Chemistry examinations can favour the deployment of algorithmic procedures like Le Chatelier's Principle (LCP) rather than reasoning using chemical principles. This study investigated the explanatory resources which high school students use to answer equilibrium problems and whether the marks given for examination answers require students to use approaches beyond direct application of LCP. Sample : The questionnaire was administered to 162 students studying their first year of advanced chemistry (age 16/17) in three high achieving London high schools. Design and methods : The students' explanations of reversible chemical systems were inductively coded to identify the explanatory approaches used and interviews with 13 students were used to check for consistency. AS level examination questions on reversible reactions were analysed to identify the types of explanations sought and the students' performance in these examinations was compared to questionnaire answers. Results : 19% of students used a holistic explanatory approach: when the rates of forward and reverse reactions are correctly described, recognising their simultaneous and mutually dependent nature. 36% used a mirrored reactions approach when the connected nature of the forward and reverse reactions is identified, but not their mutual dependency. 42% failed to recognize the interdependence of forward and reverse reactions (reactions not connected approach). Only 4% of marks for AS examination questions on reversible chemical systems asked for responses which went beyond either direct application of LCP or recall of equilibrium knowledge. 37% of students attained an A grade in their AS national examinations. Conclusions : Examinations favour the application of LCP making it possible to obtain the highest grade with little understanding of reversible chemical systems beyond a direct application of this algorithm. Therefore students' understanding may be attenuated so that they are

  5. Using water chemistry time series to model dissolved inorganic carbon dynamics in the western Amazon basin

    NASA Astrophysics Data System (ADS)

    Vihermaa, Leena; Waldron, Susan; Newton, Jason

    2013-04-01

    Two small streams (New Colpita and Main Trail) and two rivers (Tambopata and La Torre), in the Tambopata National Reserve, Madre de Dios, Peru, were sampled for water chemistry (conductivity, pH and dissolved oxygen) and hydrology (stage height and flow velocity). In the small streams water chemistry and hydrology variables were logged at 15 minute intervals from Feb 2011 to November 2012. Water samples were collected from all four channels during field campaigns spanning different seasons and targeting the hydrological extremes. All the samples were analysed for dissolved inorganic carbon (DIC) concentration and δ13C (sample size ranging from 77 to 172 depending on the drainage system) and a smaller subset for dissolved organic carbon (DOC) and particulate organic carbon (POC) concentrations. Strong positive relationships were found between conductivity and both DIC concentration and δ13C in the New Colpita stream and the La Torre river. In Tambopata river the trends were less clear and in the Main Trail stream there was very little change in DIC and isotopic composition. The conductivity data was used to model continuous DIC time series for the New Colpita stream. The modelled DIC data agreed well with the measurements; the concordance correlation coefficients between predicted and measured data were 0.91 and 0.87 for mM-DIC and δ13C-DIC, respectively. The predictions of δ13C-DIC were improved when calendar month was included in the model, which indicates seasonal differences in the δ13C-DIC conductivity relationship. At present, continuous DIC sampling still requires expensive instrumentation. Therefore, modelling DIC from a proxy variable which can be monitored continuously with ease and at relatively low cost, such as conductivity, provides a powerful alternative method of DIC determination.

  6. FOREWORD: Focus on Combinatorial Materials Science Focus on Combinatorial Materials Science

    NASA Astrophysics Data System (ADS)

    Chikyo, Toyohiro

    2011-10-01

    About 15 years have passed since the introduction of modern combinatorial synthesis and high-throughput techniques for the development of novel inorganic materials; however, similar methods existed before. The most famous was reported in 1970 by Hanak who prepared composition-spread films of metal alloys by sputtering mixed-material targets. Although this method was innovative, it was rarely used because of the large amount of data to be processed. This problem is solved in the modern combinatorial material research, which is strongly related to computer data analysis and robotics. This field is still at the developing stage and may be enriched by new methods. Nevertheless, given the progress in measurement equipment and procedures, we believe the combinatorial approach will become a major and standard tool of materials screening and development. The first article of this journal, published in 2000, was titled 'Combinatorial solid state materials science and technology', and this focus issue aims to reintroduce this topic to the Science and Technology of Advanced Materials audience. It covers recent progress in combinatorial materials research describing new results in catalysis, phosphors, polymers and metal alloys for shape memory materials. Sophisticated high-throughput characterization schemes and innovative synthesis tools are also presented, such as spray deposition using nanoparticles or ion plating. On a technical note, data handling systems are introduced to familiarize researchers with the combinatorial methodology. We hope that through this focus issue a wide audience of materials scientists can learn about recent and future trends in combinatorial materials science and high-throughput experimentation.

  7. Collinear Collision Chemistry: 1. A Simple Model for Inelastic and Reactive Collision Dynamics

    ERIC Educational Resources Information Center

    Mahan, Bruce H.

    1974-01-01

    Discusses a model for the collinear collision of an atom with a diatomic molecule on a simple potential surface. Indicates that the model can provide a framework for thinking about molecular collisions and reveal many factors which affect the dynamics of reactive and inelastic collisions. (CC)

  8. Genetic algorithm-assisted combinatorial search for a new green phosphor for use in tricolor white LEDs.

    PubMed

    Sohn, Kee-Sun; Park, Duk Hyun; Cho, Sang Ho; Kim, Byung Il; Woo, Seong Ihl

    2006-01-01

    An evolutionary optimization process involving a genetic algorithm and combinatorial chemistry was employed for the development of green phosphors which are suitable for tricolor white-light-emitting diodes. To accomplish a high luminescent efficiency at 400 nm excitation, we screened a seven-cation oxide system including Tb, Gd, Ce, Mg, Si, Al, and B. The combination of a genetic algorithm and combinatorial chemistry enhanced the searching efficiency when applied for phosphor screening. As a result, the optimized composition was Tb(0.01)Gd(0.02)Ce(0.04)B(0.1)Si(0.83)O(delta), The luminance of this borosilicate glass was 67% that of ZnS:Cu,Al at 400-nm excitation.

  9. Exploiting Quantum Resonance to Solve Combinatorial Problems

    NASA Technical Reports Server (NTRS)

    Zak, Michail; Fijany, Amir

    2006-01-01

    Quantum resonance would be exploited in a proposed quantum-computing approach to the solution of combinatorial optimization problems. In quantum computing in general, one takes advantage of the fact that an algorithm cannot be decoupled from the physical effects available to implement it. Prior approaches to quantum computing have involved exploitation of only a subset of known quantum physical effects, notably including parallelism and entanglement, but not including resonance. In the proposed approach, one would utilize the combinatorial properties of tensor-product decomposability of unitary evolution of many-particle quantum systems for physically simulating solutions to NP-complete problems (a class of problems that are intractable with respect to classical methods of computation). In this approach, reinforcement and selection of a desired solution would be executed by means of quantum resonance. Classes of NP-complete problems that are important in practice and could be solved by the proposed approach include planning, scheduling, search, and optimal design.

  10. Programming gene expression with combinatorial promoters

    PubMed Central

    Cox, Robert Sidney; Surette, Michael G; Elowitz, Michael B

    2007-01-01

    Promoters control the expression of genes in response to one or more transcription factors (TFs). The architecture of a promoter is the arrangement and type of binding sites within it. To understand natural genetic circuits and to design promoters for synthetic biology, it is essential to understand the relationship between promoter function and architecture. We constructed a combinatorial library of random promoter architectures. We characterized 288 promoters in Escherichia coli, each containing up to three inputs from four different TFs. The library design allowed for multiple −10 and −35 boxes, and we observed varied promoter strength over five decades. To further analyze the functional repertoire, we defined a representation of promoter function in terms of regulatory range, logic type, and symmetry. Using these results, we identified heuristic rules for programming gene expression with combinatorial promoters. PMID:18004278

  11. Dynamic Cyclic Thiodepsipeptide Libraries from Thiol-Thioester Exchange

    DTIC Science & Technology

    2010-04-01

    use in a variety of dynamic combinatorial chemistry assays. The kinetic determinants of macrocycle formation and the role of amino acid structure on...were then made in AA1, AA3, and AA4 (Table 1); by design, AA2-AA3-AA4 forms the macrocycle, and AA1 remains exocyclic. Charged amino acids (Lys, Arg...was initially included in AA3 as a turn residue that favors macrocycles. 9 Various amino acids were incorporated into AA4 to study their effect on

  12. ULTRAFAST CHEMISTRY: Using Time-Resolved Vibrational Spectroscopy for Interrogation of Structural Dynamics

    NASA Astrophysics Data System (ADS)

    Nibbering, Erik T. J.; Fidder, Henk; Pines, Ehud

    2005-05-01

    Time-resolved infrared (IR) and Raman spectroscopy elucidates molecular structure evolution during ultrafast chemical reactions. Following vibrational marker modes in real time provides direct insight into the structural dynamics, as is evidenced in studies on intramolecular hydrogen transfer, bimolecular proton transfer, electron transfer, hydrogen bonding during solvation dynamics, bond fission in organometallic compounds and heme proteins, cis-trans isomerization in retinal proteins, and transformations in photochromic switch pairs. Femtosecond IR spectroscopy monitors the site-specific interactions in hydrogen bonds. Conversion between excited electronic states can be followed for intramolecular electron transfer by inspection of the fingerprint IR- or Raman-active vibrations in conjunction with quantum chemical calculations. Excess internal vibrational energy, generated either by optical excitation or by internal conversion from the electronic excited state to the ground state, is observable through transient frequency shifts of IR-active vibrations and through nonequilibrium populations as deduced by Raman resonances.

  13. Switched Systems and Motion Coordination: Combinatorial Challenges

    NASA Technical Reports Server (NTRS)

    Sadovsky, Alexander V.

    2016-01-01

    Problems of routing commercial air traffic in a terminal airspace encounter different constraints: separation assurance, aircraft performance limitations, regulations. The general setting of these problems is that of a switched control system. Such a system combines the differentiable motion of the aircraft with the combinatorial choices of choosing precedence when traffic routes merge and choosing branches when the routes diverge. This presentation gives an overview of the problem, the ATM context, related literature, and directions for future research.

  14. Combinatorial Cis-regulation in Saccharomyces Species.

    PubMed

    Spivak, Aaron T; Stormo, Gary D

    2016-01-15

    Transcriptional control of gene expression requires interactions between the cis-regulatory elements (CREs) controlling gene promoters. We developed a sensitive computational method to identify CRE combinations with conserved spacing that does not require genome alignments. When applied to seven sensu stricto and sensu lato Saccharomyces species, 80% of the predicted interactions displayed some evidence of combinatorial transcriptional behavior in several existing datasets including: (1) chromatin immunoprecipitation data for colocalization of transcription factors, (2) gene expression data for coexpression of predicted regulatory targets, and (3) gene ontology databases for common pathway membership of predicted regulatory targets. We tested several predicted CRE interactions with chromatin immunoprecipitation experiments in a wild-type strain and strains in which a predicted cofactor was deleted. Our experiments confirmed that transcription factor (TF) occupancy at the promoters of the CRE combination target genes depends on the predicted cofactor while occupancy of other promoters is independent of the predicted cofactor. Our method has the additional advantage of identifying regulatory differences between species. By analyzing the S. cerevisiae and S. bayanus genomes, we identified differences in combinatorial cis-regulation between the species and showed that the predicted changes in gene regulation explain several of the species-specific differences seen in gene expression datasets. In some instances, the same CRE combinations appear to regulate genes involved in distinct biological processes in the two different species. The results of this research demonstrate that (1) combinatorial cis-regulation can be inferred by multi-genome analysis and (2) combinatorial cis-regulation can explain differences in gene expression between species.

  15. Combinatorial Cis-regulation in Saccharomyces Species

    PubMed Central

    Spivak, Aaron T.; Stormo, Gary D.

    2016-01-01

    Transcriptional control of gene expression requires interactions between the cis-regulatory elements (CREs) controlling gene promoters. We developed a sensitive computational method to identify CRE combinations with conserved spacing that does not require genome alignments. When applied to seven sensu stricto and sensu lato Saccharomyces species, 80% of the predicted interactions displayed some evidence of combinatorial transcriptional behavior in several existing datasets including: (1) chromatin immunoprecipitation data for colocalization of transcription factors, (2) gene expression data for coexpression of predicted regulatory targets, and (3) gene ontology databases for common pathway membership of predicted regulatory targets. We tested several predicted CRE interactions with chromatin immunoprecipitation experiments in a wild-type strain and strains in which a predicted cofactor was deleted. Our experiments confirmed that transcription factor (TF) occupancy at the promoters of the CRE combination target genes depends on the predicted cofactor while occupancy of other promoters is independent of the predicted cofactor. Our method has the additional advantage of identifying regulatory differences between species. By analyzing the S. cerevisiae and S. bayanus genomes, we identified differences in combinatorial cis-regulation between the species and showed that the predicted changes in gene regulation explain several of the species-specific differences seen in gene expression datasets. In some instances, the same CRE combinations appear to regulate genes involved in distinct biological processes in the two different species. The results of this research demonstrate that (1) combinatorial cis-regulation can be inferred by multi-genome analysis and (2) combinatorial cis-regulation can explain differences in gene expression between species. PMID:26772747

  16. Dynamic Covalent Chemistry-based Sensing: Pyrenyl Derivatives of Phenylboronic Acid for Saccharide and Formaldehyde

    NASA Astrophysics Data System (ADS)

    Chang, Xingmao; Fan, Jiayun; Wang, Min; Wang, Zhaolong; Peng, Haonan; He, Gang; Fang, Yu

    2016-08-01

    We synthesized two specially designed pyrenyl (Py) derivatives of phenylboronic acid, PSNB1 and PSNB2, of which PSNB2 self-assemble to form dynamic aggregate in methanol-water mixture (1:99, v/v) via intermolecular H-bonding and pi-pi stacking. Interestingly, the dynamic aggregate shows smart response to presence of fructose (F) as evidenced by fluorescence color change from green to blue. More interestingly, the fluorescence emission of the resulted PSNB2-F changes from blue to green with the addition of formaldehyde (FA). The reason behind is formation of a PSNB2-F dimer via FA cross-linking. Based upon the reactions as found, sensitive and fast sensing of F and FA in water was realized, of which the experimental DLs could be significantly lower than 10 μM for both analytes, and the response times are less than 1 min. It is believed that not only the materials as created may have the potential to find real-life applications but also the strategy as developed can be adopted to develop other dynamic materials.

  17. Shock induced chemistry in liquids studied with ultrafast dynamic ellipsometry and visible transient absorption spectroscopy.

    PubMed

    Dang, N C; Bolme, C A; Moore, D S; McGrane, S D

    2012-10-25

    The response to ultrafast laser shock loading of nine liquids was monitored in an effort to reveal evidence of chemical changes occurring during the first 350 ps following the shock front. In an effort to compare molecular structures possessing a variety of common bonding patterns, data were acquired for the liquids: cyclohexane, cyclohexene, 1,3-cyclohexadiene, benzene, water, acetonitrile, acrylonitrile, tert-butylacetylene, and phenylacetylene. Transient absorption spectra were measured in the spectral region from 440 to 780 nm over shock stress states from 7 to 20 GPa. Ultrafast dynamic ellipsometry was used to measure the shock and particle velocity as well as the shocked refractive index. Significant transient absorption attributed to chemical reaction was observed for shocked phenylacetylene and acrylonitrile. Evidence of volume decreasing chemical reactions was also observed in the ultrafast dynamic ellipsometry data for phenylacetylene and acrylonitrile. The liquid 1,3-cyclohexadiene exhibited volume decreasing reaction in the ultrafast dynamic ellipsometry data but did not exhibit an increase in the transient absorption spectra. There was no evidence of chemical reaction in cyclohexane, cyclohexene, benzene, water, acetonitrile, or tert-butylacetylene in the first 350 ps, despite the application of shock stress that was in many cases well above the reaction threshold observed at microsecond time scales.

  18. Dynamic Covalent Chemistry-based Sensing: Pyrenyl Derivatives of Phenylboronic Acid for Saccharide and Formaldehyde

    PubMed Central

    Chang, Xingmao; Fan, Jiayun; Wang, Min; Wang, Zhaolong; Peng, Haonan; He, Gang; Fang, Yu

    2016-01-01

    We synthesized two specially designed pyrenyl (Py) derivatives of phenylboronic acid, PSNB1 and PSNB2, of which PSNB2 self-assemble to form dynamic aggregate in methanol-water mixture (1:99, v/v) via intermolecular H-bonding and pi-pi stacking. Interestingly, the dynamic aggregate shows smart response to presence of fructose (F) as evidenced by fluorescence color change from green to blue. More interestingly, the fluorescence emission of the resulted PSNB2-F changes from blue to green with the addition of formaldehyde (FA). The reason behind is formation of a PSNB2-F dimer via FA cross-linking. Based upon the reactions as found, sensitive and fast sensing of F and FA in water was realized, of which the experimental DLs could be significantly lower than 10 μM for both analytes, and the response times are less than 1 min. It is believed that not only the materials as created may have the potential to find real-life applications but also the strategy as developed can be adopted to develop other dynamic materials. PMID:27498703

  19. Methods for combinatorial and parallel library design.

    PubMed

    Schnur, Dora M; Beno, Brett R; Tebben, Andrew J; Cavallaro, Cullen

    2011-01-01

    Diversity has historically played a critical role in design of combinatorial libraries, screening sets and corporate collections for lead discovery. Large library design dominated the field in the 1990s with methods ranging anywhere from purely arbitrary through property based reagent selection to product based approaches. In recent years, however, there has been a downward trend in library size. This was due to increased information about the desirable targets gleaned from the genomics revolution and to the ever growing availability of target protein structures from crystallography and homology modeling. Creation of libraries directed toward families of receptors such as GPCRs, kinases, nuclear hormone receptors, proteases, etc., replaced the generation of libraries based primarily on diversity while single target focused library design has remained an important objective. Concurrently, computing grids and cpu clusters have facilitated the development of structure based tools that screen hundreds of thousands of molecules. Smaller "smarter" combinatorial and focused parallel libraries replaced those early un-focused large libraries in the twenty-first century drug design paradigm. While diversity still plays a role in lead discovery, the focus of current library design methods has shifted to receptor based methods, scaffold hopping/bio-isostere searching, and a much needed emphasis on synthetic feasibility. Methods such as "privileged substructures based design" and pharmacophore based design still are important methods for parallel and small combinatorial library design. This chapter discusses some of the possible design methods and presents examples where they are available.

  20. Adaptive random testing with combinatorial input domain.

    PubMed

    Huang, Rubing; Chen, Jinfu; Lu, Yansheng

    2014-01-01

    Random testing (RT) is a fundamental testing technique to assess software reliability, by simply selecting test cases in a random manner from the whole input domain. As an enhancement of RT, adaptive random testing (ART) has better failure-detection capability and has been widely applied in different scenarios, such as numerical programs, some object-oriented programs, and mobile applications. However, not much work has been done on the effectiveness of ART for the programs with combinatorial input domain (i.e., the set of categorical data). To extend the ideas to the testing for combinatorial input domain, we have adopted different similarity measures that are widely used for categorical data in data mining and have proposed two similarity measures based on interaction coverage. Then, we propose a new version named ART-CID as an extension of ART in combinatorial input domain, which selects an element from categorical data as the next test case such that it has the lowest similarity against already generated test cases. Experimental results show that ART-CID generally performs better than RT, with respect to different evaluation metrics.

  1. On schemes of combinatorial transcription logic.

    PubMed

    Buchler, Nicolas E; Gerland, Ulrich; Hwa, Terence

    2003-04-29

    Cells receive a wide variety of cellular and environmental signals, which are often processed combinatorially to generate specific genetic responses. Here we explore theoretically the potentials and limitations of combinatorial signal integration at the level of cis-regulatory transcription control. Our analysis suggests that many complex transcription-control functions of the type encountered in higher eukaryotes are already implementable within the much simpler bacterial transcription system. Using a quantitative model of bacterial transcription and invoking only specific protein-DNA interaction and weak glue-like interaction between regulatory proteins, we show explicit schemes to implement regulatory logic functions of increasing complexity by appropriately selecting the strengths and arranging the relative positions of the relevant protein-binding DNA sequences in the cis-regulatory region. The architectures that emerge are naturally modular and evolvable. Our results suggest that the transcription regulatory apparatus is a "programmable" computing machine, belonging formally to the class of Boltzmann machines. Crucial to our results is the ability to regulate gene expression at a distance. In bacteria, this can be achieved for isolated genes via DNA looping controlled by the dimerization of DNA-bound proteins. However, if adopted extensively in the genome, long-distance interaction can cause unintentional intergenic cross talk, a detrimental side effect difficult to overcome by the known bacterial transcription-regulation systems. This may be a key factor limiting the genome-wide adoption of complex transcription control in bacteria. Implications of our findings for combinatorial transcription control in eukaryotes are discussed.

  2. Combinatorially Developed Peptide Receptors for Biosensors

    NASA Astrophysics Data System (ADS)

    Nakamura, Chikashi; Miyake, Jun

    Various combinatorial libraries were screened for short peptides of 4-10 mer, which were used as sensor molecules for capturing target chemicals or biomolecules. Immuno-antibodies can be synthesized in the living bodies of higher animals even for low-molecular-weight nonnatural chemical compounds, such as dioxins or PCBs. Recently, some peptide ligands that can even bind to inorganic crystals have been reported. This indicates that the 20 natural amino acids have the potential to recognize almost all types of molecules and substances. The question arises whether one should design a “rational” mini library of peptides consisting of a limited number of amino acids according to the motifs in epitopes or paratopes or the binding pocket sequences in receptors, or a completely “random” combinatorial library containing all sequences. If one wants to obtain a peptide binder to target a small chemical compound, the answer is a “random” library, since the molecular interaction between the target compound and an amino acid cannot be precisely predicted beforehand. In this section, we discuss the possibility of using short combinatorial peptides as binders for biosensors to detect chemical compounds.

  3. Chemistry and biochemistry of 13C hyperpolarized magnetic resonance using dynamic nuclear polarization

    PubMed Central

    Keshari, Kayvan R.; Wilson, David M.

    2014-01-01

    The study of transient chemical phenomena by conventional NMR has proved elusive, particularly for non-1H nuclei. For 13C, hyperpolarization using the dynamic nuclear polarization (DNP) technique has emerged as a powerful means to improve SNR. The recent development of rapid dissolution DNP methods has facilitated previously impossible in vitro and in vivo study of small molecules. This review presents the basics of the DNP technique, identification of appropriate DNP substrates, and approaches to increase hyperpolarized signal lifetimes. Also addressed are the biochemical events to which DNP-NMR has been applied, with descriptions of several probes that have met with in vivo success. PMID:24363044

  4. High pressure chemistry of thioaldehydes: A first-principles molecular dynamics study

    NASA Astrophysics Data System (ADS)

    Zhang, Yaoting; Mosey, Nicholas J.

    2016-11-01

    First-principles molecular dynamics simulations are used to investigate the chemical behavior of bulk thioacetaldehyde (MeC(H)S) in response to changes in pressure, P. The simulations show that these molecules oligomerize in response to applied P. Oligomerization is initiated through C—S bond formation, with constrained dynamics simulations showing that the barrier to this reaction step is lowered significantly by applied P. Subsequent reactions involving the formation of additional C—S bonds or radical processes that lead to S—S and C—C bonds lengthen the oligomers. Oligomerization is terminated through proton transfer or the formation of rings. The mechanistic details of all reactions are examined. The results indicate that the P-induced reactivity of the MeC(H)S-based system differs significantly from that of analogous MeC(H)O-based systems, which have been reported previously. Comparison with the MeC(H)O study shows that replacing oxygen with sulfur significantly lowers the P required to initiate oligomerization (from 26 GPa to 5 GPa), increases the types of reactions in which systems of this type can take part, and increases the variety of products formed through these reactions. These differences can be explained in terms of the electronic structures of these systems, which may be useful for certain high P applications.

  5. Molecular Seesaw: Intricate Dynamics and Versatile Chemistry of Heteroaromatics on Metal Surfaces.

    PubMed

    Filimonov, Sergey N; Liu, Wei; Tkatchenko, Alexandre

    2017-03-03

    The design of novel elementary surface processes is important for applications in catalysis, single-molecule junctions, molecular sensors, switches, and surface-mounted molecular machines. Here we demonstrate by van der Waals inclusive density functional theory calculations that a small and relatively simple heteroaromatic compound s-triazine (C3H3N3) unexpectedly possesses five metastable states when adsorbed on the Pt(111) surface. This diversity of the adsorption states stems from an interplay between versatile molecule/surface chemical bonding and van der Waals interactions and from "softening" of the aromatic ring by nitrogen substitution, which makes folding of the aromatic ring energetically much less demanding as compared to benzene. The intricate seesaw-like surface dynamics and tunable electronic structure of s-triazine show promise for applications in molecular sensors and switches. The broad implications of our findings are demonstrated for triazine- and pyrimidine-based heteroaromatic compounds and other metal surfaces.

  6. Potential changes in arctic seasonality and plant communities may impact tundra soil chemistry and carbon dynamics

    NASA Astrophysics Data System (ADS)

    Crow, S.; Cooper, E.; Beilman, D.; Filley, T.; Reimer, P.

    2009-04-01

    On the Svalbard archipelago, as in other high Arctic regions, tundra soil organic matter (SOM) is primarily plant detritus that is largely stabilized by cold, moist conditions and low nitrogen availability. However, the resistance of SOM to decomposition is also influenced by the quality of organic matter inputs to soil. Different plant communities are likely to give different qualities to SOM, especially where lignin-rich woody species encroach into otherwise graminoid and bryophyte-dominated regions. Arctic woody plant species are particularly sensitive to changes in temperature, snow cover, and growing season length. In a changing environment, litter chemistry may emerge as an important control on tundra SOM stabilization. In summer 2007, we collected plant material and soil from the highly-organic upper horizon (appx. 0-5 cm) and the mineral-dominated lower horizon (appx. 5-10cm) from four locations in the southwest facing valleys of Svalbard, Norway. The central goal of the ongoing experiment is to determine whether a greater abundance of woody plants could provide a negative feedback to warming impacts on the carbon (C) balance of Arctic soils. Towards this, we used a combination of plant biopolymer analyses (cupric oxide oxidation and quantification of lignin-derived phenols and cutin/suberin-derived aliphatics) and radiocarbon-based estimates of C longevity and mean residence time (MRT) to characterize potential links between plant type and soil C pools. We found that graminoid species regenerate above- and belowground tissue each year, whereas woody species (Cassiope tetragona and Dryas octopetala) regenerated only leaves yearly. In contrast, C within live branches and roots persisted for 15-18 yr on average. Leaves from woody species remained nearly intact in surface litter for up to 20 yr without being incorporated into the upper soil horizon. Leaves from both graminoid and woody species were concentrated in lignin-derived phenols relative to roots, but

  7. Molecular modeling of the structural and dynamical properties of secondary plant cell walls: influence of lignin chemistry.

    PubMed

    Charlier, Landry; Mazeau, Karim

    2012-04-12

    A modeling of lignified secondary plant cell walls adapted to grass has been achieved, using molecular dynamics for time up to 180 ns, applied to systems composed of cellulose, xylan, water, and lignin. The overall model, which was 70 nm thick for a volume of 74.4 nm(3), consisted of two crystalline cellulose layers, each being two molecules deep, separated by an interlayer space where the three other components were located. Whereas the cellulose and xylan chemistry was fixed, 18 lignin systems were considered that varied not only in guaiacyl, syringyl, and p-hydroxyphenyl composition, but also in chain length, linkage types, and the presence or absence of coumaryl units. The stabilized models showed a well-defined interface between xylan and cellulose, but some interpenetration of xylan into the lignin part of the models. A survey of the 18 models showed that their lignin component was amorphous and that their density profile was very variable and essentially model dependent. This variability was also reflected in the co-orientation of the lignin phenyl rings with respect to the cellulose surfaces, some systems showing some orientation whereas others did not. The pattern of void distribution accessible to water varied from one system to the next, but the overall void volume was systematically established at around 3%, accepting around 200 water molecules. The estimated mobility of the water molecules interacting with lignin was 1.5 times greater than that interacting with carbohydrates.

  8. Effect of backbone chemistry on hybridization thermodynamics of oligonucleic acids: a coarse-grained molecular dynamics simulation study.

    PubMed

    Ghobadi, Ahmadreza F; Jayaraman, Arthi

    2016-02-28

    In this paper we study how varying oligonucleic acid backbone chemistry affects the hybridization/melting thermodynamics of oligonucleic acids. We first describe the coarse-grained (CG) model with tunable parameters that we developed to enable the study of both naturally occurring oligonucleic acids, such as DNA, and their chemically-modified analogues, such as peptide nucleic acids (PNAs) and locked nucleic acids (LNAs). The DNA melting curves obtained using such a CG model and molecular dynamics simulations in an implicit solvent and with explicit ions match with the melting curves obtained using the empirical nearest-neighbor models. We use these CG simulations to then elucidate the effect of backbone flexibility, charge, and nucleobase spacing along the backbone on the melting curves, potential energy and conformational entropy change upon hybridization and base-pair hydrogen bond residence time. We find that increasing backbone flexibility decreases duplex thermal stability and melting temperature mainly due to increased conformational entropy loss upon hybridization. Removing charges from the backbone enhances duplex thermal stability due to the elimination of electrostatic repulsion and as a result a larger energetic gain upon hybridization. Lastly, increasing nucleobase spacing decreases duplex thermal stability due to decreasing stacking interactions that are important for duplex stability.

  9. Code interoperability and standard data formats in quantum chemistry and quantum dynamics: The Q5/D5Cost data model.

    PubMed

    Rossi, Elda; Evangelisti, Stefano; Laganà, Antonio; Monari, Antonio; Rampino, Sergio; Verdicchio, Marco; Baldridge, Kim K; Bendazzoli, Gian Luigi; Borini, Stefano; Cimiraglia, Renzo; Angeli, Celestino; Kallay, Peter; Lüthi, Hans P; Ruud, Kenneth; Sanchez-Marin, José; Scemama, Anthony; Szalay, Peter G; Tajti, Attila

    2014-03-30

    Code interoperability and the search for domain-specific standard data formats represent critical issues in many areas of computational science. The advent of novel computing infrastructures such as computational grids and clouds make these issues even more urgent. The design and implementation of a common data format for quantum chemistry (QC) and quantum dynamics (QD) computer programs is discussed with reference to the research performed in the course of two Collaboration in Science and Technology Actions. The specific data models adopted, Q5Cost and D5Cost, are shown to work for a number of interoperating codes, regardless of the type and amount of information (small or large datasets) to be exchanged. The codes are either interfaced directly, or transfer data by means of wrappers; both types of data exchange are supported by the Q5/D5Cost library. Further, the exchange of data between QC and QD codes is addressed. As a proof of concept, the H + H2 reaction is discussed. The proposed scheme is shown to provide an excellent basis for cooperative code development, even across domain boundaries. Moreover, the scheme presented is found to be useful also as a production tool in the grid distributed computing environment.

  10. Combinatorial discovery of tumor targeting peptides using phage display.

    PubMed

    Landon, Linda A; Deutscher, Susan L

    2003-10-15

    Peptides possess appropriate pharmacokinetic properties to serve as cancer imaging or therapeutic targeting agents. Currently, only a small number of rationally-derived, labeled peptide analogues that target only a limited subset of antigens are available. Thus, finding new cancer targeting peptides is a central goal in the field of molecular targeting. Novel tumor-avid peptides can be efficiently identified via affinity selections using complex random peptide libraries containing millions of peptides that are displayed on bacteriophage. In vitro and in situ affinity selections may be used to identify peptides with high affinity for the target antigen in vitro. Unfortunately, it has been found that peptides selected in vitro or in situ may not effectively target tumors in vivo due to poor peptide stability and other problems. To improve in vivo targeting, methodological combinatorial chemistry innovations allow selections to be conducted in the environment of the whole animal. Thus, new targeting peptides with optimal in vivo properties can be selected in vivo in tumor-bearing animals. In vivo selections have been proven successful in identifying peptides that target the vasculature of specific organs. In addition, in vivo selections have identified peptides that bind specifically to the surface of or are internalized into tumor cells. In the future, direct selection of peptides for cancer imaging may be expedited using genetically engineered bacteriophage libraries that encode peptides with intrinsic radiometal-chelation or fluorescent sequences.

  11. The formation of Uranus and Neptune in solid-rich feeding zones: Connecting chemistry and dynamics

    NASA Astrophysics Data System (ADS)

    Dodson-Robinson, Sarah E.; Bodenheimer, Peter

    2010-05-01

    The core accretion theory of planet formation has at least two fundamental problems explaining the origins of Uranus and Neptune: (1) dynamical times in the trans-saturnian solar nebula are so long that core growth can take >15 Myr and (2) the onset of runaway gas accretion that begins when cores reach ˜10 M⊕ necessitates a sudden gas accretion cutoff just as Uranus and Neptune's cores reach critical mass. Both problems may be resolved by allowing the ice giants to migrate outward after their formation in solid-rich feeding zones with planetesimal surface densities well above the minimum-mass solar nebula. We present new simulations of the formation of Uranus and Neptune in the solid-rich disk of Dodson-Robinson et al. (Dodson-Robinson, S.E., Willacy, K., Bodenheimer, P., Turner, N.J., Beichman, C.A. [2009]. Icarus 200, 672-693) using the initial semimajor axis distribution of the Nice model (Gomes, R., Levison, H.F., Tsiganis, K., Morbidelli, A. [2005]. Nature 435, 466-469; Morbidelli, A., Levison, H.F., Tsiganis, K., Gomes, R. [2005]. Nature 435, 462-465; Tsiganis, K., Gomes, R., Morbidelli, A., Levison, H.F. [2005]. Nature 435, 459-461), with one ice giant forming at 12 AU and the other at 15 AU. The innermost ice giant reaches its present mass after 3.8-4.0 Myr and the outermost after 5.3-6 Myr, a considerable time decrease from previous one-dimensional simulations (e.g. Pollack, J.B., Hubickyj, O., Bodenheimer, P., Lissauer, J.J., Podolak, M., Greenzweig, Y. [1996]. Icarus 124, 62-85). The core masses stay subcritical, eliminating the need for a sudden gas accretion cutoff. Our calculated carbon mass fractions of 22% are in excellent agreement with the ice giant interior models of Podolak et al. (Podolak, M., Weizman, A., Marley, M. [1995]. Planet. Space Sci. 43, 1517-1522) and Marley et al. (Marley, M.S., Gómez, P., Podolak, M. [1995]. J. Geophys. Res. 100, 23349-23354). Based on the requirement that the ice giant-forming planetesimals contain >10% mass

  12. Flow path functioning identified from fundamental dynamics in sub-hourly, non-conservative stream chemistry

    NASA Astrophysics Data System (ADS)

    Chappell, N. A.; Jones, T.

    2013-12-01

    Within upland streams, concentration & load of many solutes (e.g. H+, DOC) varies very rapidly through storm periods. The shape & features of concentration or load chemographs are an expression of the fundamental dynamics in hydrologic & biogeochemical delivery mechanisms integrated at basin scales. If storm-period chemographs are grossly under-sampled so that time-series does not represent the true chemograph shape, then numerical descriptors of this shape or of the dynamic relationship between controlling variables (e.g. rainfall) & the chemograph will be distorted from true values (Littlewood 1992 IH Rpt 117; Littlewood & Croke 2013 Hydrol Res). Distortions of these dynamic response characteristics or DRCs (model parameters) can then lead to misinterpretation of hydrologic & biogeochemical processes via errors in relative contributions of identified flow paths, rates of propagation along these paths etc. A transfer function (TF) approach can be used to illustrate minimum sampling intensities needed to avoid these errors. Given 15-min observations, CAPTAIN-RIV identification routines for continuous-time TFs give Time Constants (TCs) of only 2 hrs for fast components of responses of rainfall to H+ load in Llyn Brianne streams (Chappell et al 2013 BHS). Given that Time Series Analysis dictates a sampling intensity five times finer than the TC, sampling at 24 min intervals or shorter was needed & achieved in this example. Considerable work is now focused on modeling of chemically-conservative river constituents (namely chloride & water isotopes) to help determine differences in residence times, storage & other DRCs of rainfall-streamflow & associated solute paths (Hrachowitz et al 2013 Hydrol Earth Syst Sci). Comparatively little modeling has focused on high frequency (i.e. sub-hourly), non-conservative river solutes (e.g. H+, DOC). Modeling of these basin-integrated variables should be considered complementary to that for conservative solutes, given: (1) their

  13. Quality management science in clinical chemistry: a dynamic framework for continuous improvement of quality.

    PubMed

    Westgard, J O; Burnett, R W; Bowers, G N

    1990-10-01

    Current quality assurance approaches will not be adequate to satisfy the needs for quality in the next decade. Quality management science (QMS), as evolving in industry today, provides the dynamic framework necessary to provide continuous improvement of quality. QMS emphasizes the importance of defining quality goals based on the needs and expectations (implied needs) of customers. The laboratory can develop customer-friendly goals and measures of quality by recognizing that customers' experiences are represented by a totality of results. Quality goals and measures are best communicated as "total performance" by specifying a limit and percentile of the distribution, rather than a mean and standard deviation. Application of quality goals within the laboratory will usually require partitioning the total performance goal into components and translating those components into specifications to guide the operation and management of production processes. QMS also extends beyond technical processes to people processes and provides guidance for improving the quality of worklife and caring for the laboratory's most essential resource--our people.

  14. Modelling non-equilibrium secondary organic aerosol formation and evaporation with the aerosol dynamics, gas- and particle-phase chemistry kinetic multilayer model ADCHAM

    SciTech Connect

    Roldin, P.; Eriksson, A. C.; Nordin, E. Z.; Hermansson, E.; Mogensen, Ditte; Rusanen, A.; Boy, Michael; Swietlicki, E.; Svenningsson, Birgitta; Zelenyuk, Alla; Pagels, J.

    2014-08-11

    We have developed the novel Aerosol Dynamics, gas- and particle- phase chemistry model for laboratory CHAMber studies (ADCHAM). The model combines the detailed gas phase Master Chemical Mechanism version 3.2, an aerosol dynamics and particle phase chemistry module (which considers acid catalysed oligomerization, heterogeneous oxidation reactions in the particle phase and non-ideal interactions between organic compounds, water and inorganic ions) and a kinetic multilayer module for diffusion limited transport of compounds between the gas phase, particle surface and particle bulk phase. In this article we describe and use ADCHAM to study: 1) the mass transfer limited uptake of ammonia (NH3) and formation of organic salts between ammonium (NH4+) and carboxylic acids (RCOOH), 2) the slow and almost particle size independent evaporation of α-pinene secondary organic aerosol (SOA) particles, and 3) the influence of chamber wall effects on the observed SOA formation in smog chambers.

  15. Chemistry and Molecular Dynamics Simulations of Heme b-HemQ and Coproheme-HemQ

    PubMed Central

    2016-01-01

    Recently, a novel pathway for heme b biosynthesis in Gram-positive bacteria has been proposed. The final poorly understood step is catalyzed by an enzyme called HemQ and includes two decarboxylation reactions leading from coproheme to heme b. Coproheme has been suggested to act as both substrate and redox active cofactor in this reaction. In the study presented here, we focus on HemQs from Listeria monocytogenes (LmHemQ) and Staphylococcus aureus (SaHemQ) recombinantly produced as apoproteins in Escherichia coli. We demonstrate the rapid and two-phase uptake of coproheme by both apo forms and the significant differences in thermal stability of the apo forms, coproheme-HemQ and heme b-HemQ. Reduction of ferric high-spin coproheme-HemQ to the ferrous form is shown to be enthalpically favored but entropically disfavored with standard reduction potentials of −205 ± 3 mV for LmHemQ and −207 ± 3 mV for SaHemQ versus the standard hydrogen electrode at pH 7.0. Redox thermodynamics suggests the presence of a pronounced H-bonding network and restricted solvent mobility in the heme cavity. Binding of cyanide to the sixth coproheme position is monophasic but relatively slow (∼1 × 104 M–1 s–1). On the basis of the available structures of apo-HemQ and modeling of both loaded forms, molecular dynamics simulation allowed analysis of the interaction of coproheme and heme b with the protein as well as the role of the flexibility at the proximal heme cavity and the substrate access channel for coproheme binding and heme b release. Obtained data are discussed with respect to the proposed function of HemQ in monoderm bacteria. PMID:27599156

  16. Effects of Suboptimal Bidding in Combinatorial Auctions

    NASA Astrophysics Data System (ADS)

    Schneider, Stefan; Shabalin, Pasha; Bichler, Martin

    Though the VCG auction assumes a central place in the mechanism design literature, there are a number of reasons for favoring iterative combinatorial auction designs. Several promising ascending auction formats have been developed throughout the past few years based on primal-dual and subgradient algorithms and linear programming theory. Prices are interpreted as a feasible dual solution and the provisional allocation is interpreted as a feasible primal solution. iBundle( 3) (Parkes and Ungar 2000), dVSV (de Vries et al. 2007) and the Ascending Proxy auction (Ausubel and Milgrom 2002) result in VCG payoffs when the coalitional value function satisfies the buyer submodularity condition and bidders bid straightforward, which is an expost Nash equilibrium in that case. iBEA and CreditDebit auctions (Mishra and Parkes 2007) do not even require the buyer submodularity condition and achieve the same properties for general valuations. In many situations, however, one cannot assume bidders to bid straightforward and it is not clear from the theory how these non-linear personalized price auctions (NLPPAs) perform in this case. Robustness of auctions with respect to different bidding behavior is therefore a critical issue for any application. We have conducted a large number of computational experiments to analyze the performance of NLPPA designs with respect to different bidding strategies and different valuation models. We compare the results of NLPPAs to those of the VCG auction and those of iterative combinatorial auctions with approximate linear prices, such as ALPS (Bichler et al. 2009) and the Combinatorial Clock auction (Porter et al. 2003).

  17. Polynomial Local Improvement Algorithms in Combinatorial Optimization.

    DTIC Science & Technology

    1981-11-01

    NUMBER SOL 81- 21 IIS -J O 15 14. TITLE (am#Su&Utl & YEO RPR ERO OEE Polynomial Local Improvement Algorithms in TcnclRpr Combinatorial Optimization 6...Stanford, CA 94305 II . CONTROLLING OFFICE NAME AND ADDRESS It. REPORT DATE Office of Naval Research - Dept. of the Navy November 1981 800 N. Qu~incy Street...corresponds to a node of the tree. ii ) The father of a vertex is its optimal adjacent vertex; if a vertex is a local optimum, it has no father. The tree is

  18. Apparatus for combinatorial screening of electrochemical materials

    DOEpatents

    A high throughput combinatorial screening method and apparatus for the evaluation of electrochemical materials using a single voltage source is disclosed wherein temperature changes arising from the application of an electrical load to a cell array are used to evaluate the relative electrochemical efficiency of the materials comprising the array. The apparatus may include an array of electrochemical cells that are connected to each other in parallel or in series, an electronic load for applying a voltage or current to the electrochemical cells , and a device , external to the cells, for monitoring the relative temperature of each cell when the load is applied.

    2009-12-15

    A high throughput combinatorial screening method and apparatus for the evaluation of electrochemical materials using a single voltage source (2) is disclosed wherein temperature changes arising from the application of an electrical load to a cell array (1) are used to evaluate the relative electrochemical efficiency of the materials comprising the array. The apparatus may include an array of electrochemical cells (1) that are connected to each other in parallel or in series, an electronic load (2) for applying a voltage or current to the electrochemical cells (1), and a device (3), external to the cells, for monitoring the relative temperature of each cell when the load is applied.

  19. Particulate matter chemistry and dynamics in the Twilight Zone at VERTIGO ALOHA and K2 Sites

    SciTech Connect

    Bishop, James K.B.; Wood, T.J.

    2008-03-25

    Understanding particle dynamics in the 'Twilight Zone' is critical to prediction of the ocean's carbon cycle. As part of the VERTIGO (VERtical Transformations In the Global Ocean) project, this rarely sampled regime extending from the base of the euphotic layer to 1000 m, was characterized by double-paired day/night Multiple Unit Large Volume in-situ Filtration System (MULVFS) deployments and by {approx}100 high-frequency CTD/transmissometer/turbidity sensor profiles. VERTIGO studies lasting three weeks, contrasted oligotrophic station ALOHA (22.75{sup o}N 158{sup o}W), sampled in June-July 2004, with a biologically productive location (47{sup o}N 161{sup o}E) near station K2 in the Oyashio, occupied July-August 2005. Profiles of major and minor particulate components (C{sub org}, N, P, Ca, Si, Sr, Ba, Mn) in <1, 1-51, and >51 {micro}m size fractions, in-water optics, neutrally buoyant sediment trap (NBST) fluxes, and zooplankton data were intercompared. MULVFS total C{sub org} and C-Star particle beam attenuation coefficient (C{sub P}) were consistently related at both sites with a 27 {micro}M m{sup -1} conversion factor. 26 At K2, C{sub P} profiles further showed a multitude of transient spikes throughout the water column and spike abundance profiles closely paralleled the double peaked abundance profiles of zooplankton. Also at K2, copepods contributed {approx}40% and 10%, night and day, respectively to >51 {micro}m C{sub org} of MULVFS samples in the mixed layer, but few copepods were collected in deeper waters; however, non-swimming radiolarians were quantitatively sampled. A recent hypothesis regarding POC differences between pumps and bottles is examined in light of these results. Particulate >51 {micro}m C{sub org}, N, and P at both ALOHA and K2 showed strong attenuation with depth at both sites. Notable at ALOHA were unusually high levels of >51 {micro}m Sr (up to 4 nM) in the mixed layer, a reflection of high abundances of SrSO{sub 4} precipitating

  20. Particulate matter chemistry and dynamics in the twilight zone at VERTIGO ALOHA and K2 sites

    NASA Astrophysics Data System (ADS)

    Bishop, James K. B.; Wood, T. J.

    2008-12-01

    Understanding particle dynamics in the 'Twilight Zone' is critical to prediction of the ocean's carbon cycle. As part of the VERtical Transport In the Global Ocean (VERTIGO) project, this rarely sampled regime extending from the base of the euphotic layer to 1000 m, was characterized by double-paired day/night Multiple Unit Large Volume in-situ Filtration System (MULVFS) deployments and by ˜100 high-frequency CTD/transmissometer/turbidity sensor profiles. VERTIGO studies lasting 3 weeks, contrasted oligotrophic station ALOHA (22.75°N 158°W), sampled in June-July 2004, with a biologically productive location (47 °N 161°E) near station K2 in the Oyashio, occupied July-August 2005. Profiles of major and minor particulate components (C org, N, P, Ca, Si, Sr, Ba, Mn) in <1, 1-51, and >51 μm size fractions, in-water optics, neutrally buoyant sediment trap (NBST) fluxes, and zooplankton data were intercompared. MULVFS total C org and C-Star particle beam attenuation coefficient ( C P) were consistently related at both sites with a 27 μM m -1 conversion factor. At K2, C P profiles further showed a multitude of transient spikes throughout the water column and spike abundance profiles closely paralleled the double peaked abundance profiles of zooplankton. Also at K2, copepods contributed ˜40% and 10%, night and day, respectively to >51 μm C org of MULVFS samples in the mixed layer, but few copepods were collected in deeper waters; however, non-swimming radiolarians were quantitatively sampled. A recent hypothesis regarding POC differences between pumps and bottles is examined in light of these results. Particulate >51 μm C org, N, and P at both ALOHA and K2 showed strong attenuation with depth at both sites. Notable at ALOHA were unusually high levels of >51 μm Sr (up to 4 nM) in the mixed layer, a reflection of high abundances of SrSO 4 precipitating Acantharia. Notable at K2 were major changes in water column inventories of many particulate components to 700 m

  1. Combinatorial Libraries of Bis-Heterocyclic Compounds with Skeletal Diversity

    PubMed Central

    Soural, Miroslav; Bouillon, Isabelle; Krchňák, Viktor

    2009-01-01

    Combinatorial solid-phase synthesis of bis-heterocyclic compounds, characterized by the presence of two heterocyclic cores connected by a spacer of variable length/structure, provided structurally heterogeneous libraries with skeletal diversity. Both heterocyclic rings were assembled on resin in a combinatorial fashion. PMID:18811208

  2. Self-encoding resin beads of combinatorial library screening

    NASA Astrophysics Data System (ADS)

    Lei, Du; Zhao, Yuandi; Cheng, Tongsheng; Zeng, Shaoqun; Luo, Qingming

    2003-07-01

    The latest self-encoding resin bead is a novel technology for solid phase synthesis combinatorial library screening. A new encode-positional deconvolution strategy which was based on that technology been illustrated compared with positional scanning and iterative strategies. The self-encoding resin beads technology provides an efficient method for improving the high-throughput screening of combinatorial library.

  3. Combinatorial design of textured mechanical metamaterials.

    PubMed

    Coulais, Corentin; Teomy, Eial; de Reus, Koen; Shokef, Yair; van Hecke, Martin

    2016-07-28

    The structural complexity of metamaterials is limitless, but, in practice, most designs comprise periodic architectures that lead to materials with spatially homogeneous features. More advanced applications in soft robotics, prosthetics and wearable technology involve spatially textured mechanical functionality, which requires aperiodic architectures. However, a naive implementation of such structural complexity invariably leads to geometrical frustration (whereby local constraints cannot be satisfied everywhere), which prevents coherent operation and impedes functionality. Here we introduce a combinatorial strategy for the design of aperiodic, yet frustration-free, mechanical metamaterials that exhibit spatially textured functionalities. We implement this strategy using cubic building blocks-voxels-that deform anisotropically, a local stacking rule that allows cooperative shape changes by guaranteeing that deformed building blocks fit together as in a three-dimensional jigsaw puzzle, and three-dimensional printing. These aperiodic metamaterials exhibit long-range holographic order, whereby the two-dimensional pixelated surface texture dictates the three-dimensional interior voxel arrangement. They also act as programmable shape-shifters, morphing into spatially complex, but predictable and designable, shapes when uniaxially compressed. Finally, their mechanical response to compression by a textured surface reveals their ability to perform sensing and pattern analysis. Combinatorial design thus opens up a new avenue towards mechanical metamaterials with unusual order and machine-like functionalities.

  4. Combinatorial design of textured mechanical metamaterials

    NASA Astrophysics Data System (ADS)

    Coulais, Corentin; Teomy, Eial; de Reus, Koen; Shokef, Yair; van Hecke, Martin

    2016-07-01

    The structural complexity of metamaterials is limitless, but, in practice, most designs comprise periodic architectures that lead to materials with spatially homogeneous features. More advanced applications in soft robotics, prosthetics and wearable technology involve spatially textured mechanical functionality, which requires aperiodic architectures. However, a naive implementation of such structural complexity invariably leads to geometrical frustration (whereby local constraints cannot be satisfied everywhere), which prevents coherent operation and impedes functionality. Here we introduce a combinatorial strategy for the design of aperiodic, yet frustration-free, mechanical metamaterials that exhibit spatially textured functionalities. We implement this strategy using cubic building blocks—voxels—that deform anisotropically, a local stacking rule that allows cooperative shape changes by guaranteeing that deformed building blocks fit together as in a three-dimensional jigsaw puzzle, and three-dimensional printing. These aperiodic metamaterials exhibit long-range holographic order, whereby the two-dimensional pixelated surface texture dictates the three-dimensional interior voxel arrangement. They also act as programmable shape-shifters, morphing into spatially complex, but predictable and designable, shapes when uniaxially compressed. Finally, their mechanical response to compression by a textured surface reveals their ability to perform sensing and pattern analysis. Combinatorial design thus opens up a new avenue towards mechanical metamaterials with unusual order and machine-like functionalities.

  5. A combinatorial morphospace for angiosperm pollen

    NASA Astrophysics Data System (ADS)

    Mander, Luke

    2016-04-01

    The morphology of angiosperm (flowering plant) pollen is extraordinarily diverse. This diversity results from variations in the morphology of discrete anatomical components. These components include the overall shape of a pollen grain, the stratification of the exine, the number and form of any apertures, the type of dispersal unit, and the nature of any surface ornamentation. Different angiosperm pollen morphotypes reflect different combinations of these discrete components. In this talk, I ask the following question: given the anatomical components of angiosperm pollen that are known to exist in the plant kingdom, how many unique biologically plausible combinations of these components are there? I explore this question from the perspective of enumerative combinatorics using an algorithm I have written in the Python programming language. This algorithm (1) calculates the number of combinations of these components; (2) enumerates those combinations; and (3) graphically displays those combinations. The result is a combinatorial morphospace that reflects an underlying notion that the process of morphogenesis in angiosperm pollen can be thought of as an n choose k counting problem. I compare the morphology of extant and fossil angiosperm pollen grains to this morphospace, and suggest that from a combinatorial point of view angiosperm pollen is not as diverse as it could be, which may be a result of developmental constraints.

  6. Combinatorial Multiobjective Optimization Using Genetic Algorithms

    NASA Technical Reports Server (NTRS)

    Crossley, William A.; Martin. Eric T.

    2002-01-01

    The research proposed in this document investigated multiobjective optimization approaches based upon the Genetic Algorithm (GA). Several versions of the GA have been adopted for multiobjective design, but, prior to this research, there had not been significant comparisons of the most popular strategies. The research effort first generalized the two-branch tournament genetic algorithm in to an N-branch genetic algorithm, then the N-branch GA was compared with a version of the popular Multi-Objective Genetic Algorithm (MOGA). Because the genetic algorithm is well suited to combinatorial (mixed discrete / continuous) optimization problems, the GA can be used in the conceptual phase of design to combine selection (discrete variable) and sizing (continuous variable) tasks. Using a multiobjective formulation for the design of a 50-passenger aircraft to meet the competing objectives of minimizing takeoff gross weight and minimizing trip time, the GA generated a range of tradeoff designs that illustrate which aircraft features change from a low-weight, slow trip-time aircraft design to a heavy-weight, short trip-time aircraft design. Given the objective formulation and analysis methods used, the results of this study identify where turboprop-powered aircraft and turbofan-powered aircraft become more desirable for the 50 seat passenger application. This aircraft design application also begins to suggest how a combinatorial multiobjective optimization technique could be used to assist in the design of morphing aircraft.

  7. Earle K. Plyler Prize for Molecular Spectroscopy & Dynamics Lecture: Broadband Rotational Spectroscopy for Chemical Kinetics, Molecular Structure, and Analytical Chemistry

    NASA Astrophysics Data System (ADS)

    Pate, Brooks

    2013-03-01

    Advances in high-speed digital electronics have enabled a new generation of molecular rotational spectroscopy techniques that provide instantaneous broadband spectral coverage. These techniques use a chirped excitation pulse to coherently excite the molecular sample over a spectral bandwidth of 10 GHz or larger through rapid passage. The subsequent time-domain emission is recorded using high-speed digitizers (up to 100 Gigasample/s) and the frequency domain spectrum is produced by fast Fourier transformation. The chirped-pulse Fourier transform (CP-FT) method has been implemented in the microwave frequency range (2-40 GHz) for studies of cold samples in pulsed jet sources and in the mm-wave/terahertz (THz) frequency range for studies of samples at room-temperature. The method has opened new applications for molecular rotational spectroscopy in the area of chemical kinetics where dynamic rotational spectroscopy is used to measure the rates of unimolecular isomerization reactions in highly excited molecules prepared by pulsed infrared laser excitation. In these applications, the isomerization rate is obtained from an analysis of the overall line shapes which are modified by chemical exchange leading to coalescence behavior similar to the effect in NMR spectroscopy. The sensitivity of the method and the ability to extend it to low frequency (2-8 GHz) have significantly increased the size range of molecules and molecular clusters for structure determination using isotopic substitution to build up the 3D molecular structures atom-by-atom. Application to the structure of water clusters with up to 15 water molecules will be presented. When coupled with advances in solid-state mm-wave/THz devices, this method provides a direct digital technique for analytical chemistry of room-temperature gases based on molecular rotational spectroscopy. These high-throughput methods can analyze complex sample mixtures with unmatched chemical selectivity and short analysis times. Work

  8. Techniques for analysis and purification in high-throughput chemistry.

    PubMed

    Hughes, I; Hunter, D

    2001-06-01

    The success of combinatorial chemistry, and the increased emphasis on single well-characterised compounds of high purity, has had a significant impact on analytical and purification technologies. The requirement for ever-increasing throughput has led to the automation and parallelisation of these techniques. Advances have also been made in developing faster methods to augment throughput further.

  9. Microbatteries for Combinatorial Studies of Conventional Lithium-Ion Batteries

    NASA Technical Reports Server (NTRS)

    West, William; Whitacre, Jay; Bugga, Ratnakumar

    2003-01-01

    Integrated arrays of microscopic solid-state batteries have been demonstrated in a continuing effort to develop microscopic sources of power and of voltage reference circuits to be incorporated into low-power integrated circuits. Perhaps even more importantly, arrays of microscopic batteries can be fabricated and tested in combinatorial experiments directed toward optimization and discovery of battery materials. The value of the combinatorial approach to optimization and discovery has been proven in the optoelectronic, pharmaceutical, and bioengineering industries. Depending on the specific application, the combinatorial approach can involve the investigation of hundreds or even thousands of different combinations; hence, it is time-consuming and expensive to attempt to implement the combinatorial approach by building and testing full-size, discrete cells and batteries. The conception of microbattery arrays makes it practical to bring the advantages of the combinatorial approach to the development of batteries.

  10. Asymmetric Proteome Equalization of the Skeletal Muscle Proteome Using a Combinatorial Hexapeptide Library

    PubMed Central

    Rivers, Jenny; Hughes, Chris; McKenna, Thérèse; Woolerton, Yvonne; Vissers, Johannes P. C.; Langridge, James I.; Beynon, Robert J.

    2011-01-01

    Immobilized combinatorial peptide libraries have been advocated as a strategy for equalization of the dynamic range of a typical proteome. The technology has been applied predominantly to blood plasma and other biological fluids such as urine, but has not been used extensively to address the issue of dynamic range in tissue samples. Here, we have applied the combinatorial library approach to the equalization of a tissue where there is also a dramatic asymmetry in the range of abundances of proteins; namely, the soluble fraction of skeletal muscle. We have applied QconCAT and label-free methodology to the quantification of the proteins that bind to the beads as the loading is progressively increased. Although some equalization is achieved, and the most abundant proteins no longer dominate the proteome analysis, at high protein loadings a new asymmetry of protein expression is reached, consistent with the formation of complex assembles of heat shock proteins, cytoskeletal elements and other proteins on the beads. Loading at different ionic strength values leads to capture of different subpopulations of proteins, but does not completely eliminate the bias in protein accumulation. These assemblies may impair the broader utility of combinatorial library approaches to the equalization of tissue proteomes. However, the asymmetry in equalization is manifest at either low and high ionic strength values but manipulation of the solvent conditions may extend the capacity of the method. PMID:22205978

  11. Combustion chemistry

    SciTech Connect

    Brown, N.J.

    1993-12-01

    This research is concerned with the development and use of sensitivity analysis tools to probe the response of dependent variables to model input variables. Sensitivity analysis is important at all levels of combustion modeling. This group`s research continues to be focused on elucidating the interrelationship between features in the underlying potential energy surface (obtained from ab initio quantum chemistry calculations) and their responses in the quantum dynamics, e.g., reactive transition probabilities, cross sections, and thermal rate coefficients. The goals of this research are: (i) to provide feedback information to quantum chemists in their potential surface refinement efforts, and (ii) to gain a better understanding of how various regions in the potential influence the dynamics. These investigations are carried out with the methodology of quantum functional sensitivity analysis (QFSA).

  12. Implementation of a research-based lab module in a high school chemistry curriculum: A study of classroom dynamics

    NASA Astrophysics Data System (ADS)

    Pilarz, Matthew

    For this study, a research-based lab module was implemented in two high school chemistry classes for the purpose of examining classroom dynamics throughout the process of students completing the module. A research-based lab module developed for use in undergraduate laboratories by the Center for Authentic Science Practice in Education (CASPiE) was modified and implemented in two high school settings. This module consisted of four phases: Skill Building, Experimental Design, Independent Research, and Results and Poster Presentation. Classroom dynamics were studied by considering the students' and teachers' perceptions of their experiences during the completion of the module and by examining the interactions between students and teachers that took place throughout the module. The results reveal that there are shifts in classroom dynamics throughout the four phases of the module. In the Skill Building phase there was a great deal of dependence on the teacher for help in completing tasks. However, there is a slight contrast to what the students and teachers reported about their experiences during this phase. The teachers describe the students as being very dependent on them and asking questions constantly during the Skill Building experiments. The students report that they tried to figure out their problems with their lab partners and students in other lab groups before asking the teacher for help. The teachers perceived that students came to them immediately for help and did not realize that students were coming to them as sort of a last resort when they could not solve problems on their own. In the Experimental Design phase the students and teachers both report that the lab groups were working together as groups to design their experiments, and rarely had interactions with anyone outside of their lab group. For the Independent Research phase both students and teachers report that lab groups worked very independently of any outside assistance and that they began to

  13. The Met Office HadGEM3-ES chemistry-climate model: evaluation of stratospheric dynamics and its impact on ozone

    NASA Astrophysics Data System (ADS)

    Hardiman, Steven C.; Butchart, Neal; O'Connor, Fiona M.; Rumbold, Steven T.

    2017-03-01

    Free-running and nudged versions of a Met Office chemistry-climate model are evaluated and used to investigate the impact of dynamics versus transport and chemistry within the model on the simulated evolution of stratospheric ozone. Metrics of the dynamical processes relevant for simulating stratospheric ozone are calculated, and the free-running model is found to outperform the previous model version in 10 of the 14 metrics. In particular, large biases in stratospheric transport and tropical tropopause temperature, which existed in the previous model version, are substantially reduced, making the current model more suitable for the simulation of stratospheric ozone. The spatial structure of the ozone hole, the area of polar stratospheric clouds, and the increased ozone concentrations in the Northern Hemisphere winter stratosphere following sudden stratospheric warmings, were all found to be sensitive to the accuracy of the dynamics and were better simulated in the nudged model than in the free-running model. Whilst nudging can, in general, provide a useful tool for removing the influence of dynamical biases from the evolution of chemical fields, this study shows that issues can remain in the climatology of nudged models. Significant biases in stratospheric vertical velocities, age of air, water vapour, and total column ozone still exist in the Met Office nudged model. Further, these can lead to biases in the downward flux of ozone into the troposphere.

  14. Dynamic mixtures: challenges and opportunities for the amplification and sensing of scents.

    PubMed

    Herrmann, Andreas

    2012-07-09

    Nature generates compounds as complicated mixtures, but surprisingly little is known about the synergies or inhibitory effects of compound mixtures, which is likely to become an important research area in life sciences in the near future. Some recently developed concepts in dynamic combinatorial/covalent chemistry (DCC) have been applied to amplify (increase the intensity and long-lastingness of perception) and sense (selectively detect and discriminate) individual bioactive volatile molecules in compound mixtures. This Concept article focuses on the potential of DCC to impact and modulate the biological and chemical properties of mixtures of bioactive volatile compounds to gain a more fundamental understanding of the properties of compound mixtures in molecular recognition.

  15. Dynamic nuclear polarization NMR spectroscopy allows high-throughput characterization of microporous organic polymers.

    PubMed

    Blanc, Frédéric; Chong, Samantha Y; McDonald, Tom O; Adams, Dave J; Pawsey, Shane; Caporini, Marc A; Cooper, Andrew I

    2013-10-16

    Dynamic nuclear polarization (DNP) solid-state NMR was used to obtain natural abundance (13)C and (15)N CP MAS NMR spectra of microporous organic polymers with excellent signal-to-noise ratio, allowing for unprecedented details in the molecular structure to be determined for these complex polymer networks. Sensitivity enhancements larger than 10 were obtained with bis-nitroxide radical at 14.1 T and low temperature (∼105 K). This DNP MAS NMR approach allows efficient, high-throughput characterization of libraries of porous polymers prepared by combinatorial chemistry methods.

  16. Quantum-chemistry based calibration of the alkali metal cation series (Li(+)-Cs(+)) for large-scale polarizable molecular mechanics/dynamics simulations.

    PubMed

    Dudev, Todor; Devereux, Mike; Meuwly, Markus; Lim, Carmay; Piquemal, Jean-Philip; Gresh, Nohad

    2015-02-15

    The alkali metal cations in the series Li(+)-Cs(+) act as major partners in a diversity of biological processes and in bioinorganic chemistry. In this article, we present the results of their calibration in the context of the SIBFA polarizable molecular mechanics/dynamics procedure. It relies on quantum-chemistry (QC) energy-decomposition analyses of their monoligated complexes with representative O-, N-, S-, and Se- ligands, performed with the aug-cc-pVTZ(-f) basis set at the Hartree-Fock level. Close agreement with QC is obtained for each individual contribution, even though the calibration involves only a limited set of cation-specific parameters. This agreement is preserved in tests on polyligated complexes with four and six O- ligands, water and formamide, indicating the transferability of the procedure. Preliminary extensions to density functional theory calculations are reported.

  17. Large eddy simulation of reactive pollutants in a deep urban street canyon: Coupling dynamics with O3-NOx-VOC chemistry.

    PubMed

    Zhong, Jian; Cai, Xiao-Ming; Bloss, William James

    2017-02-12

    A large eddy simulation (LES) model coupled with O3-NOx-VOC chemistry is implemented to simulate the coupled effects of emissions, mixing and chemical pre-processing within an idealised deep (aspect ratio = 2) urban street canyon under a weak wind condition. Reactive pollutants exhibit significant spatial variations in the presence of two vertically aligned unsteady vortices formed in the canyon. Comparison of the LES results from two chemical schemes (simple NOx-O3 chemistry and a more comprehensive Reduced Chemical Scheme (RCS) chemical mechanism) shows that the concentrations of NO2 and Ox inside the street canyon are enhanced by approximately 30-40% via OH/HO2 chemistry. NO, NOx, O3, OH and HO2 are chemically consumed, while NO2 and Ox (total oxidant) are chemically produced within the canyon environment. Within-canyon pre-processing increases oxidant fluxes from the canyon to the overlying boundary layer, and this effect is greater for deeper street canyons (as found in many traditional European urban centres) than shallower (lower aspect ratio) streets. There is clear evidence of distinct behaviours for emitted chemical species and entrained chemical species, and positive (or negative) values of intensities of segregations are found between pairs of species with similar (or opposite) behaviour. The simplified two-box model underestimated NO and O3 levels, but overestimated NO2 levels for both the lower and upper canyon compared with the more realistic LES-chemistry model. This suggests that the segregation effect due to incomplete mixing reduces the chemical conversion rate of NO to NO2. This study reveals the impacts of nonlinear O3-NOx-VOC photochemical processes in the incomplete mixing environment and provides a better understanding of the pre-processing of emissions within canyons, prior to their release to the urban boundary layer, through the coupling of street canyon dynamics and chemistry.

  18. Combinatorial optimization methods for disassembly line balancing

    NASA Astrophysics Data System (ADS)

    McGovern, Seamus M.; Gupta, Surendra M.

    2004-12-01

    Disassembly takes place in remanufacturing, recycling, and disposal with a line being the best choice for automation. The disassembly line balancing problem seeks a sequence which: minimizes workstations, ensures similar idle times, and is feasible. Finding the optimal balance is computationally intensive due to factorial growth. Combinatorial optimization methods hold promise for providing solutions to the disassembly line balancing problem, which is proven to belong to the class of NP-complete problems. Ant colony optimization, genetic algorithm, and H-K metaheuristics are presented and compared along with a greedy/hill-climbing heuristic hybrid. A numerical study is performed to illustrate the implementation and compare performance. Conclusions drawn include the consistent generation of optimal or near-optimal solutions, the ability to preserve precedence, the speed of the techniques, and their practicality due to ease of implementation.

  19. Combinatorial and computational challenges for biocatalyst design

    NASA Astrophysics Data System (ADS)

    Arnold, Frances H.

    2001-01-01

    Nature provides a fantastic array of catalysts extremely well suited to supporting life, but usually not so well suited for technology. Whether biocatalysis will have a significant technological impact depends on our finding robust routes for tailoring nature's catalysts or redesigning them anew. Laboratory evolution methods are now used widely to fine-tune the selectivity and activity of enzymes. The current rapid development of these combinatorial methods promises solutions to more complex problems, including the creation of new biosynthetic pathways. Computational methods are also developing quickly. The marriage of these approaches will allow us to generate the efficient, effective catalysts needed by the pharmaceutical, food and chemicals industries and should open up new opportunities for producing energy and chemicals from renewable resources.

  20. Combinatorial strategies for combating invasive fungal infections.

    PubMed

    Spitzer, Michaela; Robbins, Nicole; Wright, Gerard D

    2017-02-17

    Invasive fungal infections are an important cause of human mortality and morbidity, particularly for immunocompromised populations. However, there remains a paucity of antifungal drug treatments available to combat these fungal pathogens. Further, antifungal compounds are plagued with problems such as host toxicity, fungistatic activity, and the emergence of drug resistance in pathogen populations. A promising therapeutic strategy to increase drug effectiveness and mitigate the emergence of drug resistance is through the use of combination drug therapy. In this review we describe the current arsenal of antifungals in medicine and elaborate on the benefits of combination therapy to expand our current antifungal drug repertoire. We examine those antifungal combinations that have shown potential against fungal pathogens and discuss strategies being employed to discover novel combination therapeutics, in particular combining antifungal agents with non-antifungal bioactive compounds. The findings summarized in this review highlight the promise of combinatorial strategies in combatting invasive mycoses.

  1. Parametric and Combinatorial Problems in Constrained Optimization

    DTIC Science & Technology

    1993-02-28

    1 ).70 0.30 5 . 49 6 i 68 :ý7 3 74 76 76 17~ 7s 1711 0301 F 70 1 86 89 90) 90) 90 91 190 89...AD-A265 595 1 (),% AGE - 3 I F’ KAi/61 MfAR󈨞 Om sEB93 IIPA`ThA?4RXCTKtf COMBINATORIAL PROBLEMS IN CONSTRAINED OPTIMIZATION * ~2304/ 1 )5 AUJBREY B...POORE ~COLORADO STATE UNIVERSITY FORT COLLINS CO 80523 I SP CN SC ý N 1 -% vC iC R;N G A~ -~ S, i,’ S) 1 SCNSOR’NG M1’%C’NC (: AGENCY 4tPURT N~vBLQ

  2. Characterizing the combinatorial beam angle selection problem

    NASA Astrophysics Data System (ADS)

    Bangert, Mark; Ziegenhein, Peter; Oelfke, Uwe

    2012-10-01

    The beam angle selection (BAS) problem in intensity-modulated radiation therapy is often interpreted as a combinatorial optimization problem, i.e. finding the best combination of η beams in a discrete set of candidate beams. It is well established that the combinatorial BAS problem may be solved efficiently with metaheuristics such as simulated annealing or genetic algorithms. However, the underlying parameters of the optimization process, such as the inclusion of non-coplanar candidate beams, the angular resolution in the space of candidate beams, and the number of evaluated beam ensembles as well as the relative performance of different metaheuristics have not yet been systematically investigated. We study these open questions in a meta-analysis of four strategies for combinatorial optimization in order to provide a reference for future research related to the BAS problem in intensity-modulated radiation therapy treatment planning. We introduce a high-performance inverse planning engine for BAS. It performs a full fluence optimization for ≈3600 treatment plans per hour while handling up to 50 GB of dose influence data (≈1400 candidate beams). For three head and neck patients, we compare the relative performance of a genetic, a cross-entropy, a simulated annealing and a naive iterative algorithm. The selection of ensembles with 5, 7, 9 and 11 beams considering either only coplanar or all feasible candidate beams is studied for an angular resolution of 5°, 10°, 15° and 20° in the space of candidate beams. The impact of different convergence criteria is investigated in comparison to a fixed termination after the evaluation of 10 000 beam ensembles. In total, our simulations comprise a full fluence optimization for about 3000 000 treatment plans. All four combinatorial BAS strategies yield significant improvements of the objective function value and of the corresponding dose distributions compared to standard beam configurations with equi

  3. Dynamical amplification of the stratospheric solar response simulated with the Chemistry-Climate Model LMDz-Reprobus

    NASA Astrophysics Data System (ADS)

    Marchand, M.; Keckhut, P.; Lefebvre, S.; Claud, C.; Cugnet, D.; Hauchecorne, A.; Lefèvre, F.; Lefebvre, M.-P.; Jumelet, J.; Lott, F.; Hourdin, F.; Thuillier, G.; Poulain, V.; Bossay, S.; Lemennais, P.; David, C.; Bekki, S.

    2012-02-01

    The impact of the 11-year solar cycle on the stratosphere and, in particular, on the polar regions is investigated using simulations from the Chemistry Climate Model (CCM) LMDz-Reprobus. The annual solar signal clearly shows a stratospheric response largely driven by radiative and photochemical processes, especially in the upper stratosphere. A month-by-months analysis suggests that dynamical feedbacks play an important role in driving the stratospheric response on short timescales. CCM outputs on a 10 days frequency indicate how, in the northern hemisphere, changes in solar heating in the winter polar stratosphere may influence the upward propagation of planetary waves and thus their deposition of momentum, ultimately modifying the strength of the mean stratospheric overtuning circulation at middle and high latitudes. The model results emphasize that the main temperature and wind responses in the northern hemisphere can be explained by a different timing in the occurrence of Sudden Stratospheric Warmings (SSWs) that are caused by small changes in planetary wave propagation depending on solar conditions. The differences between simulations forced by different solar conditions indicate successive positive and negative responses during the course of the winter. The solar minimum simulation generally indicates a slightly stronger polar vortex early in the winter while the solar maximum simulation experiences more early SSWs with a stronger wave-mean flow interaction and reduced zonal wind at mid-latitudes in the upper stratosphere. The opposite response is observed during mid-winter, in February, with more SSWs simulated for solar minimum conditions while solar maximum conditions are associated with a damped planetary wave activity and a reinforced vortex after the initial stratospheric warming period. In late winter, the response is again reversed, as noticed in the temperature differences, with major SSW mostly observed in the solar maximum simulation and less

  4. Hybrid Self-Adaptive Evolution Strategies Guided by Neighborhood Structures for Combinatorial Optimization Problems.

    PubMed

    Coelho, V N; Coelho, I M; Souza, M J F; Oliveira, T A; Cota, L P; Haddad, M N; Mladenovic, N; Silva, R C P; Guimarães, F G

    2016-01-01

    This article presents an Evolution Strategy (ES)--based algorithm, designed to self-adapt its mutation operators, guiding the search into the solution space using a Self-Adaptive Reduced Variable Neighborhood Search procedure. In view of the specific local search operators for each individual, the proposed population-based approach also fits into the context of the Memetic Algorithms. The proposed variant uses the Greedy Randomized Adaptive Search Procedure with different greedy parameters for generating its initial population, providing an interesting exploration-exploitation balance. To validate the proposal, this framework is applied to solve three different [Formula: see text]-Hard combinatorial optimization problems: an Open-Pit-Mining Operational Planning Problem with dynamic allocation of trucks, an Unrelated Parallel Machine Scheduling Problem with Setup Times, and the calibration of a hybrid fuzzy model for Short-Term Load Forecasting. Computational results point out the convergence of the proposed model and highlight its ability in combining the application of move operations from distinct neighborhood structures along the optimization. The results gathered and reported in this article represent a collective evidence of the performance of the method in challenging combinatorial optimization problems from different application domains. The proposed evolution strategy demonstrates an ability of adapting the strength of the mutation disturbance during the generations of its evolution process. The effectiveness of the proposal motivates the application of this novel evolutionary framework for solving other combinatorial optimization problems.

  5. A Combinatorial Kin Discrimination System in Bacillus subtilis

    PubMed Central

    Lyons, Nicholas A.; Kraigher, Barbara; Stefanic, Polonca; Mandic-Mulec, Ines; Kolter, Roberto

    2016-01-01

    SUMMARY Multicellularity inherently involves a number of cooperative behaviors that are potentially susceptible to exploitation but can be protected by mechanisms such as kin discrimination. Discrimination of kin from non-kin has been observed in swarms of the bacterium Bacillus subtilis, but the underlying molecular mechanism has been unknown. We used genetic, transcriptomic, and bioinformatic analyses to uncover kin recognition factors in this organism. Our results identified many molecules involved in cell surface modification and antimicrobial production and response. These genes varied significantly in expression level and mutation phenotype among B. subtilis strains, suggesting interstrain variation in the exact kin discrimination mechanism used. Genome analyses revealed a substantial diversity of antimicrobial genes present in unique combinations in different strains, with many likely acquired by horizontal gene transfer. The dynamic combinatorial effect derived from this plethora of kin discrimination genes creates a tight relatedness cutoff for cooperation that has likely led to rapid diversification within the species. Our data suggest that genes likely originally selected for competitive purposes also generate preferential interactions among kin, thus stabilizing multicellular lifestyles. PMID:26923784

  6. A Combinatorial Kin Discrimination System in Bacillus subtilis.

    PubMed

    Lyons, Nicholas A; Kraigher, Barbara; Stefanic, Polonca; Mandic-Mulec, Ines; Kolter, Roberto

    2016-03-21

    Multicellularity inherently involves a number of cooperative behaviors that are potentially susceptible to exploitation but can be protected by mechanisms such as kin discrimination. Discrimination of kin from non-kin has been observed in swarms of the bacterium Bacillus subtilis, but the underlying molecular mechanism has been unknown. We used genetic, transcriptomic, and bioinformatic analyses to uncover kin recognition factors in this organism. Our results identified many molecules involved in cell-surface modification and antimicrobial production and response. These genes varied significantly in expression level and mutation phenotype among B. subtilis strains, suggesting interstrain variation in the exact kin discrimination mechanism used. Genome analyses revealed a substantial diversity of antimicrobial genes present in unique combinations in different strains, with many likely acquired by horizontal gene transfer. The dynamic combinatorial effect derived from this plethora of kin discrimination genes creates a tight relatedness cutoff for cooperation that has likely led to rapid diversification within the species. Our data suggest that genes likely originally selected for competitive purposes also generate preferential interactions among kin, thus stabilizing multicellular lifestyles.

  7. Combinatorial semantics strengthens angular-anterior temporal coupling.

    PubMed

    Molinaro, Nicola; Paz-Alonso, Pedro M; Duñabeitia, Jon Andoni; Carreiras, Manuel

    2015-04-01

    The human semantic combinatorial system allows us to create a wide number of new meanings from a finite number of existing representations. The present study investigates the neural dynamics underlying the semantic processing of different conceptual constructions based on predictions from previous neuroanatomical models of the semantic processing network. In two experiments, participants read sentences for comprehension containing noun-adjective pairs in three different conditions: prototypical (Redundant), nonsense (Anomalous) and low-typical but composable (Contrastive). In Experiment 1 we examined the processing costs associated to reading these sentences and found a processing dissociation between Anomalous and Contrastive word pairs, compared to prototypical (Redundant) stimuli. In Experiment 2, functional connectivity results showed strong co-activation across conditions between inferior frontal gyrus (IFG) and posterior middle temporal gyrus (MTG), as well as between these two regions and middle frontal gyrus (MFG), anterior temporal cortex (ATC) and fusiform gyrus (FG), consistent with previous neuroanatomical models. Importantly, processing of low-typical (but composable) meanings relative to prototypical and anomalous constructions was associated with a stronger positive coupling between ATC and angular gyrus (AG). Our results underscore the critical role of IFG-MTG co-activation during semantic processing and how other relevant nodes within the semantic processing network come into play to handle visual-orthographic information, to maintain multiple lexical-semantic representations in working memory and to combine existing representations while creatively constructing meaning.

  8. Combinatorial and high-throughput screening approaches for strain engineering.

    PubMed

    Liu, Wenshan; Jiang, Rongrong

    2015-03-01

    Microbes have long been used in the industry to produce valuable biochemicals. Combinatorial engineering approaches, new strain engineering tools derived from inverse metabolic engineering, have started to attract attention in recent years, including genome shuffling, error-prone DNA polymerase, global transcription machinery engineering (gTME), random knockout/overexpression libraries, ribosome engineering, multiplex automated genome engineering (MAGE), customized optimization of metabolic pathways by combinatorial transcriptional engineering (COMPACTER), and library construction of "tunable intergenic regions" (TIGR). Since combinatorial approaches and high-throughput screening methods are fundamentally interconnected, color/fluorescence-based, growth-based, and biosensor-based high-throughput screening methods have been reviewed. We believe that with the help of metabolic engineering tools and new combinatorial approaches, plus effective high-throughput screening methods, researchers will be able to achieve better results on improving microorganism performance under stress or enhancing biochemical yield.

  9. Incorporating Modeling and Simulations in Undergraduate Biophysical Chemistry Course to Promote Understanding of Structure-Dynamics-Function Relationships in Proteins

    ERIC Educational Resources Information Center

    Hati, Sanchita; Bhattacharyya, Sudeep

    2016-01-01

    A project-based biophysical chemistry laboratory course, which is offered to the biochemistry and molecular biology majors in their senior year, is described. In this course, the classroom study of the structure-function of biomolecules is integrated with the discovery-guided laboratory study of these molecules using computer modeling and…

  10. Combinatorial Dyson-Schwinger equations and inductive data types

    NASA Astrophysics Data System (ADS)

    Kock, Joachim

    2016-06-01

    The goal of this contribution is to explain the analogy between combinatorial Dyson-Schwinger equations and inductive data types to a readership of mathematical physicists. The connection relies on an interpretation of combinatorial Dyson-Schwinger equations as fixpoint equations for polynomial functors (established elsewhere by the author, and summarised here), combined with the now-classical fact that polynomial functors provide semantics for inductive types. The paper is expository, and comprises also a brief introduction to type theory.

  11. Combinatorial molecular optimization of cement hydrates

    PubMed Central

    Abdolhosseini Qomi, M.J.; Krakowiak, K.J.; Bauchy, M.; Stewart, K.L.; Shahsavari, R.; Jagannathan, D.; Brommer, D.B.; Baronnet, A.; Buehler, M.J.; Yip, S.; Ulm, F.-J; Van Vliet, K.J.; Pellenq, R.J-.M.

    2014-01-01

    Despite its ubiquitous presence in the built environment, concrete’s molecular-level properties are only recently being explored using experimental and simulation studies. Increasing societal concerns about concrete’s environmental footprint have provided strong motivation to develop new concrete with greater specific stiffness or strength (for structures with less material). Herein, a combinatorial approach is described to optimize properties of cement hydrates. The method entails screening a computationally generated database of atomic structures of calcium-silicate-hydrate, the binding phase of concrete, against a set of three defect attributes: calcium-to-silicon ratio as compositional index and two correlation distances describing medium-range silicon-oxygen and calcium-oxygen environments. Although structural and mechanical properties correlate well with calcium-to-silicon ratio, the cross-correlation between all three defect attributes reveals an indentation modulus-to-hardness ratio extremum, analogous to identifying optimum network connectivity in glass rheology. We also comment on implications of the present findings for a novel route to optimize the nanoscale mechanical properties of cement hydrate. PMID:25248305

  12. Combinatorial approaches for inverse metabolic engineering applications

    PubMed Central

    Skretas, Georgios; Kolisis, Fragiskos N.

    2013-01-01

    Traditional metabolic engineering analyzes biosynthetic and physiological pathways, identifies bottlenecks, and makes targeted genetic modifications with the ultimate goal of increasing the production of high-value products in living cells. Such efforts have led to the development of a variety of organisms with industrially relevant properties. However, there are a number of cellular phenotypes important for research and the industry for which the rational selection of cellular targets for modification is not easy or possible. In these cases, strain engineering can be alternatively carried out using “inverse metabolic engineering”, an approach that first generates genetic diversity by subjecting a population of cells to a particular mutagenic process, and then utilizes genetic screens or selections to identify the clones exhibiting the desired phenotype. Given the availability of an appropriate screen for a particular property, the success of inverse metabolic engineering efforts usually depends on the level and quality of genetic diversity which can be generated. Here, we review classic and recently developed combinatorial approaches for creating such genetic diversity and discuss the use of these methodologies in inverse metabolic engineering applications. PMID:24688681

  13. Fast combinatorial RNS processors for DSP applications

    SciTech Connect

    Di Claudio, E.D.; Piazza, F.; Orlandi, G.

    1995-05-01

    It is known that RNS VLSI processors can parallelize fixed-point addition and multiplication operations by the use of the Chinese Remainder Theorem (CRT). The required modular operations, however, must use specialized hardware whose design and implementation can create several problems. In this paper a modified residue arithmetic, called pseudo-RNS is introduced in order to alleviate some of the RNS problems when Digital Signal Processing (DSP) structures are implemented. Pseudo-RNS requires only the use of modified binary processors and exhibits a speed performance comparable with other RNS traditional approaches. Some applications of the pseudo-RNS to common DSP architectures, such as multipliers and filters, are also presented in this paper. They are compared in terms of the Area-Time Square product versus other RNS and weighted binary structures. It is proven that existing combinatorial or look-up table approaches for RNS are tailored to small designs or special applications, while the pseudo-RNS approach remains competitive also for complex systems. 32 refs.

  14. Combinatorial effects of odorants on mouse behavior

    PubMed Central

    Saraiva, Luis R.; Kondoh, Kunio; Ye, Xiaolan; Yoon, Kyoung-hye; Hernandez, Marcus; Buck, Linda B.

    2016-01-01

    The mechanisms by which odors induce instinctive behaviors are largely unknown. Odor detection in the mouse nose is mediated by >1, 000 different odorant receptors (ORs) and trace amine-associated receptors (TAARs). Odor perceptions are encoded combinatorially by ORs and can be altered by slight changes in the combination of activated receptors. However, the stereotyped nature of instinctive odor responses suggests the involvement of specific receptors and genetically programmed neural circuits relatively immune to extraneous odor stimuli and receptor inputs. Here, we report that, contrary to expectation, innate odor-induced behaviors can be context-dependent. First, different ligands for a given TAAR can vary in behavioral effect. Second, when combined, some attractive and aversive odorants neutralize one another’s behavioral effects. Both a TAAR ligand and a common odorant block aversion to a predator odor, indicating that this ability is not unique to TAARs and can extend to an aversive response of potential importance to survival. In vitro testing of single receptors with binary odorant mixtures indicates that behavioral blocking can occur without receptor antagonism in the nose. Moreover, genetic ablation of a single receptor prevents its cognate ligand from blocking predator odor aversion, indicating that the blocking requires sensory input from the receptor. Together, these findings indicate that innate odor-induced behaviors can depend on context, that signals from a single receptor can block innate odor aversion, and that instinctive behavioral responses to odors can be modulated by interactions in the brain among signals derived from different receptors. PMID:27208093

  15. Scalable Combinatorial Tools for Health Disparities Research

    PubMed Central

    Langston, Michael A.; Levine, Robert S.; Kilbourne, Barbara J.; Rogers, Gary L.; Kershenbaum, Anne D.; Baktash, Suzanne H.; Coughlin, Steven S.; Saxton, Arnold M.; Agboto, Vincent K.; Hood, Darryl B.; Litchveld, Maureen Y.; Oyana, Tonny J.; Matthews-Juarez, Patricia; Juarez, Paul D.

    2014-01-01

    Despite staggering investments made in unraveling the human genome, current estimates suggest that as much as 90% of the variance in cancer and chronic diseases can be attributed to factors outside an individual’s genetic endowment, particularly to environmental exposures experienced across his or her life course. New analytical approaches are clearly required as investigators turn to complicated systems theory and ecological, place-based and life-history perspectives in order to understand more clearly the relationships between social determinants, environmental exposures and health disparities. While traditional data analysis techniques remain foundational to health disparities research, they are easily overwhelmed by the ever-increasing size and heterogeneity of available data needed to illuminate latent gene x environment interactions. This has prompted the adaptation and application of scalable combinatorial methods, many from genome science research, to the study of population health. Most of these powerful tools are algorithmically sophisticated, highly automated and mathematically abstract. Their utility motivates the main theme of this paper, which is to describe real applications of innovative transdisciplinary models and analyses in an effort to help move the research community closer toward identifying the causal mechanisms and associated environmental contexts underlying health disparities. The public health exposome is used as a contemporary focus for addressing the complex nature of this subject. PMID:25310540

  16. Design of combinatorial libraries for the exploration of virtual hits from fragment space searches with LoFT.

    PubMed

    Lessel, Uta; Wellenzohn, Bernd; Fischer, J Robert; Rarey, Matthias

    2012-02-27

    A case study is presented illustrating the design of a focused CDK2 library. The scaffold of the library was detected by a feature trees search in a fragment space based on reactions from combinatorial chemistry. For the design the software LoFT (Library optimizer using Feature Trees) was used. The special feature called FTMatch was applied to restrict the parts of the queries where the reagents are permitted to match. This way a 3D scoring function could be simulated. Results were compared with alternative designs by GOLD docking and ROCS 3D alignments.

  17. Chemistry Notes.

    ERIC Educational Resources Information Center

    School Science Review, 1983

    1983-01-01

    Presents background information, laboratory procedures, classroom materials/activities, and chemistry experiments. Topics include sublimation, electronegativity, electrolysis, experimental aspects of strontianite, halide test, evaluation of present and future computer programs in chemistry, formula building, care of glass/saturated calomel…

  18. Chemistry Notes

    ERIC Educational Resources Information Center

    School Science Review, 1976

    1976-01-01

    Described are eight chemistry experiments and demonstrations applicable to introductory chemistry courses. Activities include: measure of lattice enthalpy, Le Chatelier's principle, decarboxylation of soap, use of pocket calculators in pH measurement, and making nylon. (SL)

  19. Chemistry Dashboard

    EPA Pesticide Factsheets

    The Chemistry Dashboard is part of a suite of dashboards developed by EPA to help evaluate the safety of chemicals. The Chemistry Dashboard provides access to a variety of information on over 700,000 chemicals currently in use.

  20. Combinatorially-generated library of 6-fluoroquinolone analogs as potential novel antitubercular agents: a chemometric and molecular modeling assessment.

    PubMed

    Minovski, Nikola; Perdih, Andrej; Solmajer, Tom

    2012-05-01

    The virtual combinatorial chemistry approach as a methodology for generating chemical libraries of structurally-similar analogs in a virtual environment was employed for building a general mixed virtual combinatorial library with a total of 53.871 6-FQ structural analogs, introducing the real synthetic pathways of three well known 6-FQ inhibitors. The druggability properties of the generated combinatorial 6-FQs were assessed using an in-house developed drug-likeness filter integrating the Lipinski/Veber rule-sets. The compounds recognized as drug-like were used as an external set for prediction of the biological activity values using a neural-networks (NN) model based on an experimentally-determined set of active 6-FQs. Furthermore, a subset of compounds was extracted from the pool of drug-like 6-FQs, with predicted biological activity, and subsequently used in virtual screening (VS) campaign combining pharmacophore modeling and molecular docking studies. This complex scheme, a powerful combination of chemometric and molecular modeling approaches provided novel QSAR guidelines that could aid in the further lead development of 6-FQs agents.

  1. Strategies and applications of combinatorial methods and high throughput screening to the discovery of non-noble metal catalyst

    NASA Astrophysics Data System (ADS)

    Bricker, Maureen L.; Sachtler, J. W. Adriaan; Gillespie, Ralph D.; McGonegal, Charles P.; Vega, Honorio; Bem, Dave S.; Holmgren, Jennifer S.

    2004-02-01

    The integrated End-to-End™ combinatorial process for catalyst preparation and screening, with emphasis on its capability to vary both process and compositional parameters will be demonstrated. Additionally, each step of the combinatorial screening process has been validated against results from traditional screening methods. The greatest challenge of all has been the adherence to the core concepts of the combinatorial approach. Catalyst libraries have been made and tested for naphthalene dehydrogenation chemistry. The preparation of these libraries has included the application of high throughput techniques for: metal impregnation; catalyst finishing; catalyst screening. The catalyst screening system has been used to find a non-noble metal catalyst system that can replace Pt in dehydrogenation applications in the petroleum industry. A proprietary catalytic composition was developed for the dehydrogenation of methylcyclohexane (MCH) to toluene starting with four non-noble metals of different proportions and four different supports (alumina, titania, zirconia and silica) prepared in different ways and applying a statistical design of experiments. These data demonstrate that all steps of catalyst preparation and screening are performed in a rapid, useful, high throughput manner. Data will be presented from the catalyst screening efforts will demonstrate that optimized metal composition is dependent on the support type.

  2. Dynamics of seawater carbonate chemistry, production, and calcification of a coral reef flat, central Great Barrier Reef

    NASA Astrophysics Data System (ADS)

    Albright, R.; Langdon, C.; Anthony, K. R. N.

    2013-10-01

    Ocean acidification is projected to shift coral reefs from a state of net accretion to one of net dissolution this century. Presently, our ability to predict global-scale changes to coral reef calcification is limited by insufficient data relating seawater carbonate chemistry parameters to in situ rates of reef calcification. Here, we investigate diel and seasonal trends in carbonate chemistry of the Davies Reef flat in the central Great Barrier Reef and relate these trends to benthic carbon fluxes by quantifying net ecosystem calcification (nec) and net community production (ncp). Results show that seawater carbonate chemistry of the Davies Reef flat is highly variable over both diel and seasonal cycles. pH (total scale) ranged from 7.92 to 8.17, pCO2 ranged from 272 to 542 μatm, and aragonite saturation state (Ωarag) ranged from 2.9 to 4.1. Diel cycles in carbonate chemistry were primarily driven by ncp, and warming explained 35% and 47% of the seasonal shifts in pCO2 and pH, respectively. Daytime ncp averaged 37 ± 19 mmol C m-2 h-1 in summer and 33 ± 13 mmol C m-2 h-1 in winter; nighttime ncp averaged -30 ± 25 and -7 ± 6 mmol C m-2 h-1 in summer and winter, respectively. Daytime nec averaged 11 ± 4 mmol CaCO3 m-2 h-1 in summer and 8 ± 3 mmol CaCO3 m-2 h-1 in winter, whereas nighttime nec averaged 2 ± 4 mmol and -1 ± 3 mmol CaCO3 m-2 h-1 in summer and winter, respectively. Net ecosystem calcification was highly sensitive to changes in Ωarag for both seasons, indicating that relatively small shifts in Ωarag may drive measurable shifts in calcification rates, and hence carbon budgets, of coral reefs throughout the year.

  3. A General Method for Insertion of Functional Proteins within Proteins via Combinatorial Selection of Permissive Junctions.

    PubMed

    Peng, Yingjie; Zeng, Wenwen; Ye, Hui; Han, Kyung Ho; Dharmarajan, Venkatasubramanian; Novick, Scott; Wilson, Ian A; Griffin, Patrick R; Friedman, Jeffrey M; Lerner, Richard A

    2015-08-20

    A major goal of modern protein chemistry is to create new proteins with different functions. One approach is to amalgamate secondary and tertiary structures from different proteins. This is difficult for several reasons, not the least of which is the fact that the junctions between secondary and tertiary structures are not degenerate and usually affect the function and folding of the entire complex. Here, we offer a solution to this problem by coupling a large combinatorial library of about 10(7) different N- and C-terminal junctions to a powerful system that selects for function. Using this approach, the entire Leptin and follicle-stimulating hormone (FSH) were inserted into an antibody. Complexes with full retention of function in vivo and in vitro, although rare, were found easily by using an autocrine selection system to search for hormonal activity. Such large diversity systems, when coupled to robust selection systems, should enable construction of novel therapeutic proteins.

  4. Genetic engineering of modular PKSs: from combinatorial biosynthesis to synthetic biology.

    PubMed

    Weissman, Kira J

    2016-02-01

    Multienzyme polyketide synthases (PKSs) are molecular-scale assembly lines which construct complex natural products in bacteria. The underlying modular architecture of these gigantic catalysts inspired, from the moment of their discovery, attempts to modify them by genetic engineering to produce analogues of predictable structure. These efforts have resulted in hundreds of metabolites new to nature, as detailed in this review. However, in the face of many failures, the heady days of imagining the possibilities for a truly 'combinatorial biosynthesis' of polyketides have faded. It is now more appropriate to talk about 'PKS synthetic biology' with its more modest goals of delivering specific derivatives of known structure in combination with and as a complement to synthetic chemistry approaches. The reasons for these failures will be discussed in terms of our growing understanding of the three-dimensional architectures and mechanisms of these systems. Finally, some thoughts on the future of the field will be presented.

  5. Chemistry Notes.

    ERIC Educational Resources Information Center

    School Science Review, 1982

    1982-01-01

    Presents background information, laboratory procedures, classroom materials/activities, and experiments for chemistry. Topics include superheavy elements, polarizing power and chemistry of alkali metals, particulate carbon from combustion, tips for the chemistry laboratory, interesting/colorful experiments, behavior of bismuth (III) iodine, and…

  6. CLUSTER CHEMISTRY

    SciTech Connect

    Muetterties, Earl L.

    1980-05-01

    Metal cluster chemistry is one of the most rapidly developing areas of inorganic and organometallic chemistry. Prior to 1960 only a few metal clusters were well characterized. However, shortly after the early development of boron cluster chemistry, the field of metal cluster chemistry began to grow at a very rapid rate and a structural and a qualitative theoretical understanding of clusters came quickly. Analyzed here is the chemistry and the general significance of clusters with particular emphasis on the cluster research within my group. The importance of coordinately unsaturated, very reactive metal clusters is the major subject of discussion.

  7. Forensic chemistry.

    PubMed

    Bell, Suzanne

    2009-01-01

    Forensic chemistry is unique among chemical sciences in that its research, practice, and presentation must meet the needs of both the scientific and the legal communities. As such, forensic chemistry research is applied and derivative by nature and design, and it emphasizes metrology (the science of measurement) and validation. Forensic chemistry has moved away from its analytical roots and is incorporating a broader spectrum of chemical sciences. Existing forensic practices are being revisited as the purview of forensic chemistry extends outward from drug analysis and toxicology into such diverse areas as combustion chemistry, materials science, and pattern evidence.

  8. Prominent Chemists Team Up to Review Frontiers in Chemistry.

    ERIC Educational Resources Information Center

    Baum, Rudy M.

    1989-01-01

    Discusses a symposium which focused on the influence of inorganic chemistry on organic synthesis, the impact of organic chemistry on biochemistry and vice versa, chemical reaction dynamics, and advances in inorganic chemistry. Explains the purpose of the symposium was to illustrate the intellectual dynamism of modern chemistry. (MVL)

  9. Combinatorial effects on clumped isotopes and their significance in biogeochemistry

    NASA Astrophysics Data System (ADS)

    Yeung, Laurence Y.

    2016-01-01

    The arrangement of isotopes within a collection of molecules records their physical and chemical histories. Clumped-isotope analysis interrogates these arrangements, i.e., how often rare isotopes are bound together, which in many cases can be explained by equilibrium and/or kinetic isotope fractionation. However, purely combinatorial effects, rooted in the statistics of pairing atoms in a closed system, are also relevant, and not well understood. Here, I show that combinatorial isotope effects are most important when two identical atoms are neighbors on the same molecule (e.g., O2, N2, and D-D clumping in CH4). When the two halves of an atom pair are either assembled with different isotopic preferences or drawn from different reservoirs, combinatorial effects cause depletions in clumped-isotope abundance that are most likely between zero and -1‰, although they could potentially be -10‰ or larger for D-D pairs. These depletions are of similar magnitude, but of opposite sign, to low-temperature equilibrium clumped-isotope effects for many small molecules. Enzymatic isotope-pairing reactions, which can have site-specific isotopic fractionation factors and atom reservoirs, should express this class of combinatorial isotope effect, although it is not limited to biological reactions. Chemical-kinetic isotope effects, which are related to a bond-forming transition state, arise independently and express second-order combinatorial effects related to the abundance of the rare isotope. Heteronuclear moeties (e.g., Csbnd O and Csbnd H), are insensitive to direct combinatorial influences, but secondary combinatorial influences are evident. In general, both combinatorial and chemical-kinetic factors are important for calculating and interpreting clumped-isotope signatures of kinetically controlled reactions. I apply this analytical framework to isotope-pairing reactions relevant to geochemical oxygen, carbon, and nitrogen cycling that may be influenced by combinatorial

  10. Recent advances in combinatorial biosynthesis for drug discovery

    PubMed Central

    Sun, Huihua; Liu, Zihe; Zhao, Huimin; Ang, Ee Lui

    2015-01-01

    Because of extraordinary structural diversity and broad biological activities, natural products have played a significant role in drug discovery. These therapeutically important secondary metabolites are assembled and modified by dedicated biosynthetic pathways in their host living organisms. Traditionally, chemists have attempted to synthesize natural product analogs that are important sources of new drugs. However, the extraordinary structural complexity of natural products sometimes makes it challenging for traditional chemical synthesis, which usually involves multiple steps, harsh conditions, toxic organic solvents, and byproduct wastes. In contrast, combinatorial biosynthesis exploits substrate promiscuity and employs engineered enzymes and pathways to produce novel “unnatural” natural products, substantially expanding the structural diversity of natural products with potential pharmaceutical value. Thus, combinatorial biosynthesis provides an environmentally friendly way to produce natural product analogs. Efficient expression of the combinatorial biosynthetic pathway in genetically tractable heterologous hosts can increase the titer of the compound, eventually resulting in less expensive drugs. In this review, we will discuss three major strategies for combinatorial biosynthesis: 1) precursor-directed biosynthesis; 2) enzyme-level modification, which includes swapping of the entire domains, modules and subunits, site-specific mutagenesis, and directed evolution; 3) pathway-level recombination. Recent examples of combinatorial biosynthesis employing these strategies will also be highlighted in this review. PMID:25709407

  11. Dynamics of seawater carbonate chemistry, production, and calcification of a coral reef flat, Central Great Barrier Reef

    NASA Astrophysics Data System (ADS)

    Albright, R.; Langdon, C.; Anthony, K. R. N.

    2013-05-01

    Ocean acidification is projected to shift coral reefs from a state of net accretion to one of net dissolution this century. Presently, our ability to predict global-scale changes to coral reef calcification is limited by insufficient data relating seawater carbonate chemistry parameters to in situ rates of reef calcification. Here, we investigate natural trends in carbonate chemistry of the Davies Reef flat in the central Great Barrier Reef on diel and seasonal timescales and relate these trends to benthic carbon fluxes by quantifying net ecosystem calcification (nec) and net community production (ncp). Results show that seawater carbonate chemistry of the Davies Reef flat is highly variable over both diel and seasonal timescales. pH (total scale) ranged from 7.92 to 8.17, pCO2 ranged from 272 to 542 μatm, and aragonite saturation state (Ωarag) ranged from 2.9 to 4.1. Diel cycles in carbonate chemistry were primarily driven by ncp, and warming explained 35% and 47% of the seasonal shifts in pCO2 and pH, respectively. Daytime ncp averaged 36 ± 19 mmol C m-2 h-1 in summer and 33 ± 13 mmol C m-2 h-1 in winter; nighttime ncp averaged -22 ± 20 and -7 ± 6 mmol C m-2 h-1 in summer and winter, respectively. Daytime nec averaged 11 ± 4 mmol CaCO3 m-2 h-1 in summer and 8 ± 3 mmol CaCO3 m-2 h-1 in winter, whereas nighttime nec averaged 2 ± 4 mmol and -1 ± 3 mmol CaCO3 m-2 h-1 in summer and winter, respectively. Net ecosystem calcification was positively correlated with Ωarag for both seasons. Linear correlations of nec and Ωarag indicate that the Davies Reef flat may transition from a state of net calcification to net dissolution at Ωarag values of 3.4 in summer and 3.2 in winter. Diel trends in Ωarag indicate that the reef flat is currently below this calcification threshold 29.6% of the time in summer and 14.1% of the time in winter.

  12. Perturbation-based analysis and modeling of combinatorial regulation in the yeast sulfur assimilation pathway.

    PubMed

    McIsaac, R Scott; Petti, Allegra A; Bussemaker, Harmen J; Botstein, David

    2012-08-01

    In yeast, the pathways of sulfur assimilation are combinatorially controlled by five transcriptional regulators (three DNA-binding proteins [Met31p, Met32p, and Cbf1p], an activator [Met4p], and a cofactor [Met28p]) and a ubiquitin ligase subunit (Met30p). This regulatory system exerts combinatorial control not only over sulfur assimilation and methionine biosynthesis, but also on many other physiological functions in the cell. Recently we characterized a gene induction system that, upon the addition of an inducer, results in near-immediate transcription of a gene of interest under physiological conditions. We used this to perturb levels of single transcription factors during steady-state growth in chemostats, which facilitated distinction of direct from indirect effects of individual factors dynamically through quantification of the subsequent changes in genome-wide patterns of gene expression. We were able to show directly that Cbf1p acts sometimes as a repressor and sometimes as an activator. We also found circumstances in which Met31p/Met32p function as repressors, as well as those in which they function as activators. We elucidated and numerically modeled feedback relationships among the regulators, notably feedforward regulation of Met32p (but not Met31p) by Met4p that generates dynamic differences in abundance that can account for the differences in function of these two proteins despite their identical binding sites.

  13. Surface layer ozone and nitric oxides in the Arctic: The inuence of boundary layer dynamics, snowpack chemistry, surface exchanges, and seasonality

    NASA Astrophysics Data System (ADS)

    Van Dam, Brie A.

    The snowpack is a region of active chemistry. Aqueous chemistry in a quasi-liquid layer on snow grains and gas-phase chemical reactions in snow interstitial air can lead to the production or destruction of important trace gases. Physical transport parameters such as wind pumping and diffusion affect the vertical distribution of gases within the snowpack. The resulting emission or uptake of trace gases at the atmosphere-snowpack interface can have significant in uence on the chemistry of the lower atmosphere. In this work the dynamic interactions between the snowpack and atmosphere are examined from multiple perspectives. The primary focus is on ozone (O3) and nitrogen oxides (NOx) in the Arctic, a region undergoing widespread environmental change. To investigate an ice-sheet location with year round snow cover, data from a two-year campaign at Summit, Greenland are implemented. At Summit this study examines (1) the processes contributing to vigorous chemistry in snow interstitial air, and (2) the role of the boundary layer over snow in determining surface layer NOx. Physical and chemical processes are shown to contribute to distinct seasonal and diurnal cycles of O3, NO, and NO2 in the snowpack. Boundary layer depths estimated from sonic anemometer turbulence quantities are used alongside sodar-derived values to show that the depth of the stable to weakly stable boundary layer at Summit was not a primary factor in determining NO x in early summer. Motivated by observations of an increase in the length of the snow-free season in the Arctic in recent decades, data from a one-year experiment at the seasonally-snow covered location of Toolik Lake, AK are also incorporated. This study shows the first observations of springtime ozone depletion events at a location over 200 km from the coast in the Arctic. FLEXPART analysis is used to illustrate that these inland events are linked to transport conditions. Lastly at this location, eddy-covariance O3 uxes were calculated to

  14. From linking of metal-oxide building blocks in a dynamic library to giant clusters with unique properties and towards adaptive chemistry.

    PubMed

    Müller, Achim; Gouzerh, Pierre

    2012-11-21

    Following Nature's lessons, today chemists can cross the boundary of the small molecule world to construct multifunctional and highly complex molecular nano-objects up to protein size and even cell-like nanosystems showing responsive sensing. Impressive examples emerge from studies of the solutions of some oxoanions of the early transition metals especially under reducing conditions which enable the controlled linking of metal-oxide building blocks. The latter are available from constitutional dynamic libraries, thus providing the option to generate multifunctional unique nanoscale molecular systems with exquisite architectures, which even opens the way towards adaptive and evolutive (Darwinian) chemistry. The present review presents the first comprehensive report of current knowledge (including synthesis aspects not discussed before) regarding the related giant metal-oxide clusters mainly of the type {Mo(57)M'(6)} (M' = Fe(III), V(IV)) (torus structure), {M(72)M'(30)} (M = Mo, M' = V(IV), Cr(III), Fe(III), Mo(V)), {M(72)Mo(60)} (M = Mo, W) (Keplerates), {Mo(154)}, {Mo(176)}, {Mo(248)} ("big wheels"), and {Mo(368)} ("blue lemon") - all having the important transferable pentagonal {(M)M(5)} groups in common. These discoveries expanded the frontiers of inorganic chemistry to the mesoscopic world, while there is probably no collection of discrete inorganic compounds which offers such a versatile chemistry and the option to study new phenomena of interdisciplinary interest. The variety of different properties of the sphere- and wheel-type metal-oxide-based clusters can directly be related to their unique architectures: The spherical Keplerate-type capsules having 20 crown-ether-type pores and tunable internal functionalities allow the investigation of confined matter as well as that of sphere-surface-supramolecular and encapsulation chemistry - including related new aspects of the biologically important hydrophobic effects - but also of nanoscale ion transport and

  15. Molecular dynamics simulation of organometallic reaction dynamics, and, Enhancing achievement in chemistry for African American students through innovations in pedagogy aligned with supporting assessment and curriculum and integrated under an alternative research paradigm

    NASA Astrophysics Data System (ADS)

    Mebane, Sheryl Dee

    Part I. Molecular dynamics simulation of organometallic reaction dynamics. To study the interplay of solute and solvent dynamics, large-scale molecular dynamics simulations were employed. Lennard-Jones and electrostatic models of potential energies from solvent-only studies were combined with solute potentials generated from ab-initio calculations. Radial distribution functions and other measures revealed the polar solvent's response to solute dynamics following CO dissociation. In future studies, the time-scale for solvent coordination will be confirmed with ultrafast spectroscopy data. Part II. Enhancing achievement in chemistry for African American students through innovations in pedagogy aligned with supporting assessment and curriculum and integrated under an alternative research paradigm. Much progress has been made in the area of research in education that focuses on teaching and learning in science. Much effort has also centered on documenting and exploring the disparity in academic achievement between underrepresented minority students and students comprising a majority in academic circles. However, few research projects have probed educational inequities in the context of mainstream science education. In order to enrich this research area and to better reach underserved learning communities, the educational experience of African American students in an ethnically and academically diverse high school science class has been examined throughout one, largely successful, academic year. The bulk of data gathered during the study was obtained through several qualitative research methods and was interpreted using research literature that offered fresh theoretical perspectives on equity that may better support effective action.

  16. Vertical dynamics of the aquifer microbial community associated with groundwater chemistry in the artificial recharge site in Korea

    NASA Astrophysics Data System (ADS)

    Moon, Hee Sun; Hyun, Sung Pil; Kim, Boa; Shin, Doyun; Ha, Kyoochul

    2014-05-01

    Artificial groundwater recharge offers an opportunity to better manage groundwater resources by storing water in aquifers and increasing the amount of groundwater available for abstraction during high demand periods. It is important to understand the linkage of microbial ecology to groundwater chemistry to assess changes in groundwater quality caused by artificial groundwater recharge. In this study, we investigated how the structure and diversity of this subsurface microbial community correlates with and impacts upon groundwater chemistry. Groundwater samples at two different depths (10 and 33 m) were collected from three monitoring wells (MLW 1, MLW 2 and MLW 3) in the artificial groundwater recharge demonstration site in Changwon, Korea. The groundwater samples were filtered with 0.45 um membrane filters and then used for the anion and cation analysis. A 4L of each groundwater sample was immediately filtered with 0.2 um membrane filters and the filters were used for DNA extraction using Fast DNA Spin Kit for soil (MP Bio, USA). Further molecular work processes including pyrosequencing were carried out at Chunlab, Inc. (Seoul, Korea). Pyrosequencing results showed all major phyla were OD 1, OD3, and OD 11 in shallow groundwater samples while Proteobacteria (β-proteobacteria and δ-proteobacteria) and Bacterioidetes were dominant phyla in deep groundwater. The Shannon diversity index indicated that the microbial community was much more diverse in shallow groundwater than in deep groundwater. Heat map and hierarchical cluster analysis based on the relative abundance of OTUs at genus level showed a clear distinction between shallow and deep groundwater. Differences in the vertical community structure were driven by the major species such as Sufuicurvum sp., Pseudomonas sp., Acidiferrobacter sp., Gallionella sp., and Ferribacterium sp. The results show that several distinct factors such as iron and sulfate concentration control the vertical composition of microbial

  17. Shock Induced Chemistry: Application and Development of Ultrafast Nonlinear Probes of the Energy Dynamics of Molecules in Solids

    DTIC Science & Technology

    1988-01-01

    the distribution of time scales. 9 Dephasing experiments have traditionally been treated with optical bsorption formalisms. That is, the lineshape is...7 - w Fiur: 16 D. 3as Phase Dynamics and Spectroscopy Probed with Picosecond Transient Grating Experiments Picosecond transient grating...experiments (24] have been applied recently to the study of gas phase dynamics and spectroscopy for the first time in this laboratory [25,26,27]. The approach

  18. The Lens of Chemistry

    ERIC Educational Resources Information Center

    Thalos, Mariam

    2013-01-01

    Chemistry possesses a distinctive theoretical lens--a distinctive set of theoretical concerns regarding the dynamics and transformations of a perplexing variety of organic and nonorganic substances--to which it must be faithful. Even if it is true that chemical facts bear a special (reductive) relationship to physical facts, nonetheless it will…

  19. Technetium chemistry

    SciTech Connect

    Burns, C.; Bryan, J.; Cotton, F.; Ott, K.; Kubas, G.; Haefner, S.; Barrera, J.; Hall, K.; Burrell, A.

    1996-04-01

    Technetium chemistry is a young and developing field. Despite the limited knowledge of its chemistry, technetium is the workhorse for nuclear medicine. Technetium is also a significant environmental concern because it is formed as a byproduct of nuclear weapons production and fission-power generators. Development of new technetium radio-pharmaceuticals and effective environmental control depends strongly upon knowledge of basic technetium chemistry. The authors performed research into the basic coordination and organometallic chemistry of technetium and used this knowledge to address nuclear medicine and environmental applications. This is the final report of a three-year Laboratory-Directed Research and Development (LDRD) project at the Los Alamos National Laboratory (LANL).

  20. Chemistry Notes

    ERIC Educational Resources Information Center

    School Science Review, 1972

    1972-01-01

    Twelve new chemistry expermiments are described. Broad areas covered include atomic structure, solubility, gaseous diffusion, endothermic reactions, alcohols, equilibrium, atomic volumes, and some improvised apparatus. (PS)

  1. Fast Combinatorial Algorithm for the Solution of Linearly Constrained Least Squares Problems

    DOEpatents

    Van Benthem, Mark H.; Keenan, Michael R.

    2008-11-11

    A fast combinatorial algorithm can significantly reduce the computational burden when solving general equality and inequality constrained least squares problems with large numbers of observation vectors. The combinatorial algorithm provides a mathematically rigorous solution and operates at great speed by reorganizing the calculations to take advantage of the combinatorial nature of the problems to be solved. The combinatorial algorithm exploits the structure that exists in large-scale problems in order to minimize the number of arithmetic operations required to obtain a solution.

  2. Click chemistry: 1,2,3-triazoles as pharmacophores.

    PubMed

    Agalave, Sandip G; Maujan, Suleman R; Pore, Vandana S

    2011-10-04

    The copper(I)-catalyzed 1,2,3-triazole-forming reaction between azides and terminal alkynes has become the gold standard of 'click chemistry' due to its reliability, specificity, and biocompatibility. Applications of click chemistry are increasingly found in all aspects of drug discovery; they range from lead finding through combinatorial chemistry and target-templated in vitro chemistry, to proteomics and DNA research by using bioconjugation reactions. The triazole products are more than just passive linkers; they readily associate with biological targets, through hydrogen-bonding and dipole interactions. The present review will focus mainly on the recent literature for applications of this reaction in the field of medicinal chemistry, in particular on use of the 1,2,3-triazole moiety as pharmacophore.

  3. International Society of Heterocyclic Chemistry--17th international congress. 1-6 August 1999, Vienna, Austria.

    PubMed

    Daneshtalab, M

    1999-10-01

    Approximately 1200 scientists attended this congress of heterocyclic chemistry, which focused on: New synthetic methods in heterocyclic chemistry; synthesis of bioactive heterocycles including natural products; heterocycles and asymmetric synthesis; heterocycles in bioorganic chemistry; new heterocyclic materials; structure and properties of heterocyclic compounds; solid-phase synthesis, combinatorial chemistry and heterocyclic scaffolds. These topics were covered in 600 posters and 100 plenary, invited and oral presentations. This report summarizes the highlights of the presentations related to the category of the synthesis of bioactive heterocycles including natural products.

  4. Combinatorial nanodiamond in pharmaceutical and biomedical applications.

    PubMed

    Lim, Dae Gon; Prim, Racelly Ena; Kim, Ki Hyun; Kang, Eunah; Park, Kinam; Jeong, Seong Hoon

    2016-11-30

    One of the newly emerging carbon materials, nanodiamond (ND), has been exploited for use in traditional electric materials and this has extended into biomedical and pharmaceutical applications. Recently, NDs have attained significant interests as a multifunctional and combinational drug delivery system. ND studies have provided insights into granting new potentials with their wide ranging surface chemistry, complex formation with biopolymers, and combination with biomolecules. The studies that have proved ND inertness, biocompatibility, and low toxicity have made NDs much more feasible for use in real in vivo applications. This review gives an understanding of NDs in biomedical engineering and pharmaceuticals, focusing on the classified introduction of ND/drug complexes. In addition, the diverse potential applications that can be obtained with chemical modification are presented.

  5. Chemistry Notes.

    ERIC Educational Resources Information Center

    School Science Review, 1981

    1981-01-01

    Outlines laboratory procedures, demonstrations, teaching suggestions, and content information related to chemistry. Topics include polarizing power; calorimetry and momentum; microcomputers in school chemistry; a constant-volume dispenser for liquids, floating magnets, and crystal lattices; preparation of chromium; and solvent polarity and…

  6. 5-(hydroxymethyl)oxazoles: versatile scaffolds for combinatorial solid-phase synthesis of 5-substituted oxazoles.

    PubMed

    Grabowska, U; Rizzo, A; Farnell, K; Quibell, M

    2000-01-01

    A scheme combining the preparation of building blocks in solution followed by solid-phase combinatorial chemistry has been developed to side-chain diversify 5-(hydroxymethyl)oxazole scaffold (1) into aryl ethers, thioethers, sulfones, sulfonamides, and carboxamides. Protected heterocyclic scaffolds 2 were linked to the solid phase and N-terminal derivatized using active ester chemistry, providing chemset 4¿1-4,1-4¿. The free side-chain hydroxyl of 4 was smoothly converted to aryl ethers 6 under Mitsunobu conditions, with a broad range of substituted phenols. Alternatively, quantitative conversion of hydroxyl to bromide followed by displacement with alkyl and aryl thiols gave thioethers 8. Thioethers were optionally oxidized to sulfones 9. Bromide displacement by azide, followed by reduction to amine and acylation with a range of carboxylic acids and sulfonyl chlorides gave carboxamides 11 and sulfonamides 13, respectively. Crude purity at typically >90% was observed for each of the five modifications detailed. A series of 20 compounds, exemplifying each modification, was reprepared, purified, and fully characterized.

  7. The effect of breaking gravity waves on the dynamics and chemistry of the mesosphere and lower thermosphere (invited review)

    NASA Technical Reports Server (NTRS)

    Garcia, R. R.

    1986-01-01

    The influence of breaking gravity waves on the dynamics and chemical composition of the 60 to 110 km region is investigated with a two dimensional model that includes a parameterization of gravity wave momentum deposition and diffusion. The dynamical model is described by Garcia and Solomon (1983) and Solomon and Garcia (1983) and includes a complete chemical scheme for the mesosphere and lower thermosphere. The parameterization of Lindzen (1981) is used to calculate the momentum deposited and the turbulent diffusion produced by the gravity waves. It is found that wave momentum deposition drives a very vigorous mean meridional circulation, produces a very cold summer mesopause and reverse the zonal wind jets above about 85 km. The seasonal variation of the turbulent diffusion coefficient is consistent with the behavior of mesospheric turbulences inferred from MST radar echoes. The large degree of consistency between model results and various types of dynamical and chemical data supports very strongly the hypothesis that breaking gravity waves play a major role in determining the zonally-averaged dynamical and chemical structure of the 60 to 110 km region of the atmosphere.

  8. Influence of Dynamics and Chemistry on the Diurnal Variation of VOCs in the Planetary Boundary Layer above a Mixed Forest Canopy in the Southeastern United States

    NASA Astrophysics Data System (ADS)

    Guenther, A. B.; Su, L.; Patton, E. G.; Vila-Guerau Arellano, J.; Mak, J. E.

    2014-12-01

    The planetary boundary layer (PBL) is a region of inherent interest because reactive VOCs emitted from the forest canopy are mixed with the residual and free tropospheric air masses, oxidized, and/or otherwise removed in this region. The characterization of diurnal variation of VOCs in the PBL is limited due to the lack of appropriate sampling platforms that are able to probe all the regions of interest: from the surface to the entrainment zone. Here we present the application of the Whole Air Sample Profiler (WASP) system during the 2013 Southeast Atmosphere Study (SAS) campaign. A total of 41 research flights (RFs) were carried out during the 2013 SAS campaign between June 1 and June 14 over the Alabama Aquatic Biodiversity Center (AABC) site and the SEARCH site. During each RF, ambient air sampling started from 50-100 m above the canopy top and stopped at ~1200 m above the mean sea level (a.m.s.l). The air samples were subsequently analyzed by using a proton-transfer-reaction time-of-flight mass spectrometry (PTR-TOF-MS). Here we analyze the vertical profiles and averaged diurnal variation of the mixing ratios of several reactive VOC species, including isoprene, the sum of monoterpenes, and first generation oxidation products of isoprene: methyl vinyl ketone and methacrolein (MVK+MACR). A MiXed Layer Chemistry (MXLCH) model, guided by the meteorological and chemical observations during the SAS campaign, is used to study the influence of boundary layer dynamics and new isoprene oxidation mechanism on the diurnal variation of major biogenic VOCs emitted from the forest canopy. The new scheme includes OH recycling through two pathways under low-NOx regime: (1) hydroxyl peroxy radicals (HOC5H8OO•; ISOPO2) unimolecular isomerization, and (2) ISOPO2+HO2. The model is able to reproduce the evolution of the boundary layer dynamics (including potential temperature, and boundary layer height) during the selected simulation dates. Based on the model results, budget

  9. Smooth Constrained Heuristic Optimization of a Combinatorial Chemical Space

    DTIC Science & Technology

    2015-05-01

    Proving Ground, MD 21005 primary author’s email: . Several algorithms for optimizing a combinatorial subspace of... algorithm ...............................................................6 Fig. 3 Best candidate found...Stopping criteria? d = n? Stop d = 1, λ = 0 yes no d = 1 yes no d = d+ 1 Fig. 2 Flowchart of algorithm • Algorithm 1: Complete a full sweep of all

  10. Identities for Generalized Fibonacci Numbers: A Combinatorial Approach

    ERIC Educational Resources Information Center

    Plaza, A.; Falcon, S.

    2008-01-01

    This note shows a combinatorial approach to some identities for generalized Fibonacci numbers. While it is a straightforward task to prove these identities with induction, and also by arithmetical manipulations such as rearrangements, the approach used here is quite simple to follow and eventually reduces the proof to a counting problem. (Contains…

  11. Combinatorial structure of k-semiprimitive matrix families

    NASA Astrophysics Data System (ADS)

    Al'pin, Yu A.; Al'pina, V. S.

    2016-05-01

    Protasov's Theorem on the combinatorial structure of k-primitive families of non-negative matrices is generalized to k-semiprimitive matrix families. The main tool is the binary relation of colour compatibility on the vertices of the coloured graph of the matrix family. Bibliography: 14 titles.

  12. Structure-based design of combinatorial mutagenesis libraries.

    PubMed

    Verma, Deeptak; Grigoryan, Gevorg; Bailey-Kellogg, Chris

    2015-05-01

    The development of protein variants with improved properties (thermostability, binding affinity, catalytic activity, etc.) has greatly benefited from the application of high-throughput screens evaluating large, diverse combinatorial libraries. At the same time, since only a very limited portion of sequence space can be experimentally constructed and tested, an attractive possibility is to use computational protein design to focus libraries on a productive portion of the space. We present a general-purpose method, called "Structure-based Optimization of Combinatorial Mutagenesis" (SOCoM), which can optimize arbitrarily large combinatorial mutagenesis libraries directly based on structural energies of their constituents. SOCoM chooses both positions and substitutions, employing a combinatorial optimization framework based on library-averaged energy potentials in order to avoid explicitly modeling every variant in every possible library. In case study applications to green fluorescent protein, β-lactamase, and lipase A, SOCoM optimizes relatively small, focused libraries whose variants achieve energies comparable to or better than previous library design efforts, as well as larger libraries (previously not designable by structure-based methods) whose variants cover greater diversity while still maintaining substantially better energies than would be achieved by representative random library approaches. By allowing the creation of large-scale combinatorial libraries based on structural calculations, SOCoM promises to increase the scope of applicability of computational protein design and improve the hit rate of discovering beneficial variants. While designs presented here focus on variant stability (predicted by total energy), SOCoM can readily incorporate other structure-based assessments, such as the energy gap between alternative conformational or bound states.

  13. Ligand-Based Peptide Design and Combinatorial Peptide Libraries to Target G Protein-Coupled Receptors

    PubMed Central

    Gruber, Christian W.; Muttenthaler, Markus; Freissmuth, Michael

    2016-01-01

    G protein-coupled receptors (GPCRs) are considered to represent the most promising drug targets; it has been repeatedly said that a large fraction of the currently marketed drugs elicit their actions by binding to GPCRs (with cited numbers varying from 30–50%). Closer scrutiny, however, shows that only a modest fraction of (~60) GPCRs are, in fact, exploited as drug targets, only ~20 of which are peptide-binding receptors. The vast majority of receptors in the humane genome have not yet been explored as sites of action for drugs. Given the drugability of this receptor class, it appears that opportunities for drug discovery abound. In addition, GPCRs provide for binding sites other than the ligand binding sites (referred to as the “orthosteric site”). These additional sites include (i) binding sites for ligands (referred to as “allosteric ligands”) that modulate the affinity and efficacy of orthosteric ligands, (ii) the interaction surface that recruits G proteins and arrestins, (iii) the interaction sites of additional proteins (GIPs, GPCR interacting proteins that regulate G protein signaling or give rise to G protein-independent signals). These sites can also be targeted by peptides. Combinatorial and natural peptide libraries are therefore likely to play a major role in identifying new GPCR ligands at each of these sites. In particular the diverse natural peptide libraries such as the venom peptides from marine cone-snails and plant cyclotides have been established as a rich source of drug leads. High-throughput screening and combinatorial chemistry approaches allow for progressing from these starting points to potential drug candidates. This will be illustrated by focusing on the ligand-based drug design of oxytocin (OT) and vasopressin (AVP) receptor ligands using natural peptide leads as starting points. PMID:20687879

  14. Combinatorial Investigations of High Temperature CuNb Oxide Phases for Photoelectrochemical Water Splitting.

    PubMed

    Skorupska, Katarzyna; Maggard, Paul A; Eichberger, Rainer; Schwarzburg, Klaus; Shahbazi, Paria; Zoellner, Brandon; Parkinson, Bruce A

    2015-12-14

    High-throughput combinatorial methods have been useful in identifying new oxide semiconductors with the potential to be applied to solar water splitting. Most of these techniques have been limited to producing and screening oxide phases formed at temperatures below approximately 550 °C. We report the development of a combinatorial approach to discover and optimize high temperature phases for photoelectrochemical water splitting. As a demonstration material, we chose to produce thin films of high temperature CuNb oxide phases by inkjet printing on two different substrates: fluorine-doped tin oxide and crystalline Si, which required different sample pyrolysis procedures. The selection of pyrolysis parameters, such as temperature/time programs, and the use of oxidizing, nonreactive or reducing atmospheres determines the composition of the thin film materials and their photoelectrochemical performance. XPS, XRD, and SEM analyses were used to determine the composition and oxidation states within the copper niobium oxide phases and to then guide the production of target Cu(1+)Nb(5+)-oxide phases. The charge carrier dynamics of the thin films produced by the inkjet printing are compared with pure CuNbO3 microcrystalline material obtained from inorganic bulk synthesis.

  15. FASTAptamer: A Bioinformatic Toolkit for High-throughput Sequence Analysis of Combinatorial Selections

    PubMed Central

    Alam, Khalid K; Chang, Jonathan L; Burke, Donald H

    2015-01-01

    High-throughput sequence (HTS) analysis of combinatorial selection populations accelerates lead discovery and optimization and offers dynamic insight into selection processes. An underlying principle is that selection enriches high-fitness sequences as a fraction of the population, whereas low-fitness sequences are depleted. HTS analysis readily provides the requisite numerical information by tracking the evolutionary trajectory of individual sequences in response to selection pressures. Unlike genomic data, for which a number of software solutions exist, user-friendly tools are not readily available for the combinatorial selections field, leading many users to create custom software. FASTAptamer was designed to address the sequence-level analysis needs of the field. The open source FASTAptamer toolkit counts, normalizes and ranks read counts in a FASTQ file, compares populations for sequence distribution, generates clusters of sequence families, calculates fold-enrichment of sequences throughout the course of a selection and searches for degenerate sequence motifs. While originally designed for aptamer selections, FASTAptamer can be applied to any selection strategy that can utilize next-generation DNA sequencing, such as ribozyme or deoxyribozyme selections, in vivo mutagenesis and various surface display technologies (peptide, antibody fragment, mRNA, etc.). FASTAptamer software, sample data and a user's guide are available for download at http://burkelab.missouri.edu/fastaptamer.html. PMID:25734917

  16. NON-EQUILIBRIUM CHEMISTRY OF DYNAMICALLY EVOLVING PRESTELLAR CORES. I. BASIC MAGNETIC AND NON-MAGNETIC MODELS AND PARAMETER STUDIES

    SciTech Connect

    Tassis, Konstantinos; Willacy, Karen; Yorke, Harold W.; Turner, Neal J.

    2012-07-01

    We combine dynamical and non-equilibrium chemical modeling of evolving prestellar molecular cloud cores and investigate the evolution of molecular abundances in the contracting core. We model both magnetic cores, with varying degrees of initial magnetic support, and non-magnetic cores, with varying collapse delay times. We explore, through a parameter study, the competing effects of various model parameters in the evolving molecular abundances, including the elemental C/O ratio, the temperature, and the cosmic-ray ionization rate. We find that different models show their largest quantitative differences at the center of the core, whereas the outer layers, which evolve slower, have abundances which are severely degenerate among different dynamical models. There is a large range of possible abundance values for different models at a fixed evolutionary stage (central density), which demonstrates the large potential of chemical differentiation in prestellar cores. However, degeneracies among different models, compounded with uncertainties induced by other model parameters, make it difficult to discriminate among dynamical models. To address these difficulties, we identify abundance ratios between particular molecules, the measurement of which would have maximal potential for discrimination among the different models examined here. In particular, we find that the ratios between NH{sub 3} and CO, NH{sub 2} and CO, and NH{sub 3} and HCO{sup +} are sensitive to the evolutionary timescale, and that the ratio between HCN and OH is sensitive to the C/O ratio. Finally, we demonstrate that measurements of the central deviation (central depletion or enhancement) of abundances of certain molecules are good indicators of the dynamics of the core.

  17. Parallel Combinatorial Synthesis of Azo Dyes: A Combinatorial Experiment Suitable for Undergraduate Laboratories

    ERIC Educational Resources Information Center

    Gung, Benjamin W.; Taylor, Richard T.

    2004-01-01

    An experiment in the parallel synthesis of azo dyes that demonstrates the concepts of structure-activity relationships and chemical diversity with vivid colors is described. It is seen that this experiment is suitable for the second-semester organic chemistry laboratory and also for the one-semester organic laboratory.

  18. Circumstellar chemistry

    NASA Technical Reports Server (NTRS)

    Glassgold, Alfred E.; Huggins, Patrick J.

    1987-01-01

    The study of the outer envelopes of cool evolved stars has become an active area of research. The physical properties of CS envelopes are presented. Observations of many wavelengths bands are relevant. A summary of observations and a discussion of theoretical considerations concerning the chemistry are summarized. Recent theoretical considerations show that the thermal equilibrium model is of limited use for understanding the chemistry of the outer CS envelopes. The theoretical modeling of the chemistry of CS envelopes provides a quantitive test of chemical concepts which have a broader interest than the envelopes themselves.

  19. Modelling non-equilibrium secondary organic aerosol formation and evaporation with the aerosol dynamics, gas- and particle-phase chemistry kinetic multi-layer model ADCHAM

    NASA Astrophysics Data System (ADS)

    Roldin, P.; Eriksson, A. C.; Nordin, E. Z.; Hermansson, E.; Mogensen, D.; Rusanen, A.; Boy, M.; Swietlicki, E.; Svenningsson, B.; Zelenyuk, A.; Pagels, J.

    2014-01-01

    We have developed the novel Aerosol Dynamics, gas- and particle-phase chemistry model for laboratory CHAMber studies (ADCHAM). The model combines the detailed gas phase Master Chemical Mechanism version 3.2, an aerosol dynamics and particle phase chemistry module (which considers acid catalysed oligomerization, heterogeneous oxidation reactions in the particle phase and non-ideal interactions between organic compounds, water and inorganic ions) and a kinetic multilayer module for diffusion limited transport of compounds between the gas phase, particle surface and particle bulk phase. In this article we describe and use ADCHAM to study: (1) the mass transfer limited uptake of ammonia (NH3) and formation of organic salts between ammonium (NH4+) and carboxylic acids (RCOOH), (2) the slow and almost particle size independent evaporation of α-pinene secondary organic aerosol (SOA) particles, and (3) the influence of chamber wall effects on the observed SOA formation in smog chambers. ADCHAM is able to capture the observed α-pinene SOA mass increase in the presence of NH3(g). Organic salts of ammonium and carboxylic acids predominantly form during the early stage of SOA formation. These salts contribute substantially to the initial growth of the homogeneously nucleated particles. The model simulations of evaporating α-pinene SOA particles support the recent experimental findings that these particles have a semi-solid tar like amorphous phase state. ADCHAM is able to reproduce the main features of the observed slow evaporation rates if low-volatility and viscous oligomerized SOA material accumulates in the particle surface layer upon evaporation. The evaporation rate is mainly governed by the reversible decomposition of oligomers back to monomers. Finally, we demonstrate that the mass transfer limited uptake of condensable organic compounds onto wall deposited particles or directly onto the Teflon chamber walls of smog chambers can have profound influence on the

  20. Extending students' practice of metacognitive regulation strategies in the undergraduate chemistry laboratory and investigation of Pb2+ binding to calmodulin with circular dichroism and molecular dynamics modeling

    NASA Astrophysics Data System (ADS)

    Valencia Navarro, Laura N.

    The following dissertation was composed of two projects in chemistry education and benchwork/computational biochemistry. The chemistry education research explored students' practice of metacognitive strategies while solving open-ended laboratory problems when engaged in an instructional environment, the Science Writing Heuristic (SWH), that was characterized as supporting metacognitive regulation strategy use. Through in-depth interviews with students, results demonstrated that students in the SWH environment, compared to non-SWH students, used metacognitive strategies to a greater degree and to a greater depth when solving open-ended laboratory problems. As students engaged in higher levels of metacognitive regulation, their elective use of peers became a prominent path for supporting the practice of metacognitive strategies. Students claimed that the structure of the SWH weekly laboratory experiments improved their ability to solve open-ended lab problems. This research not only provided a lens into students' descriptions of their regulation strategy practices in the laboratory, but it also supported that the way that a laboratory environment is arranged can affect these regulation strategy practices and their transfer to new situations. In the biochemical study on the binding of Pb2+ to calmodulin (CaM), data was acquired via circular dichroism (CD) and molecular dynamics modeling. CD signal data indicated a unique signal from Pb-CaM and a significantly smaller ratio theta208/theta222 for Pb-CaM than Ca-CaM. An analysis of secondary structure content indicated that alpha-helical structure decreased and random coil structure increased when CaM was saturated with Pb2+ compared to Ca2+ saturated CaM. A molecular dynamics simulation of Pb2+ binding to CaM showed that Pb2+ ions bound to sites outside of the known canonical binding sites including the linker region, and indicated change in secondary structure. These results support the theory of opportunistic binding

  1. EDITORIAL: Combinatorial and High-Throughput Materials Research

    NASA Astrophysics Data System (ADS)

    Potyrailo, Radislav A.; Takeuchi, Ichiro

    2005-01-01

    The success of combinatorial and high-throughput methodologies relies greatly on the availability of various characterization tools with new and improved capabilities [1]. Indeed, how useful can a combinatorial library of 250, 400, 25 000 or 2 000 000 compounds be [2-5] if one is unable to characterize its properties of interest fairly quickly? How useful can a set of thousands of spectra or chromatograms be if one is unable to analyse them in a timely manner? For these reasons, the development of new approaches for materials characterization is one of the most active areas in combinatorial materials science. The importance of this aspect of research in the field has been discussed in numerous conferences including the Pittsburgh Conferences, the American Chemical Society Meetings, the American Physical Society Meetings, the Materials Research Society Symposia and various Gordon Research Conferences. Naturally, the development of new measurement instrumentation attracts the attention not only of practitioners of combinatorial materials science but also of those who design new software for data manipulation and mining. Experimental designs of combinatorial libraries are pursued with available and realistic synthetic and characterization capabilities in mind. It is becoming increasingly critical to link the design of new equipment for high-throughput parallel materials synthesis with integrated measurement tools in order to enhance the efficacy of the overall experimental strategy. We have received an overwhelming response to our proposal and call for papers for this Special Issue on Combinatorial Materials Science. The papers in this issue of Measurement Science and Technology are a very timely collection that captures the state of modern combinatorial materials science. They demonstrate the significant advances that are taking place in the field. In some cases, characterization tools are now being operated in the factory mode. At the same time, major challenges

  2. Trace Chemistry

    NASA Technical Reports Server (NTRS)

    Radhakrishnan, Krishnan; Whitefield, Philip

    1999-01-01

    , in addition, of the pressure, temperature, and velocity. A near term goal of the experimental program should be to confirm the nonlinear effects of sulfur speciation, and if present, to provide an explanation for them. It is also desirable to examine if the particulate matter retains any sulfur. The recommendation is to examine the effects on SOx production of variations in fuel-bound sulfur and aromatic content (which may affect the amount of particulates formed). These experiments should help us to understand if there is a coupling between particulate formation and SO, concentration. Similarly, any coupling with NOx can be examined either by introducing NOx into the combustion air or by using fuel-bound nitrogen. Also of immediate urgency is the need to establish and validate a detailed mechanism for sulfur oxidation/aerosol formation, whose chemistry is concluded to be homogeneous, because there is not enough surface area for heterogeneous effects. It is envisaged that this work will involve both experimental and theoretical programs. The experimental work will require, in addition to the measurements described above, fundamental studies in devices such as flow reactors and shock tubes. Complementing this effort should be modeling and theoretical activities. One impediment to the successful modeling of sulfur oxidation is the lack of reliable data for thermodynamic and transport properties for several species, such as aqueous nitric acid, sulfur oxides, and sulfuric acid. Quantum mechanical calculations are recommended as a convenient means of deriving values for these properties. Such calculations would also help establish rate constants for several important reactions for which experimental measurements are inherently fraught with uncertainty. Efforts to implement sufficiently detailed chemistry into computational fluid dynamic codes should be continued. Zero- and one-dimensional flow models are also useful vehicles for elucidating the minimal set of species and

  3. Catalytic Chemistry.

    ERIC Educational Resources Information Center

    Borer, Londa; And Others

    1996-01-01

    Describes an approach for making chemistry relevant to everyday life. Involves the study of kinetics using the decomposition of hydrogen peroxide by vegetable juices. Allows students to design and carry out experiments and then draw conclusions from their results. (JRH)

  4. Chemistry Notes.

    ERIC Educational Resources Information Center

    School Science Review, 1980

    1980-01-01

    Describes equipment, activities, and experiments useful in chemistry instruction, including among others, a rapid method to determine available chlorine in bleach, simple flame testing apparatus, and a simple apparatus demonstrating the technique of flash photolysis. (SK)

  5. Chemistry Notes

    ERIC Educational Resources Information Center

    School Science Review, 1973

    1973-01-01

    Several ideas are proposed for chemistry teachers to try in their classrooms. Subjects included are polymerization of acrylate, polymerization of styrene, conductivity, pollution, preparation of chlorine, redox equations, chemiluminescence, and molecular sieves. (PS)

  6. Nuclear Chemistry.

    ERIC Educational Resources Information Center

    Chemical and Engineering News, 1979

    1979-01-01

    Provides a brief review of the latest developments in nuclear chemistry. Nuclear research today is directed toward increased activity in radiopharmaceuticals and formation of new isotopes by high-energy, heavy-ion collisions. (Author/BB)

  7. Chemistry Notes.

    ERIC Educational Resources Information Center

    School Science Review, 1981

    1981-01-01

    Describes 13 activities, experiments and demonstrations, including the preparation of iron (III) chloride, simple alpha-helix model, investigating camping gas, redox reactions of some organic compounds, a liquid crystal thermometer, and the oxidation number concept in organic chemistry. (JN)

  8. Precolumbian Chemistry.

    ERIC Educational Resources Information Center

    Robinson, Janet Bond

    1995-01-01

    Describes the content and development of a curriculum that provides an approach to descriptive chemistry and the history of technology through consideration of the pottery, metallurgy, pigments, dyes, agriculture, and medicine of pre-Columbian people. (DDR)

  9. Chemistry and isotopic composition of precipitation and surface waters in Khumbu valley (Nepal Himalaya): N dynamics of high elevation basins.

    PubMed

    Balestrini, Raffaella; Polesello, Stefano; Sacchi, Elisa

    2014-07-01

    We monitored the chemical and isotopic compositions of wet depositions, at the Pyramid International Laboratory (5050 ma.s.l.), and surrounding surface waters, in the Khumbu basin, to understand precipitation chemistry and to obtain insights regarding ecosystem responses to atmospheric inputs. The major cations in the precipitation were NH4(+) and Ca(2+), whereas the main anion was HCO3(-), which constituted approximately 69% of the anions, followed by NO3(-), SO4(2-) and Cl(-). Data analysis suggested that Na(+), Cl(-) and K(+) were derived from the long-range transport of marine aerosols. Ca(2+), Mg(2+) and HCO3(-) were related to rock and soil dust contributions and the NO3(-) and SO4(2-) concentrations were derived from anthropogenic sources. Furthermore, NH4(+) was derived from gaseous NH3 scavenging. The isotopic composition of weekly precipitation ranged from -1.9 to -23.2‰ in δ(18)O, and from -0.8 to -174‰ in δ(2)H, with depleted values characterizing the central part of the monsoon period. The chemical composition of the stream water was dominated by calcite and/or gypsum dissolution. However, the isotopic composition of the stream water did not fully reflect the composition of the monsoon precipitation, which suggested that other water sources contributed to the stream flow. Precipitation contents for all ions were the lowest ones among those measured in high elevation sites around the world. During the monsoon periods the depositions were not substantially influenced by anthropogenic inputs, while in pre- and post-monsoon seasons the Himalayas could not represent an effective barrier for airborne pollution. In the late monsoon phase, the increase of ionic contents in precipitation could also be due to a change in the moisture source. The calculated atmospheric N load (0.30 kg ha(-1) y(-1)) was considerably lower than the levels that were measured in other high-altitude environments. Nevertheless, the NO3(-) concentrations in the surface waters

  10. Basic Studies in Combinatorial and Nondifferentiable Optimization.

    DTIC Science & Technology

    1978-03-01

    control problems with linear dynamics, convex cost, and convex inequality state and control constraints is analyzed...points. S.K. MITTER, Lagrange Duality Theory for Convex Control Problems , (with W.W. Hager), Journal of Control and Optimization , 14, August 1976, pp...Lagrange Duality Theory for Convex Control Problems ,” Journal of Control and Optimization , 14, August 1976, pp. 843—856. T.

  11. The molecular dissociation of formaldehyde at medium photoexcitation energies: A quantum chemistry and direct quantum dynamics study

    SciTech Connect

    Araujo, Marta; Magalhaes, Alexandre L.; Lasorne, Benjamin; Worth, Graham A.; Bearpark, Michael J.; Robb, Michael A.

    2009-10-14

    The mechanisms of radiationless decay involved in the photodissociation of formaldehyde into H{sub 2} and CO have been investigated using complete active space self-consistent field (CASSCF) calculations and direct dynamics variational multiconfiguration Gaussian (DD-vMCG) quantum dynamics in the S{sub 1}, T{sub 1}, and S{sub 0} states. A commonly accepted scheme involves Fermi Golden Rule internal conversion from S{sub 1} followed by dissociation of vibrationally hot H{sub 2}CO in S{sub 0}. We recently proposed a novel mechanism [M. Araujo et al., J. Phys. Chem. A 112, 7489 (2008)] whereby internal conversion and dissociation take place in concert through a seam of conical intersection between S{sub 1} and S{sub 0} after the system has passed through an S{sub 1} transition barrier. The relevance of this mechanism depends on the efficiency of tunneling in S{sub 1}. At lower energy, an alternative scheme to internal conversion involves intersystem crossing via T{sub 1} to regenerate the reactant before the S{sub 0} barrier to dissociation. We propose here a previously unidentified mechanism leading directly to H{sub 2} and CO products via T{sub 1}. This channel opens at medium energies, near or above the T{sub 1} barrier to dissociation and still lower than the S{sub 1} barrier, thus making T{sub 1} a possible shortcut to molecular dissociation.

  12. Quantum adiabatic optimization and combinatorial landscapes

    NASA Astrophysics Data System (ADS)

    Smelyanskiy, V. N.; Knysh, S.; Morris, R. D.

    2004-09-01

    In this paper we analyze the performance of the Quantum Adiabatic Evolution algorithm on a variant of the satisfiability problem for an ensemble of random graphs parametrized by the ratio of clauses to variables, γ=M/N . We introduce a set of macroscopic parameters (landscapes) and put forward an ansatz of universality for random bit flips. We then formulate the problem of finding the smallest eigenvalue and the excitation gap as a statistical mechanics problem. We use the so-called annealing approximation with a refinement that a finite set of macroscopic variables (instead of only energy) is used, and are able to show the existence of a dynamic threshold γ=γd starting with some value of K —the number of variables in each clause. Beyond the dynamic threshold, the algorithm should take an exponentially long time to find a solution. We compare the results for extended and simplified sets of landscapes and provide numerical evidence in support of our universality ansatz. We have been able to map the ensemble of random graphs onto another ensemble with fluctuations significantly reduced. This enabled us to obtain tight upper bounds on the satisfiability transition and to recompute the dynamical transition using the extended set of landscapes.

  13. Stratospheric chemistry

    SciTech Connect

    Brune, W.H. )

    1991-01-01

    Advances in stratospheric chemistry made by investigators in the United States from 1987 to 1990 are reviewed. Subject areas under consideration include photochemistry of the polar stratosphere, photochemistry of the global stratosphere, and assessments of inadvertent modification of the stratosphere by anthropogenic activity. Particular attention is given to early observations and theories, gas phase chemistry, Antarctic observations, Arctic observations, odd-oxygen, odd-hydrogen, odd-nitrogen, halogens, aerosols, modeling of stratospheric ozone, and reactive nitrogen effects.

  14. Time-resolved radiation chemistry: Dynamics of electron attachment to uracil following UV excitation of iodide-uracil complexes

    SciTech Connect

    King, Sarah B.; Yandell, Margaret A.; Stephansen, Anne B.; Neumark, Daniel M.

    2014-12-14

    Electron attachment to uracil was investigated by applying time-resolved photoelectron imaging to iodide-uracil (I{sup –}U) complexes. In these studies, an ultraviolet pump pulse initiated charge transfer from the iodide to the uracil, and the resulting dynamics of the uracil temporary negative ion were probed. Five different excitation energies were used, 4.00 eV, 4.07 eV, 4.14 eV, 4.21 eV, and 4.66 eV. At the four lowest excitation energies, which lie near the vertical detachment energy of the I{sup –}U complex (4.11 eV), signatures of both the dipole bound (DB) as well as the valence bound (VB) anion of uracil were observed. In contrast, only the VB anion was observed at 4.66 eV, in agreement with previous experiments in this higher energy range. The early-time dynamics of both states were highly excitation energy dependent. The rise time of the DB anion signal was ∼250 fs at 4.00 eV and 4.07 eV, ∼120 fs at 4.14 eV and cross-correlation limited at 4.21 eV. The VB anion rise time also changed with excitation energy, ranging from 200 to 300 fs for excitation energies 4.00–4.21 eV, to a cross-correlation limited time at 4.66 eV. The results suggest that the DB state acts as a “doorway” state to the VB anion at 4.00–4.21 eV, while direct attachment to the VB anion occurs at 4.66 eV.

  15. Towards Teaching Chemistry as a Language

    NASA Astrophysics Data System (ADS)

    Laszlo, Pierre

    2013-07-01

    This paper presents views on the teaching of chemistry and directions for its further development. A detailed critical analysis is offered for the inadequacy of much of the current teaching, weighed that it is by a conventional, traditional and, as it turns out, rather outdated sense of the material to be covered. The ambient meta-discourse on the nature of chemistry is unduly dominated by the physicalist assumption, believing chemistry to be reducible to physics, which I hold to be unrefutable and thus parascientific. This all-too-tenuous link is countered with a parallel, bolstered by a slew of examples and analogies, between chemistry and linguistics: it is both more legitimate, in terms of the supporting evidence, considerably more effective than a physicalist approach. Chemical teaching needs to hybridize the bottom-up and the top-down communication vectors between the students and their teacher. It can only benefit from infusion of a strong dose of history. Chemistry ought to be taught in like manner to a language, on the dual evidence of the existence of an iconic chemical language, of formulas and equations; and of chemical science being language-like and a combinatorial art.

  16. Simulation of changes in global ozone and atmospheric dynamics in the 21st century with the chemistry-climate model SOCOL

    NASA Astrophysics Data System (ADS)

    Zubov, V. A.; Rozanov, E. V.; Rozanova, I. V.; Egorova, T. A.; Kiselev, A. A.; Karol', I. L.; Schmutz, V.

    2011-06-01

    The solar climate ozone links (SOCOL) three-dimensional chemistry-climate model is used to estimate changes in the ozone and atmospheric dynamics over the 21st century. With this model, four numerical time-slice experiments were conducted for 1980, 2000, 2050, and 2100 conditions. Boundary conditions for sea-surface temperatures, sea-ice parameters, and concentrations of greenhouse and ozone-depleting gases were set following the IPCC A1B scenario and the WMO A1 scenario. From the model results, a statistically significant cooling of the model stratosphere was obtained to be 4-5 K for 2000-2050 and 3-5 K for 2050-2100. The temperature of the lower atmosphere increases by 2-3 K over the 21st century. Tropospheric heating significantly enhances the activity of planetary-scale waves at the tropopause. As a result, the Eliassen-Palm flux divergence considerable increases in the middle and upper stratosphere. The intensity of zonal circulation decreases and the meridional residual circulation increases, especially in the winter-spring period of each hemisphere. These dynamic changes, along with a decrease in the concentrations of ozone-depleting gases, result in a faster growth of O3 outside the tropics. For example, by 2050, the total ozone in the middle and high latitudes approaches its model level of 1980 and the ozone hole in Antarctica fills up. The superrecovery of the model ozone layer in the middle and high latitudes of both hemispheres occurs in 2100. The tropical ozone layer recovers far less slowly, reaching a 1980 level only by 2100.

  17. Combinatorial geometry domain decomposition strategies for Monte Carlo simulations

    SciTech Connect

    Li, G.; Zhang, B.; Deng, L.; Mo, Z.; Liu, Z.; Shangguan, D.; Ma, Y.; Li, S.; Hu, Z.

    2013-07-01

    Analysis and modeling of nuclear reactors can lead to memory overload for a single core processor when it comes to refined modeling. A method to solve this problem is called 'domain decomposition'. In the current work, domain decomposition algorithms for a combinatorial geometry Monte Carlo transport code are developed on the JCOGIN (J Combinatorial Geometry Monte Carlo transport INfrastructure). Tree-based decomposition and asynchronous communication of particle information between domains are described in the paper. Combination of domain decomposition and domain replication (particle parallelism) is demonstrated and compared with that of MERCURY code. A full-core reactor model is simulated to verify the domain decomposition algorithms using the Monte Carlo particle transport code JMCT (J Monte Carlo Transport Code), which has being developed on the JCOGIN infrastructure. Besides, influences of the domain decomposition algorithms to tally variances are discussed. (authors)

  18. Communities of minima in local optima networks of combinatorial spaces

    NASA Astrophysics Data System (ADS)

    Daolio, Fabio; Tomassini, Marco; Vérel, Sébastien; Ochoa, Gabriela

    2011-05-01

    In this work, we present a new methodology to study the structure of the configuration spaces of hard combinatorial problems. It consists in building the network that has as nodes the locally optimal configurations and as edges the weighted oriented transitions between their basins of attraction. We apply the approach to the detection of communities in the optima networks produced by two different classes of instances of a hard combinatorial optimization problem: the quadratic assignment problem (QAP). We provide evidence indicating that the two problem instance classes give rise to very different configuration spaces. For the so-called real-like class, the networks possess a clear modular structure, while the optima networks belonging to the class of random uniform instances are less well partitionable into clusters. This is convincingly supported by using several statistical tests. Finally, we briefly discuss the consequences of the findings for heuristically searching the corresponding problem spaces.

  19. Combinatorial Gene Regulation through Kinetic Control of the Transcription Cycle.

    PubMed

    Scholes, Clarissa; DePace, Angela H; Sánchez, Álvaro

    2017-01-25

    Cells decide when, where, and to what level to express their genes by "computing" information from transcription factors (TFs) binding to regulatory DNA. How is the information contained in multiple TF-binding sites integrated to dictate the rate of transcription? The dominant conceptual and quantitative model is that TFs combinatorially recruit one another and RNA polymerase to the promoter by direct physical interactions. Here, we develop a quantitative framework to explore kinetic control, an alternative model in which combinatorial gene regulation can result from TFs working on different kinetic steps of the transcription cycle. Kinetic control can generate a wide range of analog and Boolean computations without requiring the input TFs to be simultaneously bound to regulatory DNA. We propose experiments that will illuminate the role of kinetic control in transcription and discuss implications for deciphering the cis-regulatory "code."

  20. Thermal analysis of combinatorial solid geometry models using SINDA

    NASA Technical Reports Server (NTRS)

    Gerencser, Diane; Radke, George; Introne, Rob; Klosterman, John; Miklosovic, Dave

    1993-01-01

    Algorithms have been developed using Monte Carlo techniques to determine the thermal network parameters necessary to perform a finite difference analysis on Combinatorial Solid Geometry (CSG) models. Orbital and laser fluxes as well as internal heat generation are modeled to facilitate satellite modeling. The results of the thermal calculations are used to model the infrared (IR) images of targets and assess target vulnerability. Sample analyses and validation are presented which demonstrate code products.

  1. Self-Assembled Combinatorial Nanoarrays for Multiplex Biosensing

    DTIC Science & Technology

    2010-02-05

    routinely for small to moderate scale protein profiling and gene expression detection. 2.2 Recharging the combinatorial encoding array detection...microscopy, we demonstrate direct visualization of high affinity bivalent ligands being used as pincers to capture and display protein molecules on a...spacer, an optimal inter-aptamer distance will be achieved such that the two aptamers will act as a bivalent single molecular species that displays a

  2. Visualizing the chemistry and structure dynamics in lithium-ion batteries by in-situ neutron diffraction

    PubMed Central

    Wang, Xun-Li; An, Ke; Cai, Lu; Feng, Zhili; Nagler, Stephen E.; Daniel, Claus; Rhodes, Kevin J.; Stoica, Alexandru D.; Skorpenske, Harley D.; Liang, Chengdu; Zhang, Wei; Kim, Joon; Qi, Yue; Harris, Stephen J.

    2012-01-01

    We report an in-situ neutron diffraction study of a large format pouch battery cell. The succession of Li-Graphite intercalation phases was fully captured under an 1C charge-discharge condition (i.e., charge to full capacity in 1 hour). However, the lithiation and dilithiation pathways are distinctively different and, unlike in slowing charging experiments with which the Li-Graphite phase diagram was established, no LiC24 phase was found during charge at 1C rate. Approximately 75 mol. % of the graphite converts to LiC6 at full charge, and a lattice dilation as large as 4% was observed during a charge-discharge cycle. Our work demonstrates the potential of in-situ, time and spatially resolved neutron diffraction study of the dynamic chemical and structural changes in “real-world” batteries under realistic cycling conditions, which should provide microscopic insights on degradation and the important role of diffusion kinetics in energy storage materials. PMID:23087812

  3. A combinatorial perspective of the protein inference problem.

    PubMed

    Yang, Chao; He, Zengyou; Yu, Weichuan

    2013-01-01

    In a shotgun proteomics experiment, proteins are the most biologically meaningful output. The success of proteomics studies depends on the ability to accurately and efficiently identify proteins. Many methods have been proposed to facilitate the identification of proteins from peptide identification results. However, the relationship between protein identification and peptide identification has not been thoroughly explained before. In this paper, we devote ourselves to a combinatorial perspective of the protein inference problem. We employ combinatorial mathematics to calculate the conditional protein probabilities (protein probability means the probability that a protein is correctly identified) under three assumptions, which lead to a lower bound, an upper bound, and an empirical estimation of protein probabilities, respectively. The combinatorial perspective enables us to obtain an analytical expression for protein inference. Our method achieves comparable results with ProteinProphet in a more efficient manner in experiments on two data sets of standard protein mixtures and two data sets of real samples. Based on our model, we study the impact of unique peptides and degenerate peptides (degenerate peptides are peptides shared by at least two proteins) on protein probabilities. Meanwhile, we also study the relationship between our model and ProteinProphet. We name our program ProteinInfer. Its Java source code, our supplementary document and experimental results are available at: >http://bioinformatics.ust.hk/proteininfer.

  4. Combinatorial entropy and phase diagram of partially ordered ice phases.

    PubMed

    Macdowell, Luis G; Sanz, Eduardo; Vega, Carlos; Abascal, José Luis F

    2004-11-22

    A close analytical estimate for the combinatorial entropy of partially ordered ice phases is presented. The expression obtained is very general, as it can be used for any ice phase obeying the Bernal-Fowler rules. The only input required is a number of crystallographic parameters, and the experimentally observed proton site occupancies. For fully disordered phases such as hexagonal ice, it recovers the result deduced by Pauling, while for fully ordered ice it is found to vanish. Although the space groups determined for ice I, VI, and VII require random proton site occupancies, it is found that such random allocation of protons does not necessarily imply random orientational disorder. The theoretical estimate for the combinatorial entropy is employed together with free energy calculations in order to obtain the phase diagram of ice from 0 to 10 GPa. Overall qualitative agreement with experiment is found for the TIP4P model of water. An accurate estimate of the combinatorial entropy is found to play an important role in determining the stability of partially ordered ice phases, such as ice III and ice V.

  5. Controlling Combinatorial Complexity in Software and Malware Behavior Computation

    SciTech Connect

    Pleszkoch, Mark G; Linger, Richard C

    2015-01-01

    Virtually all software is out of intellectual control in that no one knows its full behavior. Software Behavior Computation (SBC) is a new technology for understanding everything software does. SBC applies the mathematics of denotational semantics implemented by function composition in Functional Trace Tables (FTTs) to compute the behavior of programs, expressed as disjoint cases of conditional concurrent assignments. In some circumstances, combinatorial explosions in the number of cases can occur when calculating the behavior of sequences of multiple branching structures. This paper describes computational methods that avoid combinatorial explosions. The predicates that control branching structures such as ifthenelses can be organized into three categories: 1) Independent, resulting in no behavior case explosion, 2) Coordinated, resulting in two behavior cases, or 3) Goaloriented, with potential exponential growth in the number of cases. Traditional FTT-based behavior computation can be augmented by two additional computational methods, namely, Single-Value Function Abstractions (SVFAs) and, introduced in this paper, Relational Trace Tables (RTTs). These methods can be applied to the three predicate categories to avoid combinatorial growth in behavior cases while maintaining mathematical correctness.

  6. Combinatorial study of ceramic tape-casting slurries.

    PubMed

    Liu, Zhifu; Wang, Yiling; Li, Yongxiang

    2012-03-12

    Ceramic tape-casting slurries are complex systems composed of ceramic powder, solvent, and a number of organic components. Conventionally, the development of ceramic tape-casting slurries is time-consuming and of low efficiency. In this work, combinatorial approaches were applied to screen the ethanol and ethyl-acetate binary solvent based slurry for ceramic green tape-casting. The combinatorial libraries were designed considering the variation of the amount of PVB (Poly vinyl-butyral) binder, polyethylene-400, and butyl-benzyl-phthalate plasticizers, and glyceryl triacetate dispersant. A parallel magnetic stirring process was used to make the combinatorial slurry library. The properties mapping of the slurry library was obtained by investigating the sedimentation and rheological characteristics of the slurries. The slurry composition was refined by scaling up the experiments and comparing the microstructure, mechanical property, and sintering behavior of green tapes made from the selected slurries. Finally, a kind of ethanol-ethyl acetate binary solvent based slurry system suitable for making X7R dielectric ceramic green tapes was achieved.

  7. View discovery in OLAP databases through statistical combinatorial optimization

    SciTech Connect

    Hengartner, Nick W; Burke, John; Critchlow, Terence; Joslyn, Cliff; Hogan, Emilie

    2009-01-01

    OnLine Analytical Processing (OLAP) is a relational database technology providing users with rapid access to summary, aggregated views of a single large database, and is widely recognized for knowledge representation and discovery in high-dimensional relational databases. OLAP technologies provide intuitive and graphical access to the massively complex set of possible summary views available in large relational (SQL) structured data repositories. The capability of OLAP database software systems to handle data complexity comes at a high price for analysts, presenting them a combinatorially vast space of views of a relational database. We respond to the need to deploy technologies sufficient to allow users to guide themselves to areas of local structure by casting the space of 'views' of an OLAP database as a combinatorial object of all projections and subsets, and 'view discovery' as an search process over that lattice. We equip the view lattice with statistical information theoretical measures sufficient to support a combinatorial optimization process. We outline 'hop-chaining' as a particular view discovery algorithm over this object, wherein users are guided across a permutation of the dimensions by searching for successive two-dimensional views, pushing seen dimensions into an increasingly large background filter in a 'spiraling' search process. We illustrate this work in the context of data cubes recording summary statistics for radiation portal monitors at US ports.

  8. Rapid combinatorial screening by synchrotron X-ray imaging

    NASA Astrophysics Data System (ADS)

    Eba, Hiromi; Sakurai, Kenji

    2006-01-01

    An X-ray imaging system, which does not require any scans of the sample or an X-ray beam and which, therefore, dramatically reduces the amount of time required, was employed to evaluate combinatorial libraries efficiently. Two-dimensional X-ray fluorescence (XRF) images of an 8 mm × 8 mm area were observed for combinatorial substrates of manganese-cobalt spinel MnCo 2O 4 and lithium ferrite LiFeO 2 via an exposure time of 1-3 s using synchrotron X-rays. Thus, XRF signals from a whole substrate could be observed at once in a short space of time. In order to observe the chemical environment simultaneously for all materials arranged on the substrate, the fluorescent X-ray absorption fine structure (XAFS) was measured by repeating the imaging during the monochromator scans across the absorption edge for metals. This is extremely efficient because XAFS spectra for all materials placed on the common substrate are obtained from only a single energy scan. One can determine the valence numbers, as well as other aspects of the chemical environment of the metal included in each material, from the differences in spectral features and the energy shifts. Hence, combinatorial libraries can be screened very rapidly, and therefore efficiently, using the X-ray imaging system.

  9. Quantum Adiabatic Optimization and Combinatorial Landscapes

    NASA Technical Reports Server (NTRS)

    Smelyanskiy, V. N.; Knysh, S.; Morris, R. D.

    2003-01-01

    In this paper we analyze the performance of the Quantum Adiabatic Evolution (QAE) algorithm on a variant of Satisfiability problem for an ensemble of random graphs parametrized by the ratio of clauses to variables, gamma = M / N. We introduce a set of macroscopic parameters (landscapes) and put forward an ansatz of universality for random bit flips. We then formulate the problem of finding the smallest eigenvalue and the excitation gap as a statistical mechanics problem. We use the so-called annealing approximation with a refinement that a finite set of macroscopic variables (verses only energy) is used, and are able to show the existence of a dynamic threshold gamma = gammad, beyond which QAE should take an exponentially long time to find a solution. We compare the results for extended and simplified sets of landscapes and provide numerical evidence in support of our universality ansatz.

  10. Combinatorial Regulation in Yeast Transcription Networks

    NASA Astrophysics Data System (ADS)

    Li, Hao

    2006-03-01

    Yeast has evolved a complex network to regulate its transcriptional program in response to changes in environment. It is quite common that in response to an external stimulus, several transcription factors will be activated and they work in combinations to control different subsets of genes in the genome. We are interested in how the promoters of genes are designed to integrate signals from multiple transcription factors and what are the functional and evolutionary constraints. To answer how, we have developed a number of computational algorithms to systematically map the binding sites and target genes of transcription factors using sequence and gene expression data. To analyze the functional constraints, we have employed mechanistic models to study the dynamic behavior of genes regulated by multiple factors. We have also developed methods to trace the evolution of transcriptional networks via comparative analysis of multiple species.

  11. High-flexibility combinatorial peptide synthesis with laser-based transfer of monomers in solid matrix material

    NASA Astrophysics Data System (ADS)

    Loeffler, Felix F.; Foertsch, Tobias C.; Popov, Roman; Mattes, Daniela S.; Schlageter, Martin; Sedlmayr, Martyna; Ridder, Barbara; Dang, Florian-Xuan; von Bojničić-Kninski, Clemens; Weber, Laura K.; Fischer, Andrea; Greifenstein, Juliane; Bykovskaya, Valentina; Buliev, Ivan; Bischoff, F. Ralf; Hahn, Lothar; Meier, Michael A. R.; Bräse, Stefan; Powell, Annie K.; Balaban, Teodor Silviu; Breitling, Frank; Nesterov-Mueller, Alexander

    2016-06-01

    Laser writing is used to structure surfaces in many different ways in materials and life sciences. However, combinatorial patterning applications are still limited. Here we present a method for cost-efficient combinatorial synthesis of very-high-density peptide arrays with natural and synthetic monomers. A laser automatically transfers nanometre-thin solid material spots from different donor slides to an acceptor. Each donor bears a thin polymer film, embedding one type of monomer. Coupling occurs in a separate heating step, where the matrix becomes viscous and building blocks diffuse and couple to the acceptor surface. Furthermore, we can consecutively deposit two material layers of activation reagents and amino acids. Subsequent heat-induced mixing facilitates an in situ activation and coupling of the monomers. This allows us to incorporate building blocks with click chemistry compatibility or a large variety of commercially available non-activated, for example, posttranslationally modified building blocks into the array's peptides with >17,000 spots per cm2.

  12. High-flexibility combinatorial peptide synthesis with laser-based transfer of monomers in solid matrix material

    PubMed Central

    Loeffler, Felix F.; Foertsch, Tobias C.; Popov, Roman; Mattes, Daniela S.; Schlageter, Martin; Sedlmayr, Martyna; Ridder, Barbara; Dang, Florian-Xuan; von Bojničić-Kninski, Clemens; Weber, Laura K.; Fischer, Andrea; Greifenstein, Juliane; Bykovskaya, Valentina; Buliev, Ivan; Bischoff, F. Ralf; Hahn, Lothar; Meier, Michael A. R.; Bräse, Stefan; Powell, Annie K.; Balaban, Teodor Silviu; Breitling, Frank; Nesterov-Mueller, Alexander

    2016-01-01

    Laser writing is used to structure surfaces in many different ways in materials and life sciences. However, combinatorial patterning applications are still limited. Here we present a method for cost-efficient combinatorial synthesis of very-high-density peptide arrays with natural and synthetic monomers. A laser automatically transfers nanometre-thin solid material spots from different donor slides to an acceptor. Each donor bears a thin polymer film, embedding one type of monomer. Coupling occurs in a separate heating step, where the matrix becomes viscous and building blocks diffuse and couple to the acceptor surface. Furthermore, we can consecutively deposit two material layers of activation reagents and amino acids. Subsequent heat-induced mixing facilitates an in situ activation and coupling of the monomers. This allows us to incorporate building blocks with click chemistry compatibility or a large variety of commercially available non-activated, for example, posttranslationally modified building blocks into the array's peptides with >17,000 spots per cm2. PMID:27296868

  13. A Robust and Versatile Method of Combinatorial Chemical Synthesis of Gene Libraries via Hierarchical Assembly of Partially Randomized Modules.

    PubMed

    Popova, Blagovesta; Schubert, Steffen; Bulla, Ingo; Buchwald, Daniela; Kramer, Wilfried

    2015-01-01

    A major challenge in gene library generation is to guarantee a large functional size and diversity that significantly increases the chances of selecting different functional protein variants. The use of trinucleotides mixtures for controlled randomization results in superior library diversity and offers the ability to specify the type and distribution of the amino acids at each position. Here we describe the generation of a high diversity gene library using tHisF of the hyperthermophile Thermotoga maritima as a scaffold. Combining various rational criteria with contingency, we targeted 26 selected codons of the thisF gene sequence for randomization at a controlled level. We have developed a novel method of creating full-length gene libraries by combinatorial assembly of smaller sub-libraries. Full-length libraries of high diversity can easily be assembled on demand from smaller and much less diverse sub-libraries, which circumvent the notoriously troublesome long-term archivation and repeated proliferation of high diversity ensembles of phages or plasmids. We developed a generally applicable software tool for sequence analysis of mutated gene sequences that provides efficient assistance for analysis of library diversity. Finally, practical utility of the library was demonstrated in principle by assessment of the conformational stability of library members and isolating protein variants with HisF activity from it. Our approach integrates a number of features of nucleic acids synthetic chemistry, biochemistry and molecular genetics to a coherent, flexible and robust method of combinatorial gene synthesis.

  14. Long-term changes and trends in total ozone over the northern mid-latitudes: Influence of atmospheric dynamics and chemistry and contribution from extreme events

    NASA Astrophysics Data System (ADS)

    Rieder, H. E.; Staehelin, J.; Maeder, J. A.; Ribatet, M.; di Rocco, S.; Frossard, L.; Jancso, L. M.; Peter, T.; Davison, A. C.

    2010-12-01

    Downward trends in global stratospheric ozone during recent decades have been shown to be directly linked to increasing surface UV-radiation. In the past, long-term ozone trends were determined from homogenized data series by fitting with multiple linear regression models, in which suitable independent variables (so-called explanatory variables) were used to represent atmospheric variability, such as the Quasi-Biennial Oscillation (QBO), the 11-year solar cycle, and a linear trend attributed to anthropogenic ozone depletion. Previous studies have identified a number of other processes influencing total ozone at mid-latitudes, such as synoptic-scale meteorological variability, decadal or long-term climate variability, described e.g. by the Northern Atlantic Oscillation (NAO), the Arctic Oscillation (AO), atmospheric circulation indices ENSO, temperature at the 470-K isentrope level, and volcanic eruptions. Due to the successful implementation of the Montreal Protocol the discussion about a recovery or possible “super recovery” started within the scientific community. Here we address long-term changes and trends in a different framework. As statistical analysis showed that previously used concepts assuming a Gaussian distribution of total ozone data do not address the internal data structure concerning extremes adequately methods from extreme value theory are applied on local (various long-term ground based total ozone records) and regional (high resolution homogenized satellite data) scale. Within the extreme value theory framework days with extreme low (ELOs) and high (EHOs) total ozone are analyzed and their frequency is linked to changes in atmospheric chemistry and dynamics. The results show: (i) an increase in ELOs and (ii) a decrease in EHOs during the last decades and (iii) that the overall trend during the 1970s and 1980s in total ozone is strongly dominated by changes in these extreme events. After removing the extremes, the different time series show a

  15. Size and surface chemistry of nanoparticles lead to a variant behavior in the unfolding dynamics of human carbonic anhydrase

    NASA Astrophysics Data System (ADS)

    Nasir, Irem; Lundqvist, Martin; Cabaleiro-Lago, Celia

    2015-10-01

    The adsorption induced conformational changes of human carbonic anhydrase I (HCAi) and pseudo wild type human carbonic anhydrase II truncated at the 17th residue at the N-terminus (trHCAii) were studied in presence of nanoparticles of different sizes and polarities. Isothermal titration calorimetry (ITC) studies showed that the binding to apolar surfaces is affected by the nanoparticle size in combination with the inherent protein stability. 8-Anilino-1-naphthalenesulfonic acid (ANS) fluorescence revealed that HCAs adsorb to both hydrophilic and hydrophobic surfaces, however the dynamics of the unfolding at the nanoparticle surfaces drastically vary with the polarity. The size of the nanoparticles has opposite effects depending on the polarity of the nanoparticle surface. The apolar nanoparticles induce seconds timescale structural rearrangements whereas polar nanoparticles induce hours timescale structural rearrangements on the same charged HCA variant. Here, a simple model is proposed where the difference in the timescales of adsorption is correlated with the energy barriers for initial docking and structural rearrangements which are firmly regulated by the surface polarity. Near-UV circular dichorism (CD) further supports that both protein variants undergo structural rearrangements at the nanoparticle surfaces regardless of being ``hard'' or ``soft''. However, the conformational changes induced by the apolar surfaces differ for each HCA isoform and diverge from the previously reported effect of silica nanoparticles.The adsorption induced conformational changes of human carbonic anhydrase I (HCAi) and pseudo wild type human carbonic anhydrase II truncated at the 17th residue at the N-terminus (trHCAii) were studied in presence of nanoparticles of different sizes and polarities. Isothermal titration calorimetry (ITC) studies showed that the binding to apolar surfaces is affected by the nanoparticle size in combination with the inherent protein stability. 8-Anilino

  16. ISOGENIE: Linking geochemistry, isotopic chemistry and microbial dynamics & community composition in a thawing permafrost peatland, Stordalen Mire, Abisco, Sweden.

    NASA Astrophysics Data System (ADS)

    Chanton, J.; Crill, P. M.; Rich, V.; McCalley, C. K.; Hodgkins, S. B.; Tyson, G.; Logan, T.; Wehr, R.; Mondav, R.; Li, C.; Frolking, S.; Saleska, S. R.

    2011-12-01

    As permafrost thaws, increasing CH4 emissions from northern wetlands are likely to cause positive feedback to atmospheric warming. One of the over-arching goals of this project is to connect geochemical processes, particularly focusing on methane production, to underlying microbial population dynamics and genomics. Recent transformative technical advances in both high throughput investigations of microbial communities and high temporal resolution biogeochemical isotope measurements now permit a uniquely comprehensive approach to opening the microbial "black boxes" that impact carbon cycling on global scales. This project links detailed microbial sampling with detailed geochemical and isotopic sampling on seasonal and diel timescales and has an extensive modeling component. Gas exchange is monitored across the wetland gradients in a series of automated chambers and isotopes of emitted and belowground methane and carbon dioxide are measured with a QC laser system. The mire is in a state of partial thaw. With this thaw is an apparent ecological session in wetland community structure and associated changes in organic matter lability, rates of methane production and microbial community. Our group's study sites range from palsa with underlying permanently frozen peat, to recently collapsed and flooded palsa, to flooded palsa colonized by Sphagnum, to flooded eriophorum sites, to sites populated by Carex, to open water lakes. Across this environmental gradient pH ranges from 4 to 6.5. This change is driven by changes in hydrology as the surface of the thawing permafrost subsides and an adjacent lake drains into the mire. Along this environmental gradient, from palsa to Carex, the lability of the peat increases significantly as determined in incubations of peat material and monitoring of methane and carbon dioxide production rates. Coincident with this environmental gradient is a decrease in the apparent fractionation factor between methane and carbon dioxide and methane

  17. Carbonate chemistry dynamics and biological processes along a river-sea gradient (Gulf of Trieste, northern Adriatic Sea)

    NASA Astrophysics Data System (ADS)

    Ingrosso, Gianmarco; Giani, Michele; Cibic, Tamara; Karuza, Ana; Kralj, Martina; Del Negro, Paola

    2016-03-01

    In this paper we investigated, for two years and with a bi-monthly frequency, how physical, chemical, and biological processes affect the marine carbonate system in a coastal area characterized by high alkalinity riverine discharge (Gulf of Trieste, northern Adriatic Sea, Mediterranean Sea). By combining synoptic measurements of the carbonate system with in situ determinations of the primary production (14C incorporation technique) and secondary prokaryotic carbon production (3H-leucine incorporation) along a river-sea gradient, we showed that the conservative mixing between river endmember and off-shore waters was the main driver of the dissolved inorganic carbon (DIC) distribution and seasonal variation. However, during spring and summer seasons also the influence of biological uptake and release of DIC was significant. In the surface water of June 2012, the spreading and persistence of nutrient-rich freshwater stimulated the primary production (3.21 μg C L- 1 h- 1) and net biological DIC decrease (- 100 μmol kg- 1), reducing the dissolved CO2 concentration and increasing the pHT. Below the pycnocline of August 2012, instead, an elevated bacterial carbon production rate (0.92 μg C L- 1 h- 1) was related with net DIC increase (92 μmol kg- 1), low dissolved oxygen concentration, and strong pHT reduction, suggesting the predominance of bacterial heterotrophic respiration over primary production. The flux of carbon dioxide estimated at the air-sea interface exerted a low influence on the seasonal variation of the carbonate system. A complex temporal and spatial dynamic of the air-sea CO2 exchange was also detected, due to the combined effects of seawater temperature, river discharge, and water circulation. On annual scale the system was a sink of atmospheric CO2. However, in summer and during elevated riverine discharges, the area close to the river's mouth acted as a source of carbon dioxide. Also the wind speed was crucial in controlling the air-sea CO2

  18. Dynamic Processes in Biology, Chemistry, and Materials Science: Opportunities for UltraFast Transmission Electron Microscopy - Workshop Summary Report

    SciTech Connect

    Kabius, Bernd C.; Browning, Nigel D.; Thevuthasan, Suntharampillai; Diehl, Barbara L.; Stach, Eric A.

    2012-07-25

    This report summarizes a 2011 workshop that addressed the potential role of rapid, time-resolved electron microscopy measurements in accelerating the solution of important scientific and technical problems. A series of U.S. Department of Energy (DOE) and National Academy of Science workshops have highlighted the critical role advanced research tools play in addressing scientific challenges relevant to biology, sustainable energy, and technologies that will fuel economic development without degrading our environment. Among the specific capability needs for advancing science and technology are tools that extract more detailed information in realistic environments (in situ or operando) at extreme conditions (pressure and temperature) and as a function of time (dynamic and time-dependent). One of the DOE workshops, Future Science Needs and Opportunities for Electron Scattering: Next Generation Instrumentation and Beyond, specifically addressed the importance of electron-based characterization methods for a wide range of energy-relevant Grand Scientific Challenges. Boosted by the electron optical advancement in the last decade, a diversity of in situ capabilities already is available in many laboratories. The obvious remaining major capability gap in electron microscopy is in the ability to make these direct in situ observations over a broad spectrum of fast (µs) to ultrafast (picosecond [ps] and faster) temporal regimes. In an effort to address current capability gaps, EMSL, the Environmental Molecular Sciences Laboratory, organized an Ultrafast Electron Microscopy Workshop, held June 14-15, 2011, with the primary goal to identify the scientific needs that could be met by creating a facility capable of a strongly improved time resolution with integrated in situ capabilities. The workshop brought together more than 40 leading scientists involved in applying and/or advancing electron microscopy to address important scientific problems of relevance to DOE’s research

  19. Polymer Chemistry

    NASA Technical Reports Server (NTRS)

    Williams, Martha; Roberson, Luke; Caraccio, Anne

    2010-01-01

    This viewgraph presentation describes new technologies in polymer and material chemistry that benefits NASA programs and missions. The topics include: 1) What are Polymers?; 2) History of Polymer Chemistry; 3) Composites/Materials Development at KSC; 4) Why Wiring; 5) Next Generation Wiring Materials; 6) Wire System Materials and Integration; 7) Self-Healing Wire Repair; 8) Smart Wiring Summary; 9) Fire and Polymers; 10) Aerogel Technology; 11) Aerogel Composites; 12) Aerogels for Oil Remediation; 13) KSC's Solution; 14) Chemochromic Hydrogen Sensors; 15) STS-130 and 131 Operations; 16) HyperPigment; 17) Antimicrobial Materials; 18) Conductive Inks Formulations for Multiple Applications; and 19) Testing and Processing Equipment.

  20. Chemistry Experiments

    NASA Technical Reports Server (NTRS)

    Brasseur, Guy; Remsberg, Ellis; Purcell, Patrick; Bhatt, Praful; Sage, Karen H.; Brown, Donald E.; Scott, Courtney J.; Ko, Malcolm K. W.; Tie, Xue-Xi; Huang, Theresa

    1999-01-01

    The purpose of the chemistry component of the model comparison is to assess to what extent differences in the formulation of chemical processes explain the variance between model results. Observed concentrations of chemical compounds are used to estimate to what degree the various models represent realistic situations. For readability, the materials for the chemistry experiment are reported in three separate sections. This section discussed the data used to evaluate the models in their simulation of the source gases and the Nitrogen compounds (NO(y)) and Chlorine compounds (Cl(y)) species.

  1. Evolution on folding landscapes in combinatorial structures

    SciTech Connect

    Fraser, S.M.; Reidys, C.M.

    1997-11-01

    In this paper the authors investigate the evolution of molecular structures by random point mutations. They will consider two types of molecular structures: (a) (RNA) secondary structures, and (b) random structures. In both cases structure consists of: (1) a contact graph, and (2) a family of relations imposed on its adjacent vertices. The vertex set of the contact graph is simply the set of all indices of a sequence, and its edges are the bonds. The corresponding relations associated with the edges are viewed as secondary base pairing rules and tertiary interaction rules respectively. Mapping of sequences into secondary and random structures are modeled and analyzed. Here, the set of all sequences that map into a particular structure is modeled as a random graph in the sequence space, the so called neutral network and they study how neutral networks are embedded in sequence space. A basic replication of deletion experiment reveals how effective secondary and random structures can be searched by random point mutations and to what extent the structure effects the dynamics of this optimization process. In particular the authors can report a nonlinear relation between the fraction of tertiary interactions in random structures, and the times taken for a population of sequences to find a high fitness target random structure.

  2. Coupled Phases and Combinatorial Selection in Fluctuating Hydrothermal Pools: A Scenario to Guide Experimental Approaches to the Origin of Cellular Life

    PubMed Central

    Damer, Bruce; Deamer, David

    2015-01-01

    Hydrothermal fields on the prebiotic Earth are candidate environments for biogenesis. We propose a model in which molecular systems driven by cycles of hydration and dehydration in such sites undergo chemical evolution in dehydrated films on mineral surfaces followed by encapsulation and combinatorial selection in a hydrated bulk phase. The dehydrated phase can consist of concentrated eutectic mixtures or multilamellar liquid crystalline matrices. Both conditions organize and concentrate potential monomers and thereby promote polymerization reactions that are driven by reduced water activity in the dehydrated phase. In the case of multilamellar lipid matrices, polymers that have been synthesized are captured in lipid vesicles upon rehydration to produce a variety of molecular systems. Each vesicle represents a protocell, an “experiment” in a natural version of combinatorial chemistry. Two kinds of selective processes can then occur. The first is a physical process in which relatively stable molecular systems will be preferentially selected. The second is a chemical process in which rare combinations of encapsulated polymers form systems capable of capturing energy and nutrients to undergo growth by catalyzed polymerization. Given continued cycling over extended time spans, such combinatorial processes will give rise to molecular systems having the fundamental properties of life. PMID:25780958

  3. Search for new red phosphors using genetic algorithm-assisted combinatorial chemistry.

    PubMed

    Kulshreshtha, Chandramouli; Sharma, Asish Kumar; Sohn, Kee-Sun

    2008-01-01

    A genetic algorithm was employed in association with high-throughput synthesis and characterization in an attempt to search for red phosphors with high photoluminescent intensity. A tetravalent manganese-doped alkali earth germanium oxide system, with an emission color close to a desirable deep red, was screened with the assistance of a genetic algorithm to pinpoint the phosphor exhibiting the highest photoluminescence. As the genetic algorithm was in progress, the PL intensity increased and maximized in the fourth generation. The highest and the average PL intensity of the fourth generation improved by 23 and 120%, respectively, compared with that of the first generation.

  4. Combinatorial chemistry in nematodes: modular assembly of primary metabolism-derived building blocks

    PubMed Central

    2016-01-01

    The nematode Caenorhabditis elegans was the first animal to have its genome fully sequenced and has become an important model organism for biomedical research. However, like many other animal model systems, its metabolome remained largely uncharacterized, until recent investigations demonstrated the importance of small molecule-based signalling cascades for virtually every aspect of nematode biology. These studies have revealed that nematodes are amazingly skilled chemists: using simple building blocks from conserved primary metabolism and a strategy of modular assembly, C. elegans and other nematode species create complex molecular architectures to regulate their development and behaviour. These nematode-derived modular metabolites (NDMMs) are based on the dideoxysugars ascarylose or paratose, which serve as scaffolds for attachment of moieties from lipid, amino acid, carbohydrate, citrate, and nucleoside metabolism. Mutant screens and comparative metabolomics based on NMR spectroscopy and MS have so-far revealed several 100 different ascarylose (“ascarosides”) and a few paratose (“paratosides”) derivatives, many of which represent potent signalling molecules that can be active at femtomolar levels, regulating development, behaviour, body shape, and many other life history traits. NDMM biosynthesis appears to be carefully regulated as assembly of different modules proceeds with very high specificity. Preliminary biosynthetic studies have confirmed the primary metabolism origin of some NDMM building blocks, whereas the mechanisms that underlie their highly specific assembly are not understood. Considering their functions and biosynthetic origin, NDMMs represent a new class of natural products that cannot easily be classified as “primary” or “secondary”. We believe that the identification of new variants of primary metabolism-derived structures that serve important signalling functions in C. elegans and other nematodes provides a strong incentive for a comprehensive re-analysis of metabolism in higher animals, including humans. PMID:26059053

  5. Synthesis of New Water-Soluble Metal-Binding Polymers combinatorial Chemistry Approach

    SciTech Connect

    R. Bryan Miller

    2004-05-07

    (1) Synthesis of Fused Tetraheterocyclic Azepines: (2) Synthesis of Linear Bidentate Diisoxazole and Bidentate Isoxazole-Furyl/Thienyl/Pyridyl Motifs: (3) Synthesis of Pyrazolo[3,4-g] [2,1] dihydrobenzoisoxazol(in)es: (4) Synthesis of Spiro-Fused (C5)-Isozazoline-(C4)-Pyrazolones:

  6. Grafted macroporous polymer monolithic disks: a new format of scavengers for solution-phase combinatorial chemistry.

    PubMed

    Tripp, J A; Svec, F; Fréchet, J M

    2001-01-01

    Polyethylene encased porous poly(chloromethylstyrene-co-divinylbenzene) disks have been prepared by polymerization in a cylindrical glass mold and cut to a disk format. Following attachment of a free radical azo initiator 4,4'-azobis(4-cyanovaleric acid) to available functionalities at the surface of the pores, the polymerization of 2-vinyl-4,4-dimethylazlactone was initiated from the surface. To avoid an undesirable increase in flow resistance and to improve the yield of grafting, divinylbenzene was added to the polymerization mixture in order to form a layer of swellable reactive polymer gel within the pores. The use of these disks as scavenging filters to remove various amines from solutions in flow-through operations was demonstrated by effective removal of amines in a very short period of time from their solutions in a variety of solvents, even including alcohols and water.

  7. Evaluating the CALIOPE air quality modelling system: dynamics and chemistry over Europe and Iberian Peninsula for 2004 at high horizontal resolution

    NASA Astrophysics Data System (ADS)

    Piot, M.; Pay, M. T.; Jorba, O.; Baldasano, J. M.; Jiménez-Guerrero, P.; López, E.; Pérez, C.; Gassó, S.

    2009-04-01

    Often in Europe, population exposure to air pollution exceeds standards set by the EU and the World Health Organization (WHO). Urban/suburban areas are predominantly impacted upon, although exceedances of particulate matter (PM10 and PM2.5) and Ozone (O3) also take place in rural areas. In the frame of the CALIOPE project (Baldasano et al., 2008a), a high-resolution air quality forecasting system, WRF-ARW/HERMES/CMAQ/DREAM, has been developed and applied to the European domain (12km x 12km, 1hr) as well as to the Iberian Peninsula domain (4km x 4km, 1hr) to provide air quality forecasts for Spain (http://www.bsc.es/caliope/). The simulation of such high-resolution model system has been made possible by its implementation on the MareNostrum supercomputer. To reassure potential users and reduce uncertainties, the model system must be evaluated to assess its performances in terms of air quality levels and dynamics reproducibility. The present contribution describes a thorough quantitative evaluation study performed for a reference year (2004). The CALIOPE modelling system is configured with 38 vertical layers reaching up to 50 hPa for the meteorological core. Atmospheric initial and boundary conditions are obtained from the NCEP final analysis data. The vertical resolution of the CMAQ chemistry-transport model for gas-phase and aerosols has been increased from 8 to 15 layers in order to simulate vertical exchanges more accurately. Gas phase boundary conditions are provided by the LMDz-INCA2 global climate-chemistry model (see Hauglustaine et al., 2004). The DREAM model simulates long-range transport of mineral dust over the domains under study. For the European simulation, emissions are disaggregated from the EMEP expert emission inventory for 2004 to the utilized resolution using the criteria implemented in the HERMES emission model (Baldasano et al., 2008b). The HERMES model system, using a bottom-up approach, was adopted to estimate emissions for the Iberian

  8. Combinatorial Strategy to Identify Fluorescent Probes for Biothiol and Thiophenol Based on Diversified Pyrimidine Moieties and Their Biological Applications.

    PubMed

    Xie, Xilei; Li, Mengmeng; Tang, Fuyan; Li, Yong; Zhang, Leilei; Jiao, Xiaoyun; Wang, Xu; Tang, Bo

    2017-03-07

    We present a feasible paradigm of developing original fluorescent probes for target biomolecules via combinatorial chemistry. In this developmental program, pyrimidine moieties were investigated and optimized as unique recognition units for thiols for the first time through a parallel synthesis in combination with a rapid screening process. This time-efficient and cost-saving process effectively facilitated the developmental progress and provided detailed structure-reactivity relationships. As a result, Res-Biot and Flu-Pht were identified as optimal fluorescent probes for biothiol and thiophenol, respectively. Their favorable characteristics and superior applicability have been well demonstrated in both chemical and biological contexts. In particular, Res-Biot enables the direct visualization of biothiol fluctuations during oxidative stress and cell apoptosis, indicating its suitability in elucidation of a specific pathophysiological process in both living cells and living animals. Meanwhile, Flu-Pht is competent to visualize thiophenols without the interference from endogenous biothiols in living cells.

  9. Modelling non-equilibrium secondary organic aerosol formation and evaporation with the aerosol dynamics, gas- and particle-phase chemistry kinetic multilayer model ADCHAM

    NASA Astrophysics Data System (ADS)

    Roldin, P.; Eriksson, A. C.; Nordin, E. Z.; Hermansson, E.; Mogensen, D.; Rusanen, A.; Boy, M.; Swietlicki, E.; Svenningsson, B.; Zelenyuk, A.; Pagels, J.

    2014-08-01

    We have developed the novel Aerosol Dynamics, gas- and particle-phase chemistry model for laboratory CHAMber studies (ADCHAM). The model combines the detailed gas-phase Master Chemical Mechanism version 3.2 (MCMv3.2), an aerosol dynamics and particle-phase chemistry module (which considers acid-catalysed oligomerization, heterogeneous oxidation reactions in the particle phase and non-ideal interactions between organic compounds, water and inorganic ions) and a kinetic multilayer module for diffusion-limited transport of compounds between the gas phase, particle surface and particle bulk phase. In this article we describe and use ADCHAM to study (1) the evaporation of liquid dioctyl phthalate (DOP) particles, (2) the slow and almost particle-size-independent evaporation of α-pinene ozonolysis secondary organic aerosol (SOA) particles, (3) the mass-transfer-limited uptake of ammonia (NH3) and formation of organic salts between ammonium (NH4+) and carboxylic acids (RCOOH), and (4) the influence of chamber wall effects on the observed SOA formation in smog chambers. ADCHAM is able to capture the observed α-pinene SOA mass increase in the presence of NH3(g). Organic salts of ammonium and carboxylic acids predominantly form during the early stage of SOA formation. In the smog chamber experiments, these salts contribute substantially to the initial growth of the homogeneously nucleated particles. The model simulations of evaporating α-pinene SOA particles support the recent experimental findings that these particles have a semi-solid tar-like amorphous-phase state. ADCHAM is able to reproduce the main features of the observed slow evaporation rates if the concentration of low-volatility and viscous oligomerized SOA material at the particle surface increases upon evaporation. The evaporation rate is mainly governed by the reversible decomposition of oligomers back to monomers. Finally, we demonstrate that the mass-transfer-limited uptake of condensable organic compounds

  10. Chemistry Notes.

    ERIC Educational Resources Information Center

    School Science Review, 1980

    1980-01-01

    Presents 12 chemistry notes for British secondary school teachers. Some of these notes are: (1) a simple device for testing pH-meters; (2) portable fume cupboard safety screen; and (3) Mass spectroscopy-analysis of a mass peak. (HM)

  11. Chemistry Notes

    ERIC Educational Resources Information Center

    School Science Review, 1976

    1976-01-01

    Describes several chemistry projects, including solubility, formula for magnesium oxide, dissociation of dinitrogen tetroxide, use of 1-chloro-2, 4-dinitrobenzene, migration of ions, heats of neutralizations, use of pocket calculators, sonic cleaning, oxidation states of manganese, and cell potentials. Includes an extract from Chemical Age on…

  12. Chemistry Notes

    ERIC Educational Resources Information Center

    School Science Review, 1972

    1972-01-01

    Short articles on the alkylation of aniline, the preparation and properties of perbromate, using scrap copper in chemistry instruction, a safe method of burning hydrogen, and the use of an ion-charge model as an alternative to the mole concept in secondary school instruction. (AL)

  13. Confectionary Chemistry.

    ERIC Educational Resources Information Center

    Levine, Elise Hilf

    1996-01-01

    Presents activities and demonstrations that enable teachers to use various types of confections as tactile experiences to spark chemistry students' interest and generate enthusiasm for learning. Presents uses of candy in teaching about atomic structure, spontaneous nuclear decay, chemical formulas, fractoluminescence, the effect of a molecular…

  14. Chemistry Notes

    ERIC Educational Resources Information Center

    School Science Review, 1972

    1972-01-01

    Short articles on the kinetics of the hydrogen peroxide-iodide ion reaction, simulation of fluidization catalysis, the use of Newman projection diagrams to represent steric relationships in organic chemistry, the use of synthetic substrates for proteolytic enzyme reactions, and two simple clock reactions"--hydrolysis of halogenoalkanes and…

  15. Chemistry Notes.

    ERIC Educational Resources Information Center

    School Science Review, 1983

    1983-01-01

    Presents chemistry experiments, laboratory procedures, demonstrations, teaching suggestions, and classroom materials/activities. These include: game for teaching ionic formulas; method for balancing equations; description of useful redox series; computer programs (with listings) for water electrolysis simulation and for determining chemical…

  16. Chemistry Notes.

    ERIC Educational Resources Information Center

    School Science Review, 1983

    1983-01-01

    Presents chemistry experiments, laboratory procedures, demonstrations, and classroom materials/activities. These include: experiments on colloids, processing of uranium ore, action of heat on carbonates; color test for phenols and aromatic amines; solvent properties of non-electrolytes; stereoscopic applications/methods; a valency balance;…

  17. Chemistry Notes.

    ERIC Educational Resources Information Center

    School Science Review, 1982

    1982-01-01

    Presents procedures, experiments, demonstrations, teaching suggestions, and information on a variety of chemistry topics including, for example, inert gases, light-induced reactions, calculators, identification of substituted acetophenones, the elements, analysis of copper minerals, extraction of metallic strontium, equilibrium, halogens, and…

  18. Chemistry Notes.

    ERIC Educational Resources Information Center

    School Science Review, 1978

    1978-01-01

    Describes some laboratory apparatus, chemistry experiments and demonstrations, such as a Kofler block melting point apparatus, chromatographic investigation of the phosphoric acid, x-ray diffraction, the fountain experiment, endothermic sherbet, the measurement of viscosity, ionization energies and electronic configurations. (GA)

  19. Spring carbonate chemistry dynamics of surface waters in the northern East China Sea: Water mixing, biological uptake of CO2, and chemical buffering capacity

    NASA Astrophysics Data System (ADS)

    Zhai, Wei-Dong; Chen, Jian-Fang; Jin, Hai-Yan; Li, Hong-Liang; Liu, Jin-Wen; He, Xian-Qiang; Bai, Yan

    2014-09-01

    We investigated sea surface total alkalinity (TAlk), dissolved inorganic carbon (DIC), dissolved oxygen (DO), and satellite-derived chlorophyll-a in the connection between the Yellow Sea and the East China Sea (ECS) during April to early May 2007. In spring, Changjiang dilution water (CDW), ECS offshore water, and together with Yellow Sea water (YSW) occupied the northern ECS. Using 16 day composite satellite-derived chlorophyll-a images, several algal blooms were identified in the CDW and ECS offshore water. Correspondingly, biological DIC drawdown of 73 ± 20 μmol kg-1, oversaturated DO of 10-110 μmol O2 kg-1, and low fugacity of CO2 of 181-304 μatm were revealed in these two waters. YSW also showed CO2 uptake in spring, due to the very low temperature. However, its intrusion virtually counteracted CO2 uptake in the northern ECS. In the CDW and the ECS offshore water, Revelle factor was 9.3-11.7 and 8.9-10.6, respectively, while relatively high Revelle factor values of 11.4-13.0 were revealed in YSW. In the ECS offshore water, the observed relationship between DIC drawdown and oversaturated DO departed from the Redfield ratio, indicating an effect of chemical buffering capacity on the carbonate system during air-sea reequilibration. Given the fact that the chemical buffering capacity slows down the air-sea reequilibration of CO2, the early spring DIC drawdown may have durative effects on the sea surface carbonate system until early summer. Although our study is subject to limited temporal and spatial coverage of sampling, these insights are fundamental to understanding sea surface carbonate chemistry dynamics in this important ocean margin.

  20. First principles molecular dynamics studies of elastic constants, ideal tensile strength, chemistry of crack initiation, and surface and cohesive energies in amorphous silicon

    NASA Astrophysics Data System (ADS)

    Shodja, Hossein M.; Tabatabaei, Maryam; Esfarjani, Keivan

    2014-09-01

    First principles Kohn-Sham density functional theory (DFT)-based molecular dynamics (MD) is employed to investigate some physical and mechanical properties of amorphous Si (a-Si) samples, as-quenched and annealed containing dangling and floating bonds as well as distorted tetrahedral bonds. The total energy and true stress as functions of the engineering strain for a-Si samples subjected to uniaxial tensile stress as well as uniaxial extension are obtained. It is well-known that the electron density of the state of matters can be determined via ab initio DFT-based MD with high accuracy. Using this technique, such inherent properties as the elastic constants, ideal tensile strength, ultimate tensile strength, and surface and cohesive energies will be calculated. Since the employed ab initio MD, in contrast to the empirical potentials simulations, is capable of providing the evolution of the electronic charge distribution, we can afford to study the chemistry of crack initiation and reconstructed surfaces at final rupture. The calculated cohesive and surface energies are compared with the available theoretical and experimental results; Tyson's empirical relation and universal binding energy relations (UBERs) are also examined. The calculated elastic constants using the symmetry-general scheme satisfy well the isotropic relation ?. To date, the ab initio MD samples of a-Si generated from the completely melted scheme were all free of three-fold-coordinated Si. In contrast, as we will show, by implementing special thermal treatments, generation of all inherent structural defects is possible. Based on the electronic charge distribution, dative bonds and trigonal prisms for, respectively, floating and dangling bonds have been observed.

  1. Microscale Chemistry and Green Chemistry: Complementary Pedagogies

    NASA Astrophysics Data System (ADS)

    Singh, Mono M.; Szafran, Zvi; Pike, R. M.

    1999-12-01

    This paper describes the complementary nature of microscale chemistry and green chemistry. Green chemistry emphasizes the concepts of atom economy, source reduction, pathway modification, solvent substitution, and pollution prevention as means of improving the environmental impact of industrial chemistry. Microscale chemistry serves as a tool for incorporating green chemistry ideas across the curriculum in educational institutions. Examples are drawn from microscale laboratory experiments to illustrate the pedagogic connection between the two areas.

  2. Decoding Split and Pool Combinatorial Libraries with Electron Transfer Dissociation Tandem Mass Spectrometry

    PubMed Central

    Sarkar, Mohosin; Pascal, Bruce D.; Steckler, Caitlin; Aquino, Claudio; Micalizio, Glenn C.; Kodadek, Thomas; Chalmers, Michael J.

    2015-01-01

    Screening of bead-based split and pool combinatorial chemistry libraries is a powerful approach to aid the discovery of new chemical compounds able to interact with, and modulate the activities of, protein targets of interest. Split and pool synthesis provides for large and well diversified chemical libraries, in this case comprised of oligomers generated from a well-defined starting set. At the end of the synthesis, each bead in the library displays many copies of a unique oligomer sequence. Because the sequence of the oligomer is not known at the time of screening, methods for decoding of the sequence of each screening “hit” are essential. Here we describe an electron transfer dissociation (ETD) based tandem mass spectrometry approach for the decoding of mass-encoded split and pool libraries. We demonstrate that the newly described “chiral oligomers of pentenoic amides (COPAs)” yield non-sequence-specific product ions upon collisional activated dissociation; however, complete sequence information can be obtained with ETD. To aid in the decoding of libraries from MS and MS/MS data, we have incorporated 79Br/81Br isotope “tags” to differentiate N- and C-terminal product ions. In addition, we have created “Hit-Find,” a software program that allows users to generate libraries in silico. The user can then search all possible members of the chemical library for those that fall within a user-defined mass error. PMID:23636859

  3. Combinatorial development of biomaterials for clonal growth of human pluripotent stem cells

    NASA Astrophysics Data System (ADS)

    Mei, Ying; Saha, Krishanu; Bogatyrev, Said R.; Yang, Jing; Hook, Andrew L.; Kalcioglu, Z. Ilke; Cho, Seung-Woo; Mitalipova, Maisam; Pyzocha, Neena; Rojas, Fredrick; van Vliet, Krystyn J.; Davies, Martyn C.; Alexander, Morgan R.; Langer, Robert; Jaenisch, Rudolf; Anderson, Daniel G.

    2010-09-01

    Both human embryonic stem cells and induced pluripotent stem cells can self-renew indefinitely in culture; however, present methods to clonally grow them are inefficient and poorly defined for genetic manipulation and therapeutic purposes. Here we develop the first chemically defined, xeno-free, feeder-free synthetic substrates to support robust self-renewal of fully dissociated human embryonic stem and induced pluripotent stem cells. Material properties including wettability, surface topography, surface chemistry and indentation elastic modulus of all polymeric substrates were quantified using high-throughput methods to develop structure-function relationships between material properties and biological performance. These analyses show that optimal human embryonic stem cell substrates are generated from monomers with high acrylate content, have a moderate wettability and employ integrin αvβ3 and αvβ5 engagement with adsorbed vitronectin to promote colony formation. The structure-function methodology employed herein provides a general framework for the combinatorial development of synthetic substrates for stem cell culture.

  4. Analytical reduction of combinatorial complexity arising from multiple protein modification sites

    PubMed Central

    Birtwistle, Marc R.

    2015-01-01

    Combinatorial complexity is a major obstacle to ordinary differential equation (ODE) modelling of biochemical networks. For example, a protein with 10 sites that can each be unphosphorylated, phosphorylated or bound to adaptor protein requires 310 ODEs. This problem is often dealt with by making ad hoc assumptions which have unclear validity and disallow modelling of site-specific dynamics. Such site-specific dynamics, however, are important in many biological systems. We show here that for a common biological situation where adaptors bind modified sites, binding is slow relative to modification/demodification, and binding to one modified site hinders binding to other sites, for a protein with n modification sites and m adaptor proteins the number of ODEs needed to simulate the site-specific dynamics of biologically relevant, lumped bound adaptor states is independent of the number of modification sites and equal to m + 1, giving a significant reduction in system size. These considerations can be relaxed considerably while retaining reasonably accurate descriptions of the true system dynamics. We apply the theory to model, using only 11 ODEs, the dynamics of ligand-induced phosphorylation of nine tyrosines on epidermal growth factor receptor (EGFR) and primary recruitment of six signalling proteins (Grb2, PI3K, PLCγ1, SHP2, RasA1 and Shc1). The model quantitatively accounts for experimentally determined site-specific phosphorylation and dephosphorylation rates, differential affinities of binding proteins for the phosphorylated sites and binding protein expression levels. Analysis suggests that local concentration of site-specific phosphatases such as SHP2 in membrane subdomains by a factor of approximately 107 is critical for effective site-specific regulation. We further show how our framework can be extended with minimal effort to consider binding cooperativity between Grb2 and c-Cbl, which is important for receptor trafficking. Our theory has potentially broad

  5. Time-dependent combinatory effects of active mechanical loading and passive topographical cues on cell orientation.

    PubMed

    Wang, Qian; Huang, Hanyang; Wei, Kang; Zhao, Yi

    2016-10-01

    Mechanical stretching and topographical cues are both effective mechanical stimulations for regulating cell morphology, orientation, and behaviors. The competition of these two mechanical stimulations remains largely underexplored. Previous studies have suggested that a small cyclic mechanical strain is not able to reorient cells that have been pre-aligned by relatively large linear microstructures, but can reorient those pre-aligned by small linear micro/nanostructures if the characteristic dimension of these structures is below a certain threshold. Likewise, for micro/nanostructures with a given characteristic dimension, the strain must exceed a certain magnitude to overrule the topographic cues. There are however no in-depth investigations of such "thresholds" due to the lack of close examination of dynamic cell orientation during and shortly after the mechanical loading. In this study, the time-dependent combinatory effects of active and passive mechanical stimulations on cell orientation are investigated by developing a micromechanical stimulator. The results show that the cells pre-aligned by linear micro/nanostructures can be altered by cyclic in-plane strain, regardless of the structure size. During the loading, the micro/nanostructures can resist the reorientation effects by cyclic in-plane strain while the resistive capability (measured by the mean orientation angle change and the reorientation speed) increases with the increasing characteristic dimension. The micro/nanostructures also can recover the cell orientation after the cessation of cyclic in-plane strain, while the recovering capability increases with the characteristic dimension. The previously observed thresholds are largely dependent on the observation time points. In order to accurately evaluate the combinatory effects of the two mechanical stimulations, observations during the active loading with a short time interval or endpoint observations shortly after the loading are preferred. This

  6. Super and Combinatorial Harmonic Response of Flexible Elastic Cables with Small Sag

    NASA Astrophysics Data System (ADS)

    Nielsen, S. R. K.; Kirkegaard, P. H.

    2002-03-01

    The paper deals with the analysis of cables in stayed bridges and TV-towers, where the excitation is caused by harmonically varying in-plane motions of the upper support point with the amplitude U. Such cables are characterized by a sag-to-chord-length ratio below 0.02", which means that the lowest circular eigenfrequencies for in-plane and out-of-plane eigenvibrations, ω1and ω2, are closely separated. The dynamic analysis is performed by a two-degree-of-freedom modal decomposition in the lowest in-plane and out-of-plane eigenmodes. Modal parameters are evaluated based on the eigenmodes for the parabolic approximation to the equilibrium suspension. Superharmonic components of the ordern , supported by the parametric terms of the excitation and the non-linear coupling terms, are registered in the response for circular frequency ω≃ω1/n. At moderate U, the cable response takes place entirely in the static equilibrium plane. At larger amplitudes the in-plane response becomes unstable and a coupled whirling superharmonic component occurs. In the paper a first order perturbation solution to the superharmonic response is performed based on the averaging method. For ω≃(m/n)ω1, mcombinatorial harmonic component with the circular frequency (n/m)ω. Both entirely in-plane and coupled in-plane and out-of-plane responses occur. Based on an initial frequency analysis of the response, an analytical model for these vibrations is formulated with emphasis on superharmonics of the order n=3 and combinatorial harmonics of the order (n, m)=(3,2). All analytical solutions have been verified by direct numerical integration of the modal equations of motion.

  7. Identifying combinatorial regulation of transcription factors and binding motifs

    PubMed Central

    Kato, Mamoru; Hata, Naoya; Banerjee, Nilanjana; Futcher, Bruce; Zhang, Michael Q

    2004-01-01

    Background Combinatorial interaction of transcription factors (TFs) is important for gene regulation. Although various genomic datasets are relevant to this issue, each dataset provides relatively weak evidence on its own. Developing methods that can integrate different sequence, expression and localization data have become important. Results Here we use a novel method that integrates chromatin immunoprecipitation (ChIP) data with microarray expression data and with combinatorial TF-motif analysis. We systematically identify combinations of transcription factors and of motifs. The various combinations of TFs involved multiple binding mechanisms. We reconstruct a new combinatorial regulatory map of the yeast cell cycle in which cell-cycle regulation can be drawn as a chain of extended TF modules. We find that the pairwise combination of a TF for an early cell-cycle phase and a TF for a later phase is often used to control gene expression at intermediate times. Thus the number of distinct times of gene expression is greater than the number of transcription factors. We also see that some TF modules control branch points (cell-cycle entry and exit), and in the presence of appropriate signals they can allow progress along alternative pathways. Conclusions Combining different data sources can increase statistical power as demonstrated by detecting TF interactions and composite TF-binding motifs. The original picture of a chain of simple cell-cycle regulators can be extended to a chain of composite regulatory modules: different modules may share a common TF component in the same pathway or a TF component cross-talking to other pathways. PMID:15287978

  8. Combinatorial Hopf Algebras in Quantum Field Theory I

    NASA Astrophysics Data System (ADS)

    Figueroa, Héctor; Gracia-Bondía, José M.

    This paper stands at the interface between combinatorial Hopf algebra theory and renormalization theory. Its plan is as follows: Sec. 1.1 is the introduction, and contains an elementary invitation to the subject as well. The rest of Sec. 1 is devoted to the basics of Hopf algebra theory and examples in ascending level of complexity. Section 2 turns around the all-important Faà di Bruno Hopf algebra. Section 2.1 contains a first, direct approach to it. Section 2.2 gives applications of the Faà di Bruno algebra to quantum field theory and Lagrange reversion. Section 2.3 rederives the related Connes-Moscovici algebras. In Sec. 3, we turn to the Connes-Kreimer Hopf algebras of Feynman graphs and, more generally, to incidence bialgebras. In Sec. 3.1, we describe the first. Then in Sec. 3.2, we give a simple derivation of (the properly combinatorial part of) Zimmermann's cancellation-free method, in its original diagrammatic form. In Sec. 3.3, general incidence algebras are introduced, and the Faà di Bruno bialgebras are described as incidence bialgebras. In Sec. 3.4, deeper lore on Rota's incidence algebras allows us to reinterpret Connes-Kreimer algebras in terms of distributive lattices. Next, the general algebraic-combinatorial proof of the cancellation-free formula for antipodes is ascertained. The structure results for commutative Hopf algebras are found in Sec. 4. An outlook section very briefly reviews the coalgebraic aspects of quantization and the Rota-Baxter map in renormalization.

  9. Combinatorial Gene Regulatory Functions Underlie Ultraconserved Elements in Drosophila.

    PubMed

    Warnefors, Maria; Hartmann, Britta; Thomsen, Stefan; Alonso, Claudio R

    2016-09-01

    Ultraconserved elements (UCEs) are discrete genomic elements conserved across large evolutionary distances. Although UCEs have been linked to multiple facets of mammalian gene regulation their extreme evolutionary conservation remains largely unexplained. Here, we apply a computational approach to investigate this question in Drosophila, exploring the molecular functions of more than 1,500 UCEs shared across the genomes of 12 Drosophila species. Our data indicate that Drosophila UCEs are hubs for gene regulatory functions and suggest that UCE sequence invariance originates from their combinatorial roles in gene control. We also note that the gene regulatory roles of intronic and intergenic UCEs (iUCEs) are distinct from those found in exonic UCEs (eUCEs). In iUCEs, transcription factor (TF) and epigenetic factor binding data strongly support iUCE roles in transcriptional and epigenetic regulation. In contrast, analyses of eUCEs indicate that they are two orders of magnitude more likely than the expected to simultaneously include protein-coding sequence, TF-binding sites, splice sites, and RNA editing sites but have reduced roles in transcriptional or epigenetic regulation. Furthermore, we use a Drosophila cell culture system and transgenic Drosophila embryos to validate the notion of UCE combinatorial regulatory roles using an eUCE within the Hox gene Ultrabithorax and show that its protein-coding region also contains alternative splicing regulatory information. Taken together our experiments indicate that UCEs emerge as a result of combinatorial gene regulatory roles and highlight common features in mammalian and insect UCEs implying that similar processes might underlie ultraconservation in diverse animal taxa.

  10. Combinatorial Gene Regulatory Functions Underlie Ultraconserved Elements in Drosophila

    PubMed Central

    Warnefors, Maria; Hartmann, Britta; Thomsen, Stefan; Alonso, Claudio R.

    2016-01-01

    Ultraconserved elements (UCEs) are discrete genomic elements conserved across large evolutionary distances. Although UCEs have been linked to multiple facets of mammalian gene regulation their extreme evolutionary conservation remains largely unexplained. Here, we apply a computational approach to investigate this question in Drosophila, exploring the molecular functions of more than 1,500 UCEs shared across the genomes of 12 Drosophila species. Our data indicate that Drosophila UCEs are hubs for gene regulatory functions and suggest that UCE sequence invariance originates from their combinatorial roles in gene control. We also note that the gene regulatory roles of intronic and intergenic UCEs (iUCEs) are distinct from those found in exonic UCEs (eUCEs). In iUCEs, transcription factor (TF) and epigenetic factor binding data strongly support iUCE roles in transcriptional and epigenetic regulation. In contrast, analyses of eUCEs indicate that they are two orders of magnitude more likely than the expected to simultaneously include protein-coding sequence, TF-binding sites, splice sites, and RNA editing sites but have reduced roles in transcriptional or epigenetic regulation. Furthermore, we use a Drosophila cell culture system and transgenic Drosophila embryos to validate the notion of UCE combinatorial regulatory roles using an eUCE within the Hox gene Ultrabithorax and show that its protein-coding region also contains alternative splicing regulatory information. Taken together our experiments indicate that UCEs emerge as a result of combinatorial gene regulatory roles and highlight common features in mammalian and insect UCEs implying that similar processes might underlie ultraconservation in diverse animal taxa. PMID:27247329

  11. Customized optimization of metabolic pathways by combinatorial transcriptional engineering.

    PubMed

    Yuan, Yongbo; Du, Jing; Zhao, Huimin

    2013-01-01

    Introduction of a heterologous metabolic pathway into a platform microorganism for applications in metabolic engineering and synthetic biology is often technically straightforward. However, the major challenge is to balance the flux in the pathway to obtain high yield and productivity in a target microorganism. To address this limitation, we recently developed a simple, efficient, and programmable approach named "customized optimization of metabolic pathways by combinatorial transcriptional engineering" (COMPACTER) for balancing the flux in a pathway under distinct metabolic backgrounds. Here we use two examples including a cellobiose-utilizing pathway and a xylose-utilizing pathway to illustrate the key steps in the COMPACTER method.

  12. What Diagrams Argue in Late Imperial Chinese Combinatorial Texts.

    PubMed

    Bréard, Andrea

    2015-01-01

    Attitudes towards diagrammatic reasoning and visualization in mathematics were seldom spelled out in texts from pre-modern China, although illustrations figure prominently in mathematical literature since the eleventh century. Taking the sums of finite series and their combinatorial interpretation as a case study, this article investigates the epistemological function of illustrations from the eleventh to the nineteenth century that encode either the mathematical objects themselves or represent their related algorithms. It particularly focuses on the two illustrations given in Wang Lai's (1768-1813) Mathematical Principles of Sequential Combinations, arguing that they reflect a specific mode of nineteenth-century mathematical argumentative practice and served as a heuristic model for later authors.

  13. In situ etch rate measurements of thin film combinatorial libraries

    SciTech Connect

    Perkins, J. D.; van Hest, M. F. A. M.; Teplin, C. W.; Dabney, M. S.; Ginley, D. S.

    2007-11-01

    We demonstrate the use of optical reflection mapping as an in situ characterization tool to evaluate the corrosion rate of compositionally graded thin film combinatorial libraries coated with a commercial glass etching paste. A multi-channel fiber-optically coupled CCD-array-based spectrometer was used to collect a series of reflectance maps from 300 to 1000 nm versus time. The thin film interference oscillations in the measured reflection spectra have been fitted to determine the film thickness as a function of time and thereby the etch rate. Application of this technique to an In–Mo–O composition spread library is presented as an example.

  14. Discovery of methanol electro-oxidation catalysts by combinatorial analysis

    SciTech Connect

    Mallouk, T.E.; Reddington, E.; Pu, C.

    1996-12-31

    Hydrogen fuel cells are likely to become a major energy source in the next century, but they are not ideal for all applications. A safe alternative fuel with a high energy density will be necessary for transportation and mobile applications. Direct methanol-air fuel cells (DMFCs) are an attractive alternative to hydrogen fuel cells because of the high energy density and low cost of methanol as a fuel. However, in order for DMFCs to become commercially viable, better electrocatalysts for the anode reaction need to be developed. This paper describes a combinatorial technique for generating an array of electrodes with varying metal compositions.

  15. Distributed Combinatorial Optimization Using Privacy on Mobile Phones

    NASA Astrophysics Data System (ADS)

    Ono, Satoshi; Katayama, Kimihiro; Nakayama, Shigeru

    This paper proposes a method for distributed combinatorial optimization which uses mobile phones as computers. In the proposed method, an ordinary computer generates solution candidates and mobile phones evaluates them by referring privacy — private information and preferences. Users therefore does not have to send their privacy to any other computers and does not have to refrain from inputting their preferences. They therefore can obtain satisfactory solution. Experimental results have showed the proposed method solved room assignment problems without sending users' privacy to a server.

  16. Common Gamma Chain Cytokines in Combinatorial Immune Strategies against Cancer

    PubMed Central

    Pulliam, Stephanie R.; Uzhachenko, Roman V.; Adunyah, Samuel E.; Shanker, Anil

    2015-01-01

    Common γ chain (γC) cytokines, namely IL-2, IL-4, IL-7, IL-9, IL-15, and IL-21 are important for the proliferation, differentiation, and survival of lymphocytes that display antitumor activity, thus stimulating considerable interest for the use of cytokines in cancer immunotherapy. In this review, we will focus on the γC cytokines that demonstrate the greatest potential for immunotherapy, IL-2, IL-7, IL-15, and IL-21. We will briefly cover their biological function, potential applications in cancer therapy, and update on their use in combinatorial immune strategies for eradicating tumors and hematopoietic malignancies. PMID:26597610

  17. Multifunctional combinatorial-designed nanoparticles for nucleic acid therapy

    NASA Astrophysics Data System (ADS)

    Amiji, Mansoor M.

    2016-05-01

    Recent advances in biomedical sciences, especially in the field of human genetics, is increasingly considered to facilitate a new frontier in development of novel disease-modifying therapeutics. One of major challenges in the development of nucleic acid therapeutics is efficient and specific delivery of the molecules to the target tissue and cell upon systemic administration. In this report, I discuss our strategy to develop combinatorial-designed multifunctional nanoparticle assemblies based on natural biocompatible and biodegradable polymers for nucleic acid delivery in: (1) overcoming tumor drug resistance and (2) genetic modulation of macrophage functional phenotype from M1 to M2 in treatment of inflammatory diseases.

  18. Polynitrogen Chemistry

    DTIC Science & Technology

    2013-09-24

    4N3, while As(C6H5)4N3 presents a borderline case.23 Theoretical Calculations High-level theoretical studies of nitrogen, oxygen, selenium and...Dixon, D. A.; Christe, K. O., "Thermochemical Properties of Selenium Fluorides, Oxides, and Oxofluorides," Inorganic Chemistry, p. 2472, vol. 51, (2012...34Thermochemical Properties of Selenium Fluorides, Oxides, and Oxofluorides," Inorg. Chem., p. 2472, vol. 51, (2012). 26. K. S. Thanthiriwatte, M. Vasiliu

  19. Molecular Dynamics and Theoretical Chemistry

    DTIC Science & Technology

    2013-03-08

    and structural stability compared to H-Si(111) • Air- and electrochemical-stability enables advanced sensors, fuel and solar cells , etc. • Probes...Diagnostics ARO – plasmonics AFOSR - Endo fuels, combustion, solar PNNL – Institute for Integrated Catalysis Navy, DTRA – Clusters AFRL, NASA, DoD...Propellants • Real-time probing of reactions • Hybrid Chemical Lasers • Sensors for Trace Detection Distribution A: Approved for public release

  20. Computational chemistry

    NASA Technical Reports Server (NTRS)

    Arnold, J. O.

    1987-01-01

    With the advent of supercomputers, modern computational chemistry algorithms and codes, a powerful tool was created to help fill NASA's continuing need for information on the properties of matter in hostile or unusual environments. Computational resources provided under the National Aerodynamics Simulator (NAS) program were a cornerstone for recent advancements in this field. Properties of gases, materials, and their interactions can be determined from solutions of the governing equations. In the case of gases, for example, radiative transition probabilites per particle, bond-dissociation energies, and rates of simple chemical reactions can be determined computationally as reliably as from experiment. The data are proving to be quite valuable in providing inputs to real-gas flow simulation codes used to compute aerothermodynamic loads on NASA's aeroassist orbital transfer vehicles and a host of problems related to the National Aerospace Plane Program. Although more approximate, similar solutions can be obtained for ensembles of atoms simulating small particles of materials with and without the presence of gases. Computational chemistry has application in studying catalysis, properties of polymers, all of interest to various NASA missions, including those previously mentioned. In addition to discussing these applications of computational chemistry within NASA, the governing equations and the need for supercomputers for their solution is outlined.

  1. LOGICAL REASONING ABILITY AND STUDENT PERFORMANCE IN GENERAL CHEMISTRY

    PubMed Central

    Bird, Lillian

    2010-01-01

    Logical reasoning skills of students enrolled in General Chemistry at the University of Puerto Rico in Río Piedras were measured using the Group Assessment of Logical Thinking (GALT) test. The results were used to determine the students’ cognitive level (concrete, transitional, formal) as well as their level of performance by logical reasoning mode (mass/volume conservation, proportional reasoning, correlational reasoning, experimental variable control, probabilistic reasoning and combinatorial reasoning). This information was used to identify particular deficiencies and gender effects, and to determine which logical reasoning modes were the best predictors of student performance in the general chemistry course. Statistical tests to analyze the relation between (a) operational level and final grade in both semesters of the course; (b) GALT test results and performance in the ACS General Chemistry Examination; and (c) operational level and student approach (algorithmic or conceptual) towards a test question that may be answered correctly using either strategy, were also performed. PMID:21373364

  2. LOGICAL REASONING ABILITY AND STUDENT PERFORMANCE IN GENERAL CHEMISTRY.

    PubMed

    Bird, Lillian

    2010-03-01

    Logical reasoning skills of students enrolled in General Chemistry at the University of Puerto Rico in Río Piedras were measured using the Group Assessment of Logical Thinking (GALT) test. The results were used to determine the students' cognitive level (concrete, transitional, formal) as well as their level of performance by logical reasoning mode (mass/volume conservation, proportional reasoning, correlational reasoning, experimental variable control, probabilistic reasoning and combinatorial reasoning). This information was used to identify particular deficiencies and gender effects, and to determine which logical reasoning modes were the best predictors of student performance in the general chemistry course. Statistical tests to analyze the relation between (a) operational level and final grade in both semesters of the course; (b) GALT test results and performance in the ACS General Chemistry Examination; and (c) operational level and student approach (algorithmic or conceptual) towards a test question that may be answered correctly using either strategy, were also performed.

  3. Understanding the combinatorial action of transcription factors and microRNA regulation from regions of open chromatin.

    PubMed

    Zheng, Guantao; Zhang, Pan; Wu, Zhihong; Dong, Dong

    2016-02-01

    Transcriptional regulatory cascades are always triggered through the combinatorial interplay between transcription factors (TFs) and microRNAs (miRNAs) in eukaryotes. However, it is still a very substantial undertaking to dynamically profile their coordinated actions. In this work, we compared the differences in TFBS numbers between miRNA targets and non-targets, and found that miRNA targets tend to have more TFBS numbers. With the attempt to comprehensively understand the combinatorial action of TF and miRNA regulation from regions of open chromatin, we retrieved recently published DNase I hypersensitive sites (DHSs) across different human cell lines. The result showed that the differences are more statistically significant in DHS regions than non-DHS regions. Next, we trained classifiers for miRNA targets and non-targets. The result showed that TFBSs located in DHS regions achieved a competitive performance when discriminating miRNA targets and non-targets, whereas the performance of classifiers using TFBSs located in non-DHS regions is close to that of a random classifier. After the DHSs were divided into intergenic, transcription start sites (TSSs) and gene body DHS regions based on their genomic locations, only TFBSs located in TSS DHS regions provided a competitive performance. Our results provide us a clue that the coordinated activity of miRNAs and TFs describing the mechanism of gene expression control should be examined in a dynamic perspective.

  4. To Think without Thinking: The Implications of Combinatory Play and the Creative Process for Neuroaesthetics

    ERIC Educational Resources Information Center

    Stevens, Victoria

    2014-01-01

    The author considers combinatory play as an intersection between creativity, play, and neuroaesthetics. She discusses combinatory play as vital to the creative process in art and science, particularly with regard to the incubation of new ideas. She reviews findings from current neurobiological research and outlines the way that the brain activates…

  5. A barcode-free combinatorial screening platform for matrix metalloproteinase screening.

    PubMed

    Rane, Tushar D; Zec, Helena C; Wang, Tza-Huei

    2015-02-03

    Application of droplet microfluidics to combinatorial screening applications remains elusive because of the need for composition-identifying unique barcodes. Here we propose a barcode-free continuous flow droplet microfluidic platform to suit the requirements of combinatorial screening applications. We demonstrate robust and repeatable functioning of this platform with matrix metalloproteinase activity screening as a sample application.

  6. Unbiased Combinatorial Genomic Approaches to Identify Alternative Therapeutic Targets within the TSC Signaling Network

    DTIC Science & Technology

    2015-09-01

    human cells, as their depletion selectively decreases the viability of TSC2 null cells. These candidates are now strong drug candidates for TSC. 15...SUBJECT TERMS Drosophila, TSC, Drug Targets, Combinatorial Screen, Cancer 16. SECURITY CLASSIFICATION OF: 17. LIMITATION OF ABSTRACT 18. NUMBER OF...Drosophila model before determining which interactions were conserved using mammalian cell culture. 2. KEYWORDS: Drosophila, TSC, Drug Targets, Combinatorial

  7. A Barcode-Free Combinatorial Screening Platform for Matrix Metalloproteinase Screening

    PubMed Central

    2015-01-01

    Application of droplet microfluidics to combinatorial screening applications remains elusive because of the need for composition-identifying unique barcodes. Here we propose a barcode-free continuous flow droplet microfluidic platform to suit the requirements of combinatorial screening applications. We demonstrate robust and repeatable functioning of this platform with matrix metalloproteinase activity screening as a sample application. PMID:25543856

  8. Combinatorial metabolic engineering of Saccharomyces cerevisiae for terminal alkene production.

    PubMed

    Chen, Binbin; Lee, Dong-Yup; Chang, Matthew Wook

    2015-09-01

    Biological production of terminal alkenes has garnered a significant interest due to their industrial applications such as lubricants, detergents and fuels. Here, we engineered the yeast Saccharomyces cerevisiae to produce terminal alkenes via a one-step fatty acid decarboxylation pathway and improved the alkene production using combinatorial engineering strategies. In brief, we first characterized eight fatty acid decarboxylases to enable and enhance alkene production. We then increased the production titer 7-fold by improving the availability of the precursor fatty acids. We additionally increased the titer about 5-fold through genetic cofactor engineering and gene expression tuning in rich medium. Lastly, we further improved the titer 1.8-fold to 3.7 mg/L by optimizing the culturing conditions in bioreactors. This study represents the first report of terminal alkene biosynthesis in S. cerevisiae, and the abovementioned combinatorial engineering approaches collectively increased the titer 67.4-fold. We envision that these approaches could provide insights into devising engineering strategies to improve the production of fatty acid-derived biochemicals in S. cerevisiae.

  9. A combinatorial approach to the design of vaccines.

    PubMed

    Martínez, Luis; Milanič, Martin; Legarreta, Leire; Medvedev, Paul; Malaina, Iker; de la Fuente, Ildefonso M

    2015-05-01

    We present two new problems of combinatorial optimization and discuss their applications to the computational design of vaccines. In the shortest λ-superstring problem, given a family S1,...,S(k) of strings over a finite alphabet, a set Τ of "target" strings over that alphabet, and an integer λ, the task is to find a string of minimum length containing, for each i, at least λ target strings as substrings of S(i). In the shortest λ-cover superstring problem, given a collection X1,...,X(n) of finite sets of strings over a finite alphabet and an integer λ, the task is to find a string of minimum length containing, for each i, at least λ elements of X(i) as substrings. The two problems are polynomially equivalent, and the shortest λ-cover superstring problem is a common generalization of two well known combinatorial optimization problems, the shortest common superstring problem and the set cover problem. We present two approaches to obtain exact or approximate solutions to the shortest λ-superstring and λ-cover superstring problems: one based on integer programming, and a hill-climbing algorithm. An application is given to the computational design of vaccines and the algorithms are applied to experimental data taken from patients infected by H5N1 and HIV-1.

  10. Novel Heterotypic Rox Sites for Combinatorial Dre Recombination Strategies.

    PubMed

    Chuang, Katherine; Nguyen, Eileen; Sergeev, Yuri; Badea, Tudor C

    2015-12-29

    Site-specific recombinases (SSRs) such as Cre are widely used in gene targeting and genetic approaches for cell labeling and manipulation. They mediate DNA strand exchange between two DNA molecules at dedicated recognition sites. Precise understanding of the Cre recombination mechanism, including the role of individual base pairs in its loxP target site, guided the generation of mutant lox sites that specifically recombine with themselves but not with the wild type loxP. This has led to the development of a variety of combinatorial Cre-dependent genetic strategies, such as multicolor reporters, irreversible inversions, or recombination-mediated cassette exchange. Dre, a Cre-related phage integrase that recognizes roxP sites, does not cross-react with the Cre-loxP system, but has similar recombination efficiency. We have previously described intersectional genetic strategies combining Dre and Cre. We now report a mutagenesis screen aimed at identifying roxP base pairs critical for self-recognition. We describe several rox variant sites that are incompatible with roxP, but are able to efficiently recombine with themselves in either purified systems or bacterial and eukaryotic tissue culture systems. These newly identified rox sites are not recognized by Cre, thus enabling potential combinatorial strategies involving Cre, Dre, and target loci including multiple loxP and roxP variants.

  11. Combinatorial Strategies for the Development of Bulk Metallic Glasses

    NASA Astrophysics Data System (ADS)

    Ding, Shiyan

    The systematic identification of multi-component alloys out of the vast composition space is still a daunting task, especially in the development of bulk metallic glasses that are typically based on three or more elements. In order to address this challenge, combinatorial approaches have been proposed. However, previous attempts have not successfully coupled the synthesis of combinatorial libraries with high-throughput characterization methods. The goal of my dissertation is to develop efficient high-throughput characterization methods, optimized to identify glass formers systematically. Here, two innovative approaches have been invented. One is to measure the nucleation temperature in parallel for up-to 800 compositions. The composition with the lowest nucleation temperature has a reasonable agreement with the best-known glass forming composition. In addition, the thermoplastic formability of a metallic glass forming system is determined through blow molding a compositional library. Our results reveal that the composition with the largest thermoplastic deformation correlates well with the best-known formability composition. I have demonstrated both methods as powerful tools to develop new bulk metallic glasses.

  12. Novel Heterotypic Rox Sites for Combinatorial Dre Recombination Strategies

    PubMed Central

    Chuang, Katherine; Nguyen, Eileen; Sergeev, Yuri; Badea, Tudor C.

    2015-01-01

    Site-specific recombinases (SSRs) such as Cre are widely used in gene targeting and genetic approaches for cell labeling and manipulation. They mediate DNA strand exchange between two DNA molecules at dedicated recognition sites. Precise understanding of the Cre recombination mechanism, including the role of individual base pairs in its loxP target site, guided the generation of mutant lox sites that specifically recombine with themselves but not with the wild type loxP. This has led to the development of a variety of combinatorial Cre-dependent genetic strategies, such as multicolor reporters, irreversible inversions, or recombination-mediated cassette exchange. Dre, a Cre-related phage integrase that recognizes roxP sites, does not cross-react with the Cre-loxP system, but has similar recombination efficiency. We have previously described intersectional genetic strategies combining Dre and Cre. We now report a mutagenesis screen aimed at identifying roxP base pairs critical for self-recognition. We describe several rox variant sites that are incompatible with roxP, but are able to efficiently recombine with themselves in either purified systems or bacterial and eukaryotic tissue culture systems. These newly identified rox sites are not recognized by Cre, thus enabling potential combinatorial strategies involving Cre, Dre, and target loci including multiple loxP and roxP variants. PMID:26715092

  13. (Pesticide chemistry)

    SciTech Connect

    Barnthouse, L.W.

    1990-09-04

    This report summarizes a trip by L. W. Barnthouse of the Environmental Sciences Division (ESD), Oak Ridge National Laboratory (ORNL), to Hamburg, Federal Republic of Germany (FRG), where he participated in the 7th International Congress of Pesticide Chemistry. He chaired a workshop on experimental systems for determining effects of pesticides on nontarget organisms and gave an oral presentation at a symposium on pesticide risk assessment. Before returning to the United States, Dr. Barnthouse visited the Netherlands Institute for Sea Research in Texel, the Netherlands.

  14. Eighteenth annual West Coast theoretical chemistry conference

    SciTech Connect

    1997-05-01

    Abstracts are presented from the eighteenth annual west coast theoretical chemistry conference. Topics include molecular simulations; quasiclassical simulations of reactions; photodissociation reactions; molecular dynamics;interface studies; electronic structure; and semiclassical methods of reactive systems.

  15. Development of Combinatorial Methods for Alloy Design and Optimization

    SciTech Connect

    Pharr, George M.; George, Easo P.; Santella, Michael L

    2005-07-01

    The primary goal of this research was to develop a comprehensive methodology for designing and optimizing metallic alloys by combinatorial principles. Because conventional techniques for alloy preparation are unavoidably restrictive in the range of alloy composition that can be examined, combinatorial methods promise to significantly reduce the time, energy, and expense needed for alloy design. Combinatorial methods can be developed not only to optimize existing alloys, but to explore and develop new ones as well. The scientific approach involved fabricating an alloy specimen with a continuous distribution of binary and ternary alloy compositions across its surface--an ''alloy library''--and then using spatially resolved probing techniques to characterize its structure, composition, and relevant properties. The three specific objectives of the project were: (1) to devise means by which simple test specimens with a library of alloy compositions spanning the range interest can be produced; (2) to assess how well the properties of the combinatorial specimen reproduce those of the conventionally processed alloys; and (3) to devise screening tools which can be used to rapidly assess the important properties of the alloys. As proof of principle, the methodology was applied to the Fe-Ni-Cr ternary alloy system that constitutes many commercially important materials such as stainless steels and the H-series and C-series heat and corrosion resistant casting alloys. Three different techniques were developed for making alloy libraries: (1) vapor deposition of discrete thin films on an appropriate substrate and then alloying them together by solid-state diffusion; (2) co-deposition of the alloying elements from three separate magnetron sputtering sources onto an inert substrate; and (3) localized melting of thin films with a focused electron-beam welding system. Each of the techniques was found to have its own advantages and disadvantages. A new and very powerful technique for

  16. Physical chemistry and the environment

    SciTech Connect

    Dunning, T.H. Jr.; Garrett, B.C.; Kolb, C.E. Jr.; Shaw, R.W.; Choppin, G.R.; Wagner, A.F.

    1994-08-01

    From the ozone hole and the greenhouse effect to plastics recycling and hazardous waste disposal, society faces a number of issues, the solutions to which require an unprecedented understanding of the properties of molecules. We are coming to realize that the environment is a coupled set of chemical systems, its dynamics determining the welfare of the biosphere and of humans in particular. These chemical systems are governed by fundamental molecular interactions, and they present chemists with an unparalleled challenge. The application of current concepts of molecular behavior and of up-to-date experimental and computational techniques can provide us with insights into the environment that are needed to mitigate past damage, to anticipate the impact of current human activity, and to avoid future insults to the environment. Environmental chemistry encompasses a number of separate, yet interlocking, areas of research. In all of these areas progress is limited by an inadequate understanding of the underlying chemical processes involved. Participation of all chemical approaches -- experimental, theoretical and computational -- and of all disciplines of chemistry -- organic, inorganic, physical, analytical and biochemistry -- will be required to provide the necessary fundamental understanding. The Symposium on ``Physical Chemistry and the Environment`` was designed to bring the many exciting and challenging physical chemistry problems involved in environmental chemistry to the attention of a larger segment of the physical chemistry community.

  17. Rationally reduced libraries for combinatorial pathway optimization minimizing experimental effort

    PubMed Central

    Jeschek, Markus; Gerngross, Daniel; Panke, Sven

    2016-01-01

    Rational flux design in metabolic engineering approaches remains difficult since important pathway information is frequently not available. Therefore empirical methods are applied that randomly change absolute and relative pathway enzyme levels and subsequently screen for variants with improved performance. However, screening is often limited on the analytical side, generating a strong incentive to construct small but smart libraries. Here we introduce RedLibs (Reduced Libraries), an algorithm that allows for the rational design of smart combinatorial libraries for pathway optimization thereby minimizing the use of experimental resources. We demonstrate the utility of RedLibs for the design of ribosome-binding site libraries by in silico and in vivo screening with fluorescent proteins and perform a simple two-step optimization of the product selectivity in the branched multistep pathway for violacein biosynthesis, indicating a general applicability for the algorithm and the proposed heuristics. We expect that RedLibs will substantially simplify the refactoring of synthetic metabolic pathways. PMID:27029461

  18. Histone code or not? Combinatorial pattern analyses of histone modifications

    NASA Astrophysics Data System (ADS)

    Zang, Chongzhi; Peng, Weiqun; Wang, Zhibin; Schones, Dustin E.; Barski, Artem; Cuddapah, Suresh; Cui, Kairong; Roh, Tae-Young; Zhao, Keji; Rosenfeld, Jeffrey; Zhang, Michael

    2008-03-01

    Eukaryotic genomes are organized into chromatin, the structure of which plays critical role in the program of gene expression. Chromatin structure and function is regulated by a myriad of posttranslational modifications on histone tails of the nucleosomes, the fundamental unit of chromatin. It remains unclear how different modifications interact. Based on high- resolution genomic maps of close to 40 histone methylations and acetylations in human T-cells obtained experimentally by ChIP- Seq technique, we investigated the combinatorial patterns of histone modifications at gene promoter regions. We found that a very limited number of patterns dominate. Modifications within a pattern are strongly correlated and each pattern is associated with a distinct gene expression distribution. Our results suggest that it is the patterns rather than the individual modifications that affect the downstream readout.

  19. Combinatorial approach to Mathieu and Lamé equations

    SciTech Connect

    He, Wei

    2015-07-15

    Based on some recent progress on a relation between four dimensional super Yang-Mills gauge theory and quantum integrable system, we study the asymptotic spectrum of the quantum mechanical problems described by the Mathieu equation and the Lamé equation. The large momentum asymptotic expansion of the eigenvalue is related to the instanton partition function of supersymmetric gauge theories which can be evaluated by a combinatorial method. The electro-magnetic duality of gauge theory indicates that in the parameter space, there are three asymptotic expansions for the eigenvalue, and we confirm this fact by performing the Wentzel–Kramers–Brillouin (WKB) analysis in each asymptotic expansion region. The results presented here give some new perspective on the Floquet theory about periodic differential equation.

  20. PCB Drill Path Optimization by Combinatorial Cuckoo Search Algorithm

    PubMed Central

    Lim, Wei Chen Esmonde; Kanagaraj, G.; Ponnambalam, S. G.

    2014-01-01

    Optimization of drill path can lead to significant reduction in machining time which directly improves productivity of manufacturing systems. In a batch production of a large number of items to be drilled such as printed circuit boards (PCB), the travel time of the drilling device is a significant portion of the overall manufacturing process. To increase PCB manufacturing productivity and to reduce production costs, a good option is to minimize the drill path route using an optimization algorithm. This paper reports a combinatorial cuckoo search algorithm for solving drill path optimization problem. The performance of the proposed algorithm is tested and verified with three case studies from the literature. The computational experience conducted in this research indicates that the proposed algorithm is capable of efficiently finding the optimal path for PCB holes drilling process. PMID:24707198

  1. Combinatorial approach to exactly solve the 1D Ising model

    NASA Astrophysics Data System (ADS)

    Seth, Swarnadeep

    2017-01-01

    The Ising model is a well known statistical model which can be solved exactly by various methods. The most familiar one is the transfer matrix method. Sometimes it can be difficult to approach the open boundary case rather than periodic boundary ones in higher dimensions. But physically it is more intuitive to study the open boundary case, as it gives a closer view of the real system. We have introduced a new method called the pairing method to determine the exact partition function for the simplest case, a 1D Ising lattice. This method simplifies the problem's complexities and reduces it to a pure combinatorial problem. The study also reveals that it is possible to apply this pairing method in the case of a 2D square lattice. The obtained results agree perfectly with the values in the literature and this new approach provides an algorithmic insight to deal with such problems.

  2. Combinatorial Method for Overexpression of Membrane Proteins in Escherichia coli*

    PubMed Central

    Leviatan, Shani; Sawada, Keisuke; Moriyama, Yoshinori; Nelson, Nathan

    2010-01-01

    Membrane proteins constitute 20–30% of all proteins encoded by the genome of various organisms. Large amounts of purified proteins are required for activity and crystallization attempts. Thus, there is an unmet need for a heterologous membrane protein overexpression system for purification, crystallization, and activity determination. We developed a combinatorial method for overexpressing and purifying membrane proteins using Escherichia coli. This method utilizes short hydrophilic bacterial proteins, YaiN and YbeL, fused to the ends of the membrane proteins to serve as facilitating factors for expression and purification. Fourteen prokaryotic and mammalian membrane proteins were expressed using this system. Moderate to high expression was obtained for most proteins, and detergent solubilization combined with a short purification process produced stable, monodispersed membrane proteins. Five of the mammalian membrane proteins, overexpressed using our system, were reconstituted into liposomes and exhibited transport activity comparable with the native transporters. PMID:20525689

  3. Combinatorial method for overexpression of membrane proteins in Escherichia coli.

    PubMed

    Leviatan, Shani; Sawada, Keisuke; Moriyama, Yoshinori; Nelson, Nathan

    2010-07-30

    Membrane proteins constitute 20-30% of all proteins encoded by the genome of various organisms. Large amounts of purified proteins are required for activity and crystallization attempts. Thus, there is an unmet need for a heterologous membrane protein overexpression system for purification, crystallization, and activity determination. We developed a combinatorial method for overexpressing and purifying membrane proteins using Escherichia coli. This method utilizes short hydrophilic bacterial proteins, YaiN and YbeL, fused to the ends of the membrane proteins to serve as facilitating factors for expression and purification. Fourteen prokaryotic and mammalian membrane proteins were expressed using this system. Moderate to high expression was obtained for most proteins, and detergent solubilization combined with a short purification process produced stable, monodispersed membrane proteins. Five of the mammalian membrane proteins, overexpressed using our system, were reconstituted into liposomes and exhibited transport activity comparable with the native transporters.

  4. Combinatorial Clustering and the Beta Negative Binomial Process.

    PubMed

    Broderick, Tamara; Mackey, Lester; Paisley, John; Jordan, Michael I

    2015-02-01

    We develop a Bayesian nonparametric approach to a general family of latent class problems in which individuals can belong simultaneously to multiple classes and where each class can be exhibited multiple times by an individual. We introduce a combinatorial stochastic process known as the negative binomial process ( NBP ) as an infinite-dimensional prior appropriate for such problems. We show that the NBP is conjugate to the beta process, and we characterize the posterior distribution under the beta-negative binomial process ( BNBP) and hierarchical models based on the BNBP (the HBNBP). We study the asymptotic properties of the BNBP and develop a three-parameter extension of the BNBP that exhibits power-law behavior. We derive MCMC algorithms for posterior inference under the HBNBP , and we present experiments using these algorithms in the domains of image segmentation, object recognition, and document analysis.

  5. PCB drill path optimization by combinatorial cuckoo search algorithm.

    PubMed

    Lim, Wei Chen Esmonde; Kanagaraj, G; Ponnambalam, S G

    2014-01-01

    Optimization of drill path can lead to significant reduction in machining time which directly improves productivity of manufacturing systems. In a batch production of a large number of items to be drilled such as printed circuit boards (PCB), the travel time of the drilling device is a significant portion of the overall manufacturing process. To increase PCB manufacturing productivity and to reduce production costs, a good option is to minimize the drill path route using an optimization algorithm. This paper reports a combinatorial cuckoo search algorithm for solving drill path optimization problem. The performance of the proposed algorithm is tested and verified with three case studies from the literature. The computational experience conducted in this research indicates that the proposed algorithm is capable of efficiently finding the optimal path for PCB holes drilling process.

  6. Combinatorial Approach to Studying Metal Enhanced Fluorescence from Quantum Dots

    NASA Astrophysics Data System (ADS)

    Le, Nguyet; Corrigan, Timothy; Norton, Michael; Neff, David

    2013-03-01

    Fluorescence is extensively used in biochemistry for determining the concentration or purity of molecules in a biological environment. In metal-enhanced fluorescence (MEF), the fluorescence molecules separated from a metal surface by several nanometers can be enhanced. The fluorescent enhancement is dependent on the size and spacing of the nanoparticles, as has been shown previously for a number of fluorophore molecules. Fluorescence from quantum dots is of particular interest because the quantum dots do not lose fluorescence ability when exposed to light and they have higher intensity of fluorescence. The purpose of this study is to determine the effect of size and spacing on fluorescence intensity when coupling gold nano-particles with quantum dots. We employ a combinatorial approach, depositing gold particles ranging in diameter from 30 nm to 130 nm with varied spacings onto the substrate, followed by a protein spacer-layer and quantum dots. The fluorescence signal from the metal enhanced quantum dots were determined by confocal microscopy.

  7. Behavioral assessment of combinatorial semantics in baboons (Papio papio).

    PubMed

    Medam, Tiphaine; Fagot, Joël

    2016-02-01

    Combinatorial semantics is a core property of human language whose mechanisms remain poorly known. This study used computerized tasks with touch screens to investigate whether baboons (Papio papio) can understand the combination of shape and color labels in order to designate their corresponding colored shape. The baboons were trained either directly with label-pairs (Experiment 1) or with individual shape and color labels (Experiment 2), before being tested with novel compound labels from which they had to identify the referent. Compound labels understanding was found in one out of seven baboons tested in Experiment 1. Quite surprisingly, none of the 11 baboons showed this capacity in Experiment 2. We discuss several aspects of our protocols which could explain this difference between our two experiments, as well as the significance of our findings for language studies in animals and children.

  8. Combinatorial discovery of two-photon photoremovable protecting groups

    PubMed Central

    Pirrung, Michael C.; Pieper, Wolfgang H.; Kaliappan, Krishna P.; Dhananjeyan, Mugunthu R.

    2003-01-01

    A design principle for a two-photon photochemically removable protecting group based on sequential one-photon processes has been established. The expected performance of such groups in spatially directed photoactivation/photodeprotection has been shown by a kinetic analysis. One particular molecular class fitting into this design, the nitrobenzyl ethers of o-hydroxycinnamates, has been presented. An initial demonstration of two-photon deprotection of one such group prompted further optimization with respect to photochemical deprotection rate. This was accomplished by the preparation and screening of a 135-member indexed combinatorial library. Optimum performance for λ >350 nm deprotection in organic solvent was found with 4,5-dialkoxy and α-cyano substitution in the nitrobenzyl group and 4-methoxy substitution in the cinnamate. PMID:14557545

  9. Behavioural correlates of combinatorial versus temporal features of odour codes

    PubMed Central

    Saha, Debajit; Li, Chao; Peterson, Steven; Padovano, William; Katta, Nalin; Raman, Baranidharan

    2015-01-01

    Most sensory stimuli evoke spiking responses that are distributed across neurons and are temporally structured. Whether the temporal structure of ensemble activity is modulated to facilitate different neural computations is not known. Here, we investigated this issue in the insect olfactory system. We found that an odourant can generate synchronous or asynchronous spiking activity across a neural ensemble in the antennal lobe circuit depending on its relative novelty with respect to a preceding stimulus. Regardless of variations in temporal spiking patterns, the activated combinations of neurons robustly represented stimulus identity. Consistent with this interpretation, locusts reliably recognized both solitary and sequential introductions of trained odourants in a quantitative behavioural assay. However, predictable behavioural responses across locusts were observed only to novel stimuli that evoked synchronized spiking patterns across neural ensembles. Hence, our results indicate that the combinatorial ensemble response encodes for stimulus identity, whereas the temporal structure of the ensemble response selectively emphasizes novel stimuli. PMID:25912016

  10. Combinatorial Optimization of Transparent Conducting Oxides (TCOS) for PV

    SciTech Connect

    Perkins, J. D.; Taylor, M. P.; van Hest, M.F.A.M.; Teplin, C. W.; Alleman, J. L.; Dabney, M. S.; Gedvilas, L. M.; Keyes, B. M.; To, B.; Readey, D. W.; Delahoy, A. E.; Guo, S.; Ginley, D. S.

    2005-02-01

    Transparent conducting oxides (TCOs) can serve a variety of important functions in thin-film photovoltaics such as transparent electrical contacts, antireflection coatings, and chemical barriers. Two areas of particular interest are TCOs that can be deposited at low temperatures and TCOs with high carrier mobilities. We have employed combinatorial high-throughput approaches to investigate both these areas. Conductivities of s = 2500 W-1-cm-1 have been obtained for In-Zn-O (IZO) films deposited at 100 C and s > 5000 W-1-cm-1 for In-Ti-O (ITiO) and In-Mo-O (IMO) films deposited at 550 C. The highest mobility obtained was 83 cm2/V-s for ITiO deposited at 550 C.

  11. Selecting agonists from single cells infected with combinatorial antibody libraries.

    PubMed

    Zhang, Hongkai; Yea, Kyungmoo; Xie, Jia; Ruiz, Diana; Wilson, Ian A; Lerner, Richard A

    2013-05-23

    We describe a system for direct selection of antibodies that are receptor agonists. Combinatorial antibody libraries in lentiviruses are used to infect eukaryotic cells that contain a fluorescent reporter system coupled to the receptor for which receptor agonist antibodies are sought. In this embodiment of the method, very large numbers of candidate antibodies expressing lentivirus and eukaryotic reporter cells are packaged together in a format where each is capable of replication, thereby forging a direct link between genotype and phenotype. Following infection, cells that fluoresce are sorted and the integrated genes encoding the agonist antibodies recovered. We validated the system by illustrating its ability to generate rapidly potent antibody agonists that are complete thrombopoietin phenocopies. The system should be generalizable to any pathway where its activation can be linked to production of a selectable phenotype.

  12. Why Teach Environmental Chemistry?

    ERIC Educational Resources Information Center

    Gardner, Marjorie H.

    1974-01-01

    Discusses the importance of teaching environmental chemistry in secondary school science classes, and outlines five examples of environmental chemistry problems that focus on major concepts of chemistry and have critical implications for human survival and well-being. (JR)

  13. Science Update: Inorganic Chemistry

    ERIC Educational Resources Information Center

    Rawls, Rebecca

    1978-01-01

    This first in a series of articles describing the state of the art of various branches of chemistry reviews inorganic chemistry, including bioinorganic, photochemistry, organometallic, and solid state chemistries. (SL)

  14. Comparison of combinatorial clustering methods on pharmacological data sets represented by machine learning-selected real molecular descriptors.

    PubMed

    Rivera-Borroto, Oscar Miguel; Marrero-Ponce, Yovani; García-de la Vega, José Manuel; Grau-Ábalo, Ricardo del Corazón

    2011-12-27

    Cluster algorithms play an important role in diversity related tasks of modern chemoinformatics, with the widest applications being in pharmaceutical industry drug discovery programs. The performance of these grouping strategies depends on various factors such as molecular representation, mathematical method, algorithmical technique, and statistical distribution of data. For this reason, introduction and comparison of new methods are necessary in order to find the model that best fits the problem at hand. Earlier comparative studies report on Ward's algorithm using fingerprints for molecular description as generally superior in this field. However, problems still remain, i.e., other types of numerical descriptions have been little exploited, current descriptors selection strategy is trial and error-driven, and no previous comparative studies considering a broader domain of the combinatorial methods in grouping chemoinformatic data sets have been conducted. In this work, a comparison between combinatorial methods is performed,with five of them being novel in cheminformatics. The experiments are carried out using eight data sets that are well established and validated in the medical chemistry literature. Each drug data set was represented by real molecular descriptors selected by machine learning techniques, which are consistent with the neighborhood principle. Statistical analysis of the results demonstrates that pharmacological activities of the eight data sets can be modeled with a few of families with 2D and 3D molecular descriptors, avoiding classification problems associated with the presence of nonrelevant features. Three out of five of the proposed cluster algorithms show superior performance over most classical algorithms and are similar (or slightly superior in the most optimistic sense) to Ward's algorithm. The usefulness of these algorithms is also assessed in a comparative experiment to potent QSAR and machine learning classifiers, where they perform

  15. Chemistry Division: Annual progress report for period ending March 31, 1987

    SciTech Connect

    Not Available

    1987-08-01

    This report is divided into the following sections: coal chemistry; aqueous chemistry at high temperatures and pressures; geochemistry of crustal processes to high temperatures and pressures; chemistry of advanced inorganic materials; structure and dynamics of advanced polymeric materials; chemistry of transuranium elements and compounds; separations chemistry; reactions and catalysis in molten salts; surface science related to heterogeneous catalysis; electron spectroscopy; chemistry related to nuclear waste disposal; computational modeling of security document printing; and special topics. (DLC)

  16. Enumeration of virtual libraries of combinatorial modular macrocyclic (bracelet, necklace) architectures and their linear counterparts.

    PubMed

    Taniguchi, Masahiko; Du, Hai; Lindsey, Jonathan S

    2013-09-23

    A wide variety of cyclic molecular architectures are built of modular subunits and can be formed combinatorially. The mathematics for enumeration of such objects is well-developed yet lacks key features of importance in chemistry, such as specifying (i) the structures of individual members among a set of isomers, (ii) the distribution (i.e., relative amounts) of products, and (iii) the effect of nonequal ratios of reacting monomers on the product distribution. Here, a software program (Cyclaplex) has been developed to determine the number, identity (including isomers), and relative amounts of linear and cyclic architectures from a given number and ratio of reacting monomers. The program includes both mathematical formulas and generative algorithms for enumeration; the latter go beyond the former to provide desired molecular-relevant information and data-mining features. The program is equipped to enumerate four types of architectures: (i) linear architectures with directionality (macroscopic equivalent = electrical extension cords), (ii) linear architectures without directionality (batons), (iii) cyclic architectures with directionality (necklaces), and (iv) cyclic architectures without directionality (bracelets). The program can be applied to cyclic peptides, cycloveratrylenes, cyclens, calixarenes, cyclodextrins, crown ethers, cucurbiturils, annulenes, expanded meso-substituted porphyrin(ogen)s, and diverse supramolecular (e.g., protein) assemblies. The size of accessible architectures encompasses up to 12 modular subunits derived from 12 reacting monomers or larger architectures (e.g. 13-17 subunits) from fewer types of monomers (e.g. 2-4). A particular application concerns understanding the possible heterogeneity of (natural or biohybrid) photosynthetic light-harvesting oligomers (cyclic, linear) formed from distinct peptide subunits.

  17. Combinatorial synthesis of new cationic lipids and high-throughput screening of their transfection properties.

    PubMed

    Lenssen, Karl; Jantscheff, Peter; von Kiedrowski, Günter; Massing, Ulrich

    2002-09-02

    Here we describe the first synthesis-screening approach for the identification and optimization of new cationic lipids for gene transfer in various cell lines. Combinatorial solid-phase chemistry was used to synthesize a library of new cationic lipids based on 3-methylamino-1,2-dihydroxypropane as the polar, cationic lipid part. As the nonpolar lipid part, different hydrocarbon chains were bound to the amino group of the scaffold and the amino group was further methylated to afford constantly cationic lipids. Lipids were synthesized in both configurations and as racemates, and the counter ions were also varied. By using a fully automated transfection screening method and COS-7 cells, the cationic lipid N,N-ditetradecyl-N-methyl-amino-2,3-propanediol (KL-1-14) was identified as a candidate lipid for the development of an improved transfection reagent. Screening the transfection properties of KL-1-14 in numerous combinations with the helper lipids dioleoylphosphatidylethanolamine (DOPE) and cholesterol (Chol) revealed that Chol is the most suitable helper lipid and the best KL-1-14/Chol ratio is 0.5-0.7. Compared to the standard transfection lipid N-[1-(2,3-dioleoyloxy)propyl]-N,N,N-trimethylammonium methyl sulfate (DOTAP), transfection efficiency was improved by a factor of about 40. Furthermore, by using R- and S-configured KL-1-14, it could be shown that the configuration of the lipids had no significant influence on its transfection efficiency. The highest transfection efficiencies were achieved with chloride as the counter ion. The new lipofection reagent was further tested to transfect the cell lines MDA-MB-468, MCF-7, MDCK-C7, and primary dentritic cells (DC), which are important for the development of new anticancer gene therapy strategies. Even in these cells, KL-1-14/Chol (1:0.6) had improved transfection efficiencies, which were about two to four times higher than for DOTAP.

  18. Science Update: Inorganic Chemistry.

    ERIC Educational Resources Information Center

    Rawls, Rebecca

    1981-01-01

    Describes areas of inorganic chemistry which have changed dramatically in the past year or two, including photochemistry, electrochemistry, organometallic complexes, inorganic reaction theory, and solid state chemistry. (DS)

  19. Effects of phytoestrogens and synthetic combinatorial libraries on aromatase, estrogen biosynthesis, and metabolism.

    PubMed

    Brueggemeier, R W; Gu, X; Mobley, J A; Joomprabutra, S; Bhat, A S; Whetstone, J L

    2001-12-01

    -tissue aromatase by exogenous agents such as drugs and environmental agents is being investigated. The benzopyranone-ring system is a molecular scaffold of considerable interest, and this scaffold is found in flavonoid natural products that have weak aromatase inhibitory activity. Medicinal chemistry efforts focus on diversifying the benzopyranone scaffold and utilizing combinatorial chemistry approaches to construct small benzopyranone libraries as potential aro- matase inhibitors. Several compounds in the initial libraries have demonstrated moderate aromatase inhibitory activity in screening assays.

  20. Chemistry Notes.

    ERIC Educational Resources Information Center

    School Science Review, 1984

    1984-01-01

    Presents an experiment which links mass spectrometry to gas chromatography. Also presents a simulation of iron extraction using a ZX81 computer and discussions of Fehling versus Benedict's solutions, transition metal ammine complexes, electrochemical and other chemical series, and a simple model of dynamic equilibria. (JN)

  1. Proceedings of the physics and chemistry of oxide superconductors

    SciTech Connect

    Iye, Y.; Yasuoka, H.

    1992-01-01

    This book contains the proceedings of the physics and chemistry of oxide superconductors. Topics covered include: materials; electronic states; spectroscopy; lattice properties; pressure effects; carrier dynamics; doping effects; spin dynamics; magnetism; strong correlation, and superconducting properties.

  2. Laser direct writing of combinatorial libraries of idealized cellular constructs: Biomedical applications

    NASA Astrophysics Data System (ADS)

    Schiele, Nathan R.; Koppes, Ryan A.; Corr, David T.; Ellison, Karen S.; Thompson, Deanna M.; Ligon, Lee A.; Lippert, Thomas K. M.; Chrisey, Douglas B.

    2009-03-01

    The ability to control cell placement and to produce idealized cellular constructs is essential for understanding and controlling intercellular processes and ultimately for producing engineered tissue replacements. We have utilized a novel intra-cavity variable aperture excimer laser operated at 193 nm to reproducibly direct write mammalian cells with micrometer resolution to form a combinatorial array of idealized cellular constructs. We deposited patterns of human dermal fibroblasts, mouse myoblasts, rat neural stem cells, human breast cancer cells, and bovine pulmonary artery endothelial cells to study aspects of collagen network formation, breast cancer progression, and neural stem cell proliferation, respectively. Mammalian cells were deposited by matrix assisted pulsed laser evaporation direct write from ribbons comprised of a UV transparent quartz coated with either a thin layer of extracellular matrix or triazene as a dynamic release layer using CAD/CAM control. We demonstrate that through optical imaging and incorporation of a machine vision algorithm, specific cells on the ribbon can be laser deposited in spatial coherence with respect to geometrical arrays and existing cells on the receiving substrate. Having the ability to direct write cells into idealized cellular constructs can help to answer many biomedical questions and advance tissue engineering and cancer research.

  3. Combinatorial parallel synthesis and automated screening of a novel class of liquid crystalline materials.

    PubMed

    Deeg, Oliver; Kirsch, Peer; Pauluth, Detlef; Bäuerle, Peter

    2002-12-07

    Combinatorial parallel synthesis has led to the rapid generation of a single-compound library of novel fluorinated quaterphenyls. Subsequent automated screening revealed liquid crystalline (LC) behaviour and gave qualitative relationships of molecular structures and solid state properties.

  4. Application of combinatorial biocatalysis for a unique ring expansion of dihydroxymethylzearalenone

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Combinatorial biocatalysis was applied to generate a diverse set of dihydroxymethylzearalenone derivatives with modified ring structure. In one chemoenzymatic reaction sequence, dihydroxymethylzearalenone was first subjected to a unique enzyme-catalyzed oxidative ring opening reaction that creates ...

  5. Identification of combinatorial drug regimens for treatment of Huntington's disease using Drosophila

    NASA Astrophysics Data System (ADS)

    Agrawal, Namita; Pallos, Judit; Slepko, Natalia; Apostol, Barbara L.; Bodai, Laszlo; Chang, Ling-Wen; Chiang, Ann-Shyn; Michels Thompson, Leslie; Marsh, J. Lawrence

    2005-03-01

    We explore the hypothesis that pathology of Huntington's disease involves multiple cellular mechanisms whose contributions to disease are incrementally additive or synergistic. We provide evidence that the photoreceptor neuron degeneration seen in flies expressing mutant human huntingtin correlates with widespread degenerative events in the Drosophila CNS. We use a Drosophila Huntington's disease model to establish dose regimens and protocols to assess the effectiveness of drug combinations used at low threshold concentrations. These proof of principle studies identify at least two potential combinatorial treatment options and illustrate a rapid and cost-effective paradigm for testing and optimizing combinatorial drug therapies while reducing side effects for patients with neurodegenerative disease. The potential for using prescreening in Drosophila to inform combinatorial therapies that are most likely to be effective for testing in mammals is discussed. combinatorial treatments | neurodegeneration

  6. Combinatorial genetic perturbation to refine metabolic circuits for producing biofuels and biochemicals.

    PubMed

    Kim, Hyo Jin; Turner, Timothy Lee; Jin, Yong-Su

    2013-11-01

    Recent advances in metabolic engineering have enabled microbial factories to compete with conventional processes for producing fuels and chemicals. Both rational and combinatorial approaches coupled with synthetic and systematic tools play central roles in metabolic engineering to create and improve a selected microbial phenotype. Compared to knowledge-based rational approaches, combinatorial approaches exploiting biological diversity and high-throughput screening have been demonstrated as more effective tools for improving various phenotypes of interest. In particular, identification of unprecedented targets to rewire metabolic circuits for maximizing yield and productivity of a target chemical has been made possible. This review highlights general principles and the features of the combinatorial approaches using various libraries to implement desired phenotypes for strain improvement. In addition, recent applications that harnessed the combinatorial approaches to produce biofuels and biochemicals will be discussed.

  7. Combinatorial investigation of rare-earth free permanent magnets

    NASA Astrophysics Data System (ADS)

    Fackler, Sean Wu

    The combinatorial high throughput method allows one to rapidly study a large number of samples with systematically changing parameters. We apply this method to study Fe-Co-V alloys as alternatives to rare-earth permanent magnets. Rare-earth permanent magnets derive their unmatched magnetic properties from the hybridization of Fe and Co with the f-orbitals of rare-earth elements, which have strong spin-orbit coupling. It is predicted that Fe and Co may also have strong hybridization with 4d and 5d refractory transition metals with strong spin-orbit coupling. Refractory transition metals like V also have the desirable property of high temperature stability, which is important for permanent magnet applications in traction motors. In this work, we focus on the role of crystal structure, composition, and secondary phases in the origin of competitive permanent magnetic properties of a particular Fe-Co-V alloy. Fe38Co52V10, compositions are known as Vicalloys. Fe-CoV composition spreads were sputtered onto three-inch silicon wafers and patterned into discrete sample pads forming a combinatorial library. We employed highthroughput screening methods using synchrotron X-rays, wavelength dispersive spectroscopy, and magneto-optical Kerr effect (MOKE) to rapidly screen crystal structure, composition, and magnetic properties, respectively. We found that in-plane magnetic coercive fields of our Vicalloy thin films agree with known bulk values (300 G), but found a remarkable eight times increase of the out-of-plane coercive fields (˜2,500 G). To explain this, we measured the switching fields between in-plane and out-of-plane thin film directions which revealed that the Kondorsky model of 180° domain wall reversal was responsible for Vicalloy's enhanced out-of-plane coercive field and possibly its permanent magnetic properties. The Kondorsky model suggests that domain-wall pinning is the origin of Vicalloy's permanent magnetic properties, in contrast to strain, shape, or

  8. Evaluation of the Current Status of the Combinatorial Approach for the Study of Phase Diagrams

    PubMed Central

    Wong-Ng, W.

    2012-01-01

    This paper provides an evaluation of the effectiveness of using the high throughput combinatorial approach for preparing phase diagrams of thin film and bulk materials. Our evaluation is based primarily on examples of combinatorial phase diagrams that have been reported in the literature as well as based on our own laboratory experiments. Various factors that affect the construction of these phase diagrams are examined. Instrumentation and analytical approaches needed to improve data acquisition and data analysis are summarized. PMID:26900530

  9. Combinatorial Biomolecular Nanopatterning for High-Throughput Screening of Stem-Cell Behavior.

    PubMed

    Amin, Yacoub Y I; Runager, Kasper; Simoes, Fabio; Celiz, Adam; Taresco, Vincenzo; Rossi, Roberto; Enghild, Jan J; Abildtrup, Lisbeth A; Kraft, David C E; Sutherland, Duncan S; Alexander, Morgan R; Foss, Morten; Ogaki, Ryosuke

    2016-02-17

    A novel combinatorial biomolecular nanopatterning method is reported, in which multiple biomolecular ligands can be patterned in multiple nanoscale dimensions on a single surface. The applicability of the combinatorial platform toward cell-biology applications is demonstrated by screening the adhesion behavior of a population of human dental pulp stem cell (hDPSC) on 64 combinations of nanopatterned extracellular matrix (ECM) proteins in parallel.

  10. Amino acid-derived heterocycles as combinatorial library targets: spirocyclic ketal lactones.

    PubMed

    Trump, Ryan P; Bartlett, Paul A

    2003-01-01

    The spirocyclic ketal-lactone frameworks of 3 and 4 were designed as novel structures amenable to combinatorial synthesis. The synthesis of representative analogues was developed in solution and on solid support, the scope of effective input materials was determined, and the stability and stereochemistry of the products was evaluated. The spirocycles are obtained in modest overall yields (5-36%) and excellent purities (>72%) and offer a promising motif for combinatorial prospecting libraries.

  11. On the relationship between total ozone and atmospheric dynamics and chemistry at mid-latitudes - Part 2: The effects of the El Niño/Southern Oscillation, volcanic eruptions and contributions of atmospheric dynamics and chemistry to long-term total ozone changes

    NASA Astrophysics Data System (ADS)

    Rieder, H. E.; Frossard, L.; Ribatet, M.; Staehelin, J.; Maeder, J. A.; Di Rocco, S.; Davison, A. C.; Peter, T.; Weihs, P.; Holawe, F.

    2013-01-01

    We present the first spatial analysis of "fingerprints" of the El Niño/Southern Oscillation (ENSO) and atmospheric aerosol load after major volcanic eruptions (El Chichón and Mt. Pinatubo) in extreme low and high (termed ELOs and EHOs, respectively) and mean values of total ozone for the northern and southern mid-latitudes (defined as the region between 30° and 60° north and south, respectively). Significant influence on ozone extremes was found for the warm ENSO phase in both hemispheres during spring, especially towards low latitudes, indicating the enhanced ozone transport from the tropics to the extra-tropics. Further, the results confirm findings of recent work on the connection between the ENSO phase and the strength and extent of the southern ozone "collar". For the volcanic eruptions the analysis confirms findings of earlier studies for the northern mid-latitudes and gives new insights for the Southern Hemisphere. The results provide evidence that the negative effect of the eruption of El Chichón might be partly compensated by a strong warm ENSO phase in 1982-1983 at southern mid-latitudes. The strong west-east gradient in the coefficient estimates for the Mt. Pinatubo eruption and the analysis of the relationship between the AAO and ENSO phase, the extent and the position of the southern ozone "collar" and the polar vortex structure provide clear evidence for a dynamical "masking" of the volcanic signal at southern mid-latitudes. The paper also analyses the contribution of atmospheric dynamics and chemistry to long-term total ozone changes. Here, quite heterogeneous results have been found on spatial scales. In general the results show that EESC and the 11-yr solar cycle can be identified as major contributors to long-term ozone changes. However, a strong contribution of dynamical features (El Niño/Southern Oscillation (ENSO), North Atlantic Oscillation (NAO), Antarctic Oscillation (AAO), Quasi-Biennial Oscillation (QBO)) to ozone variability and

  12. Probing the Binding Site of Abl Tyrosine Kinase Using in Situ Click Chemistry

    PubMed Central

    2013-01-01

    Modern combinatorial chemistry is used to discover compounds with desired function by an alternative strategy, in which the biological target is directly involved in the choice of ligands assembled from a pool of smaller fragments. Herein, we present the first experimental result where the use of in situ click chemistry has been successfully applied to probe the ligand-binding site of Abl and the ability of this enzyme to form its inhibitor. Docking studies show that Abl is able to allow the in situ click chemistry between specific azide and alkyne fragments by binding to Abl-active sites. This report allows medicinal chemists to use protein-directed in situ click chemistry for exploring the conformational space of a ligand-binding pocket and the ability of the protein to guide its inhibitor. This approach can be a novel, valuable tool to guide drug design synthesis in the field of tyrosine kinases. PMID:24900659

  13. A high throughput approach to quantify protein adsorption on combinatorial metal/metal oxide surfaces using electron microprobe and spectroscopic ellipsometry

    NASA Astrophysics Data System (ADS)

    Byrne, T.; Lohstreter, L.; Filiaggi, M. J.; Bai, Zhijun; Dahn, J. R.

    2008-09-01

    Although metallic biomaterials are widely used, systematic studies of protein adsorption onto such materials are generally lacking. Combinatorial binary films of Al 1-xTi x and Al 1-xNb x (0 ⩽ x ⩽ 1) and corresponding pure element films were produced on glass substrates using a unique magnetron sputtering technique. Fibrinogen and albumin adsorption amounts were measured by wavelength-dispersive spectroscopy (WDS) and spectroscopic ellipsometry (SE) equipment, both high throughput techniques with automated motion stage capabilities. X-ray diffraction revealed that the binary films have crystalline phases present near the ends of the compositional gradient with an amorphous region throughout the interior of the gradient. X-ray photoelectron spectroscopy provided the surface chemistry along the binary films and showed that Al 2O 3 preferentially formed at the surface. Protein adsorption onto these films was found to be closely correlated to the alumina surface fraction, with high alumina content at the surface leading to low amounts of adsorbed fibrinogen and albumin. Protein adsorption amounts obtained with WDS and SE were in excellent agreement for all films. This suggests that this combinatorial materials approach combined with these state-of-the-art, automated high throughput instruments provides a novel way to accurately monitor protein adsorption taking place at the surfaces of these metal/metal oxide materials.

  14. [Safe improvement of drug absorption by combinatorial use of sodium laurate with amino acids: cytoprotection by amino acids and its mechanisms].

    PubMed

    Higaki, Kazutaka

    2007-04-01

    The development of combinatorial chemistry and high-throughput screening techniques has made it possible to generate many new drug candidates very rapidly, but it has also resulted in a number of poorly soluble and/or poorly absorbable candidates. A new trend in drug development based on pharmacogenomics or the development of molecular-targeted drugs is also spurring the tendency, and it does not necessarily lead to good output in terms of the development of new drugs. It is attractive to improve membrane permeability as well as solubility by using adjuvants, because this method could be applicable for various drugs. However, the practical use of absorption-enhancing adjuvants has been limited because of the potential local toxicity. Therefore suppressing the potential local toxicity would lead to the successful development of safe preparations with improved absorption using adjuvants. Our biochemical and histopathologic studies showed that several amino acids such as taurine and L-glutamine had cytoprotective activity, and it has been found that the combinatorial use of sodium laurate (C12) with these amino acids could maintain the absorption-enhancing ability of C12. A suppository preparation containing C12 and taurine remarkably improved the rectal absorption of rebamipide, classified as BCS class IV, and the preparation was safe to the rectal mucosa. For the mechanisms of cytoprotective action by these amino acids, it has been found that they suppress the intracellular calcium level, induce the expression of heat-shock protein 70, and inhibit the release of histamine and apoptosis.

  15. ProSAR: a new methodology for combinatorial library design.

    PubMed

    Chen, Hongming; Börjesson, Ulf; Engkvist, Ola; Kogej, Thierry; Svensson, Mats A; Blomberg, Niklas; Weigelt, Dirk; Burrows, Jeremy N; Lange, Tim

    2009-03-01

    A method is introduced for performing reagent selection for chemical library design based on topological (2D) pharmacophore fingerprints. Optimal reagent selection is achieved by optimizing the Shannon entropy of the 2D pharmacophore distribution for the reagent set. The method, termed ProSAR, is therefore expected to enumerate compounds that could serve as a good starting point for deriving a structure activity relationship (SAR) in combinatorial library design. This methodology is exemplified by library design examples where the active compounds were already known. The results show that most of the pharmacophores on the substituents for the active compounds are covered by the designed library. This strategy is further expanded to include product property profiles for aqueous solubility, hERG risk assessment, etc. in the optimization process so that the reagent pharmacophore diversity and the product property profile are optimized simultaneously via a genetic algorithm. This strategy is applied to a two-dimensional library design example and compared with libraries designed by a diversity based strategy which minimizes the average ensemble Tanimoto similarity. Our results show that by using the PSAR methodology, libraries can be designed with simultaneously good pharmacophore coverage and product property profile.

  16. Chromodomain Ligand Optimization via Target-Class Directed Combinatorial Repurposing.

    PubMed

    Barnash, Kimberly D; Lamb, Kelsey N; Stuckey, Jacob I; Norris, Jacqueline L; Cholensky, Stephanie H; Kireev, Dmitri B; Frye, Stephen V; James, Lindsey I

    2016-09-16

    Efforts to develop strategies for small-molecule chemical probe discovery against the readers of the methyl-lysine (Kme) post-translational modification have been met with limited success. Targeted disruption of these protein-protein interactions via peptidomimetic inhibitor optimization is a promising alternative to small-molecule hit discovery; however, recognition of identical peptide motifs by multiple Kme reader proteins presents a unique challenge in the development of selective Kme reader chemical probes. These selectivity challenges are exemplified by the Polycomb repressive complex 1 (PRC1) chemical probe, UNC3866, which demonstrates submicromolar off-target affinity toward the non-PRC1 chromodomains CDYL2 and CDYL. Moreover, since peptidomimetics are challenging subjects for structure-activity relationship (SAR) studies, traditional optimization of UNC3866 would prove costly and time-consuming. Herein, we report a broadly applicable strategy for the affinity-based, target-class screening of chromodomains via the repurposing of UNC3866 in an efficient, combinatorial peptide library. A first-generation library yielded UNC4991, a UNC3866 analogue that exhibits a distinct selectivity profile while maintaining submicromolar affinity toward the CDYL chromodomains. Additionally, in vitro pull-down experiments from HeLa nuclear lysates further demonstrate the selectivity and utility of this compound for future elucidation of CDYL protein function.

  17. Combinatorial approximation algorithms for MAXCUT using random walks.

    SciTech Connect

    Seshadhri, Comandur; Kale, Satyen

    2010-11-01

    We give the first combinatorial approximation algorithm for MaxCut that beats the trivial 0.5 factor by a constant. The main partitioning procedure is very intuitive, natural, and easily described. It essentially performs a number of random walks and aggregates the information to provide the partition. We can control the running time to get an approximation factor-running time tradeoff. We show that for any constant b > 1.5, there is an {tilde O}(n{sup b}) algorithm that outputs a (0.5 + {delta})-approximation for MaxCut, where {delta} = {delta}(b) is some positive constant. One of the components of our algorithm is a weak local graph partitioning procedure that may be of independent interest. Given a starting vertex i and a conductance parameter {phi}, unless a random walk of length {ell} = O(log n) starting from i mixes rapidly (in terms of {phi} and {ell}), we can find a cut of conductance at most {phi} close to the vertex. The work done per vertex found in the cut is sublinear in n.

  18. Rational and combinatorial tailoring of bioactive cyclic dipeptides.

    PubMed

    Giessen, Tobias W; Marahiel, Mohamed A

    2015-01-01

    Modified cyclic dipeptides represent a diverse family of microbial secondary metabolites. They display a broad variety of biological and pharmacological activities and have long been recognized as privileged structures with the ability to bind to a wide range of receptors. This is due to their conformationally constrained 2, 5-diketopiperazine (DKP) scaffold and the diverse set of DKP tailoring enzymes present in nature. After initial DKP assembly through different biosynthetic systems modifying enzymes are responsible for installing functional groups crucial for the biological activities of the resulting modified DKPs. They represent a vast and largely untapped enzyme repository very useful for synthetic biology approaches aiming at introducing structural variations into DKP scaffolds. In this review we focus on these DKP modification enzymes found in various microbial secondary metabolite gene clusters. We will give a brief overview of their distribution and highlight a select number of characterized DKP tailoring enzymes before turning to their application potential in combinatorial biosynthesis with the aim of producing molecules with improved or entirely new biological and medicinally relevant properties.

  19. Combinatorial investigation of Fe-B thin-film nanocomposites.

    PubMed

    Brunken, Hayo; Grochla, Dario; Savan, Alan; Kieschnick, Michael; Meijer, Jan D; Ludwig, Alfred

    2011-10-01

    Combinatorial magnetron sputter deposition from elemental targets was used to create Fe-B composition spread type thin film materials libraries on thermally oxidized 4-in. Si wafers. The materials libraries consisting of wedge-type multilayer thin films were annealed at 500 or 700 °C to transform the multilayers into multiphase alloys. The libraries were characterized by nuclear reaction analysis, Rutherford backscattering, nanoindentation, vibrating sample magnetometry, x-ray diffraction (XRD) and transmission electron microscopy (TEM). Young's modulus and hardness values were related to the annealing parameters, structure and composition of the films. The magnetic properties of the films were improved by annealing in a H2 atmosphere, showing a more than tenfold decrease in the coercive field values in comparison to those of the vacuum-annealed films. The hardness values increased from 8 to 18 GPa when the annealing temperature was increased from 500 to 700 °C. The appearance of Fe2B phases, as revealed by XRD and TEM, had a significant effect on the mechanical properties of the films.

  20. A combinatorial strategy for treating KRAS-mutant lung cancer.

    PubMed

    Manchado, Eusebio; Weissmueller, Susann; Morris, John P; Chen, Chi-Chao; Wullenkord, Ramona; Lujambio, Amaia; de Stanchina, Elisa; Poirier, John T; Gainor, Justin F; Corcoran, Ryan B; Engelman, Jeffrey A; Rudin, Charles M; Rosen, Neal; Lowe, Scott W

    2016-06-30

    Therapeutic targeting of KRAS-mutant lung adenocarcinoma represents a major goal of clinical oncology. KRAS itself has proved difficult to inhibit, and the effectiveness of agents that target key KRAS effectors has been thwarted by activation of compensatory or parallel pathways that limit their efficacy as single agents. Here we take a systematic approach towards identifying combination targets for trametinib, a MEK inhibitor approved by the US Food and Drug Administration, which acts downstream of KRAS to suppress signalling through the mitogen-activated protein kinase (MAPK) cascade. Informed by a short-hairpin RNA screen, we show that trametinib provokes a compensatory response involving the fibroblast growth factor receptor 1 (FGFR1) that leads to signalling rebound and adaptive drug resistance. As a consequence, genetic or pharmacological inhibition of FGFR1 in combination with trametinib enhances tumour cell death in vitro and in vivo. This compensatory response shows distinct specificities: it is dominated by FGFR1 in KRAS-mutant lung and pancreatic cancer cells, but is not activated or involves other mechanisms in KRAS wild-type lung and KRAS-mutant colon cancer cells. Importantly, KRAS-mutant lung cancer cells and patients’ tumours treated with trametinib show an increase in FRS2 phosphorylation, a biomarker of FGFR activation; this increase is abolished by FGFR1 inhibition and correlates with sensitivity to trametinib and FGFR inhibitor combinations. These results demonstrate that FGFR1 can mediate adaptive resistance to trametinib and validate a combinatorial approach for treating KRAS-mutant lung cancer.

  1. Customized optimization of metabolic pathways by combinatorial transcriptional engineering

    PubMed Central

    Du, Jing; Yuan, Yongbo; Si, Tong; Lian, Jiazhang; Zhao, Huimin

    2012-01-01

    A major challenge in metabolic engineering and synthetic biology is to balance the flux of an engineered heterologous metabolic pathway to achieve high yield and productivity in a target organism. Here, we report a simple, efficient and programmable approach named ‘customized optimization of metabolic pathways by combinatorial transcriptional engineering (COMPACTER)’ for rapid tuning of gene expression in a heterologous pathway under distinct metabolic backgrounds. Specifically, a library of mutant pathways is created by de novo assembly of promoter mutants of varying strengths for each pathway gene in a target organism followed by high-throughput screening/selection. To demonstrate this approach, a single round of COMPACTER was used to generate both a xylose utilizing pathway with near-highest efficiency and a cellobiose utilizing pathway with highest efficiency that were ever reported in literature for both laboratory and industrial yeast strains. Interestingly, these engineered xylose and cellobiose utilizing pathways were all host-specific. Therefore, COMPACTER represents a powerful approach to tailor-make metabolic pathways for different strain backgrounds, which is difficult if not impossible to achieve by existing pathway engineering methods. PMID:22718979

  2. Combinatorial neural codes from a mathematical coding theory perspective.

    PubMed

    Curto, Carina; Itskov, Vladimir; Morrison, Katherine; Roth, Zachary; Walker, Judy L

    2013-07-01

    Shannon's seminal 1948 work gave rise to two distinct areas of research: information theory and mathematical coding theory. While information theory has had a strong influence on theoretical neuroscience, ideas from mathematical coding theory have received considerably less attention. Here we take a new look at combinatorial neural codes from a mathematical coding theory perspective, examining the error correction capabilities of familiar receptive field codes (RF codes). We find, perhaps surprisingly, that the high levels of redundancy present in these codes do not support accurate error correction, although the error-correcting performance of receptive field codes catches up to that of random comparison codes when a small tolerance to error is introduced. However, receptive field codes are good at reflecting distances between represented stimuli, while the random comparison codes are not. We suggest that a compromise in error-correcting capability may be a necessary price to pay for a neural code whose structure serves not only error correction, but must also reflect relationships between stimuli.

  3. Rational and combinatorial tailoring of bioactive cyclic dipeptides

    PubMed Central

    Giessen, Tobias W.; Marahiel, Mohamed A.

    2015-01-01

    Modified cyclic dipeptides represent a diverse family of microbial secondary metabolites. They display a broad variety of biological and pharmacological activities and have long been recognized as privileged structures with the ability to bind to a wide range of receptors. This is due to their conformationally constrained 2, 5-diketopiperazine (DKP) scaffold and the diverse set of DKP tailoring enzymes present in nature. After initial DKP assembly through different biosynthetic systems modifying enzymes are responsible for installing functional groups crucial for the biological activities of the resulting modified DKPs. They represent a vast and largely untapped enzyme repository very useful for synthetic biology approaches aiming at introducing structural variations into DKP scaffolds. In this review we focus on these DKP modification enzymes found in various microbial secondary metabolite gene clusters. We will give a brief overview of their distribution and highlight a select number of characterized DKP tailoring enzymes before turning to their application potential in combinatorial biosynthesis with the aim of producing molecules with improved or entirely new biological and medicinally relevant properties. PMID:26284060

  4. An improved combinatorial geometry model for arbitrary geometry in DSMC

    NASA Astrophysics Data System (ADS)

    Kargaran, H.; Minuchehr, A.; Zolfaghari, A.

    2017-03-01

    This paper focuses on a new direct simulation Monte Carlo (DSMC) code based on combinatorial geometry (CG) for simulation of any rarefied gas flow. The developed code, called DgSMC-A, has been supplied with an improved CG modeling able to significantly optimize the particle-tracking process, resulting in a highly reduced runtime compared to the conventional codes. The improved algorithm inserts a grid over the geometry and saves those grid elements containing some part of the geometry border. Since only a small part of a grid is engaged with the geometry border, significant time can be saved using the proposed algorithm. Embedding the modified algorithm in the DgSMC-A resulted in a fast, robust and self-governing code needless to any mesh generator. The code completely handles complex geometries created with first-and second-order surfaces. In addition, we developed a new surface area calculator in the CG methodology for complex geometries based on the Monte Carlo method with acceptable accuracy. Several well-known test cases are examined to indicate the code ability to deal with a wide range of realistic problems. Results are also found to be in good agreement with references and experimental data.

  5. Customized optimization of metabolic pathways by combinatorial transcriptional engineering.

    PubMed

    Du, Jing; Yuan, Yongbo; Si, Tong; Lian, Jiazhang; Zhao, Huimin

    2012-10-01

    A major challenge in metabolic engineering and synthetic biology is to balance the flux of an engineered heterologous metabolic pathway to achieve high yield and productivity in a target organism. Here, we report a simple, efficient and programmable approach named 'customized optimization of metabolic pathways by combinatorial transcriptional engineering (COMPACTER)' for rapid tuning of gene expression in a heterologous pathway under distinct metabolic backgrounds. Specifically, a library of mutant pathways is created by de novo assembly of promoter mutants of varying strengths for each pathway gene in a target organism followed by high-throughput screening/selection. To demonstrate this approach, a single round of COMPACTER was used to generate both a xylose utilizing pathway with near-highest efficiency and a cellobiose utilizing pathway with highest efficiency that were ever reported in literature for both laboratory and industrial yeast strains. Interestingly, these engineered xylose and cellobiose utilizing pathways were all host-specific. Therefore, COMPACTER represents a powerful approach to tailor-make metabolic pathways for different strain backgrounds, which is difficult if not impossible to achieve by existing pathway engineering methods.

  6. On Some Algebraic and Combinatorial Properties of Dunkl Elements

    NASA Astrophysics Data System (ADS)

    Kirillov, Anatol N.

    2013-06-01

    We introduce and study a certain class of nonhomogeneous quadratic algebras together with the special set of mutually commuting elements inside of each, the so-called Dunkl elements. We describe relations among the Dunkl elements. This result is a further generalization of similar results obtained in [S. Fomin and A. N. Kirillov, Quadratic algebras, Dunkl elements and Schubert calculus, in Advances in Geometry (eds. J.-S. Brylinski, V. Nistor, B. Tsygan and P. Xu), Progress in Math. Vol. 172 (Birkhäuser Boston, Boston, 1995), pp. 147-182, A. Postnikov, On a quantum version of Pieri's formula, in Advances in Geometry (eds. J.-S. Brylinski, R. Brylinski, V. Nistor, B. Tsygan and P. Xu), Progress in Math. Vol. 172 (Birkhäuser Boston, 1995), pp. 371-383 and A. N. Kirillov and T. Maenor, A Note on Quantum K-Theory of Flag Varieties, preprint]. As an application we describe explicitly the set of relations among the Gaudin elements in the group ring of the symmetric group, cf. [E. Mukhin, V. Tarasov and A. Varchenko, Bethe Subalgebras of the Group Algebra of the Symmetric Group, preprint arXiv:1004.4248]. Also we describe a few combinatorial properties of some special elements in the associative quasi-classical Yang-Baxter algebra in a connection with the values of the β-Grothendieck polynomials for some special permutations, and on the other hand, with the Ehrhart polynomial of the Chan-Robbins polytope.

  7. On Some Algebraic and Combinatorial Properties of Dunkl Elements

    NASA Astrophysics Data System (ADS)

    Kirillov, Anatol N.

    2012-11-01

    We introduce and study a certain class of nonhomogeneous quadratic algebras together with the special set of mutually commuting elements inside of each, the so-called Dunkl elements. We describe relations among the Dunkl elements. This result is a further generalization of similar results obtained in [S. Fomin and A. N. Kirillov, Quadratic algebras, Dunkl elements and Schubert calculus, in Advances in Geometry (eds. J.-S. Brylinski, V. Nistor, B. Tsygan and P. Xu), Progress in Math. Vol. 172 (Birkhäuser Boston, Boston, 1995), pp. 147-182, A. Postnikov, On a quantum version of Pieri's formula, in Advances in Geometry (eds. J.-S. Brylinski, R. Brylinski, V. Nistor, B. Tsygan and P. Xu), Progress in Math. Vol. 172 (Birkhäuser Boston, 1995), pp. 371-383 and A. N. Kirillov and T. Maenor, A Note on Quantum K-Theory of Flag Varieties, preprint]. As an application we describe explicitly the set of relations among the Gaudin elements in the group ring of the symmetric group, cf. [E. Mukhin, V. Tarasov and A. Varchenko, Bethe Subalgebras of the Group Algebra of the Symmetric Group, preprint arXiv:1004.4248]. Also we describe a few combinatorial properties of some special elements in the associative quasi-classical Yang-Baxter algebra in a connection with the values of the β-Grothendieck polynomials for some special permutations, and on the other hand, with the Ehrhart polynomial of the Chan-Robbins polytope.

  8. Combinatorial investigation of Fe–B thin-film nanocomposites

    PubMed Central

    Brunken, Hayo; Grochla, Dario; Savan, Alan; Kieschnick, Michael; Meijer, Jan D; Ludwig, Alfred

    2011-01-01

    Combinatorial magnetron sputter deposition from elemental targets was used to create Fe–B composition spread type thin film materials libraries on thermally oxidized 4-in. Si wafers. The materials libraries consisting of wedge-type multilayer thin films were annealed at 500 or 700 °C to transform the multilayers into multiphase alloys. The libraries were characterized by nuclear reaction analysis, Rutherford backscattering, nanoindentation, vibrating sample magnetometry, x-ray diffraction (XRD) and transmission electron microscopy (TEM). Young's modulus and hardness values were related to the annealing parameters, structure and composition of the films. The magnetic properties of the films were improved by annealing in a H2 atmosphere, showing a more than tenfold decrease in the coercive field values in comparison to those of the vacuum-annealed films. The hardness values increased from 8 to 18 GPa when the annealing temperature was increased from 500 to 700 °C. The appearance of Fe2B phases, as revealed by XRD and TEM, had a significant effect on the mechanical properties of the films. PMID:27877435

  9. Combinatorial approaches to evaluate nanodiamond uptake and induced cellular fate

    PubMed Central

    Eldawud, Reem; Reitzig, Manuela; Opitz, Jörg; Rojansakul, Yon; Jiang, Wenjuan; Nangia, Shikha; Dinu, Cerasela Zoica

    2016-01-01

    Nanodiamonds (NDs) are an emerging class of engineered nanomaterials that hold great promise for the next generation of bionanotechnological products to be used for drug and gene delivery, or for bio-imaging and biosensing. Previous studies have shown that upon their cellular uptake, NDs exhibit high biocompatibility in various in vitro and in vivo set-ups. Herein we hypothesized that the increased NDs biocompatibility is a result of minimum membrane perturbations and their reduced ability to induce disruption or damage during cellular translocation. Using multi-scale combinatorial approaches that simulate ND-membrane interactions, we correlated NDs real-time cellular uptake and kinetics with the ND-induced membrane fluctuations to derive energy requirements for the uptake to occur. Our discrete and real-time analyses showed that the majority of NDs internalization occurs within 2 h of cellular exposure, however, with no effects on cellular viability, proliferation or cellular behavior. Furthermore, our simulation analyses using coarse-grained models identified key changes in the energy profile, membrane deformation and recovery time, all functions of the average ND or ND-based agglomerate size. Understanding the mechanisms responsible for ND-cell membrane interactions could possibly advance their implementation in various biomedical applications. PMID:26820775

  10. Combinatorial approaches to evaluate nanodiamond uptake and induced cellular fate.

    PubMed

    Eldawud, Reem; Reitzig, Manuela; Opitz, Jörg; Rojansakul, Yon; Jiang, Wenjuan; Nangia, Shikha; Dinu, Cerasela Zoica

    2016-02-26

    Nanodiamonds (NDs) are an emerging class of engineered nanomaterials that hold great promise for the next generation of bionanotechnological products to be used for drug and gene delivery, or for bio-imaging and biosensing. Previous studies have shown that upon their cellular uptake, NDs exhibit high biocompatibility in various in vitro and in vivo set-ups. Herein we hypothesized that the increased NDs biocompatibility is a result of minimum membrane perturbations and their reduced ability to induce disruption or damage during cellular translocation. Using multi-scale combinatorial approaches that simulate ND-membrane interactions, we correlated NDs real-time cellular uptake and kinetics with the ND-induced membrane fluctuations to derive energy requirements for the uptake to occur. Our discrete and real-time analyses showed that the majority of NDs internalization occurs within 2 h of cellular exposure, however, with no effects on cellular viability, proliferation or cellular behavior. Furthermore, our simulation analyses using coarse-grained models identified key changes in the energy profile, membrane deformation and recovery time, all functions of the average ND or ND-based agglomerate size. Understanding the mechanisms responsible for ND-cell membrane interactions could possibly advance their implementation in various biomedical applications.

  11. Combinatorial approaches to evaluate nanodiamond uptake and induced cellular fate

    NASA Astrophysics Data System (ADS)

    Eldawud, Reem; Reitzig, Manuela; Opitz, Jörg; Rojansakul, Yon; Jiang, Wenjuan; Nangia, Shikha; Zoica Dinu, Cerasela

    2016-02-01

    Nanodiamonds (NDs) are an emerging class of engineered nanomaterials that hold great promise for the next generation of bionanotechnological products to be used for drug and gene delivery, or for bio-imaging and biosensing. Previous studies have shown that upon their cellular uptake, NDs exhibit high biocompatibility in various in vitro and in vivo set-ups. Herein we hypothesized that the increased NDs biocompatibility is a result of minimum membrane perturbations and their reduced ability to induce disruption or damage during cellular translocation. Using multi-scale combinatorial approaches that simulate ND-membrane interactions, we correlated NDs real-time cellular uptake and kinetics with the ND-induced membrane fluctuations to derive energy requirements for the uptake to occur. Our discrete and real-time analyses showed that the majority of NDs internalization occurs within 2 h of cellular exposure, however, with no effects on cellular viability, proliferation or cellular behavior. Furthermore, our simulation analyses using coarse-grained models identified key changes in the energy profile, membrane deformation and recovery time, all functions of the average ND or ND-based agglomerate size. Understanding the mechanisms responsible for ND-cell membrane interactions could possibly advance their implementation in various biomedical applications.

  12. Combinatorial quantization of the Hamiltonian Chern-Simons theory II

    NASA Astrophysics Data System (ADS)

    Alekseev, Anton Yu.; Grosse, Harald; Schomerus, Volker

    1996-01-01

    This paper further develops the combinatorial approach to quantization of the Hamiltonian Chern Simons theory advertised in [1]. Using the theory of quantum Wilson lines, we show how the Verlinde algebra appears within the context of quantum group gauge theory. This allows to discuss flatness of quantum connections so that we can give a mathematically rigorous definition of the algebra of observables A CS of the Chern Simons model. It is a *-algebra of “functions on the quantum moduli space of flat connections” and comes equipped with a positive functional ω (“integration”). We prove that this data does not depend on the particular choices which have been made in the construction. Following ideas of Fock and Rosly [2], the algebra A CS provides a deformation quantization of the algebra of functions on the moduli space along the natural Poisson bracket induced by the Chern Simons action. We evaluate a volume of the quantized moduli space and prove that it coincides with the Verlinde number. This answer is also interpreted as a partition partition function of the lattice Yang-Mills theory corresponding to a quantum gauge group.

  13. A Combinatorial Auction among Versatile Experts and Amateurs

    NASA Astrophysics Data System (ADS)

    Ito, Takayuki; Yokoo, Makoto; Matsubara, Shigeo

    Auctions have become an integral part of electronic commerce and a promising field for applying multi-agent technologies. Correctly judging the quality of auctioned goods is often difficult for amateurs, in particular, in Internet auctions. However, experts can correctly judge the quality of goods. In this situation, it is difficult to make experts tell the truth and attain an efficient allocation, since experts have a clear advantage over amateurs and they would not reveal their valuable information without some reward. In our previous work, we have succeeded in developing such auction protocols under the following two cases: (1) the case of a single-unit auction among experts and amateurs, and (2) the case of a combinatorial auction among single-skilled experts and amateurs. In this paper, we focus on versatile experts. Versatile experts have an interest in, and expert knowledge on the qualities of several goods. In the case of versatile experts, there would be several problems, e.g., free riding problems, if we simply extended the previous VCG-style auction protocol. Thus, in this paper, we employ PORF (price-oriented, rationing-free) protocol for designing our new protocol to realize a strategy-proof auction protocol for experts. In the protocol, the dominant strategy for experts is truth-telling. Also, for amateurs, truth-telling is the best response when two or more experts select the dominant strategy. Furthermore, the protocol is false-name-proof.

  14. Models from experiments: combinatorial drug perturbations of cancer cells

    PubMed Central

    Nelander, Sven; Wang, Weiqing; Nilsson, Björn; She, Qing-Bai; Pratilas, Christine; Rosen, Neal; Gennemark, Peter; Sander, Chris

    2008-01-01

    We present a novel method for deriving network models from molecular profiles of perturbed cellular systems. The network models aim to predict quantitative outcomes of combinatorial perturbations, such as drug pair treatments or multiple genetic alterations. Mathematically, we represent the system by a set of nodes, representing molecular concentrations or cellular processes, a perturbation vector and an interaction matrix. After perturbation, the system evolves in time according to differential equations with built-in nonlinearity, similar to Hopfield networks, capable of representing epistasis and saturation effects. For a particular set of experiments, we derive the interaction matrix by minimizing a composite error function, aiming at accuracy of prediction and simplicity of network structure. To evaluate the predictive potential of the method, we performed 21 drug pair treatment experiments in a human breast cancer cell line (MCF7) with observation of phospho-proteins and cell cycle markers. The best derived network model rediscovered known interactions and contained interesting predictions. Possible applications include the discovery of regulatory interactions, the design of targeted combination therapies and the engineering of molecular biological networks. PMID:18766176

  15. Combinatorial mutagenesis and selection to understand and improve yeast promoters.

    PubMed

    Berg, Laila; Strand, Trine Aakvik; Valla, Svein; Brautaset, Trygve

    2013-01-01

    Microbial promoters are important targets both for understanding the global gene expression and developing genetic tools for heterologous expression of proteins and complex biosynthetic pathways. Previously, we have developed and used combinatorial mutagenesis methods to analyse and improve bacterial expression systems. Here, we present for the first time an analogous strategy for yeast. Our model promoter is the strong and inducible P AOX1 promoter in methylotrophic Pichia pastoris. The Zeocin resistance gene was applied as a valuable reporter for mutant P AOX1 promoter activity, and we used an episomal plasmid vector to ensure a constant reporter gene dosage in the yeast host cells. This novel design enabled direct selection for colonies of recombinant cells with altered Zeocin tolerance levels originating solely from randomly introduced point mutations in the P AOX1 promoter DNA sequence. We demonstrate that this approach can be used to select for P AOX1 promoter variants with abolished glucose repression in large mutant libraries. We also selected P AOX1 promoter variants with elevated expression level under induced conditions. The properties of the selected P AOX1 promoter variants were confirmed by expressing luciferase as an alternative reporter gene. The tools developed here should be useful for effective screening, characterization, and improvement of any yeast promoters.

  16. HIV eradication: combinatorial approaches to activate latent viruses.

    PubMed

    De Crignis, Elisa; Mahmoudi, Tokameh

    2014-11-21

    The concept of eradication of the Human Immune Deficiency Virus (HIV) from infected patients has gained much attention in the last few years. While combination Anti-Retroviral Therapy (c-ART) has been extremely effective in suppressing viral replication, it is not curative. This is due to the presence of a reservoir of latent HIV infected cells, which persist in the presence of c-ART. Recently, pharmaceutical approaches have focused on the development of molecules able to induce HIV-1 replication from latently infected cells in order to render them susceptible to viral cytopathic effects and host immune responses. Alternative pathways and transcription complexes function to regulate the activity of the HIV promoter and might serve as molecular targets for compounds to activate latent HIV. A combined therapy coupling various depressors and activators will likely be the most effective in promoting HIV replication while avoiding pleiotropic effects at the cellular level. Moreover, in light of differences among HIV subtypes and variability in integration sites, the combination of multiple agents targeting multiple pathways will increase likelihood of therapeutic effectiveness and prevent mutational escape. This review provides an overview of the mechanisms that can be targeted to induce HIV activation focusing on potential combinatorial approaches.

  17. A combinatorial strategy for treating KRAS mutant lung cancer

    PubMed Central

    Manchado, Eusebio; Weissmueller, Susann; Morris, John P.; Chen, Chi-Chao; Wullenkord, Ramona; Lujambio, Amaia; de Stanchina, Elisa; Poirier, John T.; Gainor, Justin F.; Corcoran, Ryan B.; Engelman, Jeffrey A.; Rudin, Charles M.; Rosen, Neal; Lowe, Scott W.

    2016-01-01

    Therapeutic targeting of KRAS-mutant lung adenocarcinoma represents a major goal of clinical oncology. KRAS itself has proven difficult to inhibit, and the effectiveness of agents that target key KRAS effectors has been thwarted by activation of compensatory or parallel pathways that limit their efficacy as single agents. Here we take a systematic approach towards identifying combination targets for trametinib, an FDA-approved MEK inhibitor that acts downstream of KRAS to suppress signaling through the mitogen-activated protein kinase (MAPK) cascade. Informed by a short-hairpin RNA (shRNA) screen, we show that trametinib provokes a compensatory response involving the fibroblast growth factor receptor 1 (FGFR1) that leads to signaling rebound and adaptive drug resistance. As a consequence, genetic or pharmacologic inhibition of FGFR1 in combination with trametinib enhances tumor cell death in vitro and in vivo. This compensatory response shows distinct specificities – it is dominated by FGFR1 in KRAS mutant lung and pancreatic cancer cells, but is not activated or involves other mechanisms in KRAS wild-type lung and KRAS-mutant colon cancer cells. Importantly, KRAS-mutant lung cancer cells and patient tumors treated with trametinib show an increase in FRS2 phosphorylation, a biomarker of FGFR activation; this increase is abolished by FGFR1 inhibition and correlates with sensitivity to trametinib and FGFR inhibitor combinations. These results demonstrate that FGFR1 can mediate adaptive resistance to trametinib and validate a combinatorial approach for treating KRAS-mutant lung cancer. PMID:27338794

  18. Systems and methods for the combinatorial synthesis of novel materials

    DOEpatents

    Wu, Xin Di; Wang, Youqi; Goldwasser, Isy

    2000-01-01

    Methods and apparatus for the preparation of a substrate having an array of diverse materials in predefined regions thereon. A substrate having an array of diverse materials thereon is generally prepared by depositing components of target materials to predefined regions on the substrate, and, in some embodiments, simultaneously reacting the components to form at least two resulting materials. In particular, the present invention provides novel masking systems and methods for applying components of target materials onto a substrate in a combinatorial fashion, thus creating arrays of resulting materials that differ slightly in composition, stoichiometry, and/or thickness. Using the novel masking systems of the present invention, components can be delivered to each site in a uniform distribution, or in a gradient of stoichiometries, thicknesses, compositions, etc. Resulting materials which can be prepared using the methods and apparatus of the present invention include, for example, covalent network solids, ionic solids and molecular solids. Once prepared, these resulting materials can be screened sequentially, or in parallel, for useful properties including, for example, electrical, thermal, mechanical, morphological, optical, magnetic, chemical and other properties.

  19. Chemistry Rocks: Redox Chemistry as a Geologic Tool.

    ERIC Educational Resources Information Center

    Burns, Mary Sue

    2001-01-01

    Applies chemistry to earth science, uses rocks in chemistry laboratories, and teaches about transition metal chemistry, oxidation states, and oxidation-reduction reactions from firsthand experiences. (YDS)

  20. Surface characteristics and protein adsorption on combinatorial binary Ti-M (Cr, Al, Ni) and Al-M (Ta, Zr) library films.

    PubMed

    Bai, Zhijun; Filiaggi, M J; Sanderson, R J; Lohstreter, L B; McArthur, M A; Dahn, J R

    2010-02-01

    Systematic studies of protein adsorption onto metallic biomaterial surfaces are generally lacking. Here, combinatorial binary library films with compositional gradients of Ti(1-x)Cr(x), Ti(1-x)Al(x), Ti(1-x)Ni(x) and Al(1-x)Ta(x), (0 chemistry, film microstructure, and surface roughness were subsequently correlated to fibrinogen or albumin adsorption measured using a high throughput wavelength dispersive spectroscopy technique. X-ray diffraction revealed these binary films to have crystalline phases present primarily at either extreme of the compositional library and an amorphous zone dominating along the gradient. These mirror-like films were generally found by atomic force microscopy to have a roughness of less than 8 nm, with any relative increases in roughness consistent with the development of crystalline phases. Surface chemistry by quantitative high-resolution X-ray photoelectron spectroscopy differed significantly from bulk film composition as measured by electron microprobe, with TiO(2) and Al(2)O(3) preferentially forming on the binary film surfaces. Correspondingly, protein adsorption onto these films closely correlated with their surface oxide fractions. Aluminum deposited as either a constant-composition film or as part of a binary library consistently adsorbed the least amount of albumin and fibrinogen, with alumina-enrichment of the surface oxide correlating with this adsorption. Overall, this combinatorial materials approach coupled with high-throughput surface analytical methods provides an efficient method of screening potential metallic biomaterials that may enable as well systematic studies of surface properties driving protein adsorption on these metal / metal oxide systems.

  1. Thermal Sensor Arrays for The Combinatorial Analysis of Thin Films

    NASA Astrophysics Data System (ADS)

    McCluskey, Patrick James

    2011-12-01

    Membrane-based thermal sensor arrays were developed for the high-throughput analysis of the thermophysical properties of thin films. The continuous growth of integrated circuits and microelectromechanical systems, as well as the development of functional materials and the optimization of materials properties, have produced the need for instruments capable of fast materials screening and analysis at reduced length scales. Two instruments were developed based on a similar architecture, one to measure thermal transport properties and the other to perform calorimetry measurements. Both have the capability to accelerate the pace of materials development and understanding using combinatorial measurement methods. The shared architecture of the instruments consists of a silicon-based micromachined array of thermal sensors. Each sensor consists of a SiN X membrane and a W heating element that also serves as a temperature gauge. The array design allows the simultaneous creation of a library of thin film samples by various deposition techniques while systematically varying a parameter of interest across the device. The membrane-based sensors have little thermal mass making them extremely sensitive to changes in thermal energy. The nano-thermal transport array has an array of sensors optimized for sensitivity to heat loss. The heat loss is determined from the temperature response of the sensor to an applied current. An analytical model is used with a linear regression analysis to fit the thermal properties of the samples to the temperature response. The assumptions of the analytical model are validated with a finite element model. Measured thermal properties include specific heat, thermal effusivity, thermal conductivity, and emissivity. The technique is demonstrated by measuring the thermal transport properties of sputter deposited Cu multilayers with a total film thickness from 15 to 470 nm. The experimental results compare well to a theory based on electronic thermal

  2. Deciphering the combinatorial architecture of a Drosophila homeotic gene enhancer

    PubMed Central

    Drewell, Robert A.; Nevarez, Michael J.; Kurata, Jessica S.; Winkler, Lauren N.; Li, Lily; Dresch, Jacqueline M.

    2013-01-01

    Summary In Drosophila, the 330 kb bithorax complex regulates cellular differentiation along the anterio-posterior axis during development in the thorax and abdomen and is comprised of three homeotic genes: Ultrabithorax, abdominal-A, and Abdominal-B. The expression of each of these genes is in turn controlled through interactions between transcription factors and a number of cis-regulatory modules in the neighboring intergenic regions. In this study, we examine how the sequence architecture of transcription factor binding sites mediates the functional activity of one of these cis-regulatory modules. Using computational, mathematical modeling and experimental molecular genetic approaches we investigate the IAB7b enhancer, which regulates Abdominal-B expression specifically in the presumptive seventh and ninth abdominal segments of the early embryo. A cross-species comparison of the IAB7b enhancer reveals an evolutionarily conserved signature motif containing two FUSHI-TARAZU activator transcription factor binding sites. We find that the transcriptional repressors KNIRPS, KRUPPEL and GIANT are able to restrict reporter gene expression to the posterior abdominal segments, using different molecular mechanisms including short-range repression and competitive binding. Additionally, we show the functional importance of the spacing between the two FUSHI-TARAZU binding sites and discuss the potential importance of cooperativity for transcriptional activation. Our results demonstrate that the transcriptional output of the IAB7b cis-regulatory module relies on a complex set of combinatorial inputs mediated by specific transcription factor binding and that the sequence architecture at this enhancer is critical to maintain robust regulatory function. PMID:24514265

  3. Development of a large peptoid–DOTA combinatorial library

    PubMed Central

    Singh, Jaspal; Lopes, Daniel

    2016-01-01

    Abstract Conventional one‐bead one‐compound (OBOC) library synthesis is typically used to identify molecules with therapeutic value. The design and synthesis of OBOC libraries that contain molecules with imaging or even potentially therapeutic and diagnostic capacities (e.g. theranostic agents) has been overlooked. The development of a therapeutically active molecule with a built‐in imaging component for a certain target is a daunting task, and structure‐based rational design might not be the best approach. We hypothesize to develop a combinatorial library with potentially therapeutic and imaging components fused together in each molecule. Such molecules in the library can be used to screen, identify, and validate as direct theranostic candidates against targets of interest. As the first step in achieving that aim, we developed an on‐bead library of 153,600 Peptoid–DOTA compounds in which the peptoids are the target‐recognizing and potentially therapeutic components and the DOTA is the imaging component. We attached the DOTA scaffold to TentaGel beads using one of the four arms of DOTA, and we built a diversified 6‐mer peptoid library on the remaining three arms. We evaluated both the synthesis and the mass spectrometric sequencing capacities of the test compounds and of the final library. The compounds displayed unique ionization patterns including direct breakages of the DOTA scaffold into two units, allowing clear decoding of the sequences. Our approach provides a facile synthesis method for the complete on‐bead development of large peptidomimetic–DOTA libraries for screening against biological targets for the identification of potential theranostic agents in the future. © 2016 The Authors. Biopolymers Published by Wiley Periodicals, Inc. Biopolymers (Pept Sci) 106: 673–684, 2016. PMID:27257968

  4. A Combinatorial Code for Splicing Silencing: UAGG and GGGG Motifs

    PubMed Central

    An, Ping; Burge, Christopher B

    2005-01-01

    Alternative pre-mRNA splicing is widely used to regulate gene expression by tuning the levels of tissue-specific mRNA isoforms. Few regulatory mechanisms are understood at the level of combinatorial control despite numerous sequences, distinct from splice sites, that have been shown to play roles in splicing enhancement or silencing. Here we use molecular approaches to identify a ternary combination of exonic UAGG and 5′-splice-site-proximal GGGG motifs that functions cooperatively to silence the brain-region-specific CI cassette exon (exon 19) of the glutamate NMDA R1 receptor (GRIN1) transcript. Disruption of three components of the motif pattern converted the CI cassette into a constitutive exon, while predominant skipping was conferred when the same components were introduced, de novo, into a heterologous constitutive exon. Predominant exon silencing was directed by the motif pattern in the presence of six competing exonic splicing enhancers, and this effect was retained after systematically repositioning the two exonic UAGGs within the CI cassette. In this system, hnRNP A1 was shown to mediate silencing while hnRNP H antagonized silencing. Genome-wide computational analysis combined with RT-PCR testing showed that a class of skipped human and mouse exons can be identified by searches that preserve the sequence and spatial configuration of the UAGG and GGGG motifs. This analysis suggests that the multi-component silencing code may play an important role in the tissue-specific regulation of the CI cassette exon, and that it may serve more generally as a molecular language to allow for intricate adjustments and the coordination of splicing patterns from different genes. PMID:15828859

  5. Combinatorial Contextualization of Peptidic Epitopes for Enhanced Cellular Immunity

    PubMed Central

    Ito, Masaki; Hayashi, Kazumi; Adachi, Eru; Minamisawa, Tamiko; Homma, Sadamu; Koido, Shigeo; Shiba, Kiyotaka

    2014-01-01

    Invocation of cellular immunity by epitopic peptides remains largely dependent on empirically developed protocols, such as interfusion of aluminum salts or emulsification using terpenoids and surfactants. To explore novel vaccine formulation, epitopic peptide motifs were co-programmed with structural motifs to produce artificial antigens using our “motif-programming” approach. As a proof of concept, we used an ovalbumin (OVA) system and prepared an artificial protein library by combinatorially polymerizing MHC class I and II sequences from OVA along with a sequence that tends to form secondary structures. The purified endotoxin-free proteins were then examined for their ability to activate OVA-specific T-cell hybridoma cells after being processed within dendritic cells. One clone, F37A (containing three MHC I and two MHC II OVA epitopes), possessed a greater ability to evoke cellular immunity than the native OVA or the other artificial antigens. The sensitivity profiles of drugs that interfered with the F37A uptake differed from those of the other artificial proteins and OVA, suggesting that alteration of the cross-presentation pathway is responsible for the enhanced immunogenicity. Moreover, F37A, but not an epitopic peptide, invoked cellular immunity when injected together with monophosphoryl lipid A (MPL), and retarded tumor growth in mice. Thus, an artificially synthesized protein antigen induced cellular immunity in vivo in the absence of incomplete Freund's adjuvant or aluminum salts. The method described here could be potentially used for developing vaccines for such intractable ailments as AIDS, malaria and cancer, ailments in which cellular immunity likely play a crucial role in prevention and treatment. PMID:25343355

  6. Immobilized OBOC combinatorial bead array to facilitate multiplicative screening.

    PubMed

    Xiao, Wenwu; Bononi, Fernanda C; Townsend, Jared; Li, Yuanpei; Liu, Ruiwu; Lam, Kit S

    2013-07-01

    One-bead-one-compound (OBOC) combinatorial library screening has been broadly utilized for the last two decades to identify small molecules, peptides or peptidomimetics targeting variable screening probes such as cell surface receptors, bacteria, protein kinases, phosphatases, proteases etc. In previous screening methods, library beads were suspended in solution and screened against one single probe. Only the positive beads were tracked and isolated for additional screens and finally selected for chemical decoding. During this process, the remaining negative beads were not tracked and discarded. Here we report a novel bead immobilization method such that a bead library array can be conveniently prepared and screened in its entirety, sequentially many times with a series of distinct probes. This method not only allows us to increase the screening efficiency but also permits us to determine the binding profile of each and every library bead against a large number of target receptors. As proof of concept, we serially screened a random OBOC disulfide containing cyclic heptapeptide library with three water soluble dyes as model probes: malachite green, bromocresol purple and indigo carmine. This multiplicative screening approach resulted in a rapid determination of the binding profile of each and every bead respective to each of the three dyes. Beads that interacted with malachite green only, bromocresol purple only, or both indigo carmine and bromocresol purple were isolated, and their peptide sequences were determined with microsequencer. Ultimately, the novel OBOC multiplicative screening approach could play a key role in the enhancement of existing on-bead assays such as whole cell binding, bacteria binding, protein binding, posttranslational modifications etc. with increased efficiency, capacity, and specificity.

  7. Fabrication and Characterization of Novel Refractory Coatings Using Combinatorial Nanocalorimetry

    DTIC Science & Technology

    2015-07-21

    JM Gregoire, PJ McCluskey, JJ Vlassak, A scanning AC calorimetry technique for the analysis of nano -scale quantities of materials Review of...of Physical Chemistry C 118, 21192 (2014) 8. K Xiao, D Lee, JJ Vlassak, Kinetics of solid-gas reactions characterized by scanning AC nano ...rates from 101 to 104 K/s studied by combining scanning AC and DC nano -calorimetry techniques, Thermochimica Acta 603, 29 (2015) 10. PJ McCluskey, K

  8. USSR Report, Chemistry.

    DTIC Science & Technology

    2007-11-02

    This chemistry Report from the USSR contains articles mainly on Adsorption, Analytical Chemistry, Biochemistry, Catalysis, Chemical Industry, Coal ... Gasification , Electrochemistry, Fertilizers, Food Technology, Inorganic Compounds, Nitrogen Compounds and Organometallic Compounds.

  9. Chemistry for Potters.

    ERIC Educational Resources Information Center

    Denio, Allen A.

    1980-01-01

    Relates pottery making to chemistry by providing chemical information about clay, its origin, composition, properties, and changes that occur during firing; also describes glaze compositions, examples of redox chemistry, salt glazing, crystalline glazes, and problems in toxicity. (CS)

  10. Organometallic Chemistry of Molybdenum.

    ERIC Educational Resources Information Center

    Lucas, C. Robert; Walsh, Kelly A.

    1987-01-01

    Suggests ways to avoid some of the problems students have learning the principles of organometallic chemistry. Provides a description of an experiment used in a third-year college chemistry laboratory on molybdenum. (TW)

  11. Special Report: Brain Chemistry.

    ERIC Educational Resources Information Center

    Krassner, Michael B.

    1983-01-01

    Chemical actions in the brain result in cognitive, emotional, neuroendocrine, neuromuscular, and/or neurocirculatory effects. Developments in understanding brain chemistry are discussed, considering among others, neurotransmitter chemistry, neuropeptides, drugs and the brain, antidepressants, and actions of minor tranquilizers. (JN)

  12. Environmental chemistry: Volume A

    SciTech Connect

    Yen, T.F.

    1999-08-01

    This is an extensive introduction to environmental chemistry for engineering and chemical professionals. The contents of Volume A include a brief review of basic chemistry prior to coverage of litho, atmo, hydro, pedo, and biospheres.

  13. Invited article: The fast readout low noise camera as a versatile x-ray detector for time resolved dispersive extended x-ray absorption fine structure and diffraction studies of dynamic problems in materials science, chemistry, and catalysis

    NASA Astrophysics Data System (ADS)

    Labiche, Jean-Claude; Mathon, Olivier; Pascarelli, Sakura; Newton, Mark A.; Ferre, Gemma Guilera; Curfs, Caroline; Vaughan, Gavin; Homs, Alejandro; Carreiras, David Fernandez

    2007-09-01

    Originally conceived and developed at the European Synchrotron Radiation Facility (ESRF) as an "area" detector for rapid x-ray imaging studies, the fast readout low noise (FReLoN) detector of the ESRF [J.-C. Labiche, ESRF Newsletter 25, 41 (1996)] has been demonstrated to be a highly versatile and unique detector. Charge coupled device (CCD) cameras at present available on the public market offer either a high dynamic range or a high readout speed. A compromise between signal dynamic range and readout speed is always sought. The parameters of the commercial cameras can sometimes be tuned, in order to better fulfill the needs of specific experiments, but in general these cameras have a poor duty cycle (i.e., the signal integration time is much smaller than the readout time). In order to address scientific problems such as time resolved experiments at the ESRF, a FReLoN camera has been developed by the Instrument Support Group at ESRF. This camera is a low noise CCD camera that combines high dynamic range, high readout speed, accuracy, and improved duty cycle in a single image. In this paper, we show its application in a quasi-one-dimensional sense to dynamic problems in materials science, catalysis, and chemistry that require data acquisition on a time scale of milliseconds or a few tens of milliseconds. It is demonstrated that in this mode the FReLoN can be applied equally to the investigation of rapid changes in long range order (via diffraction) and local order (via energy dispersive extended x-ray absorption fine structure) and in situations of x-ray hardness and flux beyond the capacity of other detectors.

  14. Invited article: The fast readout low noise camera as a versatile x-ray detector for time resolved dispersive extended x-ray absorption fine structure and diffraction studies of dynamic problems in materials science, chemistry, and catalysis

    SciTech Connect

    Labiche, Jean-Claude; Mathon, Olivier; Pascarelli, Sakura; Newton, Mark A.; Ferre, Gemma Guilera; Curfs, Caroline; Vaughan, Gavin; Homs, Alejandro; Carreiras, David Fernandez

    2007-09-15

    Originally conceived and developed at the European Synchrotron Radiation Facility (ESRF) as an 'area' detector for rapid x-ray imaging studies, the fast readout low noise (FReLoN) detector of the ESRF [J.-C. Labiche, ESRF Newsletter 25, 41 (1996)] has been demonstrated to be a highly versatile and unique detector. Charge coupled device (CCD) cameras at present available on the public market offer either a high dynamic range or a high readout speed. A compromise between signal dynamic range and readout speed is always sought. The parameters of the commercial cameras can sometimes be tuned, in order to better fulfill the needs of specific experiments, but in general these cameras have a poor duty cycle (i.e., the signal integration time is much smaller than the readout time). In order to address scientific problems such as time resolved experiments at the ESRF, a FReLoN camera has been developed by the Instrument Support Group at ESRF. This camera is a low noise CCD camera that combines high dynamic range, high readout speed, accuracy, and improved duty cycle in a single image. In this paper, we show its application in a quasi-one-dimensional sense to dynamic problems in materials science, catalysis, and chemistry that require data acquisition on a time scale of milliseconds or a few tens of milliseconds. It is demonstrated that in this mode the FReLoN can be applied equally to the investigation of rapid changes in long range order (via diffraction) and local order (via energy dispersive extended x-ray absorption fine structure) and in situations of x-ray hardness and flux beyond the capacity of other detectors.

  15. Combinatorial Chemical Bath Deposition of CdS Contacts for Chalcogenide Photovoltaics.

    PubMed

    Mokurala, Krishnaiah; Baranowski, Lauryn L; de Souza Lucas, Francisco W; Siol, Sebastian; van Hest, Maikel F A M; Mallick, Sudhanshu; Bhargava, Parag; Zakutayev, Andriy

    2016-09-12

    Contact layers play an important role in thin film solar cells, but new material development and optimization of its thickness is usually a long and tedious process. A high-throughput experimental approach has been used to accelerate the rate of research in photovoltaic (PV) light absorbers and transparent conductive electrodes, however the combinatorial research on contact layers is less common. Here, we report on the chemical bath deposition (CBD) of CdS thin films by combinatorial dip coating technique and apply these contact layers to Cu(In,Ga)Se2 (CIGSe) and Cu2ZnSnSe4 (CZTSe) light absorbers in PV devices. Combinatorial thickness steps of CdS thin films were achieved by removal of the substrate from the chemical bath, at regular intervals of time, and in equal distance increments. The trends in the photoconversion efficiency and in the spectral response of the PV devices as a function of thickness of CdS contacts were explained with the help of optical and morphological characterization of the CdS thin films. The maximum PV efficiency achieved for the combinatorial dip-coating CBD was similar to that for the PV devices processed using conventional CBD. The results of this study lead to the conclusion that combinatorial dip-coating can be used to accelerate the optimization of PV device performance of CdS and other candidate contact layers for a wide range of emerging absorbers.

  16. Combinatorial Chemical Bath Deposition of CdS Contacts for Chalcogenide Photovoltaics

    SciTech Connect

    Mokurala, Krishnaiah; Baranowski, Lauryn L.; de Souza Lucas, Francisco W.; Siol, Sebastian; van Hest, Maikel F. A. M.; Mallick, Sudhanshu; Bhargava, Parag; Zakutayev, Andriy

    2016-09-12

    Contact layers play an important role in thin film solar cells, but new material development and optimization of its thickness is usually a long and tedious process. A high-throughput experimental approach has been used to accelerate the rate of research in photovoltaic (PV) light absorbers and transparent conductive electrodes, however the combinatorial research on contact layers is less common. Here, we report on the chemical bath deposition (CBD) of CdS thin films by combinatorial dip coating technique and apply these contact layers to Cu(In,Ga)Se2 (CIGSe) and Cu2ZnSnSe4 (CZTSe) light absorbers in PV devices. Combinatorial thickness steps of CdS thin films were achieved by removal of the substrate from the chemical bath, at regular intervals of time, and in equal distance increments. The trends in the photoconversion efficiency and in the spectral response of the PV devices as a function of thickness of CdS contacts were explained with the help of optical and morphological characterization of the CdS thin films. The maximum PV efficiency achieved for the combinatorial dip-coating CBD was similar to that for the PV devices processed using conventional CBD. The results of this study lead to the conclusion that combinatorial dip-coating can be used to accelerate the optimization of PV device performance of CdS and other candidate contact layers for a wide range of emerging absorbers.

  17. Steam explosion and its combinatorial pretreatment refining technology of plant biomass to bio-based products.

    PubMed

    Chen, Hong-Zhang; Liu, Zhi-Hua

    2015-06-01

    Pretreatment is a key unit operation affecting the refinery efficiency of plant biomass. However, the poor efficiency of pretreatment and the lack of basic theory are the main challenges to the industrial implementation of the plant biomass refinery. The purpose of this work is to review steam explosion and its combinatorial pretreatment as a means of overcoming the intrinsic characteristics of plant biomass, including recalcitrance, heterogeneity, multi-composition, and diversity. The main advantages of the selective use of steam explosion and other combinatorial pretreatments across the diversity of raw materials are introduced. Combinatorial pretreatment integrated with other unit operations is proposed as a means to exploit the high-efficiency production of bio-based products from plant biomass. Finally, several pilot- and demonstration-scale operations of the plant biomass refinery are described. Based on the principle of selective function and structure fractionation, and multi-level and directional composition conversion, an integrated process with the combinatorial pretreatments of steam explosion and other pretreatments as the core should be feasible and conform to the plant biomass refinery concept. Combinatorial pretreatments of steam explosion and other pretreatments should be further exploited based on the type and intrinsic characteristics of the plant biomass used, the bio-based products to be made, and the complementarity of the processes.

  18. School Chemistry vs. Chemistry in Research: An Exploratory Experiment.

    ERIC Educational Resources Information Center

    Habraken, Clarisse L.; Buijs, Wim; Borkent, Hens; Ligeon, Willy; Wender, Harry; Meijer, Marijn

    2001-01-01

    Reports on a study exploring why students are not studying chemistry. Three groups of graduating high school students and their chemistry teachers stayed at a research institute working on molecular modeling and wrote essays on school chemistry versus chemistry in research. Concludes that school chemistry does not convey today's chemistry in…

  19. AttoPhotoChemistry. Probing ultrafast electron dynamics by the induced nuclear motion: The prompt and delayed predissociation of N2

    NASA Astrophysics Data System (ADS)

    Muskatel, B. H.; Remacle, F.; Levine, R. D.

    2014-05-01

    Quantum mechanical wavepacket dynamics simulation that includes the nuclear motion exhibit a prompt, few fs, dissociation of electronically attosecond excited N2 in addition to the slow dissociation evident from spectral line broadening in well resolved spectra. The simulations show that nuclear motion can probe early times electron dynamics. The separation of time scales is mimicked by a model study fashioned like chemical kinetics of unimolecular dissociation. The physical origin of the separation into prompt and delayed decay is argued to be the same in the vibrational and the present case, namely that there are more bound than dissociative channels.

  20. Chemistry on Stamps.

    ERIC Educational Resources Information Center

    Schreck, James O.

    1986-01-01

    Suggests how postage stamps can be incorporated into chemistry teaching. Categories considered include emergence of chemistry as a science, metric system, atoms (and molecules and ions), stoichiometry, energy relationships in chemical systems, chemical bonding, nuclear chemistry, biochemistry, geochemistry, matter (gases, liquids, and solids),…