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Sample records for rational combinatorial library

  1. Rationally reduced libraries for combinatorial pathway optimization minimizing experimental effort.

    Science.gov (United States)

    Jeschek, Markus; Gerngross, Daniel; Panke, Sven

    2016-03-31

    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.

  2. Tumor-targeting peptides from combinatorial libraries*

    Science.gov (United States)

    Liu, Ruiwu; Li, Xiaocen; Xiao, Wenwu; Lam, Kit S.

    2018-01-01

    Cancer is one of the major and leading causes of death worldwide. Two of the greatest challenges infighting cancer are early detection and effective treatments with no or minimum side effects. Widespread use of targeted therapies and molecular imaging in clinics requires high affinity, tumor-specific agents as effective targeting vehicles to deliver therapeutics and imaging probes to the primary or metastatic tumor sites. Combinatorial libraries such as phage-display and one-bead one-compound (OBOC) peptide libraries are powerful approaches in discovering tumor-targeting peptides. This review gives an overview of different combinatorial library technologies that have been used for the discovery of tumor-targeting peptides. Examples of tumor-targeting peptides identified from each combinatorial library method will be discussed. Published tumor-targeting peptide ligands and their applications will also be summarized by the combinatorial library methods and their corresponding binding receptors. PMID:27210583

  3. Toward Chemical Implementation of Encoded Combinatorial Libraries

    DEFF Research Database (Denmark)

    Nielsen, John; Janda, Kim D.

    1994-01-01

    The recent application of "combinatorial libraries" to supplement existing drug screening processes might simplify and accelerate the search for new lead compounds or drugs. Recently, a scheme for encoded combinatorial chemistry was put forward to surmount a number of the limitations possessed...

  4. PIPERIDINE OLIGOMERS AND COMBINATORIAL LIBRARIES THEREOF

    DEFF Research Database (Denmark)

    1999-01-01

    The present invention relates to piperidine oligomers, methods for the preparation of piperidine oligomers and compound libraries thereof, and the use of piperidine oligomers as drug substances. The present invention also relates to the use of combinatorial libraries of piperidine oligomers...... in libraries (arrays) of compounds especially suitable for screening purposes....

  5. Dynamic combinatorial libraries : new opportunities in systems chemistry

    NARCIS (Netherlands)

    Hunt, Rosemary A. R.; Otto, Sijbren; Hunt, Rosemary A.R.

    2011-01-01

    Combinatorial chemistry is a tool for selecting molecules with special properties. Dynamic combinatorial chemistry started off aiming to be just that. However, unlike ordinary combinatorial chemistry, the interconnectedness of dynamic libraries gives them an extra dimension. An understanding of

  6. Recursive deconvolution of combinatorial chemical libraries.

    OpenAIRE

    Erb, E; Janda, K D; Brenner, S

    1994-01-01

    A recursive strategy that solves for the active members of a chemical library is presented. A pentapeptide library with an alphabet of Gly, Leu, Phe, and Tyr (1024 members) was constructed on a solid support by the method of split synthesis. One member of this library (NH2-Tyr-Gly-Gly-Phe-Leu) is a native binder to a beta-endorphin antibody. A variation of the split synthesis approach is used to build the combinatorial library. In four vials, a member of the library's alphabet is coupled to a...

  7. Dendrimer-based dynamic combinatorial libraries

    NARCIS (Netherlands)

    Chang, T.; Meijer, E.W.

    2005-01-01

    The aim of this project is to create water-sol. dynamic combinatorial libraries based upon dendrimer-guest complexes. The guest mols. are designed to bind to dendrimers using multiple secondary interactions, such as electrostatics and hydrogen bonding. We have been able to incorporate various guest

  8. DNA-Encoded Dynamic Combinatorial Chemical Libraries.

    Science.gov (United States)

    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. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  9. Development of a large peptoid-DOTA combinatorial library.

    Science.gov (United States)

    Singh, Jaspal; Lopes, Daniel; Gomika Udugamasooriya, D

    2016-09-01

    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. © 2016 The Authors. Biopolymers Published by Wiley Periodicals, Inc.

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

    Science.gov (United States)

    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

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

    OpenAIRE

    Soural, Miroslav; Bouillon, Isabelle; Krchňák, Viktor

    2008-01-01

    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.

  12. Dynamic combinatorial libraries: from exploring molecular recognition to systems chemistry.

    Science.gov (United States)

    Li, Jianwei; Nowak, Piotr; Otto, Sijbren

    2013-06-26

    Dynamic combinatorial chemistry (DCC) is a subset of combinatorial chemistry where the library members interconvert continuously by exchanging building blocks with each other. Dynamic combinatorial libraries (DCLs) are powerful tools for discovering the unexpected and have given rise to many fascinating molecules, ranging from interlocked structures to self-replicators. Furthermore, dynamic combinatorial molecular networks can produce emergent properties at systems level, which provide exciting new opportunities in systems chemistry. In this perspective we will highlight some new methodologies in this field and analyze selected examples of DCLs that are under thermodynamic control, leading to synthetic receptors, catalytic systems, and complex self-assembled supramolecular architectures. Also reviewed are extensions of the principles of DCC to systems that are not at equilibrium and may therefore harbor richer functional behavior. Examples include self-replication and molecular machines.

  13. Dynamic combinatorial libraries based on hydrogen-bonde molecular boxes

    NARCIS (Netherlands)

    Kerckhoffs, J.M.C.A.; Mateos timoneda, Miguel; Reinhoudt, David; Crego Calama, Mercedes

    2007-01-01

    This article describes two different types of dynamic combinatorial libraries of host and guest molecules. The first part of this article describes the encapsulation of alizarin trimer 2 a3 by dynamic mixtures of up to twenty different self-assembled molecular receptors together with the

  14. Balancing focused combinatorial libraries based on multiple GPCR ligands

    Science.gov (United States)

    Soltanshahi, Farhad; Mansley, Tamsin E.; Choi, Sun; Clark, Robert D.

    2006-08-01

    G-Protein coupled receptors (GPCRs) are important targets for drug discovery, and combinatorial chemistry is an important tool for pharmaceutical development. The absence of detailed structural information, however, limits the kinds of combinatorial design techniques that can be applied to GPCR targets. This is particularly problematic given the current emphasis on focused combinatorial libraries. By linking an incremental construction method (OptDesign) to the very fast shape-matching capability of ChemSpace, we have created an efficient method for designing targeted sublibraries that are topomerically similar to known actives. Multi-objective scoring allows consideration of multiple queries (actives) simultaneously. This can lead to a distribution of products skewed towards one particular query structure, however, particularly when the ligands of interest are quite dissimilar to one another. A novel pivoting technique is described which makes it possible to generate promising designs even under those circumstances. The approach is illustrated by application to some serotonergic agonists and chemokine antagonists.

  15. Multi-line split DNA synthesis: a novel combinatorial method to make high quality peptide libraries

    Directory of Open Access Journals (Sweden)

    Ueno Shingo

    2004-09-01

    Full Text Available Abstract Background We developed a method to make a various high quality random peptide libraries for evolutionary protein engineering based on a combinatorial DNA synthesis. Results A split synthesis in codon units was performed with mixtures of bases optimally designed by using a Genetic Algorithm program. It required only standard DNA synthetic reagents and standard DNA synthesizers in three lines. This multi-line split DNA synthesis (MLSDS is simply realized by adding a mix-and-split process to normal DNA synthesis protocol. Superiority of MLSDS method over other methods was shown. We demonstrated the synthesis of oligonucleotide libraries with 1016 diversity, and the construction of a library with random sequence coding 120 amino acids containing few stop codons. Conclusions Owing to the flexibility of the MLSDS method, it will be able to design various "rational" libraries by using bioinformatics databases.

  16. Fabrication and characterization of thin-film phosphor combinatorial libraries

    Science.gov (United States)

    Mordkovich, V. Z.; Jin, Zhengwu; Yamada, Y.; Fukumura, T.; Kawasaki, M.; Koinuma, H.

    2002-05-01

    The laser molecular beam epitaxy method was employed to fabricate thin-film combinatorial libraries of ZnO-based phosphors on different substrates. Fabrication of both pixel libraries, on the example of Fe-doped ZnO, and spread libraries, on the example of Eu-doped ZnO, has been demonstrated. Screening of the Fe-doped ZnO libraries led to the discovery of weak green cathodoluminescence with the maximum efficiency at the Fe content of 0.58 mol %. Screening of the Eu-doped ZnO libraries led to the discovery of unusual reddish-violet cathodoluminescence which is observed in a broad range of Eu concentration. No photoluminescence was registered in either system.

  17. A binary plasmid system for shuffling combinatorial antibody libraries.

    OpenAIRE

    Collet, T A; Roben, P; O'Kennedy, R; Barbas, C F; Burton, D R; Lerner, R A

    1992-01-01

    We have used a binary system of replicon-compatible plasmids to test the potential for promiscuous recombination of heavy and light chains within sets of human Fab fragments isolated from combinatorial antibody libraries. Antibody molecules showed a surprising amount of promiscuity in that a particular heavy chain could recombine with multiple light chains with retention of binding to a protein antigen. The degree to which a given heavy chain productively paired with any light chain to bind a...

  18. Design of diversity and focused combinatorial libraries in drug discovery.

    Science.gov (United States)

    Young, S Stanley; Ge, Nanxiang

    2004-05-01

    Using well-characterized chemical reactions and readily available monomers, chemists are able to create sets of compounds, termed libraries, which are useful in drug discovery processes. The design of combinatorial chemical libraries can be complex and there has been much information recently published offering suggestions on how the design process can be carried out. This review focuses on literature with the goal of organizing current thinking. At this point in time, it is clear that benchmarking of current suggested methods is required as opposed to further new methods.

  19. Solid-Phase Synthesis of Small Molecule Libraries using Double Combinatorial Chemistry

    DEFF Research Database (Denmark)

    Nielsen, John; Jensen, Flemming R.

    1997-01-01

    The first synthesis of a combinatorial library using double combinatorial chemistry is presented. Coupling of unprotected Fmoc-tyrosine to the solid support was followed by Mitsunobu O-alkylation. Introduction of a diacid linker yields a system in which the double combinatorial step can be demons......The first synthesis of a combinatorial library using double combinatorial chemistry is presented. Coupling of unprotected Fmoc-tyrosine to the solid support was followed by Mitsunobu O-alkylation. Introduction of a diacid linker yields a system in which the double combinatorial step can...

  20. Solid-Phase Synthesis of Small Molecule Libraries using Double Combinatorial Chemistry

    DEFF Research Database (Denmark)

    Nielsen, John; Jensen, Flemming R.

    1997-01-01

    The first synthesis of a combinatorial library using double combinatorial chemistry is presented. Coupling of unprotected Fmoc-tyrosine to the solid support was followed by Mitsunobu O-alkylation. Introduction of a diacid linker yields a system in which the double combinatorial step can be demons...

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

    Science.gov (United States)

    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. PMID:26355961

  2. A binary plasmid system for shuffling combinatorial antibody libraries.

    Science.gov (United States)

    Collet, T A; Roben, P; O'Kennedy, R; Barbas, C F; Burton, D R; Lerner, R A

    1992-11-01

    We have used a binary system of replicon-compatible plasmids to test the potential for promiscuous recombination of heavy and light chains within sets of human Fab fragments isolated from combinatorial antibody libraries. Antibody molecules showed a surprising amount of promiscuity in that a particular heavy chain could recombine with multiple light chains with retention of binding to a protein antigen. The degree to which a given heavy chain productively paired with any light chain to bind antigen varied from 43% to 100% and depended strongly on the heavy-chain sequence. Such productive crosses resulted in a set of Fab fragments of similar apparent binding constants, which seemed to differ mainly in the amount of active Fab fragment produced in the bacterial cell. The dominance of the heavy chain in the antibody-antigen interaction was further explored in a set of directed crosses, in which heavy and light chains derived from antigen-specific clones were crossed with nonrelated heavy and light chains. In these crosses, an Fab fragment retained antigen binding only if it contained a heavy chain from an antigen-specific clone. In no case did the light chain confer detectable affinity when paired with indifferent heavy chains. The surprising promiscuity of heavy chains has ramifications for the evaluation of the diversity of combinatorial libraries made against protein antigens and should allow the combination of one such promiscuous heavy chain with an engineered light chain to form an Fab fragment carrying synthetic cofactors to assist in antibody catalysis.

  3. Engineering of Immunoglobulin Fc Heterodimers Using Yeast Surface-Displayed Combinatorial Fc Library Screening.

    Directory of Open Access Journals (Sweden)

    Hye-Ji Choi

    Full Text Available Immunoglobulin Fc heterodimers, which are useful scaffolds for the generation of bispecific antibodies, have been mostly generated through structure-based rational design methods that introduce asymmetric mutations into the CH3 homodimeric interface to favor heterodimeric Fc formation. Here, we report an approach to generate heterodimeric Fc variants through directed evolution combined with yeast surface display. We developed a combinatorial heterodimeric Fc library display system by mating two haploid yeast cell lines, one haploid cell line displayed an Fc chain library (displayed FcCH3A with mutations in one CH3 domain (CH3A on the yeast cell surface, and the other cell line secreted an Fc chain library (secreted FcCH3B with mutations in the other CH3 domain (CH3B. In the mated cells, secreted FcCH3B is displayed on the cell surface through heterodimerization with the displayed FcCH3A, the detection of which enabled us to screen the library for heterodimeric Fc variants. We constructed combinatorial heterodimeric Fc libraries with simultaneous mutations in the homodimer-favoring electrostatic interaction pairs K370-E357/S364 or D399-K392/K409 at the CH3 domain interface. High-throughput screening of the libraries using flow cytometry yielded heterodimeric Fc variants with heterodimer-favoring CH3 domain interface mutation pairs, some of them showed high heterodimerization yields (~80-90% with previously unidentified CH3 domain interface mutation pairs, such as hydrogen bonds and cation-π interactions. Our study provides a new approach for engineering Fc heterodimers that could be used to engineer other heterodimeric protein-protein interactions through directed evolution combined with yeast surface display.

  4. Mixture-based combinatorial libraries from small individual peptide libraries: a case study on α1-antitrypsin deficiency.

    Science.gov (United States)

    Chang, Yi-Pin; Chu, Yen-Ho

    2014-05-16

    The design, synthesis and screening of diversity-oriented peptide libraries using a "libraries from libraries" strategy for the development of inhibitors of α1-antitrypsin deficiency are described. The major buttress of the biochemical approach presented here is the use of well-established solid-phase split-and-mix method for the generation of mixture-based libraries. The combinatorial technique iterative deconvolution was employed for library screening. While molecular diversity is the general consideration of combinatorial libraries, exquisite design through systematic screening of small individual libraries is a prerequisite for effective library screening and can avoid potential problems in some cases. This review will also illustrate how large peptide libraries were designed, as well as how a conformation-sensitive assay was developed based on the mechanism of the conformational disease. Finally, the combinatorially selected peptide inhibitor capable of blocking abnormal protein aggregation will be characterized by biophysical, cellular and computational methods.

  5. Device for preparing combinatorial libraries in powder metallurgy.

    Science.gov (United States)

    Yang, Shoufeng; Evans, Julian R G

    2004-01-01

    This paper describes a powder-metering, -mixing, and -dispensing mechanism that can be used as a method for producing large numbers of samples for metallurgical evaluation or electrical or mechanical testing from multicomponent metal and cermet powder systems. It is designed to make use of the same commercial powders that are used in powder metallurgy and, therefore, to produce samples that are faithful to the microstructure of finished products. The particle assemblies produced by the device could be consolidated by die pressing, isostatic pressing, laser sintering, or direct melting. The powder metering valve provides both on/off and flow rate control of dry powders in open capillaries using acoustic vibration. The valve is simple and involves no relative movement, avoiding seizure with fine powders. An orchestra of such valves can be arranged on a building platform to prepare multicomponent combinatorial libraries. As with many combinatorial devices, identification and evaluation of sources of mixing error as a function of sample size is mandatory. Such an analysis is presented.

  6. Simultaneous Disulfide and Boronic Acid Ester Exchange in Dynamic Combinatorial Libraries

    Directory of Open Access Journals (Sweden)

    Sanna L. Diemer

    2015-09-01

    Full Text Available Dynamic combinatorial chemistry has emerged as a promising tool for the discovery of complex receptors in supramolecular chemistry. At the heart of dynamic combinatorial chemistry are the reversible reactions that enable the exchange of building blocks between library members in dynamic combinatorial libraries (DCLs ensuring thermodynamic control over the system. If more than one reversible reaction operates in a single dynamic combinatorial library, the complexity of the system increases dramatically, and so does its possible applications. One can imagine two reversible reactions that operate simultaneously or two reversible reactions that operate independently. Both these scenarios have advantages and disadvantages. In this contribution, we show how disulfide exchange and boronic ester transesterification can function simultaneous in dynamic combinatorial libraries under appropriate conditions. We describe the detailed studies necessary to establish suitable reaction conditions and highlight the analytical techniques appropriate to study this type of system.

  7. Rational and combinatorial engineering of the glucan synthesizing enzyme amylosucrase

    DEFF Research Database (Denmark)

    Albenne, C.; Van Der Veen, B.A.; Potocki-Véronèse, G.

    2003-01-01

    Rational engineering of amylosucrase required detailed investigations of the molecular basis of catalysis. Biochemical characterization of the enzyme coupled to structural analyses enabled the polymerization mechanism to be elucidated. This provided key information for successfully changing amylo...

  8. Solid-phase synthesis and screening of N-acylated polyamine (NAPA) combinatorial libraries for protein binding.

    Science.gov (United States)

    Iera, Jaclyn A; Jenkins, Lisa M Miller; Kajiyama, Hiroshi; Kopp, Jeffrey B; Appella, Daniel H

    2010-11-15

    Inhibitors for protein-protein interactions are challenging to design, in part due to the unique and complex architectures of each protein's interaction domain. Most approaches to develop inhibitors for these interactions rely on rational design, which requires prior structural knowledge of the target and its ligands. In the absence of structural information, a combinatorial approach may be the best alternative to finding inhibitors of a protein-protein interaction. Current chemical libraries, however, consist mostly of molecules designed to inhibit enzymes. In this manuscript, we report the synthesis and screening of a library based on an N-acylated polyamine (NAPA) scaffold that we designed to have specific molecular features necessary to inhibit protein-protein interactions. Screens of the library identified a member with favorable binding properties to the HIV viral protein R (Vpr), a regulatory protein from HIV, that is involved in numerous interactions with other proteins critical for viral replication. Published by Elsevier Ltd.

  9. Metal-ion induced amplification of three receptors from dynamic combinatorial libraries of peptide-hydrazones

    NARCIS (Netherlands)

    Roberts, Sarah L.; Furlan, Ricardo L.E.; Otto, Sijbren; Sanders, Jeremy K.M.

    2003-01-01

    Three building blocks of general structure (MeO)2CH–aromatic linker–Pro–amino acid–NHNH2 have been prepared and tested in acid-catalysed dynamic combinatorial libraries. Exposure of these libraries to LiI and NaI led to the amplification of three macrocyclic pseudopeptide receptors. The receptors

  10. Design and spectroscopic reflectometry characterization of pulsed laser deposition combinatorial libraries

    International Nuclear Information System (INIS)

    Schenck, Peter K.; Bassim, Nabil D.; Otani, Makoto; Oguchi, Hiroyuki; Green, Martin L.

    2007-01-01

    The goal of the design of pulsed laser deposition (PLD) combinatorial library films is to optimize the compositional coverage of the films while maintaining a uniform thickness. The deposition pattern of excimer laser PLD films can be modeled with a bimodal cos n distribution. Deposited films were characterized using a spectroscopic reflectometer (250-1000 nm) to map the thickness of both single composition calibration films and combinatorial library films. These distribution functions were used to simulate the composition and thickness of multiple target combinatorial library films. The simulations were correlated with electron-probe microanalysis wavelength-dispersive spectroscopy (EPMA-WDS) composition maps. The composition and thickness of the library films can be fine-tuned by adjusting the laser spot size, fluence, background gas pressure, target geometry and other processing parameters which affect the deposition pattern. Results from compositionally graded combinatorial library films of the ternary system Al 2 O 3 -HfO 2 -Y 2 O 3 are discussed

  11. Combinatorial chemistry

    DEFF Research Database (Denmark)

    Nielsen, John

    1994-01-01

    An overview of combinatorial chemistry is presented. Combinatorial chemistry, sometimes referred to as `irrational drug design,' involves the generation of molecular diversity. The resulting chemical library is then screened for biologically active compounds.......An overview of combinatorial chemistry is presented. Combinatorial chemistry, sometimes referred to as `irrational drug design,' involves the generation of molecular diversity. The resulting chemical library is then screened for biologically active compounds....

  12. Discovery of DNA repair inhibitors by combinatorial library profiling

    Science.gov (United States)

    Moeller, Benjamin J.; Sidman, Richard L.; Pasqualini, Renata; Arap, Wadih

    2011-01-01

    Small molecule inhibitors of DNA repair are emerging as potent and selective anti-cancer therapies, but the sheer magnitude of the protein networks involved in DNA repair processes poses obstacles to discovery of effective candidate drugs. To address this challenge, we used a subtractive combinatorial selection approach to identify a panel of peptide ligands that bind DNA repair complexes. Supporting the concept that these ligands have therapeutic potential, we show that one selected peptide specifically binds and non-competitively inactivates DNA-PKcs, a protein kinase critical in double-strand DNA break repair. In doing so, this ligand sensitizes BRCA-deficient tumor cells to genotoxic therapy. Our findings establish a platform for large-scale parallel screening for ligand-directed DNA repair inhibitors, with immediate applicability to cancer therapy. PMID:21343400

  13. Tailored Polymer-Supported Templates in Dynamic Combinatorial Libraries : Simultaneous Selection, Amplification and Isolation of Synthetic Receptors

    NARCIS (Netherlands)

    Besenius, Pol; Cormack, Peter A.G.; Liu, Jingyuan; Otto, Sijbren; Sanders, Jeremy K.M.; Sherrington, David C.

    2008-01-01

    The thermodynamically controlled synthesis and isolation of macrocyclic receptors from dynamic combinatorial libraries has been achieved in a single step using a polymer-supported template. The templates were cinchona alkaloids which show interesting enantio- and diastereoselective molecular

  14. Asymmetric proteome equalization of the skeletal muscle proteome using a combinatorial hexapeptide library.

    Directory of Open Access Journals (Sweden)

    Jenny Rivers

    Full Text Available 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.

  15. Combinatorial Dansyl Library and its Applications to pH-Responsive Probes.

    Science.gov (United States)

    Hong, Seong Cheol; Murale, Dhiraj P; Lee, Jun-Seok

    2016-01-01

    Herein, we report the first 48-membered, dansyl-based, combinatorial fluorescent library. From the electronic and structural properties of the probes, we analyzed their optical properties and chemical yields, with an average of 49 %. The molecules were examined for their pH responses, and DS-2 and DS-45 showed blue-shifts, whereas DS-7 and DS-40 showed red-shifts in wavelength with increasing pH. Finally, cell permeability was investigated by treating SNU-2292 cells. Our results demonstrate the potential application of this library in biosensors, bio-imaging and pH indicators.

  16. Construction of a virtual combinatorial library using SMILES strings to discover potential structure-diverse PPAR modulators.

    Science.gov (United States)

    Liao, Chenzhong; Liu, Bing; Shi, Leming; Zhou, Jiaju; Lu, Xian-Ping

    2005-07-01

    Based on the structural characters of PPAR modulators, a virtual combinatorial library containing 1226,625 compounds was constructed using SMILES strings. Selected ADME filters were employed to compel compounds having poor drug-like properties from this library. This library was converted to sdf and mol2 files by CONCORD 4.0, and was then docked to PPARgamma by DOCK 4.0 to identify new chemical entities that may be potential drug leads against type 2 diabetes and other metabolic diseases. The method to construct virtual combinatorial library using SMILES strings was further visualized by Visual Basic.net that can facilitate the needs of generating other type virtual combinatorial libraries.

  17. Template-based combinatorial enumeration of virtual compound libraries for lipids.

    Science.gov (United States)

    Sud, Manish; Fahy, Eoin; Subramaniam, Shankar

    2012-09-25

    A variety of software packages are available for the combinatorial enumeration of virtual libraries for small molecules, starting from specifications of core scaffolds with attachments points and lists of R-groups as SMILES or SD files. Although SD files include atomic coordinates for core scaffolds and R-groups, it is not possible to control 2-dimensional (2D) layout of the enumerated structures generated for virtual compound libraries because different packages generate different 2D representations for the same structure. We have developed a software package called LipidMapsTools for the template-based combinatorial enumeration of virtual compound libraries for lipids. Virtual libraries are enumerated for the specified lipid abbreviations using matching lists of pre-defined templates and chain abbreviations, instead of core scaffolds and lists of R-groups provided by the user. 2D structures of the enumerated lipids are drawn in a specific and consistent fashion adhering to the framework for representing lipid structures proposed by the LIPID MAPS consortium. LipidMapsTools is lightweight, relatively fast and contains no external dependencies. It is an open source package and freely available under the terms of the modified BSD license.

  18. Affinity-based screening of combinatorial libraries using automated, serial-column chromatography

    Energy Technology Data Exchange (ETDEWEB)

    Evans, D.M.; Williams, K.P.; McGuinness, B. [PerSeptive Biosystems, Framingham, MA (United States)] [and others

    1996-04-01

    The authors have developed an automated serial chromatographic technique for screening a library of compounds based upon their relative affinity for a target molecule. A {open_quotes}target{close_quotes} column containing the immobilized target molecule is set in tandem with a reversed-phase column. A combinatorial peptide library is injected onto the target column. The target-bound peptides are eluted from the first column and transferred automatically to the reversed-phase column. The target-specific peptide peaks from the reversed-phase column are identified and sequenced. Using a monoclonal antibody (3E-7) against {beta}-endorphin as a target, we selected a single peptide with sequence YGGFL from approximately 5800 peptides present in a combinatorial library. We demonstrated the applicability of the technology towards selection of peptides with predetermined affinity for bacterial lipopolysaccharide (LPS, endotoxin). We expect that this technology will have broad applications for high throughput screening of chemical libraries or natural product extracts. 21 refs., 4 figs.

  19. Uniformly constructing combinatorial solutions, combining a rational function with hyperbolic or trigonometric functions, for the (2+1) dimensional Broer-Kaup-Kupershmidt equation

    International Nuclear Information System (INIS)

    Liu Qing; Wang Zihua

    2010-01-01

    According to two dependent rational solutions to a generalized Riccati equation together with the equation itself, a rational-exponent solution to a nonlinear partial differential equation can be constructed. By selecting different parameter values in the rational-exponent solution, many families of combinatorial solutions combined with a rational function such as hyperbolic functions or trigonometric functions, are rapidly derived. This method is applied to the Whitham-Broer-Kaup equation and a series of combinatorial solutions are obtained, showing that this method is a more concise and efficient approach and can uniformly construct many types of combined solutions to nonlinear partial differential equations.

  20. The necessity to rationalize library procedures and activities

    OpenAIRE

    Matjaž Žaucer

    2007-01-01

    The necessity of the rationalization of work and procedures in libraries due to the altered requirements and needs of users and due to the expected aggravated demands of the environment are displayed in the article. The causes for the changes in the librarianship and the causes for the changes in the environment are stated. The article analyzes the searching procedure in the Slovenian union bibliographic and catalogue database using the UDC. Upon a practical experiment it was established that...

  1. Secretory Overexpression of Bacillus thermocatenulatus Lipase in Saccharomyces cerevisiae Using Combinatorial Library Strategy.

    Science.gov (United States)

    Kajiwara, Shota; Yamada, Ryosuke; Ogino, Hiroyasu

    2018-04-10

    Simple and cost-effective lipase expression host microorganisms are highly desirable. A combinatorial library strategy is used to improve the secretory expression of lipase from Bacillus thermocatenulatus (BTL2) in the culture supernatant of Saccharomyces cerevisiae. A plasmid library including expression cassettes composed of sequences encoding one of each 15 promoters, 15 secretion signals, and 15 terminators derived from yeast species, S. cerevisiae, Pichia pastoris, and Hansenula polymorpha, is constructed. The S. cerevisiae transformant YPH499/D4, comprising H. polymorpha GAP promoter, S. cerevisiae SAG1 secretion signal, and P. pastoris AOX1 terminator, is selected by high-throughput screening. This transformant expresses BTL2 extra-cellularly with a 130-fold higher than the control strain, comprising S. cerevisiae PGK1 promoter, S. cerevisiae α-factor secretion signal, and S. cerevisiae PGK1 terminator, after cultivation for 72 h. This combinatorial library strategy holds promising potential for application in the optimization of the secretory expression of proteins in yeast. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  2. Combinatorial Libraries on Rigid Scaffolds: Solid Phase Synthesis of Variably Substituted Pyrazoles and Isoxazoles

    Directory of Open Access Journals (Sweden)

    Eduard R. Felder

    1997-01-01

    Full Text Available The synthesis of combinatorial compound libraries has become a powerful lead finding tool in modern drug discovery. The ability to synthesize rapidly, in high yield, new chemical entities with low molecular weight on a solid support has a recognized strategic relevance (“small molecule libraries”. We designed and validated a novel solid phase synthesis scheme, suitable to generate diversity on small heterocycles of the pyrazole and isoxazole type. Appropriate conditions were worked out for each reaction, and a variety of more or less reactive agents (building blocks was utilized for discrete conversions, in order to exploit the system’s breadth of applicability. Four sequential reaction steps were validated, including the loading of the support with an acetyl bearing moiety, a Claisen condensation, an a-alkylation and a cyclization of a b-diketone with monosubstituted hydrazines. In a second stage, the reaction sequence was applied in a split and mix approach, in order to prepare a combinatorial library built-up from 4 acetyl carboxylic acids (R1, 35 carboxylic esters (R2 and 41 hydrazines (R4 (and 1 hydroxylamine to yield a total of 11,760 compounds divided into 41 pyrazole sublibraries with 140 pairs of regioisomers and 1 isoxazole sublibrary of equal size.

  3. The necessity to rationalize library procedures and activities

    Directory of Open Access Journals (Sweden)

    Matjaž Žaucer

    2007-01-01

    Full Text Available The necessity of the rationalization of work and procedures in libraries due to the altered requirements and needs of users and due to the expected aggravated demands of the environment are displayed in the article. The causes for the changes in the librarianship and the causes for the changes in the environment are stated. The article analyzes the searching procedure in the Slovenian union bibliographic and catalogue database using the UDC. Upon a practical experiment it was established that the users can not make a successful use of the UDC because neither on the web nor in the database there are freely accessible UDC tables; there are also no exact usage instructions available. The outcomes of some tests in public and academic libraries reveal that the assistance of librarians with retrievals by the UDC is unpractical, timeconsuming and does not always lead to the correct result. Based on an international comparison of foreign academic libraries and one Slovenian library, the latter shows a substantial ineffectiveness in cataloging which leads to the assumption of the highdemanding or incomplete cataloguing rules. The case of the digital patent documents in one of the libraries reveals the incapability of processing of a large amount of documents according to the existing rules. The conclusion of the article is the appeal for more rational cataloging rules, for the accessibility of cataloging records directly via web search engines and for an optional indication of the UDC in the records. However, as the conditions in Slovenian libraries are not critical yet, the author has doubts about a quick response to those appeals.

  4. Optical tools for high-throughput screening of abrasion resistance of combinatorial libraries of organic coatings

    Science.gov (United States)

    Potyrailo, Radislav A.; Chisholm, Bret J.; Olson, Daniel R.; Brennan, Michael J.; Molaison, Chris A.

    2002-02-01

    Design, validation, and implementation of an optical spectroscopic system for high-throughput analysis of combinatorially developed protective organic coatings are reported. Our approach replaces labor-intensive coating evaluation steps with an automated system that rapidly analyzes 8x6 arrays of coating elements that are deposited on a plastic substrate. Each coating element of the library is 10 mm in diameter and 2 to 5 micrometers thick. Performance of coatings is evaluated with respect to their resistance to wear abrasion because this parameter is one of the primary considerations in end-use applications. Upon testing, the organic coatings undergo changes that are impossible to quantitatively predict using existing knowledge. Coatings are abraded using industry-accepted abrasion test methods at single-or multiple-abrasion conditions, followed by high- throughput analysis of abrasion-induced light scatter. The developed automated system is optimized for the analysis of diffusively scattered light that corresponds to 0 to 30% haze. System precision of 0.1 to 2.5% relative standard deviation provides capability for the reliable ranking of coatings performance. While the system was implemented for high-throughput screening of combinatorially developed organic protective coatings for automotive applications, it can be applied to a variety of other applications where materials ranking can be achieved using optical spectroscopic tools.

  5. Isolation of Osteosarcoma-Associated Human Antibodies from a Combinatorial Fab Phage Display Library

    Directory of Open Access Journals (Sweden)

    Carmela Dantas-Barbosa

    2009-01-01

    Full Text Available Osteosarcoma, a highly malignant disease, is the most common primary bone tumor and is frequently found in children and adolescents. In order to isolate antibodies against osteosarcoma antigens, a combinatorial osteosarcoma Fab library displayed on the surface of phages was used. After three rounds of selection on the surface of tumor cells, several osteosarcoma-reactive Fabs were detected. From these Fabs, five were better characterized, and despite having differences in their VH (heavy chain variable domain and Vκ (kappa chain variable domain regions, they all bound to a protein with the same molecular mass. Further analysis by cell ELISA and immunocytochemistry suggested that the Fabs recognize a membrane-associated tumor antigen expressed in higher amounts in neoplasic cells than in normal tissue. These results suggest that the human Fabs selected in this work are a valuable tool for the study of this neoplasia.

  6. Application of visual basic in high-throughput mass spectrometry-directed purification of combinatorial libraries.

    Science.gov (United States)

    Li, B; Chan, E C Y

    2003-01-01

    We present an approach to customize the sample submission process for high-throughput purification (HTP) of combinatorial parallel libraries using preparative liquid chromatography electrospray ionization mass spectrometry. In this study, Visual Basic and Visual Basic for Applications programs were developed using Microsoft Visual Basic 6 and Microsoft Excel 2000, respectively. These programs are subsequently applied for the seamless electronic submission and handling of data for HTP. Functions were incorporated into these programs where medicinal chemists can perform on-line verification of the purification status and on-line retrieval of postpurification data. The application of these user friendly and cost effective programs in our HTP technology has greatly increased our work efficiency by reducing paper work and manual manipulation of data.

  7. Combinatorial hexapeptide ligand libraries (ProteoMiner): an innovative fractionation tool for differential quantitative clinical proteomics.

    Science.gov (United States)

    Hartwig, Sonja; Czibere, Akos; Kotzka, Jorg; Passlack, Waltraud; Haas, Rainer; Eckel, Jürgen; Lehr, Stefan

    2009-07-01

    Blood serum samples are the major source for clinical proteomics approaches, which aim to identify diagnostically relevant or treatment-response related proteins. But, the presence of very high-abundance proteins and the enormous dynamic range of protein distribution hinders whole serum analysis. An innovative tool to overcome these limitations, utilizes combinatorial hexapeptide ligand libraries (ProteoMiner). Here, we demonstrate that ProteoMiner can be used for comparative and quantitative analysis of complex proteomes. We spiked serum samples with increasing amounts (3 microg to 300 microg) of whole E. coli lysate, processed it with ProteoMiner and performed quantitative analyses of 2D-gels. We found, that the concentration of the spiked bacteria proteome, reflected by the maintained proportional spot intensities, was not altered by ProteoMiner treatment. Therefore, we conclude that the ProteoMiner technology can be used for quantitative analysis of low abundant proteins in complex biological samples.

  8. Virtual screening of combinatorial library of novel benzenesulfonamides on mycobacterial carbonic anhydrase II

    Directory of Open Access Journals (Sweden)

    Dikant F.

    2016-12-01

    Full Text Available Combinatorial library of novel benzenesulfonamides was docked (Schrodinger Glide into mycobacterial carbonic anhydrase (mtCA II and human (hCA II isoforms with an aim to find drug candidates with selective activity on mtCA II. The predicted selectivity was calculated based on optimized MM-GBSA free energies for ligand enzyme interactions. Selectivity, LogP (o/w and interaction energy were used to calculate the selection index which determined the subset of best scoring molecules selected for further evaluation. Structure-activity relationship was found for fragment subsets, showing us the possible way regarding how to influence lipophilicity without affecting ligand-enzyme binding properties.

  9. Intracellular directed evolution of proteins from combinatorial libraries based on conditional phage replication.

    Science.gov (United States)

    Brödel, Andreas K; Jaramillo, Alfonso; Isalan, Mark

    2017-09-01

    Directed evolution is a powerful tool to improve the characteristics of biomolecules. Here we present a protocol for the intracellular evolution of proteins with distinct differences and advantages in comparison with established techniques. These include the ability to select for a particular function from a library of protein variants inside cells, minimizing undesired coevolution and propagation of nonfunctional library members, as well as allowing positive and negative selection logics using basally active promoters. A typical evolution experiment comprises the following stages: (i) preparation of a combinatorial M13 phagemid (PM) library expressing variants of the gene of interest (GOI) and preparation of the Escherichia coli host cells; (ii) multiple rounds of an intracellular selection process toward a desired activity; and (iii) the characterization of the evolved target proteins. The system has been developed for the selection of new orthogonal transcription factors (TFs) but is capable of evolving any gene-or gene circuit function-that can be linked to conditional M13 phage replication. Here we demonstrate our approach using as an example the directed evolution of the bacteriophage λ cI TF against two synthetic bidirectional promoters. The evolved TF variants enable simultaneous activation and repression against their engineered promoters and do not cross-react with the wild-type promoter, thus ensuring orthogonality. This protocol requires no special equipment, allowing synthetic biologists and general users to evolve improved biomolecules within ∼7 weeks.

  10. Constrained Combinatorial Libraries of Gp2 Proteins Enhance Discovery of PD-L1 Binders.

    Science.gov (United States)

    Kruziki, Max A; Sarma, Vidur; Hackel, Benjamin J

    2018-06-05

    Engineered protein ligands are used for molecular therapy, diagnostics, and industrial biotechnology. The Gp2 domain is a 45-amino acid scaffold that has been evolved for specific, high-affinity binding to multiple targets by diversification of two solvent-exposed loops. Inspired by sitewise enrichment of select amino acids, including cysteine pairs, in earlier Gp2 discovery campaigns, we hypothesized that the breadth and efficiency of de novo Gp2 discovery will be aided by sitewise amino acid constraint within combinatorial library design. We systematically constructed eight libraries and comparatively evaluated their efficacy for binder discovery via yeast display against a panel of targets. Conservation of a cysteine pair at the termini of the first diversified paratope loop increased binder discovery 16-fold ( p libraries with conserved cysteine pairs, within the second loop or an interloop pair, did not aid discovery thereby indicating site-specific impact. Via a yeast display protease resistance assay, Gp2 variants from the loop one cysteine pair library were 3.3 ± 2.1-fold ( p = 0.005) more stable than nonconstrained variants. Sitewise constraint of noncysteine residues-guided by previously evolved binders, natural Gp2 homology, computed stability, and structural analysis-did not aid discovery. A panel of binders to programmed death ligand 1 (PD-L1), a key target in cancer immunotherapy, were discovered from the loop 1 cysteine constraint library. Affinity maturation via loop walking resulted in strong, specific cellular PD-L1 affinity ( K d = 6-9 nM).

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

    Science.gov (United States)

    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.

  12. Combinatorial Libraries As a Tool for the Discovery of Novel, Broad-Spectrum Antibacterial Agents Targeting the ESKAPE Pathogens.

    Science.gov (United States)

    Fleeman, Renee; LaVoi, Travis M; Santos, Radleigh G; Morales, Angela; Nefzi, Adel; Welmaker, Gregory S; Medina-Franco, José L; Giulianotti, Marc A; Houghten, Richard A; Shaw, Lindsey N

    2015-04-23

    Mixture based synthetic combinatorial libraries offer a tremendous enhancement for the rate of drug discovery, allowing the activity of millions of compounds to be assessed through the testing of exponentially fewer samples. In this study, we used a scaffold-ranking library to screen 37 different libraries for antibacterial activity against the ESKAPE pathogens. Each library contained between 10000 and 750000 structural analogues for a total of >6 million compounds. From this, we identified a bis-cyclic guanidine library that displayed strong antibacterial activity. A positional scanning library for these compounds was developed and used to identify the most effective functional groups at each variant position. Individual compounds were synthesized that were broadly active against all ESKAPE organisms at concentrations development of resistance, and displayed almost no toxicity when tested against human lung cells and erythrocytes. Using a murine model of peritonitis, we also demonstrate that these agents are highly efficacious in vivo.

  13. Two is better than one; toward a rational design of combinatorial therapy.

    Science.gov (United States)

    Chen, Sheng-Hong; Lahav, Galit

    2016-12-01

    Drug combination is an appealing strategy for combating the heterogeneity of tumors and evolution of drug resistance. However, the rationale underlying combinatorial therapy is often not well established due to lack of understandings of the specific pathways responding to the drugs, and their temporal dynamics following each treatment. Here we present several emerging trends in harnessing properties of biological systems for the optimal design of drug combinations, including the type of drugs, specific concentration, sequence of addition and the temporal schedule of treatments. We highlight recent studies showing different approaches for efficient design of drug combinations including single-cell signaling dynamics, adaption and pathway crosstalk. Finally, we discuss novel and feasible approaches that can facilitate the optimal design of combinatorial therapy. Copyright © 2016 Elsevier Ltd. All rights reserved.

  14. Scaffold architecture and pharmacophoric properties of natural products and trade drugs: application in the design of natural product-based combinatorial libraries.

    Science.gov (United States)

    Lee, M L; Schneider, G

    2001-01-01

    Natural products were analyzed to determine whether they contain appealing novel scaffold architectures for potential use in combinatorial chemistry. Ring systems were extracted and clustered on the basis of structural similarity. Several such potential scaffolds for combinatorial chemistry were identified that are not present in current trade drugs. For one of these scaffolds a virtual combinatorial library was generated. Pharmacophoric properties of natural products, trade drugs, and the virtual combinatorial library were assessed using a self-organizing map. Obviously, current trade drugs and natural products have several topological pharmacophore patterns in common. These features can be systematically explored with selected combinatorial libraries based on a combination of natural product-derived and synthetic molecular building blocks.

  15. The mathematics of a successful deconvolution: a quantitative assessment of mixture-based combinatorial libraries screened against two formylpeptide receptors.

    Science.gov (United States)

    Santos, Radleigh G; Appel, Jon R; Giulianotti, Marc A; Edwards, Bruce S; Sklar, Larry A; Houghten, Richard A; Pinilla, Clemencia

    2013-05-30

    In the past 20 years, synthetic combinatorial methods have fundamentally advanced the ability to synthesize and screen large numbers of compounds for drug discovery and basic research. Mixture-based libraries and positional scanning deconvolution combine two approaches for the rapid identification of specific scaffolds and active ligands. Here we present a quantitative assessment of the screening of 32 positional scanning libraries in the identification of highly specific and selective ligands for two formylpeptide receptors. We also compare and contrast two mixture-based library approaches using a mathematical model to facilitate the selection of active scaffolds and libraries to be pursued for further evaluation. The flexibility demonstrated in the differently formatted mixture-based libraries allows for their screening in a wide range of assays.

  16. In-depth proteomic analysis of banana (Musa spp.) fruit with combinatorial peptide ligand libraries.

    Science.gov (United States)

    Esteve, Clara; D'Amato, Alfonsina; Marina, María Luisa; García, María Concepción; Righetti, Pier Giorgio

    2013-01-01

    Musa ssp. is among the world's leading fruit crops. Although a strong interest on banana biochemistry exists in the scientific community, focused on metabolite composition, proteins have been scarcely investigated even if they play an important role in food allergy and stability, are a source of biologically active peptides, and can provide information about nutritional aspects of this fruit. In this work we have employed the combinatorial peptide ligand libraries after different types of protein extractions, for searching the very low-abundance proteins in banana. The use of advanced MS techniques and Musa ssp. mRNAs database in combination with the Uniprot_viridiplantae database allowed us to identify 1131 proteins. Among this huge amount of proteins we found several already known allergens such as Mus a 1, pectinesterase, superoxide dismutase, and potentially new allergens. Additionally several enzymes involved in degradation of starch granules and strictly correlated to ripening stage were identified. This is the first in-depth exploration of the banana fruit proteome and one of the largest descriptions of the proteome of any vegetable system. © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  17. Comparison of dissimilarity measures for cluster analysis of X-ray diffraction data from combinatorial libraries

    Science.gov (United States)

    Iwasaki, Yuma; Kusne, A. Gilad; Takeuchi, Ichiro

    2017-12-01

    Machine learning techniques have proven invaluable to manage the ever growing volume of materials research data produced as developments continue in high-throughput materials simulation, fabrication, and characterization. In particular, machine learning techniques have been demonstrated for their utility in rapidly and automatically identifying potential composition-phase maps from structural data characterization of composition spread libraries, enabling rapid materials fabrication-structure-property analysis and functional materials discovery. A key issue in development of an automated phase-diagram determination method is the choice of dissimilarity measure, or kernel function. The desired measure reduces the impact of confounding structural data issues on analysis performance. The issues include peak height changes and peak shifting due to lattice constant change as a function of composition. In this work, we investigate the choice of dissimilarity measure in X-ray diffraction-based structure analysis and the choice of measure's performance impact on automatic composition-phase map determination. Nine dissimilarity measures are investigated for their impact in analyzing X-ray diffraction patterns for a Fe-Co-Ni ternary alloy composition spread. The cosine, Pearson correlation coefficient, and Jensen-Shannon divergence measures are shown to provide the best performance in the presence of peak height change and peak shifting (due to lattice constant change) when the magnitude of peak shifting is unknown. With prior knowledge of the maximum peak shifting, dynamic time warping in a normalized constrained mode provides the best performance. This work also serves to demonstrate a strategy for rapid analysis of a large number of X-ray diffraction patterns in general beyond data from combinatorial libraries.

  18. Discovery of potent inhibitors of soluble epoxide hydrolase by combinatorial library design and structure-based virtual screening.

    Science.gov (United States)

    Xing, Li; McDonald, Joseph J; Kolodziej, Steve A; Kurumbail, Ravi G; Williams, Jennifer M; Warren, Chad J; O'Neal, Janet M; Skepner, Jill E; Roberds, Steven L

    2011-03-10

    Structure-based virtual screening was applied to design combinatorial libraries to discover novel and potent soluble epoxide hydrolase (sEH) inhibitors. X-ray crystal structures revealed unique interactions for a benzoxazole template in addition to the conserved hydrogen bonds with the catalytic machinery of sEH. By exploitation of the favorable binding elements, two iterations of library design based on amide coupling were employed, guided principally by the docking results of the enumerated virtual products. Biological screening of the libraries demonstrated as high as 90% hit rate, of which over two dozen compounds were single digit nanomolar sEH inhibitors by IC(50) determination. In total the library design and synthesis produced more than 300 submicromolar sEH inhibitors. In cellular systems consistent activities were demonstrated with biochemical measurements. The SAR understanding of the benzoxazole template provides valuable insights into discovery of novel sEH inhibitors as therapeutic agents.

  19. Cathodoluminescence and ion beam analysis of ion-implanted combinatorial materials libraries on thermally grown SiO2

    International Nuclear Information System (INIS)

    Chen, C.-M.; Pan, H.C.; Zhu, D.Z.; Hu, J.; Li, M.Q.

    1999-01-01

    A method combining ion implantation and physical masking technique has been used to generate material libraries of various ion-implanted samples. Ion species of C, Ga, N, Pb, Sn, Y have been sequentially implanted to an SiO 2 film grown on a silicon wafer through combinatorial masks and consequently a library of 64 (2 6 ) samples is generated by 6 masking combinations. This approach offers rapid synthesis of samples with potential new compounds formed in the matrix, which may have specific luminescent properties. The depth-resolved cathodoluminescence (CL) measurements revealed some specific optical property in the samples correlated with implanted ion distributions. A marker-based technique is developed for the convenient location of sample site in the analysis of Rutherford backscattering spectrometry (RBS) and proton elastic scattering (PES), intended to characterize rapidly the ion implanted film libraries. These measurements demonstrate the power of nondestructively and rapidly characterizing composition and the inhomogeneity of the combinatorial film libraries, which may determine their physical properties

  20. Virtual screening using combinatorial cyclic peptide libraries reveals protein interfaces readily targetable by cyclic peptides.

    Science.gov (United States)

    Duffy, Fergal J; O'Donovan, Darragh; Devocelle, Marc; Moran, Niamh; O'Connell, David J; Shields, Denis C

    2015-03-23

    Protein-protein and protein-peptide interactions are responsible for the vast majority of biological functions in vivo, but targeting these interactions with small molecules has historically been difficult. What is required are efficient combined computational and experimental screening methods to choose among a number of potential protein interfaces worthy of targeting lead macrocyclic compounds for further investigation. To achieve this, we have generated combinatorial 3D virtual libraries of short disulfide-bonded peptides and compared them to pharmacophore models of important protein-protein and protein-peptide structures, including short linear motifs (SLiMs), protein-binding peptides, and turn structures at protein-protein interfaces, built from 3D models available in the Protein Data Bank. We prepared a total of 372 reference pharmacophores, which were matched against 108,659 multiconformer cyclic peptides. After normalization to exclude nonspecific cyclic peptides, the top hits notably are enriched for mimetics of turn structures, including a turn at the interaction surface of human α thrombin, and also feature several protein-binding peptides. The top cyclic peptide hits also cover the critical "hot spot" interaction sites predicted from the interaction crystal structure. We have validated our method by testing cyclic peptides predicted to inhibit thrombin, a key protein in the blood coagulation pathway of important therapeutic interest, identifying a cyclic peptide inhibitor with lead-like activity. We conclude that protein interfaces most readily targetable by cyclic peptides and related macrocyclic drugs may be identified computationally among a set of candidate interfaces, accelerating the choice of interfaces against which lead compounds may be screened.

  1. Combining on-chip synthesis of a focused combinatorial library with computational target prediction reveals imidazopyridine GPCR ligands.

    Science.gov (United States)

    Reutlinger, Michael; Rodrigues, Tiago; Schneider, Petra; Schneider, Gisbert

    2014-01-07

    Using the example of the Ugi three-component reaction we report a fast and efficient microfluidic-assisted entry into the imidazopyridine scaffold, where building block prioritization was coupled to a new computational method for predicting ligand-target associations. We identified an innovative GPCR-modulating combinatorial chemotype featuring ligand-efficient adenosine A1/2B and adrenergic α1A/B receptor antagonists. Our results suggest the tight integration of microfluidics-assisted synthesis with computer-based target prediction as a viable approach to rapidly generate bioactivity-focused combinatorial compound libraries with high success rates. Copyright © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  2. Isolation of high-affinity human IgE and IgG antibodies recognising Bet v 1 and Humicola lanuginosa lipase from combinatorial phage libraries

    DEFF Research Database (Denmark)

    Jakobsen, Charlotte G; Bødtger, Uffe; Kristensen, Peter

    2004-01-01

    Allergen-specific Fab fragments isolated from combinatorial IgE and IgG libraries are useful tools for studying allergen-antibody interactions. To characterise the interaction between different allergens and antibodies we have created recombinant human phage antibody libraries in the Fab format...

  3. Computational redesign of bacterial biotin carboxylase inhibitors using structure-based virtual screening of combinatorial libraries.

    Science.gov (United States)

    Brylinski, Michal; Waldrop, Grover L

    2014-04-02

    As the spread of antibiotic resistant bacteria steadily increases, there is an urgent need for new antibacterial agents. Because fatty acid synthesis is only used for membrane biogenesis in bacteria, the enzymes in this pathway are attractive targets for antibacterial agent development. Acetyl-CoA carboxylase catalyzes the committed and regulated step in fatty acid synthesis. In bacteria, the enzyme is composed of three distinct protein components: biotin carboxylase, biotin carboxyl carrier protein, and carboxyltransferase. Fragment-based screening revealed that amino-oxazole inhibits biotin carboxylase activity and also exhibits antibacterial activity against Gram-negative organisms. In this report, we redesigned previously identified lead inhibitors to expand the spectrum of bacteria sensitive to the amino-oxazole derivatives by including Gram-positive species. Using 9,411 small organic building blocks, we constructed a diverse combinatorial library of 1.2×10⁸ amino-oxazole derivatives. A subset of 9×10⁶ of these compounds were subjected to structure-based virtual screening against seven biotin carboxylase isoforms using similarity-based docking by eSimDock. Potentially broad-spectrum antibiotic candidates were selected based on the consensus ranking by several scoring functions including non-linear statistical models implemented in eSimDock and traditional molecular mechanics force fields. The analysis of binding poses of the top-ranked compounds docked to biotin carboxylase isoforms suggests that: (1) binding of the amino-oxazole anchor is stabilized by a network of hydrogen bonds to residues 201, 202 and 204; (2) halogenated aromatic moieties attached to the amino-oxazole scaffold enhance interactions with a hydrophobic pocket formed by residues 157, 169, 171 and 203; and (3) larger substituents reach deeper into the binding pocket to form additional hydrogen bonds with the side chains of residues 209 and 233. These structural insights into drug

  4. Quantum mechanical energy-based screening of combinatorially generated library of tautomers. TauTGen: a tautomer generator program.

    Science.gov (United States)

    Harańczyk, Maciej; Gutowski, Maciej

    2007-01-01

    We describe a procedure of finding low-energy tautomers of a molecule. The procedure consists of (i) combinatorial generation of a library of tautomers, (ii) screening based on the results of geometry optimization of initial structures performed at the density functional level of theory, and (iii) final refinement of geometry for the top hits at the second-order Möller-Plesset level of theory followed by single-point energy calculations at the coupled cluster level of theory with single, double, and perturbative triple excitations. The library of initial structures of various tautomers is generated with TauTGen, a tautomer generator program. The procedure proved to be successful for these molecular systems for which common chemical knowledge had not been sufficient to predict the most stable structures.

  5. Identification of avocado (Persea americana) pulp proteins by nano-LC-MS/MS via combinatorial peptide ligand libraries.

    Science.gov (United States)

    Esteve, Clara; D'Amato, Alfonsina; Marina, María Luisa; García, María Concepción; Righetti, Pier Giorgio

    2012-09-01

    Avocado (Persea americana) proteins have been scarcely studied despite their importance, especially in food related allergies. The proteome of avocado pulp was explored in depth by extracting proteins with capture by combinatorial peptide ligand libraries at pH 7.4 and under conditions mimicking reverse-phase capture at pH 2.2. The total number of unique gene products identified amounts to 1012 proteins, of which 174 are in common with the control, untreated sample, 190 are present only in the control and 648 represent the new species detected via combinatorial peptide ligand libraries of all combined eluates and likely represent low-abundance proteins. Among the 1012 proteins, it was possible to identify the already known avocado allergen Pers a 1 and different proteins susceptible to be allergens such as a profilin, a polygalacturonase, a thaumatin-like protein, a glucanase, and an isoflavone reductase like protein. © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  6. CCLab--a multi-objective genetic algorithm based combinatorial library design software and an application for histone deacetylase inhibitor design.

    Science.gov (United States)

    Fang, Guanghua; Xue, Mengzhu; Su, Mingbo; Hu, Dingyu; Li, Yanlian; Xiong, Bing; Ma, Lanping; Meng, Tao; Chen, Yuelei; Li, Jingya; Li, Jia; Shen, Jingkang

    2012-07-15

    The introduction of the multi-objective optimization has dramatically changed the virtual combinatorial library design, which can consider many objectives simultaneously, such as synthesis cost and drug-likeness, thus may increase positive rates of biological active compounds. Here we described a software called CCLab (Combinatorial Chemistry Laboratory) for combinatorial library design based on the multi-objective genetic algorithm. Tests of the convergence ability and the ratio to re-take the building blocks in the reference library were conducted to assess the software in silico, and then it was applied to a real case of designing a 5×6 HDAC inhibitor library. Sixteen compounds in the resulted library were synthesized, and the histone deactetylase (HDAC) enzymatic assays proved that 14 compounds showed inhibitory ratios more than 50% against tested 3 HDAC enzymes at concentration of 20 μg/mL, with IC(50) values of 3 compounds comparable to SAHA. These results demonstrated that the CCLab software could enhance the hit rates of the designed library and would be beneficial for medicinal chemists to design focused library in drug development (the software can be downloaded at: http://202.127.30.184:8080/drugdesign.html). Copyright © 2012 Elsevier Ltd. All rights reserved.

  7. Identification of novel peptide ligands for the cancer-specific receptor mutation EFGRvIII using a mixture-based synthetic combinatorial library

    DEFF Research Database (Denmark)

    Denholt, Charlotte Lund; Hansen, Paul Robert; Pedersen, Nina

    2009-01-01

    We report here, the design and synthesis of a positional scanning synthetic combinatorial library for the identification of novel peptide ligands targeted against the cancer-specific epidermal growth factor tyrosine kinase receptor mutation variant III (EGFRvIII). This receptor is expressed in se...

  8. Combinatorial processing libraries for bulk BiFeO3-PbTiO3 piezoelectric ceramics

    International Nuclear Information System (INIS)

    Hu, W.; Tan, X.; Rajan, K.

    2010-01-01

    A high throughput approach for generating combinatorial libraries with varying processing conditions for bulk ceramics has been developed. This approach utilized the linear temperature gradient in a tube furnace to screen a whole temperature range for optimized preparation. With this approach, the processing of 0.98[0.6BiFeO 3 -0.4PbTiO 3 ]-0.02Pb(Mg 1/3 Nb 2/3 )O 3 ceramic powders and pellets for high-temperature piezoelectric applications was demonstrated to identify the best synthesis conditions for phase purity. The dielectric property measurement on the as-processed solid solution ceramics confirmed the high Curie temperature and the improved loss tangent with the Pb(Mg 1/3 Nb 2/3 )O 3 doping. (orig.)

  9. High Affinity, Developability and Functional Size: The Holy Grail of Combinatorial Antibody Library Generation

    Directory of Open Access Journals (Sweden)

    Kathrin Tissot

    2011-05-01

    Full Text Available Since the initial description of phage display technology for the generation of human antibodies, a variety of selection methods has been developed. The most critical parameter for all in vitro-based approaches is the quality of the antibody library. Concurrent evolution of the libraries has allowed display and selection technologies to reveal their full potential. They come in different flavors, from naïve to fully synthetic and differ in terms of size, quality, method of preparation, framework and CDR composition. Early on, the focus has mainly been on affinities and thus on library size and diversity. Subsequently, the increased awareness of developability and cost of goods as important success factors has spurred efforts to generate libraries with improved biophysical properties and favorable production characteristics. More recently a major focus on reduction of unwanted side effects through reduced immunogenicity and improved overall biophysical behavior has led to a re-evaluation of library design.

  10. Microstructural and dielectric properties of Ba0.6Sr0.4Ti1-xZrxO3 based combinatorial thin film capacitors library

    International Nuclear Information System (INIS)

    Liu Guozhen; Wolfman, Jerome; Autret-Lambert, Cecile; Sakai, Joe; Roger, Sylvain; Gervais, Monique; Gervais, Francois

    2010-01-01

    Epitaxial growth of Ba 0.6 Sr 0.4 Ti 1-x Zr x O 3 (0≤x≤0.3) composition spread thin film library on SrRuO 3 /SrTiO 3 layer by combinatorial pulsed laser deposition (PLD) is reported. X-ray diffraction and energy dispersive x-ray spectroscopy studies showed an accurate control of the film phase and composition by combinatorial PLD. A complex evolution of the microstructure and morphology with composition of the library is described, resulting from the interplay between epitaxial stress, increased chemical pressure, and reduced elastic energy upon Zr doping. Statistical and temperature-related capacitive measurements across the library showed unexpected variations in the dielectric properties. Doping windows with enhanced permittivity and tunability are identified, and correlated to microstructural properties.

  11. Generation of a Multicomponent Library of Disulfide Donor-Acceptor Architectures Using Dynamic Combinatorial Chemistry.

    Science.gov (United States)

    Drożdż, Wojciech; Kołodziejski, Michał; Markiewicz, Grzegorz; Jenczak, Anna; Stefankiewicz, Artur R

    2015-07-17

    We describe here the generation of new donor-acceptor disulfide architectures obtained in aqueous solution at physiological pH. The application of a dynamic combinatorial chemistry approach allowed us to generate a large number of new disulfide macrocyclic architectures together with a new type of [2]catenanes consisting of four distinct components. Up to fifteen types of structurally-distinct dynamic architectures have been generated through one-pot disulfide exchange reactions between four thiol-functionalized aqueous components. The distribution of disulfide products formed was found to be strongly dependent on the structural features of the thiol components employed. This work not only constitutes a success in the synthesis of topologically- and morphologically-complex targets, but it may also open new horizons for the use of this methodology in the construction of molecular machines.

  12. Screening of a Combinatorial Library of Organic Polymers for the Solid-Phase Extraction of Patulin from Apple Juice

    Science.gov (United States)

    Giovannoli, Cristina; Spano, Giulia; Di Nardo, Fabio; Anfossi, Laura; Baggiani, Claudio

    2017-01-01

    Patulin is a water-soluble mycotoxin produced by several species of fungi. Governmental bodies have placed it under scrutiny for its potential negative health effects, and maximum residue limits are fixed in specific food matrices to protect consumers’ health. Confirmatory analysis of patulin in complex food matrices can be a difficult task, and sample clean-up treatments are frequently necessary before instrumental analyses. With the aim of simplifying the clean-up step, we prepared a 256-member combinatorial polymeric library based on 16 functional monomers, four cross-linkers and four different porogenic solvents. The library was screened for the binding towards patulin in different media (acetonitrile and citrate buffer at pH 3.2), with the goal of identifying polymer formulations with good binding properties towards the target compound. As a proof of concept, a methacrylic acid-co-pentaerithrytole tetraacrylate polymer prepared in chloroform was successfully used as a solid-phase extraction material for the clean-up and extraction of patulin from apple juice. Clean chromatographic patterns and acceptable recoveries were obtained for juice spiked with patulin at concentration levels of 25 (64 ± 12%), 50 (83 ± 5.6%) and 100 μg L−1 (76 ± 4.5%). The within-day and between-day reproducibility evaluated at a concentration level of 25 μg L−1 were 5.6 and 7.6%, respectively. PMID:28531103

  13. Combinatorial library based engineering of Candida antarctica lipase A for enantioselective transacylation of sec-alcohols in organic solvent.

    Science.gov (United States)

    Wikmark, Ylva; Svedendahl Humble, Maria; Bäckvall, Jan-E

    2015-03-27

    A method for determining lipase enantioselectivity in the transacylation of sec-alcohols in organic solvent was developed. The method was applied to a model library of Candida antarctica lipase A (CalA) variants for improved enantioselectivity (E values) in the kinetic resolution of 1-phenylethanol in isooctane. A focused combinatorial gene library simultaneously targeting seven positions in the enzyme active site was designed. Enzyme variants were immobilized on nickel-coated 96-well microtiter plates through a histidine tag (His6-tag), screened for transacylation of 1-phenylethanol in isooctane, and analyzed by GC. The highest enantioselectivity was shown by the double mutant Y93L/L367I. This enzyme variant gave an E value of 100 (R), which is a dramatic improvement on the wild-type CalA (E=3). This variant also showed high to excellent enantioselectivity for other secondary alcohols tested. © 2015 The Authors. Published by Wiley-VCH Verlag GmbH & Co. KGaA. This is an open access article under the terms of the Creative Commons Attribution Non-Commercial NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.

  14. Douglass Rationalization: An Evaluation of a Team Environment and a Computer-Based Task in Academic Libraries

    Science.gov (United States)

    Denda, Kayo; Smulewitz, Gracemary

    2004-01-01

    In the contemporary library environment, the presence of the Internet and the infrastructure of the integrated library system suggest an integrated internal organization. The article describes the example of Douglass Rationalization, a team-based collaborative project to refocus the collection of Rutgers' Douglass Library, taking advantage of the…

  15. Dynamic combinatorial chemistry

    NARCIS (Netherlands)

    Otto, Sijbren; Furlan, Ricardo L.E.; Sanders, Jeremy K.M.

    2002-01-01

    A combinatorial library that responds to its target by increasing the concentration of strong binders at the expense of weak binders sounds ideal. Dynamic combinatorial chemistry has the potential to achieve exactly this. In this review, we will highlight the unique features that distinguish dynamic

  16. Enumeration of virtual libraries of combinatorial modular macrocyclic (bracelet, necklace) architectures and their linear counterparts.

    Science.gov (United States)

    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 support vector machines approach for virtual screening of selective multi-target serotonin reuptake inhibitors from large compound libraries.

    Science.gov (United States)

    Shi, Z; Ma, X H; Qin, C; Jia, J; Jiang, Y Y; Tan, C Y; Chen, Y Z

    2012-02-01

    Selective multi-target serotonin reuptake inhibitors enhance antidepressant efficacy. Their discovery can be facilitated by multiple methods, including in silico ones. In this study, we developed and tested an in silico method, combinatorial support vector machines (COMBI-SVMs), for virtual screening (VS) multi-target serotonin reuptake inhibitors of seven target pairs (serotonin transporter paired with noradrenaline transporter, H(3) receptor, 5-HT(1A) receptor, 5-HT(1B) receptor, 5-HT(2C) receptor, melanocortin 4 receptor and neurokinin 1 receptor respectively) from large compound libraries. COMBI-SVMs trained with 917-1951 individual target inhibitors correctly identified 22-83.3% (majority >31.1%) of the 6-216 dual inhibitors collected from literature as independent testing sets. COMBI-SVMs showed moderate to good target selectivity in misclassifying as dual inhibitors 2.2-29.8% (majority virtual hits correlate with the reported effects of their predicted targets. COMBI-SVM is potentially useful for searching selective multi-target agents without explicit knowledge of these agents. Copyright © 2011 Elsevier Inc. All rights reserved.

  18. Protection from the 2009 H1N1 pandemic influenza by an antibody from combinatorial survivor-based libraries.

    Directory of Open Access Journals (Sweden)

    Arun K Kashyap

    2010-07-01

    Full Text Available Influenza viruses elude immune responses and antiviral chemotherapeutics through genetic drift and reassortment. As a result, the development of new strategies that attack a highly conserved viral function to prevent and/or treat influenza infection is being pursued. Such novel broadly acting antiviral therapies would be less susceptible to virus escape and provide a long lasting solution to the evolving virus challenge. Here we report the in vitro and in vivo activity of a human monoclonal antibody (A06 against two isolates of the 2009 H1N1 pandemic influenza virus. This antibody, which was obtained from a combinatorial library derived from a survivor of highly pathogenic H5N1 infection, neutralizes H5N1, seasonal H1N1 and 2009 "Swine" H1N1 pandemic influenza in vitro with similar potency and is capable of preventing and treating 2009 H1N1 influenza infection in murine models of disease. These results demonstrate broad activity of the A06 antibody and its utility as an anti-influenza treatment option, even against newly evolved influenza strains to which there is limited immunity in the general population.

  19. Crystallographic Structure Analysis of a Ti-Ta Thin Film Materials Library Fabricated by Combinatorial Magnetron Sputtering.

    Science.gov (United States)

    Kadletz, Peter M; Motemani, Yahya; Iannotta, Joy; Salomon, Steffen; Khare, Chinmay; Grossmann, Lukas; Maier, Hans Jürgen; Ludwig, Alfred; Schmahl, Wolfgang W

    2018-03-12

    Ti-Ta thin films exhibit properties that are of interest for applications as microactuators and as biomedical implants. A Ti-Ta thin film materials library was deposited at T = 25 °C by magnetron sputtering employing the combinatorial approach, which led to a compositional range of Ti 87 Ta 13 to Ti 14 Ta 86 . Subsequent high-throughput characterization methods permitted a quick and comprehensive study of the crystallographic, microstructural, and morphological properties, which strongly depend on the chemical composition. SEM investigation revealed a columnar morphology having pyramidal, sharp tips with coarser columns in the Ti-rich and finer columns in the Ta-rich region. By grazing incidence X-ray diffraction four phases were identified, from Ta-lean to Ta-rich: ω phase, α″ martensite, β phase, and a tetragonal Ta-rich phase (Ta (tetr) ). The crystal structure and microstructure were analyzed by Rietveld refinement and clear trends could be determined as a function of Ta-content. The lattice correspondences between β as the parent phase and α″ and ω as derivative phases were expressed in matrix form. The β ⇌ α″ phase transition shows a discontinuity at the composition where the martensitic transformation temperatures fall below room temperature (between 34 and 38 at. % Ta) rendering it first order and confirming its martensitic nature. A short study of the α″ martensite employing the Landau theory is included for a mathematical quantification of the spontaneous lattice strain at room temperature (ϵ̂ max = 22.4(6) % for pure Ti). Martensitic properties of Ti-Ta are beneficial for the development of high-temperature actuators with actuation response at transformation temperatures higher than 100 °C.

  20. Development of hydrogel TentaGel shell-core beads for ultrahigh throughput solution-phase screening of encoded OBOC combinatorial small molecule libraries.

    Science.gov (United States)

    Baek, Hyoung Gee; Liu, Ruiwu; Lam, Kit S

    2009-01-01

    The one-bead one-compound (OBOC) combinatorial library method enables the rapid generation and screening of millions of discrete chemical compounds on beads. Most of the OBOC screening methods require the library compounds to remain tethered to the bead during screening process. Methods have also been developed to release library compounds from immobilized beads for in situ solution phase or "lawn" assays. However, this latter approach, while extremely powerful, is severely limited by the lack of suitable solid supports for such assays. Here, we report on the development of a novel hydrogel TentaGel shell-core (HTSC) bead in which hydrogel is grafted onto the polystyrene-based TentaGel (TG) bead as an outer shell (5-80 mum thick) via free radical surface-initiated polymerization. This novel shell-core bilayer resin enables the preparation of encoded OBOC combinatorial small molecule libraries, such that the library compounds reside on the highly hydrophilic outer layer and the coding tags reside in the polystyrene-based TG core. Using fluorescein as a model small molecule compound, we have demonstrated that fluorescein molecules that have been linked covalently to the hydrogel shell via a disulfide bond could readily diffuse out of the hydrogel layer into the bead surrounding after reduction with dithiothreitol. In contrast, under identical condition, the released fluorescein molecules remained bound to unmodified TG bead. We have prepared an encoded OBOC small molecule library on the novel shell-core beads and demonstrated that the beads can be readily decoded.

  1. Beating Bias in the Directed Evolution of Proteins: Combining High-Fidelity on-Chip Solid-Phase Gene Synthesis with Efficient Gene Assembly for Combinatorial Library Construction.

    Science.gov (United States)

    Li, Aitao; Acevedo-Rocha, Carlos G; Sun, Zhoutong; Cox, Tony; Xu, Jia Lucy; Reetz, Manfred T

    2018-02-02

    Saturation mutagenesis (SM) constitutes a widely used technique in the directed evolution of selective enzymes as catalysts in organic chemistry and in the manipulation of metabolic paths and genomes, but the quality of the libraries is far from optimal due to the inherent amino acid bias. Herein, it is shown how this fundamental problem can be solved by applying high-fidelity solid-phase chemical gene synthesis on silicon chips followed by efficient gene assembly. Limonene epoxide hydrolase was chosen as the catalyst in the model desymmetrization of cyclohexene oxide with the stereoselective formation of (R,R)- and (S,S)-cyclohexane-1,2-diol. A traditional combinatorial PCR-based SM library, produced by simultaneous randomization at several residues by using a reduced amino acid alphabet, and the respective synthetic library were constructed and compared. Statistical analysis at the DNA level with massive sequencing demonstrates that, in the synthetic approach, 97 % of the theoretically possible DNA mutants are formed, whereas the traditional SM library contained only about 50 %. Screening at the protein level also showed the superiority of the synthetic library; many highly (R,R)- and (S,S)-selective variants being discovered are not found in the traditional SM library. With the prices of synthetic genes decreasing, this approach may point the way to future directed evolution. © 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  2. Combinatorial chemistry on solid support in the search for central nervous system agents.

    Science.gov (United States)

    Zajdel, Paweł; Pawłowski, Maciej; Martinez, Jean; Subra, Gilles

    2009-08-01

    The advent of combinatorial chemistry was one of the most important developments, that has significantly contributed to the drug discovery process. Within just a few years, its initial concept aimed at production of libraries containing huge number of compounds (thousands to millions), so called screening libraries, has shifted towards preparation of small and medium-sized rationally designed libraries. When applicable, the use of solid supports for the generation of libraries has been a real breakthrough in enhancing productivity. With a limited amount of resin and simple manual workups, the split/mix procedure may generate thousands of bead-tethered compounds. Beads can be chemically or physically encoded to facilitate the identification of a hit after the biological assay. Compartmentalization of solid supports using small reactors like teabags, kans or pellicular discrete supports like Lanterns resulted in powerful sort and combine technologies, relying on codes 'written' on the reactor, and thus reducing the need for automation and improving the number of compounds synthesized. These methods of solid-phase combinatorial chemistry have been recently supported by introduction of solid-supported reagents and scavenger resins. The first part of this review discusses the general premises of combinatorial chemistry and some methods used in the design of primary and focused combinatorial libraries. The aim of the second part is to present combinatorial chemistry methodologies aimed at discovering bioactive compounds acting on diverse GPCR involved in central nervous system disorders.

  3. Implementation of a combinatorial cleavage and deprotection scheme

    DEFF Research Database (Denmark)

    Nielsen, John; Rasmussen, Palle H.

    1996-01-01

    Phthalhydrazide libraries are synthesized in solution from substituted hydrazines and phthalimides in several different library formats including single compounds, indexed sub-libraries and a full library. When carried out during solid-phase synthesis, this combinatorial cleavage and deprotection...

  4. Isolation of scFv antibody fragments against HER2 and CEA tumor antigens from combinatorial antibody libraries derived from cancer patients.

    Science.gov (United States)

    Ayat, Hoda; Burrone, Oscar R; Sadghizadeh, Majid; Jahanzad, Eissa; Rastgou, Nasrin; Moghadasi, Sarrira; Arbabi, Mehdi

    2013-11-01

    Tumor cells expressing HER-2/neu and CEA antigens are potentially ideal targets for antibody-targeted therapy. In this study, two large human combinatorial libraries have been generated from the lymph nodes of breast cancer patients that express HER2 and CEA antigens in their tumors. These 'immune' libraries have been constructed in two different formats of scFv, differing in the length of the peptide linker connecting the two variable VH and VL domains. Libraries derived from these patients may contain a larger pool of anti-tumor antigen antibodies and are useful repertoire for isolating scFvs against any tumor markers. The results of this study showed that we were successful in obtaining human scFvs against HER-2/neu and CEA. For HER-2, cell-panning strategy was performed and resulted in two scFv binders that detected the complete HER-2 receptor on the cell membrane and internalized to the cells. Also, preliminary ELISA data showed that several anti-CEA scFv binders were isolated by panning. Copyright © 2013 The International Alliance for Biological Standardization. All rights reserved.

  5. A rational workflow for sequential virtual screening of chemical libraries on searching for new tyrosinase inhibitors.

    Science.gov (United States)

    Le-Thi-Thu, Huong; Casanola-Martín, Gerardo M; Marrero-Ponce, Yovani; Rescigno, Antonio; Abad, Concepcion; Khan, Mahmud Tareq Hassan

    2014-01-01

    The tyrosinase is a bifunctional, copper-containing enzyme widely distributed in the phylogenetic tree. This enzyme is involved in the production of melanin and some other pigments in humans, animals and plants, including skin pigmentations in mammals, and browning process in plants and vegetables. Therefore, enzyme inhibitors has been under the attention of the scientist community, due to its broad applications in food, cosmetic, agricultural and medicinal fields, to avoid the undesirable effects of abnormal melanin overproduction. However, the research of novel chemical with antityrosinase activity demands the use of more efficient tools to speed up the tyrosinase inhibitors discovery process. This chapter is focused in the different components of a predictive modeling workflow for the identification and prioritization of potential new compounds with activity against the tyrosinase enzyme. In this case, two structure chemical libraries Spectrum Collection and Drugbank are used in this attempt to combine different virtual screening data mining techniques, in a sequential manner helping to avoid the usually expensive and time consuming traditional methods. Some of the sequential steps summarize here comprise the use of drug-likeness filters, similarity searching, classification and potency QSAR multiclassifier systems, modeling molecular interactions systems, and similarity/diversity analysis. Finally, the methodologies showed here provide a rational workflow for virtual screening hit analysis and selection as a promissory drug discovery strategy for use in target identification phase.

  6. Molecular Pathogenesis of Rickettsioses and Development of Novel Anti-Rickettsial Treatment by Combinatorial Peptide-Based Libraries

    National Research Council Canada - National Science Library

    Walker, David H; Olano, Juan P

    2007-01-01

    ...) library and challenge with R. prowazekii, R. rickettsii, and O. tsutsugamushi; 2) To determine the role of NF-kB, cytokines, ROS and NO in intracellular killing of rickettsia-infected monolayers containing adapteins and 3...

  7. PR01 Molecular Pathogenesis of Rickettsioses and Development of Anti-Rickettsial Treatment by Combinatorial Peptide-Based Libraries

    National Research Council Canada - National Science Library

    Walker, David H

    2006-01-01

    ...) library and challenge with R. prowazekii, R. rickettsii, and O. tsutsugamushi; 2) To determine the role of NF-kB, cytokines, ROS and NO in intracellular killing of rickettsia-infected monolayers containing adapteins and 3...

  8. PR01 Molecular Pathogenesis of Rickettsioses and Development of Anti-Rickettsial Treatment by Combinatorial Peptide-Based Libraries

    National Research Council Canada - National Science Library

    Walker, David H

    2006-01-01

    The purpose of this study is to utilize adaptein libraries coded within pantropic retroviral vectors that confer protection against rickettsial pathogens and to study the molecular pathogenesis of rickettsioses...

  9. Human recombinant Fab fragment from combinatorial libraries of a B-cell lymphoma patient recognizes core protein of chondroitin sulphate proteoglycan 4.

    Science.gov (United States)

    Egami, Yoko; Narushima, Yuta; Ohshima, Motohiro; Yoshida, Akira; Yoneta, Naruki; Masaki, Yasufumi; Itoh, Kunihiko

    2018-01-01

    CD antigens are well known as therapeutic targets of B-cell lymphoma. To isolate therapeutic antibodies that recognize novel targets other than CD antigens, we constructed a phage display combinatorial antibody Fab library from bone marrow lymphocytes of B-cell lymphoma patient. To eliminate antibodies reactive with known B-cell lymphoma antigen, non-hematopoietic and patient's sera reactive HeLaS3 cells was selected as a target of whole cell panning. Five rounds of panning against live HeLaS3 cells retrieved single Fab clone, termed AHSA (Antibody to HeLa Surface Antigen). Using phage display random peptide library, LSYLEP was identified as an epitope sequence of AHSA. LC-MS/MS analysis of AHSA-precipitated HeLaS3 cell lysates detected several fragments corresponding to the sequence of chondroitin sulphate proteoglycan 4 (CSPG4) core protein. Since LSYLEP sequence was at the position of 313-318 of CSPG4, we considered that CSPG4 was AHSA-associated antigen. Double staining of CSPG4-postive MDA-MB-435S cells with AHSA and anti-CSPG4 rabbit antibody showed identical staining position, and reduced AHSA reactivity was observed in CSPG4-siRNA treated MDA-MB-435S cells. In conclusion, we retrieved a human Fab from antibody library of B-cell lymphoma patient, and identified CSPG4 as a recognizing antigen. AHSA may have potential benefits for development of CSPG4-targeting theranostics for B-cell lymphoma. © The Authors 2017. Published by Oxford University Press on behalf of the Japanese Biochemical Society. All rights reserved.

  10. Dynamic combinatorial chemistry with diselenides and disulfides in water

    DEFF Research Database (Denmark)

    Rasmussen, Brian; Sørensen, Anne; Gotfredsen, Henrik

    2014-01-01

    Diselenide exchange is introduced as a reversible reaction in dynamic combinatorial chemistry in water. At neutral pH, diselenides are found to mix with disulfides and form dynamic combinatorial libraries of diselenides, disulfides, and selenenylsulfides. This journal is......Diselenide exchange is introduced as a reversible reaction in dynamic combinatorial chemistry in water. At neutral pH, diselenides are found to mix with disulfides and form dynamic combinatorial libraries of diselenides, disulfides, and selenenylsulfides. This journal is...

  11.   Cell Penetrating Peptoids (CPPos: Synthesis of a Small Combinatorial Library by Using IRORI MiniKans

    Directory of Open Access Journals (Sweden)

    Dominik K. Kölmel

    2012-11-01

    Full Text Available Cell penetrating peptoids (CPPos are potent mimics of the corresponding cell penetrating peptides (CPPs. The synthesis of diverse oligomeric libraries that display a variety of backbone scaffolds and side-chain appendages are a very promising source of novel CPPos, which can be used to either target different cellular organelles or even different tissues and organs. In this study we established the submonomer-based solid phase synthesis of a “proof of principle” peptoid library in IRORI MiniKans to expand the amount for phenotypic high throughput screens of CPPos. The library consisting of tetrameric peptoids [oligo(N-alkylglycines] was established on Rink amide resin in a split and mix approach with hydrophilic and hydrophobic peptoid side chains. All CPPos of the presented library were labeled with rhodamine B to allow for the monitoring of cellular uptake by fluorescent confocal microscopy. Eventually, all the purified peptoids were subjected to live cell imaging to screen for CPPos with organelle specificity. While highly charged CPPos enter the cells by endocytosis with subsequent endosomal release, critical levels of lipophilicity allow other CPPos to specifically localize to mitochondria once a certain lipophilicity threshold is reached.

  12. Combinatorial Nano-Bio Interfaces.

    Science.gov (United States)

    Cai, Pingqiang; Zhang, Xiaoqian; Wang, Ming; Wu, Yun-Long; Chen, Xiaodong

    2018-06-08

    Nano-bio interfaces are emerging from the convergence of engineered nanomaterials and biological entities. Despite rapid growth, clinical translation of biomedical nanomaterials is heavily compromised by the lack of comprehensive understanding of biophysicochemical interactions at nano-bio interfaces. In the past decade, a few investigations have adopted a combinatorial approach toward decoding nano-bio interfaces. Combinatorial nano-bio interfaces comprise the design of nanocombinatorial libraries and high-throughput bioevaluation. In this Perspective, we address challenges in combinatorial nano-bio interfaces and call for multiparametric nanocombinatorics (composition, morphology, mechanics, surface chemistry), multiscale bioevaluation (biomolecules, organelles, cells, tissues/organs), and the recruitment of computational modeling and artificial intelligence. Leveraging combinatorial nano-bio interfaces will shed light on precision nanomedicine and its potential applications.

  13. Towards an animal model of ovarian cancer: cataloging chicken blood proteins using combinatorial peptide ligand libraries coupled with shotgun proteomic analysis for translational research.

    Science.gov (United States)

    Ma, Yingying; Sun, Zeyu; de Matos, Ricardo; Zhang, Jing; Odunsi, Kunle; Lin, Biaoyang

    2014-05-01

    Epithelial ovarian cancer is the most deadly gynecological cancer around the world, with high morbidity in industrialized countries. Early diagnosis is key in reducing its morbidity rate. Yet, robust biomarkers, diagnostics, and animal models are still limited for ovarian cancer. This calls for broader omics and systems science oriented diagnostics strategies. In this vein, the domestic chicken has been used as an ovarian cancer animal model, owing to its high rate of developing spontaneous epithelial ovarian tumors. Chicken blood has thus been considered a surrogate reservoir from which cancer biomarkers can be identified. However, the presence of highly abundant proteins in chicken blood has compromised the applicability of proteomics tools to study chicken blood owing to a lack of immunodepletion methods. Here, we demonstrate that a combinatorial peptide ligand library (CPLL) can efficiently remove highly abundant proteins from chicken blood samples, consequently doubling the number of identified proteins. Using an integrated CPLL-1DGE-LC-MSMS workflow, we identified a catalog of 264 unique proteins. Functional analyses further suggested that most proteins were coagulation and complement factors, blood transport and binding proteins, immune- and defense-related proteins, proteases, protease inhibitors, cellular enzymes, or cell structure and adhesion proteins. Semiquantitative spectral counting analysis identified 10 potential biomarkers from the present chicken ovarian cancer model. Additionally, many human homologs of chicken blood proteins we have identified have been independently suggested as diagnostic biomarkers for ovarian cancer, further triangulating our novel observations reported here. In conclusion, the CPLL-assisted proteomic workflow using the chicken ovarian cancer model provides a feasible platform for translational research to identify ovarian cancer biomarkers and understand ovarian cancer biology. To the best of our knowledge, we report here

  14. Combinatorial synthesis of natural products

    DEFF Research Database (Denmark)

    Nielsen, John

    2002-01-01

    Combinatorial syntheses allow production of compound libraries in an expeditious and organized manner immediately applicable for high-throughput screening. Natural products possess a pedigree to justify quality and appreciation in drug discovery and development. Currently, we are seeing a rapid...... increase in application of natural products in combinatorial chemistry and vice versa. The therapeutic areas of infectious disease and oncology still dominate but many new areas are emerging. Several complex natural products have now been synthesised by solid-phase methods and have created the foundation...... for preparation of combinatorial libraries. In other examples, natural products or intermediates have served as building blocks or scaffolds in the synthesis of complex natural products, bioactive analogues or designed hybrid molecules. Finally, structural motifs from the biologically active parent molecule have...

  15. Combinatorial synthesis of ceramic materials

    Science.gov (United States)

    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.

  16. A two-channel detection method for autofluorescence correction and efficient on-bead screening of one-bead one-compound combinatorial libraries using the COPAS fluorescence activated bead sorting system

    International Nuclear Information System (INIS)

    Hintersteiner, Martin; Auer, Manfred

    2013-01-01

    One-bead one-compound combinatorial library beads exhibit varying levels of autofluorescence after solid phase combinatorial synthesis. Very often this causes significant problems for automated on-bead screening using TentaGel beads and fluorescently labeled target proteins. Herein, we present a method to overcome this limitation when fluorescence activated bead sorting is used as the screening method. We have equipped the COPAS bead sorting instrument with a high-speed profiling unit and developed a spectral autofluorescence correction method. The correction method is based on a simple algebraic operation using the fluorescence data from two detection channels and is applied on-the-fly in order to reliably identify hit beads by COPAS bead sorting. Our method provides a practical tool for the fast and efficient isolation of hit beads from one-bead one-compound library screens using either fluorescently labeled target proteins or biotinylated target proteins. This method makes hit bead identification easier and more reliable. It reduces false positives and eliminates the need for time-consuming pre-sorting of library beads in order to remove autofluorescent beads. (technical note)

  17. Identification of cancer specific ligands from one-bead one compound combinatorial libraries to develop theranostics agents against oral squamous cell carcinoma

    Science.gov (United States)

    Yang, Frances Fan

    Background: Oral squamous cell carcinoma (OSCC) is one of the most prevalent disease worldwide. One-bead one-compound (OBOC) combinatorial technology is a powerful method to identify peptidomimetic ligands against a variety of receptors on cell surfaces. We therefore hypothesized that cancer specific ligands against OSCC might be identified and can be conjugated to optical dyes or nanocarriers to develop theranostic agents against OSCC. Material and methods: Different OSCC cell lines were incubated with OBOC libraries and beads with cell binding were sorted and then screened with normal human cells to identify peptide-beads binding to different OSCC cell lines but not binding to normal human cells. The molecular probes of OSCC were developed by biotinylating the carboxyl end of the ligands. OSCC theranostic agents were developed by decorating LLY13 with NPs and evaluated by using orthotopic bioluminescent oral cancer model. Results: Six OSCC specific ligands were discovered. Initial peptide-histochemistry study indicated that LLY12 and LLY13 were able to specifically detect OSCC cells grown on chamber slides at the concentration of 1 muM. In addition, LLY13 was found to penetrate into the OSCC cells and accumulate in the cytoplasm, and nucleus. After screened with a panel of integrin antibodies, only anti-alpha3 antibody was able to block most of OSCC cells binding to the LLY13 beads. OSCC theranostic agents developed using targeting LLY13 micelles (25+/- 4nm in diameter) were more efficient in binding to HSC-3 cancer cells compared to non-targeting micelles. Ex vivo images demonstrated that xenografts from the mice with targeting micelles appeared to have higher signals than the non-targeting groups. Conclusion: LLY13 has promising in vitro and in vivo targeting activity against OSCC. In addition, LLY13 is also able to penetrate into cancer cells via endocytosis. Initial study indicated that alpha3 integrin might partially be the corresponding receptor involved

  18. Reiterative Recombination for the in vivo assembly of libraries of multigene pathways

    OpenAIRE

    Wingler, Laura M.; Cornish, Virginia W.

    2011-01-01

    The increasing sophistication of synthetic biology is creating a demand for robust, broadly accessible methodology for constructing multigene pathways inside of the cell. Due to the difficulty of rationally designing pathways that function as desired in vivo, there is a further need to assemble libraries of pathways in parallel, in order to facilitate the combinatorial optimization of performance. While some in vitro DNA assembly methods can theoretically make libraries of pathways, these tec...

  19. DPN-Generated Combinatorial Libraries

    Science.gov (United States)

    2012-02-29

    µM final concentration) is added (Fig. 6). Control over deposition parameters was examined for two model proteins, cholera toxin β subunit (CTβ...conjugated anti- cholera toxin beta (anti-CTb). The wells in the mould are inverted pyramids with an average depth of 86 µm, edge length of 120 µm, and...Therapeutics,” (2011). 91. University of New Mexico , Chemistry Department Colloquium, Albuquerque, NM, “The Polyvalent Gold Nanoparticle Conjugate

  20. Heterogenous phase as a mean in combinatorial chemistry

    International Nuclear Information System (INIS)

    Abdel-Hamid, S.G.

    2007-01-01

    Combinatorial chemistry is a rapid and inexpensive technique for the synthesis of hundreds of thousands of organic compounds of potential medicinal activity. In the past few decades a large number of combinatorial libraries have been constructed, and significantly supplement the chemical diversity of the traditional collections of the potentially active medicinal compounds. Solid phase synthesis was used to enrich the combinatorial chemistry libraries, through the use of solid supports (resins) and their modified forms. Most of the new libraries of compounds appeared recently, were synthesized by the use of solid-phase. Solid-phase combinatorial chemistry (SPCC) is now considered as an outstanding branch in pharmaceutical chemistry research and used extensively as a tool for drug discovery within the context of high-throughput chemical synthesis. The best pure libraries synthesized by the use of solid phase combinatorial chemistry (SPCC) may well be those of intermediate complexity that are free of artifact-causing nuisance compounds. (author)

  1. Applications of combinatorial optimization

    CERN Document Server

    Paschos, Vangelis Th

    2013-01-01

    Combinatorial optimization is a multidisciplinary scientific area, lying in the interface of three major scientific domains: mathematics, theoretical computer science and management. The three volumes of the Combinatorial Optimization series aims to cover a wide range of topics in this area. These topics also deal with fundamental notions and approaches as with several classical applications of combinatorial optimization. "Applications of Combinatorial Optimization" is presenting a certain number among the most common and well-known applications of Combinatorial Optimization.

  2. Local formulae for combinatorial Pontryagin classes

    International Nuclear Information System (INIS)

    Gaifullin, Alexander A

    2004-01-01

    Let p(|K|) be the characteristic class of a combinatorial manifold K given by a polynomial p in the rational Pontryagin classes of K. We prove that for any polynomial p there is a function taking each combinatorial manifold K to a cycle z p (K) in its rational simplicial chains such that: 1) the Poincare dual of z p (K) represents the cohomology class p(|K|); 2) the coefficient of each simplex Δ in the cycle z p (K) is determined solely by the combinatorial type of linkΔ. We explicitly describe all such functions for the first Pontryagin class. We obtain estimates for the denominators of the coefficients of the simplices in the cycles z p (K)

  3. Model, prediction, and experimental verification of composition and thickness in continuous spread thin film combinatorial libraries grown by pulsed laser deposition

    International Nuclear Information System (INIS)

    Bassim, N. D.; Schenck, P. K.; Otani, M.; Oguchi, H.

    2007-01-01

    Pulsed laser deposition was used to grow continuous spread thin film libraries of continuously varying composition as a function of position on a substrate. The thickness of each component that contributes to a library can be empirically modeled to a bimodal cosine power distribution. We deposited ternary continuous spread thin film libraries from Al 2 O 3 , HfO 2 , and Y 2 O 3 targets, at two different background pressures of O 2 : 1.3 and 13.3 Pa. Prior to library deposition, we deposited single component calibration films at both pressures in order to measure and fit the thickness distribution. Following the deposition and fitting of the single component films, we predict both the compositional coverage and the thickness of the libraries. Then, we map the thickness of the continuous spread libraries using spectroscopic reflectometry and measure the composition of the libraries as a function of position using mapping wavelength-dispersive spectrometry (WDS). We then compare the compositional coverage of the libraries and observe that compositional coverage is enhanced in the case of 13.3 Pa library. Our models demonstrate linear correlation coefficients of 0.98 for 1.3 Pa and 0.98 for 13.3 Pa with the WDS

  4. Concepts of combinatorial optimization

    CERN Document Server

    Paschos, Vangelis Th

    2014-01-01

    Combinatorial optimization is a multidisciplinary scientific area, lying in the interface of three major scientific domains: mathematics, theoretical computer science and management.  The three volumes of the Combinatorial Optimization series aim to cover a wide range  of topics in this area. These topics also deal with fundamental notions and approaches as with several classical applications of combinatorial optimization.Concepts of Combinatorial Optimization, is divided into three parts:- On the complexity of combinatorial optimization problems, presenting basics about worst-case and randomi

  5. Extension of P-adic Exact Scientific Computational Library (ESCL) to Compute the Exponential of Rational Matrix

    National Research Council Canada - National Science Library

    Lu, Chao

    2008-01-01

    ...) using p-adic arithmetic. New algorithms have been designed and implemented for matrix operations with rational numbers by representing numerator and denominator with arbitrary length integers, all integers and fractional...

  6. Combinatorial commutative algebra

    CERN Document Server

    Miller, Ezra

    2005-01-01

    Offers an introduction to combinatorial commutative algebra, focusing on combinatorial techniques for multigraded polynomial rings, semigroup algebras, and determined rings. The chapters in this work cover topics ranging from homological invariants of monomial ideals and their polyhedral resolutions, to tools for studying algebraic varieties.

  7. Directed combinatorial mutagenesis of Escherichia coli for complex phenotype engineering

    Energy Technology Data Exchange (ETDEWEB)

    Liu, Rongming; Liang, Liya; Garst, Andrew D.; Choudhury, Alaksh; Nogué, Violeta Sànchez i.; Beckham, Gregg T.; Gill, Ryan T.

    2018-05-01

    Strain engineering for industrial production requires a targeted improvement of multiple complex traits, which range from pathway flux to tolerance to mixed sugar utilization. Here, we report the use of an iterative CRISPR EnAbled Trackable genome Engineering (iCREATE) method to engineer rapid glucose and xylose co-consumption and tolerance to hydrolysate inhibitors in E. coli. Deep mutagenesis libraries were rationally designed, constructed, and screened to target ~40,000 mutations across 30 genes. These libraries included global and high-level regulators that regulate global gene expression, transcription factors that play important roles in genome-level transcription, enzymes that function in the sugar transport system, NAD(P)H metabolism, and the aldehyde reduction system. Specific mutants that conferred increased growth in mixed sugars and hydrolysate tolerance conditions were isolated, confirmed, and evaluated for changes in genome-wide expression levels. We tested the strain with positive combinatorial mutations for 3-hydroxypropionic acid (3HP) production under high furfural and high acetate hydrolysate fermentation, which demonstrated a 7- and 8-fold increase in 3HP productivity relative to the parent strain, respectively.

  8. Library

    OpenAIRE

    Dulaney, Ronald E. Jr.

    1997-01-01

    This study began with the desire to design a public town library of the future and became a search for an inkling of what is essential to Architecture. It is murky and full of contradictions. It asks more than it proposes, and the traces of its windings are better ordered through collage than logical synthesis. This study is neither a thesis nor a synthesis. When drawing out the measure of this study it may be beneficial to state what it attempts to place at the ...

  9. Integer and combinatorial optimization

    CERN Document Server

    Nemhauser, George L

    1999-01-01

    Rave reviews for INTEGER AND COMBINATORIAL OPTIMIZATION ""This book provides an excellent introduction and survey of traditional fields of combinatorial optimization . . . It is indeed one of the best and most complete texts on combinatorial optimization . . . available. [And] with more than 700 entries, [it] has quite an exhaustive reference list.""-Optima ""A unifying approach to optimization problems is to formulate them like linear programming problems, while restricting some or all of the variables to the integers. This book is an encyclopedic resource for such f

  10. Design and combinatorial library generation of 1H 1,4 benzodiazepine 2,5 diones as photosystem-II inhibitors: A public QSAR approach

    Directory of Open Access Journals (Sweden)

    Purusottam Banjare

    2017-09-01

    Full Text Available Exponential rise in the population around the word increased the demand of food grains/crops with limited expansion of the agricultural land. To meet the demand, generation of new herbicidal agents is of primary need for the manufacturing firm. In silico tool like QSAR is one of the regularly used in designing newer compounds along with wet experiment. Photosystem-II (PS-II regarded as one of the major target for the herbicidal agents. With this aim in the present study a series of 1H, 1,4 benzodiazepine 2,5-dione analogues as herbicidal (PS-II inhibitors agents were subjected to QSAR analysis using 2D PaDEL descriptors (open source. Two different splitting techniques namely, kennard stone based and k-means clustering splitting were used to divide the whole data set and GFA based on MAE criteria was used a statistical method to develop a model to investigate the physicochemical and structural requirement of potential PS-II inhibitors. All the models are statistically robust both internally and externally (Q2: 0.540–0.693, R2pred: 0.722–0.810. The activity is mostly affected by polarizabilities, electro negativities as well as substituents at the phenyl ring. Based on the results, a library of compounds was generated using SmiLib v2.0 tool (open source and better predicted inside applicability domain compounds were identified by applying three different applicability domain (AD approaches. Therefore the developed public QSAR models may be helpful for the scientific community for the further research.

  11. Nonparametric combinatorial sequence models.

    Science.gov (United States)

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

    2011-11-01

    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 article 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 biological sequence families 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 over sequence representations induced by the prior. By integrating out the posterior, our method compares favorably to leading binding predictors.

  12. Combining rational and random strategies in β-glucosidase Zm-p60.1 protein library construction.

    Directory of Open Access Journals (Sweden)

    Dušan Turek

    Full Text Available Saturation mutagenesis is a cornerstone technique in protein engineering because of its utility (in conjunction with appropriate analytical techniques for assessing effects of varying residues at selected positions on proteins' structures and functions. Site-directed mutagenesis with degenerate primers is the simplest and most rapid saturation mutagenesis technique. Thus, it is highly appropriate for assessing whether or not variation at certain sites is permissible, but not necessarily the most time- and cost-effective technique for detailed assessment of variations' effects. Thus, in the presented study we applied the technique to randomize position W373 in β-glucosidase Zm-p60.1, which is highly conserved among β-glucosidases. Unexpectedly, β-glucosidase activity screening of the generated variants showed that most variants were active, although they generally had significantly lower activity than the wild type enzyme. Further characterization of the library led us to conclude that a carefully selected combination of randomized codon-based saturation mutagenesis and site-directed mutagenesis may be most efficient, particularly when constructing and investigating randomized libraries with high fractions of positive hits.

  13. Combining rational and random strategies in β-glucosidase Zm-p60.1 protein library construction.

    Science.gov (United States)

    Turek, Dušan; Klimeš, Pavel; Mazura, Pavel; Brzobohatý, Břetislav

    2014-01-01

    Saturation mutagenesis is a cornerstone technique in protein engineering because of its utility (in conjunction with appropriate analytical techniques) for assessing effects of varying residues at selected positions on proteins' structures and functions. Site-directed mutagenesis with degenerate primers is the simplest and most rapid saturation mutagenesis technique. Thus, it is highly appropriate for assessing whether or not variation at certain sites is permissible, but not necessarily the most time- and cost-effective technique for detailed assessment of variations' effects. Thus, in the presented study we applied the technique to randomize position W373 in β-glucosidase Zm-p60.1, which is highly conserved among β-glucosidases. Unexpectedly, β-glucosidase activity screening of the generated variants showed that most variants were active, although they generally had significantly lower activity than the wild type enzyme. Further characterization of the library led us to conclude that a carefully selected combination of randomized codon-based saturation mutagenesis and site-directed mutagenesis may be most efficient, particularly when constructing and investigating randomized libraries with high fractions of positive hits.

  14. Combinatorial Hybrid Systems

    DEFF Research Database (Denmark)

    Larsen, Jesper Abildgaard; Wisniewski, Rafal; Grunnet, Jacob Deleuran

    2008-01-01

    indicates for a given face the future simplex. In the suggested definition we allow nondeterminacy in form of splitting and merging of solution trajectories. The combinatorial vector field gives rise to combinatorial counterparts of most concepts from dynamical systems, such as duals to vector fields, flow......, flow lines, fixed points and Lyapunov functions. Finally it will be shown how this theory extends to switched dynamical systems and an algorithmic overview of how to do supervisory control will be shown towards the end....

  15. Solidified self-nanoemulsifying formulation for oral delivery of combinatorial therapeutic regimen

    DEFF Research Database (Denmark)

    Jain, Amit K; Thanki, Kaushik; Jain, Sanyog

    2014-01-01

    PURPOSE: The present work reports rationalized development and characterization of solidified self-nanoemulsifying drug delivery system for oral delivery of combinatorial (tamoxifen and quercetin) therapeutic regimen. METHODS: Suitable oil for the preparation of liquid SNEDDS was selected based...

  16. Combinatorial techniques to efficiently investigate and optimize organic thin film processing and properties.

    Science.gov (United States)

    Wieberger, Florian; Kolb, Tristan; Neuber, Christian; Ober, Christopher K; Schmidt, Hans-Werner

    2013-04-08

    In this article we present several developed and improved combinatorial techniques to optimize processing conditions and material properties of organic thin films. The combinatorial approach allows investigations of multi-variable dependencies and is the perfect tool to investigate organic thin films regarding their high performance purposes. In this context we develop and establish the reliable preparation of gradients of material composition, temperature, exposure, and immersion time. Furthermore we demonstrate the smart application of combinations of composition and processing gradients to create combinatorial libraries. First a binary combinatorial library is created by applying two gradients perpendicular to each other. A third gradient is carried out in very small areas and arranged matrix-like over the entire binary combinatorial library resulting in a ternary combinatorial library. Ternary combinatorial libraries allow identifying precise trends for the optimization of multi-variable dependent processes which is demonstrated on the lithographic patterning process. Here we verify conclusively the strong interaction and thus the interdependency of variables in the preparation and properties of complex organic thin film systems. The established gradient preparation techniques are not limited to lithographic patterning. It is possible to utilize and transfer the reported combinatorial techniques to other multi-variable dependent processes and to investigate and optimize thin film layers and devices for optical, electro-optical, and electronic applications.

  17. Combinatorial Techniques to Efficiently Investigate and Optimize Organic Thin Film Processing and Properties

    Directory of Open Access Journals (Sweden)

    Hans-Werner Schmidt

    2013-04-01

    Full Text Available In this article we present several developed and improved combinatorial techniques to optimize processing conditions and material properties of organic thin films. The combinatorial approach allows investigations of multi-variable dependencies and is the perfect tool to investigate organic thin films regarding their high performance purposes. In this context we develop and establish the reliable preparation of gradients of material composition, temperature, exposure, and immersion time. Furthermore we demonstrate the smart application of combinations of composition and processing gradients to create combinatorial libraries. First a binary combinatorial library is created by applying two gradients perpendicular to each other. A third gradient is carried out in very small areas and arranged matrix-like over the entire binary combinatorial library resulting in a ternary combinatorial library. Ternary combinatorial libraries allow identifying precise trends for the optimization of multi-variable dependent processes which is demonstrated on the lithographic patterning process. Here we verify conclusively the strong interaction and thus the interdependency of variables in the preparation and properties of complex organic thin film systems. The established gradient preparation techniques are not limited to lithographic patterning. It is possible to utilize and transfer the reported combinatorial techniques to other multi-variable dependent processes and to investigate and optimize thin film layers and devices for optical, electro-optical, and electronic applications.

  18. Introduction to combinatorial designs

    CERN Document Server

    Wallis, WD

    2007-01-01

    Combinatorial theory is one of the fastest growing areas of modern mathematics. Focusing on a major part of this subject, Introduction to Combinatorial Designs, Second Edition provides a solid foundation in the classical areas of design theory as well as in more contemporary designs based on applications in a variety of fields. After an overview of basic concepts, the text introduces balanced designs and finite geometries. The author then delves into balanced incomplete block designs, covering difference methods, residual and derived designs, and resolvability. Following a chapter on the e

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

    Science.gov (United States)

    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.

  20. Infinitary Combinatory Reduction Systems

    DEFF Research Database (Denmark)

    Ketema, Jeroen; Simonsen, Jakob Grue

    2011-01-01

    We define infinitary Combinatory Reduction Systems (iCRSs), thus providing the first notion of infinitary higher-order rewriting. The systems defined are sufficiently general that ordinary infinitary term rewriting and infinitary ¿-calculus are special cases. Furthermore,we generalise a number...

  1. Manipulating Combinatorial Structures.

    Science.gov (United States)

    Labelle, Gilbert

    This set of transparencies shows how the manipulation of combinatorial structures in the context of modern combinatorics can easily lead to interesting teaching and learning activities at every level of education from elementary school to university. The transparencies describe: (1) the importance and relations of combinatorics to science and…

  2. Introduction to combinatorial geometry

    International Nuclear Information System (INIS)

    Gabriel, T.A.; Emmett, M.B.

    1985-01-01

    The combinatorial geometry package as used in many three-dimensional multimedia Monte Carlo radiation transport codes, such as HETC, MORSE, and EGS, is becoming the preferred way to describe simple and complicated systems. Just about any system can be modeled using the package with relatively few input statements. This can be contrasted against the older style geometry packages in which the required input statements could be large even for relatively simple systems. However, with advancements come some difficulties. The users of combinatorial geometry must be able to visualize more, and, in some instances, all of the system at a time. Errors can be introduced into the modeling which, though slight, and at times hard to detect, can have devastating effects on the calculated results. As with all modeling packages, the best way to learn the combinatorial geometry is to use it, first on a simple system then on more complicated systems. The basic technique for the description of the geometry consists of defining the location and shape of the various zones in terms of the intersections and unions of geometric bodies. The geometric bodies which are generally included in most combinatorial geometry packages are: (1) box, (2) right parallelepiped, (3) sphere, (4) right circular cylinder, (5) right elliptic cylinder, (6) ellipsoid, (7) truncated right cone, (8) right angle wedge, and (9) arbitrary polyhedron. The data necessary to describe each of these bodies are given. As can be easily noted, there are some subsets included for simplicity

  3. Isocyanide based multi component reactions in combinatorial chemistry.

    NARCIS (Netherlands)

    Dömling, A.

    1998-01-01

    Although usually regarded as a recent development, the combinatorial approach to the synthesis of libraries of new drug candidates was first described as early as 1961 using the isocyanide-based one-pot multicomponent Ugi reaction. Isocyanide-based multi component reactions (MCR's) markedly differ

  4. Combinatorial Solid-Phase Synthesis of Balanol Analogues

    DEFF Research Database (Denmark)

    Nielsen, John; Lyngsø, Lars Ole

    1996-01-01

    The natural product balanol has served as a template for the design and synthesis of a combinatorial library using solid-phase chemistry. Using a retrosynthetic analysis, the structural analogues have been assembled from three relatively accessible building blocks. The solid-phase chemistry inclu...

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

    Science.gov (United States)

    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…

  6. Rapid mapping of protein functional epitopes by combinatorial alanine scanning

    OpenAIRE

    Weiss, GA; Watanabe, CK; Zhong, A; Goddard, A; Sidhu, SS

    2000-01-01

    A combinatorial alanine-scanning strategy was used to determine simultaneously the functional contributions of 19 side chains buried at the interface between human growth hormone and the extracellular domain of its receptor. A phage-displayed protein library was constructed in which the 19 side chains were preferentially allowed to vary only as the wild type or alanine. The library pool was subjected to binding selections to isolate functional clones, and DNA sequencing was used to determine ...

  7. The combinatorial derivation

    Directory of Open Access Journals (Sweden)

    Igor V. Protasov

    2013-09-01

    $\\Delta(A=\\{g\\in G:|gA\\cap A|=\\infty\\}$. The mapping $\\Delta:\\mathcal{P}_G\\rightarrow\\mathcal{P}_G$, $A\\mapsto\\Delta(A$, is called a combinatorial derivation and can be considered as an analogue of the topological derivation $d:\\mathcal{P}_X\\rightarrow\\mathcal{P}_X$, $A\\mapsto A^d$, where $X$ is a topological space and $A^d$ is the set of all limit points of $A$. Content: elementary properties, thin and almost thin subsets, partitions, inverse construction and $\\Delta$-trajectories,  $\\Delta$ and $d$.

  8. Dynamic Combinatorial Chemistry

    DEFF Research Database (Denmark)

    Lisbjerg, Micke

    This thesis is divided into seven chapters, which can all be read individually. The first chapter, however, contains a general introduction to the chemistry used in the remaining six chapters, and it is therefore recommended to read chapter one before reading the other chapters. Chapter 1...... is a general introductory chapter for the whole thesis. The history and concepts of dynamic combinatorial chemistry are described, as are some of the new and intriguing results recently obtained. Finally, the properties of a broad range of hexameric macrocycles are described in detail. Chapter 2 gives...

  9. Boltzmann Oracle for Combinatorial Systems

    OpenAIRE

    Pivoteau , Carine; Salvy , Bruno; Soria , Michèle

    2008-01-01

    International audience; Boltzmann random generation applies to well-defined systems of recursive combinatorial equations. It relies on oracles giving values of the enumeration generating series inside their disk of convergence. We show that the combinatorial systems translate into numerical iteration schemes that provide such oracles. In particular, we give a fast oracle based on Newton iteration.

  10. The construction of combinatorial manifolds with prescribed sets of links of vertices

    International Nuclear Information System (INIS)

    Gaifullin, A A

    2008-01-01

    To every oriented closed combinatorial manifold we assign the set (with repetitions) of isomorphism classes of links of its vertices. The resulting transformation L is the main object of study in this paper. We pose an inversion problem for L and show that this problem is closely related to Steenrod's problem on the realization of cycles and to the Rokhlin-Schwartz-Thom construction of combinatorial Pontryagin classes. We obtain a necessary condition for a set of isomorphism classes of combinatorial spheres to belong to the image of L. (Sets satisfying this condition are said to be balanced.) We give an explicit construction showing that every balanced set of isomorphism classes of combinatorial spheres falls into the image of L after passing to a multiple set and adding several pairs of the form (Z,-Z), where -Z is the sphere Z with the orientation reversed. Given any singular simplicial cycle ξ of a space X, this construction enables us to find explicitly a combinatorial manifold M and a map φ:M→X such that φ * [M]=r[ξ] for some positive integer r. The construction is based on resolving singularities of ξ. We give applications of the main construction to cobordisms of manifolds with singularities and cobordisms of simple cells. In particular, we prove that every rational additive invariant of cobordisms of manifolds with singularities admits a local formula. Another application is the construction of explicit (though inefficient) local combinatorial formulae for polynomials in the rational Pontryagin classes of combinatorial manifolds

  11. Combinatorial matrix theory

    CERN Document Server

    Mitjana, Margarida

    2018-01-01

    This book contains the notes of the lectures delivered at an Advanced Course on Combinatorial Matrix Theory held at Centre de Recerca Matemàtica (CRM) in Barcelona. These notes correspond to five series of lectures. The first series is dedicated to the study of several matrix classes defined combinatorially, and was delivered by Richard A. Brualdi. The second one, given by Pauline van den Driessche, is concerned with the study of spectral properties of matrices with a given sign pattern. Dragan Stevanović delivered the third one, devoted to describing the spectral radius of a graph as a tool to provide bounds of parameters related with properties of a graph. The fourth lecture was delivered by Stephen Kirkland and is dedicated to the applications of the Group Inverse of the Laplacian matrix. The last one, given by Ángeles Carmona, focuses on boundary value problems on finite networks with special in-depth on the M-matrix inverse problem.

  12. Cryptographic Combinatorial Securities Exchanges

    Science.gov (United States)

    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.

  13. Technostress and Library Values.

    Science.gov (United States)

    Gorman, Michael

    2001-01-01

    Discusses information overload and society's and libraries' responses to technology. Considers eight values that libraries should focus on and how they relate to technology in libraries: democracy, stewardship, service, intellectual freedom, privacy, rationalism, equity of access, and building harmony and balance. (LRW)

  14. Evaluation of the Optimum Composition of Low-Temperature Fuel Cell Electrocatalysts for Methanol Oxidation by Combinatorial Screening.

    Science.gov (United States)

    Antolini, Ermete

    2017-02-13

    Combinatorial chemistry and high-throughput screening represent an innovative and rapid tool to prepare and evaluate a large number of new materials, saving time and expense for research and development. Considering that the activity and selectivity of catalysts depend on complex kinetic phenomena, making their development largely empirical in practice, they are prime candidates for combinatorial discovery and optimization. This review presents an overview of recent results of combinatorial screening of low-temperature fuel cell electrocatalysts for methanol oxidation. Optimum catalyst compositions obtained by combinatorial screening were compared with those of bulk catalysts, and the effect of the library geometry on the screening of catalyst composition is highlighted.

  15. Combinatorial optimization games

    Energy Technology Data Exchange (ETDEWEB)

    Deng, X. [York Univ., North York, Ontario (Canada); Ibaraki, Toshihide; Nagamochi, Hiroshi [Kyoto Univ. (Japan)

    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.

  16. Combinatorial Testing for VDM

    DEFF Research Database (Denmark)

    Larsen, Peter Gorm; Lausdahl, Kenneth; Battle, Nick

    2010-01-01

    by forgotten preconditions as well as broken invariants and post-conditions. Trace definitions are defined as regular expressions describing possible sequences of operation calls, and are conceptually similar to UML sequence diagrams. In this paper we present a tool enabling test automation based on VDM traces......Abstract—Combinatorial testing in VDM involves the automatic generation and execution of a large collection of test cases derived from templates provided in the form of trace definitions added to a VDM specification. The main value of this is the rapid detection of run-time errors caused......, and explain how it is possible to reduce large collections of test cases in different ways. Its use is illustrated with a small case study....

  17. Library fingerprints: a novel approach to the screening of virtual libraries.

    Science.gov (United States)

    Klon, Anthony E; Diller, David J

    2007-01-01

    We propose a novel method to prioritize libraries for combinatorial synthesis and high-throughput screening that assesses the viability of a particular library on the basis of the aggregate physical-chemical properties of the compounds using a naïve Bayesian classifier. This approach prioritizes collections of related compounds according to the aggregate values of their physical-chemical parameters in contrast to single-compound screening. The method is also shown to be useful in screening existing noncombinatorial libraries when the compounds in these libraries have been previously clustered according to their molecular graphs. We show that the method used here is comparable or superior to the single-compound virtual screening of combinatorial libraries and noncombinatorial libraries and is superior to the pairwise Tanimoto similarity searching of a collection of combinatorial libraries.

  18. On an extension of a combinatorial identity

    Indian Academy of Sciences (India)

    to an infinite family of 4-way combinatorial identities. In some particular cases we get even 5-way combinatorial identities which give us four new combinatorial versions of. Göllnitz–Gordon identities. Keywords. n-Color partitions; lattice paths; Frobenius partitions; Göllnitz–Gordon identities; combinatorial interpretations. 1.

  19. A Convergent Solid-Phase Synthesis of Actinomycin Analogues - Towards Implementation of Double-Combinatorial Chemistry

    DEFF Research Database (Denmark)

    Tong, Glenn; Nielsen, John

    1996-01-01

    The actinomycin antibiotics bind to nucleic acids via both intercalation and hydrogen bonding. We found this 'double-action attack' mechanism very attractive in our search for a novel class of nucleic acid binders. A highly convergent, solid-phase synthetic strategy has been developed for a class...... with the requirements for combinatorial synthesis and furthermore, the final segment condensation allows, for the first time, double-combinatorial chemistry to be performed where two combinatorial libraries can be reacted with each other. Copyright (C) 1996 Elsevier Science Ltd....

  20. Combinatorial designs constructions and analysis

    CERN Document Server

    Stinson, Douglas R

    2004-01-01

    Created to teach students many of the most important techniques used for constructing combinatorial designs, this is an ideal textbook for advanced undergraduate and graduate courses in combinatorial design theory. The text features clear explanations of basic designs, such as Steiner and Kirkman triple systems, mutual orthogonal Latin squares, finite projective and affine planes, and Steiner quadruple systems. In these settings, the student will master various construction techniques, both classic and modern, and will be well-prepared to construct a vast array of combinatorial designs. Design theory offers a progressive approach to the subject, with carefully ordered results. It begins with simple constructions that gradually increase in complexity. Each design has a construction that contains new ideas or that reinforces and builds upon similar ideas previously introduced. A new text/reference covering all apsects of modern combinatorial design theory. Graduates and professionals in computer science, applie...

  1. Combinatorial Mathematics: Research into Practice

    Science.gov (United States)

    Sriraman, Bharath; English, Lyn D.

    2004-01-01

    Implications and suggestions for using combinatorial mathematics in the classroom through a survey and synthesis of numerous research studies are presented. The implications revolve around five major themes that emerge from analysis of these studies.

  2. Combinatorial methods with computer applications

    CERN Document Server

    Gross, Jonathan L

    2007-01-01

    Combinatorial Methods with Computer Applications provides in-depth coverage of recurrences, generating functions, partitions, and permutations, along with some of the most interesting graph and network topics, design constructions, and finite geometries. Requiring only a foundation in discrete mathematics, it can serve as the textbook in a combinatorial methods course or in a combined graph theory and combinatorics course.After an introduction to combinatorics, the book explores six systematic approaches within a comprehensive framework: sequences, solving recurrences, evaluating summation exp

  3. Number systems and combinatorial problems

    OpenAIRE

    Yordzhev, Krasimir

    2014-01-01

    The present work has been designed for students in secondary school and their teachers in mathematics. We will show how with the help of our knowledge of number systems we can solve problems from other fields of mathematics for example in combinatorial analysis and most of all when proving some combinatorial identities. To demonstrate discussed in this article method we have chosen several suitable mathematical tasks.

  4. Relativity in Combinatorial Gravitational Fields

    Directory of Open Access Journals (Sweden)

    Mao Linfan

    2010-04-01

    Full Text Available A combinatorial spacetime $(mathscr{C}_G| uboverline{t}$ is a smoothly combinatorial manifold $mathscr{C}$ underlying a graph $G$ evolving on a time vector $overline{t}$. As we known, Einstein's general relativity is suitable for use only in one spacetime. What is its disguise in a combinatorial spacetime? Applying combinatorial Riemannian geometry enables us to present a combinatorial spacetime model for the Universe and suggest a generalized Einstein gravitational equation in such model. Forfinding its solutions, a generalized relativity principle, called projective principle is proposed, i.e., a physics law ina combinatorial spacetime is invariant under a projection on its a subspace and then a spherically symmetric multi-solutions ofgeneralized Einstein gravitational equations in vacuum or charged body are found. We also consider the geometrical structure in such solutions with physical formations, and conclude that an ultimate theory for the Universe maybe established if all such spacetimes in ${f R}^3$. Otherwise, our theory is only an approximate theory and endless forever.

  5. Pragmatics & rationality.

    OpenAIRE

    Allott, N. E.

    2007-01-01

    This thesis is about the reconciliation of realistic views of rationality with inferential-intentional theories of communication. Grice (1957 1975) argued that working out what a speaker meant by an utterance is a matter of inferring the speaker's intentions on the presumption that she is acting rationally. This is abductive inference: inference to the best explanation for the utterance. Thus an utterance both rationalises and causes the interpretation the hearer constructs. Human rationality...

  6. A Simple Combinatorial Codon Mutagenesis Method for Targeted Protein Engineering.

    Science.gov (United States)

    Belsare, Ketaki D; Andorfer, Mary C; Cardenas, Frida S; Chael, Julia R; Park, Hyun June; Lewis, Jared C

    2017-03-17

    Directed evolution is a powerful tool for optimizing enzymes, and mutagenesis methods that improve enzyme library quality can significantly expedite the evolution process. Here, we report a simple method for targeted combinatorial codon mutagenesis (CCM). To demonstrate the utility of this method for protein engineering, CCM libraries were constructed for cytochrome P450 BM3 , pfu prolyl oligopeptidase, and the flavin-dependent halogenase RebH; 10-26 sites were targeted for codon mutagenesis in each of these enzymes, and libraries with a tunable average of 1-7 codon mutations per gene were generated. Each of these libraries provided improved enzymes for their respective transformations, which highlights the generality, simplicity, and tunability of CCM for targeted protein engineering.

  7. Coherent states and rational surfaces

    International Nuclear Information System (INIS)

    Brody, Dorje C; Graefe, Eva-Maria

    2010-01-01

    The state spaces of generalized coherent states associated with special unitary groups are shown to form rational curves and surfaces in the space of pure states. These curves and surfaces are generated by the various Veronese embeddings of the underlying state space into higher dimensional state spaces. This construction is applied to the parameterization of generalized coherent states, which is useful for practical calculations, and provides an elementary combinatorial approach to the geometry of the coherent state space. The results are extended to Hilbert spaces with indefinite inner products, leading to the introduction of a new kind of generalized coherent states.

  8. Combinatorial optimization theory and algorithms

    CERN Document Server

    Korte, Bernhard

    2018-01-01

    This comprehensive textbook on combinatorial optimization places special emphasis on theoretical results and algorithms with provably good performance, in contrast to heuristics. It is based on numerous courses on combinatorial optimization and specialized topics, mostly at graduate level. This book reviews the fundamentals, covers the classical topics (paths, flows, matching, matroids, NP-completeness, approximation algorithms) in detail, and proceeds to advanced and recent topics, some of which have not appeared in a textbook before. Throughout, it contains complete but concise proofs, and also provides numerous exercises and references. This sixth edition has again been updated, revised, and significantly extended. Among other additions, there are new sections on shallow-light trees, submodular function maximization, smoothed analysis of the knapsack problem, the (ln 4+ɛ)-approximation for Steiner trees, and the VPN theorem. Thus, this book continues to represent the state of the art of combinatorial opti...

  9. Dynamic combinatorial chemistry to identify binders of ThiT, an S-component of the energy-coupling factor transporter for thiamine

    NARCIS (Netherlands)

    Monjas, Leticia; Swier, Lotteke J Y M; Setyawati, Inda; Slotboom, Dirk Jan; Hirsch, Anna Katharina Herta

    2017-01-01

    We applied dynamic combinatorial chemistry (DCC) to identify ligands of ThiT, the S-component of the energy-coupling factor (ECF) transporter for thiamine in Lactococcus lactis. We used a pre-equilibrated dynamic combinatorial library (DCL) and saturation-transfer difference (STD) NMR spectroscopy

  10. Effect of the Implicit Combinatorial Model on Combinatorial Reasoning in Secondary School Pupils.

    Science.gov (United States)

    Batanero, Carmen; And Others

    1997-01-01

    Elementary combinatorial problems may be classified into three different combinatorial models: (1) selection; (2) partition; and (3) distribution. The main goal of this research was to determine the effect of the implicit combinatorial model on pupils' combinatorial reasoning before and after instruction. Gives an analysis of variance of the…

  11. Baseline rationing

    DEFF Research Database (Denmark)

    Hougaard, Jens Leth; Moreno-Ternero, Juan D.; Østerdal, Lars Peter Raahave

    The standard problem of adjudicating conflicting claims describes a situation in which a given amount of a divisible good has to be allocated among agents who hold claims against it exceeding the available amount. This paper considers more general rationing problems in which, in addition to claims...... to international protocols for the reduction of greenhouse emissions, or water distribution in drought periods. We define a family of allocation methods for such general rationing problems - called baseline rationing rules - and provide an axiomatic characterization for it. Any baseline rationing rule within...... the family is associated with a standard rule and we show that if the latter obeys some properties reflecting principles of impartiality, priority and solidarity, the former obeys them too....

  12. Adolescent rationality.

    Science.gov (United States)

    Moshman, David

    2013-01-01

    Adolescents are commonly seen as irrational, a position supported to varying degrees by many developmentalists, who often appeal to recent research on adolescent brains. Careful review of relevant evidence, however, shows that (1) adults are less rational than is generally assumed, (2) adolescents (and adults) are categorically different from children with respect to the attainment of advanced levels of rationality and psychological functioning, and (3) adolescents and adults do not differ categorically from each other with respect to any rational competencies, irrational tendencies, brain structures, or neurological functioning. Development often continues in adolescence and beyond but categorical claims about adolescents as distinct from adults cannot be justified. A review of U.S. Supreme Court decisions concerning intellectual freedom, reproductive freedom, and criminal responsibility shows ongoing ambivalence and confusion about the rationality of adolescents. Developmental theory and research suggest that adolescents should be conceptualized as young adults, not immature brains, with important implications for their roles, rights, and responsibilities.

  13. Combinatorial optimization networks and matroids

    CERN Document Server

    Lawler, Eugene

    2011-01-01

    Perceptively written text examines optimization problems that can be formulated in terms of networks and algebraic structures called matroids. Chapters cover shortest paths, network flows, bipartite matching, nonbipartite matching, matroids and the greedy algorithm, matroid intersections, and the matroid parity problems. A suitable text or reference for courses in combinatorial computing and concrete computational complexity in departments of computer science and mathematics.

  14. Algorithms in combinatorial design theory

    CERN Document Server

    Colbourn, CJ

    1985-01-01

    The scope of the volume includes all algorithmic and computational aspects of research on combinatorial designs. Algorithmic aspects include generation, isomorphism and analysis techniques - both heuristic methods used in practice, and the computational complexity of these operations. The scope within design theory includes all aspects of block designs, Latin squares and their variants, pairwise balanced designs and projective planes and related geometries.

  15. Computational Complexity of Combinatorial Surfaces

    NARCIS (Netherlands)

    Vegter, Gert; Yap, Chee K.

    1990-01-01

    We investigate the computational problems associated with combinatorial surfaces. Specifically, we present an algorithm (based on the Brahana-Dehn-Heegaard approach) for transforming the polygonal schema of a closed triangulated surface into its canonical form in O(n log n) time, where n is the

  16. Combinatorial auctions for electronic business

    Indian Academy of Sciences (India)

    R. Narasimhan (Krishtel eMaging) 1461 1996 Oct 15 13:05:22

    (6) Information feedback: An auction protocol may be a direct mechanism or an .... transparency of allocation decisions arise in resolving these ties. .... bidding, however more recently, combinatorial bids are allowed [50] making ...... Also, truth revelation and other game theoretic considerations are not taken into account.

  17. Combinatorial Proofs and Algebraic Proofs

    Indian Academy of Sciences (India)

    Permanent link: https://www.ias.ac.in/article/fulltext/reso/018/07/0630-0645. Keywords. Combinatorial proof; algebraic proof; binomial identity; recurrence relation; composition; Fibonacci number; Fibonacci identity; Pascal triangle. Author Affiliations. Shailesh A Shirali1. Sahyadri School Tiwai Hill, Rajgurunagar Pune 410 ...

  18. Embodying rationality

    OpenAIRE

    Mastrogiorgio, Antonio; Petracca, Enrico

    2016-01-01

    The current notions of bounded rationality in economics share distinctive features with Simon’s original notion, which still influences the theoretical and experimental research in the fields of choice, judgment, decision making, problem solving, and social cognition. All these notions of bounded rationality are in fact equally rooted in the information-processing approach to human cognition, expressing the view that reasoning is disembodied and that it can be reduced to the processing of abs...

  19. Combinatorial Speculations and the Combinatorial Conjecture for Mathematics

    OpenAIRE

    Mao, Linfan

    2006-01-01

    Combinatorics is a powerful tool for dealing with relations among objectives mushroomed in the past century. However, an more important work for mathematician is to apply combinatorics to other mathematics and other sciences not merely to find combinatorial behavior for objectives. Recently, such research works appeared on journals for mathematics and theoretical physics on cosmos. The main purpose of this paper is to survey these thinking and ideas for mathematics and cosmological physics, s...

  20. Deciphering the Structural Requirements of Nucleoside Bisubstrate Analogues for Inhibition of MbtA in Mycobacterium tuberculosis: A FB-QSAR Study and Combinatorial Library Generation for Identifying Potential Hits.

    Science.gov (United States)

    Maganti, Lakshmi; Das, Sanjit Kumar; Mascarenhas, Nahren Manuel; Ghoshal, Nanda

    2011-10-01

    The re-emergence of tuberculosis infections, which are resistant to conventional drug therapy, has steadily risen in the last decade. Inhibitors of aryl acid adenylating enzyme known as MbtA, involved in siderophore biosynthesis in Mycobacterium tuberculosis, are being explored as potential antitubercular agents. The ability to identify fragments that interact with a biological target is a key step in fragment based drug design (FBDD). To expand the boundaries of quantitative structure activity relationship (QSAR) paradigm, we have proposed a Fragment Based QSAR methodology, referred here in as FB-QSAR, for deciphering the structural requirements of a series of nucleoside bisubstrate analogs for inhibition of MbtA, a key enzyme involved in siderophore biosynthetic pathway. For the development of FB-QSAR models, statistical techniques such as stepwise multiple linear regression (SMLR), genetic function approximation (GFA) and GFAspline were used. The predictive ability of the generated models was validated using different statistical metrics, and similarity-based coverage estimation was carried out to define applicability boundaries. To aid the creation of novel antituberculosis compounds, a bioisosteric database was enumerated using the combichem approach endorsed mining in a lead-like chemical space. The generated library was screened using an integrated in-silico approach and potential hits identified. Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  1. Rational BRDF.

    Science.gov (United States)

    Pacanowski, Romain; Salazar Celis, Oliver; Schlick, Christophe; Granier, Xavier; Poulin, Pierre; Cuyt, Annie

    2012-11-01

    Over the last two decades, much effort has been devoted to accurately measuring Bidirectional Reflectance Distribution Functions (BRDFs) of real-world materials and to use efficiently the resulting data for rendering. Because of their large size, it is difficult to use directly measured BRDFs for real-time applications, and fitting the most sophisticated analytical BRDF models is still a complex task. In this paper, we introduce Rational BRDF, a general-purpose and efficient representation for arbitrary BRDFs, based on Rational Functions (RFs). Using an adapted parametrization, we demonstrate how Rational BRDFs offer 1) a more compact and efficient representation using low-degree RFs, 2) an accurate fitting of measured materials with guaranteed control of the residual error, and 3) efficient importance sampling by applying the same fitting process to determine the inverse of the Cumulative Distribution Function (CDF) generated from the BRDF for use in Monte-Carlo rendering.

  2. Rational emotions.

    Science.gov (United States)

    Meshulam, Meir; Winter, Eyal; Ben-Shakhar, Gershon; Aharon, Itzhak

    2012-01-01

    We present here the concept of rational emotions: Emotions may be directly controlled and utilized in a conscious, analytic fashion, enabling an individual to size up a situation, to determine that a certain "mental state" is strategically advantageous and adjust accordingly. Building on the growing body of literature recognizing the vital role of emotions in determining decisions, we explore the complementary role of rational choice in choosing emotional states. Participants played the role of "recipient" in the dictator game, in which an anonymous "dictator" decides how to split an amount of money between himself and the recipient. A subset of recipients was given a monetary incentive to be angry at low-split offers. That subset demonstrated increased physiological arousal at low offers relative to high offers as well as more anger than other participants. These results provide a fresh outlook on human decision-making and contribute to the continuing effort to build more complete models of rational behavior.

  3. Combinatorial algebra syntax and semantics

    CERN Document Server

    Sapir, Mark V

    2014-01-01

    Combinatorial Algebra: Syntax and Semantics provides a comprehensive account of many areas of combinatorial algebra. It contains self-contained proofs of  more than 20 fundamental results, both classical and modern. This includes Golod–Shafarevich and Olshanskii's solutions of Burnside problems, Shirshov's solution of Kurosh's problem for PI rings, Belov's solution of Specht's problem for varieties of rings, Grigorchuk's solution of Milnor's problem, Bass–Guivarc'h theorem about the growth of nilpotent groups, Kleiman's solution of Hanna Neumann's problem for varieties of groups, Adian's solution of von Neumann-Day's problem, Trahtman's solution of the road coloring problem of Adler, Goodwyn and Weiss. The book emphasize several ``universal" tools, such as trees, subshifts, uniformly recurrent words, diagrams and automata.   With over 350 exercises at various levels of difficulty and with hints for the more difficult problems, this book can be used as a textbook, and aims to reach a wide and diversified...

  4. Combinatorial synthesis of oxazol-thiazole bis-heterocyclic compounds.

    Science.gov (United States)

    Murru, Siva; Nefzi, Adel

    2014-01-13

    A combinatorial library of novel oxazol-thiazole bis-heterocycles was synthesized in good to excellent overall yields with high purity using a solution and solid-phase parallel synthesis approach. Oxazole amino acids, prepared from serine methyl ester and amino acids via coupling and cyclodehydration, were treated with Fmoc-NCS and α-haloketones for the parallel synthesis of diverse bis-heterocycles. Fmoc-isothiocyanate is used as a traceless reagent for thiazole formation. Oxazole diversity can be achieved by using variety of amino acids, whereas thiazole diversity is produced with various haloketones.

  5. Combinatorial aspects of covering arrays

    Directory of Open Access Journals (Sweden)

    Charles J. Colbourn

    2004-11-01

    Full Text Available Covering arrays generalize orthogonal arrays by requiring that t -tuples be covered, but not requiring that the appearance of t -tuples be balanced.Their uses in screening experiments has found application in software testing, hardware testing, and a variety of fields in which interactions among factors are to be identified. Here a combinatorial view of covering arrays is adopted, encompassing basic bounds, direct constructions, recursive constructions, algorithmic methods, and applications.

  6. Confucian Rationalism

    Science.gov (United States)

    Lam, Chi-Ming

    2014-01-01

    Nowadays, there is still a widely held view that the Chinese and Western modes of thought are quite distinct from each other. In particular, the Chinese mode of thought derived from Confucianism is considered as comparatively less rational than the Western one. In this article, I first argue that although the analogical mode of argumentation,…

  7. Development of Combinatorial Methods for Alloy Design and Optimization

    International Nuclear Information System (INIS)

    Pharr, George M.; George, Easo P.; Santella, Michael L

    2005-01-01

    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

  8. Rational valuations

    Directory of Open Access Journals (Sweden)

    Georg Spielthenner

    2007-01-01

    Full Text Available Valuations are ubiquitous. We may be for or against genetically modified food; we find some politicians irresponsible; we prefer Beethoven to rock ‘n’ roll or vice versa; some enjoy bird-watching while others find it boring; and we may think that we have to tighten up on green-house gas emissions. Valuing is pervasive and often we are not even aware that we are valuing. However, many of ourvaluations are ill grounded and rationally defective. They are frequently based on misinformation, sloppy thinking, prejudice, and are biased in many ways as psychological research shows. For this reason there is widespread agreement among phi-losophers that we need an account of substantive valuational rationality, both for the theory of practical reasoning and for ethics as well. My main objectin this paper is to outline such an account and to present a principle that allows a non-technical rational criticism of valuations

  9. The Yoccoz Combinatorial Analytic Invariant

    DEFF Research Database (Denmark)

    Petersen, Carsten Lunde; Roesch, Pascale

    2008-01-01

    In this paper we develop a combinatorial analytic encoding of the Mandelbrot set M. The encoding is implicit in Yoccoz' proof of local connectivity of M at any Yoccoz parameter, i.e. any at most finitely renormalizable parameter for which all periodic orbits are repelling. Using this encoding we ...... to reprove that the dyadic veins of M are arcs and that more generally any two Yoccoz parameters are joined by a unique ruled (in the sense of Douady-Hubbard) arc in M....

  10. Probabilistic methods in combinatorial analysis

    CERN Document Server

    Sachkov, Vladimir N

    2014-01-01

    This 1997 work explores the role of probabilistic methods for solving combinatorial problems. These methods not only provide the means of efficiently using such notions as characteristic and generating functions, the moment method and so on but also let us use the powerful technique of limit theorems. The basic objects under investigation are nonnegative matrices, partitions and mappings of finite sets, with special emphasis on permutations and graphs, and equivalence classes specified on sequences of finite length consisting of elements of partially ordered sets; these specify the probabilist

  11. Log-balanced combinatorial sequences

    Directory of Open Access Journals (Sweden)

    Tomislav Došlic

    2005-01-01

    Full Text Available We consider log-convex sequences that satisfy an additional constraint imposed on their rate of growth. We call such sequences log-balanced. It is shown that all such sequences satisfy a pair of double inequalities. Sufficient conditions for log-balancedness are given for the case when the sequence satisfies a two- (or more- term linear recurrence. It is shown that many combinatorially interesting sequences belong to this class, and, as a consequence, that the above-mentioned double inequalities are valid for all of them.

  12. Combinatorial optimization on a Boltzmann machine

    NARCIS (Netherlands)

    Korst, J.H.M.; Aarts, E.H.L.

    1989-01-01

    We discuss the problem of solving (approximately) combinatorial optimization problems on a Boltzmann machine. It is shown for a number of combinatorial optimization problems how they can be mapped directly onto a Boltzmann machine by choosing appropriate connection patterns and connection strengths.

  13. Combinatorial Interpretation of General Eulerian Numbers

    OpenAIRE

    Tingyao Xiong; Jonathan I. Hall; Hung-Ping Tsao

    2014-01-01

    Since 1950s, mathematicians have successfully interpreted the traditional Eulerian numbers and $q-$Eulerian numbers combinatorially. In this paper, the authors give a combinatorial interpretation to the general Eulerian numbers defined on general arithmetic progressions { a, a+d, a+2d,...}.

  14. Fourier analysis in combinatorial number theory

    International Nuclear Information System (INIS)

    Shkredov, Il'ya D

    2010-01-01

    In this survey applications of harmonic analysis to combinatorial number theory are considered. Discussion topics include classical problems of additive combinatorics, colouring problems, higher-order Fourier analysis, theorems about sets of large trigonometric sums, results on estimates for trigonometric sums over subgroups, and the connection between combinatorial and analytic number theory. Bibliography: 162 titles.

  15. Fourier analysis in combinatorial number theory

    Energy Technology Data Exchange (ETDEWEB)

    Shkredov, Il' ya D [M. V. Lomonosov Moscow State University, Moscow (Russian Federation)

    2010-09-16

    In this survey applications of harmonic analysis to combinatorial number theory are considered. Discussion topics include classical problems of additive combinatorics, colouring problems, higher-order Fourier analysis, theorems about sets of large trigonometric sums, results on estimates for trigonometric sums over subgroups, and the connection between combinatorial and analytic number theory. Bibliography: 162 titles.

  16. Rational decisions

    CERN Document Server

    Binmore, Ken

    2008-01-01

    It is widely held that Bayesian decision theory is the final word on how a rational person should make decisions. However, Leonard Savage--the inventor of Bayesian decision theory--argued that it would be ridiculous to use his theory outside the kind of small world in which it is always possible to ""look before you leap."" If taken seriously, this view makes Bayesian decision theory inappropriate for the large worlds of scientific discovery and macroeconomic enterprise. When is it correct to use Bayesian decision theory--and when does it need to be modified? Using a minimum of mathematics,

  17. Rationalization: A Bibliography.

    Science.gov (United States)

    Pedrini, D. T.; Pedrini, Bonnie C.

    Rationalization was studied by Sigmund Freud and was specifically labeled by Ernest Jones. Rationalization ought to be differentiated from rational, rationality, logical analysis, etc. On the one hand, rationalization is considered a defense mechanism, on the other hand, rationality is not. Haan has done much work with self-report inventories and…

  18. Combinatorial Strategies for Synthesis and Characterization of Alloy Microstructures over Large Compositional Ranges.

    Science.gov (United States)

    Li, Yanglin; Jensen, Katharine E; Liu, Yanhui; Liu, Jingbei; Gong, Pan; Scanley, B Ellen; Broadbridge, Christine C; Schroers, Jan

    2016-10-10

    The exploration of new alloys with desirable properties has been a long-standing challenge in materials science because of the complex relationship between composition and microstructure. In this Research Article, we demonstrate a combinatorial strategy for the exploration of composition dependence of microstructure. This strategy is comprised of alloy library synthesis followed by high-throughput microstructure characterization. As an example, we synthesized a ternary Au-Cu-Si composition library containing over 1000 individual alloys using combinatorial sputtering. We subsequently melted and resolidified the entire library at controlled cooling rates. We used scanning optical microscopy and X-ray diffraction mapping to explore trends in phase formation and microstructural length scale with composition across the library. The integration of combinatorial synthesis with parallelizable analysis methods provides a efficient method for examining vast compositional ranges. The availability of microstructures from this vast composition space not only facilitates design of new alloys by controlling effects of composition on phase selection, phase sequence, length scale, and overall morphology, but also will be instrumental in understanding the complex process of microstructure formation in alloys.

  19. Rational inattention or rational overreaction?

    DEFF Research Database (Denmark)

    Browning, Martin; Hansen, Lars Gårn; Smed, Sinne

    We investigate differences in how consumers of fish react to health information in the mass media. We specify a dynamic empirical model that allows for heterogeneity in all basic parameters of consumer behavior as well as in how consumers react to information. We estimate the model using a unique...... houshold panel tracking consumption, prices, news stories and media habits over 24 quarters. We fi nd that the consumers most likely to be ’rationally ignorant’ of health effects react more dramatically to health news than the consumers who most likely are well informed....

  20. Rationality of limited rationality : some aggregate implications

    OpenAIRE

    Uri M. Possen; Mikko Puhakka

    1994-01-01

    In this paper we let economic agents choose whether to become fully rational or stay boundedly rational. Boundedly rational agents are less sophisticated in their information processing abilities. It is costly to acquire information needed to become fully rational, and thus not all agents are willing to incur those costs. We then explore the aggregate effects of endogenizing the decision whether the agent should or should not become fully rational in handling information. Since fully and boun...

  1. Combinatorial Micro-Macro Dynamical Systems

    OpenAIRE

    Diaz, Rafael; Villamarin, Sergio

    2015-01-01

    The second law of thermodynamics states that the entropy of an isolated system is almost always increasing. We propose combinatorial formalizations of the second law and explore their conditions of possibilities.

  2. Rational kinematics

    CERN Document Server

    Angeles, Jorge

    1988-01-01

    A rational study of kinematics is a treatment of the subject based on invariants, i.e., quantities that remain essentially unchanged under a change of observer. An observer is understood to be a reference frame supplied with a clock (Truesdell 1966). This study will therefore include an introduction to invariants. The language of these is tensor analysis and multilinear algebra, both of which share many isomorphic relations, These subjects are treated in full detail in Ericksen (1960) and Bowen and Wang (1976), and hence will not be included here. Only a short account of notation and definitions will be presented. Moreover, definitions and basic concepts pertaining to the kinematics of rigid bodies will be also included. Although the kinematics of rigid bodies can be regarded as a particular case of the kinematics of continua, the former deserves attention on its own merits for several reasons. One of these is that it describes locally the motions undergone by continua. Another reason is that a whole area of ...

  3. Cubical version of combinatorial differential forms

    DEFF Research Database (Denmark)

    Kock, Anders

    2010-01-01

    The theory of combinatorial differential forms is usually presented in simplicial terms. We present here a cubical version; it depends on the possibility of forming affine combinations of mutual neighbour points in a manifold, in the context of synthetic differential geometry.......The theory of combinatorial differential forms is usually presented in simplicial terms. We present here a cubical version; it depends on the possibility of forming affine combinations of mutual neighbour points in a manifold, in the context of synthetic differential geometry....

  4. Conferences on Combinatorial and Additive Number Theory

    CERN Document Server

    2014-01-01

    This proceedings volume is based on papers presented at the Workshops on Combinatorial and Additive Number Theory (CANT), which were held at the Graduate Center of the City University of New York in 2011 and 2012. The goal of the workshops is to survey recent progress in combinatorial number theory and related parts of mathematics. The workshop attracts researchers and students who discuss the state-of-the-art, open problems, and future challenges in number theory.

  5. Jack superpolynomials: physical and combinatorial definitions

    International Nuclear Information System (INIS)

    Desrosiers, P.; Mathieu, P.; Lapointe, L.

    2004-01-01

    Jack superpolynomials are eigenfunctions of the supersymmetric extension of the quantum trigonometric Calogero-Moser-Sutherland Hamiltonian. They are orthogonal with respect to the scalar product, dubbed physical, that is naturally induced by this quantum-mechanical problem. But Jack superpolynomials can also be defined more combinatorially, starting from the multiplicative bases of symmetric superpolynomials, enforcing orthogonality with respect to a one-parameter deformation of the combinatorial scalar product. Both constructions turn out to be equivalent. (author)

  6. Featured Library: Parrish Library

    OpenAIRE

    Kirkwood, Hal P, Jr

    2015-01-01

    The Roland G. Parrish Library of Management & Economics is located within the Krannert School of Management at Purdue University. Between 2005 - 2007 work was completed on a white paper that focused on a student-centered vision for the Management & Economics Library. The next step was a massive collection reduction and a re-envisioning of both the services and space of the library. Thus began a 3 phase renovation from a 2 floor standard, collection-focused library into a single floor, 18,000s...

  7. Systematic identification of combinatorial drivers and targets in cancer cell lines.

    Directory of Open Access Journals (Sweden)

    Adel Tabchy

    Full Text Available There is an urgent need to elicit and validate highly efficacious targets for combinatorial intervention from large scale ongoing molecular characterization efforts of tumors. We established an in silico bioinformatic platform in concert with a high throughput screening platform evaluating 37 novel targeted agents in 669 extensively characterized cancer cell lines reflecting the genomic and tissue-type diversity of human cancers, to systematically identify combinatorial biomarkers of response and co-actionable targets in cancer. Genomic biomarkers discovered in a 141 cell line training set were validated in an independent 359 cell line test set. We identified co-occurring and mutually exclusive genomic events that represent potential drivers and combinatorial targets in cancer. We demonstrate multiple cooperating genomic events that predict sensitivity to drug intervention independent of tumor lineage. The coupling of scalable in silico and biologic high throughput cancer cell line platforms for the identification of co-events in cancer delivers rational combinatorial targets for synthetic lethal approaches with a high potential to pre-empt the emergence of resistance.

  8. Systematic identification of combinatorial drivers and targets in cancer cell lines.

    Science.gov (United States)

    Tabchy, Adel; Eltonsy, Nevine; Housman, David E; Mills, Gordon B

    2013-01-01

    There is an urgent need to elicit and validate highly efficacious targets for combinatorial intervention from large scale ongoing molecular characterization efforts of tumors. We established an in silico bioinformatic platform in concert with a high throughput screening platform evaluating 37 novel targeted agents in 669 extensively characterized cancer cell lines reflecting the genomic and tissue-type diversity of human cancers, to systematically identify combinatorial biomarkers of response and co-actionable targets in cancer. Genomic biomarkers discovered in a 141 cell line training set were validated in an independent 359 cell line test set. We identified co-occurring and mutually exclusive genomic events that represent potential drivers and combinatorial targets in cancer. We demonstrate multiple cooperating genomic events that predict sensitivity to drug intervention independent of tumor lineage. The coupling of scalable in silico and biologic high throughput cancer cell line platforms for the identification of co-events in cancer delivers rational combinatorial targets for synthetic lethal approaches with a high potential to pre-empt the emergence of resistance.

  9. Reiterative Recombination for the in vivo assembly of libraries of multigene pathways.

    Science.gov (United States)

    Wingler, Laura M; Cornish, Virginia W

    2011-09-13

    The increasing sophistication of synthetic biology is creating a demand for robust, broadly accessible methodology for constructing multigene pathways inside of the cell. Due to the difficulty of rationally designing pathways that function as desired in vivo, there is a further need to assemble libraries of pathways in parallel, in order to facilitate the combinatorial optimization of performance. While some in vitro DNA assembly methods can theoretically make libraries of pathways, these techniques are resource intensive and inherently require additional techniques to move the DNA back into cells. All previously reported in vivo assembly techniques have been low yielding, generating only tens to hundreds of constructs at a time. Here, we develop "Reiterative Recombination," a robust method for building multigene pathways directly in the yeast chromosome. Due to its use of endonuclease-induced homologous recombination in conjunction with recyclable markers, Reiterative Recombination provides a highly efficient, technically simple strategy for sequentially assembling an indefinite number of DNA constructs at a defined locus. In this work, we describe the design and construction of the first Reiterative Recombination system in Saccharomyces cerevisiae, and we show that it can be used to assemble multigene constructs. We further demonstrate that Reiterative Recombination can construct large mock libraries of at least 10(4) biosynthetic pathways. We anticipate that our system's simplicity and high efficiency will make it a broadly accessible technology for pathway construction and render it a valuable tool for optimizing pathways in vivo.

  10. Combinatorial Pooling Enables Selective Sequencing of the Barley Gene Space

    Science.gov (United States)

    Lonardi, Stefano; Duma, Denisa; Alpert, Matthew; Cordero, Francesca; Beccuti, Marco; Bhat, Prasanna R.; Wu, Yonghui; Ciardo, Gianfranco; Alsaihati, Burair; Ma, Yaqin; Wanamaker, Steve; Resnik, Josh; Bozdag, Serdar; Luo, Ming-Cheng; Close, Timothy J.

    2013-01-01

    For the vast majority of species – including many economically or ecologically important organisms, progress in biological research is hampered due to the lack of a reference genome sequence. Despite recent advances in sequencing technologies, several factors still limit the availability of such a critical resource. At the same time, many research groups and international consortia have already produced BAC libraries and physical maps and now are in a position to proceed with the development of whole-genome sequences organized around a physical map anchored to a genetic map. We propose a BAC-by-BAC sequencing protocol that combines combinatorial pooling design and second-generation sequencing technology to efficiently approach denovo selective genome sequencing. We show that combinatorial pooling is a cost-effective and practical alternative to exhaustive DNA barcoding when preparing sequencing libraries for hundreds or thousands of DNA samples, such as in this case gene-bearing minimum-tiling-path BAC clones. The novelty of the protocol hinges on the computational ability to efficiently compare hundred millions of short reads and assign them to the correct BAC clones (deconvolution) so that the assembly can be carried out clone-by-clone. Experimental results on simulated data for the rice genome show that the deconvolution is very accurate, and the resulting BAC assemblies have high quality. Results on real data for a gene-rich subset of the barley genome confirm that the deconvolution is accurate and the BAC assemblies have good quality. While our method cannot provide the level of completeness that one would achieve with a comprehensive whole-genome sequencing project, we show that it is quite successful in reconstructing the gene sequences within BACs. In the case of plants such as barley, this level of sequence knowledge is sufficient to support critical end-point objectives such as map-based cloning and marker-assisted breeding. PMID:23592960

  11. Combinatorial pooling enables selective sequencing of the barley gene space.

    Directory of Open Access Journals (Sweden)

    Stefano Lonardi

    2013-04-01

    Full Text Available For the vast majority of species - including many economically or ecologically important organisms, progress in biological research is hampered due to the lack of a reference genome sequence. Despite recent advances in sequencing technologies, several factors still limit the availability of such a critical resource. At the same time, many research groups and international consortia have already produced BAC libraries and physical maps and now are in a position to proceed with the development of whole-genome sequences organized around a physical map anchored to a genetic map. We propose a BAC-by-BAC sequencing protocol that combines combinatorial pooling design and second-generation sequencing technology to efficiently approach denovo selective genome sequencing. We show that combinatorial pooling is a cost-effective and practical alternative to exhaustive DNA barcoding when preparing sequencing libraries for hundreds or thousands of DNA samples, such as in this case gene-bearing minimum-tiling-path BAC clones. The novelty of the protocol hinges on the computational ability to efficiently compare hundred millions of short reads and assign them to the correct BAC clones (deconvolution so that the assembly can be carried out clone-by-clone. Experimental results on simulated data for the rice genome show that the deconvolution is very accurate, and the resulting BAC assemblies have high quality. Results on real data for a gene-rich subset of the barley genome confirm that the deconvolution is accurate and the BAC assemblies have good quality. While our method cannot provide the level of completeness that one would achieve with a comprehensive whole-genome sequencing project, we show that it is quite successful in reconstructing the gene sequences within BACs. In the case of plants such as barley, this level of sequence knowledge is sufficient to support critical end-point objectives such as map-based cloning and marker-assisted breeding.

  12. Combinatorial pooling enables selective sequencing of the barley gene space.

    Science.gov (United States)

    Lonardi, Stefano; Duma, Denisa; Alpert, Matthew; Cordero, Francesca; Beccuti, Marco; Bhat, Prasanna R; Wu, Yonghui; Ciardo, Gianfranco; Alsaihati, Burair; Ma, Yaqin; Wanamaker, Steve; Resnik, Josh; Bozdag, Serdar; Luo, Ming-Cheng; Close, Timothy J

    2013-04-01

    For the vast majority of species - including many economically or ecologically important organisms, progress in biological research is hampered due to the lack of a reference genome sequence. Despite recent advances in sequencing technologies, several factors still limit the availability of such a critical resource. At the same time, many research groups and international consortia have already produced BAC libraries and physical maps and now are in a position to proceed with the development of whole-genome sequences organized around a physical map anchored to a genetic map. We propose a BAC-by-BAC sequencing protocol that combines combinatorial pooling design and second-generation sequencing technology to efficiently approach denovo selective genome sequencing. We show that combinatorial pooling is a cost-effective and practical alternative to exhaustive DNA barcoding when preparing sequencing libraries for hundreds or thousands of DNA samples, such as in this case gene-bearing minimum-tiling-path BAC clones. The novelty of the protocol hinges on the computational ability to efficiently compare hundred millions of short reads and assign them to the correct BAC clones (deconvolution) so that the assembly can be carried out clone-by-clone. Experimental results on simulated data for the rice genome show that the deconvolution is very accurate, and the resulting BAC assemblies have high quality. Results on real data for a gene-rich subset of the barley genome confirm that the deconvolution is accurate and the BAC assemblies have good quality. While our method cannot provide the level of completeness that one would achieve with a comprehensive whole-genome sequencing project, we show that it is quite successful in reconstructing the gene sequences within BACs. In the case of plants such as barley, this level of sequence knowledge is sufficient to support critical end-point objectives such as map-based cloning and marker-assisted breeding.

  13. Similarity searching and scaffold hopping in synthetically accessible combinatorial chemistry spaces.

    Science.gov (United States)

    Boehm, Markus; Wu, Tong-Ying; Claussen, Holger; Lemmen, Christian

    2008-04-24

    Large collections of combinatorial libraries are an integral element in today's pharmaceutical industry. It is of great interest to perform similarity searches against all virtual compounds that are synthetically accessible by any such library. Here we describe the successful application of a new software tool CoLibri on 358 combinatorial libraries based on validated reaction protocols to create a single chemistry space containing over 10 (12) possible products. Similarity searching with FTrees-FS allows the systematic exploration of this space without the need to enumerate all product structures. The search result is a set of virtual hits which are synthetically accessible by one or more of the existing reaction protocols. Grouping these virtual hits by their synthetic protocols allows the rapid design and synthesis of multiple follow-up libraries. Such library ideas support hit-to-lead design efforts for tasks like follow-up from high-throughput screening hits or scaffold hopping from one hit to another attractive series.

  14. Rationality in Society

    NARCIS (Netherlands)

    Flache, Andreas; Dijkstra, Jacob; Wright, James D.

    2015-01-01

    Contemporary theories of rational behavior in human society augment the orthodox model of rationality both by adding various forms of bounded rationality and relaxing the assumptions of self-interest and materialistic preferences. This entry discusses how these extensions of the theory of rational

  15. Combinatorial stresses kill pathogenic Candida species

    Science.gov (United States)

    Kaloriti, Despoina; Tillmann, Anna; Cook, Emily; Jacobsen, Mette; You, Tao; Lenardon, Megan; Ames, Lauren; Barahona, Mauricio; Chandrasekaran, Komelapriya; Coghill, George; Goodman, Daniel; Gow, Neil A. R.; Grebogi, Celso; Ho, Hsueh-Lui; Ingram, Piers; McDonagh, Andrew; De Moura, Alessandro P. S.; Pang, Wei; Puttnam, Melanie; Radmaneshfar, Elahe; Romano, Maria Carmen; Silk, Daniel; Stark, Jaroslav; Stumpf, Michael; Thiel, Marco; Thorne, Thomas; Usher, Jane; Yin, Zhikang; Haynes, Ken; Brown, Alistair J. P.

    2012-01-01

    Pathogenic microbes exist in dynamic niches and have evolved robust adaptive responses to promote survival in their hosts. The major fungal pathogens of humans, Candida albicans and Candida glabrata, are exposed to a range of environmental stresses in their hosts including osmotic, oxidative and nitrosative stresses. Significant efforts have been devoted to the characterization of the adaptive responses to each of these stresses. In the wild, cells are frequently exposed simultaneously to combinations of these stresses and yet the effects of such combinatorial stresses have not been explored. We have developed a common experimental platform to facilitate the comparison of combinatorial stress responses in C. glabrata and C. albicans. This platform is based on the growth of cells in buffered rich medium at 30°C, and was used to define relatively low, medium and high doses of osmotic (NaCl), oxidative (H 2O2) and nitrosative stresses (e.g., dipropylenetriamine (DPTA)-NONOate). The effects of combinatorial stresses were compared with the corresponding individual stresses under these growth conditions. We show for the first time that certain combinations of combinatorial stress are especially potent in terms of their ability to kill C. albicans and C. glabrata and/or inhibit their growth. This was the case for combinations of osmotic plus oxidative stress and for oxidative plus nitrosative stress. We predict that combinatorial stresses may be highly signif cant in host defences against these pathogenic yeasts. PMID:22463109

  16. Chemical Space of DNA-Encoded Libraries.

    Science.gov (United States)

    Franzini, Raphael M; Randolph, Cassie

    2016-07-28

    In recent years, DNA-encoded chemical libraries (DECLs) have attracted considerable attention as a potential discovery tool in drug development. Screening encoded libraries may offer advantages over conventional hit discovery approaches and has the potential to complement such methods in pharmaceutical research. As a result of the increased application of encoded libraries in drug discovery, a growing number of hit compounds are emerging in scientific literature. In this review we evaluate reported encoded library-derived structures and identify general trends of these compounds in relation to library design parameters. We in particular emphasize the combinatorial nature of these libraries. Generally, the reported molecules demonstrate the ability of this technology to afford hits suitable for further lead development, and on the basis of them, we derive guidelines for DECL design.

  17. Accessing Specific Peptide Recognition by Combinatorial Chemistry

    DEFF Research Database (Denmark)

    Li, Ming

    Molecular recognition is at the basis of all processes for life, and plays a central role in many biological processes, such as protein folding, the structural organization of cells and organelles, signal transduction, and the immune response. Hence, my PhD project is entitled “Accessing Specific...... Peptide Recognition by Combinatorial Chemistry”. Molecular recognition is a specific interaction between two or more molecules through noncovalent bonding, such as hydrogen bonding, metal coordination, van der Waals forces, π−π, hydrophobic, or electrostatic interactions. The association involves kinetic....... Combinatorial chemistry was invented in 1980s based on observation of functional aspects of the adaptive immune system. It was employed for drug development and optimization in conjunction with high-throughput synthesis and screening. (chapter 2) Combinatorial chemistry is able to rapidly produce many thousands...

  18. Gas-Foamed Scaffold Gradients for Combinatorial Screening in 3D

    Directory of Open Access Journals (Sweden)

    Joachim Kohn

    2012-03-01

    Full Text Available Current methods for screening cell-material interactions typically utilize a two-dimensional (2D culture format where cells are cultured on flat surfaces. However, there is a need for combinatorial and high-throughput screening methods to systematically screen cell-biomaterial interactions in three-dimensional (3D tissue scaffolds for tissue engineering. Previously, we developed a two-syringe pump approach for making 3D scaffold gradients for use in combinatorial screening of salt-leached scaffolds. Herein, we demonstrate that the two-syringe pump approach can also be used to create scaffold gradients using a gas-foaming approach. Macroporous foams prepared by a gas-foaming technique are commonly used for fabrication of tissue engineering scaffolds due to their high interconnectivity and good mechanical properties. Gas-foamed scaffold gradient libraries were fabricated from two biodegradable tyrosine-derived polycarbonates: poly(desaminotyrosyl-tyrosine ethyl ester carbonate (pDTEc and poly(desaminotyrosyl-tyrosine octyl ester carbonate (pDTOc. The composition of the libraries was assessed with Fourier transform infrared spectroscopy (FTIR and showed that pDTEc/pDTOc gas-foamed scaffold gradients could be repeatably fabricated. Scanning electron microscopy showed that scaffold morphology was similar between the pDTEc-rich ends and the pDTOc-rich ends of the gradient. These results introduce a method for fabricating gas-foamed polymer scaffold gradients that can be used for combinatorial screening of cell-material interactions in 3D.

  19. A quark interpretation of the combinatorial hierarchy

    International Nuclear Information System (INIS)

    Enqvist, Kari.

    1979-01-01

    We propose a physical interpretation of the second level of the combinatorial hierarchy in terms of three quarks, three antiquarks and the vacuum. This interpretation allows us to introduce a new quantum number, which measures electromagnetic mass splitting of the quarks. We extend our argument by analogue to baryons, and find some SU(3) and some new mass formulas for baryons. The generalization of our approach to other hierarchy levels is discussed. We present also an empirical mass formula for baryons, which seems to be loosely connected with the combinatorial hierarchy. (author)

  20. Combinatorial designs a tribute to Haim Hanani

    CERN Document Server

    Hartman, A

    1989-01-01

    Haim Hanani pioneered the techniques for constructing designs and the theory of pairwise balanced designs, leading directly to Wilson''s Existence Theorem. He also led the way in the study of resolvable designs, covering and packing problems, latin squares, 3-designs and other combinatorial configurations.The Hanani volume is a collection of research and survey papers at the forefront of research in combinatorial design theory, including Professor Hanani''s own latest work on Balanced Incomplete Block Designs. Other areas covered include Steiner systems, finite geometries, quasigroups, and t-designs.

  1. Rational design of peptide affinity ligands for the purification of therapeutic enzymes.

    Science.gov (United States)

    Trasatti, John P; Woo, James; Ladiwala, Asif; Cramer, Steven; Karande, Pankaj

    2018-04-25

    Non-mAb biologics represent a growing class of therapeutics under clinical development. Although affinity chromatography is a potentially attractive approach for purification, the development of platform technologies, such as Protein A for mAbs, has been challenging due to the inherent chemical and structural diversity of these molecules. Here, we present our studies on the rapid development of peptide affinity ligands for the purification of biologics using a prototypical enzyme therapeutic in clinical use. Employing a suite of de novo rational and combinatorial design strategies we designed and screened a library of peptides on microarray platforms for their ability to bind to the target with high affinity and selectivity in cell culture fluid. Lead peptides were evaluated on resin in batch conditions and compared with a commercially available resin to evaluate their efficacy. Two lead candidates identified from microarray studies provided high binding capacity to the target while demonstrating high selectivity against culture contaminants and product variants compared to a commercial resin system. These findings provide a proof-of-concept for developing affinity peptide-based bioseparations processes for a target biologic. Peptide affinity ligand design and screening approaches presented in this work can also be easily translated to other biologics of interest. © 2018 American Institute of Chemical Engineers Biotechnol. Prog., 2018. © 2018 American Institute of Chemical Engineers.

  2. On rationally supported surfaces

    DEFF Research Database (Denmark)

    Gravesen, Jens; Juttler, B.; Sir, Z.

    2008-01-01

    We analyze the class of surfaces which are equipped with rational support functions. Any rational support function can be decomposed into a symmetric (even) and an antisymmetric (odd) part. We analyze certain geometric properties of surfaces with odd and even rational support functions....... In particular it is shown that odd rational support functions correspond to those rational surfaces which can be equipped with a linear field of normal vectors, which were discussed by Sampoli et al. (Sampoli, M.L., Peternell, M., Juttler, B., 2006. Rational surfaces with linear normals and their convolutions...... with rational surfaces. Comput. Aided Geom. Design 23, 179-192). As shown recently, this class of surfaces includes non-developable quadratic triangular Bezier surface patches (Lavicka, M., Bastl, B., 2007. Rational hypersurfaces with rational convolutions. Comput. Aided Geom. Design 24, 410426; Peternell, M...

  3. A New Approach for Proving or Generating Combinatorial Identities

    Science.gov (United States)

    Gonzalez, Luis

    2010-01-01

    A new method for proving, in an immediate way, many combinatorial identities is presented. The method is based on a simple recursive combinatorial formula involving n + 1 arbitrary real parameters. Moreover, this formula enables one not only to prove, but also generate many different combinatorial identities (not being required to know them "a…

  4. Asessing for Structural Understanding in Childrens' Combinatorial Problem Solving.

    Science.gov (United States)

    English, Lyn

    1999-01-01

    Assesses children's structural understanding of combinatorial problems when presented in a variety of task situations. Provides an explanatory model of students' combinatorial understandings that informs teaching and assessment. Addresses several components of children's structural understanding of elementary combinatorial problems. (Contains 50…

  5. Individualized Pixel Synthesis and Characterization of Combinatorial Materials Chips

    Directory of Open Access Journals (Sweden)

    Xiao-Dong Xiang

    2015-06-01

    Full Text Available Conventionally, an experimentally determined phase diagram requires studies of phase formation at a range of temperatures for each composition, which takes years of effort from multiple research groups. Combinatorial materials chip technology, featuring high-throughput synthesis and characterization, is able to determine the phase diagram of an entire composition spread of a binary or ternary system at a single temperature on one materials library, which, though significantly increasing efficiency, still requires many libraries processed at a series of temperatures in order to complete a phase diagram. In this paper, we propose a “one-chip method” to construct a complete phase diagram by individually synthesizing each pixel step by step with a progressive pulse of energy to heat at different temperatures while monitoring the phase evolution on the pixel in situ in real time. Repeating this process pixel by pixel throughout the whole chip allows the entire binary or ternary phase diagram to be mapped on one chip in a single experiment. The feasibility of this methodology is demonstrated in a study of a Ge-Sb-Te ternary alloy system, on which the amorphous-crystalline phase boundary is determined.

  6. Research Library

    Science.gov (United States)

    Los Alamos National Laboratory Research Library Search Site submit Contact Us | Remote Access Standards Theses/Dissertations Research Help Subject Guides Library Training Video Tutorials Alerts Research Library: delivering essential knowledge services for national security sciences since 1947 Los

  7. Discovery of Cationic Polymers for Non-viral Gene Delivery using Combinatorial Approaches

    Science.gov (United States)

    Barua, Sutapa; Ramos, James; Potta, Thrimoorthy; Taylor, David; Huang, Huang-Chiao; Montanez, Gabriela; Rege, Kaushal

    2015-01-01

    Gene therapy is an attractive treatment option for diseases of genetic origin, including several cancers and cardiovascular diseases. While viruses are effective vectors for delivering exogenous genes to cells, concerns related to insertional mutagenesis, immunogenicity, lack of tropism, decay and high production costs necessitate the discovery of non-viral methods. Significant efforts have been focused on cationic polymers as non-viral alternatives for gene delivery. Recent studies have employed combinatorial syntheses and parallel screening methods for enhancing the efficacy of gene delivery, biocompatibility of the delivery vehicle, and overcoming cellular level barriers as they relate to polymer-mediated transgene uptake, transport, transcription, and expression. This review summarizes and discusses recent advances in combinatorial syntheses and parallel screening of cationic polymer libraries for the discovery of efficient and safe gene delivery systems. PMID:21843141

  8. A Rational Approach to Rational Suicide.

    Science.gov (United States)

    Richman, Joseph

    1992-01-01

    Describes suicide as reaction to internal and external sources of stress and the impact of life events. Notes that, in the elderly, these situations are prevalent in many who are not suicidal. Contends that much more is written about rational suicide than its alternative (rational nonsuicide). Reviews reasons for this and suggests rational…

  9. Combinatorial biosynthesis of medicinal plant secondary metabolites

    NARCIS (Netherlands)

    Julsing, Mattijs K.; Koulman, Albert; Woerdenbag, Herman J.; Quax, Wim J.; Kayser, Oliver

    2006-01-01

    Combinatorial biosynthesis is a new tool in the generation of novel natural products and for the production of rare and expensive natural products. The basic concept is combining metabolic pathways in different organisms on a genetic level. As a consequence heterologous organisms provide precursors

  10. Infinitary Combinatory Reduction Systems: Normalising Reduction Strategies

    NARCIS (Netherlands)

    Ketema, J.; Simonsen, Jakob Grue

    2010-01-01

    We study normalising reduction strategies for infinitary Combinatory Reduction Systems (iCRSs). We prove that all fair, outermost-fair, and needed-fair strategies are normalising for orthogonal, fully-extended iCRSs. These facts properly generalise a number of results on normalising strategies in

  11. Gian-Carlos Rota and Combinatorial Math.

    Science.gov (United States)

    Kolata, Gina Bari

    1979-01-01

    Presents the first of a series of occasional articles about mathematics as seen through the eyes of its prominent scholars. In an interview with Gian-Carlos Rota of the Massachusetts Institute of Technology he discusses how combinatorial mathematics began as a field and its future. (HM)

  12. A Model of Students' Combinatorial Thinking

    Science.gov (United States)

    Lockwood, Elise

    2013-01-01

    Combinatorial topics have become increasingly prevalent in K-12 and undergraduate curricula, yet research on combinatorics education indicates that students face difficulties when solving counting problems. The research community has not yet addressed students' ways of thinking at a level that facilitates deeper understanding of how students…

  13. Torus actions, combinatorial topology, and homological algebra

    International Nuclear Information System (INIS)

    Bukhshtaber, V M; Panov, T E

    2000-01-01

    This paper is a survey of new results and open problems connected with fundamental combinatorial concepts, including polytopes, simplicial complexes, cubical complexes, and arrangements of subspaces. Attention is concentrated on simplicial and cubical subdivisions of manifolds, and especially on spheres. Important constructions are described that enable one to study these combinatorial objects by using commutative and homological algebra. The proposed approach to combinatorial problems is based on the theory of moment-angle complexes recently developed by the authors. The crucial construction assigns to each simplicial complex K with m vertices a T m -space Z K with special bigraded cellular decomposition. In the framework of this theory, well-known non-singular toric varieties arise as orbit spaces of maximally free actions of subtori on moment-angle complexes corresponding to simplicial spheres. It is shown that diverse invariants of simplicial complexes and related combinatorial-geometric objects can be expressed in terms of bigraded cohomology rings of the corresponding moment-angle complexes. Finally, it is shown that the new relationships between combinatorics, geometry, and topology lead to solutions of some well-known topological problems

  14. Combinatorial Aspects of the Generalized Euler's Totient

    Directory of Open Access Journals (Sweden)

    Nittiya Pabhapote

    2010-01-01

    Full Text Available A generalized Euler's totient is defined as a Dirichlet convolution of a power function and a product of the Souriau-Hsu-Möbius function with a completely multiplicative function. Two combinatorial aspects of the generalized Euler's totient, namely, its connections to other totients and its relations with counting formulae, are investigated.

  15. Quantum Resonance Approach to Combinatorial Optimization

    Science.gov (United States)

    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.

  16. Logging to Facilitate Combinatorial System Testing

    NARCIS (Netherlands)

    Kruse, P.M.; Prasetya, I.S.W.B.; Hage, J; Elyasov, Alexander

    2014-01-01

    Testing a web application is typically very complicated. Imposing simple coverage criteria such as function or line coverage is often not sufficient to uncover bugs due to incorrect components integration. Combinatorial testing can enforce a stronger criterion, while still allowing the

  17. High-throughput combinatorial chemical bath deposition: The case of doping Cu (In, Ga) Se film with antimony

    Science.gov (United States)

    Yan, Zongkai; Zhang, Xiaokun; Li, Guang; Cui, Yuxing; Jiang, Zhaolian; Liu, Wen; Peng, Zhi; Xiang, Yong

    2018-01-01

    The conventional methods for designing and preparing thin film based on wet process remain a challenge due to disadvantages such as time-consuming and ineffective, which hinders the development of novel materials. Herein, we present a high-throughput combinatorial technique for continuous thin film preparation relied on chemical bath deposition (CBD). The method is ideally used to prepare high-throughput combinatorial material library with low decomposition temperatures and high water- or oxygen-sensitivity at relatively high-temperature. To check this system, a Cu(In, Ga)Se (CIGS) thin films library doped with 0-19.04 at.% of antimony (Sb) was taken as an example to evaluate the regulation of varying Sb doping concentration on the grain growth, structure, morphology and electrical properties of CIGS thin film systemically. Combined with the Energy Dispersive Spectrometer (EDS), X-ray Photoelectron Spectroscopy (XPS), automated X-ray Diffraction (XRD) for rapid screening and Localized Electrochemical Impedance Spectroscopy (LEIS), it was confirmed that this combinatorial high-throughput system could be used to identify the composition with the optimal grain orientation growth, microstructure and electrical properties systematically, through accurately monitoring the doping content and material composition. According to the characterization results, a Sb2Se3 quasi-liquid phase promoted CIGS film-growth model has been put forward. In addition to CIGS thin film reported here, the combinatorial CBD also could be applied to the high-throughput screening of other sulfide thin film material systems.

  18. Combinatorial structures to modeling simple games and applications

    Science.gov (United States)

    Molinero, Xavier

    2017-09-01

    We connect three different topics: combinatorial structures, game theory and chemistry. In particular, we establish the bases to represent some simple games, defined as influence games, and molecules, defined from atoms, by using combinatorial structures. First, we characterize simple games as influence games using influence graphs. It let us to modeling simple games as combinatorial structures (from the viewpoint of structures or graphs). Second, we formally define molecules as combinations of atoms. It let us to modeling molecules as combinatorial structures (from the viewpoint of combinations). It is open to generate such combinatorial structures using some specific techniques as genetic algorithms, (meta-)heuristics algorithms and parallel programming, among others.

  19. Rationing medical education.

    African Journals Online (AJOL)

    This paper discussed the pros and cons of the application of rationing to medical education and the different ... Different types of rationing exist in healthcare professional education. ... state-of-the-art resources, technology and tutors con-.

  20. Rationing with baselines

    DEFF Research Database (Denmark)

    Hougaard, Jens Leth; Moreno-Ternero, Juan D.; Østerdal, Lars Peter Raahave

    2013-01-01

    We introduce a new operator for general rationing problems in which, besides conflicting claims, individual baselines play an important role in the rationing process. The operator builds onto ideas of composition, which are not only frequent in rationing, but also in related problems...... such as bargaining, choice, and queuing. We characterize the operator and show how it preserves some standard axioms in the literature on rationing. We also relate it to recent contributions in such literature....

  1. CONTRIBUTIONS TO RATIONAL APPROXIMATION,

    Science.gov (United States)

    Some of the key results of linear Chebyshev approximation theory are extended to generalized rational functions. Prominent among these is Haar’s...linear theorem which yields necessary and sufficient conditions for uniqueness. Some new results in the classic field of rational function Chebyshev...Furthermore a Weierstrass type theorem is proven for rational Chebyshev approximation. A characterization theorem for rational trigonometric Chebyshev approximation in terms of sign alternation is developed. (Author)

  2. Assistant in design of tissue targeting leads with radio-combinatorial screening vivo

    International Nuclear Information System (INIS)

    Liu Ciyi; Zeng Jun; Xie Wenhui; Hu Silong; Jin Muxiu

    2004-01-01

    The diagnostic and therapeutic efficiency of drug depends highly on the drug distribution in target tissues (tumor for example) both specifically and accumulatively. We report here a powerful approach in design of tissue targeting leads with the assistant of radio-combinatorial screening technique developed in our laboratory. Methods: The C-terminal amide tripeptide libraries were synthesized on Rink Amide-MBHA resin in the OXX aO1OXaO1O2O positional scanning format and iterative protoco. A technetium (V) oxo core[(TcO)3+] was bound to the N4-triligands of tripeptide libraries via four deprotonated anfide nitrogen atoms to form a structure of 99Tcm-tripeptoid libraries. The radio-combinatorial screening (RCS) in vivo was then carried out after SD rats and A549 tumor bearing mice received i.v. with 99Tcm-tripeptoid libraries. Results: Signals of tissue distribution and metabolism of libraries were recorded by g counting or imaging. From library of 8,000 99Tcm-tripeptoid members, the tissue targeting leads had been identified by RCS. Those included 99Tcm-DSG (RES), 99Tcm-VAA, and 99Tcm-VIG that had specific tissue targeting in kidney, stomach, and liver respectively. The percent injected dose per gram tissue (%ID/g) of 99Tcm labeled leads in their target tissues was highly structure-dependent The discovery of 99Tcm-VAA and 99Tcm-VIG indicates that side chain methyl at positionl and 2 are crucial for stomach and liver accumulating 99Tcm-tripeptoids. In the case of kidney targeting, Ser in the position 2 and 3 is crucial for 99Tcm-tripeptoids renal excretion and accumulation characteristics respectively. Conclusion: RCS in vivo is a powerful tool for design of tissue targeting leads. (authors)

  3. Iterative optimization of xylose catabolism in Saccharomyces cerevisiae using combinatorial expression tuning.

    Science.gov (United States)

    Latimer, Luke N; Dueber, John E

    2017-06-01

    A common challenge in metabolic engineering is rapidly identifying rate-controlling enzymes in heterologous pathways for subsequent production improvement. We demonstrate a workflow to address this challenge and apply it to improving xylose utilization in Saccharomyces cerevisiae. For eight reactions required for conversion of xylose to ethanol, we screened enzymes for functional expression in S. cerevisiae, followed by a combinatorial expression analysis to achieve pathway flux balancing and identification of limiting enzymatic activities. In the next round of strain engineering, we increased the copy number of these limiting enzymes and again tested the eight-enzyme combinatorial expression library in this new background. This workflow yielded a strain that has a ∼70% increase in biomass yield and ∼240% increase in xylose utilization. Finally, we chromosomally integrated the expression library. This library enriched for strains with multiple integrations of the pathway, which likely were the result of tandem integrations mediated by promoter homology. Biotechnol. Bioeng. 2017;114: 1301-1309. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

  4. Combinatorial Models for Assembly and Decomposition of Products

    Directory of Open Access Journals (Sweden)

    A. N. Bojko

    2015-01-01

    Full Text Available The paper discusses the most popular combinatorial models that are used for the synthesis of design solutions at the stage of the assembly process flow preparation. It shows that while assembling the product the relations of parts can be represented as a structure of preferences, which is formed on the basis of objective design restrictions put in at the stage of the product design. This structure is a binary preference relation pre-order. Its symmetrical part is equivalence and describes the entry of parts into the assembly unit. The asymmetric part is a partial order. It specifies part- ordering time in in the course of the assembly process. The structure of preferences is a minimal description of the restrictions and constraints in the assembly process. It can serve as a source for generating multiple assembly sequences of a product and its components, which are allowed by design. This multiplicity increases the likelihood of rational choice under uncertainty, unpredictable changes in the properties of technological or industrial systems.Incomplete dominance relation gives grounds for further examination and better understanding of the project situation. Operation field of the study is limited to a set of disparate elements of the partial order. Different strategies for processing the disparate elements may be offered, e.g. selection of the most informative pairs, comparison of which foremost linearizes the original partial order.

  5. Quantum fields and processes a combinatorial approach

    CERN Document Server

    Gough, John

    2018-01-01

    Wick ordering of creation and annihilation operators is of fundamental importance for computing averages and correlations in quantum field theory and, by extension, in the Hudson-Parthasarathy theory of quantum stochastic processes, quantum mechanics, stochastic processes, and probability. This book develops the unified combinatorial framework behind these examples, starting with the simplest mathematically, and working up to the Fock space setting for quantum fields. Emphasizing ideas from combinatorics such as the role of lattice of partitions for multiple stochastic integrals by Wallstrom-Rota and combinatorial species by Joyal, it presents insights coming from quantum probability. It also introduces a 'field calculus' which acts as a succinct alternative to standard Feynman diagrams and formulates quantum field theory (cumulant moments, Dyson-Schwinger equation, tree expansions, 1-particle irreducibility) in this language. Featuring many worked examples, the book is aimed at mathematical physicists, quant...

  6. Gems of combinatorial optimization and graph algorithms

    CERN Document Server

    Skutella, Martin; Stiller, Sebastian; Wagner, Dorothea

    2015-01-01

    Are you looking for new lectures for your course on algorithms, combinatorial optimization, or algorithmic game theory?  Maybe you need a convenient source of relevant, current topics for a graduate student or advanced undergraduate student seminar?  Or perhaps you just want an enjoyable look at some beautiful mathematical and algorithmic results, ideas, proofs, concepts, and techniques in discrete mathematics and theoretical computer science?   Gems of Combinatorial Optimization and Graph Algorithms is a handpicked collection of up-to-date articles, carefully prepared by a select group of international experts, who have contributed some of their most mathematically or algorithmically elegant ideas.  Topics include longest tours and Steiner trees in geometric spaces, cartograms, resource buying games, congestion games, selfish routing, revenue equivalence and shortest paths, scheduling, linear structures in graphs, contraction hierarchies, budgeted matching problems, and motifs in networks.   This ...

  7. Quantum fields and processes a combinatorial approach

    CERN Document Server

    Gough, John

    2018-01-01

    Wick ordering of creation and annihilation operators is of fundamental importance for computing averages and correlations in quantum field theory and, by extension, in the Hudson–Parthasarathy theory of quantum stochastic processes, quantum mechanics, stochastic processes, and probability. This book develops the unified combinatorial framework behind these examples, starting with the simplest mathematically, and working up to the Fock space setting for quantum fields. Emphasizing ideas from combinatorics such as the role of lattice of partitions for multiple stochastic integrals by Wallstrom–Rota and combinatorial species by Joyal, it presents insights coming from quantum probability. It also introduces a 'field calculus' which acts as a succinct alternative to standard Feynman diagrams and formulates quantum field theory (cumulant moments, Dyson–Schwinger equation, tree expansions, 1-particle irreducibility) in this language. Featuring many worked examples, the book is aimed at mathematical physicists,...

  8. Three Syntactic Theories for Combinatory Graph Reduction

    DEFF Research Database (Denmark)

    Danvy, Olivier; Zerny, Ian

    2011-01-01

    in a third syntactic theory. The structure of the store-based abstract machine corresponding to this third syntactic theory oincides with that of Turner's original reduction machine. The three syntactic theories presented here The three syntactic heories presented here therefore have the following......We present a purely syntactic theory of graph reduction for the canonical combinators S, K, and I, where graph vertices are represented with evaluation contexts and let expressions. We express this syntactic theory as a reduction semantics, which we refocus into the first storeless abstract machine...... for combinatory graph reduction, which we refunctionalize into the first storeless natural semantics for combinatory graph reduction.We then factor out the introduction of let expressions to denote as many graph vertices as possible upfront instead of on demand, resulting in a second syntactic theory, this one...

  9. Three Syntactic Theories for Combinatory Graph Reduction

    DEFF Research Database (Denmark)

    Danvy, Olivier; Zerny, Ian

    2013-01-01

    , as a store-based reduction semantics of combinatory term graphs. We then refocus this store-based reduction semantics into a store-based abstract machine. The architecture of this store-based abstract machine coincides with that of Turner's original reduction machine. The three syntactic theories presented......We present a purely syntactic theory of graph reduction for the canonical combinators S, K, and I, where graph vertices are represented with evaluation contexts and let expressions. We express this rst syntactic theory as a storeless reduction semantics of combinatory terms. We then factor out...... the introduction of let expressions to denote as many graph vertices as possible upfront instead of on demand . The factored terms can be interpreted as term graphs in the sense of Barendregt et al. We express this second syntactic theory, which we prove equivalent to the rst, as a storeless reduction semantics...

  10. Exploiting Quantum Resonance to Solve Combinatorial Problems

    Science.gov (United States)

    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.

  11. Application of combinatorial biocatalysis for a unique ring expansion of dihydroxymethylzearalenone.

    Science.gov (United States)

    Rich, Joseph O; Budde, Cheryl L; McConeghey, Luke D; Cotterill, Ian C; Mozhaev, Vadim V; Singh, Sheo B; Goetz, Michael A; Zhao, Annie; Michels, Peter C; Khmelnitsky, Yuri L

    2009-06-01

    Combinatorial biocatalysis was applied to generate a diverse set of dihydroxymethylzearalenone analogs with modified ring structure. In one representative chemoenzymatic reaction sequence, dihydroxymethylzearalenone was first subjected to a unique enzyme-catalyzed oxidative ring opening reaction that creates two new carboxylic groups on the molecule. These groups served as reaction sites for further derivatization involving biocatalytic ring closure reactions with structurally diverse bifunctional reagents, including different diols and diamines. As a result, a library of cyclic bislactones and bislactams was created, with modified ring structures covering chemical space and structure activity relationships unattainable by conventional synthetic means.

  12. Combinatorial Cis-regulation in Saccharomyces Species

    Directory of Open Access Journals (Sweden)

    Aaron T. Spivak

    2016-03-01

    Full Text Available 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.

  13. The Combinatorial Trace Method in Action

    Science.gov (United States)

    Krebs, Mike; Martinez, Natalie C.

    2013-01-01

    On any finite graph, the number of closed walks of length k is equal to the sum of the kth powers of the eigenvalues of any adjacency matrix. This simple observation is the basis for the combinatorial trace method, wherein we attempt to count (or bound) the number of closed walks of a given length so as to obtain information about the graph's…

  14. Bounded Rationality and Budgeting

    OpenAIRE

    Ibrahim, Mukdad

    2016-01-01

    This article discusses the theory of bounded rationality which had been introduced by Herbert Simon in the 1950s. Simon introduced the notion of bounded rationality stating that while decision-makers strive for rationality, they are limited by the effect of the environment, their information process capacity and by the constraints on their information storage and retrieval capabilities. Moreover, this article tries to specifically blend this notion into budgeting, using the foundations of inc...

  15. Rational Multiparty Computation

    OpenAIRE

    Wallrabenstein, John Ross

    2014-01-01

    The field of rational cryptography considers the design of cryptographic protocols in the presence of rational agents seeking to maximize local utility functions. This departs from the standard secure multiparty computation setting, where players are assumed to be either honest or malicious. ^ We detail the construction of both a two-party and a multiparty game theoretic framework for constructing rational cryptographic protocols. Our framework specifies the utility function assumptions neces...

  16. Determinants of Actor Rationality

    DEFF Research Database (Denmark)

    Ellegaard, Chris

    Industrial companies must exercise influence on their suppliers (or supplier actors). Actor rationality is a central theme connected to this management task. In this article, relevant literature is studied with the purpose of shedding light on determinants of actor rationality. Two buyer-supplier...... relations are investigated in a multiple case study, leading to the proposal of various additional factors that determine and shape actor rationality. Moreover a conceptual model of rationality determinants in the buyer-supplier relation is proposed, a model that may help supply managers analyse...

  17. MIFT: GIFT Combinatorial Geometry Input to VCS Code

    Science.gov (United States)

    1977-03-01

    r-w w-^ H ^ß0318is CQ BRL °RCUMr REPORT NO. 1967 —-S: ... MIFT: GIFT COMBINATORIAL GEOMETRY INPUT TO VCS CODE Albert E...TITLE (and Subtitle) MIFT: GIFT Combinatorial Geometry Input to VCS Code S. TYPE OF REPORT & PERIOD COVERED FINAL 6. PERFORMING ORG. REPORT NUMBER...Vehicle Code System (VCS) called MORSE was modified to accept the GIFT combinatorial geometry package. GIFT , as opposed to the geometry package

  18. Neural Meta-Memes Framework for Combinatorial Optimization

    Science.gov (United States)

    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).

  19. Combinatorial Approaches for the Identification of Brain Drug Delivery Targets

    Science.gov (United States)

    Stutz, Charles C.; Zhang, Xiaobin; Shusta, Eric V.

    2018-01-01

    The blood-brain barrier (BBB) represents a large obstacle for the treatment of central nervous system diseases. Targeting endogenous nutrient transporters that transcytose the BBB is one promising approach to selectively and noninvasively deliver a drug payload to the brain. The main limitations of the currently employed transcytosing receptors are their ubiquitous expression in the peripheral vasculature and the inherent low levels of transcytosis mediated by such systems. In this review, approaches designed to increase the repertoire of transcytosing receptors which can be targeted for the purpose of drug delivery are discussed. In particular, combinatorial protein libraries can be screened on BBB cells in vitro or in vivo to isolate targeting peptides or antibodies that can trigger transcytosis. Once these targeting reagents are discovered, the cognate BBB transcytosis system can be identified using techniques such as expression cloning or immunoprecipitation coupled with mass spectrometry. Continued technological advances in BBB genomics and proteomics, membrane protein manipulation, and in vitro BBB technology promise to further advance the capability to identify and optimize peptides and antibodies capable of mediating drug transport across the BBB. PMID:23789958

  20. Binary Cockroach Swarm Optimization for Combinatorial Optimization Problem

    Directory of Open Access Journals (Sweden)

    Ibidun Christiana Obagbuwa

    2016-09-01

    Full Text Available The Cockroach Swarm Optimization (CSO algorithm is inspired by cockroach social behavior. It is a simple and efficient meta-heuristic algorithm and has been applied to solve global optimization problems successfully. The original CSO algorithm and its variants operate mainly in continuous search space and cannot solve binary-coded optimization problems directly. Many optimization problems have their decision variables in binary. Binary Cockroach Swarm Optimization (BCSO is proposed in this paper to tackle such problems and was evaluated on the popular Traveling Salesman Problem (TSP, which is considered to be an NP-hard Combinatorial Optimization Problem (COP. A transfer function was employed to map a continuous search space CSO to binary search space. The performance of the proposed algorithm was tested firstly on benchmark functions through simulation studies and compared with the performance of existing binary particle swarm optimization and continuous space versions of CSO. The proposed BCSO was adapted to TSP and applied to a set of benchmark instances of symmetric TSP from the TSP library. The results of the proposed Binary Cockroach Swarm Optimization (BCSO algorithm on TSP were compared to other meta-heuristic algorithms.

  1. "One-sample concept" micro-combinatory for high throughput TEM of binary films.

    Science.gov (United States)

    Sáfrán, György

    2018-04-01

    Phases of thin films may remarkably differ from that of bulk. Unlike to the comprehensive data files of Binary Phase Diagrams [1] available for bulk, complete phase maps for thin binary layers do not exist. This is due to both the diverse metastable, non-equilibrium or instable phases feasible in thin films and the required volume of characterization work with analytical techniques like TEM, SAED and EDS. The aim of the present work was to develop a method that remarkably facilitates the TEM study of the diverse binary phases of thin films, or the creation of phase maps. A micro-combinatorial method was worked out that enables both preparation and study of a gradient two-component film within a single TEM specimen. For a demonstration of the technique thin Mn x Al 1- x binary samples with evolving concentration from x = 0 to x = 1 have been prepared so that the transition from pure Mn to pure Al covers a 1.5 mm long track within the 3 mm diameter TEM grid. The proposed method enables the preparation and study of thin combinatorial samples including all feasible phases as a function of composition or other deposition parameters. Contrary to known "combinatorial chemistry", in which a series of different samples are deposited in one run, and investigated, one at a time, the present micro-combinatorial method produces a single specimen condensing a complete library of a binary system that can be studied, efficiently, within a single TEM session. That provides extremely high throughput for TEM characterization of composition-dependent phases, exploration of new materials, or the construction of phase diagrams of binary films. Copyright © 2018 Elsevier B.V. All rights reserved.

  2. Library Computing

    Science.gov (United States)

    Library Computing, 1985

    1985-01-01

    Special supplement to "Library Journal" and "School Library Journal" covers topics of interest to school, public, academic, and special libraries planning for automation: microcomputer use, readings in automation, online searching, databases of microcomputer software, public access to microcomputers, circulation, creating a…

  3. Use of combinatorial chemistry to speed drug discovery.

    Science.gov (United States)

    Rádl, S

    1998-10-01

    IBC's International Conference on Integrating Combinatorial Chemistry into the Discovery Pipeline was held September 14-15, 1998. The program started with a pre-conference workshop on High-Throughput Compound Characterization and Purification. The agenda of the main conference was divided into sessions of Synthesis, Automation and Unique Chemistries; Integrating Combinatorial Chemistry, Medicinal Chemistry and Screening; Combinatorial Chemistry Applications for Drug Discovery; and Information and Data Management. This meeting was an excellent opportunity to see how big pharma, biotech and service companies are addressing the current bottlenecks in combinatorial chemistry to speed drug discovery. (c) 1998 Prous Science. All rights reserved.

  4. Advanced Aqueous Phase Catalyst Development using Combinatorial Methods, Phase II

    Data.gov (United States)

    National Aeronautics and Space Administration — Combinatorial methods are proposed to develop advanced Aqueous Oxidation Catalysts (AOCs) with the capability to mineralize organic contaminants present in effluents...

  5. Standby Gasoline Rationing Plan

    Energy Technology Data Exchange (ETDEWEB)

    None

    1980-06-01

    The final rules adopted by the President for a Standby Gasoline Rationing Plan are presented. The plan provides that eligibility for ration allotments will be determined primarily on the basis of motor vehicle registrations, taking into account historical differences in the use of gasoline among states. The regulations also provide authority for supplemental allotments to firms so that their allotment will equal a specified percentage of gasoline use during a base period. Priority classifications, i.e., agriculture, defense, etc., are established to assure adequate gasoline supplies for designated essential services. Ration rights must be provided by end-users to their suppliers for each gallon sold. DOE will regulate the distribution of gasoline at the wholesale level according to the transfer by suppliers of redeemed ration rights and the gasoline allocation regulations. Ration rights are transferable. A ration banking system is created to facilitate transfers of ration rights. Each state will be provided with a reserve of ration rights to provide for hardship needs and to alleviate inequities. (DC)

  6. Two Concepts of Rationality

    Directory of Open Access Journals (Sweden)

    Danny Frederick

    2010-02-01

    Full Text Available The dominant tradition in Western philosophy sees rationality as dictating. Thus rationality may require that we believe the best explanation and simple conceptual truths and that we infer in accordance with evident rules of inference. I argue that, given what we know about the growth of knowledge, this authoritarian concept of rationality leads to absurdities and should be abandoned. I then outline a libertarian concept of rationality, derived from Popper, which eschews the dictates and which sees a rational agent as one who questions, criticises, conjectures and experiments. I argue that, while the libertarian approach escapes the absurdities of the authoritarian, it requires two significant developments and an important clarification to be made fully consistent with itself.

  7. Exploring rationality in schizophrenia

    DEFF Research Database (Denmark)

    Revsbech, Rasmus; Mortensen, Erik Lykke; Owen, Gareth

    2015-01-01

    Background Empirical studies of rationality (syllogisms) in patients with schizophrenia have obtained different results. One study found that patients reason more logically if the syllogism is presented through an unusual content. Aims To explore syllogism-based rationality in schizophrenia. Meth...... differences became non-significant. Conclusions When taking intelligence and neuropsychological performance into account, patients with schizophrenia and controls perform similarly on syllogism tests of rationality.......Background Empirical studies of rationality (syllogisms) in patients with schizophrenia have obtained different results. One study found that patients reason more logically if the syllogism is presented through an unusual content. Aims To explore syllogism-based rationality in schizophrenia. Method...... Thirty-eight first-admitted patients with schizophrenia and 38 healthy controls solved 29 syllogisms that varied in presentation content (ordinary v. unusual) and validity (valid v. invalid). Statistical tests were made of unadjusted and adjusted group differences in models adjusting for intelligence...

  8. Irrational Rationality of Terrorism

    Directory of Open Access Journals (Sweden)

    Robert Nalbandov

    2013-12-01

    Full Text Available The present article deals with the ontological problem of applying the rational choice frameworks to the study of terrorism. It testing the application of the rational choice to the “old” (before the end of the Cold War and the “new” (after the end of the Cold War terrorisms. It starts with analyzing the fundamentals of rationality and applies it at two levels: the individual (actors and group (collective via two outlooks: tactical (short-term and strategic (long-term. The main argument of the article is that while the “old” terrorism can be explained by the rational choice theory its “new” version represents a substantial departure from rationality.

  9. Respect for rational autonomy.

    Science.gov (United States)

    Walker, Rebecca L

    2009-12-01

    The standard notion of autonomy in medical ethics does not require that autonomous choices not be irrational. The paper gives three examples of seemingly irrational patient choices and discusses how a rational autonomy analysis differs from the standard view. It then considers whether a switch to the rational autonomy view would lead to overriding more patient decisions but concludes that this should not be the case. Rather, a determination of whether individual patient decisions are autonomous is much less relevant than usually considered in determining whether health care providers must abide by these decisions. Furthermore, respect for rational autonomy entails strong positive requirements of respect for the autonomy of the person as a rational decision maker. The rationality view of autonomy is conceptually stronger than the standard view, allows for a more nuanced understanding of the practical moral calculus involved in respecting patient autonomy, and promotes positive respect for patient autonomy.

  10. A diversity-oriented synthesis strategy enabling the combinatorial-type variation of macrocyclic peptidomimetic scaffolds.

    Science.gov (United States)

    Isidro-Llobet, Albert; Hadje Georgiou, Kathy; Galloway, Warren R J D; Giacomini, Elisa; Hansen, Mette R; Méndez-Abt, Gabriela; Tan, Yaw Sing; Carro, Laura; Sore, Hannah F; Spring, David R

    2015-04-21

    Macrocyclic peptidomimetics are associated with a broad range of biological activities. However, despite such potentially valuable properties, the macrocyclic peptidomimetic structural class is generally considered as being poorly explored within drug discovery. This has been attributed to the lack of general methods for producing collections of macrocyclic peptidomimetics with high levels of structural, and thus shape, diversity. In particular, there is a lack of scaffold diversity in current macrocyclic peptidomimetic libraries; indeed, the efficient construction of diverse molecular scaffolds presents a formidable general challenge to the synthetic chemist. Herein we describe a new, advanced strategy for the diversity-oriented synthesis (DOS) of macrocyclic peptidomimetics that enables the combinatorial variation of molecular scaffolds (core macrocyclic ring architectures). The generality and robustness of this DOS strategy is demonstrated by the step-efficient synthesis of a structurally diverse library of over 200 macrocyclic peptidomimetic compounds, each based around a distinct molecular scaffold and isolated in milligram quantities, from readily available building-blocks. To the best of our knowledge this represents an unprecedented level of scaffold diversity in a synthetically derived library of macrocyclic peptidomimetics. Cheminformatic analysis indicated that the library compounds access regions of chemical space that are distinct from those addressed by top-selling brand-name drugs and macrocyclic natural products, illustrating the value of our DOS approach to sample regions of chemical space underexploited in current drug discovery efforts. An analysis of three-dimensional molecular shapes illustrated that the DOS library has a relatively high level of shape diversity.

  11. Effects of Suboptimal Bidding in Combinatorial Auctions

    Science.gov (United States)

    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).

  12. Library Consortia in Croatia

    Directory of Open Access Journals (Sweden)

    Maja Jokic

    2001-07-01

    Full Text Available The problem of the increasing number of information sources and their costs as well as more demanding users on the one side, and limited financial resources on the other, has not avoided Croatia. One of the attempts to deal with this state of affairs is associating libraries into consortia. A consortium could, through cooperative cataloguing, help optimise the processing of library material, it could help in solving the problem of rational ways of continuous education of staff and users and coordinate acquisition policy through common purchasing of information resources, from bibliographic databases to electronic journals under various licensing conditions. This last aspect of cooperation in a consortium will be dealt with in detail in the text that follows.

  13. Combinatorial Screening for Transgenic Yeasts with High Cellulase Activities in Combination with a Tunable Expression System.

    Directory of Open Access Journals (Sweden)

    Yoichiro Ito

    Full Text Available Combinatorial screening used together with a broad library of gene expression cassettes is expected to produce a powerful tool for the optimization of the simultaneous expression of multiple enzymes. Recently, we proposed a highly tunable protein expression system that utilized multiple genome-integrated target genes to fine-tune enzyme expression in yeast cells. This tunable system included a library of expression cassettes each composed of three gene-expression control elements that in different combinations produced a wide range of protein expression levels. In this study, four gene expression cassettes with graded protein expression levels were applied to the expression of three cellulases: cellobiohydrolase 1, cellobiohydrolase 2, and endoglucanase 2. After combinatorial screening for transgenic yeasts simultaneously secreting these three cellulases, we obtained strains with higher cellulase expressions than a strain harboring three cellulase-expression constructs within one high-performance gene expression cassette. These results show that our method will be of broad use throughout the field of metabolic engineering.

  14. Concept of combinatorial de novo design of drug-like molecules by particle swarm optimization.

    Science.gov (United States)

    Hartenfeller, Markus; Proschak, Ewgenij; Schüller, Andreas; Schneider, Gisbert

    2008-07-01

    We present a fast stochastic optimization algorithm for fragment-based molecular de novo design (COLIBREE, Combinatorial Library Breeding). The search strategy is based on a discrete version of particle swarm optimization. Molecules are represented by a scaffold, which remains constant during optimization, and variable linkers and side chains. Different linkers represent virtual chemical reactions. Side-chain building blocks were obtained from pseudo-retrosynthetic dissection of large compound databases. Here, ligand-based design was performed using chemically advanced template search (CATS) topological pharmacophore similarity to reference ligands as fitness function. A weighting scheme was included for particle swarm optimization-based molecular design, which permits the use of many reference ligands and allows for positive and negative design to be performed simultaneously. In a case study, the approach was applied to the de novo design of potential peroxisome proliferator-activated receptor subtype-selective agonists. The results demonstrate the ability of the technique to cope with large combinatorial chemistry spaces and its applicability to focused library design. The technique was able to perform exploitation of a known scheme and at the same time explorative search for novel ligands within the framework of a given molecular core structure. It thereby represents a practical solution for compound screening in the early hit and lead finding phase of a drug discovery project.

  15. Combinatorial Screening for Transgenic Yeasts with High Cellulase Activities in Combination with a Tunable Expression System

    Science.gov (United States)

    Ito, Yoichiro; Yamanishi, Mamoru; Ikeuchi, Akinori; Imamura, Chie; Matsuyama, Takashi

    2015-01-01

    Combinatorial screening used together with a broad library of gene expression cassettes is expected to produce a powerful tool for the optimization of the simultaneous expression of multiple enzymes. Recently, we proposed a highly tunable protein expression system that utilized multiple genome-integrated target genes to fine-tune enzyme expression in yeast cells. This tunable system included a library of expression cassettes each composed of three gene-expression control elements that in different combinations produced a wide range of protein expression levels. In this study, four gene expression cassettes with graded protein expression levels were applied to the expression of three cellulases: cellobiohydrolase 1, cellobiohydrolase 2, and endoglucanase 2. After combinatorial screening for transgenic yeasts simultaneously secreting these three cellulases, we obtained strains with higher cellulase expressions than a strain harboring three cellulase-expression constructs within one high-performance gene expression cassette. These results show that our method will be of broad use throughout the field of metabolic engineering. PMID:26692026

  16. Dynamical System Approaches to Combinatorial Optimization

    DEFF Research Database (Denmark)

    Starke, Jens

    2013-01-01

    of large times as an asymptotically stable point of the dynamics. The obtained solutions are often not globally optimal but good approximations of it. Dynamical system and neural network approaches are appropriate methods for distributed and parallel processing. Because of the parallelization......Several dynamical system approaches to combinatorial optimization problems are described and compared. These include dynamical systems derived from penalty methods; the approach of Hopfield and Tank; self-organizing maps, that is, Kohonen networks; coupled selection equations; and hybrid methods...... thereof can be used as models for many industrial problems like manufacturing planning and optimization of flexible manufacturing systems. This is illustrated for an example in distributed robotic systems....

  17. Quantum resonance for simulating combinatorial problems

    International Nuclear Information System (INIS)

    Zak, Michail; Fijany, Amir

    2005-01-01

    Quantum computing by simulations is based upon similarity between mathematical formalism of a quantum phenomenon and phenomena to be analyzed. In this Letter, the mathematical formalism of quantum resonance combined with tensor product decomposability of unitary evolutions is mapped onto a class of NP-complete combinatorial problems. It has been demonstrated that nature has polynomial resources for solving NP-complete problems and that will help to develop a new strategy for artificial intelligence, as well as to re-evaluate the role of natural selection in biological evolution

  18. Automatic generation of combinatorial test data

    CERN Document Server

    Zhang, Jian; Ma, Feifei

    2014-01-01

    This book reviews the state-of-the-art in combinatorial testing, with particular emphasis on the automatic generation of test data. It describes the most commonly used approaches in this area - including algebraic construction, greedy methods, evolutionary computation, constraint solving and optimization - and explains major algorithms with examples. In addition, the book lists a number of test generation tools, as well as benchmarks and applications. Addressing a multidisciplinary topic, it will be of particular interest to researchers and professionals in the areas of software testing, combi

  19. Method and apparatus for combinatorial chemistry

    Science.gov (United States)

    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.

  20. On Definitions and Existence of Combinatorial Entropy of 2d Fields

    DEFF Research Database (Denmark)

    Forchhammer, Søren Otto; Shtarkov, Yuri; Justesen, Jørn

    1998-01-01

    Different definitions of combinatorial entropy is presented and conditions for their existence examined.......Different definitions of combinatorial entropy is presented and conditions for their existence examined....

  1. Combinatorial Quantum Field Theory and Gluing Formula for Determinants

    NARCIS (Netherlands)

    Reshetikhin, N.; Vertman, B.

    2015-01-01

    We define the combinatorial Dirichlet-to-Neumann operator and establish a gluing formula for determinants of discrete Laplacians using a combinatorial Gaussian quantum field theory. In case of a diagonal inner product on cochains we provide an explicit local expression for the discrete

  2. Combinatorial identities for tenth order mock theta functions

    Indian Academy of Sciences (India)

    44

    which lead us to one 4-way and one 3-way combinatorial identity. ... mock theta functions, partition identities and different combinatorial parameters, see for ... 3. Example 1.1. There are twelve (n + 1)–color partitions of 2: 21, 21 + 01, 11 + 11, ...

  3. Exact model reduction of combinatorial reaction networks

    Directory of Open Access Journals (Sweden)

    Fey Dirk

    2008-08-01

    Full Text Available Abstract Background Receptors and scaffold proteins usually possess a high number of distinct binding domains inducing the formation of large multiprotein signaling complexes. Due to combinatorial reasons the number of distinguishable species grows exponentially with the number of binding domains and can easily reach several millions. Even by including only a limited number of components and binding domains the resulting models are very large and hardly manageable. A novel model reduction technique allows the significant reduction and modularization of these models. Results We introduce methods that extend and complete the already introduced approach. For instance, we provide techniques to handle the formation of multi-scaffold complexes as well as receptor dimerization. Furthermore, we discuss a new modeling approach that allows the direct generation of exactly reduced model structures. The developed methods are used to reduce a model of EGF and insulin receptor crosstalk comprising 5,182 ordinary differential equations (ODEs to a model with 87 ODEs. Conclusion The methods, presented in this contribution, significantly enhance the available methods to exactly reduce models of combinatorial reaction networks.

  4. Protocols for the Design of Kinase-focused Compound Libraries.

    Science.gov (United States)

    Jacoby, Edgar; Wroblowski, Berthold; Buyck, Christophe; Neefs, Jean-Marc; Meyer, Christophe; Cummings, Maxwell D; van Vlijmen, Herman

    2018-05-01

    Protocols for the design of kinase-focused compound libraries are presented. Kinase-focused compound libraries can be differentiated based on the design goal. Depending on whether the library should be a discovery library specific for one particular kinase, a general discovery library for multiple distinct kinase projects, or even phenotypic screening, there exists today a variety of in silico methods to design candidate compound libraries. We address the following scenarios: 1) Datamining of SAR databases and kinase focused vendor catalogues; 2) Predictions and virtual screening; 3) Structure-based design of combinatorial kinase inhibitors; 4) Design of covalent kinase inhibitors; 5) Design of macrocyclic kinase inhibitors; and 6) Design of allosteric kinase inhibitors and activators. © 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  5. History of Economic Rationalities

    DEFF Research Database (Denmark)

    This book concentrates upon how economic rationalities have been embedded into particular historical practices, cultures, and moral systems. Through multiple case-studies, situated in different historical contexts of the modern West, the book shows that the development of economic rationalities...... takes place in the meeting with other regimes of thought, values, and moral discourses. The book offers new and refreshing insights, ranging from the development of early economic thinking to economic aspects and concepts in the works of classical thinkers such as Thomas Hobbes, John Locke and Karl Marx......, to the role of economic reasoning in contemporary policies of art and health care. With economic rationalities as the read thread, the reader is offered a unique chance of historical self-awareness and recollection of how economic rationality became the powerful ideological and moral force that it is today....

  6. Rationing medical education.

    African Journals Online (AJOL)

    This paper discussed the pros and cons of the application of rationing to medical education and the different ... Even though some stakeholders in medical education might be taken aback at .... Walsh K. Online educational tools to improve the.

  7. Crab Rationalization Permit Program

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — The Crab Rationalization Program (Program) allocates BSAI crab resources among harvesters, processors, and coastal communities. The North Pacific Fishery Management...

  8. THE HICKSIAN RATIONAL CONSUMER

    OpenAIRE

    Manuel FERNÁNDEZ-GRELA

    2005-01-01

    The aim of this paper is to trace the evolution of the concept of ''rational consumer'' in Hicks's writings. After being one of the pioneers in the introduction of rationality assumptions about consumer behaviour in economic models, Hicks gradually developed a sceptical view about some of the uses to which those assumptions were put into. The focus of the paper is on continuity in Hicksian views, providing a picture of gradual changes in the long series of Hicks's works

  9. About the Library - Betty Petersen Memorial Library

    Science.gov (United States)

    branch library of the NOAA Central Library. The library serves the NOAA Science Center in Camp Springs , Maryland. History and Mission: Betty Petersen Memorial Library began as a reading room in the NOAA Science Science Center staff and advises the library on all aspects of the library program. Library Newsletters

  10. Approaches towards the automated interpretation and prediction of electrospray tandem mass spectra of non-peptidic combinatorial compounds.

    Science.gov (United States)

    Klagkou, Katerina; Pullen, Frank; Harrison, Mark; Organ, Andy; Firth, Alistair; Langley, G John

    2003-01-01

    Combinatorial chemistry is widely used within the pharmaceutical industry as a means of rapid identification of potential drugs. With the growth of combinatorial libraries, mass spectrometry (MS) became the key analytical technique because of its speed of analysis, sensitivity, accuracy and ability to be coupled with other analytical techniques. In the majority of cases, electrospray mass spectrometry (ES-MS) has become the default ionisation technique. However, due to the absence of fragment ions in the resulting spectra, tandem mass spectrometry (MS/MS) is required to provide structural information for the identification of an unknown analyte. This work discusses the first steps of an investigation into the fragmentation pathways taking place in electrospray tandem mass spectrometry. The ultimate goal for this project is to set general fragmentation rules for non-peptidic, pharmaceutical, combinatorial compounds. As an aid, an artificial intelligence (AI) software package is used to facilitate interpretation of the spectra. This initial study has focused on determining the fragmentation rules for some classes of compound types that fit the remit as outlined above. Based on studies carried out on several combinatorial libraries of these compounds, it was established that different classes of drug molecules follow unique fragmentation pathways. In addition to these general observations, the specific ionisation processes and the fragmentation pathways involved in the electrospray mass spectra of these systems were explored. The ultimate goal will be to incorporate our findings into the computer program and allow identification of an unknown, non-peptidic compound following insertion of its ES-MS/MS spectrum into the AI package. The work herein demonstrates the potential benefit of such an approach in addressing the issue of high-throughput, automated MS/MS data interpretation. Copyright 2003 John Wiley & Sons, Ltd.

  11. Library Use

    DEFF Research Database (Denmark)

    Konzack, Lars

    2012-01-01

    A seminar paper about a survey of role-playing games in public libraries combined with three cases and a presentation of a model.......A seminar paper about a survey of role-playing games in public libraries combined with three cases and a presentation of a model....

  12. Combinatorial experiment in Ni-Ti thin films by laser interference structuring

    International Nuclear Information System (INIS)

    Liu, K.W.; Gachot, C.; Leibenguth, P.; Muecklich, F.

    2005-01-01

    Combinatorial experiments are achieved on periodically structured Ni-Ti thin film composition spreads by laser interference irradiation using a Nd:YAG laser. Continuous Ni-Ti compositional spreads covering almost the whole binary system are prepared by combining sputter mask, shutter and movement of substrate. The continuous compositional spread is subsequently micro-structured into a sample library consisting of well-defined lines of individual samples by laser interference irradiation. The composition and microstructure effects in continuous spread and sample libraries after laser structuring are explored by scanning electron microscopy (SEM) with energy dispersive spectroscopy (EDS), X-ray diffraction (XRD) and white light interferometry (WLI) microscopy. The sample library consists of individual samples with a distance of about 5 μm and a composition resolution as high as 0.1 at.% in between. Although, there are certain difficulties so far in obtaining the optimized laser fluence for the spread, the laser interference irradiation provides an effective way to prepare thin film libraries with around 200 sample lines within 1 mm

  13. cDREM: inferring dynamic combinatorial gene regulation.

    Science.gov (United States)

    Wise, Aaron; Bar-Joseph, Ziv

    2015-04-01

    Genes are often combinatorially regulated by multiple transcription factors (TFs). Such combinatorial regulation plays an important role in development and facilitates the ability of cells to respond to different stresses. While a number of approaches have utilized sequence and ChIP-based datasets to study combinational regulation, these have often ignored the combinational logic and the dynamics associated with such regulation. Here we present cDREM, a new method for reconstructing dynamic models of combinatorial regulation. cDREM integrates time series gene expression data with (static) protein interaction data. The method is based on a hidden Markov model and utilizes the sparse group Lasso to identify small subsets of combinatorially active TFs, their time of activation, and the logical function they implement. We tested cDREM on yeast and human data sets. Using yeast we show that the predicted combinatorial sets agree with other high throughput genomic datasets and improve upon prior methods developed to infer combinatorial regulation. Applying cDREM to study human response to flu, we were able to identify several combinatorial TF sets, some of which were known to regulate immune response while others represent novel combinations of important TFs.

  14. Bifurcation-based approach reveals synergism and optimal combinatorial perturbation.

    Science.gov (United States)

    Liu, Yanwei; Li, Shanshan; Liu, Zengrong; Wang, Ruiqi

    2016-06-01

    Cells accomplish the process of fate decisions and form terminal lineages through a series of binary choices in which cells switch stable states from one branch to another as the interacting strengths of regulatory factors continuously vary. Various combinatorial effects may occur because almost all regulatory processes are managed in a combinatorial fashion. Combinatorial regulation is crucial for cell fate decisions because it may effectively integrate many different signaling pathways to meet the higher regulation demand during cell development. However, whether the contribution of combinatorial regulation to the state transition is better than that of a single one and if so, what the optimal combination strategy is, seem to be significant issue from the point of view of both biology and mathematics. Using the approaches of combinatorial perturbations and bifurcation analysis, we provide a general framework for the quantitative analysis of synergism in molecular networks. Different from the known methods, the bifurcation-based approach depends only on stable state responses to stimuli because the state transition induced by combinatorial perturbations occurs between stable states. More importantly, an optimal combinatorial perturbation strategy can be determined by investigating the relationship between the bifurcation curve of a synergistic perturbation pair and the level set of a specific objective function. The approach is applied to two models, i.e., a theoretical multistable decision model and a biologically realistic CREB model, to show its validity, although the approach holds for a general class of biological systems.

  15. Target-directed Dynamic Combinatorial Chemistry: A Study on Potentials and Pitfalls as Exemplified on a Bacterial Target.

    Science.gov (United States)

    Frei, Priska; Pang, Lijuan; Silbermann, Marleen; Eriş, Deniz; Mühlethaler, Tobias; Schwardt, Oliver; Ernst, Beat

    2017-08-25

    Target-directed dynamic combinatorial chemistry (DCC) is an emerging technique for the efficient identification of inhibitors of pharmacologically relevant targets. In this contribution, we present an application for a bacterial target, the lectin FimH, a crucial virulence factor of uropathogenic E. coli being the main cause of urinary tract infections. A small dynamic library of acylhydrazones was formed from aldehydes and hydrazides and equilibrated at neutral pH in presence of aniline as nucleophilic catalyst. The major success factors turned out to be an accordingly adjusted ratio of scaffolds and fragments, an adequate sample preparation prior to HPLC analysis, and the data processing. Only then did the ranking of the dynamic library constituents correlate well with affinity data. Furthermore, as a support of DCC applications especially to larger libraries, a new protocol for improved hit identification was established. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  16. Characterizing the combinatorial beam angle selection problem

    Science.gov (United States)

    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

  17. Combinatorial nanomedicines for colon cancer therapy.

    Science.gov (United States)

    Anitha, A; Maya, S; Sivaram, Amal J; Mony, U; Jayakumar, R

    2016-01-01

    Colon cancer is one of the major causes of cancer deaths worldwide. Even after surgical resection and aggressive chemotherapy, 50% of colorectal carcinoma patients develop recurrent disease. Thus, the rationale of developing new therapeutic approaches to improve the current chemotherapeutic regimen would be highly recommended. There are reports on the effectiveness of combination chemotherapy in colon cancer and it has been practiced in clinics for long time. These approaches are associated with toxic side effects. Later, the drug delivery research had shown the potential of nanoencapsulation techniques and active targeting as an effective method to improve the effectiveness of chemotherapy with less toxicity. This current focus article provides a brief analysis of the ongoing research in the colon cancer area using the combinatorial nanomedicines and its outcome. © 2015 Wiley Periodicals, Inc.

  18. Identification and Interrogation of Combinatorial Histone Modifications

    Directory of Open Access Journals (Sweden)

    Kelly R Karch

    2013-12-01

    Full Text Available Histone proteins are dynamically modified to mediate a variety of cellular processes including gene transcription, DNA damage repair, and apoptosis. Regulation of these processes occurs through the recruitment of non-histone proteins to chromatin by specific combinations of histone post-translational modifications (PTMs. Mass spectrometry has emerged as an essential tool to discover and quantify histone PTMs both within and between samples in an unbiased manner. Developments in mass spectrometry that allow for characterization of large histone peptides or intact protein has made it possible to determine which modifications occur simultaneously on a single histone polypeptide. A variety of techniques from biochemistry, biophysics, and chemical biology have been employed to determine the biological relevance of discovered combinatorial codes. This review first describes advancements in the field of mass spectrometry that have facilitated histone PTM analysis and then covers notable approaches to probe the biological relevance of these modifications in their nucleosomal context.

  19. Characterizing the combinatorial beam angle selection problem

    International Nuclear Information System (INIS)

    Bangert, Mark; Ziegenhein, Peter; Oelfke, Uwe

    2012-01-01

    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

  20. Combinatorial nuclear level-density model

    International Nuclear Information System (INIS)

    Uhrenholt, H.; Åberg, S.; Dobrowolski, A.; Døssing, Th.; Ichikawa, T.; Möller, P.

    2013-01-01

    A microscopic nuclear level-density model is presented. The model is a completely combinatorial (micro-canonical) model based on the folded-Yukawa single-particle potential and includes explicit treatment of pairing, rotational and vibrational states. The microscopic character of all states enables extraction of level-distribution functions with respect to pairing gaps, parity and angular momentum. The results of the model are compared to available experimental data: level spacings at neutron separation energy, data on total level-density functions from the Oslo method, cumulative level densities from low-lying discrete states, and data on parity ratios. Spherical and deformed nuclei follow basically different coupling schemes, and we focus on deformed nuclei

  1. Reference Service and Bounded Rationality: Helping Students with Research.

    Science.gov (United States)

    Chu, Felix T.

    1994-01-01

    In university libraries, reference librarians often get ambiguous questions to which they try to give appropriate answers. Because of limitations on resources, time, and mental capability for information processing, the decision-making process involved in answering reference questions becomes bounded by the rationality of these constraints.…

  2. Standby Gasoline Rationing Plan. Contingency gasoline rationing regulations

    Energy Technology Data Exchange (ETDEWEB)

    1979-02-01

    The Economic Regulatory Administration issues final rules with respect to standby gasoline rationing. The plan is designed for and would be used only in the event of a severe gasoline shortage. The plan provides that eligibility for ration allotments will be primarily on the basis of motor vehicle registrations. DOE will mail government ration checks to the parties named in a national vehicle registration file to be maintained by DOE. Ration recipients may cash these checks for ration coupons at various designated coupon issuance points. Retail outlets and other suppliers will be required to redeem the ration coupons received in exchange for gasoline sold. Supplemental gas will be given to high-priority activities. A ration banking system will be established with two separate and distinct of ration accounts: retail outlets and other suppliers will open redemption accounts for the deposit of redeemed ration rights; and individuals or firms may open ration rights accounts, which will operate in much the same manner as monetary checking accounts. A white market will be permitted for the sale of transfer of ration rights. A percentage of the total ration rights to be issued will be reserved for distribution to the states as a State Ration Reserve, to be used by the states primarily for the relief of hardship. A National Ration Reserave will also be established. All sections of the Standby Gasoline Rationing Regulations are analyzed. (MCW)

  3. On the Cut-off Point for Combinatorial Group Testing

    DEFF Research Database (Denmark)

    Fischer, Paul; Klasner, N.; Wegener, I.

    1999-01-01

    is answered by 1 if Q contains at least one essential object and by 0 otherwise. In the statistical setting the objects are essential, independently of each other, with a given probability p combinatorial setting the number k ... group testing is equal to p* = 12(3 - 5), i.e., the strategy of testing each object individually minimizes the average number of queries iff p >= p* or n = 1. In the combinatorial setting the worst case number of queries is of interest. It has been conjectured that the cut-off point of combinatorial...

  4. Maximization of Tsallis entropy in the combinatorial formulation

    International Nuclear Information System (INIS)

    Suyari, Hiroki

    2010-01-01

    This paper presents the mathematical reformulation for maximization of Tsallis entropy S q in the combinatorial sense. More concretely, we generalize the original derivation of Maxwell-Boltzmann distribution law to Tsallis statistics by means of the corresponding generalized multinomial coefficient. Our results reveal that maximization of S 2-q under the usual expectation or S q under q-average using the escort expectation are naturally derived from the combinatorial formulations for Tsallis statistics with respective combinatorial dualities, that is, one for additive duality and the other for multiplicative duality.

  5. Nigerian Libraries

    African Journals Online (AJOL)

    Bridging the digital divide: the potential role of the National Library of Nigeria · EMAIL FULL TEXT EMAIL FULL TEXT · DOWNLOAD FULL TEXT DOWNLOAD FULL TEXT. Juliana Obiageri Akidi, Joy Chituru Onyenachi, 11-19 ...

  6. Library Locations

    Data.gov (United States)

    Allegheny County / City of Pittsburgh / Western PA Regional Data Center — Carnegie Library of Pittsburgh locations including address, coordinates, phone number, square footage, and standard operating hours. The map below does not display...

  7. academic libraries

    African Journals Online (AJOL)

    Information Impact: Journal of Information and Knowledge Management

    Information Impact: Journal of Information and Knowledge Management ... Key words: academic libraries, open access, research, researchers, technology ... European commission (2012) reports that affordable and easy access to the results ...

  8. ON 3-WAY COMBINATORIAL IDENTITIES A. K. AGARWAL MEGHA ...

    Indian Academy of Sciences (India)

    36

    ∗Corresponding author: Department of Basic and Applied Sciences, University College of Engineering,. Punjabi ... In this paper we provide combinatorial meanings to two generalized basic ... 2010 Mathematics Subject Classification. 05A15 ...

  9. Analysis and design of algorithms for combinatorial problems

    CERN Document Server

    Ausiello, G

    1985-01-01

    Combinatorial problems have been from the very beginning part of the history of mathematics. By the Sixties, the main classes of combinatorial problems had been defined. During that decade, a great number of research contributions in graph theory had been produced, which laid the foundations for most of the research in graph optimization in the following years. During the Seventies, a large number of special purpose models were developed. The impressive growth of this field since has been strongly determined by the demand of applications and influenced by the technological increases in computing power and the availability of data and software. The availability of such basic tools has led to the feasibility of the exact or well approximate solution of large scale realistic combinatorial optimization problems and has created a number of new combinatorial problems.

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

    National Research Council Canada - National Science Library

    Low, Tammy K

    2006-01-01

    .... Our research goals consisted of employing olefin metathesis in the synthesis of peptidomimetics, and studying the feasibility of this method in dynamic combinatorial chemistry and molecular imprinting of nerve agents...

  11. Novel Combinatorial Chemistry-Derived Inhibitors of Oncogenic Phosphatases

    National Research Council Canada - National Science Library

    Lazo, John

    1999-01-01

    Our overall goal of this US Army Breast Cancer Grant entitled "Novel Combinatorial Chemistry-Derived Inhibitors of Oncogenic Phosphatases" is to identity and develop novel therapeutic agents for human breast cancer...

  12. Hit discovery of 4-amino-N-(4-(3-(trifluoromethyl)phenoxy)pyrimidin-5-yl)benzamide: A novel EGFR inhibitor from a designed small library.

    Science.gov (United States)

    Elkamhawy, Ahmed; Paik, Sora; Hassan, Ahmed H E; Lee, Yong Sup; Roh, Eun Joo

    2017-12-01

    Searching for hit compounds within the huge chemical space resembles the attempt to find a needle in a haystack. Cheminformatics-guided selection of few representative molecules of a rationally designed virtual combinatorial library is a powerful tool to confront this challenge, speed up hit identification and cut off costs. Herein, this approach has been applied to identify hit compounds with novel scaffolds able to inhibit EGFR kinase. From a generated virtual library, six 4-aryloxy-5-aminopyrimidine scaffold-derived compounds were selected, synthesized and evaluated as hit EGFR inhibitors. 4-Aryloxy-5-benzamidopyrimidines inhibited EGFR with IC 50 1.05-5.37 μM. Cell-based assay of the most potent EGFR inhibitor hit (10ac) confirmed its cytotoxicity against different cancerous cells. In spite of no EGFR, HER2 or VEGFR1 inhibition was elicited by 4-aryloxy-5-(thio)ureidopyrimidine derivatives, cell-based evaluation suggested them as antiproliferative hits acting by other mechanism(s). Molecular docking study provided a plausible explanation of incapability of 4-aryloxy-5-(thio)ureidopyrimidines to inhibit EGFR and suggested a reasonable binding mode of 4-aryloxy-5-benzamidopyrimidines which provides a basis to develop more optimized ligands. Copyright © 2017 Elsevier Inc. All rights reserved.

  13. The Combinatorial Rigidity Conjecture is False for Cubic Polynomials

    DEFF Research Database (Denmark)

    Henriksen, Christian

    2003-01-01

    We show that there exist two cubic polynomials with connected Julia sets which are combinatorially equivalent but not topologically conjugate on their Julia sets. This disproves a conjecture by McMullen from 1995.......We show that there exist two cubic polynomials with connected Julia sets which are combinatorially equivalent but not topologically conjugate on their Julia sets. This disproves a conjecture by McMullen from 1995....

  14. Distributing the computation in combinatorial optimization experiments over the cloud

    OpenAIRE

    Mario Brcic; Nikica Hlupic; Nenad Katanic

    2017-01-01

    Combinatorial optimization is an area of great importance since many of the real-world problems have discrete parameters which are part of the objective function to be optimized. Development of combinatorial optimization algorithms is guided by the empirical study of the candidate ideas and their performance over a wide range of settings or scenarios to infer general conclusions. Number of scenarios can be overwhelming, especially when modeling uncertainty in some of the problem’s parameters....

  15. Enabling high performance computational science through combinatorial algorithms

    International Nuclear Information System (INIS)

    Boman, Erik G; Bozdag, Doruk; Catalyurek, Umit V; Devine, Karen D; Gebremedhin, Assefaw H; Hovland, Paul D; Pothen, Alex; Strout, Michelle Mills

    2007-01-01

    The Combinatorial Scientific Computing and Petascale Simulations (CSCAPES) Institute is developing algorithms and software for combinatorial problems that play an enabling role in scientific and engineering computations. Discrete algorithms will be increasingly critical for achieving high performance for irregular problems on petascale architectures. This paper describes recent contributions by researchers at the CSCAPES Institute in the areas of load balancing, parallel graph coloring, performance improvement, and parallel automatic differentiation

  16. On the combinatorial foundations of Regge-calculus

    International Nuclear Information System (INIS)

    Budach, L.

    1989-01-01

    Lipschitz-Killing curvatures of piecewise flat spaces are combinatorial analogues of Lipschitz-Killing curvatures of Riemannian manifolds. In the following paper rigorous combinatorial representations and proofs of all basic results for Lipschitz-Killing curvatures not using analytic arguments are given. The principal tools for an elementary representation of Regge calculus can be developed by means of basic properties of dihedral angles. (author)

  17. Immune-Stimulating Combinatorial Therapy for Prostate Cancer

    Science.gov (United States)

    2016-10-01

    Overlap: None 20 90061946 (Drake) Title: Epigenetic Drugs and Immuno Therapy for Prostate Cancer (EDIT-PC) Effort: 1.2 calendar months (10% effort...AWARD NUMBER: W81XWH-15-1-0667 TITLE: Immune-Stimulating Combinatorial Therapy for Prostate Cancer PRINCIPAL INVESTIGATOR: Robert Ivkov...Stimulating Combinatorial Therapy for Prostate Cancer 5a. CONTRACT NUMBER 5b. GRANT NUMBER W81XWH-15-1-0667 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S

  18. Enabling high performance computational science through combinatorial algorithms

    Energy Technology Data Exchange (ETDEWEB)

    Boman, Erik G [Discrete Algorithms and Math Department, Sandia National Laboratories (United States); Bozdag, Doruk [Biomedical Informatics, and Electrical and Computer Engineering, Ohio State University (United States); Catalyurek, Umit V [Biomedical Informatics, and Electrical and Computer Engineering, Ohio State University (United States); Devine, Karen D [Discrete Algorithms and Math Department, Sandia National Laboratories (United States); Gebremedhin, Assefaw H [Computer Science and Center for Computational Science, Old Dominion University (United States); Hovland, Paul D [Mathematics and Computer Science Division, Argonne National Laboratory (United States); Pothen, Alex [Computer Science and Center for Computational Science, Old Dominion University (United States); Strout, Michelle Mills [Computer Science, Colorado State University (United States)

    2007-07-15

    The Combinatorial Scientific Computing and Petascale Simulations (CSCAPES) Institute is developing algorithms and software for combinatorial problems that play an enabling role in scientific and engineering computations. Discrete algorithms will be increasingly critical for achieving high performance for irregular problems on petascale architectures. This paper describes recent contributions by researchers at the CSCAPES Institute in the areas of load balancing, parallel graph coloring, performance improvement, and parallel automatic differentiation.

  19. Combinatorial Dyson-Schwinger equations and inductive data types

    Science.gov (United States)

    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.

  20. Intrinsic information carriers in combinatorial dynamical systems

    Science.gov (United States)

    Harmer, Russ; Danos, Vincent; Feret, Jérôme; Krivine, Jean; Fontana, Walter

    2010-09-01

    Many proteins are composed of structural and chemical features—"sites" for short—characterized by definite interaction capabilities, such as noncovalent binding or covalent modification of other proteins. This modularity allows for varying degrees of independence, as the behavior of a site might be controlled by the state of some but not all sites of the ambient protein. Independence quickly generates a startling combinatorial complexity that shapes most biological networks, such as mammalian signaling systems, and effectively prevents their study in terms of kinetic equations—unless the complexity is radically trimmed. Yet, if combinatorial complexity is key to the system's behavior, eliminating it will prevent, not facilitate, understanding. A more adequate representation of a combinatorial system is provided by a graph-based framework of rewrite rules where each rule specifies only the information that an interaction mechanism depends on. Unlike reactions, which deal with molecular species, rules deal with patterns, i.e., multisets of molecular species. Although the stochastic dynamics induced by a collection of rules on a mixture of molecules can be simulated, it appears useful to capture the system's average or deterministic behavior by means of differential equations. However, expansion of the rules into kinetic equations at the level of molecular species is not only impractical, but conceptually indefensible. If rules describe bona fide patterns of interaction, molecular species are unlikely to constitute appropriate units of dynamics. Rather, we must seek aggregate variables reflective of the causal structure laid down by the rules. We call these variables "fragments" and the process of identifying them "fragmentation." Ideally, fragments are aspects of the system's microscopic population that the set of rules can actually distinguish on average; in practice, it may only be feasible to identify an approximation to this. Most importantly, fragments are

  1. Intrinsic information carriers in combinatorial dynamical systems.

    Science.gov (United States)

    Harmer, Russ; Danos, Vincent; Feret, Jérôme; Krivine, Jean; Fontana, Walter

    2010-09-01

    Many proteins are composed of structural and chemical features--"sites" for short--characterized by definite interaction capabilities, such as noncovalent binding or covalent modification of other proteins. This modularity allows for varying degrees of independence, as the behavior of a site might be controlled by the state of some but not all sites of the ambient protein. Independence quickly generates a startling combinatorial complexity that shapes most biological networks, such as mammalian signaling systems, and effectively prevents their study in terms of kinetic equations-unless the complexity is radically trimmed. Yet, if combinatorial complexity is key to the system's behavior, eliminating it will prevent, not facilitate, understanding. A more adequate representation of a combinatorial system is provided by a graph-based framework of rewrite rules where each rule specifies only the information that an interaction mechanism depends on. Unlike reactions, which deal with molecular species, rules deal with patterns, i.e., multisets of molecular species. Although the stochastic dynamics induced by a collection of rules on a mixture of molecules can be simulated, it appears useful to capture the system's average or deterministic behavior by means of differential equations. However, expansion of the rules into kinetic equations at the level of molecular species is not only impractical, but conceptually indefensible. If rules describe bona fide patterns of interaction, molecular species are unlikely to constitute appropriate units of dynamics. Rather, we must seek aggregate variables reflective of the causal structure laid down by the rules. We call these variables "fragments" and the process of identifying them "fragmentation." Ideally, fragments are aspects of the system's microscopic population that the set of rules can actually distinguish on average; in practice, it may only be feasible to identify an approximation to this. Most importantly, fragments are

  2. Consumer rationality in choice

    NARCIS (Netherlands)

    Conlon, B.J.

    2001-01-01

    The dissertation concentrates on consumer choice and the ability of current modelling approaches to capture the underlying behaviour of the individual decision-makers. The standard assumption of a rational utility maximising individual and its implications for observed behaviour are examined and

  3. Universal and Relative Rationality

    Directory of Open Access Journals (Sweden)

    Nathaniel Goldberg

    2009-01-01

    Full Text Available In this paper I illustrate how a basic kind of universal rationality can be profitably combined with undeniable instances of relativism. I do so by engaging Michael Friedman’s recent response to a challenge from Thomas Kuhn.

  4. The rational complementarity problem

    NARCIS (Netherlands)

    Heemels, W.P.M.H.; Schumacher, J.M.; Weiland, S.

    1999-01-01

    An extension of the linear complementarity problem (LCP) of mathematical programming is the so-called rational complementarity problem (RCP). This problem occurs if complementarity conditions are imposed on input and output variables of linear dynamical input/state/output systems. The resulting

  5. Rational equity bubbles

    OpenAIRE

    Zhou, Ge

    2012-01-01

    This paper discusses the existence of a bubble in the pricing of an asset that pays positive dividends. I show that rational bubbles can exist in a growing economy. The existence of bubbles depends on the relative magnitudes of risk aversion to consumption and to wealth. Furthermore, I examine how an exogenous shock in technology might trigger bubbles.

  6. Ideal Theory, Real Rationality

    DEFF Research Database (Denmark)

    Flyvbjerg, Bent

    Understanding rationality and power are key to understanding actual political and administrative behavior. Political and administrative theory that ignores this fact stand in danger of being at best irrelevant or, at worst part of the problem it whishes to solve. The paper presents Jürgen Habermas...

  7. Diagnosis, Dogmatism, and Rationality.

    Science.gov (United States)

    Rabinowitz, Jonathan; Efron, Noah J.

    1997-01-01

    Presents findings suggesting that misdiagnoses frequently stem from flaws in human information processing, particularly in collecting and using information. Claims that improved diagnostic tools will not remedy the problem. Drawing on the work of Karl Popper and Robin Collingwood, proposes operational principles to ensure a rational diagnostic…

  8. Rational Emotive Education

    Science.gov (United States)

    Knaus, William

    1977-01-01

    Rational Emotive Education--an outgrowth of theories developed by Albert Ellis--is a teaching design of mental health concepts and problem-solving activities designed to help students to approach and cope with their problems through experiential learning, via a structured, thematic sequence of emotive education lessons. (MJB)

  9. Hegel's phenomenology of rationality

    DEFF Research Database (Denmark)

    Huggler, Jørgen

    2009-01-01

    The aim of this chapter is to elucidate Hegel's conception of rationality in the Phänomenologie des Geistes (1807), and to defend the thesis that he is an author engaged in discussion with a wide variety of sources. He uses sceptical reasoning to form a line of argument with a necessary progression...

  10. Combinatorial discovery of new methanol-tolerant non-noble metal cathode electrocatalysts for direct methanol fuel cells.

    Science.gov (United States)

    Yu, Jong-Sung; Kim, Min-Sik; Kim, Jung Ho

    2010-12-14

    Combinatorial synthesis and screening were used to identify methanol-tolerant non-platinum cathode electrocatalysts for use in direct methanol fuel cells (DMFCs). Oxygen reduction consumes protons at the surface of DMFC cathode catalysts. In combinatorial screening, this pH change allows one to differentiate active catalysts using fluorescent acid-base indicators. Combinatorial libraries of carbon-supported catalyst compositions containing Ru, Mo, W, Sn, and Se were screened. Ternary and quaternary compositions containing Ru, Sn, Mo, Se were more active than the "standard" Alonso-Vante catalyst, Ru(3)Mo(0.08)Se(2), when tested in liquid-feed DMFCs. Physical characterization of the most active catalysts by powder X-ray diffraction, gas adsorption, and X-ray photoelectron spectroscopy revealed that the predominant crystalline phase was hexagonal close-packed (hcp) ruthenium, and showed a surface mostly covered with oxide. The best new catalyst, Ru(7.0)Sn(1.0)Se(1.0), was significantly more active than Ru(3)Se(2)Mo(0.08), even though the latter contained smaller particles.

  11. Utilizing pulsed laser deposition lateral inhomogeneity as a tool in combinatorial material science.

    Science.gov (United States)

    Keller, David A; Ginsburg, Adam; Barad, Hannah-Noa; Shimanovich, Klimentiy; Bouhadana, Yaniv; Rosh-Hodesh, Eli; Takeuchi, Ichiro; Aviv, Hagit; Tischler, Yaakov R; Anderson, Assaf Y; Zaban, Arie

    2015-04-13

    Pulsed laser deposition (PLD) is widely used in combinatorial material science, as it enables rapid fabrication of different composite materials. Nevertheless, this method was usually limited to small substrates, since PLD deposition on large substrate areas results in severe lateral inhomogeneity. A few technical solutions for this problem have been suggested, including the use of different designs of masks, which were meant to prevent inhomogeneity in the thickness, density, and oxidation state of a layer, while only the composition is allowed to be changed. In this study, a possible way to take advantage of the large scale deposition inhomogeneity is demonstrated, choosing an iron oxide PLD-deposited library with continuous compositional spread (CCS) as a model system. An Fe₂O₃-Nb₂O₅ library was fabricated using PLD, without any mask between the targets and the substrate. The library was measured using high-throughput scanners for electrical, structural, and optical properties. A decrease in electrical resistivity that is several orders of magnitude lower than pure α-Fe₂O₃ was achieved at ∼20% Nb-O (measured at 47 and 267 °C) but only at points that are distanced from the center of the PLD plasma plume. Using hierarchical clustering analysis, we show that the PLD inhomogeneity can be used as an additional degree of freedom, helping, in this case, to achieve iron oxide with much lower resistivity.

  12. A combinatorial approach to angiosperm pollen morphology.

    Science.gov (United States)

    Mander, Luke

    2016-11-30

    Angiosperms (flowering plants) are strikingly diverse. This is clearly expressed in the morphology of their pollen grains, which are characterized by enormous variety in their shape and patterning. In this paper, I approach angiosperm pollen morphology from the perspective of enumerative combinatorics. This involves generating angiosperm pollen morphotypes by algorithmically combining character states and enumerating the results of these combinations. I use this approach to generate 3 643 200 pollen morphotypes, which I visualize using a parallel-coordinates plot. This represents a raw morphospace. To compare real-world and theoretical morphologies, I map the pollen of 1008 species of Neotropical angiosperms growing on Barro Colorado Island (BCI), Panama, onto this raw morphospace. This highlights that, in addition to their well-documented taxonomic diversity, Neotropical rainforests also represent an enormous reservoir of morphological diversity. Angiosperm pollen morphospace at BCI has been filled mostly by pollen morphotypes that are unique to single plant species. Repetition of pollen morphotypes among higher taxa at BCI reflects both constraint and convergence. This combinatorial approach to morphology addresses the complexity that results from large numbers of discrete character combinations and could be employed in any situation where organismal form can be captured by discrete morphological characters. © 2016 The Author(s).

  13. Exact combinatorial approach to finite coagulating systems

    Science.gov (United States)

    Fronczak, Agata; Chmiel, Anna; Fronczak, Piotr

    2018-02-01

    This paper outlines an exact combinatorial approach to finite coagulating systems. In this approach, cluster sizes and time are discrete and the binary aggregation alone governs the time evolution of the systems. By considering the growth histories of all possible clusters, an exact expression is derived for the probability of a coagulating system with an arbitrary kernel being found in a given cluster configuration when monodisperse initial conditions are applied. Then this probability is used to calculate the time-dependent distribution for the number of clusters of a given size, the average number of such clusters, and that average's standard deviation. The correctness of our general expressions is proved based on the (analytical and numerical) results obtained for systems with the constant kernel. In addition, the results obtained are compared with the results arising from the solutions to the mean-field Smoluchowski coagulation equation, indicating its weak points. The paper closes with a brief discussion on the extensibility to other systems of the approach presented herein, emphasizing the issue of arbitrary initial conditions.

  14. Scalable Combinatorial Tools for Health Disparities Research

    Directory of Open Access Journals (Sweden)

    Michael A. Langston

    2014-10-01

    Full Text Available 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.

  15. Combinatorial effects of odorants on mouse behavior

    Science.gov (United States)

    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

  16. The library

    International Nuclear Information System (INIS)

    1980-01-01

    A specialized library is essential for conducting the research work of the Uranium Institute. The need was recognized at the foundation of the Institute and a full-time librarian was employed in 1976 to establish the necessary systems and begin the task of building up the collection. A brief description is given of the services offered by the library which now contains books, periodicals, pamphlets and press cuttings, focussed on uranium and nuclear energy, but embracing economics, politics, trade, legislation, geology, mining and mineral processing, environmental protection and nuclear technology. (author)

  17. Capital Requirements and Credit Rationing

    OpenAIRE

    Itai Agur

    2010-01-01

    This paper analyzes the trade-off between financial stability and credit rationing that arises when increasing capital requirements. It extends the Stiglitz-Weiss model of credit rationing to allow for bank default. Bank capital structure then matters for lending incentives. With default and rationing endogenous, optimal capital requirements can be analyzed. Introducing bank financiers, the paper also shows that uninsured funding raises the sensitivity of rationing to capital requirements. In...

  18. Libraries on the MOVE.

    Science.gov (United States)

    Edgar, Jim; And Others

    1986-01-01

    Presents papers from Illinois State Library and Shawnee Library System's "Libraries on the MOVE" conference focusing on how libraries can impact economic/cultural climate of an area. Topics addressed included information services of rural libraries; marketing; rural library development; library law; information access; interagency…

  19. Personal Virtual Libraries

    Science.gov (United States)

    Pappas, Marjorie L.

    2004-01-01

    Virtual libraries are becoming more and more common. Most states have a virtual library. A growing number of public libraries have a virtual presence on the Web. Virtual libraries are a growing addition to school library media collections. The next logical step would be personal virtual libraries. A personal virtual library (PVL) is a collection…

  20. America's Star Libraries

    Science.gov (United States)

    Lyons, Ray; Lance, Keith Curry

    2009-01-01

    "Library Journal"'s new national rating of public libraries, the "LJ" Index of Public Library Service, identifies 256 "star" libraries. It rates 7,115 public libraries. The top libraries in each group get five, four, or three Michelin guide-like stars. All included libraries, stars or not, can use their scores to learn from their peers and improve…

  1. Computational design of auxotrophy-dependent microbial biosensors for combinatorial metabolic engineering experiments.

    Science.gov (United States)

    Tepper, Naama; Shlomi, Tomer

    2011-01-21

    Combinatorial approaches in metabolic engineering work by generating genetic diversity in a microbial population followed by screening for strains with improved phenotypes. One of the most common goals in this field is the generation of a high rate chemical producing strain. A major hurdle with this approach is that many chemicals do not have easy to recognize attributes, making their screening expensive and time consuming. To address this problem, it was previously suggested to use microbial biosensors to facilitate the detection and quantification of chemicals of interest. Here, we present novel computational methods to: (i) rationally design microbial biosensors for chemicals of interest based on substrate auxotrophy that would enable their high-throughput screening; (ii) predict engineering strategies for coupling the synthesis of a chemical of interest with the production of a proxy metabolite for which high-throughput screening is possible via a designed bio-sensor. The biosensor design method is validated based on known genetic modifications in an array of E. coli strains auxotrophic to various amino-acids. Predicted chemical production rates achievable via the biosensor-based approach are shown to potentially improve upon those predicted by current rational strain design approaches. (A Matlab implementation of the biosensor design method is available via http://www.cs.technion.ac.il/~tomersh/tools).

  2. Rationality and ritual

    International Nuclear Information System (INIS)

    Wynne, B.

    1982-01-01

    The book concerns the Windscale Public Inquiry, held to investigate the application by British Nuclear Fuels to build a 1200 tonne per year thermal oxide reprocessing plant (THORP) for spent nuclear fuels from Britain and overseas. The subject is discussed under the headings: introduction (international dimensions; the Windscale Inquiry; conflict resolution and social drama; public debate and the sociology of knowledge); the decision-making legacy; oxide reprocessing - the background; the public inquiry tradition - a comparative perspective; the emergence of THORP from a private to a public issue (local and national planning politics); the process and impact of the Inquiry (opposition groups); judicial rationality, expert conflict, and political authority); the rationality and politics of analysis (proliferation; radiation risks; relative risks; the Ravenglass issue; discharge targets; general radiation protection arrangements); conclusion. (U.K.)

  3. Rational management of epilepsy.

    Science.gov (United States)

    Viswanathan, Venkataraman

    2014-09-01

    Management of epilepsies in children has improved considerably over the last decade, all over the world due to the advances seen in the understanding of the patho-physiology of epileptogenesis, availability of both structural and functional imaging studies along with better quality EEG/video-EEG recordings and the availability of a plethora of newer anti-epileptic drugs which are tailormade to act on specific pathways. In spite of this, there is still a long way to go before one is able to be absolutely rational about which drug to use for which type of epilepsy. There have been a lot of advances in the area of epilepsy surgery and is certainly gaining ground for specific cases. Better understanding of the genetic basis of epilepsies will hopefully lead to a more rational treatment plan in the future. Also, a lot of work needs to be done to dispel various misunderstandings and myths about epilepsy which still exists in our country.

  4. Multivariate rational data fitting

    Science.gov (United States)

    Cuyt, Annie; Verdonk, Brigitte

    1992-12-01

    Sections 1 and 2 discuss the advantages of an object-oriented implementation combined with higher floating-point arithmetic, of the algorithms available for multivariate data fitting using rational functions. Section 1 will in particular explain what we mean by "higher arithmetic". Section 2 will concentrate on the concepts of "object orientation". In sections 3 and 4 we shall describe the generality of the data structure that can be dealt with: due to some new results virtually every data set is acceptable right now, with possible coalescence of coordinates or points. In order to solve the multivariate rational interpolation problem the data sets are fed to different algorithms depending on the structure of the interpolation points in then-variate space.

  5. Models for Rational Number Bases

    Science.gov (United States)

    Pedersen, Jean J.; Armbruster, Frank O.

    1975-01-01

    This article extends number bases to negative integers, then to positive rationals and finally to negative rationals. Methods and rules for operations in positive and negative rational bases greater than one or less than negative one are summarized in tables. Sample problems are explained and illustrated. (KM)

  6. Rational Unified Process

    OpenAIRE

    Kopal, Nils

    2016-01-01

    In this German seminar paper, which was written in the year 2011 at the University of Duisburg for a Bachelor Colloquium in Applied computer science, we show a brief overview of the Rational Unified Process (RUP). Thus, interested students or generally interested people in software development gain a first impression of RUP. The paper includes a survey and overview of the underlying process structure, the phases of the process, its workflows, and describes the always by the RUP developers pos...

  7. Maps of Bounded Rationality

    OpenAIRE

    Kahneman, Daniel

    2002-01-01

    The work cited by the Nobel committee was done jointly with the late Amos Tversky (1937-1996) during a long and unusually close collaboration. Together, we explored the psychology of intuitive beliefs and choices and examined their bounded rationality. This essay presents a current perspective on the three major topics of our joint work: heuristics of judgment, risky choice, and framing effects. In all three domains we studied intuitions - thoughts and preferences that come to mind quickly an...

  8. Emotional Theory of Rationality

    OpenAIRE

    Garcés, Mario; Finkel, Lucila

    2011-01-01

    In recent decades, it has been definitely established the existence of a close relationship between the emotional phenomena and rational processes, but we still do not have a unified definition, or effective models to describe any of them well. To advance our understanding of the mechanisms governing the behavior of living beings we must integrate multiple theories, experiments and models from both fields. In this paper we propose a new theoretical framework that allows integrating and unders...

  9. On hereditarily rational functions

    OpenAIRE

    Nowak, Krzysztof Jan

    2012-01-01

    In this paper, we give a short proof of a theorem by Koll\\'{a}r on hereditarily rational functions. This is an answer to his appeal to find an elementary proof which does not rely so much on resolution of singularities. Our approach does not make use of desingularization techniques. Instead, we apply a stronger version of the \\L{}ojasiewicz inequality. Moreover, this allows us to sharpen Koll\\'{a}r's theorem.

  10. Probability and rational choice

    Directory of Open Access Journals (Sweden)

    David Botting

    2014-05-01

    Full Text Available http://dx.doi.org/10.5007/1808-1711.2014v18n1p1 In this paper I will discuss the rationality of reasoning about the future. There are two things that we might like to know about the future: which hypotheses are true and what will happen next. To put it in philosophical language, I aim to show that there are methods by which inferring to a generalization (selecting a hypothesis and inferring to the next instance (singular predictive inference can be shown to be normative and the method itself shown to be rational, where this is due in part to being based on evidence (although not in the same way and in part on a prior rational choice. I will also argue that these two inferences have been confused, being distinct not only conceptually (as nobody disputes but also in their results (the value given to the probability of the hypothesis being not in general that given to the next instance and that methods that are adequate for one are not by themselves adequate for the other. A number of debates over method founder on this confusion and do not show what the debaters think they show.

  11. Physical interpretation of the combinatorial hierarchy

    International Nuclear Information System (INIS)

    Bastin, T.; Noyes, H.P.

    1978-01-01

    The combinatorial hierarchy model for base particle processes is compared and contrasted with the Ur-theory as developed at the Tutzing Conferences. It agrees with Ur-theory about a finite basis, the ''fixed past--uncertain future'' aspects of physics, and the necessity of dropping Bohr's requirement of reduction to the haptic language of commonsense and classical physics. However, it retains a constructive, hierarchial approach with can yield only an approximate and discrete ''space time'', and introduces the observation metaphysic at the start. Concrete interpretation of the four levels of the hierarchy (with cardinals 3, 7, 127, 2 127 -1 approx. =10 38 ) associates the three levels which map up and down with three absolute conservation laws (charge, baryon number, lepton number) and the spin dichotomy. The first level represents +, -, and +- unit charge. The second has the quantum nubmers of a baryon--antibaryon pair and associated charged meson (e.g., n anti n, p anti n, p anti p, n anti p, π + , π 0 , π - ). The third level associates this pair, now including four spin states as well as four charge states, with a neutral lepton--antilepton pair (e anti e or ν anti ν) in four spin states (total, 64 states): three charged spinless, three charged spin-1, and neutral spin-1 mesons (15 states), and a neutral vector boson associated with the leptons; this gives 3 + 15 + 3 x 15 = 63 possible boson states, so a total correct count of 63 + 64 = 127 states. Something like SU 2 X SU 3 and other indications of quark quantum numbers can occur as substructures at the fourth (unstable) level. A slight extension gives the usual static approximation to the building energy of the hydrogen atom, α 2 m/sub e/c 2 . Cosmological implications of the theory are in accord with current experience. A beginning in the physical interpretation of a theory which could eventually encompass all branches of physics was made. 3 figures, 6 tables

  12. Combinatorial explosion in model gene networks

    Science.gov (United States)

    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. Morphological Constraints on Cerebellar Granule Cell Combinatorial Diversity.

    Science.gov (United States)

    Gilmer, Jesse I; Person, Abigail L

    2017-12-13

    Combinatorial expansion by the cerebellar granule cell layer (GCL) is fundamental to theories of cerebellar contributions to motor control and learning. Granule cells (GrCs) sample approximately four mossy fiber inputs and are thought to form a combinatorial code useful for pattern separation and learning. We constructed a spatially realistic model of the cerebellar GCL and examined how GCL architecture contributes to GrC combinatorial diversity. We found that GrC combinatorial diversity saturates quickly as mossy fiber input diversity increases, and that this saturation is in part a consequence of short dendrites, which limit access to diverse inputs and favor dense sampling of local inputs. This local sampling also produced GrCs that were combinatorially redundant, even when input diversity was extremely high. In addition, we found that mossy fiber clustering, which is a common anatomical pattern, also led to increased redundancy of GrC input combinations. We related this redundancy to hypothesized roles of temporal expansion of GrC information encoding in service of learned timing, and we show that GCL architecture produces GrC populations that support both temporal and combinatorial expansion. Finally, we used novel anatomical measurements from mice of either sex to inform modeling of sparse and filopodia-bearing mossy fibers, finding that these circuit features uniquely contribute to enhancing GrC diversification and redundancy. Our results complement information theoretic studies of granule layer structure and provide insight into the contributions of granule layer anatomical features to afferent mixing. SIGNIFICANCE STATEMENT Cerebellar granule cells are among the simplest neurons, with tiny somata and, on average, just four dendrites. These characteristics, along with their dense organization, inspired influential theoretical work on the granule cell layer as a combinatorial expander, where each granule cell represents a unique combination of inputs

  14. The priming of basic combinatory responses in MEG.

    Science.gov (United States)

    Blanco-Elorrieta, Esti; Ferreira, Victor S; Del Prato, Paul; Pylkkänen, Liina

    2018-01-01

    Priming has been a powerful tool for the study of human memory and especially the memory representations relevant for language. However, although it is well established that lexical access can be primed, we do not know exactly what types of computations can be primed above the word level. This work took a neurobiological approach and assessed the ways in which the complex representation of a minimal combinatory phrase, such as red boat, can be primed, as evidenced by the spatiotemporal profiles of magnetoencephalography (MEG) signals. Specifically, we built upon recent progress on the neural signatures of phrasal composition and tested whether the brain activities implicated for the basic combination of two words could be primed. In two experiments, MEG was recorded during a picture naming task where the prime trials were designed to replicate previously reported combinatory effects and the target trials to test whether those combinatory effects could be primed. The manipulation of the primes was successful in eliciting larger activity for adjective-noun combinations than single nouns in left anterior temporal and ventromedial prefrontal cortices, replicating prior MEG studies on parallel contrasts. Priming of similarly timed activity was observed during target trials in anterior temporal cortex, but only when the prime and target shared an adjective. No priming in temporal cortex was observed for single word repetition and two control tasks showed that the priming effect was not elicited if the prime pictures were simply viewed but not named. In sum, this work provides evidence that very basic combinatory operations can be primed, with the necessity for some lexical overlap between prime and target suggesting combinatory conceptual, as opposed to syntactic processing. Both our combinatory and priming effects were early, onsetting between 100 and 150ms after picture onset and thus are likely to reflect the very earliest planning stages of a combinatory message

  15. Library Automation.

    Science.gov (United States)

    Husby, Ole

    1990-01-01

    The challenges and potential benefits of automating university libraries are reviewed, with special attention given to cooperative systems. Aspects discussed include database size, the role of the university computer center, storage modes, multi-institutional systems, resource sharing, cooperative system management, networking, and intelligent…

  16. MARKETING LIBRARY SERVICES IN ACADEMIC LIBRARIES: A ...

    African Journals Online (AJOL)

    MARKETING LIBRARY SERVICES IN ACADEMIC LIBRARIES: A TOOL FOR SURVIVAL IN THE ... This article discusses the concept of marketing library and information services as an ... EMAIL FREE FULL TEXT EMAIL FREE FULL TEXT

  17. DNA-encoded chemical libraries - achievements and remaining challenges.

    Science.gov (United States)

    Favalli, Nicholas; Bassi, Gabriele; Scheuermann, Jörg; Neri, Dario

    2018-04-23

    DNA-encoded chemical libraries (DECLs) are collections of compounds, individually coupled to DNA tags serving as amplifiable identification barcodes. Since individual compounds can be identified by the associated DNA tag, they can be stored as a mixture, allowing the synthesis and screening of combinatorial libraries of unprecedented size, facilitated by the implementation of split-and-pool synthetic procedures or other experimental methodologies. In this review, we briefly present relevant concepts and technologies, which are required for the implementation and interpretation of screening procedures with DNA-encoded chemical libraries. Moreover, we illustrate some success stories, detailing how novel ligands were discovered from encoded libraries. Finally, we critically review what can realistically be achieved with the technology at the present time, highlighting challenges and opportunities for the future. © 2018 Federation of European Biochemical Societies.

  18. Summation on the basis of combinatorial representation of equal powers

    Directory of Open Access Journals (Sweden)

    Alexander I. Nikonov

    2016-03-01

    Full Text Available In the paper the conclusion of combinatorial expressions for the sums of members of several sequences is considered. Conclusion is made on the basis of combinatorial representation of the sum of the weighted equal powers. The weighted members of a geometrical progression, the simple arithmetic-geometrical and combined progressions are subject to summation. One of principal places in the given conclusion occupies representation of members of each of the specified progressions in the form of matrix elements. The row of this matrix is formed with use of a gang of equal powers with the set weight factor. Besides, in work formulas of combinatorial identities with participation of free components of the sums of equal powers, and also separate power-member of sequence of equal powers or a geometrical progression are presented. All presented formulas have the general basis-components of the sums of equal powers.

  19. Combinatorial vector fields and the valley structure of fitness landscapes.

    Science.gov (United States)

    Stadler, Bärbel M R; Stadler, Peter F

    2010-12-01

    Adaptive (downhill) walks are a computationally convenient way of analyzing the geometric structure of fitness landscapes. Their inherently stochastic nature has limited their mathematical analysis, however. Here we develop a framework that interprets adaptive walks as deterministic trajectories in combinatorial vector fields and in return associate these combinatorial vector fields with weights that measure their steepness across the landscape. We show that the combinatorial vector fields and their weights have a product structure that is governed by the neutrality of the landscape. This product structure makes practical computations feasible. The framework presented here also provides an alternative, and mathematically more convenient, way of defining notions of valleys, saddle points, and barriers in landscape. As an application, we propose a refined approximation for transition rates between macrostates that are associated with the valleys of the landscape.

  20. Recent advances in combinatorial biosynthesis for drug discovery

    Directory of Open Access Journals (Sweden)

    Sun H

    2015-02-01

    Full Text Available Huihua Sun,1,* Zihe Liu,1,* Huimin Zhao,1,2 Ee Lui Ang1 1Metabolic Engineering Research Laboratory, Institute of Chemical and Engineering Sciences, Agency for Science, Technology and Research, Singapore; 2Department of Chemical and Biomolecular Engineering, University of Illinois at Urbana-Champaign, Urbana, IL, USA *These authors contributed equally to this work Abstract: 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

  1. Library news

    CERN Multimedia

    CERN Library

    2010-01-01

    The CERN Library has been providing electronic access to the "Techniques de l'Ingénieur" database for the past 8 months. As a reminder, this is a multidisciplinary database of over 4000 technical and scientific articles in French, covering a broad range of topics such as mechanical engineering, safety, electronics and the environment. In a few simple steps, you can create your own account, select the types of documents you are interested in and configure your settings so as to receive alerts when articles in your field of activity are published. You can now access this resource from outside CERN using the "remote access to electronic resources" service. Further information is available here. Direct access to the database. Remote access to electronic resources. If you have any questions or comments, don't hesitate to contact us at: library.desk@cern.ch.

  2. Are security analysts rational? a literature review

    OpenAIRE

    Peixinho, Rúben; Coelho, Luís; Taffler, Richard J.

    2005-01-01

    Rational choice theory and bounded rationality constitute the basis for the discussion in several areas regarding human rationality. In finance, this discussion has been made between traditional finance and behavioural finance approach, which have different perspectives concerning market agents’ rationality. This paper reviews several studies addressing rationality among security analysts. The analysis shows that analysts’systematic optimism seems to be inconsistent with rationality....

  3. Combinatorial methods for advanced materials research and development

    Energy Technology Data Exchange (ETDEWEB)

    Cremer, R.; Dondorf, S.; Hauck, M.; Horbach, D.; Kaiser, M.; Krysta, S.; Kyrylov, O.; Muenstermann, E.; Philipps, M.; Reichert, K.; Strauch, G. [Rheinisch-Westfaelische Technische Hochschule Aachen (Germany). Lehrstuhl fuer Theoretische Huettenkunde

    2001-10-01

    The applicability of combinatorial methods in developing advanced materials is illustrated presenting four examples for the deposition and characterization of one- and two-dimensionally laterally graded coatings, which were deposited by means of (reactive) magnetron sputtering and plasma-enhanced chemical vapor deposition. To emphasize the advantages of combinatorial approaches, metastable hard coatings like (Ti,Al)N and (Ti,Al,Hf)N respectively, as well as Ge-Sb-Te based films for rewritable optical data storage were investigated with respect to the relations between structure, composition, and the desired materials properties. (orig.)

  4. Combinatorial algebraic geometry selected papers from the 2016 apprenticeship program

    CERN Document Server

    Sturmfels, Bernd

    2017-01-01

    This volume consolidates selected articles from the 2016 Apprenticeship Program at the Fields Institute, part of the larger program on Combinatorial Algebraic Geometry that ran from July through December of 2016. Written primarily by junior mathematicians, the articles cover a range of topics in combinatorial algebraic geometry including curves, surfaces, Grassmannians, convexity, abelian varieties, and moduli spaces. This book bridges the gap between graduate courses and cutting-edge research by connecting historical sources, computation, explicit examples, and new results.

  5. Combinatorial reasoning an introduction to the art of counting

    CERN Document Server

    DeTemple, Duane

    2014-01-01

    Written by well-known scholars in the field, this book introduces combinatorics alongside modern techniques, showcases the interdisciplinary aspects of the topic, and illustrates how to problem solve with a multitude of exercises throughout. The authors' approach is very reader-friendly and avoids the ""scholarly tone"" found in many books on this topic. Combinatorial Reasoning: An Introduction to the Art of Counting: Focuses on enumeration and combinatorial thinking as a way to develop a variety of effective approaches to solving counting problemsIncludes brief summaries of basic concepts f

  6. Mitigation of Control Channel Jamming via Combinatorial Key Distribution

    Science.gov (United States)

    Falahati, Abolfazl; Azarafrooz, Mahdi

    The problem of countering control channel jamming against internal adversaries in wireless ad hoc networks is addressed. Using combinatorial key distribution, a new method to secure the control channel access is introduced. This method, utilizes the established keys in the key establishment phase to hide the location of control channels without the need for a secure BS. This is in obtained by combination of a collision free one-way function and a combinatorial key establishment method. The proposed scheme can be considered as a special case of the ALOHA random access schemes which uses the common established keys as its seeds to generate the pattern of transmission.

  7. Polyhedral and semidefinite programming methods in combinatorial optimization

    CERN Document Server

    Tunçel, Levent

    2010-01-01

    Since the early 1960s, polyhedral methods have played a central role in both the theory and practice of combinatorial optimization. Since the early 1990s, a new technique, semidefinite programming, has been increasingly applied to some combinatorial optimization problems. The semidefinite programming problem is the problem of optimizing a linear function of matrix variables, subject to finitely many linear inequalities and the positive semidefiniteness condition on some of the matrix variables. On certain problems, such as maximum cut, maximum satisfiability, maximum stable set and geometric r

  8. Some results from the combinatorial approach to quantum logic

    International Nuclear Information System (INIS)

    Greechie, R.J.

    1976-01-01

    The combinatorial approach to quantum logic focuses on certain interconnections between graphs, combinatorial designs, and convex sets as applied to a quantum logic. This article is concerned only with orthomodular lattices and associated structures. A class of complete atomic irreducible semimodular orthomodular lattices is derived which may not be represented as linear subspaces of a vector space over a division ring. Each of these lattices is a proposition system of dimension three. These proposition systems form orthocomplemented non-Desarguesian projective geometries. (B.R.H.)

  9. Markov's theorem and algorithmically non-recognizable combinatorial manifolds

    International Nuclear Information System (INIS)

    Shtan'ko, M A

    2004-01-01

    We prove the theorem of Markov on the existence of an algorithmically non-recognizable combinatorial n-dimensional manifold for every n≥4. We construct for the first time a concrete manifold which is algorithmically non-recognizable. A strengthened form of Markov's theorem is proved using the combinatorial methods of regular neighbourhoods and handle theory. The proofs coincide for all n≥4. We use Borisov's group with insoluble word problem. It has two generators and twelve relations. The use of this group forms the base for proving the strengthened form of Markov's theorem

  10. On some interconnections between combinatorial optimization and extremal graph theory

    Directory of Open Access Journals (Sweden)

    Cvetković Dragoš M.

    2004-01-01

    Full Text Available The uniting feature of combinatorial optimization and extremal graph theory is that in both areas one should find extrema of a function defined in most cases on a finite set. While in combinatorial optimization the point is in developing efficient algorithms and heuristics for solving specified types of problems, the extremal graph theory deals with finding bounds for various graph invariants under some constraints and with constructing extremal graphs. We analyze by examples some interconnections and interactions of the two theories and propose some conclusions.

  11. Library Benchmarking

    Directory of Open Access Journals (Sweden)

    Wiji Suwarno

    2017-02-01

    Full Text Available The term benchmarking has been encountered in the implementation of total quality (TQM or in Indonesian termed holistic quality management because benchmarking is a tool to look for ideas or learn from the library. Benchmarking is a processof measuring and comparing for continuous business process of systematic and continuous measurement, the process of measuring and comparing for continuous business process of an organization to get information that can help these organization improve their performance efforts.

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

    Science.gov (United States)

    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.

  13. 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.

    Science.gov (United States)

    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.

  14. We are planning a library

    Directory of Open Access Journals (Sweden)

    Silva Novljan

    2000-01-01

    Full Text Available The article presents the procedures for planning a library, which must fulfil its mission: to enable free access to information, education and culture for everyone at any tirne. The aim of the described procedure is to test the usefulness and appropriateness of professional recommendations for planning, in order to support rational organisation for a maximal effect. A planning model is being set up which would enable the procedures to be repeated and verified on other local communities. It was developed on the basis of a performed analysis of a situation and a chosen case from that situation: a local self-governing community which already has, according to the recommen¬dations of the standards, the necessary conditions to establish a library.

  15. Combinatorial effect of maytansinol and radiation in Drosophila and human cancer cells

    Directory of Open Access Journals (Sweden)

    Anthony Edwards

    2011-07-01

    Combination therapy, in which two or more agents are applied, is more effective than single therapies for combating cancer. For this reason, combinations of chemotherapy with radiation are being explored in clinical trials, albeit with an empirical approach. We developed a screen to identify, from the onset, molecules that act in vivo in conjunction with radiation, using Drosophila as a model. Screens through two small molecule libraries from the NCI Developmental Therapeutics Program yielded microtubule poisons; this class of agents is known to enhance the effect of radiation in mammalian cancer models. Here we report an analysis of one microtubule depolymerizing agent, maytansinol isobutyrate (NSC292222; maytansinol, in Drosophila and in human cancer cells. We find that the effect of maytansinol is p53 dependent in Drosophila cells and human cancer cells, that maytansinol enhances the effect of radiation in both systems, and that the combinatorial effect of drug and radiation is additive. We also uncover a differential sensitivity to maytansinol between Drosophila cells and Drosophila larvae, which illustrates the value of studying cell behavior in the context of a whole organism. On the basis of these results, we propose that Drosophila might be a useful model for unbiased screens through new molecule libraries to find cancer drugs for combination therapy.

  16. Data Mining and Machine Learning Tools for Combinatorial Material Science of All-Oxide Photovoltaic Cells.

    Science.gov (United States)

    Yosipof, Abraham; Nahum, Oren E; Anderson, Assaf Y; Barad, Hannah-Noa; Zaban, Arie; Senderowitz, Hanoch

    2015-06-01

    Growth in energy demands, coupled with the need for clean energy, are likely to make solar cells an important part of future energy resources. In particular, cells entirely made of metal oxides (MOs) have the potential to provide clean and affordable energy if their power conversion efficiencies are improved. Such improvements require the development of new MOs which could benefit from combining combinatorial material sciences for producing solar cells libraries with data mining tools to direct synthesis efforts. In this work we developed a data mining workflow and applied it to the analysis of two recently reported solar cell libraries based on Titanium and Copper oxides. Our results demonstrate that QSAR models with good prediction statistics for multiple solar cells properties could be developed and that these models highlight important factors affecting these properties in accord with experimental findings. The resulting models are therefore suitable for designing better solar cells. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  17. Expediting Combinatorial Data Set Analysis by Combining Human and Algorithmic Analysis.

    Science.gov (United States)

    Stein, Helge Sören; Jiao, Sally; Ludwig, Alfred

    2017-01-09

    A challenge in combinatorial materials science remains the efficient analysis of X-ray diffraction (XRD) data and its correlation to functional properties. Rapid identification of phase-regions and proper assignment of corresponding crystal structures is necessary to keep pace with the improved methods for synthesizing and characterizing materials libraries. Therefore, a new modular software called htAx (high-throughput analysis of X-ray and functional properties data) is presented that couples human intelligence tasks used for "ground-truth" phase-region identification with subsequent unbiased verification by an algorithm to efficiently analyze which phases are present in a materials library. Identified phases and phase-regions may then be correlated to functional properties in an expedited manner. For the functionality of htAx to be proven, two previously published XRD benchmark data sets of the materials systems Al-Cr-Fe-O and Ni-Ti-Cu are analyzed by htAx. The analysis of ∼1000 XRD patterns takes less than 1 day with htAx. The proposed method reliably identifies phase-region boundaries and robustly identifies multiphase structures. The method also addresses the problem of identifying regions with previously unpublished crystal structures using a special daisy ternary plot.

  18. Dynamic Combinatorial Chemistry with Diselenides, Disulfides, Imines and Metal Coordination

    DEFF Research Database (Denmark)

    Sørensen, Anne

    combinatorial chemistry, namely the reversible diselenide exchange reaction. The first part of the thesis describes the development of a thermally induced OAr → SeAr migration reaction. Here, it was proven possible to rearrange a variety of substituted O-aryl selenocarbamates into the corresponding Se...

  19. Dynamic combinatorial chemistry at the phospholipid bilayer interface

    NARCIS (Netherlands)

    Mansfeld, Friederike M.; Au-Yeung, Ho Yu; Sanders, Jeremy K.M.; Otto, Sijbren

    2010-01-01

    Background: Molecular recognition at the environment provided by the phospholipid bilayer interface plays an important role in biology and is subject of intense investigation. Dynamic combinatorial chemistry is a powerful approach for exploring molecular recognition, but has thus far not been

  20. Confluence of an extension of combinatory logic by Boolean constants

    DEFF Research Database (Denmark)

    Czajka, Łukasz

    2017-01-01

    We show confluence of a conditional term rewriting system CL-pc1, which is an extension of Combinatory Logic by Boolean constants. This solves problem 15 from the RTA list of open problems. The proof has been fully formalized in the Coq proof assistant....

  1. Combinatorial algorithms enabling computational science: tales from the front

    International Nuclear Information System (INIS)

    Bhowmick, Sanjukta; Boman, Erik G; Devine, Karen; Gebremedhin, Assefaw; Hendrickson, Bruce; Hovland, Paul; Munson, Todd; Pothen, Alex

    2006-01-01

    Combinatorial algorithms have long played a crucial enabling role in scientific and engineering computations. The importance of discrete algorithms continues to grow with the demands of new applications and advanced architectures. This paper surveys some recent developments in this rapidly changing and highly interdisciplinary field

  2. Combinatorial structures and processing in neural blackboard architectures

    NARCIS (Netherlands)

    van der Velde, Frank; van der Velde, Frank; de Kamps, Marc; Besold, Tarek R.; d'Avila Garcez, Artur; Marcus, Gary F.; Miikkulainen, Risto

    2015-01-01

    We discuss and illustrate Neural Blackboard Architectures (NBAs) as the basis for variable binding and combinatorial processing the brain. We focus on the NBA for sentence structure. NBAs are based on the notion that conceptual representations are in situ, hence cannot be copied or transported.

  3. Combinatorial chemistry approach to development of molecular plastic solar cells

    NARCIS (Netherlands)

    Godovsky, Dmitri; Inganäs, Olle; Brabec, Christoph J.; Sariciftci, N. Serdar; Hummelen, Jan C.; Janssen, Rene A.J.; Prato, M.; Maggini, M.; Segura, Jose; Martin, Nazario

    1999-01-01

    We used a combinatorial chemistry approach to develop the molecular plastic solar cells based on soluble fullerene derivatives or solubilized TCNQ molecules in combination with conjugated polymers. Profiles, formed by the diffusion of low molecular weight component in the spin-cast polymer host were

  4. Anti-termite efficacy of Capparis decidua and its combinatorial ...

    African Journals Online (AJOL)

    Michael Horsfall

    ABSTRACT: Capparis deciduas and its combinatorial mixtures were evaluated to observe the anti-termite efficacy against Indian white termite Odontotermes obesus. These have shown very high termiticidal activity and wood protection in the soil. It is proved by very low LD50 values i.e. 0.0218mg/g and 0.021mg/g obtained ...

  5. Combinatorial algorithms enabling computational science: tales from the front

    Energy Technology Data Exchange (ETDEWEB)

    Bhowmick, Sanjukta [Mathematics and Computer Science Division, Argonne National Laboratory (United States); Boman, Erik G [Discrete Algorithms and Math Department, Sandia National Laboratories (United States); Devine, Karen [Discrete Algorithms and Math Department, Sandia National Laboratories (United States); Gebremedhin, Assefaw [Computer Science Department, Old Dominion University (United States); Hendrickson, Bruce [Discrete Algorithms and Math Department, Sandia National Laboratories (United States); Hovland, Paul [Mathematics and Computer Science Division, Argonne National Laboratory (United States); Munson, Todd [Mathematics and Computer Science Division, Argonne National Laboratory (United States); Pothen, Alex [Computer Science Department, Old Dominion University (United States)

    2006-09-15

    Combinatorial algorithms have long played a crucial enabling role in scientific and engineering computations. The importance of discrete algorithms continues to grow with the demands of new applications and advanced architectures. This paper surveys some recent developments in this rapidly changing and highly interdisciplinary field.

  6. Some Combinatorial Interpretations and Applications of Fuss-Catalan Numbers

    OpenAIRE

    Lin, Chin-Hung

    2011-01-01

    Fuss-Catalan number is a family of generalized Catalan numbers. We begin by two definitions of Fuss-Catalan numbers and some basic properties. And we give some combinatorial interpretations different from original Catalan numbers. Finally we generalize the Jonah's theorem as its applications.

  7. A Combinatorial Proof of a Result on Generalized Lucas Polynomials

    Directory of Open Access Journals (Sweden)

    Laugier Alexandre

    2016-09-01

    Full Text Available We give a combinatorial proof of an elementary property of generalized Lucas polynomials, inspired by [1]. These polynomials in s and t are defined by the recurrence relation 〈n〉 = s〈n-1〉+t〈n-2〉 for n ≥ 2. The initial values are 〈0〉 = 2; 〈1〉= s, respectively.

  8. Some experience of shielding calculations by combinatorial method

    International Nuclear Information System (INIS)

    Korobejnikov, V.V.; Oussanov, V.I.

    1996-01-01

    Some aspects of the compound systems shielding calculations by a combinatorial approach are discussed. The effectiveness of such an approach is based on the fundamental characteristic of a compound system: if some element of the system have in itself mathematical or physical properties favorable for calculation, these properties may be used in a combinatorial approach and are lost when the system is being calculated in the whole by a direct approach. The combinatorial technique applied is well known. A compound system are being splitting for two or more auxiliary subsystems (so that calculation each of them is a more simple problem than calculation of the original problem (or at last is a soluble problem if original one is not). Calculation of every subsystem are carried out by suitable method and code, the coupling being made through boundary conditions or boundary source. The special consideration in the paper is given to a fast reactor shielding combinatorial analysis and to the testing of the results received. (author)

  9. A combinatorial approximation algorithm for CDMA downlink rate allocation

    NARCIS (Netherlands)

    Boucherie, Richardus J.; Bumb, A.F.; Endrayanto, A.I.; Woeginger, Gerhard; Raghavan, S.; Anandalingam, G.

    2006-01-01

    This paper presents a combinatorial algorithm for downlink rate allocation in Code Division Multiple Access (CDMA) mobile networks. By discretizing the coverage area into small segments, the transmit power requirements are characterized via a matrix representation that separates user and system

  10. A combinatorial approximation algorithm for CDMA downlink rate allocation

    NARCIS (Netherlands)

    Boucherie, Richardus J.; Bumb, A.F.; Endrayanto, A.I.; Woeginger, Gerhard

    2004-01-01

    This paper presents a combinatorial algorithm for downlink rate allocation in Code Division Multiple Access (CDMA) mobile networks. By discretizing the coverage area into small segments, the transmit power requirements are characterized via a matrix representation that separates user and system

  11. A combinatorial enumeration problem of RNA secondary structures

    African Journals Online (AJOL)

    use

    2011-12-21

    Dec 21, 2011 ... interesting combinatorial questions (Chen et al., 2005;. Liu, 2006; Schmitt and Waterman 1994; Stein and. Waterman 1978). The research on the enumeration of. RNA secondary structures becomes one of the hot topics in Computational Molecular Biology. An RNA molecule is described by its sequences of.

  12. Libraries for users services in academic libraries

    CERN Document Server

    Alvite, Luisa

    2010-01-01

    This book reviews the quality and evolution of academic library services. It revises service trends offered by academic libraries and the challenge of enhancing traditional ones such as: catalogues, repositories and digital collections, learning resources centres, virtual reference services, information literacy and 2.0 tools.studies the role of the university library in the new educational environment of higher educationrethinks libraries in academic contextredefines roles for academic libraries

  13. Rational Approximations to Rational Models: Alternative Algorithms for Category Learning

    Science.gov (United States)

    Sanborn, Adam N.; Griffiths, Thomas L.; Navarro, Daniel J.

    2010-01-01

    Rational models of cognition typically consider the abstract computational problems posed by the environment, assuming that people are capable of optimally solving those problems. This differs from more traditional formal models of cognition, which focus on the psychological processes responsible for behavior. A basic challenge for rational models…

  14. Realization theory for rational systems: Minimal rational realizations

    NARCIS (Netherlands)

    J. Nemcová (Jana); J.H. van Schuppen (Jan)

    2010-01-01

    htmlabstractThe study of realizations of response maps is a topic of control and system theory. Realization theory is used in system identification and control synthesis. A minimal rational realization of a given response map p is a rational realization of p such that the dimension of its state

  15. Dynamic peptide libraries for the discovery of supramolecular nanomaterials

    Science.gov (United States)

    Pappas, Charalampos G.; Shafi, Ramim; Sasselli, Ivan R.; Siccardi, Henry; Wang, Tong; Narang, Vishal; Abzalimov, Rinat; Wijerathne, Nadeesha; Ulijn, Rein V.

    2016-11-01

    Sequence-specific polymers, such as oligonucleotides and peptides, can be used as building blocks for functional supramolecular nanomaterials. The design and selection of suitable self-assembling sequences is, however, challenging because of the vast combinatorial space available. Here we report a methodology that allows the peptide sequence space to be searched for self-assembling structures. In this approach, unprotected homo- and heterodipeptides (including aromatic, aliphatic, polar and charged amino acids) are subjected to continuous enzymatic condensation, hydrolysis and sequence exchange to create a dynamic combinatorial peptide library. The free-energy change associated with the assembly process itself gives rise to selective amplification of self-assembling candidates. By changing the environmental conditions during the selection process, different sequences and consequent nanoscale morphologies are selected.

  16. Paths and partitions: Combinatorial descriptions of the parafermionic states

    Science.gov (United States)

    Mathieu, Pierre

    2009-09-01

    The Zk parafermionic conformal field theories, despite the relative complexity of their modes algebra, offer the simplest context for the study of the bases of states and their different combinatorial representations. Three bases are known. The classic one is given by strings of the fundamental parafermionic operators whose sequences of modes are in correspondence with restricted partitions with parts at distance k -1 differing at least by 2. Another basis is expressed in terms of the ordered modes of the k -1 different parafermionic fields, which are in correspondence with the so-called multiple partitions. Both types of partitions have a natural (Bressoud) path representation. Finally, a third basis, formulated in terms of different paths, is inherited from the solution of the restricted solid-on-solid model of Andrews-Baxter-Forrester. The aim of this work is to review, in a unified and pedagogical exposition, these four different combinatorial representations of the states of the Zk parafermionic models. The first part of this article presents the different paths and partitions and their bijective relations; it is purely combinatorial, self-contained, and elementary; it can be read independently of the conformal-field-theory applications. The second part links this combinatorial analysis with the bases of states of the Zk parafermionic theories. With the prototypical example of the parafermionic models worked out in detail, this analysis contributes to fix some foundations for the combinatorial study of more complicated theories. Indeed, as we briefly indicate in ending, generalized versions of both the Bressoud and the Andrews-Baxter-Forrester paths emerge naturally in the description of the minimal models.

  17. Rational customs clearance technology choice

    OpenAIRE

    Shramenko, N.; Andriets, V.

    2008-01-01

    Issues concerning cargo delivery efficiencyincrease by choice of rational customs clearance technology have been considered. Three possible variants of customs clearance andmethods which allow to define the most rational version of cargo delivery in international road communication based on main efficiency criteria for definite distance have been presented.

  18. Differential Rationality and Personal Development.

    Science.gov (United States)

    Fincher, Cameron

    This publication discusses differential rationality; it asserts that the development of institutions, professions, and individuals involves the differentiation of forms and styles of thinking and knowing that are, in various ways, idiosyncratic. Based on this understanding, differential rationality can be seen as a developmental construct that…

  19. Rationality problem for algebraic tori

    CERN Document Server

    Hoshi, Akinari

    2017-01-01

    The authors give the complete stably rational classification of algebraic tori of dimensions 4 and 5 over a field k. In particular, the stably rational classification of norm one tori whose Chevalley modules are of rank 4 and 5 is given. The authors show that there exist exactly 487 (resp. 7, resp. 216) stably rational (resp. not stably but retract rational, resp. not retract rational) algebraic tori of dimension 4, and there exist exactly 3051 (resp. 25, resp. 3003) stably rational (resp. not stably but retract rational, resp. not retract rational) algebraic tori of dimension 5. The authors make a procedure to compute a flabby resolution of a G-lattice effectively by using the computer algebra system GAP. Some algorithms may determine whether the flabby class of a G-lattice is invertible (resp. zero) or not. Using the algorithms, the suthors determine all the flabby and coflabby G-lattices of rank up to 6 and verify that they are stably permutation. The authors also show that the Krull-Schmidt theorem for G-...

  20. Product differentiation under bounded rationality

    NARCIS (Netherlands)

    Vermeulen, B.; Poutré, La J.A.; Kok, de A.G.; Pyka, A.; Handa, H.; Ishibuchi, H.; Ong, Y.-S.; Tan, K.-C.

    2015-01-01

    We study product differentiation equilibria and dynamics on the Salop circle under bounded rationality. Due to bounded rationality, firms tend to agglomerate in pairs. Upon adding a second tier of component suppliers, downstream assemblers may escape pairwise horizontal agglomeration. Moreover, we

  1. The concept of rational suicide.

    Science.gov (United States)

    Mayo, D J

    1986-05-01

    Suicide has been condemned in our culture in one way or another since Augustine offered theological arguments against it in the sixth century. More recently, theological condemnation has given way to the view that suicidal behavior must always be symptomatic of emotional disturbance and mental illness. However, suicide has not always been viewed so negatively. In other times and cultures, it has been held that circumstances might befall a person in which suicide would be a perfectly rational course of action, in the same sense that any other course of action could be rational: that it could be sensible, i.e., defensible by good reasons, or that it could be in keeping with the agent's fundamental interests. Indiscriminate use of modern life-sustaining technologies has renewed interest in the possibility of rational suicide. Today proponents of rational suicide tend to equate the rationality of suicide with the competence of the decision to commit suicide.

  2. Limited rationality and strategic interaction

    DEFF Research Database (Denmark)

    Fehr, Ernst; Tyran, Jean-Robert

    2008-01-01

    Much evidence suggests that people are heterogeneous with regard to their abilities to make rational, forward-looking decisions. This raises the question as to when the rational types are decisive for aggregate outcomes and when the boundedly rational types shape aggregate results. We examine...... this question in the context of a long-standing and important economic problem: the adjustment of nominal prices after an anticipated monetary shock. Our experiments suggest that two types of bounded rationality-money illusion and anchoring-are important behavioral forces behind nominal inertia. However......, depending on the strategic environment, bounded rationality has vastly different effects on aggregate price adjustment. If agents' actions are strategic substitutes, adjustment to the new equilibrium is extremely quick, whereas under strategic complementarity, adjustment is both very slow and associated...

  3. Marketing the Virtual Library

    Science.gov (United States)

    Fagan, Jody Condit

    2009-01-01

    Far more people are familiar with their local public or college library facility than their library's website and online resources. In fact, according to a recent survey, 96% of Americans said they had visited a library in person, but less than one-third have visited their online library. Since everyone agrees that online library resources are…

  4. State Virtual Libraries

    Science.gov (United States)

    Pappas, Marjorie L.

    2003-01-01

    Virtual library? Electronic library? Digital library? Online information network? These all apply to the growing number of Web-based resource collections managed by consortiums of state library entities. Some, like "INFOhio" and "KYVL" ("Kentucky Virtual Library"), have been available for a few years, but others are just starting. Searching for…

  5. Public Libraries in Bangladesh.

    Science.gov (United States)

    Khan, M. H.

    1984-01-01

    Overview of library movement in Bangladesh highlights British (1851-1947) and Pakistan periods (1947-1971), separation of Bangladesh from Pakistan, libraries in development plans (1951-1970), three important public libraries, development of national library, book resources, a library network plan, legislation, finance, leadership, library…

  6. Combinatorial solid-phase glycopeptide libraries - Synthesis and application in biomolecular interaction studies and biosensors

    NARCIS (Netherlands)

    Maljaars, C.E.P.

    2006-01-01

    Carbohydrates play vital roles in all forms of life. Attached to proteins and lipids they serve as recognition elements in several biological interaction processes, such as intercellular communication, immune response, viral and parasitical infections, signal transduction, and development. Synthetic

  7. Virtual Combinatorial Library Design, Synthesis and In vitro Anticancer Assessment of -2-Amino-3-Cyanopyridine Derivatives.

    Science.gov (United States)

    Dev, Sanal; Dhaneshwar, Sunil R; Mathew, Bijo

    2018-01-01

    For the development of new class of anticancer agents, a series of novel 2-amino-3-cyanopyridine derivatives were designed from virtual screening with Glide program by setting Topoisomerase II as the target. The top ranked ten molecules from the virtual screening were synthesized by microwave assisted technique and investigated for their cytotoxic activity against MCF-7 and A- 549 cell lines by using sulforhodamine B assay method. The most active compound 2-amino-4-(3,5-dibromo-4-hydroxyphenyl)-6-(2,4- dichlorophenyl) nicotinonitrile (CG-5) showed significant cytotoxic profile with (LC50 = 97.1, TGI = 29.9 and GI50 = <0.1 µM) in MCF-7 and (LC50= 93.0, TGI= 50.0 and GI50= <7 µM) in A-549 cell lines. A molecular docking study was performed to explore the binding interaction of CG-5with the active site of Topoisomerase II. It can be concluded that halogen substituent pyridine ring was benefit for cytotoxicity. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  8. A Combinatorial Library of Micro-Topographies and Chemical Compositions for Tailored Surface Wettability

    DEFF Research Database (Denmark)

    Kolind, Kristian; Bennetsen, Dines Tilsted; Arpanaei, Ayyoob

    2011-01-01

    than surfaces modified with ODS, while the unmodified silicon surfaces were hydrophilic. For the PFS modified surfaces the largest CAs were achieved with a small pillar size of X = 1 µm and an intermediate inter-pillar gap size of Y = 4 µm with superhydrophobic CAs over 170°. Surface analysis with X......-ray photoelectron spectroscopy (XPS) revealed that CF3 groups were present at the surface, contributing to the superhydrophobic effect. The ODS modified surfaces had intermediate wettabilities with CAs between 100 and 150°, which were dependent on the pillar size, the inter-pillar gap size, and the specific pillar...... different applications. The measured CAs did not follow the simple Wenzel model. Furthermore, the adaptation of the Cassie model introduces Φs, the fraction of solid surface in contact with the liquid, which is difficult to estimate, thereby emphasizing the need for an experimental determination...

  9. Solid-phase synthesis and biological evaluation of a combinatorial library of philanthotoxin analogues

    DEFF Research Database (Denmark)

    Strømgaard, K; Brier, T J; Andersen, K

    2000-01-01

    ,12-dodecanediamine as amine components, and butanoyl, phenylacetyl, and cyclohexylacetyl as N-acyl groups. Following automated preparative HPLC, the resulting 18 compounds were isolated as the S-forms in 40-70% yields. The purity of the products was determined by HPLC with evaporative light scattering detection...... generally exhibited lower activity and different response to alterations of the N-acyl groups as compared to the 4-hydroxy analogues. Since the acyl group alterations in PhTX-343 and 4,9-dioxa-PhTX-12 have a similar effect on potency, which is distinctly different from that observed for PhTX-12, the two...

  10. Design of focused and restrained subsets from extremely large virtual libraries.

    Science.gov (United States)

    Jamois, Eric A; Lin, Chien T; Waldman, Marvin

    2003-11-01

    With the current and ever-growing offering of reagents along with the vast palette of organic reactions, virtual libraries accessible to combinatorial chemists can reach sizes of billions of compounds or more. Extracting practical size subsets for experimentation has remained an essential step in the design of combinatorial libraries. A typical approach to computational library design involves enumeration of structures and properties for the entire virtual library, which may be unpractical for such large libraries. This study describes a new approach termed as on the fly optimization (OTFO) where descriptors are computed as needed within the subset optimization cycle and without intermediate enumeration of structures. Results reported herein highlight the advantages of coupling an ultra-fast descriptor calculation engine to subset optimization capabilities. We also show that enumeration of properties for the entire virtual library may not only be unpractical but also wasteful. Successful design of focused and restrained subsets can be achieved while sampling only a small fraction of the virtual library. We also investigate the stability of the method and compare results obtained from simulated annealing (SA) and genetic algorithms (GA).

  11. [Rational use of medicines].

    Science.gov (United States)

    Helali, A

    2006-12-01

    Every body speaks about inappropriate use of medicines and each one gives his own explanation. Politicians are telling about the waste of medicines and the money of their national budget. Citizens are saying that the physicians prescribe more than necessary for treatment and blame them as one part of the financial burden weighting on their family budget. Physicians give different explanation and think that the rational use of medicines is a sort of pressure to limit their freedom to prescribe what it seems to them necessary and better for their patients. Pharmacists dispensing medicines consider the prescription as a physician's prerogative and prefer to stay neutral in this debate. Within this large range of opinions, it is difficult to find general consensus, so that every body take care to not declare his proper opinion about the subject, the causes and the adequate solutions. Finally no changes take place in this issue. However, neither the government as responsible for the citizen's health, nor the health professionals and international organisations, are facing their complete obligations toward the populations by ensuring to them that the medicines are administered according to the health need of the patients, efficacious and safe , in doses that meet their own individual requirements, for an adequate period of time, and at the lower cost, and be secured against misuse by the pharmacist before the delivery to the patients. This is a worthwhile programme, but unfortunately without designate takers or promoters until now.

  12. Rational points on varieties

    CERN Document Server

    Poonen, Bjorn

    2017-01-01

    This book is motivated by the problem of determining the set of rational points on a variety, but its true goal is to equip readers with a broad range of tools essential for current research in algebraic geometry and number theory. The book is unconventional in that it provides concise accounts of many topics instead of a comprehensive account of just one-this is intentionally designed to bring readers up to speed rapidly. Among the topics included are Brauer groups, faithfully flat descent, algebraic groups, torsors, étale and fppf cohomology, the Weil conjectures, and the Brauer-Manin and descent obstructions. A final chapter applies all these to study the arithmetic of surfaces. The down-to-earth explanations and the over 100 exercises make the book suitable for use as a graduate-level textbook, but even experts will appreciate having a single source covering many aspects of geometry over an unrestricted ground field and containing some material that cannot be found elsewhere. The origins of arithmetic (o...

  13. Plural rationalities and risk

    International Nuclear Information System (INIS)

    James, P.; Thompson, M.

    1989-01-01

    Like many social scientists, we attribute public unwillingness to accept certain low probability risks not to 'irrationality' but rather to the everyday application of qualitative as well as quantitative criteria. Just as most people buying a video or hi-fi do not base their decision solely on price or performance data but also consider such intangibles as design and the reputation of the manufacturer, individuals faced with a given risk take into account not merely the probability of harm but also the credibility and trustworthiness of whoever generates the information and manages the safety and other precautions which ensure its accuracy. To analyse these qualitative dimensions we utilise the grid/-group methodology developed by the cultural anthropologist Mary Douglas, and her co-workers. Douglas identifies four basic forms of society and four associated 'thought worlds' which serve to legitimise and reproduce them. Differences in concepts of human cognition, time and many other variables between the different thought worlds are so profound that they can be regarded as different kinds of rationality. The acceptability of risks is partially determined by the extent to which they support or threaten the existence of the different societies. (author)

  14. On-bead combinatorial synthesis and imaging of chemical exchange saturation transfer magnetic resonance imaging agents to identify factors that influence water exchange.

    Science.gov (United States)

    Napolitano, Roberta; Soesbe, Todd C; De León-Rodríguez, Luis M; Sherry, A Dean; Udugamasooriya, D Gomika

    2011-08-24

    The sensitivity of magnetic resonance imaging (MRI) contrast agents is highly dependent on the rate of water exchange between the inner sphere of a paramagnetic ion and bulk water. Normally, identifying a paramagnetic complex that has optimal water exchange kinetics is done by synthesizing and testing one compound at a time. We report here a rapid, economical on-bead combinatorial synthesis of a library of imaging agents. Eighty different 1,4,7,10-tetraazacyclododecan-1,4,7,10-tetraacetic acid (DOTA)-tetraamide peptoid derivatives were prepared on beads using a variety of charged, uncharged but polar, hydrophobic, and variably sized primary amines. A single chemical exchange saturation transfer image of the on-bead library easily distinguished those compounds having the most favorable water exchange kinetics. This combinatorial approach will allow rapid screening of libraries of imaging agents to identify the chemical characteristics of a ligand that yield the most sensitive imaging agents. This technique could be automated and readily adapted to other types of MRI or magnetic resonance/positron emission tomography agents as well.

  15. Transferrin targeted core-shell nanomedicine for combinatorial delivery of doxorubicin and sorafenib against hepatocellular carcinoma.

    Science.gov (United States)

    Malarvizhi, Giridharan Loghanathan; Retnakumari, Archana Payickattu; Nair, Shantikumar; Koyakutty, Manzoor

    2014-11-01

    Combinatorial drug delivery is an attractive, but challenging requirement of next generation cancer nanomedicines. Here, we report a transferrin-targeted core-shell nanomedicine formed by encapsulating two clinically used single-agent drugs, doxorubicin and sorafenib against liver cancer. Doxorubicin was loaded in poly(vinyl alcohol) nano-core and sorafenib in albumin nano-shell, both formed by a sequential freeze-thaw/coacervation method. While sorafenib from the nano-shell inhibited aberrant oncogenic signaling involved in cell proliferation, doxorubicin from the nano-core evoked DNA intercalation thereby killing >75% of cancer cells. Upon targeting using transferrin ligands, the nanoparticles showed enhanced cellular uptake and synergistic cytotoxicity in ~92% of cells, particularly in iron-deficient microenvironment. Studies using 3D spheroids of liver tumor indicated efficient penetration of targeted core-shell nanoparticles throughout the tissue causing uniform cell killing. Thus, we show that rationally designed core-shell nanoparticles can effectively combine clinically relevant single-agent drugs for exerting synergistic activity against liver cancer. Transferrin-targeted core-shell nanomedicine encapsulating doxorubicin and sorafenib was studied as a drug delivery system against hepatocellular carcinoma, resulting in enhanced and synergistic therapeutic effects, paving the way towards potential future clinical applications of similar techniques. Copyright © 2014 Elsevier Inc. All rights reserved.

  16. Multigroup cross section library; WIMS library

    International Nuclear Information System (INIS)

    Kannan, Umasankari

    2000-01-01

    The WIMS library has been extensively used in thermal reactor calculations. This multigroup constants library was originally developed from the UKNDL in the late 60's and has been updated in 1986. This library has been distributed with the WIMS-D code by NEA data bank. The references to WIMS library in literature are the 'old' which is the original as developed by the AEA Winfrith and the 'new' which is the current 1986 WIMS library. IAEA has organised a CRP where a new and fully updated WIMS library will soon be available. This paper gives an overview of the definitions of the group constants that go into any basic nuclear data library used for reactor calculations. This paper also outlines the contents of the WIMS library and some of its shortcomings

  17. Discrete Choice and Rational Inattention

    DEFF Research Database (Denmark)

    Fosgerau, Mogens; Melo, Emerson; de Palma, André

    2017-01-01

    This paper establishes a general equivalence between discrete choice and rational inattention models. Matejka and McKay (2015, AER) showed that when information costs are modelled using the Shannon entropy, the result- ing choice probabilities in the rational inattention model take the multinomial...... logit form. We show that when information costs are modelled using a class of generalized entropies, then the choice probabilities in any rational inattention model are observationally equivalent to some additive random utility discrete choice model and vice versa. This equivalence arises from convex...

  18. Testing bounded rationality against full rationality in job changing behavior

    OpenAIRE

    Contini, Bruno; Morini, Matteo

    2007-01-01

    In this paper we question the hypothesis of full rationality in the context of job changing behaviour, via simple econometric explorations on microdata drawn from WHIP (Worker Histories Italian Panel). Workers' performance is compared at the end of a three-year time window that starts when choices are expressed, under the accepted notion that the main driving forces of job change are future real wages and expected job quality. Bounded rationality suggests that individuals will search for new ...

  19. Testing Bounded Rationality Against Full Rationality in Job Changing Behavior

    OpenAIRE

    Bruno Contini

    2008-01-01

    In this paper I question the hypothesis of full rationality in the context of job changing behaviour, via simple econometric explorations on microdata drawn from WHIP (Worker Histories Italian Panel). Workers’ performance is compared at the end of a three-year time window that starts when choices are expressed, under the accepted notion that the main driving forces of job change are future real wages and expected job quality. Bounded rationality suggests that individuals will search for new o...

  20. Programme for test generation for combinatorial and sequential systems

    International Nuclear Information System (INIS)

    Tran Huy Hoan

    1973-01-01

    This research thesis reports the computer-assisted search for tests aimed at failure detection in combinatorial and sequential logic circuits. As he wants to deal with complex circuits with many modules such as those met in large scale integrated circuits (LSI), the author used propagation paths. He reports the development of a method which is valid for combinatorial systems and for several sequential circuits comprising elementary logic modules and JK and RS flip-flops. This method is developed on an IBM 360/91 computer in PL/1 language. The used memory space is limited and adjustable with respect to circuit dimension. Computing time is short when compared to that needed by other programmes. The solution is practical and efficient for failure test and localisation

  1. Bioinspired computation in combinatorial optimization: algorithms and their computational complexity

    DEFF Research Database (Denmark)

    Neumann, Frank; Witt, Carsten

    2012-01-01

    Bioinspired computation methods, such as evolutionary algorithms and ant colony optimization, are being applied successfully to complex engineering and combinatorial optimization problems, and it is very important that we understand the computational complexity of these algorithms. This tutorials...... problems. Classical single objective optimization is examined first. They then investigate the computational complexity of bioinspired computation applied to multiobjective variants of the considered combinatorial optimization problems, and in particular they show how multiobjective optimization can help...... to speed up bioinspired computation for single-objective optimization problems. The tutorial is based on a book written by the authors with the same title. Further information about the book can be found at www.bioinspiredcomputation.com....

  2. An Atlas of Combinatorial Transcriptional Regulation in Mouse and Man

    KAUST Repository

    Ravasi, Timothy; Suzuki, Harukazu; Cannistraci, Carlo; Katayama, Shintaro; Bajic, Vladimir B.; Tan, Kai; Akalin, Altuna; Schmeier, Sebastian; Kanamori-Katayama, Mutsumi; Bertin, Nicolas; Carninci, Piero; Daub, Carsten O.; Forrest, Alistair R.R.; Gough, Julian; Grimmond, Sean; Han, Jung-Hoon; Hashimoto, Takehiro; Hide, Winston; Hofmann, Oliver; Kamburov, Atanas; Kaur, Mandeep; Kawaji, Hideya; Kubosaki, Atsutaka; Lassmann, Timo; van Nimwegen, Erik; MacPherson, Cameron Ross; Ogawa, Chihiro; Radovanovic, Aleksandar; Schwartz, Ariel; Teasdale, Rohan D.; Tegné r, Jesper; Lenhard, Boris; Teichmann, Sarah A.; Arakawa, Takahiro; Ninomiya, Noriko; Murakami, Kayoko; Tagami, Michihira; Fukuda, Shiro; Imamura, Kengo; Kai, Chikatoshi; Ishihara, Ryoko; Kitazume, Yayoi; Kawai, Jun; Hume, David A.; Ideker, Trey; Hayashizaki, Yoshihide

    2010-01-01

    Combinatorial interactions among transcription factors are critical to directing tissue-specific gene expression. To build a global atlas of these combinations, we have screened for physical interactions among the majority of human and mouse DNA-binding transcription factors (TFs). The complete networks contain 762 human and 877 mouse interactions. Analysis of the networks reveals that highly connected TFs are broadly expressed across tissues, and that roughly half of the measured interactions are conserved between mouse and human. The data highlight the importance of TF combinations for determining cell fate, and they lead to the identification of a SMAD3/FLI1 complex expressed during development of immunity. The availability of large TF combinatorial networks in both human and mouse will provide many opportunities to study gene regulation, tissue differentiation, and mammalian evolution.

  3. CUNY Graduate Center Workshops on Combinatorial and Additive Number Theory

    CERN Document Server

    2017-01-01

    Based on talks from the 2015 and 2016 Combinatorial and Additive Number Theory (CANT) workshops at the City University of New York, these proceedings offer 19 peer-reviewed and edited papers on current topics in number theory. Held every year since 2003, the workshop series surveys state-of-the-art open problems in combinatorial and additive number theory and related parts of mathematics. Sumsets, partitions, convex polytopes and discrete geometry, Ramsey theory, primality testing, and cryptography are among the topics featured in this volume. Each contribution is dedicated to a specific topic that reflects the latest results by experts in the field. Researchers and graduate students interested in the current progress in number theory will find this selection of articles relevant and compelling. .

  4. Combinatorial geometry domain decomposition strategies for Monte Carlo simulations

    Energy Technology Data Exchange (ETDEWEB)

    Li, G.; Zhang, B.; Deng, L.; Mo, Z.; Liu, Z.; Shangguan, D.; Ma, Y.; Li, S.; Hu, Z. [Institute of Applied Physics and Computational Mathematics, Beijing, 100094 (China)

    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)

  5. Combinatorial geometry domain decomposition strategies for Monte Carlo simulations

    International Nuclear Information System (INIS)

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

    2013-01-01

    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)

  6. Laguerre-type derivatives: Dobinski relations and combinatorial identities

    International Nuclear Information System (INIS)

    Penson, K. A.; Blasiak, P.; Horzela, A.; Duchamp, G. H. E.; Solomon, A. I.

    2009-01-01

    We consider properties of the operators D(r,M)=a r (a † a) M (which we call generalized Laguerre-type derivatives), with r=1,2,..., M=0,1,..., where a and a † are boson annihilation and creation operators, respectively, satisfying [a,a † ]=1. We obtain explicit formulas for the normally ordered form of arbitrary Taylor-expandable functions of D(r,M) with the help of an operator relation that generalizes the Dobinski formula. Coherent state expectation values of certain operator functions of D(r,M) turn out to be generating functions of combinatorial numbers. In many cases the corresponding combinatorial structures can be explicitly identified.

  7. An Atlas of Combinatorial Transcriptional Regulation in Mouse and Man

    KAUST Repository

    Ravasi, Timothy

    2010-03-01

    Combinatorial interactions among transcription factors are critical to directing tissue-specific gene expression. To build a global atlas of these combinations, we have screened for physical interactions among the majority of human and mouse DNA-binding transcription factors (TFs). The complete networks contain 762 human and 877 mouse interactions. Analysis of the networks reveals that highly connected TFs are broadly expressed across tissues, and that roughly half of the measured interactions are conserved between mouse and human. The data highlight the importance of TF combinations for determining cell fate, and they lead to the identification of a SMAD3/FLI1 complex expressed during development of immunity. The availability of large TF combinatorial networks in both human and mouse will provide many opportunities to study gene regulation, tissue differentiation, and mammalian evolution.

  8. Combinatorial Optimization in Project Selection Using Genetic Algorithm

    Science.gov (United States)

    Dewi, Sari; Sawaluddin

    2018-01-01

    This paper discusses the problem of project selection in the presence of two objective functions that maximize profit and minimize cost and the existence of some limitations is limited resources availability and time available so that there is need allocation of resources in each project. These resources are human resources, machine resources, raw material resources. This is treated as a consideration to not exceed the budget that has been determined. So that can be formulated mathematics for objective function (multi-objective) with boundaries that fulfilled. To assist the project selection process, a multi-objective combinatorial optimization approach is used to obtain an optimal solution for the selection of the right project. It then described a multi-objective method of genetic algorithm as one method of multi-objective combinatorial optimization approach to simplify the project selection process in a large scope.

  9. Non-unique factorizations algebraic, combinatorial and analytic theory

    CERN Document Server

    Geroldinger, Alfred

    2006-01-01

    From its origins in algebraic number theory, the theory of non-unique factorizations has emerged as an independent branch of algebra and number theory. Focused efforts over the past few decades have wrought a great number and variety of results. However, these remain dispersed throughout the vast literature. For the first time, Non-Unique Factorizations: Algebraic, Combinatorial, and Analytic Theory offers a look at the present state of the theory in a single, unified resource.Taking a broad look at the algebraic, combinatorial, and analytic fundamentals, this book derives factorization results and applies them in concrete arithmetical situations using appropriate transfer principles. It begins with a basic introduction that can be understood with knowledge of standard basic algebra. The authors then move to the algebraic theory of monoids, arithmetic theory of monoids, the structure of sets of lengths, additive group theory, arithmetical invariants, and the arithmetic of Krull monoids. They also provide a s...

  10. Combinatorial nuclear level density by a Monte Carlo method

    International Nuclear Information System (INIS)

    Cerf, N.

    1994-01-01

    We present a new combinatorial method for the calculation of the nuclear level density. It is based on a Monte Carlo technique, in order to avoid a direct counting procedure which is generally impracticable for high-A nuclei. The Monte Carlo simulation, making use of the Metropolis sampling scheme, allows a computationally fast estimate of the level density for many fermion systems in large shell model spaces. We emphasize the advantages of this Monte Carlo approach, particularly concerning the prediction of the spin and parity distributions of the excited states,and compare our results with those derived from a traditional combinatorial or a statistical method. Such a Monte Carlo technique seems very promising to determine accurate level densities in a large energy range for nuclear reaction calculations

  11. LIBRARY SKILL INSTRUCTION IN NIGERIAN ACADEMIC LIBRARIES

    African Journals Online (AJOL)

    DJFLEX

    www.globaljournalseries.com; Info@globaljournalseries.com. LIBRARY SKILL INSTRUCTION IN NIGERIAN ACADEMIC. LIBRARIES. P. C. AZIAGBA AND E. H. UZOEZI. (Received 10, September 2009; Revision Accepted 8, February 2010). ABSTRACT. This survey was undertaken to portray the level of library involvement ...

  12. Obfuscation Framework Based on Functionally Equivalent Combinatorial Logic Families

    Science.gov (United States)

    2008-03-01

    of Defense, or the United States Government . AFIT/GCS/ENG/08-12 Obfuscation Framework Based on Functionally Equivalent Combinatorial Logic Families...time, United States policy strongly encourages the sale and transfer of some military equipment to foreign governments and makes it easier for...Proceedings of the International Conference on Availability, Reliability and Security, 2007. 14. McDonald, J. Todd and Alec Yasinsac. “Of unicorns and random

  13. Combinatorial drug screening identifies Ewing sarcoma-specific sensitivities

    OpenAIRE

    Radic-Sarikas, Branka; Tsafou, Kalliopi P.; Emdal, Kristina B.; Papamarkou, Theodore; Huber, Kilian V.M.; Mutz, Cornelia; Toretsky, Jeffrey A.; Bennett, Keiryn L.; Olsen, Jesper V.; Brunak, Søren; Kovar, Heinrich; Superti-Furga, Giulio

    2017-01-01

    Improvements in survival for Ewing sarcoma pediatric and adolescent patients have been modest over the past 20 years. Combinations of anticancer agents endure as an option to overcome resistance to single treatments caused by compensatory pathways. Moreover, combinations are thought to lessen any associated adverse side effects through reduced dosing, which is particularly important in childhood tumors. Using a parallel phenotypic combinatorial screening approach of cells derived from three p...

  14. Combinatorial Models for Assembly and Decomposition of Products

    OpenAIRE

    A. N. Bojko

    2015-01-01

    The paper discusses the most popular combinatorial models that are used for the synthesis of design solutions at the stage of the assembly process flow preparation. It shows that while assembling the product the relations of parts can be represented as a structure of preferences, which is formed on the basis of objective design restrictions put in at the stage of the product design. This structure is a binary preference relation pre-order. Its symmetrical part is equivalence and describes the...

  15. From combinatorial optimization to real algebraic geometry and back

    Directory of Open Access Journals (Sweden)

    Janez Povh

    2014-12-01

    Full Text Available In this paper, we explain the relations between combinatorial optimization and real algebraic geometry with a special focus to the quadratic assignment problem. We demonstrate how to write a quadratic optimization problem over discrete feasible set as a linear optimization problem over the cone of completely positive matrices. The latter formulation enables a hierarchy of approximations which rely on results from polynomial optimization, a sub-eld of real algebraic geometry.

  16. Distributing the computation in combinatorial optimization experiments over the cloud

    Directory of Open Access Journals (Sweden)

    Mario Brcic

    2017-12-01

    Full Text Available Combinatorial optimization is an area of great importance since many of the real-world problems have discrete parameters which are part of the objective function to be optimized. Development of combinatorial optimization algorithms is guided by the empirical study of the candidate ideas and their performance over a wide range of settings or scenarios to infer general conclusions. Number of scenarios can be overwhelming, especially when modeling uncertainty in some of the problem’s parameters. Since the process is also iterative and many ideas and hypotheses may be tested, execution time of each experiment has an important role in the efficiency and successfulness. Structure of such experiments allows for significant execution time improvement by distributing the computation. We focus on the cloud computing as a cost-efficient solution in these circumstances. In this paper we present a system for validating and comparing stochastic combinatorial optimization algorithms. The system also deals with selection of the optimal settings for computational nodes and number of nodes in terms of performance-cost tradeoff. We present applications of the system on a new class of project scheduling problem. We show that we can optimize the selection over cloud service providers as one of the settings and, according to the model, it resulted in a substantial cost-savings while meeting the deadline.

  17. View discovery in OLAP databases through statistical combinatorial optimization

    Energy Technology Data Exchange (ETDEWEB)

    Hengartner, Nick W [Los Alamos National Laboratory; Burke, John [PNNL; Critchlow, Terence [PNNL; Joslyn, Cliff [PNNL; Hogan, Emilie [PNNL

    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.

  18. A combinatorial perspective of the protein inference problem.

    Science.gov (United States)

    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.

  19. View Discovery in OLAP Databases through Statistical Combinatorial Optimization

    Energy Technology Data Exchange (ETDEWEB)

    Joslyn, Cliff A.; Burke, Edward J.; Critchlow, Terence J.

    2009-05-01

    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.

  20. DNA-encoded chemical libraries: advancing beyond conventional small-molecule libraries.

    Science.gov (United States)

    Franzini, Raphael M; Neri, Dario; Scheuermann, Jörg

    2014-04-15

    DNA-encoded chemical libraries (DECLs) represent a promising tool in drug discovery. DECL technology allows the synthesis and screening of chemical libraries of unprecedented size at moderate costs. In analogy to phage-display technology, where large antibody libraries are displayed on the surface of filamentous phage and are genetically encoded in the phage genome, DECLs feature the display of individual small organic chemical moieties on DNA fragments serving as amplifiable identification barcodes. The DNA-tag facilitates the synthesis and allows the simultaneous screening of very large sets of compounds (up to billions of molecules), because the hit compounds can easily be identified and quantified by PCR-amplification of the DNA-barcode followed by high-throughput DNA sequencing. Several approaches have been used to generate DECLs, differing both in the methods used for library encoding and for the combinatorial assembly of chemical moieties. For example, DECLs can be used for fragment-based drug discovery, displaying a single molecule on DNA or two chemical moieties at the extremities of complementary DNA strands. DECLs can vary substantially in the chemical structures and the library size. While ultralarge libraries containing billions of compounds have been reported containing four or more sets of building blocks, also smaller libraries have been shown to be efficient for ligand discovery. In general, it has been found that the overall library size is a poor predictor for library performance and that the number and diversity of the building blocks are rather important indicators. Smaller libraries consisting of two to three sets of building blocks better fulfill the criteria of drug-likeness and often have higher quality. In this Account, we present advances in the DECL field from proof-of-principle studies to practical applications for drug discovery, both in industry and in academia. DECL technology can yield specific binders to a variety of target

  1. Rational reconstructions of modern physics

    CERN Document Server

    Mittelstaedt, Peter

    2013-01-01

    Newton’s classical physics and its underlying ontology are loaded with several metaphysical hypotheses that cannot be justified by rational reasoning nor by experimental evidence. Furthermore, it is well known that some of these hypotheses are not contained in the great theories of Modern Physics, such as the theory of Special Relativity and Quantum Mechanics. This book shows that, on the basis of Newton’s classical physics and by rational reconstruction, the theory of Special Relativity as well as Quantum Mechanics can be obtained by partly eliminating or attenuating the metaphysical hypotheses. Moreover, it is shown that these reconstructions do not require additional hypotheses or new experimental results. In the second edition the rational reconstructions are completed with respect to General Relativity and Cosmology. In addition, the statistics of quantum objects is elaborated in more detail with respect to the rational reconstruction of quantum mechanics. The new material completes the approach of t...

  2. Rational-Emotive Staff Development.

    Science.gov (United States)

    Forman, Susan G.; Forman, Bruce D.

    1980-01-01

    The application of Rational-Emotive Therapy principles and techniques in in-service education for school personnel is discussed. Teacher and counselor participation in a staff development program is described. (Author)

  3. Use of Mixed Micelles for Presentation of Building Blocks in a New Combinatorial Discovery Methodology: Proof-of-Concept Studies

    Directory of Open Access Journals (Sweden)

    Istvan Toth

    2013-03-01

    Full Text Available We describe a new method of combinatorial screening in which building blocks, instead of being linked together chemically, are placed on the surface of nanoparticles. Two- or three-dimensional structures form on the surface of these particles through the close approach of different building blocks, with sufficient flexibility to be able to adapt and interact with putative binding sites in biological systems. The particles assemble without the need for formation of chemical bonds, so libraries comprised of many structures can be prepared rapidly, with large quantities of material available for testing. Screening methods can include solid and solution-phase binding assays, or tissue culture models, for example looking for structures which can change the behaviour of cells in a disease-modifying manner.

  4. Management between Rationality and Irrationality

    OpenAIRE

    Cene Bavec

    2012-01-01

    In the paper, we discuss theoretical and practical aspects of management and its rational and irrational behavior in the light of traditional management theories and contemporary social theories and theories of complexity. We exposed differences between middle and top management, where rationality is ascribed mainly to middle management, while top management often acts on seemingly irrational way. For the part of this irrationality, we cannot blame management because it originates from the na...

  5. Choice, internal consistency, and rationality

    OpenAIRE

    Aditi Bhattacharyya; Prasanta K. Pattanaik; Yongsheng Xu

    2010-01-01

    The classical theory of rational choice is built on several important internal consistency conditions. In recent years, the reasonableness of those internal consistency conditions has been questioned and criticized, and several responses to accommodate such criticisms have been proposed in the literature. This paper develops a general framework to accommodate the issues raised by the criticisms of classical rational choice theory, and examines the broad impact of these criticisms from both no...

  6. Preparation of 24 ternary thin film materials libraries on a single substrate in one experiment for irreversible high-throughput studies.

    Science.gov (United States)

    Buenconsejo, Pio John S; Siegel, Alexander; Savan, Alan; Thienhaus, Sigurd; Ludwig, Alfred

    2012-01-09

    For different areas of combinatorial materials science, it is desirable to have multiple materials libraries: especially for irreversible high-throughput studies, like, for example, corrosion resistance testing in different media or annealing of complete materials libraries at different temperatures. Therefore a new combinatorial sputter-deposition process was developed which yields 24 materials libraries in one experiment on a single substrate. It is discussed with the example of 24 Ti-Ni-Ag materials libraries. They are divided based on the composition coverage and orientation of composition gradient into two sets of 12 nearly identical materials libraries. Each materials library covers at least 30-40% of the complete ternary composition range. An acid etch test in buffered-HF solution was performed, illustrating the feasibility of our approach for destructive materials characterization. The results revealed that within the composition range of Ni < 30 at.%, the films were severely etched. The composition range which shows reversible martensitic transformations was confirmed to be outside this region. The high output of the present method makes it attractive for combinatorial studies requiring multiple materials libraries.

  7. Interpolation of rational matrix functions

    CERN Document Server

    Ball, Joseph A; Rodman, Leiba

    1990-01-01

    This book aims to present the theory of interpolation for rational matrix functions as a recently matured independent mathematical subject with its own problems, methods and applications. The authors decided to start working on this book during the regional CBMS conference in Lincoln, Nebraska organized by F. Gilfeather and D. Larson. The principal lecturer, J. William Helton, presented ten lectures on operator and systems theory and the interplay between them. The conference was very stimulating and helped us to decide that the time was ripe for a book on interpolation for matrix valued functions (both rational and non-rational). When the work started and the first partial draft of the book was ready it became clear that the topic is vast and that the rational case by itself with its applications is already enough material for an interesting book. In the process of writing the book, methods for the rational case were developed and refined. As a result we are now able to present the rational case as an indepe...

  8. DC-Analyzer-facilitated combinatorial strategy for rapid directed evolution of functional enzymes with multiple mutagenesis sites.

    Science.gov (United States)

    Wang, Xiong; Zheng, Kai; Zheng, Huayu; Nie, Hongli; Yang, Zujun; Tang, Lixia

    2014-12-20

    Iterative saturation mutagenesis (ISM) has been shown to be a powerful method for directed evolution. In this study, the approach was modified (termed M-ISM) by combining the single-site saturation mutagenesis method with a DC-Analyzer-facilitated combinatorial strategy, aiming to evolve novel biocatalysts efficiently in the case where multiple sites are targeted simultaneously. Initially, all target sites were explored individually by constructing single-site saturation mutagenesis libraries. Next, the top two to four variants in each library were selected and combined using the DC-Analyzer-facilitated combinatorial strategy. In addition to site-saturation mutagenesis, iterative saturation mutagenesis also needed to be performed. The advantages of M-ISM over ISM were that the screening effort is greatly reduced, and the entire M-ISM procedure was less time-consuming. The M-ISM strategy was successfully applied to the randomization of halohydrin dehalogenase from Agrobacterium radiobacter AD1 (HheC) when five interesting sites were targeted simultaneously. After screening 900 clones in total, six positive mutants were obtained. These mutants exhibited 4.0- to 9.3-fold higher k(cat) values than did the wild-type HheC toward 1,3-dichloro-2-propanol. However, with the ISM strategy, the best hit showed a 5.9-fold higher k(cat) value toward 1,3-DCP than the wild-type HheC, which was obtained after screening 4000 clones from four rounds of mutagenesis. Therefore, M-ISM could serve as a simple and efficient version of ISM for the randomization of target genes with multiple positions of interest.

  9. Libraries and Learning

    Science.gov (United States)

    Rainie, Lee

    2016-01-01

    The majority of Americans think local libraries serve the educational needs of their communities and families pretty well and library users often outpace others in learning activities. But many do not know about key education services libraries provide. This report provides statistics on library usage and presents key education services provided…

  10. Growing Competition for Libraries.

    Science.gov (United States)

    Gibbons, Susan

    2001-01-01

    Describes the Questia subscription-based online academic digital books library. Highlights include weaknesses of the collection; what college students want from a library; importance of marketing; competition for traditional academic libraries that may help improve library services; and the ability of Questia to overcome barriers and…

  11. The library marketing toolkit

    CERN Document Server

    Potter, Ned

    2012-01-01

    A guide that offers coverage of various elements of library marketing and branding for different sectors including archives and academic, public and special libraries. It is suitable for those who are involved in promoting their library or information service, whether at an academic, public or special library or in archives or records management.

  12. Automating the Small Library.

    Science.gov (United States)

    Skapura, Robert

    1987-01-01

    Discusses the use of microcomputers for automating school libraries, both for entire systems and for specific library tasks. Highlights include available library management software, newsletters that evaluate software, constructing an evaluation matrix, steps to consider in library automation, and a brief discussion of computerized card catalogs.…

  13. A combinatorial approach towards the design of nanofibrous scaffolds for chondrogenesis

    Science.gov (United States)

    Ahmed, Maqsood; Ramos, Tiago André Da Silva; Damanik, Febriyani; Quang Le, Bach; Wieringa, Paul; Bennink, Martin; van Blitterswijk, Clemens; de Boer, Jan; Moroni, Lorenzo

    2015-10-01

    The extracellular matrix (ECM) is a three-dimensional (3D) structure composed of proteinaceous fibres that provide physical and biological cues to direct cell behaviour. Here, we build a library of hybrid collagen-polymer fibrous scaffolds with nanoscale dimensions and screen them for their ability to grow chondrocytes for cartilage repair. Poly(lactic acid) and poly (lactic-co-glycolic acid) at two different monomer ratios (85:15 and 50:50) were incrementally blended with collagen. Physical properties (wettability and stiffness) of the scaffolds were characterized and related to biological performance (proliferation, ECM production, and gene expression) and structure-function relationships were developed. We found that soft scaffolds with an intermediate wettability composed of the highly biodegradable PLGA50:50 and collagen, in two ratios (40:60 and 60:40), were optimal for chondrogenic differentiation of ATDC5 cells as determined by increased ECM production and enhanced cartilage specific gene expression. Long-term cultures indicated a stable phenotype with minimal de-differentiation or hypertrophy. The combinatorial methodology applied herein is a promising approach for the design and development of scaffolds for regenerative medicine.

  14. Love and rationality: on some possible rational effects of love

    Directory of Open Access Journals (Sweden)

    Gustavo Ortiz-Millán

    Full Text Available In this paper I defend the idea that rather than disrupting rationality, as the common-sense conception has done it, love may actually help us to develop rational ways of thinking and acting. I make the case for romantic or erotic love, since this is the kind of love that is more frequently associated with irrationality in acting and thinking. I argue that this kind of love may make us develop epistemic and practical forms of rationality. Based on an analysis of its characteristic action tendencies, I argue that love may help us to develop an instrumental form of rationality in determining the best means to achieve the object of love. It may also narrow down the number of practical considerations that may help us to achieve our goals. Finally, love may generate rational ways of belief-formation by framing the parameters taken into account in perception and attention, and by bringing into light only a small portion of the epistemic information available. Love may make us perceive reality more acutely.

  15. A novel glutamine–RNA interaction identified by screening libraries in mammalian cells

    OpenAIRE

    Tan, Ruoying; Frankel, Alan D.

    1998-01-01

    The arginine-rich motif provides a versatile framework for RNA recognition in which few amino acids other than arginine are needed to mediate specific binding. Using a mammalian screening system based on transcriptional activation by HIV Tat, we identified novel arginine-rich peptides from combinatorial libraries that bind tightly to the Rev response element of HIV. Remarkably, a single glutamine, but not asparagine, within a stretch of polyarginine can mediate high-affinity binding. These re...

  16. Rational Decision Making as Performative Praxis: Explaining Rationality's Éternel Retour

    OpenAIRE

    Cabantous, L.; Gond, J-P.

    2011-01-01

    Organizational theorists built their knowledge of decision making through a progressive critique of rational choice theory. Their positioning towards rationality, however, is at odds with the observation of rationality persistence in organizational life. This paper addresses this paradox. It proposes a new perspective on rationality that allows the theorizing of the production of rational decisions by organizations. To account for rationality's éternel retour, we approach rational decision ma...

  17. Rationing medical education | Walsh | African Health Sciences

    African Journals Online (AJOL)

    Even though some stakeholders in medical education might be taken aback at the prospect of rationing, the truth is that rationing has always occurred in one form or another in medical education and in healthcare more broadly. Different types of rationing exist in healthcare professional education. For example rationing may ...

  18. Strategy selection as rational metareasoning.

    Science.gov (United States)

    Lieder, Falk; Griffiths, Thomas L

    2017-11-01

    Many contemporary accounts of human reasoning assume that the mind is equipped with multiple heuristics that could be deployed to perform a given task. This raises the question of how the mind determines when to use which heuristic. To answer this question, we developed a rational model of strategy selection, based on the theory of rational metareasoning developed in the artificial intelligence literature. According to our model people learn to efficiently choose the strategy with the best cost-benefit tradeoff by learning a predictive model of each strategy's performance. We found that our model can provide a unifying explanation for classic findings from domains ranging from decision-making to arithmetic by capturing the variability of people's strategy choices, their dependence on task and context, and their development over time. Systematic model comparisons supported our theory, and 4 new experiments confirmed its distinctive predictions. Our findings suggest that people gradually learn to make increasingly more rational use of fallible heuristics. This perspective reconciles the 2 poles of the debate about human rationality by integrating heuristics and biases with learning and rationality. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

  19. America's Star Libraries, 2010: Top-Rated Libraries

    Science.gov (United States)

    Lyons, Ray; Lance, Keith Curry

    2010-01-01

    The "LJ" Index of Public Library Service 2010, "Library Journal"'s national rating of public libraries, identifies 258 "star" libraries. Created by Ray Lyons and Keith Curry Lance, and based on 2008 data from the IMLS, it rates 7,407 public libraries. The top libraries in each group get five, four, or three stars. All included libraries, stars or…

  20. DISTRIBUTED RC NETWORKS WITH RATIONAL TRANSFER FUNCTIONS,

    Science.gov (United States)

    A distributed RC circuit analogous to a continuously tapped transmission line can be made to have a rational short-circuit transfer admittance and...one rational shortcircuit driving-point admittance. A subcircuit of the same structure has a rational open circuit transfer impedance and one rational ...open circuit driving-point impedance. Hence, rational transfer functions may be obtained while considering either generator impedance or load

  1. Combinatorial effects of arginine and fluoride on oral bacteria.

    Science.gov (United States)

    Zheng, X; Cheng, X; Wang, L; Qiu, W; Wang, S; Zhou, Y; Li, M; Li, Y; Cheng, L; Li, J; Zhou, X; Xu, X

    2015-02-01

    Dental caries is closely associated with the microbial disequilibrium between acidogenic/aciduric pathogens and alkali-generating commensal residents within the dental plaque. Fluoride is a widely used anticaries agent, which promotes tooth hard-tissue remineralization and suppresses bacterial activities. Recent clinical trials have shown that oral hygiene products containing both fluoride and arginine possess a greater anticaries effect compared with those containing fluoride alone, indicating synergy between fluoride and arginine in caries management. Here, we hypothesize that arginine may augment the ecological benefit of fluoride by enriching alkali-generating bacteria in the plaque biofilm and thus synergizes with fluoride in controlling dental caries. Specifically, we assessed the combinatory effects of NaF/arginine on planktonic and biofilm cultures of Streptococcus mutans, Streptococcus sanguinis, and Porphyromonas gingivalis with checkerboard microdilution assays. The optimal NaF/arginine combinations were selected, and their combinatory effects on microbial composition were further examined in single-, dual-, and 3-species biofilm using bacterial species-specific fluorescence in situ hybridization and quantitative polymerase chain reaction. We found that arginine synergized with fluoride in suppressing acidogenic S. mutans in both planktonic and biofilm cultures. In addition, the NaF/arginine combination synergistically reduced S. mutans but enriched S. sanguinis within the multispecies biofilms. More importantly, the optimal combination of NaF/arginine maintained a "streptococcal pressure" against the potential growth of oral anaerobe P. gingivalis within the alkalized biofilm. Taken together, we conclude that the combinatory application of fluoride and arginine has a potential synergistic effect in maintaining a healthy oral microbial equilibrium and thus represents a promising ecological approach to caries management. © International & American

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

    Science.gov (United States)

    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

  3. Rational points on elliptic curves

    CERN Document Server

    Silverman, Joseph H

    2015-01-01

    The theory of elliptic curves involves a pleasing blend of algebra, geometry, analysis, and number theory. This book stresses this interplay as it develops the basic theory, thereby providing an opportunity for advanced undergraduates to appreciate the unity of modern mathematics. At the same time, every effort has been made to use only methods and results commonly included in the undergraduate curriculum. This accessibility, the informal writing style, and a wealth of exercises make Rational Points on Elliptic Curves an ideal introduction for students at all levels who are interested in learning about Diophantine equations and arithmetic geometry. Most concretely, an elliptic curve is the set of zeroes of a cubic polynomial in two variables. If the polynomial has rational coefficients, then one can ask for a description of those zeroes whose coordinates are either integers or rational numbers. It is this number theoretic question that is the main subject of this book. Topics covered include the geometry and ...

  4. Rationality in the Cryptographic Model

    DEFF Research Database (Denmark)

    Hubacek, Pavel

    This thesis presents results in the field of rational cryptography. In the first part we study the use of cryptographic protocols to avoid mediation and binding commitment when implementing game theoretic equilibrium concepts. First, we concentrate on the limits of cryptographic cheap talk...... to implement correlated equilibria of two-player strategic games in a sequentially rational way. We show that there exist two-player games for which no cryptographic protocol can implement the mediator in a sequentially rational way; that is, without introducing empty threats. In the context of computational...... with appealing economic applications. Our implementation puts forward a notion of cryptographically blinded games that exploits the power of encryption to selectively restrict the information available to players about sampled action profiles, such that these desirable equilibria can be stably achieved...

  5. Combinatorial interpretations of binomial coefficient analogues related to Lucas sequences

    OpenAIRE

    Sagan, Bruce; Savage, Carla

    2009-01-01

    Let s and t be variables. Define polynomials {n} in s, t by {0}=0, {1}=1, and {n}=s{n-1}+t{n-2} for n >= 2. If s, t are integers then the corresponding sequence of integers is called a Lucas sequence. Define an analogue of the binomial coefficients by C{n,k}={n}!/({k}!{n-k}!) where {n}!={1}{2}...{n}. It is easy to see that C{n,k} is a polynomial in s and t. The purpose of this note is to give two combinatorial interpretations for this polynomial in terms of statistics on integer partitions in...

  6. First steps in combinatorial optimization on graphons: matchings

    Czech Academy of Sciences Publication Activity Database

    Doležal, Martin; Hladký, J.; Hu, P.; Piguet, Diana

    2017-01-01

    Roč. 61, August (2017), s. 359-365 ISSN 1571-0653 R&D Projects: GA ČR GA16-07378S; GA ČR GJ16-07822Y EU Projects: European Commission(XE) 628974 - PAECIDM Institutional support: RVO:67985840 ; RVO:67985807 Keywords : graphon * graph limits * matching * combinatorial optimization Subject RIV: BA - General Mathematics ; BA - General Mathematics (UIVT-O) OBOR OECD: Pure mathematics ; Pure mathematics (UIVT-O) http://www.sciencedirect.com/science/article/pii/S1571065317301452

  7. Advances in bio-inspired computing for combinatorial optimization problems

    CERN Document Server

    Pintea, Camelia-Mihaela

    2013-01-01

    Advances in Bio-inspired Combinatorial Optimization Problems' illustrates several recent bio-inspired efficient algorithms for solving NP-hard problems.Theoretical bio-inspired concepts and models, in particular for agents, ants and virtual robots are described. Large-scale optimization problems, for example: the Generalized Traveling Salesman Problem and the Railway Traveling Salesman Problem, are solved and their results are discussed.Some of the main concepts and models described in this book are: inner rule to guide ant search - a recent model in ant optimization, heterogeneous sensitive a

  8. Proceedings of the 8th Nordic Combinatorial Conference

    DEFF Research Database (Denmark)

    Geil, Olav; Andersen, Lars Døvling

    The Nordic Combinatorial Conferences were initiated in 1981 by mathematicians from Stavanger. Held approximately every three years since then, the conferences have been able to sustain the interest from combinatorialists all over the Nordic countries. In 2004 the 8th conference is held in Aalborg......, Denmark. We are pleased that so many people have chosen to attend, and that lectures were offered from more participants than we had originally reserved time for. We asked two mathematicians to give special lectures and are happy that both accepted immediately. Andries Brouwer from the Technical...

  9. Combinatorial interpretation of Haldane-Wu fractional exclusion statistics.

    Science.gov (United States)

    Aringazin, A K; Mazhitov, M I

    2002-08-01

    Assuming that the maximal allowed number of identical particles in a state is an integer parameter, q, we derive the statistical weight and analyze the associated equation that defines the statistical distribution. The derived distribution covers Fermi-Dirac and Bose-Einstein ones in the particular cases q=1 and q--> infinity (n(i)/q-->1), respectively. We show that the derived statistical weight provides a natural combinatorial interpretation of Haldane-Wu fractional exclusion statistics, and present exact solutions of the distribution equation.

  10. What Diagrams Argue in Late Imperial Chinese Combinatorial Texts.

    Science.gov (United States)

    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.

  11. First steps in combinatorial optimization on graphons: matchings

    Czech Academy of Sciences Publication Activity Database

    Doležal, Martin; Hladký, J.; Hu, P.; Piguet, Diana

    2017-01-01

    Roč. 61, August (2017), s. 359-365 ISSN 1571-0653 R&D Projects: GA ČR GA16-07378S; GA ČR GJ16-07822Y EU Projects: European Commission(XE) 628974 - PAECIDM Institutional support: RVO:67985840 ; RVO:67985807 Keywords : graphon * graph limits * matching * combinatorial optimization Subject RIV: BA - General Mathematics; BA - General Mathematics (UIVT-O) OBOR OECD: Pure mathematics; Pure mathematics (UIVT-O) http://www.sciencedirect.com/science/article/pii/S1571065317301452

  12. Rational choice in field archaelology

    Directory of Open Access Journals (Sweden)

    Cătălin Pavel

    2011-11-01

    Full Text Available In the present article I attempt to apply advances in the study of instrumental and epistemic rationality to field archaeology in order to gain insights into the ways archaeologists reason. The cognitive processes, particularly processes of decision making, that enable archaeologists to conduct the excavation in the trench have not been adequately studied so far. I take my cues from two different bodies of theory. I first inquire into the potential that rational choice theory (RCT may have in modeling archaeological behaviour, and I define subjective expected utility, which archaeologists attempt to maximize, in terms of knowledge acquisition and social gain. Following Elster’s criticism of RCT, I conclude that RCT’s standards for rational action do not correspond with those ostensibly used in field archaeology, but that instrumental rationality has a prominent role in the “archaeological experiment”. I further explore if models proposed as reaction to RCT may account for archaeological decision making. I focus on fast and frugal heuristics, and search for archaeological illustrations for some of the cognitive biases that are better documented in psychological literature. I document confirmation and congruence biases, the endowment effect, observer-expectancy bias, illusory correlation, clustering illusion, sunk cost bias, and anchoring, among others and I propose that some of these biases are used as cognitive tools by archaeologists at work and retain epistemic value. However, I find formal logic to be secondary in the development of archaeological reasoning, with default logic and defeasible logic being used instead. I emphasize scientific knowledge as an actively negotiated social product of human inquiry, and conclude that to describe rationality in field archaeology a bounded rationality model is the most promising avenue of investigation.

  13. Rationalizing the Promotion of Non-Rational Behaviors in Organizations.

    Science.gov (United States)

    Smith, Peter A. C.; Sharma, Meenakshi

    2002-01-01

    Organizations must balance rational/technical efficiency and emotions. Action learning has been proven to be effective for developing emotional openness in the workplace. Facilitators of action learning should draw upon the disciplines of counseling, Gestalt, psychodynamics, and Eastern philosophies. (Contains 23 references.) (SK)

  14. Re-visions of rationality?

    Science.gov (United States)

    Newell, Ben R

    2005-01-01

    The appeal of simple algorithms that take account of both the constraints of human cognitive capacity and the structure of environments has been an enduring theme in cognitive science. A novel version of such a boundedly rational perspective views the mind as containing an 'adaptive toolbox' of specialized cognitive heuristics suited to different problems. Although intuitively appealing, when this version was proposed, empirical evidence for the use of such heuristics was scant. I argue that in the light of empirical studies carried out since then, it is time this 'vision of rationality' was revised. An alternative view based on integrative models rather than collections of heuristics is proposed.

  15. Mental health as rational autonomy.

    Science.gov (United States)

    Edwards, R B

    1981-08-01

    Rather than eliminate the terms "mental health and illness" because of the grave moral consequences of psychiatric labeling, conservative definitions are proposed and defended. Mental health is rational autonomy, and mental illness is the sustained loss of such. Key terms are explained, advantages are explored, and alternative concepts are criticized. The value and descriptive components of all such definitions are consciously acknowledged. Where rational autonomy is intact, mental hospitals and psychotherapists should not think of themselves as treating an illness. Instead, they are functioning as applied axiologists, moral educators, spiritual mentors, etc. They deal with what Szasz has called "personal, social, and ethical problems in living." But mental illness is real.

  16. Public policy, rationality and reason

    Directory of Open Access Journals (Sweden)

    Rodolfo Canto Sáenz

    2015-07-01

    Full Text Available This work suggests the incorporation of practical reason in the design, implementation and evaluation of public policies, alongside instrumental rationality. It takes two proposals that today point in this direction: Rawls distinction between reasonable (practical reason and rational (instrumental reason and what this author calls the CI Procedure (categorical imperative procedure and Habermas model of deliberative democracy. The main conclusion is that the analysis of public policies can not be limited to rather narrow limits of science, but requires the contribution of political and moral philosophy.

  17. Libraries and Accessibility: Istanbul Public Libraries Case

    Directory of Open Access Journals (Sweden)

    Gül Yücel

    2016-12-01

    Full Text Available In the study; the assessment of accessibility has been conducted in Istanbul public libraries within the scope of public area. Public libraries commonly serve with its user of more than 20 million in total, spread to the general of Turkey, having more than one thousand branches in the centrums and having more than one million registered members. The building principles and standards covering the subjects such as the selection of place, historical and architectural specification of the region, distance to the centre of population and design in a way that the disabled people could benefit from the library services fully have been determined with regulations in the construction of new libraries. There are works for the existent libraries such as access for the disabled, fire safety precautions etc. within the scope of the related standards. Easy access by everyone is prioritized in the public libraries having a significant role in life-long learning. The purpose of the study is to develop solution suggestions for the accessibility problems in the public libraries. The study based on the eye inspection and assessments carried out within the scope of accessibility in the public libraries subsidiary to Istanbul Culture and Tourism Provincial Directorate Library and Publications Department within the provincial borders of Istanbul. The arrangements such as reading halls, study areas, book shelves etc. have been examined within the frame of accessible building standards. Building entrances, ramps and staircases, horizontal and vertical circulation of building etc. have been taken into consideration within the scope of accessible building standards. The subjects such as the reading and studying areas and book shelf arrangements for the library have been assessed within the scope of specific buildings. There are a total of 34 public libraries subsidiary to Istanbul Culture and Tourism Provincial Directorate on condition that 20 ea. of them are in the

  18. Enumeration of Combinatorial Classes of Single Variable Complex Polynomial Vector Fields

    DEFF Research Database (Denmark)

    Dias, Kealey

    A vector field in the space of degree d monic, centered single variable complex polynomial vector fields has a combinatorial structure which can be fully described by a combinatorial data set consisting of an equivalence relation and a marked subset on the integers mod 2d-2, satisfying certain...

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

    Science.gov (United States)

    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. Validation of an Instrument and Testing Protocol for Measuring the Combinatorial Analysis Schema.

    Science.gov (United States)

    Staver, John R.; Harty, Harold

    1979-01-01

    Designs a testing situation to examine the presence of combinatorial analysis, to establish construct validity in the use of an instrument, Combinatorial Analysis Behavior Observation Scheme (CABOS), and to investigate the presence of the schema in young adolescents. (Author/GA)

  1. Solving the neutron diffusion equation on combinatorial geometry computational cells for reactor physics calculations

    International Nuclear Information System (INIS)

    Azmy, Y. Y.

    2004-01-01

    An approach is developed for solving the neutron diffusion equation on combinatorial geometry computational cells, that is computational cells composed by combinatorial operations involving simple-shaped component cells. The only constraint on the component cells from which the combinatorial cells are assembled is that they possess a legitimate discretization of the underlying diffusion equation. We use the Finite Difference (FD) approximation of the x, y-geometry diffusion equation in this work. Performing the same combinatorial operations involved in composing the combinatorial cell on these discrete-variable equations yields equations that employ new discrete variables defined only on the combinatorial cell's volume and faces. The only approximation involved in this process, beyond the truncation error committed in discretizing the diffusion equation over each component cell, is a consistent-order Legendre series expansion. Preliminary results for simple configurations establish the accuracy of the solution to the combinatorial geometry solution compared to straight FD as the system dimensions decrease. Furthermore numerical results validate the consistent Legendre-series expansion order by illustrating the second order accuracy of the combinatorial geometry solution, the same as standard FD. Nevertheless the magnitude of the error for the new approach is larger than FD's since it incorporates the additional truncated series approximation. (authors)

  2. An Investigation into Post-Secondary Students' Understanding of Combinatorial Questions

    Science.gov (United States)

    Bulone, Vincent William

    2017-01-01

    The purpose of this dissertation was to study aspects of how post-secondary students understand combinatorial problems. Within this dissertation, I considered understanding through two different lenses: i) student connections to previous problems; and ii) common combinatorial distinctions such as ordered versus unordered and repetitive versus…

  3. Optimal public rationing and price response.

    Science.gov (United States)

    Grassi, Simona; Ma, Ching-To Albert

    2011-12-01

    We study optimal public health care rationing and private sector price responses. Consumers differ in their wealth and illness severity (defined as treatment cost). Due to a limited budget, some consumers must be rationed. Rationed consumers may purchase from a monopolistic private market. We consider two information regimes. In the first, the public supplier rations consumers according to their wealth information (means testing). In equilibrium, the public supplier must ration both rich and poor consumers. Rationing some poor consumers implements price reduction in the private market. In the second information regime, the public supplier rations consumers according to consumers' wealth and cost information. In equilibrium, consumers are allocated the good if and only if their costs are below a threshold (cost effectiveness). Rationing based on cost results in higher equilibrium consumer surplus than rationing based on wealth. Copyright © 2011 Elsevier B.V. All rights reserved.

  4. ON range searching in the group model and combinatorial discrepancy

    DEFF Research Database (Denmark)

    Larsen, Kasper Green

    2014-01-01

    In this paper we establish an intimate connection between dynamic range searching in the group model and combinatorial discrepancy. Our result states that, for a broad class of range searching data structures (including all known upper bounds), it must hold that $t_u t_q=\\Omega(\\mbox{disc}^2......)$, where $t_u$ is the worst case update time, $t_q$ is the worst case query time, and disc is the combinatorial discrepancy of the range searching problem in question. This relation immediately implies a whole range of exceptionally high and near-tight lower bounds for all of the basic range searching...... problems. We list a few of them in the following: (1) For $d$-dimensional halfspace range searching, we get a lower bound of $t_u t_q=\\Omega(n^{1-1/d})$. This comes within an lg lg $n$ factor of the best known upper bound. (2) For orthogonal range searching, we get a lower bound of $t_u t...

  5. Combinatorial therapy discovery using mixed integer linear programming.

    Science.gov (United States)

    Pang, Kaifang; Wan, Ying-Wooi; Choi, William T; Donehower, Lawrence A; Sun, Jingchun; Pant, Dhruv; Liu, Zhandong

    2014-05-15

    Combinatorial therapies play increasingly important roles in combating complex diseases. Owing to the huge cost associated with experimental methods in identifying optimal drug combinations, computational approaches can provide a guide to limit the search space and reduce cost. However, few computational approaches have been developed for this purpose, and thus there is a great need of new algorithms for drug combination prediction. Here we proposed to formulate the optimal combinatorial therapy problem into two complementary mathematical algorithms, Balanced Target Set Cover (BTSC) and Minimum Off-Target Set Cover (MOTSC). Given a disease gene set, BTSC seeks a balanced solution that maximizes the coverage on the disease genes and minimizes the off-target hits at the same time. MOTSC seeks a full coverage on the disease gene set while minimizing the off-target set. Through simulation, both BTSC and MOTSC demonstrated a much faster running time over exhaustive search with the same accuracy. When applied to real disease gene sets, our algorithms not only identified known drug combinations, but also predicted novel drug combinations that are worth further testing. In addition, we developed a web-based tool to allow users to iteratively search for optimal drug combinations given a user-defined gene set. Our tool is freely available for noncommercial use at http://www.drug.liuzlab.org/. zhandong.liu@bcm.edu Supplementary data are available at Bioinformatics online.

  6. Causal gene identification using combinatorial V-structure search.

    Science.gov (United States)

    Cai, Ruichu; Zhang, Zhenjie; Hao, Zhifeng

    2013-07-01

    With the advances of biomedical techniques in the last decade, the costs of human genomic sequencing and genomic activity monitoring are coming down rapidly. To support the huge genome-based business in the near future, researchers are eager to find killer applications based on human genome information. Causal gene identification is one of the most promising applications, which may help the potential patients to estimate the risk of certain genetic diseases and locate the target gene for further genetic therapy. Unfortunately, existing pattern recognition techniques, such as Bayesian networks, cannot be directly applied to find the accurate causal relationship between genes and diseases. This is mainly due to the insufficient number of samples and the extremely high dimensionality of the gene space. In this paper, we present the first practical solution to causal gene identification, utilizing a new combinatorial formulation over V-Structures commonly used in conventional Bayesian networks, by exploring the combinations of significant V-Structures. We prove the NP-hardness of the combinatorial search problem under a general settings on the significance measure on the V-Structures, and present a greedy algorithm to find sub-optimal results. Extensive experiments show that our proposal is both scalable and effective, particularly with interesting findings on the causal genes over real human genome data. Copyright © 2013 Elsevier Ltd. All rights reserved.

  7. A combinatorial approach to diffeomorphism invariant quantum gauge theories

    International Nuclear Information System (INIS)

    Zapata, J.A.

    1997-01-01

    Quantum gauge theory in the connection representation uses functions of holonomies as configuration observables. Physical observables (gauge and diffeomorphism invariant) are represented in the Hilbert space of physical states; physical states are gauge and diffeomorphism invariant distributions on the space of functions of the holonomies of the edges of a certain family of graphs. Then a family of graphs embedded in the space manifold (satisfying certain properties) induces a representation of the algebra of physical observables. We construct a quantum model from the set of piecewise linear graphs on a piecewise linear manifold, and another manifestly combinatorial model from graphs defined on a sequence of increasingly refined simplicial complexes. Even though the two models are different at the kinematical level, they provide unitarily equivalent representations of the algebra of physical observables in separable Hilbert spaces of physical states (their s-knot basis is countable). Hence, the combinatorial framework is compatible with the usual interpretation of quantum field theory. copyright 1997 American Institute of Physics

  8. A combinatorial approach to the design of vaccines.

    Science.gov (United States)

    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.

  9. Dissection of combinatorial control by the Met4 transcriptional complex.

    Science.gov (United States)

    Lee, Traci A; Jorgensen, Paul; Bognar, Andrew L; Peyraud, Caroline; Thomas, Dominique; Tyers, Mike

    2010-02-01

    Met4 is the transcriptional activator of the sulfur metabolic network in Saccharomyces cerevisiae. Lacking DNA-binding ability, Met4 must interact with proteins called Met4 cofactors to target promoters for transcription. Two types of DNA-binding cofactors (Cbf1 and Met31/Met32) recruit Met4 to promoters and one cofactor (Met28) stabilizes the DNA-bound Met4 complexes. To dissect this combinatorial system, we systematically deleted each category of cofactor(s) and analyzed Met4-activated transcription on a genome-wide scale. We defined a core regulon for Met4, consisting of 45 target genes. Deletion of both Met31 and Met32 eliminated activation of the core regulon, whereas loss of Met28 or Cbf1 interfered with only a subset of targets that map to distinct sectors of the sulfur metabolic network. These transcriptional dependencies roughly correlated with the presence of Cbf1 promoter motifs. Quantitative analysis of in vivo promoter binding properties indicated varying levels of cooperativity and interdependency exists between members of this combinatorial system. Cbf1 was the only cofactor to remain fully bound to target promoters under all conditions, whereas other factors exhibited different degrees of regulated binding in a promoter-specific fashion. Taken together, Met4 cofactors use a variety of mechanisms to allow differential transcription of target genes in response to various cues.

  10. Teaching Rational Decision-Making.

    Science.gov (United States)

    Woolever, Roberts

    1978-01-01

    Presented is an outline of a college course, "Education in American Society," that focused on teaching students rational decision-making skills while examining current issues in American Education. The outline is followed by student comments, reactions, and evaluations of the course. (JMD)

  11. Rational Suicide among the Elderly.

    Science.gov (United States)

    Humphry, Derek

    1992-01-01

    Contends that old age, in and of itself, should never need to be a cause for self-destruction. Further argues that suicide and assisted suicide carried out in the face of terminal illness causing unbearable suffering should be ethically and legally acceptable. Outlines a perspective on rational suicide among the elderly. (Author/NB)

  12. On a CO2 ration

    International Nuclear Information System (INIS)

    De Wit, P.

    2003-01-01

    In 2 years all the large energy companies in the European Union will have a CO2 ration, including a system to trade a shortage or surplus of emission rights. A cost effective system to reduce emission, provided that the government does not auction the emission rights [nl

  13. On Counting the Rational Numbers

    Science.gov (United States)

    Almada, Carlos

    2010-01-01

    In this study, we show how to construct a function from the set N of natural numbers that explicitly counts the set Q[superscript +] of all positive rational numbers using a very intuitive approach. The function has the appeal of Cantor's function and it has the advantage that any high school student can understand the main idea at a glance…

  14. Personal Autonomy and Rational Suicide.

    Science.gov (United States)

    Webber, May A.; Shulman, Ernest

    That certain suicides (which can be designated as rational) ought not to be interfered with is closely tied to the notion of the "right to autonomy." Specifically it is because the individual in question has this right that interference is prohibited. A proper understanding of the right to autonomy, while essential to understanding why…

  15. Libraries serving dialogue

    CERN Document Server

    Dupont, Odile

    2014-01-01

    This book based on experiences of libraries serving interreligious dialogue, presents themes like library tools serving dialogue between cultures, collections dialoguing, children and young adults dialoguing beyond borders, story telling as dialog, librarians serving interreligious dialogue.

  16. Israeli Special Libraries

    Science.gov (United States)

    Foster, Barbara

    1974-01-01

    Israel is sprinkled with a noteworthy representation of special libraries which run the gamut from modest kibbutz efforts to highly technical scientific and humanities libraries. A few examples are discussed here. (Author/CH)

  17. Marketing library and information services in academic libraries in ...

    African Journals Online (AJOL)

    Marketing library and information services in academic libraries in Niger State, Nigeria. ... This study was designed to investigate the marketing of library services in academic libraries in Niger state, ... EMAIL FULL TEXT EMAIL FULL TEXT

  18. The alternative library

    OpenAIRE

    Collinson, Timothy; Williams, A.

    2004-01-01

    Much time and effort has been devoted to designing and developing library Web sites that are easy to navigate by both new students and experienced researchers. In a review of the Southampton Institute Library it was decided that in addition to updating the existing homepage an alternative would be offered. Drawing on theory relating to user interface design, learning styles and creative thinking, an Alternative Library navigation system was added to the more traditional library homepage. The ...

  19. FENDL multigroup libraries

    International Nuclear Information System (INIS)

    Ganesan, S.; Muir, D.W.

    1992-01-01

    Selected neutron reaction nuclear data libraries and photon-atomic interaction cross section libraries for elements of interest to the IAEA's program on Fusion Evaluated Nuclear Data Library (FENDL) have been processed into MATXSR format using the NJOY system on the VAX4000 computer of the IAEA. This document lists the resulting multigroup data libraries. All the multigroup data generated are available cost-free upon request from the IAEA Nuclear Data Section. (author). 9 refs

  20. Combinatorial assembly of small molecules into bivalent antagonists of TrkC or TrkA receptors.

    Directory of Open Access Journals (Sweden)

    Fouad Brahimi

    Full Text Available A library of peptidomimetics was assembled combinatorially into dimers on a triazine-based core. The pharmacophore corresponds to β-turns of the neurotrophin polypeptides neurotrophin-3 (NT-3, nerve growth factor (NGF, or brain-derived neurotrophic factor (BDNF. These are the natural ligands for TrkC, TrkA, and TrkB receptors, respectively. The linker length and the side-chain orientation of each monomer within the bivalent mimics were systematically altered, and the impact of these changes on the function of each ligand was evaluated. While the monovalent peptidomimetics had no detectable binding or bioactivity, four bivalent peptidomimetics (2c, 2d, 2e, 3f are selective TrkC ligands with antagonistic activity, and two bivalent peptidomimetics (1a, 1b are TrkC and TrkA ligands with antagonistic activity. All these bivalent compounds block ligand-dependent receptor activation and cell survival, without affecting neuritogenic differentiation. This work adds to our understanding of how the neurotrophins function through Trk receptors, and demonstrates that peptidomimetics can be designed to selectively disturb specific biological signals, and may be used as pharmacological probes or as therapeutic leads. The concept of altering side-chain, linker length, and sequence orientation of a subunit within a pharmacophore provides an easy modular approach to generate larger libraries with diversified bioactivity.

  1. Changing State Digital Libraries

    Science.gov (United States)

    Pappas, Marjorie L.

    2006-01-01

    Research has shown that state virtual or digital libraries are evolving into websites that are loaded with free resources, subscription databases, and instructional tools. In this article, the author explores these evolving libraries based on the following questions: (1) How user-friendly are the state digital libraries?; (2) How do state digital…

  2. School Libraries and Innovation

    Science.gov (United States)

    McGrath, Kevin G.

    2015-01-01

    School library programs have measured success by improved test scores. But how do next-generation school libraries demonstrate success as they strive to be centers of innovation and creativity? These libraries offer solutions for school leaders who struggle to restructure existing systems built around traditional silos of learning (subjects and…

  3. Reforming Prison Libraries.

    Science.gov (United States)

    Coyle, William J.

    1989-01-01

    Discusses the current widespread acceptance of the public library model for prison libraries, in which preferences of the inmates are the chief consideration in programing and collection development. It is argued that this model results in recreational programs and collections that fail to fulfill the prison library's role in education and…

  4. LANL Research Library

    Science.gov (United States)

    Los Alamos National Laboratory The LANL Research Library website has been moved to http ://www.lanl.gov/library/. Please update your bookmarks. If you are not redirected to the new location within 10 http:// | Last Modified: Send email to the Library

  5. Joint-Use Libraries

    Science.gov (United States)

    Casstevens, Susan

    2017-01-01

    The joint-use library is a place where people of all ages, interests, and income levels can find items of interest at no personal cost. The mission of A. H. Meadows Public and High School Library in Midlothian, Texas, is to offer what other public libraries provide: educational and entertainment resources to a community. Yet, the staff also wants…

  6. Learning Boost C++ libraries

    CERN Document Server

    Mukherjee, Arindam

    2015-01-01

    If you are a C++ programmer who has never used Boost libraries before, this book will get you up-to-speed with using them. Whether you are developing new C++ software or maintaining existing code written using Boost libraries, this hands-on introduction will help you decide on the right library and techniques to solve your practical programming problems.

  7. Marketing and Library Management.

    Science.gov (United States)

    Murphy, Kurt R.

    1991-01-01

    Examines the role of marketing in the management of libraries. The role of public relations (PR) in the total marketing concept is discussed, surveys that have explored PR efforts in academic and public libraries are described, and changes affecting libraries that marketing efforts could help to manage are discussed. (seven references) (LRW)

  8. Virtual Libraries: Service Realities.

    Science.gov (United States)

    Novak, Jan

    2002-01-01

    Discussion of changes in society that have resulted from information and communication technologies focuses on changes in libraries and a new market for library services with new styles of clients. Highlights client service issues to be considered when transitioning to a virtual library situation. (Author/LRW)

  9. Merchandising Your Library.

    Science.gov (United States)

    Sivulich, Kenneth G.

    1989-01-01

    Discusses library circulation figures as a reflection of the success of library services and describes merchandising techniques that have produced a 137 percent circulation increase at Queens Borough Public Library over the past seven years. Merchandising techniques such as minibranches, displays, signage, dumps, and modified shelving are…

  10. Editorial Library: User Survey.

    Science.gov (United States)

    Surace, Cecily J.

    This report presents the findings of a survey conducted by the editorial library of the Los Angeles Times to measure usage and satisfaction with library service, provide background information on library user characteristics, collect information on patterns of use of the Times' clipping files, relate data on usage and satisfaction parameters to…

  11. Marketing Academic Libraries

    Science.gov (United States)

    Mallon, Melissa, Ed.

    2013-01-01

    Ask any academic librarian if marketing their library and its services is an important task, and the answer will most likely be a resounding "yes!" Particularly in economically troubled times, librarians are increasingly called upon to promote their services and defend their library's worth. Since few academic libraries have in-house marketing…

  12. Development of combinatorial chemistry methods for coatings: high-throughput adhesion evaluation and scale-up of combinatorial leads.

    Science.gov (United States)

    Potyrailo, Radislav A; Chisholm, Bret J; Morris, William G; Cawse, James N; Flanagan, William P; Hassib, Lamyaa; Molaison, Chris A; Ezbiansky, Karin; Medford, George; Reitz, Hariklia

    2003-01-01

    Coupling of combinatorial chemistry methods with high-throughput (HT) performance testing and measurements of resulting properties has provided a powerful set of tools for the 10-fold accelerated discovery of new high-performance coating materials for automotive applications. Our approach replaces labor-intensive steps with automated systems for evaluation of adhesion of 8 x 6 arrays of coating elements that are discretely deposited on a single 9 x 12 cm plastic substrate. Performance of coatings is evaluated with respect to their resistance to adhesion loss, because this parameter is one of the primary considerations in end-use automotive applications. Our HT adhesion evaluation provides previously unavailable capabilities of high speed and reproducibility of testing by using a robotic automation, an expanded range of types of tested coatings by using the coating tagging strategy, and an improved quantitation by using high signal-to-noise automatic imaging. Upon testing, the coatings undergo changes that are impossible to quantitatively predict using existing knowledge. Using our HT methodology, we have developed several coatings leads. These HT screening results for the best coating compositions have been validated on the traditional scales of coating formulation and adhesion loss testing. These validation results have confirmed the superb performance of combinatorially developed coatings over conventional coatings on the traditional scale.

  13. FY 2009 Public Libraries Survey

    Data.gov (United States)

    Institute of Museum and Library Services — Dig into FY 2009 data on public library systems (referred to as administrative entities in the Public Libraries Survey) and main libraries, branches, and bookmobiles...

  14. FY 2010 Public Libraries Survey

    Data.gov (United States)

    Institute of Museum and Library Services — Dig into FY 2010 data on public library systems (referred to as administrative entities in the Public Libraries Survey) and main libraries, branches, and bookmobiles...

  15. FY 2011 Public Libraries Survey

    Data.gov (United States)

    Institute of Museum and Library Services — Dig into FY 2011 data on public library systems (referred to as administrative entities in the Public Libraries Survey) and main libraries, branches, and bookmobiles...

  16. FY 2008 Public Libraries Survey

    Data.gov (United States)

    Institute of Museum and Library Services — Dig into FY 2008 data on public library systems (referred to as administrative entities in the Public Libraries Survey) and main libraries, branches, and bookmobiles...

  17. German Librarianship and Munich Libraries

    Directory of Open Access Journals (Sweden)

    Osman Ümit Özen

    1994-06-01

    Full Text Available There are 27 municipal libraries including the Central Public Library in Munich. The other important libraries in the city are Bayern State National Library, Maximillian University Library, a technical highschool library and the "Deutsches Musuem" Library. All these libraries are financed locally. The author introduces these libraries briefly and compares German libraries with Turkish libraries. He concludes that although theoretically there are not distinctive differences, in practice, buildings and their layout are better in Germany where more variety of services are offered. In Turkey standardization has not been realized yet. Turkey needs to computerize and network to improve the services offered in an efficient way.

  18. Library/vendor relationships

    CERN Document Server

    Brooks, Sam

    2014-01-01

    A view of the mutual dependence between libraries and vendorsAs technology advances, libraries are forced to reach beyond their own resources to find effective ways to maintain accuracy and superior service levels. Vendors provide databases and integrated library systems that perform those functions for profit. Library/Vendor Relationships examines the increasing cooperation in which libraries find they must participate in, and vice versa, with the vendors that provide system infrastructure and software. Expert contributors provide insights from all sides of this unique collaboration, offering

  19. Teleporting the library?

    DEFF Research Database (Denmark)

    Heilesen, Simon

    2009-01-01

    In 2007, six Danish public libraries established a virtual library, Info Island DK, in Second Life. This article discusses the library project in terms of design. The design processes include the planning and implementation of the virtual library structure and its equipment, as well...... as the organizing and carrying out of activities in the virtual setting. It will be argued that, to a large extent, conventions have determined design and use of the virtual library, and also that design has had an impact on the attitudes and understanding of the participants....

  20. Rationality, mental causation and social sciences

    Directory of Open Access Journals (Sweden)

    Mladenović Ivan

    2009-01-01

    Full Text Available The aim of this paper is to investigate the role of mental causation in the context of rational choice theory. The author defends psychological aspect of rational explanation against the challenge of contemporary reductive materialism.