WorldWideScience

Sample records for block-transitive combinatorial designs

  1. 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

  2. An explicit combinatorial design

    CERN Document Server

    Ma, Xiongfeng

    2011-01-01

    A combinatorial design is a family of sets that are almost disjoint, which is applied in pseudo random number generations and randomness extractions. The parameter, $\\rho$, quantifying the overlap between the sets within the family, is directly related to the length of a random seed needed and the efficiency of an extractor. Nisan and Wigderson proposed an explicit construction of designs in 1994. Later in 2003, Hartman and Raz proved a bound of $\\rho\\le e^2$ for the Nisan-Wigderson construction. In this work, we prove a tighter bound of $\\rhodesign with $\\rho=1$.

  3. 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...

  4. 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.

  5. 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.

  6. Methods for combinatorial and parallel library design.

    Science.gov (United States)

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

    2011-01-01

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

  7. COMBINATORIAL DESIGN APPROACHES FOR TEST GENERATION

    Institute of Scientific and Technical Information of China (English)

    Shi Liang; Xu Baowen; Nie Changhai

    2005-01-01

    The n-way combination testing is a specification-based testing criterion, which requires that for a system consisted of a few parameters, every combination of valid values of arbitrary n(n ≥ 2) parameters be covered by at least one test. This letter proposed two different test generation algorithms based on combinatorial design for the n-way coverage criterion. The automatic test generators are implemented and some valuable empirical results are obtained.

  8. Combinatorial design of textured mechanical metamaterials.

    Science.gov (United States)

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

    2016-07-28

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

  9. Combinatorial design of textured mechanical metamaterials

    Science.gov (United States)

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

    2016-07-01

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

  10. Key Updating Methods for Combinatorial Design Based Key Management Schemes

    Directory of Open Access Journals (Sweden)

    Chonghuan Xu

    2014-01-01

    Full Text Available Wireless sensor network (WSN has become one of the most promising network technologies for many useful applications. However, for the lack of resources, it is different but important to ensure the security of the WSNs. Key management is a corner stone on which to build secure WSNs for it has a fundamental role in confidentiality, authentication, and so on. Combinatorial design theory has been used to generate good-designed key rings for each sensor node in WSNs. A large number of combinatorial design based key management schemes have been proposed but none of them have taken key updating into consideration. In this paper, we point out the essence of key updating for the unital design based key management scheme and propose two key updating methods; then, we conduct performance analysis on the two methods from three aspects; at last, we generalize the two methods to other combinatorial design based key management schemes and enhance the second method.

  11. The existence of block-transitive 7-(v,k,λ) designs with%λ≤5的区传递7-(v,k,λ)设计的存在性

    Institute of Scientific and Technical Information of China (English)

    龚罗中; 刘伟俊

    2013-01-01

    In 1993,CAMERON and PRAEGER proved that there are no nontrivial block-transitive t-designs with t >7 and conjectured that there are no nontrivial block-transitive 6-designs.But the existence of block-transitive 7-designs is still an open problem.In this paper,this open problem is studied and the fact that there are no nontrivial block-transitive 7-(v,k,λ) designs with γ≤5 is proved.%1993年,CAMERON和PRAGEGER证明了不存在t>7的非平凡的区传递t-设计,并且猜想不存在非平凡的区传递6设计.然而区传递7-设计的存在性仍然是一个公开的问题.本文研究了这一公开问题,证明了当λ≤5时不存在非平凡的区传递7-(v,k,λ)设计.

  12. Structure-based design of combinatorial mutagenesis libraries.

    Science.gov (United States)

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

    2015-05-01

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

  13. 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....

  14. 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....

  15. Constructions for Anonymous Secret Sharing Schemes Using Combinatorial Designs

    Institute of Scientific and Technical Information of China (English)

    Ying-pu Deng; Li-feng Guo; Mu-lan Liu

    2007-01-01

    In an anonymous secret sharing scheme the secret can be reconstructed without knowledge of which participants hold which shares. In this paper some constructions of anonymous secret sharing schemes with 2 thresholds by using combinatorial designs are given. Let υ(t, ω, q) denote the minimum size of the set of shares of a perfect anonymous (t, ω) threshold secret sharing scheme with q secrets. In this paper we prove that υ(t, ω, q) = Θ(q) if t and ω are fixed and that the lower bound of the size of the set of shares in [4] is not optimal under certain condition.

  16. Multifunctional combinatorial-designed nanoparticles for nucleic acid therapy

    Science.gov (United States)

    Amiji, Mansoor M.

    2016-05-01

    Recent advances in biomedical sciences, especially in the field of human genetics, is increasingly considered to facilitate a new frontier in development of novel disease-modifying therapeutics. One of major challenges in the development of nucleic acid therapeutics is efficient and specific delivery of the molecules to the target tissue and cell upon systemic administration. In this report, I discuss our strategy to develop combinatorial-designed multifunctional nanoparticle assemblies based on natural biocompatible and biodegradable polymers for nucleic acid delivery in: (1) overcoming tumor drug resistance and (2) genetic modulation of macrophage functional phenotype from M1 to M2 in treatment of inflammatory diseases.

  17. ProSAR: a new methodology for combinatorial library design.

    Science.gov (United States)

    Chen, Hongming; Börjesson, Ulf; Engkvist, Ola; Kogej, Thierry; Svensson, Mats A; Blomberg, Niklas; Weigelt, Dirk; Burrows, Jeremy N; Lange, Tim

    2009-03-01

    A method is introduced for performing reagent selection for chemical library design based on topological (2D) pharmacophore fingerprints. Optimal reagent selection is achieved by optimizing the Shannon entropy of the 2D pharmacophore distribution for the reagent set. The method, termed ProSAR, is therefore expected to enumerate compounds that could serve as a good starting point for deriving a structure activity relationship (SAR) in combinatorial library design. This methodology is exemplified by library design examples where the active compounds were already known. The results show that most of the pharmacophores on the substituents for the active compounds are covered by the designed library. This strategy is further expanded to include product property profiles for aqueous solubility, hERG risk assessment, etc. in the optimization process so that the reagent pharmacophore diversity and the product property profile are optimized simultaneously via a genetic algorithm. This strategy is applied to a two-dimensional library design example and compared with libraries designed by a diversity based strategy which minimizes the average ensemble Tanimoto similarity. Our results show that by using the PSAR methodology, libraries can be designed with simultaneously good pharmacophore coverage and product property profile.

  18. Development of Combinatorial Methods for Alloy Design and Optimization

    Energy Technology Data Exchange (ETDEWEB)

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

    2005-07-01

    The primary goal of this research was to develop a comprehensive methodology for designing and optimizing metallic alloys by combinatorial principles. Because conventional techniques for alloy preparation are unavoidably restrictive in the range of alloy composition that can be examined, combinatorial methods promise to significantly reduce the time, energy, and expense needed for alloy design. Combinatorial methods can be developed not only to optimize existing alloys, but to explore and develop new ones as well. The scientific approach involved fabricating an alloy specimen with a continuous distribution of binary and ternary alloy compositions across its surface--an ''alloy library''--and then using spatially resolved probing techniques to characterize its structure, composition, and relevant properties. The three specific objectives of the project were: (1) to devise means by which simple test specimens with a library of alloy compositions spanning the range interest can be produced; (2) to assess how well the properties of the combinatorial specimen reproduce those of the conventionally processed alloys; and (3) to devise screening tools which can be used to rapidly assess the important properties of the alloys. As proof of principle, the methodology was applied to the Fe-Ni-Cr ternary alloy system that constitutes many commercially important materials such as stainless steels and the H-series and C-series heat and corrosion resistant casting alloys. Three different techniques were developed for making alloy libraries: (1) vapor deposition of discrete thin films on an appropriate substrate and then alloying them together by solid-state diffusion; (2) co-deposition of the alloying elements from three separate magnetron sputtering sources onto an inert substrate; and (3) localized melting of thin films with a focused electron-beam welding system. Each of the techniques was found to have its own advantages and disadvantages. A new and very

  19. 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.

  20. 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.

  1. Application of self-organizing maps in compounds pattern recognition and combinatorial library design.

    Science.gov (United States)

    Yan, Aixia

    2006-07-01

    In the computer-aided drug design, in order to find some new leads from a large library of compounds, the pattern recognition study of the diversity and similarity assessment of the chemical compounds is required; meanwhile in the combinatorial library design, more attention is given to design target focusing library along with diversity and drug-likeness criteria. This review presents the current state-of-art applications of Kohonen self-organizing maps (SOM) for studying the compounds pattern recognition, comparing the property of molecular surfaces, distinguishing drug-like and nondrug-like molecules, splitting a dataset into the proper training and test sets before constructing a QSAR (Quantitative Structural-Activity Relationship) model, and also for the combinatorial libraries comparison and the combinatorial library design. The Kohonen self-organizing map will continue to play an important role in drug discovery and library design.

  2. Analysis of selection methodologies for combinatorial library design.

    Science.gov (United States)

    Pascual, Rosalia; Borrell, José I; Teixidó, Jordi

    2003-01-01

    We have implemented and adapted in Pralins (Program for Rational Analysis of Libraries in silico), the most popular sparse (cherry picking) and full array (sublibrary) selection algorithms: hierarchical clustering, k-means clustering, Optimum Binning, Jarvis Patrick, Pral-SE (partitioning techniques) and MaxSum, MaxMin, MaxMin averaged, DN2, CTD (distance-based methods). We have validated the program with an already synthesized three-component combinatorial library of FXR partial agonists characterized by standard computational chemistry descriptors as case study. This has let us analyze the goodness of both the partitioning techniques for space division and all the selection methodologies with respect to representativity in terms of population and space coverage for different selection sizes. Within the chemical space analyzed, both hierarchical clustering and Optimum Binning division strategies are found to be the most advantageous reference space divisions to be used in the subsequent population and space coverage studies. Complete hierarchical clustering appears also to be the preferred selection methodology for both sparse and full array problems. The full array restriction fulfillment can easily be overcome by convenient optimization algorithms that allow optimal reagent selection preserving > 90% of the population coverage.

  3. Rational principles of compound selection for combinatorial library design.

    Science.gov (United States)

    Tropsha, Alexander; Zheng, Weifan

    2002-03-01

    It is practically impossible in a short period of time to synthesize and test all compounds in any large exhaustive chemical library. We discuss rational approaches to selecting representative subsets of virtual libraries that help direct experimental synthetic efforts for both targeted and diverse library design. For targeted library design, we consider principles based on the similarity to lead molecules. In the case of diverse library design, we discuss algorithms aimed at the selection of both diverse and representative subsets of the entire chemical library space. We illustrate methodologies with several practical examples.

  4. Combinatorial problems arising from pooling designs for dna library screening

    Directory of Open Access Journals (Sweden)

    Masakazu Jimbo

    2004-11-01

    Full Text Available Colbourn (1999 developed some strategy for nonadaptive group testing when the items are linearly ordered and the positive items form a consecutive subset of all items.Müller and Jimbo (2004 improved his strategy by introducing the concept of 2-consecutive positive detectable matrices (2CPD-matrix requiring that all columns and bitwise OR-sum of each two consecutive columns are pairwise distinct. Such a matrix is called maximal if it has a maximal possible number of columns with respect to some obvious constraints. Using a recursive construction they proved the existence of maximal 2CPD-matrices for any column size m ∈ N except for the case m = 3. Moreover, maximal 2CPD-matrices such that each column is of some fixed constant weight areconstructed. This leads to pooling designs, where each item appears in the same number of pools and all pools are of the same size.Secondly, we investigate 2CPD-matrices of some constant column weight τ ∈ N. We give some recursive construction of such matrices having the maximal possible number of columns. Thirdly, error correction capability of group testing procedures is essential in view of applications such as DNA library screening. We consider a error correcting 2CPD-matrices.

  5. Absolutely Maximally Entangled states, combinatorial designs and multi-unitary matrices

    CERN Document Server

    Goyeneche, Dardo; Latorre, José I; Riera, Arnau; Życzkowski, Karol

    2015-01-01

    Absolutely Maximally Entangled (AME) states are those multipartite quantum states that carry absolute maximum entanglement in all possible partitions. AME states are known to play a relevant role in multipartite teleportation, in quantum secret sharing and they provide the basis novel tensor networks related to holography. We present alternative constructions of AME states and show their link with combinatorial designs. We also analyze a key property of AME, namely their relation to tensors that can be understood as unitary transformations in every of its bi-partitions. We call this property multi-unitarity.

  6. Combinatorial Origami

    Science.gov (United States)

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

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

  7. A Rapid Python-Based Methodology for Target-Focused Combinatorial Library Design.

    Science.gov (United States)

    Li, Shiliang; Song, Yuwei; Liu, Xiaofeng; Li, Honglin

    2016-01-01

    The chemical space is so vast that only a small portion of it has been examined. As a complementary approach to systematically probe the chemical space, virtual combinatorial library design has extended enormous impacts on generating novel and diverse structures for drug discovery. Despite the favorable contributions, high attrition rates in drug development that mainly resulted from lack of efficacy and side effects make it increasingly challenging to discover good chemical starting points. In most cases, focused libraries, which are restricted to particular regions of the chemical space, are deftly exploited to maximize hit rate and improve efficiency at the beginning of the drug discovery and drug development pipeline. This paper presented a valid methodology for fast target-focused combinatorial library design in both reaction-based and production-based ways with the library creating rates of approximately 70,000 molecules per second. Simple, quick and convenient operating procedures are the specific features of the method. SHAFTS, a hybrid 3D similarity calculation software, was embedded to help refine the size of the libraries and improve hit rates. Two target-focused (p38-focused and COX2-focused) libraries were constructed efficiently in this study. This rapid library enumeration method is portable and applicable to any other targets for good chemical starting points identification collaborated with either structure-based or ligand-based virtual screening.

  8. Predictive Array Design. A method for sampling combinatorial chemistry library space.

    Science.gov (United States)

    Lipkin, M J; Rose, V S; Wood, J

    2002-01-01

    A method, Predictive Array Design, is presented for sampling combinatorial chemistry space and selecting a subarray for synthesis based on the experimental design method of Latin Squares. The method is appropriate for libraries with three sites of variation. Libraries with four sites of variation can be designed using the Graeco-Latin Square. Simulated annealing is used to optimise the physicochemical property profile of the sub-array. The sub-array can be used to make predictions of the activity of compounds in the all combinations array if we assume each monomer has a relatively constant contribution to activity and that the activity of a compound is composed of the sum of the activities of its constitutive monomers.

  9. A Structure-Based Design Protocol for Optimizing Combinatorial Protein Libraries.

    Science.gov (United States)

    Lunt, Mark W; Snow, Christopher D

    2016-01-01

    Protein variant libraries created via site-directed mutagenesis are a powerful approach to engineer improved proteins for numerous applications such as altering enzyme substrate specificity. Conventional libraries commonly use a brute force approach: saturation mutagenesis via degenerate codons that encode all 20 natural amino acids. In contrast, this chapter describes a protocol for designing "smarter" degenerate codon libraries via direct combinatorial optimization in "library space." Several case studies illustrate how it is possible to design degenerate codon libraries that are highly enriched for favorable, low-energy sequences as assessed using a standard all-atom scoring function. There is much to gain for experimental protein engineering laboratories willing to think beyond site saturation mutagenesis. In the common case that the exact experimental screening budget is not fixed, it is particularly helpful to perform a Pareto analysis to inspect favorable libraries at a range of possible library sizes.

  10. Design of dimerization inhibitors of HIV-1 aspartic proteinase: A computer-based combinatorial approach

    Science.gov (United States)

    Caflisch, Amedeo; Schramm, Hans J.; Karplus, Martin

    2000-02-01

    Inhibition of dimerization to the active form of the HIV-1 aspartic proteinase (HIV-1 PR) may be a way to decrease the probability of escape mutations for this viral protein. The Multiple Copy Simultaneous Search (MCSS) methodology was used to generate functionality maps for the dimerization interface of HIV-1 PR. The positions of the MCSS minima of 19 organic fragments, once postprocessed to take into account solvation effects, are in good agreement with experimental data on peptides that bind to the interface. The MCSS minima combined with an approach for computational combinatorial ligand design yielded a set of modified HIV-1 PR C-terminal peptides that are similar to known nanomolar inhibitors of HIV-1 PR dimerization. A number of N-substituted 2,5-diketopiperazines are predicted to be potential dimerization inhibitors of HIV-1 PR.

  11. Boronic acid functionalized peptidyl synthetic lectins: Combinatorial library design, peptide sequencing, and selective glycoprotein recognition

    Science.gov (United States)

    Bicker, Kevin L.; Sun, Jing; Lavigne, John J.; Thompson, Paul R.

    2011-01-01

    Aberrant glycosylation of cell membrane and secreted glycoproteins is a hallmark of various disease states, including cancer. The natural lectins currently used in the recognition of these glycoproteins are costly, difficult to produce, and unstable towards rigorous use. Herein we describe the design and synthesis of several boronic acid functionalized peptide-based synthetic lectin (SL) libraries, as well as the optimized methodology for obtaining peptide sequences of these SLs. SL libraries were subsequently used to identify SLs with as high as 5-fold selectivity for various glycoproteins. SLs will inevitably find a role in cancer diagnositics, given that they do not suffer from the drawbacks of natural lectins and that the combinatorial nature of these libraries allows for the identification of an SL for nearly any glycosylated biomolecule. PMID:21405093

  12. Double Dutch: A Tool for Designing Combinatorial Libraries of Biological Systems.

    Science.gov (United States)

    Roehner, Nicholas; Young, Eric M; Voigt, Christopher A; Gordon, D Benjamin; Densmore, Douglas

    2016-06-17

    Recently, semirational approaches that rely on combinatorial assembly of characterized DNA components have been used to engineer biosynthetic pathways. In practice, however, it is not practical to assemble and test millions of pathway variants in order to elucidate how different DNA components affect the behavior of a pathway. To address this challenge, we apply a rigorous mathematical approach known as design of experiments (DOE) that can be used to construct empirical models of system behavior without testing all variants. To support this approach, we have developed a tool named Double Dutch, which uses a formal grammar and heuristic algorithms to automate the process of DOE library design. Compared to designing by hand, Double Dutch enables users to more efficiently and scalably design libraries of pathway variants that can be used in a DOE framework and uniquely provides a means to flexibly balance design considerations of statistical analysis, construction cost, and risk of homologous recombination, thereby demonstrating the utility of automating decision making when faced with complex design trade-offs.

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

    Science.gov (United States)

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

    2007-02-01

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

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

    Directory of Open Access Journals (Sweden)

    Naama Tepper

    Full Text Available 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.

  15. Adaptive combinatorial design to explore large experimental spaces: approach and validation.

    Science.gov (United States)

    Lejay, L V; Shasha, D E; Palenchar, P M; Kouranov, A Y; Cruikshank, A A; Chou, M F; Coruzzi, G M

    2004-12-01

    Systems biology requires mathematical tools not only to analyse large genomic datasets, but also to explore large experimental spaces in a systematic yet economical way. We demonstrate that two-factor combinatorial design (CD), shown to be useful in software testing, can be used to design a small set of experiments that would allow biologists to explore larger experimental spaces. Further, the results of an initial set of experiments can be used to seed further 'Adaptive' CD experimental designs. As a proof of principle, we demonstrate the usefulness of this Adaptive CD approach by analysing data from the effects of six binary inputs on the regulation of genes in the N-assimilation pathway of Arabidopsis. This CD approach identified the more important regulatory signals previously discovered by traditional experiments using far fewer experiments, and also identified examples of input interactions previously unknown. Tests using simulated data show that Adaptive CD suffers from fewer false positives than traditional experimental designs in determining decisive inputs, and succeeds far more often than traditional or random experimental designs in determining when genes are regulated by input interactions. We conclude that Adaptive CD offers an economical framework for discovering dominant inputs and interactions that affect different aspects of genomic outputs and organismal responses.

  16. A transcription blocker isolated from a designed repeat protein combinatorial library by in vivo functional screen.

    Science.gov (United States)

    Tikhonova, Elena B; Ethayathulla, Abdul S; Su, Yue; Hariharan, Parameswaran; Xie, Shicong; Guan, Lan

    2015-01-28

    A highly diverse DNA library coding for ankyrin seven-repeat proteins (ANK-N5C) was designed and constructed by a PCR-based combinatorial assembly strategy. A bacterial melibiose fermentation assay was adapted for in vivo functional screen. We isolated a transcription blocker that completely inhibits the melibiose-dependent expression of α-galactosidase (MelA) and melibiose permease (MelB) of Escherichia coli by specifically preventing activation of the melAB operon. High-resolution crystal structural determination reveals that the designed ANK-N5C protein has a typical ankyrin fold, and the specific transcription blocker, ANK-N5C-281, forms a domain-swapped dimer. Functional tests suggest that the activity of MelR, a DNA-binding transcription activator and a member of AraC family of transcription factors, is inhibited by ANK-N5C-281 protein. All ANK-N5C proteins are expected to have a concave binding area with negative surface potential, suggesting that the designed ANK-N5C library proteins may facilitate the discovery of binders recognizing structural motifs with positive surface potential, like in DNA-binding proteins. Overall, our results show that the established library is a useful tool for the discovery of novel bioactive reagents.

  17. The combinatorial approach

    Directory of Open Access Journals (Sweden)

    Wilhelm F. Maier

    2004-10-01

    Full Text Available Two recently published books examine combinatorial materials synthesis, high-throughput screening of libraries, and the design of successful experiments. Both are a must for those interested in materials development and discovery, says Wilhelm F. Maier

  18. 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.

  19. Design and development of an ultra-compact drum-shaped chamber for combinatorial pulsed laser deposition

    Science.gov (United States)

    Katayama, M.; Itaka, K.; Matsumoto, Y.; Koinuma, H.

    2006-01-01

    We have designed a compact combinatorial pulsed laser deposition (PLD) chamber as a building block of a desktop laboratory for advanced materials research. Development of small-size systems for the growth and characterization of films would greatly help in interconnecting a variety of analytical tools for rapid screening of advanced materials. This PLD chamber has four special features: (1) a drum-shaped growth chamber, (2) a waterwheel-like combinatorial masking system, (3) a multi-target system having one feedthrough, and (4) a small reflection high-energy electron diffraction (RHEED) system. The performance of this system is demonstrated by the RHEED intensity oscillation during homoepitaxial growth of SrTiO 3 as well as by simultaneous fabrication of a ternary phase diagram of rare earth-doped Y 2O 3 phosphors.

  20. Assembly of Designed Oligonucleotides: a useful tool in synthetic biology for creating high-quality combinatorial DNA libraries.

    Science.gov (United States)

    Acevedo-Rocha, Carlos G; Reetz, Manfred T

    2014-01-01

    The method dubbed Assembly of Designed Oligonucleotides (ADO) is a powerful tool in synthetic biology to create combinatorial DNA libraries for gene, protein, metabolic, and genome engineering. In directed evolution of proteins, ADO benefits from using reduced amino acid alphabets for saturation mutagenesis and/or DNA shuffling, but all 20 canonical amino acids can be also used as building blocks. ADO is performed in a two-step reaction. The first involves a primer-free, polymerase cycling assembly or overlap extension PCR step using carefully designed overlapping oligonucleotides. The second step is a PCR amplification using the outer primers, resulting in a high-quality and bias-free double-stranded DNA library that can be assembled with other gene fragments and/or cloned into a suitable plasmid subsequently. The protocol can be performed in a few hours. In theory, neither the length of the DNA library nor the number of DNA changes has any limits. Furthermore, with the costs of synthetic DNA dropping every year, after an initial investment is made in the oligonucleotides, these can be exchanged for alternative ones with different sequences at any point in the process, fully exploiting the potential of creating highly diverse combinatorial libraries. In the example chosen here, we show the construction of a high-quality combinatorial ADO library targeting sixteen different codons simultaneously with nonredundant degenerate codons encoding various reduced alphabets of four amino acids along the heme region of the monooxygenase P450-BM3.

  1. Combinatorial auctions for electronic business

    Indian Academy of Sciences (India)

    Y Narahari; Pankaj Dayama

    2005-04-01

    Combinatorial auctions (CAs) have recently generated significant interest as an automated mechanism for buying and selling bundles of goods. They are proving to be extremely useful in numerous e-business applications such as eselling, e-procurement, e-logistics, and B2B exchanges. In this article, we introduce combinatorial auctions and bring out important issues in the design of combinatorial auctions. We also highlight important contributions in current research in this area. This survey emphasizes combinatorial auctions as applied to electronic business situations.

  2. COMBINATORIAL LIBRARIES

    DEFF Research Database (Denmark)

    1997-01-01

    The invention provides a method for the production of a combinatorial library of compound of general formula (I) using solid phase methodologies. The cleavage of the array of immobilised compounds of the phthalimido type from the solid support matrix is accomplished by using an array of dinucleop......The invention provides a method for the production of a combinatorial library of compound of general formula (I) using solid phase methodologies. The cleavage of the array of immobilised compounds of the phthalimido type from the solid support matrix is accomplished by using an array...... of dinucleophiles, e.g. hydrazines (hydrazinolysis) or N-hydroxylamines, whereby a combinatorial dimension is introduced in the cleavage step. The invention also provides a compound library....

  3. Combinatorial Optimization

    CERN Document Server

    Chvátal, V

    2011-01-01

    This book is a collection of six articles arising from the meeting of the NATO Advanced Study Institute (ASI) "Combinatorial Optimization: Methods and Applications," which was held at the University of Montreal in June 2006. This ASI consisted of seven series of five one-hour lectures and one series of four one-hour lectures. It was attended by some sixty students of graduate or postdoctoral level from fifteen countries worldwide. It includes topics such as: integer and mixed integer programming, facility location, branching on split disjunctions, convexity in combinatorial optimizat

  4. Design considerations and computer modeling related to the development of molecular scaffolds and peptide mimetics for combinatorial chemistry.

    Science.gov (United States)

    Hruby, V J; Shenderovich, M; Lam, K S; Lebl, M

    1996-10-01

    A critical issue in drug discovery utilizing combinatorial chemistry as part of the discovery process is the choice of scaffolds to be used for a proper presentation, in a three-dimensional space, of the critical elements of structure necessary for molecular recognition (binding) and information transfer (agonist/ antagonist). In the case of polypeptide ligands, considerations related to the properties of various backbone structures (alpha-helix, beta-sheets, etc.; phi, psi space) and those related to three-dimensional presentation of side-chain moieties (topography; chi (chi) space) must be addressed, although they often present quite different elements in the molecular recognition puzzle. We have addressed aspects of this problem by examining the three-dimensional structures of chemically different scaffolds at various distances from the scaffold to evaluate their putative diversity. We find that chemically diverse scaffolds can readily become topographically similar. We suggest a topographical approach involving design in chi space to deal with these problems.

  5. Algorithmic Strategies in Combinatorial Chemistry

    Energy Technology Data Exchange (ETDEWEB)

    GOLDMAN,DEBORAH; ISTRAIL,SORIN; LANCIA,GIUSEPPE; PICCOLBONI,ANTONIO; WALENZ,BRIAN

    2000-08-01

    Combinatorial Chemistry is a powerful new technology in drug design and molecular recognition. It is a wet-laboratory methodology aimed at ``massively parallel'' screening of chemical compounds for the discovery of compounds that have a certain biological activity. The power of the method comes from the interaction between experimental design and computational modeling. Principles of ``rational'' drug design are used in the construction of combinatorial libraries to speed up the discovery of lead compounds with the desired biological activity. This paper presents algorithms, software development and computational complexity analysis for problems arising in the design of combinatorial libraries for drug discovery. The authors provide exact polynomial time algorithms and intractability results for several Inverse Problems-formulated as (chemical) graph reconstruction problems-related to the design of combinatorial libraries. These are the first rigorous algorithmic results in the literature. The authors also present results provided by the combinatorial chemistry software package OCOTILLO for combinatorial peptide design using real data libraries. The package provides exact solutions for general inverse problems based on shortest-path topological indices. The results are superior both in accuracy and computing time to the best software reports published in the literature. For 5-peptoid design, the computation is rigorously reduced to an exhaustive search of about 2% of the search space; the exact solutions are found in a few minutes.

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

    Science.gov (United States)

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

    2016-01-01

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

  7. 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

  8. Combinatorial chemistry in the agrosciences.

    Science.gov (United States)

    Lindell, Stephen D; Pattenden, Lisa C; Shannon, Jonathan

    2009-06-15

    Combinatorial chemistry and high throughput screening have had a profound effect upon the way in which agrochemical companies conduct their lead discovery research. The article reviews recent applications of combinatorial synthesis in the lead discovery process for new fungicides, herbicides and insecticides. The role and importance of bioavailability guidelines, natural products, privileged structures, virtual screening and X-ray crystallographic protein structures on the design of solid- and solution-phase compound libraries is discussed and illustrated.

  9. Vector design Tour de Force: integrating combinatorial and rational approaches to derive novel adeno-associated virus variants.

    Science.gov (United States)

    Marsic, Damien; Govindasamy, Lakshmanan; Currlin, Seth; Markusic, David M; Tseng, Yu-Shan; Herzog, Roland W; Agbandje-McKenna, Mavis; Zolotukhin, Sergei

    2014-11-01

    Methodologies to improve existing adeno-associated virus (AAV) vectors for gene therapy include either rational approaches or directed evolution to derive capsid variants characterized by superior transduction efficiencies in targeted tissues. Here, we integrated both approaches in one unified design strategy of "virtual family shuffling" to derive a combinatorial capsid library whereby only variable regions on the surface of the capsid are modified. Individual sublibraries were first assembled in order to preselect compatible amino acid residues within restricted surface-exposed regions to minimize the generation of dead-end variants. Subsequently, the successful families were interbred to derive a combined library of ~8 × 10(5) complexity. Next-generation sequencing of the packaged viral DNA revealed capsid surface areas susceptible to directed evolution, thus providing guidance for future designs. We demonstrated the utility of the library by deriving an AAV2-based vector characterized by a 20-fold higher transduction efficiency in murine liver, now equivalent to that of AAV8.

  10. Computer-assisted combinatorial design of bicyclic thymidine analogs as inhibitors of Mycobacterium tuberculosis thymidine monophosphate kinase

    Science.gov (United States)

    Frecer, Vladimir; Seneci, Pierfausto; Miertus, Stanislav

    2011-01-01

    Thymidine monophosphate kinase (TMPKmt) is an essential enzyme for nucleotide metabolism in Mycobacterium tuberculosis, and thus an attractive target for novel antituberculosis agents. In this work, we have explored the chemical space around the 2',3'-bicyclic thymidine nucleus by designing and in silico screening of a virtual focused library selected via structure based methods to identify more potent analogs endowed with favorable ADME-related properties. In all the library members we have exchanged the ribose ring of the template with a cyclopentane moiety that is less prone to enzymatic degradation. In addition, we have replaced the six-membered 2',3'-ring by a number of five-membered and six-membered heterocyclic rings containing alternative proton donor and acceptor groups, to exploit the interaction with the carboxylate groups of Asp9 and Asp163 as well as with several cationic residues present in the vicinity of the TMPKmt binding site. The three-dimensional structure of the TMPKmt complexed with 5-hydroxymethyl-dUMP, an analog of dTMP, was employed to develop a QSAR model, to parameterize a scoring function specific for the TMPKmt target and to select analogues which display the highest predicted binding to the target. As a result, we identified a small highly focused combinatorial subset of bicyclic thymidine analogues as virtual hits that are predicted to inhibit the mycobacterial TMPK in the submicromolar concentration range and to display favorable ADME-related properties.

  11. 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.

  12. Fundamentals of Combinatorial Optimization and Algorithm Design: Report for April 1 2006-March 31 2007

    Science.gov (United States)

    2007-03-01

    applications to optical network design., ESA (Susanne Albers and Tomasz Radzik, eds.), Lecture Notes in Computer Science, vol. 3221, Springer, 2004, pp. 28...Treewidth Manuscript Jan . 2006. [19) C. Chekuri, S. Khanna and F.B. Shepherd. Edge-disjoint paths in planar graphs with constant congestion STOC 2006. [20] C

  13. Polynomial-time Approximability Results for combinatorial problems arising in Optimal Experimental Design

    CERN Document Server

    Sagnol, Guillaume

    2010-01-01

    The theory of "optimal experimental design" explains how to best select experiments in order to estimate a set of parameters. The quality of the estimation can be measured by the confidence ellipsoids of a certain estimator. This leads to concave maximization problems in which the objective function is nondecreasing with respect to the L\\"owner ordering of symmetric matrices, and is applied to the "information matrix" describing the structure of these confidence ellipsoids. In a number of real-world applications, the variables controlling the experimental design are discrete, or binary. This paper provides approximability bounds for this NP-hard problem. In particular, we establish a matrix inequality which shows that the objective function is submodular, from which it follows that the greedy approach, which has often been used for this problem, always gives a design within $1-1/e$ of the optimum. We next study the design found by rounding the solution of the continuous relaxed problem, an approach which has ...

  14. Design of a combinatorial dna microarray for protein-dnainteraction studies

    Energy Technology Data Exchange (ETDEWEB)

    Mintseris, Julian; Eisen, Michael B.

    2006-07-07

    Background: Discovery of precise specificity oftranscription factors is an important step on the way to understandingthe complex mechanisms of gene regulation in eukaryotes. Recently,doublestranded protein-binding microarrays were developed as apotentially scalable approach to tackle transcription factor binding siteidentification. Results: Here we present an algorithmic approach toexperimental design of a microarray that allows for testing fullspecificity of a transcription factor binding to all possible DNA bindingsites of a given length, with optimally efficient use of the array. Thisdesign is universal, works for any factor that binds a sequence motif andis not species-specific. Furthermore, simulation results show that dataproduced with the designed arrays is easier to analyze and would resultin more precise identification of binding sites. Conclusion: In thisstudy, we present a design of a double stranded DNA microarray forprotein-DNA interaction studies and show that our algorithm allowsoptimally efficient use of the arrays for this purpose. We believe such adesign will prove useful for transcription factor binding siteidentification and other biological problems.

  15. Combinatorial instruments in the design of a heuristic for the quadratic assignment problem

    Directory of Open Access Journals (Sweden)

    Paulo Oswaldo Boaventura-Netto

    2003-12-01

    Full Text Available This work discusses the use of a neighbouring structure in the design of specific heuristics for the Quadratic Assignment Problem (QAP. This structure is formed by the 4- and 6-cycles adjacent to a vertex in the Hasse diagram of the permutation lattice and it can be adequately partitioned in subsets of linear and quadratic cardinalities, a characteristics which frequently allows an economy in the processing time. We propose also a restart strategy and a mechanism for generating initial solutions which constitute, together with the neighbouring structure, a possible QAP-specific heuristic proposal. For the construction of these instruments we used the relaxed ordered set of QAP solutions.Este trabalho discute o uso de uma estrutura de vizinhança em heurísticas específicas para o Problema Quadrático de Alocação (PQA. Esta estrutura envolve os ciclos de comprimento 4 e 6 adjacentes a um vértice do diagrama de Hasse do reticulado das permutações e pode ser particionada em subconjuntos de cardinalidade linear e quadrática em relação à ordem da instância, o que permite frequentemente uma economia de tempo de processamento. Propõem-se ainda uma estratégia de repartida e um mecanismo de geração de soluções iniciais, que constituem, ao lado da estrutura de vizinhança, uma proposta de heurística específica para o PQA. Na construção desses instrumentos foi utilizada a noção de conjunto relaxado ordenado das soluções do PQA.

  16. Combinatorial synthesis of natural products

    DEFF Research Database (Denmark)

    Nielsen, John

    2002-01-01

    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......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...

  17. 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

  18. Combinatorial Theory

    CERN Document Server

    Hall, Marshall

    2011-01-01

    Includes proof of van der Waerden's 1926 conjecture on permanents, Wilson's theorem on asymptotic existence, and other developments in combinatorics since 1967. Also covers coding theory and its important connection with designs, problems of enumeration, and partition. Presents fundamentals in addition to latest advances, with illustrative problems at the end of each chapter. Enlarged appendixes include a longer list of block designs.

  19. 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

  20. Combinatorial Floer Homology

    CERN Document Server

    de Silva, Vin; Salamon, Dietmar

    2012-01-01

    We define combinatorial Floer homology of a transverse pair of noncontractibe nonisotopic embedded loops in an oriented 2-manifold without boundary, prove that it is invariant under isotopy, and prove that it is isomorphic to the original Lagrangian Floer homology.

  1. Normal Order: Combinatorial Graphs

    CERN Document Server

    Solomon, A I; Blasiak, P; Horzela, A; Penson, K A; Solomon, Allan I.; Duchamp, Gerard; Blasiak, Pawel; Horzela, Andrzej; Penson, Karol A.

    2004-01-01

    A conventional context for supersymmetric problems arises when we consider systems containing both boson and fermion operators. In this note we consider the normal ordering problem for a string of such operators. In the general case, upon which we touch briefly, this problem leads to combinatorial numbers, the so-called Rook numbers. Since we assume that the two species, bosons and fermions, commute, we subsequently restrict ourselves to consideration of a single species, single-mode boson monomials. This problem leads to elegant generalisations of well-known combinatorial numbers, specifically Bell and Stirling numbers. We explicitly give the generating functions for some classes of these numbers. In this note we concentrate on the combinatorial graph approach, showing how some important classical results of graph theory lead to transparent representations of the combinatorial numbers associated with the boson normal ordering problem.

  2. PNA-COMBO-FISH: From combinatorial probe design in silico to vitality compatible, specific labelling of gene targets in cell nuclei.

    Science.gov (United States)

    Müller, Patrick; Rößler, Jens; Schwarz-Finsterle, Jutta; Schmitt, Eberhard; Hausmann, Michael

    2016-07-01

    Recently, advantages concerning targeting specificity of PCR constructed oligonucleotide FISH probes in contrast to established FISH probes, e.g. BAC clones, have been demonstrated. These techniques, however, are still using labelling protocols with DNA denaturing steps applying harsh heat treatment with or without further denaturing chemical agents. COMBO-FISH (COMBinatorial Oligonucleotide FISH) allows the design of specific oligonucleotide probe combinations in silico. Thus, being independent from primer libraries or PCR laboratory conditions, the probe sequences extracted by computer sequence data base search can also be synthesized as single stranded PNA-probes (Peptide Nucleic Acid probes). Gene targets can be specifically labelled with at least about 20 PNA-probes obtaining visibly background free specimens. By using appropriately designed triplex forming oligonucleotides, the denaturing procedures can completely be omitted. These results reveal a significant step towards oligonucleotide-FISH maintaining the 3d-nanostructure and even the viability of the cell target. The method is demonstrated with the detection of Her2/neu and GRB7 genes, which are indicators in breast cancer diagnosis and therapy.

  3. Combinatorial Hybrid Systems

    DEFF Research Database (Denmark)

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

    2008-01-01

    As initially suggested by E. Sontag, it is possible to approximate an arbitrary nonlinear system by a set of piecewise linear systems. In this work we concentrate on how to control a system given by a set of piecewise linear systems defined on simplices. By using the results of L. Habets and J. van...... Schuppen, it is possible to find a controller for the system on each of the simplices thus guaranteeing that the system flow on the simplex only will leave the simplex through a subset of its faces. Motivated by R. Forman, on the triangulated state space we define a combinatorial vector field, which...... 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...

  4. Designing and Validating Ternary Pd Alloys for Optimum Sulfur/Carbon Resistance in Hydrogen Separation and Carbon Capture Membrane Systems Using High-Throughput Combinatorial Methods

    Energy Technology Data Exchange (ETDEWEB)

    Lewis, Amanda [Pall Corporation, Port Washington, NY (United States); Zhao, Hongbin [Pall Corporation, Port Washington, NY (United States); Hopkins, Scott [Pall Corporation, Port Washington, NY (United States)

    2014-12-01

    This report summarizes the work completed under the U.S. Department of Energy Project Award No.: DE-FE0001181 titled “Designing and Validating Ternary Pd Alloys for Optimum Sulfur/Carbon Resistance in Hydrogen Separation and Carbon Capture Membrane Systems Using High-Throughput Combinatorial Methods.” The project started in October 1, 2009 and was finished September 30, 2014. Pall Corporation worked with Cornell University to sputter and test palladium-based ternary alloys onto silicon wafers to examine many alloys at once. With the specialized equipment at Georgia Institute of Technology that analyzed the wafers for adsorbed carbon and sulfur species six compositions were identified to have resistance to carbon and sulfur species. These compositions were deposited on Pall AccuSep® supports by Colorado School of Mines and then tested in simulated synthetic coal gas at the Pall Corporation. Two of the six alloys were chosen for further investigations based on their performance. Alloy reproducibility and long-term testing of PdAuAg and PdZrAu provided insight to the ability to manufacture these compositions for testing. PdAuAg is the most promising alloy found in this work based on the fabrication reproducibility and resistance to carbon and sulfur. Although PdZrAu had great initial resistance to carbon and sulfur species, the alloy composition has a very narrow range that hindered testing reproducibility.

  5. Designing and Validating Ternary Pd Alloys for Optimum Sulfur/Carbon Resistance in Hydrogen Separation and Carbon Capture Membrane Systems Using High-Throughput Combinatorial Methods

    Energy Technology Data Exchange (ETDEWEB)

    Lewis, Amanda; Zhao, Hongbin; Hopkins, Scott

    2014-09-30

    This report summarizes the work completed under the U.S. Department of Energy Project Award No.: DE-FE0001181 titled “Designing and Validating Ternary Pd Alloys for Optimum Sulfur/Carbon Resistance in Hydrogen Separation and Carbon Capture Membrane Systems Using High-Throughput Combinatorial Methods.” The project started in October 1, 2009 and was finished September 30, 2014. Pall Corporation worked with Cornell University to sputter and test palladium-based ternary alloys onto silicon wafers to examine many alloys at once. With the specialized equipment at Georgia Institute of Technology that analyzed the wafers for adsorbed carbon and sulfur species six compositions were identified to have resistance to carbon and sulfur species. These compositions were deposited on Pall AccuSep® supports by Colorado School of Mines and then tested in simulated synthetic coal gas at the Pall Corporation. Two of the six alloys were chosen for further investigations based on their performance. Alloy reproducibility and long-term testing of PdAuAg and PdZrAu provided insight to the ability to manufacture these compositions for testing. PdAuAg is the most promising alloy found in this work based on the fabrication reproducibility and resistance to carbon and sulfur. Although PdZrAu had great initial resistance to carbon and sulfur species, the alloy composition has a very narrow range that hindered testing reproducibility.

  6. 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…

  7. Research on universal combinatorial coding.

    Science.gov (United States)

    Lu, Jun; Zhang, Zhuo; Mo, Juan

    2014-01-01

    The conception of universal combinatorial coding is proposed. Relations exist more or less in many coding methods. It means that a kind of universal coding method is objectively existent. It can be a bridge connecting many coding methods. Universal combinatorial coding is lossless and it is based on the combinatorics theory. The combinational and exhaustive property make it closely related with the existing code methods. Universal combinatorial coding does not depend on the probability statistic characteristic of information source, and it has the characteristics across three coding branches. It has analyzed the relationship between the universal combinatorial coding and the variety of coding method and has researched many applications technologies of this coding method. In addition, the efficiency of universal combinatorial coding is analyzed theoretically. The multicharacteristic and multiapplication of universal combinatorial coding are unique in the existing coding methods. Universal combinatorial coding has theoretical research and practical application value.

  8. Design, structure-based focusing and in silico screening of combinatorial library of peptidomimetic inhibitors of Dengue virus NS2B-NS3 protease

    Science.gov (United States)

    Frecer, Vladimir; Miertus, Stanislav

    2010-03-01

    Serine protease activity of the NS3 protein of Dengue virus is an important target of antiviral agents that interfere with the viral polyprotein precursor processing catalyzed by the NS3 protease (NS3pro), which is important for the viral replication and maturation. Recent studies showed that substrate-based peptidomimetics carrying an electrophilic warhead inhibit the NS2B-NS3pro cofactor-protease complex with inhibition constants in the low micromolar concentration range when basic amino acid residues occupy P1 and P2 positions of the inhibitor, and an aldehyde warhead is attached to the P1. We have used computer-assisted combinatorial techniques to design, focus using the NS2B-NS3pro receptor 3D structure, and in silico screen a virtual library of more than 9,200 peptidomimetic analogs targeted around the template inhibitor Bz-Nle-Lys-Arg-Arg- H (Bz—benzoyl) that are composed mainly of unusual amino acid residues in all positions P1-P4. The most promising virtual hits were analyzed in terms of computed enzyme-inhibitor interactions and Adsorption, Distribution, Metabolism and Excretion (ADME) related physico-chemical properties. Our study can direct the interest of medicinal chemists working on a next generation of antiviral chemotherapeutics against the Dengue Fever towards the explored subset of the chemical space that is predicted to contain peptide aldehydes with NS3pro inhibition potencies in nanomolar range which display ADME-related properties comparable to the training set inhibitors.

  9. A combinatorial approach for the design of complementarity-determining region-derived peptidomimetics with in vitro anti-tumoral activity

    NARCIS (Netherlands)

    Timmerman, P.; Barderas, R.; Desmet, J.; Altschuh, D.; Shochat, S.; Hollestelle, M.J.; Höppener, J.W.M.; Monasterio, A.; Casal, J.I.; Meloen, R.H.

    2009-01-01

    The great success of therapeutic monoclonal antibodies has fueled research toward mimicry of their binding sites and the development of new strategies for peptide-based mimetics production. Here, we describe a new combinatorial approach for the production of peptidomimetics using the

  10. Combinatorial materials synthesis

    Directory of Open Access Journals (Sweden)

    Ichiro Takeuchi

    2005-10-01

    Full Text Available The pace at which major technological changes take place is often dictated by the rate at which new materials are discovered, and the timely arrival of new materials has always played a key role in bringing advances to our society. It is no wonder then that the so-called combinatorial or high-throughput strategy has been embraced by practitioners of materials science in virtually every field. High-throughput experimentation allows simultaneous synthesis and screening of large arrays of different materials. Pioneered by the pharmaceutical industry, the combinatorial method is now widely considered to be a watershed in accelerating the discovery and optimization of new materials1–5.

  11. Combinatorial Reciprocity Theorems

    CERN Document Server

    Beck, Matthias

    2012-01-01

    A common theme of enumerative combinatorics is formed by counting functions that are polynomials evaluated at positive integers. In this expository paper, we focus on four families of such counting functions connected to hyperplane arrangements, lattice points in polyhedra, proper colorings of graphs, and $P$-partitions. We will see that in each instance we get interesting information out of a counting function when we evaluate it at a \\emph{negative} integer (and so, a priori the counting function does not make sense at this number). Our goals are to convey some of the charm these "alternative" evaluations of counting functions exhibit, and to weave a unifying thread through various combinatorial reciprocity theorems by looking at them through the lens of geometry, which will include some scenic detours through other combinatorial concepts.

  12. Pseudorandomness and Combinatorial Constructions

    OpenAIRE

    2006-01-01

    In combinatorics, the probabilistic method is a very powerful tool to prove the existence of combinatorial objects with interesting and useful properties. Explicit constructions of objects with such properties are often very difficult, or unknown. In computer science, probabilistic algorithms are sometimes simpler and more efficient than the best known deterministic algorithms for the same problem. Despite this evidence for the power of random choices, the computational theory of pseudorandom...

  13. Combinatorial group theory

    CERN Document Server

    Lyndon, Roger C

    2001-01-01

    From the reviews: "This book (...) defines the boundaries of the subject now called combinatorial group theory. (...)it is a considerable achievement to have concentrated a survey of the subject into 339 pages. This includes a substantial and useful bibliography; (over 1100 ÄitemsÜ). ...the book is a valuable and welcome addition to the literature, containing many results not previously available in a book. It will undoubtedly become a standard reference." Mathematical Reviews, AMS, 1979.

  14. Combinatorial Quantum Gravity

    CERN Document Server

    Trugenberger, Carlo A

    2016-01-01

    In a recently developed approach, geometry is modelled as an emergent property of random networks. Here I show that one of these models I proposed is exactly quantum gravity defined in terms of the combinatorial Ricci curvature recently derived by Ollivier. Geometry in the weak (classical) gravity regime arises in a phase transition driven by the condensation of short graph cycles. The strong (quantum) gravity regime corresponds to "small world" random graphs with logarithmic distance scaling.

  15. 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...... define an explicit combinatorial analytic modelspace, which is sufficiently abstract that it can serve as a go-between for proving that other sets such as the parabolic Mandelbrot set M1 has the same combinatorial structure as M. As an immediate application we use here the combinatorial-analytic model...

  16. A Combinatorial Approach for the Design of Complementarity-determining Region-derived Peptidomimetics with in Vitro Anti-tumoral Activity*

    OpenAIRE

    Timmerman, Peter; Barderas, Rodrigo; Desmet, Johan; Altschuh, Danièle; Shochat, Susana; Hollestelle, Martine J.; Höppener, Jo W. M.; Monasterio, Alberto; Casal, J. Ignacio; Meloen, Rob H.

    2009-01-01

    The great success of therapeutic monoclonal antibodies has fueled research toward mimicry of their binding sites and the development of new strategies for peptide-based mimetics production. Here, we describe a new combinatorial approach for the production of peptidomimetics using the complementarity-determining regions (CDRs) from gastrin17 (pyroEGPWLEEEEEAYGWMDF-NH2) antibodies as starting material for cyclic peptide synthesis in a microarray format. Gastrin17 is a trophic factor in gastroin...

  17. Introduction to combinatorial analysis

    CERN Document Server

    Riordan, John

    2002-01-01

    This introduction to combinatorial analysis defines the subject as ""the number of ways there are of doing some well-defined operation."" Chapter 1 surveys that part of the theory of permutations and combinations that finds a place in books on elementary algebra, which leads to the extended treatment of generation functions in Chapter 2, where an important result is the introduction of a set of multivariable polynomials.Chapter 3 contains an extended treatment of the principle of inclusion and exclusion which is indispensable to the enumeration of permutations with restricted position given

  18. 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...... of knownresults fromfirst-order infinitary rewriting and infinitary ¿-calculus to iCRSs. In particular, for fully-extended, left-linear iCRSs we prove the well-known compression property, and for orthogonal iCRSs we prove that (1) if a set of redexes U has a complete development, then all complete developments...

  19. 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...

  20. 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...

  1. Simple Combinatorial Optimisation Cost Games

    NARCIS (Netherlands)

    van Velzen, S.

    2005-01-01

    In this paper we introduce the class of simple combinatorial optimisation cost games, which are games associated to {0, 1}-matrices.A coalitional value of a combinatorial optimisation game is determined by solving an integer program associated with this matrix and the characteristic vector of the

  2. Polyhedral Techniques in Combinatorial Optimization

    NARCIS (Netherlands)

    Aardal, K.I.; van Hoesel, S.

    1995-01-01

    Combinatorial optimization problems arise in several areas ranging from management to mathematics and graph theory. Most combinatorial optimization problems are compu- tationally hard due to the restriction that a subset of the variables have to take integral values. During the last two decades

  3. A combinatorial approach to metamaterials discovery

    CERN Document Server

    Plum, E; Chen, W T; Fedotov, V A; Tsai, D P; Zheludev, N I

    2010-01-01

    We report a high through-put combinatorial approach to photonic metamaterial optimization. The new approach is based on parallel synthesis and consecutive optical characterization of large numbers of spatially addressable nano-fabricated metamaterial samples (libraries) with quasi-continuous variation of design parameters under real manufacturing conditions. We illustrate this method for Fano-resonance plasmonic nanostructures arriving at explicit recipes for high quality factors needed for switching and sensing applications.

  4. A combinatorial approach for the design of complementarity-determining region-derived peptidomimetics with in vitro anti-tumoral activity.

    Science.gov (United States)

    Timmerman, Peter; Barderas, Rodrigo; Desmet, Johan; Altschuh, Danièle; Shochat, Susana; Hollestelle, Martine J; Höppener, Jo W M; Monasterio, Alberto; Casal, J Ignacio; Meloen, Rob H

    2009-12-04

    The great success of therapeutic monoclonal antibodies has fueled research toward mimicry of their binding sites and the development of new strategies for peptide-based mimetics production. Here, we describe a new combinatorial approach for the production of peptidomimetics using the complementarity-determining regions (CDRs) from gastrin17 (pyroEGPWLEEEEEAYGWMDF-NH(2)) antibodies as starting material for cyclic peptide synthesis in a microarray format. Gastrin17 is a trophic factor in gastrointestinal tumors, including pancreatic cancer, which makes it an interesting target for development of therapeutic antibodies. Screening of microarrays containing bicyclic peptidomimetics identified a high number of gastrin binders. A strong correlation was observed between gastrin binding and overall charge of the peptidomimetic. Most of the best gastrin binders proceeded from CDRs containing charged residues. In contrast, CDRs from high affinity antibodies containing mostly neutral residues failed to yield good binders. Our experiments revealed essential differences in the mode of antigen binding between CDR-derived peptidomimetics (K(d) values in micromolar range) and the parental monoclonal antibodies (K(d) values in nanomolar range). However, chemically derived peptidomimetics from gastrin binders were very effective in gastrin neutralization studies using cell-based assays, yielding a neutralizing activity in pancreatic tumoral cell lines comparable with that of gastrin-specific monoclonal antibodies. These data support the use of combinatorial CDR-peptide microarrays as a tool for the development of a new generation of chemically synthesized cyclic peptidomimetics with functional activity.

  5. Combinatorial Maps with Normalized Knot

    CERN Document Server

    Zeps, Dainis

    2010-01-01

    We consider combinatorial maps with fixed combinatorial knot numbered with augmenting numeration called normalized knot. We show that knot's normalization doesn't affect combinatorial map what concerns its generality. Knot's normalization leads to more concise numeration of corners in maps, e.g., odd or even corners allow easy to follow distinguished cycles in map caused by the fixation of the knot. Knot's normalization may be applied to edge structuring knot too. If both are normalized then one is fully and other partially normalized mutually.

  6. 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.

  7. Combinatorial fractal Brownian motion model

    Institute of Scientific and Technical Information of China (English)

    朱炬波; 梁甸农

    2000-01-01

    To solve the problem of how to determine the non-scaled interval when processing radar clutter using fractal Brownian motion (FBM) model, a concept of combinatorial FBM model is presented. Since the earth (or sea) surface varies diversely with space, a radar clutter contains several fractal structures, which coexist on all scales. Taking the combination of two FBMs into account, via theoretical derivation we establish a combinatorial FBM model and present a method to estimate its fractal parameters. The correctness of the model and the method is proved by simulation experiments and computation of practial data. Furthermore, we obtain the relationship between fractal parameters when processing combinatorial model with a single FBM model. Meanwhile, by theoretical analysis it is concluded that when combinatorial model is observed on different scales, one of the fractal structures is more obvious.

  8. Stochastic integrals: a combinatorial approach

    OpenAIRE

    Rota, Gian-Carlo; Wallstrom, Timothy C.

    1997-01-01

    A combinatorial definition of multiple stochastic integrals is given in the setting of random measures. It is shown that some properties of such stochastic integrals, formerly known to hold in special cases, are instances of combinatorial identities on the lattice of partitions of a set. The notion of stochastic sequences of binomial type is introduced as a generalization of special polynomial sequences occuring in stochastic integration, such as Hermite, Poisson–Charlier an...

  9. Combinatorial Multiobjective Optimization Using Genetic Algorithms

    Science.gov (United States)

    Crossley, William A.; Martin. Eric T.

    2002-01-01

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

  10. 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.

  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. Universally Balanced Combinatorial Optimization Games

    Directory of Open Access Journals (Sweden)

    Xiaotie Deng

    2010-09-01

    Full Text Available This article surveys studies on universally balanced properties of cooperative games defined in a succinct form. In particular, we focus on combinatorial optimization games in which the values to coalitions are defined through linear optimization programs, possibly combinatorial, that is subject to integer constraints. In economic settings, the integer requirement reflects some forms of indivisibility. We are interested in the classes of games that guarantee a non-empty core no matter what are the admissible values assigned to the parameters defining these programs. We call such classes universally balanced. We present characterization and complexity results on the universally balancedness property for some classes of interesting combinatorial optimization games. In particular, we focus on the algorithmic properties for identifying universally balancedness for the games under discussion.

  13. Combinatorial optimization theory and algorithms

    CERN Document Server

    Korte, Bernhard

    2002-01-01

    Combinatorial optimization is one of the youngest and most active areas of discrete mathematics, and is probably its driving force today. This book describes the most important ideas, theoretical results, and algorithms of this field. It is conceived as an advanced graduate text, and it can also be used as an up-to-date reference work for current research. The book includes the essential fundamentals of graph theory, linear and integer programming, and complexity theory. It covers classical topics in combinatorial optimization as well as very recent ones. The emphasis is on theoretical results and algorithms with provably good performance. Some applications and heuristics are mentioned, too.

  14. On an Extension of a Combinatorial Identity

    Indian Academy of Sciences (India)

    M Rana; A K Agarwal

    2009-02-01

    Using Frobenius partitions we extend the main results of [4]. This leads 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.

  15. 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.

  16. Combinatorial reasoning to solve problems

    NARCIS (Netherlands)

    Coenen, Tom; Hof, Frits; Verhoef, Nellie

    2016-01-01

    This study reports combinatorial reasoning to solve problems. We observed the mathematical thinking of students aged 14-16. We study the variation of the students’ solution strategies in the context of emergent modelling. The results show that the students are tempted to begin the problem solving pr

  17. The evolution of combinatorial phonology

    NARCIS (Netherlands)

    Zuidema, Willem; de Boer, Bart

    2009-01-01

    A fundamental, universal property of human language is that its phonology is combinatorial. That is, one can identify a set of basic, distinct units (phonemes, syllables) that can be productively combined in many different ways. In this paper, we develop a methodological framework based on evolution

  18. 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...

  19. 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 ...

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

    DEFF Research Database (Denmark)

    Sørensen, Anne

    The design and preparation of strong and selective artificial receptors, especially biomi-metic receptors that function in aqueous solution, has proved truly challenging. In this thesis it will be described how the strengths of dynamic combinatorial chemistry can be used to great advantage...... in this field. The aim of this project has therefore been to develop new ways of using dynamic combinatorial libraries for molecular recognition in aqueous media. The focus has been on using what has been learned from the well-established di-sulfide exchange chemistry to incorporate a new reaction into dynamic...... 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...

  1. The priming of basic combinatory responses in MEG.

    Science.gov (United States)

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

    2017-09-21

    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

  2. Combinatorial Auctions without Money

    Science.gov (United States)

    2014-05-01

    auctions. ICALP, pp. 90-101, 2010. [2] P. Briest, P. Krysta, and B. Vöcking. Approximation techniques for utilitarian mechanism design. STOC, pp. 39-48...Grandoni, P. Krysta, S. Leonardi, and C. Ventre. Utilitarian mechanism design for multi-objective optimization. SODA, pp. 573-584, 2010. [11] J. R

  3. A Synthetic Receptor for Nicotine from a Dynamic Combinatorial Library

    NARCIS (Netherlands)

    Hamieh, Saleh; Ludlow, R. Frederick; Perraud, Olivier; West, Kevin R.; Mattia, Elio; Otto, Sijbren

    2012-01-01

    Designing synthetic receptors that bind biologically relevant guests in an aqueous solution remains a considerable challenge. We now report a new synthetic receptor for nicotine, selected from a dynamic combinatorial library, that binds this guest in water at neutral pH through a combination of hydr

  4. Solids: a combinatorial auction for a housing corporation

    NARCIS (Netherlands)

    Goossens, D.R.; Onderstal, S.; Spieksma, F.C.R.; Coles, P.; Das, S.; Lahaie, S.; Szymanski, B.

    2012-01-01

    On May 7, 2011, over one hundred bidders took part in a combinatorial auction for housing space in a newly erected building in Amsterdam (the Netherlands). This paper describes the development of this auction. We sketch our collaboration with the housing corporation that resulted in design choices

  5. Combinatorial Model Involving Stochastic Choices of Destination, Mode and Route

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    Traffic assignment models are one of the basic tools for the analysis and design of transportation systems. However, the existing models have some defects. Considering the characteristics of Chinese urban mixed traffic and the randomness of transportation information, the author develops a combinatorial model involving stochastic choices of destination, mode and route. Its uniqueness and equivalance are also proved by the optimization theory.

  6. 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...

  7. Combinatorial Properties of Finite Models

    CERN Document Server

    Hubicka, Jan

    2010-01-01

    We study countable embedding-universal and homomorphism-universal structures and unify results related to both of these notions. We show that many universal and ultrahomogeneous structures allow a concise description (called here a finite presentation). Extending classical work of Rado (for the random graph), we find a finite presentation for each of the following classes: homogeneous undirected graphs, homogeneous tournaments and homogeneous partially ordered sets. We also give a finite presentation of the rational Urysohn metric space and some homogeneous directed graphs. We survey well known structures that are finitely presented. We focus on structures endowed with natural partial orders and prove their universality. These partial orders include partial orders on sets of words, partial orders formed by geometric objects, grammars, polynomials and homomorphism orders for various combinatorial objects. We give a new combinatorial proof of the existence of embedding-universal objects for homomorphism-defined...

  8. Stem cells and combinatorial science.

    Science.gov (United States)

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

    2007-09-01

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

  9. Combinatorial Approach of Associative Classification

    OpenAIRE

    P. R. Pal; R.C. Jain

    2010-01-01

    Association rule mining and classification are two important techniques of data mining in knowledge discovery process. Integration of these two has produced class association rule mining or associative classification techniques, which in many cases have shown better classification accuracy than conventional classifiers. Motivated by this study we have explored and applied the combinatorial mathematics in class association rule mining in this paper. Our algorithm is based on producing co...

  10. 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.

  11. Some polyhedral results in combinatorial optimization

    OpenAIRE

    Xiao, Han; 肖汉

    2016-01-01

    Many combinatorial optimization problems can be conceived of as optimizing a linear function over a polyhedron. Investigating properties of the associated polyhedron has been evidenced to be a powerful schema for solving combinatorial optimization problems, especially for characterizing min-max relations. Three different topics in combinatorial optimization are explored in this thesis, which fall within a unified characterization: integrality of polyhedra. Various min-max relations in com...

  12. Dynamic Combinatorial Libraries : From Exploring Molecular Recognition to Systems Chemistry

    NARCIS (Netherlands)

    Li, Jianwei; Nowak, Piotr; Otto, Sijbren

    2013-01-01

    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

  13. 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

  14. Statistical mechanics of combinatorial auctions

    Science.gov (United States)

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

    2006-05-01

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

  15. Fairness in Combinatorial Auctioning Systems

    CERN Document Server

    Saini, Megha

    2008-01-01

    One of the Multi-Agent Systems that is widely used by various government agencies, buyers and sellers in a market economy, in such a manner so as to attain optimized resource allocation, is the Combinatorial Auctioning System (CAS). We study another important aspect of resource allocations in CAS, namely fairness. We present two important notions of fairness in CAS, extended fairness and basic fairness. We give an algorithm that works by incorporating a metric to ensure fairness in a CAS that uses the Vickrey-Clark-Groves (VCG) mechanism, and uses an algorithm of Sandholm to achieve optimality. Mathematical formulations are given to represent measures of extended fairness and basic fairness.

  16. Cubature formulas on combinatorial graphs

    CERN Document Server

    Pesenson, Isaac Z

    2011-01-01

    Many contemporary applications, for example, cataloging of galaxies, document analysis, face recognition, learning theory, image processing, operate with a large amount of data which is often represented as a graph embedded into a high dimensional Euclidean space. The variety of problems arising in contemporary data processing requires development on graphs such topics of the classical harmonic analysis as Shannon sampling, splines, wavelets, cubature formulas. The goal of the paper is to establish cubature formulas on finite combinatorial graphs. The results have direct applications to problems that arise in connection with data filtering, data denoising and data dimension reduction.

  17. Combinatorial algorithms for the seriation problem

    NARCIS (Netherlands)

    Seminaroti, Matteo

    2016-01-01

    In this thesis we study the seriation problem, a combinatorial problem arising in data analysis, which asks to sequence a set of objects in such a way that similar objects are ordered close to each other. We focus on the combinatorial structure and properties of Robinsonian matrices, a special class

  18. Combinatorial Interpretation of General Eulerian Numbers

    Directory of Open Access Journals (Sweden)

    Tingyao Xiong

    2014-01-01

    Full Text Available Since the 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,….

  19. Combinatorial Solutions to Normal Ordering of Bosons

    CERN Document Server

    Blasiak, P; Horzela, A; Penson, K A; Solomon, A I

    2005-01-01

    We present a combinatorial method of constructing solutions to the normal ordering of boson operators. Generalizations of standard combinatorial notions - the Stirling and Bell numbers, Bell polynomials and Dobinski relations - lead to calculational tools which allow to find explicitly normally ordered forms for a large class of operator functions.

  20. Combinatorial Properties of Finite Models

    Science.gov (United States)

    Hubicka, Jan

    2010-09-01

    We study countable embedding-universal and homomorphism-universal structures and unify results related to both of these notions. We show that many universal and ultrahomogeneous structures allow a concise description (called here a finite presentation). Extending classical work of Rado (for the random graph), we find a finite presentation for each of the following classes: homogeneous undirected graphs, homogeneous tournaments and homogeneous partially ordered sets. We also give a finite presentation of the rational Urysohn metric space and some homogeneous directed graphs. We survey well known structures that are finitely presented. We focus on structures endowed with natural partial orders and prove their universality. These partial orders include partial orders on sets of words, partial orders formed by geometric objects, grammars, polynomials and homomorphism orders for various combinatorial objects. We give a new combinatorial proof of the existence of embedding-universal objects for homomorphism-defined classes of structures. This relates countable embedding-universal structures to homomorphism dualities (finite homomorphism-universal structures) and Urysohn metric spaces. Our explicit construction also allows us to show several properties of these structures.

  1. EDITORIAL: Combinatorial and High-Throughput Materials Research

    Science.gov (United States)

    Potyrailo, Radislav A.; Takeuchi, Ichiro

    2005-01-01

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

  2. 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...... including MSNT-mediated esterification of both support-bound alcohols and carboxylic acids has been implemented successfully. Copyright (C) 1996 Elsevier Science Ltd....

  3. 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...... including MSNT-mediated esterification of both support-bound alcohols and carboxylic acids has been implemented successfully. Copyright (C) 1996 Elsevier Science Ltd....

  4. Combinatorial Chemistry for Optical Sensing Applications

    Science.gov (United States)

    Díaz-García, M. E.; Luis, G. Pina; Rivero-Espejel, I. A.

    The recent interest in combinatorial chemistry for the synthesis of selective recognition materials for optical sensing applications is presented. The preparation, screening, and applications of libraries of ligands and chemosensors against molecular species and metal ions are first considered. Included in this chapter are also the developments involving applications of combinatorial approaches to the discovery of sol-gel and acrylic-based imprinted materials for optical sensing of antibiotics and pesticides, as well as libraries of doped sol-gels for high-throughput optical sensing of oxygen. The potential of combinatorial chemistry applied to the discovery of new sensing materials is highlighted.

  5. Dynamic combinatorial libraries of artificial repeat proteins.

    Science.gov (United States)

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

    2013-06-15

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

  6. Accessing Specific Peptide Recognition by Combinatorial Chemistry

    DEFF Research Database (Denmark)

    Li, Ming

    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...... was studied with this hook peptide library via the beadbead adhesion screening approach. The recognition pairs interlocked and formed a complex. (chapter 8) During accessing peptide molecular recognition by combinatorial chemistry, we faced several problems, which were solved by a range of analytical...

  7. Combinatorial Discovery and Optimization of New Materials

    Institute of Scientific and Technical Information of China (English)

    Gao Chen; Zhang Xinyi; Yan Dongsheng

    2001-01-01

    The concept of the combinatorial discovery and optimization of new materials, and its background,importance, and application, as well as its current status in the world, are briefly reviewed in this paper.

  8. 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.

  9. A product formula and combinatorial field theory

    CERN Document Server

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

    2004-01-01

    We treat the problem of normally ordering expressions involving the standard boson operators a, a* where [a,a*]=1. We show that a simple product formula for formal power series - essentially an extension of the Taylor expansion - leads to a double exponential formula which enables a powerful graphical description of the generating functions of the combinatorial sequences associated with such functions - in essence, a combinatorial field theory. We apply these techniques to some examples related to specific physical Hamiltonians.

  10. 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....

  11. Combinatorial study of ceramic tape-casting slurries.

    Science.gov (United States)

    Liu, Zhifu; Wang, Yiling; Li, Yongxiang

    2012-03-12

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

  12. 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

    2012-10-01

    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(2)O(2)) 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 significant in host defences against these pathogenic yeasts.

  13. Partition functions and graphs: A combinatorial approach

    CERN Document Server

    Solomon, A I; Duchamp, G; Horzela, A; Penson, K A; Solomon, Allan I.; Blasiak, Pawel; Duchamp, Gerard; Horzela, Andrzej; Penson, Karol A.

    2004-01-01

    Although symmetry methods and analysis are a necessary ingredient in every physicist's toolkit, rather less use has been made of combinatorial methods. One exception is in the realm of Statistical Physics, where the calculation of the partition function, for example, is essentially a combinatorial problem. In this talk we shall show that one approach is via the normal ordering of the second quantized operators appearing in the partition function. This in turn leads to a combinatorial graphical description, giving essentially Feynman-type graphs associated with the theory. We illustrate this methodology by the explicit calculation of two model examples, the free boson gas and a superfluid boson model. We show how the calculation of partition functions can be facilitated by knowledge of the combinatorics of the boson normal ordering problem; this naturally gives rise to the Bell numbers of combinatorics. The associated graphical representation of these numbers gives a perturbation expansion in terms of a sequen...

  14. 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...

  15. Pricing in combinatorial double auction-based grid allocation model

    Institute of Scientific and Technical Information of China (English)

    LI Li; LIU Yuan-an; LIU Kai-ming; MA Xiao-lei; YANG Ming

    2009-01-01

    This article proposes a novel grid resource allocation model, in which the users and the grid service providers participate in the combinatorial double auction for the resource allocation. To obtain the detailed resource allocation status and the price information, a novel pricing algorithm is designed for the allocation model. Simulation results demonstrate that the proposed algorithm completes the resource allocation and pricing efficiently, and exhibits incentive compatible characteristic. Moreover,users with the higher average price and providers with the lower average price get compensation during the pricing process.

  16. Combinatorial study of colored Hurwitz polyz\\^etas

    OpenAIRE

    Enjalbert, Jean-Yves; Minh, Hoang Ngoc

    2012-01-01

    A combinatorial study discloses two surjective morphisms between generalized shuffle algebras and algebras generated by the colored Hurwitz polyz\\^etas. The combinatorial aspects of the products and co-products involved in these algebras will be examined.

  17. Combinatorial set theory partition relations for cardinals

    CERN Document Server

    Erdös, P; Hajnal, A; Rado, P

    2011-01-01

    This work presents the most important combinatorial ideas in partition calculus and discusses ordinary partition relations for cardinals without the assumption of the generalized continuum hypothesis. A separate section of the book describes the main partition symbols scattered in the literature. A chapter on the applications of the combinatorial methods in partition calculus includes a section on topology with Arhangel''skii''s famous result that a first countable compact Hausdorff space has cardinality, at most continuum. Several sections on set mappings are included as well as an account of

  18. Toward Chemical Implementation of Encoded Combinatorial Libraries

    DEFF Research Database (Denmark)

    Nielsen, John; Janda, Kim D.

    1994-01-01

    by existing methodologies. Here we detail the synthesis of several matrices and the necessary chemistry to implement the conceptual scheme. In addition, we disclose how this novel technology permits a controlled ′dendritic" display of the chemical libraries. © 1994 Academic Press. All rights reserved.......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...

  19. Mapping the Materials Genome through Combinatorial Informatics

    Science.gov (United States)

    Rajan, Krishna

    2012-02-01

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

  20. 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…

  1. 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

  2. Polyhredral techniques in combinatorial optimization I: theory

    NARCIS (Netherlands)

    Aardal, K.; Hoesel, S. van

    2001-01-01

    Combinatorial optimization problems appear in many disciplines ranging from management and logistics to mathematics, physics, and chemistry. These problems are usually relatively easy to formulate mathematically, but most of them are computationally hard due to the restriction that a subset of the v

  3. Combinatorial optimization tolerances calculated in linear time

    NARCIS (Netherlands)

    Goldengorin, Boris; Sierksma, Gerard

    2003-01-01

    For a given optimal solution to a combinatorial optimization problem, we show, under very natural conditions, the equality of the minimal values of upper and lower tolerances, where the upper tolerances are calculated for the given optimal solution and the lower tolerances outside the optimal

  4. Grobner Basis Approach to Some Combinatorial Problems

    Directory of Open Access Journals (Sweden)

    Victor Ufnarovski

    2012-10-01

    Full Text Available We consider several simple combinatorial problems and discuss different ways to express them using polynomial equations and try to describe the \\GB of the corresponding ideals. The main instruments are complete symmetric polynomials that help to express different conditions in rather compact way.

  5. Grobner Basis Approach to Some Combinatorial Problems

    OpenAIRE

    2012-01-01

    We consider several simple combinatorial problems and discuss different ways to express them using polynomial equations and try to describe the \\GB of the corresponding ideals. The main instruments are complete symmetric polynomials that help to express different conditions in rather compact way.

  6. Infinitary Combinatory Reduction Systems: Normalising Reduction Strategies

    NARCIS (Netherlands)

    Ketema, Jeroen; 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 fi

  7. Erratum to Ordered Partial Combinatory Algebras

    NARCIS (Netherlands)

    Hofstra, P.; Oosten, J. van

    2003-01-01

    To our regret the paper Ordered Partial Combinatory Algebras contains a mistake which we correct here The flaw concerns the definition of compu tational density definition 3.5 which appeared in section 3.3 page 451 This definition is too rigid and as a consequence Lemma 3.6 on page 452

  8. 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…

  9. 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…

  10. Combinatorial optimization tolerances calculated in linear time

    NARCIS (Netherlands)

    Goldengorin, Boris; Sierksma, Gerard

    2003-01-01

    For a given optimal solution to a combinatorial optimization problem, we show, under very natural conditions, the equality of the minimal values of upper and lower tolerances, where the upper tolerances are calculated for the given optimal solution and the lower tolerances outside the optimal soluti

  11. Recent developments in dynamic combinatorial chemistry

    NARCIS (Netherlands)

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

    2002-01-01

    Generating combinatorial libraries under equilibrium conditions has the important advantage that the libraries are adaptive (i.e. they can respond to exterior influences in the form of molecular recognition events). Thus, a ligand will direct and amplify the formation of its ideal receptor and vice

  12. Boltzmann Samplers for Colored Combinatorial Objects

    CERN Document Server

    Bodini, Olivier

    2009-01-01

    In this paper, we give a general framework for the Boltzmann generation of colored objects belonging to combinatorial constructible classes. We propose an intuitive notion called profiled objects which allows the sampling of size-colored objects (and also of k-colored objects) although the corresponding class cannot be described by an analytic ordinary generating function.

  13. 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

  14. 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....

  15. Models of optimum discrete signals on the vector combinatorial configurations

    Directory of Open Access Journals (Sweden)

    V. V. Riznyk

    2016-06-01

    Full Text Available Method for construction of optimum discrete signals, based on a new conceptual combinatorial model of the systems - Ideal Ring Vector sequences (clusters of the IRV is proposed. IRV clusters are cyclic ordered sequences of t- integer sub-sequences of sequence, which form perfect relationships of t-dimensional partitions over a virtual t-dimensional lattice covered surface of a finite space interval. The sums of connected sub-sequences of an IRV enumerate the set of t- coordinates specified with respect to cyclic frame reference exactly R-times. This property makes IRVs useful in applications, which need to partition multidimensional objects with the smallest possible number of intersections. There are discover a great class of new two- and multidimensional combinatorial constructions, which being in excess classic models of discrete systems with respect to number and combinatorial varieties with theoretically non-limited values of upper boundaries on order of dimensionality –IRV. It shows that remarkable properties of IRVs encoded in fine structure of torus circular symmetry. There are regarded basic properties these models and made shortest comparative analysis of the models with classical models. Indicate that the IRVs to be in exceed of difference sets multiply, and set of the classical difference sets is subset of the IRVs. Some of useful examples for constructing of the optimum discrete signals, error-correcting codes, and ring monolithic optimum vector codes using IRVs are considered. The problem statement involves development the regular method for construction of the optimum discrete signals using two- and multidimensional IRVs. The favorable technical merits of IRVs sets named “Gloria to Ukraine Stars”, which remarkable properties hold for the same set of the IRVs in varieties permutations of its terms is demonstrated, and method for design of two- or multidimensional vector signals coded based on the optimum binary monolithic

  16. Combinatorial Clustering Algorithm of Quantum-Behaved Particle Swarm Optimization and Cloud Model

    Directory of Open Access Journals (Sweden)

    Mi-Yuan Shan

    2013-01-01

    Full Text Available We propose a combinatorial clustering algorithm of cloud model and quantum-behaved particle swarm optimization (COCQPSO to solve the stochastic problem. The algorithm employs a novel probability model as well as a permutation-based local search method. We are setting the parameters of COCQPSO based on the design of experiment. In the comprehensive computational study, we scrutinize the performance of COCQPSO on a set of widely used benchmark instances. By benchmarking combinatorial clustering algorithm with state-of-the-art algorithms, we can show that its performance compares very favorably. The fuzzy combinatorial optimization algorithm of cloud model and quantum-behaved particle swarm optimization (FCOCQPSO in vague sets (IVSs is more expressive than the other fuzzy sets. Finally, numerical examples show the clustering effectiveness of COCQPSO and FCOCQPSO clustering algorithms which are extremely remarkable.

  17. 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.

  18. An Allosteric Receptor by Simultaneous "Casting" and "Molding" in a Dynamic Combinatorial Library

    NARCIS (Netherlands)

    Li, Jianwei; Nowak, Piotr; Otto, Sijbren

    2015-01-01

    Allosteric synthetic receptors are difficult to access by design. Herein we report a dynamic combinatorial strategy towards such systems based on the simultaneous use of two different templates. Through a process of simultaneous casting (the assembly of a library member around a template) and moldin

  19. A model-based combinatorial optimisation approach for energy-efficient processing of microalgae

    NARCIS (Netherlands)

    Slegers, P.M.; Koetzier, B.J.; Fasaei, F.; Wijffels, R.H.; Straten, van G.; Boxtel, van A.J.B.

    2014-01-01

    The analyses of algae biorefinery performance are commonly based on fixed performance data for each processing step. In this work, we demonstrate a model-based combinatorial approach to derive the design-specific upstream energy consumption and biodiesel yield in the production of biodiesel from mic

  20. A model-based combinatorial optimisation approach for energy-efficient processing of microalgae

    NARCIS (Netherlands)

    Slegers, P.M.; Koetzier, B.J.; Fasaei, F.; Wijffels, R.H.; Straten, van G.; Boxtel, van A.J.B.

    2014-01-01

    The analyses of algae biorefinery performance are commonly based on fixed performance data for each processing step. In this work, we demonstrate a model-based combinatorial approach to derive the design-specific upstream energy consumption and biodiesel yield in the production of biodiesel from

  1. Designs 2002 further computational and constructive design theory

    CERN Document Server

    2003-01-01

    This volume is a sequel to the 1996 compilation, Computational and Constructive Design Theory. It contains research papers and surveys of recent research work on two closely related aspects of the study of combinatorial designs: design construction and computer-aided study of designs. Audience: This volume is suitable for researchers in the theory of combinatorial designs

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

    Science.gov (United States)

    Jeschek, Markus; Gerngross, Daniel; Panke, Sven

    2016-01-01

    Rational flux design in metabolic engineering approaches remains difficult since important pathway information is frequently not available. Therefore empirical methods are applied that randomly change absolute and relative pathway enzyme levels and subsequently screen for variants with improved performance. However, screening is often limited on the analytical side, generating a strong incentive to construct small but smart libraries. Here we introduce RedLibs (Reduced Libraries), an algorithm that allows for the rational design of smart combinatorial libraries for pathway optimization thereby minimizing the use of experimental resources. We demonstrate the utility of RedLibs for the design of ribosome-binding site libraries by in silico and in vivo screening with fluorescent proteins and perform a simple two-step optimization of the product selectivity in the branched multistep pathway for violacein biosynthesis, indicating a general applicability for the algorithm and the proposed heuristics. We expect that RedLibs will substantially simplify the refactoring of synthetic metabolic pathways.

  3. 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.

  4. Single-Parameter Combinatorial Auctions with Partially Public Valuations

    Science.gov (United States)

    Goel, Gagan; Karande, Chinmay; Wang, Lei

    We consider the problem of designing truthful auctions, when the bidders' valuations have a public and a private component. In particular, we consider combinatorial auctions where the valuation of an agent i for a set S of items can be expressed as v i f(S), where v i is a private single parameter of the agent, and the function f is publicly known. Our motivation behind studying this problem is two-fold: (a) Such valuation functions arise naturally in the case of ad-slots in broadcast media such as Television and Radio. For an ad shown in a set S of ad-slots, f(S) is, say, the number of unique viewers reached by the ad, and v i is the valuation per-unique-viewer. (b) From a theoretical point of view, this factorization of the valuation function simplifies the bidding language, and renders the combinatorial auction more amenable to better approximation factors. We present a general technique, based on maximal-in-range mechanisms, that converts any α-approximation non-truthful algorithm (α ≤ 1) for this problem into Ω(α/log{n}) and Ω(α)-approximate truthful mechanisms which run in polynomial time and quasi-polynomial time, respectively.

  5. 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 ...

  6. Three Syntactic Theories for Combinatory Graph Reduction

    DEFF Research Database (Denmark)

    Danvy, Olivier; Zerny, Ian

    2011-01-01

    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...... of term graphs in the sense of Barendregt et al. The corresponding storeless abstract machine and natural semantics follow mutatis mutandis. We then interpret let expressions as operations over a global store (thus shifting, in Strachey's words, from denotable entities to storable entities), resulting...

  7. Three Syntactic Theories for Combinatory Graph Reduction

    DEFF Research Database (Denmark)

    Danvy, Olivier; Zerny, Ian

    2013-01-01

    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...... of combinatory term graphs. We then recast let bindings as bindings in a global store, thus shifting, in Strachey's words, from denotable entities to storable entities. The store-based terms can still be interpreted as term graphs. We express this third syntactic theory, which we prove equivalent to the second...

  8. Dynamical System Approaches to Combinatorial Optimization

    DEFF Research Database (Denmark)

    Starke, Jens

    2013-01-01

    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....... Many of them are investigated analytically, and the costs of the solutions are compared numerically with those of solutions obtained by simulated annealing and the costs of a global optimal solution. Using dynamical systems, a solution to the combinatorial optimization problem emerges in the limit...... 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...

  9. Dynamic combinatorial self-replicating systems.

    Science.gov (United States)

    Moulin, Emilie; Giuseppone, Nicolas

    2012-01-01

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

  10. Stochastic Combinatorial Optimization under Probabilistic Constraints

    CERN Document Server

    Agrawal, Shipra; Ye, Yinyu

    2008-01-01

    In this paper, we present approximation algorithms for combinatorial optimization problems under probabilistic constraints. Specifically, we focus on stochastic variants of two important combinatorial optimization problems: the k-center problem and the set cover problem, with uncertainty characterized by a probability distribution over set of points or elements to be covered. We consider these problems under adaptive and non-adaptive settings, and present efficient approximation algorithms for the case when underlying distribution is a product distribution. In contrast to the expected cost model prevalent in stochastic optimization literature, our problem definitions support restrictions on the probability distributions of the total costs, via incorporating constraints that bound the probability with which the incurred costs may exceed a given threshold.

  11. Assessment of structural diversity in combinatorial synthesis.

    Science.gov (United States)

    Fergus, Suzanne; Bender, Andreas; Spring, David R

    2005-06-01

    This article covers the combinatorial synthesis of small molecules with maximal structural diversity to generate a collection of pure compounds that are attractive for lead generation in a phenotypic, high-throughput screening approach. Nature synthesises diverse small molecules, but there are disadvantages with using natural product sources. The efficient chemical synthesis of structural diversity (and complexity) is the aim of diversity-oriented synthesis, and recent progress is reviewed. Specific highlights include a discussion of strategies to obtain structural diversity and an analysis of molecular descriptors used to classify compounds. The assessment of how successful one synthesis is versus another is subjective, therefore we test-drive software to assess structural diversity in combinatorial synthesis, which is freely available via a web interface.

  12. Memetic firefly algorithm for combinatorial optimization

    CERN Document Server

    Fister, Iztok; Fister, Iztok; Brest, Janez

    2012-01-01

    Firefly algorithms belong to modern meta-heuristic algorithms inspired by nature that can be successfully applied to continuous optimization problems. In this paper, we have been applied the firefly algorithm, hybridized with local search heuristic, to combinatorial optimization problems, where we use graph 3-coloring problems as test benchmarks. The results of the proposed memetic firefly algorithm (MFFA) were compared with the results of the Hybrid Evolutionary Algorithm (HEA), Tabucol, and the evolutionary algorithm with SAW method (EA-SAW) by coloring the suite of medium-scaled random graphs (graphs with 500 vertices) generated using the Culberson random graph generator. The results of firefly algorithm were very promising and showed a potential that this algorithm could successfully be applied in near future to the other combinatorial optimization problems as well.

  13. High throughput combinatorial screening of semiconductor materials

    Science.gov (United States)

    Mao, Samuel S.

    2011-11-01

    This article provides an overview of an advanced combinatorial material discovery platform developed recently for screening semiconductor materials with properties that may have applications ranging from radiation detectors to solar cells. Semiconductor thin-film libraries, each consisting of 256 materials of different composition arranged into a 16×16 matrix, were fabricated using laser-assisted evaporation process along with a combinatorial mechanism to achieve variations. The composition and microstructure of individual materials on each thin-film library were characterized with an integrated scanning micro-beam x-ray fluorescence and diffraction system, while the band gaps were determined by scanning optical reflection and transmission of the libraries. An ultrafast ultraviolet photon-induced charge probe was devised to measure the mobility and lifetime of individual thin-film materials on semiconductor libraries. Selected results on the discovery of semiconductors with desired band gaps and transport properties are illustrated.

  14. Switched Systems and Motion Coordination: Combinatorial Challenges

    Science.gov (United States)

    Sadovsky, Alexander V.

    2016-01-01

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

  15. One-parameter groups and combinatorial physics

    CERN Document Server

    Duchamp, G; Solomon, A I; Horzela, A; Blasiak, P; Duchamp, Gerard; Penson, Karol A.; Solomon, Allan I.; Horzela, Andrej; Blasiak, Pawel

    2004-01-01

    In this communication, we consider the normal ordering of sums of elements of the form (a*^r a a*^s), where a* and a are boson creation and annihilation operators. We discuss the integration of the associated one-parameter groups and their combinatorial by-products. In particular, we show how these groups can be realized as groups of substitutions with prefunctions.

  16. The Combinatorial Retention Auction Mechanism (CRAM)

    OpenAIRE

    Coughlan, Peter; Gates, William (Bill); Myung, Noah

    2013-01-01

    Approved for public release; distribution is unlimited. Revised version We propose a reverse uniform price auction called Combinatorial Retention Auction Mechanism (CRAM) that integrates both monetary and non-monetary incentives (NMIs). CRAM computes the cash bonus and NMIs to a single cost parameter, retains the lowest cost employees and provides them with compensation equal to the cost of the first excluded employee. CRAM is dominant strategy incentive compatible. We provide optimal b...

  17. 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.

  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. Generalized topological spaces in evolutionary theory and combinatorial chemistry.

    Science.gov (United States)

    Stadler, Bärbel M R; Stadler, Peter F

    2002-01-01

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

  20. 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.

  1. Mixture-Based Combinatorial Libraries from Small Individual Peptide Libraries: A Case Study on α1-Antitrypsin Deficiency

    Directory of Open Access Journals (Sweden)

    Yi-Pin Chang

    2014-05-01

    Full Text Available 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.

  2. Advanced Aqueous Phase Catalyst Development using Combinatorial Methods Project

    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...

  3. Combinatorial optimization problem solution based on improved genetic algorithm

    Science.gov (United States)

    Zhang, Peng

    2017-08-01

    Traveling salesman problem (TSP) is a classic combinatorial optimization problem. It is a simplified form of many complex problems. In the process of study and research, it is understood that the parameters that affect the performance of genetic algorithm mainly include the quality of initial population, the population size, and crossover probability and mutation probability values. As a result, an improved genetic algorithm for solving TSP problems is put forward. The population is graded according to individual similarity, and different operations are performed to different levels of individuals. In addition, elitist retention strategy is adopted at each level, and the crossover operator and mutation operator are improved. Several experiments are designed to verify the feasibility of the algorithm. Through the experimental results analysis, it is proved that the improved algorithm can improve the accuracy and efficiency of the solution.

  4. Criticality and parallelism in combinatorial optimization

    Energy Technology Data Exchange (ETDEWEB)

    Macready, W.G.; Kauffman, S.A. [Santa Fe Institute, NM (United States); Siapas, A.G. [Massachusetts Institute of Technology, Cambridge, MA (United States)

    1996-01-05

    Local search methods constitute one of the most successful approaches to solving large-scale combinatorial optimization problems. As these methods are increasingly parallelized, optimization performance initially improves, but then abruptly degrades to no matter than that of random search beyond a certain point. The existence of this transition is demonstrated for a family of generalized spin-glass models and the traveling salesman problem. Finite-size scaling is used to characterize size-dependent effects near the transition, and analytical insight is obtained through a mean-field approximation. 17 refs., 5 figs.

  5. Algebraic and combinatorial Brill-Noether theory

    OpenAIRE

    Caporaso, Lucia

    2011-01-01

    The interplay between algebro-geometric and combinatorial Brill-Noether theory is studied. The Brill-Noether variety of a graph shown to be non-empty if the Brill-Noether number is non-negative, as a consequence of the analogous fact for smooth projective curves. Similarly, the existence of a graph for which the Brill-Noether variety is empty implies the emptiness of the corresponding Brill-Noether variety for a general curve. The main tool is a refinement of Baker's Specialization Lemma.

  6. Method and apparatus for combinatorial chemistry

    Science.gov (United States)

    Foote, Robert S.

    2007-02-20

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

  7. Apparatus for combinatorial screening of electrochemical materials

    Science.gov (United States)

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

    2009-12-15

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

  8. Combinatorial level densities for practical applications

    Directory of Open Access Journals (Sweden)

    Sin M.

    2010-03-01

    Full Text Available We review our calculated energy-, spin- and parity-dependent nuclear level densities based on the microscopic combinatorial model described in ref. [1]. We show that this model predicts the experimental sand p-wave neutron resonance spacings with a degree of accuracy comparable to that of the best global models available and also provides reasonable description of low energies cumulative number of levels as well as of the experimental data obtained by the Oslo group [2]. We also provide a renormalization recipe which enables to play with the tabulated results for practical applications. Finally, we study the impact of temperature dependent calculation on s-wave neutron resonance spacings.

  9. 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

  10. Combinatorial nuclear level-density model

    Energy Technology Data Exchange (ETDEWEB)

    Moller, Peter [Los Alamos National Laboratory; Aberg, Sven [LUND SWEDEN; Uhrenhoit, Henrik [LUND SWEDEN; Ickhikawa, Takatoshi [RIKEN

    2008-01-01

    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: neutron separation energy level spacings, data on total level-density functions from the Oslo method and data on parity ratios.

  11. A Novel Human scFv Library with Non-Combinatorial Synthetic CDR Diversity.

    Science.gov (United States)

    Bai, Xuelian; Kim, Jihye; Kang, Seungmin; Kim, Wankyu; Shim, Hyunbo

    2015-01-01

    The present work describes the construction and validation of a human scFv library with a novel design approach to synthetic complementarity determining region (CDR) diversification. The advantage of synthetic antibody libraries includes the possibility of exerting fine control over factors like framework sequences, amino acid and codon usage, and CDR diversity. However, random combinatorial synthesis of oligonucleotides for CDR sequence diversity also produces many clones with unnatural sequences and/or undesirable modification motifs. To alleviate these issues, we designed and constructed a novel semi-synthetic human scFv library with non-combinatorial, pre-designed CDR diversity and a single native human framework each for heavy, kappa, and lambda chain variable domains. Next-generation sequencing analysis indicated that the library consists of antibody clones with highly nature-like CDR sequences and the occurrence of the post-translational modification motifs is minimized. Multiple unique clones with nanomolar affinity could be isolated from the library against a number of target antigens, validating the library design strategy. The results demonstrate that it is possible to construct a functional antibody library using low, non-combinatorial synthetic CDR diversity, and provides a new strategy for the design of antibody libraries suitable for demanding applications.

  12. 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....

  13. Self-encoding resin beads of combinatorial library screening

    Science.gov (United States)

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

    2003-07-01

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

  14. A combinatorial morphospace for angiosperm pollen

    Science.gov (United States)

    Mander, Luke

    2016-04-01

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

  15. Cryptographic Combinatorial Clock-Proxy Auctions

    Science.gov (United States)

    Parkes, David C.; Rabin, Michael O.; Thorpe, Christopher

    We present a cryptographic protocol for conducting efficient, provably correct and secrecy-preserving combinatorial clock-proxy auctions. The “clock phase” functions as a trusted auction despite price discovery: bidders submit encrypted bids, and prove for themselves that they meet activity rules, and can compute total demand and thus verify price increases without revealing any information about individual demands. In the sealed-bid “proxy phase”, all bids are revealed the auctioneer via time-lapse cryptography and a branch-and-bound algorithm is used to solve the winner-determination problem. Homomorphic encryption is used to prove the correctness of the solution, and establishes the correctness of the solution to any interested party. Still an NP-hard optimization problem, the use of homomorphic encryption imposes additional computational time on winner-determination that is linear in the size of the branch-and-bound search tree, and thus roughly linear in the original (search-based) computational time. The result is a solution that avoids, in the usual case, the exponential complexity of previous cryptographically-secure combinatorial auctions.

  16. Locating Minimal Fault Interaction in Combinatorial Testing

    Directory of Open Access Journals (Sweden)

    Wei Zheng

    2016-01-01

    Full Text Available Combinatorial testing (CT technique could significantly reduce testing cost and increase software system quality. By using the test suite generated by CT as input to conduct black-box testing towards a system, we are able to detect interactions that trigger the system’s faults. Given a test case, there may be only part of all its parameters relevant to the defects in system and the interaction constructed by those partial parameters is key factor of triggering fault. If we can locate those parameters accurately, this will facilitate the software diagnosing and testing process. This paper proposes a novel algorithm named complete Fault Interaction Location (comFIL to locate those interactions that cause system’s failures and meanwhile obtains the minimal set of target interactions in test suite produced by CT. By applying this method, testers can analyze and locate the factors relevant to defects of system more precisely, thus making the process of software testing and debugging easier and more efficient. The results of our empirical study indicate that comFIL performs better compared with known fault location techniques in combinatorial testing because of its improved effectiveness and precision.

  17. 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.

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

    Science.gov (United States)

    West, William; Whitacre, Jay; Bugga, Ratnakumar

    2003-01-01

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

  19. Constructing virtual combinatorial fragment libraries based upon MDL Drug Data Report database

    Institute of Scientific and Technical Information of China (English)

    ZHANG Min; SHENG ChunQuan; XU Hui; SONG YunLong; ZHANG WanNian

    2007-01-01

    Structural analysis of known drugs or drug-like compounds provides important information for drug design. The 142553 drug molecules in the MDL Drug Data Report database were analyzed, and then the common structural features were extracted. According to the common structural features, drug molecules were segmented into 32017 fragments, including 13642 ring fragments, 10076 linker fragments,and 8299 side chain fragments. These fragments were further used to establish three types of virtual combinatorial fragment libraries: a basic framework library containing 13574 rings; a linker library of 8051 linkers and a pharmacophore library of 34244 fragments combined by rings and side chains. After energy minimization, all fragments in the above three libraries maintain reasonable geometrical features and spatial conformations, and would be useful for building a virtual combinatorial database and de novo drug design.

  20. Constructing virtual combinatorial fragment libraries based upon MDL Drug Data Report database

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    Structural analysis of known drugs or drug-like compounds provides important information for drug design. The 142553 drug molecules in the MDL Drug Data Report database were analyzed, and then the common structural features were extracted. According to the common structural features, drug molecules were segmented into 32017 fragments, including 13642 ring fragments, 10076 linker fragments, and 8299 side chain fragments. These fragments were further used to establish three types of virtual combinatorial fragment libraries: a basic framework library containing 13574 rings; a linker library of 8051 linkers and a pharmacophore library of 34244 fragments combined by rings and side chains. After energy minimization, all fragments in the above three libraries maintain reasonable geometrical features and spatial conformations, and would be useful for building a virtual combinatorial database and de novo drug design.

  1. Mental Disorder Diagnostic System Based on Logical-Combinatorial Methods of Pattern Recognition

    Directory of Open Access Journals (Sweden)

    Anna Yankovskaya

    2013-11-01

    Full Text Available The authors describe mental disorder diagnostic system based on logical-combinatorial methods of pattern recognition called as the intelligent system DIAPROD-LOG. The system is designed for diagnostics and prevention of depression. The mathematical apparatus for creation of the proposed system based on a matrix model of data and knowledge representation, as well as various kinds of regularities in data and knowledge are presented. The description of the system is given.

  2. 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.

  3. Synthesis of two D-glucosamine derived 3,4-epoxides as potential scaffolds for combinatorial chemistry

    DEFF Research Database (Denmark)

    Svejgaard, L.; Fuglsang, H.; Jensen, P.B.

    2003-01-01

    Combinatorial chemistry allows the synthesis of libraries of compounds by combination of building blocks or by combinatorial elaboration of a central scaffold.([1,2]) Carbohydrates hold great promise as scaffolds due to their high degree of functionalization, relative conformational rigidity......, commercial availability of many stereoisomeric forms, and their well-described chemistry. Hirschmann, Nicolaou, Smith, and their coworkers pioneered the use of carbohydrates as scaffolds in their design and synthesis Of beta-D-glucose derived non-peptide peptidomimetics of the peptide hormone somatostatin...... (SRIF).([3,4]) However, only relatively few examples on the application of carbohydrates as scaffolds in combinatorial chemistry have been described.([5-11]) For example, Brill et al. anchored a 1,6-anhydro-beta-D-glucopyranoside (levoglucosan) derived epoxide to a solid support and introduced diversity...

  4. 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.

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

    Science.gov (United States)

    Fuller, Amelia A.

    2016-01-01

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

  6. Combinatorial Synthesis and Discovery of an Antibiotic Compound. An Experiment Suitable for High School and Undergraduate Laboratories

    Science.gov (United States)

    Wolkenberg, Scott E.; Su, Andrew I.

    2001-06-01

    An exercise demonstrating solution-phase combinatorial chemistry and its application to drug discovery is described. The experiment involves the synthesis of six libraries of three hydrazones, screening the libraries for antibiotic activity, and deconvolution to determine the active individual compound. The laboratory was designed for a high school classroom, though it can easily be expanded to suit a college introductory organic laboratory course.

  7. Combinatorial Algorithms to Enable Computational Science and Engineering: The CSCAPES Institute

    Energy Technology Data Exchange (ETDEWEB)

    Pothen, Alex [Purdue University

    2015-01-16

    This final progress report summarizes the work accomplished at the Combinatorial Scientific Computing and Petascale Simulations Institute. We developed Zoltan, a parallel mesh partitioning library that made use of accurate hyeprgraph models to provide load balancing in mesh-based computations. We developed several graph coloring algorithms for computing Jacobian and Hessian matrices and organized them into a software package called ColPack. We developed parallel algorithms for graph coloring and graph matching problems, and also designed multi-scale graph algorithms. Three PhD students graduated, six more are continuing their PhD studies, and four postdoctoral scholars were advised. Six of these students and Fellows have joined DOE Labs (Sandia, Berkeley, as staff scientists or as postdoctoral scientists. We also organized the SIAM Workshop on Combinatorial Scientific Computing (CSC) in 2007, 2009, and 2011 to continue to foster the CSC community.

  8. Combinatorial Algorithms to Enable Computational Science and Engineering: Work from the CSCAPES Institute

    Energy Technology Data Exchange (ETDEWEB)

    Boman, Erik G. [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States). Scalable Algorithms Dept.; Catalyurek, Umit V. [The Ohio State Univ., Columbus, OH (United States). Biomedical Informatics. Electrical and Computer Engineering; Chevalier, Cedric [Alternative Energies and Atomic Energy Commission (CEA), Cadarache (France); Devine, Karen D. [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States). Scalable Algorithms Dept.; Gebremedhin, Assefaw H. [Purdue Univ., West Lafayette, IN (United States). Computer Science; Hovland, Paul D. [Argonne National Lab. (ANL), Argonne, IL (United States). Mathematics and Computer Science Division; Pothen, Alex [Purdue Univ., West Lafayette, IN (United States). Computer Science; Rajamanickam, Sivasankaran [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States). Scalable Algorithms Dept.; Safro, Ilya [Argonne National Lab. (ANL), Argonne, IL (United States). Mathematics and Computer Science Division; Wolf, Michael M. [Massachusetts Inst. of Technology (MIT), Lexington, MA (United States). Lincoln Lab.; Zhou, Min [Rensselaer Polytechnic Inst., Troy, NY (United States). Scientific Computation Research Center

    2015-01-16

    This final progress report summarizes the work accomplished at the Combinatorial Scientific Computing and Petascale Simulations Institute. We developed Zoltan, a parallel mesh partitioning library that made use of accurate hypergraph models to provide load balancing in mesh-based computations. We developed several graph coloring algorithms for computing Jacobian and Hessian matrices and organized them into a software package called ColPack. We developed parallel algorithms for graph coloring and graph matching problems, and also designed multi-scale graph algorithms. Three PhD students graduated, six more are continuing their PhD studies, and four postdoctoral scholars were advised. Six of these students and Fellows have joined DOE Labs (Sandia, Berkeley), as staff scientists or as postdoctoral scientists. We also organized the SIAM Workshop on Combinatorial Scientific Computing (CSC) in 2007, 2009, and 2011 to continue to foster the CSC community.

  9. A drop-on-demand ink-jet printer for combinatorial libraries and functionally graded ceramics.

    Science.gov (United States)

    Mohebi, Mohammad Masoud; Evans, Julian R G

    2002-01-01

    A printer has been designed and built for the preparation of combinatorial libraries of ceramics and for solid freeforming of functionally graded ceramics with three-dimensionally programmable spatial variation in composition. Several ceramic suspensions (as inks) can be subjected to micromixing behind the nozzle and printed at precise positions. Both mixing and positioning are computer-controlled. The machine consists of an XY table to control the geometry, a set of electromagnetic valves that manage the mixing, a combined electromagnetic valve and sapphire nozzle that form the print head, and a computer that controls the whole system. The mixing valves can eject as little as 1 mg/s ink into the mixing chamber. The printer has been controlled, run, calibrated and tested; the composition and geometry of printed mixtures can be controlled precisely. This method for the controlled mixing of powders facilitates the advance of combinatorial methods within the materials sciences.

  10. 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...

  11. Combinatorial polynomials as moments, Hankel transforms and exponential Riordan arrays

    CERN Document Server

    Barry, Paul

    2011-01-01

    In the case of two combinatorial polynomials, we show that they can exhibited as moments of paramaterized families of orthogonal polynomials, and hence derive their Hankel transforms. Exponential Riordan arrays are the main vehicles used for this.

  12. 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...

  13. Advanced Aqueous Phase Catalyst Development using Combinatorial Methods Project

    Data.gov (United States)

    National Aeronautics and Space Administration — The use of combinatorial methods is proposed to rapidly screen catalyst formulations for the advanced development of aqueous phase oxidation catalysts with greater...

  14. New opioid peptides, peptidomimetics, and heterocyclic compounds from combinatorial libraries.

    Science.gov (United States)

    Dooley, C T; Houghten, R A

    1999-01-01

    Here we review the use of combinatorial libraries in opioid receptor assays. Following a brief description of the history of the combinatorial field, methods for the generation of synthetic libraries and the deconvolution of mixture-based libraries are presented. Case studies involving opioid assays used to demonstrate the viability of combinatorial libraries are described. The identification of new opioid peptides from combinatorial libraries is reviewed. The peptides found are composed of L-amino acids, D-amino acids, or L-, D-, and unnatural amino acids, and range from tetrapeptides to decapeptides. Likewise, new opioid compounds identified from peptidomimetic libraries, such as peptoids and alkylated dipeptides, and those identified from acyclic (e.g., polyamine, urea) and heterocyclic (e.g., bicyclic guanidine) libraries, are reviewed.

  15. Combinatorial Hopf Algebras in (Noncommutative) Quantum Field Theory

    CERN Document Server

    Tanasa, Adrian

    2010-01-01

    We briefly review the r\\^ole played by algebraic structures like combinatorial Hopf algebras in the renormalizability of (noncommutative) quantum field theory. After sketching the commutative case, we analyze the noncommutative Grosse-Wulkenhaar model.

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

    Science.gov (United States)

    Liu, Wenshan; Jiang, Rongrong

    2015-03-01

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

  17. Reinvigorating natural product combinatorial biosynthesis with synthetic biology.

    Science.gov (United States)

    Kim, Eunji; Moore, Bradley S; Yoon, Yeo Joon

    2015-09-01

    Natural products continue to play a pivotal role in drug-discovery efforts and in the understanding if human health. The ability to extend nature's chemistry through combinatorial biosynthesis--altering functional groups, regiochemistry and scaffold backbones through the manipulation of biosynthetic enzymes--offers unique opportunities to create natural product analogs. Incorporating emerging synthetic biology techniques has the potential to further accelerate the refinement of combinatorial biosynthesis as a robust platform for the diversification of natural chemical drug leads. Two decades after the field originated, we discuss the current limitations, the realities and the state of the art of combinatorial biosynthesis, including the engineering of substrate specificity of biosynthetic enzymes and the development of heterologous expression systems for biosynthetic pathways. We also propose a new perspective for the combinatorial biosynthesis of natural products that could reinvigorate drug discovery by using synthetic biology in combination with synthetic chemistry.

  18. Dynamic Combinatorial Libraries of Disulfide Cages in Water

    NARCIS (Netherlands)

    West, Kevin R.; Bake, Kyle D.; Otto, Sijbren

    2005-01-01

    Dynamic combinatorial libraries (DCLs) containing water-soluble disulfide-linked cages (alongside macrocyclic structures) have been generated and characterized. Unlike most other strategies for generating molecular cages, the structures are held together by covalent bonds, which are formed under

  19. Variational Splines and Paley--Wiener Spaces on Combinatorial Graphs

    CERN Document Server

    Pesenson, Isaac

    2011-01-01

    Notions of interpolating variational splines and Paley-Wiener spaces are introduced on a combinatorial graph G. Both of these definitions explore existence of a combinatorial Laplace operator onG. The existence and uniqueness of interpolating variational splines on a graph is shown. As an application of variational splines, the paper presents a reconstruction algorithm of Paley-Wiener functions on graphs from their uniqueness sets.

  20. Variational Splines and Paley--Wiener Spaces on Combinatorial Graphs

    OpenAIRE

    Pesenson, Isaac

    2011-01-01

    Notions of interpolating variational splines and Paley-Wiener spaces are introduced on a combinatorial graph G. Both of these definitions explore existence of a combinatorial Laplace operator onG. The existence and uniqueness of interpolating variational splines on a graph is shown. As an application of variational splines, the paper presents a reconstruction algorithm of Paley-Wiener functions on graphs from their uniqueness sets.

  1. TARCMO: Theory and Algorithms for Robust, Combinatorial, Multicriteria Optimization

    Science.gov (United States)

    2016-11-28

    magnitude in computational experiments on portfolio optimization problems. The research on this topic has been published as [CG15a], where details can...AFRL-AFOSR-UK-TR-2017-0001 TARCMO: Theory and Algorithms for Robust, Combinatorial, Multicriteria Optimization Horst Hamacher Technische Universität...To)  15 May 2013 to 12 May 2016 4. TITLE AND SUBTITLE TARCMO: Theory and Algorithms for Robust, Combinatorial, Multicriteria Optimization 5a.  CONTRACT

  2. Sampling, Filtering and Sparse Approximations on Combinatorial Graphs

    CERN Document Server

    Pesenson, Isaac Z

    2011-01-01

    In this paper we address sampling and approximation of functions on combinatorial graphs. We develop filtering on graphs by using Schr\\"odinger's group of operators generated by combinatorial Laplace operator. Then we construct a sampling theory by proving Poincare and Plancherel-Polya-type inequalities for functions on graphs. These results lead to a theory of sparse approximations on graphs and have potential applications to filtering, denoising, data dimension reduction, image processing, image compression, computer graphics, visualization and learning theory.

  3. 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.

  4. Combinatorial Dyson-Schwinger equations and inductive data types

    OpenAIRE

    Kock, Joachim

    2015-01-01

    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 co...

  5. Simultaneous detection and differentiates of Brucella abortus and Brucella melitensis by combinatorial PCR

    Institute of Scientific and Technical Information of China (English)

    Reza Mirnejad; Reza Hosseini Doust; Reza Kachuei; Seied Mojtaba Mortazavi; Mehdi Khoobdel; Ali Ahamadi

    2012-01-01

    Objective:To evaluate simultaneous detection and differentiates of Brucella abortus(B. abortus) and Brucella melitensis (B. melitensis) through the combinatorial PCR method. Methods:This study was designed using three primers that could simultaneously identify and differentiate two major species of pathogenic Brucella in humans and animals. Identification and differentiation of each species using the size of the PCR product were determined. To determine the specificity of the method, bacteria close to the genus Brucella were used. Finally, to confirm PCR products, In addition to the products sequence, RFLP was performed on PCR products using restriction enzymes. Results:The method of optimized combinatorial PCR in this study could simultaneously detect and differentiate B. abortus and B. melitensis with high specificity and sensitivity in clinical samples. Differentiation of species is based on the resulting bands;therefore, the band 494 bp for B. abortus and 733 bp for B. melitensis were obtained. RFLP and sequencing results confirmed PCR results. Conclusions:The results of this study shows that without routine diagnostic methods such as culture and serology tests, using the molecular method of combinatorial PCR, important species of Brucella can be simultaneously identified and differentiated in clinical samples.

  6. Geometric and Combinatorial Structure of Hypersurface Coamoebas

    CERN Document Server

    Nisse, Mounir

    2009-01-01

    Let $V$ be a complex algebraic hypersurface defined by a polynomial $f$ with Newton polytope $\\Delta$. It is well known that the spine of its amoeba has a structure of a tropical hypersurface. We prove in this paper that there exists a complex tropical hypersurface $V_{\\infty, f}$ such that its coamoeba is homeomorphic to the closure in the real torus of the coamoeba of $V$. Moreover, the coamoeba of $V_{\\infty, f}$ contains an arrangement of $(n-1)$-torus depending only on the geometry of $\\Delta$ and the coefficients of $f$. In addition, we can consider this arrangement, as a weighted codual hyperplanes arrangement in the universal covering of the real torus, and the balancing condition (the analogous to that of tropical hypersurfaces) is satisfied. This codual hyperplanes arrangement is called the {\\em shell} of the complex coamoeba (the cousin of the spine of the complex amoeba). %(or the {\\em average contour} of the complex coamoeba). Using this combinatorial coamoebas structure, we show that the amoebas...

  7. Similarity searching in large combinatorial chemistry spaces

    Science.gov (United States)

    Rarey, Matthias; Stahl, Martin

    2001-06-01

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

  8. 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.

  9. AN ADAPTIVE MEMBRANE ALGORITHM FOR SOLVING COMBINATORIAL OPTIMIZATION PROBLEMS

    Institute of Scientific and Technical Information of China (English)

    Juanjuan HE; Jianhua XIAO; Zehui SHAO

    2014-01-01

    Membrane algorithms (MAs), which inherit from P systems, constitute a new parallel and distribute framework for approximate computation. In the paper, a membrane algorithm is proposed with the improvement that the involved parameters can be adaptively chosen. In the algorithm, some membranes can evolve dynamically during the computing process to specify the values of the requested parameters. The new algorithm is tested on a well-known combinatorial optimization problem, the travelling salesman problem. The em-pirical evidence suggests that the proposed approach is efficient and reliable when dealing with 11 benchmark instances, particularly obtaining the best of the known solutions in eight instances. Compared with the genetic algorithm, simulated annealing algorithm, neural net-work and a fine-tuned non-adaptive membrane algorithm, our algorithm performs better than them. In practice, to design the airline network that minimize the total routing cost on the CAB data with twenty-five US cities, we can quickly obtain high quality solutions using our algorithm.

  10. Free-Riding and Free-Labor in Combinatorial Agency

    Science.gov (United States)

    Babaioff, Moshe; Feldman, Michal; Nisan, Noam

    This paper studies a setting where a principal needs to motivate teams of agents whose efforts lead to an outcome that stochastically depends on the combination of agents’ actions, which are not directly observable by the principal. In [1] we suggest and study a basic “combinatorial agency” model for this setting. In this paper we expose a somewhat surprising phenomenon found in this setting: cases where the principal can gain by asking agents to reduce their effort level, even when this increased effort comes for free. This phenomenon cannot occur in a setting where the principal can observe the agents’ actions, but we show that it can occur in the hidden-actions setting. We prove that for the family of technologies that exhibit “increasing returns to scale” this phenomenon cannot happen, and that in some sense this is a maximal family of technologies for which the phenomenon cannot occur. Finally, we relate our results to a basic question in production design in firms.

  11. Combinatorial Mutagenesis and Selection to Understand and Improve Yeast Promoters

    Directory of Open Access Journals (Sweden)

    Laila Berg

    2013-01-01

    Full Text Available Microbial promoters are important targets both for understanding the global gene expression and developing genetic tools for heterologous expression of proteins and complex biosynthetic pathways. Previously, we have developed and used combinatorial mutagenesis methods to analyse and improve bacterial expression systems. Here, we present for the first time an analogous strategy for yeast. Our model promoter is the strong and inducible promoter in methylotrophic Pichia pastoris. The Zeocin resistance gene was applied as a valuable reporter for mutant promoter activity, and we used an episomal plasmid vector to ensure a constant reporter gene dosage in the yeast host cells. This novel design enabled direct selection for colonies of recombinant cells with altered Zeocin tolerance levels originating solely from randomly introduced point mutations in the promoter DNA sequence. We demonstrate that this approach can be used to select for promoter variants with abolished glucose repression in large mutant libraries. We also selected promoter variants with elevated expression level under induced conditions. The properties of the selected promoter variants were confirmed by expressing luciferase as an alternative reporter gene. The tools developed here should be useful for effective screening, characterization, and improvement of any yeast promoters.

  12. Combinatorial approaches for the identification of brain drug delivery targets.

    Science.gov (United States)

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

    2014-01-01

    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.

  13. A Combinatorial Auction among Versatile Experts and Amateurs

    Science.gov (United States)

    Ito, Takayuki; Yokoo, Makoto; Matsubara, Shigeo

    Auctions have become an integral part of electronic commerce and a promising field for applying multi-agent technologies. Correctly judging the quality of auctioned goods is often difficult for amateurs, in particular, in Internet auctions. However, experts can correctly judge the quality of goods. In this situation, it is difficult to make experts tell the truth and attain an efficient allocation, since experts have a clear advantage over amateurs and they would not reveal their valuable information without some reward. In our previous work, we have succeeded in developing such auction protocols under the following two cases: (1) the case of a single-unit auction among experts and amateurs, and (2) the case of a combinatorial auction among single-skilled experts and amateurs. In this paper, we focus on versatile experts. Versatile experts have an interest in, and expert knowledge on the qualities of several goods. In the case of versatile experts, there would be several problems, e.g., free riding problems, if we simply extended the previous VCG-style auction protocol. Thus, in this paper, we employ PORF (price-oriented, rationing-free) protocol for designing our new protocol to realize a strategy-proof auction protocol for experts. In the protocol, the dominant strategy for experts is truth-telling. Also, for amateurs, truth-telling is the best response when two or more experts select the dominant strategy. Furthermore, the protocol is false-name-proof.

  14. Neural blackboard architectures of combinatorial structures in cognition.

    Science.gov (United States)

    van der Velde, Frank; de Kamps, Marc

    2006-02-01

    Human cognition is unique in the way in which it relies on combinatorial (or compositional) structures. Language provides ample evidence for the existence of combinatorial structures, but they can also be found in visual cognition. To understand the neural basis of human cognition, it is therefore essential to understand how combinatorial structures can be instantiated in neural terms. In his recent book on the foundations of language, Jackendoff described four fundamental problems for a neural instantiation of combinatorial structures: the massiveness of the binding problem, the problem of 2, the problem of variables, and the transformation of combinatorial structures from working memory to long-term memory. This paper aims to show that these problems can be solved by means of neural "blackboard" architectures. For this purpose, a neural blackboard architecture for sentence structure is presented. In this architecture, neural structures that encode for words are temporarily bound in a manner that preserves the structure of the sentence. It is shown that the architecture solves the four problems presented by Jackendoff. The ability of the architecture to instantiate sentence structures is illustrated with examples of sentence complexity observed in human language performance. Similarities exist between the architecture for sentence structure and blackboard architectures for combinatorial structures in visual cognition, derived from the structure of the visual cortex. These architectures are briefly discussed, together with an example of a combinatorial structure in which the blackboard architectures for language and vision are combined. In this way, the architecture for language is grounded in perception. Perspectives and potential developments of the architectures are discussed.

  15. 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...... be demonstrated. The resulting library of model compounds was verified by LC-MS analysis. (C) 1997 Elsevier Science Ltd....

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

    Science.gov (United States)

    Yeung, Laurence Y.

    2016-01-01

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

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

    Science.gov (United States)

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

    2015-05-06

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

  18. Combinatorial Synthesis of and high-throughput protein release from polymer film and nanoparticle libraries.

    Science.gov (United States)

    Petersen, Latrisha K; Chavez-Santoscoy, Ana V; Narasimhan, Balaji

    2012-09-06

    Polyanhydrides are a class of biomaterials with excellent biocompatibility and drug delivery capabilities. While they have been studied extensively with conventional one-sample-at-a-time synthesis techniques, a more recent high-throughput approach has been developed enabling the synthesis and testing of large libraries of polyanhydrides(1). This will facilitate more efficient optimization and design process of these biomaterials for drug and vaccine delivery applications. The method in this work describes the combinatorial synthesis of biodegradable polyanhydride film and nanoparticle libraries and the high-throughput detection of protein release from these libraries. In this robotically operated method (Figure 1), linear actuators and syringe pumps are controlled by LabVIEW, which enables a hands-free automated protocol, eliminating user error. Furthermore, this method enables the rapid fabrication of micro-scale polymer libraries, reducing the batch size while resulting in the creation of multivariant polymer systems. This combinatorial approach to polymer synthesis facilitates the synthesis of up to 15 different polymers in an equivalent amount of time it would take to synthesize one polymer conventionally. In addition, the combinatorial polymer library can be fabricated into blank or protein-loaded geometries including films or nanoparticles upon dissolution of the polymer library in a solvent and precipitation into a non-solvent (for nanoparticles) or by vacuum drying (for films). Upon loading a fluorochrome-conjugated protein into the polymer libraries, protein release kinetics can be assessed at high-throughput using a fluorescence-based detection method (Figures 2 and 3) as described previously(1). This combinatorial platform has been validated with conventional methods(2) and the polyanhydride film and nanoparticle libraries have been characterized with (1)H NMR and FTIR. The libraries have been screened for protein release kinetics, stability and

  19. Development of a large peptoid–DOTA combinatorial library

    Science.gov (United States)

    Singh, Jaspal; Lopes, Daniel

    2016-01-01

    Abstract Conventional one‐bead one‐compound (OBOC) library synthesis is typically used to identify molecules with therapeutic value. The design and synthesis of OBOC libraries that contain molecules with imaging or even potentially therapeutic and diagnostic capacities (e.g. theranostic agents) has been overlooked. The development of a therapeutically active molecule with a built‐in imaging component for a certain target is a daunting task, and structure‐based rational design might not be the best approach. We hypothesize to develop a combinatorial library with potentially therapeutic and imaging components fused together in each molecule. Such molecules in the library can be used to screen, identify, and validate as direct theranostic candidates against targets of interest. As the first step in achieving that aim, we developed an on‐bead library of 153,600 Peptoid–DOTA compounds in which the peptoids are the target‐recognizing and potentially therapeutic components and the DOTA is the imaging component. We attached the DOTA scaffold to TentaGel beads using one of the four arms of DOTA, and we built a diversified 6‐mer peptoid library on the remaining three arms. We evaluated both the synthesis and the mass spectrometric sequencing capacities of the test compounds and of the final library. The compounds displayed unique ionization patterns including direct breakages of the DOTA scaffold into two units, allowing clear decoding of the sequences. Our approach provides a facile synthesis method for the complete on‐bead development of large peptidomimetic–DOTA libraries for screening against biological targets for the identification of potential theranostic agents in the future. © 2016 The Authors. Biopolymers Published by Wiley Periodicals, Inc. Biopolymers (Pept Sci) 106: 673–684, 2016. PMID:27257968

  20. 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.

  1. Combinatorial Evolution and Forecasting of Communication Protocol ZigBee

    CERN Document Server

    Levin, Mark Sh; Kistler, Rolf; Klapproth, Alexander

    2012-01-01

    The article addresses combinatorial evolution and forecasting of communication protocol for wireless sensor networks (ZigBee). Morphological tree structure (a version of and-or tree) is used as a hierarchical model for the protocol. Three generations of ZigBee protocol are examined. A set of protocol change operations is generated and described. The change operations are used as items for forecasting based on combinatorial problems (e.g., clustering, knapsack problem, multiple choice knapsack problem). Two kinds of preliminary forecasts for the examined communication protocol are considered: (i) direct expert (expert judgment) based forecast, (ii) computation of the forecast(s) (usage of multicriteria decision making and combinatorial optimization problems). Finally, aggregation of the obtained preliminary forecasts is considered (two aggregation strategies are used).

  2. Combinatorial Constructions for Sifting Primes and Enumerating the Rationals

    CERN Document Server

    Gnang, Edinah K

    2012-01-01

    We describe a combinatorial approach for investigating properties of rational numbers. The overall approach rests on structural bijections between rational numbers and familiar combinatorial objects, namely rooted trees. We emphasize that such mappings achieve much more than enumeration of rooted trees. We discuss two related structural bijections. The first corresponds to a bijective map between integers and rooted trees. The first bijection also suggests a new algorithm for sifting primes. The second bijection extends the first one in order to map rational numbers to a family of rooted trees. The second bijection suggests a new combinatorial construction for generating reduced rational numbers, thereby producing refinements of the output of the Wilf-Calkin[1] Algorithm.

  3. Combinatorial Selection and Least Absolute Shrinkage via the CLASH Algorithm

    CERN Document Server

    Kyrillidis, Anastasios

    2012-01-01

    The least absolute shrinkage and selection operator (LASSO) for linear regression exploits the geometric interplay of the $\\ell_2$-data error objective and the $\\ell_1$-norm constraint to arbitrarily select sparse models. Guiding this uninformed selection process with sparsity models has been precisely the center of attention over the last decade in order to improve learning performance. To this end, we alter the selection process of LASSO to explicitly leverage combinatorial sparsity models (CSMs) via the combinatorial selection and least absolute shrinkage (CLASH) operator. We provide concrete guidelines how to leverage combinatorial constraints within CLASH, and characterize CLASH's guarantees as a function of the set restricted isometry constants of the sensing matrix. Finally, our experimental results show that CLASH can outperform both LASSO and model-based compressive sensing in sparse estimation.

  4. Combinatorial realizations of crystals via torus actions on quiver varieties

    CERN Document Server

    Sam, Steven V

    2012-01-01

    Consider Kashiwara's crystal associated to a highest weight representation of a symmetric Kac--Moody algebra. There is a geometric realization of this object using Nakajima's quiver varieties. In many particular cases it can also be realized by elementary combinatorial methods. Here we propose a framework for extracting combinatorial realizations from the geometric picture: we construct certain torus actions on the quiver varieties and use Morse theory to index the irreducible components by connected components of the subvariety of torus fixed points. We then discuss the case of affine sl(n). There the fixed point components are just points, and are naturally indexed by multi-partitions. There is some choice in our construction, leading to a family of combinatorial realizations for each highest weight crystal. In the case of the crystal of the fundamental representation we recover a family of realizations which was recently constructed by Fayers. This gives a more conceptual proof of Fayers' result as well as...

  5. Multiobjective Optimization in Combinatorial Wind Farms System Integration and Resistive SFCL Using Analytical Hierarchy Process

    DEFF Research Database (Denmark)

    Moghadasi, Amirhasan; Sarwat, Arif; Guerrero, Josep M.

    2016-01-01

    on the extreme load reduction is effectively demonstrated. A large WPP has a complicated structure using several components, and the inclusion of RSFCL composes this layout more problematic for optimal performance of the system. Hence, the most-widely decision-making technique based on the analytic hierarchy...... process (AHP) is proposed for the optimal design of the combinatorial RSFCL and 50MW WPP to compute the three-dimensional alignment in Pareto front at the end of the optimization run. The numerical simulations verify effectiveness of the proposed approach, using the Pareto optimality concept....

  6. 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

  7. 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.

  8. Improving Combinatorial Ambiguities of ttbar Events Using Neural Networks

    CERN Document Server

    Shim, Ji Hyun

    2014-01-01

    We present a method for resolving the combinatorial issues in the \\ttbar lepton+jets events occurring at the Tevatron collider. By incorporating multiple information into an artificial neural network, we introduce a novel event reconstruction method for such events. We find that this method significantly reduces the number of combinatorial ambiguities. Compared to the classical reconstruction method, our method provides significantly higher purity with same efficiency. We illustrate the reconstructed observables for the realistic top-quark mass and the forward-backward asymmetry measurements. A Monte Carlo study shows that our method provides meaningful improvements in the top-quark measurements using same amount of data as other methods.

  9. Revisiting Combinatorial Ambiguities at Hadron Colliders with MT2

    CERN Document Server

    Baringer, Philip; McCaskey, Mathew; Noonan, Daniel

    2011-01-01

    We present a method to resolve combinatorial issues in multi-particle final states at hadron colliders. The use of kinematic variables such as MT2 and invariant mass significantly reduces combinatorial ambiguities in the signal, but at a cost of losing statistics. We illustrate this idea with gluino pair production leading to 4 jets $+\\met$ in the final state as well as $t\\bar{t}$ production in the dilepton channel. Compared to results in recent studies, our method provides greater efficiency with similar purity

  10. Combinatorial theory of Macdonald polynomials I: Proof of Haglund's formula

    OpenAIRE

    Haglund, J.; Haiman, M.; Loehr, N

    2005-01-01

    Haglund recently proposed a combinatorial interpretation of the modified Macdonald polynomials H̃μ. We give a combinatorial proof of this conjecture, which establishes the existence and integrality of H̃μ. As corollaries, we obtain the cocharge formula of Lascoux and Schützenberger for Hall–Littlewood polynomials, a formula of Sahi and Knop for Jack's symmetric functions, a generalization of this result to the integral Macdonald polynomials Jμ, a formula for H̃μ in terms of Lascoux–Leclerc–Th...

  11. 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

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

    Energy Technology Data Exchange (ETDEWEB)

    Weber, Stephen G. [University of Pittsburgh, Pittsburgh, Pennsylvania

    1998-08-22

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

  14. 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...

  15. A Basic Study of Metaheuristics Based on Higher Level Structure in Solution Space of Combinatorial Optimization Problems

    Science.gov (United States)

    Kanazawa, Takahiko; Yasuda, Keiichiro

    Metaheuristics is a new paradigm that aims to obtain an approximate solution within a feasible computation time. To design the effective metaheuristics, strategies of intensification and diversification are essential. This paper proposes an algorithm that has long term policy for realizing intensification and diversification based on higher level structure in solution space. In order to verify the performance, the proposed algorithm is applied to some traveling salesman problems which are typical combinatorial optimization problems.

  16. Leading log expansion of combinatorial Dyson Schwinger equations

    CERN Document Server

    Delage, Lucas

    2016-01-01

    We study combinatorial Dyson Schwinger equations, expressed in the Hopf algebra of words with a quasi shuffle product. We map them into an algebra of polynomials in one indeterminate L and show that the leading log expansion one obtains with such a mapping are simple power law like expression

  17. Dynamic Combinatorial Libraries of Disulfide Cages in Water

    NARCIS (Netherlands)

    West, Kevin R.; Bake, Kyle D.; Otto, Sijbren

    2005-01-01

    Dynamic combinatorial libraries (DCLs) containing water-soluble disulfide-linked cages (alongside macrocyclic structures) have been generated and characterized. Unlike most other strategies for generating molecular cages, the structures are held together by covalent bonds, which are formed under the

  18. Combinatorial conditions for low rank solutions in semidefinite programming

    NARCIS (Netherlands)

    Varvitsiotis, A.

    2013-01-01

    In this thesis we investigate combinatorial conditions that guarantee the existence of low-rank optimal solutions to semidefinite programs. Results of this type are important for approximation algorithms and for the study of geometric representations of graphs. The structure of the thesis is as

  19. Combinatorial conditions for low rank solutions in semidefinite programming

    NARCIS (Netherlands)

    A. Varvitsiotis (Antonios)

    2013-01-01

    htmlabstractIn this thesis we investigate combinatorial conditions that guarantee the existence of low-rank optimal solutions to semidefinite programs. Results of this type are important for approximation algorithms and for the study of geometric representations of graphs. The structure of the

  20. 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 f

  1. Identities for Generalized Fibonacci Numbers: A Combinatorial Approach

    Science.gov (United States)

    Plaza, A.; Falcon, S.

    2008-01-01

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

  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. A graphical formalism for mixed multi-unit combinatorial auctions

    NARCIS (Netherlands)

    Gionvannucci, A.; Cerquides, J.; Endriss, U.; Rodríguez-Aguilar, J.A.

    2010-01-01

    Mixed multi-unit combinatorial auctions are auctions that allow participants to bid for bundles of goods to buy, for bundles of goods to sell, and for transformations of goods. The intuitive meaning of a bid for a transformation is that the bidder is offering to produce a set of output goods after h

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

    Science.gov (United States)

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

    2016-05-10

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

  5. Automated Combinatorial Chemistry in the Organic Chemistry Majors Laboratory

    Science.gov (United States)

    Nichols, Christopher J.; Hanne, Larry F.

    2010-01-01

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

  6. Synthetic receptors for ammonium ions using dynamic combinatorial chemistry

    NARCIS (Netherlands)

    Hamieh, Saleh

    2015-01-01

    The general topic of this dissertation is the development of synthetic receptors for organic ammonium ions in near physiological conditions using disulfide dynamic combinatorial chemistry (DCC). Chapter 1 explains the importance of this development and the associated difficulties when using the conv

  7. Combinatorial conditions for low rank solutions in semidefinite programming

    NARCIS (Netherlands)

    Varvitsiotis, A.

    2013-01-01

    In this thesis we investigate combinatorial conditions that guarantee the existence of low-rank optimal solutions to semidefinite programs. Results of this type are important for approximation algorithms and for the study of geometric representations of graphs. The structure of the thesis is as foll

  8. 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

  9. 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

  10. 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...

  11. Combinatorial optimization of CO2 transport and fixation to improve succinate production by promoter engineering.

    Science.gov (United States)

    Yu, Jun-Han; Zhu, Li-Wen; Xia, Shi-Tao; Li, Hong-Mei; Tang, Ya-Ling; Liang, Xin-Hua; Chen, Tao; Tang, Ya-Jie

    2016-07-01

    To balance the flux of an engineered metabolic pathway to achieve high yield of target product is a major challenge in metabolic engineering. In previous work, the collaborative regulation of CO2 transport and fixation was investigated with co-overexpressing exogenous genes regulating both CO2 transport (sbtA and bicA) and PEP carboxylation (phosphoenolpyruvate (PEP) carboxylase (ppc) and carboxykinase (pck)) under trc promoter in Escherichia coli for succinate biosynthesis. For balancing metabolic flux to maximize succinate titer, a combinatorial optimization strategy to fine-tuning CO2 transport and fixation process was implemented by promoter engineering in this study. Firstly, based on the energy matrix a synthetic promoter library containing 20 rationally designed promoters with strengths ranging from 0.8% to 100% compared with the widely used trc promoter was generated. Evaluations of rfp and cat reporter genes provided evidence that the synthetic promoters were stably and had certain applicability. Secondly, four designed promoters with different strengths were used for combinatorial assembly of single CO2 transport gene (sbtA or bicA) and single CO2 fixation gene (ppc or pck) expression. Three combinations, such as Tang1519 (P4 -bicA + pP19 -pck), Tang1522 (P4 -sbtA + P4 -ppc), Tang1523 (P4 -sbtA + P17 -ppc) with a more than 10% increase in succinate production were screened in bioreactor. Finally, based on the above results, co-expression of the four transport and fixation genes were further investigated. Co-expression of sbtA, bicA, and ppc with weak promoter P4 and pck with strong promoter P19 (AFP111/pT-P4 -bicA-P4 -sbtA + pACYC-P19 -pck-P4 -ppc) provided the best succinate production among all the combinations. The highest succinate production of 89.4 g/L was 37.5% higher than that obtained with empty vector control. This work significantly enhanced succinate production through combinatorial optimization of CO2 transport and fixation

  12. Microfluidic platform for combinatorial synthesis in picolitre droplets.

    Science.gov (United States)

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

    2012-04-07

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

  13. An optimization spiking neural p system for approximately solving combinatorial optimization problems.

    Science.gov (United States)

    Zhang, Gexiang; Rong, Haina; Neri, Ferrante; Pérez-Jiménez, Mario J

    2014-08-01

    Membrane systems (also called P systems) refer to the computing models abstracted from the structure and the functioning of the living cell as well as from the cooperation of cells in tissues, organs, and other populations of cells. Spiking neural P systems (SNPS) are a class of distributed and parallel computing models that incorporate the idea of spiking neurons into P systems. To attain the solution of optimization problems, P systems are used to properly organize evolutionary operators of heuristic approaches, which are named as membrane-inspired evolutionary algorithms (MIEAs). This paper proposes a novel way to design a P system for directly obtaining the approximate solutions of combinatorial optimization problems without the aid of evolutionary operators like in the case of MIEAs. To this aim, an extended spiking neural P system (ESNPS) has been proposed by introducing the probabilistic selection of evolution rules and multi-neurons output and a family of ESNPS, called optimization spiking neural P system (OSNPS), are further designed through introducing a guider to adaptively adjust rule probabilities to approximately solve combinatorial optimization problems. Extensive experiments on knapsack problems have been reported to experimentally prove the viability and effectiveness of the proposed neural system.

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

    Directory of Open Access Journals (Sweden)

    Khalid K Alam

    2015-01-01

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

  15. 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.

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

    DEFF Research Database (Denmark)

    Diemer, Sanna L.; Kristensen, Morten; Rasmussen, Brian

    2015-01-01

    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 combinato......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...

  17. Expression, purification, and characterization of proteins from high-quality combinatorial libraries of the mammalian calmodulin central linker.

    Science.gov (United States)

    Bradley, Luke H; Bricken, Michael L; Randle, Charlotte

    2011-02-01

    Combinatorial libraries offer an attractive approach towards exploring protein sequence, structure and function. Although several strategies introduce sequence diversity, the likelihood of identifying proteins with novel functions is increased when the library of genes encodes for folded and soluble structures. Here we present the first application of the binary patterning approach of combinatorial protein library design to the unique central linker region of the highly-conserved protein, calmodulin (CaM). We show that this high-quality approach translates very well to the CaM protein scaffold: all library members over-express and are functionally diverse, having a range of conformations in the presence and absence of calcium as determined by circular dichroism spectroscopy. Collectively, these data support that the binary patterning approach, when applied to the highly-conserved protein fold, can yield large collections of folded, soluble and highly-expressible proteins.

  18. The Group of Automorphisms of Transitive 2-(v, 23, 1) Designs

    Institute of Scientific and Technical Information of China (English)

    LI Shang-zhao

    2015-01-01

    This paper is a contribution to the study of the automorphism groups of 2−(v, k, 1) designs. Let D be a 2−(v, 23, 1) design and G a block-transitive and point-primitive group of automorphism of D. Then the socle of G is not Sz(q) and 2G2(q).

  19. From CFTR biology toward combinatorial pharmacotherapy: expanded classification of cystic fibrosis mutations.

    Science.gov (United States)

    Veit, Gudio; Avramescu, Radu G; Chiang, Annette N; Houck, Scott A; Cai, Zhiwei; Peters, Kathryn W; Hong, Jeong S; Pollard, Harvey B; Guggino, William B; Balch, William E; Skach, William R; Cutting, Garry R; Frizzell, Raymond A; Sheppard, David N; Cyr, Douglas M; Sorscher, Eric J; Brodsky, Jeffrey L; Lukacs, Gergely L

    2016-02-01

    More than 2000 mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) have been described that confer a range of molecular cell biological and functional phenotypes. Most of these mutations lead to compromised anion conductance at the apical plasma membrane of secretory epithelia and cause cystic fibrosis (CF) with variable disease severity. Based on the molecular phenotypic complexity of CFTR mutants and their susceptibility to pharmacotherapy, it has been recognized that mutations may impose combinatorial defects in CFTR channel biology. This notion led to the conclusion that the combination of pharmacotherapies addressing single defects (e.g., transcription, translation, folding, and/or gating) may show improved clinical benefit over available low-efficacy monotherapies. Indeed, recent phase 3 clinical trials combining ivacaftor (a gating potentiator) and lumacaftor (a folding corrector) have proven efficacious in CF patients harboring the most common mutation (deletion of residue F508, ΔF508, or Phe508del). This drug combination was recently approved by the U.S. Food and Drug Administration for patients homozygous for ΔF508. Emerging studies of the structural, cell biological, and functional defects caused by rare mutations provide a new framework that reveals a mixture of deficiencies in different CFTR alleles. Establishment of a set of combinatorial categories of the previously defined basic defects in CF alleles will aid the design of even more efficacious therapeutic interventions for CF patients.

  20. 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.

  1. From CFTR biology toward combinatorial pharmacotherapy: expanded classification of cystic fibrosis mutations

    Science.gov (United States)

    Veit, Gudio; Avramescu, Radu G.; Chiang, Annette N.; Houck, Scott A.; Cai, Zhiwei; Peters, Kathryn W.; Hong, Jeong S.; Pollard, Harvey B.; Guggino, William B.; Balch, William E.; Skach, William R.; Cutting, Garry R.; Frizzell, Raymond A.; Sheppard, David N.; Cyr, Douglas M.; Sorscher, Eric J.; Brodsky, Jeffrey L.; Lukacs, Gergely L.

    2016-01-01

    More than 2000 mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) have been described that confer a range of molecular cell biological and functional phenotypes. Most of these mutations lead to compromised anion conductance at the apical plasma membrane of secretory epithelia and cause cystic fibrosis (CF) with variable disease severity. Based on the molecular phenotypic complexity of CFTR mutants and their susceptibility to pharmacotherapy, it has been recognized that mutations may impose combinatorial defects in CFTR channel biology. This notion led to the conclusion that the combination of pharmacotherapies addressing single defects (e.g., transcription, translation, folding, and/or gating) may show improved clinical benefit over available low-efficacy monotherapies. Indeed, recent phase 3 clinical trials combining ivacaftor (a gating potentiator) and lumacaftor (a folding corrector) have proven efficacious in CF patients harboring the most common mutation (deletion of residue F508, ΔF508, or Phe508del). This drug combination was recently approved by the U.S. Food and Drug Administration for patients homozygous for ΔF508. Emerging studies of the structural, cell biological, and functional defects caused by rare mutations provide a new framework that reveals a mixture of deficiencies in different CFTR alleles. Establishment of a set of combinatorial categories of the previously defined basic defects in CF alleles will aid the design of even more efficacious therapeutic interventions for CF patients. PMID:26823392

  2. The Zoltan and Isorropia Parallel Toolkits for Combinatorial Scientific Computing: Partitioning, Ordering and Coloring

    Directory of Open Access Journals (Sweden)

    Erik G. Boman

    2012-01-01

    Full Text Available Partitioning and load balancing are important problems in scientific computing that can be modeled as combinatorial problems using graphs or hypergraphs. The Zoltan toolkit was developed primarily for partitioning and load balancing to support dynamic parallel applications, but has expanded to support other problems in combinatorial scientific computing, including matrix ordering and graph coloring. Zoltan is based on abstract user interfaces and uses callback functions. To simplify the use and integration of Zoltan with other matrix-based frameworks, such as the ones in Trilinos, we developed Isorropia as a Trilinos package, which supports most of Zoltan's features via a matrix-based interface. In addition to providing an easy-to-use matrix-based interface to Zoltan, Isorropia also serves as a platform for additional matrix algorithms. In this paper, we give an overview of the Zoltan and Isorropia toolkits, their design, capabilities and use. We also show how Zoltan and Isorropia enable large-scale, parallel scientific simulations, and describe current and future development in the next-generation package Zoltan2.

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

    Science.gov (United States)

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

    2011-05-01

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

  4. Parsing Combinatory Categorial Grammar with Answer Set Programming: Preliminary Report

    CERN Document Server

    Lierler, Yuliya

    2011-01-01

    Combinatory categorial grammar (CCG) is a grammar formalism used for natural language parsing. CCG assigns structured lexical categories to words and uses a small set of combinatory rules to combine these categories to parse a sentence. In this work we propose and implement a new approach to CCG parsing that relies on a prominent knowledge representation formalism, answer set programming (ASP) - a declarative programming paradigm. We formulate the task of CCG parsing as a planning problem and use an ASP computational tool to compute solutions that correspond to valid parses. Compared to other approaches, there is no need to implement a specific parsing algorithm using such a declarative method. Our approach aims at producing all semantically distinct parse trees for a given sentence. From this goal, normalization and efficiency issues arise, and we deal with them by combining and extending existing strategies. We have implemented a CCG parsing tool kit - AspCcgTk - that uses ASP as its main computational mean...

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

    CERN Document Server

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

    2009-01-01

    We consider properties of the operators D(r,M)=a^r(a^\\dag a)^M (which we call generalized Laguerre-type derivatives), with r=1,2,..., M=0,1,..., where a and a^\\dag are boson annihilation and creation operators respectively, satisfying [a,a^\\dag]=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 which 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.

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

    Science.gov (United States)

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

    2017-01-25

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

  7. Quasi-combinatorial energy landscapes for nanoalloy structure optimisation.

    Science.gov (United States)

    Schebarchov, D; Wales, D J

    2015-11-14

    We formulate nanoalloy structure prediction as a mixed-variable optimisation problem, where the homotops can be associated with an effective, quasi-combinatorial energy landscape in permutation space. We survey this effective landscape for a representative set of binary systems modelled by the Gupta potential. In segregating systems with small lattice mismatch, we find that homotops have a relatively straightforward landscape with few local optima - a scenario well-suited for local (combinatorial) optimisation techniques that scale quadratically with system size. Combining these techniques with multiple local-neighbourhood structures yields a search for multiminima, and we demonstrate that generalised basin-hopping with a metropolis acceptance criterion in the space of multiminima can then be effective for global optimisation of binary and ternary nanoalloys.

  8. 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.

  9. 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.

  10. Immobilized OBOC combinatorial bead array to facilitate multiplicative screening

    OpenAIRE

    Xiao, Wenwu; Bononi, Fernanda C.; Townsend, Jared; Li, Yuanpei; Liu, Ruiwu; Lam, Kit S.

    2013-01-01

    One-bead-one-compound (OBOC) combinatorial library screening has been broadly utilized for the last two decades to identify small molecules, peptides or peptidomimetics targeting variable screening probes such as cell surface receptors, bacteria, protein kinases, phosphatases, proteases etc. In previous screening methods, library beads were suspended in solution and screened against one single probe. Only the positive beads were tracked and isolated for additional screens and finally selected...

  11. The evolution of combinatorial gene regulation in fungi.

    OpenAIRE

    Tuch, Brian B.; Galgoczy, David J.; Hernday, Aaron D.; Hao Li; Johnson, Alexander D.

    2008-01-01

    It is widely suspected that gene regulatory networks are highly plastic. The rapid turnover of transcription factor binding sites has been predicted on theoretical grounds and has been experimentally demonstrated in closely related species. We combined experimental approaches with comparative genomics to focus on the role of combinatorial control in the evolution of a large transcriptional circuit in the fungal lineage. Our study centers on Mcm1, a transcriptional regulator that, in combinati...

  12. A Combinatorial interpretation of Hofstadter's G-sequence

    CERN Document Server

    Rahman, Mustazee

    2011-01-01

    We give a combinatorial interpretation of a classical meta-Fibonacci sequence defined by G(n) = n - G(G(n-1)) with the initial condition G(1) = 1, which appears in Hofstadter's 'Godel, Escher, Bach: An Eternal Golden Braid'. The interpretation is in terms of an infinite labelled tree. We then show a few corollaries about the behaviour of the sequence G(n) directly from the interpretation.

  13. Accelerated Discovery of Thermoelectric Materials: Combinatorial Facility and High-Throughput Measurement of Thermoelectric Power Factor.

    Science.gov (United States)

    García-Cañadas, Jorge; Adkins, Nicholas J E; McCain, Stephen; Hauptstein, Bastian; Brew, Ashley; Jarvis, David J; Min, Gao

    2016-06-13

    A series of processes have been developed to facilitate the rapid discovery of new promising thermoelectric alloys. A novel combinatorial facility where elements are wire-fed and laser-melted was designed and constructed. Different sample compositions can be achieved by feeding different element wires at specific rates. The composition of all the samples prepared was tested by energy dispersive X-ray spectroscopy (EDS). Then, their thermoelectric properties (power factor) at room temperature were screened in a specially designed new high-throughput setup. After the screening, the thermoelectric properties can be mapped with the possibility of identifying compositional trends. As a proof-of-concept, a promising thermoelectric ternary system, Al-Fe-Ti, has been identified, demonstrating the capability of this accelerated approach.

  14. 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.

  15. 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.

  16. Controlling Combinatorial Complexity in Software and Malware Behavior Computation

    Energy Technology Data Exchange (ETDEWEB)

    Pleszkoch, Mark G [ORNL; Linger, Richard C [ORNL

    2015-01-01

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

  17. Hybrid Genetic Algorithm with PSO Effect for Combinatorial Optimisation Problems

    Directory of Open Access Journals (Sweden)

    M. H. Mehta

    2012-12-01

    Full Text Available In engineering field, many problems are hard to solve in some definite interval of time. These problems known as “combinatorial optimisation problems” are of the category NP. These problems are easy to solve in some polynomial time when input size is small but as input size grows problems become toughest to solve in some definite interval of time. Long known conventional methods are not able to solve the problems and thus proper heuristics is necessary. Evolutionary algorithms based on behaviours of different animals and species have been invented and studied for this purpose. Genetic Algorithm is considered a powerful algorithm for solving combinatorial optimisation problems. Genetic algorithms work on these problems mimicking the human genetics. It follows principle of “survival of the fittest” kind of strategy. Particle swarm optimisation is a new evolutionary approach that copies behaviour of swarm in nature. However, neither traditional genetic algorithms nor particle swarm optimisation alone has been completely successful for solving combinatorial optimisation problems. Here a hybrid algorithm is proposed in which strengths of both algorithms are merged and performance of proposed algorithm is compared with simple genetic algorithm. Results show that proposed algorithm works definitely better than the simple genetic algorithm.

  18. An intelligent approach to the discovery of luminescent materials using a combinatorial approach combined with Taguchi methodology.

    Science.gov (United States)

    Chen, Lei; Chu, Cheng-I; Chen, Kuo-Ju; Chen, Po-Yuan; Hu, Shu-Fen; Liu, Ru-Shi

    2011-01-01

    A significant advance made in combinatorial approach research was that the emphasis shifted from simple mixing to intelligent screening, so as to improve the efficiency and accuracy of discovering new materials from a larger number of diverse compositions. In this study, the long-lasting luminescence of SrAl(2)O(4), which is co-doped with Eu(2+), Ce(3+), Dy(3+), Li(+) and H(3)BO(3), was investigated based on a combinatorial approach in conjunction with the Taguchi method. The minimal number of 16 samples to be tested (five dopants and four levels of concentration) were designed using the Taguchi method. The samples to be screened were synthesized using a parallel combinatorial strategy based on ink-jetting of precursors into an array of micro-reactor wells. The relative brightness of luminescence of the different phosphors over a particular period was assessed. Ce(3+) was identified as the constituent that detrimentally affected long-lasting luminescence. Its concentration was optimized to zero. Li(+) had a minor effect on long-lasting luminescence but the main factors that contributed to the objective property (long-lasting luminescence) were Eu(2+), Dy(3+) and H(3)BO(3), and the concentrations of these dopants were optimized to 0.020, 0.030 and 0.300, respectively, for co-doping into SrAl(2)O(4). This study demonstrates that the utility of the combinatorial approach for evaluating the effect of components on an objective property (e.g. phosphorescence) and estimating the expected performance under the optimal conditions can be improved by the Taguchi method.

  19. The algorithm design manual

    CERN Document Server

    Skiena, Steven S

    2008-01-01

    Explaining designing algorithms, and analyzing their efficacy and efficiency, this book covers combinatorial algorithms technology, stressing design over analysis. It presents instruction on methods for designing and analyzing computer algorithms. It contains the catalog of algorithmic resources, implementations and a bibliography

  20. Combinatorial Regulation in Yeast Transcription Networks

    Science.gov (United States)

    Li, Hao

    2006-03-01

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

  1. Combinatorial analysis of interacting RNA molecules

    CERN Document Server

    Li, Thomas J X

    2010-01-01

    Recently several minimum free energy (MFE) folding algorithms for predicting the joint structure of two interacting RNA molecules have been proposed. Their folding targets are interaction structures, that can be represented as diagrams with two backbones drawn horizontally on top of each other such that (1) intramolecular and intermolecular bonds are noncrossing and (2) there is no "zig-zag" configuration. This paper studies joint structures with arc-length at least four in which both, interior and exterior stack-lengths are at least two (no isolated arcs). The key idea in this paper is to consider a new type of shape, based on which joint structures can be derived via symbolic enumeration. Our results imply simple asymptotic formulas for the number of joint structures with surprisingly small exponential growth rates. They are of interest in the context of designing prediction algorithms for RNA-RNA interactions.

  2. Combinatorial Gene Regulation Using Auto-Regulation

    Science.gov (United States)

    Hermsen, Rutger; Ursem, Bas; ten Wolde, Pieter Rein

    2010-01-01

    As many as 59% of the transcription factors in Escherichia coli regulate the transcription rate of their own genes. This suggests that auto-regulation has one or more important functions. Here, one possible function is studied. Often the transcription rate of an auto-regulator is also controlled by additional transcription factors. In these cases, the way the expression of the auto-regulator responds to changes in the concentrations of the “input” regulators (the response function) is obviously affected by the auto-regulation. We suggest that, conversely, auto-regulation may be used to optimize this response function. To test this hypothesis, we use an evolutionary algorithm and a chemical–physical model of transcription regulation to design model cis-regulatory constructs with predefined response functions. In these simulations, auto-regulation can evolve if this provides a functional benefit. When selecting for a series of elementary response functions—Boolean logic gates and linear responses—the cis-regulatory regions resulting from the simulations indeed often exploit auto-regulation. Surprisingly, the resulting constructs use auto-activation rather than auto-repression. Several design principles show up repeatedly in the simulation results. They demonstrate how auto-activation can be used to generate sharp, switch-like activation and repression circuits and how linearly decreasing response functions can be obtained. Auto-repression, on the other hand, resulted only when a high response speed or a suppression of intrinsic noise was also selected for. The results suggest that, while auto-repression may primarily be valuable to improve the dynamical properties of regulatory circuits, auto-activation is likely to evolve even when selection acts on the shape of response function only. PMID:20548950

  3. 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.

  4. Minimal Substrate Features for Erm Methyltransferases Defined by Using a Combinatorial Oligonucleotide Library

    DEFF Research Database (Denmark)

    Hansen, Lykke H; Lobedanz, Sune; Douthwaite, Stephen

    2011-01-01

    , the main role played by the bottom strand appears to be in maintaining the conformation of the top strand. The addition of multiple LNA residues to the top strand impeded methylation; this indicates that the RNA substrate requires a certain amount of flexibility for accommodation into the active site...... of Erm. The combinatorial approach for identifying small but functional RNA substrates is a step towards making RNA-Erm complexes suitable for cocrystal determination, and for designing molecules that might block the substrate-recognition site of the enzyme.......Erm methyltransferases are prevalent in pathogenic bacteria and confer resistance to macrolide, lincosamide, and streptogramin B antibiotics by specifically methylating the 23S ribosomal RNA at nucleotide A2058. We have identified motifs within the rRNA substrate that are required for methylation...

  5. 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

  6. Combinatorial Hopf Algebras in Quantum Field Theory I

    Science.gov (United States)

    Figueroa, Héctor; Gracia-Bondía, José M.

    This paper stands at the interface between combinatorial Hopf algebra theory and renormalization theory. Its plan is as follows: Sec. 1.1 is the introduction, and contains an elementary invitation to the subject as well. The rest of Sec. 1 is devoted to the basics of Hopf algebra theory and examples in ascending level of complexity. Section 2 turns around the all-important Faà di Bruno Hopf algebra. Section 2.1 contains a first, direct approach to it. Section 2.2 gives applications of the Faà di Bruno algebra to quantum field theory and Lagrange reversion. Section 2.3 rederives the related Connes-Moscovici algebras. In Sec. 3, we turn to the Connes-Kreimer Hopf algebras of Feynman graphs and, more generally, to incidence bialgebras. In Sec. 3.1, we describe the first. Then in Sec. 3.2, we give a simple derivation of (the properly combinatorial part of) Zimmermann's cancellation-free method, in its original diagrammatic form. In Sec. 3.3, general incidence algebras are introduced, and the Faà di Bruno bialgebras are described as incidence bialgebras. In Sec. 3.4, deeper lore on Rota's incidence algebras allows us to reinterpret Connes-Kreimer algebras in terms of distributive lattices. Next, the general algebraic-combinatorial proof of the cancellation-free formula for antipodes is ascertained. The structure results for commutative Hopf algebras are found in Sec. 4. An outlook section very briefly reviews the coalgebraic aspects of quantization and the Rota-Baxter map in renormalization.

  7. Combinatorial antibody libraries: new advances, new immunological insights.

    Science.gov (United States)

    Lerner, Richard A

    2016-08-01

    Immunochemists have become quite proficient in engineering existing antibody molecules to control their pharmacological properties. However, in terms of generating new antibodies, the combinatorial antibody library has become a central feature of modern immunochemistry. These libraries are essentially an immune system in a test tube and enable the selection of antibodies without the constraints of whole animal or cell-based systems. This Review provides an overview of how antibody libraries are constructed and discusses what can be learnt from these synthetic systems. In particular, the Review focuses on new biological insights from antibody libraries - such as the concept of 'SOS antibodies' - and the growing use of intracellular antibodies to perturb cellular functions.

  8. Combinatorial Yang-Baxter maps arising from the tetrahedron equation

    Science.gov (United States)

    Kuniba, A.

    2016-10-01

    We survey the matrix product solutions of the Yang-Baxter equation recently obtained from the tetrahedron equation. They form a family of quantum R-matrices of generalized quantum groups interpolating the symmetric tensor representations of U q ( A n-1 (1)) and the antisymmetric tensor representations of {U_{ - {q^{ - 1}}}}( {A_{n - 1}^{( 1 )}} ) . We show that at q = 0, they all reduce to the Yang-Baxter maps called combinatorial R-matrices and describe the latter by an explicit algorithm.

  9. Space-efficient parallel algorithms for combinatorial search problems

    DEFF Research Database (Denmark)

    Pietrcaprina, Andrea; Pucci, Geppino; Silvestri, Francesco;

    2015-01-01

    We present space-efficient parallel strategies for two fundamental combinatorial search problems, namely, backtrack search and branch-and-bound , both involving the visit of an n-node tree of height h under the assumption that a node can be accessed only through its father or its children. For both...... problems we propose efficient algorithms that run on a p-processor distributed-memory machine. For backtrack search, we give a deterministic algorithm running in O(n/p+hlogp) time, and a Las Vegas algorithm requiring optimal O(n/p+h) time, with high probability. Building on the backtrack search algorithm...

  10. 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...

  11. Learning Combinatorial Map Information from Permutations of Landmarks

    Science.gov (United States)

    2010-10-04

    Learning Combinatorial Map Information from Permutations of Landmarks Benjamı́n Tovar ∗, Luigi Freda†, and Steven M. LaValle‡ Abstract This paper...is B. Tovar . This work was founded by NSF grant 0904501 (IIS robotics), DARPA SToMP grant HR0011-05-1-0008, and MURI/ONR grant N00014-09-1-1052. ∗B... Tovar is with the Dept. of Mechanical Engineering, Northwestern University, 2145 Sheridan Road, Evanston, IL 602081, USA. email: b- tovar

  12. Combinatorial polarization, code loops, and codes of high level

    Directory of Open Access Journals (Sweden)

    Petr Vojtěchovský

    2004-07-01

    Full Text Available We first find the combinatorial degree of any map f:V→F, where F is a finite field and V is a finite-dimensional vector space over F. We then simplify and generalize a certain construction, due to Chein and Goodaire, that was used in characterizing code loops as finite Moufang loops that possess at most two squares. The construction yields binary codes of high divisibility level with prescribed Hamming weights of intersections of codewords.

  13. 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

  14. Applications of combinatorial matrix theory to Laplacian matrices of graphs

    CERN Document Server

    Molitierno, Jason J

    2012-01-01

    On the surface, matrix theory and graph theory seem like very different branches of mathematics. However, adjacency, Laplacian, and incidence matrices are commonly used to represent graphs, and many properties of matrices can give us useful information about the structure of graphs. Applications of Combinatorial Matrix Theory to Laplacian Matrices of Graphs is a compilation of many of the exciting results concerning Laplacian matrices developed since the mid 1970s by well-known mathematicians such as Fallat, Fiedler, Grone, Kirkland, Merris, Mohar, Neumann, Shader, Sunder, and more. The text i

  15. Yeast surface display for screening combinatorial polypeptide libraries.

    Science.gov (United States)

    Boder, E T; Wittrup, K D

    1997-06-01

    Display on the yeast cell wall is well suited for engineering mammalian cell-surface and secreted proteins (e.g., antibodies, receptors, cytokines) that require endoplasmic reticulum-specific post-translational processing for efficient folding and activity. C-terminal fusion to the Aga2p mating adhesion receptor of Saccharomyces cerevisiae has been used for the selection of scFv antibody fragments with threefold decreased antigen dissociation rate from a randomly mutated library. A eukaryotic host should alleviate expression biases present in bacterially propagated combinatorial libraries. Quantitative flow cytometric analysis enables fine discrimination of kinetic parameters for protein binding to soluble ligands.

  16. A multi-objective stochastic approach to combinatorial technology space exploration

    Science.gov (United States)

    Patel, Chirag B.

    Historically, aerospace development programs have frequently been marked by performance shortfalls, cost growth, and schedule slippage. New technologies included in systems are considered to be one of the major sources of this programmatic risk. Decisions regarding the choice of technologies to include in a design are therefore crucial for a successful development program. This problem of technology selection is a challenging exercise in multi-objective decision making. The complexity of this selection problem is compounded by the geometric growth of the combinatorial space with the number of technologies being considered and the uncertainties inherent in the knowledge of the technological attributes. These problems are not typically addressed in the selection methods employed in common practice. Consequently, a method is desired to aid the selection of technologies for complex systems design with consideration of the combinatorial complexity, multi-dimensionality, and the presence of uncertainties. Several categories of techniques are explored to address the shortcomings of current approaches and to realize the goal of an efficient and effective combinatorial technology space exploration method. For the multi-objective decision making, a posteriori preference articulation is implemented. To realize this, a stochastic algorithm for Pareto optimization is formulated based on the concepts of SPEA2. Techniques to address the uncertain nature of technology impact on the system are also examined. Monte Carlo simulations using the surrogate models are used for uncertainty quantification. The concepts of graph theory are used for modeling and analyzing compatibility constraints among technologies and assessing their impact on the technology combinatorial space. The overall decision making approach is enabled by the application of an uncertainty quantification technique under the framework of an efficient probabilistic Pareto optimization algorithm. As a result, multiple

  17. A Barcode-Free Combinatorial Screening Platform for Matrix Metalloproteinase Screening

    OpenAIRE

    Rane, Tushar D.; Zec, Helena C.; Wang, Tza-Huei

    2014-01-01

    Application of droplet microfluidics to combinatorial screening applications remains elusive because of the need for composition-identifying unique barcodes. Here we propose a barcode-free continuous flow droplet microfluidic platform to suit the requirements of combinatorial screening applications. We demonstrate robust and repeatable functioning of this platform with matrix metalloproteinase activity screening as a sample application.

  18. Parallel detection of antigen-specific T cell responses by combinatorial encoding of MHC multimers

    DEFF Research Database (Denmark)

    Andersen, Rikke Sick; Kvistborg, Pia; Frøsig, Thomas Mørch;

    2012-01-01

    -dimensional combinatorial matrix, these eight fluorochromes are combined to generate 28 unique two-color codes. By the use of combinatorial encoding, a large number of different T cell populations can be detected in a single sample. The method can be used for T cell epitope mapping, and also for the monitoring of CD8...

  19. A barcode-free combinatorial screening platform for matrix metalloproteinase screening.

    Science.gov (United States)

    Rane, Tushar D; Zec, Helena C; Wang, Tza-Huei

    2015-02-03

    Application of droplet microfluidics to combinatorial screening applications remains elusive because of the need for composition-identifying unique barcodes. Here we propose a barcode-free continuous flow droplet microfluidic platform to suit the requirements of combinatorial screening applications. We demonstrate robust and repeatable functioning of this platform with matrix metalloproteinase activity screening as a sample application.

  20. 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...

  1. Comparing winner determination algorithms for mixed multi-unit combinatorial auctions

    NARCIS (Netherlands)

    Ottens, B.; Endriss, U.; Padgham, L.; Parkes, D.; Müller, J.; Parsons, S.

    2008-01-01

    Mixed multi-unit combinatorial auctions are combinatorial auctions in which the auctioneer and the bidders negotiate over transformations rather than over simple goods. By proposing a transformation a bidder is offering to produce a certain set of output goods after having received the specified inp

  2. Combinatorial metabolic engineering of Saccharomyces cerevisiae for terminal alkene production.

    Science.gov (United States)

    Chen, Binbin; Lee, Dong-Yup; Chang, Matthew Wook

    2015-09-01

    Biological production of terminal alkenes has garnered a significant interest due to their industrial applications such as lubricants, detergents and fuels. Here, we engineered the yeast Saccharomyces cerevisiae to produce terminal alkenes via a one-step fatty acid decarboxylation pathway and improved the alkene production using combinatorial engineering strategies. In brief, we first characterized eight fatty acid decarboxylases to enable and enhance alkene production. We then increased the production titer 7-fold by improving the availability of the precursor fatty acids. We additionally increased the titer about 5-fold through genetic cofactor engineering and gene expression tuning in rich medium. Lastly, we further improved the titer 1.8-fold to 3.7 mg/L by optimizing the culturing conditions in bioreactors. This study represents the first report of terminal alkene biosynthesis in S. cerevisiae, and the abovementioned combinatorial engineering approaches collectively increased the titer 67.4-fold. We envision that these approaches could provide insights into devising engineering strategies to improve the production of fatty acid-derived biochemicals in S. cerevisiae.

  3. Combinatorial arrays and parallel screening for positive electrode discovery

    Science.gov (United States)

    Spong, A. D.; Vitins, G.; Guerin, S.; Hayden, B. E.; Russell, A. E.; Owen, John R.

    Combinatorial techniques have been applied to the preparation and screening of positive electrode candidates for lithium batteries. This work describes the automated parallel synthesis of 64-electrode arrays using a Packard Multiprobe II liquid handling system. A cell was constructed with a single lithium reference-counter electrode and 64, three-millimeter-diameter working electrodes containing Li xMn 2O 4 active material, PVdF-HFP binder and carbon black as a conducting additive. Eight duplicate electrodes, each of eight respective compositions, were deposited on the array and the mass fraction of carbon was varied in steps from 1 to 25%. The results showed a rapid increase in capacity at the percolation limit of 3% for most cells. Some groups of nominally identical cells showed random variations in capacity, especially at low carbon loadings. The overall result is a demonstration of advantages of the combinatorial concept, which were time-saving and an improved statistical significance of the results compared with on-off experiments.

  4. Combinatorial Hopf algebras in quantum field theory I

    CERN Document Server

    Figueroa, H; Figueroa, Hector; Gracia-Bondia, Jose M.

    2004-01-01

    This manuscript collects and expands for the most part a series of lectures on the interface between combinatorial Hopf algebra theory (CHAT) and renormalization theory, delivered by the second-named author in the framework of the joint mathematical physics seminar of the Universites d'Artois and Lille 1, from late January till mid-February 2003. The plan is as follows: Section 1 is the introduction, and Section 2 contains an elementary invitation to the subject. Sections 3-7 are devoted to the basics of Hopf algebra theory and examples, in ascending level of complexity. Section 8 contains a first, direct approach to the Faa di Bruno Hopf algebra. Section 9 gives applications of that to quantum field theory and Lagrange reversion. Section 10 rederives the Connes-Moscovici algebras. In Section 11 we turn to Hopf algebras of Feynman graphs. Then in Section 12 we give an extremely simple derivation of (the properly combinatorial part of) Zimmermann's method, in its original diagrammatic form. In Section 13 gener...

  5. Combinatorial particle swarm optimization for solving blocking flowshop scheduling problem

    Directory of Open Access Journals (Sweden)

    Mansour Eddaly

    2016-10-01

    Full Text Available This paper addresses to the flowshop scheduling problem with blocking constraints. The objective is to minimize the makespan criterion. We propose a hybrid combinatorial particle swarm optimization algorithm (HCPSO as a resolution technique for solving this problem. At the initialization, different priority rules are exploited. Experimental study and statistical analysis were performed to select the most adapted one for this problem. Then, the swarm behavior is tested for solving a combinatorial optimization problem such as a sequencing problem under constraints. Finally, an iterated local search algorithm based on probabilistic perturbation is sequentially introduced to the particle swarm optimization algorithm for improving the quality of solution. The computational results show that our approach is able to improve several best known solutions of the literature. In fact, 76 solutions among 120 were improved. Moreover, HCPSO outperforms the compared methods in terms of quality of solutions in short time requirements. Also, the performance of the proposed approach is evaluated according to a real-world industrial problem.

  6. On Range Searching in the Group Model and Combinatorial Discrepancy

    DEFF Research Database (Denmark)

    Larsen, Kasper Green

    2011-01-01

    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 $t_ut_q = Omega(disc^2/lg n)$ where...... $t_u$ is the worst case update time, $t_q$ 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:begin{itemize}item For half space range searching in $d$-dimensional space, we get a lower bound of $t_u t_q = Omega(n^{1-1/d}/lg n)$. This comes within a $lg n lg lg n$ factor of the best known upper bound. item For orthogonal range searching in $d...

  7. 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...

  8. NIST Combinatorial Methods Center: Model for Industrial Outreach

    Science.gov (United States)

    Amis, Eric J.; Karim, Alamgir

    2002-03-01

    The measurements, standards, and test methods developed by NIST, in partnership with other organizations, often help unlock the potential of new discoveries and budding technologies. Combinatorial methods are a textbook example. These emerging tools can speed innovation in many fields - pharmaceuticals, chemistry, and, most recently, materials. In the diverse realm of materials, combinatorial methods hold promise for all classes, including metals, polymers, ceramics, and biomaterials. NIST has established the NCMC as a model for collaboration, in order to share expertise, facilities, resources, and information thereby reducing obstacles to participating in this fast-moving and instrument-intensive area. Although collaborations with multiple partners can be difficult, the goal is to foster cross-fertilization of ideas and research strategies, and to spur progress on many fronts by crossing boundaries of organizations, disciplines, and interests. Members have access to technical workshops, short courses, data libraries, and electronic bulletin boards; they can participate in non-proprietary focused projects; and they can enter into specific cooperative research and development agreements with controlled intellectual property.

  9. Algebraic and combinatorial aspects of sandpile monoids on directed graphs

    CERN Document Server

    Chapman, Scott; Garcia, Rebecca; Malandro, Martin E; Smith, Ken W

    2011-01-01

    We study the abelian sandpile model on a finite directed graph. We begin by reviewing the necessary background material starting with the identification, by Babai and Toumpakari, of the sandpile group on a directed graph as the minimal ideal of its sandpile monoid, and continuing through some of their recent results concerning the connections between the idempotent structure of a sandpile monoid and the cycle structure of its graph. We then build on these results to give our first main result, which is a combinatorial classification of the maximal subgroups of a sandpile monoid on a directed graph X in terms of the sandpile groups of certain easily-identifiable subgraphs of X. We then return to undirected graphs and give our second main result, which is a combinatorial classification of the sandpile group identity of every undirected distance regular graph. Along the way we give several new algebraic results for sandpiles based on directed graphs, and we point out parallels to previously known results for und...

  10. 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.

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

    Science.gov (United States)

    Choi, Hye-Ji; Kim, Ye-Jin; Choi, Dong-Ki; Kim, Yong-Sung

    2015-01-01

    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.

  12. Combinatorial pharmacophore modeling of organic cation transporter 2 (OCT2) inhibitors: insights into multiple inhibitory mechanisms.

    Science.gov (United States)

    Xu, Yuan; Liu, Xian; Li, Shanshan; Zhou, Nannan; Gong, Likun; Luo, Cheng; Luo, Xiaomin; Zheng, Mingyue; Jiang, Hualiang; Chen, Kaixian

    2013-12-02

    Organic cation transporter 2 (OCT2) is responsible for the entry step of many drugs in renal elimination, of which the changing activity may cause unwanted drug-drug interactions (DDIs). To develop drugs with favorable safety profile and provide instruction for rational clinical drug administration, it is of great interest to investigate the multiple mechanisms of OCT2 inhibition. In this study, we designed a combinatorial scheme to screen the optimum combination of pharmacophores from a pool of hypotheses established based on 162 OCT2 inhibitors. Among them, one single pharmacophore hypothesis represents a potential binding mode that may account for one unique inhibitory mechanism, and the obtained pharmacophore combination describes the multimechanisms of OCT2 inhibition. The final model consists of four individual pharmacophores, i.e., DHPR18, APR2, PRR5 and HHR4. Given a query ligand, it is considered as an inhibitor if it matches at least one of the hypotheses, or a noninhibitor if it fails to match any of four hypotheses. Our combinatorial pharmacophore model performs reasonably well to discriminate inhibitors and noninhibitors, yielding an overall accuracy around 0.70 for a test set containing 81 OCT2 inhibitors and 218 noninhibitors. Intriguingly, we found that the number of matched hypotheses was positively correlated with inhibition rate, which coincides with the pharmacophore modeling result of P-gp substrate binding. Further analysis suggested that the hypothesis PRR5 was responsible for competitive inhibition of OCT2, and other hypotheses were important for interaction between the inhibitor and OCT2. In light of the results, a hypothetical model for inhibiting transporting mediated by OCT2 was proposed.

  13. Combinatorial analysis and algorithms for quasispecies reconstruction using next-generation sequencing

    Directory of Open Access Journals (Sweden)

    Vincenti Donatella

    2011-01-01

    Full Text Available Abstract Background Next-generation sequencing (NGS offers a unique opportunity for high-throughput genomics and has potential to replace Sanger sequencing in many fields, including de-novo sequencing, re-sequencing, meta-genomics, and characterisation of infectious pathogens, such as viral quasispecies. Although methodologies and software for whole genome assembly and genome variation analysis have been developed and refined for NGS data, reconstructing a viral quasispecies using NGS data remains a challenge. This application would be useful for analysing intra-host evolutionary pathways in relation to immune responses and antiretroviral therapy exposures. Here we introduce a set of formulae for the combinatorial analysis of a quasispecies, given a NGS re-sequencing experiment and an algorithm for quasispecies reconstruction. We require that sequenced fragments are aligned against a reference genome, and that the reference genome is partitioned into a set of sliding windows (amplicons. The reconstruction algorithm is based on combinations of multinomial distributions and is designed to minimise the reconstruction of false variants, called in-silico recombinants. Results The reconstruction algorithm was applied to error-free simulated data and reconstructed a high percentage of true variants, even at a low genetic diversity, where the chance to obtain in-silico recombinants is high. Results on empirical NGS data from patients infected with hepatitis B virus, confirmed its ability to characterise different viral variants from distinct patients. Conclusions The combinatorial analysis provided a description of the difficulty to reconstruct a quasispecies, given a determined amplicon partition and a measure of population diversity. The reconstruction algorithm showed good performance both considering simulated data and real data, even in presence of sequencing errors.

  14. Investigation of thermal protection system by forward-facing cavity and opposing jet combinatorial configuration

    Institute of Scientific and Technical Information of China (English)

    Lu Haibo; Liu Weiqiang

    2013-01-01

    This paper focuses on the usage of the forward-facing cavity and opposing jet combinatorial configuration as the thermal protection system (TPS) for hypersonic vehicles.A hemispherecone nose-tip with the combinatorial configuration is investigated numerically in hypersonic free stream.Some numerical results are validated by experiments.The flow field parameters,aerodynamic force and surface heat flux distribution are obtained.The influence of the opposing jet stagnation pressure on cooling efficiency of the combinatorial TPS is discussed.The detailed numerical results show that the aerodynamic heating is reduced remarkably by the combinatorial system.The recirculation region plays a pivotal role for the reduction of heat flux.The larger the stagnation pressure of opposing jet is,the more the heating reduction is.This kind of combinatorial system is suitable to be the TPS for the high-speed vehicles which need long-range and long time flight.

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

    Science.gov (United States)

    Diemer, Sanna L.; Kristensen, Morten; Rasmussen, Brian; Beeren, Sophie R.; Pittelkow, Michael

    2015-01-01

    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. PMID:26378519

  16. 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.

  17. 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.

  18. Optimization combinatorial for expansion of gas distribution networks; Otimizacao combinatoria para expansao de redes de distribuicao de gas

    Energy Technology Data Exchange (ETDEWEB)

    Costa, Wagner Emanoel; Gouvea, Elizabeth Ferreira; Goldbarg, Marco Cesar [Rio Grande do Norte Univ., Natal, RN (Brazil). Dept. de Informatica e Matematica Aplicada]. E-mail: wemano@digi.com.br; beth@dimap.ufrn.br; gold@dimap.ufrn.br

    2003-07-01

    Brazil is in a excellent context for the development of natural gas as energy source. The responsibility of design a network to deliver gas increases with the new investments made every day. However the computer aided design (CAD) technologies for gas network design were poor developed because in EUA and Europe have their gas networks from long time ago, in such that only a little of the potential of computer had been explored for the gas network design. This work studies the use of combinatorial optimization techniques and others techniques from evolutionary computing to find layouts to create and expand a network and make the pipeline optimization looking for costs minimizations and respecting all demands of pressures and flow. (author)

  19. Combinatorial method for overexpression of membrane proteins in Escherichia coli.

    Science.gov (United States)

    Leviatan, Shani; Sawada, Keisuke; Moriyama, Yoshinori; Nelson, Nathan

    2010-07-30

    Membrane proteins constitute 20-30% of all proteins encoded by the genome of various organisms. Large amounts of purified proteins are required for activity and crystallization attempts. Thus, there is an unmet need for a heterologous membrane protein overexpression system for purification, crystallization, and activity determination. We developed a combinatorial method for overexpressing and purifying membrane proteins using Escherichia coli. This method utilizes short hydrophilic bacterial proteins, YaiN and YbeL, fused to the ends of the membrane proteins to serve as facilitating factors for expression and purification. Fourteen prokaryotic and mammalian membrane proteins were expressed using this system. Moderate to high expression was obtained for most proteins, and detergent solubilization combined with a short purification process produced stable, monodispersed membrane proteins. Five of the mammalian membrane proteins, overexpressed using our system, were reconstituted into liposomes and exhibited transport activity comparable with the native transporters.

  20. Combinatorial Method for Overexpression of Membrane Proteins in Escherichia coli*

    Science.gov (United States)

    Leviatan, Shani; Sawada, Keisuke; Moriyama, Yoshinori; Nelson, Nathan

    2010-01-01

    Membrane proteins constitute 20–30% of all proteins encoded by the genome of various organisms. Large amounts of purified proteins are required for activity and crystallization attempts. Thus, there is an unmet need for a heterologous membrane protein overexpression system for purification, crystallization, and activity determination. We developed a combinatorial method for overexpressing and purifying membrane proteins using Escherichia coli. This method utilizes short hydrophilic bacterial proteins, YaiN and YbeL, fused to the ends of the membrane proteins to serve as facilitating factors for expression and purification. Fourteen prokaryotic and mammalian membrane proteins were expressed using this system. Moderate to high expression was obtained for most proteins, and detergent solubilization combined with a short purification process produced stable, monodispersed membrane proteins. Five of the mammalian membrane proteins, overexpressed using our system, were reconstituted into liposomes and exhibited transport activity comparable with the native transporters. PMID:20525689

  1. Rapid thermal conductivity measurements for combinatorial thin films.

    Science.gov (United States)

    McDowell, Matthew G; Hill, Ian G

    2013-05-01

    A simple and inexpensive automated method for determining the thermal conductivity of a combinatorial library of thin films is demonstrated by measuring the thermal conductivity of a sputtered silicon dioxide film of varying thickness deposited on single crystal silicon. Using 3ω measurements, two methods for calculating the substrate thermal conductivity and two methods for determining the film thermal conductivity are demonstrated and compared. The substrate thermal conductivity was found to be 139 ± 3 W/m·K. Using the measured variation in film thickness, the film thermal conductivity was found to be 1.11 ± 0.05 W/m·K, in excellent agreement with published values for sputtered SiO2, demonstrating the accuracy of the method.

  2. Non-orthodox combinatorial models based on discordant structures

    CERN Document Server

    Romanov, V F

    2010-01-01

    This paper introduces a novel method for compact representation of sets of n-dimensional binary sequences in a form of compact triplets structures (CTS), supposing both logic and arithmetic interpretations of data. Suitable illustration of CTS application is the unique graph-combinatorial model for the classic intractable 3-Satisfiability problem and a polynomial algorithm for the model synthesis. The method used for Boolean formulas analysis and classification by means of the model is defined as a bijective mapping principle for sets of components of discordant structures to a basic set. The statistic computer-aided experiment showed efficiency of the algorithm in a large scale of problem dimension parameters, including those that make enumeration procedures of no use. The formulated principle expands resources of constructive approach to investigation of intractable problems.

  3. High resolution MAS-NMR in combinatorial chemistry.

    Science.gov (United States)

    Shapiro, M J; Gounarides, J S

    High-resolution magic angle spinning (hr-MAS) NMR is a powerful tool for characterizing organic reactions on solid support. Because magic angle spinning reduces the line-broadening due to dipolar coupling and variations in bulk magnetic susceptibility, line widths approaching those obtained in solution-phase NMR can be obtained. The magic angle spinning method is amenable for use in conjunction with a variety of NMR-pulse sequences, making it possible to perform full-structure determinations and conformational analysis on compounds attached to a polymer support. Diffusion-weighted MAS-NMR methods such as SPEEDY (Spin-Echo-Enhanced Diffusion-Filtered Spectroscopy) can be used to remove unwanted signals from the solvent, residual reactants, and the polymer support from the MAS-NMR spectrum, leaving only those signals arising from the resin-bound product. This review will present the applications of high-resolution magic angle spinning NMR for use in combinatorial chemistry research.

  4. PCB Drill Path Optimization by Combinatorial Cuckoo Search Algorithm

    Directory of Open Access Journals (Sweden)

    Wei Chen Esmonde Lim

    2014-01-01

    Full Text Available Optimization of drill path can lead to significant reduction in machining time which directly improves productivity of manufacturing systems. In a batch production of a large number of items to be drilled such as printed circuit boards (PCB, the travel time of the drilling device is a significant portion of the overall manufacturing process. To increase PCB manufacturing productivity and to reduce production costs, a good option is to minimize the drill path route using an optimization algorithm. This paper reports a combinatorial cuckoo search algorithm for solving drill path optimization problem. The performance of the proposed algorithm is tested and verified with three case studies from the literature. The computational experience conducted in this research indicates that the proposed algorithm is capable of efficiently finding the optimal path for PCB holes drilling process.

  5. PCB drill path optimization by combinatorial cuckoo search algorithm.

    Science.gov (United States)

    Lim, Wei Chen Esmonde; Kanagaraj, G; Ponnambalam, S G

    2014-01-01

    Optimization of drill path can lead to significant reduction in machining time which directly improves productivity of manufacturing systems. In a batch production of a large number of items to be drilled such as printed circuit boards (PCB), the travel time of the drilling device is a significant portion of the overall manufacturing process. To increase PCB manufacturing productivity and to reduce production costs, a good option is to minimize the drill path route using an optimization algorithm. This paper reports a combinatorial cuckoo search algorithm for solving drill path optimization problem. The performance of the proposed algorithm is tested and verified with three case studies from the literature. The computational experience conducted in this research indicates that the proposed algorithm is capable of efficiently finding the optimal path for PCB holes drilling process.

  6. Combinatorial Analysis of a Subtraction Game on Graphs

    Directory of Open Access Journals (Sweden)

    Richard Adams

    2016-01-01

    Full Text Available We define a two-player combinatorial game in which players take alternate turns; each turn consists of deleting a vertex of a graph, together with all the edges containing such vertex. If any vertex became isolated by a player’s move then it would also be deleted. A player wins the game when the other player has no moves available. We study this game under various viewpoints: by finding specific strategies for certain families of graphs, through using properties of a graph’s automorphism group, by writing a program to look at Sprague-Grundy numbers, and by studying the game when played on random graphs. When analyzing Grim played on paths, using the Sprague-Grundy function, we find a connection to a standing open question about Octal games.

  7. Combinatorial Algebra for second-quantized Quantum Theory

    CERN Document Server

    Blasiak, P; Solomon, A I; Horzela, A; Penson, K A

    2010-01-01

    We describe an algebra G of diagrams which faithfully gives a diagrammatic representation of the structures of both the Heisenberg-Weyl algebra H - the associative algebra of the creation and annihilation operators of quantum mechanics - and U(L_H), the enveloping algebra of the Heisenberg Lie algebra L_H. We show explicitly how G may be endowed with the structure of a Hopf algebra, which is also mirrored in the structure of U(L_H). While both H and U(L_H) are images of G, the algebra G has a richer structure and therefore embodies a finer combinatorial realization of the creation-annihilation system, of which it provides a concrete model.

  8. Some combinatorial models for reduced expressions in Coxeter groups

    CERN Document Server

    Denoncourt, Hugh

    2011-01-01

    Stanley's formula for the number of reduced expressions of a permutation regarded as a Coxeter group element raises the question of how to enumerate the reduced expressions of an arbitrary Coxeter group element. We provide a framework for answering this question by constructing combinatorial objects that represent the inversion set and the reduced expressions for an arbitrary Coxeter group element. The framework also provides a formula for the length of an element formed by deleting a generator from a Coxeter group element. Fan and Hagiwara, et al$.$ showed that for certain Coxeter groups, the short-braid avoiding elements characterize those elements that give reduced expressions when any generator is deleted from a reduced expression. We provide a characterization that holds in all Coxeter groups. Lastly, we give applications to the freely braided elements introduced by Green and Losonczy, generalizing some of their results that hold in simply-laced Coxeter groups to the arbitrary Coxeter group setting.

  9. Combinatorial Optimization of Transparent Conducting Oxides (TCOS) for PV

    Energy Technology Data Exchange (ETDEWEB)

    Perkins, J. D.; Taylor, M. P.; van Hest, M.F.A.M.; Teplin, C. W.; Alleman, J. L.; Dabney, M. S.; Gedvilas, L. M.; Keyes, B. M.; To, B.; Readey, D. W.; Delahoy, A. E.; Guo, S.; Ginley, D. S.

    2005-02-01

    Transparent conducting oxides (TCOs) can serve a variety of important functions in thin-film photovoltaics such as transparent electrical contacts, antireflection coatings, and chemical barriers. Two areas of particular interest are TCOs that can be deposited at low temperatures and TCOs with high carrier mobilities. We have employed combinatorial high-throughput approaches to investigate both these areas. Conductivities of s = 2500 W-1-cm-1 have been obtained for In-Zn-O (IZO) films deposited at 100 C and s > 5000 W-1-cm-1 for In-Ti-O (ITiO) and In-Mo-O (IMO) films deposited at 550 C. The highest mobility obtained was 83 cm2/V-s for ITiO deposited at 550 C.

  10. Yeast mating for combinatorial Fab library generation and surface display

    Energy Technology Data Exchange (ETDEWEB)

    Feldhaus, Jane M.; Lou, Jianlong; Coleman, James R.; Siegel, Robert W.; Marks, James D.; Feldhaus, Michael

    2004-04-23

    Yeast display of antibody fragments has proven to be an efficient and productive means for directed evolution of single chain Fv (scFv) antibodies for increased affinity and thermal stability, and more recently for the display and screening of a non-immune library. In this paper, we describe an elegant and simple method for constructing large combinatorial Fab libraries for display on the surface of Saccharomyces cerevisiae, from modestly sized, and easily constructed, heavy and light chain libraries. To this end, we have constructed a set of yeast strains and a two vector system for heavy chain and light chain surface display of Fab fragments with free native amino termini. Through yeast mating of the haploid libraries, a very large heterodimeric immune Fab library was displayed on the diploids and high affinity antigen specific Fabs were isolated from the library.

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

    Science.gov (United States)

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

    2015-11-01

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

  12. Spreadsheet modelling for solving combinatorial problems: The vendor selection problem

    CERN Document Server

    Ipsilandis, Pandelis G

    2008-01-01

    Spreadsheets have grown up and became very powerful and easy to use tools in applying analytical techniques for solving business problems. Operations managers, production managers, planners and schedulers can work with them in developing solid and practical Do-It-Yourself Decision Support Systems. Small and Medium size organizations, can apply OR methodologies without the presence of specialized software and trained personnel, which in many cases cannot afford anyway. This paper examines an efficient approach in solving combinatorial programming problems with the use of spreadsheets. A practical application, which demonstrates the approach, concerns the development of a spreadsheet-based DSS for the Multi Item Procurement Problem with Fixed Vendor Cost. The DSS has been build using exclusively standard spreadsheet feature and can solve real problems of substantial size. The benefits and limitations of the approach are also discussed.

  13. Histone code or not? Combinatorial pattern analyses of histone modifications

    Science.gov (United States)

    Zang, Chongzhi; Peng, Weiqun; Wang, Zhibin; Schones, Dustin E.; Barski, Artem; Cuddapah, Suresh; Cui, Kairong; Roh, Tae-Young; Zhao, Keji; Rosenfeld, Jeffrey; Zhang, Michael

    2008-03-01

    Eukaryotic genomes are organized into chromatin, the structure of which plays critical role in the program of gene expression. Chromatin structure and function is regulated by a myriad of posttranslational modifications on histone tails of the nucleosomes, the fundamental unit of chromatin. It remains unclear how different modifications interact. Based on high- resolution genomic maps of close to 40 histone methylations and acetylations in human T-cells obtained experimentally by ChIP- Seq technique, we investigated the combinatorial patterns of histone modifications at gene promoter regions. We found that a very limited number of patterns dominate. Modifications within a pattern are strongly correlated and each pattern is associated with a distinct gene expression distribution. Our results suggest that it is the patterns rather than the individual modifications that affect the downstream readout.

  14. A Combinatorial Auction Based Algorithm for Flexible Seat Reservation Systems

    Science.gov (United States)

    Otomura, Kazutoshi; Tomii, Norio

    We present algorithms for flexible seat distribution problems, which is defined as a problem to give an appropriate travel plan to each passenger after receiving their requests concerning their travel demands. Seat distribution problems occur when a flexible seat reservation system is implemented in which passengers are allowed to reserve seats by submitting their demands instead of specifying trains. To solve the seat distribution problem, we have formalized it as a winner determination problem of the combinatorial auction mechanism. It should be noted that difficulty of the seat distribution problem varies depending on instances of the problem, because the number of demands often varies and users' requests sometimes converge on particular trains. This suggests that in order to get solutions with high quality, algorithms that appropriately control the search space are indispensable. In this paper, we present three kinds of such algorithms for the seat distribution problem together with the results of several experiments.

  15. Combinatorial strategies for the induction of immunogenic cell death

    Directory of Open Access Journals (Sweden)

    Lorenzo eGalluzzi

    2015-04-01

    Full Text Available The term immunogenic cell death (ICD is commonly employed to indicate a peculiar instance of regulated cell death (RCD that engages the adaptive arm of the immune system. The inoculation of cancer cells undergoing ICD into immunocompetent animals elicits a specific immune response associated with the establishment of immunological memory. Only a few agents are intrinsically endowed with the ability to trigger ICD. These include a few chemotherapeutics that are routinely employed in the clinic, like doxorubicin, mitoxantrone, oxaliplatin and cyclophosphamide, as well as some agents that have not yet been approved for use in humans. Accumulating clinical data indicate that the activation of adaptive immune responses against dying cancer cells is associated with improved disease outcome in patients affected by various neoplasms. Thus, novel therapeutic regimens that trigger ICD are urgently awaited. Here, we discuss current combinatorial approaches to convert otherwise non-immunogenic instances of RCD into bona fide ICD.

  16. Consistency and axiomatization of a natural extensional combinatory logic

    Institute of Scientific and Technical Information of China (English)

    蒋颖

    1996-01-01

    In the light of a question of J. L. Krivine about the consistency of an extensional λ-theory,an extensional combinatory logic ECL+U(G)+RU_∞+ is established, with its consistency model provedtheoretically and it is shown the it is not equivalent to any system of universal axioms. It is expressed bythe theory in first order logic that, for every given group G of order n, there simultaneously exist infinitelymany universal retractions and a surjective n-tuple notion, such that each element of G acts as a permutationof the components of the n-tuple, and as an Ap-automorphism of the model; further each of the universalretractions is invarian under the action of the Ap-automorphisms induced by G The difference between thetheory and that of Krivine is the G need not be a symmetric group.

  17. Combinatorial Clustering and the Beta Negative Binomial Process.

    Science.gov (United States)

    Broderick, Tamara; Mackey, Lester; Paisley, John; Jordan, Michael I

    2015-02-01

    We develop a Bayesian nonparametric approach to a general family of latent class problems in which individuals can belong simultaneously to multiple classes and where each class can be exhibited multiple times by an individual. We introduce a combinatorial stochastic process known as the negative binomial process ( NBP ) as an infinite-dimensional prior appropriate for such problems. We show that the NBP is conjugate to the beta process, and we characterize the posterior distribution under the beta-negative binomial process ( BNBP) and hierarchical models based on the BNBP (the HBNBP). We study the asymptotic properties of the BNBP and develop a three-parameter extension of the BNBP that exhibits power-law behavior. We derive MCMC algorithms for posterior inference under the HBNBP , and we present experiments using these algorithms in the domains of image segmentation, object recognition, and document analysis.

  18. Combinatorial microfluidic droplet engineering for biomimetic material synthesis

    Science.gov (United States)

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

    2016-01-01

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

  19. Reactive combinatorial synthesis and characterization of a gradient Ag-Ti oxide thin film with antibacterial properties.

    Science.gov (United States)

    Unosson, Erik; Rodriguez, Daniel; Welch, Ken; Engqvist, Håkan

    2015-01-01

    The growing demand for orthopedic and dental implants has spurred researchers to develop multifunctional coatings, combining tissue integration with antibacterial features. A possible strategy to endow titanium (Ti) with antibacterial properties is by incorporating silver (Ag), but designing a structure with adequate Ag(+) release while maintaining biocompatibility has been shown difficult. To further explore the composition-structure-property relationships between Ag and Ti, and its effects against bacteria, this study utilized a combinatorial approach to manufacture and test a single sample containing a binary Ag-Ti oxide gradient. The sample, sputter-deposited in a reactive (O2) environment using a custom-built combinatorial physical vapor deposition system, was shown to be effective against Staphylococcus aureus with viability reductions ranging from 17 to above 99%, depending on the amount of Ag(+) released from its different parts. The Ag content along the gradient ranged from 35 to 62 wt.%, but it was found that structural properties such as varied porosity and degree of crystallinity, rather than the amount of incorporated Ag, governed the Ag(+) release and resulting antibacterial activity. The coating also demonstrated in vitro apatite-forming abilities, where structural variety along the sample was shown to alter the hydrophilic behavior, with the degree of hydroxyapatite deposition varying accordingly. By means of combinatorial synthesis, a single gradient sample was able to display intricate compositional and structural features affecting its biological response, which would otherwise require a series of coatings. The current findings suggest that future implant coatings incorporating Ag as an antibacterial agent could be structurally enhanced to better suit clinical requirements.

  20. Quantitative control of organ shape by combinatorial gene activity.

    Directory of Open Access Journals (Sweden)

    Min-Long Cui

    Full Text Available The development of organs with particular shapes, like wings or flowers, depends on regional activity of transcription factors and signalling molecules. However, the mechanisms that link these molecular activities to the morphogenetic events underlying shape are poorly understood. Here we describe a combination of experimental and computational approaches that address this problem, applying them to a group of genes controlling flower shape in the Snapdragon (Antirrhinum. Four transcription factors are known to play a key role in the control of floral shape and asymmetry in Snapdragon. We use quantitative shape analysis of mutants for these factors to define principal components underlying flower shape variation. We show that each transcription factor has a specific effect on the shape and size of regions within the flower, shifting the position of the flower in shape space. These shifts are further analysed by generating double mutants and lines that express some of the genes ectopically. By integrating these observations with known gene expression patterns and interactions, we arrive at a combinatorial scheme for how regional effects on shape are genetically controlled. We evaluate our scheme by incorporating the proposed interactions into a generative model, where the developing flower is treated as a material sheet that grows according to how genes modify local polarities and growth rates. The petal shapes generated by the model show a good quantitative match with those observed experimentally for each petal in numerous genotypes, thus validating the hypothesised scheme. This article therefore shows how complex shapes can be accounted for by combinatorial effects of transcription factors on regional growth properties. This finding has implications not only for how shapes develop but also for how they may have evolved through tinkering with transcription factors and their targets.

  1. Combinatorial approach to generalized Bell and Stirling numbers and boson normal ordering problem

    CERN Document Server

    Mendez, M A; Penson, K A

    2005-01-01

    We consider the numbers arising in the problem of normal ordering of expressions in canonical boson creation and annihilation operators. We treat a general form of a boson string which is shown to be associated with generalizations of Stirling and Bell numbers. The recurrence relations and closed-form expressions (Dobiski-type formulas) are obtained for these quantities by both algebraic and combinatorial methods. By extensive use of methods of combinatorial analysis we prove the equivalence of the aforementioned problem to the enumeration of special families of graphs. This link provides a combinatorial interpretation of the numbers arising in this normal ordering problem.

  2. Extraction of Phenylalanine Phase Systems Containing Enantiomers by Aqueous Two Combinatorial Chiral Selector

    Institute of Scientific and Technical Information of China (English)

    陈晓青; 刘莉; 焦飞鹏; 王珍

    2012-01-01

    In order to obtain a better enantioselectivity of phenylalanine enantiomers and establish the optimal chiral ex- traction conditions, the distribution behavior was investigated in aqueous two-phase systems which were composed of polyethylene glycol and ammonium sulfate containing combinatorial chiral selector: β-cyclodextrin and HP-β-cyclodextrin. The influence of the molar concentration ratio of combinatorial chiral selectors, the total molar concentration of combinatorial chiral selectors, pH value, buffer type and its concentration were thoroughly studied, respectively. The results show that the enantioselectivity reaches 1.53 under the optimal chiral extraction conditions This extraction is a potential economical and effective way for chiral resolution.

  3. 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....

  4. Multi-Objective Combinatorial Optimization of Trigeneration Plants Based on Metaheuristics

    Directory of Open Access Journals (Sweden)

    Mirko M. Stojiljković

    2014-12-01

    Full Text Available In this paper, a methodology for multi-objective optimization of trigeneration plants is presented. It is primarily applicable to the systems for buildings’ energy supply characterized by high load variations on daily, weekly and annual bases, as well as the components applicable for flexible operation. The idea is that this approach should enable high accuracy and flexibility in mathematical modeling, while remaining efficient enough. The optimization problem is structurally decomposed into two new problems. The main problem of synthesis and design optimization is combinatorial and solved with different metaheuristic methods. For each examined combination of the synthesis and design variables, when calculating the values of the objective functions, the inner, mixed integer linear programming operation optimization problem is solved with the branch-and-cut method. The applicability of the exploited metaheuristic methods is demonstrated. This approach is compared with the alternative, superstructure-based approach. The potential for combining them is also examined. The methodology is applied for multi-objective optimization of a trigeneration plant that could be used for the energy supply of a real residential settlement in Niš, Serbia. Here, two objectives are considered: annual total costs and primary energy consumption. Results are obtained in the form of a Pareto chart using the epsilon-constraint method.

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

    DEFF Research Database (Denmark)

    Diemer, Sanna L.; Kristensen, Morten; Rasmussen, Brian

    2015-01-01

    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...

  6. Allocation of advertising space by a web service provider using combinatorial auctions

    Indian Academy of Sciences (India)

    Sandeep Dulluri; N R Srinivasa Raghavan

    2005-04-01

    Advertising is a critical process for promoting both products and services in global trade. Internet has emerged as a powerful medium for trade and commerce. Online advertising over the internet has increased more than hundredfold since 2001. In the present work, we address problems faced by online advertisement service providers. In this paper, we propose a multi-slot and multi-site combinatorial auction for allocating scarce advertisement slots available on multiple sites. We observe that combinatorial auctions serve as effective mechanisms for allocating advertising slots over the internet. We resort to “ant” systems (ant – social insect/intelligent agent) to solve the above $\\mathcal{NP}$-hard combinatorial optimization problem which involves winner-determination in multi-item and multi-unit combinatorial auctions.

  7. INdAM conference "CoMeTA 2013 - Combinatorial Methods in Topology and Algebra"

    CERN Document Server

    Delucchi, Emanuele; Moci, Luca

    2015-01-01

    Combinatorics plays a prominent role in contemporary mathematics, due to the vibrant development it has experienced in the last two decades and its many interactions with other subjects. This book arises from the INdAM conference "CoMeTA 2013 - Combinatorial Methods in Topology and Algebra,'' which was held in Cortona in September 2013. The event brought together emerging and leading researchers at the crossroads of Combinatorics, Topology and Algebra, with a particular focus on new trends in subjects such as: hyperplane arrangements; discrete geometry and combinatorial topology; polytope theory and triangulations of manifolds; combinatorial algebraic geometry and commutative algebra; algebraic combinatorics; and combinatorial representation theory. The book is divided into two parts. The first expands on the topics discussed at the conference by providing additional background and explanations, while the second presents original contributions on new trends in the topics addressed by the conference.

  8. 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 o...

  9. Genetic Algorithm Based Combinatorial Auction Method for Multi-Robot Task Allocation

    Institute of Scientific and Technical Information of China (English)

    GONG Jian-wei; HUANG Wan-ning; XIONG Guang-ming; MAN Yi-ming

    2007-01-01

    An improved genetic algorithm is proposed to solve the problem of bad real-time performance or inability to get a global optimal/better solution when applying single-item auction (SIA) method or combinatorial auction method to multi-robot task allocation.The genetic algorithm based combinatorial auction (GACA) method which combines the basic-genetic algorithm with a new concept of ringed chromosome is used to solve the winner determination problem (WDP) of combinatorial auction.The simulation experiments are conducted in OpenSim, a multi-robot simulator.The results show that GACA can get a satisfying solution in a reasonable shot time, and compared with SIA or parthenogenesis algorithm combinatorial auction (PGACA) method, it is the simplest and has higher search efficiency, also, GACA can get a global better/optimal solution and satisfy the high real-time requirement of multi-robot task allocation.

  10. Combinatorial parallel synthesis and automated screening of a novel class of liquid crystalline materials.

    Science.gov (United States)

    Deeg, Oliver; Kirsch, Peer; Pauluth, Detlef; Bäuerle, Peter

    2002-12-07

    Combinatorial parallel synthesis has led to the rapid generation of a single-compound library of novel fluorinated quaterphenyls. Subsequent automated screening revealed liquid crystalline (LC) behaviour and gave qualitative relationships of molecular structures and solid state properties.

  11. A light emitting diode based photoelectrochemical screener for distributed combinatorial materials discovery.

    Science.gov (United States)

    Winkler, Gates R; Winkler, Jay R

    2011-11-01

    Combinatorial approaches for targeted discovery of new materials require rapid screening systems to evaluate large numbers of new material compositions. High-throughput combinatorial materials discovery is a capital-intensive undertaking requiring sophisticated robotic sample preparation and rapid screening assays. A distributed approach to combinatorial materials discovery can achieve similar goals by increasing the breadth of participation and reducing the size of the capital investment. The discovery of new photoactive materials for solar fuels production demands a screening device to probe materials for electrochemical current production upon irradiation with visible light. We have developed a system that uses an array of pulsed light-emitting diodes (LEDs) synchronized with a two-electrode potentiostat that can measure the photoelectrochemical responses of combinatorial sample arrays deposited on conducting glass plates. Compared to raster scanning methods, this LED system trades spatial resolution for a substantial reduction in scan time. © 2011 American Institute of Physics

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

    Science.gov (United States)

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

    2006-12-01

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

  13. Creating the New from the Old: Combinatorial Libraries Generation with Machine-Learning-Based Compound Structure Optimization.

    Science.gov (United States)

    Podlewska, Sabina; Czarnecki, Wojciech M; Kafel, Rafał; Bojarski, Andrzej J

    2017-02-15

    The growing computational abilities of various tools that are applied in the broadly understood field of computer-aided drug design have led to the extreme popularity of virtual screening in the search for new biologically active compounds. Most often, the source of such molecules consists of commercially available compound databases, but they can also be searched for within the libraries of structures generated in silico from existing ligands. Various computational combinatorial approaches are based solely on the chemical structure of compounds, using different types of substitutions for new molecules formation. In this study, the starting point for combinatorial library generation was the fingerprint referring to the optimal substructural composition in terms of the activity toward a considered target, which was obtained using a machine learning-based optimization procedure. The systematic enumeration of all possible connections between preferred substructures resulted in the formation of target-focused libraries of new potential ligands. The compounds were initially assessed by machine learning methods using a hashed fingerprint to represent molecules; the distribution of their physicochemical properties was also investigated, as well as their synthetic accessibility. The examination of various fingerprints and machine learning algorithms indicated that the Klekota-Roth fingerprint and support vector machine were an optimal combination for such experiments. This study was performed for 8 protein targets, and the obtained compound sets and their characterization are publically available at http://skandal.if-pan.krakow.pl/comb_lib/ .

  14. A novel combinatorial approach for understanding microstructural evolution and its relationship to mechanical properties in metallic biomaterials.

    Science.gov (United States)

    Nag, S; Banerjee, R; Fraser, H L

    2007-05-01

    The new generation of metallic biomaterials for prosthesis implantation (orthopedic and dental) typically have a Ti base with fully biocompatible alloying additions such as Nb, Ta, Zr, Mo, Fe and Sn. While the binary Ti-Ta and the ternary Ti-Nb-Ta systems are promising, the large composition space afforded by these systems offers tremendous scope in terms of alloy design via optimization of alloy composition and thermomechanical treatment. In the present paper a novel combinatorial approach has been developed for rapidly exploring the microstructural evolution and microstructure-microhardness (or elastic modulus) relationships in these systems. Using directed laser deposition, compositionally graded alloy samples have been fabricated and subsequently heat-treated to affect different microstructures in terms of the volume fraction and distribution of the alpha phase in the beta matrix as a function of composition. Subsequently, composition-specific indentation-based hardness and modulus information has been obtained from these graded samples, and the resulting data have been used to develop relationships between the composition, microstructure and mechanical properties. Such rapid combinatorial assessments can be very useful in optimizing not only the alloy composition but also the desired microstructure for achieving the best combination of properties for specific orthopedic or dental applications.

  15. Combinatorial investigation of rare-earth free permanent magnets

    Science.gov (United States)

    Fackler, Sean Wu

    The combinatorial high throughput method allows one to rapidly study a large number of samples with systematically changing parameters. We apply this method to study Fe-Co-V alloys as alternatives to rare-earth permanent magnets. Rare-earth permanent magnets derive their unmatched magnetic properties from the hybridization of Fe and Co with the f-orbitals of rare-earth elements, which have strong spin-orbit coupling. It is predicted that Fe and Co may also have strong hybridization with 4d and 5d refractory transition metals with strong spin-orbit coupling. Refractory transition metals like V also have the desirable property of high temperature stability, which is important for permanent magnet applications in traction motors. In this work, we focus on the role of crystal structure, composition, and secondary phases in the origin of competitive permanent magnetic properties of a particular Fe-Co-V alloy. Fe38Co52V10, compositions are known as Vicalloys. Fe-CoV composition spreads were sputtered onto three-inch silicon wafers and patterned into discrete sample pads forming a combinatorial library. We employed highthroughput screening methods using synchrotron X-rays, wavelength dispersive spectroscopy, and magneto-optical Kerr effect (MOKE) to rapidly screen crystal structure, composition, and magnetic properties, respectively. We found that in-plane magnetic coercive fields of our Vicalloy thin films agree with known bulk values (300 G), but found a remarkable eight times increase of the out-of-plane coercive fields (˜2,500 G). To explain this, we measured the switching fields between in-plane and out-of-plane thin film directions which revealed that the Kondorsky model of 180° domain wall reversal was responsible for Vicalloy's enhanced out-of-plane coercive field and possibly its permanent magnetic properties. The Kondorsky model suggests that domain-wall pinning is the origin of Vicalloy's permanent magnetic properties, in contrast to strain, shape, or

  16. An Indexed Combinatorial Library: The Synthesis and Testing of Insect Repellents

    Science.gov (United States)

    Miles, William H.; Gelato, Kathy A.; Pompizzi, Kristen M.; Scarbinsky, Aislinn M.; Albrecht, Brian K.; Reynolds, Elaine R.

    2001-04-01

    An indexed combinatorial library of amides was prepared by the reaction of amines and acid chlorides. A simple test for insect repellency using fruit flies (Drosophila melanogaster) allowed the determination of the most repellent sublibraries. The student-generated data were collected and analyzed to determine the most active amide(s) in the library. This experiment illustrates the fundamentals of combinatorial chemistry, a field that has undergone explosive growth in the last decade.

  17. Self-encoding Functional Resin Applying for Combinatorial Chemistry and High Throughput Screening

    Institute of Scientific and Technical Information of China (English)

    DU Lei; CHEN Tong-sheng

    2004-01-01

    A novel solid phase organic synthesis resin was synthesized for combinatorial high-throughput screening,which based on FTIR spectra self-encoding functional resin technology. A new deconvolution strategy termed position encoding deconvolution had illustrated and was compared with some popular combinatorial deconvolution strategies in efficiency and information content. The mimic high throughput screening of hexapeptide library successfully proved the applying of the self-encoding functional resin technology and the position encoding deconvolution strategy.

  18. Verb meaning and combinatory semantics: a corpus based study of Spanish change of state verbs

    OpenAIRE

    Spalek, Alexandra Anna

    2014-01-01

    Even though it is an intuitive and perhaps obvious idea that composition leads to non-trivial semantic interactions between words, and these interactions affect the contents of predication, there has still been little work done on how verbs restrict their arguments and how flexible these restrictions are. This dissertation thus starts out with the observation that verbs have very rich combinatorial paradigms and raises the question of what this wide combinatorial capacity of ve...

  19. Phase Transitions in Combinatorial Optimization Problems Basics, Algorithms and Statistical Mechanics

    CERN Document Server

    Hartmann, Alexander K

    2005-01-01

    A concise, comprehensive introduction to the topic of statistical physics of combinatorial optimization, bringing together theoretical concepts and algorithms from computer science with analytical methods from physics. The result bridges the gap between statistical physics and combinatorial optimization, investigating problems taken from theoretical computing, such as the vertex-cover problem, with the concepts and methods of theoretical physics. The authors cover rapid developments and analytical methods that are both extremely complex and spread by word-of-mouth, providing all the necessary

  20. Combinatorial interpretations of particular evaluations of complete and elementary symmetric functions

    OpenAIRE

    Mongelli, Pietro

    2011-01-01

    The Jacobi-Stirling numbers and the Legendre-Stirling numbers of the first and second kind were first introduced in [6], [7]. In this paper we note that Jacobi-Stirling numbers and Legendre-Stirling numbers are specializations of elementary and complete symmetric functions. We then study combinatorial interpretations of this specialization and obtain new combinatorial interpretations of the Jacobi-Stirling and Legendre-Stirling numbers.

  1. Evaluation of the Current Status of the Combinatorial Approach for the Study of Phase Diagrams.

    Science.gov (United States)

    Wong-Ng, W

    2012-01-01

    This paper provides an evaluation of the effectiveness of using the high throughput combinatorial approach for preparing phase diagrams of thin film and bulk materials. Our evaluation is based primarily on examples of combinatorial phase diagrams that have been reported in the literature as well as based on our own laboratory experiments. Various factors that affect the construction of these phase diagrams are examined. Instrumentation and analytical approaches needed to improve data acquisition and data analysis are summarized.

  2. Combinatorial and off-shell effects in new physics cascades

    Energy Technology Data Exchange (ETDEWEB)

    Wiesler, Daniel

    2012-12-15

    Up to now, the Standard Model of elementary particle physics is in very good agreement with most data. However, it has various shortcomings which motivate the presence of new physics at the TeV scale. The first major step following a potential discovery of new particles at the Large Hadron Collider (LHC) is the determination of their intrinsic properties, foremost masses and spins. Event topologies of new physics signals with a conserved parity motivated by precision data and the dark matter paradigm require for sophisticated measurement procedures, which have been developed in recent years. These techniques often rely on simplifying assumptions, albeit they need not necessarily be fulfilled. In this thesis we investigate the impact of combinatorial and off-shell effects on new physics cascades in three different contexts. A detailed understanding of these effects is essential for the topic of model parameter determination of new physics signatures at the LHC. First, we study the non-resonant contributions of a broad gluino on mass and spin measurements as a prime example for the importance of off-shell effects. A phenomenological scan over the gluino's width-to-mass ratio yields a severe smearing of invariant mass distributions and as a consequence thereof drastically shifted endpoint positions. Spin determinations, on the other hand, are barely affected and a model discrimination of the two prime candidates SUSY and UED is not at risk. In the second part, we assess the feasibility of the gluino dijet endpoint measurement in three fully inclusive scenarios at the LHC to investigate the impact of combinatorial and SUSY backgrounds on its precise determination. We develop a method to disentangle two major signal contributions and extract their associated edges with good accuracy. For this we use existent kinematic variables and propose new ones to overcome the former's deficiencies. The last part governs the issue of so-called 'fake combinatorics

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

    Science.gov (United States)

    Scott-Phillips, Thomas C; Blythe, Richard A

    2013-11-06

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

  4. Web matrices: structural properties and generating combinatorial identities

    CERN Document Server

    Dukes, Mark

    2016-01-01

    In this paper we present new results for the combinatorics of web diagrams and web worlds. These are discrete objects that arise in the physics of calculating scattering amplitudes in non-abelian gauge theories. Web-colouring and web-mixing matrices (collectively known as web matrices) are indexed by ordered pairs of web-diagrams and contain information relating the number of colourings of the first web diagram that will produce the second diagram. We introduce the black diamond product on power series and show how it determines the web-colouring matrix of disjoint web worlds. Furthermore, we show that combining known physical results with the black diamond product gives a new technique for generating combinatorial identities. Due to the complicated action of the product on power series, the resulting identities appear highly non-trivial. We present two results to explain repeated entries that appear in the web matrices. The first of these shows how diagonal web matrix entries will be the same if the comparab...

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

    Science.gov (United States)

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

    2014-11-24

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

  6. Combinatorial semantics strengthens angular-anterior temporal coupling.

    Science.gov (United States)

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

    2015-04-01

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

  7. Photoelectrochemical Hydrogen Production Using New Combinatorial Chemistry Derived Materials

    Energy Technology Data Exchange (ETDEWEB)

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

    2004-10-25

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

  8. Synergy from Silence in a Combinatorial Neural Code

    Science.gov (United States)

    Schneidman, Elad; Puchalla, Jason L.; Segev, Ronen; Harris, Robert A.; Bialek, William; Berry, Michael J.

    2011-01-01

    The manner in which groups of neurons represent events in the external world is a central question in neuroscience. Estimation of the information encoded by small groups of neurons has shown that in many neural systems, cells carry mildly redundant information. These measures average over all the activity patterns of a neural population. Here, we analyze the population code of the salamander and guinea pig retinas by quantifying the information conveyed by specific multi-cell activity patterns. Synchronous spikes, even though they are relatively rare and highly informative, convey less information than the sum of either spike alone, making them redundant coding symbols. Instead, patterns of spiking in one cell and silence in others, which are relatively common and often overlooked as special coding symbols, were found to be mostly synergistic. Our results reflect that the mild average redundancy between ganglion cells that was previously reported is actually the result of redundant and synergistic multi-cell patterns, whose contributions partially cancel each other when taking the average over all patterns. We further show that similar coding properties emerge in a generic model of neural responses, suggesting that this form of combinatorial coding, in which specific compound patterns carry synergistic or redundant information, may exist in other neural circuits. PMID:22049416

  9. Combinatorial Labeling Method for Improving Peptide Fragmentation in Mass Spectrometry

    Science.gov (United States)

    Kuchibhotla, Bhanuramanand; Kola, Sankara Rao; Medicherla, Jagannadham V.; Cherukuvada, Swamy V.; Dhople, Vishnu M.; Nalam, Madhusudhana Rao

    2017-06-01

    Annotation of peptide sequence from tandem mass spectra constitutes the central step of mass spectrometry-based proteomics. Peptide mass spectra are obtained upon gas-phase fragmentation. Identification of the protein from a set of experimental peptide spectral matches is usually referred as protein inference. Occurrence and intensity of these fragment ions in the MS/MS spectra are dependent on many factors such as amino acid composition, peptide basicity, activation mode, protease, etc. Particularly, chemical derivatizations of peptides were known to alter their fragmentation. In this study, the influence of acetylation, guanidinylation, and their combination on peptide fragmentation was assessed initially on a lipase (LipA) from Bacillus subtilis followed by a bovine six protein mix digest. The dual modification resulted in improved fragment ion occurrence and intensity changes, and this resulted in the equivalent representation of b- and y-type fragment ions in an ion trap MS/MS spectrum. The improved representation has allowed us to accurately annotate the peptide sequences de novo. Dual labeling has significantly reduced the false positive protein identifications in standard bovine six peptide digest. Our study suggests that the combinatorial labeling of peptides is a useful method to validate protein identifications for high confidence protein inference. [Figure not available: see fulltext.

  10. Combinatorial approaches to evaluate nanodiamond uptake and induced cellular fate.

    Science.gov (United States)

    Eldawud, Reem; Reitzig, Manuela; Opitz, Jörg; Rojansakul, Yon; Jiang, Wenjuan; Nangia, Shikha; Dinu, Cerasela Zoica

    2016-02-26

    Nanodiamonds (NDs) are an emerging class of engineered nanomaterials that hold great promise for the next generation of bionanotechnological products to be used for drug and gene delivery, or for bio-imaging and biosensing. Previous studies have shown that upon their cellular uptake, NDs exhibit high biocompatibility in various in vitro and in vivo set-ups. Herein we hypothesized that the increased NDs biocompatibility is a result of minimum membrane perturbations and their reduced ability to induce disruption or damage during cellular translocation. Using multi-scale combinatorial approaches that simulate ND-membrane interactions, we correlated NDs real-time cellular uptake and kinetics with the ND-induced membrane fluctuations to derive energy requirements for the uptake to occur. Our discrete and real-time analyses showed that the majority of NDs internalization occurs within 2 h of cellular exposure, however, with no effects on cellular viability, proliferation or cellular behavior. Furthermore, our simulation analyses using coarse-grained models identified key changes in the energy profile, membrane deformation and recovery time, all functions of the average ND or ND-based agglomerate size. Understanding the mechanisms responsible for ND-cell membrane interactions could possibly advance their implementation in various biomedical applications.

  11. Combinatorial approaches to evaluate nanodiamond uptake and induced cellular fate

    Science.gov (United States)

    Eldawud, Reem; Reitzig, Manuela; Opitz, Jörg; Rojansakul, Yon; Jiang, Wenjuan; Nangia, Shikha; Zoica Dinu, Cerasela

    2016-02-01

    Nanodiamonds (NDs) are an emerging class of engineered nanomaterials that hold great promise for the next generation of bionanotechnological products to be used for drug and gene delivery, or for bio-imaging and biosensing. Previous studies have shown that upon their cellular uptake, NDs exhibit high biocompatibility in various in vitro and in vivo set-ups. Herein we hypothesized that the increased NDs biocompatibility is a result of minimum membrane perturbations and their reduced ability to induce disruption or damage during cellular translocation. Using multi-scale combinatorial approaches that simulate ND-membrane interactions, we correlated NDs real-time cellular uptake and kinetics with the ND-induced membrane fluctuations to derive energy requirements for the uptake to occur. Our discrete and real-time analyses showed that the majority of NDs internalization occurs within 2 h of cellular exposure, however, with no effects on cellular viability, proliferation or cellular behavior. Furthermore, our simulation analyses using coarse-grained models identified key changes in the energy profile, membrane deformation and recovery time, all functions of the average ND or ND-based agglomerate size. Understanding the mechanisms responsible for ND-cell membrane interactions could possibly advance their implementation in various biomedical applications.

  12. Convex-Faced Combinatorially Regular Polyhedra of Small Genus

    Directory of Open Access Journals (Sweden)

    Jörg M. Wills

    2011-12-01

    Full Text Available Combinatorially regular polyhedra are polyhedral realizations (embeddings in Euclidean 3-space E3 of regular maps on (orientable closed compact surfaces. They are close analogues of the Platonic solids. A surface of genus g ≥ 2 admits only finitely many regular maps, and generally only a small number of them can be realized as polyhedra with convex faces. When the genus g is small, meaning that g is in the historically motivated range 2 ≤ g ≤ 6, only eight regular maps of genus g are known to have polyhedral realizations, two discovered quite recently. These include spectacular convex-faced polyhedra realizing famous maps of Klein, Fricke, Dyck, and Coxeter. We provide supporting evidence that this list is complete; in other words, we strongly conjecture that in addition to those eight there are no other regular maps of genus g, with 2 ≤ g ≤ 6, admitting realizations as convex-faced polyhedra in E3. For all admissible maps in this range, save Gordan’s map of genus 4, and its dual, we rule out realizability by a polyhedron in E3.

  13. Combinatorial Formulae for Finite-Type Invariants via Parities

    CERN Document Server

    Chrisman, Micah

    2010-01-01

    The celebrated theorem of Goussarov states that all finite-type (Vassiliev-Goussarov) invariants of classical knots can be expressed in terms of Polyak-Viro combinatorial formulae. These formulae intrinsically use non-realizable Gauss diagrams and virtual knots. Some of these formulae can be naturally extended to virtual knots; however, the class of finite-type invariants of virtual knots obtained by using these formulae (so-called Goussarov-Polyak-Viro finite-type invariants) is very small. Kauffman gave a more natural notion of finite-type invariants, which, however, turned out to be quite complicated: even invariants of order zero form an infinite-dimensional space. Recently, the second named author introduced the notion of {\\em parity} which turned out to be extremely useful for many purposes in virtual knot theory and low-dimensional topology; in particular, they turned out to be useful for constructing invariants of {\\em free knots}, the latter being very close to the notion of order 0 invariants. In th...

  14. 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.

  15. 2D Toda \\tau-functions as combinatorial generating functions

    CERN Document Server

    Guay-Paquet, Mathieu

    2014-01-01

    Two methods of constructing 2D Toda $\\tau$-functions that are generating functions for certain geometrical invariants of a combinatorial nature are related. The first involves generation of paths in the Cayley graph of the symmetric group $S_n$ by multiplication of the conjugacy class sums $C_\\lambda \\in C[S_n]$ in the group algebra by elements of an abelian group of central elements. Extending the characteristic map to the tensor product $C[S_n]\\otimes C[S_n]$ leads to double expansions in terms of power sum symmetric functions, in which the coefficients count the number of such paths. Applying the same map to sums over the orthogonal idempotents leads to diagonal double Schur function expansions that are identified as $\\tau$-functions of hypergeometric type. The second method is the standard construction of $\\tau$-functions as vacuum state matrix elements of products of vertex operators in a fermionic Fock space with elements of the abelian group of convolution symmetries. A homomorphism between these two g...

  16. Trajectory and Population Metaheuristics applied to Combinatorial Optimization Problems

    Directory of Open Access Journals (Sweden)

    Natalia Alancay

    2016-04-01

    Full Text Available In the world there are a multitude of everyday problems that require a solution that meets a set of requirements in the most appropriate way maximizing or minimizing a certain value. However, finding an optimal solution for certain optimization problems can be an incredibly difficult or an impossible task. This is because when a problem becomes large enough, we have to look through a huge number of possible solutions, the most efficient solution, that is, the one that has the lower cost. The ways to treat feasible solutions for their practical application are varied. One of the strategy that has gained a great acceptance and that has been getting an important formal body are the metaheuristics since it is established strategies to cross and explore the space of solutions of the problem usually generated in a random and iterative way. The main advantage of this technique is their flexibility and robustness, which allows them to be applied to a wide range of problems. In this work we focus on a metaheuristic based on Simulated Annealing trajectory and a population - based Cellular Genetic Algorithm with the objective of carrying out a study and comparison of the results obtained in its application for the resolution of a set of academic problems of combinatorial optimization.

  17. Combinatorial Identities Via Phi Functions and Relatively Prime Subsets

    CERN Document Server

    Bachraoui, Mohamed El

    2010-01-01

    Let $n$ be a positive integer and let $A$ be nonempty finite set of positive integers. We say that $A$ is relatively prime if $\\gcd(A) =1$ and that $A$ is relatively prime to $n$ if $\\gcd(A,n)=1$. In this work we count the number of nonempty subsets of $A$ which are relatively prime and the number of nonempty subsets of $A$ which are relatively prime to $n$. Related formulas are also obtained for the number of such subsets having some fixed cardinality. This extends previous work for the cases where $A$ is an interval or a set in arithmetic progression. Applications include: a) An exact formula is obtained for the number of elements of $A$ which are co-prime to $n$; note that this number is $\\phi(n)$ if $A=[1,n]$. b) Algebraic characterizations are found for a nonempty finite set of positive integers to have elements which are all pairwise co-prime and consequently a formula is given for the number of nonempty subsets of $A$ whose elements are pairwise co-prime. c) We provide combinatorial formulas involving ...

  18. An improved combinatorial geometry model for arbitrary geometry in DSMC

    Science.gov (United States)

    Kargaran, H.; Minuchehr, A.; Zolfaghari, A.

    2017-03-01

    This paper focuses on a new direct simulation Monte Carlo (DSMC) code based on combinatorial geometry (CG) for simulation of any rarefied gas flow. The developed code, called DgSMC-A, has been supplied with an improved CG modeling able to significantly optimize the particle-tracking process, resulting in a highly reduced runtime compared to the conventional codes. The improved algorithm inserts a grid over the geometry and saves those grid elements containing some part of the geometry border. Since only a small part of a grid is engaged with the geometry border, significant time can be saved using the proposed algorithm. Embedding the modified algorithm in the DgSMC-A resulted in a fast, robust and self-governing code needless to any mesh generator. The code completely handles complex geometries created with first-and second-order surfaces. In addition, we developed a new surface area calculator in the CG methodology for complex geometries based on the Monte Carlo method with acceptable accuracy. Several well-known test cases are examined to indicate the code ability to deal with a wide range of realistic problems. Results are also found to be in good agreement with references and experimental data.

  19. Combinatorial quantization of the Hamiltonian Chern-Simons theory, 2

    CERN Document Server

    Alekseev, A Yu; Schomerus, V; Grosse, H; Schomerus, V

    1994-01-01

    This paper further develops the combinatorial approach to quantization of the Hamiltonian Chern Simons theory advertised in \\cite{AGS}. Using the theory of quantum Wilson lines, we show how the Verlinde algebra appears within the context of quantum group gauge theory. This allows to discuss flatness of quantum connections so that we can give a mathe- matically rigorous definition of the algebra of observables \\A_{CS} of the Chern Simons model. It is a *-algebra of ``functions on the quantum moduli space of flat connections'' and comes equipped with a positive functional \\omega (``integration''). We prove that this data does not depend on the particular choices which have been made in the construction. Following ideas of Fock and Rosly \\cite{FoRo}, the algebra \\A_{CS} provides a deformation quantization of the algebra of functions on the moduli space along the natural Poisson bracket induced by the Chern Simons action. We evaluate a volume of the quantized moduli space and prove that it coincides with the Verl...

  20. Combinatorial Approximation Algorithms for MaxCut using Random Walks

    CERN Document Server

    Kale, Satyen

    2010-01-01

    We give the first combinatorial approximation algorithm for Maxcut that beats the trivial 0.5 factor by a constant. The main partitioning procedure is very intuitive, natural, and easily described. It essentially performs a number of random walks and aggregates the information to provide the partition. We can control the running time to get an approximation factor-running time tradeoff. We show that for any constant b > 1.5, there is an O(n^{b}) algorithm that outputs a (0.5+delta)-approximation for Maxcut, where delta = delta(b) is some positive constant. One of the components of our algorithm is a weak local graph partitioning procedure that may be of independent interest. Given a starting vertex $i$ and a conductance parameter phi, unless a random walk of length ell = O(log n) starting from i mixes rapidly (in terms of phi and ell), we can find a cut of conductance at most phi close to the vertex. The work done per vertex found in the cut is sublinear in n.

  1. Combinatorial biosynthesis of flavones and flavonols in Escherichia coli.

    Science.gov (United States)

    Miyahisa, Ikuo; Funa, Nobutaka; Ohnishi, Yasuo; Martens, Stefan; Moriguchi, Takaya; Horinouchi, Sueharu

    2006-06-01

    (2S)-Flavanones (naringenin and pinocembrin) are key intermediates in the flavonoid biosynthetic pathway in plants. Recombinant Escherichia coli cells containing four genes for a phenylalanine ammonia-lyase, cinnamate/coumarate:CoA ligase, chalcone synthase, and chalcone isomerase, in addition to the acetyl-CoA carboxylase, have been established for efficient production of (2S)-naringenin from tyrosine and (2S)-pinocembrin from phenylalanine. Further introduction of the flavone synthase I gene from Petroselinum crispum under the control of the T7 promoter and the synthetic ribosome-binding sequence in pACYCDuet-1 caused the E. coli cells to produce flavones: apigenin (13 mg/l) from tyrosine and chrysin (9.4 mg/l) from phenylalanine. Introduction into the E. coli cells of the flavanone 3beta-hydroxylase and flavonol synthase genes from the plant Citrus species led to production of flavonols: kaempferol (15.1 mg/l) from tyrosine and galangin (1.1 mg/l) from phenylalanine. The combinatorial biosynthesis of the flavones and flavonols in E. coli is promising for the construction of a library of various flavonoid compounds and un-natural flavonoids in bacteria.

  2. On Some Algebraic and Combinatorial Properties of Dunkl Elements

    Science.gov (United States)

    Kirillov, Anatol N.

    2013-06-01

    We introduce and study a certain class of nonhomogeneous quadratic algebras together with the special set of mutually commuting elements inside of each, the so-called Dunkl elements. We describe relations among the Dunkl elements. This result is a further generalization of similar results obtained in [S. Fomin and A. N. Kirillov, Quadratic algebras, Dunkl elements and Schubert calculus, in Advances in Geometry (eds. J.-S. Brylinski, V. Nistor, B. Tsygan and P. Xu), Progress in Math. Vol. 172 (Birkhäuser Boston, Boston, 1995), pp. 147-182, A. Postnikov, On a quantum version of Pieri's formula, in Advances in Geometry (eds. J.-S. Brylinski, R. Brylinski, V. Nistor, B. Tsygan and P. Xu), Progress in Math. Vol. 172 (Birkhäuser Boston, 1995), pp. 371-383 and A. N. Kirillov and T. Maenor, A Note on Quantum K-Theory of Flag Varieties, preprint]. As an application we describe explicitly the set of relations among the Gaudin elements in the group ring of the symmetric group, cf. [E. Mukhin, V. Tarasov and A. Varchenko, Bethe Subalgebras of the Group Algebra of the Symmetric Group, preprint arXiv:1004.4248]. Also we describe a few combinatorial properties of some special elements in the associative quasi-classical Yang-Baxter algebra in a connection with the values of the β-Grothendieck polynomials for some special permutations, and on the other hand, with the Ehrhart polynomial of the Chan-Robbins polytope.

  3. Rational and combinatorial tailoring of bioactive cyclic dipeptides

    Directory of Open Access Journals (Sweden)

    Tobias Wolfgang Giessen

    2015-07-01

    Full Text Available Modified cyclic dipeptides represent a diverse family of microbial secondary metabolites. They display a broad variety of biological and pharmacological activities and have long been recognized as privileged structures with the ability to bind to a wide range of receptors. This is due to their conformationally constrained 2, 5-diketopiperazine (DKP scaffold and the diverse set of DKP tailoring enzymes present in nature. After initial DKP assembly through different biosynthetic systems modifying enzymes are responsible for installing functional groups crucial for the biological activities of the resulting modified DKPs. They represent a vast and largely untapped enzyme repository very useful for synthetic biology approaches aiming at introducing structural variations into DKP scaffolds. In this review we focus on these DKP modification enzymes found in various microbial secondary metabolite gene clusters. We will give a brief overview of their distribution and highlight a select number of characterized DKP tailoring enzymes before turning to their application potential in combinatorial biosynthesis with the aim of producing molecules with improved or entirely new biological and medicinally relevant properties.

  4. Efficient combinatorial filtering for desired molecular properties of reaction products.

    Science.gov (United States)

    Shi, S; Peng, Z; Kostrowicki, J; Paderes, G; Kuki, A

    2000-01-01

    Two combinatorial filtering methods for efficiently selecting reaction products with desired properties are presented. The first, "direct reactants" method is applicable only to those molecular properties that are strictly additive or approximately additive, with relatively small interference between neighboring fragments. This method uses only the molecular properties of reactants. The second, "basis products" method can be used to filter not only the strictly additive properties but also the approximately additive molecular properties where a certain degree of mutual influence occurs between neighboring fragments. This method requires the molecular properties of the "basis products," which are the products formed by combining all the reactants for a given reaction component with the simplest set of complementary reactant partners. There is a one-to-one correspondence between the reactants and the "basis products." The latter is a product representation of the former. High efficiency of both methods is enhanced further by a tree-sorting and hierarchical selection algorithm, which is performed on the reaction components in a limited space determined systematically from the filtering criteria. The methods are illustrated with product logPs, van der Waals volumes, solvent accessible surface areas, and other product properties. Good results are obtained when filtering for a number of important molecular properties in a virtual library of 1.5 billion.

  5. High-Throughput Identification of Combinatorial Ligands for DNA Delivery in Cell Culture

    Science.gov (United States)

    Svahn, Mathias G.; Rabe, Kersten S.; Barger, Geoffrey; EL-Andaloussi, Samir; Simonson, Oscar E.; Didier, Boturyn; Olivier, Renaudet; Dumy, Pascal; Brandén, Lars J.; Niemeyer, Christof M.; Smith, C. I. Edvard

    2008-10-01

    Finding the optimal combinations of ligands for tissue-specific delivery is tedious even if only a few well-established compounds are tested. The cargo affects the receptor-ligand interaction, especially when it is charged like DNA. The ligand should therefore be evaluated together with its cargo. Several viruses have been shown to interact with more than one receptor, for efficient internalization. We here present a DNA oligonucleotide-based method for inexpensive and rapid screening of biotin labeled ligands for combinatorial effects on cellular binding and uptake. The oligonucleotide complex was designed as a 44 bp double-stranded DNA oligonucleotide with one central streptavidin molecule and a second streptavidin at the terminus. The use of a highly advanced robotic platform ensured stringent processing and execution of the experiments. The oligonucleotides were fluorescently labeled and used for detection and analysis of cell-bound, internalized and intra-cellular compartmentalized constructs by an automated line-scanning confocal microscope, IN Cell Analyzer 3000. All possible combinations of 22 ligands were explored in sets of 2 and tested on 6 different human cell lines in triplicates. In total, 10 000 transfections were performed on the automation platform. Cell-specific combinations of ligands were identified and their relative position on the scaffold oligonucleotide was found to be of importance. The ligands were found to be cargo dependent, carbohydrates were more potent for DNA delivery whereas cell penetrating peptides were more potent for delivery of less charged particles.

  6. Combinatorial development of antibacterial Zr-Cu-Al-Ag thin film metallic glasses

    Science.gov (United States)

    Liu, Yanhui; Padmanabhan, Jagannath; Cheung, Bettina; Liu, Jingbei; Chen, Zheng; Scanley, B. Ellen; Wesolowski, Donna; Pressley, Mariyah; Broadbridge, Christine C.; Altman, Sidney; Schwarz, Udo D.; Kyriakides, Themis R.; Schroers, Jan

    2016-05-01

    Metallic alloys are normally composed of multiple constituent elements in order to achieve integration of a plurality of properties required in technological applications. However, conventional alloy development paradigm, by sequential trial-and-error approach, requires completely unrelated strategies to optimize compositions out of a vast phase space, making alloy development time consuming and labor intensive. Here, we challenge the conventional paradigm by proposing a combinatorial strategy that enables parallel screening of a multitude of alloys. Utilizing a typical metallic glass forming alloy system Zr-Cu-Al-Ag as an example, we demonstrate how glass formation and antibacterial activity, two unrelated properties, can be simultaneously characterized and the optimal composition can be efficiently identified. We found that in the Zr-Cu-Al-Ag alloy system fully glassy phase can be obtained in a wide compositional range by co-sputtering, and antibacterial activity is strongly dependent on alloy compositions. Our results indicate that antibacterial activity is sensitive to Cu and Ag while essentially remains unchanged within a wide range of Zr and Al. The proposed strategy not only facilitates development of high-performing alloys, but also provides a tool to unveil the composition dependence of properties in a highly parallel fashion, which helps the development of new materials by design.

  7. Combinatorial clustering of residue position subsets predicts inhibitor affinity across the human kinome.

    Directory of Open Access Journals (Sweden)

    Drew H Bryant

    Full Text Available The protein kinases are a large family of enzymes that play fundamental roles in propagating signals within the cell. Because of the high degree of binding site similarity shared among protein kinases, designing drug compounds with high specificity among the kinases has proven difficult. However, computational approaches to comparing the 3-dimensional geometry and physicochemical properties of key binding site residue positions have been shown to be informative of inhibitor selectivity. The Combinatorial Clustering Of Residue Position Subsets (ccorps method, introduced here, provides a semi-supervised learning approach for identifying structural features that are correlated with a given set of annotation labels. Here, ccorps is applied to the problem of identifying structural features of the kinase atp binding site that are informative of inhibitor binding. ccorps is demonstrated to make perfect or near-perfect predictions for the binding affinity profile of 8 of the 38 kinase inhibitors studied, while only having overall poor predictive ability for 1 of the 38 compounds. Additionally, ccorps is shown to identify shared structural features across phylogenetically diverse groups of kinases that are correlated with binding affinity for particular inhibitors; such instances of structural similarity among phylogenetically diverse kinases are also shown to not be rare among kinases. Finally, these function-specific structural features may serve as potential starting points for the development of highly specific kinase inhibitors.

  8. Combinatorial clustering of residue position subsets predicts inhibitor affinity across the human kinome.

    Science.gov (United States)

    Bryant, Drew H; Moll, Mark; Finn, Paul W; Kavraki, Lydia E

    2013-01-01

    The protein kinases are a large family of enzymes that play fundamental roles in propagating signals within the cell. Because of the high degree of binding site similarity shared among protein kinases, designing drug compounds with high specificity among the kinases has proven difficult. However, computational approaches to comparing the 3-dimensional geometry and physicochemical properties of key binding site residue positions have been shown to be informative of inhibitor selectivity. The Combinatorial Clustering Of Residue Position Subsets (ccorps) method, introduced here, provides a semi-supervised learning approach for identifying structural features that are correlated with a given set of annotation labels. Here, ccorps is applied to the problem of identifying structural features of the kinase atp binding site that are informative of inhibitor binding. ccorps is demonstrated to make perfect or near-perfect predictions for the binding affinity profile of 8 of the 38 kinase inhibitors studied, while only having overall poor predictive ability for 1 of the 38 compounds. Additionally, ccorps is shown to identify shared structural features across phylogenetically diverse groups of kinases that are correlated with binding affinity for particular inhibitors; such instances of structural similarity among phylogenetically diverse kinases are also shown to not be rare among kinases. Finally, these function-specific structural features may serve as potential starting points for the development of highly specific kinase inhibitors.

  9. Rapid, combinatorial analysis of membrane compartments in intact plants with a multicolor marker set.

    Science.gov (United States)

    Geldner, Niko; Dénervaud-Tendon, Valérie; Hyman, Derek L; Mayer, Ulrike; Stierhof, York-Dieter; Chory, Joanne

    2009-07-01

    Plant membrane compartments and trafficking pathways are highly complex, and are often distinct from those of animals and fungi. Progress has been made in defining trafficking in plants using transient expression systems. However, many processes require a precise understanding of plant membrane trafficking in a developmental context, and in diverse, specialized cell types. These include defense responses to pathogens, regulation of transporter accumulation in plant nutrition or polar auxin transport in development. In all of these cases a central role is played by the endosomal membrane system, which, however, is the most divergent and ill-defined aspect of plant cell compartmentation. We have designed a new vector series, and have generated a large number of stably transformed plants expressing membrane protein fusions to spectrally distinct, fluorescent tags. We selected lines with distinct subcellular localization patterns, and stable, non-toxic expression. We demonstrate the power of this multicolor 'Wave' marker set for rapid, combinatorial analysis of plant cell membrane compartments, both in live-imaging and immunoelectron microscopy. Among other findings, our systematic co-localization analysis revealed that a class of plant Rab1-homologs has a much more extended localization than was previously assumed, and also localizes to trans-Golgi/endosomal compartments. Constructs that can be transformed into any genetic background or species, as well as seeds from transgenic Arabidopsis plants, will be freely available, and will promote rapid progress in diverse areas of plant cell biology.

  10. Precursor-Directed Combinatorial Biosynthesis of Cinnamoyl, Dihydrocinnamoyl, and Benzoyl Anthranilates in Saccharomyces cerevisiae.

    Directory of Open Access Journals (Sweden)

    Aymerick Eudes

    Full Text Available Biological synthesis of pharmaceuticals and biochemicals offers an environmentally friendly alternative to conventional chemical synthesis. These alternative methods require the design of metabolic pathways and the identification of enzymes exhibiting adequate activities. Cinnamoyl, dihydrocinnamoyl, and benzoyl anthranilates are natural metabolites which possess beneficial activities for human health, and the search is expanding for novel derivatives that might have enhanced biological activity. For example, biosynthesis in Dianthus caryophyllus is catalyzed by hydroxycinnamoyl/benzoyl-CoA:anthranilate N-hydroxycinnamoyl/ benzoyltransferase (HCBT, which couples hydroxycinnamoyl-CoAs and benzoyl-CoAs to anthranilate. We recently demonstrated the potential of using yeast (Saccharomyces cerevisiae for the biological production of a few cinnamoyl anthranilates by heterologous co-expression of 4-coumaroyl:CoA ligase from Arabidopsis thaliana (4CL5 and HCBT. Here we report that, by exploiting the substrate flexibility of both 4CL5 and HCBT, we achieved rapid biosynthesis of more than 160 cinnamoyl, dihydrocinnamoyl, and benzoyl anthranilates in yeast upon feeding with both natural and non-natural cinnamates, dihydrocinnamates, benzoates, and anthranilates. Our results demonstrate the use of enzyme promiscuity in biological synthesis to achieve high chemical diversity within a defined class of molecules. This work also points to the potential for the combinatorial biosynthesis of diverse and valuable cinnamoylated, dihydrocinnamoylated, and benzoylated products by using the versatile biological enzyme 4CL5 along with characterized cinnamoyl-CoA- and benzoyl-CoA-utilizing transferases.

  11. Precursor-Directed Combinatorial Biosynthesis of Cinnamoyl, Dihydrocinnamoyl, and Benzoyl Anthranilates in Saccharomyces cerevisiae

    Science.gov (United States)

    Eudes, Aymerick; Teixeira Benites, Veronica; Wang, George; Baidoo, Edward E. K.; Lee, Taek Soon; Keasling, Jay D.; Loqué, Dominique

    2015-01-01

    Biological synthesis of pharmaceuticals and biochemicals offers an environmentally friendly alternative to conventional chemical synthesis. These alternative methods require the design of metabolic pathways and the identification of enzymes exhibiting adequate activities. Cinnamoyl, dihydrocinnamoyl, and benzoyl anthranilates are natural metabolites which possess beneficial activities for human health, and the search is expanding for novel derivatives that might have enhanced biological activity. For example, biosynthesis in Dianthus caryophyllus is catalyzed by hydroxycinnamoyl/benzoyl-CoA:anthranilate N-hydroxycinnamoyl/ benzoyltransferase (HCBT), which couples hydroxycinnamoyl-CoAs and benzoyl-CoAs to anthranilate. We recently demonstrated the potential of using yeast (Saccharomyces cerevisiae) for the biological production of a few cinnamoyl anthranilates by heterologous co-expression of 4-coumaroyl:CoA ligase from Arabidopsis thaliana (4CL5) and HCBT. Here we report that, by exploiting the substrate flexibility of both 4CL5 and HCBT, we achieved rapid biosynthesis of more than 160 cinnamoyl, dihydrocinnamoyl, and benzoyl anthranilates in yeast upon feeding with both natural and non-natural cinnamates, dihydrocinnamates, benzoates, and anthranilates. Our results demonstrate the use of enzyme promiscuity in biological synthesis to achieve high chemical diversity within a defined class of molecules. This work also points to the potential for the combinatorial biosynthesis of diverse and valuable cinnamoylated, dihydrocinnamoylated, and benzoylated products by using the versatile biological enzyme 4CL5 along with characterized cinnamoyl-CoA- and benzoyl-CoA-utilizing transferases. PMID:26430899

  12. Precursor-Directed Combinatorial Biosynthesis of Cinnamoyl, Dihydrocinnamoyl, and Benzoyl Anthranilates in Saccharomyces cerevisiae.

    Science.gov (United States)

    Eudes, Aymerick; Teixeira Benites, Veronica; Wang, George; Baidoo, Edward E K; Lee, Taek Soon; Keasling, Jay D; Loqué, Dominique

    2015-01-01

    Biological synthesis of pharmaceuticals and biochemicals offers an environmentally friendly alternative to conventional chemical synthesis. These alternative methods require the design of metabolic pathways and the identification of enzymes exhibiting adequate activities. Cinnamoyl, dihydrocinnamoyl, and benzoyl anthranilates are natural metabolites which possess beneficial activities for human health, and the search is expanding for novel derivatives that might have enhanced biological activity. For example, biosynthesis in Dianthus caryophyllus is catalyzed by hydroxycinnamoyl/benzoyl-CoA:anthranilate N-hydroxycinnamoyl/ benzoyltransferase (HCBT), which couples hydroxycinnamoyl-CoAs and benzoyl-CoAs to anthranilate. We recently demonstrated the potential of using yeast (Saccharomyces cerevisiae) for the biological production of a few cinnamoyl anthranilates by heterologous co-expression of 4-coumaroyl:CoA ligase from Arabidopsis thaliana (4CL5) and HCBT. Here we report that, by exploiting the substrate flexibility of both 4CL5 and HCBT, we achieved rapid biosynthesis of more than 160 cinnamoyl, dihydrocinnamoyl, and benzoyl anthranilates in yeast upon feeding with both natural and non-natural cinnamates, dihydrocinnamates, benzoates, and anthranilates. Our results demonstrate the use of enzyme promiscuity in biological synthesis to achieve high chemical diversity within a defined class of molecules. This work also points to the potential for the combinatorial biosynthesis of diverse and valuable cinnamoylated, dihydrocinnamoylated, and benzoylated products by using the versatile biological enzyme 4CL5 along with characterized cinnamoyl-CoA- and benzoyl-CoA-utilizing transferases.

  13. MARCC (Matrix-Assisted Reader Chromatin Capture): An Antibody-Free Method to Enrich and Analyze Combinatorial Nucleosome Modifications.

    Science.gov (United States)

    Su, Zhangli; Denu, John M

    2015-07-01

    Combinatorial patterns of histone modifications are key indicators of different chromatin states. Most of the current approaches rely on the usage of antibodies to analyze combinatorial histone modifications. Here we detail an antibody-free method named MARCC (Matrix-Assisted Reader Chromatin Capture) to enrich combinatorial histone modifications. The combinatorial patterns are enriched on native nucleosomes extracted from cultured mammalian cells and prepared by micrococcal nuclease digestion. Such enrichment is achieved by recombinant chromatin-interacting protein modules, or so-called reader domains, which can bind in a combinatorial modification-dependent manner. The enriched chromatin can be quantified by immunoblotting or mass spectrometry for the co-existence of histone modifications, while the associated DNA content can be analyzed by qPCR or next-generation sequencing. Altogether, MARCC provides a reproducible, efficient and customizable solution to enrich and analyze combinatorial histone modifications. Copyright © 2015 John Wiley & Sons, Inc.

  14. Immobilized OBOC combinatorial bead array to facilitate multiplicative screening.

    Science.gov (United States)

    Xiao, Wenwu; Bononi, Fernanda C; Townsend, Jared; Li, Yuanpei; Liu, Ruiwu; Lam, Kit S

    2013-07-01

    One-bead-one-compound (OBOC) combinatorial library screening has been broadly utilized for the last two decades to identify small molecules, peptides or peptidomimetics targeting variable screening probes such as cell surface receptors, bacteria, protein kinases, phosphatases, proteases etc. In previous screening methods, library beads were suspended in solution and screened against one single probe. Only the positive beads were tracked and isolated for additional screens and finally selected for chemical decoding. During this process, the remaining negative beads were not tracked and discarded. Here we report a novel bead immobilization method such that a bead library array can be conveniently prepared and screened in its entirety, sequentially many times with a series of distinct probes. This method not only allows us to increase the screening efficiency but also permits us to determine the binding profile of each and every library bead against a large number of target receptors. As proof of concept, we serially screened a random OBOC disulfide containing cyclic heptapeptide library with three water soluble dyes as model probes: malachite green, bromocresol purple and indigo carmine. This multiplicative screening approach resulted in a rapid determination of the binding profile of each and every bead respective to each of the three dyes. Beads that interacted with malachite green only, bromocresol purple only, or both indigo carmine and bromocresol purple were isolated, and their peptide sequences were determined with microsequencer. Ultimately, the novel OBOC multiplicative screening approach could play a key role in the enhancement of existing on-bead assays such as whole cell binding, bacteria binding, protein binding, posttranslational modifications etc. with increased efficiency, capacity, and specificity.

  15. Combinatorial Contextualization of Peptidic Epitopes for Enhanced Cellular Immunity

    Science.gov (United States)

    Ito, Masaki; Hayashi, Kazumi; Adachi, Eru; Minamisawa, Tamiko; Homma, Sadamu; Koido, Shigeo; Shiba, Kiyotaka

    2014-01-01

    Invocation of cellular immunity by epitopic peptides remains largely dependent on empirically developed protocols, such as interfusion of aluminum salts or emulsification using terpenoids and surfactants. To explore novel vaccine formulation, epitopic peptide motifs were co-programmed with structural motifs to produce artificial antigens using our “motif-programming” approach. As a proof of concept, we used an ovalbumin (OVA) system and prepared an artificial protein library by combinatorially polymerizing MHC class I and II sequences from OVA along with a sequence that tends to form secondary structures. The purified endotoxin-free proteins were then examined for their ability to activate OVA-specific T-cell hybridoma cells after being processed within dendritic cells. One clone, F37A (containing three MHC I and two MHC II OVA epitopes), possessed a greater ability to evoke cellular immunity than the native OVA or the other artificial antigens. The sensitivity profiles of drugs that interfered with the F37A uptake differed from those of the other artificial proteins and OVA, suggesting that alteration of the cross-presentation pathway is responsible for the enhanced immunogenicity. Moreover, F37A, but not an epitopic peptide, invoked cellular immunity when injected together with monophosphoryl lipid A (MPL), and retarded tumor growth in mice. Thus, an artificially synthesized protein antigen induced cellular immunity in vivo in the absence of incomplete Freund's adjuvant or aluminum salts. The method described here could be potentially used for developing vaccines for such intractable ailments as AIDS, malaria and cancer, ailments in which cellular immunity likely play a crucial role in prevention and treatment. PMID:25343355

  16. Cellular phosphatases facilitate combinatorial processing of receptor-activated signals

    Directory of Open Access Journals (Sweden)

    Siddiqui Zaved

    2008-09-01

    Full Text Available Abstract Background Although reciprocal regulation of protein phosphorylation represents a key aspect of signal transduction, a larger perspective on how these various interactions integrate to contribute towards signal processing is presently unclear. For example, a key unanswered question is that of how phosphatase-mediated regulation of phosphorylation at the individual nodes of the signaling network translates into modulation of the net signal output and, thereby, the cellular phenotypic response. Results To address the above question we, in the present study, examined the dynamics of signaling from the B cell antigen receptor (BCR under conditions where individual cellular phosphatases were selectively depleted by siRNA. Results from such experiments revealed a highly enmeshed structure for the signaling network where each signaling node was linked to multiple phosphatases on the one hand, and each phosphatase to several nodes on the other. This resulted in a configuration where individual signaling intermediates could be influenced by a spectrum of regulatory phosphatases, but with the composition of the spectrum differing from one intermediate to another. Consequently, each node differentially experienced perturbations in phosphatase activity, yielding a unique fingerprint of nodal signals characteristic to that perturbation. This heterogeneity in nodal experiences, to a given perturbation, led to combinatorial manipulation of the corresponding signaling axes for the downstream transcription factors. Conclusion Our cumulative results reveal that it is the tight integration of phosphatases into the signaling network that provides the plasticity by which perturbation-specific information can be transmitted in the form of a multivariate output to the downstream transcription factor network. This output in turn specifies a context-defined response, when translated into the resulting gene expression profile.

  17. A combinatorial code for splicing silencing: UAGG and GGGG motifs.

    Directory of Open Access Journals (Sweden)

    Kyoungha Han

    2005-05-01

    Full Text Available Alternative pre-mRNA splicing is widely used to regulate gene expression by tuning the levels of tissue-specific mRNA isoforms. Few regulatory mechanisms are understood at the level of combinatorial control despite numerous sequences, distinct from splice sites, that have been shown to play roles in splicing enhancement or silencing. Here we use molecular approaches to identify a ternary combination of exonic UAGG and 5'-splice-site-proximal GGGG motifs that functions cooperatively to silence the brain-region-specific CI cassette exon (exon 19 of the glutamate NMDA R1 receptor (GRIN1 transcript. Disruption of three components of the motif pattern converted the CI cassette into a constitutive exon, while predominant skipping was conferred when the same components were introduced, de novo, into a heterologous constitutive exon. Predominant exon silencing was directed by the motif pattern in the presence of six competing exonic splicing enhancers, and this effect was retained after systematically repositioning the two exonic UAGGs within the CI cassette. In this system, hnRNP A1 was shown to mediate silencing while hnRNP H antagonized silencing. Genome-wide computational analysis combined with RT-PCR testing showed that a class of skipped human and mouse exons can be identified by searches that preserve the sequence and spatial configuration of the UAGG and GGGG motifs. This analysis suggests that the multi-component silencing code may play an important role in the tissue-specific regulation of the CI cassette exon, and that it may serve more generally as a molecular language to allow for intricate adjustments and the coordination of splicing patterns from different genes.

  18. A combinatorial code for splicing silencing: UAGG and GGGG motifs.

    Science.gov (United States)

    Han, Kyoungha; Yeo, Gene; An, Ping; Burge, Christopher B; Grabowski, Paula J

    2005-05-01

    Alternative pre-mRNA splicing is widely used to regulate gene expression by tuning the levels of tissue-specific mRNA isoforms. Few regulatory mechanisms are understood at the level of combinatorial control despite numerous sequences, distinct from splice sites, that have been shown to play roles in splicing enhancement or silencing. Here we use molecular approaches to identify a ternary combination of exonic UAGG and 5'-splice-site-proximal GGGG motifs that functions cooperatively to silence the brain-region-specific CI cassette exon (exon 19) of the glutamate NMDA R1 receptor (GRIN1) transcript. Disruption of three components of the motif pattern converted the CI cassette into a constitutive exon, while predominant skipping was conferred when the same components were introduced, de novo, into a heterologous constitutive exon. Predominant exon silencing was directed by the motif pattern in the presence of six competing exonic splicing enhancers, and this effect was retained after systematically repositioning the two exonic UAGGs within the CI cassette. In this system, hnRNP A1 was shown to mediate silencing while hnRNP H antagonized silencing. Genome-wide computational analysis combined with RT-PCR testing showed that a class of skipped human and mouse exons can be identified by searches that preserve the sequence and spatial configuration of the UAGG and GGGG motifs. This analysis suggests that the multi-component silencing code may play an important role in the tissue-specific regulation of the CI cassette exon, and that it may serve more generally as a molecular language to allow for intricate adjustments and the coordination of splicing patterns from different genes.

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

    Science.gov (United States)

    Herrmann, Andreas

    2009-08-21

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

  20. Solid-phase Synthesis of Combinatorial 2,4-Disubstituted-1,3,5-Triazine via Amine Nucleophilic Reaction

    Energy Technology Data Exchange (ETDEWEB)

    Moon, Sung Won [KIST Gangneung Institute, Gangneung (Korea, Republic of); Ham, Jungyeob [Gangneung-Wonju National University, Gangneung (Korea, Republic of); Chang, Young-Tae [National University of Singapore, Singapore (Singapore); Lee, Jae Wook [University of Science and Technology, Daejon (Korea, Republic of)

    2015-01-15

    In combinatorial chemistry, solid-phase synthesis is a popular approach formass production of small molecules. Compared to solution-phase synthesis, it is easy to prepare and purify a large number of heterocyclic small molecules via solid-phase chemistry; the overall reaction time is decreased as well. 1,3,5-Triazine is a nitrogen-containing heterocyclic aromatic scaffold that was shown to be a druggable scaffold in recent studies. These structures have been reported as anticancer, antimicrobial, and antiretroviral compounds, as CDKs and p38 MAP kinase inhibitors, as estrogen receptor modulators, and as inosine monophosphate dehydrogenase inhibitors. we designed and synthesized disubstituted triazine compounds as an analog of disubstituted pyrimidine compounds. These disubstituted triazine compounds possess a linear structure which may have biological activity similar to that of disubstituted pyrimidine. Here we report the solid-phase synthesis of disubstituted triazine compounds.

  1. Combinatorial Chemical Bath Deposition of CdS Contacts for Chalcogenide Photovoltaics.

    Science.gov (United States)

    Mokurala, Krishnaiah; Baranowski, Lauryn L; de Souza Lucas, Francisco W; Siol, Sebastian; van Hest, Maikel F A M; Mallick, Sudhanshu; Bhargava, Parag; Zakutayev, Andriy

    2016-09-12

    Contact layers play an important role in thin film solar cells, but new material development and optimization of its thickness is usually a long and tedious process. A high-throughput experimental approach has been used to accelerate the rate of research in photovoltaic (PV) light absorbers and transparent conductive electrodes, however the combinatorial research on contact layers is less common. Here, we report on the chemical bath deposition (CBD) of CdS thin films by combinatorial dip coating technique and apply these contact layers to Cu(In,Ga)Se2 (CIGSe) and Cu2ZnSnSe4 (CZTSe) light absorbers in PV devices. Combinatorial thickness steps of CdS thin films were achieved by removal of the substrate from the chemical bath, at regular intervals of time, and in equal distance increments. The trends in the photoconversion efficiency and in the spectral response of the PV devices as a function of thickness of CdS contacts were explained with the help of optical and morphological characterization of the CdS thin films. The maximum PV efficiency achieved for the combinatorial dip-coating CBD was similar to that for the PV devices processed using conventional CBD. The results of this study lead to the conclusion that combinatorial dip-coating can be used to accelerate the optimization of PV device performance of CdS and other candidate contact layers for a wide range of emerging absorbers.

  2. Combinatorial Chemical Bath Deposition of CdS Contacts for Chalcogenide Photovoltaics

    Energy Technology Data Exchange (ETDEWEB)

    Mokurala, Krishnaiah; Baranowski, Lauryn L.; de Souza Lucas, Francisco W.; Siol, Sebastian; van Hest, Maikel F. A. M.; Mallick, Sudhanshu; Bhargava, Parag; Zakutayev, Andriy

    2016-09-12

    Contact layers play an important role in thin film solar cells, but new material development and optimization of its thickness is usually a long and tedious process. A high-throughput experimental approach has been used to accelerate the rate of research in photovoltaic (PV) light absorbers and transparent conductive electrodes, however the combinatorial research on contact layers is less common. Here, we report on the chemical bath deposition (CBD) of CdS thin films by combinatorial dip coating technique and apply these contact layers to Cu(In,Ga)Se2 (CIGSe) and Cu2ZnSnSe4 (CZTSe) light absorbers in PV devices. Combinatorial thickness steps of CdS thin films were achieved by removal of the substrate from the chemical bath, at regular intervals of time, and in equal distance increments. The trends in the photoconversion efficiency and in the spectral response of the PV devices as a function of thickness of CdS contacts were explained with the help of optical and morphological characterization of the CdS thin films. The maximum PV efficiency achieved for the combinatorial dip-coating CBD was similar to that for the PV devices processed using conventional CBD. The results of this study lead to the conclusion that combinatorial dip-coating can be used to accelerate the optimization of PV device performance of CdS and other candidate contact layers for a wide range of emerging absorbers.

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

    Directory of Open Access Journals (Sweden)

    Renjie Huang

    2016-07-01

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

  4. Steam explosion and its combinatorial pretreatment refining technology of plant biomass to bio-based products.

    Science.gov (United States)

    Chen, Hong-Zhang; Liu, Zhi-Hua

    2015-06-01

    Pretreatment is a key unit operation affecting the refinery efficiency of plant biomass. However, the poor efficiency of pretreatment and the lack of basic theory are the main challenges to the industrial implementation of the plant biomass refinery. The purpose of this work is to review steam explosion and its combinatorial pretreatment as a means of overcoming the intrinsic characteristics of plant biomass, including recalcitrance, heterogeneity, multi-composition, and diversity. The main advantages of the selective use of steam explosion and other combinatorial pretreatments across the diversity of raw materials are introduced. Combinatorial pretreatment integrated with other unit operations is proposed as a means to exploit the high-efficiency production of bio-based products from plant biomass. Finally, several pilot- and demonstration-scale operations of the plant biomass refinery are described. Based on the principle of selective function and structure fractionation, and multi-level and directional composition conversion, an integrated process with the combinatorial pretreatments of steam explosion and other pretreatments as the core should be feasible and conform to the plant biomass refinery concept. Combinatorial pretreatments of steam explosion and other pretreatments should be further exploited based on the type and intrinsic characteristics of the plant biomass used, the bio-based products to be made, and the complementarity of the processes.

  5. Combinatorial application of two aldehyde oxidoreductases on isobutanol production in the presence of furfural.

    Science.gov (United States)

    Seo, Hyung-Min; Jeon, Jong-Min; Lee, Ju Hee; Song, Hun-Suk; Joo, Han-Byul; Park, Sung-Hee; Choi, Kwon-Young; Kim, Yong Hyun; Park, Kyungmoon; Ahn, Jungoh; Lee, Hongweon; Yang, Yung-Hun

    2016-01-01

    Furfural is a toxic by-product formulated from pretreatment processes of lignocellulosic biomass. In order to utilize the lignocellulosic biomass on isobutanol production, inhibitory effect of the furfural on isobutanol production was investigated and combinatorial application of two oxidoreductases, FucO and YqhD, was suggested as an alternative strategy. Furfural decreased cell growth and isobutanol production when only YqhD or FucO was employed as an isobutyraldehyde oxidoreductase. However, combinatorial overexpression of FucO and YqhD could overcome the inhibitory effect of furfural giving higher isobutanol production by 110% compared with overexpression of YqhD. The combinatorial oxidoreductases increased furfural detoxification rate 2.1-fold and also accelerated glucose consumption 1.4-fold. When it compares to another known system increasing furfural tolerance, membrane-bound transhydrogenase (pntAB), the combinatorial aldehyde oxidoreductases were better on cell growth and production. Thus, to control oxidoreductases is important to produce isobutanol using furfural-containing biomass and the combinatorial overexpression of FucO and YqhD can be an alternative strategy.

  6. Synthetic molecular evolution of pore-forming peptides by iterative combinatorial library screening.

    Science.gov (United States)

    Krauson, Aram J; He, Jing; Wimley, Andrew W; Hoffmann, Andrew R; Wimley, William C

    2013-04-19

    We previously reported the de novo design of a combinatorial peptide library that was subjected to high-throughput screening to identify membrane-permeabilizing antimicrobial peptides that have β-sheet-like secondary structure. Those peptides do not form discrete pores in membranes but instead partition into membrane interfaces and cause transient permeabilization by membrane disruption, but only when present at high concentration. In this work, we used a consensus sequence from that initial screen as a template to design an iterative, second generation library. In the 24-26-residue, 16,200-member second generation library we varied six residues. Two diad repeat motifs of alternating polar and nonpolar amino acids were preserved to maintain a propensity for non-helical secondary structure. We used a new high-throughput assay to identify members that self-assemble into equilibrium pores in synthetic lipid bilayers. This screen was done at a very stringent peptide to lipid ratio of 1:1000 where most known membrane-permeabilizing peptides, including the template peptide, are not active. In a screen of 10,000 library members we identified 16 (~0.2%) that are equilibrium pore-formers at this high stringency. These rare and highly active peptides, which share a common sequence motif, are as potent as the most active pore-forming peptides known. Furthermore, they are not α-helical, which makes them unusual, as most of the highly potent pore-forming peptides are amphipathic α-helices. Here we demonstrate that this synthetic molecular evolution-based approach, taken together with the new high-throughput tools we have developed, enables the identification, refinement, and optimization of unique membrane active peptides.

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

    Science.gov (United States)

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

    2015-02-01

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

  8. Combinatorial approach for development of new metal oxides materials for all oxide photovoltaics

    CERN Document Server

    Shimanovich, Klimentiy

    2015-01-01

    The combinatorial approach to all oxide material and device research is based on the synthesis of hundreds of related materials in a single experiment. This approach requires the development of new tools to rapidly characterize these materials libraries and new techniques to analyze the resulting data. The research presented here is intended to make a contribution towards meeting this demand, and thereby advance the pace of materials research. In many cases photovoltaic determinations are well-suited for high throughput methodologies, enabling direct quantitative analysis of properties whose implementation I demonstrate my thesis. This thesis focuses on the development and utilization of high throughput and combinatorial methods that have incorporated, or are associated with, the all-oxide photovoltaic field. The development of new absorbers often requires novel buffer layers, contact materials, and interface engineering. The importance and contribution of the combinatorial material science approach for the d...

  9. 一组新的恒等式的推导%Derived Several New Combinatorial Identities

    Institute of Scientific and Technical Information of China (English)

    刘玉堂; 张秦

    2011-01-01

    In this paper,through the expansion and differentiation of the known identity we derived several new combinatorial identities,and by calculating higher order derivatives we get the general condition,so we make the new combinatorial identities unified,we got series new combinatorial identities.%通过对已知恒等式sum[2nn]from n=0 to ∞x~n=1/(1-4x)展开和微分,推导出几个新的组合恒等式,并通过计算高阶导数推得一般情况,使前面几个组合恒等式得到了统一,得到一组新的组合恒等式。

  10. Creative thought as blind-variation and selective-retention: Combinatorial models of exceptional creativity

    Science.gov (United States)

    Simonton, Dean Keith

    2010-06-01

    Campbell (1960) proposed that creative thought should be conceived as a blind-variation and selective-retention process (BVSR). This article reviews the developments that have taken place in the half century that has elapsed since his proposal, with special focus on the use of combinatorial models as formal representations of the general theory. After defining the key concepts of blind variants, creative thought, and disciplinary context, the combinatorial models are specified in terms of individual domain samples, variable field size, ideational combination, and disciplinary communication. Empirical implications are then derived with respect to individual, domain, and field systems. These abstract combinatorial models are next provided substantive reinforcement with respect to findings concerning the cognitive processes, personality traits, developmental factors, and social contexts that contribute to creativity. The review concludes with some suggestions regarding future efforts to explicate creativity according to BVSR theory.

  11. Enabling techniques in the search for new antibiotics: Combinatorial biosynthesis of sugar-containing antibiotics.

    Science.gov (United States)

    Park, Je Won; Nam, Sang-Jip; Yoon, Yeo Joon

    2017-06-15

    Nature has a talent for inventing a vast number of natural products, including hybrids generated by blending different scaffolds, resulting in a myriad of bioactive chemical entities. Herein, we review the highlights and recent trends (2010-2016) in the combinatorial biosynthesis of sugar-containing antibiotics where nature's structural diversification capabilities are exploited to enable the creation of new anti-infective and anti-proliferative drugs. In this review, we describe the modern combinatorial biosynthetic approaches for polyketide synthase-derived complex and aromatic polyketides, non-ribosomal peptide synthetase-directed lipo-/glycopeptides, aminoglycosides, nucleoside antibiotics, and alkaloids, along with their therapeutic potential. Finally, we present the feasible nexus between combinatorial biosynthesis, systems biology, and synthetic biology as a toolbox to provide new antibiotics that will be indispensable in the post-antibiotic era. Copyright © 2016 Elsevier Inc. All rights reserved.

  12. New Meta-Heuristic for Combinatorial Optimization Problems:Intersection Based Scaling

    Institute of Scientific and Technical Information of China (English)

    Peng Zou; Zhi Zhou; Ying-Yu Wan; Guo-Liang Chen; Jun Gu

    2004-01-01

    Combinatorial optimization problems are found in many application fields such as computer science, engineering and economy. In this paper, a new efficient meta-heuristic, Intersection-Based Scaling (IBS for abbreviation),is proposed and it can be applied to the combinatorial optimization problems. The main idea of IBS is to scale the size of the instance based on the intersection of some local optima, and to simplify the search space by extracting the intersection from the instance, which makes the search more efficient. The combination of IBS with some local search heuristics of different combinatorial optimization problems such as Traveling Salesman Problem (TSP) and Graph Partitioning Problem (GPP) is studied, and comparisons are made with some of the best heuristic algorithms and meta-heuristic algorithms. It is found that it has significantly improved the performance of existing local search heuristics and significantly outperforms the known best algorithms.

  13. Optimized Reaction Conditions for Amide Bond Formation in DNA-Encoded Combinatorial Libraries.

    Science.gov (United States)

    Li, Yizhou; Gabriele, Elena; Samain, Florent; Favalli, Nicholas; Sladojevich, Filippo; Scheuermann, Jörg; Neri, Dario

    2016-08-08

    DNA-encoded combinatorial libraries are increasingly being used as tools for the discovery of small organic binding molecules to proteins of biological or pharmaceutical interest. In the majority of cases, synthetic procedures for the formation of DNA-encoded combinatorial libraries incorporate at least one step of amide bond formation between amino-modified DNA and a carboxylic acid. We investigated reaction conditions and established a methodology by using 1-ethyl-3-(3-(dimethylamino)propyl)carbodiimide, 1-hydroxy-7-azabenzotriazole and N,N'-diisopropylethylamine (EDC/HOAt/DIPEA) in combination, which provided conversions greater than 75% for 423/543 (78%) of the carboxylic acids tested. These reaction conditions were efficient with a variety of primary and secondary amines, as well as with various types of amino-modified oligonucleotides. The reaction conditions, which also worked efficiently over a broad range of DNA concentrations and reaction scales, should facilitate the synthesis of novel DNA-encoded combinatorial libraries.

  14. Combinatorial G-CSF/AMD3100 treatment in cardiac repair after myocardial infarction.

    Directory of Open Access Journals (Sweden)

    Constantin Rüder

    Full Text Available Several studies suggest that circulating bone marrow derived stem cells promote the regeneration of ischemic tissues. For hematopoietic stem cell transplantation combinatorial granulocyte-colony stimulating factor (G-CSF/Plerixafor (AMD3100 administration was shown to enhance mobilization of bone marrow derived stem cells compared to G-CSF monotherapy. Here we tested the hypothesis whether combinatorial G-CSF/AMD3100 therapy has beneficial effects in cardiac recovery in a mouse model of myocardial infarction.We analyzed the effect of single G-CSF (250 µg/kg/day and combinatorial G-CSF/AMD3100 (100 µg/kg/day treatment on cardiac morphology, vascularization, and hemodynamics 28 days after permanent ligation of the left anterior descending artery (LAD. G-CSF treatment started directly after induction of myocardial infarction (MI for 3 consecutive days followed by a single AMD3100 application on day three after MI in the G-CSF/AMD3100 group. Cell mobilization was assessed by flow cytometry of blood samples drawn from tail vein on day 0, 7, and 14.Peripheral blood analysis 7 days after MI showed enhanced mobilization of white blood cells (WBC and endothelial progenitor cells (EPC upon G-CSF and combinatorial G-CSF/AMD3100 treatment. However, single or combinatorial treatment showed no improvement in survival, left ventricular function, and infarction size compared to the saline treated control group 28 days after MI. Furthermore, no differences in histology and vascularization of infarcted hearts could be observed.Although the implemented treatment regimen caused no adverse effects, our data show that combinatorial G-CSF/AMD therapy does not promote myocardial regeneration after permanent LAD occlusion.

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

    Science.gov (United States)

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

    2016-01-01

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

  16. Combinatorial Hopf algebra for the Ben Geloun-Rivasseau tensor field theory

    CERN Document Server

    Raasakka, Matti

    2013-01-01

    The Ben Geloun-Rivasseau quantum field theoretical model is the first tensor model shown to be perturbatively renormalizable. We define here an appropriate Hopf algebra describing the combinatorics of this new tensorial renormalization. The structure we propose is significantly different from the previously defined Connes-Kreimer combinatorial Hopf algebras due to the involved combinatorial and topological properties of the tensorial Feynman graphs. In particular, the 2- and 4-point function insertions must be defined to be non-trivial only if the superficial divergence degree of the associated Feynman integral is conserved.

  17. 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

    The modular structure of philanthotoxins was exploited for construction of the first combinatorial library of these compounds using solid-phase parallel synthesis. (S)-Tyrosine and (S)-3-hydroxyphenylalanine were used as amino acid components, spermine, 1,12-dodecanediamine, and 4,9-dioxa-1...... former compounds may bind to nAChR in a similar fashion but differently from that of PhTX-12. The combinatorial library approach described in this work represents a prototype methodology for future exploration of structure-activity relationships of philanthotoxins....

  18. HPLC-SPE-NMR for combinatorial biosynthetic investigations – expanding the landscape of diterpene structural diversity

    DEFF Research Database (Denmark)

    Kongstad, Kenneth Thermann; Andersen-Ranberg, Johan; Hamberger, Björn Robert

    In this work, the analytical technique, HPLC-HRMS-SPE-NMR was used for the first time in combination with combinatorial biosynthetic investigations in N. benthamiana. This efficient setup allowed for identification of several diterpene synthase (diTPS) combinations responsible for stereospecific ......In this work, the analytical technique, HPLC-HRMS-SPE-NMR was used for the first time in combination with combinatorial biosynthetic investigations in N. benthamiana. This efficient setup allowed for identification of several diterpene synthase (diTPS) combinations responsible for...

  19. LAS0811: From Combinatorial Chemistry to Activation of Antioxidant Response Element

    OpenAIRE

    Ming Zhu; Hyounggee Baek; Ruiwu Liu; Aimin Song; Kit Lam; Derick Lau

    2009-01-01

    The antioxidant response element (ARE) and its transcription factor, nuclear factor-erythroid 2 p45-related factor 2 (Nrf2), are potential targets for cancer chemoprevention. We sought to screen small molecules synthesized with combinatorial chemistry for activation of ARE. By high-throughput screening of 9400 small molecules from 10 combinatorial chemical libraries using HepG2 cells with an ARE-driven reporter, we have identified a novel small molecule, 1,2-dimethoxy-4,5-dinitrobenzene (LAS0...

  20. Solutions manual to accompany Combinatorial reasoning an introduction to the art of counting

    CERN Document Server

    DeTemple, Duane

    2014-01-01

    This is a solutions manual to accompany Combinatorial Reasoning: An Introduction to the Art of CountingWritten by well-known scholars in the field, Combinatorial Reasoning: An Introduction to the Art of Counting 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.  

  1. Combinatorial Hopf algebraic description of the multiscale renormalization in quantum field theory

    CERN Document Server

    Krajewski, Thomas; Tanasa, Adrian

    2012-01-01

    We define in this paper several Hopf algebras describing the combinatorics of the so-called multi-scale renormalization in quantum field theory. After a brief recall of the main mathematical features of multi-scale renormalization, we define assigned graphs, that are graphs with appropriate decorations for the multi-scale framework. We then define Hopf algebras on these assigned graphs and on the Gallavotti-Nicol\\`o trees, particular class of trees encoding the supplementary informations of the assigned graphs. Several morphisms between these combinatorial Hopf algebras and the Connes-Kreimer algebra are given. Finally, scale dependent couplings are analyzed via this combinatorial algebraic setting.

  2. Effects of fractionation and combinatorial evaluation of Tamarindus indica fractions for antibacterial activity.

    Science.gov (United States)

    Nwodo, Uchechukwu U; Iroegbu, Christian U; Ngene, Augustine A; Chigor, Vincent N; Okoh, Anthony I

    2011-06-09

    Six fractions, named TiA - TiF, were obtained by fractionating the crude ethanol extract of the stem bark of Tamarindus indica using column chromatographic techniques. On TLC, fraction TiB showed five bands, TiC three bands, while TiD and TiE showed two bands each. TiC, TiD and TiE were re-eluted with different solvent systems to yield two fractions each, while TiB yielded four. These subfractions were designated B1-B4; C1-C2; D1-D2 and E1-E2, respectively. Tannins, flavonoids and alkaloids, among other components, were detected, albeit in different proportions with respect to fractions and subfractions and were compartmentalized with respect to the solvent systems used. The in vitro antibacterial activity of fractions and subfractions was tested separately and in combinations using the agar well diffusion technique. The susceptibly of test strains (expressed as %) were: 83.3% (TiA and TiB), 75.0% (crude extract and TiC), 66.7% (TiD), 50.0% (TiE) and 16.7% (TiF) when used singly, whereas in combination, the corresponding susceptibilities were 100% (CE), 83.3% (DE), 66.7% (AB, AF, BC, BD, DE and EF), 50% (AC and CD), 33.3% (BE and BF) and 16.7% (AD) against Gram negative bacteria strains and 100% (EF), 80% (DE), 60% (AB, BC and CE), 40% (AC, BD, BF, CF and DF) and 20% (AE, AF, BE and CD) against Gram positive strains. Percentage susceptibility with combinatorial use of re-fractions ranged from 85.7-57.1% and 60-40% against Gram negative and positive strains (TiB subfractions), respectively, 100-85.7% and 40-0% against Gram negative and positive strains (TiC, TiD and TiE sub-fractions).

  3. Lead identification for the K-Ras protein: virtual screening and combinatorial fragment-based approaches

    Directory of Open Access Journals (Sweden)

    Pathan AAK

    2016-05-01

    Full Text Available Akbar Ali Khan Pathan,1,2,* Bhavana Panthi,3,* Zahid Khan,1 Purushotham Reddy Koppula,4–6 Mohammed Saud Alanazi,1 Sachchidanand,3 Narasimha Reddy Parine,1 Mukesh Chourasia3,* 1Genome Research Chair (GRC, Department of Biochemistry, College of Science, King Saud University, 2Integrated Gulf Biosystems, Riyadh, Kingdom of Saudi Arabia; 3Department of Pharmacoinformatics, National Institute of Pharmaceutical Education and Research, Hajipur, India; 4Department of Internal Medicine, School of Medicine, 5Harry S. Truman Memorial Veterans Affairs Hospital, 6Department of Radiology, School of Medicine, Columbia, MO, USA *These authors contributed equally to this work Objective: Kirsten rat sarcoma (K-Ras protein is a member of Ras family belonging to the small guanosine triphosphatases superfamily. The members of this family share a conserved structure and biochemical properties, acting as binary molecular switches. The guanosine triphosphate-bound active K-Ras interacts with a range of effectors, resulting in the stimulation of downstream signaling pathways regulating cell proliferation, differentiation, and apoptosis. Efforts to target K-Ras have been unsuccessful until now, placing it among high-value molecules against which developing a therapy would have an enormous impact. K-Ras transduces signals when it binds to guanosine triphosphate by directly binding to downstream effector proteins, but in case of guanosine diphosphate-bound conformation, these interactions get disrupted. Methods: In the present study, we targeted the nucleotide-binding site in the “on” and “off” state conformations of the K-Ras protein to find out suitable lead compounds. A structure-based virtual screening approach has been used to screen compounds from different databases, followed by a combinatorial fragment-based approach to design the apposite lead for the K-Ras protein. Results: Interestingly, the designed compounds exhibit a binding preference for the

  4. Design of compound libraries based on natural product scaffolds and protein structure similarity clustering (PSSC)

    NARCIS (Netherlands)

    Balamurugan, Rengarajan; Dekker, Frank J; Waldmann, Herbert; Dekker, Frans

    Recent advances in structural biology, bioinformatics and combinatorial chemistry have significantly impacted the discovery of small molecules that modulate protein functions. Natural products which have evolved to bind to proteins may serve as biologically validated starting points for the design

  5. Algebraic Methods to Design Signals

    Science.gov (United States)

    2015-08-27

    AFRL-AFOSR-VA-TR-2015-0257 Algebraic Methods to Design Signals Krishnasany Arasu WRIGHT STATE UNIVERSITY Final Report 08/27/2015 DISTRIBUTION A...REPORT TYPE FINAL 3. DATES COVERED (From - To) June 2012 - May 2015 4. TITLE AND SUBTITLE ALGEBRAIC METHODS TO DESIGN SIGNALS 5a. CONTRACT NUMBER...to date on designing signals using algebraic and combinatorial methods. Mathematical tools from algebraic number theory, representation theory and

  6. Combinatorial materials approach to accelerate materials discovery for transportation (Conference Presentation)

    Science.gov (United States)

    Tong, Wei

    2017-04-01

    Combinatorial material research offers fast and efficient solutions to identify promising and advanced materials. It has revolutionized the pharmaceutical industry and now is being applied to accelerate the discovery of other new compounds, e.g. superconductors, luminescent materials, catalysts etc. Differing from the traditional trial-and-error process, this approach allows for the synthesis of a large number of compositionally diverse compounds by varying the combinations of the components and adjusting the ratios. It largely reduces the cost of single-sample synthesis/characterization, along with the turnaround time in the material discovery process, therefore, could dramatically change the existing paradigm for discovering and commercializing new materials. This talk outlines the use of combinatorial materials approach in the material discovery in transportation sector. It covers the general introduction to the combinatorial material concept, state of art for its application in energy-related research. At the end, LBNL capabilities in combinatorial materials synthesis and high throughput characterization that are applicable for material discovery research will be highlighted.

  7. Synthesis of aromatic glycoconjugates. Building blocks for the construction of combinatorial glycopeptide libraries

    Directory of Open Access Journals (Sweden)

    Markus Nörrlinger

    2014-10-01

    Full Text Available New aromatic glycoconjugate building blocks based on the trifunctional 3-aminomethyl-5-aminobenzoic acid backbone and sugars linked to the backbone by a malonyl moiety were prepared via peptide coupling. The orthogonally protected glycoconjugates, bearing an acetyl-protected glycoside, were converted into their corresponding acids which are suitable building blocks for combinatorial glycopeptide synthesis.

  8. A Special Role of Boolean Quadratic Polytopes among Other Combinatorial Polytopes

    Directory of Open Access Journals (Sweden)

    A. N. Maksimenko

    2016-01-01

    Full Text Available We consider several families of combinatorial polytopes associated with the following NP-complete problems: maximum cut, Boolean quadratic programming, quadratic linear ordering, quadratic assignment, set partition, set packing, stable set, 3-assignment. For comparing two families of polytopes we use the following method. We say that a family

  9. Differential combinatorial coding of pheromones in two olfactory subsystems of the honey bee brain.

    Science.gov (United States)

    Carcaud, Julie; Giurfa, Martin; Sandoz, Jean-Christophe

    2015-03-11

    Neural coding of pheromones has been intensively studied in insects with a particular focus on sex pheromones. These studies favored the view that pheromone compounds are processed within specific antennal lobe glomeruli following a specialized labeled-line system. However, pheromones play crucial roles in an insect's life beyond sexual attraction, and some species use many different pheromones making such a labeled-line organization unrealistic. A combinatorial coding scheme, in which each component activates a set of broadly tuned units, appears more adapted in this case. However, this idea has not been tested thoroughly. We focused here on the honey bee Apis mellifera, a social insect that relies on a wide range of pheromones to ensure colony cohesion. Interestingly, the honey bee olfactory system harbors two central parallel pathways, whose functions remain largely unknown. Using optophysiological recordings of projection neurons, we compared the responses of these two pathways to 27 known honey bee pheromonal compounds emitted by the brood, the workers, and the queen. We show that while queen mandibular pheromone is processed by l-ALT (lateral antennal lobe tract) neurons and brood pheromone is mainly processed by m-ALT (median antennal lobe tract) neurons, worker pheromones induce redundant activity in both pathways. Moreover, all tested pheromonal compounds induce combinatorial activity from several AL glomeruli. These findings support the combinatorial coding scheme and suggest that higher-order brain centers reading out these combinatorial activity patterns may eventually classify olfactory signals according to their biological meaning.

  10. The Pictet-Spengler reaction in solid-phase combinatorial chemistry

    DEFF Research Database (Denmark)

    Nielsen, Thomas E; Diness, Frederik; Meldal, Morten

    2003-01-01

    -phase routes toward a range of complex heterocyclic ring systems, with focus on experimental conditions, efficiency and diastereoselectivity. This is illustrated by the application of this reaction to the synthesis of combinatorial libraries, natural product analogs and drug-like scaffolds....

  11. Localized Template-Driven Functionalization of Nanoparticles by Dynamic Combinatorial Chemistry

    NARCIS (Netherlands)

    Nowak, Piotr; Saggiomo, Vittorio; Salehian, Fatemeh; Colomb-Delsuc, Mathieu; Han, Yang; Otto, Sijbren

    2015-01-01

    We have developed a method for the localized functionalization of gold nanoparticles using imine-based dynamic combinatorial chemistry. By using DNA templates, amines were grafted on the aldehyde-functionalized nanoparticles only if and where the nanoparticles interacted with the template molecules.

  12. Localized Template-Driven Functionalization of Nanoparticles by Dynamic Combinatorial Chemistry

    NARCIS (Netherlands)

    Nowak, Piotr; Saggiomo, Vittorio; Salehian, Fatemeh; Colomb-Delsuc, Mathieu; Han, Yang; Otto, Sijbren

    2015-01-01

    We have developed a method for the localized functionalization of gold nanoparticles using imine-based dynamic combinatorial chemistry. By using DNA templates, amines were grafted on the aldehyde-functionalized nanoparticles only if and where the nanoparticles interacted with the template molecules.

  13. An Onto-Semiotic Analysis of Combinatorial Problems and the Solving Processes by University Students

    Science.gov (United States)

    Godino, Juan D.; Batanero, Carmen; Roa, Rafael

    2005-01-01

    In this paper we describe an ontological and semiotic model for mathematical knowledge, using elementary combinatorics as an example. We then apply this model to analyze the solving process of some combinatorial problems by students with high mathematical training, and show its utility in providing a semiotic explanation for the difficulty of…

  14. Nonconvex continuous models for combinatorial optimization problems with application to satisfiability and node packing problems

    NARCIS (Netherlands)

    Warners, J.P.

    1997-01-01

    We show how a large class of combinatorial optimization problems can be reformulated as a nonconvex minimization problem over the unit hyper cube with continuous variables. No additional constraints are required; all constraints are incorporated in the n onconvex objective function, which is a polyn

  15. A new combinatorial approach to the construction of constant composition codes

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    Constant composition codes(CCCs)are a new generalization of binary constant weight codes and have attracted recent interest due to their numerous applications. In this paper, a new combinatorial approach to the construction of CCCs is proposed, and used to establish new optimal CCCs.

  16. Enhancing Throughput of Combinatorial Droplet Devices via Droplet Bifurcation, Parallelized Droplet Fusion, and Parallelized Detection

    Directory of Open Access Journals (Sweden)

    Kuangwen Hsieh

    2015-10-01

    Full Text Available Combinatorial droplet microfluidic devices with programmable microfluidic valves have recently emerged as a viable approach for performing multiplexed experiments in microfluidic droplets. However, the serial operation in these devices restricts their throughput. To address this limitation, we present a parallelized combinatorial droplet device that enhances device throughput via droplet bifurcation, parallelized droplet fusion, and parallelized droplet detection. In this device, sample droplets split evenly at bifurcating Y-junctions before multiple independent reagent droplets are injected directly into the split sample droplets for robust droplet fusion. Finally, the fused sample and reagent droplets can be imaged in parallel via microscopy. The combination of these approaches enabled us to improve the throughput over traditional, serially-operated combinatorial droplet devices by 16-fold—with ready potential for further enhancement. Given its current performance and prospect for future improvements, we believe the parallelized combinatorial droplet device has the potential to meet the demand as a flexible and cost-effective tool that can perform high throughput screening applications.

  17. Microbiome profiling by illumina sequencing of combinatorial sequence-tagged PCR products

    NARCIS (Netherlands)

    G.B. Gloor (Gregory); R.B.S. Hummelen (Ruben); J.M. Macklaim (Jean); R.J. Dickson (Russell); A.D. Fernandes (Andrew); R.A. MacPhee (Roderick); G. Reid (Gregor)

    2010-01-01

    textabstractWe developed a low-cost, high-throughput microbiome profiling method that uses combinatorial sequence tags attached to PCR primers that amplify the rRNA V6 region. Amplified PCR products are sequenced using an Illumina paired-end protocol to generate millions of overlapping reads.

  18. Molecular profile of an antibody response to HIV-1 as probed by combinatorial libraries

    NARCIS (Netherlands)

    Barbas, C F; Collet, T A; Amberg, W; Roben, P; Binley, J M; Hoekstra, Dick; Cababa, D; Jones, T M; Williamson, R A; Pilkington, G R

    1993-01-01

    A large number (33) of human Fab fragments reacting with HIV-1 surface glycoprotein gp120 have been generated by selection from a combinatorial IgG1 kappa library displayed on the surface of phage. The library was prepared from a long term asymptomatic HIV-seropositive donor. Analysis of the sequenc

  19. Winner determination in combinatorial auctions with logic-based bidding languages

    NARCIS (Netherlands)

    Uckelman, J.; Endriss, U.; Padgham, L.; Parkes, D.; Müller, J.; Parsons, S.

    2008-01-01

    We propose the use of logic-based preference representation languages based on weighted propositional formulas for specifying bids in a combinatorial auction. We then develop several heuristics for a branch-and-bound search algorithm for determining the winning bids in this framework and report on t

  20. Microfluidic-Enabled Print-to-Screen Platform for High-Throughput Screening of Combinatorial Chemotherapy.

    Science.gov (United States)

    Ding, Yuzhe; Li, Jiannan; Xiao, Wenwu; Xiao, Kai; Lee, Joyce; Bhardwaj, Urvashi; Zhu, Zijie; Digiglio, Philip; Yang, Gaomai; Lam, Kit S; Pan, Tingrui

    2015-10-20

    Since the 1960s, combination chemotherapy has been widely utilized as a standard method to treat cancer. However, because of the potentially enormous number of drug candidates and combinations, conventional identification methods of the effective drug combinations are usually associated with significantly high operational costs, low throughput screening, laborious and time-consuming procedures, and ethical concerns. In this paper, we present a low-cost, high-efficiency microfluidic print-to-screen (P2S) platform, which integrates combinatorial screening with biomolecular printing for high-throughput screening of anticancer drug combinations. This P2S platform provides several distinct advantages and features, including automatic combinatorial printing, high-throughput parallel drug screening, modular disposable cartridge, and biocompatibility, which can potentially speed up the entire discovery cycle of potent drug combinations. Microfluidic impact printing utilizing plug-and-play microfluidic cartridges is experimentally characterized with controllable droplet volume and accurate positioning. Furthermore, the combinatorial print-to-screen assay is demonstrated in a proof-of-concept biological experiment which can identify the positive hits among the entire drug combination library in a parallel and rapid manner. Overall, this microfluidic print-to-screen platform offers a simple, low-cost, high-efficiency solution for high-throughput large-scale combinatorial screening and can be applicable for various emerging applications in drug cocktail discovery.

  1. HPLC-SPE-NMR for combinatorial biosynthetic investigations – Expanding the landscape of diterpene structural diversity

    DEFF Research Database (Denmark)

    Kongstad, Kenneth Thermann; Andersen-Ranberg, Johan; Hamberger, Björn Robert;

    In this work, the analytical technique, HPLC-HRMS-SPE-NMR was used for the first time in combination with combinatorial biosynthetic investigations in N. benthamiana. This efficient setup allowed for identification of several diterpene synthase (diTPS) combinations responsible for stereospecific...

  2. Modular system design and evaluation

    CERN Document Server

    Levin, Mark Sh

    2015-01-01

    This book examines seven key combinatorial engineering frameworks (composite schemes consisting of algorithms and/or interactive procedures) for hierarchical modular (composite) systems. These frameworks are based on combinatorial optimization problems (e.g., knapsack problem, multiple choice problem, assignment problem, morphological clique problem), with the author’s version of morphological design approach – Hierarchical Morphological Multicritieria Design (HMMD) – providing a conceptual lens with which to elucidate the examples discussed. This approach is based on ordinal estimates of design alternatives for systems parts/components, however, the book also puts forward an original version of HMMD that is based on new interval multiset estimates for the design alternatives with special attention paid to the aggregation of modular solutions (system versions). The second part of ‘Modular System Design and Evaluation’ provides ten information technology case studies that enriches understanding of th...

  3. Comprehensive human transcription factor binding site map for combinatory binding motifs discovery.

    Directory of Open Access Journals (Sweden)

    Arnoldo J Müller-Molina

    Full Text Available To know the map between transcription factors (TFs and their binding sites is essential to reverse engineer the regulation process. Only about 10%-20% of the transcription factor binding motifs (TFBMs have been reported. This lack of data hinders understanding gene regulation. To address this drawback, we propose a computational method that exploits never used TF properties to discover the missing TFBMs and their sites in all human gene promoters. The method starts by predicting a dictionary of regulatory "DNA words." From this dictionary, it distills 4098 novel predictions. To disclose the crosstalk between motifs, an additional algorithm extracts TF combinatorial binding patterns creating a collection of TF regulatory syntactic rules. Using these rules, we narrowed down a list of 504 novel motifs that appear frequently in syntax patterns. We tested the predictions against 509 known motifs confirming that our system can reliably predict ab initio motifs with an accuracy of 81%-far higher than previous approaches. We found that on average, 90% of the discovered combinatorial binding patterns target at least 10 genes, suggesting that to control in an independent manner smaller gene sets, supplementary regulatory mechanisms are required. Additionally, we discovered that the new TFBMs and their combinatorial patterns convey biological meaning, targeting TFs and genes related to developmental functions. Thus, among all the possible available targets in the genome, the TFs tend to regulate other TFs and genes involved in developmental functions. We provide a comprehensive resource for regulation analysis that includes a dictionary of "DNA words," newly predicted motifs and their corresponding combinatorial patterns. Combinatorial patterns are a useful filter to discover TFBMs that play a major role in orchestrating other factors and thus, are likely to lock/unlock cellular functional clusters.

  4. Applications of high throughput (combinatorial) methodologies to electronic, magnetic, optical, and energy-related materials

    Science.gov (United States)

    Green, Martin L.; Takeuchi, Ichiro; Hattrick-Simpers, Jason R.

    2013-06-01

    High throughput (combinatorial) materials science methodology is a relatively new research paradigm that offers the promise of rapid and efficient materials screening, optimization, and discovery. The paradigm started in the pharmaceutical industry but was rapidly adopted to accelerate materials research in a wide variety of areas. High throughput experiments are characterized by synthesis of a "library" sample that contains the materials variation of interest (typically composition), and rapid and localized measurement schemes that result in massive data sets. Because the data are collected at the same time on the same "library" sample, they can be highly uniform with respect to fixed processing parameters. This article critically reviews the literature pertaining to applications of combinatorial materials science for electronic, magnetic, optical, and energy-related materials. It is expected that high throughput methodologies will facilitate commercialization of novel materials for these critically important applications. Despite the overwhelming evidence presented in this paper that high throughput studies can effectively inform commercial practice, in our perception, it remains an underutilized research and development tool. Part of this perception may be due to the inaccessibility of proprietary industrial research and development practices, but clearly the initial cost and availability of high throughput laboratory equipment plays a role. Combinatorial materials science has traditionally been focused on materials discovery, screening, and optimization to combat the extremely high cost and long development times for new materials and their introduction into commerce. Going forward, combinatorial materials science will also be driven by other needs such as materials substitution and experimental verification of materials properties predicted by modeling and simulation, which have recently received much attention with the advent of the Materials Genome

  5. 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.

  6. Design

    DEFF Research Database (Denmark)

    Volf, Mette

    This publication is unique in its demystification and operationalization of the complex and elusive nature of the design process. The publication portrays the designer’s daily work and the creative process, which the designer is a part of. Apart from displaying the designer’s work methods...... and design parameters, the publication shows examples from renowned Danish design firms. Through these examples the reader gets an insight into the designer’s reality....

  7. Combinatorial chemistry: libraries from libraries, the art of the diversity-oriented transformation of resin-bound peptides and chiral polyamides to low molecular weight acyclic and heterocyclic compounds.

    Science.gov (United States)

    Nefzi, Adel; Ostresh, John M; Yu, Yongping; Yu, Jongping; Houghten, Richard A

    2004-05-28

    Combinatorial chemistry has deeply impacted the drug discovery process by accelerating the synthesis and screening of large numbers of compounds having therapeutic and/or diagnostic potential. These techniques offer unique enhancement in the potential identification of new and/or therapeutic candidates. Our efforts over the past 10 years in the design and diversity-oriented synthesis of low molecular weight acyclic and heterocyclic combinatorial libraries derived from amino acids, peptides, and/or peptidomimetics are described. Employing a "toolbox" of various chemical transformations, including alkylation, oxidation, reduction, acylation, and the use of a variety of multifunctional reagents, the "libraries from libraries" concept has enabled the continued development of an ever-expanding, structurally varied series of organic chemical libraries.

  8. The application of combinatorial approach to the optimization of dielectric/ferroelectric materials

    Science.gov (United States)

    Chang, Hauyee

    Combinatorial approaches are methods developed to facilitate the rapid discovery and optimization of materials by the simultaneous synthesis and screening of a large number of compounds within a short period of time. This work describes its application to dielectric and ferroelectric thin film materials, in particular, (Ba,SrCa)TiO3. New methods and instruments for thin film fabrication and measurement are developed to handle the synthesis and analysis of up to thousands of samples simultaneously. Thin films are fabricated with a novel multilayer precursor method. Precursors of the various elemental components within the target compound, such as BaF 2 and TiO2 for BaTiO3, are deposited at room temperature as separate layers. These multilayers are thermally processed under a two step procedure. A low temperature treatment over a period of days interdiffuses the layers to form a homogeneous amorphous intermediate. This is followed by a high temperature crystallization step, which forms the final crystalline product. Effects of dopants on the dielectric constant and loss of (BaSr)TiO 3 are studied with the discrete combinatorial approach, where up to thousands of discrete thin film samples are fabricated on an individual single crystal substrate. A continuous combinatorial sample resembling a ternary phase diagram of (Ba,Sr,Ca)TiO3 is also fabricated in search of the lowest loss compositions that are useful for various applications such as the storage node capacitors in dynamic random access memories. These combinatorial samples of (BaSr,Ca)TiO3 are measured with the newly developed scanning evanescent microwave microscope (SEMM). This instrument is capable of rapid and accurate non-contact characterization of the thin film dielectric constants and losses. The measured results show good agreement with results from more conventional methods such as the interdigital electrodes measurements. Various issues concerning the combinatorial approach in materials science are

  9. Optical cell for combinatorial in situ Raman spectroscopic measurements of hydrogen storage materials at high pressures and temperatures

    Science.gov (United States)

    Hattrick-Simpers, Jason R.; Hurst, Wilbur S.; Srinivasan, Sesha S.; Maslar, James E.

    2011-03-01

    An optical cell is described for high-throughput backscattering Raman spectroscopic measurements of hydrogen storage materials at pressures up to 10 MPa and temperatures up to 823 K. High throughput is obtained by employing a 60 mm diameter × 9 mm thick sapphire window, with a corresponding 50 mm diameter unobstructed optical aperture. To reproducibly seal this relatively large window to the cell body at elevated temperatures and pressures, a gold o-ring is employed. The sample holder-to-window distance is adjustable, making this cell design compatible with optical measurement systems incorporating lenses of significantly different focal lengths, e.g., microscope objectives and single element lenses. For combinatorial investigations, up to 19 individual powder samples can be loaded into the optical cell at one time. This cell design is also compatible with thin-film samples. To demonstrate the capabilities of the cell, in situ measurements of the Ca(BH4)2 and nano-LiBH4-LiNH2-MgH2 hydrogen storage systems at elevated temperatures and pressures are reported.

  10. Optical cell for combinatorial in situ Raman spectroscopic measurements of hydrogen storage materials at high pressures and temperatures.

    Science.gov (United States)

    Hattrick-Simpers, Jason R; Hurst, Wilbur S; Srinivasan, Sesha S; Maslar, James E

    2011-03-01

    An optical cell is described for high-throughput backscattering Raman spectroscopic measurements of hydrogen storage materials at pressures up to 10 MPa and temperatures up to 823 K. High throughput is obtained by employing a 60 mm diameter × 9 mm thick sapphire window, with a corresponding 50 mm diameter unobstructed optical aperture. To reproducibly seal this relatively large window to the cell body at elevated temperatures and pressures, a gold o-ring is employed. The sample holder-to-window distance is adjustable, making this cell design compatible with optical measurement systems incorporating lenses of significantly different focal lengths, e.g., microscope objectives and single element lenses. For combinatorial investigations, up to 19 individual powder samples can be loaded into the optical cell at one time. This cell design is also compatible with thin-film samples. To demonstrate the capabilities of the cell, in situ measurements of the Ca(BH(4))(2) and nano-LiBH(4)-LiNH(2)-MgH(2) hydrogen storage systems at elevated temperatures and pressures are reported.

  11. Combinatorial Screening Identifies Novel Promiscuous Matrix Metalloproteinase Activities that Lead to Inhibition of the Therapeutic Target IL-13

    NARCIS (Netherlands)

    Urbach, Carole; Gordon, Nathaniel C; Strickland, Ian; Lowne, David; Joberty-Candotti, Cathy; May, Richard; Herath, Athula; Hijnen, DirkJan; Thijs, Judith L; Bruijnzeel-Koomen, Carla A; Minter, Ralph R; Hollfelder, Florian; Jermutus, Lutz

    2015-01-01

    The practical realization of disease modulation by catalytic degradation of a therapeutic target protein suffers from the difficulty to identify candidate proteases, or to engineer their specificity. We identified 23 measurable, specific, and new protease activities using combinatorial screening of

  12. Design of survivable networks

    CERN Document Server

    Stoer, Mechthild

    1992-01-01

    The problem of designing a cost-efficient network that survives the failure of one or more nodes or edges of the network is critical to modern telecommunications engineering. The method developed in this book is designed to solve such problems to optimality. In particular, a cutting plane approach is described, based on polyhedral combinatorics, that is ableto solve real-world problems of this type in short computation time. These results are of interest for practitioners in the area of communication network design. The book is addressed especially to the combinatorial optimization community, but also to those who want to learn polyhedral methods. In addition, interesting new research problemsare formulated.

  13. Effects of Fractionation and Combinatorial Evaluation of Tamarindus indica Fractions for Antibacterial Activity

    Directory of Open Access Journals (Sweden)

    Augustine A. Ngene

    2011-06-01

    Full Text Available Six fractions, named TiA – TiF, were obtained by fractionating the crude ethanol extract of the stem bark of Tamarindus indica using column chromatographic techniques. On TLC, fraction TiB showed five bands, TiC three bands, while TiD and TiE showed two bands each. TiC, TiD and TiE were re-eluted with different solvent systems to yield two fractions each, while TiB yielded four. These subfractions were designated B1-B4; C1-C2; D1-D2 and E1-E2, respectively. Tannins, flavonoids and alkaloids, among other components, were detected, albeit in different proportions with respect to fractions and subfractions and were compartmentalized with respect to the solvent systems used. The in vitro antibacterial activity of fractions and subfractions was tested separately and in combinations using the agar well diffusion technique. The susceptibly of test strains (expressed as % were: 83.3% (TiA and TiB, 75.0% (crude extract and TiC, 66.7% (TiD, 50.0% (TiE and 16.7% (TiF when used singly, whereas in combination, the corresponding susceptibilities were 100% (CE, 83.3% (DE, 66.7% (AB, AF, BC, BD, DE and EF, 50% (AC and CD, 33.3% (BE and BF and 16.7% (AD against Gram negative bacteria strains and 100% (EF, 80% (DE, 60% (AB, BC and CE, 40% (AC, BD, BF, CF and DF and 20% (AE, AF, BE and CD against Gram positive strains. Percentage susceptibility with combinatorial use of re-fractions ranged from 85.7–57.1% and 60–40% against Gram negative and positive strains (TiB subfractions, respectively, 100–85.7% and 40–0% against Gram negative and positive strains (TiC, TiD and TiE sub-fractions.

  14. Application of combinatorial approach in packaging material selection

    Science.gov (United States)

    Jarupan, Lerpong; Kamarthi, Sagar V.; Gupta, Surendra M.

    2004-12-01

    Packaging material selection (PMS) problems have always been important to packaging designers and engineers. Not only does the selection of packaging material determine the costs and the environmental impacts of packaging, but also influences packaging physical characteristics and associated manufacturing methods. In order to reduce economic and environmental impacts, one has to take a holistic approach to packaging material selection by considering material effects throughout the packaging life cycle. To evaluate economic costs and environmental impacts both quantitative factors and subjective criteria play an important role in the packaging design. In the present work, fuzzy set theory is used for representing and manipulating the vague and subjective descriptions of packaging performance and design attributes. Further a genetic algorithm based approach is used for addressing the packaging material selection problem through multiple criteria decision-making. The overall approach comprises of two phases. In the first phase, fuzzy set theory is used for the linguistic transformation of performance attributes into numerical values. It results in a decision matrix that contains crisp scores. Also in this phase, a weight is assigned to each sub-criterion to show its importance compared to others. In the second phase, a GA is used to globally search for near-optimal or optimal design solutions. The implementation of the proposed methodology is illustrated through a numerical example.

  15. Dynamic Combinatorial Chemistry and Organocatalysis with Thiosemicarbazones and Organocatalysts for Hydrazone and Oxime Bioconjugations

    DEFF Research Database (Denmark)

    Larsen, Dennis

    is presented. This represents the first use, to the best of the author’s knowledge, of thiosemicarbazones for organocatalysis. Guided by kinetics studies, a range of catalysts were developed and evaluated, and this showed that thiosemicarbazone catalysts are highly tuneable. The best thiosemicarbazone catalyst......The first part of this thesis describes the use of thiosemicarbazones for dynamic combinatorial chemistry. Building blocks incorporating thiosemicarbazides and acetalprotected aldehydes were synthesised and conditions where these building blocks formed dynamic combinatorial libraries under...... gave a 50-fold higher second-order rate constant than the best thiourea catalyst reported for this transformation. A dual Hammett plot analysis and interaction studies by NMR spectroscopy lends support to a reaction mechanism proceeding via an asynchronous [2+2] cycloaddition. The third and final part...

  16. Discovery of antibiotics-derived polymers for gene delivery using combinatorial synthesis and cheminformatics modeling.

    Science.gov (United States)

    Potta, Thrimoorthy; Zhen, Zhuo; Grandhi, Taraka Sai Pavan; Christensen, Matthew D; Ramos, James; Breneman, Curt M; Rege, Kaushal

    2014-02-01

    We describe the combinatorial synthesis and cheminformatics modeling of aminoglycoside antibiotics-derived polymers for transgene delivery and expression. Fifty-six polymers were synthesized by polymerizing aminoglycosides with diglycidyl ether cross-linkers. Parallel screening resulted in identification of several lead polymers that resulted in high transgene expression levels in cells. The role of polymer physicochemical properties in determining efficacy of transgene expression was investigated using Quantitative Structure-Activity Relationship (QSAR) cheminformatics models based on Support Vector Regression (SVR) and 'building block' polymer structures. The QSAR model exhibited high predictive ability, and investigation of descriptors in the model, using molecular visualization and correlation plots, indicated that physicochemical attributes related to both, aminoglycosides and diglycidyl ethers facilitated transgene expression. This work synergistically combines combinatorial synthesis and parallel screening with cheminformatics-based QSAR models for discovery and physicochemical elucidation of effective antibiotics-derived polymers for transgene delivery in medicine and biotechnology. Copyright © 2013 Elsevier Ltd. All rights reserved.

  17. Combinatorial Library Screening Coupled to Mass Spectrometry to Identify Valuable Cyclic Peptides.

    Science.gov (United States)

    Camperi, Silvia A; Giudicessi, Silvana L; Martínez-Ceron, María C; Gurevich-Messina, Juan M; Saavedra, Soledad L; Acosta, Gerardo; Cascone, Osvaldo; Erra-Balsells, Rosa; Albericio, Fernando

    2016-06-02

    Combinatorial library screening coupled to mass spectrometry (MS) analysis is a practical approach to identify useful peptides. Cyclic peptides can have high biological activity, selectivity, and affinity for target proteins, and high stability against proteolytic degradation. Here we describe two strategies to prepare combinatorial libraries suitable for MS analysis to accelerate the discovery of cyclic peptide structures. Both approaches use ChemMatrix resin and the linker 4-hydroxymethylbenzoic acid. One strategy involves the synthesis of a one-bead-two-peptides library in which each bead contains both the cyclic peptide and its linear counterpart to facilitate MS analysis. The other protocol is based on the synthesis of a cyclic depsipeptide library in which a glycolamidic ester group is incorporated by adding glycolic acid. After library screening, the ring is opened and the peptide is released simultaneously for subsequent MS analysis. © 2016 by John Wiley & Sons, Inc.

  18. An Asymptotic Faber-Krahn Inequality for the Combinatorial Laplacian on Z^2

    CERN Document Server

    Shlapentokh-Rothman, Yakov

    2010-01-01

    The Faber-Krahn inequality states that among all open domains with a fixed volume in R^n, the ball minimizes the first Dirichlet eigenvalue of the Laplacian. We study an asymptotic discrete analogue of this for the combinatorial Dirichlet Laplacian acting on induced subgraphs of Z^2. Namely, an induced subgraph G with n vertices is called a minimizing subgraph if it minimizes the first eigenvalue of the combinatorial Dirichlet Laplacian among all induced subgraphs with n vertices. Consider an induced subgraph G and take the interior of the union of closed squares of area 1 about each point of G. Let G* denote this domain scaled down to have area 1. Our main theorem states that if {G_n} is a sequence of minimizing subgraphs where each G_n has n vertices, then after translation the measure of the symmetric difference of G_n* and the unit disk converges to 0.

  19. The Poetics of Combinatory Cinema: David Jhave Johnston interviews Roderick Coover and Scott Rettberg

    Directory of Open Access Journals (Sweden)

    Roderick Coover

    2014-12-01

    Full Text Available For the past several years filmmaker Roderick Coover and fiction writer Scott Rettberg have collaborated on a series of film and digital media projects that address climate change, environmental catastrophe, cross-cultural communication and combinatory poetics. Working between Philadelphia, USA, where Coover directs the graduate programme in Film and Media Arts at Temple University, and Bergen, Norway, where Rettberg is Professor of Digital Culture at the University of Bergen. Their projects, including The Last Volcano, Rats and Cats, Three Rails Live (with Nick Montfort and Toxi•City, deal thematically with contemporary and past moments of environmental change and human loss, and formally with interdisciplinary practice and combinatory poetics. Coover and Rettberg were interviewed by digital poet and experimental filmmaker David Jhave Johnston, Assistant Professor in the School of Creative Media at City University of Hong Kong.

  20. Optimal weighted combinatorial forecasting model of QT dispersion of ECGs in Chinese adults.

    Science.gov (United States)

    Wen, Zhang; Miao, Ge; Xinlei, Liu; Minyi, Cen

    2016-07-01

    This study aims to provide a scientific basis for unifying the reference value standard of QT dispersion of ECGs in Chinese adults. Three predictive models including regression model, principal component model, and artificial neural network model are combined to establish the optimal weighted combination model. The optimal weighted combination model and single model are verified and compared. Optimal weighted combinatorial model can reduce predicting risk of single model and improve the predicting precision. The reference value of geographical distribution of Chinese adults' QT dispersion was precisely made by using kriging methods. When geographical factors of a particular area are obtained, the reference value of QT dispersion of Chinese adults in this area can be estimated by using optimal weighted combinatorial model and reference value of the QT dispersion of Chinese adults anywhere in China can be obtained by using geographical distribution figure as well.

  1. PTRcombiner: mining combinatorial regulation of gene expression from post-transcriptional interaction maps.

    Science.gov (United States)

    Corrado, Gianluca; Tebaldi, Toma; Bertamini, Giulio; Costa, Fabrizio; Quattrone, Alessandro; Viero, Gabriella; Passerini, Andrea

    2014-04-23

    The progress in mapping RNA-protein and RNA-RNA interactions at the transcriptome-wide level paves the way to decipher possible combinatorial patterns embedded in post-transcriptional regulation of gene expression. Here we propose an innovative computational tool to extract clusters of mRNA trans-acting co-regulators (RNA binding proteins and non-coding RNAs) from pairwise interaction annotations. In addition the tool allows to analyze the binding site similarity of co-regulators belonging to the same cluster, given their positional binding information. The tool has been tested on experimental collections of human and yeast interactions, identifying modules that coordinate functionally related messages. This tool is an original attempt to uncover combinatorial patterns using all the post-transcriptional interaction data available so far. PTRcombiner is available at http://disi.unitn.it/~passerini/software/PTRcombiner/.

  2. Combinatorial Game Theory, Well-Tempered Scoring Games, and a Knot Game

    CERN Document Server

    Johnson, Will

    2011-01-01

    We begin by reviewing and proving the basic facts of combinatorial game theory. We then consider scoring games (also known as Milnor games or positional games), focusing on the "fixed-length" games for which all sequences of play terminate after the same number of moves. The theory of fixed-length scoring games is shown to have properties similar to the theory of loopy combinatorial games, with operations similar to onsides and offsides. We give a complete description of the structure of fixed-length scoring games in terms of the class of short partizan games. We also consider fixed-length scoring games taking values in the two-element boolean algebra, and classify these games up to indistinguishability. We then apply these results to analyze some positions in the knotting-unknotting game of Pechenik, Townsend, Henrich, MacNaughton, and Silversmith.

  3. Research on Li Shanlan's Combinatorial Thought%李善兰组合思想研究

    Institute of Scientific and Technical Information of China (English)

    张必胜

    2016-01-01

    This paper reviews Li Shanlan traditional mathematics works on combinatorial problems of historical documents, obtained Li Shanlan combinatorial identities and Western mathematics is consistent. Li Shanlan in his book "DuoJiBiLei" got some mathematical expressions combination summation.%基于李善兰传统数学著作中关于组合问题历史文献的研究,得出李善兰组合恒等式与西方数学是保持一致的。李善兰在其著作《垛积比类》得到了一些组合求和的数学表达式。

  4. Hollow fiber liquid-supported membrane technology for enantioseparation of racemic salbutamol by combinatorial chiral selectors

    Institute of Scientific and Technical Information of China (English)

    2006-01-01

    Enantioseparation of salbutamol solute was carried out in liquid-supported membrane by using a polyvinylidene fluoride hollow-fiber module. The enantioselective transport of solute was facilitated by combinatorial chiral selectors, which were dissolved in toluene organic solvent. The effects of molar concentration ratios of salbutamol to combinatorial chiral selectors, and the pH value of buffer solution on enantioseparation were investigated. The results show that when the molar concentration ratio is 2: 1:1, the maximum separation factor and enantiomer excess are 1.49 and 19.74%, respectively, and the R-enantiomer flux is more than S-enantiomer; the pH value of buffer solution influences the performances of enantioseparartion obviously, and the appropriate range of pH value is7.0-7.2.

  5. Combinatorial identities for Stirling numbers the unpublished notes of H. W. Gould

    CERN Document Server

    Quaintance, Jocelyn

    2016-01-01

    This book is a unique work which provides an in-depth exploration into the mathematical expertise, philosophy, and knowledge of H W Gould. It is written in a style that is accessible to the reader with basic mathematical knowledge, and yet contains material that will be of interest to the specialist in enumerative combinatorics. This book begins with exposition on the combinatorial and algebraic techniques that Professor Gould uses for proving binomial identities. These techniques are then applied to develop formulas which relate Stirling numbers of the second kind to Stirling numbers of the first kind. Professor Gould's techniques also provide connections between both types of Stirling numbers and Bernoulli numbers. Professor Gould believes his research success comes from his intuition on how to discover combinatorial identities.This book will appeal to a wide audience and may be used either as lecture notes for a beginning graduate level combinatorics class, or as a research supplement for the specialist in...

  6. Geometric Generalisation of Surrogate Model-Based Optimisation to Combinatorial and Program Spaces

    Directory of Open Access Journals (Sweden)

    Yong-Hyuk Kim

    2014-01-01

    Full Text Available Surrogate models (SMs can profitably be employed, often in conjunction with evolutionary algorithms, in optimisation in which it is expensive to test candidate solutions. The spatial intuition behind SMs makes them naturally suited to continuous problems, and the only combinatorial problems that have been previously addressed are those with solutions that can be encoded as integer vectors. We show how radial basis functions can provide a generalised SM for combinatorial problems which have a geometric solution representation, through the conversion of that representation to a different metric space. This approach allows an SM to be cast in a natural way for the problem at hand, without ad hoc adaptation to a specific representation. We test this adaptation process on problems involving binary strings, permutations, and tree-based genetic programs.

  7. Using animal models to overcome temporal, spatial and combinatorial challenges in HIV persistence research

    DEFF Research Database (Denmark)

    Denton, Paul W.; Søgaard, Ole Schmeltz; Tolstrup, Martin

    2016-01-01

    regard the anatomical locations and cell subsets that harbor persistent HIV. Combinatorial research challenges pertain to the order of administration, timing of administration and specific combinations of compounds to be administered during HIV eradication therapy. Overcoming these challenges...... for directly addressing these research challenges. The aim of this manuscript is to provide a comprehensive review of these recent translational advances made in animal models of HIV persistence....

  8. Quantum-Inspired Genetic Algorithm Based on Simulated Annealing for Combinatorial Optimization Problem

    OpenAIRE

    Wanneng Shu

    2009-01-01

    Quantum-inspired genetic algorithm (QGA) is applied to simulated annealing (SA) to develop a class of quantum-inspired simulated annealing genetic algorithm (QSAGA) for combinatorial optimization. With the condition of preserving QGA advantages, QSAGA takes advantage of the SA algorithm so as to avoid premature convergence. To demonstrate its effectiveness and applicability, experiments are carried out on the knapsack problem. The results show that QSAGA performs well, without premature conve...

  9. Theoretical principles of in vitro selection using combinatorial nucleic acid libraries.

    Science.gov (United States)

    Vant-Hull, B; Gold, L; Zichi, D A

    2000-02-01

    A new paradigm for drug discovery and biological research has developed from technologies that integrate combinatorial chemistry with rounds of selection and amplification, a technique called in vitro selection or systematic evolution of ligands by exponential enrichment (SELEX). This overview unit discusses nucleic acid libraries that can be used, affinity probability distributions, an equilibrium model for SELEX, and optimal conditions including concentrations and signal-to-noise ratios.

  10. Sin(x)**2 + cos(x)**2 = 1. [programming identities using comparative combinatorial substitutions

    Science.gov (United States)

    Stoutemyer, D. R.

    1977-01-01

    Attempts to achieve tasteful automatic employment of the identities sin sq x + cos sq x = 1 and cos sq h x -sin sq h x = 1 in a manner which truly minimizes the complexity of the resulting expression are described. The disappointments of trigonometric reduction, trigonometric expansion, pattern matching, Poisson series, and Demoivre's theorem are related. The advantages of using the method of comparative combinatorial substitutions are illustrated.

  11. An Optimal Multi-Unit Combinatorial Procurement Auction with Single Minded Bidders

    CERN Document Server

    Gujar, Sujit

    2009-01-01

    The current art in optimal combinatorial auctions is limited to handling the case of single units of multiple items, with each bidder bidding on exactly one bundle (single minded bidders). This paper extends the current art by proposing an optimal auction for procuring multiple units of multiple items when the bidders are single minded. The auction minimizes the cost of procurement while satisfying Bayesian incentive compatibility and interim individual rationality. Under appropriate regularity conditions, this optimal auction also satisfies dominant strategy incentive compatibility.

  12. Some applications of W. Rudin's inequality to problems of combinatorial number theory

    CERN Document Server

    Shkredov, I D

    2010-01-01

    In the paper we obtain some new applications of well--known W. Rudin's theorem concerning lacunary series to problems of combinatorial number theory. We generalize a result of M.-C. Chang on L_2 (L)-norm of Fourier coefficients of a set (here L is a dissociated set), and prove a dual version of the theorem. Our main instrument is computing of eigenvalues of some operators.

  13. LDRD final report : robust analysis of large-scale combinatorial applications.

    Energy Technology Data Exchange (ETDEWEB)

    Carr, Robert D.; Morrison, Todd (University of Colorado, Denver, CO); Hart, William Eugene; Benavides, Nicolas L. (Santa Clara University, Santa Clara, CA); Greenberg, Harvey J. (University of Colorado, Denver, CO); Watson, Jean-Paul; Phillips, Cynthia Ann

    2007-09-01

    Discrete models of large, complex systems like national infrastructures and complex logistics frameworks naturally incorporate many modeling uncertainties. Consequently, there is a clear need for optimization techniques that can robustly account for risks associated with modeling uncertainties. This report summarizes the progress of the Late-Start LDRD 'Robust Analysis of Largescale Combinatorial Applications'. This project developed new heuristics for solving robust optimization models, and developed new robust optimization models for describing uncertainty scenarios.

  14. Deciphering Cis-Regulatory Element Mediated Combinatorial Regulation in Rice under Blast Infected Condition.

    Directory of Open Access Journals (Sweden)

    Arindam Deb

    Full Text Available Combinations of cis-regulatory elements (CREs present at the promoters facilitate the binding of several transcription factors (TFs, thereby altering the consequent gene expressions. Due to the eminent complexity of the regulatory mechanism, the combinatorics of CRE-mediated transcriptional regulation has been elusive. In this work, we have developed a new methodology that quantifies the co-occurrence tendencies of CREs present in a set of promoter sequences; these co-occurrence scores are filtered in three consecutive steps to test their statistical significance; and the significantly co-occurring CRE pairs are presented as networks. These networks of co-occurring CREs are further transformed to derive higher order of regulatory combinatorics. We have further applied this methodology on the differentially up-regulated gene-sets of rice tissues under fungal (Magnaporthe infected conditions to demonstrate how it helps to understand the CRE-mediated combinatorial gene regulation. Our analysis includes a wide spectrum of biologically important results. The CRE pairs having a strong tendency to co-occur often exhibit very similar joint distribution patterns at the promoters of rice. We couple the network approach with experimental results of plant gene regulation and defense mechanisms and find evidences of auto and cross regulation among TF families, cross-talk among multiple hormone signaling pathways, similarities and dissimilarities in regulatory combinatorics between different tissues, etc. Our analyses have pointed a highly distributed nature of the combinatorial gene regulation facilitating an efficient alteration in response to fungal attack. All together, our proposed methodology could be an important approach in understanding the combinatorial gene regulation. It can be further applied to unravel the tissue and/or condition specific combinatorial gene regulation in other eukaryotic systems with the availability of annotated genomic

  15. Deciphering Cis-Regulatory Element Mediated Combinatorial Regulation in Rice under Blast Infected Condition.

    Science.gov (United States)

    Deb, Arindam; Kundu, Sudip

    2015-01-01

    Combinations of cis-regulatory elements (CREs) present at the promoters facilitate the binding of several transcription factors (TFs), thereby altering the consequent gene expressions. Due to the eminent complexity of the regulatory mechanism, the combinatorics of CRE-mediated transcriptional regulation has been elusive. In this work, we have developed a new methodology that quantifies the co-occurrence tendencies of CREs present in a set of promoter sequences; these co-occurrence scores are filtered in three consecutive steps to test their statistical significance; and the significantly co-occurring CRE pairs are presented as networks. These networks of co-occurring CREs are further transformed to derive higher order of regulatory combinatorics. We have further applied this methodology on the differentially up-regulated gene-sets of rice tissues under fungal (Magnaporthe) infected conditions to demonstrate how it helps to understand the CRE-mediated combinatorial gene regulation. Our analysis includes a wide spectrum of biologically important results. The CRE pairs having a strong tendency to co-occur often exhibit very similar joint distribution patterns at the promoters of rice. We couple the network approach with experimental results of plant gene regulation and defense mechanisms and find evidences of auto and cross regulation among TF families, cross-talk among multiple hormone signaling pathways, similarities and dissimilarities in regulatory combinatorics between different tissues, etc. Our analyses have pointed a highly distributed nature of the combinatorial gene regulation facilitating an efficient alteration in response to fungal attack. All together, our proposed methodology could be an important approach in understanding the combinatorial gene regulation. It can be further applied to unravel the tissue and/or condition specific combinatorial gene regulation in other eukaryotic systems with the availability of annotated genomic sequences and suitable

  16. Combinatorial Laplacian and entropy of simplicial complexes associated with complex networks

    Science.gov (United States)

    Maletić, S.; Rajković, M.

    2012-09-01

    Simplicial complexes represent useful and accurate models of complex networks and complex systems in general. We explore the properties of spectra of combinatorial Laplacian operator of simplicial complexes and show its relationship with connectivity properties of the Q-vector and with connectivities of cliques in the simplicial clique complex. We demonstrate the need for higher order analysis in complex networks and compare the results with ordinary graph spectra. Methods and results are obtained using social network of the Zachary karate club.

  17. A review of simheuristics: Extending metaheuristics to deal with stochastic combinatorial optimization problems

    OpenAIRE

    Juan, Angel A.; Javier Faulin; Scott E. Grasman; Markus Rabe; Gonçalo Figueira

    2015-01-01

    Many combinatorial optimization problems (COPs) encountered in real-world logistics, transportation, production, healthcare, financial, telecommunication, and computing applications are NP-hard in nature. These real-life COPs are frequently characterized by their large-scale sizes and the need for obtaining high-quality solutions in short computing times, thus requiring the use of metaheuristic algorithms. Metaheuristics benefit from different random-search and parallelization paradigms, but ...

  18. Sin(x)**2 + cos(x)**2 = 1. [programming identities using comparative combinatorial substitutions

    Science.gov (United States)

    Stoutemyer, D. R.

    1977-01-01

    Attempts to achieve tasteful automatic employment of the identities sin sq x + cos sq x = 1 and cos sq h x -sin sq h x = 1 in a manner which truly minimizes the complexity of the resulting expression are described. The disappointments of trigonometric reduction, trigonometric expansion, pattern matching, Poisson series, and Demoivre's theorem are related. The advantages of using the method of comparative combinatorial substitutions are illustrated.

  19. Radical scavenging potentials of single and combinatorial herbal formulations in vitro

    OpenAIRE

    2015-01-01

    Reactive oxygen and nitrogen species (RONS) are involved in deleterious/beneficial biological processes. The present study sought to investigate the capacity of single and combinatorial herbal formulations of Acanthus montanus, Emilia coccinea, Hibiscus rosasinensis, and Asystasia gangetica to act as superoxide radicals (SOR), hydrogen peroxide (HP), nitric oxide radical (NOR), hydroxyl radical (HR), and 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical antagonists using in vitro models. The herba...

  20. Characterization of photoelectric properties and composition effect of TiO(2)/ZnO/Fe(2)O(3) composite by combinatorial methodology.

    Science.gov (United States)

    Liao, Yichuan; Li, Huayao; Liu, Yuan; Zou, Zhijun; Zeng, Dawen; Xie, Changsheng

    2010-11-01

    On the basis of combinatorial methodology and the idea of an equilateral ingredient triangle, the TiO(2)/ZnO/Fe(2)O(3) composite system including 66 ingredient points was designed. The photocurrents under different light sources and bias voltages were measured, and the photocurrent amplitude at 300 s was chosen as a parameter to evaluate the photoelectric response of the composite. To appraise the composition effect of the composite compared with pure materials, the quantitative formula of the composition effect has been provided for the first time in this paper. We found that not all the ingredient points demonstrated the enhanced composition effect in the as-designed ingredient triangle material library. The reasons of different composition effect for different ingredient points have been discussed in detail. X-ray diffraction (XRD) and field emission scanning electron microscopy (FE-SEM) were used to investigate the phase structure and the grain morphology of the composite.