Graphs and Matrices: Combinatorial Analysis, Competitions, Covers and Ranks

DTIC Science & Technology

1993-09-30

Math (J.R. Lundgren and S. Merz). 6. "Competition Graphs of Strongly Connected and Hamiltonian Digraphs," submitted to SIAM Journal of Discrete Math (K...34 Congressus Numerantium 91 (1992), 55-62 (J.R. Lundgren and J. Maybee with G. Bain). 14. "Interval Competition Graphs of Symmetric Digraphs," Discrete Math 119...1993), 113-122 (J.R. Lundgren and J. Maybee with C. Rasmussen). 15. "Two-Step Graphs of Trees," Discrete Math 119 (1993), 123-139 (J.R. Lundgren

Analytical instrumentation infrastructure for combinatorial and high-throughput development of formulated discrete and gradient polymeric sensor materials arrays

NASA Astrophysics Data System (ADS)

Potyrailo, Radislav A.; Hassib, Lamyaa

2005-06-01

Multicomponent polymer-based formulations of optical sensor materials are difficult and time consuming to optimize using conventional approaches. To address these challenges, our long-term goal is to determine relationships between sensor formulation and sensor response parameters using new scientific methodologies. As the first step, we have designed and implemented an automated analytical instrumentation infrastructure for combinatorial and high-throughput development of polymeric sensor materials for optical sensors. Our approach is based on the fabrication and performance screening of discrete and gradient sensor arrays. Simultaneous formation of multiple sensor coatings into discrete 4×6, 6×8, and 8×12 element arrays (3-15μL volume per element) and their screening provides not only a well-recognized acceleration in the screening rate, but also considerably reduces or even eliminates sources of variability, which are randomly affecting sensors response during a conventional one-at-a-time sensor coating evaluation. The application of gradient sensor arrays provides additional capabilities for rapid finding of the optimal formulation parameters.

One-Dimensional Czedli-Type Islands

ERIC Educational Resources Information Center

Horvath, Eszter K.; Mader, Attila; Tepavcevic, Andreja

2011-01-01

The notion of an island has surfaced in recent algebra and coding theory research. Discrete versions provide interesting combinatorial problems. This paper presents the one-dimensional case with finitely many heights, a topic convenient for student research.

Combinatorial-topological framework for the analysis of global dynamics.

PubMed

Bush, Justin; Gameiro, Marcio; Harker, Shaun; Kokubu, Hiroshi; Mischaikow, Konstantin; Obayashi, Ippei; Pilarczyk, Paweł

2012-12-01

We discuss an algorithmic framework based on efficient graph algorithms and algebraic-topological computational tools. The framework is aimed at automatic computation of a database of global dynamics of a given m-parameter semidynamical system with discrete time on a bounded subset of the n-dimensional phase space. We introduce the mathematical background, which is based upon Conley's topological approach to dynamics, describe the algorithms for the analysis of the dynamics using rectangular grids both in phase space and parameter space, and show two sample applications.

Combinatorial-topological framework for the analysis of global dynamics

NASA Astrophysics Data System (ADS)

Bush, Justin; Gameiro, Marcio; Harker, Shaun; Kokubu, Hiroshi; Mischaikow, Konstantin; Obayashi, Ippei; Pilarczyk, Paweł

2012-12-01

We discuss an algorithmic framework based on efficient graph algorithms and algebraic-topological computational tools. The framework is aimed at automatic computation of a database of global dynamics of a given m-parameter semidynamical system with discrete time on a bounded subset of the n-dimensional phase space. We introduce the mathematical background, which is based upon Conley's topological approach to dynamics, describe the algorithms for the analysis of the dynamics using rectangular grids both in phase space and parameter space, and show two sample applications.

Precursors to language: Social cognition and pragmatic inference in primates.

PubMed

Seyfarth, Robert M; Cheney, Dorothy L

2017-02-01

Despite their differences, human language and the vocal communication of nonhuman primates share many features. Both constitute forms of coordinated activity, rely on many shared neural mechanisms, and involve discrete, combinatorial cognition that includes rich pragmatic inference. These common features suggest that during evolution the ancestors of all modern primates faced similar social problems and responded with similar systems of communication and cognition. When language later evolved from this common foundation, many of its distinctive features were already present.

Partial differential equations constrained combinatorial optimization on an adiabatic quantum computer

NASA Astrophysics Data System (ADS)

Chandra, Rishabh

Partial differential equation-constrained combinatorial optimization (PDECCO) problems are a mixture of continuous and discrete optimization problems. PDECCO problems have discrete controls, but since the partial differential equations (PDE) are continuous, the optimization space is continuous as well. Such problems have several applications, such as gas/water network optimization, traffic optimization, micro-chip cooling optimization, etc. Currently, no efficient classical algorithm which guarantees a global minimum for PDECCO problems exists. A new mapping has been developed that transforms PDECCO problem, which only have linear PDEs as constraints, into quadratic unconstrained binary optimization (QUBO) problems that can be solved using an adiabatic quantum optimizer (AQO). The mapping is efficient, it scales polynomially with the size of the PDECCO problem, requires only one PDE solve to form the QUBO problem, and if the QUBO problem is solved correctly and efficiently on an AQO, guarantees a global optimal solution for the original PDECCO problem.

Projective Ponzano-Regge spin networks and their symmetries

NASA Astrophysics Data System (ADS)

Aquilanti, Vincenzo; Marzuoli, Annalisa

2018-02-01

We present a novel hierarchical construction of projective spin networks of the Ponzano-Regge type from an assembling of five quadrangles up to the combinatorial 4-simplex compatible with a geometrical realization in Euclidean 4-space. The key ingredients are the projective Desargues configuration and the incidence structure given by its space-dual, on the one hand, and the Biedenharn-Elliott identity for the 6j symbol of SU(2), on the other. The interplay between projective-combinatorial and algebraic features relies on the recoupling theory of angular momenta, an approach to discrete quantum gravity models carried out successfully over the last few decades. The role of Regge symmetry-an intriguing discrete symmetry of the 6j which goes beyond the standard tetrahedral symmetry of this symbol-will be also discussed in brief to highlight its role in providing a natural regularization of projective spin networks that somehow mimics the standard regularization through a q-deformation of SU(2).

Beyond Aztec Castles: Toric Cascades in the dP 3 Quiver

NASA Astrophysics Data System (ADS)

Lai, Tri; Musiker, Gregg

2017-12-01

Given one of an infinite class of supersymmetric quiver gauge theories, string theorists can associate a corresponding toric variety (which is a Calabi-Yau 3-fold) as well as an associated combinatorial model known as a brane tiling. In combinatorial language, a brane tiling is a bipartite graph on a torus and its perfect matchings are of interest to both combinatorialists and physicists alike. A cluster algebra may also be associated to such quivers and in this paper we study the generators of this algebra, known as cluster variables, for the quiver associated to the cone over the del Pezzo surface d P 3. In particular, mutation sequences involving mutations exclusively at vertices with two in-coming arrows and two out-going arrows are referred to as toric cascades in the string theory literature. Such toric cascades give rise to interesting discrete integrable systems on the level of cluster variable dynamics. We provide an explicit algebraic formula for all cluster variables that are reachable by toric cascades as well as a combinatorial interpretation involving perfect matchings of subgraphs of the d P 3 brane tiling for these formulas in most cases.

An application of different dioids in public key cryptography

DOE Office of Scientific and Technical Information (OSTI.GOV)

Durcheva, Mariana I., E-mail: mdurcheva66@gmail.com

2014-11-18

Dioids provide a natural framework for analyzing a broad class of discrete event dynamical systems such as the design and analysis of bus and railway timetables, scheduling of high-throughput industrial processes, solution of combinatorial optimization problems, the analysis and improvement of flow systems in communication networks. They have appeared in several branches of mathematics such as functional analysis, optimization, stochastic systems and dynamic programming, tropical geometry, fuzzy logic. In this paper we show how to involve dioids in public key cryptography. The main goal is to create key – exchange protocols based on dioids. Additionally the digital signature scheme ismore » presented.« less

A combinatorial morphospace for angiosperm pollen

NASA Astrophysics Data System (ADS)

Mander, Luke

2016-04-01

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

Applications of algebraic topology to compatible spatial discretizations.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bochev, Pavel Blagoveston; Hyman, James M.

We provide a common framework for compatible discretizations using algebraic topology to guide our analysis. The main concept is the natural inner product on cochains, which induces a combinatorial Hodge theory. The framework comprises of mutually consistent operations of differentiation and integration, has a discrete Stokes theorem, and preserves the invariants of the DeRham cohomology groups. The latter allows for an elementary calculation of the kernel of the discrete Laplacian. Our framework provides an abstraction that includes examples of compatible finite element, finite volume and finite difference methods. We describe how these methods result from the choice of a reconstructionmore » operator and when they are equivalent.« less

Combinatorial invariants and covariants as tools for conical intersections.

PubMed

Ryb, Itai; Baer, Roi

2004-12-01

The combinatorial invariant and covariant are introduced as practical tools for analysis of conical intersections in molecules. The combinatorial invariant is a quantity depending on adiabatic electronic states taken at discrete nuclear configuration points. It is invariant to the phase choice (gauge) of these states. In the limit that the points trace a loop in nuclear configuration space, the value of the invariant approaches the corresponding Berry phase factor. The Berry phase indicates the presence of an odd or even number of conical intersections on surfaces bounded by these loops. Based on the combinatorial invariant, we develop a computationally simple and efficient method for locating conical intersections. The method is robust due to its use of gauge invariant nature. It does not rely on the landscape of intersecting potential energy surfaces nor does it require the computation of nonadiabatic couplings. We generalize the concept to open paths and combinatorial covariants for higher dimensions obtaining a technique for the construction of the gauge-covariant adiabatic-diabatic transformation matrix. This too does not make use of nonadiabatic couplings. The importance of using gauge-covariant expressions is underlined throughout. These techniques can be readily implemented by standard quantum chemistry codes. (c) 2004 American Institute of Physics.

Computation of the area in the discrete plane: Green's theorem revisited

NASA Astrophysics Data System (ADS)

Chalifour, Alain; Nouboud, Fathallah; Voisin, Yvon

2017-11-01

The detection of the contour of a binary object is a common problem; however, the area of a region, and its moments, can be a significant parameter. In several metrology applications, the area of planar objects must be measured. The area is obtained by counting the pixels inside the contour or using a discrete version of Green's formula. Unfortunately, we obtain the area enclosed by the polygonal line passing through the centers of the pixels along the contour. We present a modified version of Green's theorem in the discrete plane, which allows for the computation of the exact area of a two-dimensional region in the class of polyominoes. Penalties are introduced and associated with each successive pair of Freeman displacements along the contour in an eight-connectivity system. The proposed equation is shown to be true and properties of the equation related to the topology of the regions are presented. The proposed approach is adapted for faster computation than the combinatorial approach proposed in the literature.

Gesellschaft fuer angewandte Mathematik und Mechanik, Annual Scientific Meeting, Technische Universitaet Berlin, Berlin, West Germany, April 8-11, 1980, Reports. Parts 1 & 2

NASA Astrophysics Data System (ADS)

1981-04-01

The main topics discussed were related to nonparametric statistics, plane and antiplane states in finite elasticity, free-boundary-variational inequalities, the numerical solution of free boundary-value problems, discrete and combinatorial optimization, mathematical modelling in fluid mechanics, a survey and comparison regarding thermodynamic theories, invariant and almost invariant subspaces in linear systems with applications to disturbance isolation, nonlinear acoustics, and methods of function theory in the case of partial differential equations, giving particular attention to elliptic problems in the plane.

Landscape Encodings Enhance Optimization

PubMed Central

Klemm, Konstantin; Mehta, Anita; Stadler, Peter F.

2012-01-01

Hard combinatorial optimization problems deal with the search for the minimum cost solutions (ground states) of discrete systems under strong constraints. A transformation of state variables may enhance computational tractability. It has been argued that these state encodings are to be chosen invertible to retain the original size of the state space. Here we show how redundant non-invertible encodings enhance optimization by enriching the density of low-energy states. In addition, smooth landscapes may be established on encoded state spaces to guide local search dynamics towards the ground state. PMID:22496860

Fractional Programming for Communication Systems—Part II: Uplink Scheduling via Matching

NASA Astrophysics Data System (ADS)

Shen, Kaiming; Yu, Wei

2018-05-01

This two-part paper develops novel methodologies for using fractional programming (FP) techniques to design and optimize communication systems. Part I of this paper proposes a new quadratic transform for FP and treats its application for continuous optimization problems. In this Part II of the paper, we study discrete problems, such as those involving user scheduling, which are considerably more difficult to solve. Unlike the continuous problems, discrete or mixed discrete-continuous problems normally cannot be recast as convex problems. In contrast to the common heuristic of relaxing the discrete variables, this work reformulates the original problem in an FP form amenable to distributed combinatorial optimization. The paper illustrates this methodology by tackling the important and challenging problem of uplink coordinated multi-cell user scheduling in wireless cellular systems. Uplink scheduling is more challenging than downlink scheduling, because uplink user scheduling decisions significantly affect the interference pattern in nearby cells. Further, the discrete scheduling variable needs to be optimized jointly with continuous variables such as transmit power levels and beamformers. The main idea of the proposed FP approach is to decouple the interaction among the interfering links, thereby permitting a distributed and joint optimization of the discrete and continuous variables with provable convergence. The paper shows that the well-known weighted minimum mean-square-error (WMMSE) algorithm can also be derived from a particular use of FP; but our proposed FP-based method significantly outperforms WMMSE when discrete user scheduling variables are involved, both in term of run-time efficiency and optimizing results.

Cuisenaire Rods Go to College.

ERIC Educational Resources Information Center

Chinn, Phyllis; And Others

1992-01-01

Presents examples of questions and answers arising from a hands-on and exploratory approach to discrete mathematics using cuisenaire rods. Combinatorial questions about trains formed of cuisenaire rods provide the setting for discovering numerical patterns by experimentation and organizing the results using induction and successive differences.…

Solar Proton Transport Within an ICRU Sphere Surrounded by a Complex Shield: Ray-trace Geometry

NASA Technical Reports Server (NTRS)

Slaba, Tony C.; Wilson, John W.; Badavi, Francis F.; Reddell, Brandon D.; Bahadori, Amir A.

2015-01-01

A computationally efficient 3DHZETRN code with enhanced neutron and light ion (Z is less than or equal to 2) propagation was recently developed for complex, inhomogeneous shield geometry described by combinatorial objects. Comparisons were made between 3DHZETRN results and Monte Carlo (MC) simulations at locations within the combinatorial geometry, and it was shown that 3DHZETRN agrees with the MC codes to the extent they agree with each other. In the present report, the 3DHZETRN code is extended to enable analysis in ray-trace geometry. This latest extension enables the code to be used within current engineering design practices utilizing fully detailed vehicle and habitat geometries. Through convergence testing, it is shown that fidelity in an actual shield geometry can be maintained in the discrete ray-trace description by systematically increasing the number of discrete rays used. It is also shown that this fidelity is carried into transport procedures and resulting exposure quantities without sacrificing computational efficiency.

Solar proton exposure of an ICRU sphere within a complex structure part II: Ray-trace geometry.

PubMed

Slaba, Tony C; Wilson, John W; Badavi, Francis F; Reddell, Brandon D; Bahadori, Amir A

2016-06-01

A computationally efficient 3DHZETRN code with enhanced neutron and light ion (Z ≤ 2) propagation was recently developed for complex, inhomogeneous shield geometry described by combinatorial objects. Comparisons were made between 3DHZETRN results and Monte Carlo (MC) simulations at locations within the combinatorial geometry, and it was shown that 3DHZETRN agrees with the MC codes to the extent they agree with each other. In the present report, the 3DHZETRN code is extended to enable analysis in ray-trace geometry. This latest extension enables the code to be used within current engineering design practices utilizing fully detailed vehicle and habitat geometries. Through convergence testing, it is shown that fidelity in an actual shield geometry can be maintained in the discrete ray-trace description by systematically increasing the number of discrete rays used. It is also shown that this fidelity is carried into transport procedures and resulting exposure quantities without sacrificing computational efficiency. Published by Elsevier Ltd.

The Building Game: From Enumerative Combinatorics to Conformational Diffusion

NASA Astrophysics Data System (ADS)

Johnson-Chyzhykov, Daniel; Menon, Govind

2016-08-01

We study a discrete attachment model for the self-assembly of polyhedra called the building game. We investigate two distinct aspects of the model: (i) enumerative combinatorics of the intermediate states and (ii) a notion of Brownian motion for the polyhedral linkage defined by each intermediate that we term conformational diffusion. The combinatorial configuration space of the model is computed for the Platonic, Archimedean, and Catalan solids of up to 30 faces, and several novel enumerative results are generated. These represent the most exhaustive computations of this nature to date. We further extend the building game to include geometric information. The combinatorial structure of each intermediate yields a systems of constraints specifying a polyhedral linkage and its moduli space. We use a random walk to simulate a reflected Brownian motion in each moduli space. Empirical statistics of the random walk may be used to define the rates of transition for a Markov process modeling the process of self-assembly.

Discrete exterior calculus discretization of incompressible Navier-Stokes equations over surface simplicial meshes

NASA Astrophysics Data System (ADS)

Mohamed, Mamdouh S.; Hirani, Anil N.; Samtaney, Ravi

2016-05-01

A conservative discretization of incompressible Navier-Stokes equations is developed based on discrete exterior calculus (DEC). A distinguishing feature of our method is the use of an algebraic discretization of the interior product operator and a combinatorial discretization of the wedge product. The governing equations are first rewritten using the exterior calculus notation, replacing vector calculus differential operators by the exterior derivative, Hodge star and wedge product operators. The discretization is then carried out by substituting with the corresponding discrete operators based on the DEC framework. Numerical experiments for flows over surfaces reveal a second order accuracy for the developed scheme when using structured-triangular meshes, and first order accuracy for otherwise unstructured meshes. By construction, the method is conservative in that both mass and vorticity are conserved up to machine precision. The relative error in kinetic energy for inviscid flow test cases converges in a second order fashion with both the mesh size and the time step.

Combinatorial Multiobjective Optimization Using Genetic Algorithms

NASA Technical Reports Server (NTRS)

Crossley, William A.; Martin. Eric T.

2002-01-01

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

Counting It Twice.

ERIC Educational Resources Information Center

Schattschneider, Doris

1991-01-01

Provided are examples from many domains of mathematics that illustrate the Fubini Principle in its discrete version: the value of a summation over a rectangular array is independent of the order of summation. Included are: counting using partitions as in proof by pictures, combinatorial arguments, indirect counting as in the inclusion-exclusion…

Genetic Networks and Anticipation of Gene Expression Patterns

NASA Astrophysics Data System (ADS)

Gebert, J.; Lätsch, M.; Pickl, S. W.; Radde, N.; Weber, G.-W.; Wünschiers, R.

2004-08-01

An interesting problem for computational biology is the analysis of time-series expression data. Here, the application of modern methods from dynamical systems, optimization theory, numerical algorithms and the utilization of implicit discrete information lead to a deeper understanding. In [1], we suggested to represent the behavior of time-series gene expression patterns by a system of ordinary differential equations, which we analytically and algorithmically investigated under the parametrical aspect of stability or instability. Our algorithm strongly exploited combinatorial information. In this paper, we deepen, extend and exemplify this study from the viewpoint of underlying mathematical modelling. This modelling consists in evaluating DNA-microarray measurements as the basis of anticipatory prediction, in the choice of a smooth model given by differential equations, in an approach of the right-hand side with parametric matrices, and in a discrete approximation which is a least squares optimization problem. We give a mathematical and biological discussion, and pay attention to the special case of a linear system, where the matrices do not depend on the state of expressions. Here, we present first numerical examples.

Optimal Iterative Task Scheduling for Parallel Simulations.

DTIC Science & Technology

1991-03-01

State University, Pullman, Washington. November 1976. 19. Grimaldi , Ralph P . Discrete and Combinatorial Mathematics. Addison-Wesley. June 1989. 20...2 4.8.1 Problem Description .. .. .. .. ... .. ... .... 4-25 4.8.2 Reasons for Level-Strate- p Failure. .. .. .. .. ... 4-26...f- I CA A* overview................................ C-1 C .2 Sample A* r......................... .... C-I C-3 Evaluation P

Transversal homoclinic orbits in a transiently chaotic neural network.

PubMed

Chen, Shyan-Shiou; Shih, Chih-Wen

2002-09-01

We study the existence of snap-back repellers, hence the existence of transversal homoclinic orbits in a discrete-time neural network. Chaotic behaviors for the network system in the sense of Li and Yorke or Marotto can then be concluded. The result is established by analyzing the structures of the system and allocating suitable parameters in constructing the fixed points and their pre-images for the system. The investigation provides a theoretical confirmation on the scenario of transient chaos for the system. All the parameter conditions for the theory can be examined numerically. The numerical ranges for the parameters which yield chaotic dynamics and convergent dynamics provide significant information in the annealing process in solving combinatorial optimization problems using this transiently chaotic neural network. (c) 2002 American Institute of Physics.

Quadratic constrained mixed discrete optimization with an adiabatic quantum optimizer

NASA Astrophysics Data System (ADS)

Chandra, Rishabh; Jacobson, N. Tobias; Moussa, Jonathan E.; Frankel, Steven H.; Kais, Sabre

2014-07-01

We extend the family of problems that may be implemented on an adiabatic quantum optimizer (AQO). When a quadratic optimization problem has at least one set of discrete controls and the constraints are linear, we call this a quadratic constrained mixed discrete optimization (QCMDO) problem. QCMDO problems are NP-hard, and no efficient classical algorithm for their solution is known. Included in the class of QCMDO problems are combinatorial optimization problems constrained by a linear partial differential equation (PDE) or system of linear PDEs. An essential complication commonly encountered in solving this type of problem is that the linear constraint may introduce many intermediate continuous variables into the optimization while the computational cost grows exponentially with problem size. We resolve this difficulty by developing a constructive mapping from QCMDO to quadratic unconstrained binary optimization (QUBO) such that the size of the QUBO problem depends only on the number of discrete control variables. With a suitable embedding, taking into account the physical constraints of the realizable coupling graph, the resulting QUBO problem can be implemented on an existing AQO. The mapping itself is efficient, scaling cubically with the number of continuous variables in the general case and linearly in the PDE case if an efficient preconditioner is available.

The disadvantage of combinatorial communication.

PubMed Central

Lachmann, Michael; Bergstrom, Carl T.

2004-01-01

Combinatorial communication allows rapid and efficient transfer of detailed information, yet combinatorial communication is used by few, if any, non-human species. To complement recent studies illustrating the advantages of combinatorial communication, we highlight a critical disadvantage. We use the concept of information value to show that deception poses a greater and qualitatively different threat to combinatorial signalling than to non-combinatorial systems. This additional potential for deception may represent a strategic barrier that has prevented widespread evolution of combinatorial communication. Our approach has the additional benefit of drawing clear distinctions among several types of deception that can occur in communication systems. PMID:15556886

The disadvantage of combinatorial communication.

PubMed

Lachmann, Michael; Bergstrom, Carl T

2004-11-22

Combinatorial communication allows rapid and efficient transfer of detailed information, yet combinatorial communication is used by few, if any, non-human species. To complement recent studies illustrating the advantages of combinatorial communication, we highlight a critical disadvantage. We use the concept of information value to show that deception poses a greater and qualitatively different threat to combinatorial signalling than to non-combinatorial systems. This additional potential for deception may represent a strategic barrier that has prevented widespread evolution of combinatorial communication. Our approach has the additional benefit of drawing clear distinctions among several types of deception that can occur in communication systems.

Simulating Serious Games: A Discrete-Time Computational Model Based on Cognitive Flow Theory

ERIC Educational Resources Information Center

Westera, Wim

2018-01-01

This paper presents a computational model for simulating how people learn from serious games. While avoiding the combinatorial explosion of a games micro-states, the model offers a meso-level pathfinding approach, which is guided by cognitive flow theory and various concepts from learning sciences. It extends a basic, existing model by exposing…

An Analysis of Statements of the Multiplication Principle in Combinatorics, Discrete, and Finite Mathematics Textbooks

ERIC Educational Resources Information Center

Lockwood, Elise; Reed, Zackery; Caughman, John S.

2017-01-01

The multiplication principle serves as a cornerstone in enumerative combinatorics. The principle underpins many basic counting formulas and provides students with a critical element of combinatorial justification. Given its importance, the way in which it is presented in textbooks is surprisingly varied. In this paper, we analyze a number of…

RNA Secondary Structure Prediction by Using Discrete Mathematics: An Interdisciplinary Research Experience for Undergraduate Students

ERIC Educational Resources Information Center

Ellington, Roni; Wachira, James; Nkwanta, Asamoah

2010-01-01

The focus of this Research Experience for Undergraduates (REU) project was on RNA secondary structure prediction by using a lattice walk approach. The lattice walk approach is a combinatorial and computational biology method used to enumerate possible secondary structures and predict RNA secondary structure from RNA sequences. The method uses…

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

PubMed

Scott-Phillips, Thomas C; Blythe, Richard A

2013-11-06

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

Dynamic combinatorial libraries: new opportunities in systems chemistry.

PubMed

Hunt, Rosemary A R; Otto, Sijbren

2011-01-21

Combinatorial chemistry is a tool for selecting molecules with special properties. Dynamic combinatorial chemistry started off aiming to be just that. However, unlike ordinary combinatorial chemistry, the interconnectedness of dynamic libraries gives them an extra dimension. An understanding of these molecular networks at systems level is essential for their use as a selection tool and creates exciting new opportunities in systems chemistry. In this feature article we discuss selected examples and considerations related to the advanced exploitation of dynamic combinatorial libraries for their originally conceived purpose of identifying strong binding interactions. Also reviewed are examples illustrating a trend towards increasing complexity in terms of network behaviour and reversible chemistry. Finally, new applications of dynamic combinatorial chemistry in self-assembly, transport and self-replication are discussed.

A combinatorial approach to angiosperm pollen morphology.

PubMed

Mander, Luke

2016-11-30

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

A combinatorial approach to angiosperm pollen morphology

PubMed Central

2016-01-01

Angiosperms (flowering plants) are strikingly diverse. This is clearly expressed in the morphology of their pollen grains, which are characterized by enormous variety in their shape and patterning. In this paper, I approach angiosperm pollen morphology from the perspective of enumerative combinatorics. This involves generating angiosperm pollen morphotypes by algorithmically combining character states and enumerating the results of these combinations. I use this approach to generate 3 643 200 pollen morphotypes, which I visualize using a parallel-coordinates plot. This represents a raw morphospace. To compare real-world and theoretical morphologies, I map the pollen of 1008 species of Neotropical angiosperms growing on Barro Colorado Island (BCI), Panama, onto this raw morphospace. This highlights that, in addition to their well-documented taxonomic diversity, Neotropical rainforests also represent an enormous reservoir of morphological diversity. Angiosperm pollen morphospace at BCI has been filled mostly by pollen morphotypes that are unique to single plant species. Repetition of pollen morphotypes among higher taxa at BCI reflects both constraint and convergence. This combinatorial approach to morphology addresses the complexity that results from large numbers of discrete character combinations and could be employed in any situation where organismal form can be captured by discrete morphological characters. PMID:27881756

Ant algorithms for discrete optimization.

PubMed

Dorigo, M; Di Caro, G; Gambardella, L M

1999-01-01

This article presents an overview of recent work on ant algorithms, that is, algorithms for discrete optimization that took inspiration from the observation of ant colonies' foraging behavior, and introduces the ant colony optimization (ACO) metaheuristic. In the first part of the article the basic biological findings on real ants are reviewed and their artificial counterparts as well as the ACO metaheuristic are defined. In the second part of the article a number of applications of ACO algorithms to combinatorial optimization and routing in communications networks are described. We conclude with a discussion of related work and of some of the most important aspects of the ACO metaheuristic.

Analysis of Streamline Separation at Infinity Using Time-Discrete Markov Chains.

PubMed

Reich, W; Scheuermann, G

2012-12-01

Existing methods for analyzing separation of streamlines are often restricted to a finite time or a local area. In our paper we introduce a new method that complements them by allowing an infinite-time-evaluation of steady planar vector fields. Our algorithm unifies combinatorial and probabilistic methods and introduces the concept of separation in time-discrete Markov-Chains. We compute particle distributions instead of the streamlines of single particles. We encode the flow into a map and then into a transition matrix for each time direction. Finally, we compare the results of our grid-independent algorithm to the popular Finite-Time-Lyapunov-Exponents and discuss the discrepancies.

Combinatorial materials synthesis and high-throughput screening: an integrated materials chip approach to mapping phase diagrams and discovery and optimization of functional materials.

PubMed

Xiang, X D

Combinatorial materials synthesis methods and high-throughput evaluation techniques have been developed to accelerate the process of materials discovery and optimization and phase-diagram mapping. Analogous to integrated circuit chips, integrated materials chips containing thousands of discrete different compositions or continuous phase diagrams, often in the form of high-quality epitaxial thin films, can be fabricated and screened for interesting properties. Microspot x-ray method, various optical measurement techniques, and a novel evanescent microwave microscope have been used to characterize the structural, optical, magnetic, and electrical properties of samples on the materials chips. These techniques are routinely used to discover/optimize and map phase diagrams of ferroelectric, dielectric, optical, magnetic, and superconducting materials.

Multiclass Data Segmentation using Diffuse Interface Methods on Graphs

DTIC Science & Technology

2014-01-01

37] that performs interac- tive image segmentation using the solution to a combinatorial Dirichlet problem. Elmoataz et al . have developed general...izations of the graph Laplacian [25] for image denoising and manifold smoothing. Couprie et al . in [18] define a conve- niently parameterized graph...continuous setting carry over to the discrete graph representation. For general data segmentation, Bresson et al . in [8], present rigorous convergence

Further Results on Constructions of Generalized Bent Boolean Functions

DTIC Science & Technology

2016-03-01

China; 2Naval Postgraduate School, Applied Mathematics Department, Monterey, CA 93943, USA; 3Science and Technology on Communication Security...in 1976 as an interesting combinatorial object with the important property of having op- timal nonlinearity [1]. Since bent functions have many...77–94 10 Zhao Y, Li H L. On bent functions with some symmet- ric properties. Discret Appl Math, 2006, 154: 2537– 2543

Some unsolved problems in discrete mathematics and mathematical cybernetics

NASA Astrophysics Data System (ADS)

Korshunov, Aleksei D.

2009-10-01

There are many unsolved problems in discrete mathematics and mathematical cybernetics. Writing a comprehensive survey of such problems involves great difficulties. First, such problems are rather numerous and varied. Second, they greatly differ from each other in degree of completeness of their solution. Therefore, even a comprehensive survey should not attempt to cover the whole variety of such problems; only the most important and significant problems should be reviewed. An impersonal choice of problems to include is quite hard. This paper includes 13 unsolved problems related to combinatorial mathematics and computational complexity theory. The problems selected give an indication of the author's studies for 50 years; for this reason, the choice of the problems reviewed here is, to some extent, subjective. At the same time, these problems are very difficult and quite important for discrete mathematics and mathematical cybernetics. Bibliography: 74 items.

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

PubMed

Li, Jianwei; Nowak, Piotr; Otto, Sijbren

2013-06-26

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

Utilization of the Discrete Differential Evolution for Optimization in Multidimensional Point Clouds.

PubMed

Uher, Vojtěch; Gajdoš, Petr; Radecký, Michal; Snášel, Václav

2016-01-01

The Differential Evolution (DE) is a widely used bioinspired optimization algorithm developed by Storn and Price. It is popular for its simplicity and robustness. This algorithm was primarily designed for real-valued problems and continuous functions, but several modified versions optimizing both integer and discrete-valued problems have been developed. The discrete-coded DE has been mostly used for combinatorial problems in a set of enumerative variants. However, the DE has a great potential in the spatial data analysis and pattern recognition. This paper formulates the problem as a search of a combination of distinct vertices which meet the specified conditions. It proposes a novel approach called the Multidimensional Discrete Differential Evolution (MDDE) applying the principle of the discrete-coded DE in discrete point clouds (PCs). The paper examines the local searching abilities of the MDDE and its convergence to the global optimum in the PCs. The multidimensional discrete vertices cannot be simply ordered to get a convenient course of the discrete data, which is crucial for good convergence of a population. A novel mutation operator utilizing linear ordering of spatial data based on the space filling curves is introduced. The algorithm is tested on several spatial datasets and optimization problems. The experiments show that the MDDE is an efficient and fast method for discrete optimizations in the multidimensional point clouds.

Utilization of the Discrete Differential Evolution for Optimization in Multidimensional Point Clouds

PubMed Central

Radecký, Michal; Snášel, Václav

2016-01-01

The Differential Evolution (DE) is a widely used bioinspired optimization algorithm developed by Storn and Price. It is popular for its simplicity and robustness. This algorithm was primarily designed for real-valued problems and continuous functions, but several modified versions optimizing both integer and discrete-valued problems have been developed. The discrete-coded DE has been mostly used for combinatorial problems in a set of enumerative variants. However, the DE has a great potential in the spatial data analysis and pattern recognition. This paper formulates the problem as a search of a combination of distinct vertices which meet the specified conditions. It proposes a novel approach called the Multidimensional Discrete Differential Evolution (MDDE) applying the principle of the discrete-coded DE in discrete point clouds (PCs). The paper examines the local searching abilities of the MDDE and its convergence to the global optimum in the PCs. The multidimensional discrete vertices cannot be simply ordered to get a convenient course of the discrete data, which is crucial for good convergence of a population. A novel mutation operator utilizing linear ordering of spatial data based on the space filling curves is introduced. The algorithm is tested on several spatial datasets and optimization problems. The experiments show that the MDDE is an efficient and fast method for discrete optimizations in the multidimensional point clouds. PMID:27974884

Multiclass Data Segmentation Using Diffuse Interface Methods on Graphs

DTIC Science & Technology

2014-01-01

interac- tive image segmentation using the solution to a combinatorial Dirichlet problem. Elmoataz et al . have developed general- izations of the graph...Laplacian [25] for image denoising and manifold smoothing. Couprie et al . in [18] define a conve- niently parameterized graph-based energy function that...over to the discrete graph representation. For general data segmentation, Bresson et al . in [8], present rigorous convergence results for two algorithms

Improved Modeling of Side-Chain–Base Interactions and Plasticity in Protein–DNA Interface Design

PubMed Central

Thyme, Summer B.; Baker, David; Bradley, Philip

2012-01-01

Combinatorial sequence optimization for protein design requires libraries of discrete side-chain conformations. The discreteness of these libraries is problematic, particularly for long, polar side chains, since favorable interactions can be missed. Previously, an approach to loop remodeling where protein backbone movement is directed by side-chain rotamers predicted to form interactions previously observed in native complexes (termed “motifs”) was described. Here, we show how such motif libraries can be incorporated into combinatorial sequence optimization protocols and improve native complex recapitulation. Guided by the motif rotamer searches, we made improvements to the underlying energy function, increasing recapitulation of native interactions. To further test the methods, we carried out a comprehensive experimental scan of amino acid preferences in the I-AniI protein–DNA interface and found that many positions tolerated multiple amino acids. This sequence plasticity is not observed in the computational results because of the fixed-backbone approximation of the model. We improved modeling of this diversity by introducing DNA flexibility and reducing the convergence of the simulated annealing algorithm that drives the design process. In addition to serving as a benchmark, this extensive experimental data set provides insight into the types of interactions essential to maintain the function of this potential gene therapy reagent. PMID:22426128

Improved modeling of side-chain--base interactions and plasticity in protein--DNA interface design.

PubMed

Thyme, Summer B; Baker, David; Bradley, Philip

2012-06-08

Combinatorial sequence optimization for protein design requires libraries of discrete side-chain conformations. The discreteness of these libraries is problematic, particularly for long, polar side chains, since favorable interactions can be missed. Previously, an approach to loop remodeling where protein backbone movement is directed by side-chain rotamers predicted to form interactions previously observed in native complexes (termed "motifs") was described. Here, we show how such motif libraries can be incorporated into combinatorial sequence optimization protocols and improve native complex recapitulation. Guided by the motif rotamer searches, we made improvements to the underlying energy function, increasing recapitulation of native interactions. To further test the methods, we carried out a comprehensive experimental scan of amino acid preferences in the I-AniI protein-DNA interface and found that many positions tolerated multiple amino acids. This sequence plasticity is not observed in the computational results because of the fixed-backbone approximation of the model. We improved modeling of this diversity by introducing DNA flexibility and reducing the convergence of the simulated annealing algorithm that drives the design process. In addition to serving as a benchmark, this extensive experimental data set provides insight into the types of interactions essential to maintain the function of this potential gene therapy reagent. Published by Elsevier Ltd.

Designing a multiroute synthesis scheme in combinatorial chemistry.

PubMed

Akavia, Adi; Senderowitz, Hanoch; Lerner, Alon; Shamir, Ron

2004-01-01

Solid-phase mix-and-split combinatorial synthesis is often used to produce large arrays of compounds to be tested during the various stages of the drug development process. This method can be represented by a synthesis graph in which nodes correspond to grow operations and arcs to beads transferred among the different reaction vessels. In this work, we address the problem of designing such a graph which maximizes the number of produced target compounds (namely, compounds out of an input library of desired molecules), given constraints on the number of beads used for library synthesis and on the number of reaction vessels available for concurrent grow steps. We present a heuristic based on a discrete search for solving this problem, test our solution on several data sets, explore its behavior, and show that it achieves good performance.

Galaxy Redshifts from Discrete Optimization of Correlation Functions

NASA Astrophysics Data System (ADS)

Lee, Benjamin C. G.; Budavári, Tamás; Basu, Amitabh; Rahman, Mubdi

2016-12-01

We propose a new method of constraining the redshifts of individual extragalactic sources based on celestial coordinates and their ensemble statistics. Techniques from integer linear programming (ILP) are utilized to optimize simultaneously for the angular two-point cross- and autocorrelation functions. Our novel formalism introduced here not only transforms the otherwise hopelessly expensive, brute-force combinatorial search into a linear system with integer constraints but also is readily implementable in off-the-shelf solvers. We adopt Gurobi, a commercial optimization solver, and use Python to build the cost function dynamically. The preliminary results on simulated data show potential for future applications to sky surveys by complementing and enhancing photometric redshift estimators. Our approach is the first application of ILP to astronomical analysis.

An instructive model of entropy

NASA Astrophysics Data System (ADS)

Zimmerman, Seth

2010-09-01

This article first notes the misinterpretation of a common thought experiment, and the misleading comment that 'systems tend to flow from less probable to more probable macrostates'. It analyses the experiment, generalizes it and introduces a new tool of investigation, the simplectic structure. A time-symmetric model is built upon this structure, yielding several non-intuitive results. The approach is combinatorial rather than statistical, and assumes that entropy is equivalent to 'missing information'. The intention of this article is not only to present interesting results, but also, by deliberately starting with a simple example and developing it through proof and computer simulation, to clarify the often confusing subject of entropy. The article should be particularly stimulating to students and instructors of discrete mathematics or undergraduate physics.

A discrete scattering series representation for lattice embedded models of chain cyclization

NASA Astrophysics Data System (ADS)

Fraser, Simon J.; Winnik, Mitchell A.

1980-01-01

In this paper we develop a lattice based model of chain cyclization in the presence of a set of occupied sites V in the lattice. We show that within the approximation of a Markovian chain propagator the effect of V on the partition function for the system can be written as a time-ordered exponential series in which V behaves like a scattering potential and chainlength is the timelike parameter. The discrete and finite nature of this model allows us to obtain rigorous upper and lower bounds to the series limit. We adapt these formulas to calculation of the partition functions and cyclization probabilities of terminally and globally cyclizing chains. Two classes of cyclization are considered: in the first model the target set H may be visited repeatedly (the Markovian model); in the second case vertices in H may be visited at most once(the non-Markovian or taboo model). This formulation depends on two fundamental combinatorial structures, namely the inclusion-exclusion principle and the set of subsets of a set. We have tried to interpret these abstract structures with physical analogies throughout the paper.

A Design Method for Topologically Insulating Metamaterials

NASA Astrophysics Data System (ADS)

Matlack, Kathryn; Serra-Garcia, Marc; Palermo, Antonio; Huber, Sebastian; Daraio, Chiara

Topological insulators are a unique class of electronic materials that exhibit protected edge states that are insulating in the bulk, and immune to back-scattering and defects. Discrete models, such as mass-spring systems, provide a means to translate these properties, based on the quantum hall spin effect, to the mechanical domain. This talk will present how to engineer a 2D mechanical metamaterial that supports topologically-protected and defect-immune edge states, directly from the mass-spring model of a topological insulator. The design method uses combinatorial searches plus gradient-based optimizations to determine the configuration of the metamaterials building blocks that leads to the global behavior specified by the target mass-spring model. We use metamaterials with weakly coupled unit cells to isolate the dynamics within our frequency range of interest and to enable a systematic design process. This approach can generally be applied to implement behaviors of a discrete model directly in mechanical, acoustic, or photonic metamaterials within the weak-coupling regime. This work was partially supported by the ETH Postdoctoral Fellowship, and by the Swiss National Science Foundation.

Generalised Spin Dynamics and Induced Bounds of Automorphic [A]nX, [AX]n NMR Systems via Dual Tensorial Sets: An Invariant Cardinality Role for CFP

NASA Astrophysics Data System (ADS)

Temme, Francis P.

For uniform spins and their indistinguishable point sets of tensorial bases defining automorphic group-based Liouvillian NMR spin dynamics, the role of recursively-derived coefficients of fractional parentage (CFP) bijections and Schur duality-defined CFP(0)(n) ≡ ¦GI¦(n) group invariant cardinality is central both to understanding the impact of time-reversal invariance(TRI) spin physics, and to analysis as density-matrix formalisms over democratic recoupled (DR) dual tensorial sets, {T{ṽ}k(11.1)(SU2 × ln)}. Over abstract spin space, these tensorial sets are (ṽ) invariant-theoretic forms which lie beyond the Liouvillian graph recoupling and Racah-forms envisaged by Sanctuary [1]. This is a direct consequence of the dominance of the ln group. It leads to new views on the value of projective group actions as mappings over specialised Liouvillian carrier spaces, and on the need for the replacement of Racah-Wigner (R-W) orthogonality for distinct point sets, by criteria based on explicit properties of invariants [J. Phys.: Math. & Theor. A 41, 015210 (2008)] for multiple invariant systems. Ũ × P group actions over disjoint (L) carrier subspaces, leading to exclusively combinatorial views of the nature of quantal completeness for indistinguishable point-based tensorial sets. Such generalised invariant-theoretic approaches lie beyond the range of Lévi-Civitá generator views, or of Lévy-Leblond and Lévy-Nahas [9] with its additional cyclic-commutators defining mono-invariant DR forms. Comparison of the latter with generalised multiple-invariant techniques provides an answer to the question of precisely why [A]n≥4(X) and [AX]n≥4 NMR system spin dynamics are not ameniable to conventional R-W analysis of recoupled discrete-point tensorial systems. Our work augments earlier Hilbert space views, both of Louck and Biedenharn [21] on boson pattern projective mapping, and of Corio [19]. The roles of recent ln group action and (λ ⊢ n)-Schur combinatorial concepts, as well as of polyhedral-combinatorial modelling over invariance algebras, contribute significantly to our understanding of invariant-based techniques of Liouville dual tensorial sets for automorphic NMR spin physics.1

MIFT: GIFT Combinatorial Geometry Input to VCS Code

DTIC Science & Technology

1977-03-01

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

Research on thermal protection mechanism of forward-facing cavity and opposing jet combinatorial thermal protection system

NASA Astrophysics Data System (ADS)

Lu, Hai-Bo; Liu, Wei-Qiang

2014-04-01

Validated by the correlated experiments, a nose-tip with forward-facing cavity/opposing jet/the combinatorial configuration of forward-facing cavity and opposing jet thermal protection system (TPS) are investigated numerically. The physical mechanism of these TPS is discussed, and the cooling efficiency of them is compared. The combinatorial system is more suitable to be the TPS for the high speed vehicles which need fly under various flow conditions with long-range and long time.

Combinatorial approach to the representation of the Schur-Weyl duality in one-dimensional spin systems

NASA Astrophysics Data System (ADS)

Jakubczyk, Dorota; Jakubczyk, Paweł

2018-02-01

We propose combinatorial approach to the representation of Schur-Weyl duality in physical systems on the example of one-dimensional spin chains. Exploiting the Robinson-Schensted-Knuth algorithm, we perform decomposition of the dual group representations into irreducible representations in a fully combinatorial way. As representation space, we choose the Hilbert space of the spin chains, but this approach can be easily generalized to an arbitrary physical system where the Schur-Weyl duality works.

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

PubMed

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

2008-07-01

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

Combinatorial Problems of Applied Discrete Mathematics.

DTIC Science & Technology

1979-12-01

204 .I (30) 3. Steiner, Combinatorische Aufgabe, Z. Reine Angew. Math. 45 (1853) 18 1—182. (31) IC. Takeuchi, A table of difference sets generating...Assoc. Fr. Ay. Sd . 1 (1900) 122— 123; 2 (1901) 170—203. • (33) R.M. Wilson, Cyclotomy and difference fam ilies in elementary Abelian groups , 3. Number...the differe nt cliques containing either A or B. Let us first introduce the following notations. If A is a vertex in G, then 1(A) denotes the set of

A new multi-objective optimization model for preventive maintenance and replacement scheduling of multi-component systems

NASA Astrophysics Data System (ADS)

Moghaddam, Kamran S.; Usher, John S.

2011-07-01

In this article, a new multi-objective optimization model is developed to determine the optimal preventive maintenance and replacement schedules in a repairable and maintainable multi-component system. In this model, the planning horizon is divided into discrete and equally-sized periods in which three possible actions must be planned for each component, namely maintenance, replacement, or do nothing. The objective is to determine a plan of actions for each component in the system while minimizing the total cost and maximizing overall system reliability simultaneously over the planning horizon. Because of the complexity, combinatorial and highly nonlinear structure of the mathematical model, two metaheuristic solution methods, generational genetic algorithm, and a simulated annealing are applied to tackle the problem. The Pareto optimal solutions that provide good tradeoffs between the total cost and the overall reliability of the system can be obtained by the solution approach. Such a modeling approach should be useful for maintenance planners and engineers tasked with the problem of developing recommended maintenance plans for complex systems of components.

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

PubMed

Lee, M L; Schneider, G

2001-01-01

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

CRAVE: a database, middleware and visualization system for phenotype ontologies.

PubMed

Gkoutos, Georgios V; Green, Eain C J; Greenaway, Simon; Blake, Andrew; Mallon, Ann-Marie; Hancock, John M

2005-04-01

A major challenge in modern biology is to link genome sequence information to organismal function. In many organisms this is being done by characterizing phenotypes resulting from mutations. Efficiently expressing phenotypic information requires combinatorial use of ontologies. However tools are not currently available to visualize combinations of ontologies. Here we describe CRAVE (Concept Relation Assay Value Explorer), a package allowing storage, active updating and visualization of multiple ontologies. CRAVE is a web-accessible JAVA application that accesses an underlying MySQL database of ontologies via a JAVA persistent middleware layer (Chameleon). This maps the database tables into discrete JAVA classes and creates memory resident, interlinked objects corresponding to the ontology data. These JAVA objects are accessed via calls through the middleware's application programming interface. CRAVE allows simultaneous display and linking of multiple ontologies and searching using Boolean and advanced searches.

Three-state combinatorial switch models as applied to the binding of oxygen by human hemoglobin.

PubMed

Straume, M; Johnson, M L

1988-02-23

We have generated a series of all 6561 unique, discrete three-state combinatorial switch models to describe the partitioning of the cooperative oxygen-binding free change among the 10 variously ligated forms of human hemoglobin tetramers. These models were inspired by the experimental observation of Smith and Ackers that the cooperative free energy of the intersubunit contact regions of the 10 possible ligated forms of human hemoglobin tetramers can be represented by a particular distribution of three distinct energy levels [Smith, F. R., & Ackers, G. K. (1985) Proc. Natl. Acad. Sci. U.S.A. 82, 5347-5351]. A statistical thermodynamic formulation accounting for both dimer-tetramer equilibria and ligand binding properties of hemoglobin solutions as a function of oxygen and protein concentrations was utilized to exhaustively test these thermodynamic models. In this series of models each of the 10 ligated forms of the hemoglobin tetramer can exist in one, and only one, of three possible energy levels; i.e., each ligated form was assumed to be associated with a discrete energy state. This series of models includes all possible ways that the 10 ligation states of hemoglobin can be distributed into three distinct cooperative energy levels. The mathematical models, as presented here, do not permit equilibria between energy states to exist for any of the 10 unique ligated forms of hemoglobin tetramers. These models were analyzed by nonlinear least-squares estimation of the free energy parameters characteristic of this statistical thermodynamic development.(ABSTRACT TRUNCATED AT 250 WORDS)

Multitriangulations, pseudotriangulations and some problems of realization of polytopes

NASA Astrophysics Data System (ADS)

Pilaud, Vincent

2010-09-01

This thesis explores two specific topics of discrete geometry, the multitriangulations and the polytopal realizations of products, whose connection is the problem of finding polytopal realizations of a given combinatorial structure. A k-triangulation is a maximal set of chords of the convex n-gon such that no k+1 of them mutually cross. We propose a combinatorial and geometric study of multitriangulations based on their stars, which play the same role as triangles of triangulations. This study leads to interpret multitriangulations by duality as pseudoline arrangements with contact points covering a given support. We exploit finally these results to discuss some open problems on multitriangulations, in particular the question of the polytopal realization of their flip graphs. We study secondly the polytopality of Cartesian products. We investigate the existence of polytopal realizations of cartesian products of graphs, and we study the minimal dimension that can have a polytope whose k-skeleton is that of a product of simplices.

A Combinatorial Approach to Detecting Gene-Gene and Gene-Environment Interactions in Family Studies

PubMed Central

Lou, Xiang-Yang; Chen, Guo-Bo; Yan, Lei; Ma, Jennie Z.; Mangold, Jamie E.; Zhu, Jun; Elston, Robert C.; Li, Ming D.

2008-01-01

Widespread multifactor interactions present a significant challenge in determining risk factors of complex diseases. Several combinatorial approaches, such as the multifactor dimensionality reduction (MDR) method, have emerged as a promising tool for better detecting gene-gene (G × G) and gene-environment (G × E) interactions. We recently developed a general combinatorial approach, namely the generalized multifactor dimensionality reduction (GMDR) method, which can entertain both qualitative and quantitative phenotypes and allows for both discrete and continuous covariates to detect G × G and G × E interactions in a sample of unrelated individuals. In this article, we report the development of an algorithm that can be used to study G × G and G × E interactions for family-based designs, called pedigree-based GMDR (PGMDR). Compared to the available method, our proposed method has several major improvements, including allowing for covariate adjustments and being applicable to arbitrary phenotypes, arbitrary pedigree structures, and arbitrary patterns of missing marker genotypes. Our Monte Carlo simulations provide evidence that the PGMDR method is superior in performance to identify epistatic loci compared to the MDR-pedigree disequilibrium test (PDT). Finally, we applied our proposed approach to a genetic data set on tobacco dependence and found a significant interaction between two taste receptor genes (i.e., TAS2R16 and TAS2R38) in affecting nicotine dependence. PMID:18834969

Integrating Multiple Data Sources for Combinatorial Marker Discovery: A Study in Tumorigenesis.

PubMed

Bandyopadhyay, Sanghamitra; Mallik, Saurav

2018-01-01

Identification of combinatorial markers from multiple data sources is a challenging task in bioinformatics. Here, we propose a novel computational framework for identifying significant combinatorial markers ( s) using both gene expression and methylation data. The gene expression and methylation data are integrated into a single continuous data as well as a (post-discretized) boolean data based on their intrinsic (i.e., inverse) relationship. A novel combined score of methylation and expression data (viz., ) is introduced which is computed on the integrated continuous data for identifying initial non-redundant set of genes. Thereafter, (maximal) frequent closed homogeneous genesets are identified using a well-known biclustering algorithm applied on the integrated boolean data of the determined non-redundant set of genes. A novel sample-based weighted support ( ) is then proposed that is consecutively calculated on the integrated boolean data of the determined non-redundant set of genes in order to identify the non-redundant significant genesets. The top few resulting genesets are identified as potential s. Since our proposed method generates a smaller number of significant non-redundant genesets than those by other popular methods, the method is much faster than the others. Application of the proposed technique on an expression and a methylation data for Uterine tumor or Prostate Carcinoma produces a set of significant combination of markers. We expect that such a combination of markers will produce lower false positives than individual markers.

Combinatorial games with a pass: a dynamical systems approach.

PubMed

Morrison, Rebecca E; Friedman, Eric J; Landsberg, Adam S

2011-12-01

By treating combinatorial games as dynamical systems, we are able to address a longstanding open question in combinatorial game theory, namely, how the introduction of a "pass" move into a game affects its behavior. We consider two well known combinatorial games, 3-pile Nim and 3-row Chomp. In the case of Nim, we observe that the introduction of the pass dramatically alters the game's underlying structure, rendering it considerably more complex, while for Chomp, the pass move is found to have relatively minimal impact. We show how these results can be understood by recasting these games as dynamical systems describable by dynamical recursion relations. From these recursion relations, we are able to identify underlying structural connections between these "games with passes" and a recently introduced class of "generic (perturbed) games." This connection, together with a (non-rigorous) numerical stability analysis, allows one to understand and predict the effect of a pass on a game.

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

PubMed

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

2013-04-08

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

PROBABILISTIC CROSS-IDENTIFICATION IN CROWDED FIELDS AS AN ASSIGNMENT PROBLEM

DOE Office of Scientific and Technical Information (OSTI.GOV)

Budavári, Tamás; Basu, Amitabh, E-mail: budavari@jhu.edu, E-mail: basu.amitabh@jhu.edu

2016-10-01

One of the outstanding challenges of cross-identification is multiplicity: detections in crowded regions of the sky are often linked to more than one candidate associations of similar likelihoods. We map the resulting maximum likelihood partitioning to the fundamental assignment problem of discrete mathematics and efficiently solve the two-way catalog-level matching in the realm of combinatorial optimization using the so-called Hungarian algorithm. We introduce the method, demonstrate its performance in a mock universe where the true associations are known, and discuss the applicability of the new procedure to large surveys.

Probabilistic Cross-identification in Crowded Fields as an Assignment Problem

NASA Astrophysics Data System (ADS)

Budavári, Tamás; Basu, Amitabh

2016-10-01

One of the outstanding challenges of cross-identification is multiplicity: detections in crowded regions of the sky are often linked to more than one candidate associations of similar likelihoods. We map the resulting maximum likelihood partitioning to the fundamental assignment problem of discrete mathematics and efficiently solve the two-way catalog-level matching in the realm of combinatorial optimization using the so-called Hungarian algorithm. We introduce the method, demonstrate its performance in a mock universe where the true associations are known, and discuss the applicability of the new procedure to large surveys.

Discrete Optimization Model for Vehicle Routing Problem with Scheduling Side Cosntraints

NASA Astrophysics Data System (ADS)

Juliandri, Dedy; Mawengkang, Herman; Bu'ulolo, F.

2018-01-01

Vehicle Routing Problem (VRP) is an important element of many logistic systems which involve routing and scheduling of vehicles from a depot to a set of customers node. This is a hard combinatorial optimization problem with the objective to find an optimal set of routes used by a fleet of vehicles to serve the demands a set of customers It is required that these vehicles return to the depot after serving customers’ demand. The problem incorporates time windows, fleet and driver scheduling, pick-up and delivery in the planning horizon. The goal is to determine the scheduling of fleet and driver and routing policies of the vehicles. The objective is to minimize the overall costs of all routes over the planning horizon. We model the problem as a linear mixed integer program. We develop a combination of heuristics and exact method for solving the model.

Replicator equations, maximal cliques, and graph isomorphism.

PubMed

Pelillo, M

1999-11-15

We present a new energy-minimization framework for the graph isomorphism problem that is based on an equivalent maximum clique formulation. The approach is centered around a fundamental result proved by Motzkin and Straus in the mid-1960s, and recently expanded in various ways, which allows us to formulate the maximum clique problem in terms of a standard quadratic program. The attractive feature of this formulation is that a clear one-to-one correspondence exists between the solutions of the quadratic program and those in the original, combinatorial problem. To solve the program we use the so-called replicator equations--a class of straightforward continuous- and discrete-time dynamical systems developed in various branches of theoretical biology. We show how, despite their inherent inability to escape from local solutions, they nevertheless provide experimental results that are competitive with those obtained using more elaborate mean-field annealing heuristics.

Implementing finite state machines in a computer-based teaching system

NASA Astrophysics Data System (ADS)

Hacker, Charles H.; Sitte, Renate

1999-09-01

Finite State Machines (FSM) are models for functions commonly implemented in digital circuits such as timers, remote controls, and vending machines. Teaching FSM is core in the curriculum of many university digital electronic or discrete mathematics subjects. Students often have difficulties grasping the theoretical concepts in the design and analysis of FSM. This has prompted the author to develop an MS-WindowsTM compatible software, WinState, that provides a tutorial style teaching aid for understanding the mechanisms of FSM. The animated computer screen is ideal for visually conveying the required design and analysis procedures. WinState complements other software for combinatorial logic previously developed by the author, and enhances the existing teaching package by adding sequential logic circuits. WinState enables the construction of a students own FSM, which can be simulated, to test the design for functionality and possible errors.

On the information content of discrete phylogenetic characters.

PubMed

Bordewich, Magnus; Deutschmann, Ina Maria; Fischer, Mareike; Kasbohm, Elisa; Semple, Charles; Steel, Mike

2017-12-16

Phylogenetic inference aims to reconstruct the evolutionary relationships of different species based on genetic (or other) data. Discrete characters are a particular type of data, which contain information on how the species should be grouped together. However, it has long been known that some characters contain more information than others. For instance, a character that assigns the same state to each species groups all of them together and so provides no insight into the relationships of the species considered. At the other extreme, a character that assigns a different state to each species also conveys no phylogenetic signal. In this manuscript, we study a natural combinatorial measure of the information content of an individual character and analyse properties of characters that provide the maximum phylogenetic information, particularly, the number of states such a character uses and how the different states have to be distributed among the species or taxa of the phylogenetic tree.

Applications of Derandomization Theory in Coding

NASA Astrophysics Data System (ADS)

Cheraghchi, Mahdi

2011-07-01

Randomized techniques play a fundamental role in theoretical computer science and discrete mathematics, in particular for the design of efficient algorithms and construction of combinatorial objects. The basic goal in derandomization theory is to eliminate or reduce the need for randomness in such randomized constructions. In this thesis, we explore some applications of the fundamental notions in derandomization theory to problems outside the core of theoretical computer science, and in particular, certain problems related to coding theory. First, we consider the wiretap channel problem which involves a communication system in which an intruder can eavesdrop a limited portion of the transmissions, and construct efficient and information-theoretically optimal communication protocols for this model. Then we consider the combinatorial group testing problem. In this classical problem, one aims to determine a set of defective items within a large population by asking a number of queries, where each query reveals whether a defective item is present within a specified group of items. We use randomness condensers to explicitly construct optimal, or nearly optimal, group testing schemes for a setting where the query outcomes can be highly unreliable, as well as the threshold model where a query returns positive if the number of defectives pass a certain threshold. Finally, we design ensembles of error-correcting codes that achieve the information-theoretic capacity of a large class of communication channels, and then use the obtained ensembles for construction of explicit capacity achieving codes. [This is a shortened version of the actual abstract in the thesis.

Microprocessor-based integration of microfluidic control for the implementation of automated sensor monitoring and multithreaded optimization algorithms.

PubMed

Ezra, Elishai; Maor, Idan; Bavli, Danny; Shalom, Itai; Levy, Gahl; Prill, Sebastian; Jaeger, Magnus S; Nahmias, Yaakov

2015-08-01

Microfluidic applications range from combinatorial synthesis to high throughput screening, with platforms integrating analog perfusion components, digitally controlled micro-valves and a range of sensors that demand a variety of communication protocols. Currently, discrete control units are used to regulate and monitor each component, resulting in scattered control interfaces that limit data integration and synchronization. Here, we present a microprocessor-based control unit, utilizing the MS Gadgeteer open framework that integrates all aspects of microfluidics through a high-current electronic circuit that supports and synchronizes digital and analog signals for perfusion components, pressure elements, and arbitrary sensor communication protocols using a plug-and-play interface. The control unit supports an integrated touch screen and TCP/IP interface that provides local and remote control of flow and data acquisition. To establish the ability of our control unit to integrate and synchronize complex microfluidic circuits we developed an equi-pressure combinatorial mixer. We demonstrate the generation of complex perfusion sequences, allowing the automated sampling, washing, and calibrating of an electrochemical lactate sensor continuously monitoring hepatocyte viability following exposure to the pesticide rotenone. Importantly, integration of an optical sensor allowed us to implement automated optimization protocols that require different computational challenges including: prioritized data structures in a genetic algorithm, distributed computational efforts in multiple-hill climbing searches and real-time realization of probabilistic models in simulated annealing. Our system offers a comprehensive solution for establishing optimization protocols and perfusion sequences in complex microfluidic circuits.

How communication changes when we cannot mime the world: Experimental evidence for the effect of iconicity on combinatoriality.

PubMed

Roberts, Gareth; Lewandowski, Jirka; Galantucci, Bruno

2015-08-01

Communication systems are exposed to two different pressures: a pressure for transmission efficiency, such that messages are simple to produce and perceive, and a pressure for referential efficiency, such that messages are easy to understand with their intended meaning. A solution to the first pressure is combinatoriality--the recombination of a few basic meaningless forms to express an infinite number of meanings. A solution to the second is iconicity--the use of forms that resemble what they refer to. These two solutions appear to be incompatible with each other, as iconic forms are ill-suited for use as meaningless combinatorial units. Furthermore, in the early stages of a communication system, when basic referential forms are in the process of being established, the pressure for referential efficiency is likely to be particularly strong, which may lead it to trump the pressure for transmission efficiency. This means that, where iconicity is available as a strategy, it is likely to impede the emergence of combinatoriality. Although this hypothesis seems consistent with some observations of natural language, it was unclear until recently how it could be soundly tested. This has changed thanks to the development of a line of research, known as Experimental Semiotics, in which participants construct novel communication systems in the laboratory using an unfamiliar medium. We conducted an Experimental Semiotic study in which we manipulated the opportunity for iconicity by varying the kind of referents to be communicated, while keeping the communication medium constant. We then measured the combinatoriality and transmission efficiency of the communication systems. We found that, where iconicity was available, it provided scaffolding for the construction of communication systems and was overwhelmingly adopted. Where it was not available, however, the resulting communication systems were more combinatorial and their forms more efficient to produce. This study enriches our understanding of the fundamental design principles of human communication and contributes tools to enrich it further. Copyright © 2015 Elsevier B.V. All rights reserved.

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

NASA Astrophysics Data System (ADS)

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

2018-01-01

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

Invention as a combinatorial process: evidence from US patents

PubMed Central

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

2015-01-01

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

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

PubMed

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.

FOREWORD: Focus on Combinatorial Materials Science Focus on Combinatorial Materials Science

NASA Astrophysics Data System (ADS)

Chikyo, Toyohiro

2011-10-01

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

RNA Secondary Structure Prediction by Using Discrete Mathematics: An Interdisciplinary Research Experience for Undergraduate Students

PubMed Central

Ellington, Roni; Wachira, James

2010-01-01

The focus of this Research Experience for Undergraduates (REU) project was on RNA secondary structure prediction by using a lattice walk approach. The lattice walk approach is a combinatorial and computational biology method used to enumerate possible secondary structures and predict RNA secondary structure from RNA sequences. The method uses discrete mathematical techniques and identifies specified base pairs as parameters. The goal of the REU was to introduce upper-level undergraduate students to the principles and challenges of interdisciplinary research in molecular biology and discrete mathematics. At the beginning of the project, students from the biology and mathematics departments of a mid-sized university received instruction on the role of secondary structure in the function of eukaryotic RNAs and RNA viruses, RNA related to combinatorics, and the National Center for Biotechnology Information resources. The student research projects focused on RNA secondary structure prediction on a regulatory region of the yellow fever virus RNA genome and on an untranslated region of an mRNA of a gene associated with the neurological disorder epilepsy. At the end of the project, the REU students gave poster and oral presentations, and they submitted written final project reports to the program director. The outcome of the REU was that the students gained transferable knowledge and skills in bioinformatics and an awareness of the applications of discrete mathematics to biological research problems. PMID:20810968

RNA secondary structure prediction by using discrete mathematics: an interdisciplinary research experience for undergraduate students.

PubMed

Ellington, Roni; Wachira, James; Nkwanta, Asamoah

2010-01-01

The focus of this Research Experience for Undergraduates (REU) project was on RNA secondary structure prediction by using a lattice walk approach. The lattice walk approach is a combinatorial and computational biology method used to enumerate possible secondary structures and predict RNA secondary structure from RNA sequences. The method uses discrete mathematical techniques and identifies specified base pairs as parameters. The goal of the REU was to introduce upper-level undergraduate students to the principles and challenges of interdisciplinary research in molecular biology and discrete mathematics. At the beginning of the project, students from the biology and mathematics departments of a mid-sized university received instruction on the role of secondary structure in the function of eukaryotic RNAs and RNA viruses, RNA related to combinatorics, and the National Center for Biotechnology Information resources. The student research projects focused on RNA secondary structure prediction on a regulatory region of the yellow fever virus RNA genome and on an untranslated region of an mRNA of a gene associated with the neurological disorder epilepsy. At the end of the project, the REU students gave poster and oral presentations, and they submitted written final project reports to the program director. The outcome of the REU was that the students gained transferable knowledge and skills in bioinformatics and an awareness of the applications of discrete mathematics to biological research problems.

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

PubMed Central

Damer, Bruce; Deamer, David

2015-01-01

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

Research on parallel combinatory spread spectrum communication system with double information matching

NASA Astrophysics Data System (ADS)

Xue, Wei; Wang, Qi; Wang, Tianyu

2018-04-01

This paper presents an improved parallel combinatory spread spectrum (PC/SS) communication system with the method of double information matching (DIM). Compared with conventional PC/SS system, the new model inherits the advantage of high transmission speed, large information capacity and high security. Besides, the problem traditional system will face is the high bit error rate (BER) and since its data-sequence mapping algorithm. Hence the new model presented shows lower BER and higher efficiency by its optimization of mapping algorithm.

Bifurcation-based approach reveals synergism and optimal combinatorial perturbation.

PubMed

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

2016-06-01

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

In silico modeling of axonal reconnection within a discrete fiber tract after spinal cord injury.

PubMed

Woolfe, Franco; Waxman, Stephen G; Hains, Bryan C

2007-02-01

Following spinal cord injury (SCI), descending axons that carry motor commands from the brain to the spinal cord are injured or transected, producing chronic motor dysfunction and paralysis. Reconnection of these axons is a major prerequisite for restoration of function after SCI. Thus far, only modest gains in motor function have been achieved experimentally or in the clinic after SCI, identifying the practical limitations of current treatment approaches. In this paper, we use an ordinary differential equation (ODE) to simulate the relative and synergistic contributions of several experimentally-established biological factors related to inhibition or promotion of axonal repair and restoration of function after SCI. The factors were mathematically modeled by the ODE. The results of our simulation show that in a model system, many factors influenced the achievability of axonal reconnection. Certain factors more strongly affected axonal reconnection in isolation, and some factors interacted in a synergistic fashion to produce further improvements in axonal reconnection. Our data suggest that mathematical modeling may be useful in evaluating the complex interactions of discrete therapeutic factors not possible in experimental preparations, and highlight the benefit of a combinatorial therapeutic approach focused on promoting axonal sprouting, attraction of cut ends, and removal of growth inhibition for achieving axonal reconnection. Predictions of this simulation may be of utility in guiding future experiments aimed at restoring function after SCI.

Switched Systems and Motion Coordination: Combinatorial Challenges

NASA Technical Reports Server (NTRS)

Sadovsky, Alexander V.

2016-01-01

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

Emergent latent symbol systems in recurrent neural networks

NASA Astrophysics Data System (ADS)

Monner, Derek; Reggia, James A.

2012-12-01

Fodor and Pylyshyn [(1988). Connectionism and cognitive architecture: A critical analysis. Cognition, 28(1-2), 3-71] famously argued that neural networks cannot behave systematically short of implementing a combinatorial symbol system. A recent response from Frank et al. [(2009). Connectionist semantic systematicity. Cognition, 110(3), 358-379] claimed to have trained a neural network to behave systematically without implementing a symbol system and without any in-built predisposition towards combinatorial representations. We believe systems like theirs may in fact implement a symbol system on a deeper and more interesting level: one where the symbols are latent - not visible at the level of network structure. In order to illustrate this possibility, we demonstrate our own recurrent neural network that learns to understand sentence-level language in terms of a scene. We demonstrate our model's learned understanding by testing it on novel sentences and scenes. By paring down our model into an architecturally minimal version, we demonstrate how it supports combinatorial computation over distributed representations by using the associative memory operations of Vector Symbolic Architectures. Knowledge of the model's memory scheme gives us tools to explain its errors and construct superior future models. We show how the model designs and manipulates a latent symbol system in which the combinatorial symbols are patterns of activation distributed across the layers of a neural network, instantiating a hybrid of classical symbolic and connectionist representations that combines advantages of both.

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

PubMed

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

2009-01-01

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

Past tense in the brain's time: neurophysiological evidence for dual-route processing of past-tense verbs.

PubMed

Bakker, Iske; Macgregor, Lucy J; Pulvermüller, Friedemann; Shtyrov, Yury

2013-05-01

A controversial issue in neuro- and psycholinguistics is whether regular past-tense forms of verbs are stored lexically or generated productively by the application of abstract combinatorial schemas, for example affixation rules. The success or failure of models in accounting for this particular issue can be used to draw more general conclusions about cognition and the degree to which abstract, symbolic representations and rules are psychologically and neurobiologically real. This debate can potentially be resolved using a neurophysiological paradigm, in which alternative predictions of the brain response patterns for lexical and syntactic processing are put to the test. We used magnetoencephalography (MEG) to record neural responses to spoken monomorphemic words ('hide'), pseudowords ('smide'), regular past-tense forms ('cried') and ungrammatical (overregularised) past-tense forms ('flied') in a passive listening oddball paradigm, in which lexically and syntactically modulated stimuli are known to elicit distinct patterns of the mismatch negativity (MMN) brain response. We observed an enhanced ('lexical') MMN to monomorphemic words relative to pseudowords, but a reversed ('syntactic') MMN to ungrammatically inflected past tenses relative to grammatical forms. This dissociation between responses to monomorphemic and bimorphemic stimuli indicates that regular past tenses are processed more similarly to syntactic sequences than to lexically stored monomorphemic words, suggesting that regular past tenses are generated productively by the application of a combinatorial scheme to their separately represented stems and affixes. We suggest discrete combinatorial neuronal assemblies, which bind classes of sequentially occurring lexical elements into morphologically complex units, as the neurobiological basis of regular past tense inflection. Copyright © 2013 Elsevier Inc. All rights reserved.

Composite solvers for linear saddle point problems arising from the incompressible Stokes equations with highly heterogeneous viscosity structure

NASA Astrophysics Data System (ADS)

Sanan, P.; Schnepp, S. M.; May, D.; Schenk, O.

2014-12-01

Geophysical applications require efficient forward models for non-linear Stokes flow on high resolution spatio-temporal domains. The bottleneck in applying the forward model is solving the linearized, discretized Stokes problem which takes the form of a large, indefinite (saddle point) linear system. Due to the heterogeniety of the effective viscosity in the elliptic operator, devising effective preconditioners for saddle point problems has proven challenging and highly problem-dependent. Nevertheless, at least three approaches show promise for preconditioning these difficult systems in an algorithmically scalable way using multigrid and/or domain decomposition techniques. The first is to work with a hierarchy of coarser or smaller saddle point problems. The second is to use the Schur complement method to decouple and sequentially solve for the pressure and velocity. The third is to use the Schur decomposition to devise preconditioners for the full operator. These involve sub-solves resembling inexact versions of the sequential solve. The choice of approach and sub-methods depends crucially on the motivating physics, the discretization, and available computational resources. Here we examine the performance trade-offs for preconditioning strategies applied to idealized models of mantle convection and lithospheric dynamics, characterized by large viscosity gradients. Due to the arbitrary topological structure of the viscosity field in geodynamical simulations, we utilize low order, inf-sup stable mixed finite element spatial discretizations which are suitable when sharp viscosity variations occur in element interiors. Particular attention is paid to possibilities within the decoupled and approximate Schur complement factorization-based monolithic approaches to leverage recently-developed flexible, communication-avoiding, and communication-hiding Krylov subspace methods in combination with `heavy' smoothers, which require solutions of large per-node sub-problems, well-suited to solution on hybrid computational clusters. To manage the combinatorial explosion of solver options (which include hybridizations of all the approaches mentioned above), we leverage the modularity of the PETSc library.

Tanglegrams: A Reduction Tool for Mathematical Phylogenetics.

PubMed

Matsen, Frederick A; Billey, Sara C; Kas, Arnold; Konvalinka, Matjaz

2018-01-01

Many discrete mathematics problems in phylogenetics are defined in terms of the relative labeling of pairs of leaf-labeled trees. These relative labelings are naturally formalized as tanglegrams, which have previously been an object of study in coevolutionary analysis. Although there has been considerable work on planar drawings of tanglegrams, they have not been fully explored as combinatorial objects until recently. In this paper, we describe how many discrete mathematical questions on trees "factor" through a problem on tanglegrams, and how understanding that factoring can simplify analysis. Depending on the problem, it may be useful to consider a unordered version of tanglegrams, and/or their unrooted counterparts. For all of these definitions, we show how the isomorphism types of tanglegrams can be understood in terms of double cosets of the symmetric group, and we investigate their automorphisms. Understanding tanglegrams better will isolate the distinct problems on leaf-labeled pairs of trees and reveal natural symmetries of spaces associated with such problems.

Graph Theory

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sanfilippo, Antonio P.

2005-12-27

Graph theory is a branch of discrete combinatorial mathematics that studies the properties of graphs. The theory was pioneered by the Swiss mathematician Leonhard Euler in the 18th century, commenced its formal development during the second half of the 19th century, and has witnessed substantial growth during the last seventy years, with applications in areas as diverse as engineering, computer science, physics, sociology, chemistry and biology. Graph theory has also had a strong impact in computational linguistics by providing the foundations for the theory of features structures that has emerged as one of the most widely used frameworks for themore » representation of grammar formalisms.« less

Locality for quantum systems on graphs depends on the number field

NASA Astrophysics Data System (ADS)

Hall, H. Tracy; Severini, Simone

2013-07-01

Adapting a definition of Aaronson and Ambainis (2005 Theory Comput. 1 47-79), we call a quantum dynamics on a digraph saturated Z-local if the nonzero transition amplitudes specifying the unitary evolution are in exact correspondence with the directed edges (including loops) of the digraph. This idea appears recurrently in a variety of contexts including angular momentum, quantum chaos, and combinatorial matrix theory. Complete characterization of the digraph properties that allow such a process to exist is a long-standing open question that can also be formulated in terms of minimum rank problems. We prove that saturated Z-local dynamics involving complex amplitudes occur on a proper superset of the digraphs that allow restriction to the real numbers or, even further, the rationals. Consequently, among these fields, complex numbers guarantee the largest possible choice of topologies supporting a discrete quantum evolution. A similar construction separates complex numbers from the skew field of quaternions. The result proposes a concrete ground for distinguishing between complex and quaternionic quantum mechanics.

Signal dimensionality and the emergence of combinatorial structure.

PubMed

Little, Hannah; Eryılmaz, Kerem; de Boer, Bart

2017-11-01

In language, a small number of meaningless building blocks can be combined into an unlimited set of meaningful utterances. This is known as combinatorial structure. One hypothesis for the initial emergence of combinatorial structure in language is that recombining elements of signals solves the problem of overcrowding in a signal space. Another hypothesis is that iconicity may impede the emergence of combinatorial structure. However, how these two hypotheses relate to each other is not often discussed. In this paper, we explore how signal space dimensionality relates to both overcrowding in the signal space and iconicity. We use an artificial signalling experiment to test whether a signal space and a meaning space having similar topologies will generate an iconic system and whether, when the topologies differ, the emergence of combinatorially structured signals is facilitated. In our experiments, signals are created from participants' hand movements, which are measured using an infrared sensor. We found that participants take advantage of iconic signal-meaning mappings where possible. Further, we use trajectory predictability, measures of variance, and Hidden Markov Models to measure the use of structure within the signals produced and found that when topologies do not match, then there is more evidence of combinatorial structure. The results from these experiments are interpreted in the context of the differences between the emergence of combinatorial structure in different linguistic modalities (speech and sign). Copyright © 2017 Elsevier B.V. All rights reserved.

A combinatorial approach to protein docking with flexible side chains.

PubMed

Althaus, Ernst; Kohlbacher, Oliver; Lenhof, Hans-Peter; Müller, Peter

2002-01-01

Rigid-body docking approaches are not sufficient to predict the structure of a protein complex from the unbound (native) structures of the two proteins. Accounting for side chain flexibility is an important step towards fully flexible protein docking. This work describes an approach that allows conformational flexibility for the side chains while keeping the protein backbone rigid. Starting from candidates created by a rigid-docking algorithm, we demangle the side chains of the docking site, thus creating reasonable approximations of the true complex structure. These structures are ranked with respect to the binding free energy. We present two new techniques for side chain demangling. Both approaches are based on a discrete representation of the side chain conformational space by the use of a rotamer library. This leads to a combinatorial optimization problem. For the solution of this problem, we propose a fast heuristic approach and an exact, albeit slower, method that uses branch-and-cut techniques. As a test set, we use the unbound structures of three proteases and the corresponding protein inhibitors. For each of the examples, the highest-ranking conformation produced was a good approximation of the true complex structure.

Combinatorial approaches to evaluate nanodiamond uptake and induced cellular fate

NASA Astrophysics Data System (ADS)

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

2016-02-01

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

Combinatorial approaches to evaluate nanodiamond uptake and induced cellular fate

PubMed Central

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

2016-01-01

Nanodiamonds (NDs) are an emerging class of engineered nanomaterials that hold great promise for the next generation of bionanotechnological products to be used for drug and gene delivery, or for bio-imaging and biosensing. Previous studies have shown that upon their cellular uptake, NDs exhibit high biocompatibility in various in vitro and in vivo set-ups. Herein we hypothesized that the increased NDs biocompatibility is a result of minimum membrane perturbations and their reduced ability to induce disruption or damage during cellular translocation. Using multi-scale combinatorial approaches that simulate ND-membrane interactions, we correlated NDs real-time cellular uptake and kinetics with the ND-induced membrane fluctuations to derive energy requirements for the uptake to occur. Our discrete and real-time analyses showed that the majority of NDs internalization occurs within 2 h of cellular exposure, however, with no effects on cellular viability, proliferation or cellular behavior. Furthermore, our simulation analyses using coarse-grained models identified key changes in the energy profile, membrane deformation and recovery time, all functions of the average ND or ND-based agglomerate size. Understanding the mechanisms responsible for ND-cell membrane interactions could possibly advance their implementation in various biomedical applications. PMID:26820775

Synthesizing optimal waste blends

DOE Office of Scientific and Technical Information (OSTI.GOV)

Narayan, V.; Diwekar, W.M.; Hoza, M.

Vitrification of tank wastes to form glass is a technique that will be used for the disposal of high-level waste at Hanford. Process and storage economics show that minimizing the total number of glass logs produced is the key to keeping cost as low as possible. The amount of glass produced can be reduced by blending of the wastes. The optimal way to combine the tanks to minimize the vole of glass can be determined from a discrete blend calculation. However, this problem results in a combinatorial explosion as the number of tanks increases. Moreover, the property constraints make thismore » problem highly nonconvex where many algorithms get trapped in local minima. In this paper the authors examine the use of different combinatorial optimization approaches to solve this problem. A two-stage approach using a combination of simulated annealing and nonlinear programming (NLP) is developed. The results of different methods such as the heuristics approach based on human knowledge and judgment, the mixed integer nonlinear programming (MINLP) approach with GAMS, and branch and bound with lower bound derived from the structure of the given blending problem are compared with this coupled simulated annealing and NLP approach.« less

Combinatorial Study of the Li-Ni-Mn-Co Oxide Pseudoquaternary System for Use in Li-Ion Battery Materials Research.

PubMed

Brown, Colby R; McCalla, Eric; Watson, Cody; Dahn, J R

2015-06-08

Combinatorial synthesis has proven extremely effective in screening for new battery materials for Li-ion battery electrodes. Here, a study in the Li-Ni-Mn-Co-O system is presented, wherein samples with nearly 800 distinct compositions were prepared using a combinatorial and high-throughput method to screen for single-phase materials of high interest as next generation positive electrode materials. X-ray diffraction is used to determine the crystal structure of each sample. The Gibbs' pyramid representing the pseudoquaternary system was studied by making samples within three distinct pseudoternary planes defined at fractional cobalt metal contents of 10%, 20%, and 30% within the Li-Ni-Mn-Co-O system. Two large single-phase regions were observed in the system: the layered region (ordered rocksalt) and cubic spinel region; both of which are of interest for next-generation positive electrodes in lithium-ion batteries. These regions were each found to stretch over a wide range of compositions within the Li-Ni-Mn-Co-O pseudoquaternary system and had complex coexistence regions existing between them. The sample cooling rate was found to have a significant effect on the position of the phase boundaries of the single-phase regions. The results of this work are intended to guide further research by narrowing the composition ranges worthy of study and to illustrate the broad range of applications where solution-based combinatorial synthesis can have significant impact.

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

PubMed

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.

Combinatorial effects on clumped isotopes and their significance in biogeochemistry

NASA Astrophysics Data System (ADS)

Yeung, Laurence Y.

2016-01-01

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

A general spectral method for the numerical simulation of one-dimensional interacting fermions

NASA Astrophysics Data System (ADS)

Clason, Christian; von Winckel, Gregory

2012-08-01

This software implements a general framework for the direct numerical simulation of systems of interacting fermions in one spatial dimension. The approach is based on a specially adapted nodal spectral Galerkin method, where the basis functions are constructed to obey the antisymmetry relations of fermionic wave functions. An efficient Matlab program for the assembly of the stiffness and potential matrices is presented, which exploits the combinatorial structure of the sparsity pattern arising from this discretization to achieve optimal run-time complexity. This program allows the accurate discretization of systems with multiple fermions subject to arbitrary potentials, e.g., for verifying the accuracy of multi-particle approximations such as Hartree-Fock in the few-particle limit. It can be used for eigenvalue computations or numerical solutions of the time-dependent Schrödinger equation. The new version includes a Python implementation of the presented approach. New version program summaryProgram title: assembleFermiMatrix Catalogue identifier: AEKO_v1_1 Program summary URL:http://cpc.cs.qub.ac.uk/summaries/AEKO_v1_1.html Program obtainable from: CPC Program Library, Queen's University, Belfast, N. Ireland Licensing provisions: Standard CPC licence, http://cpc.cs.qub.ac.uk/licence/licence.html No. of lines in distributed program, including test data, etc.: 332 No. of bytes in distributed program, including test data, etc.: 5418 Distribution format: tar.gz Programming language: MATLAB/GNU Octave, Python Computer: Any architecture supported by MATLAB, GNU Octave or Python Operating system: Any supported by MATLAB, GNU Octave or Python RAM: Depends on the data Classification: 4.3, 2.2. External routines: Python 2.7+, NumPy 1.3+, SciPy 0.10+ Catalogue identifier of previous version: AEKO_v1_0 Journal reference of previous version: Comput. Phys. Commun. 183 (2012) 405 Does the new version supersede the previous version?: Yes Nature of problem: The direct numerical solution of the multi-particle one-dimensional Schrödinger equation in a quantum well is challenging due to the exponential growth in the number of degrees of freedom with increasing particles. Solution method: A nodal spectral Galerkin scheme is used where the basis functions are constructed to obey the antisymmetry relations of the fermionic wave function. The assembly of these matrices is performed efficiently by exploiting the combinatorial structure of the sparsity patterns. Reasons for new version: A Python implementation is now included. Summary of revisions: Added a Python implementation; small documentation fixes in Matlab implementation. No change in features of the package. Restrictions: Only one-dimensional computational domains with homogeneous Dirichlet or periodic boundary conditions are supported. Running time: Seconds to minutes.

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

NASA Astrophysics Data System (ADS)

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.

Single cell systems biology by super-resolution imaging and combinatorial labeling

PubMed Central

Lubeck, Eric; Cai, Long

2012-01-01

Fluorescence microscopy is a powerful quantitative tool for exploring regulatory networks in single cells. However, the number of molecular species that can be measured simultaneously is limited by the spectral separability of fluorophores. Here we demonstrate a simple but general strategy to drastically increase the capacity for multiplex detection of molecules in single cells by using optical super-resolution microscopy (SRM) and combinatorial labeling. As a proof of principle, we labeled mRNAs with unique combinations of fluorophores using Fluorescence in situ Hybridization (FISH), and resolved the sequences and combinations of fluorophores with SRM. We measured the mRNA levels of 32 genes simultaneously in single S. cerevisiae cells. These experiments demonstrate that combinatorial labeling and super-resolution imaging of single cells provides a natural approach to bring systems biology into single cells. PMID:22660740

Homology groups for particles on one-connected graphs

NASA Astrophysics Data System (ADS)

MaciÄ Żek, Tomasz; Sawicki, Adam

2017-06-01

We present a mathematical framework for describing the topology of configuration spaces for particles on one-connected graphs. In particular, we compute the homology groups over integers for different classes of one-connected graphs. Our approach is based on some fundamental combinatorial properties of the configuration spaces, Mayer-Vietoris sequences for different parts of configuration spaces, and some limited use of discrete Morse theory. As one of the results, we derive the closed-form formulae for ranks of the homology groups for indistinguishable particles on tree graphs. We also give a detailed discussion of the second homology group of the configuration space of both distinguishable and indistinguishable particles. Our motivation is the search for new kinds of quantum statistics.

A programmable microfluidic static droplet array for droplet generation, transportation, fusion, storage, and retrieval.

PubMed

Jin, Si Hyung; Jeong, Heon-Ho; Lee, Byungjin; Lee, Sung Sik; Lee, Chang-Soo

2015-01-01

We present a programmable microfluidic static droplet array (SDA) device that can perform user-defined multistep combinatorial protocols. It combines the passive storage of aqueous droplets without any external control with integrated microvalves for discrete sample dispensing and dispersion-free unit operation. The addressable picoliter-volume reaction is systematically achieved by consecutively merging programmable sequences of reagent droplets. The SDA device is remarkably reusable and able to perform identical enzyme kinetic experiments at least 30 times via automated cross-contamination-free removal of droplets from individual hydrodynamic traps. Taking all these features together, this programmable and reusable universal SDA device will be a general microfluidic platform that can be reprogrammed for multiple applications.

Combinatorial FSK modulation for power-efficient high-rate communications

NASA Technical Reports Server (NTRS)

Wagner, Paul K.; Budinger, James M.; Vanderaar, Mark J.

1991-01-01

Deep-space and satellite communications systems must be capable of conveying high-rate data accurately with low transmitter power, often through dispersive channels. A class of noncoherent Combinatorial Frequency Shift Keying (CFSK) modulation schemes is investigated which address these needs. The bit error rate performance of this class of modulation formats is analyzed and compared to the more traditional modulation types. Candidate modulator, demodulator, and digital signal processing (DSP) hardware structures are examined in detail. System-level issues are also discussed.

Coarse-grained molecular dynamics simulations of depletion-induced interactions for soft matter systems

DOE Office of Scientific and Technical Information (OSTI.GOV)

Shendruk, Tyler N., E-mail: tyler.shendruk@physics.ox.ac.uk; Bertrand, Martin; Harden, James L.

2014-12-28

Given the ubiquity of depletion effects in biological and other soft matter systems, it is desirable to have coarse-grained Molecular Dynamics (MD) simulation approaches appropriate for the study of complex systems. This paper examines the use of two common truncated Lennard-Jones (Weeks-Chandler-Andersen (WCA)) potentials to describe a pair of colloidal particles in a thermal bath of depletants. The shifted-WCA model is the steeper of the two repulsive potentials considered, while the combinatorial-WCA model is the softer. It is found that the depletion-induced well depth for the combinatorial-WCA model is significantly deeper than the shifted-WCA model because the resulting overlap ofmore » the colloids yields extra accessible volume for depletants. For both shifted- and combinatorial-WCA simulations, the second virial coefficients and pair potentials between colloids are demonstrated to be well approximated by the Morphometric Thermodynamics (MT) model. This agreement suggests that the presence of depletants can be accurately modelled in MD simulations by implicitly including them through simple, analytical MT forms for depletion-induced interactions. Although both WCA potentials are found to be effective generic coarse-grained simulation approaches for studying depletion effects in complicated soft matter systems, combinatorial-WCA is the more efficient approach as depletion effects are enhanced at lower depletant densities. The findings indicate that for soft matter systems that are better modelled by potentials with some compressibility, predictions from hard-sphere systems could greatly underestimate the magnitude of depletion effects at a given depletant density.« less

GALAXY: A new hybrid MOEA for the optimal design of Water Distribution Systems

NASA Astrophysics Data System (ADS)

Wang, Q.; Savić, D. A.; Kapelan, Z.

2017-03-01

A new hybrid optimizer, called genetically adaptive leaping algorithm for approximation and diversity (GALAXY), is proposed for dealing with the discrete, combinatorial, multiobjective design of Water Distribution Systems (WDSs), which is NP-hard and computationally intensive. The merit of GALAXY is its ability to alleviate to a great extent the parameterization issue and the high computational overhead. It follows the generational framework of Multiobjective Evolutionary Algorithms (MOEAs) and includes six search operators and several important strategies. These operators are selected based on their leaping ability in the objective space from the global and local search perspectives. These strategies steer the optimization and balance the exploration and exploitation aspects simultaneously. A highlighted feature of GALAXY lies in the fact that it eliminates majority of parameters, thus being robust and easy-to-use. The comparative studies between GALAXY and three representative MOEAs on five benchmark WDS design problems confirm its competitiveness. GALAXY can identify better converged and distributed boundary solutions efficiently and consistently, indicating a much more balanced capability between the global and local search. Moreover, its advantages over other MOEAs become more substantial as the complexity of the design problem increases.

Optimum Design of PIλDμ Controller for an Automatic Voltage Regulator System Using Combinatorial Test Design

PubMed Central

Sahib, Mouayad A.; Gambardella, Luca M.; Afzal, Wasif; Zamli, Kamal Z.

2016-01-01

Combinatorial test design is a plan of test that aims to reduce the amount of test cases systematically by choosing a subset of the test cases based on the combination of input variables. The subset covers all possible combinations of a given strength and hence tries to match the effectiveness of the exhaustive set. This mechanism of reduction has been used successfully in software testing research with t-way testing (where t indicates the interaction strength of combinations). Potentially, other systems may exhibit many similarities with this approach. Hence, it could form an emerging application in different areas of research due to its usefulness. To this end, more recently it has been applied in a few research areas successfully. In this paper, we explore the applicability of combinatorial test design technique for Fractional Order (FO), Proportional-Integral-Derivative (PID) parameter design controller, named as FOPID, for an automatic voltage regulator (AVR) system. Throughout the paper, we justify this new application theoretically and practically through simulations. In addition, we report on first experiments indicating its practical use in this field. We design different algorithms and adapted other strategies to cover all the combinations with an optimum and effective test set. Our findings indicate that combinatorial test design can find the combinations that lead to optimum design. Besides this, we also found that by increasing the strength of combination, we can approach to the optimum design in a way that with only 4-way combinatorial set, we can get the effectiveness of an exhaustive test set. This significantly reduced the number of tests needed and thus leads to an approach that optimizes design of parameters quickly. PMID:27829025

A path-oriented knowledge representation system: Defusing the combinatorial system

NASA Technical Reports Server (NTRS)

Karamouzis, Stamos T.; Barry, John S.; Smith, Steven L.; Feyock, Stefan

1995-01-01

LIMAP is a programming system oriented toward efficient information manipulation over fixed finite domains, and quantification over paths and predicates. A generalization of Warshall's Algorithm to precompute paths in a sparse matrix representation of semantic nets is employed to allow questions involving paths between components to be posed and answered easily. LIMAP's ability to cache all paths between two components in a matrix cell proved to be a computational obstacle, however, when the semantic net grew to realistic size. The present paper describes a means of mitigating this combinatorial explosion to an extent that makes the use of the LIMAP representation feasible for problems of significant size. The technique we describe radically reduces the size of the search space in which LIMAP must operate; semantic nets of more than 500 nodes have been attacked successfully. Furthermore, it appears that the procedure described is applicable not only to LIMAP, but to a number of other combinatorially explosive search space problems found in AI as well.

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

PubMed Central

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

2015-01-01

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

A stochastic discrete optimization model for designing container terminal facilities

NASA Astrophysics Data System (ADS)

Zukhruf, Febri; Frazila, Russ Bona; Burhani, Jzolanda Tsavalista

2017-11-01

As uncertainty essentially affect the total transportation cost, it remains important in the container terminal that incorporates several modes and transshipments process. This paper then presents a stochastic discrete optimization model for designing the container terminal, which involves the decision of facilities improvement action. The container terminal operation model is constructed by accounting the variation of demand and facilities performance. In addition, for illustrating the conflicting issue that practically raises in the terminal operation, the model also takes into account the possible increment delay of facilities due to the increasing number of equipment, especially the container truck. Those variations expectantly reflect the uncertainty issue in the container terminal operation. A Monte Carlo simulation is invoked to propagate the variations by following the observed distribution. The problem is constructed within the framework of the combinatorial optimization problem for investigating the optimal decision of facilities improvement. A new variant of glow-worm swarm optimization (GSO) is thus proposed for solving the optimization, which is rarely explored in the transportation field. The model applicability is tested by considering the actual characteristics of the container terminal.

PMD compensation in fiber-optic communication systems with direct detection using LDPC-coded OFDM.

PubMed

Djordjevic, Ivan B

2007-04-02

The possibility of polarization-mode dispersion (PMD) compensation in fiber-optic communication systems with direct detection using a simple channel estimation technique and low-density parity-check (LDPC)-coded orthogonal frequency division multiplexing (OFDM) is demonstrated. It is shown that even for differential group delay (DGD) of 4/BW (BW is the OFDM signal bandwidth), the degradation due to the first-order PMD can be completely compensated for. Two classes of LDPC codes designed based on two different combinatorial objects (difference systems and product of combinatorial designs) suitable for use in PMD compensation are introduced.

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

ERIC Educational Resources Information Center

Batanero, Carmen; And Others

1997-01-01

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

On the suitability of different representations of solid catalysts for combinatorial library design by genetic algorithms.

PubMed

Gobin, Oliver C; Schüth, Ferdi

2008-01-01

Genetic algorithms are widely used to solve and optimize combinatorial problems and are more often applied for library design in combinatorial chemistry. Because of their flexibility, however, their implementation can be challenging. In this study, the influence of the representation of solid catalysts on the performance of genetic algorithms was systematically investigated on the basis of a new, constrained, multiobjective, combinatorial test problem with properties common to problems in combinatorial materials science. Constraints were satisfied by penalty functions, repair algorithms, or special representations. The tests were performed using three state-of-the-art evolutionary multiobjective algorithms by performing 100 optimization runs for each algorithm and test case. Experimental data obtained during the optimization of a noble metal-free solid catalyst system active in the selective catalytic reduction of nitric oxide with propene was used to build up a predictive model to validate the results of the theoretical test problem. A significant influence of the representation on the optimization performance was observed. Binary encodings were found to be the preferred encoding in most of the cases, and depending on the experimental test unit, repair algorithms or penalty functions performed best.

Learning to generate combinatorial action sequences utilizing the initial sensitivity of deterministic dynamical systems.

PubMed

Nishimoto, Ryu; Tani, Jun

2004-09-01

This study shows how sensory-action sequences of imitating finite state machines (FSMs) can be learned by utilizing the deterministic dynamics of recurrent neural networks (RNNs). Our experiments indicated that each possible combinatorial sequence can be recalled by specifying its respective initial state value and also that fractal structures appear in this initial state mapping after the learning converges. We also observed that the sequences of mimicking FSMs are encoded utilizing the transient regions rather than the invariant sets of the evolved dynamical systems of the RNNs.

Polynomial functors and combinatorial Dyson-Schwinger equations

NASA Astrophysics Data System (ADS)

Kock, Joachim

2017-04-01

We present a general abstract framework for combinatorial Dyson-Schwinger equations, in which combinatorial identities are lifted to explicit bijections of sets, and more generally equivalences of groupoids. Key features of combinatorial Dyson-Schwinger equations are revealed to follow from general categorical constructions and universal properties. Rather than beginning with an equation inside a given Hopf algebra and referring to given Hochschild 1-cocycles, our starting point is an abstract fixpoint equation in groupoids, shown canonically to generate all the algebraic structures. Precisely, for any finitary polynomial endofunctor P defined over groupoids, the system of combinatorial Dyson-Schwinger equations X = 1 + P(X) has a universal solution, namely the groupoid of P-trees. The isoclasses of P-trees generate naturally a Connes-Kreimer-like bialgebra, in which the abstract Dyson-Schwinger equation can be internalised in terms of canonical B+-operators. The solution to this equation is a series (the Green function), which always enjoys a Faà di Bruno formula, and hence generates a sub-bialgebra isomorphic to the Faà di Bruno bialgebra. Varying P yields different bialgebras, and cartesian natural transformations between various P yield bialgebra homomorphisms and sub-bialgebras, corresponding for example to truncation of Dyson-Schwinger equations. Finally, all constructions can be pushed inside the classical Connes-Kreimer Hopf algebra of trees by the operation of taking core of P-trees. A byproduct of the theory is an interpretation of combinatorial Green functions as inductive data types in the sense of Martin-Löf type theory (expounded elsewhere).

Measurement problem in Program Universe. Revision

NASA Astrophysics Data System (ADS)

Noyes, H. P.; Gefwert, C.; Manthey, M. J.

1985-07-01

The measurement problem of contemporary physics is in our view an artifact of its philosophical and mathematical underpinnings. We describe a new philosophical view of theory formation, rooted in Wittgenstein, and Bishop's and Martin-Loef's constructivity, which obviates such discussions. We present an unfinished, but very encouraging, theory which is compatible with this philosophical framework. The theory is based on the concepts of counting and combinatorics in the framework provided by the combinatorial hierarchy, a unique hierarchy of bit strings which interact by an operation called discrimination. Measurement criteria incorporate c, h-bar and m/sub p/ or (not and) G. The resulting theory is discrete throughout, contains no infinities, and, as far as we have developed it, is in agreement with quantum mechanical and cosmological fact.

'Extremotaxis': computing with a bacterial-inspired algorithm.

PubMed

Nicolau, Dan V; Burrage, Kevin; Nicolau, Dan V; Maini, Philip K

2008-01-01

We present a general-purpose optimization algorithm inspired by "run-and-tumble", the biased random walk chemotactic swimming strategy used by the bacterium Escherichia coli to locate regions of high nutrient concentration The method uses particles (corresponding to bacteria) that swim through the variable space (corresponding to the attractant concentration profile). By constantly performing temporal comparisons, the particles drift towards the minimum or maximum of the function of interest. We illustrate the use of our method with four examples. We also present a discrete version of the algorithm. The new algorithm is expected to be useful in combinatorial optimization problems involving many variables, where the functional landscape is apparently stochastic and has local minima, but preserves some derivative structure at intermediate scales.

Diversity-oriented combinatorial biosynthesis of benzenediol lactone scaffolds by subunit shuffling of fungal polyketide synthases.

PubMed

Xu, Yuquan; Zhou, Tong; Zhang, Shuwei; Espinosa-Artiles, Patricia; Wang, Luoyi; Zhang, Wei; Lin, Min; Gunatilaka, A A Leslie; Zhan, Jixun; Molnár, István

2014-08-26

Combinatorial biosynthesis aspires to exploit the promiscuity of microbial anabolic pathways to engineer the synthesis of new chemical entities. Fungal benzenediol lactone (BDL) polyketides are important pharmacophores with wide-ranging bioactivities, including heat shock response and immune system modulatory effects. Their biosynthesis on a pair of sequentially acting iterative polyketide synthases (iPKSs) offers a test case for the modularization of secondary metabolic pathways into "build-couple-pair" combinatorial synthetic schemes. Expression of random pairs of iPKS subunits from four BDL model systems in a yeast heterologous host created a diverse library of BDL congeners, including a polyketide with an unnatural skeleton and heat shock response-inducing activity. Pairwise heterocombinations of the iPKS subunits also helped to illuminate the innate, idiosyncratic programming of these enzymes. Even in combinatorial contexts, these biosynthetic programs remained largely unchanged, so that the iPKSs built their cognate biosynthons, coupled these building blocks into chimeric polyketide intermediates, and catalyzed intramolecular pairing to release macrocycles or α-pyrones. However, some heterocombinations also provoked stuttering, i.e., the relaxation of iPKSs chain length control to assemble larger homologous products. The success of such a plug and play approach to biosynthesize novel chemical diversity bodes well for bioprospecting unnatural polyketides for drug discovery.

Successful application of the dual-vector system II in creating a reliable phage-displayed combinatorial Fab library.

PubMed

Song, Suk-yoon; Hur, Byung-ung; Lee, Kyung-woo; Choi, Hyo-jung; Kim, Sung-soo; Kang, Goo; Cha, Sang-hoon

2009-03-31

The dual-vector system-II (DVS-II), which allows efficient display of Fab antibodies on phage, has been reported previously, but its practical applicability in a phage-displayed antibody library has not been verified. To resolve this issue, we created two small combinatorial human Fab antibody libraries using the DVS-II, and isolation of target-specific antibodies was attempted. Biopanning of one antibody library, termed DVFAB-1L library, which has a 1.3 x 10(7) combinatorial antibody complexity, against fluorescein-BSA resulted in successful isolation of human Fab clones specific for the antigen despite the presence of only a single light chain in the library. By using the unique feature of the DVS-II, an antibody library of a larger size, named DVFAB-131L, which has a 1.5 x 10(9) combinatorial antibody complexity, was also generated in a rapid manner by combining 1.3 x 10(7) heavy chains and 131 light chains and more diverse anti-fluorescein-BSA Fab antibody clones were successfully obtained. Our results demonstrate that the DVS-II can be applied readily in creating phage-displayed antibody libraries with much less effort, and target-specific antibody clones can be isolated reliably via light chain promiscuity of antibody molecule.

Magnetohydrodynamic pump with a system for promoting flow of fluid in one direction

DOEpatents

Lemoff, Asuncion V [Union City, CA; Lee, Abraham P [Irvine, CA

2010-07-13

A magnetohydrodynamic pump for pumping a fluid. The pump includes a microfluidic channel for channeling the fluid, a MHD electrode/magnet system operatively connected to the microfluidic channel, and a system for promoting flow of the fluid in one direction in the microfluidic channel. The pump has uses in the medical and biotechnology industries for blood-cell-separation equipment, biochemical assays, chemical synthesis, genetic analysis, drug screening, an array of antigen-antibody reactions, combinatorial chemistry, drug testing, medical and biological diagnostics, and combinatorial chemistry. The pump also has uses in electrochromatography, surface micromachining, laser ablation, inkjet printers, and mechanical micromilling.

Combinatorial screening of halide perovskite thin films and solar cells by mask-defined IR laser molecular beam epitaxy

NASA Astrophysics Data System (ADS)

Kawashima, Kazuhiro; Okamoto, Yuji; Annayev, Orazmuhammet; Toyokura, Nobuo; Takahashi, Ryota; Lippmaa, Mikk; Itaka, Kenji; Suzuki, Yoshikazu; Matsuki, Nobuyuki; Koinuma, Hideomi

2017-12-01

As an extension of combinatorial molecular layer epitaxy via ablation of perovskite oxides by a pulsed excimer laser, we have developed a laser molecular beam epitaxy (MBE) system for parallel integration of nano-scaled thin films of organic-inorganic hybrid materials. A pulsed infrared (IR) semiconductor laser was adopted for thermal evaporation of organic halide (A-site: CH3NH3I) and inorganic halide (B-site: PbI2) powder targets to deposit repeated A/B bilayer films where the thickness of each layer was controlled on molecular layer scale by programming the evaporation IR laser pulse number, length, or power. The layer thickness was monitored with an in situ quartz crystal microbalance and calibrated against ex situ stylus profilometer measurements. A computer-controlled movable mask system enabled the deposition of combinatorial thin film libraries, where each library contains a vertically homogeneous film with spatially programmable A- and B-layer thicknesses. On the composition gradient film, a hole transport Spiro-OMeTAD layer was spin-coated and dried followed by the vacuum evaporation of Ag electrodes to form the solar cell. The preliminary cell performance was evaluated by measuring I-V characteristics at seven different positions on the 12.5 mm × 12.5 mm combinatorial library sample with seven 2 mm × 4 mm slits under a solar simulator irradiation. The combinatorial solar cell library clearly demonstrated that the energy conversion efficiency sharply changes from nearly zero to 10.2% as a function of the illumination area in the library. The exploration of deposition parameters for obtaining optimum performance could thus be greatly accelerated. Since the thickness ratio of PbI2 and CH3NH3I can be freely chosen along the shadow mask movement, these experiments show the potential of this system for high-throughput screening of optimum chemical composition in the binary film library and application to halide perovskite solar cell.

Combinatorial screening of halide perovskite thin films and solar cells by mask-defined IR laser molecular beam epitaxy.

PubMed

Kawashima, Kazuhiro; Okamoto, Yuji; Annayev, Orazmuhammet; Toyokura, Nobuo; Takahashi, Ryota; Lippmaa, Mikk; Itaka, Kenji; Suzuki, Yoshikazu; Matsuki, Nobuyuki; Koinuma, Hideomi

2017-01-01

As an extension of combinatorial molecular layer epitaxy via ablation of perovskite oxides by a pulsed excimer laser, we have developed a laser molecular beam epitaxy (MBE) system for parallel integration of nano-scaled thin films of organic-inorganic hybrid materials. A pulsed infrared (IR) semiconductor laser was adopted for thermal evaporation of organic halide (A-site: CH 3 NH 3 I) and inorganic halide (B-site: PbI 2 ) powder targets to deposit repeated A/B bilayer films where the thickness of each layer was controlled on molecular layer scale by programming the evaporation IR laser pulse number, length, or power. The layer thickness was monitored with an in situ quartz crystal microbalance and calibrated against ex situ stylus profilometer measurements. A computer-controlled movable mask system enabled the deposition of combinatorial thin film libraries, where each library contains a vertically homogeneous film with spatially programmable A- and B-layer thicknesses. On the composition gradient film, a hole transport Spiro-OMeTAD layer was spin-coated and dried followed by the vacuum evaporation of Ag electrodes to form the solar cell. The preliminary cell performance was evaluated by measuring I - V characteristics at seven different positions on the 12.5 mm × 12.5 mm combinatorial library sample with seven 2 mm × 4 mm slits under a solar simulator irradiation. The combinatorial solar cell library clearly demonstrated that the energy conversion efficiency sharply changes from nearly zero to 10.2% as a function of the illumination area in the library. The exploration of deposition parameters for obtaining optimum performance could thus be greatly accelerated. Since the thickness ratio of PbI 2 and CH 3 NH 3 I can be freely chosen along the shadow mask movement, these experiments show the potential of this system for high-throughput screening of optimum chemical composition in the binary film library and application to halide perovskite solar cell.

Thermoelectric properties of the LaCoO3-LaCrO3 system using a high-throughput combinatorial approach

NASA Astrophysics Data System (ADS)

Talley, K. R.; Barron, S. C.; Nguyen, N.; Wong-Ng, W.; Martin, J.; Zhang, Y. L.; Song, X.

2017-02-01

A combinatorial film of the LaCo1-xCrxO3 system was fabricated using the LaCoO3 and LaCrO3 targets at the NIST Pulsed Laser Deposition (PLD) facility. As the ionic size of Cr3+ is greater than that of Co3+, the unit cell volume of the series increases with increasing x. Using a custom screening tool, the Seebeck coefficient of LaCo1-xCrxO3 approaches a measured maximum of 286 μV/K, near to the cobalt-rich end of the film library (with x ≈ 0.49). The resistivity value increases continuously with increasing x. The measured power factor, PF, of this series, which is related to the efficiency of energy conversion, also exhibits a maximum at the composition of x ≈ 0.49, which corresponds to the maximum value of the Seebeck coefficient. Our results illustrate the efficiency of applying the high-throughput combinatorial technique to study thermoelectric materials.

A dynamical systems model for combinatorial cancer therapy enhances oncolytic adenovirus efficacy by MEK-inhibition.

PubMed

Bagheri, Neda; Shiina, Marisa; Lauffenburger, Douglas A; Korn, W Michael

2011-02-01

Oncolytic adenoviruses, such as ONYX-015, have been tested in clinical trials for currently untreatable tumors, but have yet to demonstrate adequate therapeutic efficacy. The extent to which viruses infect targeted cells determines the efficacy of this approach but many tumors down-regulate the Coxsackievirus and Adenovirus Receptor (CAR), rendering them less susceptible to infection. Disrupting MAPK pathway signaling by pharmacological inhibition of MEK up-regulates CAR expression, offering possible enhanced adenovirus infection. MEK inhibition, however, interferes with adenovirus replication due to resulting G1-phase cell cycle arrest. Therefore, enhanced efficacy will depend on treatment protocols that productively balance these competing effects. Predictive understanding of how to attain and enhance therapeutic efficacy of combinatorial treatment is difficult since the effects of MEK inhibitors, in conjunction with adenovirus/cell interactions, are complex nonlinear dynamic processes. We investigated combinatorial treatment strategies using a mathematical model that predicts the impact of MEK inhibition on tumor cell proliferation, ONYX-015 infection, and oncolysis. Specifically, we fit a nonlinear differential equation system to dedicated experimental data and analyzed the resulting simulations for favorable treatment strategies. Simulations predicted enhanced combinatorial therapy when both treatments were applied simultaneously; we successfully validated these predictions in an ensuing explicit test study. Further analysis revealed that a CAR-independent mechanism may be responsible for amplified virus production and cell death. We conclude that integrated computational and experimental analysis of combinatorial therapy provides a useful means to identify treatment/infection protocols that yield clinically significant oncolysis. Enhanced oncolytic therapy has the potential to dramatically improve non-surgical cancer treatment, especially in locally advanced or metastatic cases where treatment options remain limited.

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

NASA Astrophysics Data System (ADS)

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

2002-02-01

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

Bulk combinatorial synthesis and high throughput characterization for rapid assessment of magnetic materials: Application of laser engineered net shaping (LENS)

DOE PAGES

Geng, J.; Nlebedim, I. C.; Besser, M. F.; ...

2016-04-15

A bulk combinatorial approach for synthesizing alloy libraries using laser engineered net shaping (LENS; i.e., 3D printing) was utilized to rapidly assess material systems for magnetic applications. The LENS system feeds powders in different ratios into a melt pool created by a laser to synthesize samples with bulk (millimeters) dimensions. By analyzing these libraries with autosampler differential scanning calorimeter/thermal gravimetric analysis and vibrating sample magnetometry, we are able to rapidly characterize the thermodynamic and magnetic properties of the libraries. Furthermore, the Fe-Co binary alloy was used as a model system and the results were compared with data in the literature.

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

PubMed

Chen, Sheng-Hong; Lahav, Galit

2016-12-01

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

Set-Based Discrete Particle Swarm Optimization Based on Decomposition for Permutation-Based Multiobjective Combinatorial Optimization Problems.

PubMed

Yu, Xue; Chen, Wei-Neng; Gu, Tianlong; Zhang, Huaxiang; Yuan, Huaqiang; Kwong, Sam; Zhang, Jun

2018-07-01

This paper studies a specific class of multiobjective combinatorial optimization problems (MOCOPs), namely the permutation-based MOCOPs. Many commonly seen MOCOPs, e.g., multiobjective traveling salesman problem (MOTSP), multiobjective project scheduling problem (MOPSP), belong to this problem class and they can be very different. However, as the permutation-based MOCOPs share the inherent similarity that the structure of their search space is usually in the shape of a permutation tree, this paper proposes a generic multiobjective set-based particle swarm optimization methodology based on decomposition, termed MS-PSO/D. In order to coordinate with the property of permutation-based MOCOPs, MS-PSO/D utilizes an element-based representation and a constructive approach. Through this, feasible solutions under constraints can be generated step by step following the permutation-tree-shaped structure. And problem-related heuristic information is introduced in the constructive approach for efficiency. In order to address the multiobjective optimization issues, the decomposition strategy is employed, in which the problem is converted into multiple single-objective subproblems according to a set of weight vectors. Besides, a flexible mechanism for diversity control is provided in MS-PSO/D. Extensive experiments have been conducted to study MS-PSO/D on two permutation-based MOCOPs, namely the MOTSP and the MOPSP. Experimental results validate that the proposed methodology is promising.

Adapting an Ant Colony Metaphor for Multi-Robot Chemical Plume Tracing

PubMed Central

Meng, Qing-Hao; Yang, Wei-Xing; Wang, Yang; Li, Fei; Zeng, Ming

2012-01-01

We consider chemical plume tracing (CPT) in time-varying airflow environments using multiple mobile robots. The purpose of CPT is to approach a gas source with a previously unknown location in a given area. Therefore, the CPT could be considered as a dynamic optimization problem in continuous domains. The traditional ant colony optimization (ACO) algorithm has been successfully used for combinatorial optimization problems in discrete domains. To adapt the ant colony metaphor to the multi-robot CPT problem, the two-dimension continuous search area is discretized into grids and the virtual pheromone is updated according to both the gas concentration and wind information. To prevent the adapted ACO algorithm from being prematurely trapped in a local optimum, the upwind surge behavior is adopted by the robots with relatively higher gas concentration in order to explore more areas. The spiral surge (SS) algorithm is also examined for comparison. Experimental results using multiple real robots in two indoor natural ventilated airflow environments show that the proposed CPT method performs better than the SS algorithm. The simulation results for large-scale advection-diffusion plume environments show that the proposed method could also work in outdoor meandering plume environments. PMID:22666056

Adapting an ant colony metaphor for multi-robot chemical plume tracing.

PubMed

Meng, Qing-Hao; Yang, Wei-Xing; Wang, Yang; Li, Fei; Zeng, Ming

2012-01-01

We consider chemical plume tracing (CPT) in time-varying airflow environments using multiple mobile robots. The purpose of CPT is to approach a gas source with a previously unknown location in a given area. Therefore, the CPT could be considered as a dynamic optimization problem in continuous domains. The traditional ant colony optimization (ACO) algorithm has been successfully used for combinatorial optimization problems in discrete domains. To adapt the ant colony metaphor to the multi-robot CPT problem, the two-dimension continuous search area is discretized into grids and the virtual pheromone is updated according to both the gas concentration and wind information. To prevent the adapted ACO algorithm from being prematurely trapped in a local optimum, the upwind surge behavior is adopted by the robots with relatively higher gas concentration in order to explore more areas. The spiral surge (SS) algorithm is also examined for comparison. Experimental results using multiple real robots in two indoor natural ventilated airflow environments show that the proposed CPT method performs better than the SS algorithm. The simulation results for large-scale advection-diffusion plume environments show that the proposed method could also work in outdoor meandering plume environments.

Evolution, learning, and cognition

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lee, Y.C.

1988-01-01

The book comprises more than fifteen articles in the areas of neural networks and connectionist systems, classifier systems, adaptive network systems, genetic algorithm, cellular automata, artificial immune systems, evolutionary genetics, cognitive science, optical computing, combinatorial optimization, and cybernetics.

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

ERIC Educational Resources Information Center

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

2004-01-01

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

Quantum Efficiency and Bandgap Analysis for Combinatorial Photovoltaics: Sorting Activity of Cu–O Compounds in All-Oxide Device Libraries

PubMed Central

2014-01-01

All-oxide-based photovoltaics (PVs) encompass the potential for extremely low cost solar cells, provided they can obtain an order of magnitude improvement in their power conversion efficiencies. To achieve this goal, we perform a combinatorial materials study of metal oxide based light absorbers, charge transporters, junctions between them, and PV devices. Here we report the development of a combinatorial internal quantum efficiency (IQE) method. IQE measures the efficiency associated with the charge separation and collection processes, and thus is a proxy for PV activity of materials once placed into devices, discarding optical properties that cause uncontrolled light harvesting. The IQE is supported by high-throughput techniques for bandgap fitting, composition analysis, and thickness mapping, which are also crucial parameters for the combinatorial investigation cycle of photovoltaics. As a model system we use a library of 169 solar cells with a varying thickness of sprayed titanium dioxide (TiO2) as the window layer, and covarying thickness and composition of binary compounds of copper oxides (Cu–O) as the light absorber, fabricated by Pulsed Laser Deposition (PLD). The analysis on the combinatorial devices shows the correlation between compositions and bandgap, and their effect on PV activity within several device configurations. The analysis suggests that the presence of Cu4O3 plays a significant role in the PV activity of binary Cu–O compounds. PMID:24410367

Evolution of speech-specific cognitive adaptations.

PubMed

de Boer, Bart

2015-01-01

This paper argues that an evolutionary perspective is natural when investigating cognitive adaptations related to language. This is because there appears to be correspondence between traits that linguists consider interesting and traits that have undergone selective pressure related to language. The paper briefly reviews theoretical results that shed light on what kind of adaptations we can expect to have evolved and then reviews concrete work related to the evolution of adaptations for combinatorial speech. It turns out that there is as yet no strong direct evidence for cognitive traits that have undergone selection related to speech, but there is indirect evidence that indicates selection. However, the traits that may have undergone selection are expected to be continuously variable ones, rather than the discrete ones that linguists have focused on traditionally.

FOURTH SEMINAR TO THE MEMORY OF D.N. KLYSHKO: Algebraic solution of the synthesis problem for coded sequences

NASA Astrophysics Data System (ADS)

Leukhin, Anatolii N.

2005-08-01

The algebraic solution of a 'complex' problem of synthesis of phase-coded (PC) sequences with the zero level of side lobes of the cyclic autocorrelation function (ACF) is proposed. It is shown that the solution of the synthesis problem is connected with the existence of difference sets for a given code dimension. The problem of estimating the number of possible code combinations for a given code dimension is solved. It is pointed out that the problem of synthesis of PC sequences is related to the fundamental problems of discrete mathematics and, first of all, to a number of combinatorial problems, which can be solved, as the number factorisation problem, by algebraic methods by using the theory of Galois fields and groups.

Multiple-variable neighbourhood search for the single-machine total weighted tardiness problem

NASA Astrophysics Data System (ADS)

Chung, Tsui-Ping; Fu, Qunjie; Liao, Ching-Jong; Liu, Yi-Ting

2017-07-01

The single-machine total weighted tardiness (SMTWT) problem is a typical discrete combinatorial optimization problem in the scheduling literature. This problem has been proved to be NP hard and thus provides a challenging area for metaheuristics, especially the variable neighbourhood search algorithm. In this article, a multiple variable neighbourhood search (m-VNS) algorithm with multiple neighbourhood structures is proposed to solve the problem. Special mechanisms named matching and strengthening operations are employed in the algorithm, which has an auto-revising local search procedure to explore the solution space beyond local optimality. Two aspects, searching direction and searching depth, are considered, and neighbourhood structures are systematically exchanged. Experimental results show that the proposed m-VNS algorithm outperforms all the compared algorithms in solving the SMTWT problem.

Asessing for Structural Understanding in Childrens' Combinatorial Problem Solving.

ERIC Educational Resources Information Center

English, Lyn

1999-01-01

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

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

PubMed

Müller-Molina, Arnoldo J; Schöler, Hans R; Araúzo-Bravo, Marcos J

2012-01-01

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.

Comprehensive Human Transcription Factor Binding Site Map for Combinatory Binding Motifs Discovery

PubMed Central

Müller-Molina, Arnoldo J.; Schöler, Hans R.; Araúzo-Bravo, Marcos J.

2012-01-01

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. PMID:23209563

Hypergraph-Based Combinatorial Optimization of Matrix-Vector Multiplication

ERIC Educational Resources Information Center

Wolf, Michael Maclean

2009-01-01

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

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

PubMed Central

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

2015-01-01

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

Combinatorial structures to modeling simple games and applications

NASA Astrophysics Data System (ADS)

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.

Using Synchronous Boolean Networks to Model Several Phenomena of Collective Behavior

PubMed Central

Kochemazov, Stepan; Semenov, Alexander

2014-01-01

In this paper, we propose an approach for modeling and analysis of a number of phenomena of collective behavior. By collectives we mean multi-agent systems that transition from one state to another at discrete moments of time. The behavior of a member of a collective (agent) is called conforming if the opinion of this agent at current time moment conforms to the opinion of some other agents at the previous time moment. We presume that at each moment of time every agent makes a decision by choosing from the set (where 1-decision corresponds to action and 0-decision corresponds to inaction). In our approach we model collective behavior with synchronous Boolean networks. We presume that in a network there can be agents that act at every moment of time. Such agents are called instigators. Also there can be agents that never act. Such agents are called loyalists. Agents that are neither instigators nor loyalists are called simple agents. We study two combinatorial problems. The first problem is to find a disposition of instigators that in several time moments transforms a network from a state where the majority of simple agents are inactive to a state with the majority of active agents. The second problem is to find a disposition of loyalists that returns the network to a state with the majority of inactive agents. Similar problems are studied for networks in which simple agents demonstrate the contrary to conforming behavior that we call anticonforming. We obtained several theoretical results regarding the behavior of collectives of agents with conforming or anticonforming behavior. In computational experiments we solved the described problems for randomly generated networks with several hundred vertices. We reduced corresponding combinatorial problems to the Boolean satisfiability problem (SAT) and used modern SAT solvers to solve the instances obtained. PMID:25526612

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

DOEpatents

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

2008-11-11

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

Roles of type II thioesterases and their application for secondary metabolite yield improvement.

PubMed

Kotowska, Magdalena; Pawlik, Krzysztof

2014-09-01

A large number of antibiotics and other industrially important microbial secondary metabolites are synthesized by polyketide synthases (PKSs) and nonribosomal peptide synthetases (NRPSs). These multienzymatic complexes provide an enormous flexibility in formation of diverse chemical structures from simple substrates, such as carboxylic acids and amino acids. Modular PKSs and NRPSs, often referred to as megasynthases, have brought about a special interest due to the colinearity between enzymatic domains in the proteins working as an "assembly line" and the chain elongation and modification steps. Extensive efforts toward modified compound biosynthesis by changing organization of PKS and NRPS domains in a combinatorial manner laid good grounds for rational design of new structures and their controllable biosynthesis as proposed by the synthetic biology approach. Despite undeniable progress made in this field, the yield of such "unnatural" natural products is often not satisfactory. Here, we focus on type II thioesterases (TEIIs)--discrete hydrolytic enzymes often encoded within PKS and NRPS gene clusters which can be used to enhance product yield. We review diverse roles of TEIIs (removal of aberrant residues blocking the megasynthase, participation in substrate selection, intermediate, and product release) and discuss their application in new biosynthetic systems utilizing PKS and NRPS parts.

Non-rigid image registration using graph-cuts.

PubMed

Tang, Tommy W H; Chung, Albert C S

2007-01-01

Non-rigid image registration is an ill-posed yet challenging problem due to its supernormal high degree of freedoms and inherent requirement of smoothness. Graph-cuts method is a powerful combinatorial optimization tool which has been successfully applied into image segmentation and stereo matching. Under some specific constraints, graph-cuts method yields either a global minimum or a local minimum in a strong sense. Thus, it is interesting to see the effects of using graph-cuts in non-rigid image registration. In this paper, we formulate non-rigid image registration as a discrete labeling problem. Each pixel in the source image is assigned a displacement label (which is a vector) indicating which position in the floating image it is spatially corresponding to. A smoothness constraint based on first derivative is used to penalize sharp changes in displacement labels across pixels. The whole system can be optimized by using the graph-cuts method via alpha-expansions. We compare 2D and 3D registration results of our method with two state-of-the-art approaches. It is found that our method is more robust to different challenging non-rigid registration cases with higher registration accuracy.

Sparse signals recovered by non-convex penalty in quasi-linear systems.

PubMed

Cui, Angang; Li, Haiyang; Wen, Meng; Peng, Jigen

2018-01-01

The goal of compressed sensing is to reconstruct a sparse signal under a few linear measurements far less than the dimension of the ambient space of the signal. However, many real-life applications in physics and biomedical sciences carry some strongly nonlinear structures, and the linear model is no longer suitable. Compared with the compressed sensing under the linear circumstance, this nonlinear compressed sensing is much more difficult, in fact also NP-hard, combinatorial problem, because of the discrete and discontinuous nature of the [Formula: see text]-norm and the nonlinearity. In order to get a convenience for sparse signal recovery, we set the nonlinear models have a smooth quasi-linear nature in this paper, and study a non-convex fraction function [Formula: see text] in this quasi-linear compressed sensing. We propose an iterative fraction thresholding algorithm to solve the regularization problem [Formula: see text] for all [Formula: see text]. With the change of parameter [Formula: see text], our algorithm could get a promising result, which is one of the advantages for our algorithm compared with some state-of-art algorithms. Numerical experiments show that our method performs much better than some state-of-the-art methods.

Functional autonomy of distant-acting human enhancers

DOE Office of Scientific and Technical Information (OSTI.GOV)

Visel, Axel; Akiyama, Jennifer A.; Shoukry, Malak

2009-02-19

Many human genes are associated with dispersed arrays of transcriptional enhancers that regulate their expression in time and space. Studies in invertebrate model systems have suggested that these elements function as discrete and independent regulatory units, but the in vivo combinatorial properties of vertebrate enhancers remain poorly understood. To explore the modularity and regulatory autonomy of human developmental enhancers, we experimentally concatenated up to four enhancers from different genes and used a transgenic mouse assay to compare the in vivo activity of these compound elements with that of the single modules. In all of the six different combinations of elementsmore » tested, the reporter gene activity patterns were additive without signs of interference between the individual modules, indicating that regulatory specificity was maintained despite the presence of closely-positioned heterologous enhancers. Even in cases where two elements drove expression in close anatomical proximity, such as within neighboring subregions of the developing limb bud, the compound patterns did not show signs of cross-inhibition between individual elements or novel expression sites. These data indicate that human developmental enhancers are highly modular and functionally autonomous and suggest that genomic enhancer shuffling may have contributed to the evolution of complex gene expression patterns in vertebrates« less

MARCC (Matrix-Assisted Reader Chromatin Capture): an antibody-free method to enrich and analyze combinatorial nucleosome modifications

PubMed Central

Su, Zhangli

2016-01-01

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 western blotting 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. PMID:26131849

Combinatorial screening of halide perovskite thin films and solar cells by mask-defined IR laser molecular beam epitaxy

PubMed Central

Kawashima, Kazuhiro; Okamoto, Yuji; Annayev, Orazmuhammet; Toyokura, Nobuo; Takahashi, Ryota; Lippmaa, Mikk; Itaka, Kenji; Suzuki, Yoshikazu; Matsuki, Nobuyuki; Koinuma, Hideomi

2017-01-01

Abstract As an extension of combinatorial molecular layer epitaxy via ablation of perovskite oxides by a pulsed excimer laser, we have developed a laser molecular beam epitaxy (MBE) system for parallel integration of nano-scaled thin films of organic–inorganic hybrid materials. A pulsed infrared (IR) semiconductor laser was adopted for thermal evaporation of organic halide (A-site: CH3NH3I) and inorganic halide (B-site: PbI2) powder targets to deposit repeated A/B bilayer films where the thickness of each layer was controlled on molecular layer scale by programming the evaporation IR laser pulse number, length, or power. The layer thickness was monitored with an in situ quartz crystal microbalance and calibrated against ex situ stylus profilometer measurements. A computer-controlled movable mask system enabled the deposition of combinatorial thin film libraries, where each library contains a vertically homogeneous film with spatially programmable A- and B-layer thicknesses. On the composition gradient film, a hole transport Spiro-OMeTAD layer was spin-coated and dried followed by the vacuum evaporation of Ag electrodes to form the solar cell. The preliminary cell performance was evaluated by measuring I-V characteristics at seven different positions on the 12.5 mm × 12.5 mm combinatorial library sample with seven 2 mm × 4 mm slits under a solar simulator irradiation. The combinatorial solar cell library clearly demonstrated that the energy conversion efficiency sharply changes from nearly zero to 10.2% as a function of the illumination area in the library. The exploration of deposition parameters for obtaining optimum performance could thus be greatly accelerated. Since the thickness ratio of PbI2 and CH3NH3I can be freely chosen along the shadow mask movement, these experiments show the potential of this system for high-throughput screening of optimum chemical composition in the binary film library and application to halide perovskite solar cell. PMID:28567176

A New Approach for Proving or Generating Combinatorial Identities

ERIC Educational Resources Information Center

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…

Synergism and Combinatorial Coding for Binary Odor Mixture Perception in Drosophila

PubMed Central

Chakraborty, Tuhin Subhra; Siddiqi, Obaid

2016-01-01

Most odors in the natural environment are mixtures of several compounds. Olfactory receptors housed in the olfactory sensory neurons detect these odors and transmit the information to the brain, leading to decision-making. But whether the olfactory system detects the ingredients of a mixture separately or treats mixtures as different entities is not well understood. Using Drosophila melanogaster as a model system, we have demonstrated that fruit flies perceive binary odor mixtures in a manner that is heavily dependent on both the proportion and the degree of dilution of the components, suggesting a combinatorial coding at the peripheral level. This coding strategy appears to be receptor specific and is independent of interneuronal interactions. PMID:27588303

Combinatorial study of Ni-Ti-Pt ternary metal gate electrodes on HfO{sub 2} for the advanced gate stack

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chang, K.-S.; Green, M. L.; Suehle, J.

2006-10-02

The authors have fabricated combinatorial Ni-Ti-Pt ternary metal gate thin film libraries on HfO{sub 2} using magnetron co-sputtering to investigate flatband voltage shift ({delta}V{sub fb}), work function ({phi}{sub m}), and leakage current density (J{sub L}) variations. A more negative {delta}V{sub fb} is observed close to the Ti-rich corner than at the Ni- and Pt-rich corners, implying smaller {phi}{sub m} near the Ti-rich corners and higher {phi}{sub m} near the Ni- and Pt-rich corners. In addition, measured J{sub L} values can be explained consistently with the observed {phi}{sub m} variations. Combinatorial methodologies prove to be useful in surveying the large compositionalmore » space of ternary alloy metal gate electrode systems.« less

Exploiting Quantum Resonance to Solve Combinatorial Problems

NASA Technical Reports Server (NTRS)

Zak, Michail; Fijany, Amir

2006-01-01

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

A gradient system solution to Potts mean field equations and its electronic implementation.

PubMed

Urahama, K; Ueno, S

1993-03-01

A gradient system solution method is presented for solving Potts mean field equations for combinatorial optimization problems subject to winner-take-all constraints. In the proposed solution method the optimum solution is searched by using gradient descent differential equations whose trajectory is confined within the feasible solution space of optimization problems. This gradient system is proven theoretically to always produce a legal local optimum solution of combinatorial optimization problems. An elementary analog electronic circuit implementing the presented method is designed on the basis of current-mode subthreshold MOS technologies. The core constituent of the circuit is the winner-take-all circuit developed by Lazzaro et al. Correct functioning of the presented circuit is exemplified with simulations of the circuits implementing the scheme for solving the shortest path problems.

Gene-network inference by message passing

NASA Astrophysics Data System (ADS)

Braunstein, A.; Pagnani, A.; Weigt, M.; Zecchina, R.

2008-01-01

The inference of gene-regulatory processes from gene-expression data belongs to the major challenges of computational systems biology. Here we address the problem from a statistical-physics perspective and develop a message-passing algorithm which is able to infer sparse, directed and combinatorial regulatory mechanisms. Using the replica technique, the algorithmic performance can be characterized analytically for artificially generated data. The algorithm is applied to genome-wide expression data of baker's yeast under various environmental conditions. We find clear cases of combinatorial control, and enrichment in common functional annotations of regulated genes and their regulators.

Second quantization in bit-string physics

NASA Technical Reports Server (NTRS)

Noyes, H. Pierre

1993-01-01

Using a new fundamental theory based on bit-strings, a finite and discrete version of the solutions of the free one particle Dirac equation as segmented trajectories with steps of length h/mc along the forward and backward light cones executed at velocity +/- c are derived. Interpreting the statistical fluctuations which cause the bends in these segmented trajectories as emission and absorption of radiation, these solutions are analogous to a fermion propagator in a second quantized theory. This allows us to interpret the mass parameter in the step length as the physical mass of the free particle. The radiation in interaction with it has the usual harmonic oscillator structure of a second quantized theory. How these free particle masses can be generated gravitationally using the combinatorial hierarchy sequence (3,10,137,2(sup 127) + 136), and some of the predictive consequences are sketched.

Automated phase mapping with AgileFD and its application to light absorber discovery in the V–Mn–Nb oxide system

DOE PAGES

Suram, Santosh K.; Xue, Yexiang; Bai, Junwen; ...

2016-11-21

Rapid construction of phase diagrams is a central tenet of combinatorial materials science with accelerated materials discovery efforts often hampered by challenges in interpreting combinatorial X-ray diffraction data sets, which we address by developing AgileFD, an artificial intelligence algorithm that enables rapid phase mapping from a combinatorial library of X-ray diffraction patterns. AgileFD models alloying-based peak shifting through a novel expansion of convolutional nonnegative matrix factorization, which not only improves the identification of constituent phases but also maps their concentration and lattice parameter as a function of composition. By incorporating Gibbs’ phase rule into the algorithm, physically meaningful phase mapsmore » are obtained with unsupervised operation, and more refined solutions are attained by injecting expert knowledge of the system. The algorithm is demonstrated through investigation of the V–Mn–Nb oxide system where decomposition of eight oxide phases, including two with substantial alloying, provides the first phase map for this pseudoternary system. This phase map enables interpretation of high-throughput band gap data, leading to the discovery of new solar light absorbers and the alloying-based tuning of the direct-allowed band gap energy of MnV 2O 6. Lastly, the open-source family of AgileFD algorithms can be implemented into a broad range of high throughput workflows to accelerate materials discovery.« less

Automated phase mapping with AgileFD and its application to light absorber discovery in the V–Mn–Nb oxide system

DOE Office of Scientific and Technical Information (OSTI.GOV)

Suram, Santosh K.; Xue, Yexiang; Bai, Junwen

Rapid construction of phase diagrams is a central tenet of combinatorial materials science with accelerated materials discovery efforts often hampered by challenges in interpreting combinatorial X-ray diffraction data sets, which we address by developing AgileFD, an artificial intelligence algorithm that enables rapid phase mapping from a combinatorial library of X-ray diffraction patterns. AgileFD models alloying-based peak shifting through a novel expansion of convolutional nonnegative matrix factorization, which not only improves the identification of constituent phases but also maps their concentration and lattice parameter as a function of composition. By incorporating Gibbs’ phase rule into the algorithm, physically meaningful phase mapsmore » are obtained with unsupervised operation, and more refined solutions are attained by injecting expert knowledge of the system. The algorithm is demonstrated through investigation of the V–Mn–Nb oxide system where decomposition of eight oxide phases, including two with substantial alloying, provides the first phase map for this pseudoternary system. This phase map enables interpretation of high-throughput band gap data, leading to the discovery of new solar light absorbers and the alloying-based tuning of the direct-allowed band gap energy of MnV 2O 6. Lastly, the open-source family of AgileFD algorithms can be implemented into a broad range of high throughput workflows to accelerate materials discovery.« less

cDREM: inferring dynamic combinatorial gene regulation.

PubMed

Wise, Aaron; Bar-Joseph, Ziv

2015-04-01

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

Use of combinatorial chemistry to speed drug discovery.

PubMed

Rádl, S

1998-10-01

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

A Discrete Fruit Fly Optimization Algorithm for the Traveling Salesman Problem.

PubMed

Jiang, Zi-Bin; Yang, Qiong

2016-01-01

The fruit fly optimization algorithm (FOA) is a newly developed bio-inspired algorithm. The continuous variant version of FOA has been proven to be a powerful evolutionary approach to determining the optima of a numerical function on a continuous definition domain. In this study, a discrete FOA (DFOA) is developed and applied to the traveling salesman problem (TSP), a common combinatorial problem. In the DFOA, the TSP tour is represented by an ordering of city indices, and the bio-inspired meta-heuristic search processes are executed with two elaborately designed main procedures: the smelling and tasting processes. In the smelling process, an effective crossover operator is used by the fruit fly group to search for the neighbors of the best-known swarm location. During the tasting process, an edge intersection elimination (EXE) operator is designed to improve the neighbors of the non-optimum food location in order to enhance the exploration performance of the DFOA. In addition, benchmark instances from the TSPLIB are classified in order to test the searching ability of the proposed algorithm. Furthermore, the effectiveness of the proposed DFOA is compared to that of other meta-heuristic algorithms. The results indicate that the proposed DFOA can be effectively used to solve TSPs, especially large-scale problems.

A Discrete Fruit Fly Optimization Algorithm for the Traveling Salesman Problem

PubMed Central

Jiang, Zi-bin; Yang, Qiong

2016-01-01

The fruit fly optimization algorithm (FOA) is a newly developed bio-inspired algorithm. The continuous variant version of FOA has been proven to be a powerful evolutionary approach to determining the optima of a numerical function on a continuous definition domain. In this study, a discrete FOA (DFOA) is developed and applied to the traveling salesman problem (TSP), a common combinatorial problem. In the DFOA, the TSP tour is represented by an ordering of city indices, and the bio-inspired meta-heuristic search processes are executed with two elaborately designed main procedures: the smelling and tasting processes. In the smelling process, an effective crossover operator is used by the fruit fly group to search for the neighbors of the best-known swarm location. During the tasting process, an edge intersection elimination (EXE) operator is designed to improve the neighbors of the non-optimum food location in order to enhance the exploration performance of the DFOA. In addition, benchmark instances from the TSPLIB are classified in order to test the searching ability of the proposed algorithm. Furthermore, the effectiveness of the proposed DFOA is compared to that of other meta-heuristic algorithms. The results indicate that the proposed DFOA can be effectively used to solve TSPs, especially large-scale problems. PMID:27812175

A versatile modular vector system for rapid combinatorial mammalian genetics.

PubMed

Albers, Joachim; Danzer, Claudia; Rechsteiner, Markus; Lehmann, Holger; Brandt, Laura P; Hejhal, Tomas; Catalano, Antonella; Busenhart, Philipp; Gonçalves, Ana Filipa; Brandt, Simone; Bode, Peter K; Bode-Lesniewska, Beata; Wild, Peter J; Frew, Ian J

2015-04-01

Here, we describe the multiple lentiviral expression (MuLE) system that allows multiple genetic alterations to be introduced simultaneously into mammalian cells. We created a toolbox of MuLE vectors that constitute a flexible, modular system for the rapid engineering of complex polycistronic lentiviruses, allowing combinatorial gene overexpression, gene knockdown, Cre-mediated gene deletion, or CRISPR/Cas9-mediated (where CRISPR indicates clustered regularly interspaced short palindromic repeats) gene mutation, together with expression of fluorescent or enzymatic reporters for cellular assays and animal imaging. Examples of tumor engineering were used to illustrate the speed and versatility of performing combinatorial genetics using the MuLE system. By transducing cultured primary mouse cells with single MuLE lentiviruses, we engineered tumors containing up to 5 different genetic alterations, identified genetic dependencies of molecularly defined tumors, conducted genetic interaction screens, and induced the simultaneous CRISPR/Cas9-mediated knockout of 3 tumor-suppressor genes. Intramuscular injection of MuLE viruses expressing oncogenic H-RasG12V together with combinations of knockdowns of the tumor suppressors cyclin-dependent kinase inhibitor 2A (Cdkn2a), transformation-related protein 53 (Trp53), and phosphatase and tensin homolog (Pten) allowed the generation of 3 murine sarcoma models, demonstrating that genetically defined autochthonous tumors can be rapidly generated and quantitatively monitored via direct injection of polycistronic MuLE lentiviruses into mouse tissues. Together, our results demonstrate that the MuLE system provides genetic power for the systematic investigation of the molecular mechanisms that underlie human diseases.

A review on data mining and continuous optimization applications in computational biology and medicine.

PubMed

Weber, Gerhard-Wilhelm; Ozöğür-Akyüz, Süreyya; Kropat, Erik

2009-06-01

An emerging research area in computational biology and biotechnology is devoted to mathematical modeling and prediction of gene-expression patterns; it nowadays requests mathematics to deeply understand its foundations. This article surveys data mining and machine learning methods for an analysis of complex systems in computational biology. It mathematically deepens recent advances in modeling and prediction by rigorously introducing the environment and aspects of errors and uncertainty into the genetic context within the framework of matrix and interval arithmetics. Given the data from DNA microarray experiments and environmental measurements, we extract nonlinear ordinary differential equations which contain parameters that are to be determined. This is done by a generalized Chebychev approximation and generalized semi-infinite optimization. Then, time-discretized dynamical systems are studied. By a combinatorial algorithm which constructs and follows polyhedra sequences, the region of parametric stability is detected. In addition, we analyze the topological landscape of gene-environment networks in terms of structural stability. As a second strategy, we will review recent model selection and kernel learning methods for binary classification which can be used to classify microarray data for cancerous cells or for discrimination of other kind of diseases. This review is practically motivated and theoretically elaborated; it is devoted to a contribution to better health care, progress in medicine, a better education, and more healthy living conditions.

On evolutionary systems.

PubMed

Alvarez de Lorenzana, J M; Ward, L M

1987-01-01

This paper develops a metatheoretical framework for understanding evolutionary systems (systems that develop in ways that increase their own variety). The framework addresses shortcomings seen in other popular systems theories. It concerns both living and nonliving systems, and proposes a metahierarchy of hierarchical systems. Thus, it potentially addresses systems at all descriptive levels. We restrict our definition of system to that of a core system whose parts have a different ontological status than the system, and characterize the core system in terms of five global properties: minimal length interval, minimal time interval, system cycle, total receptive capacity, and system potential. We propose two principles through the interaction of which evolutionary systems develop. The Principle of Combinatorial Expansion describes how a core system realizes its developmental potential through a process of progressive differentiation of the single primal state up to a limit stage. The Principle of Generative Condensation describes how the components of the last stage of combinatorial expansion condense and become the environment for and components of new, enriched systems. The early evolution of the Universe after the "big bang" is discussed in light of these ideas as an example of the application of the framework.

Combinatorial Investigation of ZrO2-Based Dielectric Materials for Dynamic Random-Access Memory Capacitors

NASA Astrophysics Data System (ADS)

Kiyota, Yuji; Itaka, Kenji; Iwashita, Yuta; Adachi, Tetsuya; Chikyow, Toyohiro; Ogura, Atsushi

2011-06-01

We investigated zirconia (ZrO2)-based material libraries in search of new dielectric materials for dynamic random-access memory (DRAM) by combinatorial-pulsed laser deposition (combi-PLD). We found that the substitution of yttrium (Y) to Zr sites in the ZrO2 system suppressed the leakage current effectively. The metal-insulator-metal (MIM) capacitor property of this system showed a leakage current density of less than 5×10-7 A/cm2 and the dielectric constant was 20. Moreover, the addition of titanium (Ti) or tantalum (Ta) to this system caused the dielectric constant to increase to ˜25 within the allowed leakage level of 5×10-7 A/cm2. Therefore, Zr-Y-Ti-O and Zr-Y-Ta-O systems have good potentials for use as new materials with high dielectric constants of DRAM capacitors instead of silicon dioxides (SiO2).

Encoding Schemes For A Digital Optical Multiplier Using The Modified Signed-Digit Number Representation

NASA Astrophysics Data System (ADS)

Lasher, Mark E.; Henderson, Thomas B.; Drake, Barry L.; Bocker, Richard P.

1986-09-01

The modified signed-digit (MSD) number representation offers full parallel, carry-free addition. A MSD adder has been described by the authors. This paper describes how the adder can be used in a tree structure to implement an optical multiply algorithm. Three different optical schemes, involving position, polarization, and intensity encoding, are proposed for realizing the trinary logic system. When configured in the generic multiplier architecture, these schemes yield the combinatorial logic necessary to carry out the multiplication algorithm. The optical systems are essentially three dimensional arrangements composed of modular units. Of course, this modularity is important for design considerations, while the parallelism and noninterfering communication channels of optical systems are important from the standpoint of reduced complexity. The authors have also designed electronic hardware to demonstrate and model the combinatorial logic required to carry out the algorithm. The electronic and proposed optical systems will be compared in terms of complexity and speed.

High-throughput flow injection analysis mass spectroscopy with networked delivery of color-rendered results. 2. Three-dimensional spectral mapping of 96-well combinatorial chemistry racks.

PubMed

Görlach, E; Richmond, R; Lewis, I

1998-08-01

For the last two years, the mass spectroscopy section of the Novartis Pharma Research Core Technology group has analyzed tens of thousands of multiple parallel synthesis samples from the Novartis Pharma Combinatorial Chemistry program, using an in-house developed automated high-throughput flow injection analysis electrospray ionization mass spectroscopy system. The electrospray spectra of these samples reflect the many structures present after the cleavage step from the solid support. The overall success of the sequential synthesis is mirrored in the purity of the expected end product, but the partial success of individual synthesis steps is evident in the impurities in the mass spectrum. However this latter reaction information, which is of considerable utility to the combinatorial chemist, is effectively hidden from view by the very large number of analyzed samples. This information is now revealed at the workbench of the combinatorial chemist by a novel three-dimensional display of each rack's complete mass spectral ion current using the in-house RackViewer Visual Basic application. Colorization of "forbidden loss" and "forbidden gas-adduct" zones, normalization to expected monoisotopic molecular weight, colorization of ionization intensity, and sorting by row or column were used in combination to highlight systematic patterns in the mass spectroscopy data.

Neural Meta-Memes Framework for Combinatorial Optimization

NASA Astrophysics Data System (ADS)

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

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

Perspective: Rapid synthesis of complex oxides by combinatorial molecular beam epitaxy

DOE PAGES

A. T. Bollinger; Wu, J.; Bozovic, I.

2016-03-15

In this study, the molecular beam epitaxy(MBE) technique is well known for producing atomically smooth thin films as well as impeccable interfaces in multilayers of many different materials. In particular, molecular beam epitaxy is well suited to the growth of complex oxides, materials that hold promise for many applications. Rapid synthesis and high throughput characterization techniques are needed to tap into that potential most efficiently. We discuss our approach to doing that, leaving behind the traditional one-growth-one-compound scheme and instead implementing combinatorial oxide molecular beam epitaxy in a custom built system.

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

PubMed

Antolini, Ermete

2017-02-13

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

Combinatorial Nano-Bio Interfaces.

PubMed

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

2018-06-08

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

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

PubMed

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

2007-02-01

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

Inhibition of Hepatitis C Virus Replication by Intracellular Delivery of Multiple siRNAs by Nanosomes

PubMed Central

Chandra, Partha K; Kundu, Anup K; Hazari, Sidhartha; Chandra, Sruti; Bao, Lili; Ooms, Tara; Morris, Gilbert F; Wu, Tong; Mandal, Tarun K; Dash, Srikanta

2012-01-01

Sustained antiviral responses of chronic hepatitis C virus (HCV) infection have improved recently by the use of direct-acting antiviral agents along with interferon (IFN)-α and ribavirin. However, the emergence of drug-resistant variants is expected to be a major problem. We describe here a novel combinatorial small interfering RNA (siRNA) nanosome-based antiviral approach to clear HCV infection. Multiple siRNAs targeted to the highly conserved 5′-untranslated region (UTR) of the HCV genome were synthesized and encapsulated into lipid nanoparticles called nanosomes. We show that siRNA can be repeatedly delivered to 100% of cells in culture using nanosomes without toxicity. Six siRNAs dramatically reduced HCV replication in both the replicon and infectious cell culture model. Repeated treatments with two siRNAs were better than a single siRNA treatment in minimizing the development of an escape mutant, resulting in rapid inhibition of viral replication. Systemic administration of combinatorial siRNA-nanosomes is well tolerated in BALB/c mice without liver injury or histological toxicity. As a proof-of-principle, we showed that systemic injections of siRNA nanosomes significantly reduced HCV replication in a liver tumor-xenotransplant mouse model of HCV. Our results indicate that systemic delivery of combinatorial siRNA nanosomes can be used to minimize the development of escape mutants and inhibition of HCV infection. PMID:22617108

Nucleophilic catalysis of acylhydrazone equilibration for protein-directed dynamic covalent chemistry

PubMed Central

Bhat, Venugopal T.; Caniard, Anne M.; Luksch, Torsten; Brenk, Ruth; Campopiano, Dominic J.; Greaney, Michael F.

2010-01-01

Dynamic covalent chemistry uses reversible chemical reactions to set up an equilibrating network of molecules at thermodynamic equilibrium, which can adjust its composition in response to any agent capable of altering the free energy of the system. When the target is a biological macromolecule, such as a protein, the process corresponds to the protein directing the synthesis of its own best ligand. Here, we demonstrate that reversible acylhydrazone formation is an effective chemistry for biological dynamic combinatorial library formation. In the presence of aniline as a nucleophilic catalyst, dynamic combinatorial libraries equilibrate rapidly at pH 6.2, are fully reversible, and may be switched on or off by means of a change in pH. We have interfaced these hydrazone dynamic combinatorial libraries with two isozymes from the glutathione S-transferase class of enzyme, and observed divergent amplification effects, where each protein selects the best-fitting hydrazone for the hydrophobic region of its active site. PMID:20489719

Device for preparing combinatorial libraries in powder metallurgy.

PubMed

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.

Combinatorial Strategies for the Development of Bulk Metallic Glasses

NASA Astrophysics Data System (ADS)

Ding, Shiyan

The systematic identification of multi-component alloys out of the vast composition space is still a daunting task, especially in the development of bulk metallic glasses that are typically based on three or more elements. In order to address this challenge, combinatorial approaches have been proposed. However, previous attempts have not successfully coupled the synthesis of combinatorial libraries with high-throughput characterization methods. The goal of my dissertation is to develop efficient high-throughput characterization methods, optimized to identify glass formers systematically. Here, two innovative approaches have been invented. One is to measure the nucleation temperature in parallel for up-to 800 compositions. The composition with the lowest nucleation temperature has a reasonable agreement with the best-known glass forming composition. In addition, the thermoplastic formability of a metallic glass forming system is determined through blow molding a compositional library. Our results reveal that the composition with the largest thermoplastic deformation correlates well with the best-known formability composition. I have demonstrated both methods as powerful tools to develop new bulk metallic glasses.

Gain-Sparsity and Symmetry-Forced Rigidity in the Plane.

PubMed

Jordán, Tibor; Kaszanitzky, Viktória E; Tanigawa, Shin-Ichi

We consider planar bar-and-joint frameworks with discrete point group symmetry in which the joint positions are as generic as possible subject to the symmetry constraint. We provide combinatorial characterizations for symmetry-forced rigidity of such structures with rotation symmetry or dihedral symmetry of order 2 k with odd k , unifying and extending previous work on this subject. We also explore the matroidal background of our results and show that the matroids induced by the row independence of the orbit matrices of the symmetric frameworks are isomorphic to gain sparsity matroids defined on the quotient graph of the framework, whose edges are labeled by elements of the corresponding symmetry group. The proofs are based on new Henneberg type inductive constructions of the gain graphs that correspond to the bases of the matroids in question, which can also be seen as symmetry preserving graph operations in the original graph.

An Analytical Framework for Runtime of a Class of Continuous Evolutionary Algorithms.

PubMed

Zhang, Yushan; Hu, Guiwu

2015-01-01

Although there have been many studies on the runtime of evolutionary algorithms in discrete optimization, relatively few theoretical results have been proposed on continuous optimization, such as evolutionary programming (EP). This paper proposes an analysis of the runtime of two EP algorithms based on Gaussian and Cauchy mutations, using an absorbing Markov chain. Given a constant variation, we calculate the runtime upper bound of special Gaussian mutation EP and Cauchy mutation EP. Our analysis reveals that the upper bounds are impacted by individual number, problem dimension number n, searching range, and the Lebesgue measure of the optimal neighborhood. Furthermore, we provide conditions whereby the average runtime of the considered EP can be no more than a polynomial of n. The condition is that the Lebesgue measure of the optimal neighborhood is larger than a combinatorial calculation of an exponential and the given polynomial of n.

Maintaining Consistency of Spatial Information in the Hippocampal Network: A Combinatorial Geometry Model.

PubMed

Dabaghian, Y

2016-06-01

Place cells in the rat hippocampus play a key role in creating the animal's internal representation of the world. During active navigation, these cells spike only in discrete locations, together encoding a map of the environment. Electrophysiological recordings have shown that the animal can revisit this map mentally during both sleep and awake states, reactivating the place cells that fired during its exploration in the same sequence in which they were originally activated. Although consistency of place cell activity during active navigation is arguably enforced by sensory and proprioceptive inputs, it remains unclear how a consistent representation of space can be maintained during spontaneous replay. We propose a model that can account for this phenomenon and suggest that a spatially consistent replay requires a number of constraints on the hippocampal network that affect its synaptic architecture and the statistics of synaptic connection strengths.

Gradient Material Strategies for Hydrogel Optimization in Tissue Engineering Applications

PubMed Central

2018-01-01

Although a number of combinatorial/high-throughput approaches have been developed for biomaterial hydrogel optimization, a gradient sample approach is particularly well suited to identify hydrogel property thresholds that alter cellular behavior in response to interacting with the hydrogel due to reduced variation in material preparation and the ability to screen biological response over a range instead of discrete samples each containing only one condition. This review highlights recent work on cell–hydrogel interactions using a gradient material sample approach. Fabrication strategies for composition, material and mechanical property, and bioactive signaling gradient hydrogels that can be used to examine cell–hydrogel interactions will be discussed. The effects of gradients in hydrogel samples on cellular adhesion, migration, proliferation, and differentiation will then be examined, providing an assessment of the current state of the field and the potential of wider use of the gradient sample approach to accelerate our understanding of matrices on cellular behavior. PMID:29485612

On the way to language: event segmentation in homesign and gesture*

PubMed Central

ÖZYÜREK, ASLI; FURMAN, REYHAN; GOLDIN-MEADOW, SUSAN

2014-01-01

Languages typically express semantic components of motion events such as manner (roll) and path (down) in separate lexical items. We explore how these combinatorial possibilities of language arise by focusing on (i) gestures produced by deaf children who lack access to input from a conventional language (homesign); (ii) gestures produced by hearing adults and children while speaking; and (iii) gestures used by hearing adults without speech when asked to do so in elicited descriptions of motion events with simultaneous manner and path. Homesigners tended to conflate manner and path in one gesture, but also used a mixed form, adding a manner and/or path gesture to the conflated form sequentially. Hearing speakers, with or without speech, used the conflated form, gestured manner, or path, but rarely used the mixed form. Mixed form may serve as an intermediate structure on the way to the discrete and sequenced forms found in natural languages. PMID:24650738

Geometry Helps to Compare Persistence Diagrams

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kerber, Michael; Morozov, Dmitriy; Nigmetov, Arnur

2015-11-16

Exploiting geometric structure to improve the asymptotic complexity of discrete assignment problems is a well-studied subject. In contrast, the practical advantages of using geometry for such problems have not been explored. We implement geometric variants of the Hopcroft--Karp algorithm for bottleneck matching (based on previous work by Efrat el al.), and of the auction algorithm by Bertsekas for Wasserstein distance computation. Both implementations use k-d trees to replace a linear scan with a geometric proximity query. Our interest in this problem stems from the desire to compute distances between persistence diagrams, a problem that comes up frequently in topological datamore » analysis. We show that our geometric matching algorithms lead to a substantial performance gain, both in running time and in memory consumption, over their purely combinatorial counterparts. Moreover, our implementation significantly outperforms the only other implementation available for comparing persistence diagrams.« less

Exome sequence analysis suggests genetic burden contributes to phenotypic variability and complex neuropathy

PubMed Central

Gonzaga-Jauregui, Claudia; Harel, Tamar; Gambin, Tomasz; Kousi, Maria; Griffin, Laurie B.; Francescatto, Ludmila; Ozes, Burcak; Karaca, Ender; Jhangiani, Shalini; Bainbridge, Matthew N.; Lawson, Kim S.; Pehlivan, Davut; Okamoto, Yuji; Withers, Marjorie; Mancias, Pedro; Slavotinek, Anne; Reitnauer, Pamela J; Goksungur, Meryem T.; Shy, Michael; Crawford, Thomas O.; Koenig, Michel; Willer, Jason; Flores, Brittany N.; Pediaditrakis, Igor; Us, Onder; Wiszniewski, Wojciech; Parman, Yesim; Antonellis, Anthony; Muzny, Donna M.; Katsanis, Nicholas; Battaloglu, Esra; Boerwinkle, Eric; Gibbs, Richard A.; Lupski, James R.

2015-01-01

Charcot-Marie-Tooth (CMT) disease is a clinically and genetically heterogeneous distal symmetric polyneuropathy. Whole-exome sequencing (WES) of 40 individuals from 37 unrelated families with CMT-like peripheral neuropathy refractory to molecular diagnosis identified apparent causal mutations in ~45% (17/37) of families. Three candidate disease genes are proposed, supported by a combination of genetic and in vivo studies. Aggregate analysis of mutation data revealed a significantly increased number of rare variants across 58 neuropathy associated genes in subjects versus controls; confirmed in a second ethnically discrete neuropathy cohort, suggesting mutation burden potentially contributes to phenotypic variability. Neuropathy genes shown to have highly penetrant Mendelizing variants (HMPVs) and implicated by burden in families were shown to interact genetically in a zebrafish assay exacerbating the phenotype established by the suppression of single genes. Our findings suggest that the combinatorial effect of rare variants contributes to disease burden and variable expressivity. PMID:26257172

Theory of Stochastic Laplacian Growth

NASA Astrophysics Data System (ADS)

Alekseev, Oleg; Mineev-Weinstein, Mark

2017-07-01

We generalize the diffusion-limited aggregation by issuing many randomly-walking particles, which stick to a cluster at the discrete time unit providing its growth. Using simple combinatorial arguments we determine probabilities of different growth scenarios and prove that the most probable evolution is governed by the deterministic Laplacian growth equation. A potential-theoretical analysis of the growth probabilities reveals connections with the tau-function of the integrable dispersionless limit of the two-dimensional Toda hierarchy, normal matrix ensembles, and the two-dimensional Dyson gas confined in a non-uniform magnetic field. We introduce the time-dependent Hamiltonian, which generates transitions between different classes of equivalence of closed curves, and prove the Hamiltonian structure of the interface dynamics. Finally, we propose a relation between probabilities of growth scenarios and the semi-classical limit of certain correlation functions of "light" exponential operators in the Liouville conformal field theory on a pseudosphere.

A new discrete dynamic model of ABA-induced stomatal closure predicts key feedback loops

PubMed Central

Acharya, Biswa R.; Jeon, Byeong Wook; Zañudo, Jorge G. T.; Zhu, Mengmeng; Osman, Karim; Assmann, Sarah M.

2017-01-01

Stomata, microscopic pores in leaf surfaces through which water loss and carbon dioxide uptake occur, are closed in response to drought by the phytohormone abscisic acid (ABA). This process is vital for drought tolerance and has been the topic of extensive experimental investigation in the last decades. Although a core signaling chain has been elucidated consisting of ABA binding to receptors, which alleviates negative regulation by protein phosphatases 2C (PP2Cs) of the protein kinase OPEN STOMATA 1 (OST1) and ultimately results in activation of anion channels, osmotic water loss, and stomatal closure, over 70 additional components have been identified, yet their relationships with each other and the core components are poorly elucidated. We integrated and processed hundreds of disparate observations regarding ABA signal transduction responses underlying stomatal closure into a network of 84 nodes and 156 edges and, as a result, established those relationships, including identification of a 36-node, strongly connected (feedback-rich) component as well as its in- and out-components. The network’s domination by a feedback-rich component may reflect a general feature of rapid signaling events. We developed a discrete dynamic model of this network and elucidated the effects of ABA plus knockout or constitutive activity of 79 nodes on both the outcome of the system (closure) and the status of all internal nodes. The model, with more than 1024 system states, is far from fully determined by the available data, yet model results agree with existing experiments in 82 cases and disagree in only 17 cases, a validation rate of 75%. Our results reveal nodes that could be engineered to impact stomatal closure in a controlled fashion and also provide over 140 novel predictions for which experimental data are currently lacking. Noting the paucity of wet-bench data regarding combinatorial effects of ABA and internal node activation, we experimentally confirmed several predictions of the model with regard to reactive oxygen species, cytosolic Ca2+ (Ca2+c), and heterotrimeric G-protein signaling. We analyzed dynamics-determining positive and negative feedback loops, thereby elucidating the attractor (dynamic behavior) repertoire of the system and the groups of nodes that determine each attractor. Based on this analysis, we predict the likely presence of a previously unrecognized feedback mechanism dependent on Ca2+c. This mechanism would provide model agreement with 10 additional experimental observations, for a validation rate of 85%. Our research underscores the importance of feedback regulation in generating robust and adaptable biological responses. The high validation rate of our model illustrates the advantages of discrete dynamic modeling for complex, nonlinear systems common in biology. PMID:28937978

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

PubMed

Sáfrán, György

2018-04-01

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

Combinatorial anticancer effects of curcumin and 5-fluorouracil loaded thiolated chitosan nanoparticles towards colon cancer treatment.

PubMed

Anitha, A; Deepa, N; Chennazhi, K P; Lakshmanan, Vinoth-Kumar; Jayakumar, R

2014-09-01

Evaluation of the combinatorial anticancer effects of curcumin/5-fluorouracil loaded thiolated chitosan nanoparticles (CRC-TCS-NPs/5-FU-TCS-NPs) on colon cancer cells and the analysis of pharmacokinetics and biodistribution of CRC-TCS-NPs/5-FU-TCS-NPs in a mouse model. CRC-TCS-NPs/5-FU-TCS-NPs were developed by ionic cross-linking. The in vitro combinatorial anticancer effect of the nanomedicine was proven by different assays. Further the pharmacokinetics and biodistribution analyses were performed in Swiss Albino mouse using HPLC. The 5-FU-TCS-NPs (size: 150±40nm, zeta potential: +48.2±5mV) and CRC-TCS-NPs (size: 150±20nm, zeta potential: +35.7±3mV) were proven to be compatible with blood. The in vitro drug release studies at pH4.5 and 7.4 showed a sustained release profile over a period of 4 days, where both the systems exhibited a higher release in acidic pH. The in vitro combinatorial anticancer effects in colon cancer (HT29) cells using MTT, live/dead, mitochondrial membrane potential and cell cycle analysis measurements confirmed the enhanced anticancer effects (2.5 to 3 fold). The pharmacokinetic studies confirmed the improved plasma concentrations of 5-FU and CRC up to 72h, unlike bare CRC and 5-FU. To conclude, the combination of 5-FU-TCS-NPs and CRC-TCS-NPs showed enhanced anticancer effects on colon cancer cells in vitro and improved the bioavailability of the drugs in vivo. The enhanced anticancer effects of combinatorial nanomedicine are advantageous in terms of reduction in the dosage of 5-FU, thereby improving the chemotherapeutic efficacy and patient compliance of colorectal cancer cases. Copyright © 2014 Elsevier B.V. All rights reserved.

Novel drug metabolism indices for pharmacogenetic functional status based on combinatory genotyping of CYP2C9, CYP2C19 and CYP2D6 genes

PubMed Central

Villagra, David; Goethe, John; Schwartz, Harold I; Szarek, Bonnie; Kocherla, Mohan; Gorowski, Krystyna; Windemuth, Andreas; Ruaño, Gualberto

2011-01-01

Aims We aim to demonstrate clinical relevance and utility of four novel drug-metabolism indices derived from a combinatory (multigene) approach to CYP2C9, CYP2C19 and CYP2D6 allele scoring. Each index considers all three genes as complementary components of a liver enzyme drug metabolism system and uniquely benchmarks innate hepatic drug metabolism reserve or alteration through CYP450 combinatory genotype scores. Methods A total of 1199 psychiatric referrals were genotyped for polymorphisms in the CYP2C9, CYP2C19 and CYP2D6 gene loci and were scored on each of the four indices. The data were used to create distributions and rankings of innate drug metabolism capacity to which individuals can be compared. Drug-specific indices are a combination of the drug metabolism indices with substrate-specific coefficients. Results The combinatory drug metabolism indices proved useful in positioning individuals relative to a population with regard to innate drug metabolism capacity prior to pharmacotherapy. Drug-specific indices generate pharmacogenetic guidance of immediate clinical relevance, and can be further modified to incorporate covariates in particular clinical cases. Conclusions We believe that this combinatory approach represents an improvement over the current gene-by-gene reporting by providing greater scope while still allowing for the resolution of a single-gene index when needed. This method will result in novel clinical and research applications, facilitating the translation from pharmacogenomics to personalized medicine, particularly in psychiatry where many drugs are metabolized or activated by multiple CYP450 isoenzymes. PMID:21861665

Chemoinformatic Analysis of Combinatorial Libraries, Drugs, Natural Products and Molecular Libraries Small Molecule Repository

PubMed Central

Singh, Narender; Guha, Rajarshi; Giulianotti, Marc; Pinilla, Clemencia; Houghten, Richard; Medina-Franco, Jose L.

2009-01-01

A multiple criteria approach is presented, that is used to perform a comparative analysis of four recently developed combinatorial libraries to drugs, Molecular Libraries Small Molecule Repository (MLSMR) and natural products. The compound databases were assessed in terms of physicochemical properties, scaffolds and fingerprints. The approach enables the analysis of property space coverage, degree of overlap between collections, scaffold and structural diversity and overall structural novelty. The degree of overlap between combinatorial libraries and drugs was assessed using the R-NN curve methodology, which measures the density of chemical space around a query molecule embedded in the chemical space of a target collection. The combinatorial libraries studied in this work exhibit scaffolds that were not observed in the drug, MLSMR and natural products collections. The fingerprint-based comparisons indicate that these combinatorial libraries are structurally different to current drugs. The R-NN curve methodology revealed that a proportion of molecules in the combinatorial libraries are located within the property space of the drugs. However, the R-NN analysis also showed that there are a significant number of molecules in several combinatorial libraries that are located in sparse regions of the drug space. PMID:19301827

Rapid identification of areas of interest in thin film materials libraries by combining electrical, optical, X-ray diffraction, and mechanical high-throughput measurements: a case study for the system Ni-Al.

PubMed

Thienhaus, S; Naujoks, D; Pfetzing-Micklich, J; König, D; Ludwig, A

2014-12-08

The efficient identification of compositional areas of interest in thin film materials systems fabricated by combinatorial deposition methods is essential in combinatorial materials science. We use a combination of compositional screening by EDX together with high-throughput measurements of electrical and optical properties of thin film libraries to determine efficiently the areas of interest in a materials system. Areas of interest are compositions which show distinctive properties. The crystallinity of the thus determined areas is identified by X-ray diffraction. Additionally, by using automated nanoindentation across the materials library, mechanical data of the thin films can be obtained which complements the identification of areas of interest. The feasibility of this approach is demonstrated by using a Ni-Al thin film library as a reference system. The obtained results promise that this approach can be used for the case of ternary and higher order systems.

DNA-mediated gold nanoparticle signal transducers for combinatorial logic operations and heavy metal ions sensing.

PubMed

Zhang, Yuhuan; Liu, Wei; Zhang, Wentao; Yu, Shaoxuan; Yue, Xiaoyue; Zhu, Wenxin; Zhang, Daohong; Wang, Yanru; Wang, Jianlong

2015-10-15

Herein, the structure of two DNA strands which are complementary except fourteen T-T and C-C mismatches was programmed for the design of the combinatorial logic operation by utilizing the different protective capacities of single chain DNA, part-hybridized DNA and completed-hybridized DNA on unmodified gold nanoparticles. In the presence of either Hg(2+) or Ag(+), the T-Hg(2+)-T or C-Ag(+)-C coordination chemistry could lead to the formation of part-hybridized DNA which keeps gold nanoparticles from clumping after the addition of 40 μL 0.2M NaClO4 solution, but the protection would be screened by 120 μL 0.2M NaClO4 solution. While the coexistence of Hg(2+), Ag(+) caused the formation of completed-hybridized DNA and the protection for gold nanoparticles lost in either 40 μL or 120 μL NaClO4 solutions. Benefiting from sharing of the same inputs of Hg(2+) and Ag(+), OR and AND logic gates were easily integrated into a simple colorimetric combinatorial logic operation in one system, which make it possible to execute logic gates in parallel to mimic arithmetic calculations on a binary digit. Furthermore, two other logic gates including INHIBIT1 and INHIBIT2 were realized to integrated with OR logic gate both for simultaneous qualitative discrimination and quantitative determination of Hg(2+) and Ag(+). Results indicate that the developed logic system based on the different protective capacities of DNA structure on gold nanoparticles provides a new pathway for the design of the combinatorial logic operation in one system and presents a useful strategy for development of advanced sensors, which may have potential applications in multiplex chemical analysis and molecular-scale computer design. Copyright © 2015 Elsevier B.V. All rights reserved.

Smooth Constrained Heuristic Optimization of a Combinatorial Chemical Space

DTIC Science & Technology

2015-05-01

ARL-TR-7294•MAY 2015 US Army Research Laboratory Smooth ConstrainedHeuristic Optimization of a Combinatorial Chemical Space by Berend Christopher...7294•MAY 2015 US Army Research Laboratory Smooth ConstrainedHeuristic Optimization of a Combinatorial Chemical Space by Berend Christopher...

Preparation of cherry-picked combinatorial libraries by string synthesis.

PubMed

Furka, Arpád; Dibó, Gábor; Gombosuren, Naran

2005-03-01

String synthesis [1-3] is an efficient and cheap manual method for preparation of combinatorial libraries by using macroscopic solid support units. Sorting the units between two synthetic steps is an important operation of the procedure. The software developed to guide sorting can be used only when complete combinatorial libraries are prepared. Since very often only selected components of the full libraries are needed, new software was constructed that guides sorting in preparation of non-complete combinatorial libraries. Application of the software is described in details.

Extending double modulation: combinatorial rules for identifying the modulations necessary for determining elasticities in metabolic pathways.

PubMed

Giersch, C; Cornish-Bowden, A

1996-10-07

The double modulation method for determining the elasticities of pathway enzymes, originally devised by Kacser & Burns (Biochem. Soc. Trans. 7, 1149-1160, 1979), is extended to pathways of complex topological structure, including branching and feedback loops. An explicit system of linear equations for the unknown elasticities is derived. The constraints imposed on this linear system imply that modulations of more than one enzyme are not necessarily independent. Simple combinatorial rules are described for identifying without using any algebra the set of independent modulations that allow the determination of the elasticities of any enzyme. By repeated application, the minimum numbers of modulations required to determine the elasticities of all enzymes of a given pathway can be determined. The procedure is illustrated with numerous examples.

Cell-cycle progress in obligate predatory bacteria is dependent upon sequential sensing of prey recognition and prey quality cues.

PubMed

Rotem, Or; Pasternak, Zohar; Shimoni, Eyal; Belausov, Eduard; Porat, Ziv; Pietrokovski, Shmuel; Jurkevitch, Edouard

2015-11-03

Predators feed on prey to acquire the nutrients necessary to sustain their survival, growth, and replication. In Bdellovibrio bacteriovorus, an obligate predator of Gram-negative bacteria, cell growth and replication are tied to a shift from a motile, free-living phase of search and attack to a sessile, intracellular phase of growth and replication during which a single prey cell is consumed. Engagement and sustenance of growth are achieved through the sensing of two unidentified prey-derived cues. We developed a novel ex vivo cultivation system for B. bacteriovorus composed of prey ghost cells that are recognized and invaded by the predator. By manipulating their content, we demonstrated that an early cue is located in the prey envelope and a late cue is found within the prey soluble fraction. These spatially and temporally separated cues elicit discrete and combinatory regulatory effects on gene transcription. Together, they delimit a poorly characterized transitory phase between the attack phase and the growth phase, during which the bdelloplast (the invaded prey cell) is constructed. This transitory phase constitutes a checkpoint in which the late cue presumably acts as a determinant of the prey's nutritional value before the predator commits. These regulatory adaptations to a unique bacterial lifestyle have not been reported previously.

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

ERIC Educational Resources Information Center

Staver, John R.; Harty, Harold

1979-01-01

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

Combinatorial treatments enhance recovery following facial nerve crush.

PubMed

Sharma, Nijee; Moeller, Carl W; Marzo, Sam J; Jones, Kathryn J; Foecking, Eileen M

2010-08-01

To investigate the effects of various combinatorial treatments, consisting of a tapering dose of prednisone (P), a brief period of nerve electrical stimulation (ES), and systemic testosterone propionate (TP) on improving functional recovery following an intratemporal facial nerve crush injury. Prospective, controlled animal study. After a right intratemporal facial nerve crush, adult male Sprague-Dawley rats were divided into the following eight treatment groups: 1) no treatment, 2) P only, 3) ES only, 4) ES + P, 5) TP only, 6) TP + P, 7) ES + TP, and 8) ES + TP + P. For each group n = 4-8. Recovery of the eyeblink reflex and vibrissae orientation and movement were assessed. Changes in peak amplitude and latency of evoked response, in response to facial nerve stimulation, was also recorded weekly. : Brief ES of the proximal nerve stump most effectively accelerated the initiation of functional recovery. Also, ES or TP treatments enhanced recovery of some functional parameters more than P treatment. When administered alone, none of the three treatments improved recovery of complete facial function. Only the combinatorial treatment of ES + TP, regardless of the presence of P, accelerated complete functional recovery and return of normal motor nerve conduction. Our findings suggest that a combinatorial treatment strategy of using brief ES and TP together promises to be an effective therapeutic intervention for promoting regeneration following facial nerve injury. Administration of P neither augments nor hinders recovery.

Developing recombinant antibodies for biomarker detection

DOE Office of Scientific and Technical Information (OSTI.GOV)

Baird, Cheryl L.; Fischer, Christopher J.; Pefaur, Noah B.

2010-10-01

Monoclonal antibodies (mAbs) have an essential role in biomarker validation and diagnostic assays. A barrier to pursuing these applications is the reliance on immunization and hybridomas to produce mAbs, which is time-consuming and may not yield the desired mAb. We recommend a process flow for affinity reagent production that utilizes combinatorial protein display systems (eg, yeast surface display or phage display) rather than hybridomas. These systems link a selectable phenotype-binding conferred by an antibody fragment-with a means for recovering the encoding gene. Recombinant libraries obtained from immunizations can produce high-affinity antibodies (<10 nM) more quickly than other methods. Non-immune librariesmore » provide an alternate route when immunizations are not possible, or when suitable mAbs are not recovered from an immune library. Directed molecular evolution (DME) is an integral part of optimizing mAbs obtained from combinatorial protein display, but can also be used on hybridoma-derived mAbs. Variants can easily be obtained and screened to increase the affinity of the parent mAb (affinity maturation). We discuss examples where DME has been used to tailor affinity reagents to specific applications. Combinatorial protein display also provides an accessible method for identifying antibody pairs, which are necessary for sandwich-type diagnostic assays.« less

Defining Clonal Color in Fluorescent Multi-Clonal Tracking

PubMed Central

Wu, Juwell W.; Turcotte, Raphaël; Alt, Clemens; Runnels, Judith M.; Tsao, Hensin; Lin, Charles P.

2016-01-01

Clonal heterogeneity and selection underpin many biological processes including development and tumor progression. Combinatorial fluorescent protein expression in germline cells has proven its utility for tracking the formation and regeneration of different organ systems. Such cell populations encoded by combinatorial fluorescent proteins are also attractive tools for understanding clonal expansion and clonal competition in cancer. However, the assignment of clonal identity requires an analytical framework in which clonal markings can be parameterized and validated. Here we present a systematic and quantitative method for RGB analysis of fluorescent melanoma cancer clones. We then demonstrate refined clonal trackability of melanoma cells using this scheme. PMID:27073117

Multifunctional combinatorial-designed nanoparticles for nucleic acid therapy

NASA Astrophysics Data System (ADS)

Amiji, Mansoor M.

2016-05-01

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

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

USDA-ARS?s Scientific Manuscript database

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

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

ERIC Educational Resources Information Center

Bulone, Vincent William

2017-01-01

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

Applications of Evolutionary Technology to Manufacturing and Logistics Systems : State-of-the Art Survey

NASA Astrophysics Data System (ADS)

Gen, Mitsuo; Lin, Lin

Many combinatorial optimization problems from industrial engineering and operations research in real-world are very complex in nature and quite hard to solve them by conventional techniques. Since the 1960s, there has been an increasing interest in imitating living beings to solve such kinds of hard combinatorial optimization problems. Simulating the natural evolutionary process of human beings results in stochastic optimization techniques called evolutionary algorithms (EAs), which can often outperform conventional optimization methods when applied to difficult real-world problems. In this survey paper, we provide a comprehensive survey of the current state-of-the-art in the use of EA in manufacturing and logistics systems. In order to demonstrate the EAs which are powerful and broadly applicable stochastic search and optimization techniques, we deal with the following engineering design problems: transportation planning models, layout design models and two-stage logistics models in logistics systems; job-shop scheduling, resource constrained project scheduling in manufacturing system.

Strategies for Efficient Charge Separation and Transfer in Artificial Photosynthesis of Solar Fuels.

PubMed

Xu, Yuxing; Li, Ailong; Yao, Tingting; Ma, Changtong; Zhang, Xianwen; Shah, Jafar Hussain; Han, Hongxian

2017-11-23

Converting sunlight to solar fuels by artificial photosynthesis is an innovative science and technology for renewable energy. Light harvesting, photogenerated charge separation and transfer (CST), and catalytic reactions are the three primary steps in the processes involved in the conversion of solar energy to chemical energy (SE-CE). Among the processes, CST is the key "energy pump and delivery" step in determining the overall solar-energy conversion efficiency. Efficient CST is always high priority in designing and assembling artificial photosynthesis systems for solar-fuel production. This Review not only introduces the fundamental strategies for CST but also the combinatory application of these strategies to five types of the most-investigated semiconductor-based artificial photosynthesis systems: particulate, Z-scheme, hybrid, photoelectrochemical, and photovoltaics-assisted systems. We show that artificial photosynthesis systems with high SE-CE efficiency can be rationally designed and constructed through combinatory application of these strategies, setting a promising blueprint for the future of solar fuels. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

SCRIB and PUF60 Are Primary Drivers of the Multisystemic Phenotypes of the 8q24.3 Copy-Number Variant

PubMed Central

Dauber, Andrew; Golzio, Christelle; Guenot, Cécile; Jodelka, Francine M.; Kibaek, Maria; Kjaergaard, Susanne; Leheup, Bruno; Martinet, Danielle; Nowaczyk, Malgorzata J.M.; Rosenfeld, Jill A.; Zeesman, Susan; Zunich, Janice; Beckmann, Jacques S.; Hirschhorn, Joel N.; Hastings, Michelle L.; Jacquemont, Sebastien; Katsanis, Nicholas

2013-01-01

Copy-number variants (CNVs) represent a significant interpretative challenge, given that each CNV typically affects the dosage of multiple genes. Here we report on five individuals with coloboma, microcephaly, developmental delay, short stature, and craniofacial, cardiac, and renal defects who harbor overlapping microdeletions on 8q24.3. Fine mapping localized a commonly deleted 78 kb region that contains three genes: SCRIB, NRBP2, and PUF60. In vivo dissection of the CNV showed discrete contributions of the planar cell polarity effector SCRIB and the splicing factor PUF60 to the syndromic phenotype, and the combinatorial suppression of both genes exacerbated some, but not all, phenotypic components. Consistent with these findings, we identified an individual with microcephaly, short stature, intellectual disability, and heart defects with a de novo c.505C>T variant leading to a p.His169Tyr change in PUF60. Functional testing of this allele in vivo and in vitro showed that the mutation perturbs the relative dosage of two PUF60 isoforms and, subsequently, the splicing efficiency of downstream PUF60 targets. These data inform the functions of two genes not associated previously with human genetic disease and demonstrate how CNVs can exhibit complex genetic architecture, with the phenotype being the amalgam of both discrete dosage dysfunction of single transcripts and also of binary genetic interactions. PMID:24140112

cGRNB: a web server for building combinatorial gene regulatory networks through integrated engineering of seed-matching sequence information and gene expression datasets.

PubMed

Xu, Huayong; Yu, Hui; Tu, Kang; Shi, Qianqian; Wei, Chaochun; Li, Yuan-Yuan; Li, Yi-Xue

2013-01-01

We are witnessing rapid progress in the development of methodologies for building the combinatorial gene regulatory networks involving both TFs (Transcription Factors) and miRNAs (microRNAs). There are a few tools available to do these jobs but most of them are not easy to use and not accessible online. A web server is especially needed in order to allow users to upload experimental expression datasets and build combinatorial regulatory networks corresponding to their particular contexts. In this work, we compiled putative TF-gene, miRNA-gene and TF-miRNA regulatory relationships from forward-engineering pipelines and curated them as built-in data libraries. We streamlined the R codes of our two separate forward-and-reverse engineering algorithms for combinatorial gene regulatory network construction and formalized them as two major functional modules. As a result, we released the cGRNB (combinatorial Gene Regulatory Networks Builder): a web server for constructing combinatorial gene regulatory networks through integrated engineering of seed-matching sequence information and gene expression datasets. The cGRNB enables two major network-building modules, one for MPGE (miRNA-perturbed gene expression) datasets and the other for parallel miRNA/mRNA expression datasets. A miRNA-centered two-layer combinatorial regulatory cascade is the output of the first module and a comprehensive genome-wide network involving all three types of combinatorial regulations (TF-gene, TF-miRNA, and miRNA-gene) are the output of the second module. In this article we propose cGRNB, a web server for building combinatorial gene regulatory networks through integrated engineering of seed-matching sequence information and gene expression datasets. Since parallel miRNA/mRNA expression datasets are rapidly accumulated by the advance of next-generation sequencing techniques, cGRNB will be very useful tool for researchers to build combinatorial gene regulatory networks based on expression datasets. The cGRNB web-server is free and available online at http://www.scbit.org/cgrnb.

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

NASA Astrophysics Data System (ADS)

Gaifullin, A. A.

2008-10-01

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

Training and Transfer in Combinatorial Problem Solving: The Development of Formal Reasoning During Early Adolescence

ERIC Educational Resources Information Center

Barratt, Barnaby B.

1975-01-01

This study investigated the emergence of combinatorial competence in early adolescence and the effectiveness of a programmed discovery training procedure. Significant increases in combinatorial skill with age were shown; it was found that the expression of this skill was significantly facilitated if problems involved concrete material of low…

Combinatorial Methods for Exploring Complex Materials

NASA Astrophysics Data System (ADS)

Amis, Eric J.

2004-03-01

Combinatorial and high-throughput methods have changed the paradigm of pharmaceutical synthesis and have begun to have a similar impact on materials science research. Already there are examples of combinatorial methods used for inorganic materials, catalysts, and polymer synthesis. For many investigations the primary goal has been discovery of new material compositions that optimize properties such as phosphorescence or catalytic activity. In the midst of the excitement generated to "make things", another opportunity arises for materials science to "understand things" by using the efficiency of combinatorial methods. We have shown that combinatorial methods hold potential for rapid and systematic generation of experimental data over the multi-parameter space typical of investigations in polymer physics. We have applied the combinatorial approach to studies of polymer thin films, biomaterials, polymer blends, filled polymers, and semicrystalline polymers. By combining library fabrication, high-throughput measurements, informatics, and modeling we can demonstrate validation of the methodology, new observations, and developments toward predictive models. This talk will present some of our latest work with applications to coating stability, multi-component formulations, and nanostructure assembly.

Integration of language and sensor information

NASA Astrophysics Data System (ADS)

Perlovsky, Leonid I.; Weijers, Bertus

2003-04-01

The talk describes the development of basic technologies of intelligent systems fusing data from multiple domains and leading to automated computational techniques for understanding data contents. Understanding involves inferring appropriate decisions and recommending proper actions, which in turn requires fusion of data and knowledge about objects, situations, and actions. Data might include sensory data, verbal reports, intelligence intercepts, or public records, whereas knowledge ought to encompass the whole range of objects, situations, people and their behavior, and knowledge of languages. In the past, a fundamental difficulty in combining knowledge with data was the combinatorial complexity of computations, too many combinations of data and knowledge pieces had to be evaluated. Recent progress in understanding of natural intelligent systems, including the human mind, leads to the development of neurophysiologically motivated architectures for solving these challenging problems, in particular the role of emotional neural signals in overcoming combinatorial complexity of old logic-based approaches. Whereas past approaches based on logic tended to identify logic with language and thinking, recent studies in cognitive linguistics have led to appreciation of more complicated nature of linguistic models. Little is known about the details of the brain mechanisms integrating language and thinking. Understanding and fusion of linguistic information with sensory data represent a novel challenging aspect of the development of integrated fusion systems. The presentation will describe a non-combinatorial approach to this problem and outline techniques that can be used for fusing diverse and uncertain knowledge with sensory and linguistic data.

Tumor-targeting peptides from combinatorial libraries*

PubMed Central

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

2018-01-01

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

Identification of combinatorial drug regimens for treatment of Huntington's disease using Drosophila

NASA Astrophysics Data System (ADS)

Agrawal, Namita; Pallos, Judit; Slepko, Natalia; Apostol, Barbara L.; Bodai, Laszlo; Chang, Ling-Wen; Chiang, Ann-Shyn; Michels Thompson, Leslie; Marsh, J. Lawrence

2005-03-01

We explore the hypothesis that pathology of Huntington's disease involves multiple cellular mechanisms whose contributions to disease are incrementally additive or synergistic. We provide evidence that the photoreceptor neuron degeneration seen in flies expressing mutant human huntingtin correlates with widespread degenerative events in the Drosophila CNS. We use a Drosophila Huntington's disease model to establish dose regimens and protocols to assess the effectiveness of drug combinations used at low threshold concentrations. These proof of principle studies identify at least two potential combinatorial treatment options and illustrate a rapid and cost-effective paradigm for testing and optimizing combinatorial drug therapies while reducing side effects for patients with neurodegenerative disease. The potential for using prescreening in Drosophila to inform combinatorial therapies that are most likely to be effective for testing in mammals is discussed. combinatorial treatments | neurodegeneration

Nonparametric Combinatorial Sequence Models

NASA Astrophysics Data System (ADS)

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

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

Synergistic Effect of Combinatorial Treatment with Curcumin and Mitomycin C on the Induction of Apoptosis of Breast Cancer Cells: A cDNA Microarray Analysis

PubMed Central

Zhou, Qian-Mei; Chen, Qi-Long; Du, Jia; Wang, Xiu-Feng; Lu, Yi-Yu; Zhang, Hui; Su, Shi-Bing

2014-01-01

In order to explore the synergistic mechanisms of combinatorial treatment using curcumin and mitomycin C (MMC) for breast cancer, MCF-7 breast cancer xenografts were conducted to observe the synergistic effect of combinatorial treatment using curcumin and MMC at various dosages. The synergistic mechanisms of combinatorial treatment using curcumin and MMC on the inhibition of tumor growth were explored by differential gene expression profile, gene ontology (GO), ingenuity pathway analysis (IPA) and Signal–Net network analysis. The expression levels of selected genes identified by cDNA microarray expression profiling were validated by quantitative RT-PCR (qRT-PCR) and Western blot analysis. Effect of combinatorial treatment on the inhibition of cell growth was observed by MTT assay. Apoptosis was detected by flow cytometric analysis and Hoechst 33258 staining. The combinatorial treatment of 100 mg/kg curcumin and 1.5 mg/kg MMC revealed synergistic inhibition on tumor growth. Among 1501 differentially expressed genes, the expression of 25 genes exhibited an obvious change and a significant difference in 27 signal pathways was observed (p < 0.05). In addition, Mapk1 (ERK) and Mapk14 (MAPK p38) had more cross-interactions with other genes and revealed an increase in expression by 8.14- and 11.84-fold, respectively during the combinatorial treatment by curcumin and MMC when compared with the control. Moreover, curcumin can synergistically improve tumoricidal effect of MMC in another human breast cancer MDA-MB-231 cells. Apoptosis was significantly induced by the combinatorial treatment (p < 0.05) and significantly inhibited by ERK inhibitor (PD98059) in MCF-7 cells (p < 0.05). The synergistic effect of combinatorial treatment by curcumin and MMC on the induction of apoptosis in breast cancer cells may be via the ERK pathway. PMID:25226537

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

PubMed

Haglund, J; Haiman, M; Loehr, N

2005-02-22

Haglund recently proposed a combinatorial interpretation of the modified Macdonald polynomials H(mu). We give a combinatorial proof of this conjecture, which establishes the existence and integrality of H(mu). As corollaries, we obtain the cocharge formula of Lascoux and Schutzenberger 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 J(mu), a formula for H(mu) in terms of Lascoux-Leclerc-Thibon polynomials, and combinatorial expressions for the Kostka-Macdonald coefficients K(lambda,mu) when mu is a two-column shape.

Resource Limitation Issues In Real-Time Intelligent Systems

NASA Astrophysics Data System (ADS)

Green, Peter E.

1986-03-01

This paper examines resource limitation problems that can occur in embedded AI systems which have to run in real-time. It does this by examining two case studies. The first is a system which acoustically tracks low-flying aircraft and has the problem of interpreting a high volume of often ambiguous input data to produce a model of the system's external world. The second is a robotics problem in which the controller for a robot arm has to dynamically plan the order in which to pick up pieces from a conveyer belt and sort them into bins. In this case the system starts with a continuously changing model of its environment and has to select which action to perform next. This latter case emphasizes the issues in designing a system which must operate in an uncertain and rapidly changing environment. The first system uses a distributed HEARSAY methodology running on multiple processors. It is shown, in this case, how the com-binatorial growth of possible interpretation of the input data can require large and unpredictable amounts of computer resources for data interpretation. Techniques are presented which achieve real-time operation by limiting the combinatorial growth of alternate hypotheses and processing those hypotheses that are most likely to lead to meaningful interpretation of the input data. The second system uses a decision tree approach to generate and evaluate possible plans of action. It is shown how the combina-torial growth of possible alternate plans can, as in the previous case, require large and unpredictable amounts of computer time to evalu-ate and select from amongst the alternative. The use of approximate decisions to limit the amount of computer time needed is discussed. The use of concept of using incremental evidence is then introduced and it is shown how this can be used as the basis of systems that can combine heuristic and approximate evidence in making real-time decisions.

A new approach to the rationale discovery of polymeric biomaterials

PubMed Central

Kohn, Joachim; Welsh, William J.; Knight, Doyle

2007-01-01

This paper attempts to illustrate both the need for new approaches to biomaterials discovery as well as the significant promise inherent in the use of combinatorial and computational design strategies. The key observation of this Leading Opinion Paper is that the biomaterials community has been slow to embrace advanced biomaterials discovery tools such as combinatorial methods, high throughput experimentation, and computational modeling in spite of the significant promise shown by these discovery tools in materials science, medicinal chemistry and the pharmaceutical industry. It seems that the complexity of living cells and their interactions with biomaterials has been a conceptual as well as a practical barrier to the use of advanced discovery tools in biomaterials science. However, with the continued increase in computer power, the goal of predicting the biological response of cells in contact with biomaterials surfaces is within reach. Once combinatorial synthesis, high throughput experimentation, and computational modeling are integrated into the biomaterials discovery process, a significant acceleration is possible in the pace of development of improved medical implants, tissue regeneration scaffolds, and gene/drug delivery systems. PMID:17644176

Integrated microfluidic devices for combinatorial cell-based assays.

PubMed

Yu, Zeta Tak For; Kamei, Ken-ichiro; Takahashi, Hiroko; Shu, Chengyi Jenny; Wang, Xiaopu; He, George Wenfu; Silverman, Robert; Radu, Caius G; Witte, Owen N; Lee, Ki-Bum; Tseng, Hsian-Rong

2009-06-01

The development of miniaturized cell culture platforms for performing parallel cultures and combinatorial assays is important in cell biology from the single-cell level to the system level. In this paper we developed an integrated microfluidic cell-culture platform, Cell-microChip (Cell-microChip), for parallel analyses of the effects of microenvironmental cues (i.e., culture scaffolds) on different mammalian cells and their cellular responses to external stimuli. As a model study, we demonstrated the ability of culturing and assaying several mammalian cells, such as NIH 3T3 fibroblast, B16 melanoma and HeLa cell lines, in a parallel way. For functional assays, first we tested drug-induced apoptotic responses from different cell lines. As a second functional assay, we performed "on-chip" transfection of a reporter gene encoding an enhanced green fluorescent protein (EGFP) followed by live-cell imaging of transcriptional activation of cyclooxygenase 2 (Cox-2) expression. Collectively, our Cell-microChip approach demonstrated the capability to carry out parallel operations and the potential to further integrate advanced functions and applications in the broader space of combinatorial chemistry and biology.

Integrated microfluidic devices for combinatorial cell-based assays

PubMed Central

Yu, Zeta Tak For; Kamei, Ken-ichiro; Takahashi, Hiroko; Shu, Chengyi Jenny; Wang, Xiaopu; He, George Wenfu; Silverman, Robert

2010-01-01

The development of miniaturized cell culture platforms for performing parallel cultures and combinatorial assays is important in cell biology from the single-cell level to the system level. In this paper we developed an integrated microfluidic cell-culture platform, Cell-microChip (Cell-μChip), for parallel analyses of the effects of microenvir-onmental cues (i.e., culture scaffolds) on different mammalian cells and their cellular responses to external stimuli. As a model study, we demonstrated the ability of culturing and assaying several mammalian cells, such as NIH 3T3 fibro-blast, B16 melanoma and HeLa cell lines, in a parallel way. For functional assays, first we tested drug-induced apoptotic responses from different cell lines. As a second functional assay, we performed "on-chip" transfection of a reporter gene encoding an enhanced green fluorescent protein (EGFP) followed by live-cell imaging of transcriptional activation of cyclooxygenase 2 (Cox-2) expression. Collectively, our Cell-μChip approach demonstrated the capability to carry out parallel operations and the potential to further integrate advanced functions and applications in the broader space of combinatorial chemistry and biology. PMID:19130244

To Think without Thinking: The Implications of Combinatory Play and the Creative Process for Neuroaesthetics

ERIC Educational Resources Information Center

Stevens, Victoria

2014-01-01

The author considers combinatory play as an intersection between creativity, play, and neuroaesthetics. She discusses combinatory play as vital to the creative process in art and science, particularly with regard to the incubation of new ideas. She reviews findings from current neurobiological research and outlines the way that the brain activates…

Bifurcations of 2-Periodic Nonautonomous Stunted Tent Systems

NASA Astrophysics Data System (ADS)

Silva, L.; Rocha, J. Leonel; Silva, M. T.

2017-06-01

In this paper, we will consider a family of 2-periodic nonautonomous dynamical systems, generated by the alternate iteration of two stunted tent maps and study its bifurcation skeleton. We will describe the bifurcation phenomena along and around the bones accomplished with the combinatorial data furnished by the respective symbolic dynamics.

Solubility limits in quaternary SnTe-based alloys [Metastability and solubility limits in quaternary SnTe-based alloys guided by combinatorial sputtering

DOE PAGES

Siol, Sebastian; Holder, Aaron; Ortiz, Brenden R.; ...

2017-05-09

Here, the controlled decomposition of metastable alloys is an attractive route to form nanostructured thermoelectric materials with reduced thermal conductivity. The ternary SnTe–MnTe and SnTe–SnSe heterostructural alloys have been demonstrated as promising materials for thermoelectric applications. In this work, the quaternary Sn 1–yMnyTe 1–xSe x phase space serves as a relevant model system to explore how a combination of computational and combinatorial-growth methods can be used to study equilibrium and non-equilibrium solubility limits. Results from first principle calculations indicate low equilibrium solubility for x,y < 0.05 that are in good agreement with results obtained from bulk equilibrium synthesis experiments andmore » predict significantly higher spinodal limits. An experimental screening using sputtered combinatorial thin film sample libraries showed a remarkable increase in non-equilibrium solubility for x,y > 0.2. These theoretical and experimental results were used to guide the bulk synthesis of metastable alloys. The ability to reproduce the non-equilibrium solubility levels in bulk materials indicates that such theoretical calculations and combinatorial growth can inform bulk synthetic routes. Further, the large difference between equilibrium and non-equilibrium solubility limits in Sn 1–yMn yTe 1–xSe x indicates these metastable alloys are attractive in terms of nano-precipitate formation for potential thermoelectric applications.« less

Combinatorial genetic perturbation to refine metabolic circuits for producing biofuels and biochemicals.

PubMed

Kim, Hyo Jin; Turner, Timothy Lee; Jin, Yong-Su

2013-11-01

Recent advances in metabolic engineering have enabled microbial factories to compete with conventional processes for producing fuels and chemicals. Both rational and combinatorial approaches coupled with synthetic and systematic tools play central roles in metabolic engineering to create and improve a selected microbial phenotype. Compared to knowledge-based rational approaches, combinatorial approaches exploiting biological diversity and high-throughput screening have been demonstrated as more effective tools for improving various phenotypes of interest. In particular, identification of unprecedented targets to rewire metabolic circuits for maximizing yield and productivity of a target chemical has been made possible. This review highlights general principles and the features of the combinatorial approaches using various libraries to implement desired phenotypes for strain improvement. In addition, recent applications that harnessed the combinatorial approaches to produce biofuels and biochemicals will be discussed. Copyright © 2013 Elsevier Inc. All rights reserved.

Tumor-targeting peptides from combinatorial libraries.

PubMed

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

2017-02-01

Cancer is one of the major and leading causes of death worldwide. Two of the greatest challenges in fighting cancer are early detection and effective treatments with no or minimum side effects. Widespread use of targeted therapies and molecular imaging in clinics requires high affinity, tumor-specific agents as effective targeting vehicles to deliver therapeutics and imaging probes to the primary or metastatic tumor sites. Combinatorial libraries such as phage-display and one-bead one-compound (OBOC) peptide libraries are powerful approaches in discovering tumor-targeting peptides. This review gives an overview of different combinatorial library technologies that have been used for the discovery of tumor-targeting peptides. Examples of tumor-targeting peptides identified from each combinatorial library method will be discussed. Published tumor-targeting peptide ligands and their applications will also be summarized by the combinatorial library methods and their corresponding binding receptors. Copyright © 2017. Published by Elsevier B.V.

Simulation of the zero-temperature behavior of a three-dimensional elastic medium

NASA Astrophysics Data System (ADS)

McNamara, David; Middleton, A. Alan; Zeng, Chen

1999-10-01

We have performed numerical simulation of a three-dimensional elastic medium, with scalar displacements, subject to quenched disorder. In the absence of topological defects this system is equivalent to a (3+1)-dimensional interface subject to a periodic pinning potential. We have applied an efficient combinatorial optimization algorithm to generate exact ground states for this interface representation. Our results indicate that this Bragg glass is characterized by power law divergences in the structure factor S(k)~Ak-3. We have found numerically consistent values of the coefficient A for two lattice discretizations of the medium, supporting universality for A in the isotropic systems considered here. We also examine the response of the ground state to the change in boundary conditions that corresponds to introducing a single dislocation loop encircling the system. The rearrangement of the ground state caused by this change is equivalent to the domain wall of elastic deformations which span the dislocation loop. Our results indicate that these domain walls are highly convoluted, with a fractal dimension df=2.60(5). We also discuss the implications of the domain wall energetics for the stability of the Bragg glass phase. Elastic excitations similar to these domain walls arise when the pinning potential is slightly perturbed. As in other disordered systems, perturbations of relative strength δ introduce a new length scale L*~δ-1/ζ beyond which the perturbed ground state becomes uncorrelated with the reference (unperturbed) ground state. We have performed a scaling analysis of the response of the ground state to the perturbations and obtain ζ=0.385(40). This value is consistent with the scaling relation ζ=df/2-θ, where θ characterizes the scaling of the energy fluctuations of low energy excitations.

Fabrication and characterization of thin-film phosphor combinatorial libraries

NASA Astrophysics Data System (ADS)

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

2002-05-01

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

Molecular mechanisms of floral organ specification by MADS domain proteins.

PubMed

Yan, Wenhao; Chen, Dijun; Kaufmann, Kerstin

2016-02-01

Flower development is a model system to understand organ specification in plants. The identities of different types of floral organs are specified by homeotic MADS transcription factors that interact in a combinatorial fashion. Systematic identification of DNA-binding sites and target genes of these key regulators show that they have shared and unique sets of target genes. DNA binding by MADS proteins is not based on 'simple' recognition of a specific DNA sequence, but depends on DNA structure and combinatorial interactions. Homeotic MADS proteins regulate gene expression via alternative mechanisms, one of which may be to modulate chromatin structure and accessibility in their target gene promoters. Copyright © 2015 Elsevier Ltd. All rights reserved.

DOE Office of Scientific and Technical Information (OSTI.GOV)

None, None

The Second SIAM Conference on Computational Science and Engineering was held in San Diego from February 10-12, 2003. Total conference attendance was 553. This is a 23% increase in attendance over the first conference. The focus of this conference was to draw attention to the tremendous range of major computational efforts on large problems in science and engineering, to promote the interdisciplinary culture required to meet these large-scale challenges, and to encourage the training of the next generation of computational scientists. Computational Science & Engineering (CS&E) is now widely accepted, along with theory and experiment, as a crucial third modemore » of scientific investigation and engineering design. Aerospace, automotive, biological, chemical, semiconductor, and other industrial sectors now rely on simulation for technical decision support. For federal agencies also, CS&E has become an essential support for decisions on resources, transportation, and defense. CS&E is, by nature, interdisciplinary. It grows out of physical applications and it depends on computer architecture, but at its heart are powerful numerical algorithms and sophisticated computer science techniques. From an applied mathematics perspective, much of CS&E has involved analysis, but the future surely includes optimization and design, especially in the presence of uncertainty. Another mathematical frontier is the assimilation of very large data sets through such techniques as adaptive multi-resolution, automated feature search, and low-dimensional parameterization. The themes of the 2003 conference included, but were not limited to: Advanced Discretization Methods; Computational Biology and Bioinformatics; Computational Chemistry and Chemical Engineering; Computational Earth and Atmospheric Sciences; Computational Electromagnetics; Computational Fluid Dynamics; Computational Medicine and Bioengineering; Computational Physics and Astrophysics; Computational Solid Mechanics and Materials; CS&E Education; Meshing and Adaptivity; Multiscale and Multiphysics Problems; Numerical Algorithms for CS&E; Discrete and Combinatorial Algorithms for CS&E; Inverse Problems; Optimal Design, Optimal Control, and Inverse Problems; Parallel and Distributed Computing; Problem-Solving Environments; Software and Wddleware Systems; Uncertainty Estimation and Sensitivity Analysis; and Visualization and Computer Graphics.« less

Development of the Architectural Simulation Model for Future Launch Systems and its Application to an Existing Launch Fleet

NASA Technical Reports Server (NTRS)

Rabadi, Ghaith

2005-01-01

A significant portion of lifecycle costs for launch vehicles are generated during the operations phase. Research indicates that operations costs can account for a large percentage of the total life-cycle costs of reusable space transportation systems. These costs are largely determined by decisions made early during conceptual design. Therefore, operational considerations are an important part of vehicle design and concept analysis process that needs to be modeled and studied early in the design phase. However, this is a difficult and challenging task due to uncertainties of operations definitions, the dynamic and combinatorial nature of the processes, and lack of analytical models and the scarcity of historical data during the conceptual design phase. Ultimately, NASA would like to know the best mix of launch vehicle concepts that would meet the missions launch dates at the minimum cost. To answer this question, we first need to develop a model to estimate the total cost, including the operational cost, to accomplish this set of missions. In this project, we have developed and implemented a discrete-event simulation model using ARENA (a simulation modeling environment) to determine this cost assessment. Discrete-event simulation is widely used in modeling complex systems, including transportation systems, due to its flexibility, and ability to capture the dynamics of the system. The simulation model accepts manifest inputs including the set of missions that need to be accomplished over a period of time, the clients (e.g., NASA or DoD) who wish to transport the payload to space, the payload weights, and their destinations (e.g., International Space Station, LEO, or GEO). A user of the simulation model can define an architecture of reusable or expendable launch vehicles to achieve these missions. Launch vehicles may belong to different families where each family may have it own set of resources, processing times, and cost factors. The goal is to capture the required resource levels of the major launch elements and their required facilities. The model s output can show whether or not a certain architecture of vehicles can meet the launch dates, and if not, how much the delay cost would be. It will also produce aggregate figures of missions cost based on element procurement cost, processing cost, cargo integration cost, delay cost, and mission support cost. One of the most useful features of this model is that it is stochastic where it accepts statistical distributions to represent the processing times mimicking the stochastic nature of real systems.

A Lie algebraic condition for exponential stability of discrete hybrid systems and application to hybrid synchronization.

PubMed

Zhao, Shouwei

2011-06-01

A Lie algebraic condition for global exponential stability of linear discrete switched impulsive systems is presented in this paper. By considering a Lie algebra generated by all subsystem matrices and impulsive matrices, when not all of these matrices are Schur stable, we derive new criteria for global exponential stability of linear discrete switched impulsive systems. Moreover, simple sufficient conditions in terms of Lie algebra are established for the synchronization of nonlinear discrete systems using a hybrid switching and impulsive control. As an application, discrete chaotic system's synchronization is investigated by the proposed method.

Morphological Constraints on Cerebellar Granule Cell Combinatorial Diversity.

PubMed

Gilmer, Jesse I; Person, Abigail L

2017-12-13

Combinatorial expansion by the cerebellar granule cell layer (GCL) is fundamental to theories of cerebellar contributions to motor control and learning. Granule cells (GrCs) sample approximately four mossy fiber inputs and are thought to form a combinatorial code useful for pattern separation and learning. We constructed a spatially realistic model of the cerebellar GCL and examined how GCL architecture contributes to GrC combinatorial diversity. We found that GrC combinatorial diversity saturates quickly as mossy fiber input diversity increases, and that this saturation is in part a consequence of short dendrites, which limit access to diverse inputs and favor dense sampling of local inputs. This local sampling also produced GrCs that were combinatorially redundant, even when input diversity was extremely high. In addition, we found that mossy fiber clustering, which is a common anatomical pattern, also led to increased redundancy of GrC input combinations. We related this redundancy to hypothesized roles of temporal expansion of GrC information encoding in service of learned timing, and we show that GCL architecture produces GrC populations that support both temporal and combinatorial expansion. Finally, we used novel anatomical measurements from mice of either sex to inform modeling of sparse and filopodia-bearing mossy fibers, finding that these circuit features uniquely contribute to enhancing GrC diversification and redundancy. Our results complement information theoretic studies of granule layer structure and provide insight into the contributions of granule layer anatomical features to afferent mixing. SIGNIFICANCE STATEMENT Cerebellar granule cells are among the simplest neurons, with tiny somata and, on average, just four dendrites. These characteristics, along with their dense organization, inspired influential theoretical work on the granule cell layer as a combinatorial expander, where each granule cell represents a unique combination of inputs. Despite the centrality of these theories to cerebellar physiology, the degree of expansion supported by anatomically realistic patterns of inputs is unknown. Using modeling and anatomy, we show that realistic input patterns constrain combinatorial diversity by producing redundant combinations, which nevertheless could support temporal diversification of like combinations, suitable for learned timing. Our study suggests a neural substrate for producing high levels of both combinatorial and temporal diversity in the granule cell layer. Copyright © 2017 the authors 0270-6474/17/3712153-14$15.00/0.

Dissection of combinatorial control by the Met4 transcriptional complex.

PubMed

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

2010-02-01

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

Intrinsic information carriers in combinatorial dynamical systems

NASA Astrophysics Data System (ADS)

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

2010-09-01

Many proteins are composed of structural and chemical features—"sites" for short—characterized by definite interaction capabilities, such as noncovalent binding or covalent modification of other proteins. This modularity allows for varying degrees of independence, as the behavior of a site might be controlled by the state of some but not all sites of the ambient protein. Independence quickly generates a startling combinatorial complexity that shapes most biological networks, such as mammalian signaling systems, and effectively prevents their study in terms of kinetic equations—unless the complexity is radically trimmed. Yet, if combinatorial complexity is key to the system's behavior, eliminating it will prevent, not facilitate, understanding. A more adequate representation of a combinatorial system is provided by a graph-based framework of rewrite rules where each rule specifies only the information that an interaction mechanism depends on. Unlike reactions, which deal with molecular species, rules deal with patterns, i.e., multisets of molecular species. Although the stochastic dynamics induced by a collection of rules on a mixture of molecules can be simulated, it appears useful to capture the system's average or deterministic behavior by means of differential equations. However, expansion of the rules into kinetic equations at the level of molecular species is not only impractical, but conceptually indefensible. If rules describe bona fide patterns of interaction, molecular species are unlikely to constitute appropriate units of dynamics. Rather, we must seek aggregate variables reflective of the causal structure laid down by the rules. We call these variables "fragments" and the process of identifying them "fragmentation." Ideally, fragments are aspects of the system's microscopic population that the set of rules can actually distinguish on average; in practice, it may only be feasible to identify an approximation to this. Most importantly, fragments are self-consistent descriptors of system dynamics in that their time-evolution is governed by a closed system of kinetic equations. Taken together, fragments are endogenous distinctions that matter for the dynamics of a system, which warrants viewing them as the carriers of information. Although fragments can be thought of as multisets of molecular species (an extensional view), their self-consistency suggests treating them as autonomous aspects cut off from their microscopic realization (an intensional view). Fragmentation is a seeded process that depends on the choice of observables whose dynamics one insists to describe. Different observables can cause distinct fragmentations, in effect altering the set of information carriers that govern the behavior of a system, even though nothing has changed in its microscopic constitution. In this contribution, we present a mathematical specification of fragments, but not an algorithmic implementation. We have described the latter elsewhere in rather technical terms that, although effective, were lacking an embedding into a more general conceptual framework, which we here provide.

Intrinsic information carriers in combinatorial dynamical systems.

PubMed

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

2010-09-01

Many proteins are composed of structural and chemical features--"sites" for short--characterized by definite interaction capabilities, such as noncovalent binding or covalent modification of other proteins. This modularity allows for varying degrees of independence, as the behavior of a site might be controlled by the state of some but not all sites of the ambient protein. Independence quickly generates a startling combinatorial complexity that shapes most biological networks, such as mammalian signaling systems, and effectively prevents their study in terms of kinetic equations-unless the complexity is radically trimmed. Yet, if combinatorial complexity is key to the system's behavior, eliminating it will prevent, not facilitate, understanding. A more adequate representation of a combinatorial system is provided by a graph-based framework of rewrite rules where each rule specifies only the information that an interaction mechanism depends on. Unlike reactions, which deal with molecular species, rules deal with patterns, i.e., multisets of molecular species. Although the stochastic dynamics induced by a collection of rules on a mixture of molecules can be simulated, it appears useful to capture the system's average or deterministic behavior by means of differential equations. However, expansion of the rules into kinetic equations at the level of molecular species is not only impractical, but conceptually indefensible. If rules describe bona fide patterns of interaction, molecular species are unlikely to constitute appropriate units of dynamics. Rather, we must seek aggregate variables reflective of the causal structure laid down by the rules. We call these variables "fragments" and the process of identifying them "fragmentation." Ideally, fragments are aspects of the system's microscopic population that the set of rules can actually distinguish on average; in practice, it may only be feasible to identify an approximation to this. Most importantly, fragments are self-consistent descriptors of system dynamics in that their time-evolution is governed by a closed system of kinetic equations. Taken together, fragments are endogenous distinctions that matter for the dynamics of a system, which warrants viewing them as the carriers of information. Although fragments can be thought of as multisets of molecular species (an extensional view), their self-consistency suggests treating them as autonomous aspects cut off from their microscopic realization (an intensional view). Fragmentation is a seeded process that depends on the choice of observables whose dynamics one insists to describe. Different observables can cause distinct fragmentations, in effect altering the set of information carriers that govern the behavior of a system, even though nothing has changed in its microscopic constitution. In this contribution, we present a mathematical specification of fragments, but not an algorithmic implementation. We have described the latter elsewhere in rather technical terms that, although effective, were lacking an embedding into a more general conceptual framework, which we here provide.

Combinatorial discovery of enzymes with utility in biomass transformation

DOEpatents

Fox, Brian G; Elsen, Nathaniel L

2015-02-03

Methods for the cell-free identification of polypeptide and polypeptide combinations with utility in biomass transformation, as well as specific novel polypeptides and cell-free systems containing polypeptide combinations discovered by such methods are disclosed.

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

NASA Astrophysics Data System (ADS)

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

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

Lectures on algebraic system theory: Linear systems over rings

NASA Technical Reports Server (NTRS)

Kamen, E. W.

1978-01-01

The presentation centers on four classes of systems that can be treated as linear systems over a ring. These are: (1) discrete-time systems over a ring of scalars such as the integers; (2) continuous-time systems containing time delays; (3) large-scale discrete-time systems; and (4) time-varying discrete-time systems.

Automatic Summarization as a Combinatorial Optimization Problem

NASA Astrophysics Data System (ADS)

Hirao, Tsutomu; Suzuki, Jun; Isozaki, Hideki

We derived the oracle summary with the highest ROUGE score that can be achieved by integrating sentence extraction with sentence compression from the reference abstract. The analysis results of the oracle revealed that summarization systems have to assign an appropriate compression rate for each sentence in the document. In accordance with this observation, this paper proposes a summarization method as a combinatorial optimization: selecting the set of sentences that maximize the sum of the sentence scores from the pool which consists of the sentences with various compression rates, subject to length constrains. The score of the sentence is defined by its compression rate, content words and positional information. The parameters for the compression rates and positional information are optimized by minimizing the loss between score of oracles and that of candidates. The results obtained from TSC-2 corpus showed that our method outperformed the previous systems with statistical significance.

A hybrid Q-learning sine-cosine-based strategy for addressing the combinatorial test suite minimization problem

PubMed Central

Zamli, Kamal Z.; Din, Fakhrud; Bures, Miroslav

2018-01-01

The sine-cosine algorithm (SCA) is a new population-based meta-heuristic algorithm. In addition to exploiting sine and cosine functions to perform local and global searches (hence the name sine-cosine), the SCA introduces several random and adaptive parameters to facilitate the search process. Although it shows promising results, the search process of the SCA is vulnerable to local minima/maxima due to the adoption of a fixed switch probability and the bounded magnitude of the sine and cosine functions (from -1 to 1). In this paper, we propose a new hybrid Q-learning sine-cosine- based strategy, called the Q-learning sine-cosine algorithm (QLSCA). Within the QLSCA, we eliminate the switching probability. Instead, we rely on the Q-learning algorithm (based on the penalty and reward mechanism) to dynamically identify the best operation during runtime. Additionally, we integrate two new operations (Lévy flight motion and crossover) into the QLSCA to facilitate jumping out of local minima/maxima and enhance the solution diversity. To assess its performance, we adopt the QLSCA for the combinatorial test suite minimization problem. Experimental results reveal that the QLSCA is statistically superior with regard to test suite size reduction compared to recent state-of-the-art strategies, including the original SCA, the particle swarm test generator (PSTG), adaptive particle swarm optimization (APSO) and the cuckoo search strategy (CS) at the 95% confidence level. However, concerning the comparison with discrete particle swarm optimization (DPSO), there is no significant difference in performance at the 95% confidence level. On a positive note, the QLSCA statistically outperforms the DPSO in certain configurations at the 90% confidence level. PMID:29771918

A hybrid Q-learning sine-cosine-based strategy for addressing the combinatorial test suite minimization problem.

PubMed

Zamli, Kamal Z; Din, Fakhrud; Ahmed, Bestoun S; Bures, Miroslav

2018-01-01

The sine-cosine algorithm (SCA) is a new population-based meta-heuristic algorithm. In addition to exploiting sine and cosine functions to perform local and global searches (hence the name sine-cosine), the SCA introduces several random and adaptive parameters to facilitate the search process. Although it shows promising results, the search process of the SCA is vulnerable to local minima/maxima due to the adoption of a fixed switch probability and the bounded magnitude of the sine and cosine functions (from -1 to 1). In this paper, we propose a new hybrid Q-learning sine-cosine- based strategy, called the Q-learning sine-cosine algorithm (QLSCA). Within the QLSCA, we eliminate the switching probability. Instead, we rely on the Q-learning algorithm (based on the penalty and reward mechanism) to dynamically identify the best operation during runtime. Additionally, we integrate two new operations (Lévy flight motion and crossover) into the QLSCA to facilitate jumping out of local minima/maxima and enhance the solution diversity. To assess its performance, we adopt the QLSCA for the combinatorial test suite minimization problem. Experimental results reveal that the QLSCA is statistically superior with regard to test suite size reduction compared to recent state-of-the-art strategies, including the original SCA, the particle swarm test generator (PSTG), adaptive particle swarm optimization (APSO) and the cuckoo search strategy (CS) at the 95% confidence level. However, concerning the comparison with discrete particle swarm optimization (DPSO), there is no significant difference in performance at the 95% confidence level. On a positive note, the QLSCA statistically outperforms the DPSO in certain configurations at the 90% confidence level.

Generalized probabilistic theories and conic extensions of polytopes

NASA Astrophysics Data System (ADS)

Fiorini, Samuel; Massar, Serge; Patra, Manas K.; Tiwary, Hans Raj

2015-01-01

Generalized probabilistic theories (GPT) provide a general framework that includes classical and quantum theories. It is described by a cone C and its dual C*. We show that whether some one-way communication complexity problems can be solved within a GPT is equivalent to the recently introduced cone factorization of the corresponding communication matrix M. We also prove an analogue of Holevo's theorem: when the cone C is contained in {{{R}}n}, the classical capacity of the channel realized by sending GPT states and measuring them is bounded by log n. Polytopes and optimising functions over polytopes arise in many areas of discrete mathematics. A conic extension of a polytope is the intersection of a cone C with an affine subspace whose projection onto the original space yields the desired polytope. Extensions of polytopes can sometimes be much simpler geometric objects than the polytope itself. The existence of a conic extension of a polytope is equivalent to that of a cone factorization of the slack matrix of the polytope, on the same cone. We show that all 0/1 polytopes whose vertices can be recognized by a polynomial size circuit, which includes as a special case the travelling salesman polytope and many other polytopes from combinatorial optimization, have small conic extension complexity when the cone is the completely positive cone. Using recent exponential lower bounds on the linear extension complexity of polytopes, this provides an exponential gap between the communication complexity of GPT based on the completely positive cone and classical communication complexity, and a conjectured exponential gap with quantum communication complexity. Our work thus relates the communication complexity of generalizations of quantum theory to questions of mainstream interest in the area of combinatorial optimization.

Generating chaos for discrete time-delayed systems via impulsive control.

PubMed

Guan, Zhi-Hong; Liu, Na

2010-03-01

Generating chaos for a class of discrete time-delayed systems via impulsive control is investigated in this paper. With the augmented matrix method, the time-delay impulsive systems can be transformed into a new class of linear discrete impulsive systems. Based on the largest Lyapunov exponent and the boundedness of the systems, some theoretical results about the chaotification for the discrete impulsive systems with time delay are derived and an example is given to visualize the satisfactory control performance.

Discretization chaos - Feedback control and transition to chaos

NASA Technical Reports Server (NTRS)

Grantham, Walter J.; Athalye, Amit M.

1990-01-01

Problems in the design of feedback controllers for chaotic dynamical systems are considered theoretically, focusing on two cases where chaos arises only when a nonchaotic continuous-time system is discretized into a simpler discrete-time systems (exponential discretization and pseudo-Euler integration applied to Lotka-Volterra competition and prey-predator systems). Numerical simulation results are presented in extensive graphs and discussed in detail. It is concluded that care must be taken in applying standard dynamical-systems methods to control systems that may be discontinuous or nondifferentiable.

Rule-based spatial modeling with diffusing, geometrically constrained molecules.

PubMed

Gruenert, Gerd; Ibrahim, Bashar; Lenser, Thorsten; Lohel, Maiko; Hinze, Thomas; Dittrich, Peter

2010-06-07

We suggest a new type of modeling approach for the coarse grained, particle-based spatial simulation of combinatorially complex chemical reaction systems. In our approach molecules possess a location in the reactor as well as an orientation and geometry, while the reactions are carried out according to a list of implicitly specified reaction rules. Because the reaction rules can contain patterns for molecules, a combinatorially complex or even infinitely sized reaction network can be defined. For our implementation (based on LAMMPS), we have chosen an already existing formalism (BioNetGen) for the implicit specification of the reaction network. This compatibility allows to import existing models easily, i.e., only additional geometry data files have to be provided. Our simulations show that the obtained dynamics can be fundamentally different from those simulations that use classical reaction-diffusion approaches like Partial Differential Equations or Gillespie-type spatial stochastic simulation. We show, for example, that the combination of combinatorial complexity and geometric effects leads to the emergence of complex self-assemblies and transportation phenomena happening faster than diffusion (using a model of molecular walkers on microtubules). When the mentioned classical simulation approaches are applied, these aspects of modeled systems cannot be observed without very special treatment. Further more, we show that the geometric information can even change the organizational structure of the reaction system. That is, a set of chemical species that can in principle form a stationary state in a Differential Equation formalism, is potentially unstable when geometry is considered, and vice versa. We conclude that our approach provides a new general framework filling a gap in between approaches with no or rigid spatial representation like Partial Differential Equations and specialized coarse-grained spatial simulation systems like those for DNA or virus capsid self-assembly.

Rule-based spatial modeling with diffusing, geometrically constrained molecules

PubMed Central

2010-01-01

Background We suggest a new type of modeling approach for the coarse grained, particle-based spatial simulation of combinatorially complex chemical reaction systems. In our approach molecules possess a location in the reactor as well as an orientation and geometry, while the reactions are carried out according to a list of implicitly specified reaction rules. Because the reaction rules can contain patterns for molecules, a combinatorially complex or even infinitely sized reaction network can be defined. For our implementation (based on LAMMPS), we have chosen an already existing formalism (BioNetGen) for the implicit specification of the reaction network. This compatibility allows to import existing models easily, i.e., only additional geometry data files have to be provided. Results Our simulations show that the obtained dynamics can be fundamentally different from those simulations that use classical reaction-diffusion approaches like Partial Differential Equations or Gillespie-type spatial stochastic simulation. We show, for example, that the combination of combinatorial complexity and geometric effects leads to the emergence of complex self-assemblies and transportation phenomena happening faster than diffusion (using a model of molecular walkers on microtubules). When the mentioned classical simulation approaches are applied, these aspects of modeled systems cannot be observed without very special treatment. Further more, we show that the geometric information can even change the organizational structure of the reaction system. That is, a set of chemical species that can in principle form a stationary state in a Differential Equation formalism, is potentially unstable when geometry is considered, and vice versa. Conclusions We conclude that our approach provides a new general framework filling a gap in between approaches with no or rigid spatial representation like Partial Differential Equations and specialized coarse-grained spatial simulation systems like those for DNA or virus capsid self-assembly. PMID:20529264

Computer-Aided Diagnosis System for Alzheimer's Disease Using Different Discrete Transform Techniques.

PubMed

Dessouky, Mohamed M; Elrashidy, Mohamed A; Taha, Taha E; Abdelkader, Hatem M

2016-05-01

The different discrete transform techniques such as discrete cosine transform (DCT), discrete sine transform (DST), discrete wavelet transform (DWT), and mel-scale frequency cepstral coefficients (MFCCs) are powerful feature extraction techniques. This article presents a proposed computer-aided diagnosis (CAD) system for extracting the most effective and significant features of Alzheimer's disease (AD) using these different discrete transform techniques and MFCC techniques. Linear support vector machine has been used as a classifier in this article. Experimental results conclude that the proposed CAD system using MFCC technique for AD recognition has a great improvement for the system performance with small number of significant extracted features, as compared with the CAD system based on DCT, DST, DWT, and the hybrid combination methods of the different transform techniques. © The Author(s) 2015.

Generalizing Gillespie’s Direct Method to Enable Network-Free Simulations

DOE PAGES

Suderman, Ryan T.; Mitra, Eshan David; Lin, Yen Ting; ...

2018-03-28

Gillespie’s direct method for stochastic simulation of chemical kinetics is a staple of computational systems biology research. However, the algorithm requires explicit enumeration of all reactions and all chemical species that may arise in the system. In many cases, this is not feasible due to the combinatorial explosion of reactions and species in biological networks. Rule-based modeling frameworks provide a way to exactly represent networks containing such combinatorial complexity, and generalizations of Gillespie’s direct method have been developed as simulation engines for rule-based modeling languages. Here, we provide both a high-level description of the algorithms underlying the simulation engines, termedmore » network-free simulation algorithms, and how they have been applied in systems biology research. We also define a generic rule-based modeling framework and describe a number of technical details required for adapting Gillespie’s direct method for network-free simulation. Lastly, we briefly discuss potential avenues for advancing network-free simulation and the role they continue to play in modeling dynamical systems in biology.« less

Generalizing Gillespie’s Direct Method to Enable Network-Free Simulations

DOE Office of Scientific and Technical Information (OSTI.GOV)

Suderman, Ryan T.; Mitra, Eshan David; Lin, Yen Ting

Gillespie’s direct method for stochastic simulation of chemical kinetics is a staple of computational systems biology research. However, the algorithm requires explicit enumeration of all reactions and all chemical species that may arise in the system. In many cases, this is not feasible due to the combinatorial explosion of reactions and species in biological networks. Rule-based modeling frameworks provide a way to exactly represent networks containing such combinatorial complexity, and generalizations of Gillespie’s direct method have been developed as simulation engines for rule-based modeling languages. Here, we provide both a high-level description of the algorithms underlying the simulation engines, termedmore » network-free simulation algorithms, and how they have been applied in systems biology research. We also define a generic rule-based modeling framework and describe a number of technical details required for adapting Gillespie’s direct method for network-free simulation. Lastly, we briefly discuss potential avenues for advancing network-free simulation and the role they continue to play in modeling dynamical systems in biology.« less

Self-Organization: Complex Dynamical Systems in the Evolution of Speech

NASA Astrophysics Data System (ADS)

Oudeyer, Pierre-Yves

Human vocalization systems are characterized by complex structural properties. They are combinatorial, based on the systematic reuse of phonemes, and the set of repertoires in human languages is characterized by both strong statistical regularities—universals—and a great diversity. Besides, they are conventional codes culturally shared in each community of speakers. What are the origins of the forms of speech? What are the mechanisms that permitted their evolution in the course of phylogenesis and cultural evolution? How can a shared speech code be formed in a community of individuals? This chapter focuses on the way the concept of self-organization, and its interaction with natural selection, can throw light on these three questions. In particular, a computational model is presented which shows that a basic neural equipment for adaptive holistic vocal imitation, coupling directly motor and perceptual representations in the brain, can generate spontaneously shared combinatorial systems of vocalizations in a society of babbling individuals. Furthermore, we show how morphological and physiological innate constraints can interact with these self-organized mechanisms to account for both the formation of statistical regularities and diversity in vocalization systems.

Combinatorial chemistry has matured in the last three decades: dedicated to Professor Árpád Furka on the occasion of his 80th birthday.

PubMed

Dibó, Gábor

2012-02-01

Combinatorial chemistry was introduced in the 1980s. It provided the possibility to produce new compounds in practically unlimited number. New strategies and technologies have also been developed that made it possible to screen very large number of compounds and to identify useful components in mixtures containing millions of different substances. This dramatically changed the drug discovery process and the way of thinking of synthetic chemists. In addition, combinatorial strategies became useful in areas such as pharmaceutical research, agrochemistry, catalyst design, and materials research. Prof. Árpád Furka is one of the pioneers of combinatorial chemistry.

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

PubMed

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

2005-07-01

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

On discrete control of nonlinear systems with applications to robotics

NASA Technical Reports Server (NTRS)

Eslami, Mansour

1989-01-01

Much progress has been reported in the areas of modeling and control of nonlinear dynamic systems in a continuous-time framework. From implementation point of view, however, it is essential to study these nonlinear systems directly in a discrete setting that is amenable for interfacing with digital computers. But to develop discrete models and discrete controllers for a nonlinear system such as robot is a nontrivial task. Robot is also inherently a variable-inertia dynamic system involving additional complications. Not only the computer-oriented models of these systems must satisfy the usual requirements for such models, but these must also be compatible with the inherent capabilities of computers and must preserve the fundamental physical characteristics of continuous-time systems such as the conservation of energy and/or momentum. Preliminary issues regarding discrete systems in general and discrete models of a typical industrial robot that is developed with full consideration of the principle of conservation of energy are presented. Some research on the pertinent tactile information processing is reviewed. Finally, system control methods and how to integrate these issues in order to complete the task of discrete control of a robot manipulator are also reviewed.

Efficient search, mapping, and optimization of multi-protein genetic systems in diverse bacteria

PubMed Central

Farasat, Iman; Kushwaha, Manish; Collens, Jason; Easterbrook, Michael; Guido, Matthew; Salis, Howard M

2014-01-01

Developing predictive models of multi-protein genetic systems to understand and optimize their behavior remains a combinatorial challenge, particularly when measurement throughput is limited. We developed a computational approach to build predictive models and identify optimal sequences and expression levels, while circumventing combinatorial explosion. Maximally informative genetic system variants were first designed by the RBS Library Calculator, an algorithm to design sequences for efficiently searching a multi-protein expression space across a > 10,000-fold range with tailored search parameters and well-predicted translation rates. We validated the algorithm's predictions by characterizing 646 genetic system variants, encoded in plasmids and genomes, expressed in six gram-positive and gram-negative bacterial hosts. We then combined the search algorithm with system-level kinetic modeling, requiring the construction and characterization of 73 variants to build a sequence-expression-activity map (SEAMAP) for a biosynthesis pathway. Using model predictions, we designed and characterized 47 additional pathway variants to navigate its activity space, find optimal expression regions with desired activity response curves, and relieve rate-limiting steps in metabolism. Creating sequence-expression-activity maps accelerates the optimization of many protein systems and allows previous measurements to quantitatively inform future designs. PMID:24952589

Systematic Identification of Combinatorial Drivers and Targets in Cancer Cell Lines

PubMed Central

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

2013-01-01

There is an urgent need to elicit and validate highly efficacious targets for combinatorial intervention from large scale ongoing molecular characterization efforts of tumors. We established an in silico bioinformatic platform in concert with a high throughput screening platform evaluating 37 novel targeted agents in 669 extensively characterized cancer cell lines reflecting the genomic and tissue-type diversity of human cancers, to systematically identify combinatorial biomarkers of response and co-actionable targets in cancer. Genomic biomarkers discovered in a 141 cell line training set were validated in an independent 359 cell line test set. We identified co-occurring and mutually exclusive genomic events that represent potential drivers and combinatorial targets in cancer. We demonstrate multiple cooperating genomic events that predict sensitivity to drug intervention independent of tumor lineage. The coupling of scalable in silico and biologic high throughput cancer cell line platforms for the identification of co-events in cancer delivers rational combinatorial targets for synthetic lethal approaches with a high potential to pre-empt the emergence of resistance. PMID:23577104

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

PubMed

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

2013-01-01

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

An evaluation of methods for estimating the number of local optima in combinatorial optimization problems.

PubMed

Hernando, Leticia; Mendiburu, Alexander; Lozano, Jose A

2013-01-01

The solution of many combinatorial optimization problems is carried out by metaheuristics, which generally make use of local search algorithms. These algorithms use some kind of neighborhood structure over the search space. The performance of the algorithms strongly depends on the properties that the neighborhood imposes on the search space. One of these properties is the number of local optima. Given an instance of a combinatorial optimization problem and a neighborhood, the estimation of the number of local optima can help not only to measure the complexity of the instance, but also to choose the most convenient neighborhood to solve it. In this paper we review and evaluate several methods to estimate the number of local optima in combinatorial optimization problems. The methods reviewed not only come from the combinatorial optimization literature, but also from the statistical literature. A thorough evaluation in synthetic as well as real problems is given. We conclude by providing recommendations of methods for several scenarios.

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

NASA Astrophysics Data System (ADS)

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.

Controllability of discrete bilinear systems with bounded control.

NASA Technical Reports Server (NTRS)

Tarn, T. J.; Elliott, D. L.; Goka, T.

1973-01-01

The subject of this paper is the controllability of time-invariant discrete-time bilinear systems. Bilinear systems are classified into two categories; homogeneous and inhomogeneous. Sufficient conditions which ensure the global controllability of discrete-time bilinear systems are obtained by localized analysis in control variables.

SMITHERS: An object-oriented modular mapping methodology for MCNP-based neutronic–thermal hydraulic multiphysics

DOE PAGES

Richard, Joshua; Galloway, Jack; Fensin, Michael; ...

2015-04-04

A novel object-oriented modular mapping methodology for externally coupled neutronics–thermal hydraulics multiphysics simulations was developed. The Simulator using MCNP with Integrated Thermal-Hydraulics for Exploratory Reactor Studies (SMITHERS) code performs on-the-fly mapping of material-wise power distribution tallies implemented by MCNP-based neutron transport/depletion solvers for use in estimating coolant temperature and density distributions with a separate thermal-hydraulic solver. The key development of SMITHERS is that it reconstructs the hierarchical geometry structure of the material-wise power generation tallies from the depletion solver automatically, with only a modicum of additional information required from the user. In addition, it performs the basis mapping from themore » combinatorial geometry of the depletion solver to the required geometry of the thermal-hydraulic solver in a generalizable manner, such that it can transparently accommodate varying levels of thermal-hydraulic solver geometric fidelity, from the nodal geometry of multi-channel analysis solvers to the pin-cell level of discretization for sub-channel analysis solvers.« less

Molecular dynamics simulation on HP1 protein binding by histone H3 tail methylation and phosphorylation

NASA Astrophysics Data System (ADS)

Jiang, Yan-Ke; Zou, Jian-Wei; Wu, Yu-Qian; Zhang, Na; Yu, Qing-Sen; Jiang, Yong-Jun

Trimethylation of histone H3 lysine 9 is important for recruiting heterochromatin protein 1 (HP1) to discrete regions of the genome, thereby regulating gene expression, chromatin packaging, and heterochromatin formation. Phosphorylation of histone H3 has been linked with mitotic chromatin condensation. During mitosis in vivo, H3 lysine 9 methylation and serine 10 phosphorylation can occur concomitantly on the same histone tail, whereas the influence of phosphorylation to trimethylation H3 tail recruiting HP1 remains controversial. In this work, molecular dynamics simulation of HP1 complexed with both trimethylated and phosphorylated H3 tail were performed and compared with the results from the previous methylated H3-HP1 trajectory. It is clear from the 10-ns dynamics simulation that two adjacent posttranslational modifications directly increase the flexibility of the H3 tail and weaken HP1 binding to chromatin. A combinatorial readout of two adjacent posttranslational modifications-a stable methylation and a dynamic phosphorylation mark-establish a regulatory mechanism of protein-protein interactions.

Broad Integration of Expression Maps and Co-Expression Networks Compassing Novel Gene Functions in the Brain

PubMed Central

Okamura-Oho, Yuko; Shimokawa, Kazuro; Nishimura, Masaomi; Takemoto, Satoko; Sato, Akira; Furuichi, Teiichi; Yokota, Hideo

2014-01-01

Using a recently invented technique for gene expression mapping in the whole-anatomy context, termed transcriptome tomography, we have generated a dataset of 36,000 maps of overall gene expression in the adult-mouse brain. Here, using an informatics approach, we identified a broad co-expression network that follows an inverse power law and is rich in functional interaction and gene-ontology terms. Our framework for the integrated analysis of expression maps and graphs of co-expression networks revealed that groups of combinatorially expressed genes, which regulate cell differentiation during development, were present in the adult brain and each of these groups was associated with a discrete cell types. These groups included non-coding genes of unknown function. We found that these genes specifically linked developmentally conserved groups in the network. A previously unrecognized robust expression pattern covering the whole brain was related to the molecular anatomy of key biological processes occurring in particular areas. PMID:25382412

State-Transition Structures in Physics and in Computation

NASA Astrophysics Data System (ADS)

Petri, C. A.

1982-12-01

In order to establish close connections between physical and computational processes, it is assumed that the concepts of “state” and of “transition” are acceptable both to physicists and to computer scientists, at least in an informal way. The aim of this paper is to propose formal definitions of state and transition elements on the basis of very low level physical concepts in such a way that (1) all physically possible computations can be described as embedded in physical processes; (2) the computational aspects of physical processes can be described on a well-defined level of abstraction; (3) the gulf between the continuous models of physics and the discrete models of computer science can be bridged by simple mathematical constructs which may be given a physical interpretation; (4) a combinatorial, nonstatistical definition of “information” can be given on low levels of abstraction which may serve as a basis to derive higher-level concepts of information, e.g., by a statistical or probabilistic approach. Conceivable practical consequences are discussed.

A characterization of horizontal visibility graphs and combinatorics on words

NASA Astrophysics Data System (ADS)

Gutin, Gregory; Mansour, Toufik; Severini, Simone

2011-06-01

A Horizontal Visibility Graph (HVG) is defined in association with an ordered set of non-negative reals. HVGs realize a methodology in the analysis of time series, their degree distribution being a good discriminator between randomness and chaos Luque et al. [B. Luque, L. Lacasa, F. Ballesteros, J. Luque, Horizontal visibility graphs: exact results for random time series, Phys. Rev. E 80 (2009), 046103]. We prove that a graph is an HVG if and only if it is outerplanar and has a Hamilton path. Therefore, an HVG is a noncrossing graph, as defined in algebraic combinatorics Flajolet and Noy [P. Flajolet, M. Noy, Analytic combinatorics of noncrossing configurations, Discrete Math., 204 (1999) 203-229]. Our characterization of HVGs implies a linear time recognition algorithm. Treating ordered sets as words, we characterize subfamilies of HVGs highlighting various connections with combinatorial statistics and introducing the notion of a visible pair. With this technique, we determine asymptotically the average number of edges of HVGs.

A phase transition in energy-filtered RNA secondary structures.

PubMed

Han, Hillary S W; Reidys, Christian M

2012-10-01

In this article we study the effect of energy parameters on minimum free energy (mfe) RNA secondary structures. Employing a simplified combinatorial energy model that is only dependent on the diagram representation and is not sequence-specific, we prove the following dichotomy result. Mfe structures derived via the Turner energy parameters contain only finitely many complex irreducible substructures, and just minor parameter changes produce a class of mfe structures that contain a large number of small irreducibles. We localize the exact point at which the distribution of irreducibles experiences this phase transition from a discrete limit to a central limit distribution and, subsequently, put our result into the context of quantifying the effect of sparsification of the folding of these respective mfe structures. We show that the sparsification of realistic mfe structures leads to a constant time and space reduction, and that the sparsification of the folding of structures with modified parameters leads to a linear time and space reduction. We, furthermore, identify the limit distribution at the phase transition as a Rayleigh distribution.

Automated Classification and Removal of EEG Artifacts With SVM and Wavelet-ICA.

PubMed

Sai, Chong Yeh; Mokhtar, Norrima; Arof, Hamzah; Cumming, Paul; Iwahashi, Masahiro

2018-05-01

Brain electrical activity recordings by electroencephalography (EEG) are often contaminated with signal artifacts. Procedures for automated removal of EEG artifacts are frequently sought for clinical diagnostics and brain-computer interface applications. In recent years, a combination of independent component analysis (ICA) and discrete wavelet transform has been introduced as standard technique for EEG artifact removal. However, in performing the wavelet-ICA procedure, visual inspection or arbitrary thresholding may be required for identifying artifactual components in the EEG signal. We now propose a novel approach for identifying artifactual components separated by wavelet-ICA using a pretrained support vector machine (SVM). Our method presents a robust and extendable system that enables fully automated identification and removal of artifacts from EEG signals, without applying any arbitrary thresholding. Using test data contaminated by eye blink artifacts, we show that our method performed better in identifying artifactual components than did existing thresholding methods. Furthermore, wavelet-ICA in conjunction with SVM successfully removed target artifacts, while largely retaining the EEG source signals of interest. We propose a set of features including kurtosis, variance, Shannon's entropy, and range of amplitude as training and test data of SVM to identify eye blink artifacts in EEG signals. This combinatorial method is also extendable to accommodate multiple types of artifacts present in multichannel EEG. We envision future research to explore other descriptive features corresponding to other types of artifactual components.

An evolutionary strategy based on partial imitation for solving optimization problems

NASA Astrophysics Data System (ADS)

Javarone, Marco Alberto

2016-12-01

In this work we introduce an evolutionary strategy to solve combinatorial optimization tasks, i.e. problems characterized by a discrete search space. In particular, we focus on the Traveling Salesman Problem (TSP), i.e. a famous problem whose search space grows exponentially, increasing the number of cities, up to becoming NP-hard. The solutions of the TSP can be codified by arrays of cities, and can be evaluated by fitness, computed according to a cost function (e.g. the length of a path). Our method is based on the evolution of an agent population by means of an imitative mechanism, we define 'partial imitation'. In particular, agents receive a random solution and then, interacting among themselves, may imitate the solutions of agents with a higher fitness. Since the imitation mechanism is only partial, agents copy only one entry (randomly chosen) of another array (i.e. solution). In doing so, the population converges towards a shared solution, behaving like a spin system undergoing a cooling process, i.e. driven towards an ordered phase. We highlight that the adopted 'partial imitation' mechanism allows the population to generate solutions over time, before reaching the final equilibrium. Results of numerical simulations show that our method is able to find, in a finite time, both optimal and suboptimal solutions, depending on the size of the considered search space.

Discovery of the leinamycin family of natural products by mining actinobacterial genomes

PubMed Central

Xu, Zhengren; Guo, Zhikai; Hindra; Ma, Ming; Zhou, Hao; Gansemans, Yannick; Zhu, Xiangcheng; Huang, Yong; Zhao, Li-Xing; Jiang, Yi; Cheng, Jinhua; Van Nieuwerburgh, Filip; Suh, Joo-Won; Duan, Yanwen

2017-01-01

Nature’s ability to generate diverse natural products from simple building blocks has inspired combinatorial biosynthesis. The knowledge-based approach to combinatorial biosynthesis has allowed the production of designer analogs by rational metabolic pathway engineering. While successful, structural alterations are limited, with designer analogs often produced in compromised titers. The discovery-based approach to combinatorial biosynthesis complements the knowledge-based approach by exploring the vast combinatorial biosynthesis repertoire found in Nature. Here we showcase the discovery-based approach to combinatorial biosynthesis by targeting the domain of unknown function and cysteine lyase domain (DUF–SH) didomain, specific for sulfur incorporation from the leinamycin (LNM) biosynthetic machinery, to discover the LNM family of natural products. By mining bacterial genomes from public databases and the actinomycetes strain collection at The Scripps Research Institute, we discovered 49 potential producers that could be grouped into 18 distinct clades based on phylogenetic analysis of the DUF–SH didomains. Further analysis of the representative genomes from each of the clades identified 28 lnm-type gene clusters. Structural diversities encoded by the LNM-type biosynthetic machineries were predicted based on bioinformatics and confirmed by in vitro characterization of selected adenylation proteins and isolation and structural elucidation of the guangnanmycins and weishanmycins. These findings demonstrate the power of the discovery-based approach to combinatorial biosynthesis for natural product discovery and structural diversity and highlight Nature’s rich biosynthetic repertoire. Comparative analysis of the LNM-type biosynthetic machineries provides outstanding opportunities to dissect Nature’s biosynthetic strategies and apply these findings to combinatorial biosynthesis for natural product discovery and structural diversity. PMID:29229819

Discovery of the leinamycin family of natural products by mining actinobacterial genomes.

PubMed

Pan, Guohui; Xu, Zhengren; Guo, Zhikai; Hindra; Ma, Ming; Yang, Dong; Zhou, Hao; Gansemans, Yannick; Zhu, Xiangcheng; Huang, Yong; Zhao, Li-Xing; Jiang, Yi; Cheng, Jinhua; Van Nieuwerburgh, Filip; Suh, Joo-Won; Duan, Yanwen; Shen, Ben

2017-12-26

Nature's ability to generate diverse natural products from simple building blocks has inspired combinatorial biosynthesis. The knowledge-based approach to combinatorial biosynthesis has allowed the production of designer analogs by rational metabolic pathway engineering. While successful, structural alterations are limited, with designer analogs often produced in compromised titers. The discovery-based approach to combinatorial biosynthesis complements the knowledge-based approach by exploring the vast combinatorial biosynthesis repertoire found in Nature. Here we showcase the discovery-based approach to combinatorial biosynthesis by targeting the domain of unknown function and cysteine lyase domain (DUF-SH) didomain, specific for sulfur incorporation from the leinamycin (LNM) biosynthetic machinery, to discover the LNM family of natural products. By mining bacterial genomes from public databases and the actinomycetes strain collection at The Scripps Research Institute, we discovered 49 potential producers that could be grouped into 18 distinct clades based on phylogenetic analysis of the DUF-SH didomains. Further analysis of the representative genomes from each of the clades identified 28 lnm -type gene clusters. Structural diversities encoded by the LNM-type biosynthetic machineries were predicted based on bioinformatics and confirmed by in vitro characterization of selected adenylation proteins and isolation and structural elucidation of the guangnanmycins and weishanmycins. These findings demonstrate the power of the discovery-based approach to combinatorial biosynthesis for natural product discovery and structural diversity and highlight Nature's rich biosynthetic repertoire. Comparative analysis of the LNM-type biosynthetic machineries provides outstanding opportunities to dissect Nature's biosynthetic strategies and apply these findings to combinatorial biosynthesis for natural product discovery and structural diversity.

Combinatorial pretreatment and fermentation optimization enabled a record yield on lignin bioconversion.

PubMed

Liu, Zhi-Hua; Xie, Shangxian; Lin, Furong; Jin, Mingjie; Yuan, Joshua S

2018-01-01

Lignin valorization has recently been considered to be an essential process for sustainable and cost-effective biorefineries. Lignin represents a potential new feedstock for value-added products. Oleaginous bacteria such as Rhodococcus opacus can produce intracellular lipids from biodegradation of aromatic substrates. These lipids can be used for biofuel production, which can potentially replace petroleum-derived chemicals. However, the low reactivity of lignin produced from pretreatment and the underdeveloped fermentation technology hindered lignin bioconversion to lipids. In this study, combinatorial pretreatment with an optimized fermentation strategy was evaluated to improve lignin valorization into lipids using R. opacus PD630. As opposed to single pretreatment, combinatorial pretreatment produced a 12.8-75.6% higher lipid concentration in fermentation using lignin as the carbon source. Gas chromatography-mass spectrometry analysis showed that combinatorial pretreatment released more aromatic monomers, which could be more readily utilized by lignin-degrading strains. Three detoxification strategies were used to remove potential inhibitors produced from pretreatment. After heating detoxification of the lignin stream, the lipid concentration further increased by 2.9-9.7%. Different fermentation strategies were evaluated in scale-up lipid fermentation using a 2.0-l fermenter. With laccase treatment of the lignin stream produced from combinatorial pretreatment, the highest cell dry weight and lipid concentration were 10.1 and 1.83 g/l, respectively, in fed-batch fermentation, with a total soluble substrate concentration of 40 g/l. The improvement of the lipid fermentation performance may have resulted from lignin depolymerization by the combinatorial pretreatment and laccase treatment, reduced inhibition effects by fed-batch fermentation, adequate oxygen supply, and an accurate pH control in the fermenter. Overall, these results demonstrate that combinatorial pretreatment, together with fermentation optimization, favorably improves lipid production using lignin as the carbon source. Combinatorial pretreatment integrated with fed-batch fermentation was an effective strategy to improve the bioconversion of lignin into lipids, thus facilitating lignin valorization in biorefineries.

The discrete hungry Lotka Volterra system and a new algorithm for computing matrix eigenvalues

NASA Astrophysics Data System (ADS)

Fukuda, Akiko; Ishiwata, Emiko; Iwasaki, Masashi; Nakamura, Yoshimasa

2009-01-01

The discrete hungry Lotka-Volterra (dhLV) system is a generalization of the discrete Lotka-Volterra (dLV) system which stands for a prey-predator model in mathematical biology. In this paper, we show that (1) some invariants exist which are expressed by dhLV variables and are independent from the discrete time and (2) a dhLV variable converges to some positive constant or zero as the discrete time becomes sufficiently large. Some characteristic polynomial is then factorized with the help of the dhLV system. The asymptotic behaviour of the dhLV system enables us to design an algorithm for computing complex eigenvalues of a certain band matrix.

A solid-phase combinatorial approach for indoloquinolizidine-peptides with high affinity at D(1) and D(2) dopamine receptors.

PubMed

Molero, Anabel; Vendrell, Marc; Bonaventura, Jordi; Zachmann, Julian; López, Laura; Pardo, Leonardo; Lluis, Carme; Cortés, Antoni; Albericio, Fernando; Casadó, Vicent; Royo, Miriam

2015-06-05

Ligands acting at multiple dopamine receptors hold potential as therapeutic agents for a number of neurodegenerative disorders. Specifically, compounds able to bind at D1R and D2R with high affinity could restore the effects of dopamine depletion and enhance motor activation on degenerated nigrostriatal dopaminergic systems. We have directed our research towards the synthesis and characterisation of heterocycle-peptide hybrids based on the indolo[2,3-a]quinolizidine core. This privileged structure is a water-soluble and synthetically accessible scaffold with affinity for diverse GPCRs. Herein we have prepared a solid-phase combinatorial library of 80 indoloquinolizidine-peptides to identify compounds with enhanced binding affinity at D2R, a receptor that is crucial to re-establish activity on dopamine-depleted degenerated GABAergic neurons. We applied computational tools and high-throughput screening assays to identify 9a{1,3,3} as a ligand for dopamine receptors with nanomolar affinity and agonist activity at D2R. Our results validate the application of indoloquinolizidine-peptide combinatorial libraries to fine-tune the pharmacological profiles of multiple ligands at D1 and D2 dopamine receptors. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

A theoretical introduction to "combinatory SYBRGreen qPCR screening", a matrix-based approach for the detection of materials derived from genetically modified plants.

PubMed

Van den Bulcke, Marc; Lievens, Antoon; Barbau-Piednoir, Elodie; MbongoloMbella, Guillaume; Roosens, Nancy; Sneyers, Myriam; Casi, Amaya Leunda

2010-03-01

The detection of genetically modified (GM) materials in food and feed products is a complex multi-step analytical process invoking screening, identification, and often quantification of the genetically modified organisms (GMO) present in a sample. "Combinatory qPCR SYBRGreen screening" (CoSYPS) is a matrix-based approach for determining the presence of GM plant materials in products. The CoSYPS decision-support system (DSS) interprets the analytical results of SYBRGREEN qPCR analysis based on four values: the C(t)- and T(m) values and the LOD and LOQ for each method. A theoretical explanation of the different concepts applied in CoSYPS analysis is given (GMO Universe, "Prime number tracing", matrix/combinatory approach) and documented using the RoundUp Ready soy GTS40-3-2 as an example. By applying a limited set of SYBRGREEN qPCR methods and through application of a newly developed "prime number"-based algorithm, the nature of subsets of corresponding GMO in a sample can be determined. Together, these analyses provide guidance for semi-quantitative estimation of GMO presence in a food and feed product.

Oscillatory Critical Amplitudes in Hierarchical Models and the Harris Function of Branching Processes

NASA Astrophysics Data System (ADS)

Costin, Ovidiu; Giacomin, Giambattista

2013-02-01

Oscillatory critical amplitudes have been repeatedly observed in hierarchical models and, in the cases that have been taken into consideration, these oscillations are so small to be hardly detectable. Hierarchical models are tightly related to iteration of maps and, in fact, very similar phenomena have been repeatedly reported in many fields of mathematics, like combinatorial evaluations and discrete branching processes. It is precisely in the context of branching processes with bounded off-spring that T. Harris, in 1948, first set forth the possibility that the logarithm of the moment generating function of the rescaled population size, in the super-critical regime, does not grow near infinity as a power, but it has an oscillatory prefactor (the Harris function). These oscillations have been observed numerically only much later and, while the origin is clearly tied to the discrete character of the iteration, the amplitude size is not so well understood. The purpose of this note is to reconsider the issue for hierarchical models and in what is arguably the most elementary setting—the pinning model—that actually just boils down to iteration of polynomial maps (and, notably, quadratic maps). In this note we show that the oscillatory critical amplitude for pinning models and the Harris function coincide. Moreover we make explicit the link between these oscillatory functions and the geometry of the Julia set of the map, making thus rigorous and quantitative some ideas set forth in Derrida et al. (Commun. Math. Phys. 94:115-132, 1984).

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

NASA Astrophysics Data System (ADS)

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.

Comparing performance in discrete and continuous comparison tasks.

PubMed

Leibovich, Tali; Henik, Avishai

2014-05-01

The approximate number system (ANS) theory suggests that all magnitudes, discrete (i.e., number of items) or continuous (i.e., size, density, etc.), are processed by a shared system and comply with Weber's law. The current study reexamined this notion by comparing performance in discrete (comparing numerosities of dot arrays) and continuous (comparisons of area of squares) tasks. We found that: (a) threshold of discrimination was higher for continuous than for discrete comparisons; (b) while performance in the discrete task complied with Weber's law, performance in the continuous task violated it; and (c) performance in the discrete task was influenced by continuous properties (e.g., dot density, dot cumulative area) of the dot array that were not predictive of numerosities or task relevant. Therefore, we propose that the magnitude processing system (MPS) is actually divided into separate (yet interactive) systems for discrete and continuous magnitude processing. Further subdivisions are discussed. We argue that cooperation between these systems results in a holistic comparison of magnitudes, one that takes into account continuous properties in addition to numerosities. Considering the MPS as two systems opens the door to new and important questions that shed light on both normal and impaired development of the numerical system.

Systems-level analysis of microbial community organization through combinatorial labeling and spectral imaging.

PubMed

Valm, Alex M; Mark Welch, Jessica L; Rieken, Christopher W; Hasegawa, Yuko; Sogin, Mitchell L; Oldenbourg, Rudolf; Dewhirst, Floyd E; Borisy, Gary G

2011-03-08

Microbes in nature frequently function as members of complex multitaxon communities, but the structural organization of these communities at the micrometer level is poorly understood because of limitations in labeling and imaging technology. We report here a combinatorial labeling strategy coupled with spectral image acquisition and analysis that greatly expands the number of fluorescent signatures distinguishable in a single image. As an imaging proof of principle, we first demonstrated visualization of Escherichia coli labeled by fluorescence in situ hybridization (FISH) with 28 different binary combinations of eight fluorophores. As a biological proof of principle, we then applied this Combinatorial Labeling and Spectral Imaging FISH (CLASI-FISH) strategy using genus- and family-specific probes to visualize simultaneously and differentiate 15 different phylotypes in an artificial mixture of laboratory-grown microbes. We then illustrated the utility of our method for the structural analysis of a natural microbial community, namely, human dental plaque, a microbial biofilm. We demonstrate that 15 taxa in the plaque community can be imaged simultaneously and analyzed and that this community was dominated by early colonizers, including species of Streptococcus, Prevotella, Actinomyces, and Veillonella. Proximity analysis was used to determine the frequency of inter- and intrataxon cell-to-cell associations which revealed statistically significant intertaxon pairings. Cells of the genera Prevotella and Actinomyces showed the most interspecies associations, suggesting a central role for these genera in establishing and maintaining biofilm complexity. The results provide an initial systems-level structural analysis of biofilm organization.

Systemic combinatorial peptide selection yields a non-canonical iron-mimicry mechanism for targeting tumors in a mouse model of human glioblastoma

PubMed Central

Staquicini, Fernanda I.; Ozawa, Michael G.; Moya, Catherine A.; Driessen, Wouter H.P.; Barbu, E. Magda; Nishimori, Hiroyuki; Soghomonyan, Suren; Flores, Leo G.; Liang, Xiaowen; Paolillo, Vincenzo; Alauddin, Mian M.; Basilion, James P.; Furnari, Frank B.; Bogler, Oliver; Lang, Frederick F.; Aldape, Kenneth D.; Fuller, Gregory N.; Höök, Magnus; Gelovani, Juri G.; Sidman, Richard L.; Cavenee, Webster K.; Pasqualini, Renata; Arap, Wadih

2010-01-01

The management of CNS tumors is limited by the blood-brain barrier (BBB), a vascular interface that restricts the passage of most molecules from the blood into the brain. Here we show that phage particles targeted with certain ligand motifs selected in vivo from a combinatorial peptide library can cross the BBB under normal and pathological conditions. Specifically, we demonstrated that phage clones displaying an iron-mimic peptide were able to target a protein complex of transferrin and transferrin receptor (TfR) through a non-canonical allosteric binding mechanism and that this functional protein complex mediated transport of the corresponding viral particles into the normal mouse brain. We also showed that, in an orthotopic mouse model of human glioblastoma, a combination of TfR overexpression plus extended vascular permeability and ligand retention resulted in remarkable brain tumor targeting of chimeric adeno-associated virus/phage particles displaying the iron-mimic peptide and carrying a gene of interest. As a proof of concept, we delivered the HSV thymidine kinase gene for molecular-genetic imaging and targeted therapy of intracranial xenografted tumors. Finally, we established that these experimental findings might be clinically relevant by determining through human tissue microarrays that many primary astrocytic tumors strongly express TfR. Together, our combinatorial selection system and results may provide a translational avenue for the targeted detection and treatment of brain tumors. PMID:21183793

A binary plasmid system for shuffling combinatorial antibody libraries.

PubMed

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

1992-11-01

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

A binary plasmid system for shuffling combinatorial antibody libraries.

PubMed Central

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

1992-01-01

We have used a binary system of replicon-compatible plasmids to test the potential for promiscuous recombination of heavy and light chains within sets of human Fab fragments isolated from combinatorial antibody libraries. Antibody molecules showed a surprising amount of promiscuity in that a particular heavy chain could recombine with multiple light chains with retention of binding to a protein antigen. The degree to which a given heavy chain productively paired with any light chain to bind antigen varied from 43% to 100% and depended strongly on the heavy-chain sequence. Such productive crosses resulted in a set of Fab fragments of similar apparent binding constants, which seemed to differ mainly in the amount of active Fab fragment produced in the bacterial cell. The dominance of the heavy chain in the antibody-antigen interaction was further explored in a set of directed crosses, in which heavy and light chains derived from antigen-specific clones were crossed with nonrelated heavy and light chains. In these crosses, an Fab fragment retained antigen binding only if it contained a heavy chain from an antigen-specific clone. In no case did the light chain confer detectable affinity when paired with indifferent heavy chains. The surprising promiscuity of heavy chains has ramifications for the evaluation of the diversity of combinatorial libraries made against protein antigens and should allow the combination of one such promiscuous heavy chain with an engineered light chain to form an Fab fragment carrying synthetic cofactors to assist in antibody catalysis. Images PMID:1438192

Achieving Remission in Gulf War Illness: A Simulation-Based Approach to Treatment Design.

PubMed

Craddock, Travis J A; Del Rosario, Ryan R; Rice, Mark; Zysman, Joel P; Fletcher, Mary Ann; Klimas, Nancy G; Broderick, Gordon

2015-01-01

Gulf War Illness (GWI) is a chronic multi-symptom disorder affecting up to one-third of the 700,000 returning veterans of the 1991 Persian Gulf War and for which there is no known cure. GWI symptoms span several of the body's principal regulatory systems and include debilitating fatigue, severe musculoskeletal pain, cognitive and neurological problems. Using computational models, our group reported previously that GWI might be perpetuated at least in part by natural homeostatic regulation of the neuroendocrine-immune network. In this work, we attempt to harness these regulatory dynamics to identify treatment courses that might produce lasting remission. Towards this we apply a combinatorial optimization scheme to the Monte Carlo simulation of a discrete ternary logic model that represents combined hypothalamic-pituitary-adrenal (HPA), gonadal (HPG), and immune system regulation in males. In this work we found that no single intervention target allowed a robust return to normal homeostatic control. All combined interventions leading to a predicted remission involved an initial inhibition of Th1 inflammatory cytokines (Th1Cyt) followed by a subsequent inhibition of glucocorticoid receptor function (GR). These first two intervention events alone ended in stable and lasting return to the normal regulatory control in 40% of the simulated cases. Applying a second cycle of this combined treatment improved this predicted remission rate to 2 out of 3 simulated subjects (63%). These results suggest that in a complex illness such as GWI, a multi-tiered intervention strategy that formally accounts for regulatory dynamics may be required to reset neuroendocrine-immune homeostasis and support extended remission.

Reinforcement-learning-based dual-control methodology for complex nonlinear discrete-time systems with application to spark engine EGR operation.

PubMed

Shih, Peter; Kaul, Brian C; Jagannathan, S; Drallmeier, James A

2008-08-01

A novel reinforcement-learning-based dual-control methodology adaptive neural network (NN) controller is developed to deliver a desired tracking performance for a class of complex feedback nonlinear discrete-time systems, which consists of a second-order nonlinear discrete-time system in nonstrict feedback form and an affine nonlinear discrete-time system, in the presence of bounded and unknown disturbances. For example, the exhaust gas recirculation (EGR) operation of a spark ignition (SI) engine is modeled by using such a complex nonlinear discrete-time system. A dual-controller approach is undertaken where primary adaptive critic NN controller is designed for the nonstrict feedback nonlinear discrete-time system whereas the secondary one for the affine nonlinear discrete-time system but the controllers together offer the desired performance. The primary adaptive critic NN controller includes an NN observer for estimating the states and output, an NN critic, and two action NNs for generating virtual control and actual control inputs for the nonstrict feedback nonlinear discrete-time system, whereas an additional critic NN and an action NN are included for the affine nonlinear discrete-time system by assuming the state availability. All NN weights adapt online towards minimization of a certain performance index, utilizing gradient-descent-based rule. Using Lyapunov theory, the uniformly ultimate boundedness (UUB) of the closed-loop tracking error, weight estimates, and observer estimates are shown. The adaptive critic NN controller performance is evaluated on an SI engine operating with high EGR levels where the controller objective is to reduce cyclic dispersion in heat release while minimizing fuel intake. Simulation and experimental results indicate that engine out emissions drop significantly at 20% EGR due to reduction in dispersion in heat release thus verifying the dual-control approach.

Observability of discretized partial differential equations

NASA Technical Reports Server (NTRS)

Cohn, Stephen E.; Dee, Dick P.

1988-01-01

It is shown that complete observability of the discrete model used to assimilate data from a linear partial differential equation (PDE) system is necessary and sufficient for asymptotic stability of the data assimilation process. The observability theory for discrete systems is reviewed and applied to obtain simple observability tests for discretized constant-coefficient PDEs. Examples are used to show how numerical dispersion can result in discrete dynamics with multiple eigenvalues, thereby detracting from observability.

Combinatorial fabrication and screening of organic light-emitting device arrays

NASA Astrophysics Data System (ADS)

Shinar, Joseph; Shinar, Ruth; Zhou, Zhaoqun

2007-11-01

The combinatorial fabrication and screening of 2-dimensional (2-d) small molecular UV-violet organic light-emitting device (OLED) arrays, 1-d blue-to-red arrays, 1-d intense white OLED libraries, 1-d arrays to study Förster energy transfer in guest-host OLEDs, and 2-d arrays to study exciplex emission from OLEDs is described. The results demonstrate the power of combinatorial approaches for screening OLED materials and configurations, and for studying their basic properties.

Combinatorial Dyson-Schwinger equations and inductive data types

NASA Astrophysics Data System (ADS)

Kock, Joachim

2016-06-01

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

Combinatorial stresses kill pathogenic Candida species

PubMed Central

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

2012-01-01

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

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

PubMed

Chen, Hong-Zhang; Liu, Zhi-Hua

2015-06-01

Pretreatment is a key unit operation affecting the refinery efficiency of plant biomass. However, the poor efficiency of pretreatment and the lack of basic theory are the main challenges to the industrial implementation of the plant biomass refinery. The purpose of this work is to review steam explosion and its combinatorial pretreatment as a means of overcoming the intrinsic characteristics of plant biomass, including recalcitrance, heterogeneity, multi-composition, and diversity. The main advantages of the selective use of steam explosion and other combinatorial pretreatments across the diversity of raw materials are introduced. Combinatorial pretreatment integrated with other unit operations is proposed as a means to exploit the high-efficiency production of bio-based products from plant biomass. Finally, several pilot- and demonstration-scale operations of the plant biomass refinery are described. Based on the principle of selective function and structure fractionation, and multi-level and directional composition conversion, an integrated process with the combinatorial pretreatments of steam explosion and other pretreatments as the core should be feasible and conform to the plant biomass refinery concept. Combinatorial pretreatments of steam explosion and other pretreatments should be further exploited based on the type and intrinsic characteristics of the plant biomass used, the bio-based products to be made, and the complementarity of the processes. Copyright © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Economy of Command

ERIC Educational Resources Information Center

Medeiros, David Peter

2012-01-01

This dissertation proposes a principle of "economy of command", arguing that it provides a simple and natural explanation for some well-known properties of human language syntax. The focus is on the abstract combinatorial system that constructs the hierarchical structure of linguistic expressions, with long-distance dependencies…

Variational discretization of the nonequilibrium thermodynamics of simple systems

NASA Astrophysics Data System (ADS)

Gay-Balmaz, François; Yoshimura, Hiroaki

2018-04-01

In this paper, we develop variational integrators for the nonequilibrium thermodynamics of simple closed systems. These integrators are obtained by a discretization of the Lagrangian variational formulation of nonequilibrium thermodynamics developed in (Gay-Balmaz and Yoshimura 2017a J. Geom. Phys. part I 111 169–93 Gay-Balmaz and Yoshimura 2017b J. Geom. Phys. part II 111 194–212) and thus extend the variational integrators of Lagrangian mechanics, to include irreversible processes. In the continuous setting, we derive the structure preserving property of the flow of such systems. This property is an extension of the symplectic property of the flow of the Euler–Lagrange equations. In the discrete setting, we show that the discrete flow solution of our numerical scheme verifies a discrete version of this property. We also present the regularity conditions which ensure the existence of the discrete flow. We finally illustrate our discrete variational schemes with the implementation of an example of a simple and closed system.

Systems and methods for the combinatorial synthesis of novel materials

DOEpatents

Wu, Xin Di; Wang, Youqi; Goldwasser, Isy

2000-01-01

Methods and apparatus for the preparation of a substrate having an array of diverse materials in predefined regions thereon. A substrate having an array of diverse materials thereon is generally prepared by depositing components of target materials to predefined regions on the substrate, and, in some embodiments, simultaneously reacting the components to form at least two resulting materials. In particular, the present invention provides novel masking systems and methods for applying components of target materials onto a substrate in a combinatorial fashion, thus creating arrays of resulting materials that differ slightly in composition, stoichiometry, and/or thickness. Using the novel masking systems of the present invention, components can be delivered to each site in a uniform distribution, or in a gradient of stoichiometries, thicknesses, compositions, etc. Resulting materials which can be prepared using the methods and apparatus of the present invention include, for example, covalent network solids, ionic solids and molecular solids. Once prepared, these resulting materials can be screened sequentially, or in parallel, for useful properties including, for example, electrical, thermal, mechanical, morphological, optical, magnetic, chemical and other properties.

Combinatorial Approaches for the Identification of Brain Drug Delivery Targets

PubMed Central

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

2018-01-01

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

Energy thresholds of discrete breathers in thermal equilibrium and relaxation processes.

PubMed

Ming, Yi; Ling, Dong-Bo; Li, Hui-Min; Ding, Ze-Jun

2017-06-01

So far, only the energy thresholds of single discrete breathers in nonlinear Hamiltonian systems have been analytically obtained. In this work, the energy thresholds of discrete breathers in thermal equilibrium and the energy thresholds of long-lived discrete breathers which can remain after a long time relaxation are analytically estimated for nonlinear chains. These energy thresholds are size dependent. The energy thresholds of discrete breathers in thermal equilibrium are the same as the previous analytical results for single discrete breathers. The energy thresholds of long-lived discrete breathers in relaxation processes are different from the previous results for single discrete breathers but agree well with the published numerical results known to us. Because real systems are either in thermal equilibrium or in relaxation processes, the obtained results could be important for experimental detection of discrete breathers.

Perfect discretization of reparametrization invariant path integrals

NASA Astrophysics Data System (ADS)

Bahr, Benjamin; Dittrich, Bianca; Steinhaus, Sebastian

2011-05-01

To obtain a well-defined path integral one often employs discretizations. In the case of gravity and reparametrization-invariant systems, the latter of which we consider here as a toy example, discretizations generically break diffeomorphism and reparametrization symmetry, respectively. This has severe implications, as these symmetries determine the dynamics of the corresponding system. Indeed we will show that a discretized path integral with reparametrization-invariance is necessarily also discretization independent and therefore uniquely determined by the corresponding continuum quantum mechanical propagator. We use this insight to develop an iterative method for constructing such a discretized path integral, akin to a Wilsonian RG flow. This allows us to address the problem of discretization ambiguities and of an anomaly-free path integral measure for such systems. The latter is needed to obtain a path integral, that can act as a projector onto the physical states, satisfying the quantum constraints. We will comment on implications for discrete quantum gravity models, such as spin foams.

Adaptive Event-Triggered Control Based on Heuristic Dynamic Programming for Nonlinear Discrete-Time Systems.

PubMed

Dong, Lu; Zhong, Xiangnan; Sun, Changyin; He, Haibo

2017-07-01

This paper presents the design of a novel adaptive event-triggered control method based on the heuristic dynamic programming (HDP) technique for nonlinear discrete-time systems with unknown system dynamics. In the proposed method, the control law is only updated when the event-triggered condition is violated. Compared with the periodic updates in the traditional adaptive dynamic programming (ADP) control, the proposed method can reduce the computation and transmission cost. An actor-critic framework is used to learn the optimal event-triggered control law and the value function. Furthermore, a model network is designed to estimate the system state vector. The main contribution of this paper is to design a new trigger threshold for discrete-time systems. A detailed Lyapunov stability analysis shows that our proposed event-triggered controller can asymptotically stabilize the discrete-time systems. Finally, we test our method on two different discrete-time systems, and the simulation results are included.

A discrete control model of PLANT

NASA Technical Reports Server (NTRS)

Mitchell, C. M.

1985-01-01

A model of the PLANT system using the discrete control modeling techniques developed by Miller is described. Discrete control models attempt to represent in a mathematical form how a human operator might decompose a complex system into simpler parts and how the control actions and system configuration are coordinated so that acceptable overall system performance is achieved. Basic questions include knowledge representation, information flow, and decision making in complex systems. The structure of the model is a general hierarchical/heterarchical scheme which structurally accounts for coordination and dynamic focus of attention. Mathematically, the discrete control model is defined in terms of a network of finite state systems. Specifically, the discrete control model accounts for how specific control actions are selected from information about the controlled system, the environment, and the context of the situation. The objective is to provide a plausible and empirically testable accounting and, if possible, explanation of control behavior.

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

PubMed Central

Wong-Ng, W.

2012-01-01

This paper provides an evaluation of the effectiveness of using the high throughput combinatorial approach for preparing phase diagrams of thin film and bulk materials. Our evaluation is based primarily on examples of combinatorial phase diagrams that have been reported in the literature as well as based on our own laboratory experiments. Various factors that affect the construction of these phase diagrams are examined. Instrumentation and analytical approaches needed to improve data acquisition and data analysis are summarized. PMID:26900530

Massively multiplex single-cell Hi-C

PubMed Central

Ramani, Vijay; Deng, Xinxian; Qiu, Ruolan; Gunderson, Kevin L; Steemers, Frank J; Disteche, Christine M; Noble, William S; Duan, Zhijun; Shendure, Jay

2016-01-01

We present single-cell combinatorial indexed Hi-C (sciHi-C), which applies the concept of combinatorial cellular indexing to chromosome conformation capture. In this proof-of-concept, we generate and sequence six sciHi-C libraries comprising a total of 10,696 single cells. We use sciHi-C data to separate cells by karytoypic and cell-cycle state differences and identify cell-to-cell heterogeneity in mammalian chromosomal conformation. Our results demonstrate that combinatorial indexing is a generalizable strategy for single-cell genomics. PMID:28135255

Conservative, unconditionally stable discretization methods for Hamiltonian equations, applied to wave motion in lattice equations modeling protein molecules

NASA Astrophysics Data System (ADS)

LeMesurier, Brenton

2012-01-01

A new approach is described for generating exactly energy-momentum conserving time discretizations for a wide class of Hamiltonian systems of DEs with quadratic momenta, including mechanical systems with central forces; it is well-suited in particular to the large systems that arise in both spatial discretizations of nonlinear wave equations and lattice equations such as the Davydov System modeling energetic pulse propagation in protein molecules. The method is unconditionally stable, making it well-suited to equations of broadly “Discrete NLS form”, including many arising in nonlinear optics. Key features of the resulting discretizations are exact conservation of both the Hamiltonian and quadratic conserved quantities related to continuous linear symmetries, preservation of time reversal symmetry, unconditional stability, and respecting the linearity of certain terms. The last feature allows a simple, efficient iterative solution of the resulting nonlinear algebraic systems that retain unconditional stability, avoiding the need for full Newton-type solvers. One distinction from earlier work on conservative discretizations is a new and more straightforward nearly canonical procedure for constructing the discretizations, based on a “discrete gradient calculus with product rule” that mimics the essential properties of partial derivatives. This numerical method is then used to study the Davydov system, revealing that previously conjectured continuum limit approximations by NLS do not hold, but that sech-like pulses related to NLS solitons can nevertheless sometimes arise.

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

PubMed

Harańczyk, Maciej; Gutowski, Maciej

2007-01-01

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

Combinatorial therapy with adenoviral-mediated PTEN and a PI3K inhibitor suppresses malignant glioma cell growth in vitro and in vivo by regulating the PI3K/AKT signaling pathway.

PubMed

Nan, Yang; Guo, Liyun; Song, Yunpeng; Wang, Le; Yu, Kai; Huang, Qiang; Zhong, Yue

2017-08-01

Glioblastoma is a highly invasive and challenging tumor of the central nervous system. The mutation/deletion of the tumor suppressor phosphatase and tensin homolog (PTEN) gene is the main genetic change identified in glioblastomas. PTEN plays a critical role in tumorigenesis and has been shown to be an important therapeutic target. The phosphatidylinositol 3-kinase (PI3K) inhibitor LY294002 is commonly used to inhibit glioma cell growth via regulation of the PI3K/AKT signaling pathway. In this study, we examined the growth inhibitory effects of a combinatorial therapy of adenoviral-mediated PTEN (Ad-PTEN) and LY294002 on LN229 and U251 glioma cells in vitro and on tumor xenografts in vivo. In vitro, LN229 and U251 glioma cells were treated by combinatorial therapy with Ad-PTEN and LY294002. The growth ability was determined by MTT assay. The cell cycle distribution was analyzed by flow cytometry. Cell invasive ability was analyzed by transwell invasion assay and cell apoptosis analysis via FITC-Annexin V analysis. In vivo, U251 subcutaneous glioblastoma xenograft was used to assay anti-tumor effect of combinatorial therapy with Ad-PTEN and LY294002 by mean volume of tumors, immunohistochemistry and TUNEL method. The combinatorial treatment clearly suppressed cell proliferation, arrested the cell cycle, reduced cell invasion and promoted cell apoptosis compared with the Ad-PTEN or LY294002 treatment alone. The treatment worked by inhibiting the PI3K/AKT pathway. In addition, the growth of U251 glioma xenografts treated with the combination of Ad-PTEN and LY294002 was significantly inhibited compared with those treated with Ad-PTEN or LY294002 alone. Our data indicated that the combination of Ad-PTEN and LY294002 effectively suppressed the malignant growth of human glioma cells in vitro and in tumor xenografts, suggesting a promising new approach for glioma gene therapy that warrants further investigation.

Reliability and mass analysis of dynamic power conversion systems with parallel of standby redundancy

NASA Technical Reports Server (NTRS)

Juhasz, A. J.; Bloomfield, H. S.

1985-01-01

A combinatorial reliability approach is used to identify potential dynamic power conversion systems for space mission applications. A reliability and mass analysis is also performed, specifically for a 100 kWe nuclear Brayton power conversion system with parallel redundancy. Although this study is done for a reactor outlet temperature of 1100K, preliminary system mass estimates are also included for reactor outlet temperatures ranging up to 1500 K.

Combinatorial Interdependence in Lottery

ERIC Educational Resources Information Center

Helman, Danny

2005-01-01

This paper examines a real life question of gamble facing lottery players. Combinatorial dependence plays a central role in shaping the game probabilistic structure, but might not carry the merited weight in punters' considerations.

The natural antibody repertoire of sharks and humans recognizes the potential universe of antigens.

PubMed

Adelman, Miranda K; Schluter, Samuel F; Marchalonis, John J

2004-02-01

In ancestral sharks, a rapid emergence in the evolution of the immune system occurred, giving jawed-vertebrates the necessary components for the combinatorial immune response (CIR). To compare the natural antibody (NAb) repertoires of the most divergent vertebrates with the capacity to produce antibodies, we isolated NAbs to the same set of antigens by affinity chromatography from two species of Carcharhine sharks and from human polyclonal IgG and IgM antibody preparations. The activities of the affinity-purified anti-T-cell receptor (anti-TCR) NAbs were compared with those of monoclonal anti-TCR NAbs that were generated from a systemic lupus erythematosus patient. We report that sharks and humans, representing the evolutionary extremes of vertebrate species sharing the CIR, have NAbs to human TCRs, Igs, the human senescent cell antigen, and to numerous retroviral antigens, indicating that essential features of the combinatorial repertoire and the capacity to recognize the potential universe of antigens is shared among all jawed-vertebrates.

A germination bioassay as a toxicological screening system for studying the effects of potential prodrugs of naproxen.

PubMed

Gonzalez-de la Parra, M; Ramos-Mundo, C; Jimenez-Estrada, M; Ponce-de Leon, C; Castillo, R; Tejeda, V; Cuevas, K G; Enriquez, R G

1998-01-01

A germination bioassay with radish (Raphanus sativus L.) seeds was developed as a toxicological screening system for assessing the effects of new potential prodrugs of naproxen, as an alternative to animals and animal cell toxicity screens. Both enantiomers of naproxen (6-methoxy-α-methyl-2-naphthaleneacetic acid) and naproxol (6-methoxy-β-2-naphthaleneethanol), and their racemic mixtures, inhibited the radicle growth of R. sativus at a concentration of 1mM, while only (R)-(+ )-naproxol and racemic naproxol inhibited the hypocotyl growth of R. sativus at the same concentration. Four novel combinatorial esters, naproxen naproxyl esters (6-methoxy-β-methyl-2-naphthaleneethyl 6-methoxy-α-methyl-2-naphthaleneacetate), resulting from the combinatorial chemistry of the esterification reaction between naproxen and naproxol, were synthesised and then tested in the germination bioassay, at a concentration of 0.5mM. It was found that they did not inhibit either the radicle or the hypocotyl growth of R. sativus. 1998 FRAME.

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

PubMed

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.

NEUROTROPHIC FACTORS IN COMBINATORIAL APPROACHES FOR SPINAL CORD REGENERATION

PubMed Central

McCall, Julianne; Weidner, Norbert; Blesch, Armin

2012-01-01

Axonal regeneration is inhibited by a plethora of different mechanisms in the adult central nervous system (CNS). While neurotrophic factors have been shown to stimulate axonal growth in numerous animal models of nervous system injury, a lack of suitable growth substrates, an insufficient activation of neuron-intrinsic regenerative programs and extracellular inhibitors of regeneration limit the efficacy of neurotrophic factor delivery for anatomical and functional recovery after spinal cord injury. Thus, growth-stimulating factors will likely have to be combined with other treatment approaches to tap into the full potential of growth factor therapy for axonal regeneration. In addition, the temporal and spatial distribution of growth factors have to be tightly controlled to achieve biologically active concentrations, to allow for the chemotropic guidance of axons and to prevent adverse effects related to the widespread distribution of neurotrophic factors. Here, we will review the rationale for combinatorial treatments in axonal regeneration and summarize some recent progress in promoting axonal regeneration in the injured CNS using such approaches. PMID:22526621

Erythrocyte membrane-coated nanogel for combinatorial antivirulence and responsive antimicrobial delivery against Staphylococcus aureus infection.

PubMed

Zhang, Yue; Zhang, Jianhua; Chen, Wansong; Angsantikul, Pavimol; Spiekermann, Kevin A; Fang, Ronnie H; Gao, Weiwei; Zhang, Liangfang

2017-10-10

We reported an erythrocyte membrane-coated nanogel (RBC-nanogel) system with combinatorial antivirulence and responsive antibiotic delivery for the treatment of methicillin-resistant Staphylococcus aureus (MRSA) infection. RBC membrane was coated onto the nanogel via a membrane vesicle templated in situ gelation process, whereas the redox-responsiveness was achieved by using a disulfide bond-based crosslinker. We demonstrated that the RBC-nanogels effectively neutralized MRSA-associated toxins in extracellular environment and the toxin neutralization in turn promoted bacterial uptake by macrophages. In intracellular reducing environment, the RBC-nanogels showed an accelerated drug release profile, which resulted in more effective bacterial inhibition. When added to the macrophages infected with intracellular MRSA bacteria, the RBC-nanogels significantly inhibited bacterial growth compared to free antibiotics and non-responsive nanogel counterparts. These results indicate the great potential of the RBC-nanogel system as a new and effective antimicrobial agent against MRSA infection. Copyright © 2017 Elsevier B.V. All rights reserved.

Development of a Novel, Bicombinatorial Approach to Alloy Development, and Application to Rapid Screening of Creep Resistant Titanium Alloys

NASA Astrophysics Data System (ADS)

Martin, Brian

Combinatorial approaches have proven useful for rapid alloy fabrication and optimization. A new method of producing controlled isothermal gradients using the Gleeble Thermomechanical simulator has been developed, and demonstrated on the metastable beta-Ti alloy beta-21S, achieving a thermal gradient of 525-700 °C. This thermal gradient method has subsequently been coupled with existing combinatorial methods of producing composition gradients using the LENS(TM) additive manufacturing system, through the use of elemental blended powders. This has been demonstrated with a binary Ti-(0-15) wt% Cr build, which has subsequently been characterized with optical and electron microscopy, with special attention to the precipitate of TiCr2 Laves phases. The TiCr2 phase has been explored for its high temperature mechanical properties in a new oxidation resistant beta-Ti alloy, which serves as a demonstration of the new bicombinatorial methods developed as applied to a multicomponent alloy system.

Quantitative Tracking of Combinatorially Engineered Populations with Multiplexed Binary Assemblies.

PubMed

Zeitoun, Ramsey I; Pines, Gur; Grau, Willliam C; Gill, Ryan T

2017-04-21

Advances in synthetic biology and genomics have enabled full-scale genome engineering efforts on laboratory time scales. However, the absence of sufficient approaches for mapping engineered genomes at system-wide scales onto performance has limited the adoption of more sophisticated algorithms for engineering complex biological systems. Here we report on the development and application of a robust approach to quantitatively map combinatorially engineered populations at scales up to several dozen target sites. This approach works by assembling genome engineered sites with cell-specific barcodes into a format compatible with high-throughput sequencing technologies. This approach, called barcoded-TRACE (bTRACE) was applied to assess E. coli populations engineered by recursive multiplex recombineering across both 6-target sites and 31-target sites. The 31-target library was then tracked throughout growth selections in the presence and absence of isopentenol (a potential next-generation biofuel). We also use the resolution of bTRACE to compare the influence of technical and biological noise on genome engineering efforts.

pK(a) based protonation states and microspecies for protein-ligand docking.

PubMed

ten Brink, Tim; Exner, Thomas E

2010-11-01

In this paper we present our reworked approach to generate ligand protonation states with our structure preparation tool SPORES (Structure PrOtonation and REcognition System). SPORES can be used for the preprocessing of proteins and protein-ligand complexes as e.g. taken from the Protein Data Bank as well as for the setup of 3D ligand databases. It automatically assigns atom and bond types, generates different protonation, tautomeric states as well as different stereoisomers. In the revised version, pKa calculations with the ChemAxon software MARVIN are used either to determine the likeliness of a combinatorial generated protonation state or to determine the titrable atoms used in the combinatorial approach. Additionally, the MARVIN software is used to predict microspecies distributions of ligand molecules. Docking studies were performed with our recently introduced program PLANTS (Protein-Ligand ANT System) on all protomers resulting from the three different selection methods for the well established CCDC/ASTEX clean data set demonstrating the usefulness of especially the latter approach.

pKa based protonation states and microspecies for protein-ligand docking

NASA Astrophysics Data System (ADS)

ten Brink, Tim; Exner, Thomas E.

2010-11-01

In this paper we present our reworked approach to generate ligand protonation states with our structure preparation tool SPORES (Structure PrOtonation and REcognition System). SPORES can be used for the preprocessing of proteins and protein-ligand complexes as e.g. taken from the Protein Data Bank as well as for the setup of 3D ligand databases. It automatically assigns atom and bond types, generates different protonation, tautomeric states as well as different stereoisomers. In the revised version, pKa calculations with the ChemAxon software MARVIN are used either to determine the likeliness of a combinatorial generated protonation state or to determine the titrable atoms used in the combinatorial approach. Additionally, the MARVIN software is used to predict microspecies distributions of ligand molecules. Docking studies were performed with our recently introduced program PLANTS (Protein-Ligand ANT System) on all protomers resulting from the three different selection methods for the well established CCDC/ASTEX clean data set demonstrating the usefulness of especially the latter approach.

Structural Validation of Nursing Terminologies

PubMed Central

Hardiker, Nicholas R.; Rector, Alan L.

2001-01-01

Objective: The purpose of the study is twofold: 1) to explore the applicability of combinatorial terminologies as the basis for building enumerated classifications, and 2) to investigate the usefulness of formal terminological systems for performing such classification and for assisting in the refinement of both combinatorial terminologies and enumerated classifications. Design: A formal model of the beta version of the International Classification for Nursing Practice (ICNP) was constructed in the compositional terminological language GRAIL (GALEN Representation and Integration Language). Terms drawn from the North American Nursing Diagnosis Association Taxonomy I (NANDA taxonomy) were mapped into the model and classified automatically using GALEN technology. Measurements: The resulting generated hierarchy was compared with the NANDA taxonomy to assess coverage and accuracy of classification. Results: In terms of coverage, in this study ICNP was able to capture 77 percent of NANDA terms using concepts drawn from five of its eight axes. Three axes—Body Site, Topology, and Frequency—were not needed. In terms of accuracy, where hierarchic relationships existed in the generated hierarchy or the NANDA taxonomy, or both, 6 were identical, 19 existed in the generated hierarchy alone (2 of these were considered suitable for incorporation into the NANDA taxonomy and 17 were considered inaccurate), and 23 appeared in the NANDA taxonomy alone (8 of these were considered suitable for incorporation into ICNP, 9 were considered inaccurate, and 6 reflected different, equally valid perspectives). Sixty terms appeared at the top level, with no indenting, in both the generated hierarchy and the NANDA taxonomy. Conclusions: With appropriate refinement, combinatorial terminologies such as ICNP have the potential to provide a useful foundation for representing enumerated classifications such as NANDA. Technologies such as GALEN make possible the process of building automatically enumerated classifications while providing a useful means of validating and refining both combinatorial terminologies and enumerated classifications. PMID:11320066

Nonlinear Light Dynamics in Multi-Core Structures

DTIC Science & Technology

2017-02-27

be generated in continuous- discrete optical media such as multi-core optical fiber or waveguide arrays; localisation dynamics in a continuous... discrete nonlinear system. Detailed theoretical analysis is presented of the existence and stability of the discrete -continuous light bullets using a very...and pulse compression using wave collapse (self-focusing) energy localisation dynamics in a continuous- discrete nonlinear system, as implemented in a

Rex fortran 4 system for combinatorial screening or conventional analysis of multivariate regressions

Treesearch

L.R. Grosenbaugh

1967-01-01

Describes an expansible computerized system that provides data needed in regression or covariance analysis of as many as 50 variables, 8 of which may be dependent. Alternatively, it can screen variously generated combinations of independent variables to find the regression with the smallest mean-squared-residual, which will be fitted if desired. The user can easily...

Neural representations of the sense of self

PubMed Central

Klemm, William R.

2011-01-01

The brain constructs representations of what is sensed and thought about in the form of nerve impulses that propagate in circuits and network assemblies (Circuit Impulse Patterns, CIPs). CIP representations of which humans are consciously aware occur in the context of a sense of self. Thus, research on mechanisms of consciousness might benefit from a focus on how a conscious sense of self is represented in brain. Like all senses, the sense of self must be contained in patterns of nerve impulses. Unlike the traditional senses that are registered by impulse flow in relatively simple, pauci-synaptic projection pathways, the sense of self is a system- level phenomenon that may be generated by impulse patterns in widely distributed complex and interacting circuits. The problem for researchers then is to identify the CIPs that are unique to conscious experience. Also likely to be of great relevance to constructing the representation of self are the coherence shifts in activity timing relations among the circuits. Consider that an embodied sense of self is generated and contained as unique combinatorial temporal patterns across multiple neurons in each circuit that contributes to constructing the sense of self. As with other kinds of CIPs, those representing the sense of self can be learned from experience, stored in memory, modified by subsequent experiences, and expressed in the form of decisions, choices, and commands. These CIPs are proposed here to be the actual physical basis for conscious thought and the sense of self. When active in wakefulness or dream states, the CIP representations of self act as an agent of the brain, metaphorically as an avatar. Because the selfhood CIP patterns may only have to represent the self and not directly represent the inner and outer worlds of embodied brain, the self representation should have more degrees of freedom than subconscious mind and may therefore have some capacity for a free-will mind of its own. S everal lines of evidence for this theory are reviewed. Suggested new research includes identifying distinct combinatorially coded impulse patterns and their temporal coherence shifts in defined circuitry, such as neocortical microcolumns. This task might be facilitated by identifying the micro-topography of field-potential oscillatory coherences among various regions and between different frequencies associated with specific conscious mentation. Other approaches can include identifying the changes in discrete conscious operations produced by focal trans-cranial magnetic stimulation. PMID:21826192

Discrete rational and breather solution in the spatial discrete complex modified Korteweg-de Vries equation and continuous counterparts.

PubMed

Zhao, Hai-Qiong; Yu, Guo-Fu

2017-04-01

In this paper, a spatial discrete complex modified Korteweg-de Vries equation is investigated. The Lax pair, conservation laws, Darboux transformations, and breather and rational wave solutions to the semi-discrete system are presented. The distinguished feature of the model is that the discrete rational solution can possess new W-shape rational periodic-solitary waves that were not reported before. In addition, the first-order rogue waves reach peak amplitudes which are at least three times of the background amplitude, whereas their continuous counterparts are exactly three times the constant background. Finally, the integrability of the discrete system, including Lax pair, conservation laws, Darboux transformations, and explicit solutions, yields the counterparts of the continuous system in the continuum limit.

A Systematic Study of Simple Combinatorial Configurations.

ERIC Educational Resources Information Center

Dubois, Jean-Guy

1984-01-01

A classification of the simple combinatorial configurations which correspond to various cases of distribution and ordering of objects into boxes is given (in French). Concrete descriptions, structured relations, translations, and formalizations are discussed. (MNS)

Combinatorial Mathematics: Research into Practice

ERIC Educational Resources Information Center

Sriraman, Bharath; English, Lyn D.

2004-01-01

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

Local bounds preserving stabilization for continuous Galerkin discretization of hyperbolic systems

NASA Astrophysics Data System (ADS)

Mabuza, Sibusiso; Shadid, John N.; Kuzmin, Dmitri

2018-05-01

The objective of this paper is to present a local bounds preserving stabilized finite element scheme for hyperbolic systems on unstructured meshes based on continuous Galerkin (CG) discretization in space. A CG semi-discrete scheme with low order artificial dissipation that satisfies the local extremum diminishing (LED) condition for systems is used to discretize a system of conservation equations in space. The low order artificial diffusion is based on approximate Riemann solvers for hyperbolic conservation laws. In this case we consider both Rusanov and Roe artificial diffusion operators. In the Rusanov case, two designs are considered, a nodal based diffusion operator and a local projection stabilization operator. The result is a discretization that is LED and has first order convergence behavior. To achieve high resolution, limited antidiffusion is added back to the semi-discrete form where the limiter is constructed from a linearity preserving local projection stabilization operator. The procedure follows the algebraic flux correction procedure usually used in flux corrected transport algorithms. To further deal with phase errors (or terracing) common in FCT type methods, high order background dissipation is added to the antidiffusive correction. The resulting stabilized semi-discrete scheme can be discretized in time using a wide variety of time integrators. Numerical examples involving nonlinear scalar Burgers equation, and several shock hydrodynamics simulations for the Euler system are considered to demonstrate the performance of the method. For time discretization, Crank-Nicolson scheme and backward Euler scheme are utilized.

Combinatorial vector fields and the valley structure of fitness landscapes.

PubMed

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.

Measuring and Specifying Combinatorial Coverage of Test Input Configurations

PubMed Central

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

2015-01-01

A key issue in testing is how many tests are needed for a required level of coverage or fault detection. Estimates are often based on error rates in initial testing, or on code coverage. For example, tests may be run until a desired level of statement or branch coverage is achieved. Combinatorial methods present an opportunity for a different approach to estimating required test set size, using characteristics of the test set. This paper describes methods for estimating the coverage of, and ability to detect, t-way interaction faults of a test set based on a covering array. We also develop a connection between (static) combinatorial coverage and (dynamic) code coverage, such that if a specific condition is satisfied, 100% branch coverage is assured. Using these results, we propose practical recommendations for using combinatorial coverage in specifying test requirements. PMID:28133442

Combinatorial chemical bath deposition of CdS contacts for chalcogenide photovoltaics

DOE PAGES

Mokurala, Krishnaiah; Baranowski, Lauryn L.; de Souza Lucas, Francisco W.; ...

2016-08-01

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)Se 2 (CIGSe) and Cu 2ZnSnSe 4 (CZTSe) light absorbers in PV devices. Combinatorial thickness steps ofmore » 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. Finally, 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.« less

Dynamical quantum phase transitions in discrete time crystals

NASA Astrophysics Data System (ADS)

Kosior, Arkadiusz; Sacha, Krzysztof

2018-05-01

Discrete time crystals are related to nonequilibrium dynamics of periodically driven quantum many-body systems where the discrete time-translation symmetry of the Hamiltonian is spontaneously broken into another discrete symmetry. Recently, the concept of phase transitions has been extended to nonequilibrium dynamics of time-independent systems induced by a quantum quench, i.e., a sudden change of some parameter of the Hamiltonian. There, the return probability of a system to the ground state reveals singularities in time which are dubbed dynamical quantum phase transitions. We show that the quantum quench in a discrete time crystal leads to dynamical quantum phase transitions where the return probability of a periodically driven system to a Floquet eigenstate before the quench reveals singularities in time. It indicates that dynamical quantum phase transitions are not restricted to time-independent systems and can be also observed in systems that are periodically driven. We discuss how the phenomenon can be observed in ultracold atomic gases.

Final Technical Report for GO15052 Intematix: Combinatorial Synthesis and High Throughput Screening of Effective Catalysts for Chemical Hydrides

DOE Office of Scientific and Technical Information (OSTI.GOV)

Melman, Jonathan

The objectives of this project are: to discover cost-effective catalysts for release of hydrogen from chemical hydrogen storage systems; and to discover cost-effective catalysts for the regeneration of spent chemical hydrogen storage materials.

Upon Generating Discrete Expanding Integrable Models of the Toda Lattice Systems and Infinite Conservation Laws

NASA Astrophysics Data System (ADS)

Zhang, Yufeng; Zhang, Xiangzhi; Wang, Yan; Liu, Jiangen

2017-01-01

With the help of R-matrix approach, we present the Toda lattice systems that have extensive applications in statistical physics and quantum physics. By constructing a new discrete integrable formula by R-matrix, the discrete expanding integrable models of the Toda lattice systems and their Lax pairs are generated, respectively. By following the constructing formula again, we obtain the corresponding (2+1)-dimensional Toda lattice systems and their Lax pairs, as well as their (2+1)-dimensional discrete expanding integrable models. Finally, some conservation laws of a (1+1)-dimensional generalised Toda lattice system and a new (2+1)-dimensional lattice system are generated, respectively.

Phthalocyanine-loaded graphene nanoplatform for imaging-guided combinatorial phototherapy

PubMed Central

Taratula, Olena; Patel, Mehulkumar; Schumann, Canan; Naleway, Michael A; Pang, Addison J; He, Huixin; Taratula, Oleh

2015-01-01

We report a novel cancer-targeted nanomedicine platform for imaging and prospect for future treatment of unresected ovarian cancer tumors by intraoperative multimodal phototherapy. To develop the required theranostic system, novel low-oxygen graphene nanosheets were chemically modified with polypropylenimine dendrimers loaded with phthalocyanine (Pc) as a photosensitizer. Such a molecular design prevents fluorescence quenching of the Pc by graphene nanosheets, providing the possibility of fluorescence imaging. Furthermore, the developed nanoplatform was conjugated with poly(ethylene glycol), to improve biocompatibility, and with luteinizing hormone-releasing hormone (LHRH) peptide, for tumor-targeted delivery. Notably, a low-power near-infrared (NIR) irradiation of single wavelength was used for both heat generation by the graphene nanosheets (photothermal therapy [PTT]) and for reactive oxygen species (ROS)-production by Pc (photodynamic therapy [PDT]). The combinatorial phototherapy resulted in an enhanced destruction of ovarian cancer cells, with a killing efficacy of 90%–95% at low Pc and low-oxygen graphene dosages, presumably conferring cytotoxicity to the synergistic effects of generated ROS and mild hyperthermia. An animal study confirmed that Pc loaded into the nanoplatform can be employed as a NIR fluorescence agent for imaging-guided drug delivery. Hence, the newly developed Pc-graphene nanoplatform has the significant potential as an effective NIR theranostic probe for imaging and combinatorial phototherapy. PMID:25848255

DOE Office of Scientific and Technical Information (OSTI.GOV)

Siol, Sebastian; Holder, Aaron; Ortiz, Brenden R.

Here, the controlled decomposition of metastable alloys is an attractive route to form nanostructured thermoelectric materials with reduced thermal conductivity. The ternary SnTe–MnTe and SnTe–SnSe heterostructural alloys have been demonstrated as promising materials for thermoelectric applications. In this work, the quaternary Sn 1–yMnyTe 1–xSe x phase space serves as a relevant model system to explore how a combination of computational and combinatorial-growth methods can be used to study equilibrium and non-equilibrium solubility limits. Results from first principle calculations indicate low equilibrium solubility for x,y < 0.05 that are in good agreement with results obtained from bulk equilibrium synthesis experiments andmore » predict significantly higher spinodal limits. An experimental screening using sputtered combinatorial thin film sample libraries showed a remarkable increase in non-equilibrium solubility for x,y > 0.2. These theoretical and experimental results were used to guide the bulk synthesis of metastable alloys. The ability to reproduce the non-equilibrium solubility levels in bulk materials indicates that such theoretical calculations and combinatorial growth can inform bulk synthetic routes. Further, the large difference between equilibrium and non-equilibrium solubility limits in Sn 1–yMn yTe 1–xSe x indicates these metastable alloys are attractive in terms of nano-precipitate formation for potential thermoelectric applications.« less

Cascaded Optimization for a Persistent Data Ferrying Unmanned Aircraft

NASA Astrophysics Data System (ADS)

Carfang, Anthony

This dissertation develops and assesses a cascaded method for designing optimal periodic trajectories and link schedules for an unmanned aircraft to ferry data between stationary ground nodes. This results in a fast solution method without the need to artificially constrain system dynamics. Focusing on a fundamental ferrying problem that involves one source and one destination, but includes complex vehicle and Radio-Frequency (RF) dynamics, a cascaded structure to the system dynamics is uncovered. This structure is exploited by reformulating the nonlinear optimization problem into one that reduces the independent control to the vehicle's motion, while the link scheduling control is folded into the objective function and implemented as an optimal policy that depends on candidate motion control. This formulation is proven to maintain optimality while reducing computation time in comparison to traditional ferry optimization methods. The discrete link scheduling problem takes the form of a combinatorial optimization problem that is known to be NP-Hard. A derived necessary condition for optimality guides the development of several heuristic algorithms, specifically the Most-Data-First Algorithm and the Knapsack Adaptation. These heuristics are extended to larger ferrying scenarios, and assessed analytically and through Monte Carlo simulation, showing better throughput performance in the same order of magnitude of computation time in comparison to other common link scheduling policies. The cascaded optimization method is implemented with a novel embedded software system on a small, unmanned aircraft to validate the simulation results with field experiments. To address the sensitivity of results on trajectory tracking performance, a system that combines motion and link control with waypoint-based navigation is developed and assessed through field experiments. The data ferrying algorithms are further extended by incorporating a Gaussian process to opportunistically learn the RF environment. By continuously improving RF models, the cascaded planner can continually improve the ferrying system's overall performance.

Direct Profiling the Post-Translational Modification Codes of a Single Protein Immobilized on a Surface Using Cu-free Click Chemistry.

PubMed

Kim, Kyung Lock; Park, Kyeng Min; Murray, James; Kim, Kimoon; Ryu, Sung Ho

2018-05-23

Combinatorial post-translational modifications (PTMs), which can serve as dynamic "molecular barcodes", have been proposed to regulate distinct protein functions. However, studies of combinatorial PTMs on single protein molecules have been hindered by a lack of suitable analytical methods. Here, we describe erasable single-molecule blotting (eSiMBlot) for combinatorial PTM profiling. This assay is performed in a highly multiplexed manner and leverages the benefits of covalent protein immobilization, cyclic probing with different antibodies, and single molecule fluorescence imaging. Especially, facile and efficient covalent immobilization on a surface using Cu-free click chemistry permits multiple rounds (>10) of antibody erasing/reprobing without loss of antigenicity. Moreover, cumulative detection of coregistered multiple data sets for immobilized single-epitope molecules, such as HA peptide, can be used to increase the antibody detection rate. Finally, eSiMBlot enables direct visualization and quantitative profiling of combinatorial PTM codes at the single-molecule level, as we demonstrate by revealing the novel phospho-codes of ligand-induced epidermal growth factor receptor. Thus, eSiMBlot provides an unprecedentedly simple, rapid, and versatile platform for analyzing the vast number of combinatorial PTMs in biological pathways.

Direct Profiling the Post-Translational Modification Codes of a Single Protein Immobilized on a Surface Using Cu-free Click Chemistry

PubMed Central

2018-01-01

Combinatorial post-translational modifications (PTMs), which can serve as dynamic “molecular barcodes”, have been proposed to regulate distinct protein functions. However, studies of combinatorial PTMs on single protein molecules have been hindered by a lack of suitable analytical methods. Here, we describe erasable single-molecule blotting (eSiMBlot) for combinatorial PTM profiling. This assay is performed in a highly multiplexed manner and leverages the benefits of covalent protein immobilization, cyclic probing with different antibodies, and single molecule fluorescence imaging. Especially, facile and efficient covalent immobilization on a surface using Cu-free click chemistry permits multiple rounds (>10) of antibody erasing/reprobing without loss of antigenicity. Moreover, cumulative detection of coregistered multiple data sets for immobilized single-epitope molecules, such as HA peptide, can be used to increase the antibody detection rate. Finally, eSiMBlot enables direct visualization and quantitative profiling of combinatorial PTM codes at the single-molecule level, as we demonstrate by revealing the novel phospho-codes of ligand-induced epidermal growth factor receptor. Thus, eSiMBlot provides an unprecedentedly simple, rapid, and versatile platform for analyzing the vast number of combinatorial PTMs in biological pathways.

Lexicographic goal programming and assessment tools for a combinatorial production problem.

DOT National Transportation Integrated Search

2008-01-01

NP-complete combinatorial problems often necessitate the use of near-optimal solution techniques including : heuristics and metaheuristics. The addition of multiple optimization criteria can further complicate : comparison of these solution technique...

A review and experimental study on the application of classifiers and evolutionary algorithms in EEG-based brain-machine interface systems

NASA Astrophysics Data System (ADS)

Tahernezhad-Javazm, Farajollah; Azimirad, Vahid; Shoaran, Maryam

2018-04-01

Objective. Considering the importance and the near-future development of noninvasive brain-machine interface (BMI) systems, this paper presents a comprehensive theoretical-experimental survey on the classification and evolutionary methods for BMI-based systems in which EEG signals are used. Approach. The paper is divided into two main parts. In the first part, a wide range of different types of the base and combinatorial classifiers including boosting and bagging classifiers and evolutionary algorithms are reviewed and investigated. In the second part, these classifiers and evolutionary algorithms are assessed and compared based on two types of relatively widely used BMI systems, sensory motor rhythm-BMI and event-related potentials-BMI. Moreover, in the second part, some of the improved evolutionary algorithms as well as bi-objective algorithms are experimentally assessed and compared. Main results. In this study two databases are used, and cross-validation accuracy (CVA) and stability to data volume (SDV) are considered as the evaluation criteria for the classifiers. According to the experimental results on both databases, regarding the base classifiers, linear discriminant analysis and support vector machines with respect to CVA evaluation metric, and naive Bayes with respect to SDV demonstrated the best performances. Among the combinatorial classifiers, four classifiers, Bagg-DT (bagging decision tree), LogitBoost, and GentleBoost with respect to CVA, and Bagging-LR (bagging logistic regression) and AdaBoost (adaptive boosting) with respect to SDV had the best performances. Finally, regarding the evolutionary algorithms, single-objective invasive weed optimization (IWO) and bi-objective nondominated sorting IWO algorithms demonstrated the best performances. Significance. We present a general survey on the base and the combinatorial classification methods for EEG signals (sensory motor rhythm and event-related potentials) as well as their optimization methods through the evolutionary algorithms. In addition, experimental and statistical significance tests are carried out to study the applicability and effectiveness of the reviewed methods.

Discrete Time-Crystalline Order in Cavity and Circuit QED Systems

NASA Astrophysics Data System (ADS)

Gong, Zongping; Hamazaki, Ryusuke; Ueda, Masahito

2018-01-01

Discrete time crystals are a recently proposed and experimentally observed out-of-equilibrium dynamical phase of Floquet systems, where the stroboscopic dynamics of a local observable repeats itself at an integer multiple of the driving period. We address this issue in a driven-dissipative setup, focusing on the modulated open Dicke model, which can be implemented by cavity or circuit QED systems. In the thermodynamic limit, we employ semiclassical approaches and find rich dynamical phases on top of the discrete time-crystalline order. In a deep quantum regime with few qubits, we find clear signatures of a transient discrete time-crystalline behavior, which is absent in the isolated counterpart. We establish a phenomenology of dissipative discrete time crystals by generalizing the Landau theory of phase transitions to Floquet open systems.

ON THE ROLE OF INVOLUTIONS IN THE DISCONTINUOUS GALERKIN DISCRETIZATION OF MAXWELL AND MAGNETOHYDRODYNAMIC SYSTEMS

NASA Technical Reports Server (NTRS)

Barth, Timothy

2005-01-01

The role of involutions in energy stability of the discontinuous Galerkin (DG) discretization of Maxwell and magnetohydrodynamic (MHD) systems is examined. Important differences are identified in the symmetrization of the Maxwell and MHD systems that impact the construction of energy stable discretizations using the DG method. Specifically, general sufficient conditions to be imposed on the DG numerical flux and approximation space are given so that energy stability is retained These sufficient conditions reveal the favorable energy consequence of imposing continuity in the normal component of the magnetic induction field at interelement boundaries for MHD discretizations. Counterintuitively, this condition is not required for stability of Maxwell discretizations using the discontinuous Galerkin method.

From Discrete Space-Time to Minkowski Space: Basic Mechanisms, Methods and Perspectives

NASA Astrophysics Data System (ADS)

Finster, Felix

This survey article reviews recent results on fermion systems in discrete space-time and corresponding systems in Minkowski space. After a basic introduction to the discrete setting, we explain a mechanism of spontaneous symmetry breaking which leads to the emergence of a discrete causal structure. As methods to study the transition between discrete space-time and Minkowski space, we describe a lattice model for a static and isotropic space-time, outline the analysis of regularization tails of vacuum Dirac sea configurations, and introduce a Lorentz invariant action for the masses of the Dirac seas. We mention the method of the continuum limit, which allows to analyze interacting systems. Open problems are discussed.

"Anticlumping" and Other Combinatorial Effects on Clumped Isotopes: Implications for Tracing Biogeochemical Cycling

NASA Astrophysics Data System (ADS)

Yeung, L.

2015-12-01

I present a mode of isotopic ordering that has purely combinatorial origins. It can be important when identical rare isotopes are paired by coincidence (e.g., they are neighbors on the same molecule), or when extrinsic factors govern the isotopic composition of the two atoms that share a chemical bond. By itself, combinatorial isotope pairing yields products with isotopes either randomly distributed or with a deficit relative to a random distribution of isotopes. These systematics arise because of an unconventional coupling between the formation of singly- and multiply-substituted isotopic moieties. In a random distribution, rare isotopes are symmetrically distributed: Single isotopic substitutions (e.g., H‒D and D‒H in H2) occur with equal probability, and double isotopic substitutions (e.g., D2) occur according to random chance. The absence of symmetry in a bond-making complex can yield unequal numbers of singly-substituted molecules (e.g., more H‒D than D‒H in H2), which is recorded in the product molecule as a deficit in doubly-substituted moieties and an "anticlumped" isotope distribution (i.e., Δn < 0). Enzymatic isotope pairing reactions, which can have site-specific isotopic fractionation factors and atom reservoirs, should express this class of combinatorial isotope effect. Chemical-kinetic isotope effects, which are related to the bond-forming transition state, arise independently and express second-order combinatorial effects. In general, both combinatorial and chemical factors are important for calculating and interpreting clumped-isotope signatures of individual reactions. In many reactions relevant to geochemical oxygen, carbon, and nitrogen cycling, combinatorial isotope pairing likely plays a strong role in the clumped isotope distribution of the products. These isotopic signatures, manifest as either directly bound isotope clumps or as features of a molecule's isotopic anatomy, could be exploited as tracers of biogeochemistry that can relate molecular mechanisms to signals observable at environmentally relevant spatial scales.

Multifunctional nanomedicine platform for concurrent delivery of chemotherapeutic drugs and mild hyperthermia to ovarian cancer cells.

PubMed

Taratula, Olena; Dani, Raj Kumar; Schumann, Canan; Xu, Hong; Wang, Andrew; Song, Han; Dhagat, Pallavi; Taratula, Oleh

2013-12-15

A multifunctional tumor-targeting delivery system was developed and evaluated for an efficient treatment of drug-resistant ovarian cancer by combinatorial therapeutic modality based on chemotherapy and mild hyperthermia. The engineered iron oxide nanoparticle (IONPs)-based nanocarrier served as an efficient delivery vehicle for doxorubicin and provided the ability to heat cancer cells remotely upon exposure to an alternating magnetic field (AMF). The nanocarrier was additionally modified with polyethylene glycol and LHRH peptide to improve its biocompatibility and ability to target tumor cells. The synthesized delivery system has an average size of 97.1 nm and a zeta potential close to zero, both parameters favorable for increased stability in biological media and decreased elimination by the immune system. The nanocarrier demonstrated faster drug release in acidic conditions that mimic the tumor environment. It was also observed that the LHRH targeted delivery system could effectively enter drug resistant ovarian cancer cells, and the fate of doxorubicin was tracked with fluorescence microscope. Mild hyperthermia (40°C) generated by IONPs under exposure to AMF synergistically increased the cytotoxicity of doxorubicin delivered by the developed nanocarrier to cancer cells. Thus, the developed IONPs-based delivery system has high potential in the effective treatment of ovarian cancer by combinatorial approach. Copyright © 2013 Elsevier B.V. All rights reserved.

ADAM: analysis of discrete models of biological systems using computer algebra.

PubMed

Hinkelmann, Franziska; Brandon, Madison; Guang, Bonny; McNeill, Rustin; Blekherman, Grigoriy; Veliz-Cuba, Alan; Laubenbacher, Reinhard

2011-07-20

Many biological systems are modeled qualitatively with discrete models, such as probabilistic Boolean networks, logical models, Petri nets, and agent-based models, to gain a better understanding of them. The computational complexity to analyze the complete dynamics of these models grows exponentially in the number of variables, which impedes working with complex models. There exist software tools to analyze discrete models, but they either lack the algorithmic functionality to analyze complex models deterministically or they are inaccessible to many users as they require understanding the underlying algorithm and implementation, do not have a graphical user interface, or are hard to install. Efficient analysis methods that are accessible to modelers and easy to use are needed. We propose a method for efficiently identifying attractors and introduce the web-based tool Analysis of Dynamic Algebraic Models (ADAM), which provides this and other analysis methods for discrete models. ADAM converts several discrete model types automatically into polynomial dynamical systems and analyzes their dynamics using tools from computer algebra. Specifically, we propose a method to identify attractors of a discrete model that is equivalent to solving a system of polynomial equations, a long-studied problem in computer algebra. Based on extensive experimentation with both discrete models arising in systems biology and randomly generated networks, we found that the algebraic algorithms presented in this manuscript are fast for systems with the structure maintained by most biological systems, namely sparseness and robustness. For a large set of published complex discrete models, ADAM identified the attractors in less than one second. Discrete modeling techniques are a useful tool for analyzing complex biological systems and there is a need in the biological community for accessible efficient analysis tools. ADAM provides analysis methods based on mathematical algorithms as a web-based tool for several different input formats, and it makes analysis of complex models accessible to a larger community, as it is platform independent as a web-service and does not require understanding of the underlying mathematics.

Fermion systems in discrete space-time

NASA Astrophysics Data System (ADS)

Finster, Felix

2007-05-01

Fermion systems in discrete space-time are introduced as a model for physics on the Planck scale. We set up a variational principle which describes a non-local interaction of all fermions. This variational principle is symmetric under permutations of the discrete space-time points. We explain how for minimizers of the variational principle, the fermions spontaneously break this permutation symmetry and induce on space-time a discrete causal structure.

Image compression system and method having optimized quantization tables

NASA Technical Reports Server (NTRS)

Ratnakar, Viresh (Inventor); Livny, Miron (Inventor)

1998-01-01

A digital image compression preprocessor for use in a discrete cosine transform-based digital image compression device is provided. The preprocessor includes a gathering mechanism for determining discrete cosine transform statistics from input digital image data. A computing mechanism is operatively coupled to the gathering mechanism to calculate a image distortion array and a rate of image compression array based upon the discrete cosine transform statistics for each possible quantization value. A dynamic programming mechanism is operatively coupled to the computing mechanism to optimize the rate of image compression array against the image distortion array such that a rate-distortion-optimal quantization table is derived. In addition, a discrete cosine transform-based digital image compression device and a discrete cosine transform-based digital image compression and decompression system are provided. Also, a method for generating a rate-distortion-optimal quantization table, using discrete cosine transform-based digital image compression, and operating a discrete cosine transform-based digital image compression and decompression system are provided.

Balancing focused combinatorial libraries based on multiple GPCR ligands

NASA Astrophysics Data System (ADS)

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

2006-08-01

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

Combinatorial Color Space Models for Skin Detection in Sub-continental Human Images

NASA Astrophysics Data System (ADS)

Khaled, Shah Mostafa; Saiful Islam, Md.; Rabbani, Md. Golam; Tabassum, Mirza Rehenuma; Gias, Alim Ul; Kamal, Md. Mostafa; Muctadir, Hossain Muhammad; Shakir, Asif Khan; Imran, Asif; Islam, Saiful

Among different color models HSV, HLS, YIQ, YCbCr, YUV, etc. have been most popular for skin detection. Most of the research done in the field of skin detection has been trained and tested on human images of African, Mongolian and Anglo-Saxon ethnic origins, skin colors of Indian sub-continentals have not been focused separately. Combinatorial algorithms, without affecting asymptotic complexity can be developed using the skin detection concepts of these color models for boosting detection performance. In this paper a comparative study of different combinatorial skin detection algorithms have been made. For training and testing 200 images (skin and non skin) containing pictures of sub-continental male and females have been used to measure the performance of the combinatorial approaches, and considerable development in success rate with True Positive of 99.5% and True Negative of 93.3% have been observed.

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

PubMed

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.

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

PubMed

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.

Quantum circuit dynamics via path integrals: Is there a classical action for discrete-time paths?

NASA Astrophysics Data System (ADS)

Penney, Mark D.; Enshan Koh, Dax; Spekkens, Robert W.

2017-07-01

It is straightforward to compute the transition amplitudes of a quantum circuit using the sum-over-paths methodology when the gates in the circuit are balanced, where a balanced gate is one for which all non-zero transition amplitudes are of equal magnitude. Here we consider the question of whether, for such circuits, the relative phases of different discrete-time paths through the configuration space can be defined in terms of a classical action, as they are for continuous-time paths. We show how to do so for certain kinds of quantum circuits, namely, Clifford circuits where the elementary systems are continuous-variable systems or discrete systems of odd-prime dimension. These types of circuit are distinguished by having phase-space representations that serve to define their classical counterparts. For discrete systems, the phase-space coordinates are also discrete variables. We show that for each gate in the generating set, one can associate a symplectomorphism on the phase-space and to each of these one can associate a generating function, defined on two copies of the configuration space. For discrete systems, the latter association is achieved using tools from algebraic geometry. Finally, we show that if the action functional for a discrete-time path through a sequence of gates is defined using the sum of the corresponding generating functions, then it yields the correct relative phases for the path-sum expression. These results are likely to be relevant for quantizing physical theories where time is fundamentally discrete, characterizing the classical limit of discrete-time quantum dynamics, and proving complexity results for quantum circuits.

Optical triple-in digital logic using nonlinear optical four-wave mixing

NASA Astrophysics Data System (ADS)

Widjaja, Joewono; Tomita, Yasuo

1995-08-01

A new programmable optical processor is proposed for implementing triple-in combinatorial digital logic that uses four-wave mixing. Binary-coded decimal-to-octal decoding is experimentally demonstrated by use of a photorefractive BaTiO 3 crystal. The result confirms the feasibility of the proposed system.

Combinatorial evaluation of the laccase-mediator system (LMS) in the oxidation of veratryl alcohol

USDA-ARS?s Scientific Manuscript database

Identifying suitable reaction conditions remains an important task in the development of practical enzyme catalysts. Laccases play an important role in the biological break down of lignin and have great potential in the deconstruction of lignocellulosic feedstocks. We examined 16 laccases, both co...

Selective oxidation of lignin model compounds – a combinatorial application of the laccase-mediator system

USDA-ARS?s Scientific Manuscript database

Identifying suitable reaction conditions remains an important task in the development of practical enzyme catalysts. Laccases play an important role in the biological break down of lignin and have great potential in the deconstruction of lignocellulosic feedstocks. We examined 16 laccases, both comm...

An extension of the OpenModelica compiler for using Modelica models in a discrete event simulation

DOE PAGES

Nutaro, James

2014-11-03

In this article, a new back-end and run-time system is described for the OpenModelica compiler. This new back-end transforms a Modelica model into a module for the adevs discrete event simulation package, thereby extending adevs to encompass complex, hybrid dynamical systems. The new run-time system that has been built within the adevs simulation package supports models with state-events and time-events and that comprise differential-algebraic systems with high index. Finally, although the procedure for effecting this transformation is based on adevs and the Discrete Event System Specification, it can be adapted to any discrete event simulation package.

XML Encoding of Features Describing Rule-Based Modeling of Reaction Networks with Multi-Component Molecular Complexes

PubMed Central

Blinov, Michael L.; Moraru, Ion I.

2011-01-01

Multi-state molecules and multi-component complexes are commonly involved in cellular signaling. Accounting for molecules that have multiple potential states, such as a protein that may be phosphorylated on multiple residues, and molecules that combine to form heterogeneous complexes located among multiple compartments, generates an effect of combinatorial complexity. Models involving relatively few signaling molecules can include thousands of distinct chemical species. Several software tools (StochSim, BioNetGen) are already available to deal with combinatorial complexity. Such tools need information standards if models are to be shared, jointly evaluated and developed. Here we discuss XML conventions that can be adopted for modeling biochemical reaction networks described by user-specified reaction rules. These could form a basis for possible future extensions of the Systems Biology Markup Language (SBML). PMID:21464833

Exploring the formation pathways of donor-acceptor catenanes in aqueous dynamic combinatorial libraries.

PubMed

Cougnon, Fabien B L; Au-Yeung, Ho Yu; Pantoş, G Dan; Sanders, Jeremy K M

2011-03-09

The discovery through dynamic combinatorial chemistry (DCC) of a new generation of donor-acceptor [2]catenanes highlights the power of DCC to access unprecedented structures. While conventional thinking has limited the scope of donor-acceptor catenanes to strictly alternating stacks of donor (D) and acceptor (A) aromatic units, DCC is demonstrated in this paper to give access to unusual DAAD, DADD, and ADAA stacks. Each of these catenanes has specific structural requirements, allowing control of their formation. On the basis of these results, and on the observation that the catenanes represent kinetic bottlenecks in the reaction pathway, we propose a mechanism that explains and predicts the structures formed. Furthermore, the spontaneous assembly of catenanes in aqueous dynamic systems gives a fundamental insight into the role played by hydrophobic effect and donor-acceptor interactions when building such complex architectures.

A Discriminative Sentence Compression Method as Combinatorial Optimization Problem

NASA Astrophysics Data System (ADS)

Hirao, Tsutomu; Suzuki, Jun; Isozaki, Hideki

In the study of automatic summarization, the main research topic was `important sentence extraction' but nowadays `sentence compression' is a hot research topic. Conventional sentence compression methods usually transform a given sentence into a parse tree or a dependency tree, and modify them to get a shorter sentence. However, this method is sometimes too rigid. In this paper, we regard sentence compression as an combinatorial optimization problem that extracts an optimal subsequence of words. Hori et al. also proposed a similar method, but they used only a small number of features and their weights were tuned by hand. We introduce a large number of features such as part-of-speech bigrams and word position in the sentence. Furthermore, we train the system by discriminative learning. According to our experiments, our method obtained better score than other methods with statistical significance.

Structure-based design of combinatorial mutagenesis libraries

PubMed Central

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

2015-01-01

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. PMID:25611189

Structure-based design of combinatorial mutagenesis libraries.

PubMed

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

2015-05-01

The development of protein variants with improved properties (thermostability, binding affinity, catalytic activity, etc.) has greatly benefited from the application of high-throughput screens evaluating large, diverse combinatorial libraries. At the same time, since only a very limited portion of sequence space can be experimentally constructed and tested, an attractive possibility is to use computational protein design to focus libraries on a productive portion of the space. We present a general-purpose method, called "Structure-based Optimization of Combinatorial Mutagenesis" (SOCoM), which can optimize arbitrarily large combinatorial mutagenesis libraries directly based on structural energies of their constituents. SOCoM chooses both positions and substitutions, employing a combinatorial optimization framework based on library-averaged energy potentials in order to avoid explicitly modeling every variant in every possible library. In case study applications to green fluorescent protein, β-lactamase, and lipase A, SOCoM optimizes relatively small, focused libraries whose variants achieve energies comparable to or better than previous library design efforts, as well as larger libraries (previously not designable by structure-based methods) whose variants cover greater diversity while still maintaining substantially better energies than would be achieved by representative random library approaches. By allowing the creation of large-scale combinatorial libraries based on structural calculations, SOCoM promises to increase the scope of applicability of computational protein design and improve the hit rate of discovering beneficial variants. While designs presented here focus on variant stability (predicted by total energy), SOCoM can readily incorporate other structure-based assessments, such as the energy gap between alternative conformational or bound states. © 2015 The Protein Society.

Principles of Discrete Time Mechanics

NASA Astrophysics Data System (ADS)

Jaroszkiewicz, George

2014-04-01

1. Introduction; 2. The physics of discreteness; 3. The road to calculus; 4. Temporal discretization; 5. Discrete time dynamics architecture; 6. Some models; 7. Classical cellular automata; 8. The action sum; 9. Worked examples; 10. Lee's approach to discrete time mechanics; 11. Elliptic billiards; 12. The construction of system functions; 13. The classical discrete time oscillator; 14. Type 2 temporal discretization; 15. Intermission; 16. Discrete time quantum mechanics; 17. The quantized discrete time oscillator; 18. Path integrals; 19. Quantum encoding; 20. Discrete time classical field equations; 21. The discrete time Schrodinger equation; 22. The discrete time Klein-Gordon equation; 23. The discrete time Dirac equation; 24. Discrete time Maxwell's equations; 25. The discrete time Skyrme model; 26. Discrete time quantum field theory; 27. Interacting discrete time scalar fields; 28. Space, time and gravitation; 29. Causality and observation; 30. Concluding remarks; Appendix A. Coherent states; Appendix B. The time-dependent oscillator; Appendix C. Quaternions; Appendix D. Quantum registers; References; Index.

An Automated Analyzer System to Strengthen Teaching and Research Infrastructure at West Virginia State University

DTIC Science & Technology

2015-08-18

SECURITY CLASSIFICATION OF: Arena 60 Discrete Photometric Analyzer System and ancillary instrumentation were acquired to increase our analytical...Infrastructure at West Virginia State University Report Title Arena 60 Discrete Photometric Analyzer System and ancillary instrumentation were acquired...Progress Principal Accomplishments: a. One Postdoctoral fellow was trained using the automated Arena 60 Discrete Photometric Analyzer and

Bootstrapping on Undirected Binary Networks Via Statistical Mechanics

NASA Astrophysics Data System (ADS)

Fushing, Hsieh; Chen, Chen; Liu, Shan-Yu; Koehl, Patrice

2014-09-01

We propose a new method inspired from statistical mechanics for extracting geometric information from undirected binary networks and generating random networks that conform to this geometry. In this method an undirected binary network is perceived as a thermodynamic system with a collection of permuted adjacency matrices as its states. The task of extracting information from the network is then reformulated as a discrete combinatorial optimization problem of searching for its ground state. To solve this problem, we apply multiple ensembles of temperature regulated Markov chains to establish an ultrametric geometry on the network. This geometry is equipped with a tree hierarchy that captures the multiscale community structure of the network. We translate this geometry into a Parisi adjacency matrix, which has a relative low energy level and is in the vicinity of the ground state. The Parisi adjacency matrix is then further optimized by making block permutations subject to the ultrametric geometry. The optimal matrix corresponds to the macrostate of the original network. An ensemble of random networks is then generated such that each of these networks conforms to this macrostate; the corresponding algorithm also provides an estimate of the size of this ensemble. By repeating this procedure at different scales of the ultrametric geometry of the network, it is possible to compute its evolution entropy, i.e. to estimate the evolution of its complexity as we move from a coarse to a fine description of its geometric structure. We demonstrate the performance of this method on simulated as well as real data networks.

Transport of calcium ions through a bulk membrane by use of a dynamic combinatorial library.

PubMed

Saggiomo, Vittorio; Lüning, Ulrich

2009-07-07

In a bulk membrane transport experiment, a dynamic combinatorial library (DCL) has been used to transport calcium ions; the calcium ions amplify the formation of a macrocyclic carrier which results in transport.

Counting Pizza Pieces and Other Combinatorial Problems.

ERIC Educational Resources Information Center

Maier, Eugene

1988-01-01

The general combinatorial problem of counting the number of regions into which the interior of a circle is divided by a family of lines is considered. A general formula is developed and its use is illustrated in two situations. (PK)

On the existence of binary simplex codes. [using combinatorial construction

NASA Technical Reports Server (NTRS)

Taylor, H.

1977-01-01

Using a simple combinatorial construction, the existence of a binary simplex code with m codewords for all m is greater than or equal to 1 is proved. The problem of the shortest possible length is left open.

Application of combinatorial biocatalysis for a unique ring expansion of dihydroxymethylzearalenone

USDA-ARS?s Scientific Manuscript database

Combinatorial biocatalysis was applied to generate a diverse set of dihydroxymethylzearalenone derivatives with modified ring structure. In one chemoenzymatic reaction sequence, dihydroxymethylzearalenone was first subjected to a unique enzyme-catalyzed oxidative ring opening reaction that creates ...

A road to practical dielectric elastomer actuators based robotics and mechatronics: discrete actuation

NASA Astrophysics Data System (ADS)

Plante, Jean-Sébastien; Devita, Lauren M.; Dubowsky, Steven

2007-04-01

Fundamental studies of Dielectric Elastomer Actuators (DEAs) using viscoelastic materials such as VHB 4905/4910 from 3M showed significant advantages at high stretch rates. The film's viscous forces increase actuator life and the short power-on times minimize energy losses through current leakage. This paper presents a design paradigm that exploits these fundamental properties of DEAs called discrete actuation. Discrete actuation uses DEAs at high stretch rates to change the states of robotic or mechatronic systems in discrete steps. Each state of the system is stable and can be maintained without actuator power. Discrete actuation can be used in robotic and mechatronic applications such as manipulation and locomotion. The resolution of such systems increases with the number of discrete states, 10 to 100 being sufficient for many applications. An MRI-guided needle positioning device for cancer treatments and a space exploration robot using hopping for locomotion are presented as examples of this concept.

Supervisory Control of Discrete Event Systems Modeled by Mealy Automata with Nondeterministic Output Functions

NASA Astrophysics Data System (ADS)

Ushio, Toshimitsu; Takai, Shigemasa

Supervisory control is a general framework of logical control of discrete event systems. A supervisor assigns a set of control-disabled controllable events based on observed events so that the controlled discrete event system generates specified languages. In conventional supervisory control, it is assumed that observed events are determined by internal events deterministically. But, this assumption does not hold in a discrete event system with sensor errors and a mobile system, where each observed event depends on not only an internal event but also a state just before the occurrence of the internal event. In this paper, we model such a discrete event system by a Mealy automaton with a nondeterministic output function. We introduce two kinds of supervisors: one assigns each control action based on a permissive policy and the other based on an anti-permissive one. We show necessary and sufficient conditions for the existence of each supervisor. Moreover, we discuss the relationship between the supervisors in the case that the output function is determinisitic.

Metriplectic integrators for the Landau collision operator

DOE PAGES

Kraus, Michael; Hirvijoki, Eero

2017-10-02

Here, we present a novel framework for addressing the nonlinear Landau collision integral in terms of finite element and other subspace projection methods. We employ the underlying metriplectic structure of the Landau collision integral and, using a Galerkin discretization for the velocity space, we transform the infinite-dimensional system into a finite-dimensional, time-continuous metriplectic system. Temporal discretization is accomplished using the concept of discrete gradients. The conservation of energy, momentum, and particle densities, as well as the production of entropy is demonstrated algebraically for the fully discrete system. Due to the generality of our approach, the conservation properties and the monotonicmore » behavior of entropy are guaranteed for finite element discretizations, in general, independently of the mesh configuration.« less

Conceptual Modeling of a Quantum Key Distribution Simulation Framework Using the Discrete Event System Specification

DTIC Science & Technology

2014-09-18

and full/scale experimental verifications towards ground/ satellite quantum key distribution0 Oat Qhotonics 4235>9+7,=5;9!អ \\58^ Zin K. Dao Z. Miu T...Conceptual Modeling of a Quantum Key Distribution Simulation Framework Using the Discrete Event System Specification DISSERTATION Jeffrey D. Morris... QUANTUM KEY DISTRIBUTION SIMULATION FRAMEWORK USING THE DISCRETE EVENT SYSTEM SPECIFICATION DISSERTATION Presented to the Faculty Department of Systems

Criticism of EFSA's scientific opinion on combinatorial effects of 'stacked' GM plants.

PubMed

Bøhn, Thomas

2018-01-01

Recent genetically modified plants tend to include both insect resistance and herbicide tolerance traits. Some of these 'stacked' GM plants have multiple Cry-toxins expressed as well as tolerance to several herbicides. This means that non-target organisms in the environment (biodiversity) will be co-exposed to multiple stressors simultaneously. A similar co-exposure may happen to consumers through chemical residues in the food chain. EFSA, the responsible unit for minimizing risk of harm in European food chains, has expressed its scientific interest in combinatorial effects. However, when new data showed how two Cry-toxins acted in combination (added toxicity), and that the same Cry-toxins showed combinatorial effects when co-exposed with Roundup (Bøhn et al., 2016), EFSA dismissed these new peer-reviewed results. In effect, EFSA claimed that combinatorial effects are not relevant for itself. EFSA was justifying this by referring to a policy question, and by making invalid assumptions, which could have been checked directly with the lead-author. With such approach, EFSA may miss the opportunity to improve its environmental and health risk assessment of toxins and pesticides in the food chain. Failure to follow its own published requests for combinatorial effects research, may also risk jeopardizing EFSA's scientific and public reputation. Copyright © 2017. Published by Elsevier Ltd.

Border and surface tracing--theoretical foundations.

PubMed

Brimkov, Valentin E; Klette, Reinhard

2008-04-01

In this paper we define and study digital manifolds of arbitrary dimension, and provide (in particular)a general theoretical basis for curve or surface tracing in picture analysis. The studies involve properties such as one-dimensionality of digital curves and (n-1)-dimensionality of digital hypersurfaces that makes them discrete analogs of corresponding notions in continuous topology. The presented approach is fully based on the concept of adjacency relation and complements the concept of dimension as common in combinatorial topology. This work appears to be the first one on digital manifolds based ona graph-theoretical definition of dimension. In particular, in the n-dimensional digital space, a digital curve is a one-dimensional object and a digital hypersurface is an (n-1)-dimensional object, as it is in the case of curves and hypersurfaces in the Euclidean space. Relying on the obtained properties of digital hypersurfaces, we propose a uniform approach for studying good pairs defined by separations and obtain a classification of good pairs in arbitrary dimension. We also discuss possible applications of the presented definitions and results.

Approximate labeling via graph cuts based on linear programming.

PubMed

Komodakis, Nikos; Tziritas, Georgios

2007-08-01

A new framework is presented for both understanding and developing graph-cut-based combinatorial algorithms suitable for the approximate optimization of a very wide class of Markov Random Fields (MRFs) that are frequently encountered in computer vision. The proposed framework utilizes tools from the duality theory of linear programming in order to provide an alternative and more general view of state-of-the-art techniques like the \\alpha-expansion algorithm, which is included merely as a special case. Moreover, contrary to \\alpha-expansion, the derived algorithms generate solutions with guaranteed optimality properties for a much wider class of problems, for example, even for MRFs with nonmetric potentials. In addition, they are capable of providing per-instance suboptimality bounds in all occasions, including discrete MRFs with an arbitrary potential function. These bounds prove to be very tight in practice (that is, very close to 1), which means that the resulting solutions are almost optimal. Our algorithms' effectiveness is demonstrated by presenting experimental results on a variety of low-level vision tasks, such as stereo matching, image restoration, image completion, and optical flow estimation, as well as on synthetic problems.

Core and region-enriched networks of behaviorally regulated genes and the singing genome

PubMed Central

Whitney, Osceola; Pfenning, Andreas R.; Howard, Jason T.; Blatti, Charles A; Liu, Fang; Ward, James M.; Wang, Rui; Audet, Jean-Nicolas; Kellis, Manolis; Mukherjee, Sayan; Sinha, Saurabh; Hartemink, Alexander J.; West, Anne E.; Jarvis, Erich D.

2015-01-01

Songbirds represent an important model organism for elucidating molecular mechanisms that link genes with complex behaviors, in part because they have discrete vocal learning circuits that have parallels with those that mediate human speech. We found that ~10% of the genes in the avian genome were regulated by singing, and we found a striking regional diversity of both basal and singing-induced programs in the four key song nuclei of the zebra finch, a vocal learning songbird. The region-enriched patterns were a result of distinct combinations of region-enriched transcription factors (TFs), their binding motifs, and presinging acetylation of histone 3 at lysine 27 (H3K27ac) enhancer activity in the regulatory regions of the associated genes. RNA interference manipulations validated the role of the calcium-response transcription factor (CaRF) in regulating genes preferentially expressed in specific song nuclei in response to singing. Thus, differential combinatorial binding of a small group of activity-regulated TFs and predefined epigenetic enhancer activity influences the anatomical diversity of behaviorally regulated gene networks. PMID:25504732

A Novel Hybrid Clonal Selection Algorithm with Combinatorial Recombination and Modified Hypermutation Operators for Global Optimization

PubMed Central

Lin, Jingjing; Jing, Honglei

2016-01-01

Artificial immune system is one of the most recently introduced intelligence methods which was inspired by biological immune system. Most immune system inspired algorithms are based on the clonal selection principle, known as clonal selection algorithms (CSAs). When coping with complex optimization problems with the characteristics of multimodality, high dimension, rotation, and composition, the traditional CSAs often suffer from the premature convergence and unsatisfied accuracy. To address these concerning issues, a recombination operator inspired by the biological combinatorial recombination is proposed at first. The recombination operator could generate the promising candidate solution to enhance search ability of the CSA by fusing the information from random chosen parents. Furthermore, a modified hypermutation operator is introduced to construct more promising and efficient candidate solutions. A set of 16 common used benchmark functions are adopted to test the effectiveness and efficiency of the recombination and hypermutation operators. The comparisons with classic CSA, CSA with recombination operator (RCSA), and CSA with recombination and modified hypermutation operator (RHCSA) demonstrate that the proposed algorithm significantly improves the performance of classic CSA. Moreover, comparison with the state-of-the-art algorithms shows that the proposed algorithm is quite competitive. PMID:27698662

Improved robustness and performance of discrete time sliding mode control systems.

PubMed

Chakrabarty, Sohom; Bartoszewicz, Andrzej

2016-11-01

This paper presents a theoretical analysis along with simulations to show that increased robustness can be achieved for discrete time sliding mode control systems by choosing the sliding variable, or the output, to be of relative degree two instead of relative degree one. In other words it successfully reduces the ultimate bound of the sliding variable compared to the ultimate bound for standard discrete time sliding mode control systems. It is also found out that for such a selection of relative degree two output of the discrete time system, the reduced order system during sliding becomes finite time stable in absence of disturbance. With disturbance, it becomes finite time ultimately bounded. Copyright © 2016 ISA. Published by Elsevier Ltd. All rights reserved.

Adaptive NN controller design for a class of nonlinear MIMO discrete-time systems.

PubMed

Liu, Yan-Jun; Tang, Li; Tong, Shaocheng; Chen, C L Philip

2015-05-01

An adaptive neural network tracking control is studied for a class of multiple-input multiple-output (MIMO) nonlinear systems. The studied systems are in discrete-time form and the discretized dead-zone inputs are considered. In addition, the studied MIMO systems are composed of N subsystems, and each subsystem contains unknown functions and external disturbance. Due to the complicated framework of the discrete-time systems, the existence of the dead zone and the noncausal problem in discrete-time, it brings about difficulties for controlling such a class of systems. To overcome the noncausal problem, by defining the coordinate transformations, the studied systems are transformed into a special form, which is suitable for the backstepping design. The radial basis functions NNs are utilized to approximate the unknown functions of the systems. The adaptation laws and the controllers are designed based on the transformed systems. By using the Lyapunov method, it is proved that the closed-loop system is stable in the sense that the semiglobally uniformly ultimately bounded of all the signals and the tracking errors converge to a bounded compact set. The simulation examples and the comparisons with previous approaches are provided to illustrate the effectiveness of the proposed control algorithm.

Combinatorial explosion in model gene networks

NASA Astrophysics Data System (ADS)

Edwards, R.; Glass, L.

2000-09-01

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

Combinatorial explosion in model gene networks.

PubMed

Edwards, R.; Glass, L.

2000-09-01

The explosive growth in knowledge of the genome of humans and other organisms leaves open the question of how the functioning of genes in interacting networks is coordinated for orderly activity. One approach to this problem is to study mathematical properties of abstract network models that capture the logical structures of gene networks. The principal issue is to understand how particular patterns of activity can result from particular network structures, and what types of behavior are possible. We study idealized models in which the logical structure of the network is explicitly represented by Boolean functions that can be represented by directed graphs on n-cubes, but which are continuous in time and described by differential equations, rather than being updated synchronously via a discrete clock. The equations are piecewise linear, which allows significant analysis and facilitates rapid integration along trajectories. We first give a combinatorial solution to the question of how many distinct logical structures exist for n-dimensional networks, showing that the number increases very rapidly with n. We then outline analytic methods that can be used to establish the existence, stability and periods of periodic orbits corresponding to particular cycles on the n-cube. We use these methods to confirm the existence of limit cycles discovered in a sample of a million randomly generated structures of networks of 4 genes. Even with only 4 genes, at least several hundred different patterns of stable periodic behavior are possible, many of them surprisingly complex. We discuss ways of further classifying these periodic behaviors, showing that small mutations (reversal of one or a few edges on the n-cube) need not destroy the stability of a limit cycle. Although these networks are very simple as models of gene networks, their mathematical transparency reveals relationships between structure and behavior, they suggest that the possibilities for orderly dynamics in such networks are extremely rich and they offer novel ways to think about how mutations can alter dynamics. (c) 2000 American Institute of Physics.

The transmission process: A combinatorial stochastic process for the evolution of transmission trees over networks.

PubMed

Sainudiin, Raazesh; Welch, David

2016-12-07

We derive a combinatorial stochastic process for the evolution of the transmission tree over the infected vertices of a host contact network in a susceptible-infected (SI) model of an epidemic. Models of transmission trees are crucial to understanding the evolution of pathogen populations. We provide an explicit description of the transmission process on the product state space of (rooted planar ranked labelled) binary transmission trees and labelled host contact networks with SI-tags as a discrete-state continuous-time Markov chain. We give the exact probability of any transmission tree when the host contact network is a complete, star or path network - three illustrative examples. We then develop a biparametric Beta-splitting model that directly generates transmission trees with exact probabilities as a function of the model parameters, but without explicitly modelling the underlying contact network, and show that for specific values of the parameters we can recover the exact probabilities for our three example networks through the Markov chain construction that explicitly models the underlying contact network. We use the maximum likelihood estimator (MLE) to consistently infer the two parameters driving the transmission process based on observations of the transmission trees and use the exact MLE to characterize equivalence classes over the space of contact networks with a single initial infection. An exploratory simulation study of the MLEs from transmission trees sampled from three other deterministic and four random families of classical contact networks is conducted to shed light on the relation between the MLEs of these families with some implications for statistical inference along with pointers to further extensions of our models. The insights developed here are also applicable to the simplest models of "meme" evolution in online social media networks through transmission events that can be distilled from observable actions such as "likes", "mentions", "retweets" and "+1s" along with any concomitant comments. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

Running Clubs--A Combinatorial Investigation.

ERIC Educational Resources Information Center

Nissen, Phillip; Taylor, John

1991-01-01

Presented is a combinatorial problem based on the Hash House Harriers rule which states that the route of the run should not have previously been traversed by the club. Discovered is how many weeks the club can meet before the rule has to be broken. (KR)

Quantum Resonance Approach to Combinatorial Optimization

NASA Technical Reports Server (NTRS)

Zak, Michail

1997-01-01

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

Combinatorial Fusion Analysis for Meta Search Information Retrieval

NASA Astrophysics Data System (ADS)

Hsu, D. Frank; Taksa, Isak

Leading commercial search engines are built as single event systems. In response to a particular search query, the search engine returns a single list of ranked search results. To find more relevant results the user must frequently try several other search engines. A meta search engine was developed to enhance the process of multi-engine querying. The meta search engine queries several engines at the same time and fuses individual engine results into a single search results list. The fusion of multiple search results has been shown (mostly experimentally) to be highly effective. However, the question of why and how the fusion should be done still remains largely unanswered. In this chapter, we utilize the combinatorial fusion analysis proposed by Hsu et al. to analyze combination and fusion of multiple sources of information. A rank/score function is used in the design and analysis of our framework. The framework provides a better understanding of the fusion phenomenon in information retrieval. For example, to improve the performance of the combined multiple scoring systems, it is necessary that each of the individual scoring systems has relatively high performance and the individual scoring systems are diverse. Additionally, we illustrate various applications of the framework using two examples from the information retrieval domain.

Breast cancer prognosis by combinatorial analysis of gene expression data.

PubMed

Alexe, Gabriela; Alexe, Sorin; Axelrod, David E; Bonates, Tibérius O; Lozina, Irina I; Reiss, Michael; Hammer, Peter L

2006-01-01

The potential of applying data analysis tools to microarray data for diagnosis and prognosis is illustrated on the recent breast cancer dataset of van 't Veer and coworkers. We re-examine that dataset using the novel technique of logical analysis of data (LAD), with the double objective of discovering patterns characteristic for cases with good or poor outcome, using them for accurate and justifiable predictions; and deriving novel information about the role of genes, the existence of special classes of cases, and other factors. Data were analyzed using the combinatorics and optimization-based method of LAD, recently shown to provide highly accurate diagnostic and prognostic systems in cardiology, cancer proteomics, hematology, pulmonology, and other disciplines. LAD identified a subset of 17 of the 25,000 genes, capable of fully distinguishing between patients with poor, respectively good prognoses. An extensive list of 'patterns' or 'combinatorial biomarkers' (that is, combinations of genes and limitations on their expression levels) was generated, and 40 patterns were used to create a prognostic system, shown to have 100% and 92.9% weighted accuracy on the training and test sets, respectively. The prognostic system uses fewer genes than other methods, and has similar or better accuracy than those reported in other studies. Out of the 17 genes identified by LAD, three (respectively, five) were shown to play a significant role in determining poor (respectively, good) prognosis. Two new classes of patients (described by similar sets of covering patterns, gene expression ranges, and clinical features) were discovered. As a by-product of the study, it is shown that the training and the test sets of van 't Veer have differing characteristics. The study shows that LAD provides an accurate and fully explanatory prognostic system for breast cancer using genomic data (that is, a system that, in addition to predicting good or poor prognosis, provides an individualized explanation of the reasons for that prognosis for each patient). Moreover, the LAD model provides valuable insights into the roles of individual and combinatorial biomarkers, allows the discovery of new classes of patients, and generates a vast library of biomedical research hypotheses.

A Study of the Use of a Handheld Computer Algebra System in Discrete Mathematics

ERIC Educational Resources Information Center

Powers, Robert A.; Allison, Dean E.; Grassl, Richard M.

2005-01-01

This study investigated the impact of the TI-92 handheld Computer Algebra System (CAS) on student achievement in a discrete mathematics course. Specifically, the researchers examined the differences between a CAS section and a control section of discrete mathematics on students' in-class examinations. Additionally, they analysed student approaches…

Image compression-encryption algorithms by combining hyper-chaotic system with discrete fractional random transform

NASA Astrophysics Data System (ADS)

Gong, Lihua; Deng, Chengzhi; Pan, Shumin; Zhou, Nanrun

2018-07-01

Based on hyper-chaotic system and discrete fractional random transform, an image compression-encryption algorithm is designed. The original image is first transformed into a spectrum by the discrete cosine transform and the resulting spectrum is compressed according to the method of spectrum cutting. The random matrix of the discrete fractional random transform is controlled by a chaotic sequence originated from the high dimensional hyper-chaotic system. Then the compressed spectrum is encrypted by the discrete fractional random transform. The order of DFrRT and the parameters of the hyper-chaotic system are the main keys of this image compression and encryption algorithm. The proposed algorithm can compress and encrypt image signal, especially can encrypt multiple images once. To achieve the compression of multiple images, the images are transformed into spectra by the discrete cosine transform, and then the spectra are incised and spliced into a composite spectrum by Zigzag scanning. Simulation results demonstrate that the proposed image compression and encryption algorithm is of high security and good compression performance.

Fast and Efficient Discrimination of Traveling Salesperson Problem Stimulus Difficulty

ERIC Educational Resources Information Center

Dry, Matthew J.; Fontaine, Elizabeth L.

2014-01-01

The Traveling Salesperson Problem (TSP) is a computationally difficult combinatorial optimization problem. In spite of its relative difficulty, human solvers are able to generate close-to-optimal solutions in a close-to-linear time frame, and it has been suggested that this is due to the visual system's inherent sensitivity to certain geometric…

Resonance assignment of disordered protein with repetitive and overlapping sequence using combinatorial approach reveals initial structural propensities and local restrictions in the denatured state.

PubMed

Malik, Nikita; Kumar, Ashutosh

2016-09-01

NMR resonance assignment of intrinsically disordered proteins poses a challenge because of the limited dispersion of amide proton chemical shifts. This becomes even more complex with the increase in the size of the system. Residue specific selective labeling/unlabeling experiments have been used to resolve the overlap, but require multiple sample preparations. Here, we demonstrate an assignment strategy requiring only a single sample of uniformly labeled (13)C,(15)N-protein. We have used a combinatorial approach, involving 3D-HNN, CC(CO)NH and 2D-MUSIC, which allowed us to assign a denatured centromeric protein Cse4 of 229 residues. Further, we show that even the less sensitive experiments, when used in an efficient manner can lead to the complete assignment of a complex system without the use of specialized probes in a relatively short time frame. The assignment of the amino acids discloses the presence of local structural propensities even in the denatured state accompanied by restricted motion in certain regions that provides insights into the early folding events of the protein.

Directed combinatorial mutagenesis of Escherichia coli for complex phenotype engineering

DOE Office of Scientific and Technical Information (OSTI.GOV)

Liu, Rongming; Liang, Liya; Garst, Andrew D.

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

Directed combinatorial mutagenesis of Escherichia coli for complex phenotype engineering

DOE PAGES

Liu, Rongming; Liang, Liya; Garst, Andrew D.; ...

2018-03-29

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

On the relationship of steady states of continuous and discrete models arising from biology.

PubMed

Veliz-Cuba, Alan; Arthur, Joseph; Hochstetler, Laura; Klomps, Victoria; Korpi, Erikka

2012-12-01

For many biological systems that have been modeled using continuous and discrete models, it has been shown that such models have similar dynamical properties. In this paper, we prove that this happens in more general cases. We show that under some conditions there is a bijection between the steady states of continuous and discrete models arising from biological systems. Our results also provide a novel method to analyze certain classes of nonlinear models using discrete mathematics.

ADAM: Analysis of Discrete Models of Biological Systems Using Computer Algebra

PubMed Central

2011-01-01

Background Many biological systems are modeled qualitatively with discrete models, such as probabilistic Boolean networks, logical models, Petri nets, and agent-based models, to gain a better understanding of them. The computational complexity to analyze the complete dynamics of these models grows exponentially in the number of variables, which impedes working with complex models. There exist software tools to analyze discrete models, but they either lack the algorithmic functionality to analyze complex models deterministically or they are inaccessible to many users as they require understanding the underlying algorithm and implementation, do not have a graphical user interface, or are hard to install. Efficient analysis methods that are accessible to modelers and easy to use are needed. Results We propose a method for efficiently identifying attractors and introduce the web-based tool Analysis of Dynamic Algebraic Models (ADAM), which provides this and other analysis methods for discrete models. ADAM converts several discrete model types automatically into polynomial dynamical systems and analyzes their dynamics using tools from computer algebra. Specifically, we propose a method to identify attractors of a discrete model that is equivalent to solving a system of polynomial equations, a long-studied problem in computer algebra. Based on extensive experimentation with both discrete models arising in systems biology and randomly generated networks, we found that the algebraic algorithms presented in this manuscript are fast for systems with the structure maintained by most biological systems, namely sparseness and robustness. For a large set of published complex discrete models, ADAM identified the attractors in less than one second. Conclusions Discrete modeling techniques are a useful tool for analyzing complex biological systems and there is a need in the biological community for accessible efficient analysis tools. ADAM provides analysis methods based on mathematical algorithms as a web-based tool for several different input formats, and it makes analysis of complex models accessible to a larger community, as it is platform independent as a web-service and does not require understanding of the underlying mathematics. PMID:21774817

Combinatorial RNA Interference Therapy Prevents Selection of Pre-existing HBV Variants in Human Liver Chimeric Mice

PubMed Central

Shih, Yao-Ming; Sun, Cheng-Pu; Chou, Hui-Hsien; Wu, Tzu-Hui; Chen, Chun-Chi; Wu, Ping-Yi; Enya Chen, Yu-Chen; Bissig, Karl-Dimiter; Tao, Mi-Hua

2015-01-01

Selection of escape mutants with mutations within the target sequence could abolish the antiviral RNA interference activity. Here, we investigated the impact of a pre-existing shRNA-resistant HBV variant on the efficacy of shRNA therapy. We previously identified a highly potent shRNA, S1, which, when delivered by an adeno-associated viral vector, effectively inhibits HBV replication in HBV transgenic mice. We applied the “PICKY” software to systemically screen the HBV genome, then used hydrodynamic transfection and HBV transgenic mice to identify additional six highly potent shRNAs. Human liver chimeric mice were infected with a mixture of wild-type and T472C HBV, a S1-resistant HBV variant, and then treated with a single or combined shRNAs. The presence of T472C mutant compromised the therapeutic efficacy of S1 and resulted in replacement of serum wild-type HBV by T472C HBV. In contrast, combinatorial therapy using S1 and P28, one of six potent shRNAs, markedly reduced titers for both wild-type and T472C HBV. Interestingly, treatment with P28 alone led to the emergence of escape mutants with mutations in the P28 target region. Our results demonstrate that combinatorial RNAi therapy can minimize the escape of resistant viral mutants in chronic HBV patients. PMID:26482836

HnRNP L and L-like cooperate in multiple-exon regulation of CD45 alternative splicing

PubMed Central

Preußner, Marco; Schreiner, Silke; Hung, Lee-Hsueh; Porstner, Martina; Jäck, Hans-Martin; Benes, Vladimir; Rätsch, Gunnar; Bindereif, Albrecht

2012-01-01

CD45 encodes a trans-membrane protein-tyrosine phosphatase expressed in diverse cells of the immune system. By combinatorial use of three variable exons 4–6, isoforms are generated that differ in their extracellular domain, thereby modulating phosphatase activity and immune response. Alternative splicing of these CD45 exons involves two heterogeneous ribonucleoproteins, hnRNP L and its cell-type specific paralog hnRNP L-like (LL). To address the complex combinatorial splicing of exons 4–6, we investigated hnRNP L/LL protein expression in human B-cells in relation to CD45 splicing patterns, applying RNA-Seq. In addition, mutational and RNA-binding analyses were carried out in HeLa cells. We conclude that hnRNP LL functions as the major CD45 splicing repressor, with two CA elements in exon 6 as its primary target. In exon 4, one element is targeted by both hnRNP L and LL. In contrast, exon 5 was never repressed on its own and only co-regulated with exons 4 and 6. Stable L/LL interaction requires CD45 RNA, specifically exons 4 and 6. We propose a novel model of combinatorial alternative splicing: HnRNP L and LL cooperate on the CD45 pre-mRNA, bridging exons 4 and 6 and looping out exon 5, thereby achieving full repression of the three variable exons. PMID:22402488

Formal Operations and Ego Identity in Adolescence.

ERIC Educational Resources Information Center

Wagner, Janis A.

1987-01-01

Investigated the relationship between the development of formal operations and the formation of ego identity in adolescence. Obtained significant positive correlations between combinatorial ability and degree of identity, suggesting that high identity may facilitate the application of combinatorial operations. Found some gender differences in task…

Manipulating Combinatorial Structures.

ERIC Educational Resources Information Center

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…

Gian-Carlos Rota and Combinatorial Math.

ERIC Educational Resources Information Center

Kolata, Gina Bari

1979-01-01

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

A Model of Students' Combinatorial Thinking

ERIC Educational Resources Information Center

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…

The LATL as locus of composition: MEG evidence from English and Arabic.

PubMed

Westerlund, Masha; Kastner, Itamar; Al Kaabi, Meera; Pylkkänen, Liina

2015-02-01

Neurolinguistic investigations into the processing of structured sentences as well as simple adjective-noun phrases point to the left anterior temporal lobe (LATL) as a leading candidate for basic linguistic composition. Here, we characterized the combinatory profile of the LATL over a variety of syntactic and semantic environments, and across two languages, English and Arabic. The contribution of the LATL was investigated across two types of composition: the optional modification of a predicate (modification) and the satisfaction of a predicate's argument position (argument saturation). Target words were presented during MEG recordings, either in combinatory contexts (e.g. "eats meat") or in non-combinatory contexts (preceded by an unpronounceable consonant string, e.g. "xqkr meat"). Across both languages, the LATL showed increased responses to words in combinatory contexts, an effect that was robust to composition type and word order. Together with related findings, these results solidify the role of the LATL in basic semantic composition. Copyright © 2014 Elsevier Inc. All rights reserved.

DNA Assembly Techniques for Next Generation Combinatorial Biosynthesis of Natural Products

PubMed Central

Cobb, Ryan E.; Ning, Jonathan C.; Zhao, Huimin

2013-01-01

Natural product scaffolds remain important leads for pharmaceutical development. However, transforming a natural product into a drug entity often requires derivatization to enhance the compound’s therapeutic properties. A powerful method by which to perform this derivatization is combinatorial biosynthesis, the manipulation of the genes in the corresponding pathway to divert synthesis towards novel derivatives. While these manipulations have traditionally been carried out via restriction digestion/ligation-based cloning, the shortcomings of such techniques limit their throughput and thus the scope of corresponding combinatorial biosynthesis experiments. In the burgeoning field of synthetic biology, the demand for facile DNA assembly techniques has promoted the development of a host of novel DNA assembly strategies. Here we describe the advantages of these recently-developed tools for rapid, efficient synthesis of large DNA constructs. We also discuss their potential to facilitate the simultaneous assembly of complete libraries of natural product biosynthetic pathways, ushering in the next generation of combinatorial biosynthesis. PMID:24127070

Novel Design Strategy for Checkpoint Kinase 2 Inhibitors Using Pharmacophore Modeling, Combinatorial Fusion, and Virtual Screening

PubMed Central

Wang, Yen-Ling

2014-01-01

Checkpoint kinase 2 (Chk2) has a great effect on DNA-damage and plays an important role in response to DNA double-strand breaks and related lesions. In this study, we will concentrate on Chk2 and the purpose is to find the potential inhibitors by the pharmacophore hypotheses (PhModels), combinatorial fusion, and virtual screening techniques. Applying combinatorial fusion into PhModels and virtual screening techniques is a novel design strategy for drug design. We used combinatorial fusion to analyze the prediction results and then obtained the best correlation coefficient of the testing set (r test) with the value 0.816 by combining the BesttrainBesttest and FasttrainFasttest prediction results. The potential inhibitors were selected from NCI database by screening according to BesttrainBesttest + FasttrainFasttest prediction results and molecular docking with CDOCKER docking program. Finally, the selected compounds have high interaction energy between a ligand and a receptor. Through these approaches, 23 potential inhibitors for Chk2 are retrieved for further study. PMID:24864236

A methodology to find the elementary landscape decomposition of combinatorial optimization problems.

PubMed

Chicano, Francisco; Whitley, L Darrell; Alba, Enrique

2011-01-01

A small number of combinatorial optimization problems have search spaces that correspond to elementary landscapes, where the objective function f is an eigenfunction of the Laplacian that describes the neighborhood structure of the search space. Many problems are not elementary; however, the objective function of a combinatorial optimization problem can always be expressed as a superposition of multiple elementary landscapes if the underlying neighborhood used is symmetric. This paper presents theoretical results that provide the foundation for algebraic methods that can be used to decompose the objective function of an arbitrary combinatorial optimization problem into a sum of subfunctions, where each subfunction is an elementary landscape. Many steps of this process can be automated, and indeed a software tool could be developed that assists the researcher in finding a landscape decomposition. This methodology is then used to show that the subset sum problem is a superposition of two elementary landscapes, and to show that the quadratic assignment problem is a superposition of three elementary landscapes.

Parallelization of combinatorial search when solving knapsack optimization problem on computing systems based on multicore processors

NASA Astrophysics Data System (ADS)

Rahman, P. A.

2018-05-01

This scientific paper deals with the model of the knapsack optimization problem and method of its solving based on directed combinatorial search in the boolean space. The offered by the author specialized mathematical model of decomposition of the search-zone to the separate search-spheres and the algorithm of distribution of the search-spheres to the different cores of the multi-core processor are also discussed. The paper also provides an example of decomposition of the search-zone to the several search-spheres and distribution of the search-spheres to the different cores of the quad-core processor. Finally, an offered by the author formula for estimation of the theoretical maximum of the computational acceleration, which can be achieved due to the parallelization of the search-zone to the search-spheres on the unlimited number of the processor cores, is also given.

A novel method for multifactorial bio-chemical experiments design based on combinational design theory.

PubMed

Wang, Xun; Sun, Beibei; Liu, Boyang; Fu, Yaping; Zheng, Pan

2017-01-01

Experimental design focuses on describing or explaining the multifactorial interactions that are hypothesized to reflect the variation. The design introduces conditions that may directly affect the variation, where particular conditions are purposely selected for observation. Combinatorial design theory deals with the existence, construction and properties of systems of finite sets whose arrangements satisfy generalized concepts of balance and/or symmetry. In this work, borrowing the concept of "balance" in combinatorial design theory, a novel method for multifactorial bio-chemical experiments design is proposed, where balanced templates in combinational design are used to select the conditions for observation. Balanced experimental data that covers all the influencing factors of experiments can be obtianed for further processing, such as training set for machine learning models. Finally, a software based on the proposed method is developed for designing experiments with covering influencing factors a certain number of times.

Combinatorial search for green and blue phosphors of high thermal stabilities under UV excitation based on the K(Sr1-x-y)PO4:Tb3+ xEu2+y system.

PubMed

Chan, Ting-Shan; Liu, Yao-Min; Liu, Ru-Shi

2008-01-01

The present investigation aims at the synthesis of KSr 1-x-y PO 4:Tb(3+) x Eu(2+) y phosphors using the combinatorial chemistry method. We have developed square-type arrays consisting of 121 compositions to investigate the optimum composition and luminescence properties of KSrPO 4 host matrix under 365 nm ultraviolet (UV) light. The optimized compositions of phosphors were found to be KSr 0.93PO 4:Tb(3+) 0.07 (green) and KSr 0.995PO 4:Eu(2+) 0.005 (blue). These phosphors showed good thermal luminescence stability better than commercially available YAG:Ce at temperature above 200 degrees C. The result indicates that the KSr 1-x-y PO 4:Tb(3+) x Eu (2+)y can be potentially useful as a UV radiation-converting phosphor for light-emitting diodes.

Phage display for the discovery of hydroxyapatite-associated peptides.

PubMed

Jin, Hyo-Eon; Chung, Woo-Jae; Lee, Seung-Wuk

2013-01-01

In nature, proteins play a critical role in the biomineralization process. Understanding how different peptide or protein sequences selectively interact with the target crystal is of great importance. Identifying such protein structures is one of the critical steps in verifying the molecular mechanisms of biomineralization. One of the promising ways to obtain such information for a particular crystal surface is to screen combinatorial peptide libraries in a high-throughput manner. Among the many combinatorial library screening procedures, phage display is a powerful method to isolate such proteins and peptides. In this chapter, we will describe our established methods to perform phage display with inorganic crystal surfaces. Specifically, we will use hydroxyapatite as a model system for discovery of apatite-associated proteins in bone or tooth biomineralization studies. This model approach can be generalized to other desired crystal surfaces using the same experimental design principles with a little modification of the procedures. © 2013 Elsevier Inc. All rights reserved.

Combinatorial Methodology for Screening Selectivity in Polymeric Pervaporation Membranes.

PubMed

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

2015-11-09

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

Combinatorial microfluidic droplet engineering for biomimetic material synthesis

PubMed Central

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

2016-01-01

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

Synthesis and cell-free cloning of DNA libraries using programmable microfluidics

PubMed Central

Yehezkel, Tuval Ben; Rival, Arnaud; Raz, Ofir; Cohen, Rafael; Marx, Zipora; Camara, Miguel; Dubern, Jean-Frédéric; Koch, Birgit; Heeb, Stephan; Krasnogor, Natalio; Delattre, Cyril; Shapiro, Ehud

2016-01-01

Microfluidics may revolutionize our ability to write synthetic DNA by addressing several fundamental limitations associated with generating novel genetic constructs. Here we report the first de novo synthesis and cell-free cloning of custom DNA libraries in sub-microliter reaction droplets using programmable digital microfluidics. Specifically, we developed Programmable Order Polymerization (POP), Microfluidic Combinatorial Assembly of DNA (M-CAD) and Microfluidic In-vitro Cloning (MIC) and applied them to de novo synthesis, combinatorial assembly and cell-free cloning of genes, respectively. Proof-of-concept for these methods was demonstrated by programming an autonomous microfluidic system to construct and clone libraries of yeast ribosome binding sites and bacterial Azurine, which were then retrieved in individual droplets and validated. The ability to rapidly and robustly generate designer DNA molecules in an autonomous manner should have wide application in biological research and development. PMID:26481354

Uncoupling of sgRNAs from their associated barcodes during PCR amplification of combinatorial CRISPR screens

PubMed Central

2018-01-01

Many implementations of pooled screens in mammalian cells rely on linking an element of interest to a barcode, with the latter subsequently quantitated by next generation sequencing. However, substantial uncoupling between these paired elements during lentiviral production has been reported, especially as the distance between elements increases. We detail that PCR amplification is another major source of uncoupling, and becomes more pronounced with increased amounts of DNA template molecules and PCR cycles. To lessen uncoupling in systems that use paired elements for detection, we recommend minimizing the distance between elements, using low and equal template DNA inputs for plasmid and genomic DNA during PCR, and minimizing the number of PCR cycles. We also present a vector design for conducting combinatorial CRISPR screens that enables accurate barcode-based detection with a single short sequencing read and minimal uncoupling. PMID:29799876

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

PubMed

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

2011-03-10

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

On the lagrangian 1-form structure of the hyperbolic calogero-moser system

NASA Astrophysics Data System (ADS)

Jairuk, Umpon; Tanasittikosol, Monsit; Yoo-Kong, Sikarin

2017-06-01

In this work, we present the Lagrangian 1-form structure of the hyperbolic Calogero-Moser system in both discrete-time level and continuous-time level. The discrete-time hyperbolic Calogero-Moser system is obtained by considering pole reduction of the semi-discrete Kadomtsev-Petviashvili (KP) equation. Furthermore, it is shown that the hyperbolic Calogero-Moser system possesses the key relation, known as the discrete-time closure relation. This relation is a consequence of the compatibility property of the temporal Lax matrices. The continuous-time hierarchy of the hyperbolic Calogero-Moser system is obtained by taking two successive continuum limits, namely, the skewed limit and full limit. With these successive limits, the continuous-time closure relation is also obtained and is shown to hold at the continuous level.

Microscopic description of pair transfer between two superfluid Fermi systems: Combining phase-space averaging and combinatorial techniques

NASA Astrophysics Data System (ADS)

Regnier, David; Lacroix, Denis; Scamps, Guillaume; Hashimoto, Yukio

2018-03-01

In a mean-field description of superfluidity, particle number and gauge angle are treated as quasiclassical conjugated variables. This level of description was recently used to describe nuclear reactions around the Coulomb barrier. Important effects of the relative gauge angle between two identical superfluid nuclei (symmetric collisions) on transfer probabilities and fusion barrier have been uncovered. A theory making contact with experiments should at least average over different initial relative gauge-angles. In the present work, we propose a new approach to obtain the multiple pair transfer probabilities between superfluid systems. This method, called phase-space combinatorial (PSC) technique, relies both on phase-space averaging and combinatorial arguments to infer the full pair transfer probability distribution at the cost of multiple mean-field calculations only. After benchmarking this approach in a schematic model, we apply it to the collision 20O+20O at various energies below the Coulomb barrier. The predictions for one pair transfer are similar to results obtained with an approximated projection method, whereas significant differences are found for two pairs transfer. Finally, we investigated the applicability of the PSC method to the contact between nonidentical superfluid systems. A generalization of the method is proposed and applied to the schematic model showing that the pair transfer probabilities are reasonably reproduced. The applicability of the PSC method to asymmetric nuclear collisions is investigated for the 14O+20O collision and it turns out that unrealistically small single- and multiple pair transfer probabilities are obtained. This is explained by the fact that relative gauge angle play in this case a minor role in the particle transfer process compared to other mechanisms, such as equilibration of the charge/mass ratio. We conclude that the best ground for probing gauge-angle effects in nuclear reaction and/or for applying the proposed PSC approach on pair transfer is the collisions of identical open-shell spherical nuclei.

Entropy-conservative spatial discretization of the multidimensional quasi-gasdynamic system of equations

NASA Astrophysics Data System (ADS)

Zlotnik, A. A.

2017-04-01

The multidimensional quasi-gasdynamic system written in the form of mass, momentum, and total energy balance equations for a perfect polytropic gas with allowance for a body force and a heat source is considered. A new conservative symmetric spatial discretization of these equations on a nonuniform rectangular grid is constructed (with the basic unknown functions—density, velocity, and temperature—defined on a common grid and with fluxes and viscous stresses defined on staggered grids). Primary attention is given to the analysis of entropy behavior: the discretization is specially constructed so that the total entropy does not decrease. This is achieved via a substantial revision of the standard discretization and applying numerous original features. A simplification of the constructed discretization serves as a conservative discretization with nondecreasing total entropy for the simpler quasi-hydrodynamic system of equations. In the absence of regularizing terms, the results also hold for the Navier-Stokes equations of a viscous compressible heat-conducting gas.

Discrete-time model reduction in limited frequency ranges

NASA Technical Reports Server (NTRS)

Horta, Lucas G.; Juang, Jer-Nan; Longman, Richard W.

1991-01-01

A mathematical formulation for model reduction of discrete time systems such that the reduced order model represents the system in a particular frequency range is discussed. The algorithm transforms the full order system into balanced coordinates using frequency weighted discrete controllability and observability grammians. In this form a criterion is derived to guide truncation of states based on their contribution to the frequency range of interest. Minimization of the criterion is accomplished without need for numerical optimization. Balancing requires the computation of discrete frequency weighted grammians. Close form solutions for the computation of frequency weighted grammians are developed. Numerical examples are discussed to demonstrate the algorithm.

Fractional discrete-time consensus models for single- and double-summator dynamics

NASA Astrophysics Data System (ADS)

Wyrwas, Małgorzata; Mozyrska, Dorota; Girejko, Ewa

2018-04-01

The leader-following consensus problem of fractional-order multi-agent discrete-time systems is considered. In the systems, interactions between opinions are defined like in Krause and Cucker-Smale models but the memory is included by taking the fractional-order discrete-time operator on the left-hand side of the nonlinear systems. In this paper, we investigate fractional-order models of opinions for the single- and double-summator dynamics of discrete-time by analytical methods as well as by computer simulations. The necessary and sufficient conditions for the leader-following consensus are formulated by proposing a consensus control law for tracking the virtual leader.

The Semigeostrophic Equations Discretized in Reference and Dual Variables

NASA Astrophysics Data System (ADS)

Cullen, Mike; Gangbo, Wilfrid; Pisante, Giovanni

2007-08-01

We study the evolution of a system of n particles {\\{(x_i, v_i)\\}_{i=1}n} in {mathbb{R}^{2d}} . That system is a conservative system with a Hamiltonian of the form {H[μ]=W22(μ, νn)} , where W 2 is the Wasserstein distance and μ is a discrete measure concentrated on the set {\\{(x_i, v_i)\\}_{i=1}n} . Typically, μ(0) is a discrete measure approximating an initial L ∞ density and can be chosen randomly. When d = 1, our results prove convergence of the discrete system to a variant of the semigeostrophic equations. We obtain that the limiting densities are absolutely continuous with respect to the Lebesgue measure. When {\\{ν^n\\}_{n=1}^infty} converges to a measure concentrated on a special d-dimensional set, we obtain the Vlasov-Monge-Ampère (VMA) system. When, d = 1 the VMA system coincides with the standard Vlasov-Poisson system.

In vitro and direct in vivo testing of mixture-based combinatorial libraries for the identification of highly active and specific opiate ligands.

PubMed

Houghten, Richard A; Dooley, Colette T; Appel, Jon R

2006-05-26

The use of combinatorial libraries for the identification of novel opiate and related ligands in opioid receptor assays is reviewed. Case studies involving opioid assays used to demonstrate the viability of combinatorial libraries are described. The identification of new opioid peptides composed of L-amino acids, D-amino acids, or L-, D-, and unnatural amino acids is reviewed. New opioid compounds have also been identified from peptidomimetic libraries, such as peptoids and alkylated dipeptides, and those identified from acyclic (eg, polyamine, urea) and heterocyclic (eg, bicyclic guanidine) libraries are reviewed.

78 FR 73900 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing of...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-12-09

... discrete unit of an effective system of internal controls at a member firm are presumed to be related, and provided the following examples of the ``most discrete unit of an effective system of internal controls... that there should not be a presumption that algorithms within the most discrete trading units are...

Time Span of Discretion and Administrative Work in School Systems: Results of a Pilot Study.

ERIC Educational Resources Information Center

Allison, Derek J.; Morfitt, Grace

This paper presents findings of a study that utilized Elliott Jaques' theories of organizational depth structure and time span of discretion in administrative work to examine administrators' responsibilities in two Ontario (Canada) school systems. The theory predicts that the time-span of discretion associated with the administrative tasks will…

Sentence Processing in an Artificial Language: Learning and Using Combinatorial Constraints

ERIC Educational Resources Information Center

Amato, Michael S.; MacDonald, Maryellen C.

2010-01-01

A study combining artificial grammar and sentence comprehension methods investigated the learning and online use of probabilistic, nonadjacent combinatorial constraints. Participants learned a small artificial language describing cartoon monsters acting on objects. Self-paced reading of sentences in the artificial language revealed comprehenders'…

Optimal generalized multistep integration formulae for real-time digital simulation

NASA Technical Reports Server (NTRS)

Moerder, D. D.; Halyo, N.

1985-01-01

The problem of discretizing a dynamical system for real-time digital simulation is considered. Treating the system and its simulation as stochastic processes leads to a statistical characterization of simulator fidelity. A plant discretization procedure based on an efficient matrix generalization of explicit linear multistep discrete integration formulae is introduced, which minimizes a weighted sum of the mean squared steady-state and transient error between the system and simulator outputs.

Conception of discrete systems decomposition algorithm using p-invariants and hypergraphs

NASA Astrophysics Data System (ADS)

Stefanowicz, Ł.

2016-09-01

In the article author presents an idea of decomposition algorithm of discrete systems described by Petri Nets using pinvariants. Decomposition process is significant from the point of view of discrete systems design, because it allows separation of the smaller sequential parts. Proposed algorithm uses modified Martinez-Silva method as well as author's selection algorithm. The developed method is a good complement of classical decomposition algorithms using graphs and hypergraphs.

A method for aircraft concept exploration using multicriteria interactive genetic algorithms

NASA Astrophysics Data System (ADS)

Buonanno, Michael Alexander

2005-08-01

The problem of aircraft concept selection has become increasingly difficult in recent years due to changes in the primary evaluation criteria of concepts. In the past, performance was often the primary discriminator, whereas modern programs have placed increased emphasis on factors such as environmental impact, economics, supportability, aesthetics, and other metrics. The revolutionary nature of the vehicles required to simultaneously meet these conflicting requirements has prompted a shift from design using historical data regression techniques for metric prediction to the use of sophisticated physics-based analysis tools that are capable of analyzing designs outside of the historical database. The use of optimization methods with these physics-based tools, however, has proven difficult because of the tendency of optimizers to exploit assumptions present in the models and drive the design towards a solution which, while promising to the computer, may be infeasible due to factors not considered by the computer codes. In addition to this difficulty, the number of discrete options available at this stage may be unmanageable due to the combinatorial nature of the concept selection problem, leading the analyst to select a sub-optimum baseline vehicle. Some extremely important concept decisions, such as the type of control surface arrangement to use, are frequently made without sufficient understanding of their impact on the important system metrics due to a lack of historical guidance, computational resources, or analysis tools. This thesis discusses the difficulties associated with revolutionary system design, and introduces several new techniques designed to remedy them. First, an interactive design method has been developed that allows the designer to provide feedback to a numerical optimization algorithm during runtime, thereby preventing the optimizer from exploiting weaknesses in the analytical model. This method can be used to account for subjective criteria, or as a crude measure of un-modeled quantitative criteria. Other contributions of the work include a modified Structured Genetic Algorithm that enables the efficient search of large combinatorial design hierarchies and an improved multi-objective optimization procedure that can effectively optimize several objectives simultaneously. A new conceptual design method has been created by drawing upon each of these new capabilities and aspects of more traditional design methods. The ability of this new technique to assist in the design of revolutionary vehicles has been demonstrated using a problem of contemporary interest: the concept exploration of a supersonic business jet. This problem was found to be a good demonstration case because of its novelty and unique requirements, and the results of this proof of concept exercise indicate that the new method is effective at providing additional insight into the relationship between a vehicle's requirements and its favorable attributes.

Quantization of systems with temporally varying discretization. II. Local evolution moves

NASA Astrophysics Data System (ADS)

Höhn, Philipp A.

2014-10-01

Several quantum gravity approaches and field theory on an evolving lattice involve a discretization changing dynamics generated by evolution moves. Local evolution moves in variational discrete systems (1) are a generalization of the Pachner evolution moves of simplicial gravity models, (2) update only a small subset of the dynamical data, (3) change the number of kinematical and physical degrees of freedom, and (4) generate a dynamical (or canonical) coarse graining or refining of the underlying discretization. To systematically explore such local moves and their implications in the quantum theory, this article suitably expands the quantum formalism for global evolution moves, constructed in Paper I [P. A. Höhn, "Quantization of systems with temporally varying discretization. I. Evolving Hilbert spaces," J. Math. Phys. 55, 083508 (2014); e-print arXiv:1401.6062 [gr-qc

Experimental Design for Combinatorial and High Throughput Materials Development

NASA Astrophysics Data System (ADS)

Cawse, James N.

2002-12-01

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

Modulation and coding for a compatible Discrete Address Beacon System.

DOT National Transportation Integrated Search

1972-02-01

One of several possible candidate configurations for the Discrete Address System is described. The configuration presented is compatible with the Air Traffic Control Radar Beacon System, and it provides for gradual transition from one system to the o...

DEVS representation of dynamical systems - Event-based intelligent control. [Discrete Event System Specification

NASA Technical Reports Server (NTRS)

Zeigler, Bernard P.

1989-01-01

It is shown how systems can be advantageously represented as discrete-event models by using DEVS (discrete-event system specification), a set-theoretic formalism. Such DEVS models provide a basis for the design of event-based logic control. In this control paradigm, the controller expects to receive confirming sensor responses to its control commands within definite time windows determined by its DEVS model of the system under control. The event-based contral paradigm is applied in advanced robotic and intelligent automation, showing how classical process control can be readily interfaced with rule-based symbolic reasoning systems.

Combinatorial enzyme technology: Conversion of pectin to oligo species and its effect on microbial growth

USDA-ARS?s Scientific Manuscript database

Plant cell wall polysaccharides, which consist of polymeric backbones with various types of substitution, were studied using the concept of combinatorial enzyme technology for conversion of agricultural fibers to functional products. Using citrus pectin as the starting substrate, an active oligo spe...

Students' Verification Strategies for Combinatorial Problems

ERIC Educational Resources Information Center

Mashiach Eizenberg, Michal; Zaslavsky, Orit

2004-01-01

We focus on a major difficulty in solving combinatorial problems, namely, on the verification of a solution. Our study aimed at identifying undergraduate students' tendencies to verify their solutions, and the verification strategies that they employ when solving these problems. In addition, an attempt was made to evaluate the level of efficiency…

Applications of Combinatorial Programming to Data Analysis: The Traveling Salesman and Related Problems

ERIC Educational Resources Information Center

Hubert, Lawrence J.; Baker, Frank B.

1978-01-01

The "Traveling Salesman" and similar combinatorial programming tasks encountered in operations research are discussed as possible data analysis models in psychology, for example, in developmental scaling, Guttman scaling, profile smoothing, and data array clustering. A short overview of various computational approaches from this area of…

Generalized Detectability for Discrete Event Systems

PubMed Central

Shu, Shaolong; Lin, Feng

2011-01-01

In our previous work, we investigated detectability of discrete event systems, which is defined as the ability to determine the current and subsequent states of a system based on observation. For different applications, we defined four types of detectabilities: (weak) detectability, strong detectability, (weak) periodic detectability, and strong periodic detectability. In this paper, we extend our results in three aspects. (1) We extend detectability from deterministic systems to nondeterministic systems. Such a generalization is necessary because there are many systems that need to be modeled as nondeterministic discrete event systems. (2) We develop polynomial algorithms to check strong detectability. The previous algorithms are based on observer whose construction is of exponential complexity, while the new algorithms are based on a new automaton called detector. (3) We extend detectability to D-detectability. While detectability requires determining the exact state of a system, D-detectability relaxes this requirement by asking only to distinguish certain pairs of states. With these extensions, the theory on detectability of discrete event systems becomes more applicable in solving many practical problems. PMID:21691432

Perfect discretization of path integrals

NASA Astrophysics Data System (ADS)

Steinhaus, Sebastian

2012-05-01

In order to obtain a well-defined path integral one often employs discretizations. In the case of General Relativity these generically break diffeomorphism symmetry, which has severe consequences since these symmetries determine the dynamics of the corresponding system. In this article we consider the path integral of reparametrization invariant systems as a toy example and present an improvement procedure for the discretized propagator. Fixed points and convergence of the procedure are discussed. Furthermore we show that a reparametrization invariant path integral implies discretization independence and acts as a projector onto physical states.

Non-Lipschitz Dynamics Approach to Discrete Event Systems

NASA Technical Reports Server (NTRS)

Zak, M.; Meyers, R.

1995-01-01

This paper presents and discusses a mathematical formalism for simulation of discrete event dynamics (DED) - a special type of 'man- made' system designed to aid specific areas of information processing. A main objective is to demonstrate that the mathematical formalism for DED can be based upon the terminal model of Newtonian dynamics which allows one to relax Lipschitz conditions at some discrete points.

Improving the Teaching of Discrete-Event Control Systems Using a LEGO Manufacturing Prototype

ERIC Educational Resources Information Center

Sanchez, A.; Bucio, J.

2012-01-01

This paper discusses the usefulness of employing LEGO as a teaching-learning aid in a post-graduate-level first course on the control of discrete-event systems (DESs). The final assignment of the course is presented, which asks students to design and implement a modular hierarchical discrete-event supervisor for the coordination layer of a…

Generation Algorithm of Discrete Line in Multi-Dimensional Grids

NASA Astrophysics Data System (ADS)

Du, L.; Ben, J.; Li, Y.; Wang, R.

2017-09-01

Discrete Global Grids System (DGGS) is a kind of digital multi-resolution earth reference model, in terms of structure, it is conducive to the geographical spatial big data integration and mining. Vector is one of the important types of spatial data, only by discretization, can it be applied in grids system to make process and analysis. Based on the some constraint conditions, this paper put forward a strict definition of discrete lines, building a mathematic model of the discrete lines by base vectors combination method. Transforming mesh discrete lines issue in n-dimensional grids into the issue of optimal deviated path in n-minus-one dimension using hyperplane, which, therefore realizing dimension reduction process in the expression of mesh discrete lines. On this basis, we designed a simple and efficient algorithm for dimension reduction and generation of the discrete lines. The experimental results show that our algorithm not only can be applied in the two-dimensional rectangular grid, also can be applied in the two-dimensional hexagonal grid and the three-dimensional cubic grid. Meanwhile, when our algorithm is applied in two-dimensional rectangular grid, it can get a discrete line which is more similar to the line in the Euclidean space.

Approximation-Based Discrete-Time Adaptive Position Tracking Control for Interior Permanent Magnet Synchronous Motors.

PubMed

Yu, Jinpeng; Shi, Peng; Yu, Haisheng; Chen, Bing; Lin, Chong

2015-07-01

This paper considers the problem of discrete-time adaptive position tracking control for a interior permanent magnet synchronous motor (IPMSM) based on fuzzy-approximation. Fuzzy logic systems are used to approximate the nonlinearities of the discrete-time IPMSM drive system which is derived by direct discretization using Euler method, and a discrete-time fuzzy position tracking controller is designed via backstepping approach. In contrast to existing results, the advantage of the scheme is that the number of the adjustable parameters is reduced to two only and the problem of coupling nonlinearity can be overcome. It is shown that the proposed discrete-time fuzzy controller can guarantee the tracking error converges to a small neighborhood of the origin and all the signals are bounded. Simulation results illustrate the effectiveness and the potentials of the theoretic results obtained.

An 8-Fold Parallel Reactor System for Combinatorial Catalysis Research

PubMed Central

Stoll, Norbert; Allwardt, Arne; Dingerdissen, Uwe

2006-01-01

Increasing economic globalization and mounting time and cost pressure on the development of new raw materials for the chemical industry as well as materials and environmental engineering constantly raise the demands on technologies to be used. Parallelization, miniaturization, and automation are the main concepts involved in increasing the rate of chemical and biological experimentation. PMID:17671621

Stability of Dynamical Systems with Discontinuous Motions:

NASA Astrophysics Data System (ADS)

Michel, Anthony N.; Hou, Ling

In this paper we present a stability theory for discontinuous dynamical systems (DDS): continuous-time systems whose motions are not necessarily continuous with respect to time. We show that this theory is not only applicable in the analysis of DDS, but also in the analysis of continuous dynamical systems (continuous-time systems whose motions are continuous with respect to time), discrete-time dynamical systems (systems whose motions are defined at discrete points in time) and hybrid dynamical systems (HDS) (systems whose descriptions involve simultaneously continuous-time and discrete-time). We show that the stability results for DDS are in general less conservative than the corresponding well-known classical Lyapunov results for continuous dynamical systems and discrete-time dynamical systems. Although the DDS stability results are applicable to general dynamical systems defined on metric spaces (divorced from any kind of description by differential equations, or any other kinds of equations), we confine ourselves to finite-dimensional dynamical systems defined by ordinary differential equations and difference equations, to make this paper as widely accessible as possible. We present only sample results, namely, results for uniform asymptotic stability in the large.

On pseudo-spectral time discretizations in summation-by-parts form

NASA Astrophysics Data System (ADS)

Ruggiu, Andrea A.; Nordström, Jan

2018-05-01

Fully-implicit discrete formulations in summation-by-parts form for initial-boundary value problems must be invertible in order to provide well functioning procedures. We prove that, under mild assumptions, pseudo-spectral collocation methods for the time derivative lead to invertible discrete systems when energy-stable spatial discretizations are used.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bhatia, Harsh

This dissertation presents research on addressing some of the contemporary challenges in the analysis of vector fields—an important type of scientific data useful for representing a multitude of physical phenomena, such as wind flow and ocean currents. In particular, new theories and computational frameworks to enable consistent feature extraction from vector fields are presented. One of the most fundamental challenges in the analysis of vector fields is that their features are defined with respect to reference frames. Unfortunately, there is no single “correct” reference frame for analysis, and an unsuitable frame may cause features of interest to remain undetected, thusmore » creating serious physical consequences. This work develops new reference frames that enable extraction of localized features that other techniques and frames fail to detect. As a result, these reference frames objectify the notion of “correctness” of features for certain goals by revealing the phenomena of importance from the underlying data. An important consequence of using these local frames is that the analysis of unsteady (time-varying) vector fields can be reduced to the analysis of sequences of steady (timeindependent) vector fields, which can be performed using simpler and scalable techniques that allow better data management by accessing the data on a per-time-step basis. Nevertheless, the state-of-the-art analysis of steady vector fields is not robust, as most techniques are numerical in nature. The residing numerical errors can violate consistency with the underlying theory by breaching important fundamental laws, which may lead to serious physical consequences. This dissertation considers consistency as the most fundamental characteristic of computational analysis that must always be preserved, and presents a new discrete theory that uses combinatorial representations and algorithms to provide consistency guarantees during vector field analysis along with the uncertainty visualization of unavoidable discretization errors. Together, the two main contributions of this dissertation address two important concerns regarding feature extraction from scientific data: correctness and precision. The work presented here also opens new avenues for further research by exploring more-general reference frames and more-sophisticated domain discretizations.« less

From globally coupled maps to complex-systems biology

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kaneko, Kunihiko, E-mail: kaneko@complex.c.u-tokyo.ac.jp

Studies of globally coupled maps, introduced as a network of chaotic dynamics, are briefly reviewed with an emphasis on novel concepts therein, which are universal in high-dimensional dynamical systems. They include clustering of synchronized oscillations, hierarchical clustering, chimera of synchronization and desynchronization, partition complexity, prevalence of Milnor attractors, chaotic itinerancy, and collective chaos. The degrees of freedom necessary for high dimensionality are proposed to equal the number in which the combinatorial exceeds the exponential. Future analysis of high-dimensional dynamical systems with regard to complex-systems biology is briefly discussed.

Experimental realization of a highly secure chaos communication under strong channel noise

NASA Astrophysics Data System (ADS)

Ye, Weiping; Dai, Qionglin; Wang, Shihong; Lu, Huaping; Kuang, Jinyu; Zhao, Zhenfeng; Zhu, Xiangqing; Tang, Guoning; Huang, Ronghuai; Hu, Gang

2004-09-01

A one-way coupled spatiotemporally chaotic map lattice is used to construct cryptosystem. With the combinatorial applications of both chaotic computations and conventional algebraic operations, our system has optimal cryptographic properties much better than the separative applications of known chaotic and conventional methods. We have realized experiments to practice duplex voice secure communications in realistic Wired Public Switched Telephone Network by applying our chaotic system and the system of Advanced Encryption Standard (AES), respectively, for cryptography. Our system can work stably against strong channel noise when AES fails to work.

A scalable block-preconditioning strategy for divergence-conforming B-spline discretizations of the Stokes problem

DOE Office of Scientific and Technical Information (OSTI.GOV)

Cortes, Adriano M.; Dalcin, Lisandro; Sarmiento, Adel F.

The recently introduced divergence-conforming B-spline discretizations allow the construction of smooth discrete velocity–pressure pairs for viscous incompressible flows that are at the same time inf–sup stable and pointwise divergence-free. When applied to the discretized Stokes problem, these spaces generate a symmetric and indefinite saddle-point linear system. The iterative method of choice to solve such system is the Generalized Minimum Residual Method. This method lacks robustness, and one remedy is to use preconditioners. For linear systems of saddle-point type, a large family of preconditioners can be obtained by using a block factorization of the system. In this paper, we show howmore » the nesting of “black-box” solvers and preconditioners can be put together in a block triangular strategy to build a scalable block preconditioner for the Stokes system discretized by divergence-conforming B-splines. Lastly, besides the known cavity flow problem, we used for benchmark flows defined on complex geometries: an eccentric annulus and hollow torus of an eccentric annular cross-section.« less

A scalable block-preconditioning strategy for divergence-conforming B-spline discretizations of the Stokes problem

DOE PAGES

Cortes, Adriano M.; Dalcin, Lisandro; Sarmiento, Adel F.; ...

2016-10-19

The recently introduced divergence-conforming B-spline discretizations allow the construction of smooth discrete velocity–pressure pairs for viscous incompressible flows that are at the same time inf–sup stable and pointwise divergence-free. When applied to the discretized Stokes problem, these spaces generate a symmetric and indefinite saddle-point linear system. The iterative method of choice to solve such system is the Generalized Minimum Residual Method. This method lacks robustness, and one remedy is to use preconditioners. For linear systems of saddle-point type, a large family of preconditioners can be obtained by using a block factorization of the system. In this paper, we show howmore » the nesting of “black-box” solvers and preconditioners can be put together in a block triangular strategy to build a scalable block preconditioner for the Stokes system discretized by divergence-conforming B-splines. Lastly, besides the known cavity flow problem, we used for benchmark flows defined on complex geometries: an eccentric annulus and hollow torus of an eccentric annular cross-section.« less

Observation of Discrete-Time-Crystal Signatures in an Ordered Dipolar Many-Body System

NASA Astrophysics Data System (ADS)

Rovny, Jared; Blum, Robert L.; Barrett, Sean E.

2018-05-01

A discrete time crystal (DTC) is a robust phase of driven systems that breaks the discrete time translation symmetry of the driving Hamiltonian. Recent experiments have observed DTC signatures in two distinct systems. Here we show nuclear magnetic resonance observations of DTC signatures in a third, strikingly different system: an ordered spatial crystal. We use a novel DTC echo experiment to probe the coherence of the driven system. Finally, we show that interactions during the pulse of the DTC sequence contribute to the decay of the signal, complicating attempts to measure the intrinsic lifetime of the DTC.

Observation of Discrete-Time-Crystal Signatures in an Ordered Dipolar Many-Body System.

PubMed

Rovny, Jared; Blum, Robert L; Barrett, Sean E

2018-05-04

A discrete time crystal (DTC) is a robust phase of driven systems that breaks the discrete time translation symmetry of the driving Hamiltonian. Recent experiments have observed DTC signatures in two distinct systems. Here we show nuclear magnetic resonance observations of DTC signatures in a third, strikingly different system: an ordered spatial crystal. We use a novel DTC echo experiment to probe the coherence of the driven system. Finally, we show that interactions during the pulse of the DTC sequence contribute to the decay of the signal, complicating attempts to measure the intrinsic lifetime of the DTC.

Using a new discretization approach to design a delayed LQG controller

NASA Astrophysics Data System (ADS)

Haraguchi, M.; Hu, H. Y.

2008-07-01

In general, discrete-time controls have become more and more preferable in engineering because of their easy implementation and simple computations. However, the available discretization approaches for the systems having time delays increase the system dimensions and have a high computational cost. This paper presents an effective discretization approach for the continuous-time systems with an input delay. The approach enables one to transform the input-delay system into a delay-free system, but retain the system dimensions unchanged in the state transformation. To demonstrate an application of the approach, this paper presents the design of an LQ regulator for continuous-time systems with an input delay and gives a state observer with a Kalman filter for estimating the full-state vector from some measurements of the system as well. The case studies in the paper well support the efficacy and efficiency of the proposed approach applied to the vibration control of a three-story structure model with the actuator delay taken into account.

Building polyhedra by self-assembly: theory and experiment.

PubMed

Kaplan, Ryan; Klobušický, Joseph; Pandey, Shivendra; Gracias, David H; Menon, Govind

2014-01-01

We investigate the utility of a mathematical framework based on discrete geometry to model biological and synthetic self-assembly. Our primary biological example is the self-assembly of icosahedral viruses; our synthetic example is surface-tension-driven self-folding polyhedra. In both instances, the process of self-assembly is modeled by decomposing the polyhedron into a set of partially formed intermediate states. The set of all intermediates is called the configuration space, pathways of assembly are modeled as paths in the configuration space, and the kinetics and yield of assembly are modeled by rate equations, Markov chains, or cost functions on the configuration space. We review an interesting interplay between biological function and mathematical structure in viruses in light of this framework. We discuss in particular: (i) tiling theory as a coarse-grained description of all-atom models; (ii) the building game-a growth model for the formation of polyhedra; and (iii) the application of these models to the self-assembly of the bacteriophage MS2. We then use a similar framework to model self-folding polyhedra. We use a discrete folding algorithm to compute a configuration space that idealizes surface-tension-driven self-folding and analyze pathways of assembly and dominant intermediates. These computations are then compared with experimental observations of a self-folding dodecahedron with side 300 μm. In both models, despite a combinatorial explosion in the size of the configuration space, a few pathways and intermediates dominate self-assembly. For self-folding polyhedra, the dominant intermediates have fewer degrees of freedom than comparable intermediates, and are thus more rigid. The concentration of assembly pathways on a few intermediates with distinguished geometric properties is biologically and physically important, and suggests deeper mathematical structure.

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

PubMed

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

2014-01-07

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

Generation of Dynamic Combinatorial Libraries Using Hydrazone‐Functionalized Surface Mimetics

PubMed Central

Hewitt, Sarah H.

2018-01-01

Dynamic combinatorial chemistry (DCC) represents an approach, whereby traditional supramolecular scaffolds used for protein surface recognition might be exploited to achieve selective high affinity target recognition. Synthesis, in situ screening and amplification under selection pressure allows the generation of ligands, which bear different moieties capable of making multivalent non‐covalent interactions with target proteins. Generic tetracarboxyphenyl porphyrin scaffolds bearing four hydrazide moieties have been used to form dynamic combinatorial libraries (DCLs) using aniline‐catalyzed reversible hydrazone exchange reactions, in 10 % DMSO, 5 mm NH4OAc, at pH 6.75. High resolution mass spectrometry (HRMS) was used to monitor library composition and establish conditions under which equilibria were established.

A continuous-discrete approach for evaluation of natural frequencies and mode shapes of high-rise buildings

NASA Astrophysics Data System (ADS)

Malekinejad, Mohsen; Rahgozar, Reza; Malekinejad, Ali; Rahgozar, Peyman

2016-09-01

In this paper, a continuous-discrete approach based on the concept of lumped mass and equivalent continuous approach is proposed for free vibration analysis of combined system of framed tube, shear core and outrigger-belt truss in high-rise buildings. This system is treated as a continuous system (i.e., discrete beams and columns are replaced with equivalent continuous membranes) and a discrete system (or lumped mass system) at different stages of dynamic analysis. The structure is discretized at each floor of the building as a series of lumped masses placed at the center of shear core. Each mass has two transitional degrees of freedom (lateral and axial( and one rotational. The effect of shear core and outrigger-belt truss on framed tube system is modeled as a rotational spring placed at the location of outrigger-belt truss system along structure's height. By solving the resulting eigen problem, natural frequencies and mode-shapes are obtained. Numerical examples are presented to show acceptable accuracy of the procedure in estimating the fundamental frequencies and corresponding mode shapes of the combined system as compared to finite element analysis of the complete structure. The simplified proposed method is much faster and should be more suitable for rapid interactive design.

Test Operations Procedure (TOP) 02-2-546 Teleoperated Unmanned Ground Vehicle (UGV) Latency Measurements

DTIC Science & Technology

2017-01-11

discrete system components or measurements of latency in autonomous systems. 15. SUBJECT TERMS Unmanned Ground Vehicles, Basic Video Latency, End-to... discrete system components or measurements of latency in autonomous systems. 1.1 Basic Video Latency. Teleoperation latency, or lag, describes

Terminal Dynamics Approach to Discrete Event Systems

NASA Technical Reports Server (NTRS)

Zak, Michail; Meyers, Ronald

1995-01-01

This paper presents and discusses a mathematical formalism for simulation of discrete event dynamic (DED)-a special type of 'man-made' systems to serve specific purposes of information processing. The main objective of this work is to demonstrate that the mathematical formalism for DED can be based upon a terminal model of Newtonian dynamics which allows one to relax Lipschitz conditions at some discrete points.!.

Automated Combinatorial Chemistry in the Organic Chemistry Majors Laboratory

ERIC Educational Resources Information Center

Nichols, Christopher J.; Hanne, Larry F.

2010-01-01

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

More Combinatorial Proofs via Flagpole Arrangements

ERIC Educational Resources Information Center

DeTemple, Duane; Reynolds, H. David, II

2006-01-01

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

Using Combinatorial Approach to Improve Students' Learning of the Distributive Law and Multiplicative Identities

ERIC Educational Resources Information Center

Tsai, Yu-Ling; Chang, Ching-Kuch

2009-01-01

This article reports an alternative approach, called the combinatorial model, to learning multiplicative identities, and investigates the effects of implementing results for this alternative approach. Based on realistic mathematics education theory, the new instructional materials or modules of the new approach were developed by the authors. From…

Children's Strategies for Solving Two- and Three-Dimensional Combinatorial Problems.

ERIC Educational Resources Information Center

English, Lyn D.

1993-01-01

Investigated strategies that 7- to 12-year-old children (n=96) spontaneously applied in solving novel combinatorial problems. With experience in solving two-dimensional problems, children were able to refine their strategies and adapt them to three dimensions. Results on some problems indicated significant effects of age. (Contains 32 references.)…

Identities for Generalized Fibonacci Numbers: A Combinatorial Approach

ERIC Educational Resources Information Center

Plaza, A.; Falcon, S.

2008-01-01

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

Combinatorial Partial Hydrogenation Reactions of 4-Nitroacetophenone: An Undergraduate Organic Laboratory

ERIC Educational Resources Information Center

Kittredge, Kevin W.; Marine, Susan S.; Taylor, Richard T.

2004-01-01

A molecule possessing other functional groups that could be hydrogenerated is examined, where a variety of metal catalysts are evaluated under similar reaction conditions. Optimizing organic reactions is both time and labor intensive, and the use of a combinatorial parallel synthesis reactor was great time saving device, as per summary.

Human Performance on the Traveling Salesman and Related Problems: A Review

ERIC Educational Resources Information Center

MacGregor, James N.; Chu, Yun

2011-01-01

The article provides a review of recent research on human performance on the traveling salesman problem (TSP) and related combinatorial optimization problems. We discuss what combinatorial optimization problems are, why they are important, and why they may be of interest to cognitive scientists. We next describe the main characteristics of human…

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

ERIC Educational Resources Information Center

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

2008-01-01

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

Crossover versus mutation: a comparative analysis of the evolutionary strategy of genetic algorithms applied to combinatorial optimization problems.

PubMed

Osaba, E; Carballedo, R; Diaz, F; Onieva, E; de la Iglesia, I; Perallos, A

2014-01-01

Since their first formulation, genetic algorithms (GAs) have been one of the most widely used techniques to solve combinatorial optimization problems. The basic structure of the GAs is known by the scientific community, and thanks to their easy application and good performance, GAs are the focus of a lot of research works annually. Although throughout history there have been many studies analyzing various concepts of GAs, in the literature there are few studies that analyze objectively the influence of using blind crossover operators for combinatorial optimization problems. For this reason, in this paper a deep study on the influence of using them is conducted. The study is based on a comparison of nine techniques applied to four well-known combinatorial optimization problems. Six of the techniques are GAs with different configurations, and the remaining three are evolutionary algorithms that focus exclusively on the mutation process. Finally, to perform a reliable comparison of these results, a statistical study of them is made, performing the normal distribution z-test.

Crossover versus Mutation: A Comparative Analysis of the Evolutionary Strategy of Genetic Algorithms Applied to Combinatorial Optimization Problems

PubMed Central

Osaba, E.; Carballedo, R.; Diaz, F.; Onieva, E.; de la Iglesia, I.; Perallos, A.

2014-01-01

Since their first formulation, genetic algorithms (GAs) have been one of the most widely used techniques to solve combinatorial optimization problems. The basic structure of the GAs is known by the scientific community, and thanks to their easy application and good performance, GAs are the focus of a lot of research works annually. Although throughout history there have been many studies analyzing various concepts of GAs, in the literature there are few studies that analyze objectively the influence of using blind crossover operators for combinatorial optimization problems. For this reason, in this paper a deep study on the influence of using them is conducted. The study is based on a comparison of nine techniques applied to four well-known combinatorial optimization problems. Six of the techniques are GAs with different configurations, and the remaining three are evolutionary algorithms that focus exclusively on the mutation process. Finally, to perform a reliable comparison of these results, a statistical study of them is made, performing the normal distribution z-test. PMID:25165731

Novel design strategy for checkpoint kinase 2 inhibitors using pharmacophore modeling, combinatorial fusion, and virtual screening.

PubMed

Lin, Chun-Yuan; Wang, Yen-Ling

2014-01-01

Checkpoint kinase 2 (Chk2) has a great effect on DNA-damage and plays an important role in response to DNA double-strand breaks and related lesions. In this study, we will concentrate on Chk2 and the purpose is to find the potential inhibitors by the pharmacophore hypotheses (PhModels), combinatorial fusion, and virtual screening techniques. Applying combinatorial fusion into PhModels and virtual screening techniques is a novel design strategy for drug design. We used combinatorial fusion to analyze the prediction results and then obtained the best correlation coefficient of the testing set (r test) with the value 0.816 by combining the Best(train)Best(test) and Fast(train)Fast(test) prediction results. The potential inhibitors were selected from NCI database by screening according to Best(train)Best(test) + Fast(train)Fast(test) prediction results and molecular docking with CDOCKER docking program. Finally, the selected compounds have high interaction energy between a ligand and a receptor. Through these approaches, 23 potential inhibitors for Chk2 are retrieved for further study.

A combinatorial filtering method for magnetotelluric time-series based on Hilbert-Huang transform

NASA Astrophysics Data System (ADS)

Cai, Jianhua

2014-11-01

Magnetotelluric (MT) time-series are often contaminated with noise from natural or man-made processes. A substantial improvement is possible when the time-series are presented as clean as possible for further processing. A combinatorial method is described for filtering of MT time-series based on the Hilbert-Huang transform that requires a minimum of human intervention and leaves good data sections unchanged. Good data sections are preserved because after empirical mode decomposition the data are analysed through hierarchies, morphological filtering, adaptive threshold and multi-point smoothing, allowing separation of noise from signals. The combinatorial method can be carried out without any assumption about the data distribution. Simulated data and the real measured MT time-series from three different regions, with noise caused by baseline drift, high frequency noise and power-line contribution, are processed to demonstrate the application of the proposed method. Results highlight the ability of the combinatorial method to pick out useful signals, and the noise is suppressed greatly so that their deleterious influence is eliminated for the MT transfer function estimation.

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

PubMed

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

2010-12-14

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

Combinatorial Characterization of TiO2 Chemical Vapor Deposition Utilizing Titanium Isopropoxide.

PubMed

Reinke, Michael; Ponomarev, Evgeniy; Kuzminykh, Yury; Hoffmann, Patrik

2015-07-13

The combinatorial characterization of the growth kinetics in chemical vapor deposition processes is challenging because precise information about the local precursor flow is usually difficult to access. In consequence, combinatorial chemical vapor deposition techniques are utilized more to study functional properties of thin films as a function of chemical composition, growth rate or crystallinity than to study the growth process itself. We present an experimental procedure which allows the combinatorial study of precursor surface kinetics during the film growth using high vacuum chemical vapor deposition. As consequence of the high vacuum environment, the precursor transport takes place in the molecular flow regime, which allows predicting and modifying precursor impinging rates on the substrate with comparatively little experimental effort. In this contribution, we study the surface kinetics of titanium dioxide formation using titanium tetraisopropoxide as precursor molecule over a large parameter range. We discuss precursor flux and temperature dependent morphology, crystallinity, growth rates, and precursor deposition efficiency. We conclude that the surface reaction of the adsorbed precursor molecules comprises a higher order reaction component with respect to precursor surface coverage.

Combinatorial programming of human neuronal progenitors using magnetically-guided stoichiometric mRNA delivery.

PubMed

Azimi, Sayyed M; Sheridan, Steven D; Ghannad-Rezaie, Mostafa; Eimon, Peter M; Yanik, Mehmet Fatih

2018-05-01

Identification of optimal transcription-factor expression patterns to direct cellular differentiation along a desired pathway presents significant challenges. We demonstrate massively combinatorial screening of temporally-varying mRNA transcription factors to direct differentiation of neural progenitor cells using a dynamically-reconfigurable magnetically-guided spotting technology for localizing mRNA, enabling experiments on millimetre size spots. In addition, we present a time-interleaved delivery method that dramatically reduces fluctuations in the delivered transcription-factor copy-numbers per cell. We screened combinatorial and temporal delivery of a pool of midbrain-specific transcription factors to augment the generation of dopaminergic neurons. We show that the combinatorial delivery of LMX1A, FOXA2 and PITX3 is highly effective in generating dopaminergic neurons from midbrain progenitors. We show that LMX1A significantly increases TH -expression levels when delivered to neural progenitor cells either during proliferation or after induction of neural differentiation, while FOXA2 and PITX3 increase expression only when delivered prior to induction, demonstrating temporal dependence of factor addition. © 2018, Azimi et al.

Particle-Based Microarrays of Oligonucleotides and Oligopeptides.

PubMed

Nesterov-Mueller, Alexander; Maerkle, Frieder; Hahn, Lothar; Foertsch, Tobias; Schillo, Sebastian; Bykovskaya, Valentina; Sedlmayr, Martyna; Weber, Laura K; Ridder, Barbara; Soehindrijo, Miriam; Muenster, Bastian; Striffler, Jakob; Bischoff, F Ralf; Breitling, Frank; Loeffler, Felix F

2014-10-28

In this review, we describe different methods of microarray fabrication based on the use of micro-particles/-beads and point out future tendencies in the development of particle-based arrays. First, we consider oligonucleotide bead arrays, where each bead is a carrier of one specific sequence of oligonucleotides. This bead-based array approach, appearing in the late 1990s, enabled high-throughput oligonucleotide analysis and had a large impact on genome research. Furthermore, we consider particle-based peptide array fabrication using combinatorial chemistry. In this approach, particles can directly participate in both the synthesis and the transfer of synthesized combinatorial molecules to a substrate. Subsequently, we describe in more detail the synthesis of peptide arrays with amino acid polymer particles, which imbed the amino acids inside their polymer matrix. By heating these particles, the polymer matrix is transformed into a highly viscous gel, and thereby, imbedded monomers are allowed to participate in the coupling reaction. Finally, we focus on combinatorial laser fusing of particles for the synthesis of high-density peptide arrays. This method combines the advantages of particles and combinatorial lithographic approaches.

Particle-Based Microarrays of Oligonucleotides and Oligopeptides

PubMed Central

Nesterov-Mueller, Alexander; Maerkle, Frieder; Hahn, Lothar; Foertsch, Tobias; Schillo, Sebastian; Bykovskaya, Valentina; Sedlmayr, Martyna; Weber, Laura K.; Ridder, Barbara; Soehindrijo, Miriam; Muenster, Bastian; Striffler, Jakob; Bischoff, F. Ralf; Breitling, Frank; Loeffler, Felix F.

2014-01-01

In this review, we describe different methods of microarray fabrication based on the use of micro-particles/-beads and point out future tendencies in the development of particle-based arrays. First, we consider oligonucleotide bead arrays, where each bead is a carrier of one specific sequence of oligonucleotides. This bead-based array approach, appearing in the late 1990s, enabled high-throughput oligonucleotide analysis and had a large impact on genome research. Furthermore, we consider particle-based peptide array fabrication using combinatorial chemistry. In this approach, particles can directly participate in both the synthesis and the transfer of synthesized combinatorial molecules to a substrate. Subsequently, we describe in more detail the synthesis of peptide arrays with amino acid polymer particles, which imbed the amino acids inside their polymer matrix. By heating these particles, the polymer matrix is transformed into a highly viscous gel, and thereby, imbedded monomers are allowed to participate in the coupling reaction. Finally, we focus on combinatorial laser fusing of particles for the synthesis of high-density peptide arrays. This method combines the advantages of particles and combinatorial lithographic approaches. PMID:27600347

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

PubMed

Minovski, Nikola; Perdih, Andrej; Solmajer, Tom

2012-05-01

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

Analysis hierarchical model for discrete event systems

NASA Astrophysics Data System (ADS)

Ciortea, E. M.

2015-11-01

The This paper presents the hierarchical model based on discrete event network for robotic systems. Based on the hierarchical approach, Petri network is analysed as a network of the highest conceptual level and the lowest level of local control. For modelling and control of complex robotic systems using extended Petri nets. Such a system is structured, controlled and analysed in this paper by using Visual Object Net ++ package that is relatively simple and easy to use, and the results are shown as representations easy to interpret. The hierarchical structure of the robotic system is implemented on computers analysed using specialized programs. Implementation of hierarchical model discrete event systems, as a real-time operating system on a computer network connected via a serial bus is possible, where each computer is dedicated to local and Petri model of a subsystem global robotic system. Since Petri models are simplified to apply general computers, analysis, modelling, complex manufacturing systems control can be achieved using Petri nets. Discrete event systems is a pragmatic tool for modelling industrial systems. For system modelling using Petri nets because we have our system where discrete event. To highlight the auxiliary time Petri model using transport stream divided into hierarchical levels and sections are analysed successively. Proposed robotic system simulation using timed Petri, offers the opportunity to view the robotic time. Application of goods or robotic and transmission times obtained by measuring spot is obtained graphics showing the average time for transport activity, using the parameters sets of finished products. individually.

GDSCalc: A Web-Based Application for Evaluating Discrete Graph Dynamical Systems

PubMed Central

Elmeligy Abdelhamid, Sherif H.; Kuhlman, Chris J.; Marathe, Madhav V.; Mortveit, Henning S.; Ravi, S. S.

2015-01-01

Discrete dynamical systems are used to model various realistic systems in network science, from social unrest in human populations to regulation in biological networks. A common approach is to model the agents of a system as vertices of a graph, and the pairwise interactions between agents as edges. Agents are in one of a finite set of states at each discrete time step and are assigned functions that describe how their states change based on neighborhood relations. Full characterization of state transitions of one system can give insights into fundamental behaviors of other dynamical systems. In this paper, we describe a discrete graph dynamical systems (GDSs) application called GDSCalc for computing and characterizing system dynamics. It is an open access system that is used through a web interface. We provide an overview of GDS theory. This theory is the basis of the web application; i.e., an understanding of GDS provides an understanding of the software features, while abstracting away implementation details. We present a set of illustrative examples to demonstrate its use in education and research. Finally, we compare GDSCalc with other discrete dynamical system software tools. Our perspective is that no single software tool will perform all computations that may be required by all users; tools typically have particular features that are more suitable for some tasks. We situate GDSCalc within this space of software tools. PMID:26263006

GDSCalc: A Web-Based Application for Evaluating Discrete Graph Dynamical Systems.

PubMed

Elmeligy Abdelhamid, Sherif H; Kuhlman, Chris J; Marathe, Madhav V; Mortveit, Henning S; Ravi, S S

2015-01-01

Discrete dynamical systems are used to model various realistic systems in network science, from social unrest in human populations to regulation in biological networks. A common approach is to model the agents of a system as vertices of a graph, and the pairwise interactions between agents as edges. Agents are in one of a finite set of states at each discrete time step and are assigned functions that describe how their states change based on neighborhood relations. Full characterization of state transitions of one system can give insights into fundamental behaviors of other dynamical systems. In this paper, we describe a discrete graph dynamical systems (GDSs) application called GDSCalc for computing and characterizing system dynamics. It is an open access system that is used through a web interface. We provide an overview of GDS theory. This theory is the basis of the web application; i.e., an understanding of GDS provides an understanding of the software features, while abstracting away implementation details. We present a set of illustrative examples to demonstrate its use in education and research. Finally, we compare GDSCalc with other discrete dynamical system software tools. Our perspective is that no single software tool will perform all computations that may be required by all users; tools typically have particular features that are more suitable for some tasks. We situate GDSCalc within this space of software tools.

Combinatorial investigation of rare-earth free permanent magnets

NASA Astrophysics Data System (ADS)

Fackler, Sean Wu

The combinatorial high throughput method allows one to rapidly study a large number of samples with systematically changing parameters. We apply this method to study Fe-Co-V alloys as alternatives to rare-earth permanent magnets. Rare-earth permanent magnets derive their unmatched magnetic properties from the hybridization of Fe and Co with the f-orbitals of rare-earth elements, which have strong spin-orbit coupling. It is predicted that Fe and Co may also have strong hybridization with 4d and 5d refractory transition metals with strong spin-orbit coupling. Refractory transition metals like V also have the desirable property of high temperature stability, which is important for permanent magnet applications in traction motors. In this work, we focus on the role of crystal structure, composition, and secondary phases in the origin of competitive permanent magnetic properties of a particular Fe-Co-V alloy. Fe38Co52V10, compositions are known as Vicalloys. Fe-CoV composition spreads were sputtered onto three-inch silicon wafers and patterned into discrete sample pads forming a combinatorial library. We employed highthroughput screening methods using synchrotron X-rays, wavelength dispersive spectroscopy, and magneto-optical Kerr effect (MOKE) to rapidly screen crystal structure, composition, and magnetic properties, respectively. We found that in-plane magnetic coercive fields of our Vicalloy thin films agree with known bulk values (300 G), but found a remarkable eight times increase of the out-of-plane coercive fields (˜2,500 G). To explain this, we measured the switching fields between in-plane and out-of-plane thin film directions which revealed that the Kondorsky model of 180° domain wall reversal was responsible for Vicalloy's enhanced out-of-plane coercive field and possibly its permanent magnetic properties. The Kondorsky model suggests that domain-wall pinning is the origin of Vicalloy's permanent magnetic properties, in contrast to strain, shape, or crystalline anisotropy mechanisms suggested in the literature. We also studied the thickness dependence of an Fe70Co30- V thin film library to consider the unique effects of our thin film libraries which are not found in bulk samples. We present results of data mining of synchrotron X-ray diffraction data using non-negative matrix factorization (NMF). NMF can automatically identify pure crystal phases that make up an unknown phase mixture. We found a strong correlation between magnetic properties and crystal phase quantity using this valuable visualization. In addition to the combinatorial study, this dissertation includes a study of strain controlled properties of magnetic thin films for future applications in random access memories. We investigated the local coupling between dense magnetic stripe domains in transcritical Permalloy (tPy) thin films and ferroelectric domains of BaTiO3 single crystals in a tPy/BaTiO3 heterostructure. Two distinct changes in the magnetic stripe domains of tPy were observed from the magnetic force microscopy images after cooling the heterostructure from above the ferroelectric Curie temperature of BaTiO3 (120°C) to room temperature. First, an abrupt break in the magnetic stripe domain direction was found at the ferroelectric a-c-domain boundaries due to an induced change in in-plane magnetic anisotropy. Second, the magnetic stripe domain period increased when coupled to a ferroelectric a-domain due to a change in out-of-plane magnetic anisotropy. Micromagnetic simulations reveal that local magnetic anisotropy energy from inverse magnetostriction is conserved between in-plane and out-of-plane components.

Combinatorial effect of substratum properties on mesenchymal stem cell sheet engineering and subsequent multi-lineage differentiation.

PubMed

Chuah, Yon Jin; Zhang, Ying; Wu, Yingnan; Menon, Nishanth V; Goh, Ghim Hian; Lee, Ann Charlene; Chan, Vincent; Zhang, Yilei; Kang, Yuejun

2015-09-01

Cell sheet engineering has been exploited as an alternative approach in tissue regeneration and the use of stem cells to generate cell sheets has further showed its potential in stem cell-mediated tissue regeneration. There exist vast interests in developing strategies to enhance the formation of stem cell sheets for downstream applications. It has been proved that stem cells are sensitive to the biophysical cues of the microenvironment. Therefore we hypothesized that the combinatorial substratum properties could be tailored to modulate the development of cell sheet formation and further influence its multipotency. For validation, polydimethylsiloxane (PDMS) of different combinatorial substratum properties (including stiffness, roughness and wettability) were created, on which the human bone marrow derived mesenchymal stem cells (BMSCs) were cultured to form cell sheets with their multipotency evaluated after induced differentiation. The results showed that different combinatorial effects of these substratum properties were able to influence BMSC behavior such as adhesion, spreading and proliferation during cell sheet development. Collagen formation within the cell sheet was enhanced on substrates with lower stiffness, higher hydrophobicity and roughness, which further assisted the induced chondrogenesis and osteogenesis, respectively. These findings suggested that combinatorial substratum properties had profound effects on BMSC cell sheet integrity and multipotency, which had significant implications for future biomaterials and scaffold designs in the field of BMSC-mediated tissue regeneration. Copyright © 2015 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Ecological monitoring in a discrete-time prey-predator model.

PubMed

Gámez, M; López, I; Rodríguez, C; Varga, Z; Garay, J

2017-09-21

The paper is aimed at the methodological development of ecological monitoring in discrete-time dynamic models. In earlier papers, in the framework of continuous-time models, we have shown how a systems-theoretical methodology can be applied to the monitoring of the state process of a system of interacting populations, also estimating certain abiotic environmental changes such as pollution, climatic or seasonal changes. In practice, however, there may be good reasons to use discrete-time models. (For instance, there may be discrete cycles in the development of the populations, or observations can be made only at discrete time steps.) Therefore the present paper is devoted to the development of the monitoring methodology in the framework of discrete-time models of population ecology. By monitoring we mean that, observing only certain component(s) of the system, we reconstruct the whole state process. This may be necessary, e.g., when in a complex ecosystem the observation of the densities of certain species is impossible, or too expensive. For the first presentation of the offered methodology, we have chosen a discrete-time version of the classical Lotka-Volterra prey-predator model. This is a minimal but not trivial system where the methodology can still be presented. We also show how this methodology can be applied to estimate the effect of an abiotic environmental change, using a component of the population system as an environmental indicator. Although this approach is illustrated in a simplest possible case, it can be easily extended to larger ecosystems with several interacting populations and different types of abiotic environmental effects. Copyright © 2017 Elsevier Ltd. All rights reserved.