Bibliografías temáticas / Evolutionary problems

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Literatura académica sobre el tema "Evolutionary problems"

Autor: Grafiati
Publicado: 10 de marzo de 2023

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Artículos de revistas sobre el tema "Evolutionary problems"

1

Dmitriev, V. I. "Solving evolutionary inverse problems". Computational Mathematics and Modeling 22, n.º 3 (julio de 2011): 342–46. http://dx.doi.org/10.1007/s10598-011-9105-y.

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Preston, Mark D., Jonathan W. Pitchford y A. Jamie Wood. "Evolutionary optimality in stochastic search problems". Journal of The Royal Society Interface 7, n.º 50 (24 de marzo de 2010): 1301–10. http://dx.doi.org/10.1098/rsif.2010.0090.

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‘Optimal’ behaviour in a biological system is not simply that which maximizes a mean, or temporally and spatially averaged, fitness function. Rather, population dynamics and demographic and environmental stochasticity are fundamental evolutionary ingredients. Here, we revisit the problem of optimal foraging, where some recent studies claim that organisms should forage according to Lévy walks. We show that, in an ecological scenario dominated by uncertainty and high mortality, Lévy walks can indeed be evolutionarily favourable. However, this conclusion is dependent on the definition of efficiency and the details of the simulations. We analyse measures of efficiency that incorporate population-level characteristics, such as variance, superdiffusivity and heavy tails, and compare the results with those generated by simple maximizing of the average encounter rate. These results have implications on stochastic search problems in general, and also on computational models of evolutionary optima.
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Karpov, V. E. "Methodological problems in evolutionary computation". Scientific and Technical Information Processing 40, n.º 5 (diciembre de 2013): 286–91. http://dx.doi.org/10.3103/s0147688213050031.

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Vishnevskii, M. P. y V. I. Priimenko. "Evolutionary Problems of Nonlinear Magnetoelasticity". Siberian Mathematical Journal 61, n.º 1 (enero de 2020): 47–61. http://dx.doi.org/10.1134/s0037446620010048.

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Harvey, Paul H. "Parasitological teeth for evolutionary problems". Nature 342, n.º 6247 (noviembre de 1989): 230. http://dx.doi.org/10.1038/342230a0.

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Picard, Rainer, Sascha Trostorff, Marcus Waurick y Maria Wehowski. "On non-autonomous evolutionary problems". Journal of Evolution Equations 13, n.º 4 (15 de septiembre de 2013): 751–76. http://dx.doi.org/10.1007/s00028-013-0201-7.

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Baker, Christopher T. H., Kevin Burrage y Neville J. Ford. "Special issue on evolutionary problems". Journal of Computational and Applied Mathematics 205, n.º 2 (agosto de 2007): 667–68. http://dx.doi.org/10.1016/j.cam.2006.06.007.

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Haccou, Patsy y Wim J. van der Steen. "Methodological problems in evolutionary biology". Acta Biotheoretica 40, n.º 4 (diciembre de 1992): 285–95. http://dx.doi.org/10.1007/bf00046328.

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Bittnar, Zdenek y Barry H. V. Topping. "Evolutionary optimization of engineering problems". Advances in Engineering Software 36, n.º 1 (enero de 2005): 1–2. http://dx.doi.org/10.1016/j.advengsoft.2004.09.002.

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Nerukh, A. G. "Evolutionary approach in transient electrodynamics problems". Radio Science 30, n.º 3 (mayo de 1995): 481–91. http://dx.doi.org/10.1029/94rs03377.

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Tesis sobre el tema "Evolutionary problems"

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Weicker, Karsten. "Evolutionary algorithms and dynamic optimization problems /". Osnabrück : Der Andere Verl, 2003. http://www.gbv.de/dms/ilmenau/toc/365163716weick.PDF.

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Soylu, Banu. "An Evolutionary Algorithm For Multiple Criteria Problems". Phd thesis, METU, 2007. http://etd.lib.metu.edu.tr/upload/2/12608134/index.pdf.

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In this thesis, we develop an evolutionary algorithm for approximating the Pareto frontier of multi-objective continuous and combinatorial optimization problems. The algorithm tries to evolve the population of solutions towards the Pareto frontier and distribute it over the frontier in order to maintain a well-spread representation. The fitness score of each solution is computed with a Tchebycheff distance function and non-dominating sorting approach. Each solution chooses its own favorable weights according to the Tchebycheff distance function. Some seed solutions at initial population and a crowding measure also help to achieve satisfactory results. In order to test the performance of our evolutionary algorithm, we use some continuous and combinatorial problems. The continuous test problems taken from the literature have special difficulties that an evolutionary algorithm has to deal with. Experimental results of our algorithm on these problems are provided. One of the combinatorial problems we address is the multi-objective knapsack problem. We carry out experiments on test data for this problem given in the literature. We work on two bi-criteria p-hub location problems and propose an evolutionary algorithm to approximate the Pareto frontiers of these problems. We test the performance of our algorithm on Turkish Postal System (PTT) data set (TPDS), AP (Australian Post) and CAB (US Civil Aeronautics Board) data sets. The main contribution of this thesis is in the field of developing a multi-objective evolutionary algorithm and applying it to a number of multi-objective continuous and combinatorial optimization problems.
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Guenther, Chris. "Pseudospectral techniques for non-smooth evolutionary problems". Morgantown, W. Va. : [West Virginia University Libraries], 1998. http://etd.wvu.edu/templates/showETD.cfm?recnum=202.

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Thesis (Ph. D.)--West Virginia University, 1998.
Title from document title page. Document formatted into pages; contains xi, 116 p. : ill. (some col.) Includes abstract. Includes bibliographical references (p. 94-98).
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Mason, Andrew J. "Genetic algorithms and scheduling problems". Thesis, University of Cambridge, 1992. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.335134.

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Demir, Erdem. "Analysis Of Evolutionary Algorithms For Constrained Routing Problems". Master's thesis, METU, 2004. http://etd.lib.metu.edu.tr/upload/12605083/index.pdf.

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This study focuses on two types of routing problems based on standard Traveling Salesman Problem, which are TSP with pickup and delivery (TSPPD) and TSP with backhauls (TSPB). In both of these problems, there are two types of customers, i.e. &ldquo
delivery customers&rdquo
demanding goods from depot and &ldquo
pickup customers&rdquo
sending goods to depot. The objective is to minimize the cost of the tour that visits every customer once without violating the side constraints. In TSPB, delivery customers should precede the pickup customers, whereas the vehicle capacity should not be exceeded in TSPPD. The aim of the study is to propose good Evolutionary Algorithms (EA) for these two problems and also analyze the adaptability of an EA, originally designed for the standard TSP, to the problems with side constraints. This effort includes commenting on the importance of feasibility of the solutions in the population with respect to these side constraints. Having this in mind, different EA strategies involving feasible or infeasible solutions are designed. These strategies are compared by quantitative experiments realized over a set of problem instances and the results are given.
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Barkat, Ullah Abu Saleh Shah Muhammad Engineering &amp Information Technology Australian Defence Force Academy UNSW. "An integrated evolutionary system for solving optimization problems". Awarded by:University of New South Wales - Australian Defence Force Academy. Engineering & Information Technology, 2009. http://handle.unsw.edu.au/1959.4/43764.

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Many real-world decision processes require solving optimization problems which may involve different types of constraints such as inequality and equality constraints. The hurdles in solving these Constrained Optimization Problems (COPs) arise from the challenge of searching a huge variable space in order to locate feasible points with acceptable solution quality. Over the last decades Evolutionary Algorithms (EAs) have brought a tremendous advancement in the area of computer science and optimization with their ability to solve various problems. However, EAs have inherent difficulty in dealing with constraints when solving COPs. This thesis presents a new Agent-based Memetic Algorithm (AMA) for solving COPs, where the agents have the ability to independently select a suitable Life Span Learning Process (LSLP) from a set of LSLPs. Each agent represents a candidate solution of the optimization problem and tries to improve its solution through cooperation with other agents. Evolutionary operators consist of only crossover and one of the self-adaptively selected LSLPs. The performance of the proposed algorithm is tested on benchmark problems, and the experimental results show convincing performance. The quality of individuals in the initial population influences the performance of evolutionary algorithms, especially when the feasible region of the constrained optimization problems is very tiny in comparison to the entire search space. This thesis proposes a method that improves the quality of randomly generated initial solutions by sacrificing very little in diversity of the population. The proposed Search Space Reduction Technique (SSRT) is tested using five different existing EAs, including AMA, by solving a number of state-of-the-art test problems and a real world case problem. The experimental results show SSRT improves the solution quality, and speeds up the performance of the algorithms. The handling of equality constraints has long been a difficult issue for evolutionary optimization methods, although several methods are available in the literature for handling functional constraints. In any optimization problems with equality constraints, to satisfy the condition of feasibility and optimality the solution points must lie on each and every equality constraint. This reduces the size of the feasible space and makes it difficult for EAs to locate feasible and optimal solutions. A new Equality Constraint Handling Technique (ECHT) is presented in this thesis, to enhance the performance of AMA in solving constrained optimization problems with equality constraints. The basic concept is to reach a point on the equality constraint from its current position by the selected individual solution and then explore on the constraint landscape. The technique is used as an agent learning process in AMA. The experimental results confirm the improved performance of the proposed algorithm. This thesis also proposes a Modified Genetic Algorithm (MGA) for solving COPs with equality constraints. After achieving inspiring performance in AMA when dealing with equality constraints, the new technique is used in the design of MGA. The experimental results show that the proposed algorithm overcomes the limitations of GA in solving COPs with equality constraints, and provides good quality solutions.
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Priestley, A. "Lagrange and characteristic Galerkin methods for evolutionary problems". Thesis, University of Oxford, 1986. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.376942.

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Liu, Wudong. "Evolutionary multiobjective optimisation for expensive and complex problems". Thesis, University of Essex, 2010. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.537937.

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Garcia, Najera Abel. "Multi-Objective evolutionary algorithms for vehicle routing problems". Thesis, University of Birmingham, 2010. http://etheses.bham.ac.uk//id/eprint/1069/.

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The Vehicle Routing Problem, which main objective is to find the lowest-cost set of routes to deliver goods to customers, has many applications in transportation services. In the past, costs have been mainly associated to the number of routes and the travel distance, however, in real-world problems there exist additional objectives. Since there is no known exact method to efficiently solve the problem in polynomial time, many heuristic techniques have been considered, among which, evolutionary methods have proved to be suitable for solving the problem. Despite this method being able to provide a set of solutions that represent the trade-offs between multiple objectives, very few studies have concentrated on the optimisation of more than one objective, and even fewer have explicitly considered the diversity of solutions, which is crucial for the good performance of any evolutionary computation technique. This thesis proposes a novel Multi-Objective Evolutionary Algorithm to solve two variants of the Vehicle Routing Problem, regarding the optimisation of at least two objectives. This approach incorporates a method for measuring the similarity of solutions, which is used to enhance population diversity, and operators that effectively explore and exploit the search space. The algorithm is applied to typical benchmark problems and empirical analyses indicate that it efficiently solves the variants being studied. Moreover, the proposed method has proved to be competitive with recent approaches and outperforms the successful multi-objective optimiser NSGA-II.
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Mohammed, Ali Hind. "Behavior study of an evolutionary design for permutation problems". Thesis, Bourgogne Franche-Comté, 2018. http://www.theses.fr/2018UBFCD033.

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Cette thèse étudie une combinaison évolutionnaire représentation_croisement pour des problèmes de permutation. Ceux-ci sont très étudiés dans la littérature en raison de leur complexité et de la diversité de leurs applications. Des méthodes efficaces existent pour résoudre les problèmes de permutation. Mais les états de l’art récents montrent que les applications réelles font émerger de nouvelles instances qui sont fortement dynamiques et conjuguent de nombreux objectifs et contraintes, notamment de synchronisation. Cette contribution se concentre sur les approches évolutionnaires. Elle explore en détail le comportement d’une combinaison représentation_croisement donnée. Le but est de vérifier si cette conception évolutive pourrait constituer un moyen complémentaire intéressant de s’attaquer efficacement à certaines contraintes. Ce travail étudie le lien entre la représentation utilisée, les opérateurs de recombinaison choisis et les caractéristiquesdu problème à résoudre, en se focalisant sur une représentation par code de Lehmer et le croisement à k-points. Ceci permet de déduire certaines hypothèses (certaines d’entre elles étant contradictoires) concernant le comportement de lacombinaison de croisements k-points appliqués à la représentation Lehmer. Une phase d’expérience est utilisée pour vérifier ces hypothèses. Elle est réalisée par comparaison avec un codage direct de permutation classique, couplé à un croisement PMX. Des mesures sont utilisées pour observer le comportement des mécanismes évolutifs, à la fois dans l’espace de recherche (en termes de génotype) et dans l’espace objectif (en termes de phénotype et de critère de qualité associé). Les remarques de conclusion, les implications et les directions de recherche futures concluent le travail
This thesis studies an evolutionary representation - crossover combination for permutation problems. These are widely studied in literature due to their hardness and the diversity of their application fields. Efficient methods exist to solve permutation problems. But several recent surveys show that real applications induce new instances that are strongly dynamic and characterized by the conjunction of particular constraints and objectives, particularly synchronization. This contribution focuses on evolutionary approaches. It explores in details the behaviour of a given representation crossovercombination. The goal is to check if this evolutionary design could be an interesting complementary way to tackle efficiently some of the constraints. This work studies the link between the representation used, the chosen recombination operators and the characteristics of the problem to be solved, focusing on Lehmer code representation and kpoint crossover. This review permits to deduce some assumptions (some of them being contradictory) regarding the behaviour of the Lehmer Code representation k-point crossover combination. Experiments are used to verify these assumptions, performed by comparison with permutation encoding coupled with PMX crossover. Measurements are used to observe the behavior of evolutionary mechanisms, both in the search space (in terms of genotype) and in the objective space ( in terms of phenotype and associated quality criterion). Concluding remarks, implications and future research directions conclude the work
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Libros sobre el tema "Evolutionary problems"

1

J, Penn Dustin y Mysterud Iver, eds. Evolutionary perspectives on environmental problems. New Brunswick, N.J: Aldine Transaction, 2007.

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J, Penn Dustin y Mysterud Iver, eds. Evolutionary perspectives in environmental problems. New Brunswick, N.J: Aldine Transaction, 2005.

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Yang, Shengxiang y Xin Yao, eds. Evolutionary Computation for Dynamic Optimization Problems. Berlin, Heidelberg: Springer Berlin Heidelberg, 2013. http://dx.doi.org/10.1007/978-3-642-38416-5.

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Yang, Shengxiang. Evolutionary Computation for Dynamic Optimization Problems. Berlin, Heidelberg: Springer Berlin Heidelberg, 2013.

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Coello, Carlos A. Coello. Evolutionary algorithms for solving multi-objective problems. New York: Kluwer Academic, 2002.

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Coello Coello, Carlos A., David A. Van Veldhuizen y Gary B. Lamont. Evolutionary Algorithms for Solving Multi-Objective Problems. Boston, MA: Springer US, 2002. http://dx.doi.org/10.1007/978-1-4757-5184-0.

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Coello, Carlos A. Coello. Evolutionary Algorithms for Solving Multi-Objective Problems. Boston, MA: Springer US, 2002.

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A, Vorotnikov Dmitry, ed. Topological approximation methods for evolutionary problems of nonlinear hydrodynamics. Berlin: Walter de Gruyter, 2008.

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Evolutionary genetics. Oxford: Oxford University Press, 1989.

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Evolutionary genetics. 2a ed. Oxford: Oxford University Press, 1998.

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Capítulos de libros sobre el tema "Evolutionary problems"

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Buss, David M. "Problems of Parenting". En Evolutionary Psychology, 189–217. 6th Edition. | New York : Routledge, 2019. | Revised edition of the author’s Evolutionary psychology, [2015]: Routledge, 2019. http://dx.doi.org/10.4324/9780429061417-11.

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Buss, David M. "Problems of Kinship". En Evolutionary Psychology, 218–44. 6th Edition. | New York : Routledge, 2019. | Revised edition of the author’s Evolutionary psychology, [2015]: Routledge, 2019. http://dx.doi.org/10.4324/9780429061417-12.

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Watanabe, Keigo y M. M. A. Hashem. "Evolutionary Optimization of Constrained Problems". En Evolutionary Computations, 53–64. Berlin, Heidelberg: Springer Berlin Heidelberg, 2004. http://dx.doi.org/10.1007/978-3-540-39883-7_3.

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Watanabe, Keigo y M. M. A. Hashem. "Evolutionary Solution of Optimal Control Problems". En Evolutionary Computations, 77–87. Berlin, Heidelberg: Springer Berlin Heidelberg, 2004. http://dx.doi.org/10.1007/978-3-540-39883-7_5.

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Burke, Edmund, David Elliman y Rupert Weare. "Specialised recombinative operators for timetabling problems". En Evolutionary Computing, 75–85. Berlin, Heidelberg: Springer Berlin Heidelberg, 1995. http://dx.doi.org/10.1007/3-540-60469-3_26.

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Seifert, Christian, Sascha Trostorff y Marcus Waurick. "Initial Value Problems and Extrapolation Spaces". En Evolutionary Equations, 131–48. Cham: Springer International Publishing, 2021. http://dx.doi.org/10.1007/978-3-030-89397-2_9.

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AbstractUp until now we have dealt with evolutionary equations of the form $$\displaystyle \big (\overline {\partial _{t,\nu }M(\partial _{t,\nu })+A}\big )U=F $$ ( ∂ t , ν M ( ∂ t , ν ) + A ¯ ) U = F for some given $$F\in L_{2,\nu }(\mathbb {R};H)$$ F ∈ L 2 , ν ( ℝ ; H ) for some Hilbert space H, a skew-selfadjoint operator A in H and a material law M defined on a suitable half-plane satisfying an appropriate positive definiteness condition with $$\nu \in \mathbb {R}$$ ν ∈ ℝ chosen suitably large. Under these conditions, we established that the solution operator, "Equation missing", is eventually independent of ν and causal; that is, if F = 0 on $$\left (-\infty ,a\right ]$$ − ∞ , a for some $$a\in \mathbb {R}$$ a ∈ ℝ , then so too is U.
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Field, Paul. "Nonbinary transforms for genetic algorithm problems". En Evolutionary Computing, 38–50. Berlin, Heidelberg: Springer Berlin Heidelberg, 1994. http://dx.doi.org/10.1007/3-540-58483-8_4.

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Joshi, Ramprasad, Bharat Deshpande y Paritosh Gote. "Objective Dimension and Problem Structurein Multiobjective Optimization Problems". En Applications of Evolutionary Computation, 639–50. Berlin, Heidelberg: Springer Berlin Heidelberg, 2014. http://dx.doi.org/10.1007/978-3-662-45523-4_52.

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Macready, William G. "Problems in Optimization". En Frontiers of Evolutionary Computation, 115–28. Boston, MA: Springer US, 2004. http://dx.doi.org/10.1007/1-4020-7782-3_6.

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Seifert, Christian, Sascha Trostorff y Marcus Waurick. "Boundary Value Problems and Boundary Value Spaces". En Evolutionary Equations, 189–204. Cham: Springer International Publishing, 2021. http://dx.doi.org/10.1007/978-3-030-89397-2_12.

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AbstractThis chapter is devoted to the study of inhomogeneous boundary value problems. For this, we shall reformulate the boundary value problem again into a form which fits within the general framework of evolutionary equations. In order to have an idea of the type of boundary values which make sense to study, we start off with a section that deals with the boundary values of functions in the domain of the gradient operator defined on a half-space in $$\mathbb {R}^d$$ ℝ d (for d = 1 we have $$L_2(\mathbb {R}^{d-1})=\mathbb {K}$$ L 2 ( ℝ d − 1 ) = 𝕂 ).
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Actas de conferencias sobre el tema "Evolutionary problems"

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Bonyadi, Mohammad Reza, Zbigniew Michalewicz y Luigi Barone. "The travelling thief problem: The first step in the transition from theoretical problems to realistic problems". En 2013 IEEE Congress on Evolutionary Computation (CEC). IEEE, 2013. http://dx.doi.org/10.1109/cec.2013.6557681.

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Ullrich, Markus, Thomas Weise, Abhishek Awasthi y Jörg Lässig. "A generic problem instance generator for discrete optimization problems". En GECCO '18: Genetic and Evolutionary Computation Conference. New York, NY, USA: ACM, 2018. http://dx.doi.org/10.1145/3205651.3208284.

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Li, Yangyang, Zhenghan Chen, Yang Wang y Licheng Jiao. "Evolutionary algorithm using converted problems". En TENCON 2016 - 2016 IEEE Region 10 Conference. IEEE, 2016. http://dx.doi.org/10.1109/tencon.2016.7848634.

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Hamada, Naoki. "Simple problems". En GECCO '17: Genetic and Evolutionary Computation Conference. New York, NY, USA: ACM, 2017. http://dx.doi.org/10.1145/3067695.3076069.

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Schuetze, Oliver, Adriana Lara y Carlos A. Coello Coello. "Evolutionary continuation methods for optimization problems". En the 11th Annual conference. New York, New York, USA: ACM Press, 2009. http://dx.doi.org/10.1145/1569901.1569991.

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Yang, Shengxiang y Jürgen Branke. "Evolutionary algorithms for dynamic optimization problems". En the 2005 workshops. New York, New York, USA: ACM Press, 2005. http://dx.doi.org/10.1145/1102256.1102261.

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Sastry, Kumara, Alexandre C. B. Delbem y David E. Goldberg. "Evolutionary Algorithm for Large Scale Problems". En Seventh International Conference on Intelligent Systems Design and Applications (ISDA 2007). IEEE, 2007. http://dx.doi.org/10.1109/isda.2007.114.

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Sastry, Kumara, Alexandre C. B. Delbem y David E. Goldberg. "Evolutionary Algorithm for Large Scale Problems". En Seventh International Conference on Intelligent Systems Design and Applications (ISDA 2007). IEEE, 2007. http://dx.doi.org/10.1109/isda.2007.4389709.

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Yang, Shengxiang. "Evolutionary computation for dynamic optimization problems". En Proceeding of the fifteenth annual conference companion. New York, New York, USA: ACM Press, 2013. http://dx.doi.org/10.1145/2464576.2480805.

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Yang, Shengxiang. "Evolutionary Computation for Dynamic Optimization Problems". En GECCO '15: Genetic and Evolutionary Computation Conference. New York, NY, USA: ACM, 2015. http://dx.doi.org/10.1145/2739482.2756589.

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Informes sobre el tema "Evolutionary problems"

1

Homaifar, Abdollah, Albert Esterline y Bahram Kimiaghalam. Hybrid Projected Gradient-Evolutionary Search Algorithm for Mixed Integer Nonlinear Optimization Problems. Fort Belvoir, VA: Defense Technical Information Center, abril de 2005. http://dx.doi.org/10.21236/ada455904.

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Fogel, David B. Addressing the Travelling Salesman Problem through Evolutionary Adaptation. Fort Belvoir, VA: Defense Technical Information Center, enero de 1987. http://dx.doi.org/10.21236/ada179992.

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Balda, Taras. ISSUES OF PACIFISM AND MILITARISM OF LIBERATION STRUGGLE IN UKRAINIAN DIASPORA PUBLICATIONS. Ivan Franko National University of Lviv, febrero de 2022. http://dx.doi.org/10.30970/vjo.2022.51.11390.

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Subject of the article’s study – journalism of Ukrainian diaspora publications on the topic of liberation struggle of Ukrainian nation. The author emphasizes on variations of such a struggle, in particular on traditions of militarism and pacifism. A lot of Ukrainians who lived outside of Ukraine, because of third wave of emigration, used to believe that the USA will start another world war, will deal with the USSR and in this way will help Ukraine become independent. Similar thoughts were fundamental thesis of so-called «liberation conception». Such theories and hopes were outlined in columns of such magazines as «Visti Combatanta», «Vyzvolnyi Shliakh». But another part of political emigrants, concentrated around OUN (w) and URDP, positions of which were represented in such publications as «Ukrainskyi samostiynyk» and «Nashi posytsii», problem of Ukrainian independence tried not to deceive to war between the USA and the USSR and considered nonviolent methods of government change. Similar thoughts had the authors of «Suchasnist» and «Lysty do Pryiateliv». Time and historical realities showed that were right those journalists who believed in evolutionary, not revolutionary, theory of state development. Ukraine was able to become independent peacefully after the USSR decay and creation of sovereign states. Among this, modern Ukrainian society still lacks respect to Ukrainian army, nurturing of traditions of military valor, honor and justice, to which even diaspora journalists paid attention in the previous century.
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4

Shpigel, Nahum Y., Ynte Schukken y Ilan Rosenshine. Identification of genes involved in virulence of Escherichia coli mastitis by signature tagged mutagenesis. United States Department of Agriculture, enero de 2014. http://dx.doi.org/10.32747/2014.7699853.bard.

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Mastitis, an inflammatory response of the mammary tissue to invading pathogenic bacteria, is the largest health problem in the dairy industry and is responsible for multibillion dollar economic losses. E. coli are a leading cause of acute mastitis in dairy animals worldwide and certainly in Israel and North America. The species E. coli comprises a highly heterogeneous group of pathogens, some of which are commensal residents of the gut, infecting the mammary gland after contamination of the teat skin from the environment. As compared to other gut microflora, mammary pathogenic E. coli (MPEC) may have undergone evolutionary adaptations that improve their fitness for colonization of the unique and varied environmental niches found within the mammary gland. These niches include competing microbes already present or accompanying the new colonizer, soluble and cellular antimicrobials in milk, and the innate immune response elicited by mammary cells and recruited immune cells. However, to date, no specific virulence factors have been identified in E. coli isolates associated with mastitis. The original overall research objective of this application was to develop a genome-wide, transposon-tagged mutant collection of MPEC strain P4 and to use this technology to identify E. coli genes that are specifically involved in mammary virulence and pathogenicity. In the course of the project we decided to take an alternative genome-wide approach and to use whole genomes bioinformatics analysis. Using genome sequencing and analysis of six MPEC strains, our studies have shown that type VI secretion system (T6SS) gene clusters were present in all these strains. Furthermore, using unbiased screening of MPEC strains for reduced colonization, fitness and virulence in the murine mastitis model, we have identified in MPEC P4-NR a new pathogenicity island (PAI-1) encoding the core components of T6SS and its hallmark effectors Hcp, VgrG and Rhs. Next, we have shown that specific deletions of T6SS genes reduced colonization, fitness and virulence in lactating mouse mammary glands. Our long-term goal is to understand the molecular mechanisms of host-pathogen interactions in the mammary gland and to relate these mechanisms to disease processes and pathogenesis. We have been able to achieve our research objectives to identify E. coli genes that are specifically involved in mammary virulence and pathogenicity. The project elucidated a new basic concept in host pathogen interaction of MPEC, which for the best of our knowledge was never described or investigated before. This research will help us to shed new light on principles behind the infection strategy of MPEC. The new targets now enable prevalence and epidemiology studies of T6SS in field strains of MPEC which might unveil new geographic, management and ecological risk factors. These will contribute to development of new approaches to treat and prevent mastitis by MPEC and perhaps other mammary pathogens. The use of antibiotics in farm animals and specifically to treat mastitis is gradually precluded and thus new treatment and prevention strategies are needed. Effective mastitis vaccines are currently not available, structural components and effectors of T6SS might be new targets for the development of novel vaccines and therapeutics.
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5

Chamovitz, Daniel A. y Albrecht G. Von Arnim. eIF3 Complexes and the eIF3e Subunit in Arabidopsis Development and Translation Initiation. United States Department of Agriculture, septiembre de 2009. http://dx.doi.org/10.32747/2009.7696545.bard.

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The original working hypothesis of our proposal was that The “e” subunit of eIF3 has multiple functions from both within the nucleus and in the cytoplasm. Within this model, we further hypothesized that the “e” subunit of eIF3 functions in translation as a repressor. We proposed to test these hypotheses along the following specific aims: 1) Determine the subcellular localization of the interaction between eIF3e and other eIF3 subunits, or the COP9 signalosome. 2) Elucidate the biological significance of the varied subcellular localizations of eIF3e through generating Arabidopsis eIF3e alleles with altered subcellular localization. 3.) Purify different eIF3e complexes by tandem affinity purification (TAP). 4) Study the role of eIF3e in translational repression using both in vitro and in planta assays. eIF3 is an evolutionarily ancient and essential component of the translational apparatus in both the plant and animal kingdoms. eIF3 is the largest, and in some ways the most mysterious, of the translation factors. It is a multi-subunit protein complex that has a structural/scaffolding role in translation initiation. However, despite years of study, only recently have differential roles for eIF3 in the developmental regulation of translation been experimentally grounded. Furthermore, the roles of individual eIF3 subunits are not clear, and indeed some, such as the “e” subunit may have roles independent of translation initiation. The original three goals of the proposal were technically hampered by a finding that became evident during the course of the research – Any attempt to make transgenic plants that expressed eIF3e wt or eIF3e variants resulted in seedling lethality or seed inviability. That is, it was impossible to regenerate any transgenic plants that expressed eIF3e. We did manage to generate plants that expressed an inducible form of eIF3e. This also eventually led to lethality, but was very useful in elucidating the 4th goal of the research (Yahalom et al., 2008), where we showed, for the first time in any organism, that eIF3e has a repressory role in translation. In attempt to solve the expression problems, we also tried expression from the native promoter, and as such analyzed this promoter in transgenic plants (Epel, 2008). As such, several additional avenues were pursued. 1) We investigated protein-protein interactions of eIF3e (Paz-Aviram et al., 2008). 2) The results from goal #4 led to a novel hypothesis that the interaction of eIF3e and the CSN meets at the control of protein degradation of nascent proteins. In other words, that the block in translation seen in csn and eIF3e-overexpressing plants (Yahalom et al., 2008) leads to proteasome stress. Indeed we showed that both over expression of eIF3e and the csn mutants lead to the unfolded protein response. 3) We further investigated the role of an additional eIF3 subunit, eIF3h, in transalational regulation in the apical meristem (Zhou et al., 2009). Epel, A. (2008). Characterization of eIF3e in the model plant Arabidopsis thaliana. In Plant Sciences (Tel Aviv, Tel Aviv University). Paz-Aviram, T., Yahalom, A., and Chamovitz, D.A. (2008). Arabidopsis eIF3e interacts with subunits of the ribosome, Cop9 signalosome and proteasome. Plant Signaling and Behaviour 3, 409-411. Yahalom, A., Kim, T.H., Roy, B., Singer, R., von Arnim, A.G., and Chamovitz, D.A. (2008). Arabidopsis eIF3e is regulated by the COP9 signalosome and has an impact on development and protein translation. Plant J 53, 300-311. Zhou, F., Dunlap, J.R., and von Arnim, A.G. The translation initiation factor subunit eIF3h is .1 involved in Arabidopsis shoot apical meristem maintenance and auxin response. (submitted to Development).
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Altstein, Miriam y Ronald J. Nachman. Rational Design of Insect Control Agent Prototypes Based on Pyrokinin/PBAN Neuropeptide Antagonists. United States Department of Agriculture, agosto de 2013. http://dx.doi.org/10.32747/2013.7593398.bard.

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The general objective of this study was to develop rationally designed mimetic antagonists (and agonists) of the PK/PBAN Np class with enhanced bio-stability and bioavailability as prototypes for effective and environmentally friendly pest insect management agents. The PK/PBAN family is a multifunctional group of Nps that mediates key functions in insects (sex pheromone biosynthesis, cuticular melanization, myotropic activity, diapause and pupal development) and is, therefore, of high scientific and applied interest. The objectives of the current study were: (i) to identify an antagonist biophores (ii) to develop an arsenal of amphiphilic topically active PK/PBAN antagonists with an array of different time-release profiles based on the previously developed prototype analog; (iii) to develop rationally designed non-peptide SMLs based on the antagonist biophore determined in (i) and evaluate them in cloned receptor microplate binding assays and by pheromonotropic, melanotropic and pupariation in vivo assays. (iv) to clone PK/PBAN receptors (PK/PBAN-Rs) for further understanding of receptor-ligand interactions; (v) to develop microplate binding assays for screening the above SMLs. In the course of the granting period A series of amphiphilic PK/PBAN analogs based on a linear lead antagonist from the previous BARD grant was synthesized that incorporated a diverse array of hydrophobic groups (HR-Suc-A[dF]PRLa). Others were synthesized via the attachment of polyethylene glycol (PEG) polymers. A hydrophobic, biostablePK/PBAN/DH analog DH-2Abf-K prevented the onset of the protective state of diapause in H. zea pupae [EC50=7 pmol/larva] following injection into the preceding larval stage. It effectively induces the crop pest to commit a form of ‘ecological suicide’. Evaluation of a set of amphiphilic PK analogs with a diverse array of hydrophobic groups of the formula HR-Suc-FTPRLa led to the identification of analog T-63 (HR=Decyl) that increased the extent of diapause termination by a factor of 70% when applied topically to newly emerged pupae. Another biostablePK analog PK-Oic-1 featured anti-feedant and aphicidal properties that matched the potency of some commercial aphicides. Native PK showed no significant activity. The aphicidal effects were blocked by a new PEGylated PK antagonist analog PK-dF-PEG4, suggesting that the activity is mediated by a PK/PBAN receptor and therefore indicative of a novel and selective mode-of-action. Using a novel transPro mimetic motif (dihydroimidazole; ‘Jones’) developed in previous BARD-sponsored work, the first antagonist for the diapause hormone (DH), DH-Jo, was developed and shown to block over 50% of H. zea pupal diapause termination activity of native DH. This novel antagonist development strategy may be applicable to other invertebrate and vertebrate hormones that feature a transPro in the active core. The research identifies a critical component of the antagonist biophore for this PK/PBAN receptor subtype, i.e. a trans-oriented Pro. Additional work led to the molecular cloning and functional characterization of the DH receptor from H. zea, allowing for the discovery of three other DH antagonist analogs: Drosophila ETH, a β-AA analog, and a dF analog. The receptor experiments identified an agonist (DH-2Abf-dA) with a maximal response greater than native DH. ‘Deconvolution’ of a rationally-designed nonpeptide heterocyclic combinatorial library with a cyclic bis-guanidino (BG) scaffold led to discovery of several members that elicited activity in a pupariation acceleration assay, and one that also showed activity in an H. zea diapause termination assay, eliciting a maximal response of 90%. Molecular cloning and functional characterization of a CAP2b antidiuretic receptor from the kissing bug (R. prolixus) as well as the first CAP2b and PK receptors from a tick was also achieved. Notably, the PK/PBAN-like receptor from the cattle fever tick is unique among known PK/PBAN and CAP2b receptors in that it can interact with both ligand types, providing further evidence for an evolutionary relationship between these two NP families. In the course of the granting period we also managed to clone the PK/PBAN-R of H. peltigera, to express it and the S. littoralis-R Sf-9 cells and to evaluate their interaction with a variety of PK/PBAN ligands. In addition, three functional microplate assays in a HTS format have been developed: a cell-membrane competitive ligand binding assay; a Ca flux assay and a whole cell cAMP ELISA. The Ca flux assay has been used for receptor characterization due to its extremely high sensitivity. Computer homology studies were carried out to predict both receptor’s SAR and based on this analysis 8 mutants have been generated. The bioavailability of small linear antagonistic peptides has been evaluated and was found to be highly effective as sex pheromone biosynthesis inhibitors. The activity of 11 new amphiphilic analogs has also been evaluated. Unfortunately, due to a problem with the Heliothis moth colony we were unable to select those with pheromonotropic antagonistic activity and further check their bioavailability. Six peptides exhibited some melanotropic antagonistic activity but due to the low inhibitory effect the peptides were not further tested for bioavailability in S. littoralis larvae. Despite the fact that no new antagonistic peptides were discovered in the course of this granting period the results contribute to a better understanding of the interaction of the PK/PBAN family of Nps with their receptors, provided several HT assays for screening of libraries of various origin for presence of PK/PBAN-Ragonists and antagonists and provided important practical information for the further design of new, peptide-based insecticide prototypes aimed at the disruption of key neuroendocrine physiological functions in pest insects.
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