Modeling Techniques for the High-Resolution Interpretation of Cryo-Electron Microscopy Reconstructions

Essential biological processes are governed by organized, dynamic interactions between multiple biomolecular systems. Complexes are thus formed to enable the biological function and get dissembled as the process is completed. Examples of such processes include the translation of the messenger RNA into protein by the ribosome, the folding of proteins by chaperonins or the entry of viruses in host cells. Understanding these fundamental processes by characterizing the molecular mechanisms that enable then, would allow the (better) design of therapies and drugs. Such molecular mechanisms may be revealed trough the structural elucidation of the biomolecular assemblies at the core of these processes. Various experimental techniques may be applied to investigate the molecular architecture of biomolecular assemblies. High-resolution techniques, such as X-ray crystallography, may solve the atomic structure of the system, but are typically constrained to biomolecules of reduced flexibility and dimensions. In particular, X-ray crystallography requires the sample to form a three dimensional (3D) crystal lattice which is technically di‑cult, if not impossible, to obtain, especially for large, dynamic systems. Often these techniques solve the structure of the different constituent components within the assembly, but encounter difficulties when investigating the entire system. On the other hand, imaging techniques, such as cryo-electron microscopy (cryo-EM), are able to depict large systems in near-native environment, without requiring the formation of crystals. The structures solved by cryo-EM cover a wide range of resolutions, from very low level of detail where only the overall shape of the system is visible, to high-resolution that approach, but not yet reach, atomic level of detail. In this dissertation, several modeling methods are introduced to either integrate cryo-EM datasets with structural data from X-ray crystallography, or to directly interpret the cryo-EM reconstruction. Such computational techniques were developed with the goal of creating an atomic model for the cryo-EM data. The low-resolution reconstructions lack the level of detail to permit a direct atomic interpretation, i.e. one cannot reliably locate the atoms or amino-acid residues within the structure obtained by cryo-EM. Thereby one needs to consider additional information, for example, structural data from other sources such as X-ray crystallography, in order to enable such a high-resolution interpretation. Modeling techniques are thus developed to integrate the structural data from the different biophysical sources, examples including the work described in the manuscript I and II of this dissertation. At intermediate and high-resolution, cryo-EM reconstructions depict consistent 3D folds such as tubular features which in general correspond to alpha-helices. Such features can be annotated and later on used to build the atomic model of the system, see manuscript III as alternative. Three manuscripts are presented as part of the PhD dissertation, each introducing a computational technique that facilitates the interpretation of cryo-EM reconstructions. The first manuscript is an application paper that describes a heuristics to generate the atomic model for the protein envelope of the Rift Valley fever virus. The second manuscript introduces the evolutionary tabu search strategies to enable the integration of multiple component atomic structures with the cryo-EM map of their assembly. Finally, the third manuscript develops further the latter technique and apply it to annotate consistent 3D patterns in intermediate-resolution cryo-EM reconstructions. The first manuscript, titled An assembly model for Rift Valley fever virus, was submitted for publication in the Journal of Molecular Biology. The cryo-EM structure of the Rift Valley fever virus was previously solved at 27Å-resolution by Dr. Freiberg and collaborators. Such reconstruction shows the overall shape of the virus envelope, yet the reduced level of detail prevents the direct atomic interpretation. High-resolution structures are not yet available for the entire virus nor for the two different component glycoproteins that form its envelope. However, homology models may be generated for these glycoproteins based on similar structures that are available at atomic resolutions. The manuscript presents the steps required to identify an atomic model of the entire virus envelope, based on the low-resolution cryo-EM map of the envelope and the homology models of the two glycoproteins. Starting with the results of the exhaustive search to place the two glycoproteins, the model is built iterative by running multiple multi-body refinements to hierarchically generate models for the different regions of the envelope. The generated atomic model is supported by prior knowledge regarding virus biology and contains valuable information about the molecular architecture of the system. It provides the basis for further investigations seeking to reveal different processes in which the virus is involved such as assembly or fusion. The second manuscript was recently published in the of Journal of Structural Biology (doi:10.1016/j.jsb.2009.12.028) under the title Evolutionary tabu search strategies for the simultaneous registration of multiple atomic structures in cryo-EM reconstructions. This manuscript introduces the evolutionary tabu search strategies applied to enable a multi-body registration. This technique is a hybrid approach that combines a genetic algorithm with a tabu search strategy to promote the proper exploration of the high-dimensional search space. Similar to the Rift Valley fever virus, it is common that the structure of a large multi-component assembly is available at low-resolution from cryo-EM, while high-resolution structures are solved for the different components but lack for the entire system. Evolutionary tabu search strategies enable the building of an atomic model for the entire system by considering simultaneously the different components. Such registration indirectly introduces spatial constrains as all components need to be placed within the assembly, enabling the proper docked in the low-resolution map of the entire assembly. Along with the method description, the manuscript covers the validation, presenting the benefit of the technique in both synthetic and experimental test cases. Such approach successfully docked multiple components up to resolutions of 40Å. The third manuscript is entitled Evolutionary Bidirectional Expansion for the Annotation of Alpha Helices in Electron Cryo-Microscopy Reconstructions and was submitted for publication in the Journal of Structural Biology. The modeling approach described in this manuscript applies the evolutionary tabu search strategies in combination with the bidirectional expansion to annotate secondary structure elements in intermediate resolution cryo-EM reconstructions. In particular, secondary structure elements such as alpha helices show consistent patterns in cryo-EM data, and are visible as rod-like patterns of high density. The evolutionary tabu search strategy is applied to identify the placement of the different alpha helices, while the bidirectional expansion characterizes their length and curvature. The manuscript presents the validation of the approach at resolutions ranging between 6 and 14Å, a level of detail where alpha helices are visible. Up to resolution of 12 Å, the method measures sensitivities between 70-100% as estimated in experimental test cases, i.e. 70-100% of the alpha-helices were correctly predicted in an automatic manner in the experimental data. The three manuscripts presented in this PhD dissertation cover different computation methods for the integration and interpretation of cryo-EM reconstructions. The methods were developed in the molecular modeling software Sculptor (http://sculptor.biomachina.org) and are available for the scientific community interested in the multi-resolution modeling of cryo-EM data. The work spans a wide range of resolution covering multi-body refinement and registration at low-resolution along with annotation of consistent patterns at high-resolution. Such methods are essential for the modeling of cryo-EM data, and may be applied in other fields where similar spatial problems are encountered, such as medical imaging.

Differential Evoluiton - Particle Swarm Optimization

This paper shows the Particle Swarm Optimization algorithm with a Differential Evolution. Each candidate solution is sampled uniformly in [!5,5] D, whereDdenotes the search space dimension, and the evolution is performed with a classical PSO algorithm and a classical DE/x/1 algorithm according to a random threshold.

Grammar-Guided Evolutionary Construction of Bayesian networks

This paper proposes the EvoBANE system. EvoBANE automatically generates Bayesian networks for solving special-purpose problems. EvoBANE evolves a population of individuals that codify Bayesian networks until it finds near optimal individual that solves a given classification problem. EvoBANE has the flexibility to modify the constraints that condition the solution search space, self-adapting to the specifications of the problem to be solved. The system extends the GGEAS architecture. GGEAS is a general-purpose grammar-guided evolutionary automatic system, whose modular structure favors its application to the automatic construction of intelligent systems. EvoBANE has been applied to two classification benchmark datasets belonging to different application domains, and statistically compared with a genetic algorithm performing the same tasks. Results show that the proposed system performed better, as it manages different complexity constraints in order to find the simplest solution that best solves every problem.

Independence in CLP Languages

Studying independence of goals has proven very useful in the context of logic programming. In particular, it has provided a formal basis for powerful automatic parallelization tools, since independence ensures that two goals may be evaluated in parallel while preserving correctness and eciency. We extend the concept of independence to constraint logic programs (CLP) and prove that it also ensures the correctness and eciency of the parallel evaluation of independent goals. Independence for CLP languages is more complex than for logic programming as search space preservation is necessary but no longer sucient for ensuring correctness and eciency. Two additional issues arise. The rst is that the cost of constraint solving may depend upon the order constraints are encountered. The second is the need to handle dynamic scheduling. We clarify these issues by proposing various types of search independence and constraint solver independence, and show how they can be combined to allow dierent optimizations, from parallelism to intelligent backtracking. Sucient conditions for independence which can be evaluated \a priori" at run-time are also proposed. Our study also yields new insights into independence in logic programming languages. In particular, we show that search space preservation is not only a sucient but also a necessary condition for ensuring correctness and eciency of parallel execution.

An Interval-based Multiobjective Approach to Feature Subset Selection Using Joint Modeling of Objectives and Variables

This paper studies feature subset selection in classification using a multiobjective estimation of distribution algorithm. We consider six functions, namely area under ROC curve, sensitivity, specificity, precision, F1 measure and Brier score, for evaluation of feature subsets and as the objectives of the problem. One of the characteristics of these objective functions is the existence of noise in their values that should be appropriately handled during optimization. Our proposed algorithm consists of two major techniques which are specially designed for the feature subset selection problem. The first one is a solution ranking method based on interval values to handle the noise in the objectives of this problem. The second one is a model estimation method for learning a joint probabilistic model of objectives and variables which is used to generate new solutions and advance through the search space. To simplify model estimation, l1 regularized regression is used to select a subset of problem variables before model learning. The proposed algorithm is compared with a well-known ranking method for interval-valued objectives and a standard multiobjective genetic algorithm. Particularly, the effects of the two new techniques are experimentally investigated. The experimental results show that the proposed algorithm is able to obtain comparable or better performance on the tested datasets.

Independence in constraint logic programs

Studying independence of literals, variables, and substitutions has proven very useful in the context of logic programming (LP). Here we study independence in the broader context of constraint logic programming (CLP). We show that a naive extrapolation of the LP definitions of independence to CLP is unsatisfactory (in fact, wrong) for two reasons. First, because interaction between variables through constraints is more complex than in the case of logic programming. Second, in order to ensure the efUciency of several optimizations not only must independence of the search space be considered, but also an orthogonal issue - "independence of constraint solving." We clarify these issues by proposing various types of search independence and constraint solver independence, and show how they can be combined to allow different independence-related optimizations, from parallelism to intelligent backtracking. Sufficient conditions for independence which can be evaluated "a-priori" at run-time are also proposed. Our results suggest that independence, provided a suitable definition is chosen, is even more useful in CLP than in LP.

Contribución al estudio del criptoanálisis y diseño de los criptosistemas caóticos

The extraordinary increase of new information technologies, the development of Internet, the electronic commerce, the e-government, mobile telephony and future cloud computing and storage, have provided great benefits in all areas of society. Besides these, there are new challenges for the protection of information, such as the loss of confidentiality and integrity of electronic documents. Cryptography plays a key role by providing the necessary tools to ensure the safety of these new media. It is imperative to intensify the research in this area, to meet the growing demand for new secure cryptographic techniques. The theory of chaotic nonlinear dynamical systems and the theory of cryptography give rise to the chaotic cryptography, which is the field of study of this thesis. The link between cryptography and chaotic systems is still subject of intense study. The combination of apparently stochastic behavior, the properties of sensitivity to initial conditions and parameters, ergodicity, mixing, and the fact that periodic points are dense, suggests that chaotic orbits resemble random sequences. This fact, and the ability to synchronize multiple chaotic systems, initially described by Pecora and Carroll, has generated an avalanche of research papers that relate cryptography and chaos. The chaotic cryptography addresses two fundamental design paradigms. In the first paradigm, chaotic cryptosystems are designed using continuous time, mainly based on chaotic synchronization techniques; they are implemented with analog circuits or by computer simulation. In the second paradigm, chaotic cryptosystems are constructed using discrete time and generally do not depend on chaos synchronization techniques. The contributions in this thesis involve three aspects about chaotic cryptography. The first one is a theoretical analysis of the geometric properties of some of the most employed chaotic attractors for the design of chaotic cryptosystems. The second one is the cryptanalysis of continuos chaotic cryptosystems and finally concludes with three new designs of cryptographically secure chaotic pseudorandom generators. The main accomplishments contained in this thesis are: v Development of a method for determining the parameters of some double scroll chaotic systems, including Lorenz system and Chua’s circuit. First, some geometrical characteristics of chaotic system have been used to reduce the search space of parameters. Next, a scheme based on the synchronization of chaotic systems was built. The geometric properties have been employed as matching criterion, to determine the values of the parameters with the desired accuracy. The method is not affected by a moderate amount of noise in the waveform. The proposed method has been applied to find security flaws in the continuous chaotic encryption systems. Based on previous results, the chaotic ciphers proposed by Wang and Bu and those proposed by Xu and Li are cryptanalyzed. We propose some solutions to improve the cryptosystems, although very limited because these systems are not suitable for use in cryptography. Development of a method for determining the parameters of the Lorenz system, when it is used in the design of two-channel cryptosystem. The method uses the geometric properties of the Lorenz system. The search space of parameters has been reduced. Next, the parameters have been accurately determined from the ciphertext. The method has been applied to cryptanalysis of an encryption scheme proposed by Jiang. In 2005, Gunay et al. proposed a chaotic encryption system based on a cellular neural network implementation of Chua’s circuit. This scheme has been cryptanalyzed. Some gaps in security design have been identified. Based on the theoretical results of digital chaotic systems and cryptanalysis of several chaotic ciphers recently proposed, a family of pseudorandom generators has been designed using finite precision. The design is based on the coupling of several piecewise linear chaotic maps. Based on the above results a new family of chaotic pseudorandom generators named Trident has been designed. These generators have been specially designed to meet the needs of real-time encryption of mobile technology. According to the above results, this thesis proposes another family of pseudorandom generators called Trifork. These generators are based on a combination of perturbed Lagged Fibonacci generators. This family of generators is cryptographically secure and suitable for use in real-time encryption. Detailed analysis shows that the proposed pseudorandom generator can provide fast encryption speed and a high level of security, at the same time. El extraordinario auge de las nuevas tecnologías de la información, el desarrollo de Internet, el comercio electrónico, la administración electrónica, la telefonía móvil y la futura computación y almacenamiento en la nube, han proporcionado grandes beneficios en todos los ámbitos de la sociedad. Junto a éstos, se presentan nuevos retos para la protección de la información, como la suplantación de personalidad y la pérdida de la confidencialidad e integridad de los documentos electrónicos. La criptografía juega un papel fundamental aportando las herramientas necesarias para garantizar la seguridad de estos nuevos medios, pero es imperativo intensificar la investigación en este ámbito para dar respuesta a la demanda creciente de nuevas técnicas criptográficas seguras. La teoría de los sistemas dinámicos no lineales junto a la criptografía dan lugar a la ((criptografía caótica)), que es el campo de estudio de esta tesis. El vínculo entre la criptografía y los sistemas caóticos continúa siendo objeto de un intenso estudio. La combinación del comportamiento aparentemente estocástico, las propiedades de sensibilidad a las condiciones iniciales y a los parámetros, la ergodicidad, la mezcla, y que los puntos periódicos sean densos asemejan las órbitas caóticas a secuencias aleatorias, lo que supone su potencial utilización en el enmascaramiento de mensajes. Este hecho, junto a la posibilidad de sincronizar varios sistemas caóticos descrita inicialmente en los trabajos de Pecora y Carroll, ha generado una avalancha de trabajos de investigación donde se plantean muchas ideas sobre la forma de realizar sistemas de comunicaciones seguros, relacionando así la criptografía y el caos. La criptografía caótica aborda dos paradigmas de diseño fundamentales. En el primero, los criptosistemas caóticos se diseñan utilizando circuitos analógicos, principalmente basados en las técnicas de sincronización caótica; en el segundo, los criptosistemas caóticos se construyen en circuitos discretos u ordenadores, y generalmente no dependen de las técnicas de sincronización del caos. Nuestra contribución en esta tesis implica tres aspectos sobre el cifrado caótico. En primer lugar, se realiza un análisis teórico de las propiedades geométricas de algunos de los sistemas caóticos más empleados en el diseño de criptosistemas caóticos vii continuos; en segundo lugar, se realiza el criptoanálisis de cifrados caóticos continuos basados en el análisis anterior; y, finalmente, se realizan tres nuevas propuestas de diseño de generadores de secuencias pseudoaleatorias criptográficamente seguros y rápidos. La primera parte de esta memoria realiza un análisis crítico acerca de la seguridad de los criptosistemas caóticos, llegando a la conclusión de que la gran mayoría de los algoritmos de cifrado caóticos continuos —ya sean realizados físicamente o programados numéricamente— tienen serios inconvenientes para proteger la confidencialidad de la información ya que son inseguros e ineficientes. Asimismo una gran parte de los criptosistemas caóticos discretos propuestos se consideran inseguros y otros no han sido atacados por lo que se considera necesario más trabajo de criptoanálisis. Esta parte concluye señalando las principales debilidades encontradas en los criptosistemas analizados y algunas recomendaciones para su mejora. En la segunda parte se diseña un método de criptoanálisis que permite la identificaci ón de los parámetros, que en general forman parte de la clave, de algoritmos de cifrado basados en sistemas caóticos de Lorenz y similares, que utilizan los esquemas de sincronización excitador-respuesta. Este método se basa en algunas características geométricas del atractor de Lorenz. El método diseñado se ha empleado para criptoanalizar eficientemente tres algoritmos de cifrado. Finalmente se realiza el criptoanálisis de otros dos esquemas de cifrado propuestos recientemente. La tercera parte de la tesis abarca el diseño de generadores de secuencias pseudoaleatorias criptográficamente seguras, basadas en aplicaciones caóticas, realizando las pruebas estadísticas, que corroboran las propiedades de aleatoriedad. Estos generadores pueden ser utilizados en el desarrollo de sistemas de cifrado en flujo y para cubrir las necesidades del cifrado en tiempo real. Una cuestión importante en el diseño de sistemas de cifrado discreto caótico es la degradación dinámica debida a la precisión finita; sin embargo, la mayoría de los diseñadores de sistemas de cifrado discreto caótico no ha considerado seriamente este aspecto. En esta tesis se hace hincapié en la importancia de esta cuestión y se contribuye a su esclarecimiento con algunas consideraciones iniciales. Ya que las cuestiones teóricas sobre la dinámica de la degradación de los sistemas caóticos digitales no ha sido totalmente resuelta, en este trabajo utilizamos algunas soluciones prácticas para evitar esta dificultad teórica. Entre las técnicas posibles, se proponen y evalúan varias soluciones, como operaciones de rotación de bits y desplazamiento de bits, que combinadas con la variación dinámica de parámetros y con la perturbación cruzada, proporcionan un excelente remedio al problema de la degradación dinámica. Además de los problemas de seguridad sobre la degradación dinámica, muchos criptosistemas se rompen debido a su diseño descuidado, no a causa de los defectos esenciales de los sistemas caóticos digitales. Este hecho se ha tomado en cuenta en esta tesis y se ha logrado el diseño de generadores pseudoaleatorios caóticos criptogr áficamente seguros.

Towards the Natural Optimization with Particle Swarm Optimization.

This paper shows the Particle Swarm Optimization algorithm with a Differential Evolution. Each candidate solution is sampled in the interval [?5, 5] D where D indicates the dimension of the search space, and the evolution is performed with a classical PSO algorithm and a classical DE/x/1 algorithm according to a random threshold. Moreover, this paper provides concepts to deal with non-linear optimization through the use of PSO.

Regularized logistic regression and multi-objective variable selection for classifying MEG data

This paper addresses the question of maximizing classifier accuracy for classifying task-related mental activity from Magnetoencelophalography (MEG) data. We propose the use of different sources of information and introduce an automatic channel selection procedure. To determine an informative set of channels, our approach combines a variety of machine learning algorithms: feature subset selection methods, classifiers based on regularized logistic regression, information fusion, and multiobjective optimization based on probabilistic modeling of the search space. The experimental results show that our proposal is able to improve classification accuracy compared to approaches whose classifiers use only one type of MEG information or for which the set of channels is fixed a priori.

An evolutionary algorithm for the surface structure problem

Many macroscopic properties: hardness, corrosion, catalytic activity, etc. are directly related to the surface structure, that is, to the position and chemical identity of the outermost atoms of the material. Current experimental techniques for its determination produce a “signature” from which the structure must be inferred by solving an inverse problem: a solution is proposed, its corresponding signature computed and then compared to the experiment. This is a challenging optimization problem where the search space and the number of local minima grows exponentially with the number of atoms, hence its solution cannot be achieved for arbitrarily large structures. Nowadays, it is solved by using a mixture of human knowledge and local search techniques: an expert proposes a solution that is refined using a local minimizer. If the outcome does not fit the experiment, a new solution must be proposed again. Solving a small surface can take from days to weeks of this trial and error method. Here we describe our ongoing work in its solution. We use an hybrid algorithm that mixes evolutionary techniques with trusted region methods and reuses knowledge gained during the execution to avoid repeated search of structures. Its parallelization produces good results even when not requiring the gathering of the full population, hence it can be used in loosely coupled environments such as grids. With this algorithm, the solution of test cases that previously took weeks of expert time can be automatically solved in a day or two of uniprocessor time.

SVis: A computational steering visualization environment for surface structure determination

The arrangement of atoms at the surface of a solid accounts for many of its properties: Hardness, chemical activity, corrosion, etc. are dictated by the precise surface structure. Hence, finding it, has a broad range of technical and industrial applications. The ability to solve this problem opens the possibility of designing by computer materials with properties tailored to specific applications. Since the search space grows exponentially with the number of atoms, its solution cannot be achieved for arbitrarily large structures. Presently, a trial and error procedure is used: an expert proposes an structure as a candidate solution and tries a local optimization procedure on it. The solution relaxes to the local minimum in the attractor basin corresponding to the initial point, that might be the one corresponding to the global minimum or not. This procedure is very time consuming and, for reasonably sized surfaces, can take many iterations and much effort from the expert. Here we report on a visualization environment designed to steer this process in an attempt to solve bigger structures and reduce the time needed. The idea is to use an immersive environment to interact with the computation. It has immediate feedback to assess the quality of the proposed structure in order to let the expert explore the space of candidate solutions. The visualization environment is also able to communicate with the de facto local solver used for this problem. The user is then able to send trial structures to the local minimizer and track its progress as they approach the minimum. This allows for simultaneous testing of candidate structures. The system has also proved very useful as an educational tool for the field.

Camera localization using trajectories and maps

We propose a new Bayesian framework for automatically determining the position (location and orientation) of an uncalibrated camera using the observations of moving objects and a schematic map of the passable areas of the environment. Our approach takes advantage of static and dynamic information on the scene structures through prior probability distributions for object dynamics. The proposed approach restricts plausible positions where the sensor can be located while taking into account the inherent ambiguity of the given setting. The proposed framework samples from the posterior probability distribution for the camera position via data driven MCMC, guided by an initial geometric analysis that restricts the search space. A Kullback-Leibler divergence analysis is then used that yields the final camera position estimate, while explicitly isolating ambiguous settings. The proposed approach is evaluated in synthetic and real environments, showing its satisfactory performance in both ambiguous and unambiguous settings.

Robust Image Registration with Global Intensity Transformation

This paper presents a registration method for images with global illumination variations. The method is based on a joint iterative optimization (geometric and photometric) of the L1 norm of the intensity error. Two strategies are compared to directly find the appropriate intensity transformation within each iteration: histogram specification and the solution obtained by analyzing the necessary optimality conditions. Such strategies reduce the search space of the joint optimization to that of the geometric transformation between the images.

Fail-Safe Testing of Web Applications

This dissertation introduces an approach to generate tests to test fail-safe behavior for web applications. We apply the approach to a commercial web application. We build models for both behavioral and mitigation requirements. We create mitigation tests from an existing functional black box test suite by determining failure type and points of failure in the test suite and weaving required mitigation based on weaving rules to generate a test suite that tests proper mitigation of failures. A genetic algorithm (GA) is used to determine points of failure and type of failure that needs to be tested. Mitigation test paths are woven into the behavioral test at the point of failure based on failure specific weaving rules. A simulator was developed to evaluate choice of parameters for the genetic algorithm. We showed how to tune the fitness function and performed tuning experiments for GA to determine what values to use for exploration weight and prospecting weight. We found that higher defect densities make prospecting and mining more successful, while lower mitigation defect densities need more exploration. We compare efficiency and effectiveness of the approach. First, the GA approach is compared to random selection. The results show that the GA performance was better than random selection and that the approach was robust when the search space increased. Second, we compare the GA against four coverage criteria. The results of comparison show that test requirements generated by a genetic algorithm (GA) are more efficient than three of the four coverage criteria for large search spaces. They are equally effective. For small search spaces, the genetic algorithm is less effective than three of the four coverage criteria. The fourth coverage criteria is too weak and unable to find all defects in almost all cases. We also present a large case study of a mortgage system at one of our industrial partners and show how we formalize the approach. We evaluate the use of a GA to create test requirements. The evaluation includes choice of initial population, multiplicity of runs and a discussion of the cost of evaluating fitness. Finally, we build a selective regression testing approach based on types of changes (add, delete, or modify) that could occur in the behavioral model, the fault model, the mitigation models, the weaving rules, and the state-event matrix. We provide a systematic method by showing the formalization steps for each type of change to the various models.

Algoritmos metaheurísticos en el problema del particionado hardware/software de sistemas embebidos

El particionado hardware/software es una tarea fundamental en el co-diseño de sistemas embebidos. En ella se decide, teniendo en cuenta las métricas de diseño, qué componentes se ejecutarán en un procesador de propósito general (software) y cuáles en un hardware específico. En los últimos años se han propuesto diversas soluciones al problema del particionado dirigidas por algoritmos metaheurísticos. Sin embargo, debido a la diversidad de modelos y métricas utilizadas, la elección del algoritmo más apropiado sigue siendo un problema abierto. En este trabajo se presenta una comparación de seis algoritmos metaheurísticos: Búsqueda aleatoria (Random search), Búsqueda tabú (Tabu search), Recocido simulado (Simulated annealing), Escalador de colinas estocástico (Stochastic hill climbing), Algoritmo genético (Genetic algorithm) y Estrategia evolutiva (Evolution strategy). El modelo utilizado en la comparación está dirigido a minimizar el área ocupada y el tiempo de ejecución, las restricciones del modelo son consideradas como penalizaciones para incluir en el espacio de búsqueda otras soluciones. Los resultados muestran que los algoritmos Escalador de colinas estocástico y Estrategia evolutiva son los que mejores resultados obtienen en general, seguidos por el Algoritmo genético.