Designing Novel Antitrypanosomal Agents from a Mixed Graph-Theoretical Substructural Approach

Chagas disease is nowadays the most serious parasitic health problem. This disease is caused by Trypanosoma cruzi. The great number of deaths and the insufficient effectiveness of drugs against this parasite have alarmed the scientific community worldwide. In an attempt to overcome this problem, a model for the design and prediction of new antitrypanosomal agents was obtained. This used a mixed approach, containing simple descriptors based on fragments and topological substructural molecular design descriptors. A data set was made up of 188 compounds, 99 of them characterized an antitrypanosomal activity and 88 compounds that belong to other pharmaceutical categories. The model showed sensitivity, specificity and accuracy values above 85%. Quantitative fragmental contributions were also calculated. Then, and to confirm the quality of the model, 15 structures of molecules tested as antitrypanosomal compounds (that we did not include in this study) were predicted, taking into account the information on the abovementioned calculated fragmental contributions. The model showed an accuracy of 100% which means that the ""in silico"" methodology developed by our team is promising for the rational design of new antitrypanosomal drugs. (C) 2009 Wiley Periodicals, Inc. J Comput Chem 31: 882-894. 2010

Minimum cycle cover and Chinese postman problems on mixed graphs with bounded tree-width

Let M = (V, E, A) be a mixed graph with vertex set V, edge set E and arc set A. A cycle cover of M is a family C = {C(1), ... , C(k)} of cycles of M such that each edge/arc of M belongs to at least one cycle in C. The weight of C is Sigma(k)(i=1) vertical bar C(i)vertical bar. The minimum cycle cover problem is the following: given a strongly connected mixed graph M without bridges, find a cycle cover of M with weight as small as possible. The Chinese postman problem is: given a strongly connected mixed graph M, find a minimum length closed walk using all edges and arcs of M. These problems are NP-hard. We show that they can be solved in polynomial time if M has bounded tree-width. (C) 2008 Elsevier B.V. All rights reserved.

Learning Technology in Scheduling Based on the Mixed Graphs

We propose the adaptive algorithm for solving a set of similar scheduling problems using learning technology. It is devised to combine the merits of an exact algorithm based on the mixed graph model and heuristics oriented on the real-world scheduling problems. The former may ensure high quality of the solution by means of an implicit exhausting enumeration of the feasible schedules. The latter may be developed for certain type of problems using their peculiarities. The main idea of the learning technology is to produce effective (in performance measure) and efficient (in computational time) heuristics by adapting local decisions for the scheduling problems under consideration. Adaptation is realized at the stage of learning while solving a set of sample scheduling problems using a branch-and-bound algorithm and structuring knowledge using pattern recognition apparatus.

New graph-based algorithms to efficiently solve large scale open pit mining optimisation problems

In the mining optimisation literature, most researchers focused on two strategic-level and tactical-level open-pit mine optimisation problems, which are respectively termed ultimate pit limit (UPIT) or constrained pit limit (CPIT). However, many researchers indicate that the substantial numbers of variables and constraints in real-world instances (e.g., with 50-1000 thousand blocks) make the CPIT’s mixed integer programming (MIP) model intractable for use. Thus, it becomes a considerable challenge to solve the large scale CPIT instances without relying on exact MIP optimiser as well as the complicated MIP relaxation/decomposition methods. To take this challenge, two new graph-based algorithms based on network flow graph and conjunctive graph theory are developed by taking advantage of problem properties. The performance of our proposed algorithms is validated by testing recent large scale benchmark UPIT and CPIT instances’ datasets of MineLib in 2013. In comparison to best known results from MineLib, it is shown that the proposed algorithms outperform other CPIT solution approaches existing in the literature. The proposed graph-based algorithms leads to a more competent mine scheduling optimisation expert system because the third-party MIP optimiser is no longer indispensable and random neighbourhood search is not necessary.

Popular Mixed Matchings

We study the problem of matching applicants to jobs under one-sided preferences: that is, each applicant ranks a non-empty subset of jobs under an order of preference, possibly involving ties. A matching M is said to be rnore popular than T if the applicants that prefer M to T outnumber those that prefer T to M. A matching is said to be popular if there is no matching more popular than it. Equivalently, a matching M is popular if phi(M,T) >= phi(T, M) for all matchings T, where phi(X, Y) is the number of applicants that prefer X to Y. Previously studied solution concepts based oil the popularity criterion are either not guaranteed to exist for every instance (e.g., popular matchings) or are NP-hard to compute (e.g., least unpopular matchings). This paper addresses this issue by considering mixed matchings. A mixed matching is simply a probability distributions over matchings in the input graph. The function phi that compares two matchings generalizes in a natural manner to mixed matchings by taking expectation. A mixed matching P is popular if phi(P,Q) >= phi(Q,P) for all mixed matchings Q. We show that popular mixed matchings always exist. and we design polynomial time algorithms for finding them. Then we study their efficiency and give tight bounds on the price of anarchy and price of stability of the popular matching problem.

Popular mixed matchings

We study the problem of matching applicants to jobs under one-sided preferences; that is, each applicant ranks a non-empty subset of jobs under an order of preference, possibly involving ties. A matching M is said to be more popular than T if the applicants that prefer M to T outnumber those that prefer T to M. A matching is said to be popular if there is no matching more popular than it. Equivalently, a matching M is popular if phi(M, T) >= phi(T, M) for all matchings T, where phi(X, Y) is the number of applicants that prefer X to Y. Previously studied solution concepts based on the popularity criterion are either not guaranteed to exist for every instance (e.g., popular matchings) or are NP-hard to compute (e.g., least unpopular matchings). This paper addresses this issue by considering mixed matchings. A mixed matching is simply a probability distribution over matchings in the input graph. The function phi that compares two matchings generalizes in a natural manner to mixed matchings by taking expectation. A mixed matching P is popular if phi(P, Q) >= phi(Q, P) for all mixed matchings Q. We show that popular mixed matchings always exist and we design polynomial time algorithms for finding them. Then we study their efficiency and give tight bounds on the price of anarchy and price of stability of the popular matching problem. (C) 2010 Elsevier B.V. All rights reserved.

Design of novel antituberculosis compounds using graph-theoretical and substructural approaches

The increasing resistance of Mycobacterium tuberculosis to the existing drugs has alarmed the worldwide scientific community. In an attempt to overcome this problem, two models for the design and prediction of new antituberculosis agents were obtained. The first used a mixed approach, containing descriptors based on fragments and the topological substructural molecular design approach (TOPS-MODE) descriptors. The other model used a combination of two-dimensional (2D) and three-dimensional (3D) descriptors. A data set of 167 compounds with great structural variability, 72 of them antituberculosis agents and 95 compounds belonging to other pharmaceutical categories, was analyzed. The first model showed sensitivity, specificity, and accuracy values above 80% and the second one showed values higher than 75% for these statistical indices. Subsequently, 12 structures of imidazoles not included in this study were designed, taking into account the two models. In both cases accuracy was 100%, showing that the methodology in silico developed by us is promising for the rational design of antituberculosis drugs.

System Architecture of a Mixed Reality Framework

In this paper the software architecture of a framework which simplifies the development of applications in the area of Virtual and Augmented Reality is presented. It is based on VRML/X3D to enable rendering of audio-visual information. We extended our VRML rendering system by a device management system that is based on the concept of a data-flow graph. The aim of the system is to create Mixed Reality (MR) applications simply by plugging together small prefabricated software components, instead of compiling monolithic C++ applications. The flexibility and the advantages of the presented framework are explained on the basis of an exemplary implementation of a classic Augmented Realityapplication and its extension to a collaborative remote expert scenario.

A framework for mixed-criticality partitioned real-time embedded systems

Los sistemas empotrados son cada día más comunes y complejos, de modo que encontrar procesos seguros, eficaces y baratos de desarrollo software dirigidos específicamente a esta clase de sistemas es más necesario que nunca. A diferencia de lo que ocurría hasta hace poco, en la actualidad los avances tecnológicos en el campo de los microprocesadores de los últimos tiempos permiten el desarrollo de equipos con prestaciones más que suficientes para ejecutar varios sistemas software en una única máquina. Además, hay sistemas empotrados con requisitos de seguridad (safety) de cuyo correcto funcionamiento depende la vida de muchas personas y/o grandes inversiones económicas. Estos sistemas software se diseñan e implementan de acuerdo con unos estándares de desarrollo software muy estrictos y exigentes. En algunos casos puede ser necesaria también la certificación del software. Para estos casos, los sistemas con criticidades mixtas pueden ser una alternativa muy valiosa. En esta clase de sistemas, aplicaciones con diferentes niveles de criticidad se ejecutan en el mismo computador. Sin embargo, a menudo es necesario certificar el sistema entero con el nivel de criticidad de la aplicación más crítica, lo que hace que los costes se disparen. La virtualización se ha postulado como una tecnología muy interesante para contener esos costes. Esta tecnología permite que un conjunto de máquinas virtuales o particiones ejecuten las aplicaciones con unos niveles de aislamiento tanto temporal como espacial muy altos. Esto, a su vez, permite que cada partición pueda ser certificada independientemente. Para el desarrollo de sistemas particionados con criticidades mixtas se necesita actualizar los modelos de desarrollo software tradicionales, pues estos no cubren ni las nuevas actividades ni los nuevos roles que se requieren en el desarrollo de estos sistemas. Por ejemplo, el integrador del sistema debe definir las particiones o el desarrollador de aplicaciones debe tener en cuenta las características de la partición donde su aplicación va a ejecutar. Tradicionalmente, en el desarrollo de sistemas empotrados, el modelo en V ha tenido una especial relevancia. Por ello, este modelo ha sido adaptado para tener en cuenta escenarios tales como el desarrollo en paralelo de aplicaciones o la incorporación de una nueva partición a un sistema ya existente. El objetivo de esta tesis doctoral es mejorar la tecnología actual de desarrollo de sistemas particionados con criticidades mixtas. Para ello, se ha diseñado e implementado un entorno dirigido específicamente a facilitar y mejorar los procesos de desarrollo de esta clase de sistemas. En concreto, se ha creado un algoritmo que genera el particionado del sistema automáticamente. En el entorno de desarrollo propuesto, se han integrado todas las actividades necesarias para desarrollo de un sistema particionado, incluidos los nuevos roles y actividades mencionados anteriormente. Además, el diseño del entorno de desarrollo se ha basado en la ingeniería guiada por modelos (Model-Driven Engineering), la cual promueve el uso de los modelos como elementos fundamentales en el proceso de desarrollo. Así pues, se proporcionan las herramientas necesarias para modelar y particionar el sistema, así como para validar los resultados y generar los artefactos necesarios para el compilado, construcción y despliegue del mismo. Además, en el diseño del entorno de desarrollo, la extensión e integración del mismo con herramientas de validación ha sido un factor clave. En concreto, se pueden incorporar al entorno de desarrollo nuevos requisitos no-funcionales, la generación de nuevos artefactos tales como documentación o diferentes lenguajes de programación, etc. Una parte clave del entorno de desarrollo es el algoritmo de particionado. Este algoritmo se ha diseñado para ser independiente de los requisitos de las aplicaciones así como para permitir al integrador del sistema implementar nuevos requisitos del sistema. Para lograr esta independencia, se han definido las restricciones al particionado. El algoritmo garantiza que dichas restricciones se cumplirán en el sistema particionado que resulte de su ejecución. Las restricciones al particionado se han diseñado con una capacidad expresiva suficiente para que, con un pequeño grupo de ellas, se puedan expresar la mayor parte de los requisitos no-funcionales más comunes. Las restricciones pueden ser definidas manualmente por el integrador del sistema o bien pueden ser generadas automáticamente por una herramienta a partir de los requisitos funcionales y no-funcionales de una aplicación. El algoritmo de particionado toma como entradas los modelos y las restricciones al particionado del sistema. Tras la ejecución y como resultado, se genera un modelo de despliegue en el que se definen las particiones que son necesarias para el particionado del sistema. A su vez, cada partición define qué aplicaciones deben ejecutar en ella así como los recursos que necesita la partición para ejecutar correctamente. El problema del particionado y las restricciones al particionado se modelan matemáticamente a través de grafos coloreados. En dichos grafos, un coloreado propio de los vértices representa un particionado del sistema correcto. El algoritmo se ha diseñado también para que, si es necesario, sea posible obtener particionados alternativos al inicialmente propuesto. El entorno de desarrollo, incluyendo el algoritmo de particionado, se ha probado con éxito en dos casos de uso industriales: el satélite UPMSat-2 y un demostrador del sistema de control de una turbina eólica. Además, el algoritmo se ha validado mediante la ejecución de numerosos escenarios sintéticos, incluyendo algunos muy complejos, de más de 500 aplicaciones. ABSTRACT The importance of embedded software is growing as it is required for a large number of systems. Devising cheap, efficient and reliable development processes for embedded systems is thus a notable challenge nowadays. Computer processing power is continuously increasing, and as a result, it is currently possible to integrate complex systems in a single processor, which was not feasible a few years ago.Embedded systems may have safety critical requirements. Its failure may result in personal or substantial economical loss. The development of these systems requires stringent development processes that are usually defined by suitable standards. In some cases their certification is also necessary. This scenario fosters the use of mixed-criticality systems in which applications of different criticality levels must coexist in a single system. In these cases, it is usually necessary to certify the whole system, including non-critical applications, which is costly. Virtualization emerges as an enabling technology used for dealing with this problem. The system is structured as a set of partitions, or virtual machines, that can be executed with temporal and spatial isolation. In this way, applications can be developed and certified independently. The development of MCPS (Mixed-Criticality Partitioned Systems) requires additional roles and activities that traditional systems do not require. The system integrator has to define system partitions. Application development has to consider the characteristics of the partition to which it is allocated. In addition, traditional software process models have to be adapted to this scenario. The V-model is commonly used in embedded systems development. It can be adapted to the development of MCPS by enabling the parallel development of applications or adding an additional partition to an existing system. The objective of this PhD is to improve the available technology for MCPS development by providing a framework tailored to the development of this type of system and by defining a flexible and efficient algorithm for automatically generating system partitionings. The goal of the framework is to integrate all the activities required for developing MCPS and to support the different roles involved in this process. The framework is based on MDE (Model-Driven Engineering), which emphasizes the use of models in the development process. The framework provides basic means for modeling the system, generating system partitions, validating the system and generating final artifacts. The framework has been designed to facilitate its extension and the integration of external validation tools. In particular, it can be extended by adding support for additional non-functional requirements and support for final artifacts, such as new programming languages or additional documentation. The framework includes a novel partitioning algorithm. It has been designed to be independent of the types of applications requirements and also to enable the system integrator to tailor the partitioning to the specific requirements of a system. This independence is achieved by defining partitioning constraints that must be met by the resulting partitioning. They have sufficient expressive capacity to state the most common constraints and can be defined manually by the system integrator or generated automatically based on functional and non-functional requirements of the applications. The partitioning algorithm uses system models and partitioning constraints as its inputs. It generates a deployment model that is composed by a set of partitions. Each partition is in turn composed of a set of allocated applications and assigned resources. The partitioning problem, including applications and constraints, is modeled as a colored graph. A valid partitioning is a proper vertex coloring. A specially designed algorithm generates this coloring and is able to provide alternative partitions if required. The framework, including the partitioning algorithm, has been successfully used in the development of two industrial use cases: the UPMSat-2 satellite and the control system of a wind-power turbine. The partitioning algorithm has been successfully validated by using a large number of synthetic loads, including complex scenarios with more that 500 applications.

A quantum Jensen-Shannon graph kernel for unattributed graphs

In this paper, we use the quantum Jensen-Shannon divergence as a means of measuring the information theoretic dissimilarity of graphs and thus develop a novel graph kernel. In quantum mechanics, the quantum Jensen-Shannon divergence can be used to measure the dissimilarity of quantum systems specified in terms of their density matrices. We commence by computing the density matrix associated with a continuous-time quantum walk over each graph being compared. In particular, we adopt the closed form solution of the density matrix introduced in Rossi et al. (2013) [27,28] to reduce the computational complexity and to avoid the cumbersome task of simulating the quantum walk evolution explicitly. Next, we compare the mixed states represented by the density matrices using the quantum Jensen-Shannon divergence. With the quantum states for a pair of graphs described by their density matrices to hand, the quantum graph kernel between the pair of graphs is defined using the quantum Jensen-Shannon divergence between the graph density matrices. We evaluate the performance of our kernel on several standard graph datasets from both bioinformatics and computer vision. The experimental results demonstrate the effectiveness of the proposed quantum graph kernel.

A quantum Jensen-Shannon graph kernel using discrete-time quantum walks

In this paper, we develop a new graph kernel by using the quantum Jensen-Shannon divergence and the discrete-time quantum walk. To this end, we commence by performing a discrete-time quantum walk to compute a density matrix over each graph being compared. For a pair of graphs, we compare the mixed quantum states represented by their density matrices using the quantum Jensen-Shannon divergence. With the density matrices for a pair of graphs to hand, the quantum graph kernel between the pair of graphs is defined by exponentiating the negative quantum Jensen-Shannon divergence between the graph density matrices. We evaluate the performance of our kernel on several standard graph datasets, and demonstrate the effectiveness of the new kernel.

New dimeric supramolecular structure of mixed (phthalocyaninato)(porphyrinato)-europium(III) sandwiches : preparation and spectroscopic characteristics

The mixed double-decker Eu\[Pc(15C5)4](TPP) (1) was obtained by base-catalysed tetramerisation of 4,5-dicyanobenzo-15-crown-5 using the half-sandwich complex Eu(TPP)(acac) (acac = acetylacetonate), generated in situ, as the template. For comparative studies, the mixed triple-decker complexes Eu2\[Pc(15C5)4](TPP)2 (2) and Eu2\[Pc(15C5)4]2(TPP) (3) were also synthesised by the raise-by-one-story method. These mixed ring sandwich complexes were characterised by various spectroscopic methods. Up to four one-electron oxidations and two one-electron reductions were revealed by cyclic voltammetry (CV) and differential pulse voltammetry (DPV). As shown by electronic absorption and infrared spectroscopy, supramolecular dimers (SM1 and SM3) were formed from the corresponding double-decker 1 and triple-decker 3 in the presence of potassium ions in MeOH/CHCl3.