LNCS

In this paper we propose a novel technique for constructing timed automata from properties expressed in the logic mtl, under bounded-variability assumptions. We handle full mtl and include all future operators. Our construction is based on separation of the continuous time monitoring of the input sequence and discrete predictions regarding the future. The separation of the continuous from the discrete allows us to determinize our automata in an exponential construction that does not increase the number of clocks. This leads to a doubly exponential construction from mtl to deterministic timed automata, compared with triply exponential using existing approaches. We offer an alternative to the existing approach to linear real-time model checking, which has never been implemented. It further offers a unified framework for model checking, runtime monitoring, and synthesis, in an approach that can reuse tools, implementations, and insights from the discrete setting

Validity-Guided Synthesis of Reactive Systems from Assume-Guarantee Contracts

Automated synthesis of reactive systems from specifications has been a topic of research for decades. Recently, a variety of approaches have been proposed to extend synthesis of reactive systems from proposi- tional specifications towards specifications over rich theories. We propose a novel, completely automated approach to program synthesis which reduces the problem to deciding the validity of a set of forall-exists formulas. In spirit of IC3 / PDR, our problem space is recursively refined by blocking out regions of unsafe states, aiming to discover a fixpoint that describes safe reactions. If such a fixpoint is found, we construct a witness that is directly translated into an implementation. We implemented the algorithm on top of the JKind model checker, and exercised it against contracts written using the Lustre specification language. Experimental results show how the new algorithm outperforms JKinds already existing synthesis procedure based on k-induction and addresses soundness issues in the k-inductive approach with respect to unrealizable results.Comment: 18 pages, 5 figures, 2 table

LNCS

State-transition systems communicating by shared variables have been the underlying model of choice for applications of model checking. Such formalisms, however, have difficulty with modeling process creation or death and communication reconfigurability. Here, we introduce “dynamic reactive modules” (DRM), a state-transition modeling formalism that supports dynamic reconfiguration and creation/death of processes. The resulting formalism supports two types of variables, data variables and reference variables. Reference variables enable changing the connectivity between processes and referring to instances of processes. We show how this new formalism supports parallel composition and refinement through trace containment. DRM provide a natural language for modeling (and ultimately reasoning about) biological systems and multiple threads communicating through shared variables

An Exponential Lower Bound for the Latest Deterministic Strategy Iteration Algorithms

This paper presents a new exponential lower bound for the two most popular deterministic variants of the strategy improvement algorithms for solving parity, mean payoff, discounted payoff and simple stochastic games. The first variant improves every node in each step maximizing the current valuation locally, whereas the second variant computes the globally optimal improvement in each step. We outline families of games on which both variants require exponentially many strategy iterations

Structural Synthesis for GXW Specifications

We define the GXW fragment of linear temporal logic (LTL) as the basis for synthesizing embedded control software for safety-critical applications. Since GXW includes the use of a weak-until operator we are able to specify a number of diverse programmable logic control (PLC) problems, which we have compiled from industrial training sets. For GXW controller specifications, we develop a novel approach for synthesizing a set of synchronously communicating actor-based controllers. This synthesis algorithm proceeds by means of recursing over the structure of GXW specifications, and generates a set of dedicated and synchronously communicating sub-controllers according to the formula structure. In a subsequent step, 2QBF constraint solving identifies and tries to resolve potential conflicts between individual GXW specifications. This structural approach to GXW synthesis supports traceability between requirements and the generated control code as mandated by certification regimes for safety-critical software. Synthesis for GXW specifications is in PSPACE compared to 2EXPTIME-completeness of full-fledged LTL synthesis. Indeed our experimental results suggest that GXW synthesis scales well to industrial-sized control synthesis problems with 20 input and output ports and beyond.Comment: The long (including appendix) version being reviewed by CAV'16 program committee. Compared to the submitted version, one author (out of her wish) is moved to the Acknowledgement. (v2) Corrected typos. (v3) Add an additional remark over environment assumption and easy corner case

Drug target optimization in chronic myeloid leukemia using innovative computational platform.

Chronic Myeloid Leukemia (CML) represents a paradigm for the wider cancer field. Despite the fact that tyrosine kinase inhibitors have established targeted molecular therapy in CML, patients often face the risk of developing drug resistance, caused by mutations and/or activation of alternative cellular pathways. To optimize drug development, one needs to systematically test all possible combinations of drug targets within the genetic network that regulates the disease. The BioModelAnalyzer (BMA) is a user-friendly computational tool that allows us to do exactly that. We used BMA to build a CML network-model composed of 54 nodes linked by 104 interactions that encapsulates experimental data collected from 160 publications. While previous studies were limited by their focus on a single pathway or cellular process, our executable model allowed us to probe dynamic interactions between multiple pathways and cellular outcomes, suggest new combinatorial therapeutic targets, and highlight previously unexplored sensitivities to Interleukin-3.We would like to thank the members of the Fisher laboratory, in particular to Gavin Smyth and Caroline Dahl for their help with the BMA development, and Alex Hajnal for valuable comments on the manuscript and insightful discussions. Research in BG laboratory is supported by the Medical Research Council, Leukaemia and Lymphoma Research, The Leukemia and Lymphoma Society, Microsoft Research and core support grants by the Wellcome Trust to the Cambridge Institute for Medical Research and Wellcome Trust-MRC Cambridge Stem Cell Institute.This is the final published version. It was originally published in Scientific Reports 5: 8190. DOI: 10.1038/srep08190

Exploiting the Temporal Logic Hierarchy and the Non-Confluence Property for Efficient LTL Synthesis

The classic approaches to synthesize a reactive system from a linear temporal logic (LTL) specification first translate the given LTL formula to an equivalent omega-automaton and then compute a winning strategy for the corresponding omega-regular game. To this end, the obtained omega-automata have to be (pseudo)-determinized where typically a variant of Safra's determinization procedure is used. In this paper, we show that this determinization step can be significantly improved for tool implementations by replacing Safra's determinization by simpler determinization procedures. In particular, we exploit (1) the temporal logic hierarchy that corresponds to the well-known automata hierarchy consisting of safety, liveness, Buechi, and co-Buechi automata as well as their boolean closures, (2) the non-confluence property of omega-automata that result from certain translations of LTL formulas, and (3) symbolic implementations of determinization procedures for the Rabin-Scott and the Miyano-Hayashi breakpoint construction. In particular, we present convincing experimental results that demonstrate the practical applicability of our new synthesis procedure

Regular Strategies in Pushdown Reachability Games

International audienceWe show that positional winning strategies in pushdown reachability games can be implemented by deterministic finite state au-tomata of exponential size. Such automata read the stack and control state of a given pushdown configuration and output the set of winning moves playable from that position. This result can originally be attributed to Kupferman, Piterman and Vardi using an approach based on two-way tree automata. We present a more direct approach that builds upon the popular saturation technique. Saturation for analysing pushdown systems has been successfully implemented by Moped and WALi. Thus, our approach has the potential for practical applications to controller-synthesis problems

Produção de pellets à base de hidroxiapatite contendo um fármaco modelo

Tese de mestrado, Farmacotecnia Avançada, Universidade de Lisboa, Faculdade de Farmácia, 2012Este trabalho foi realizado tendo como objectivo principal a produção de pellets à base de hidroxiapatite com diferentes dimensões e porosidades, uma vez que a utilização de pellets de dimensões variadas permite um melhor preenchimento do espaço/cavidades ósseas e que a porosidade é um factor promotor da osteointegração. Os pellets foram produzidos através da tecnologia de extrusão-esferonização utilizando fieiras de diferentes diâmetros. Como potencial promotor da formação dos poros foi incluído cloreto de sódio com diferentes granulometrias na estrutura dos pellets. Os pellets produzidos foram sinterizados e posteriormente mergulhados sob vácuo numa solução de ibuprofeno para incorporação desta substância activa na sua estrutura. Os resultados obtidos neste trabalho mostram que a tecnologia utilizada permitiu produzir pellets de diferentes dimensões por extrusão-esferonização embora não tenha sido possível optimizar a produção desses pellets com estruturas macroporosas. Foi possível verificar que o aumento da temperatura de sinterização conduziu a uma maior densificação do material com redução da porosidade e que o cloreto de sódio presente nos pellets conduziu a uma menor contracção dos mesmos quando comparados com os das formulações testadas contendo hidroxiapatite modificada sem cloreto de sódio. Adicionalmente os resultados obtidos no ensaio de dissolução indicam que o ibuprofeno deverá ter ficado apenas à superfície dos pellets. Ainda que não tenha sido possível obter as estruturas macroporosas propostas, os restantes objectivos deste trabalho foram atingidos, tendo sido possível produzir pellets de hidroxiapatite utilizando a tecnologia de extrusão-esferonização e sua caracterização.The purpose of this work was to produce pellets of hydroxyapatite with different sizes and porosity. This was done because the use of pellets with different dimensions allows a better filling of bone cavities and the porosity is an important variable of osteointegration. The pellets were produced by extrusion-spheronization using extrusion screens of different diameters. Sodium chloride with different particle sizes was added to the pellets formulation as a potencial porogenic component. The pellets were sintered and afterwards they were soaked under vacuum in an ibubrofen solution to promote its incorporation in the structure. The data produced revealed that the technology of extrusion-spheronization was adequate to manufacture pellets with different sizes although it was not possible to optimize macroporous structures. It was possible to verify that the sintering temperature led to a densification of material with porosity reduction and that the sodium chloride led to lower collapse of the pellets when compared with the tested formulations with modified hydroxyapatite without sodium chloride. Adicionally, the dissolution results indicate that ibuprofen should have stayed only on the pellets external surface. Although it was not possible to obtain the proposed macroporous structures, the other objectives of this study were attained, having been possible to produce hydroxyapatite pellets by the extrusion-spheronization technology and characterize them

Synthesis from Recursive-Components Libraries

Synthesis is the automatic construction of a system from its specification. In classical synthesis algorithms it is always assumed that the system is "constructed from scratch" rather than composed from reusable components. This, of course, rarely happens in real life. In real life, almost every non-trivial commercial software system relies heavily on using libraries of reusable components. Furthermore, other contexts, such as web-service orchestration, can be modeled as synthesis of a system from a library of components. In 2009 we introduced LTL synthesis from libraries of reusable components. Here, we extend the work and study synthesis from component libraries with "call and return"' control flow structure. Such control-flow structure is very common in software systems. We define the problem of Nested-Words Temporal Logic (NWTL) synthesis from recursive component libraries, where NWTL is a specification formalism, richer than LTL, that is suitable for "call and return" computations. We solve the problem, providing a synthesis algorithm, and show the problem is 2EXPTIME-complete, as standard synthesis.Comment: In Proceedings GandALF 2011, arXiv:1106.081