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

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

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

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

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

Impact of a referral management “gateway” on the quality of referral letters; a retrospective time series cross sectional review

Background Referral management centres (RMC) for elective referrals are designed to facilitate the primary to secondary care referral path, by improving quality of referrals and easing pressures on finite secondary care services, without inadvertently compromising patient care. This study aimed to evaluate whether the introduction of a RMC which includes triage and feedback improved the quality of elective outpatient referral letters. Methods Retrospective, time-series, cross-sectional review involving 47 general practices in one primary care trust (PCT) in South-East England. Comparison of a random sample of referral letters at baseline (n = 301) and after seven months of referral management (n = 280). Letters were assessed for inclusion of four core pieces of information which are used locally to monitor referral quality (blood pressure, body mass index, past medical history, medication history) and against research-based quality criteria for referral letters (provision of clinical information and clarity of reason for referral). Results Following introduction of the RMC, the proportion of letters containing each of the core items increased compared to baseline. Statistically significant increases in the recording of ‘past medical history’ (from 71% to 84%, p < 0.001) and ‘medication history’ (78% to 87%, p = 0.006) were observed. Forty four percent of letters met the research-based quality criteria at baseline but there was no significant change in quality of referral letters judged on these criteria across the two time periods. Conclusion Introduction of RMC has improved the inclusion of past medical history and medication history in referral letters, but not other measures of quality. In approximately half of letters there remains room for further improvement

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

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

Decoding the regulatory network of early blood development from single-cell gene expression measurements.

Reconstruction of the molecular pathways controlling organ development has been hampered by a lack of methods to resolve embryonic progenitor cells. Here we describe a strategy to address this problem that combines gene expression profiling of large numbers of single cells with data analysis based on diffusion maps for dimensionality reduction and network synthesis from state transition graphs. Applying the approach to hematopoietic development in the mouse embryo, we map the progression of mesoderm toward blood using single-cell gene expression analysis of 3,934 cells with blood-forming potential captured at four time points between E7.0 and E8.5. Transitions between individual cellular states are then used as input to develop a single-cell network synthesis toolkit to generate a computationally executable transcriptional regulatory network model of blood development. Several model predictions concerning the roles of Sox and Hox factors are validated experimentally. Our results demonstrate that single-cell analysis of a developing organ coupled with computational approaches can reveal the transcriptional programs that underpin organogenesis.We thank J. Downing (St. Jude Children's Research Hospital, Memphis, TN, USA) for the Runx1-ires-GFP mouse. Research in the authors' laboratory is supported by the Medical Research Council, Biotechnology and Biological Sciences 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. V.M. is supported by a Medical Research Council Studentship and Centenary Award and S.W. by a Microsoft Research PhD Scholarship.This is the accepted manuscript for a paper published in Nature Biotechnology 33, 269–276 (2015) doi:10.1038/nbt.315