Towards Personalized Prostate Cancer Therapy Using Delta-Reachability Analysis

Recent clinical studies suggest that the efficacy of hormone therapy for prostate cancer depends on the characteristics of individual patients. In this paper, we develop a computational framework for identifying patient-specific androgen ablation therapy schedules for postponing the potential cancer relapse. We model the population dynamics of heterogeneous prostate cancer cells in response to androgen suppression as a nonlinear hybrid automaton. We estimate personalized kinetic parameters to characterize patients and employ $\delta$-reachability analysis to predict patient-specific therapeutic strategies. The results show that our methods are promising and may lead to a prognostic tool for personalized cancer therapy.Comment: HSCC 201

Revisiting Reachability in Timed Automata

We revisit a fundamental result in real-time verification, namely that the binary reachability relation between configurations of a given timed automaton is definable in linear arithmetic over the integers and reals. In this paper we give a new and simpler proof of this result, building on the well-known reachability analysis of timed automata involving difference bound matrices. Using this new proof, we give an exponential-space procedure for model checking the reachability fragment of the logic parametric TCTL. Finally we show that the latter problem is NEXPTIME-hard

Integrated Modeling and Verification of Real-Time Systems through Multiple Paradigms

Complex systems typically have many different parts and facets, with different characteristics. In a multi-paradigm approach to modeling, formalisms with different natures are used in combination to describe complementary parts and aspects of the system. This can have a beneficial impact on the modeling activity, as different paradigms an be better suited to describe different aspects of the system. While each paradigm provides a different view on the many facets of the system, it is of paramount importance that a coherent comprehensive model emerges from the combination of the various partial descriptions. In this paper we present a technique to model different aspects of the same system with different formalisms, while keeping the various models tightly integrated with one another. In addition, our approach leverages the flexibility provided by a bounded satisfiability checker to encode the verification problem of the integrated model in the propositional satisfiability (SAT) problem; this allows users to carry out formal verification activities both on the whole model and on parts thereof. The effectiveness of the approach is illustrated through the example of a monitoring system.Comment: 27 page

Efficient CSL Model Checking Using Stratification

For continuous-time Markov chains, the model-checking problem with respect to continuous-time stochastic logic (CSL) has been introduced and shown to be decidable by Aziz, Sanwal, Singhal and Brayton in 1996. Their proof can be turned into an approximation algorithm with worse than exponential complexity. In 2000, Baier, Haverkort, Hermanns and Katoen presented an efficient polynomial-time approximation algorithm for the sublogic in which only binary until is allowed. In this paper, we propose such an efficient polynomial-time approximation algorithm for full CSL. The key to our method is the notion of stratified CTMCs with respect to the CSL property to be checked. On a stratified CTMC, the probability to satisfy a CSL path formula can be approximated by a transient analysis in polynomial time (using uniformization). We present a measure-preserving, linear-time and -space transformation of any CTMC into an equivalent, stratified one. This makes the present work the centerpiece of a broadly applicable full CSL model checker. Recently, the decision algorithm by Aziz et al. was shown to work only for stratified CTMCs. As an additional contribution, our measure-preserving transformation can be used to ensure the decidability for general CTMCs.Comment: 18 pages, preprint for LMCS. An extended abstract appeared in ICALP 201

Sciduction: Combining Induction, Deduction, and Structure for Verification and Synthesis

Even with impressive advances in automated formal methods, certain problems in system verification and synthesis remain challenging. Examples include the verification of quantitative properties of software involving constraints on timing and energy consumption, and the automatic synthesis of systems from specifications. The major challenges include environment modeling, incompleteness in specifications, and the complexity of underlying decision problems. This position paper proposes sciduction, an approach to tackle these challenges by integrating inductive inference, deductive reasoning, and structure hypotheses. Deductive reasoning, which leads from general rules or concepts to conclusions about specific problem instances, includes techniques such as logical inference and constraint solving. Inductive inference, which generalizes from specific instances to yield a concept, includes algorithmic learning from examples. Structure hypotheses are used to define the class of artifacts, such as invariants or program fragments, generated during verification or synthesis. Sciduction constrains inductive and deductive reasoning using structure hypotheses, and actively combines inductive and deductive reasoning: for instance, deductive techniques generate examples for learning, and inductive reasoning is used to guide the deductive engines. We illustrate this approach with three applications: (i) timing analysis of software; (ii) synthesis of loop-free programs, and (iii) controller synthesis for hybrid systems. Some future applications are also discussed