The Nondeterministic Waiting Time Algorithm: A Review

We present briefly the Nondeterministic Waiting Time algorithm. Our technique for the simulation of biochemical reaction networks has the ability to mimic the Gillespie Algorithm for some networks and solutions to ordinary differential equations for other networks, depending on the rules of the system, the kinetic rates and numbers of molecules. We provide a full description of the algorithm as well as specifics on its implementation. Some results for two well-known models are reported. We have used the algorithm to explore Fas-mediated apoptosis models in cancerous and HIV-1 infected T cells

The Paths to Choreography Extraction

Choreographies are global descriptions of interactions among concurrent components, most notably used in the settings of verification (e.g., Multiparty Session Types) and synthesis of correct-by-construction software (Choreographic Programming). They require a top-down approach: programmers first write choreographies, and then use them to verify or synthesize their programs. However, most existing software does not come with choreographies yet, which prevents their application. To attack this problem, we propose a novel methodology (called choreography extraction) that, given a set of programs or protocol specifications, automatically constructs a choreography that describes their behavior. The key to our extraction is identifying a set of paths in a graph that represents the symbolic execution of the programs of interest. Our method improves on previous work in several directions: we can now deal with programs that are equipped with a state and internal computation capabilities; time complexity is dramatically better; we capture programs that are correct but not necessarily synchronizable, i.e., they work because they exploit asynchronous communication

Liveness of Randomised Parameterised Systems under Arbitrary Schedulers (Technical Report)

We consider the problem of verifying liveness for systems with a finite, but unbounded, number of processes, commonly known as parameterised systems. Typical examples of such systems include distributed protocols (e.g. for the dining philosopher problem). Unlike the case of verifying safety, proving liveness is still considered extremely challenging, especially in the presence of randomness in the system. In this paper we consider liveness under arbitrary (including unfair) schedulers, which is often considered a desirable property in the literature of self-stabilising systems. We introduce an automatic method of proving liveness for randomised parameterised systems under arbitrary schedulers. Viewing liveness as a two-player reachability game (between Scheduler and Process), our method is a CEGAR approach that synthesises a progress relation for Process that can be symbolically represented as a finite-state automaton. The method is incremental and exploits both Angluin-style L*-learning and SAT-solvers. Our experiments show that our algorithm is able to prove liveness automatically for well-known randomised distributed protocols, including Lehmann-Rabin Randomised Dining Philosopher Protocol and randomised self-stabilising protocols (such as the Israeli-Jalfon Protocol). To the best of our knowledge, this is the first fully-automatic method that can prove liveness for randomised protocols.Comment: Full version of CAV'16 pape

A Hierarchy of Scheduler Classes for Stochastic Automata

Stochastic automata are a formal compositional model for concurrent stochastic timed systems, with general distributions and non-deterministic choices. Measures of interest are defined over schedulers that resolve the nondeterminism. In this paper we investigate the power of various theoretically and practically motivated classes of schedulers, considering the classic complete-information view and a restriction to non-prophetic schedulers. We prove a hierarchy of scheduler classes w.r.t. unbounded probabilistic reachability. We find that, unlike Markovian formalisms, stochastic automata distinguish most classes even in this basic setting. Verification and strategy synthesis methods thus face a tradeoff between powerful and efficient classes. Using lightweight scheduler sampling, we explore this tradeoff and demonstrate the concept of a useful approximative verification technique for stochastic automata

Discrete Nondeterministic Modeling of the Fas Pathway

Abstract: Computer modeling of molecular signaling cascades can provide useful insight into the underlying complexities of biological systems. We present a refined approach for the discrete modeling of protein interactions within the environment of a single cell. The technique we offer utilizes the Membrane Systems paradigm which, due to its hierarchical structure, lends itself readily to mimic the behavior of cells. Since our approach is nondeterministic and discrete, it provides an interesting contrast to the standard deterministic ordinary differential equations techniques. We argue that our approach may outperform ordinary differential equations when modeling systems with relatively low numbers of molecules – a frequent occurrence in cellular signaling cascades. Refinements over our previous modeling efforts include the addition of nondeterminism for handling reaction competition over limited reactants, increased efficiency in the storing and sorting of reaction waiting times, and modifications of the model reactions. Results of our discrete simulation of the type I and type II Fas-mediated apoptotic signaling cascade are illustrated and compared with two approaches: one based on ordinary differential equations and another based on the well-known Gillespie algorithm

Discrete nondeterministic modeling of biochemical networks

The ideas expressed in this work pertain to biochemical modeling. We explore our technique, the Nondeterministic Waiting Time algorithm, for modeling molecular signaling cascades. The algorithm is presented with pseudocode along with an explanation of its implementation. The entire source code can be found in the Appendices. This algorithm builds on earlier work from the lab of Dr. Andrei Nun, the advisor for this dissertation. We discuss several important extensions including: (i) a heap with special maintenance functions for sorting reaction waiting times, (ii) a nondeterministic component for handling reaction competition, and (iii) a memory enhancement allowing slower reactions to compete with faster reactions. Several example systems are provided for comparisons between modeling with systems of ordinary differential equations, the Gillespie Algorithm, and our Nondeterministic Waiting Time algorithm. Our algorithm has a unique ability to exhibit behavior similar to the solutions to systems of ordinary differential equations for certain models and parameter choices, but it also has the nondeterministic component which yields results similar stochastic methods (e.g., the Gillespie Algorithm). Next, we turn our attention to the Fas-mediated apoptotic signaling cascade. Fas signaling has important implications in the research of cancer, autoimmune and neurodegenerative disorders. We provide an exhaustive account of results from the Nondeterministic Waiting Time algorithm in comparison to solutions to the system of ordinary differential equations described by another modeling group. Our work with the Fas pathway led us to explore a new model, focusing on the effects of HIV-1 proteins on the Fas signaling cascade. There is extensive information in the literature on the effects of the HIV-1 proteins on this pathway. The model described in this work represents the first attempt ever made in modeling Fas-induced apoptosis in latently infected T cells. There are several extensions for the Fas model discussed at the end of the work. Calcium signaling would be an interesting avenue to investigate, building on some recent results reported in the literature. For the HIV model, there are several extensions discussed. We also suggest a new direction for the Nondeterministic Waiting Time algorithm exploring parallelization options