Computational Modeling for the Activation Cycle of G-proteins by G-protein-coupled Receptors

In this paper, we survey five different computational modeling methods. For comparison, we use the activation cycle of G-proteins that regulate cellular signaling events downstream of G-protein-coupled receptors (GPCRs) as a driving example. Starting from an existing Ordinary Differential Equations (ODEs) model, we implement the G-protein cycle in the stochastic Pi-calculus using SPiM, as Petri-nets using Cell Illustrator, in the Kappa Language using Cellucidate, and in Bio-PEPA using the Bio-PEPA eclipse plug in. We also provide a high-level notation to abstract away from communication primitives that may be unfamiliar to the average biologist, and we show how to translate high-level programs into stochastic Pi-calculus processes and chemical reactions.Comment: In Proceedings MeCBIC 2010, arXiv:1011.005

Evaluation and extracting factual software architecture of distributed system by process mining techniques

The factual software architectures that are actually implemented of distributed systems do not conform the planned software architectures (Beck 2010). It happens due to the complexity of distributed systems. This problem begets two main challenges; First, how to extract the factual software architectures with the proper techniques and second, how to compare the planned software architecture with the extracted factual architecture. This study aims to use process mining to discover factual software architecture from codes and represents software architecture model in Petri Net to evaluate model by the linear temporal logic and process mining. In this paper, the applicability of process mining techniques, implemented in the ProM6.7 framework is shown to extract and evaluate factual software architectures. Furthermore, capabilities of Hierarchical Colored Petri Net implemented in CPN4.0 are exploited to model and simulate software architectures. The proposed approach has been conducted on a case study to indicate applicability of the approach in the distributed data base system. The final result of the case study indicates process mining is able to extract factual software architectures and also to check its conformance

Bisimilarity and Behaviour-Preserving Reconfigurations of Open Petri Nets

We propose a framework for the specification of behaviour-preserving reconfigurations of systems modelled as Petri nets. The framework is based on open nets, a mild generalisation of ordinary Place/Transition nets suited to model open systems which might interact with the surrounding environment and endowed with a colimit-based composition operation. We show that natural notions of bisimilarity over open nets are congruences with respect to the composition operation. The considered behavioural equivalences differ for the choice of the observations, which can be single firings or parallel steps. Additionally, we consider weak forms of such equivalences, arising in the presence of unobservable actions. We also provide an up-to technique for facilitating bisimilarity proofs. The theory is used to identify suitable classes of reconfiguration rules (in the double-pushout approach to rewriting) whose application preserves the observational semantics of the net.Comment: To appear in "Logical Methods in Computer Science", 41 page

Modelling Distributed Cognition Systems in PVS

We report on our efforts to formalise DiCoT, an informal structured approach for analysing complex work systems, such as hospital and day care units, as distributed cognition systems. We focus on DiCoT's information flow model, which describes how information is transformed and propagated in the system. Our contribution is a set of generic models for the specification and verification system PVS. The developed models can be directly mapped to the informal descriptions adopted by human-computer interactions experts. The models can be verified against properties of interest in the PVS theorem prover. Also, the same models can be simulated, thus facilitating analysts to engage with stakeholders when checking the correctness of the model. We trial our ideas on a case study based on a real-world medical system

Computational Modeling, Formal Analysis, and Tools for Systems Biology.

As the amount of biological data in the public domain grows, so does the range of modeling and analysis techniques employed in systems biology. In recent years, a number of theoretical computer science developments have enabled modeling methodology to keep pace. The growing interest in systems biology in executable models and their analysis has necessitated the borrowing of terms and methods from computer science, such as formal analysis, model checking, static analysis, and runtime verification. Here, we discuss the most important and exciting computational methods and tools currently available to systems biologists. We believe that a deeper understanding of the concepts and theory highlighted in this review will produce better software practice, improved investigation of complex biological processes, and even new ideas and better feedback into computer science

Search-based system architecture development using a holistic modeling approach

This dissertation presents an innovative approach to system architecting where search algorithms are used to explore design trade space for good architecture alternatives. Such an approach is achieved by integrating certain model construction, alternative generation, simulation, and assessment processes into a coherent and automated framework. This framework is facilitated by a holistic modeling approach that combines the capabilities of Object Process Methodology (OPM), Colored Petri Net (CPN), and feature model. The resultant holistic model can not only capture the structural, behavioral, and dynamic aspects of a system, allowing simulation and strong analysis methods to be applied, it can also specify the architectural design space. Both object-oriented analysis and design (OOA/D) and domain engineering were exploited to capture design variables and their domains and define architecture generation operations. A fully realized framework (with genetic algorithms as the search algorithm) was developed. Both the proposed framework and its suggested implementation, including the proposed holistic modeling approach and architecture alternative generation operations, are generic. They are targeted at systems that can be specified using object-oriented or process-oriented paradigm. The broad applicability of the proposed approach is demonstrated on two examples. One is the configuration of reconfigurable manufacturing systems (RMSs) under multi-objective optimization and the other is the architecture design of a manned lunar landing system for the Apollo program. The test results show that the proposed approach can cover a huge number of architecture alternatives and support the assessment of several performance measures. A set of quality results was obtained after running the optimization algorithm following the proposed framework --Abstract, page iii

Multi-level model for the investigation of oncoantigen- driven vaccination effect

BACKGROUND: Cancer stem cell theory suggests that cancers are derived by a population of cells named Cancer Stem Cells (CSCs) that are involved in the growth and in the progression of tumors, and lead to a hierarchical structure characterized by differentiated cell population. This cell heterogeneity affects the choice of cancer therapies, since many current cancer treatments have limited or no impact at all on CSC population, while they reveal a positive effect on the differentiated cell populations. RESULTS: In this paper we investigated the effect of vaccination on a cancer hierarchical structure through a multi-level model representing both population and molecular aspects. The population level is modeled by a system of Ordinary Differential Equations (ODEs) describing the cancer population's dynamics. The molecular level is modeled using the Petri Net (PN) formalism to detail part of the proliferation pathway. Moreover, we propose a new methodology which exploits the temporal behavior derived from the molecular level to parameterize the ODE system modeling populations. Using this multi-level model we studied the ErbB2-driven vaccination effect in breast cancer. CONCLUSIONS: We propose a multi-level model that describes the inter-dependencies between population and genetic levels, and that can be efficiently used to estimate the efficacy of drug and vaccine therapies in cancer models, given the availability of molecular data on the cancer driving force

Connector algebras for C/E and P/T nets interactions

A quite fourishing research thread in the recent literature on component based system is concerned with the algebraic properties of different classes of connectors. In a recent paper, an algebra of stateless connectors was presented that consists of five kinds of basic connectors, namely symmetry, synchronization, mutual exclusion, hiding and inaction, plus their duals and it was shown how they can be freely composed in series and in parallel to model sophisticated "glues". In this paper we explore the expressiveness of stateful connectors obtained by adding one-place buffers or unbounded buffers to the stateless connectors. The main results are: i) we show how different classes of connectors exactly correspond to suitable classes of Petri nets equipped with compositional interfaces, called nets with boundaries; ii) we show that the difference between strong and weak semantics in stateful connectors is reflected in the semantics of nets with boundaries by moving from the classic step semantics (strong case) to a novel banking semantics (weak case), where a step can be executed by taking some "debit" tokens to be given back during the same step; iii) we show that the corresponding bisimilarities are congruences (w.r.t. composition of connectors in series and in parallel); iv) we show that suitable monoidality laws, like those arising when representing stateful connectors in the tile model, can nicely capture concurrency aspects; and v) as a side result, we provide a basic algebra, with a finite set of symbols, out of which we can compose all P/T nets, fulfilling a long standing quest

SAFE-FLOW : a systematic approach for safety analysis of clinical workflows

The increasing use of technology in delivering clinical services brings substantial benefits to the healthcare industry. At the same time, it introduces potential new complications to clinical workflows that generate new risks and hazards with the potential to affect patients’ safety. These workflows are safety critical and can have a damaging impact on all the involved parties if they fail.Due to the large number of processes included in the delivery of a clinical service, it can be difficult to determine the individuals or the processes that are responsible for adverse events. Using methodological approaches and automated tools to carry out an analysis of the workflow can help in determining the origins of potential adverse events and consequently help in avoiding preventable errors. There is a scarcity of studies addressing this problem; this was a partial motivation for this thesis.The main aim of the research is to demonstrate the potential value of computer science based dependability approaches to healthcare and in particular, the appropriateness and benefits of these dependability approaches to overall clinical workflows. A particular focus is to show that model-based safety analysis techniques can be usefully applied to such areas and then to evaluate this application.This thesis develops the SAFE-FLOW approach for safety analysis of clinical workflows in order to establish the relevance of such application. SAFE-FLOW detailed steps and guidelines for its application are explained. Then, SAFE-FLOW is applied to a case study and is systematically evaluated. The proposed evaluation design provides a generic evaluation strategy that can be used to evaluate the adoption of safety analysis methods in healthcare.It is concluded that safety of clinical workflows can be significantly improved by performing safety analysis on workflow models. The evaluation results show that SAFE-FLOW is feasible and it has the potential to provide various benefits; it provides a mechanism for a systematic identification of both adverse events and safeguards, which is helpful in terms of identifying the causes of possible adverse events before they happen and can assist in the design of workflows to avoid such occurrences. The clear definition of the workflow including its processes and tasks provides a valuable opportunity for formulation of safety improvement strategies