394 research outputs found

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

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    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

    Process Calculi Abstractions for Biology

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    Several approaches have been proposed to model biological systems by means of the formal techniques and tools available in computer science. To mention just a few of them, some representations are inspired by Petri Nets theory, and some other by stochastic processes. A most recent approach consists in interpreting the living entities as terms of process calculi where the behavior of the represented systems can be inferred by applying syntax-driven rules. A comprehensive picture of the state of the art of the process calculi approach to biological modeling is still missing. This paper goes in the direction of providing such a picture by presenting a comparative survey of the process calculi that have been used and proposed to describe the behavior of living entities. This is the preliminary version of a paper that was published in Algorithmic Bioprocesses. The original publication is available at http://www.springer.com/computer/foundations/book/978-3-540-88868-

    BlenX-based compositional modeling of complex reaction mechanisms

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    Molecular interactions are wired in a fascinating way resulting in complex behavior of biological systems. Theoretical modeling provides a useful framework for understanding the dynamics and the function of such networks. The complexity of the biological networks calls for conceptual tools that manage the combinatorial explosion of the set of possible interactions. A suitable conceptual tool to attack complexity is compositionality, already successfully used in the process algebra field to model computer systems. We rely on the BlenX programming language, originated by the beta-binders process calculus, to specify and simulate high-level descriptions of biological circuits. The Gillespie's stochastic framework of BlenX requires the decomposition of phenomenological functions into basic elementary reactions. Systematic unpacking of complex reaction mechanisms into BlenX templates is shown in this study. The estimation/derivation of missing parameters and the challenges emerging from compositional model building in stochastic process algebras are discussed. A biological example on circadian clock is presented as a case study of BlenX compositionality

    Towards Executable Biology

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    Heringa, J. [Promotor]Fokkink, W.J. [Promotor]Feenstra, K.A. [Copromotor

    A model-driven approach to teaching concurrency

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    We present an undergraduate course on concurrent programming where formal models are used in different stages of the learning process. The main practical difference with other approaches lies in the fact that the ability to develop correct concurrent software relies on a systematic transformation of formal models of inter-process interaction (so called shared resources), rather than on the specific constructs of some programming language. Using a resource-centric rather than a language-centric approach has some benefits for both teachers and students. Besides the obvious advantage of being independent of the programming language, the models help in the early validation of concurrent software design, provide students and teachers with a lingua franca that greatly simplifies communication at the classroom and during supervision, and help in the automatic generation of tests for the practical assignments. This method has been in use, with slight variations, for some 15 years, surviving changes in the programming language and course length. In this article, we describe the components and structure of the current incarnation of the course?which uses Java as target language?and some tools used to support our method. We provide a detailed description of the different outcomes that the model-driven approach delivers (validation of the initial design, automatic generation of tests, and mechanical generation of code) from a teaching perspective. A critical discussion on the perceived advantages and risks of our approach follows, including some proposals on how these risks can be minimized. We include a statistical analysis to show that our method has a positive impact in the student ability to understand concurrency and to generate correct code

    Advanced information processing system: The Army fault tolerant architecture conceptual study. Volume 2: Army fault tolerant architecture design and analysis

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    Described here is the Army Fault Tolerant Architecture (AFTA) hardware architecture and components and the operating system. The architectural and operational theory of the AFTA Fault Tolerant Data Bus is discussed. The test and maintenance strategy developed for use in fielded AFTA installations is presented. An approach to be used in reducing the probability of AFTA failure due to common mode faults is described. Analytical models for AFTA performance, reliability, availability, life cycle cost, weight, power, and volume are developed. An approach is presented for using VHSIC Hardware Description Language (VHDL) to describe and design AFTA's developmental hardware. A plan is described for verifying and validating key AFTA concepts during the Dem/Val phase. Analytical models and partial mission requirements are used to generate AFTA configurations for the TF/TA/NOE and Ground Vehicle missions

    Modeling formalisms in systems biology

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    Systems Biology has taken advantage of computational tools and high-throughput experimental data to model several biological processes. These include signaling, gene regulatory, and metabolic networks. However, most of these models are specific to each kind of network. Their interconnection demands a whole-cell modeling framework for a complete understanding of cellular systems. We describe the features required by an integrated framework for modeling, analyzing and simulating biological processes, and review several modeling formalisms that have been used in Systems Biology including Boolean networks, Bayesian networks, Petri nets, process algebras, constraint-based models, differential equations, rule-based models, interacting state machines, cellular automata, and agent-based models. We compare the features provided by different formalisms, and discuss recent approaches in the integration of these formalisms, as well as possible directions for the future.Research supported by grants SFRH/BD/35215/2007 and SFRH/BD/25506/2005 from the Fundacao para a Ciencia e a Tecnologia (FCT) and the MIT-Portugal Program through the project "Bridging Systems and Synthetic Biology for the development of improved microbial cell factories" (MIT-Pt/BS-BB/0082/2008)

    Formal verification of authentication and service authorization protocols in 5G-enabled device-to-device communications using ProVerif

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    Device-to-Device (D2D) communications will be used as an underlay technology in the Fifth Generation mobile network (5G), which will make network services of multiple Service Providers (SP) available anywhere. The end users will be allowed to access and share services using their User Equipments (UEs), and thus they will require seamless and secured connectivity. At the same time, Mobile Network Operators (MNOs) will use the UE to offload traffic and push contents closer to users relying on D2D communications network. This raises security concerns at different levels of the system architecture and highlights the need for robust authentication and authorization mechanisms to provide secure services access and sharing between D2D users. Therefore, this paper proposes a D2D level security solution that comprises two security protocols, namely, the D2D Service security (DDSec) and the D2D Attributes and Capability security (DDACap) protocols, to provide security for access, caching and sharing data in network-assisted and non-network-assisted D2D communications scenarios. The proposed solution applies Identity-based Encryption (IBE), Elliptic Curve Integrated Encryption Scheme (ECIES) and access control mechanisms for authentication and authorization procedures. We formally verified the proposed protocols using ProVerif and applied pi calculus. We also conducted a security analysis of the proposed protocols

    The Layer-Oriented Approach to Declarative Languages for Biological Modeling

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    We present a new approach to modeling languages for computational biology, which we call the layer-oriented approach. The approach stems from the observation that many diverse biological phenomena are described using a small set of mathematical formalisms (e.g. differential equations), while at the same time different domains and subdomains of computational biology require that models are structured according to the accepted terminology and classification of that domain. Our approach uses distinct semantic layers to represent the domain-specific biological concepts and the underlying mathematical formalisms. Additional functionality can be transparently added to the language by adding more layers. This approach is specifically concerned with declarative languages, and throughout the paper we note some of the limitations inherent to declarative approaches. The layer-oriented approach is a way to specify explicitly how high-level biological modeling concepts are mapped to a computational representation, while abstracting away details of particular programming languages and simulation environments. To illustrate this process, we define an example language for describing models of ionic currents, and use a general mathematical notation for semantic transformations to show how to generate model simulation code for various simulation environments. We use the example language to describe a Purkinje neuron model and demonstrate how the layer-oriented approach can be used for solving several practical issues of computational neuroscience model development. We discuss the advantages and limitations of the approach in comparison with other modeling language efforts in the domain of computational biology and outline some principles for extensible, flexible modeling language design. We conclude by describing in detail the semantic transformations defined for our language
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