The rule-based model approach. A Kappa model for hepatic stellate cells activation by TGFB1

International audienc

On the Use of Formal Methods to Model and Verify Neuronal Archetypes

International audienceHaving a formal model of neural networks can greatly help in understanding and verifying their properties, behavior, and response to external factors such as disease and medicine. In this paper, we adopt a formal model to represent neurons, some neuronal graphs, and their composition. Some specific neuronal graphs are known for having biologically relevant structures and behaviors and we call them archetypes. These archetypes are supposed to be the basis of typical instances of neuronal information processing. In this paper we study six fundamental archetypes (simple series, series with multiple outputs, parallel composition, negative loop, inhibition of a behavior, and contralateral inhibition), and we consider two ways to couple two archetypes: (i) connecting the output(s) of the first archetype to the input(s) of the second archetype and (ii) nesting the first archetype within the second one. We report and compare two key approaches to the formal modeling and verification of the proposed neuronal archetypes and some selected couplings. The first approach exploits the synchronous programming language Lustre to encode archetypes and their couplings, and to express properties concerning their dynamic behavior. These properties are verified thanks to the use of model checkers. The second approach relies on a theorem prover, the Coq Proof Assistant, to prove dynamic properties of neurons and archetype

Computational Methods in Systems Biology : 15th International Conference, CMSB 2017, Darmstadt, Germany, September 27–29, 2017, Proceedings

International audienceThis book constitutes the refereed proceedings of the 15th International Conference on Computational Methods in Systems Biology, CMSB 2017, held in Darmstadt, Germany, in September 2017. The 15 full papers, 4 tool papers and 4 posters presented together with 1 invited talk were carefully reviewed and selected from 41 regular paper submissions. Topics of interest include formalisms for modeling biological processes; models and their biological applications; frameworks for model verication, validation, analysis, and simulation of biological systems; high-performance computational systems biology and parallel implementations; model inference from experimental data; model integration from biological databases; multi-scale modeling and analysis methods; and computational approaches for synthetic biology

Parameterised bounds on the sum of variables in time-series constraints

For two families of time-series constraints with the aggregator Sum and features one and width, we provide parameterised sharp lower and upper bounds on the sum of the time-series variables wrt these families of constraints. This is important in many applications, as this sum represents the cost, for example the energy used, or the manpower effort expended. We use these bounds not only to gain a priori knowledge of the overall cost of a problem, we can also use them on increasing prefixes and suffixes of the variables to avoid infeasible partial assignments under a given cost budget. Experiments show that the bounds drastically reduce the effort to find cost limited solutions

Exact and optimal quadratization of nonlinear finite-dimensional non-autonomous dynamical systems

Quadratization of polynomial and nonpolynomial systems of ordinary differential equations is advantageous in a variety of disciplines, such as systems theory, fluid mechanics, chemical reaction modeling and mathematical analysis. A quadratization reveals new variables and structures of a model, which may be easier to analyze, simulate, control, and provides a convenient parametrization for learning. This paper presents novel theory, algorithms and software capabilities for quadratization of non-autonomous ODEs. We provide existence results, depending on the regularity of the input function, for cases when a quadratic-bilinear system can be obtained through quadratization. We further develop existence results and an algorithm that generalizes the process of quadratization for systems with arbitrary dimension that retain the nonlinear structure when the dimension grows. For such systems, we provide dimension-agnostic quadratization. An example is semi-discretized PDEs, where the nonlinear terms remain symbolically identical when the discretization size increases. As an important aspect for practical adoption of this research, we extended the capabilities of the QBee software towards both non-autonomous systems of ODEs and ODEs with arbitrary dimension. We present several examples of ODEs that were previously reported in the literature, and where our new algorithms find quadratized ODE systems with lower dimension than the previously reported lifting transformations. We further highlight an important area of quadratization: reduced-order model learning. This area can benefit significantly from working in the optimal lifting variables, where quadratic models provide a direct parametrization of the model that also avoids additional hyperreduction for the nonlinear terms. A solar wind example highlights these advantages

Tools and Algorithms for the Construction and Analysis of Systems

This book is Open Access under a CC BY licence. The LNCS 11427 and 11428 proceedings set constitutes the proceedings of the 25th International Conference on Tools and Algorithms for the Construction and Analysis of Systems, TACAS 2019, which took place in Prague, Czech Republic, in April 2019, held as part of the European Joint Conferences on Theory and Practice of Software, ETAPS 2019. The total of 42 full and 8 short tool demo papers presented in these volumes was carefully reviewed and selected from 164 submissions. The papers are organized in topical sections as follows: Part I: SAT and SMT, SAT solving and theorem proving; verification and analysis; model checking; tool demo; and machine learning. Part II: concurrent and distributed systems; monitoring and runtime verification; hybrid and stochastic systems; synthesis; symbolic verification; and safety and fault-tolerant systems