Qualitative modelling and analysis of regulations in multi-cellular systems using Petri nets and topological collections

In this paper, we aim at modelling and analyzing the regulation processes in multi-cellular biological systems, in particular tissues. The modelling framework is based on interconnected logical regulatory networks a la Rene Thomas equipped with information about their spatial relationships. The semantics of such models is expressed through colored Petri nets to implement regulation rules, combined with topological collections to implement the spatial information. Some constraints are put on the the representation of spatial information in order to preserve the possibility of an enumerative and exhaustive state space exploration. This paper presents the modelling framework, its semantics, as well as a prototype implementation that allowed preliminary experimentation on some applications.Comment: In Proceedings MeCBIC 2010, arXiv:1011.005

Symmetries and transport in site-dependently driven quantum lattices

We explore the quantum dynamics of particles in a spatiotemporally driven lattice. A powerful numerical scheme is developed, which provides us with the Floquet modes and thus enables a stroboscopic propagation of arbitrary initial states. A detailed symmetry analysis represents the cornerstone for an intricate manipulation of the Floquet spectrum. Specifically, we show how exact crossings can be converted into avoided ones, while the width of these resulting avoided crossings can be engineered by adjusting parameters of the local driving. Asymptotic currents are shown to be controllable over a certain parameter range

Adjunct hexagonal array token Petri nets and hexagonal picture languages

Adjunct Hexagonal Array Token Petri Net Structures (AHPN) are re- cently introduced hexagonal picture generating devices which extended the Hexag- onal Array Token Petri Net Structures . In this paper we consider AHPN model along with a control feature called inhibitor arcs and compare it with some ex- pressive hexagonal picture generating and recognizing models with respect to the generating power

Analysis of interface conversion processes of ballistic and diffusive motion in driven superlattices

We explore the non-equilibrium dynamics of non-interacting classical particles in a one-dimensional driven superlattice which is composed of domains exposed to different time-dependent forces. It is shown how the combination of directed transport and conversion processes from diffusive to ballistic motion causes strong correlations between velocity and phase for particles passing through a superlattice. A detailed understanding of the underlying mechanism allows us to tune the resulting velocity distributions at distinguished points in the superlattice by means of local variations of the applied driving force. As an intriguing application we present a scheme how initially diffusive particles can be transformed into a monoenergetic pulsed particle beam whose parameters such as its energy can be varied

Mini-Collagens in Hydra Nematocytes

We have isolated and characterized four collagen-related c-DNA clones (N-COL 1, N-COL 2, N-COL 3, N-COL 4) that are highly expressed in developing nematocytes in hydra. All four c-DNAs as well as their corresponding transcripts are small in size (600-1,000 bp). The deduced amino acid sequences show that they contain a central region consisting of 14 to 16 Gly-X-Y triplets. This region is flanked amino-terminal by a stretch of 14-23 proline residues and carboxy-terminal by a stretch of 6-9 prolines. At the NH2- and COOH-termini are repeated patterns of cysteine residues that are highly conserved between the molecules. A model is proposed which consists of a central stable collagen triple helix of 12-14 nm length from which three 9-22 nm long polyproline II type helices emerge at both ends. Disulfide linkage between cysteine- rich segments in these helices could lead to the formation of oligomeric network structures. Electrophoretic characterization of nematocyst extracts allows resolution of small proline-rich polypeptides that correspond in size to the cloned sequences

Botulinum Toxin as Preventive Treatment for Migraine: A Randomized Double-Blind Study

Aim: To determine if botulinum toxin type A (BoNT-A) injections can reduce the frequency and severity of migraines. Methods: Patients (n = 127) were randomized to receive placebo or two doses of BoNT-A (Dysport (R)). The primary endpoint was reduction in number of migraine attacks up to week 8 and between weeks 8 and 12 after injection. Patient diaries were used to record secondary endpoints, including frequency, severity and duration of migraine attacks. Results: There was a mean reduction of 0.54 and 0.94 attacks/month with placebo and BoNT-A, respectively, and absolute attack count was less in the verum group (3.6 vs. 4.2 attacks/month), but this was not statistically significant. The patients' global assessment of efficacy was significantly better than placebo in the high-dose group (p = 0.02) but no effects were seen for the other secondary efficacy parameters. Conclusion: Our study showed a trend towards a reduced attack rate with verum but did not show any statistically significant efficacy of BoNT-A in the prophylactic treatment of migraine. Copyright (C) 2009 S. Karger AG, Base

The Reachability Problem for Petri Nets is Not Elementary

Petri nets, also known as vector addition systems, are a long established model of concurrency with extensive applications in modelling and analysis of hardware, software and database systems, as well as chemical, biological and business processes. The central algorithmic problem for Petri nets is reachability: whether from the given initial configuration there exists a sequence of valid execution steps that reaches the given final configuration. The complexity of the problem has remained unsettled since the 1960s, and it is one of the most prominent open questions in the theory of verification. Decidability was proved by Mayr in his seminal STOC 1981 work, and the currently best published upper bound is non-primitive recursive Ackermannian of Leroux and Schmitz from LICS 2019. We establish a non-elementary lower bound, i.e. that the reachability problem needs a tower of exponentials of time and space. Until this work, the best lower bound has been exponential space, due to Lipton in 1976. The new lower bound is a major breakthrough for several reasons. Firstly, it shows that the reachability problem is much harder than the coverability (i.e., state reachability) problem, which is also ubiquitous but has been known to be complete for exponential space since the late 1970s. Secondly, it implies that a plethora of problems from formal languages, logic, concurrent systems, process calculi and other areas, that are known to admit reductions from the Petri nets reachability problem, are also not elementary. Thirdly, it makes obsolete the currently best lower bounds for the reachability problems for two key extensions of Petri nets: with branching and with a pushdown stack.Comment: Final version of STOC'1

A modular, qualitative modelling of regulatory networks using Petri nets

International audienceAdvances in high-throughput technologies have enabled the de-lineation of large networks of interactions that control cellular processes. To understand behavioural properties of these complex networks, mathematical and computational tools are required. The multi-valued logical formalism, initially defined by R. Thomas and co-workers, proved well adapted to account for the qualitative knowledge available on regulatory interactions, and also to perform analyses of their dynamical properties. In this context, we present two representations of logical models in terms of Petri nets. In a first step, we briefly show how logical models of regulatory networks can be transposed into standard (place/transition) Petri nets, and discuss the capabilities of such representation. In the second part, we focus on logical regulatory modules and their composition, demonstrating that a high-level Petri net representation greatly facilitates the modelling of interconnected modules. Doing so, we introduce an explicit means to integrate signals from various interconnected modules, taking into account their spatial distribution. This provides a flexible modelling framework to handle regulatory networks that operate at both intra-and intercellular levels. As an illustration, we describe a simplified model of the segment-polarity module involved in the segmentation of the Drosophila embryo