An Approach to Computational Complexity in Membrane Computing

In this paper we present a theory of computational complexity in the framework of membrane computing. Polynomial complexity classes in recognizer membrane systems and capturing the classical deterministic and non-deterministic modes of computation, are introduced. In this context, a characterization of the relation P = NP is described.Ministerio de Ciencia y Tecnología TIC2002-04220-C03-0

Reaching efficiency through collaboration in membrane systems: Dissolution, polarization and cooperation

From a computational complexity point of view, some syntactical ingredients play differentroles depending on the kind of combination considered. Inspired by the fact that the passing of a chemical substance through a biological membrane is often done by an interaction with the membrane itself, systems with active membranes were considered.Several combinations of different ingredients have been used in order to know which kindof problems could they solve efficientlyIn this paper, minimal cooperation with a minimal expression (the left-hand side of every object evolution rule has at most two objects and its right-hand side contains only one object) in object evolution rules is considered and a polynomial-time uniform solution to the SAT problem is presented. Consequently, a new way to tackle the P versus NP problem is provided.National Natural Science Foundation of China No 61472328National Natural Science Foundation of China No 6132010600

Advances in Rule-based Modeling: Compartments, Energy, and Hybrid Simulation, with Application to Sepsis and Cell Signaling

Biological systems are commonly modeled as reaction networks, which describe the system at the resolution of biochemical species. Cellular systems, however, are governed by events at a finer scale: local interactions among macromolecular domains. The multi-domain structure of macromolecules, combined with the local nature of interactions, can lead to a combinatorial explosion that pushes reaction network methods to their limits. As an alternative, rule-based models (RBMs) describe the domain-based structure and local interactions found in biological systems. Molecular complexes are represented by graphs: functional domains as vertices, macromolecules as groupings of vertices, and molecular bonding as edges. Reaction rules, which describe classes of reactions, govern local modifications to molecular graphs, such as binding, post-translational modification, and degradation. RBMs can be transformed to equivalent reaction networks and simulated by differential or stochastic methods, or simulated directly with a network-free approach that avoids the problem of combinatorial complexity. Although RBMs and network-free methods resolve many problems in systems modeling, challenges remain. I address three challenges here: (i) managing model complexity due to cooperative interactions, (ii) representing biochemical systems in the compartmental setting of cells and organisms, and (iii) reducing the memory burden of large-scale network-free simulations. First, I present a general theory of energy-based modeling within the BioNetGen framework. Free energy is computed under a pattern-based formalism, and contextual variations within reaction classes are enumerated automatically. Next, I extend the BioNetGen language to permit description of compartmentalized biochemical systems, with treatment of volumes, surfaces and transport. Finally, a hybrid particle/population method is developed to reduce memory requirements of network-free simulations. All methods are implemented and available as part of BioNetGen. The remainder of this work presents an application to sepsis and inflammation. A multi-organ model of peritoneal infection and systemic inflammation is constructed and calibrated to experiment. Extra-corporeal blood purification, a potential treatment for sepsis, is explored in silico. Model simulations demonstrate that removal of blood cytokines and chemokines is a sufficient mechanism for improved survival in sepsis. However, differences between model predictions and the latest experimental data suggest directions for further exploration

Communication in membrana Systems with symbol Objects.

Esta tesis está dedicada a los sistemas de membranas con objetos-símbolo como marco teórico de los sistemas paralelos y distribuidos de procesamiento de multiconjuntos.Una computación de parada puede aceptar, generar o procesar un número, un vector o una palabra; por tanto el sistema define globalmente (a través de los resultados de todas sus computaciones) un conjunto de números, de vectores, de palabras (es decir, un lenguaje), o bien una función. En esta tesis estudiamos la capacidad de estos sistemas para resolver problemas particulares, así como su potencia computacional. Por ejemplo, las familias de lenguajes definidas por diversas clases de estos sistemas se comparan con las familias clásicas, esto es, lenguajes regulares, independientes del contexto, generados por sistemas 0L tabulados extendidos, generados por gramáticas matriciales sin chequeo de apariciones, recursivamente enumerables, etc. Se prestará especial atención a la comunicación de objetos entre regiones y a las distintas formas de cooperación entre ellos.Se pretende (Sección 3.4) realizar una formalización los sistemas de membranas y construir una herramienta tipo software para la variante que usa cooperación no distribuida, el navegador de configuraciones, es decir, un simulador, en el cual el usuario selecciona la siguiente configuración entre todas las posibles, estando permitido volver hacia atrás. Se considerarán diversos modelos distribuidos. En el modelo de evolución y comunicación (Capítulo 4) separamos las reglas tipo-reescritura y las reglas de transporte (llamadas symport y antiport). Los sistemas de bombeo de protones (proton pumping, Secciones 4.8, 4.9) constituyen una variante de los sistemas de evolución y comunicación con un modo restrictivo de cooperación. Un modelo especial de computación con membranas es el modelo puramente comunicativo, en el cual los objetos traspasan juntos una membrana. Estudiamos la potencia computacional de las sistemas de membranas con symport/antiport de 2 o 3 objetos (Capítulo 5) y la potencia computacional de las sistemas de membranas con alfabeto limitado (Capítulo 6).El determinismo (Secciones 4.7, 5.5, etc.) es una característica especial (restrictiva) de los sistemas computacionales. Se pondrá especial énfasis en analizar si esta restricción reduce o no la potencia computacional de los mismos. Los resultados obtenidos para sistemas de bombeo del protones están transferidos (Sección 7.3) a sistemas con catalizadores bistabiles. Unos ejemplos de aplicación concreta de los sistemas de membranas (Secciones 7.1, 7.2) son la resolución de problemas NP-completos en tiempo polinomial y la resolución de problemas de ordenación.This thesis deals with membrane systems with symbol objects as a theoretical framework of distributed parallel multiset processing systems.A halting computation can accept, generate or process a number, a vector or a word, so the system globally defines (by the results of all its computations) a set of numbers or a set of vectors or a set of words, (i.e., a language), or a function. The ability of these systems to solve particular problems is investigated, as well as their computational power, e.g., the language families defined by different classes of these systems are compared to the classical ones, i.e., regular, context-free, languages generated by extended tabled 0L systems, languages generated by matrix grammars without appearance checking, recursively enumerable languages, etc. Special attention is paid to communication of objects between the regions and to the ways of cooperation between the objects.An attempt to formalize the membrane systems is made (Section 3.4), and a software tool is constructed for the non-distributed cooperative variant, the configuration browser, i.e., a simulator, where the user chooses the next configuration among the possible ones and can go back. Different distributed models are considered. In the evolution-communication model (Chapter 4) rewriting-like rules are separated from transport rules. Proton pumping systems (Sections 4.8, 4.9) are a variant of the evolution-communication systems with a restricted way of cooperation. A special membrane computing model is a purely communicative one: the objects are moved together through a membrane. We study the computational power of membrane systems with symport/antiport of 2 or 3 objects (Chapter 5) and the computational power of membrane systems with a limited alphabet (Chapter 6).Determinism (Sections 4.7, 5.5, etc.) is a special property of computational systems; the question of whether this restriction reduces the computational power is addressed. The results on proton pumping systems can be carried over (Section 7.3) to the systems with bi-stable catalysts. Some particular examples of membrane systems applications are solving NP-complete problems in polynomial time, and solving the sorting problem

Formal Verification of P Systems

Membrane systems, also known as P systems, constitute an innovative computational paradigm inspired by the structure and dynamics of the living cell. A P system consists of a hierarchical arrangement of compartments and a finite set of multiset rewriting and communication rules, which operate in a maximally parallel manner. The organic vision of concurrent dynamics captured by membrane systems stands in antithesis with conventional formal modelling methods which focus on algebraic descriptions of distributed systems. As a consequence, verifying such models in a mathematically rigorous way is often elusive and indeed counter-intuitive when considering established approaches, which generally require sequential process representations or highly abstract theoretical frameworks. The prevalent investigations with this objective in the field of membrane computing are ambivalent and inconclusive in the wider application scope of P systems. In this thesis we directly address the formal verification of membrane systems by means of model checking. A fundamental distinction between the agnostic perspective on parallelism, advocated by process calculi, and P systems' emblematic maximally parallel execution strategy is identified. On this basis, we establish that an intuitional translation to traditional process models is inadequate for the purpose of formal verification, due to a state space growth disparity. The observation is essential for this research project: on one hand it implies the feasibility of model checking P systems, and on the other hand it underlines the suitability of this formal verification technique in the context of membrane computing. Model checking entails an exhaustive state space exploration and does not derive inferences based on the independent instructions comprising a state transition. In this respect, we define a new sequential modelling strategy which is optimal for membrane systems and targets the SPIN formal verification tool. We introduce elementary P systems, a distributed computational model which subsumes the feature diversity of the membrane computing paradigm and distils its functional vocabulary. A suite of supporting software tools which gravitate around this formalism has also been developed, comprising of 1. the eps modelling language for elementary P systems; 2. a parser for the eps specification; 3. a model simulator and 4. a translation tool which targets the Promela specification of the SPIN model checker. The formal verification approach proposed in this thesis is progressively demonstrated in four heterogeneous case studies, featuring 1. a parallel algorithm applicable to a structured model; 2. a linear time solution to an NP-complete problem; 3. an innovative implementation of the Dining Philosophers scenario (a synchronisation problem) using an elementary P system and 4. a quantitative analysis of a simple random process implemented without the support of a probabilistic model