32 research outputs found

    Realization and Extension of the Xfrog Approach for Plant Modelling in the Graph-Grammar Based Language XL

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    Two well-known approaches for modelling virtual vegetation are grammar-based methods (L-systems) and the Xfrog method, which is based on graph transformations expanding "multiplier" nodes. We show that both approaches can be unified in the framework of "relational growth grammars", a variant of parallel graph grammars. We demonstrate this possibility and the synergistic benefits of the combination of both methods at simple plant models which were processed using our open-source software GroIMP

    A correct, precise and efficient integration of set-sharing, freeness and linearity for the analysis of finite and rational tree languages

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    It is well known that freeness and linearity information positively interact with aliasing information, allowing both the precision and the efficiency of the sharing analysis of logic programs to be improved. In this paper, we present a novel combination of set-sharing with freeness and linearity information, which is characterized by an improved abstract unification operator. We provide a new abstraction function and prove the correctness of the analysis for both the finite tree and the rational tree cases. Moreover, we show that the same notion of redundant information as identified in Bagnara et al. (2000) and Zaffanella et al. (2002) also applies to this abstract domain combination: this allows for the implementation of an abstract unification operator running in polynomial time and achieving the same precision on all the considered observable properties

    Algorithms and Software for Biological MP Modeling by Statistical and Optimization Techniques

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    I sistemi biologici sono gruppi di entit\ue0 biologiche (es. molecole ed organismi), che interagiscono producendo specifiche dinamiche. Questi sistemi sono solitamente caratterizzati da una elevata complessit\ue0 perch\ue8 coinvolgono un elevato numero di componenti con molte interconnessioni. La comprensione dei meccanismi che governano i sistemi biologici e la previsione dei loro comportamenti in condizioni normali e patologiche \ue8 una sfida cruciale della biologia dei sistemi (in inglese detta systems biology), un'area di ricerca al confine tra biologia, medicina, matematica ed informatica. In questa tesi i P sistemi metabolici, detti brevemente sistemi MP, sono stati utilizzati come modello discreto per l'analisi di dinamiche biologiche. Essi sono una classe deterministica dei P sistemi classici, che utilizzano regole di riscrittura per rappresentare le reazioni chimiche e "funzioni di regolazioni di flusso" per regolare la reattivit\ue0 di ciascuna reazione rispetto alla quantita' di sostanze presenti istantaneamente nel sistema. Dopo un excursus sulla letteratura relativa ad alcuni modelli convenzionali (come le equazioni differenziali ed i modelli stocastici proposti da Gillespie) e non-convenzionali (come i P sistemi ed i P sistemi metabolici), saranno presentati i risultati della mia ricerca. Essi riguardano tre argomenti principali: i) l'equivalenza tra sistemi MP e reti di Petri ibride funzionali, ii) le prospettive statistiche e di ottimizzazione nella generazione di sistemi MP a partire da dati sperimentali, iii) lo sviluppo di un laboratorio virtuale chiamato MetaPlab, un software Java basato sui sistemi MP. L'equivalenza tra i sistemi MP e le reti di Petri ibride funzionali \ue8 stata dimostrata per mezzo di due teoremi ed alcuni esperimenti al computer per il caso di studio del meccanismo regolativo del gene operone lac nella pathway glicolitica. Il secondo argomento di ricerca concerne nuovi approcci per la sintesi delle funzioni di regolazione di flusso. La regressione stepwise e le reti neurali sono state impiegate come approssimatori di funzioni, mentre algoritmi di ottimizzazione classici ed evolutivi (es. backpropagation, algoritmi genetici, particle swarm optimization ed algoritmi memetici) sono stati impiegati per l'addestramento dei modelli. Una completo workflow per l'analisi dei dati sperimentali \ue8 stato presentato. Esso gestisce ed indirizza l'intero processo di sintesi delle funzioni di regolazione, dalla preparazione dei dati alla selezione delle variabili, fino alla generazione dei modelli ed alla loro validazione. Le metodologie proposte sono state testate con successo tramite esperimenti al computer sui casi di studio dell'oscillatore mitotico negli embrioni anfibi e del non photochemical quenching (NPQ). L'ultimo tema di ricerca \ue8 infine piu' applicativo e riguarda la progettazione e lo sviluppo di una architettura Java basata su plugin e di una serie di plugin che consentono di automatizzare varie fasi del processo di modellazione con sistemi MP, come la simulazione di dinamiche, la determinazione dei flussi e la generazione delle funzioni di regolazione.Biological systems are groups of biological entities, (e.g., molecules and organisms), that interact together producing specific dynamics. These systems are usually characterized by a high complexity, since they involve a large number of components having many interconnections. Understanding biological system mechanisms, and predicting their behaviors in normal and pathological conditions is a crucial challenge in systems biology, which is a central research area on the border among biology, medicine, mathematics and computer science. In this thesis metabolic P systems, also called MP systems, have been employed as discrete modeling framework for the analysis of biological system dynamics. They are a deterministic class of P systems employing rewriting rules to represent chemical reactions and "flux regulation functions" to tune reactions reactivity according to the amount of substances present in the system. After an excursus on the literature about some conventional (i.e., differential equations, Gillespie's models) and unconventional (i.e., P systems and metabolic P systems) modeling frameworks, the results of my research are presented. They concern three research topics: i) equivalences between MP systems and hybrid functional Petri nets, ii) statistical and optimization perspectives in the generation of MP models from experimental data, iii) development of the virtual laboratory MetaPlab, a Java software based on MP systems. The equivalence between MP systems and hybrid functional Petri nets is proved by two theorems and some in silico experiments for the case study of the lac operon gene regulatory mechanism and glycolytic pathway. The second topic concerns new approaches to the synthesis of flux regulation functions. Stepwise linear regression and neural networks are employed as function approximators, and classical/evolutionary optimization algorithms (e.g., backpropagation, genetic algorithms, particle swarm optimization, memetic algorithms) as learning techniques. A complete pipeline for data analysis is also presented, which addresses the entire process of flux regulation function synthesis, from data preparation to feature selection, model generation and statistical validation. The proposed methodologies have been successfully tested by means of in silico experiments on the mitotic oscillator in early amphibian embryos and the non photochemical quenching (NPQ). The last research topic is more applicative, and pertains the design and development of a Java plugin architecture and several plugins which enable to automatize many tasks related to MP modeling, such as, dynamics computation, flux discovery, and regulation function synthesis

    Modelling and analysis of structure in cellular signalling systems

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    Cellular signalling is an important area of study in biology. Signalling pathways are well-known abstractions that explain the mechanisms whereby cells respond to signals. Collections of pathways form signalling networks, and interactions between pathways in a network, known as cross-talk, enables further complex signalling behaviours. Increasingly, computational modelling and analysis is required to handle the complexity of such systems. While there are several computational modelling approaches for signalling pathways, none make cross-talk explicit. We present a modular modelling framework for pathways and their cross-talk. Networks are formed by composing pathways: different cross-talks result from different synchronisations of reactions between, and overlaps of, the pathways. We formalise five types of cross-talk and give approaches to reason about possible cross-talks in a network. The complementary problem is how to handle unstructured signalling networks, i.e. networks with no explicit notion of pathways or cross-talk. We present an approach to better understand unstructured signalling networks by modelling them as a set of signal flows through the network. We introduce the Reaction Minimal Paths (RMP) algorithm that computes the set of signal flows in a model. To the best of our knowledge, current algorithms cannot guarantee both correctness and completeness of the set of signal flows in a model. The RMP algorithm is the first. Finally, the RMP algorithm suffers from the well-known state space explosion problem. We use suitable partial order reduction algorithms to improve the efficiency of this algorithm
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