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ROBERTO SERRA

PROFESSORE FUORI RUOLO Esterno presso: Dipartimento di Scienze Fisiche, Informatiche e Matematiche sede ex-Fisica


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Pubblicazioni

2021 - A Fast and Effective Method to Identify Relevant Sets of Variables in Complex Systems [Articolo su rivista]
D’Addese, Gianluca; Casari, Martina; Serra, Roberto; Villani, Marco
abstract

In many complex systems one observes the formation of medium-level structures, whose detection could allow a high-level description of the dynamical organization of the system itself, and thus to its better understanding. We have developed in the past a powerful method to achieve this goal, which however requires a heavy computational cost in several real-world cases. In this work we introduce a modified version of our approach, which reduces the computational burden. The design of the new algorithm allowed the realization of an original suite of methods able to work simultaneously at the micro level (that of the binary relationships of the single variables) and at meso level (the identification of dynamically relevant groups). We apply this suite to a particularly relevant case, in which we look for the dynamic organization of a gene regulatory network when it is subject to knock-outs. The approach combines information theory, graph analysis, and an iterated sieving algorithm in order to describe rather complex situations. Its application allowed to derive some general observations on the dynamical organization of gene regulatory networks, and to observe interesting characteristics in an experimental case


2021 - Asymptotic Information-Theoretic Detection of Dynamical Organization in Complex Systems [Articolo su rivista]
D'Addese, Gianluca; Sani, Laura; La Rocca, Luca; Serra, Roberto; Villani, Marco
abstract

The identification of emergent structures in complex dynamical systems is a formidable challenge. We propose a computationally efficient methodology to address such a challenge, based on modeling the state of the system as a set of random variables. Specifically, we present a sieving algorithm to navigate the huge space of all subsets of variables and compare them in terms of a simple index that can be computed without resorting to simulations. We obtain such a simple index by studying the asymptotic distribution of an information-theoretic measure of coordination among variables, when there is no coordination at all, which allows us to fairly compare subsets of variables having different cardinalities. We show that increasing the number of observations allows the identification of larger and larger subsets. As an example of relevant application, we make use of a paradigmatic case regarding the identification of groups in autocatalytic sets of reactions, a chemical situation related to the origin of life problem.


2021 - Dynamical properties and path dependence in a gene-network model of cell differentiation [Articolo su rivista]
Braccini, M.; Roli, A.; Villani, M.; Serra, R.
abstract

In this work, we explore the properties of a control mechanism exerted on random Boolean networks that takes inspiration from the methylation mechanisms in cell differentiation and consists in progressively freezing (i.e. clamping to 0) some nodes of the network. We study the main dynamical properties of this mechanism both theoretically and in simulation. In particular, we show that when applied to random Boolean networks, it makes it possible to attain dynamics and path dependence typical of biological cells undergoing differentiation.


2020 - Avalanches of perturbations in modular gene regulatory networks [Capitolo/Saggio]
Vezzani, A.; Villani, M.; Serra, R.
abstract

A well-known hypothesis, with far-reaching implications, is that biological evolution should preferentially lead to critical dynamic regimes. Useful information about the dynamical regime of gene regulatory networks can be obtained by studying their responses to small perturbations. The interpretation of these data requires the use of suitable models, where it is usually assumed that the system is homogeneous. On the other hand, it is widely acknowledged that biological networks display some degree of modularity, so it is interesting to ascertain how modularity can affect the estimation of their dynamical properties. In this study we introduce a well-defined degree of modularity and we study how it influences the network dynamics. In particular, we show how the estimate of the Derrida parameter from “avalanche” data may be affected by strong modularity.


2020 - Evolving always‐critical networks [Articolo su rivista]
Villani, M.; Magri, S.; Roli, A.; Serra, R.
abstract

Living beings share several common features at the molecular level, but there are very few large‐scale “operating principles” which hold for all (or almost all) organisms. However, biology is subject to a deluge of data, and as such, general concepts such as this would be extremely valuable. One interesting candidate is the “criticality” principle, which claims that biological evolution favors those dynamical regimes that are intermediaries between ordered and disordered states (i.e., “at the edge of chaos”). The reasons why this should be the case and experimental evidence are briefly discussed, observing that gene regulatory networks are indeed often found on, or close to, the critical boundaries. Therefore, assuming that criticality provides an edge, it is important to ascertain whether systems that are critical can further evolve while remaining critical. In order to explore the possibility of achieving such “always‐critical” evolution, we resort to simulated evolution, by suitably modifying a genetic algorithm in such a way that the newly‐generated individuals are constrained to be critical. It is then shown that these modified genetic algorithms can actually develop critical gene regulatory networks with two interesting (and quite different) features of biological significance, involving, in one case, the average gene activation values and, in the other case, the response to perturbations. These two cases suggest that it is often possible to evolve networks with interesting properties without losing the advantages of criticality. The evolved networks also show some interesting features which are discussed.


2020 - Exploring the Dynamic Organization of Random and Evolved Boolean Networks [Articolo su rivista]
d’Addese, Gianluca; Magrì, Salvatore; Serra, Roberto; Villani, Marco
abstract

The properties of most systems composed of many interacting elements are neither determined by the topology of the interaction network alone, nor by the dynamical laws in isolation. Rather, they are the outcome of the interplay between topology and dynamics. In this paper, we consider four different types of systems with critical dynamic regime and with increasingly complex dynamical organization (loosely defined as the emergent property of the interactions between topology and dynamics) and analyze them from a structural and dynamic point of view. A first noteworthy result, previously hypothesized but never quantified so far, is that the topology per se induces a notable increase in dynamic organization. A second observation is that evolution does not change dramatically the size distribution of the present dynamic groups, so it seems that it keeps track of the already present organization induced by the topology. Finally, and similarly to what happens in other applications of evolutionary algorithms, the types of dynamic changes strongly depend upon the used fitness functio


2020 - Selecting for positive responses to knock outs in boolean networks [Capitolo/Saggio]
Villani, M.; Magri, S.; Roli, A.; Serra, R.
abstract

Random Boolean networks are a widely acknowledged model for cell dynamics. Previous studies have shown the possibility of achieving Boolean Networks (BN) with given characteristics by means of evolutionary techniques. In this work we show that it is possible to evolve BNs exhibiting more positive than negative reactions to knock-out stresses. It is also interesting to observe that in the observed runs (i) the evolutionary processes can guide the BNs toward different dynamic regimes, depending on their internal structure and that (ii) the BNs forced to evolve by maintaining a critical dynamical regime achieve better results than those that do not have this characteristic; this observation supports the idea that criticality may be beneficial to an evolving population of dynamical systems.


2020 - The effects of a simplified model of chromatin dynamics on attractors robustness in random boolean networks with self-loops: An experimental study [Capitolo/Saggio]
Braccini, M.; Roli, A.; Villani, M.; Montagna, S.; Serra, R.
abstract

Boolean networks are currently acknowledged as a powerful model for cell dynamics phenomena. Recently, the possibility of modelling methylation mechanisms—involved in cell differentiation—in Random Boolean Networks have been discussed: methylated genes are represented in the network as nodes locked to value 0 (frozen nodes). Preliminary results show that this mechanism can reproduce dynamics with characteristics in agreement with those of cell undergoing differentiation. In a second, parallel work, the effect of nodes with self-loops in Random Boolean Networks has been studied, showing that the average number of attractors may increase with the number of self-loops, whilst the average attractor robustness tends to decrease. As these two studies are aimed at extending the applicability of Random Boolean Networks to model cell differentiation phenomena, in this work we study the combined effect of the previous two approaches. Results in simulation show that frozen nodes tend to partially dampen the effects of self-loops on attractor number and robustness. This outcome suggests that both the variants can indeed be effectively combined in Boolean models for cell differentiation.


2019 - A View of Criticality in the Ising Model Through the Relevance Index [Capitolo/Saggio]
Roli, Andrea; Villani, Marco; Serra, Roberto
abstract

The Relevance Index has been introduced to detect key features of the organization of complex dynamical systems. It is based upon Shannon entropies and can be used to identify groups of variables that change in a coordinated fashion, while they are less integrated with the rest of the system. In previous work, we have shown that the average Relevance Index attains its maximum at the phase transition in both Ising model and random Boolean networks. In this contribution we present a further study on the Ising model, showing that the relevance index is maximized for large groups of variables at criticality. These results provide further evidence to the hypothesis that this index is a powerful measure for capturing criticality.


2019 - A simplified model of chromatin dynamics drives differentiation process in Boolean models of GRN [Relazione in Atti di Convegno]
Braccini, Michele; Roli, Andrea; Villani, Marco; Montagna, Sara; Serra, Roberto
abstract

Cellular types of multicellular organisms are the stable results of complex intertwined processes that occur in biological cells. Among the many others, chromatin dynamics significantly contributes—by modulating access to genes—to differential gene expression, and ultimately to determine cell types. Here, we propose a dynamical model of differentiation based on a simplified bio-inspired methylation mechanism in Boolean models of GRNs. Preliminary results show that, as the number of methylated nodes increases, there is a decrease in attractor number and networks tend to assume dynamical behaviours typical of ordered ensembles. At the same time, results show that this mechanism does not affect the possibility of generating path dependent differentiation: cell types determined by the specific sequence of methylated genes.


2019 - An improved relevance index method to search important structures in complex systems [Relazione in Atti di Convegno]
Sani, L.; Bononi, A.; Pecori, R.; Amoretti, M.; Mordonini, M.; Roli, A.; Villani, M.; Cagnoni, S.; Serra, R.
abstract

We present an improvement of a method that aims at detecting important dynamical structures in complex systems, by identifying subsets of elements that show tight and coordinated interactions among themselves, while interplaying much more loosely with the rest of the system. Such subsets are estimated by means of a Relevance Index (RI), which is normalized with respect to a homogeneous system, usually described by independent Gaussian variables, as a reference. The strategy presented herein improves the way the homogeneous system is conceived from a theoretical viewpoint. Firstly, we consider the system components as dependent and with equal pairwise correlations, which implies a non-diagonal correlation matrix of the homogeneous system. Then, we generate the components of the homogeneous system according to a multivariate Bernoulli distribution, by exploiting the NORTA method, which is able to create samples of a desired random vector, given its marginal distributions and its correlation matrix. The proposed improvement on the RI method has been applied to three different case studies, obtaining better results compared with the traditional method based on the homogeneous system with independent Gaussian variables.


2019 - Evolving critical boolean networks [Relazione in Atti di Convegno]
Magri, S.; Villani, M.; Roli, A.; Serra, R.
abstract

Random Boolean networks are a widely acknowledged model for cell dynamics. Previous studies have shown the possibility of achieving Boolean networks with given characteristics by means of evolutionary techniques. In this work we make a further step towards more biologically plausible models by aiming at evolving networks with a given fraction of active nodes along the attractors, while constraining the evolutionary process to move across critical networks. Results show that this path along criticality does not impede to climb the mount of improbable, yet biologically realistic requirements.


2019 - Sustainable growth and synchronization in protocell models [Articolo su rivista]
Serra, R.; Villani, M.
abstract

The growth of a population of protocells requires that the two key processes of replication of the protogenetic material and reproduction of the whole protocell take place at the same rate. While in many ODE-based models such synchronization spontaneously develops, this does not happen in the important case of quadratic growth terms. Here we show that spontaneous synchronization can be recovered (i) by requiring that the transmembrane diffusion of precursors takes place at a finite rate, or (ii) by introducing a finite lifetime of the molecular complexes. We then consider reaction networks that grow by the addition of newly synthesized chemicals in a binary polymer model, and analyze their behaviors in growing and dividing protocells, thereby confirming the importance of (i) and (ii) for synchronization. We describe some interesting phenomena (like long-term oscillations of duplication times) and show that the presence of food-generated autocatalytic cycles is not sufficient to guarantee synchronization: in the case of cycles with a complex structure, it is often observed that only some subcycles survive and synchronize, while others die out. This shows the importance of truly dynamic models that can uncover effects that cannot be detected by static graph theoretical analyses.


2018 - A comparison between threshold ergodic sets and stochastic simulation of boolean networks for modelling cell differentiation [Relazione in Atti di Convegno]
Braccini, Michele; Roli, Andrea; Villani, Marco; Serra, Roberto
abstract

Recently a cell differentiation model based on noisy random Boolean networks has been proposed. This mathematical model is able to describe in an elegant way the most relevant features of cell differentiation. Noise plays a key role in this model; the different stages of the differentiation process are emergent dynamical configurations deriving from the control of the intracellular noise level. In this work we compare two approaches to this cell differentiation framework: the first one (already present in the literature) is focused on a network analysis representing the average wandering of the system among its attractors, whereas the second (new) approach takes into consideration the dynamical stories of thousands of individual cells. Results showed that under a particular noise condition the two approaches produce comparable results. Therefore both can be used to model the cell differentiation process in an integrative and complementary manner.


2018 - A relevance index method to infer global properties of biological networks [Relazione in Atti di Convegno]
Villani, Marco; Sani, Laura; Amoretti, Michele; Vicari, Emilio; Pecori, Riccardo; Mordonini, Monica; Cagnoni, Stefano; Serra, Roberto
abstract

Many complex systems, both natural and artificial, may be represented by networks of interacting nodes. Nevertheless, it is often difficult to find meaningful correspondences between the dynamics expressed by these systems and the topological description of their networks. In contrast, many of these systems may be well described in terms of coordinated behavior of their dynamically relevant parts. In this paper we use the recently proposed Relevance Index approach, based on information-theoretic measures. Starting from the observation of the dynamical states of any system, the Relevance Index is able to provide information about its organization. Moreover, we show how the application of the proposed approach leads to novel and effective interpretations in the T helper network case study.


2018 - An iterative information-theoretic approach to the detection of structures in complex systems [Articolo su rivista]
Villani, Marco; Sani, Laura; Pecori, Riccardo; Amoretti, Michele; Roli, Andrea; Mordonini, Monica; Serra, Roberto; Cagnoni, Stefano
abstract

Systems that exhibit complex behaviours often contain inherent dynamical structures which evolve over time in a coordinated way. In this paper, we present a methodology based on the Relevance Index method aimed at revealing the dynamical structures hidden in complex systems. The method iterates two basic steps: detection of relevant variable sets based on the computation of the Relevance Index, and application of a sieving algorithm, which refines the results. This approach is able to highlight the organization of a complex system into sets of variables, which interact with one another at different hierarchical levels, detected, in turn, in the different iterations of the sieve. The method can be applied directly to systems composed of a small number of variables, whereas it requires the help of a custom metaheuristic in case of systems with larger dimensions. We have evaluated the potential of the method by applying it to three case studies: synthetic data generated by a nonlinear stochastic dynamical system, a small-sized and well-known system modelling a catalytic reaction, and a larger one, which describes the interactions within a social community, that requires the use of the metaheuristic. The experiments we made to validate the method produced interesting results, effectively uncovering hidden details of the systems to which it was applied.


2018 - Dynamical Criticality in Gene Regulatory Networks [Articolo su rivista]
Villani, Marco; La Rocca, Luca; Kauffman, Stuart Alan; Serra, Roberto
abstract

A well-known hypothesis, with far-reaching implications, is that biological evolution should preferentially lead to states that are dynamically critical. In previous papers, we showed that a well-known model of genetic regulatory networks, namely, that of random Boolean networks, allows one to study in depth the relationship between the dynamical regime of a living being's gene network and its response to permanent perturbations. In this paper, we analyze a huge set of new experimental data on single gene knockouts in S. cerevisiae, laying down a statistical framework to determine its dynamical regime. We find that the S. cerevisiae network appears to be slightly ordered, but close to the critical region. Since our analysis relies on dichotomizing continuous data, we carefully consider the issue of an optimal threshold choice.


2018 - Dynamical criticality: overview and open questions [Articolo su rivista]
Roli, Andrea; Villani, Marco; Filisetti, Alessandro; Serra, Roberto
abstract

Systems that exhibit complex behaviours are often found in a particular dynamical condition, poised between order and disorder. This observation is at the core of the so-called criticality hypothesis, which states that systems in a dynamical regime between order and disorder attain the highest level of computational capabilities and achieve an optimal trade-off between robustness and flexibility. Recent results in cellular and evolutionary biology, neuroscience and computer science have revitalised the interest in the criticality hypothesis, emphasising its role as a viable candidate general law in adaptive complex systems. This paper provides an overview of the works on dynamical criticality that are - to the best of our knowledge - particularly relevant for the criticality hypothesis. The authors review the main contributions concerning dynamics and information processing at the edge of chaos, and illustrate the main achievements in the study of critical dynamics in biological systems. Finally, the authors discuss open questions and propose an agenda for future work.


2018 - Dynamical properties of a gene-protein model [Relazione in Atti di Convegno]
Sapienza, Davide; Villani, Marco; Serra, Roberto
abstract

A major limitation of the classical random Boolean network model of gene regulatory networks is its synchronous updating, which implies that all the proteins decay at the same rate. Here a model is discussed, where the network is composed of two different sets of nodes, labelled G and P with reference to “genes” and “proteins”. Each gene corresponds to a protein (the one it codes for), while several proteins can simultaneously affect the expression of a gene. Both kinds of nodes take Boolean values. If we look at the genes only, it is like adding some memory terms, so the new state of the gene subnetwork network does no longer depend upon its previous state only. In general, these terms tend to make the dynamics of the network more ordered than that of the corresponding memoryless network. The analysis is focused here mostly on dynamical critical states. It has been shown elsewhere that the usual way of computing the Derrida parameter, starting from purely random initial conditions, can be misleading in strongly non-ergodic systems. So here the effects of perturbations on both genes’ and proteins’ levels is analysed, using both the canonical Derrida procedure and an “extended” one. The results are discussed. Moreover, the stability of attractors is also analysed, measured by counting the fraction of perturbations where the system eventually falls back onto the initial attractor.


2018 - Simulating populations of protocells with uneven division [Relazione in Atti di Convegno]
Musa, Martina; Villani, Marco; Serra, Roberto
abstract

Protocells should be similar to present-day biological cells, but much simpler. They are believed to have played a key role in the origin of life, and they may also be the basis of a new technology with tremendous opportunities. In this work we study the effect of uneven division processes on the synchronization of the duplication rates of protocells’ membrane and internal materials.


2017 - Automatic design of boolean networks for cell differentiation [Relazione in Atti di Convegno]
Braccini, Michele; Roli, Andrea; Villani, Marco; Serra, Roberto
abstract

Cell differentiation is the process that denotes a cell type change, typically from a less specialised type to a more specialised one. Recently, a cell differentiation model based on Boolean networks subject to noise has been proposed. This model reproduces the main abstract properties of cell differentiation, such as the attainment of different degrees of differentiation, deterministic and stochastic differentiation, reversibility, induced pluripotency and cell type change. The generic abstract properties of the model have been already shown to match those of the real biological phenomenon. A direct comparison with specific cell differentiation processes and the identification of genetic network features that are linked to specific differentiation traits requires the design of a suitable Boolean network such that its dynamics matches a set of target properties. To the best of our knowledge, the only current method for addressing this problem is a random generate and test procedure. In this work we present an automatic design method for this purpose, based on metaheuristic algorithms. We devised two variants of the method and tested them against random search on typical abstract differentiation trees. Results, although preliminary, show that our technique is far more efficient than both random search and complete enumeration and it is able to find solutions to instances which were not solved by those techniques.


2017 - Dynamical regimes in non-ergodic random Boolean networks [Articolo su rivista]
Villani, Marco; Campioli, Davide; Damiani, Chiara; Roli, Andrea; Filisetti, Alessandro; Serra, Roberto
abstract

Random boolean networks are a model of genetic regulatory networks that has proven able to describe experimental data in biology. Random boolean networks not only reproduce important phenomena in cell dynamics, but they are also extremely interesting from a theoretical viewpoint, since it is possible to tune their asymptotic behaviour from order to disorder. The usual approach characterizes network families as a whole, either by means of static or dynamic measures. We show here that a more detailed study, based on the properties of system’s attractors, can provide information that makes it possible to predict with higher precision important properties, such as system’s response to gene knock-out. A new set of principled measures is introduced, that explains some puzzling behaviours of these networks. These results are not limited to random Boolean network models, but they are general and hold for any discrete model exhibiting similar dynamical characteristics.


2017 - GPU-based parallel search of relevant variable sets in complex systems [Relazione in Atti di Convegno]
Vicari, Emilio; Amoretti, Michele; Sani, Laura; Mordonini, Monica; Pecori, Riccardo; Roli, Andrea; Villani, Marco; Cagnoni, Stefano; Serra, Roberto
abstract

Various methods have been proposed to identify emergent dynamical structures in complex systems. In this paper, we focus on the Dynamical Cluster Index (DCI), a measure based on information theory which allows one to detect relevant sets, i.e. sets of variables that behave in a coherent and coordinated way while loosely interacting with the rest of the system. The method associates a score to each subset of system variables; therefore, for a thorough analysis of the system, it requires an exhaustive enumeration of all possible subsets. For large systems, the curse of dimensionality makes the problem solvable only using metaheuristics. Even within such approaches, however, DCI computation has to be performed for a huge number of times; thus, an efficient implementation becomes a mandatory requirement. Considering that a candidate relevant set’s DCI can be computed independently of the others, we propose a GPU-based massively parallel implementation of DCI computation. We describe the algorithm’s structure and validate it by assessing the speedup in comparison with a single-thread sequential CPU implementation when analyzing a set of dynamical systems of different sizes.


2017 - Identifying Critical States through the Relevance Index [Articolo su rivista]
Roli, Andrea; Villani, Marco; Caprari, Riccardo; Serra, Roberto
abstract

The identification of critical states is a major task in complex systems, and the availability of measures to detect such conditions is of utmost importance. In general, criticality refers to the existence of two qualitatively different behaviors that the same system can exhibit, depending on the values of some parameters. In this paper, we show that the relevance index may be effectively used to identify critical states in complex systems. The relevance index was originally developed to identify relevant sets of variables in dynamical systems, but in this paper, we show that it is also able to capture features of criticality. The index is applied to two prominent examples showing slightly different meanings of criticality, namely the Ising model and random Boolean networks. Results show that this index is maximized at critical states and is robust with respect to system size and sampling effort. It can therefore be used to detect criticality.


2017 - Locating critical regions by the Relevance Index [Relazione in Atti di Convegno]
Roli, Andrea; Villani, Marco; Serra, Roberto
abstract

The detection of critical states is a task of utmost importance in complex systems; to this aim, measures to identify such conditions are required. In general, the term criticality concerns the existence of two qualitatively different behaviours that a system can exhibit, which depends on some parameter values. In this short communication, we summarise our recent findings on the use of the Relevance Index to identify critical states in complex systems. Although the Relevance Index method was originally developed to identify relevant sets of variables in dynamical systems, we show that it is also able to detect features of criticality. The index is applied to two notable examples showing slightly different meanings of criticality, namely, the Ising model and Random Boolean Networks. Results show that this index is maximised at critical states and is robust with respect to system size and sampling effort.


2017 - Modelling Protocells [Monografia/Trattato scientifico]
Serra, Roberto; Villani, Marco
abstract

The monograph discusses models of synthetic protocells, which are cell-like structures obtained from non-living matter endowed with some rudimentary kind of metabolism and genetics, but much simpler than biological cells. They should grow and proliferate, generating offsprings that resemble in some way the parent protocells with some variation, so that selection may take place. Sustainable protocell populations have not yet been obtained experimentally and mathematical models are therefore extremely important to address key questions concerning their synthesis and behavior. Different protocell “architectures” have been proposed and high-level abstract models like those that are presented in this book are particularly relevant to gain a better understanding of the different properites. These models are able to treat all the major dynamical phenomena in a unified framework, so they can be seen as “virtual laboratories” for protocell research. Particular attention is paid to the problem of synchronization of the fission rate of the whole protocell and the duplication rate of its "protogenetic" material, which is shown to be an emergent property that spontaneously develops in successive generations. The book is of interest for a broad range of scientists working in soft matter physics, chemistry and biology, interested in the role protocells may play on the development of new technologies with medical, environmental and industrial applications as well as scientists interested in the origin of life.


2017 - New paths for the application of DCI in social sciences: Theoretical issues regarding an empirical analysis [Relazione in Atti di Convegno]
Righi, Riccardo; Roli, Andrea; Russo, Margherita; Serra, Roberto; Villani, Marco
abstract

Starting from the conceptualization of ‘Cluster Index’ (CI), Villani et al. [16, 17] implemented the ‘Dynamic Cluster Index’ (DCI), an algorithm to perform the detection of subsets of agents characterized by patterns of activity that can be considered as integrated over time. DCI methodology makes possible to shift the attention into a new dimension of groups of agents (i.e. communities of agents): the presence of a common function characterizing their actions. In this paper we discuss the implications of the use in the domain of social sciences of this methodology, up to now mainly applied in natural sciences. Developing our considerations thanks to an empirical analysis, we discuss the theoretical implications of its application in such a different field.


2017 - Synchronization in near-membrane reaction models of protocells [Relazione in Atti di Convegno]
Calvanese, Giordano; Villani, Marco; Serra, Roberto
abstract

In this paper a new model of growing and dividing protocells is described, whose main features are (i) an autocatalytic set of “genetic memory molecules” (GMMs) whose reactions happen in a thin aqueous phase shell near the membrane and (ii) a lipid container that grows according to the amphiphilic production stimulated by the GMMs. Synchronization occur when the container growth rate is equal to the GMMs self-replicative one: the behavior of this model is compared with a previous version where reactions occur in the whole internal aqueous volume. Analytical results and simulations has shown that synchronization emerges in both models for the same set of kinetic equations, the main difference being only in the time scale of the process. Moreover the introduction of finite rates in the transmembrane diffusion permits the emergence of synchronization for a significantly wide set of parameters, enough to allow the protocell evolvability (defined as the capability of cumulating novelties, by maintaining the already present capabilities).


2017 - The use of omics-based approaches in regulatory toxicology: An alternative approach to assess the no observed transcriptional effect level [Articolo su rivista]
Quercioli, Daniele; Roli, Andrea; Morandi, Elena; Perdichizzi, Stefania; Polacchini, Laura; Rotondo, Francesca; Vaccari, Monica; Villani, Marco; Serra, Roberto; Colacci, Annamaria
abstract

The evaluation of chemical hazard is based on the identification of the quality and the quantity of adverse effects as a consequence of exposure. The adverse effects that do not involve genetic damage are often related to the chemical dose or concentration. The adverse outcome is the consequence of a row of key events, each targeting a different biological trait. The identification of these key events at molecular and cellular level would provide novel biomarkers of exposure and risk. The application of toxicogenomics approaches to experimental models of chemical exposure allows the detection of gene pathways involved in response to low doses of the chemical as an early endpoint of adversity. The use of toxicogenomics would improve the knowledge on the dose-response relationship, linking the environmental exposure to the effect on the population and allowing a better refinement of the quantitative risk assessment. In this context, the gene modulation data can be used to calculate a No Observed Transcriptional Effect Level (NOTEL).In this paper we present a method for evaluating the NOTEL based on anomaly detection: a classifier is built that discriminates between target class instances, i.e., normal cases, and anomalies, i.e., samples with significant transcriptional effects. The strength of this method is that (i) it can be applied to cases in which few samples are available and the space dimension is high and (ii) it makes use of the complete gene expression profiles.


2016 - Beyond Networks: Search for Relevant Subsets in Complex Systems [Capitolo/Saggio]
Roli, Andrea; Villani, Marco; Filisetti, Alessandro; Serra, Roberto
abstract

Networks are often used to represent the relations among the variables of a dynamical system. The properties of network topology are usually exploited to understand the organization of the system. Nevertheless, the dynamical organization of a system might considerably differ from its topological one. In this paper, we describe a method to identify “relevant subsets” of variables. The variables belonging to a relevant subset should be strongly integrated and should have a much weaker interaction with the other system variables. Extending previous works on neural networks, an information-theoretic measure is introduced, i.e., the Dynamical Cluster Index, in order to identify candidate relevant subsets. The method solely relies on observations of the variables’ values in time


2016 - Dynamically critical systems and power-law distributions: Avalanches revisited [Relazione in Atti di Convegno]
Di Stefano, Marina L.; Villani, Marco; La Rocca, Luca; Kauffman, Stuart A.; Serra, Roberto
abstract

In this paper we show that a well-known model of genetic regulatory networks, namely that of Random Boolean Networks (RBNs), allows one to study in depth the relationship between two important properties of complex systems, i.e. dynamical criticality and power-law distributions. The study is based upon an analysis of the response of a RBN to permanent perturbations, that may lead to avalanches of changes in activation levels, whose statistical properties are determined by the same parameter that characterizes the dynamical state of the network (ordered, critical or disordered). Under suitable approximations, in the case of large sparse random networks an analytical expression for the probability density of avalanches of different sizes is proposed, and it is shown that for not-too-small avalanches of critical systems it may be approximated by a power law. In the case of small networks the above-mentioned formula does not maintain its validity, because of the phenomenon of self-interference of avalanches, which is also explored by numerical simulations.


2016 - Efficient search of relevant structures in complex systems [Relazione in Atti di Convegno]
Sani, Laura; Amoretti, Michele; Vicari, Emilio; Mordonini, Monica; Pecori, Riccardo; Roli, Andrea; Villani, Marco; Cagnoni, Stefano; Serra, Roberto
abstract

In a previous work, Villani et al. introduced a method to identify candidate emergent dynamical structures in complex systems. Such a method detects subsets (clusters) of the system elements which behave in a coherent and coordinated way while loosely interacting with the remainder of the system. Such clusters are assessed in terms of an index that can be associated to each subset, called Dynamical Cluster Index (DCI). When large systems are analyzed, the “curse of dimensionality” makes it impossible to compute the DCI for every possible cluster, even using massively parallel hardware such as GPUs. In this paper, we propose an efficient metaheuristic for searching relevant dynamical structures, which hybridizes an evolutionary algorithm with local search and obtains results comparable to an exhaustive search in a much shorter time. The effectiveness of the method we propose has been evaluated on a set of Boolean models of real-world systems.


2016 - On the dynamics of autocatalytic cycles in protocell models [Relazione in Atti di Convegno]
Villani, Marco; Filisetti, Alessandro; Nadini, Matthieu; Serra, Roberto
abstract

The emergence of autocatalytic sets of molecules seems to have played an important role in the origin of life, allowing a sustainable systems’ growth and reproduction. Several frameworks have been proposed, one of the most recent and promising being that of RAF (Reflexively Autocatalytic-Food generated) sets. As it often happens when topological properties only are taken into account, RAFs are however only potentially able of supporting continuous growth. Dynamics can also play a significant role: it is shown here how dynamical interactions may sometimes lead to unexpected behaviors.


2016 - On the robustness of the detection of relevant sets in complex dynamical systems [Relazione in Atti di Convegno]
Villani, Marco; Carra, Pietro; Roli, Andrea; Filisetti, Alessandro; Serra, Roberto
abstract

The identification of system’s parts that rule its dynamics and the understanding of its dynamical organisation is a paramount objective in the analysis of complex systems. In previous work we have proposed the Dynamical Cluster Index method, which is based on information-theoretical measures. This method makes it possible to identify the components of a complex system that are relevant for its dynamics as well as their relation in terms of information flow. Complex systems’ organisation is often characterised by intertwined components. The detection of such dynamical structures is a prerequisite for inferring the hierarchical organisation of the system. The method relies on a ranking based on a statistical index, which depends on a reference system (the homogeneous system) generated according to a parametrised sampling procedure. In this paper we address the issue of assessing the robustness of the method against the homogeneous system generation model. The results show that the method is robust and can be reliably applied to the analysis of data from complex system dynamics in general settings, without requiring particular hypotheses.


2015 - Dynamical Properties of Artificially Evolved Boolean Network Robots [Relazione in Atti di Convegno]
Roli, Andrea; Villani, Marco; Serra, Roberto; Benedettini, Stefano; Pinciroli, Carlo; Birattari, Mauro
abstract

In this work we investigate the dynamical properties of the Boolean networks (BN) that control a robot performing a composite task. Initially, the robot must perform phototaxis, i.e. move towards a light source located in the environment; upon perceiving a sharp sound, the robot must switch to antiphototaxis, i.e. move away from the light source. The network controlling the robot is subject to an adaptive walk and the process is subdivided in two sequential phases: in the first phase, the learning feedback is an evaluation of the robot’s performance in achieving only phototaxis; in the second phase, the learning feedback is composed of a performance measure accounting for both phototaxis and antiphototaxis. In this way, it is possible to study the properties of the evolution of the robot when its behaviour is adapted to a new operational requirement. We analyse the trajectories followed by the BNs in the state space and find that the best performing BNs (i.e. those able to maintaining the previous learned behaviour while adapting to the new task) are characterised by generalisation capabilities and the emergence of simple behaviours that are dynamically combined to attain the global task. In addition, we also observe a further remarkable property: the complexity of the best performing BNs increases during evolution. This result may provide useful indications for improving the automatic design of robot controllers and it may also help shed light on the relation and interplay among robustness, evolvability and complexity in evolving systems.


2015 - Exploring the organisation of complex systems through the dynamical interactions among their relevant subsets [Relazione in Atti di Convegno]
Filisetti, Alessandro; Villani, Marco; Roli, Andrea; Fiorucci, Marco; Serra, Roberto
abstract

Complex systems often show forms of organisation where a clear-cut hierarchy of levels with a well-defined direction of information flow cannot be found. In this paper we propose an information-theoretic method aimed at identifying the dynamically relevant parts of a system along with their relationships, interpreting in such a way the system’s dynamical organisation. The analysis is quite general and can be applied to many dynamical systems. We show here its application to two relevant biological examples, the case of mammalian cell cycle network and of Mitogen Activated Protein Kinase (MAPK) cascade. The result of our analysis shows that the elements of the mammalian cell cycle network act as a single compact group, whereas the MAPK system can be decomposed into two dynamically distinct parts, with asymmetric information flows


2015 - The Search for Candidate Relevant Subsets of Variables in Complex Systems [Articolo su rivista]
Villani, Marco; Roli, Andrea; Filisetti, Alessandro; Fiorucci, Marco; Serra, Roberto; Poli, Irene
abstract

We describe a method to identify relevant subsets of variables, useful to understand the organization of a dynamical system. The variables belonging to a relevant subset should have a strong integration with the other variables of the same relevant subset, and a much weaker interaction with the other system variables. On this basis, extending previous work on neural networks, an information-theoretic measure, the dynamical cluster index, is introduced in order to identify good candidate relevant subsets. The method does not require any previous knowledge of the relationships among the system variables, but relies on observations of their values over time. We show its usefulness in several application domains, including: (i) random Boolean networks, where the whole network is made of different subnetworks with different topological relationships (independent or interacting subnetworks); (ii) leaderfollower dynamics, subject to noise and fluctuations; (iii) catalytic reaction networks in a flow reactor; (iv) the MAPK signaling pathway in eukaryotes. The validity of the method has been tested in cases where the data are generated by a known dynamical model and the dynamical cluster index is applied in order to uncover significant aspects of its organization; however, it is important that it can also be applied to time series coming from field data without any reference to a model. Given that it is based on relative frequencies of sets of values, the method could be applied also to cases where the data are not ordered in time. Several indications to improve the scope and effectiveness of the dynamical cluster index to analyze the organization of complex systems are finally given.


2014 - A stochastic model of catalytic reaction networks in protocells [Articolo su rivista]
Serra, Roberto; Filisetti, Alessandro; Villani, Marco; Graudenzi, Alex; Damiani, Chiara; Panini, Tommaso
abstract

Protocells are supposed to have played a key role in the self-organizing processes leading to the emergence of life. Existing models either (i) describe protocell architecture and dynamics, given the existence of sets of collectively self-replicating molecules for granted, or (ii) describe the emergence of the aforementioned sets from an ensemble of random molecules in a simple experimental setting (e.g. a closed system or a steady-state flow reactor) that does not properly describe a protocell. In this paper we present a model that goes beyond these limitations by describing the dynamics of sets of replicating molecules within a lipid vesicle. We adopt the simplest possible protocell architecture, by considering a semi-permeable membrane that selects the molecular types that are allowed to enter or exit the protocell and by assuming that the reactions take place in the aqueous phase in the internal compartment. As a first approximation, we ignore the protocell growth and division dynamics. The behavior of catalytic reaction networks is then simulated by means of a stochastic model that accounts for the creation and the extinction of species and reactions. While this is not yet an exhaustive protocell model, it already provides clues regarding some processes that are relevant for understanding the conditions that can enable a population of protocells to undergo evolution and selection.


2014 - Attractors Perturbations in Biological Modelling: Avalanches and Cellular Differentiation [Capitolo/Saggio]
Villani, Marco; Serra, Roberto
abstract

We describe here and discuss in detail the model of random Boolean networks (RBNs). Although these models have been widely studied, they still present some unexpected mathematical features, and we discuss in particular their stability properties, introducing and commenting a new measure (attractor sensitivity) that seems particularly relevant for their application to the dynamics of gene regulatory networks. We also review some results that show that RBNs can properly account for data on perturbations induced by gene knock-out in real organisms. Moreover, we show that this comparison between model and data also sheds light on the important hypothesis that living beings tend to live in, or close to, critical states. Last but not least, we show that adding noise to RBNs can lead to a nice model of cell differentiation


2014 - Automatic Design of Boolean Networks for Modelling Cell Differentiation [Capitolo/Saggio]
Stefano, Benedettini; Andrea, Roli; Serra, Roberto; Villani, Marco
abstract

A mathematical model based on Random Boolean Networks (RBNs) has been recently proposed to describe the main features of cell differentiation. The model captures in a unique framework all the main phenomena involved in cell differentiation and can be subject to experimental testing. A prominent role in the model is played by cellular noise, which somehow controls the cell ontogenetic process from the stem, totipotent state to the mature, completely differentiated one. Noise is high in stem cells and decreases while the cell undergoes the differentiation process. A limitation of the current mathematical model is that RBNs, as an ensemble, are not endowed with the property of showing a smooth relation between noise level and the differentiation stages of cells. In this work, we show that it is possible to generate an ensemble of Boolean networks (BNs) that can satisfy such a requirement, while keeping the other main relevant statistical features of classical RBNs. This ensemble is designed by means of an optimisation process, in which a stochastic local search (SLS) optimises an objective function which accounts for the requirements the network ensemble has to fulfil.


2014 - Growth and division in a dynamic protocell model [Articolo su rivista]
Villani, Marco; Filisetti, Alessandro; Graudenzi, Alex; Damiani, Chiara; Carletti, Timoteo; Serra, Roberto
abstract

In this paper a new model of growing and dividing protocells is described, whose main features are (i) a lipid container that grows according to the composition of the molecular milieu (ii) a set of "genetic memory molecules" (GMMs) that undergo catalytic reactions in the internal aqueous phase and (iii) a set of stochastic kinetic equations for the GMMs. The mass exchange between the external environment and the internal phase is described by simulating a semipermeable membrane and a flow driven by the differences in chemical potentials, thereby avoiding to resort to sometimes misleading simplifications, e.g., that of a flow reactor. Under simple assumptions, it is shown that synchronization takes place between the rate of replication of the GMMs and that of the container, provided that the set of reactions hosts a so-called RAF (Reflexive Autocatalytic, Food-generated) set whose influence on synchronization is hereafter discussed. It is also shown that a slight modification of the basic model that takes into account a rate-limiting term, makes possible the growth of novelties, allowing in such a way suitable evolution: so the model represents an effective basis for understanding the main abstract properties of populations of protocells.


2014 - Identifying emergent dynamical structures in network models [Relazione in Atti di Convegno]
Villani, Marco; Stefano, Benedettini; Andrea, Roli; Lane, David Avra; Irene, Poli; Serra, Roberto
abstract

The identification of emergent structures in dynamical systems is a major challenge in complex systems science. In particular, the formation of intermediate-level dynamical structures is of particular interest for what concerns biological as well as artificial network models. In this work, we present a new technique aimed at identifying clusters of nodes in a network that behave in a coherent and coordinated way and that loosely interact with the remainder of the system. This method is based on an extension of a measure introduced for detecting clusters in biological neural networks. Even if our results are still preliminary, we have evidence for showing that our approach is able to identify these “emerging things” in some artificial network models and that it is way more powerful than usual measures based on statistical correlation. This method will make it possible to identify mesolevel dynamical structures in network models in general, from biological to social networks


2014 - Investigating the Role of Network Topology and Dynamical Regimes on the Dynamics of a Cell Differentiation Model [Relazione in Atti di Convegno]
Graudenzi, Alex; Damiani, Chiara; Paroni, Andrea; Filisetti, Alessandro; Villani, Marco; Serra, Roberto; Antoniotti, Marco
abstract

The characterization of the generic properties underlying the complex interplay ruling cell differentiation is one of the goals of modern biology. To this end, we rely on a powerful and general dynamical model of cell differentiation, which defines differentiation hierarchies on the basis of the stability of gene activation patterns against biological noise. In particular, in this work we investigate the role of the topology (i.e. scale-free or random) and of the dynamical regime (i.e. ordered, critical or disordered) of gene regulatory networks on the model dynamics. Two real lineage commitment trees, i.e. intestinal crypts and hematopoietic cells, are compared with the hierarchies emerging from the dynamics of ensembles of randomly simulated networks. Briefly, critical networks with random topology seem to display a wider range of possible behaviours as compared to the others, hence suggesting an intrinsic dynamical heterogeneity that may be fundamental in defining different differentiation trees. Conversely, scale-free networks show a generally more ordered dynamics, which limit the overall variability, yet containing the effect of possible genomic perturbations. Interestingly, a considerable number of networks across all types show emergent trees that are biologically plausible, suggesting that a relatively wide portion of the networks space may be suitable, without the need for a fine tuning of the parameters


2014 - On RAF Sets and Autocatalytic Cycles in Random Reaction Networks [Relazione in Atti di Convegno]
Filisetti, Alessandro; Villani, Marco; Damiani, Chiara; Graudenzi, Alex; Roli, Andrea; Hordijk, Wim; Serra, Roberto
abstract

The emergence of autocatalytic sets of molecules seems to have played an important role in the origin of life context. Although the possibility to reproduce this emergence in laboratory has received considerable attention, this is still far from being achieved. In order to unravel some key properties enabling the emergence of structures potentially able to sustain their own existence and growth, in this work we investigate the probability to observe them in ensembles of random catalytic reaction networks characterized by different structural properties. From the point of view of network topology, an autocatalytic set have been defined either in term of strongly connected components (SCCs) or as re exively autocatalytic and food-generated sets (RAFs). We observe that the average level of catalysis differently affects the probability to observe a SCC or a RAF, highlighting the existence of a region where the former can be observed, whereas the latter cannot. This parameter also affects the composition of the RAF, which can be further characterized into linear structures, autocatalysis or SCCs. Interestingly, we show that the different network topology (uniform as opposed to power-law catalysis systems) does not have a significantly divergent impact on SCCs and RAFs appearance, whereas the proportion between cleavages and condensations seems instead to play a role. A major factor that limits the probability of RAF appearance and that may explain some of the diffculties encountered in laboratory seems to be the presence of molecules which can accumulate without being substrate or catalyst of any reaction.


2014 - On Some Properties of Information Theoretical Measures for the Study of Complex Systems [Relazione in Atti di Convegno]
Filisetti, Alessandro; Villani, Marco; Roli, Andrea; Fiorucci, Marco; Poli, Irene; Serra, Roberto
abstract

The identification of emergent structures in dynamical sys- tems is a major challenge in complex systems science. In particular, the formation of intermediate-level dynamical structures is of particular in- terest for what concerns biological as well as artificial systems. In this work, we present a set of measures aimed at identifying groups of ele- ments that behave in a coherent and coordinated way and that loosely interact with the rest of the system (the so-called \relevant sets"). These measures are based on Shannon entropy, and they are an extension of a measure introduced for detecting clusters in biological neural networks. Even if our results are still preliminary, we have evidence for showing that our approach is able to identify and partially characterise the rele- vant sets in some artificial systems, and that this way is more powerful than usual measures based on statistical correlation. In this work, the two measures that contribute to the cluster index, previously adopted in the analysis of neural networks, i.e. integration and mutual information, are analysed separately in order to enhance the overall performance of the so-called dynamical cluster index. Although this latter variable al- ready provides useful information about highly integrated subsystems, the analysis of the different parts of the index are extremely useful to better characterise the nature of the sub-systems.


2013 - A model of protocell based on the introduction of a semi-permeable membrane in a stochastic model of catalytic reaction networks [Abstract in Rivista]
Serra, Roberto; Alessandro, Filisetti; Alex, Graudenzi; Chiara, Damiani; Villani, Marco
abstract

The theoretical characterization of the self-organizing molecular structures emerging from ensembles of distinct interacting chemicals turns to be very important in revealing those dynamics that led to the transition from the non-living to the living matter as well as in the design of artificial protocells. In this work we aim at studying the role of a semi-permeable membrane, i.e. a very simple protocell description, in the dynamics of a stochastic model describing randomly generated catalytic reaction sets (CRSs) of molecules


2013 - Dynamical regimes and learning properties of evolved Boolean networks [Articolo su rivista]
Stefano, Benedettini; Villani, Marco; Andrea, Roli; Serra, Roberto; Mattia, Manfroni; Antonio, Gagliardi; Carlo, Pinciroli; Mauro, Birattari
abstract

Boolean networks (BNs) have been mainly considered as genetic regulatory network modelsand are the subject of notable works in complex systems biology literature. Nevertheless, in spite oftheir similarities with neural networks, their potential as learning systems has not yet been fullyinvestigated and exploited.In this work, we show that by employing metaheuristic methods we can train BNs to deal with to twonotable tasks, namely, the problem of controlling the BN's trajectory to match a set of requirementsand the Density Classification Problem. These tasks represent two important categories of problems inmachine learning. The former is an example of the problems in which a dynamical system has to bedesigned such that its dynamics satisfies given requirements. The latter one is a representative task inclassification.We also analyse the performance of the optimisation techniques as a function of the characteristics ofthe networks and the objective function and we show that the learning process could influence and beinfluenced by the BNs' dynamical condition.


2013 - Emergent properties of gene regulatory networks - models and data [Capitolo/Saggio]
Serra, Roberto; Villani, Marco
abstract

We emphasize here the importance of generic models of biological systems that aim at describing the features that are common to a wide class of systems, instead of studying in detail a specific subsystem in a specific cell type or organism. Among generic models of gene regulatory networks, Random Boolean networks (RBNs) are reviewed in depth, and it is shown that they can accurately describe some important experimental data, in particular the statistical properties of the perturbations of gene expression levels induced by the knock-out of a single gene. It is also shown that this kind of study may shed light on a candidate general dynamical property of biological systems. Several biologically plausible modifications of the original model are reviewed and discussed, and it is also show how RBNs can be applied to describe cell differentiation


2013 - Identification of Dynamical Structures in Artificial Brains: An Analysis of Boolean Network Controlled Robots [Relazione in Atti di Convegno]
Andrea, Roli; Villani, Marco; Serra, Roberto; Lorenzo, Garattoni; Carlo, Pinciroli; Mauro, Birattari
abstract

Automatic techniques for the design of artificial computational systems, such as control programs for robots, are currently achieving increasing attention within the AI community. A prominent case is the design of artificial neural network systems by means of search techniques, such as genetic algorithms. Frequently, the search calibrates not only the system parameters, but also its structure. This procedure has the advantage of reducing the bias introduced by the designer and makes it possible to explore new, innovative solutions. The drawback, though, is that the analysis of the resulting system might be extremely difficult and limited to few coarse-grained characteristics. In this paper, we consider the case of robots controlled by Boolean networks that are automatically designed by means of a training process based on local search. We propose to analyse these systems by a method that detects mesolevel dynamical structures. These structures are emerging patterns composed of elements that behave in a coherent way and loosely interact with the rest of the system. In general, this method can be used to detect functional clusters and emerging structures in nonlinear discrete dynamical systems. It is based on an extension of the notion of cluster index, which has been previously proposed by Edelman and Tononi to analyse biological neural systems. Our results show that our approach makes it possible to identify the computational core of a Boolean network which controls a robot


2013 - Mechanism for the formation of density gradients through semipermeable membranes [Articolo su rivista]
Serra, Roberto; Villani, Marco
abstract

We describe and theoretically analyze here a phenomenon which can take place in a system with two different compartments, each containing the same chemicals, which undergo reactions on the surface of both sides of the membrane which separates the two compartments, in the case where the membrane permeabilities to the various chemicals are different and diffusion is fast. There are two main reasons of interest for this kind of system. First, if the overall system is isolated, starting from the case where the initial concentrations of the chemicals are the same in the two phases, one observes the formation of a transient concentration difference. This difference eventually vanishes, although it might last for a long time, depending upon the value of the relevant parameters. The second reason of interest is that, in the case of an open system, one can achieve a steady-state value of the concentration of some chemicals in the smaller compartment which is higher than that in the external one. These results may prove important, inter alia, to understand the behavior of lipid vesicles in water, a topic which is important for studies on the origin of life as well as for possible future applications.


2013 - On the dynamical properties of a model of cell differentiation [Articolo su rivista]
Villani, Marco; Serra, Roberto
abstract

One of the major challenges in complex systems biology is that of providing a general theoretical framework to describe the phenomena involved in cell differentiation, i.e., the process whereby stem cells, which can develop into different types, become progressively more specialized. The aim of this study is to briefly review a dynamical model of cell differentiation which is able to cover a broad spectrum of experimentally observed phenomena and to present some novel results.


2013 - Recent developments in research on catalytic reaction networks [Relazione in Atti di Convegno]
Chiara, Damiani; Alessandro, Filisetti; Alex, Graudenzi; Villani, Marco; Serra, Roberto
abstract

Over the last years, analyses performed on a stochastic model of catalytic reaction networks have provided some indications about the reasons why wet-lab experiments hardly ever comply with the phase transition typically predicted by theoretical models with regard to the emergence of collectively self-replicating sets of molecule (also defined as autocatalytic sets, ACSs), a phenomenon that is often observed in nature and that is supposed to have played a major role in the emergence of the primitive forms of life. The model at issue has allowed to reveal that the emerging ACSs are characterized by a general dynamical fragility, which might explain the difficulty to observe them in wet-lab experiments. In this work, the main results of the various analyses are reviewed, with particular regard to the factors able to affect the generic properties of catalytic reactions networks, for what concerns not only the probability of ACSs to be observed, but also the overall activity of the system, in terms of production of new species, reactions and matter.


2013 - The detection of intermediate-level emergent structures and patterns [Relazione in Atti di Convegno]
Villani, Marco; A., Filisetti; S., Benedettini; A., Roli; Lane, David Avra; Serra, Roberto
abstract

Artificial life is largely concerned with systems that exhibit different emergent phenomena; yet, the identification of emergent structures is frequently a difficult challenge. In this paper we introduced a system to identify candidate emergent mesolevel dynamical structures in dynamical networks. This method is based on an extension of a measure introduced for detecting clusters in biological neural networks; its main novelty in comparison to previous application of similar measures is that we used it to consider truly dynamical networks, and not only fluctuations around stable asymptotic states. The identified structures are clusters of elements that behave in a coherent and coordinated way and that loosely interact with the remainder of the system. We have evidence that our approach is able to identify these “emerging things” in some artificial network models and in more complex data coming from catalytic reaction networks and biological gene regulatory systems (A.thaliana). We think that this system could suggest interesting new ways in dealing with artificial and biological systems.


2013 - The role of backward reactions in a stochastic model of catalytic reaction networks [Relazione in Atti di Convegno]
Alessandro, Filisetti; Alex, Graudenzi; Chiara, Damiani; Villani, Marco; Serra, Roberto
abstract

We investigate the role of backward reactions in a stochastic model of catalytic reaction network, with specific regard to the influence on the emergence of autocatalytic sets (ACSs), which are supposed to be one of the pre-requisites in the transition between non-living to living matter. In particular, we analyse the impact that a variation in the kinetic rates of forward and backward reactions may have on the overall dynamics. Significant effects are indeed observed, provided that the intensity of backward reactions is sufficiently high. In spite of an invariant activity of the system in terms of production of new species, as backward reactions are intensified, the emergence of ACSs becomes more likely and an increase in their number, as well as in the proportion of species belonging to them, is observed. Furthermore, ACSs appear to be more robust to fluctuations than in the usual settings with no backward reaction. This outcome may rely not only on the higher average connectivity of the reaction graph, but also on the distinguishing property of backward reactions of recreating the substrates of the corresponding forward reactions.


2012 - Noise-Induced Emergent Hierarchies in a CA Model [Relazione in Atti di Convegno]
Villani, Marco; Serra, Roberto; Stefano, Benedettini; Andrea, Roli; Lane, David Avra
abstract

This paper introduces the notion of noise-induced emergent hierarchies and analyses the influence of the topology of the underlying network on these hierarchies. By developing upon a previous model of cell differentiation based on noisy random Boolean networks, we show that the adoption of a regular topology such that of cellular automata can lead to interesting effects, the most remarkable one being that, ceteris paribus, the resulting hierarchies have a larger number of levels and could therefore describe more “structured” complex systems.


2011 - A Dynamical Model of Cell Differentiation [Relazione in Atti di Convegno]
VILLANI, Marco; A., Barbieri; SERRA, Roberto
abstract

One of the major challenges in complex systems biologyis that of providing a general theoretical framework todescribe the phenomena involved in cell differentiation,i.e. the process whereby stem cells, which can developinto different types, become progressively more specialized.The aim of this work is that of describing a dynamicalmodel of cell differentiation which is able to cover abroad spectrum of experimentally observed phenomena


2011 - A dynamical model of genetic networks for cell differentiation [Articolo su rivista]
Villani, Marco; Barbieri, Alessia; Serra, Roberto
abstract

A mathematical model is proposed which is able to describe the most important features of cell differ- entiation, without requiring specific detailed assumptions concerning the interactions which drive the phenomenon. On the contrary, cell differentiation is described here as an emergent property of a generic model of the underlying gene regulatory network, and it can therefore be applied to a variety of different organisms. The model points to a peculiar role of cellular noise in differentiation and leads to non trivial predictions which could be sub ject to experimental testing. Moreover, a single model proves able to describe several different phenomena observed in various differentiation processes.


2011 - A stochastic model of autocatalytic reaction networks [Articolo su rivista]
Alessandro, Filisetti; Alex, Graudenzi; Serra, Roberto; Villani, Marco; Rudolf M., Füchslin; Norman, Packard; Stuart A., Kauffman; Irene, Poli
abstract

Autocatalytic cycles are rather widespread in nature and in several theoretical models of catalytic reaction networks their emergence is hypothesized to be inevitable when the network is or becomes sufficiently complex. Nevertheless, the emergence of autocatalytic cycles has been never observed in wet laboratory experiments. Here, we present a novel model of catalytic reaction networks with the explicit goal of filling the gap between theoretical predictions and experimental findings. The model is based on previous study of Kauffman, with new features in the introduction of a stochastic algorithm to describe the dynamics and in the possibility to increase the number of elements and reactions according to the dynamical evolution of the system. Furthermore, the introduction of a temporal threshold allows the detection of cycles even in our context of a stochastic model with asynchronous update. In this study, we describe the model and present results concerning the effect on the overall dynamics of varying (a) the average residence time of the elements in the reactor, (b) both the composition of the firing disk and the concentration of the molecules belonging to it, (c) the composition of the incoming flux.


2011 - A stochastic model of the emergence of autocatalytic cycles [Articolo su rivista]
Alessandro, Filisetti; Alex, Graudenzi; Serra, Roberto; Villani, Marco; Davide De, Lucrezia; Rudolf M., Füchslin; Stuart A., Kauffman; Norman, Packard; Irene, Poli
abstract

Autocatalytic cycles are rather common in biological systems and they might have played a major role in the transition from non-living to living systems. Several theoretical models have been proposed to address the experimentalists during the investigation of this issue and most of them describe a phase transition depending upon the level of heterogeneity of the chemical soup. Nevertheless, it is well known that reproducing the emergence of autocatalytic sets in wet laboratories is a hard task. Understanding the rationale at the basis of such a mismatch between theoretical predictions and experimental observations is therefore of fundamental importance.We here introduce a novel stochastic model of catalytic reaction networks, in order to investigate the emergence of autocatalytic cycles, sensibly considering the importance of noise, of small-number effects and the possible growth of the number of different elements in the system.Furthermore, the introduction of a temporal threshold that defines how long a specific reaction is kept in the reaction graph allows to univocally define cycles also within an asynchronous framework.The foremost analyses have been focused on the study of the variation of the composition of the incoming flux. It was possible to show that the activity of the system is enhanced, with particular regard to the emergence of autocatalytic sets, if a larger number of different elements is present in the incoming flux, while the specific length of the species seems to entail minor effects on the overall dynamics.


2011 - Analysis of attractor distances in random boolean networks [Relazione in Atti di Convegno]
Roli, A.; Benedettini, S.; Serra, Roberto; Villani, Marco
abstract

We study the properties of the distance between attractors in RandomBoolean Networks, a prominent model of genetic regulatory networks. We definethree distance measures, upon which attractor distance matrices are constructed andtheir main statistic parameters are computed. The experimental analysis shows thatordered networks have a very clustered set of attractors, while chaotic networks’ attractorsare scattered; critical networks show, instead, a pattern with characteristicsof both ordered and chaotic networks.


2011 - Cell differentiation in noisy random boolean networks. [Relazione in Atti di Convegno]
Barbieri, A.; Villani, Marco; Serra, Roberto; Kauffman, S. A.; Colacci,
abstract

The dynamics of genetic regulatory networks are often affected bystochastic noise, due to the small number of molecules involved in some reactions.The role of these fluctuations is analyzed in a discrete model of gene regulatorynetworks, i.e. that of noisy random Boolean networks. By relating the asymptoticstates of the noisy system to the different cell types, we show how the main featuresof the important process of cell differentiation can be described by assuming thatthe noise level changes as differentiation proceeds. Differentiation is seen as a seriesof transitions from an asymptotic state in which the system can wander amongmany states under the action of noise to other asymptotic states in which the systemcan reach fewer and fewer states. This model easily describes the fact that multipotentcells can stochastically differentiate along various routes.We show here thatthe process can also be controlled (as it happens in the embryo growth) so that it ispossible to determine the final fully differentiated state of the cell. This is achievedby forcing some genes, which are called here "swithces", to take constant values,in a way which mimicks the influence of external signals, and by simoultaneouslyvarying the noise level in the cell


2011 - Cell-cell interaction and diversity of emergent behaviours [Articolo su rivista]
Damiani, Chiara; Serra, Roberto; Villani, Marco; S. A., Kauffman; A., Colacci
abstract

Despite myriads of possible gene expression profiles, cells tend to be found a in a confined number of expression patterns. The dynamics of Boolean models of gene regulatory networks has proven to be a likely candidate for the description of such self-organization phenomena. Since cells do not leave in iso- lation, but they constantly shape their functions in order to adapt to signals from other cells, this raises the question of whether the cooperation among cells en- tails en expansion or a reduction of their possible steady states. Multi Random Boolean Networks (MRBNs) are here introduced as a model for the interaction among cells suitable for the investigation of some generic properties regarding the influence of communication on the diversity of cell behaviours. In spite of its simplicity, the model exhibits a not obvious phenomenon according to which a moderate exchange of products among adjacent cells would foster the spectra of their possible behaviours, which on the other hand would be more similar to one another. On the contrary, a more invasive coupling would lead cells towards homogeneity.


2011 - Conditions for long lasting sustainable innovation in an agent-based model [Relazione in Atti di Convegno]
Ansaloni, L.; Villani, Marco; Serra, Roberto; Lane, David Avra
abstract

contexts: in particular, a key problem is that of understanding its origins. Moreover, scientists are not able to evaluate the sustainability of innovation processes, and it is difficult to discover what sort of conditions might lead to their crisis and even collapse. In this paper we present a model where agents are able to create new artifacts and can develop and enact strategies able to sustain innovation for very long periods. We discuss some results and make observations useful for understanding the processes and the strategies that sustain the growth of diversity in social and technological organizations.


2011 - Dynamical properties of a Boolean model of gene regulatory network with memory [Articolo su rivista]
Graudenzi, G.; Serra, Roberto; Villani, Marco; Damiani, C.; Colacci, A.; Kauffman, S. A.
abstract

Classical random Boolean networks (RBN) are not well suited to describe experimental data from time-course microarray, mainly because of the strict assumptions about the synchronicity of the regulatory mechanisms. In order to overcome this setback, a generalization of the RBN model is described and analyzed. Gene products (e.g., regulatory proteins) are introduced, with each one characterized by a specific decay time, thereby introducing a form of memory in the system. The dynamics of these networks is analyzed, and it is shown that the distribution of the decay times has a strong effect that can be adequately described and understood. The implications for the dynamical criticality of the networks are also discussed.


2011 - Dynamical stability in random Boolean Networks [Relazione in Atti di Convegno]
Davide, Campioli; Villani, Marco; Irene, Poli; Serra, Roberto
abstract

In this work we propose a new approach to the stability analysis ofRandom Boolean Networks (RBNs). In particular, we focus on two families ofRBNs with k=2, in which only two subsets of canalizing Boolean function areallowed, and we show that the usual measure of RBNs stability - sometimesknown as the Derrida parameter (DP) - is similar in the two cases, while theirdynamics (e.g. number of attractors, length of cycles, number of frozen nodes) aredifferent. For this reason we have introduced a new measure, that we have calledattractor sensitivity (AS), computed in a way similar to DP, but perturbing only theattractors of the networks. It is proven that AS turns out to be different in the twocases analyzed. Finally, we investigate Boolean networks with k=3, tailored tosolve the Density Classification Problem, and we show that also in this case theAS describes the system dynamical stability.


2011 - Robustness analysis of a model of gene regulatory network with memory [Articolo su rivista]
Graudenzi, Alex; Serra, Roberto; Villani, Marco; Damiani, Chiara; A., Colacci; S. A., Kauffman
abstract

The response to different kinds of perturbations of a discrete model of gene regulatory network, which is a generalization of the random Boolean network model (RBN), is extensively discussed. The model includes memory effects and the analysis pays particular attention to the influence on the system stability of a parameter (i.e. the decay time of the gene products) that determines the duration of the memory effects. It is shown that this parameter deeply affects the overall behaviour of the system, with special regard to the dynamical regimes and the sensitivity. Furthermore, a noteworthy difference in the response of systems characterized by different memory lengths in presence of either temporary or permanent damages is highlighted, as well as a substantial difference, with respect to classical RBNs, concerning the relationship between the specific dynamical regime and the landscape of the attractors.


2011 - Stochastic Local Search to Automatically Design Boolean Networks with Maximally Distant Attractors [Relazione in Atti di Convegno]
Stefano, Benedettini; Andrea, Roli; Serra, Roberto; Villani, Marco
abstract

In this work we address the issue of designing a Boolean network such that its attractors are maximally distant. The design objective is converted into an optimisation problem, that is solved via an iterated local search algorithm. This technique proves to be effective and enables us to design networks with size up to 200 nodes. We also show that the networks obtained through the optimisation technique exhibit a mixture of characteristics typical of networks in the critical and chaotic dynamical regime


2011 - The influence of the residence time on the dynamics of catalytic reaction networks [Relazione in Atti di Convegno]
Filisetti, A.; Serra, Roberto; Villani, Marco; Graudenzi, A.; Fuechslin, R.; Poli, I.
abstract

Although autocatalytic networks are common in nature, it is very difficultto reproduce them in laboratory. Since there are several models in literaturedescribing a phase transition to an autocatalytic set once that a certain degree ofheterogeneity in the composition of the system is reached, it is interesting to understandwhy it is so difficult to observe such a phenomenon in the laboratory. Forthis reason, we here present a model designed for the study of that systems takinginto account the stochastic nature of the dynamics of interacting molecules. In particular,the analysis is focused on the emergence of autocatalytic sets in accordancewith different residence times and influx compositions


2011 - The role of energy in a stochastic model of the emergence of autocatalytic sets [Relazione in Atti di Convegno]
Filisetti, A.; Graudenzi, A.; Serra, Roberto; Villani, Marco; De Lucrezia, D.; Poli, I.
abstract

In most theories concerning the origin of life autocatalytic sets are supposed to play an important role in the phase tran- sition between non-living and living matter. Although several theoretical models describe this phase transition, it is very hard to recreate the experimental conditions in wet lab. We here introduce a stochastic model of catalytic reaction net- works with energy constraints, devoted to the study of the emergence of autocatalytic sets, in which some of the as- sumptions of the already existing model are relaxed in order to explore the possible reasons which make the emergence of autocatalytic cycles difficult or which make them unstable. Moreover, since living systems operate with a continuous ex- change of matter and energy with the environment, we inves- tigate the effects on the model behavior of changes in the rate of the energy intake.


2010 - A stochastic model of catalytic reaction networks [Relazione in Atti di Convegno]
Filisetti, A.; Serra, Roberto; Villani, Marco; Fuechslin, R.; Packard, N.; Kauffman, S. A.; Poli, I.
abstract

Autocatalytic networks are widespread in nature, but theyare diffcult to create or to reproduce in laboratory. There are however several models of coupled reactions which describe a phase transition to an autocatalytic cycle when a certain level of heterogeneity in the composition of the chemical soup is reached, so it is interesting to understand why these phenomena are not easily achieved in the laboratory. For this purpose we introduce here a model, inspired by a previous one by Kauffman, tailored for the study of such properties. In particular, we take intoaccount the stochastic nature of the dynamics of interacting molecules, in the case of a well stirred tank reactor. We describe the model and we analyse its behaviour under dierent circumstances. In particular, the onset of an autocatalytic set is studied as the feed is varied, and its stability is analysed


2010 - Dynamical stability of autocatalytic sets [Relazione in Atti di Convegno]
Fuechslin, R.; Filisetti, A.; Serra, Roberto; Villani, Marco; De Lucrezia, D.; Poli, I.
abstract

occurrence of self-sustaining sets of molecules to be a genericproperty of random reaction networks. This stands in somecontrast to the experimental difficulty to actually find suchsystems. In this work, we argue that the usual approach,which is based on the study of static properties of reactiongraphs has to be complemented with a dynamic perspectivein order to avoid overestimation of the probability of gettingautocatalytic sets. Especially under the, from the experimentalpoint of view, important flow reactor conditions, it is notsufficient just to have a pathway generating a given type ofmolecules. The respective process has also to happen with asufficient rate in order to compensate the outflow. Reactionrates are therefore of crucial importance. Furthermore, processessuch as cleavage are on one hand advantageous for thesystem, because they enhance the molecular variability andtherefore the potential for catalysis. On the other hand, cleavagemay also act in an inhibiting manner by the destructionof vital components: therefore, an optimal balance betweenligation and cleavage has to be found. If energy is included asa limiting resource, the concentration profiles of the componentsof autocatalytic sets are altered in a manner that rendersa certain range for the energy supply rate as optimal for therealization of robust autocatalytic sets.The results presented are based on a theoretical model and obtainedby numerical integration of systems of ODE. This limitsthe number of involved molecular species which impliesthat the quantitative findings of this work may have no directrelevance for experimental situations, whereas the qualitativeinsights in the dynamics of the systems under considerationmay generalize to systems of truly combinatorial size.


2010 - Information transfer among coupled Random Boolean Networks [Relazione in Atti di Convegno]
Chiara, Damiani; Stuart A., Kauffman; Serra, Roberto; Villani, Marco; Annamaria, Colacci
abstract

Information processing and information flow occur at many levels in the course of an organism’s development and throughout its lifespan. Biological networks inside cells transmit information from their inputs (e.g. the concentrations of proteins or other signaling molecules) to their outputs (e.g. the expression levels of various genes). Moreover, cells do not exist in isolation, but they constantly interact with one another. We study the information flow in a model of interacting genetic networks, which are represented as Boolean graphs. It is observed that the information transfer among the networks is not linearly dependent on the amount of nodes that are able to influence the state of genes in surrounding cells.


2010 - Noisy random boolean networks and cell differentiation [Relazione in Atti di Convegno]
Villani, Marco; Serra, Roberto; Barbieri, A.; Roli, A.; Kauffman, S. A.; Colacci, A.
abstract

Autocatalytic networks are widespread in nature, but theyare difficult to create or to reproduce in laboratory. There are howeverseveral models of coupled reactions which describe a phase transition toan autocatalytic cycle when a certain level of heterogeneity in the compositionof the chemical soup is reached, so it is interesting to understandwhy these phenomena are not easily achieved in the laboratory. For thispurpose we introduce here a model, inspired by a previous one by Kau-man, tailored for the study of such properties. In particular, we take intoaccount the stochastic nature of the dynamics of interacting molecules,in the case of a well stirred tank reactor. We describe the model andwe analyse its behaviour under dierent circumstances. In particular,the onset of an autocatalytic set is studied as the feed is varied, and itsstability is analysed.


2010 - Non-linear protocell models: synchronization and chaos [Articolo su rivista]
Filisetti, Alessandro; Serra, Roberto; T., Carletti; Villani, Marco; I., Poli
abstract

We consider generic protocells models allowing linear and non-linear kinetics for the main in- volved chemical reactions. We are interested in understanding if and how the protocell division and the metabolism do synchronize to give rise to sustainable evolution of the protocell.


2010 - On the dynamics of random Boolean networks subject to noise: attractors, ergodic sets and cell types [Articolo su rivista]
Serra, Roberto; Villani, Marco; Barbieri, Alessia; S. A., Kauffman; A., Colacci
abstract

The asymptotic dynamics of random Boolean networks sub ject to ran- dom fluctuations is investigated. Under the influence of noise, the system can escape from the attractors of the deterministic model, and a thorough study of these transitions is presented. We show that the dynamics is more properly described by sets of attractors rather than single ones. We gener- alize here a previous notion of ergodic sets, and we show that the Threshold Ergodic Sets so defined are robust with respect to noise and, at the same time, that they do not suffer from a ma jor drawback of ergodic sets. The system jumps from one attractor to another of the same Threshold Ergodic Set under the influence of noise, never leaving it. By interpreting random Boolean networks as models of genetic regulatory networks, we also propose to associate cell types to Threshold Ergodic Sets rather than to deterministic attractors or to ergodic sets, as it had been previously suggested. We also propose to associate cell differentiation to the process whereby a Thresh- old Ergodic Set composed by several attractors gives rise to another one composed by a smaller number of attractors. We show that this approach accounts for several interesting experimental facts about cell differentiation, including the possibility to obtain an induced pluripotent stem cell from a fully differentiated one by overexpressing some of its genes


2010 - WIRN 2010 - SPECIAL SESSION on THE DYNAMICS OF BIOLOGICAL NETWORKS [Esposizione]
Villani, Marco; Serra, Roberto; Carlo, Morabito
abstract

Networks have attracted considerable interests in recent years and it has become increasingly clear that many important biological and artificial processes are indeed supported by dedicated network structures. This is so not only for neural networks, which are the main topic of the WIRN workshop, but also for other relevant systems like e.g. genetic, metabolic and computer networks. The purpose of the special session is that of discussing recent advances in understanding the properties of these networks and in novel mathematical and computational techniques. The session is intended for a broad interdisciplinary audience and is also aimed at fostering a dialogue between neural network scholars and researchers in the dynamics of biological and artificial networks


2009 - A new model of genetic network: the gene protein Boolean network [Relazione in Atti di Convegno]
Graudenzi, Alex; Serra, Roberto
abstract

first paper on the new gene protein model


2009 - AI*IA 2009: Emergent Perspectives in Artificial Intelligence, XIth International Conference of the Italian Association for Artificial Intelligence [Curatela]
Serra, Roberto; Cucchiara, Rita
abstract

Proceedings of the XIth International Conference on Artificial Intelligence


2009 - Assessment of polychlorinated biphenyls: propspects for a global approach [Articolo su rivista]
F., Rotondo; A., Colacci; P., Silingardi; M., Mascolo; E., Morandi; S., Perdichizzi; S., Grilli; Serra, Roberto; M., Vaccari
abstract

the results of the risk assessment related to polychlorinated biphenils are discussed and a new approach is proposed


2009 - Continuous network models of gene expression in knock-out experiments: a preliminary study [Relazione in Atti di Convegno]
A., Roli; F., Vernocchi; Serra, Roberto
abstract

analysis of avalanche distribution in the Glass continuous model of genetic networks


2009 - Dynamical critical systems for information processing: a preliminary study [Relazione in Atti di Convegno]
Ansaloni, Luca; Villani, Marco; Serra, Roberto
abstract

A general and inspiring hypothesis states that organizationsand systems subject to evolutionary pressure tend to reach a particularstate, often called critical: in particular, in presence of changing environ-ments the critical systems could have signicant advantages with respectto ordered or chaotic systems. From the previous consideration naturallyfollows the question if also articial systems could take advantage fromoperating in critical conditions, with respect to more ordered (and lessexible) structures. In order to study this topic some methodological is-sues have to be solved; this work shows the rst results of the proposedresearch approach.


2009 - Exaptive processes: an agent-based model [Capitolo/Saggio]
VILLANI, Marco; Bonacini, Stefano; FERRARI, Davide; SERRA, Roberto
abstract

his chapter introduces an agent-based model designed to investigate the dynamics of some aspects of exaptation that have been discussed previously in this volume. It is strongly related to the model introduced in the previous chapter. Indeed, in the model described here, cognitive categories represent the main tools that the producers and users of artifacts employ in order to interpret their environment, as in the case discussed in Chapter 14. The main addition provided by the current model, however, is the explicit introduction of artifacts.


2009 - Extended notion of attractors in noisy random Boolean networks [Relazione in Atti di Convegno]
Barbieri, Alessia; Villani, Marco; Serra, Roberto; S. A., Kauffman; A., Colacci
abstract

Since real networks are noisy systems, in this work we investigate thedynamics of the random Boolean networks affected by different size of smallrandom fluctuations. In this case jumps among different attractors are possible,thereby leading to an asymptotic dynamics different from that of the underlyingdeterministic model. The significance of the jumps among attractors is investigated.The notion of “ergodic set” is discussed and generalized in terms of“threshold ergodic set”, a concept that take into account the system lifetime. Inorder to evaluate possible differences due to the topology of the nets the experimentsare effectuated on Erdos-Renyi and scale-free topologies, showing similarbehaviours


2009 - Genetic regulatory networks and neural networks [Relazione in Atti di Convegno]
Serra, Roberto; Graudenzi, Alex; Villani, Marco
abstract

comparison between neural nets and random boolean networks with different constraints on the choice of boolean functions


2009 - Investigating cell criticality [Relazione in Atti di Convegno]
Serra, Roberto; Villani, Marco; Damiani, Chiara; Graudenzi, Alex; P., Ingrami; A., Colacci
abstract

random boolean networks for investigating cell criticality


2009 - L’influenza delle perturbazioni sul paesaggio degli attrattori di una rete booleana casuale [Relazione in Atti di Convegno]
Barbieri, A.; Villani, Marco; Serra, Roberto
abstract

Le reti booleane casuali proposte più di 40 anni fa da Stuart Kauffman, rappresentano uno dei modelli più noti di sistemi complessi. Esse si sono rivelate particolarmente utili per descrivere diverse importanti proprietà delle reti di regolazione genica in cellule eucariote. In questo lavoro esaminiamo se e come il modello e la sua interpretazione possono cambiare una volta introdotta una dinamica stocastica


2009 - Modelling Innovation [Capitolo/Saggio]
Serra, Roberto; Villani, Marco; Lane, David Avra
abstract

The innovation theory (briefly, IT), which has been developed in the ISCOM project and which is presented in this book (Chapters 9 and 10), is based on the analysis of different case studies, spanning different time periods and different kinds of products, from the introduction of printing in the Renaissance, to key new technologies introduced in the 19th and 20th centuries, up to present-day ongoing innovation efforts.


2009 - Non linear protocell models: Syncronisation and Chaos [Relazione in Atti di Convegno]
Filisetti, Alessandro; Serra, Roberto; T., Carletti; Villani, Marco; I., Poli
abstract

Abstract We consider generic protocells models allowing linear and non-linear kineticsfor the main involved chemical reactions.We are interested in understanding if and howthe protocell division and the metabolism do synchronize to give rise to sustainableevolution of the protocell.


2009 - On the fate of perturbations in critical random Boolean networks [Relazione in Atti di Convegno]
Damiani, Chiara; Graudenzi, Alex; Villani, Marco; Serra, Roberto; A., Colacci; Stuart A., Kauffman
abstract

Abstract Random Boolean models of genetic regulatory networks, when subject tosmall noise, may either forget past distinctions or yield divergence in state space trajectoriesprecluding reliable action. With a specic choice of the model parameters, suchnetworks are in a critical regime and optimize capacity to bind past and future. Anin-depth study of the response to perturbation of critical random Boolean networks ishere presented. It is shown that networks built with critical values of the parametersmay, however, frequently show behaviours that are more typical of the ordered or of thedisordered regime. A further classication of critical networks is thus proposed withthe objective of isolating those networks that exhibit really critical dynamics


2009 - Quando un insieme di reazioni è autocatalitico [Relazione in Atti di Convegno]
Filisetti, A.; Serra, Roberto; Villani, Marco; Carletti, T.; Füchslin, R. M.; Poli, I.
abstract

L’emergenza di uno o più cicli auto-catalitici all’interno di una rete di molecole interagenti è una proprietà fondamentale sia nello sviluppo di possibili scenari legati all’origine della vita, sia nell’indirizzare la ricerca di laboratorio verso lo sviluppo di nuove molecole capaci di evolversi interagendo con i propri bersagli.Alcuni modelli teorici di reti catalitiche hanno dimostrato una certapredisposizione alla comparsa di cicli, fenomeno che al contrario difficilmente si riesce ad ottenere nei laboratori. UIl nostro studio prende spunto dai lavori di Stuart Kauffman eFarmer, nei quali è stato sviluppato un modello contenentedue tipi di reazioni (condensazione e cleavage) ed in cui tali reazioni vengono catalizzate dalle altre molecole presenti nel sistema.L’obiettivo del nostro lavoro è di migliorare il modello originale introducendo una dinamica stocastica delle molecole, basata sul noto algoritmo di Gillespie, in modo da poter trattare adeguatamente i problemi connessi alla numerosità degli esemplari delle varie specie molecolari, che in alcuni casi può essere anche molto bassa, e alla cinetica delle reazioni. Discutiamo il tipo di analisi di rete necessario per interpretare gli schemi di reazione stocastici


2009 - Separating internal and external fluctuation in distributed web-based services [Relazione in Atti di Convegno]
Casolari, Sara; Villani, Marco; Colajanni, Michele; Serra, Roberto
abstract

The observable behavior of a complex system reflects the mechanisms governingthe internal interactions between the system’s components and the effect ofexternal perturbations. We investigate the behavior of a distributed system providingWeb-based services and the effects of the impact of external request arrivals on theinternal system resources; the results of our study are of primary importance for takingseveral runtime decisions on load and resource management. Here we show that bycapturing the simultaneous activities of several performance indexes of the Web-basedsystem nodes we can separate the internal dynamics from the external fluctuations. Forevery internal performance index, we are able to determine the origin of fluctuations,finding that while all the considered performance indexes of the application server haverobust internal dynamics, the CPU utilization and the network throughput of the Weband database servers are mainly driven by external demand.


2009 - Studi preliminari per una rete booleana capace di apprendere da esempi [Relazione in Atti di Convegno]
Ansaloni, L.; Villani, Marco; Serra, Roberto
abstract

Le reti booleane casuali (brevemente, RBN) sono uno dei modelli più noti di sistemi complessi, e si sono rivelate utili per descrivere diverse importanti proprietà delle reti di regolazione genica in cellule eucariote. Una caratteristica originale della proposta è quella di cercare di verificare se, in presenza di un ambiente mutevole, le prestazioni di una rete critica sono superiori a quelle di reti non critiche. A tal fine però è necessario affrontare alcuni problemi preliminare, cui è dedicato questo lavoro.


2009 - Synchronization phenomena in non linear protocell model [Relazione in Atti di Convegno]
Filisetti, Alessandro; Serra, Roberto; Carletti, T.; Villani, Marco; Poli, I.
abstract

In this paper we study general protocell models aiming to un-derstand the synchronization phenomenon of genetic material and containerproductions, a necessary condition to ensure sustainable growth in protocellsand eventually leading to Darwinian evolution when applied to a populationof protocells.Synchronization has been proved to be an emergent property in many rel-evant protocell models in the class of the so–called Surface Reaction Models,assuming both linear and nonlinear dynamics for the involved chemical reac-tions.


2009 - The growth of populations of protocells [Relazione in Atti di Convegno]
Serra, Roberto; T., Carletti; I., Poli; Filisetti, Alessandro
abstract

models of synchronization in populations of protocells


2009 - The influence of noise on the dynamics of random boolean networks [Relazione in Atti di Convegno]
Barbieri, Alessia; Villani, Marco; Serra, Roberto; S. A., Kauffman; A., Colacci
abstract

noise induces transitions among attractor in random boolean networks


2009 - Timing of molecular processes in a synchronous Boolean model of genetic regulatory network [Relazione in Atti di Convegno]
Graudenzi, Alex; Serra, Roberto; Villani, Marco; Damiani, Chiara; A., Colacci; Stuart A., Kauffman
abstract

A generalization of the model of random Boolean network (RBN) is presented, in whichthe concept of timing of regulatory processes is explicitly introduced, together with novel types ofentity and interaction, directly inspired to real genetic networks. Beyond the attempt ofapproaching a higher level of faithfulness to the natural world, at the base of the development ofthe model is the need for a sensible comparison with time-series microarray data-sets, inaccessibleto the original RBN model, because of the strict assumptions about the simultaneity of theregulation mechanisms. Preliminary analysis on networks typified by “critical” parameters showeda strong, even though not univocal, influence of a variation in the distribution of the time delaysthat characterize the entities of the system on the emerging dynamics: the larger the “memory” ofthe system about its dynamical evolution is, the more ordered the behaviour would tend to be.


2009 - XI conference of the Italian Association for Artificial Intelligence [Esposizione]
Serra, Roberto
abstract

AI*IA 09 is the eleventh in a series of international scientific Conferences on Advances in Artificial Intelligence held bi-annually by the Italian Association for Artificial Intelligence (AI*IA).The conference is of the generalist type, and it broadly covers the various aspects of theoretical and applied Artificial Intelligence. Both regular papers and posters can be submitted to AI*IA09.A series of workshops dedicated to specific topics will complement the main conference program.This year particular attention will be payed to the interaction of the AI field with the emergent paradigm of complex systems.


2008 - A CA MODEL OF SPONTANEOUS FORMATION OF CONCENTRATION GRADIENTS [Relazione in Atti di Convegno]
Serra, Roberto; Villani, Marco
abstract

It is shown that a two-compartment isolated fluid system,where a chemical reaction takes place close to the surfaces of the semipermeableseparating membrane, can spontaneously develop a transient concentrationdifference across the membrane. If the system is open to theflow of chemicals, the difference can persist in the steady state. Thisallows concentrating chemicals in a single compartment, which may beuseful for chemical engineering purposes, and which is particular interestingin the study of the dynamics of vesicles and protocells. The phenomenonis investigated and demonstrated here with a CA model: it isalso shown that, in the limiting case of infinitely fast diffusion, the resultsare coherent with those of a homogeneous model.


2008 - A NEW MODEL OF GENETIC NETWORKS: THE GENE-PROTEIN NETWORK [Relazione in Atti di Convegno]
Graudenzi, Alex; Serra, Roberto
abstract

the model aims to fill one of the limitations possible limitations of the RBN model, that is the absence of the timing of the molecular processes at the basis of the mechanism of gene regulation. In real cells, proteins need time to be synthesized indeed and every protein is characterized by a specific decay time. In the classical RBN model the synthesis and the decay of proteins is considered to be instantaneous and is implicit in the links among the genes, which update synchronously in discrete time steps. In the model we are introducing, the link among every gene and its protein is made explicit and every single protein is characterized by specific synthesis and decay times, which will be fundamental in the dynamics.


2008 - ARTIFICIAL LIFE AND EVOLUTIONARY COMPUTATION [Curatela]
Serra, Roberto; Villani, Marco; I., Poli
abstract

PROCEEDINGS OF THE INTERNATIONAL CONFERENCE WIVACE 08, VENICE )ITALY) SEPTEMBER 8-10, 2008


2008 - COMUNICAZIONE CELLULARE, LIVELLI E STRUTTURE ORDINATE [Articolo su rivista]
Serra, Roberto; Villani, Marco; Damiani, Chiara; Graudenzi, Alex; A., Colacci
abstract

Le cellule interagiscono per formare strutture di ordine superiore come colonie monoclonali o tessuti cellulari. Le Reti Booleane Casuali (RBN) possono essere considerate come modello di una cellula isolata ed è dunque di estrema importanza l’analisi della relazione tra la dinamica di una singola RBN e quella di un insieme di reti interagenti. Presentiamo un modello adatto allo scopo: un automa cellulare bidimensionale in cui ogni cella è occupata da una RBN. Il meccanismo di interazione tra le reti dell’automa è ispirato alla comunicazione intercellulare. L’analisi dello stato di ordine del modello può avvenire al livello dell’automa e a quello della singola rete costituente. Si osserva che l’influenza della forza di interazione sul grado di ordine delle RBN non è univoca, in alcuni casi l’ordine è accresciuto, mentre in altri è amplificato il disordine. Sono state individuate tre tipologie di comportamento, al crescere dell’intensità dell’interazione, che appaiono correlate alla dinamica della specifica RBN in assenza di interazione.


2008 - Evolutionary experiments for self-assembling amphiphilic systems [Articolo su rivista]
M., Forlin; I., Poli; D., DE MARCH; N., Packard; G., Gazzola; Serra, Roberto
abstract

Some amphiphilic molecules in particular environments may self-assemble and originate chemical entities, such as vesicles, which are relevant11 in technological applications. Experimentation in this field is difficult because of the high dimensionality of the search space and the high cost of12 each experiment. To tackle the problem of designing a relatively small number of experiments to achieve the relevant information on the problem,13 we propose an evolutionary design of experiments based on a genetic algorithm. We built a particular algorithm where design and laboratory14 experimentation interact leading the search toward the optimality region of the space. To get insight in the process we then modelled the15 experimental results with different classes of regression models; from modelling we could identify the special role played by some molecules and16 the relevance of their relative weight in the composition. With modelling we “virtually” explored the experimental space and predicted17 compositions likely to generate very high yields. Models then provide valuable information for the redesign of the experiments and can be18 considered as an essential addition to the evolutionary approach.


2008 - GENE EXPRESSION TIME-SERIES ANALYSIS OF CAMPTHOTECIN EFFECTS IN U-87-MG AND DBTRG-05 GLIOBLASTOMA CELL LINES [Articolo su rivista]
Morandi, Elena; Severini, Cinzia; Quercioli, Daniele; D'Ario, Giovanni; Perdichizzi, Stefania; Capri, Miriam; Farruggia, Giovanna; Grazia Mascolo, Maria; Horn, Wolfango; Vaccari, Monica; Serra, Roberto; Colacci, Annamaria; Silingardi, Paola
abstract

The clinical efficacy of camptothecin (CPT), a drug specifically targetingtopoisomerase I (TopoI), is under evaluation for the treatment of malignant gliomas. Due to thehigh unresponsiveness of these tumours to chemotherapy, it would be very important to study thesignalling network that drives camptothecin outcome in this type of cancer cells. To address thisissue, we had previously compared the expression profile of human U87-MG glioblastoma cellswith that of a CPT-resistant counterpart, giving evidence that the development of a robustinflammatory response was the main transcriptional effect associated with CPT resistance.Here we report time-related changes and cell line specific patterns of gene expression after CPTtreatment by using two p53 wild-type glioblastoma cell lines, U87-MG and DBTRG-05, withdifferent sensitivities to TopoI inhibition.


2008 - Global and local processes in a model of innovation [Relazione in Atti di Convegno]
Villani, Marco; Serra, Roberto; Ansaloni, Luca; Lane, David Avra
abstract

In this work we present the introduction of spatial constraintsin a model of generation and diffusion of innovations. The presenceof spatial limitations introduces several feedbacks, whose main effectsare the decrease of global diversity in favour of a higher robustness,despite the apparent minor success of the individual agents. All thesefeatures hold contemporarily, but the individuated feedbacks are able toexplain their only apparently contradictory nature. None of these resultsis obvious, nor can it be simply deduced from the qualitative theory.Moreover, the simulations could make possible comparisons between themodel behaviours and the theory claims, indicating new ways of improvementand development


2008 - SUFFICIENT CONDITIONS FOR EMERGENT SYNCHRONIZATION IN PROTOCELL MODELS [Articolo su rivista]
T., Carletti; Serra, Roberto; I., Poli; Villani, Marco; Filisetti, Alessandro
abstract

In this paper, we study general protocell models aiming to understand the synchronizationphenomenon of genetic material and container productions, a necessary condition to ensure sustainablegrowth in protocells and eventually leading to Darwinian evolution when applied to a population ofprotocells.Synchronization has been proved to be an emergent property in many relevant protocell models inthe class of the so-called surface reaction models, assuming both linear- and non-linear dynamics forthe involved chemical reactions. We here extend this analysis by introducing and studying a new classof models where the relevant chemical reactions are assumed to occur inside the protocell, in contrastwith the former model where the reaction site was the external surface.While in our previous studies, the replicators were assumed to compete for resources,without any direct interaction among them, we here improve both models by allowing linearinteraction between replicators: catalysis and/or inhibition. Extending some techniques previouslyintroduced, we are able to give a quite general analytical answer about the synchronizationphenomenon in this more general context. We also report on results of numerical simulations tosupport the theory, where applicable, and allow the investigation of cases which are not amenable toanalytical calculations.


2008 - SYNCHRONIZATION PHENOMENA IN PROTOCELL MODELS [Relazione in Atti di Convegno]
Filisetti, Alessandro; Serra, Roberto; T., Carletti; I., Poli; Villani, Marco
abstract

A protocell comprises at least one kind of“container”(typically an amphiphile) and one kind of replicator molecule. There are therefore two kinds of reactions whichare crucial for the working of the protocell, which will be called here keyreactions: those which synthesize the container molecules and those whichsynthesize the replicators.The two key reactions may take place at different rates. However, toachieve sustained protocell growth and avoiding death by dilution it isnecessary that the two are proceed at equal rate, a condi-tion referred to as synchronization. With our models we are able to prove that synchronization is an emergent property in contrast to earlier models, like the well–knownChemoton where synchronization was achieved by ad hoc hypothesesconcerning the form of kinetic equations.We consider here several protocells models both linear and non–linear inreplicators kinetic (the overall model is definitely non–linear because of thedivision event), moreover some models posses only autoreplicator moleculeswithout interaction between them while other models has either catalyticor inhibitory interaction between replicators.


2008 - Synchronization phenomena in internal reaction models of protocells [Relazione in Atti di Convegno]
Serra, Roberto; T., Carletti; Filisetti, Alessandro; I., Poli
abstract

The present paper presents and extends our previous studies which hadconsidered synchronization in the class of so{called Internal Reaction Mod-els", IRM for short when linear kinetics were assumed for the relevantchemical reactions. Let us stress here that similar results have been ob-tained also for the Surface Reaction Models", SRM for short , hencethe synchronization phenomenom seems to be very robust with the respectto the chosen architecture once linear kinetics are considered.


2008 - THE DIFFUSION OF PERTURBATIONS IN A MODEL OF COUPLED RANDOM BOOLEAN NETWORKS [Relazione in Atti di Convegno]
Serra, Roberto; Villani, Marco; Damiani, Chiara; Graudenzi, Alex; A., Colacci
abstract

Deciphering the influence of the interaction among the constituentsof a complex system on the overall behaviour is one of themain goals of complex systems science. The model we present in thiswork is a 2D square cellular automaton whose of each cell is occupiedby a complete random Boolean network. Random Boolean networks area well-known simplified model of genetic regulatory networks and thismodel of interacting RBNs may be therefore regarded as a simplifiedmodel of a tissue or a monoclonal colony. The mechanism of cell-to-cellinteraction is here simulated letting some nodes of a particular networkbeing influenced by the state of some nodes belonging to its neighbouringcells. One possible means to investigate the overall dynamics of acomplex system is studying its response to perturbations. Our analysesfollow this methodological approach. Even though the dynamics of thesystem is far from trivial we could show in a clear way how the interactionaffects the dynamics and the global degree of order.


2008 - THE SIMULATION OF GENE KNOCK-OUT IN SCALE-FREE RANDOM BOOLEAN MODELS OF GENETIC NETWORKS [Articolo su rivista]
Serra, Roberto; Villani, Marco; Graudenzi, Alex; A., Colacci; S. A., Kauffman
abstract

This paper describes the effects of perturbations, which simulatethe knock-out of single genes, one at a time, in random Boolean models ofgenetic networks (RBN). The analysis concentrates on the probability distributionof so-called avalanches (defined in the text) in gene expression. Thetopology of the random Boolean networks considered here is of the scale-freetype, with a power-law distribution of outgoing connectivities. The results forthese scale-free random Boolean networks (SFRBN) are compared with thoseof classical RBNs, which had been previously analyzed, and with experimentaldata on S. cerevisiae. It is shown that, while both models approximatethe main features of the distribution of experimental data, SFRBNs tend tooverestimate the number of large avalanches.


2008 - WIVACE 2008Workshop Italiano di Vita Artificiale e Computazione Evolutiva [Esposizione]
Serra, Roberto; I., Poli
abstract

Artificial life (commonly Alife or alife) is a field of study and an associated art form which examine systems related to life, its processes, and its evolution through simulations using computer models, robotics, and biochemistry. There are three main kinds of alife, named for their approaches: soft, from software; hard, from hardware; and wet, from biochemistry. Artificial life imitates traditional biology by trying to recreate biological phenomena. The term "artificial life" is often used to specifically refer to soft alife.Artificial life studies the logic of living systems in artificial environments. The goal is to study the phenomena of living systems in order to come to an understanding of the complex information processing that defines such systems.Very often agent based systems are used in artificial life studies to observe the emergent properties of societies of agents.


2007 - An agent-based model of exaptive processes [Articolo su rivista]
Villani, Marco; S., Bonacini; Ferrari, Davide; Serra, Roberto; Lane, David Avra
abstract

A key problem in research on innovations is that of understanding their origins. In thispaper, we propose that radical innovations are created by a process of ’exaptation’, andwe introduce a dynamical model that describes how it may happen. In particular, ourmodel is focussed on the interplay between artefact innovation and attributions offunctionality. We propose that the explicit representation of artefacts and categories easesthe understanding of the exaptation phenomenon, seen in this context as a shift in termsof ‘leading attributions’ and allows the identification of the elements favouring theemergence of innovations.


2007 - Angiopoietin-2 expression in B-cell chronic lymphocytic leukemia: association with clinical outcome and immunoglobulin heavy-chain mutational status [Articolo su rivista]
Maffei, Rossana; Marasca, Roberto; Martinelli, Silvia; Castelli, Ilaria; Santachiara, R; Morandi, E; Zucchini, Patrizia; Fontana, M; Giacobbi, F; Silingardi, P; Bonacorsi, G; Temperani, Paola; Masini, L; Colacci, Am; Serra, Roberto; Torelli, Giuseppe
abstract

Chronic lymphocytic leukemia (CLL) has been considered for several years a disease of accumulation of relentless mature-looking malignant monoclonal B cells due to a presumeddefect in programmed cell death. However, several observations suggest that CLL cells are not immortal and that they require signals from microenvironment to maintain viability. Increased microvessel density in marrow and lymph node and increased levels of certain proangiogenetic factors in blood and urine of CLL patients were observed.2 Angiopoietin-2 (Ang-2) has a pivotal role in the disruption of stability and quiescence of mature vasculature that coincides with the reinitiation of vascular remodelling and angiogenic sprouting in adult, as occurs in tumors.


2007 - Comunicazione cellulare, livelli e strutture ordinate. [Relazione in Atti di Convegno]
Serra, Roberto; Villani, Marco; Damiani, C.; Graudenzi, A.; Colacci, A.
abstract

Le cellule interagiscono per formare strutture di ordine superiorecome colonie monoclonali o tessuti cellulari. Le Reti Booleane Casuali (RBN)possono essere considerate come modello di una cellula isolata ed è dunque diestrema importanza l’analisi della relazione tra la dinamica di una singola RBNe quella di un insieme di reti interagenti. Presentiamo un modello adatto alloscopo: un automa cellulare bidimensionale in cui ogni cella è occupata da unaRBN. Il meccanismo di interazione tra le reti dell’automa è ispirato allacomunicazione intercellulare. L’analisi dello stato di ordine del modello puòavvenire al livello dell’automa e a quello della singola rete costituente. Siosserva che l’influenza della forza di interazione sul grado di ordine delle RBNnon è univoca, in alcuni casi l’ordine è accresciuto, mentre in altri è amplificatoil disordine. Sono state individuate tre tipologie di comportamento, al cresceredell’intensità dell’interazione, che appaiono correlate alla dinamica dellaspecifica RBN in assenza di interazione.


2007 - Conditions for emergent synchronization in protocells. [Relazione in Atti di Convegno]
Serra, Roberto; Carletti, T.; Poli, I.; Villani, Marco; Filisetti, Alessandro
abstract

In this paper we study general protocell models, called Surface Reactions Models, aiming to understand the synchronization of genetic material and container productions, a necessary condition to assure sustainable growth in protocells.Synchronization has been proved to be an emergent property in many relevant protocell models , assuming both linear and nonlinear law for the replications rates. While in those previous studies the replicators were assumed to compete forresources, without any direct interaction among them, here we improve the model by allowing linear interaction between replicators: catalysis and/or inhibition.Extending some techniques introduced in, we are able to give a quite general analytical answer about the synchronization phenomenon in this more general context.We also report on the results of numerical simulations to support the theory, where applicable, and allow to investigate cases which are not amenable to analytical calculations . A short comment on preliminary results concerning fully nonlinearmodels is presented in the conclusions


2007 - Interacting random boolean networks [Relazione in Atti di Convegno]
Serra, Roberto; Villani, Marco; Damiani, Chiara; Graudenzi, Alex; A., Colacci; S. A., Kauffamn
abstract

Random Boolean networks (RBN) have been extensively studied asmodels of genetic regulatory networks. While many studies have been devoted tothe dynamics of isolated random Boolean networks, which may considered asmodels of isolated cells, in this paper we consider a set of interacting RBNs,which may be regarded as a simplified model of a tissue or a monoclonal colony.In order to do so, we introduce a cellular automata (CA) model, where each cellsite is occupied by a RBN. The mutual influence among cells is modelled byletting the activation of some genes in a RBN be affected by that of some genes inneighbouring RBNs. It is shown that the dynamics of the CA is far from trivial.Different measures are introduced to provide indications about the overallbehaviour. In a sense which is made precise in the text, it is shown that the degreeof order of the CA is affected by the interaction strength, and that markedlydifferent behaviours are observed. We propose a classification of these behavioursinto four classes, based upon the way in which the various measures of order areaffected by the interaction strength. It is shown that the dynamical properties ofisolated RBNs affect the probability that a CA composed by those RBNs belongsto one of the four classes, and therefore also affects the probability that a higherinteraction strength leads to a greater, or a smaller, degree of order.


2007 - Modelli di protocellule e sincronizzazione [Relazione in Atti di Convegno]
Serra, Roberto; Carletti, T.; Poli, I.; Villani, Marco; Filisetti, A.
abstract

L'articolo tratta delle condizioni che permettono l'emergere di sincronizzazione fra la velocità di replica delle specie chimiche interne ad una cellula e la velocità di accrescimento delle membrana cellulare


2007 - Novelties and structural changes in a dynamical model of innovation processes [Relazione in Atti di Convegno]
Villani, Marco; Ansaloni, Luca; D., Bagatti; Lane, David Avra; Serra, Roberto
abstract

We discuss the emergence of non linear behaviours andthe genesis of structures within an agent-based model of innovationprocesses based upon a theory of innovation introduced by Lane andMaxfield. This work focuses on how the innovation strategies of theagents and stable relationships among them affect systemperformance. In addition, it describes a social network analysis of theemergence of collective structures in artifact space


2007 - SURFACE REACTION MODELS OF PROTOCELLS [Relazione in Atti di Convegno]
Serra, Roberto; T., Carletti; I., Poli
abstract

We present some improved versions of a previous model10 to describe a class of genericprotocells hypotheses, inspired by the “Los Alamos bug” hypothesis but which, due totheir abstraction level, can be applied to a wider set of detailed protocell hypotheses. Inthe present paper we address in particular the question of generic non-linear growth lawfor the container and a general non-linear replication law for the self-replicatingmolecules. Our technique, combining a continuous-time formalism, for the growthbetween two successive protocell divisions, and a discrete map, relating the quantity ofself-replicating molecules in successive generations, allows one to derive severalproperties in an analytical way. It can thus be shown that, under fairly generalassumptions, the two growth rates synchronise, so that the lipid container doubles its sizewhen the quantity of self-replicating molecules has also doubled – thus giving rise toexponential growth of the population of protocells. Such synchronization had beenpostulated a priori in previous models of protocells, while it is here an emergentproperty.


2007 - Synchronization phenomena in protocell models [Relazione in Atti di Convegno]
Filisetti, Alessandro; Serra, Roberto; Carletti, T.; Poli, I.; Villani, Marco
abstract

Almost all life forms known today, are composed by cells, fundamental constituting units able to self–replicate and evolve through changes in genetic information; it is generally believed that this was not the case when first life–forms emerged on Earth almost 4 billion years ago. These protocells were much simpler, probably exhibiting only few simplified functionalities, that required a primitive embodiment structure, a protometabolism and a rudimentary genetics, so to guarantee that offsprings were similar to their parents. Artificial protocells have not yet been reproduced and intense research programs are being established aiming at developing reference models to capture the essence of the first protocells appeared on earth and enableto monitor their subsequent evolution. The interest for these researches is motivated either by the quest to understand which are the minimal requirements for a life form to exist and evolve, or by the search for indications about the way in which primitive life might have developed on earth. Moreover besides from their interest for the origin–of–life problem, protocells may be of practical interest in applications: obtain populations ofprotocells that grow and reproduce, specialized for useful tasks, like drug synthesis and reduce pollution.Because protocells didn’t yet exist, in order to study how they can develop researchers have considered simplified models able to capture general behaviors, without carefully adding complicating details.


2007 - Synchronization phenomena in surface reaction models of protocells [Articolo su rivista]
Serra, Roberto; T., Carletti; I., Poli
abstract

A class of generic models of protocells is introduced,which are inspired by the Los Alamos bug hypothesis but which,due to their abstraction level, can be applied to a wider set ofdetailed protocell hypotheses. These models describe the coupledgrowth of the lipid container and of the self-replicating molecules.A technique to analyze the dynamics of populations of such protocellsis described, which couples a continuous-time formalism for thegrowth between two successive cell divisions, and a discrete mapthat relates the quantity of self-replicating molecules in successivegenerations. This technique allows one to derive several properties inan analytical way. It is shown that, under fairly general assumptions,the two growth rates synchronize, so that the lipid container doublesits size when the number of self-replicating molecules has alsodoubled—thus giving rise to exponential growth of the populationof protocells. Such synchronization had been postulated a priori inprevious models of protocells; here it is an emergent property. We alsocompare the rate of duplication of two populations generated by twodifferent protocells with different kinds of self-replicating molecules,considering the interesting case where the rate of self-replicationof one kind is higher than that of the other, but its contribution tothe container growth rate is smaller. It is shown that in this case thepopulation of offspring of the protocell with the faster-replicatingmolecule will eventually grow faster than the other. The case wheretwo different types of self-replicating monomers are present inthe same protocell is also analyzed, and it is shown that, if thereplication follows a first-order kinetic equation, then the fasterreplicator eventually displaces the slower one, whereas if the growthis sublinear the two coexist. It is also proven by an appropriaterescaling of time that the results that concern the system asymptoticdynamics hold both for micelles and vesicles.


2007 - The influence of the topology of regulatory networks on the distribution of avalanches in gene expression data. [Relazione in Atti di Convegno]
Serra, Roberto; Villani, Marco; Graudenzi, Alex; Colacci, A.; Kauffamn, S. A.
abstract

This paper describes the effects of perturbations, whichsimulate the knock-out of single genes, one at a time, in randomBoolean models of genetic networks (RBNs). The analysis concentrates on the probability distribution of so-called avalanches (defined in the text) in gene expression. The topology of the random Boolean networks considered here is of the scale-free type, with a power-law distribution of outgoing connectivities. The results for these scale-free randomBoolean networks (SFRBNs) are firstly compared with those ofclassical RBNs, which had been previously analyzed, secondly withexperimental data on S. cerevisiae. It is shown that, while both models approximate the main features of the distribution of experimental data, SFRBNs tend to overestimate the number of large avalanches


2007 - Valanghe in reti booleane a topologia scale-free [Relazione in Atti di Convegno]
Serra, Roberto; Villani, Marco; Graudenzi, A.; Colacci, A.
abstract

L'articolo tratta della simulazione di eventi di knock-out tramite reti booleane con topologia scale-free, e del confronto dei risultati con dati reali (eventi in Saccaromicies Cerevisiae)


2007 - WHY COMPLEXITY, WHICH COMPLEXITY [Capitolo/Saggio]
Serra, Roberto
abstract

MISSING


2007 - Why a simple model of genetic regulatory networks describes the distribution of avalanches in gene expression data [Articolo su rivista]
Serra, Roberto; Villani, Marco; Graudenzi, Alex; S. A., Kauffman
abstract

In a previous study it was shown that a simple random Boolean network model, with two input connections per node, can describewith a good approximation (with the exception of the smallest avalanches) the distribution of perturbations in gene expression levelsinduced by the knock-out of single genes in Saccharomyces cerevisiae. Here we address the reason why such a simple model actuallyworks: we present a theoretical study of the distribution of avalanches and show that, in the case of a Poissonian distribution of outgoinglinks, their distribution is determined by the value of the Derrida exponent. This explains why the simulations based on the simple modelhave been effective, in spite of the unrealistic hypothesis about the number of input connections per node. Moreover, we consider herethe problem of the choice of an optimal threshold for binarizing continuous data, and we show that tuning its value provides an evenbetter agreement between model and data, valuable also in the important case of the smallest avalanches. Finally, we also discuss thechoice of an optimal value of the Derrida parameter in order to match the experimental distributions: our results indicate a value slightlybelow the critical value 1.


2006 - A NEW MODEL FOR POLLUTED SOIL RISK ASSESSMENT [Articolo su rivista]
M., Andretta; Serra, Roberto; Villani, Marco
abstract

In this paper, we discuss the most important theoretical aspects of polluted soil Risk Assessment Methodologies, whichhave been developed in order to evaluate the risk, for the exposed people, connected with the residual contaminantconcentration in polluted soil, and we make a short presentation of the major different kinds of risk assessmentmethodologies. We also underline the relevant role played, in this kind of analysis, by the pollutant transport models. Wealso describe a new and innovative model, based on the general framework of the so-called Cellular Automata (CA),initially developed in the UE-Esprit Project COLOMBO for the simulation of bioremediation processes. These kinds ofmodels, for their intrinsic ‘‘finite and discrete’’ characteristics, seem to be very well suited for a detailed analysis of theshape of the pollutant sources, the contaminant fates and the evaluation of target in the risk assessment evaluation.In particular, we will describe the future research activities we are going to develop in the area of a strict integrationbetween pollutant fate and transport models and Risk Analysis Methodologies.


2006 - A cDNA-microarray analysis of camptothecin resistance in glioblastoma cell lines [Articolo su rivista]
Morandi, E; Zingaretti, C; Chiozzotto, D; Severini, C; Semeria, A; Horn, W; Vaccari, M; Serra, Roberto; Silingardi, P; Colacci, A.
abstract

Chemotherapy, as generally available, is of a limited value in curing malignant brain tumors (gliomas), which often develop resistance to drugs, becoming completely unresponsive to any standard therapeutic approach. Camptothecins, a family of topoisomerase I inhibitor drugs, represent a new promising treatment strategy and are currently under evaluation for testing the clinical efficacy. We selected a CPT-resistant sub-line (U87CPT-R) from U87-MG grade III-IV astrocytoma cells, and compared the expression profile of the two cell lines by cDNA-microarray, as a preliminary screening of the molecular mechanisms involved in the acquisition of CPT resistance in glioma cells. The relevant role of IL-1 beta overproduction as well as a generalised up-regulation of genes implicated in angiogenesis and inflammatory response are discussed in details.


2006 - ARTIFICIAL INTELLIGENCE: 50TH ANNIVERSARY 1956-2006 [Curatela]
L., Carlucci Aiello; M., Gori; M., Schaerf; Serra, Roberto; O., Stock; P., Torasso
abstract

NUMERO SPECIALE DELLA RIVISTA "INTELLIGENZA ARTIFICIALE" (ISSN 1724-8035) DEDICATA AI 50 ANNI DALLA CONFERENZA DI DARTMOUTH. RIASSUME I RISULTATI PRINCIPALI DELLE RICERCHE ITALIANE NEL SETTORE


2006 - COMPLEX SYSTEMS [Articolo su rivista]
S., Bandini; Serra, Roberto
abstract

This paper deals with the interactions between the twoscientific communities of AI and Complex SystemsSciences. Theterm “complexity” is used since the 80’s to refer to alargely interdisciplinary endeavour, aimed atunderstanding common organizational and dynamicalproperties of nonlinear systems.The interactions between the two communities ofCSS and AI have been so far rather limited, althoughboth might benefit from closer encounters. Recentdevelopments in the context of agent-based modellingand simulation, which is receiving a growing interest invarious fields from biology to social simulation, representa new opportunity for further exploring andstrengthening these interactions and connections, inparticular between CSS and Multi-Agent Systems(MAS) .


2006 - Coupled random boolean network forming an artificial tissue [Relazione in Atti di Convegno]
Villani, Marco; Serra, Roberto; Ingrami, P; Kauffman, Sa
abstract

Random boolean networks (shortly, RBN) have proven useful in describing complex phenomena occurring at the unicellular level. It is therefore interesting to investigate how their dynamical behavior is affected by cell-cell interactions, which mimics those occurring in tissues in multicellular organisms. It has also been suggested that evolution may tend to adjust the parameters of the genetic network so that it operates close to a critical state, which should provide evolutionary advantage; this hypothesis has received intriguing, although not definitive support from recent findings. It is therefore particularly interesting to consider how the tissue-like organization alters the dynamical behavior of the networks close to a critical state. In this paper we define a model tissue, which is a cellular automaton each of whose cells hosts a full RBN, and we report preliminary studies of the way in which the dynamics is affected.


2006 - FRA BIOLOGIA E VITA ARTIFICIALE: MODELI DI RETI GENETICHE [Articolo su rivista]
Serra, Roberto
abstract

Un interessante settore della biologia teorica è quello della ricerca di «proprietà generiche» degli esseri viventi,o di alcuni loro sottoinsiemi. In questo contesto si inserisce l’opera pionieristica di Stuart Kauffman,che già alla fine degli anni ’60 ha tentato di indagare le proprietàgeneriche del sistema di regolazione dell’espressione genica. Vengono qui descritte le principali proprietà delle reti di Kauffman e vengono presentati alcuni recenti studi che consentono un confronto con dati sperimentali


2006 - On the distribution of small avalanches in random boolean networks [Relazione in Atti di Convegno]
Villani, Marco; Serra, Roberto; Graudenzi, Alex; Kauffman, S. A.
abstract

The distribution of small avalanches of gene perturbationsis analytically studied in the quenched model ofrandom Boolean networks, providing formulae whichhold at a very good approximation for networks wherethe number of connections per node is much smaller thanthe number of nodes. The expressions are particularlysimple and elegant in the case of a Poissonian distributionof outgoing connectivities. Comparisons with simulationsof a large network, with 6000 nodes, show verygood agreement.


2005 - A theory based dynamical model of innovation processes [Relazione in Atti di Convegno]
Lane, David Avra; Serra, Roberto; Villani, Marco; Ansaloni, Luca
abstract

We present an agent-based model of innovation processes, based upon a theory of innovation by Lane and Maxfield. The theory inspires and constrains the features of the model, thus reducing the embarasse de richesse that is one of the major methodological problems of agent-based modeling. Artifacts are produced by agents using recipes; the basic dynamics, absent innovation, is one of production and sales, where the external world supplies “raw materials” and external demand. Depending upon the initial conditions, self-sustaining cycles of production and exchange can emerge among the agents. Innovation – that is, the generation of new recipes, in particular desired directions, called “goals” – results in substantial modification of the system dynamics. Two innovation regimes are introduced: a “lonely” mode, in which each agent tries to introduce new products by itself, and a “relational” mode, in which two agents can improve their reciprocal knowledge and can decide to try to jointly develop a new artifact.


2005 - A theory based dynamical model of innovation processes [Relazione in Atti di Convegno]
Lane, David Avra; Serra, Roberto; Villani, Marco
abstract

We present an agent-based model of innovation processes, based upon a theory of innovationby Lane and Maxfield. The theory inspires and constrains the features of the model,thus reducing the embarasse de richesse that is one of the major methodological problems ofagent-based modeling. Artefacts are produced by agents using recipes; the basic dynamics,absent innovation, is one of production and sales, where the external world supplies "rawmaterials" and external demand. Depending upon the initial conditions, self-sustainingcycles of production and exchange can emerge among the agents. Innovation – that is,the generation of new recipes, in particular desired directions, called "goals" – results insubstantial modification of the system dynamics. Two innovation regimes are introduced:a "lonely" mode, in which each agent tries to introduce new products by itself, and a"relational" mode, in which two agents can improve their reciprocal knowledge and candecide to try to jointly develop a new artifact.


2005 - RECENT RESULTS ON RANDOM BOOLEAN NETWORKS [Relazione in Atti di Convegno]
Serra, Roberto; Villani, Marco
abstract

MISSING


2004 - A small-world network where all nodes have the same connectivity, with application to the dynamics of boolean interacting automata [Articolo su rivista]
Serra, Roberto; Villani, Marco; L., Agostini
abstract

In this paper a new algorithm (called ENL) is introduced, which generates a small-world network starting from a regular lattice, by randomly rewiring some connections. The approach is similar to the well-known Watts-Strogatz model, but the present method is different as it leaves the number of connections k of each node unchanged, while the WS algorithm gives rise to a Poisson distribution of connectivities. The motivation for the ENL algorithm stems from the interest in studying the dynamics of interacting oscillators or automata (associated to the nodes of the network): indeed, leaving k unaltered allows one to study how the dynamics of these networks is affected by rewiring only (which gives rise to small-world properties) disentangling its effects from those related to the modification of the connectivity of some nodes. The new algorithm is compared with that of Watts and Strogatz, by studying the topological properties of the network as a function of the number of rewirings. The effects on the dynamics are tested in the case of the majority rule, and it is shown that key dynamical properties (i.e. number of attractors, size of basins attraction, transient duration) are modified by rewiring. The quantitative differences between the dynamics on a ENL network and a WS one are discussed in detail. A comparison with scale-free networks of the Barabasi-Albert type and with completely random networks is also given.


2004 - Genetic network models and statistical properties of gene expression data in knock-out experiments [Articolo su rivista]
Serra, Roberto; Villani, Marco; A., Semeria
abstract

It is shown here how gene knock-out experiments can be simulatedin Random Boolean Networks (RBN), which are well-knownsimplifiedmod els of genetic networks. The results of the simulations are presentedandcomparedwith those of actual experiments inS. cerevisiae. RBN with two incoming links per node have been considered, and the Boolean functions have been chosen at randomamong the set of so-calledcanalizing functions.Genes are knocked-out (i.e. silenced) one at a time, and the variations in the expression levels of the other genes, with respect tothe unperturbed case, are considered. Two important variables are defined: (i) avalanches, which measure the size of theperturbation generatedby knocking out a single gene, and(ii) susceptibilities, which measure how often the expression of a givengene is modified in these experiments.A remarkable observation is that the distributions of avalanches and susceptibilities are very robust, i.e. they are very similar indifferent random networks; this should be contrasted with the distribution of other variables that show a high variance in RBN.Moreover, the distribution of avalanches and susceptibilities of the RBN models are close to those observed in actual experimentsperformedwith S. cerevisiae, where the changes in gene expression levels have been recorded with DNA microarrays.These findings suggest that these distributions might be ‘‘generic’’ properties, common to a wide range of genetic models and realgenetic networks. The importance of such generic properties is discussed.


2004 - ON THE DYNAMICS OF RANDOM BOOLEAN NETWORKS WITH SCALE-FREE OUTGOING CONNECTIONS [Articolo su rivista]
Serra, Roberto; Villani, Marco; L., Agostini
abstract

In the classical model of Random Boolean Networks (RBN) the number of incoming connectionsis the same for every node, while the distribution of outgoing links is Poissonian. TheseRBN are known to display two major dynamical behaviours, depending upon the value of somemodel parameters: an “ordered” and a “chaotic” regime. We introduce a modi7cation of theclassical way of building a RBN, which maintains the property that all the nodes have the samenumber of incoming links, but which gives rise to a scale-free distribution of outgoing connections.Because of this modi7cation, the dynamical properties are deeply modi7ed: the number ofattractors is much smaller than in classical RBN, their length and the duration of the transientsare shorter. Moreover, the number of di8erent attractors is almost independent of the networksize, over almost three orders of magnitudes (while in classical RBN this number grows with thesize of the network). These results are based upon a detailed study of networks where each nodehas two input connections. A limited study of networks with three input connections per nodeshows that also in this case the number of attractors is almost independent of the network size.


2004 - On the dynamics of scale-free boolean networks [Capitolo/Saggio]
Serra, Roberto; Villani, Marco; L., Agostini
abstract

The dynamical features of Random Boolean Networks (RBN) are examined, in the case where a scale-free distribution of outgoing connectivities is introduced. RBN are known to display two major dynamical behaviours, depending upon the value of some model parameters, In the ordered regime the number of attractors is a growing polynomial function of the number of nodes N, while in the chaotic regime the growth is exponential. We present here a modification of the classical way of building a RBN, which maintains the property that all the nodes have the same number of incoming links, but which gives rise to a scale-free distribution of outgoing connectivities. Because of this modification, the dynamical properties are deeply modified: the number of attractors is much smaller than in classical RBN, their length and the duration of the transients are shorter. Perhaps more surprising, the number of different attractors is almost independent of the network size, over almost three order of magnitudes. Besides pertaining to the study of the dynamics of nonlinear networks, these results may have interesting biological implications.


2004 - Perturbation in genetic regulatory networks: simulation and experiments [Capitolo/Saggio]
Serra, Roberto; Villani, Marco; A., Semeria; S. A., Kauffman
abstract

Random boolean networks (RBN) have been proposed more thanthirty years ago as models of genetic regulatory networks. Recent studies on theperturbation in gene expression levels induced by the knock-out (i.e. silencing)of single genes have shown that simple RBN models give rise to a distributionof the size of the perturbations which is very similar in different model networkrealizations, and is also very similar to the one actually found in experimentaldata concerning a unicellular organism (S.cerevisiae). In this paper we presentfurther results, based upon the same set of experiments, concerning thecorrelation between different perturbations. We compare actual data from S.cerevisiae with the results of simulations concerning RBN models with morethan 6000 nodes, and comment on the usefulness and limitations of RBNmodels.


2003 - DESCRIBING IN-VITRO CELL PROLIFERATION AND TRANSFORMATION WITH CELLULAR AUTOMATA [Relazione in Atti di Convegno]
Serra, Roberto; Villani, Marco
abstract

The importance of in-vitro carcinogenesis tests is growing, either for health risk assessments or for screening candidate drugs. Although these systems are simpler than their in-vivo counterparts, their outcomes are nonetheless the result of the interaction of several nonlinear processes. Therefore modelling their behaviour may significantly improve our understanding of these tests. A dynamical model is introduced, which describes the growth of cell cultures (coupling metabolism with proliferation) and the birth of "transformed" cells (which give rise to malignant cell clusters) under the action of a carcinogen. By averaging over the space variable, a simpler (ordinary differential equation) model is obtained, and its behaviour is compared with that of a cellular automata model which preserves space dependence and locality of interactions. It is shown that the latter may describe important phenomena which are hidden by averaging over the whole space. Experimental data are interpreted on the basis of the model, pointing to the role of a previously overlooked experimental variable. These results provide a further indication of the usefulness of cellular automata in modelling complex biological systems.


2003 - ROBUSTNESS TO DAMAGE OF BIOLOGICAL AND SYNTHETIC NETWORKS [Relazione in Atti di Convegno]
Serra, Roberto; Villani, Marco; A., Semeria
abstract

We analyze the perturbation of the expression levels of thousandsof genes when one of them is knocked-out, by measuring avalanches, the numberof genes whose expression is affected in a knock-out experiment, and genesusceptibilities, which measure how often the expression of a given gene ismodified. Experimental data concerning the yeast S. cerevisiae are available.Knock-out is simulated, using random boolean network models of gene regulation,in several experiments, using different sets of boolean functions. The majorresults (when only canalizing functions are allowed) are that the distributionsof avalanches and susceptibilities are very similar in different syntheticnetworks, with very small variance, and that these two distributions closely resemblethe experimental ones (a result which is even more surprising since noparameter optimization has been performed). These results strongly suggestthat the distribution of avalanches and susceptibilities may be generic properties,common to many different genetic networks


2002 - PERTURBING THE REGULAR TOPOLOGY OF CELLULAR AUTOMATA: IMPLICATIONS FOR THE DYNAMICS [Relazione in Atti di Convegno]
Serra, Roberto; Villani, Marco
abstract

The topology of Cellular Automata (CA) is that of regular graphs with high clustering coefficients and long characteristic path lengths. The introduction of some long range connections modifies the topology, and it may give rise to small world networks, with high clustering and short path lengths, modifying also the system dynamical properties (attractors, basins of attraction, transient duration). In order to investigate the effects on the dynamics of the introduction of long range connections it is appropriate to keep the number of connections per node constant, while the existing algorithms give rise to nodes with different connectivities. Here we present an algorithm able to re-direct the links without changing the connectivity degree of the nodes. We then analyze the effects of small topological perturbations of a regular lattice upon the system dynamical properties in the case where the transition function is the majority rule; we show that these effects are indeed important and discuss their characteristics.


2001 - Bioremediation modelling: from the pilot plant to the field [Relazione in Atti di Convegno]
Villani, Marco; M., Padovani; M., Andretta; Serra, Roberto; B., Muller; H. P., Ratzke; R., Rongo; W., Spataro; S., Di Gregorio
abstract

We report recent results achieved by applying in the field a dynamical model of in situ bioremediation that has been developed within the Colombo project, one of the major european endeavours in bioremediation modelling.Our approach relies upon the CabCol methodology, which is based upon the use of adaptive models, which are tailored to the case at hand in the pilot plant phase. The model is then used to forecast the results of real field interventions. A further original feature is that the model is based upon the cellular automata framework, instead of relying upon partial differential equations. A software environment for these models has been developed, which can make use of parallel as well as sequential hardware. Further discussion of the methodology and of the CA model can be found in the literature and in the 1999 Battelle Conference Proceedings, alongside with comparisons with experimental results on the pilot scale.We discuss here the results which have been achieved in the first two applications of the methodology to real cases, referring to two sites in Germany: one (site A) was contaminated mainly by TPH, the other (site B) by PAH. Pilot scale studies have been performed in both cases, where the indigenous bacteria were stimulated by the flow of an aqueous solution of nutrients and hydrogen peroxide. The pilot plants were composed by a series of three cylinders filled with contaminated soil coming from the site. The model has been adapted to the two different cases, in order to match both the overall degradation rate and its space-time profile. After adaptation, the model has been applied in the field without any further change. The major results are as follows: in site A, the overall degradation rate is predicted with reasonable accuracy, while the detailed spatial distribution on its boundaries is not satisfactory. This is likely to be due to the fact that site A is actually a part of a larger site, and the boundaries are affected by operations taking place outside the monitored area and not considered in the model. In site B, both the overall degradation rate and the spatial distribution are correctly forecasted.What is particularly worth noticing is that the overall pilot-plant degradation rate is similar in the two cases, while the kinetics in the field differ by about an order of magnitude. The model correctly forecasts this difference, and it also allows one to understand the reason of the difference. So, while a naive approach would have predicted similar rate constants in the two cases, the use of CabCol allows to forecast the different rates in the field. The importance of such a forecast for determining the duration and the cost of the remediation is obvious.Since two cases have been so far fully worked out, we cannot claim a general validity of the methodology; however, these first real field applications show very promising and potentially useful results in the scale-up from the lab to the field.


2001 - CELLULAR AUTOMATA AND COMPLEX SYSTEMS SIMULATION: SOME CASE STUDIES [Articolo su rivista]
Serra, Roberto
abstract

missing


2001 - Cellular automata: from a theoretical computational model to its application to complex systems [Articolo su rivista]
Bandini, S.; Mauri, G.; Serra, Roberto
abstract

This introductory paper gives a short survey of Cellular Automata (CA's), from different points of view. It starts with the main definitions and theoretical results about CA's as an abstract model of computation or as discrete dynamical systems. Then, the main applications of CA's in different fields (biology, physics…) as a model of complex systems are illustrated. Finally, implementations of the CA model on parallel computing platforms are surveyed.


2001 - Continuous genetic networks [Articolo su rivista]
Serra, Roberto; Villani, Marco; A., Salvemini
abstract

The dynamics of a continuous model of genetic networks, which generalizes the random boolean network one, is described


2001 - Differential equations and cellular automata models of the growth of cell cultures and transformation foci [Articolo su rivista]
Serra, Roberto; Villani, Marco; A., Colacci
abstract

missing


2001 - MODELLING THE BIRTH OF TRANSFORMATION FOCI IN CELL CULTURES [Articolo su rivista]
Serra, Roberto; Villani, Marco; A., Colacci
abstract

missing


2001 - PARALLEL COMPUTING: SPECIAL ISSUE ON CELLULAR AUTOMATA [Curatela]
S., Bandini; G., Mauri; Serra, Roberto
abstract

MISSING


2001 - PREFACE TO THE SECTION "MODELS OF THE MIND" [Prefazione o Postfazione]
Serra, Roberto
abstract


2001 - THE EMERGENCE OF THE MIND [Curatela]
S., Colonna; Serra, Roberto; S., Carra'; M., Di Francesco; D., Parisi
abstract

PROCEEDINGS OF AN INTERNATIONAL WORKSHOP HELD IN MILAN, MARCH 2000


2000 - A cellular automata model for the simulation of in vitro carcinogenesis tests [Relazione in Atti di Convegno]
Serra, Roberto; Villani, Marco; A., Colacci
abstract

In vitro tests are very powerful methods to assess the carcinogenic effects of different substances and to study the initial phases of tumor development. A CA model of the formation of transformation foci in cell cultures which are exposed to a carcinogen is presented here, based on known facts about carcinogenesis and about reasonable assumptions, which gives rise to a cell growth dynamics similar to the one experimentally observed. The model can be used to test formal hypotheses about different interfering phenomena and about their relative strength


2000 - A new dynamical model of biodegradation [Relazione in Atti di Convegno]
Villani, Marco; M., Mazzanti; M., Padovani; M., Andretta; Serra, Roberto; S., Di Gregorio; R., Rongo; W., Spataro
abstract

A new cellular automata model of the complex set of interacting phenomena which take place in bioremediation is described, which allows to treat a wider set of cases. The model has proven able to accurately describe several experimental data on a pilot plant. The general theory and the C.A. transition function are shown, and an example of the whole framework (fluid dynamics, chemical and biological layer) is analyzed and compared with experimental results


2000 - Cellular automata model for parallel simulation of contamination processes by oil in porous soils [Relazione in Atti di Convegno]
M., Andretta; M. A., Mazzanti; Serra, Roberto; Villani, Marco; S., Di Gregorio; R., Rongo; W., Spataro
abstract

Cellular automata (CA) can be applied for modeling the dynamics of spatially extended physical systems, representing an alternative to the classical PDE approach. Furthermore, CA implementation on large parallel computer is straightforward because of their characteristics of parallelism and acentrism. In this paper, a CA model for simulating the fluid-dynamics of contaminated porous soils is introduced. It is based on an empirical method for modeling complex phenomena from a macroscopic viewpoint; such a choice is motivated by the aim of simulating large scale systems. We report here first significant applications of this model concerning case studies and experiments in pilot plants. The results of the applications and a comparison between case studies and simulations are presented and commented on.


2000 - NEURAL NETWORKS FOR SULPHUR DIOXIDE GROUND LEVEL FORECASTING [Articolo su rivista]
M., Andretta; A., Eleuteri; F., Fortezza; F., Manco; L., Mingozzi; Serra, Roberto; R., Tagliaferri
abstract

missing


2000 - THE SCIENCE OF COMPLEX SYSTEMS [Prefazione o Postfazione]
Serra, Roberto
abstract


1999 - An empirical method for modelling and simulating some complex macroscopic phenomena by cellular automata [Articolo su rivista]
DI GREGORIO, S.; Serra, Roberto
abstract

Novel parallel computing models sometime represent a valid alternative to standard differential equation methods inmodelling complex phenomena. In particular, Cellular Automata (CA) provide such an alternative approach for some complexnatural systems, whose behaviour can be described in terms of local interactions of their constituent parts. This paper illustratesan empirical method applied with interesting results in modelling and simulating some complex macroscopic phenomena.While classical CA are based upon elementary automata, with few states and a simple transition function, in order to dealwith macroscopic phenomena it is often necessary to allow a large number of different states a more complicated transition.The notion of substate is introduced in the macroscopic case for decomposing the state of the cell. The values associatedto substates can change in time either due to interactions among substates inside the cell (internal transformations) or to localinteractions among neighbouring cells.The internal transformations are treated in a way similar to ordinary difference equations.The local interactions among cells can be often treated according to an algorithm for the minimisation of differences, whichdescribes a tendency of conserved quantities to reach an equilibrium distribution.A large class of complex macroscopic phenomena seem to satisfy the applicability conditions of such an empirical method;some of them are briefly reviewed.


1999 - Applying cellular automata to complex environmental problems: the simulation of the bioremediation of contaminated soils [Articolo su rivista]
S., DI GREGORIO; Serra, Roberto; Villani, Marco
abstract

Cellular automata can be applied to modelling the dynamics of spatially extended physicalsystems, and represent an alternative to the classical PDE approach. In this paper a macroscopiccellular automata model for simulating the bioremediation of contaminated soils is introduced.The choice of macroscopic automata is motivated by the aim to simulate large-scale systems.It is suggested that in some cases, where the basic laws of continuum mechanics cannot bedirectly applied without adding phenomenological assumptions, and where the equation systemis not amenable to analytical solution, direct discrete modelling may represent a convenientalternative to the use of continuum models, followed by numerical discretization. This hypothesisis empirically tested in the bioremediation case.The model describes the bioremediation of contaminated soils, which relies upon the use ofindigeneous microorganisms to degrade the contaminant: bioremediation models pose particularchallenges as several physical, chemical and biological phenomena interact in a disordered andpartially unknown matrix (the soil). The model is hierarchical, and is composed by a fluiddynamical layer, a solute description layer and a biological layer. The model has been testedin a pilot plant, in the case of contamination by phenol. The values of the phenomenologicalparameters have been determined by the use of genetic algorithms. The model has proven capableto carefully describe experimental results in a wide range of experimental conditions. It has alsobeen run on a MIMD parallel architecture, achieving a high speed-up. It therefore representsan example of application of cellular automata to a real-world problem which has a very highsocial and economic importance, and where progresses in modelling may greatly improve theeffectiveness of the decontamination interventions.


1999 - Biorisanamento in-situ di terreni contaminati [Relazione in Atti di Convegno]
Serra, Roberto; Mazzanti, M.; Villani, Marco; Andretta, M.; Di Gregorio, S.; Rongo, R.; Spataro, W.
abstract

Descrizione di un modello ad automi cellulari per la simulazione dei flussi di falda, del trasporto di inquinanti, e di azioni di bioremediation


1999 - Colombo: a new model for the simulation of soil remediation [Relazione in Atti di Convegno]
Serra, Roberto; M., Andretta; M., Mazzanti; Villani, Marco; S., Di Gregorio
abstract

A main goal in order to face problems concerning polluted soil is the capability of computing the multiphase flows (gas, water, oils) in the soil matrix . In this paper, a CA model for simulating the fluid-dynamics of contaminated porous soils is introduced. The choice of macroscopic automata is motivated by the aim of simulating large scale systems.


1999 - NUOVI MODELLI DI RETI GENETICHE [Articolo su rivista]
Serra, Roberto
abstract

Le reti genetiche sono, fin dalla nascita negli ormai remoti anni ’70, “strani modelli”: si tratta infatti di sistemi dinamici che tentano di catturare le proprietà generiche di reti di geni interagenti [Kauffman, 1993 e 1995]. Non si tenta quindi di descrivere la rete di interazioni di una specifica cellula, ma di capire quali comportamenti dinamici siano da attendersi quando si ha a che fare con un gran numero di geni che si influenzano reciprocamente, e quali siano le variabili principali che ne governano il comportamento.


1999 - Progetto Colombo: realizzazione di impianti pilota per la taratura e la verifica sperimentale del modello [Relazione in Atti di Convegno]
Andretta, M.; Campisi, T.; Mingozzi, L.; Villani, Marco; Serra, Roberto
abstract

L'articolo tratta la costruzione di impianti pilota per la validazione sperimentale di un modello ad automi cellulari, simulante eventi di biorisanamento


1999 - Progetto Colombo: un nuovo modello di simulazione di fenomeni di biorisanamento In-situ [Relazione in Atti di Convegno]
Andretta, M.; Mazzanti, M.; Villani, Marco; Serra, Roberto; Di Gregorio, S.
abstract

L'articolo tratta di un modello ad automi cellulari per la simulazione di eventi di biorisanamento, nato all'interno del progetto europeo COLOMBO


1998 - BIOTECHNOLOGY FOR SOIL REMEDIATION [Curatela]
Serra, Roberto
abstract

MISSING


1998 - Bioremediation simulation models [Relazione in Atti di Convegno]
Serra, Roberto; Di Gregorio, S.; Villani, Marco; Andretta, M.
abstract

The remediation of contaminated soils is one of today's major environmental problems in industrial countries. Among the different techniques which can be applied, in situ bioremediation, which relies upon the use of indigeneous microorganisms to degrade the contaminant, is one of the most attractive, both from an environmental and an economic viewpoint.A (macroscopic) cellular automata model is presented here, which describes the major phenomena which take place in bioremediation. The reasons why macroscopic cellular automata have been used are discussed. The model is hierarchical, and is composed by i) a fluid dynamical layer, which describes multiphase flow through the soil, ii) a solute description layer, which deals with solute transport, adsorption/desorption, chemical reactions and iii) a biological layer, which describes biomass growth and its interaction with the different chemicals.The model has been tested in a pilot plant, in the case of contamination by phenol.


1998 - CELLULAR AUTOMATA. RESEARCH TOWARDS INDUSTRY [Curatela]
S., Bandini; Serra, Roberto; F., Suggi Liverani
abstract

MISSING


1998 - Environmental applications of genetic algorithms [Relazione in Atti di Convegno]
Di Gregorio, S.; Serra, Roberto; Villani, Marco
abstract

An application of genetic algorithms to a problem of environmental restoration is presented. The application concerns the in-situ bioremediation of contaminated soils, where indigeneous bacteria are stimulated to degrade the contaminant, by introducing a suitable nutrient solution directly in the soil. Forecasting the results of field operations from laboratory and pilot plant data is very important, and it requires the use of simulation models, which describe the interaction between different physical, chemical and biological phenomena. The main features are briefly summarized of a bioremediation model based on the paradigm of cellular automata, which successfully describes data obtained at a pilot plant scale. Genetic algorithms have been used in order to tailor the model to a specific case, namely contamination by phenol.


1998 - Genetic network models of biodegradation [Relazione in Atti di Convegno]
Serra, Roberto; Villani, Marco; Salvemini, A.
abstract

The dynamical model of bacterial degradation of organic compounds which is discussed here provides a description of the degrading behaviour in terms of interacting genes which may switch from active to inactive state, thus providing a generalization of the well known Kauffman model of random boolean networks, which is well suited for single cells, to the multi-cell case. This generalization requires that the variables describing gene activation be real, instead of boolean. Moreover, the vast majority of the cell’s genes, which provide the standard metabolic machinery of the cell, are treated in a way different from the relatively few genes which are directly involved in the biodegradation : the latter ones are carefully described, while the effects of the former ones are described by an aggregate variable.Two different examples of specific models, which are both consistent with the overall framework, are introduced, and their dynamical behaviour is studied, in the particular case where all the genes are arranged on a 2-D regular square topology, with connections among neighbouring sites. Thus, the model is an example of a cellular-automata like model, and a continuum generalization of random boolean networks.


1998 - MODELLING THE INTERACTION OF PHYSICAL, CHEMICAL AND BIOLOGICAL PHENOMENA IN POROUS SOILS: A SUMMARY OF RESULTS [Articolo su rivista]
S., DI GREGORIO; Serra, Roberto; Villani, Marco
abstract

missing


1998 - Recent advances in dynamical models of bioremediation [Relazione in Atti di Convegno]
Serra, Roberto; Villani, Marco; Oricchio, D.; Di Gregorio, S.
abstract

A cellular automata model of the complex set of interacting phenomena which take place in bioremediation has proven able to accurately describe several experimental data on a pilot plant. There are some parameters in the model which are chosen in such a way as to match experimental data. In this paper it is shown that the model has interesting generalization capabilities, i.e. that it can lead to accurate predictions also in some cases which have not been used for parameter adaptation.Moreover, some possible variants are examined : the first one amounts to a model simplification by resorting to a local equilibrium assumption for the adsorption/desorption process, while in the second one a cellular automata with time variable step is introduced, in order to avoid some nonphysical situations which might arise in the original model. Both variants are tested and discussed, and it is shown that they do not lead to improved performance, at least on the available set of experimental data.


1997 - A CELLULAR AUTOMATA MODEL OF SOIL BIOREMEDIATION [Articolo su rivista]
S., DI GREGORIO; Serra, Roberto; Villani, Marco
abstract

The remediation of contaminated soils is one of the major environmental problems in industrial countries today. Among the different techniques that can be applied, in situ bioremediation, which relies upon the use of indigeneous microorganisms to degrade the contaminant, is one of the most attractive, both from an environmental and an economic viewpoint.A full-scale bioremediation process requires a number of laboratory and pilot-scale tests in order to assess the feasibility of the remediation, to define potential health threats, and to find optimal operating conditions.Scaling up from the laboratory to the field can greatly benefit from the development of reliable mathematical models, which need to deal with several interacting physical, chemical, and biological phenomena.A macroscopic cellular automata (CA) model is presented here, which describes the major phenomena that take place in bioremediation. The reasons for using macroscopic CA are discussed. The model is composed of three layers, each layer depending on the others.The model has been tested in a pilot plant in the case of contamination by phenol. The values of the phenomenological parameters have been determined by the use of genetic algorithms (GAs). The model has provencapable of carefully describing experimental results for a wide range of experimental conditions. It is therefore an application of CA models to a real-world problem of high social and economic relevance.


1997 - MODELLING BACTERIAL DEGRADATION OF ORGANIC COMPOUNDS WITH GENETIC NETWORKS [Articolo su rivista]
SERRA, Roberto; VILLANI, Marco
abstract

The bacterial degradation of organic compounds plays a crucial role in the biogeochemical cycles ofthe earth and in the clean!up of contaminated soils[ The processes are carried out by bacterial consortia\rather than isolated strains\ which are usually modelled by phenomenological kinetic equations whichdescribe a _ctitious\ homogeneous bacterial species which mimics the behaviour of the consortium[An alternative modelling framework is presented here\ where the bacterial consortia are consideredas networks of genes interacting with other genes as well as with chemicals\ which may be eitherintroduced from outside or produced by bacterial metabolism[ The model is based on an extension ofthe random Boolean network model of genetic networks\ which makes use of continuous dynamicalvariables[ Three di}erent models are introduced\ which di}er in the way how they account for theexistence of di}erent species] "i# a single supercell model\ where all the genes can interact strongly witheach other^ "ii# a graded interaction model\ where genes interact strongly within a species\ and weaklyamong di}erent species^ and "iii# a separate subsets model\ where genes interact only within species[It is shown how this modelling framework is sound\ as it is able to reproduce some of the genericbehaviours of bacterial consortia\ describing experimentally observed phenomena like populationchanges induced by contamination\ and preypredator dynamics[


1996 - Combining cellular automata and genetic search in complex environmental modelling [Relazione in Atti di Convegno]
Di Gregorio, S.; Serra, Roberto; Villani, Marco
abstract

Soil bioremediation is a highly complex phenomenon and involves several disciplines at the same time, including fluid dynamics, chemistry and biology. In this paper the fluid dynamical aspects of a cellular automata based model are discussed, and some comparisons with experimental data are presented. Genetic algorithms have been applied in order to tune the model to a specific case.


1996 - Mathematical models for bioremediation of contaminated soils [Relazione in Atti di Convegno]
Andretta, M.; Di Gegorio, S.; Serra, Roberto; Villani, Marco
abstract

L'articolo tratta di un modello ad automi cellulari di eventi di biorisanamento, simulante flusso di acqua e trasporto di inquinanti


1996 - Parallel simulation of soil contamination by cellular automata [Relazione in Atti di Convegno]
Di Gregorio, S.; Rongo, R.; Serra, Roberto; Spataro, W.; Spezzano, G.; Talia, D.; Villani, Marco
abstract

A new cellular automata model of the complex set of interacting phenomena which take place in bioremediation is described. The model allows the scaling between pilot plant situations and field operations, and - because its structure - shows interesting speed-up capabilities


1996 - Simulation of water flow through a porous soil by a Cellular Automaton model [Relazione in Atti di Convegno]
Di Gregorio, S.; Rongo, R.; Serra, Roberto; Spataro, W.; Villani, Marco
abstract

Soil bioremediation is a highly complex phenomenon and involves several disciplines at the same time, including fluid dynamics, chemistry and biology. A cellular automata model is currently under development, which deals with all these kinds of phenomena. In this paper the fluid dynamical aspects of this model are discussed, and some comparisons with experimental data are presented. Genetic algorithms have been applied in order to tune the model to a specific case.


1994 - SISTEMI COMPLESSI E PROCESSI COGNITIVI [Monografia/Trattato scientifico]
Serra, Roberto; G., Zanarini
abstract

MISSING


1993 - Machine learning and organizational learning processes [Articolo su rivista]
Warglien, M.; Serra, Roberto
abstract

missing


1990 - Complex systems and cognitive processes [Monografia/Trattato scientifico]
Serra, Roberto; G., Zanarini
abstract

missing


1990 - LEARNING AND BUCKET BRIGADE DYNAMICS IN CLASSIFIER SYSTEMS [Articolo su rivista]
M., Compiani; D., Montanari; Serra, Roberto
abstract

Classifier systems are rule-based adaptive systems whose learning capabilities emerge from processes of selection andcompetition within a population of rules (classifiers). These processes are ruled by the values of numerical variables whichmeasure the fitness of each rule. The system's adaptivity is ensured by a fitness reallocation mechanism (the bucket brigadealgorithm) and by genetic algorithms which are responsible for the internal dynamics of the system. In this paper we discussclassifier systems as dynamical systems, the main focus being on the asymptotic dynamics due to the bucket brigade,abstracting from the action of the genetics. This topic is discussed with reference to a specific task domain, in which the systemis used as a detector of statistical properties of periodic or fluctuating external environments. We also describe a majorconsequence of the genetics on the bucket brigade dynamics, namely the proliferation of individual rules into subpopulationsof equivalent classifiers; we then show that this can eventually lead to undesired stochastic behavior or to the destabilization ofcorrect solutions devised by the system.


1988 - COMPLEXITY IN NATURAL AND CULTURAL SYSTEMS [Articolo su rivista]
Serra, Roberto; G., Zanarini
abstract

MISSING


1988 - COOPERATIVE PHENOMENA IN ARTIFICIAL INTELLIGENCE [Articolo su rivista]
Serra, Roberto; G., Zanarini; F., Fasano
abstract

missing


1986 - ADIABATIC ELIMINATION OF FAST RELAXING VARIABLES IN SOCIO-ECONOMIC DYNAMICAL MODELS [Articolo su rivista]
H., Sedehi; Serra, Roberto; S., Vassallo
abstract

MISSING


1986 - INTRODUCTION TO THE PHYSICS OF COMPLEX SYSTEMS [Monografia/Trattato scientifico]
Serra, Roberto; G., Zanarini; M., Andretta; M., Compiani
abstract

missing


1986 - LA FISICA DEI SISTEMI COMPLESSI [Articolo su rivista]
M., Compiani; Serra, Roberto
abstract

MISSING


1986 - TRA ORDINE E CAOS [Monografia/Trattato scientifico]
Serra, Roberto; G., Zanarini
abstract

MISSING


1985 - NONEQUILIBRIUM STATISTICAL THERMODYNAMICS IN THE LIMIT OF LARGE RESISTANCE [Articolo su rivista]
B. H., Lavenda; Serra, Roberto
abstract

MISSING


1985 - THEORY OF ACTIVATED REACTION PROCESSES: NONLINEAR COUPLING BETWEEN REACTIVE AND NON REACTIVE MODES [Articolo su rivista]
M., Compiani; T., Fonseca; P., Grigolini; Serra, Roberto
abstract

Deviations from the Kramers preditions resulting from the couplmg between a reactive and a non-reactwe mode arestudied in both the low- and hi&-diction Iimits. It is alsO argued how this simple picture may provide a breakdown of theupper Iimit imposed on the relaxation rate by transdion state theory.


1985 - TRANSPORT PROPERTIES AND SOLITON MODELS OF POLYACETYLENE [Capitolo/Saggio]
M., Andretta; Serra, Roberto; G., Zanarini; K., Pendergast
abstract

MISSING


1984 - INTRODUZIONE ALLA FISICA DEI SISTEMI COMPLESSI [Monografia/Trattato scientifico]
Serra, Roberto; G., Zanarini; M., Andretta; M., Compiani
abstract

MISSING


1984 - SOLITONI E POLARONI IN POLIMERI ELETTRICAMENTE ATTIVI [Articolo su rivista]
M., Andretta; Serra, Roberto; G., Zanarini
abstract

MISSING


1984 - STOCHASTIC INTEGRALS INDUCED BY TIME SCALE CHANGES [Articolo su rivista]
B. H., Lavenda; Serra, Roberto
abstract

MISSING


1979 - A COMMENT ON PROTON ELECTRIC POLARIZABILITY [Articolo su rivista]
P., Mazzanti; Serra, Roberto; F., Cannata
abstract

MISSING