Towards a Boolean network-based Computational Model for Cell Differentiation and its applications to Robotics

Living organisms are the ultimate product of a series of complex processes that take place within—and among—biological cells. Most of these processes, such as cell differentiation, are currently poorly understood. Cell differentiation is the process by which cells progressively specialise. Being a fundamental process within cells, its dysregulations have dramatic implications in biological organisms ranging from developmental issues to cancer formation. The thesis objective is to contribute to the progress in the understanding of cell differentiation and explore the applications of its properties for designing artificial systems. The proposed approach, which relies on Boolean networks based modelling and on the theory of dynamical systems, aims at investigating the general mechanisms underlying cell differentiation. The results obtained contribute to taking a further step towards the formulation of a general theoretical framework—so far missing—for cellular differentiation. We conducted an in-depth analysis of the impact of self-loops in random Boolean networks ensembles. We proposed a new model of differentiation driven by a simplified bio-inspired methylation mechanism in Boolean models of genetic regulatory networks. On the artificial side, by introducing the conceptual metaphor of the “attractor landscape” and related proofs of concept that support its potential, we paved the way for a new research direction in robotics called behavioural differentiation robotics: a branch of robotics dealing with the designing of robots capable of expressing different behaviours in a way similar to that of biological cells that undergo differentiation. The implications of the results achieved may have beneficial effects on medical research. Indeed, the proposed approach can foster new questions, experiments and in turn, models that hopefully in the next future will take us to cure differentiation-related diseases such as cancer. Our work may also contribute to address questions concerning the evolution of complex behaviours and to help design robust and adaptive robots

Modelling and simulating in systems biology: an approach based on multi-agent systems

Systems Biology is an innovative way of doing biology recently raised in bio-informatics contexts, characterised by the study of biological systems as complex systems with a strong focus on the system level and on the interaction dimension. In other words, the objective is to understand biological systems as a whole, putting on the foreground not only the study of the individual parts as standalone parts, but also of their interaction and of the global properties that emerge at the system level by means of the interaction among the parts. This thesis focuses on the adoption of multi-agent systems (MAS) as a suitable paradigm for Systems Biology, for developing models and simulation of complex biological systems. Multi-agent system have been recently introduced in informatics context as a suitabe paradigm for modelling and engineering complex systems. Roughly speaking, a MAS can be conceived as a set of autonomous and interacting entities, called agents, situated in some kind of nvironment, where they fruitfully interact and coordinate so as to obtain a coherent global system behaviour. The claim of this work is that the general properties of MAS make them an effective approach for modelling and building simulations of complex biological systems, following the methodological principles identified by Systems Biology. In particular, the thesis focuses on cell populations as biological systems. In order to support the claim, the thesis introduces and describes (i) a MAS-based model conceived for modelling the dynamics of systems of cells interacting inside cell environment called niches. (ii) a computational tool, developed for implementing the models and executing the simulations. The tool is meant to work as a kind of virtual laboratory, on top of which kinds of virtual experiments can be performed, characterised by the definition and execution of specific models implemented as MASs, so as to support the validation, falsification and improvement of the models through the observation and analysis of the simulations. A hematopoietic stem cell system is taken as reference case study for formulating a specific model and executing virtual experiments

Rhythms and Evolution: Effects of Timing on Survival

The evolution of metabolism regulation is an intertwined process, where different strategies are constantly being developed towards a cognitive ability to perceive and respond to an environment. Organisms depend on an orchestration of a complex set of chemical reactions: maintaining homeostasis with a changing environment, while simultaneously sending material and energetic resources to where they are needed. The success of an organism requires efficient metabolic regulation, highlighting the connection between evolution, population dynamics and the underlying biochemistry. In this work, I represent organisms as coupled information-processing networks, that is, gene-regulatory networks receiving signals from the environment and acting on chemical reactions, eventually affecting material flows. I discuss the mechanisms through which metabolism control is improved during evolution and how the nonlinearities of competition influence this solution-searching process. The propagation of the populations through the resulting landscapes generally point to the role of the rhythm of cell division as an essential phenotypic feature driving evolution. Subsequently, as it naturally follows, different representations of organisms as oscillators are constructed to indicate more precisely how the interplay between competition, maturation timing and cell-division synchronisation affects the expected evolutionary outcomes, not always leading to the \"survival of the fastest\"

An Initial Framework Assessing the Safety of Complex Systems

Trabajo presentado en la Conference on Complex Systems, celebrada online del 7 al 11 de diciembre de 2020.Atmospheric blocking events, that is large-scale nearly stationary atmospheric pressure patterns, are often associated with extreme weather in the mid-latitudes, such as heat waves and cold spells which have significant consequences on ecosystems, human health and economy. The high impact of blocking events has motivated numerous studies. However, there is not yet a comprehensive theory explaining their onset, maintenance and decay and their numerical prediction remains a challenge. In recent years, a number of studies have successfully employed complex network descriptions of fluid transport to characterize dynamical patterns in geophysical flows. The aim of the current work is to investigate the potential of so called Lagrangian flow networks for the detection and perhaps forecasting of atmospheric blocking events. The network is constructed by associating nodes to regions of the atmosphere and establishing links based on the flux of material between these nodes during a given time interval. One can then use effective tools and metrics developed in the context of graph theory to explore the atmospheric flow properties. In particular, Ser-Giacomi et al. [1] showed how optimal paths in a Lagrangian flow network highlight distinctive circulation patterns associated with atmospheric blocking events. We extend these results by studying the behavior of selected network measures (such as degree, entropy and harmonic closeness centrality)at the onset of and during blocking situations, demonstrating their ability to trace the spatio-temporal characteristics of these events.This research was conducted as part of the CAFE (Climate Advanced Forecasting of sub-seasonal Extremes) Innovative Training Network which has received funding from the European Union’s Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie grant agreement No. 813844

Complexity in Economic and Social Systems

There is no term that better describes the essential features of human society than complexity. On various levels, from the decision-making processes of individuals, through to the interactions between individuals leading to the spontaneous formation of groups and social hierarchies, up to the collective, herding processes that reshape whole societies, all these features share the property of irreducibility, i.e., they require a holistic, multi-level approach formed by researchers from different disciplines. This Special Issue aims to collect research studies that, by exploiting the latest advances in physics, economics, complex networks, and data science, make a step towards understanding these economic and social systems. The majority of submissions are devoted to financial market analysis and modeling, including the stock and cryptocurrency markets in the COVID-19 pandemic, systemic risk quantification and control, wealth condensation, the innovation-related performance of companies, and more. Looking more at societies, there are papers that deal with regional development, land speculation, and the-fake news-fighting strategies, the issues which are of central interest in contemporary society. On top of this, one of the contributions proposes a new, improved complexity measure

Using MapReduce Streaming for Distributed Life Simulation on the Cloud

Distributed software simulations are indispensable in the study of large-scale life models but often require the use of technically complex lower-level distributed computing frameworks, such as MPI. We propose to overcome the complexity challenge by applying the emerging MapReduce (MR) model to distributed life simulations and by running such simulations on the cloud. Technically, we design optimized MR streaming algorithms for discrete and continuous versions of Conway’s life according to a general MR streaming pattern. We chose life because it is simple enough as a testbed for MR’s applicability to a-life simulations and general enough to make our results applicable to various lattice-based a-life models. We implement and empirically evaluate our algorithms’ performance on Amazon’s Elastic MR cloud. Our experiments demonstrate that a single MR optimization technique called strip partitioning can reduce the execution time of continuous life simulations by 64%. To the best of our knowledge, we are the first to propose and evaluate MR streaming algorithms for lattice-based simulations. Our algorithms can serve as prototypes in the development of novel MR simulation algorithms for large-scale lattice-based a-life models.https://digitalcommons.chapman.edu/scs_books/1014/thumbnail.jp

Digital control networks for virtual creatures

Robot control systems evolved with genetic algorithms traditionally take the form of floating-point neural network models. This thesis proposes that digital control systems, such as quantised neural networks and logical networks, may also be used for the task of robot control. The inspiration for this is the observation that the dynamics of discrete networks may contain cyclic attractors which generate rhythmic behaviour, and that rhythmic behaviour underlies the central pattern generators which drive lowlevel motor activity in the biological world. To investigate this a series of experiments were carried out in a simulated physically realistic 3D world. The performance of evolved controllers was evaluated on two well known control tasks—pole balancing, and locomotion of evolved morphologies. The performance of evolved digital controllers was compared to evolved floating-point neural networks. The results show that the digital implementations are competitive with floating-point designs on both of the benchmark problems. In addition, the first reported evolution from scratch of a biped walker is presented, demonstrating that when all parameters are left open to evolutionary optimisation complex behaviour can result from simple components

The emergence of self-organisation in social systems: the case of the geographic industrial clusters

The objective of this work is to use complexity theory to propose a new interpretation of industrial clusters. Industrial clusters constitute a specific type of econosphere, whose driving principles are self-organisation, economies of diversity and a configuration that optimises the exploration of diversity starting from the configuration of connectivity of the system. This work shows the centrality of diversity by linking complexity theory (intended as "a method for understanding diversity"') to different concepts such as power law distributions, self-organisation, autocatalytic cycles and connectivity.I propose a method to distinguish self-organising from non self-organising agglomerations, based on the correlation between self-organising dynamics and power law network theories. Self-organised criticality, rank-size rule and scale-free networks theories become three aspects indicating a common underlying pattern, i.e. the edge of chaos dynamic. I propose a general model of development of industrial clusters, based on the mutual interaction between social and economic autocatalytic cycle. Starting from Kauffman's idea(^2) on the autocatalytic properties of diversity, I illustrate how the loops of the economies of diversity are based on the expansion of systemic diversity (product of diversity and connectivity). My thesis provides a way to measure systemic diversity. In particular I introduce the distinction between modular innovation at the agent level and architectural innovation at the network level and show that the cluster constitutes an appropriate organisational form to manage the tension and dynamics of simultaneous modular and architectural innovation. The thesis is structured around two propositions: 1. Self-organising systems are closer to a power law than hierarchical systems or aggregates (collection of parts). For industrial agglomerations (SLLs), the closeness to a power law is related to the degree of self-organisation present in the agglomeration, and emerges in the agglomeration’s structural and/or behavioural properties subject to self-organising dynamic.2. Self-organising systems maximise the product of diversity times connectivity at a rate higher than hierarchical systems

A complex systems approach to education in Switzerland

The insights gained from the study of complex systems in biological, social, and engineered systems enables us not only to observe and understand, but also to actively design systems which will be capable of successfully coping with complex and dynamically changing situations. The methods and mindset required for this approach have been applied to educational systems with their diverse levels of scale and complexity. Based on the general case made by Yaneer Bar-Yam, this paper applies the complex systems approach to the educational system in Switzerland. It confirms that the complex systems approach is valid. Indeed, many recommendations made for the general case have already been implemented in the Swiss education system. To address existing problems and difficulties, further steps are recommended. This paper contributes to the further establishment complex systems approach by shedding light on an area which concerns us all, which is a frequent topic of discussion and dispute among politicians and the public, where billions of dollars have been spent without achieving the desired results, and where it is difficult to directly derive consequences from actions taken. The analysis of the education system's different levels, their complexity and scale will clarify how such a dynamic system should be approached, and how it can be guided towards the desired performance

Self-loops favour diversification and asymmetric transitions between attractors in boolean network models

The process of cell differentiation manifests properties such as non-uniform robustness and asymmetric transitions among cell types. In this paper we adopt Boolean networks to model cellular differentiation, where attractors (or set of attractors) in the network landscape epitomise cell types. Since changes in network topology and functions strongly impact attractor landscape characteristics, in this paper we study how self-loops influence diversified robustness and asymmetry of transitions. The purpose of this study is to identify the best configuration for a network owning these properties. Our results show that a moderate amount of self-loops make random Boolean networks more suitable to reproduce differentiation phenomena. This is a further evidence that self-loops play an important role in genetic regulatory networks