A third transition in science?

Since Newton, classical and quantum physics depend upon the 'Newtonian paradigm'. The relevant variables of the system are identified. For example, we identify the position and momentum of classical particles. Laws of motion in differential form connecting the variables are formulated. An example is Newton's three laws of motion. The boundary conditions creating the phase space of all possible values of the variables are defined. Then, given any initial condition, the differential equations of motion are integrated to yield an entailed trajectory in the prestated phase space. It is fundamental to the Newtonian paradigm that the set of possibilities that constitute the phase space is always definable and fixed ahead of time. This fails for the diachronic evolution of ever-new adaptations in any biosphere. Living cells achieve constraint closure and construct themselves. Thus, living cells, evolving via heritable variation and natural selection, adaptively construct new-in-the-universe possibilities. We can neither define nor deduce the evolving phase space: we can use no mathematics based on set theory to do so. We cannot write or solve differential equations for the diachronic evolution of ever-new adaptations in a biosphere. Evolving biospheres are outside the Newtonian paradigm. There can be no theory of everything that entails all that comes to exist. We face a third major transition in science beyond the Pythagorean dream that 'all is number' echoed by Newtonian physics. However, we begin to understand the emergent creativity of an evolving biosphere: emergence is not engineering.

The hiatus between organism and machine evolution: Contrasting mixed microbial communities with robots.

Mixed microbial communities, usually composed of various bacterial and fungal species, are fundamental in a plethora of environments, from soil to human gut and skin. Their evolution is a paradigmatic example of intertwined dynamics, where not just the relations among species plays a role, but also the opportunities - and possible harms - that each species presents to the others. These opportunities are in fact affordances, which can be seized by heritable variations and selection. In this paper, starting from a systemic viewpoint of mixed microbial communities, we focus on the pivotal role of affordances in evolution and we contrast it to the artificial evolution of programs and robots. We maintain that the two realms are neatly separated, in that natural evolution proceeds by extending the space of its possibilities in a completely open way, while the latter is inherently limited by the algorithmic framework in which it is defined. This discrepancy characterizes also an envisioned setting in which robots evolve in the physical world. We present arguments supporting our claim and we propose an experimental setting for assessing our statements. Rather than just discussing the limitations of the artificial evolution of machines, the aim of this contribution is to emphasize the tremendous potential of the evolution of the biosphere, beautifully represented by the evolution of communities of microbes.

On the Criticality of Adaptive Boolean Network Robots.

Systems poised at a dynamical critical regime, between order and disorder, have been shown capable of exhibiting complex dynamics that balance robustness to external perturbations and rich repertoires of responses to inputs. This property has been exploited in artificial network classifiers, and preliminary results have also been attained in the context of robots controlled by Boolean networks. In this work, we investigate the role of dynamical criticality in robots undergoing online adaptation, i.e., robots that adapt some of their internal parameters to improve a performance metric over time during their activity. We study the behavior of robots controlled by random Boolean networks, which are either adapted in their coupling with robot sensors and actuators or in their structure or both. We observe that robots controlled by critical random Boolean networks have higher average and maximum performance than that of robots controlled by ordered and disordered nets. Notably, in general, adaptation by change of couplings produces robots with slightly higher performance than those adapted by changing their structure. Moreover, we observe that when adapted in their structure, ordered networks tend to move to the critical dynamical regime. These results provide further support to the conjecture that critical regimes favor adaptation and indicate the advantage of calibrating robot control systems at dynamical critical states.

The World Is Not a Theorem.

The evolution of the biosphere unfolds as a luxuriant generative process of new living forms and functions. Organisms adapt to their environment, exploit novel opportunities that are created in this continuous blooming dynamics. Affordances play a fundamental role in the evolution of the biosphere, for organisms can exploit them for new morphological and behavioral adaptations achieved by heritable variations and selection. This way, the opportunities offered by affordances are then actualized as ever novel adaptations. In this paper, we maintain that affordances elude a formalization that relies on set theory: we argue that it is not possible to apply set theory to affordances; therefore, we cannot devise a set-based mathematical theory to deduce the diachronic evolution of the biosphere.

The Impact of Self-Loops on Boolean Networks Attractor Landscape and Implications for Cell Differentiation Modelling.

Boolean networks are a notable model of gene regulatory networks and, particularly, prominent theories discuss how they can capture cellular differentiation processes. One frequent motif in gene regulatory networks, especially in those circuits involved in cell differentiation, is autoregulation. In spite of this, the impact of autoregulation on Boolean network attractor landscape has not yet been extensively discussed in literature. In this paper we propose to model autoregulation as self-loops, and analyse how the number of attractors and their robustness may change once they are introduced in a well-known and widely used Boolean networks model, namely random Boolean networks. Results show that self-loops provide an evolutionary advantage in dynamic mechanisms of cells, by increasing both number and maximal robustness of attractors. These results provide evidence to the hypothesis that autoregulation is a straightforward functional component to consolidate cell dynamics, mainly in differentiation processes.

Emergence of Organisms.

Since early cybernetics studies by Wiener, Pask, and Ashby, the properties of living systems are subject to deep investigations. The goals of this endeavour are both understanding and building: abstract models and general principles are sought for describing organisms, their dynamics and their ability to produce adaptive behavior. This research has achieved prominent results in fields such as artificial intelligence and artificial life. For example, today we have robots capable of exploring hostile environments with high level of self-sufficiency, planning capabilities and able to learn. Nevertheless, the discrepancy between the emergence and evolution of life and artificial systems is still huge. In this paper, we identify the fundamental elements that characterize the evolution of the biosphere and open-ended evolution, and we illustrate their implications for the evolution of artificial systems. Subsequently, we discuss the most relevant issues and questions that this viewpoint poses both for biological and artificial systems.

Evolving Always-Critical Networks.

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.

Automatic Off-Line Design of Robot Swarms: A Manifesto.

Designing collective behaviors for robot swarms is a difficult endeavor due to their fully distributed, highly redundant, and ever-changing nature. To overcome the challenge, a few approaches have been proposed, which can be classified as manual, semi-automatic, or automatic design. This paper is intended to be the manifesto of the automatic off-line design for robot swarms. We define the off-line design problem and illustrate it via a possible practical realization, highlight the core research questions, raise a number of issues regarding the existing literature that is relevant to the automatic off-line design, and provide guidelines that we deem necessary for a healthy development of the domain and for ensuring its relevance to potential real-world applications.

Complexity Measures: Open Questions and Novel Opportunities in the Automatic Design and Analysis of Robot Swarms.

Complexity measures and information theory metrics in general have recently been attracting the interest of multi-agent and robotics communities, owing to their capability of capturing relevant features of robot behaviors, while abstracting from implementation details. We believe that theories and tools from complex systems science and information theory may be fruitfully applied in the near future to support the automatic design of robot swarms and the analysis of their dynamics. In this paper we discuss opportunities and open questions in this scenario.

Candidate germline polymorphisms of genes belonging to the pathways of four drugs used in osteosarcoma standard chemotherapy associated with risk, survival and toxicity in non-metastatic high-grade osteosarcoma.

This study aimed to identify associations between germline polymorphisms and risk of high-grade osteosarcoma (HGOS) development, event-free survival (EFS) and toxicity in HGOS patients treated with neo-adjuvant chemotherapy and surgery.Germline polymorphisms of 31 genes known to be relevant for transport or metabolism of all four drugs used in HGOS chemotherapy (methotrexate, doxorubicin, cisplatin and ifosfamide) were genotyped in 196 patients with HGOS and in 470 healthy age and gender-matched controls. Of these 196 HGOS patients, a homogeneously treated group of 126 patients was considered for survival analyses (survival cohort). For 57 of these, treatment-related toxicity data were available (toxicity cohort).Eleven polymorphisms were associated with increased risk of developing HGOS (p < 0.05). The distribution of polymorphisms in patients was characterized by a higher Shannon entropy. In the survival cohort (n = 126, median follow-up = 126 months), genotypes of ABCC2_1249A/G, GGH_452T/C, TP53_IVS2+38G/C and CYP2B6*6 were associated with EFS (p < 0.05). In the toxicity cohort (n = 57), genotypes of ABCB1_1236T/C, ABCC2_1249A/G, ABCC2_3972A/G, ERCC1_8092T/G, XPD_23591A/G, XRCC3_18067T/C, MTHFR_1298A/C and GGH_16T/C were associated with elevated risk for toxicity development (p < 0.05).The results obtained in this retrospective study indicate that the aforementioned germline polymorphisms significantly impact on the risk of HGOS development, EFS and the occurrence of chemotherapy-related toxicity. These findings should be prospectively validated with the aim of optimizing and tailoring HGOS treatment in the near future.

MAGMA: a multiagent architecture for metaheuristics.

In this work, we introduce a multiagent architecture called the MultiAGent Metaheuristic Architecture (MAGMA) conceived as a conceptual and practical framework for metaheuristic algorithms. Metaheuristics can be seen as the result of the interaction among different kinds of agents: The basic architecture contains three levels, each hosting one or more agents. Level-0 agents build solutions, level-1 agents improve solutions, and level-2 agents provide the high level strategy. In this framework, classical metaheuristic algorithms can be smoothly accommodated and extended. The basic three level architecture can be enhanced with the introduction of a fourth level of agents (level-3 agents) coordinating lower level agents. With this additional level, MAGMA can also describe, in a uniform way, cooperative search and, in general, any combination of metaheuristics. We describe the entire architecture, the structure of agents in each level in terms of tuples, and the structure of their coordination as a labeled transition system. We propose this perspective with the aim to achieve a better and clearer understanding of metaheuristics, obtain hybrid algorithms, suggest guidelines for a software engineering-oriented implementation and for didactic purposes. Some specializations of the general architecture will be provided in order to show that existing metaheuristics [e.g., greedy randomized adaptive procedure (GRASP), ant colony optimization (ACO), iterated local search (ILS), memetic algorithms (MAs)] can be easily described in our framework. We describe cooperative search and large neighborhood search (LNS) in the proposed framework exploiting level-3 agents. We show also that a simple hybrid algorithm, called guided restart ILS, can be easily conceived as a combination of existing components in our framework.