Dynamics of growth factor production in monolayers of cancer cells and evolution of resistance to anticancer therapies

Tumor heterogeneity is well documented for many characters, including the production of growth factors, which improve tumor proliferation and promote resistance against apoptosis and against immune reaction. What maintains heterogeneity remains an open question that has implications for diagnosis and treatment. While it has been suggested that therapies targeting growth factors are robust against evolved resistance, current therapies against growth factors, like antiangiogenic drugs, are not effective in the long term, as resistant mutants can evolve and lead to relapse. We use evolutionary game theory to study the dynamics of the production of growth factors by monolayers of cancer cells and to understand the effect of therapies that target growth factors. The dynamics depend on the production cost of the growth factor, on its diffusion range and on the type of benefit it confers to the cells. Stable heterogeneity is a typical outcome of the dynamics, while a pure equilibrium of nonproducer cells is possible under certain conditions. Such pure equilibrium can be the goal of new anticancer therapies. We show that current therapies, instead, can be effective only if growth factors are almost completely eliminated and if the reduction is almost immediate

Complex network analysis and nonlinear dynamics

This chapter aims at reviewing complex network and nonlinear dynamical models and methods that were either developed for or applied to socioeconomic issues, and pertinent to the theme of New Economic Geography. After an introduction to the foundations of the field of complex networks, the present summary introduces some applications of complex networks to economics, finance, epidemic spreading of innovations, and regional trade and developments. The chapter also reviews results involving applications of complex networks to other relevant socioeconomic issue

Stable Heterogeneity for the Production of Diffusible Factors in Cell Populations

The production of diffusible molecules that promote survival and growth is common in bacterial and eukaryotic cell populations, and can be considered a form of cooperation between cells. While evolutionary game theory shows that producers and non-producers can coexist in well-mixed populations, there is no consensus on the possibility of a stable polymorphism in spatially structured populations where the effect of the diffusible molecule extends beyond one-step neighbours. I study the dynamics of biological public goods using an evolutionary game on a lattice, taking into account two assumptions that have not been considered simultaneously in existing models: that the benefit of the diffusible molecule is a non-linear function of its concentration, and that the molecule diffuses according to a decreasing gradient. Stable coexistence of producers and non-producers is observed when the benefit of the molecule is a sigmoid function of its concentration, while strictly diminishing returns lead to coexistence only for very specific parameters and linear benefits never lead to coexistence. The shape of the diffusion gradient is largely irrelevant and can be approximated by a step function. Since the effect of a biological molecule is generally a sigmoid function of its concentration (as described by the Hill equation), linear benefits or strictly diminishing returns are not an appropriate approximations for the study of biological public goods. A stable polymorphism of producers and non-producers is in line with the predictions of evolutionary game theory and likely to be common in cell populations

Optimal interdependence between networks for the evolution of cooperation

Recent research has identified interactions between networks as crucial for the outcome of evolutionary games taking place on them. While the consensus is that interdependence does promote cooperation by means of organizational complexity and enhanced reciprocity that is out of reach on isolated networks, we here address the question just how much interdependence there should be. Intuitively, one might assume the more the better. However, we show that in fact only an intermediate density of sufficiently strong interactions between networks warrants an optimal resolution of social dilemmas. This is due to an intricate interplay between the heterogeneity that causes an asymmetric strategy flow because of the additional links between the networks, and the independent formation of cooperative patterns on each individual network. Presented results are robust to variations of the strategy updating rule, the topology of interdependent networks, and the governing social dilemma, thus suggesting a high degree of universality

Optimal distribution of incentives for public cooperation in heterogeneous interaction environments

In the framework of evolutionary games with institutional reciprocity, limited incentives are at disposal for rewarding cooperators and punishing defectors. In the simplest case, it can be assumed that, depending on their strategies, all players receive equal incentives from the common pool. The question arises, however, what is the optimal distribution of institutional incentives? How should we best reward and punish individuals for cooperation to thrive? We study this problem for the public goods game on a scale-free network. We show that if the synergetic effects of group interactions are weak, the level of cooperation in the population can be maximized simply by adopting the simplest "equal distribution" scheme. If synergetic effects are strong, however, it is best to reward high-degree nodes more than low-degree nodes. These distribution schemes for institutional rewards are independent of payoff normalization. For institutional punishment, however, the same optimization problem is more complex, and its solution depends on whether absolute or degree-normalized payoffs are used. We find that degree-normalized payoffs require high-degree nodes be punished more lenient than low-degree nodes. Conversely, if absolute payoffs count, then high-degree nodes should be punished stronger than low-degree nodes.Comment: 19 pages, 8 figures; accepted for publication in Frontiers in Behavioral Neuroscienc

Diffusion of shared goods in consumer coalitions. An agent-based model

This paper focuses on the process of coalition formation conditioning the common decision to adopt a shared good, which cannot be afforded by an average single consumer and whose use cannot be exhausted by any single consumer. An agent based model is developed to study the interplay between these two processes: coalition formation and diffusion of shared goods. Coalition formation is modelled in an evolutionary game theoretic setting, while adoption uses elements from both the Bass and the threshold models. Coalitions formation sets the conditions for adoption, while diffusion influences the consequent formation of coalitions. Results show that both coalitions and diffusion are subject to network effects and have an impact on the information flow though the population of consumers. Large coalitions are preferred over small ones since individual cost is lower, although it increases if higher quantities are purchased collectively. The paper concludes by connecting the model conceptualisation to the on-going discussion of diffusion of sustainable goods, discussing related policy implications

An experimental study of network effects on coordination in asymmetric games

Network structure has often proven to be important in understanding the decision behavior of individuals or agents in different interdependent situations. Computational studies predict that network structure has a crucial influence on behavior in iterated 2 by 2 asymmetric ‘battle of the sexes’ games. We test such behavioral predictions in an experiment with 240 human subjects. We found that as expected the less ‘random’ the network structure, the better the experimental results are predictable by the computational models. In particular, there is an effect of network clustering on the heterogeneity of convergence behavior in the network. We also found that degree centrality and having an even degree are important predictors of the decision behavior of the subjects in the experiment. We thus find empirical validation of predictions made by computational models in a computerized experiment with human subjects

Evolutionary stable strategies in networked games: the influence of topology

Evolutionary game theory is used to model the evolution of competing strategies in a population of players. Evolutionary stability of a strategy is a dynamic equilibrium, in which any competing mutated strategy would be wiped out from a population. If a strategy is weak evolutionarily stable, the competing strategy may manage to survive within the network. Understanding the network-related factors that affect the evolutionary stability of a strategy would be critical in making accurate predictions about the behaviour of a strategy in a real-world strategic decision making environment. In this work, we evaluate the effect of network topology on the evolutionary stability of a strategy. We focus on two well-known strategies known as the Zero-determinant strategy and the Pavlov strategy. Zero-determinant strategies have been shown to be evolutionarily unstable in a well-mixed population of players. We identify that the Zero-determinant strategy may survive, and may even dominate in a population of players connected through a non-homogeneous network. We introduce the concept of `topological stability' to denote this phenomenon. We argue that not only the network topology, but also the evolutionary process applied and the initial distribution of strategies are critical in determining the evolutionary stability of strategies. Further, we observe that topological stability could affect other well-known strategies as well, such as the general cooperator strategy and the cooperator strategy. Our observations suggest that the variation of evolutionary stability due to topological stability of strategies may be more prevalent in the social context of strategic evolution, in comparison to the biological context