Intercellular competitive growth dynamics with microenvironmental feedback.

Normal life activities between cells rely crucially on the homeostasis of the cellular microenvironment, but aging and cancer will upset this balance. In this paper we introduce the microenvironmental feedback mechanism to the growth dynamics of multicellular organisms, which changes the cellular competitive ability and thereby regulates the growth of multicellular organisms. We show that the presence of microenvironmental feedback can effectively delay aging, but cancer cells may grow uncontrollably due to the emergence of the tumor microenvironment (TME). We study the effect of the fraction of cancer cells relative to that of senescent cells on the feedback rate of the microenvironment on the lifespan of multicellular organisms and find that the average lifespan shortened is close to the data for non-Hodgkin's lymphoma in Canada from 1980 to 2015. We also investigate how the competitive ability of cancer cells affects the lifespan of multicellular organisms and reveal that there is an optimal value of the competitive ability of cancer cells allowing the organism to survive longest. Interestingly, the proposed microenvironmental feedback mechanism can give rise to the phenomenon of Parrondo's paradox: When the competitive ability of cancer cells switches between a too-high and a too-low value, multicellular organisms are able to live longer than in each case individually. Our results may provide helpful clues for targeted therapies aimed at the TME.

Nonmonotonic enhancement of diversity-induced resonance in systems of mobile oscillators.

Diversity is omnipresent in natural and synthetic extended systems, the phenomenon of diversity-induced resonance (DIR), wherein a moderate degree of the diversity can provoke an optimal collective response, provides researchers a brand-new strategy to amplify and utilize the weak signal. As yet the relevant advances focus mostly on the ideal situations where the interactions among elements are uncorrelated with the physical proximity of agents. Such a consideration overlooks interactions mediated by the motion of agents in space. Here, we investigate the signal response of an ensemble of spatial mobile heterogeneous bistable oscillators with two canonical interacting modes: dynamic and preset. The oscillators are considered as mass points and perform random walks in a two-dimensional square plane. Under the dynamic scheme, the oscillators can only interact with other oscillators within a fixed vision radius. For the preset circumstance, the interaction among oscillators occurs only when all of them are in a predefined region at the same moment. We find that the DIR can be obtained in both situations. Additionally, the strength of resonance nonmonotonically rises with respect to the increase of moving speed, and the optimal resonance is acquired by an intermediate magnitude of speed. Finally, we propose reduced equations to guarantee the occurrence of such mobility-optimized DIR on the basis of the fast switching approximation theory and also examine the robustness of such phenomenon through the excitable FitzHugh-Nagumo model and a different spatial motion mechanism. Our results reveal for the first time that the DIR can be optimized by the spatial mobility and thus has promising potential application in the communication of mobile agents.

Precision Therapy of Recurrent Breast Cancer through Targeting Different Malignant Tumor Cells with a HER2/CD44-Targeted Hydrogel Nanobot.

Heterogeneity and drug resistance of tumor cells are the leading causes of incurability and poor survival for patients with recurrent breast cancer. In order to accurately deliver the biological anticancer drugs to different subtypes of malignant tumor cells for omnidirectional targeted treatment of recurrent breast cancer, a distinct design is demonstrated by embedding liposome-based nanocomplexes containing pro-apoptotic peptide and survivin siRNA drugs (LPR) into Herceptin/hyaluronic acid cross-linked nanohydrogels (Herceptin-HA) to fabricate a HER2/CD44-targeted hydrogel nanobot (named as ALPR). ALPR delivered cargoes to the cells overexpressing CD44 and HER2, followed by Herceptin-HA biodegradation, subsequently, the exposed lipid component containing DOPE fused with the endosomal membrane and released peptide and siRNA into the cytoplasm. These experiments indicated that ALPR can specifically deliver Herceptin, peptide, and siRNA drugs to HER2-positive SKBR-3, triple-negative MDA-MB-231, and HER2-negative drug-resistant MCF-7 human breast cancer cells. ALPR completely inhibited the growth of heterogeneous breast tumors via multichannel synergistic effects: disrupting mitochondria, downregulating the survivin gene, and blocking HER2 receptors on the surface of HER2-positive cells. The present design overcomes the chemical drug resistance and opens a feasible route for the combinative treatment of recurrent breast cancer, even other solid tumors, utilizing different kinds of biological drugs.

Double resonance induced by group coupling with quenched disorder.

Results show that the astrocytes can not only listen to the talk of large assemble of neurons but also give advice to the conversations and are significant sources of heterogeneous couplings as well. In the present work, we focus on such regulation character of astrocytes and explore the role of heterogeneous couplings among interacted neuron-astrocyte components in a signal response. We consider reduced dynamics in which the listening and advising processes of astrocytes are mapped into the form of group coupling, where the couplings are normally distributed. In both globally coupled overdamped bistable oscillators and an excitable FitzHugh-Nagumo (FHN) neuron model, we numerically and analytically demonstrate that two types of bell-shaped collective response curves can be obtained as the ensemble coupling strength or the heterogeneity of group coupling rise, respectively, which can be seen as a new type of double resonance. Furthermore, through the bifurcation analysis, we verify that these resonant signal responses stem from the competition between dispersion and aggregation induced by heterogeneous group and positive pairwise couplings, respectively. Our results contribute to a better understanding of the signal propagation in coupled systems with quenched disorder.

Diversity-induced resonance in a globally coupled bistable system with diversely distributed heterogeneity.

A moderate degree of diversity, in form of quenched noise or intrinsic heterogeneity, can significantly strengthen the collective response of coupled extended systems. As yet, related discoveries on diversity-induced resonance are mainly concentrated on symmetrically distributed heterogeneity, e.g., the Gaussian or uniform distributions with zero-mean. The necessary conditions that guarantee the arise of resonance phenomenon in heterogeneous oscillators remain largely unknown. In this work, we show that the standard deviation and the ratio of negative entities of a given distribution jointly modulate diversity-induced resonance and the concomitance of negative and positive entities is the prerequisite for this resonant behavior emerging in diverse symmetrical and asymmetrical distributions. Particularly, for a proper degree of diversity of a given distribution, the collective signal response behaves like a bell-shaped curve as the ratio of negative oscillator increases, which can be termed negative-oscillator-ratio induced resonance. Furthermore, we analytically reveal that the ratio of negative oscillators plays a gating role in the resonance phenomenon on the basis of a reduced equation. Finally, we examine the robustness of these results in globally coupled bistable elements with asymmetrical potential functions. Our results suggest that the phenomenon of diversity-induced resonance can arise in arbitrarily distributed heterogeneous bistable oscillators by regulating the ratio of negative entities appropriately.

Twofold effect of self-interest in pedestrian room evacuation.

Evacuation dynamics of pedestrians in a square room with one exit is studied. The movement of the pedestrians is guided by the static floor field model. Whenever multiple pedestrians are trying to move to the same target position, a game theoretical framework is introduced to address the conflict. Depending on the payoff matrix, the game that the pedestrians are involved in may be either hawk-dove or prisoner's dilemma, from which the reaped payoffs determine the capacities, or probabilities, of the pedestrians occupying the preferred vacant sites. The pedestrians are allowed to adjust their strategies when competing with others, and a parameter κ is utilized to characterize the extent of their self-interest. It is found that self-interest may induce either positive or negative impacts on the evacuation dynamics depending on whether it can facilitate the formation of collective cooperation in the population or not. Particularly, a resonance-like performance of evacuation is realized in the regime of prisoner's dilemma. The effects of placing an obstacle in front of the exit and the diversity of responses of the pedestrians to the space competition on the evacuation dynamics are also discussed.

Collective firing patterns of neuronal networks with short-term synaptic plasticity.

We investigate the occurrence of synchronous population activities in a neuronal network composed of both excitatory and inhibitory neurons and equipped with short-term synaptic plasticity. The collective firing patterns with different macroscopic properties emerge visually with the change of system parameters, and most long-time collective evolution also shows periodic-like characteristics. We systematically discuss the pattern-formation dynamics on a microscopic level and find a lot of hidden features of the population activities. The bursty phase with power-law distributed avalanches is observed in which the population activity can be either entire or local periodic-like. In the purely spike-to-spike synchronous regime, the periodic-like phase emerges from the synchronous chaos after the backward period-doubling transition. The local periodic-like population activity and the synchronous chaotic activity show substantial trial-to-trial variability, which is unfavorable for neural code, while they are contrary to the stable periodic-like phases. We also show that the inhibitory neurons can promote the generation of cluster firing behavior and strong bursty collective firing activity by depressing the activities of postsynaptic neurons partially or wholly.

Collective motion patterns of self-propelled agents with both velocity alignment and aggregation interactions.

We combine the velocity alignment and aggregation mechanisms to study the collective motion of active agents in noisy circumstances. The agents are located on a two-dimensional square plane, and the proportion of velocity alignment and aggregation interactions are, respectively, set to be k and 1-k. In the case of k=1 our model is similar to the classical Vicsek model, while it degenerates to the view angle model for k=0. By tuning the intensity of the external noise η and the proportional coefficient k, and carrying out extensive numerical simulations, we find that the system can exhibit diverse dynamic patterns widely observed in real biological systems. By means of finite-size scaling analysis, we confirm that the presence of the aggregation interaction affects not only the position of the critical noise η_{c} (beyond which the agents display disordered motion) but also the type of the phase transition of the collective motion. In particular, under a weak external noise environment, the transition from disordered to ordered state by increasing k (i.e., by decreasing the proportion of aggregation interaction) is found to be of first order. Besides, for moderate external noise, we also find the existence of the optimal proportion of the aggregation interaction for the system to achieve the highest degree of order. Our results highlights the important role of the aggregation interaction in the collective motion and may have promising potential applications in natural self-propelled particles and artificial multiagent systems.

Solving the Dynamic Correlation Problem of the Susceptible-Infected-Susceptible Model on Networks.

The susceptible-infected-susceptible (SIS) model is a canonical model for emerging disease outbreaks. Such outbreaks are naturally modeled as taking place on networks. A theoretical challenge in network epidemiology is the dynamic correlations coming from that if one node is infected, then its neighbors are likely to be infected. By combining two theoretical approaches-the heterogeneous mean-field theory and the effective degree method-we are able to include these correlations in an analytical solution of the SIS model. We derive accurate expressions for the average prevalence (fraction of infected) and epidemic threshold. We also discuss how to generalize the approach to a larger class of stochastic population models.

Effective degree Markov-chain approach for discrete-time epidemic processes on uncorrelated networks.

Recently, Gómez et al. proposed a microscopic Markov-chain approach (MMCA) [S. Gómez, J. Gómez-Gardeñes, Y. Moreno, and A. Arenas, Phys. Rev. E 84, 036105 (2011)PLEEE81539-375510.1103/PhysRevE.84.036105] to the discrete-time susceptible-infected-susceptible (SIS) epidemic process and found that the epidemic prevalence obtained by this approach agrees well with that by simulations. However, we found that the approach cannot be straightforwardly extended to a susceptible-infected-recovered (SIR) epidemic process (due to its irreversible property), and the epidemic prevalences obtained by MMCA and Monte Carlo simulations do not match well when the infection probability is just slightly above the epidemic threshold. In this contribution we extend the effective degree Markov-chain approach, proposed for analyzing continuous-time epidemic processes [J. Lindquist, J. Ma, P. Driessche, and F. Willeboordse, J. Math. Biol. 62, 143 (2011)JMBLAJ0303-681210.1007/s00285-010-0331-2], to address discrete-time binary-state (SIS) or three-state (SIR) epidemic processes on uncorrelated complex networks. It is shown that the final epidemic size as well as the time series of infected individuals obtained from this approach agree very well with those by Monte Carlo simulations. Our results are robust to the change of different parameters, including the total population size, the infection probability, the recovery probability, the average degree, and the degree distribution of the underlying networks.

Effect of vaccination strategies on the dynamic behavior of epidemic spreading and vaccine coverage.

The transmission of infectious, yet vaccine-preventable, diseases is a typical complex social phenomenon, where the increasing level of vaccine update in the population helps to inhibit the epidemic spreading, which in turn, however, discourages more people to participate in vaccination campaigns, due to the "externality effect" raised by vaccination. We herein study the impact of vaccination strategies, pure, continuous (rather than adopt vaccination definitely, the individuals choose to taking vaccine with some probabilities), or continuous with randomly mutation, on the vaccination dynamics with a spatial susceptible-vaccinated-infected-recovered (SVIR) epidemiological model. By means of extensive Monte-Carlo simulations, we show that there is a crossover behavior of the final vaccine coverage between the pure-strategy case and the continuous-strategy case, and remarkably, both the final vaccination level and epidemic size in the continuous-strategy case are less than them in the pure-strategy case when vaccination is cheap. We explain this phenomenon by analyzing the organization process of the individuals in the continuous-strategy case in the equilibrium. Our results are robust to the SVIR dynamics defined on other spatial networks, like the Erdos-Rényi and Barabási-Albert networks.

Behavior of susceptible-vaccinated-infected-recovered epidemics with diversity in the infection rate of individuals.

We study a susceptible-vaccinated-infected-recovered (SVIR) epidemic-spreading model with diversity of infection rate of the individuals. By means of analytical arguments as well as extensive computer simulations, we demonstrate that the heterogeneity in infection rate can either impede or accelerate the epidemic spreading, which depends on the amount of vaccinated individuals introduced in the population as well as the contact pattern among the individuals. Remarkably, as long as the individuals with different capability of acquiring the disease interact with unequal frequency, there always exist a cross point for the fraction of vaccinated, below which the diversity of infection rate hinders the epidemic spreading and above which expedites it. The overall results are robust to the SVIR dynamics defined on different population models; the possible applications of the results are discussed.

Effects of inhomogeneous influence of individuals on an order-disorder transition in opinion dynamics.

We study the effects of inhomogeneous influence of individuals on collective phenomena. We focus analytically on a typical model of the majority rule, applied to the completely connected agents. Two types of individuals A and B with different influence activity are introduced. The individuals A and B are distributed randomly with concentrations nu and 1-nu at the beginning and fixed further on. Our main result is that the location of the order-disorder transition is affected due to the introduction of the inhomogeneous influence. This result highlights the importance of inhomogeneous influence between different types of individuals during the process of opinion updating.

Effects of inhomogeneous activity of players and noise on cooperation in spatial public goods games.

We study the public goods game in the noisy case by considering the players with inhomogeneous activity of teaching on a square lattice. It is shown that the introduction of the inhomogeneous activity of teaching the players can remarkably promote cooperation. By investigating the effects of noise on cooperative behavior in detail, we find that the variation of cooperator density rhoC with the noise parameter kappa displays several different behaviors: rhoC monotonically increases (decreases) with kappa; rhoC first increases (decreases) with kappa and then it decreases (increases) monotonically after reaching its maximum (minimum) value, which depends on the amount of the multiplication factor r, on whether the system is homogeneous or inhomogeneous, and on whether the adopted updating is synchronous or asynchronous. These results imply that the noise plays an important and nontrivial role in the evolution of cooperation.