Chelerythrine Inhibits Human Hepatocellular Carcinoma Metastasis in Vitro.

Chelerythrine (CHE) is a type of benzophenanthridine alkaloid found in many herbs and is also the main alkaloid constituent of Toddalia asiatica (L.) LAM. It has been proven to have various activities including antitumor, antifungal, anti-inflammatory and anti-parasitic effects. We have previously demonstrated that CHE can inhibit proliferation and promote apoptosis in human hepatocellular carcinoma (HCC) cells. However, the effect of CHE on the metastasis of HCC and its related molecular mechanisms have yet to be validated. In this study, we investigated the effects of CHE on the migration and invasion of the HCC cell line Hep3B. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), wounding healing, transwell migration and invasion assays and cytoskeleton staining demonstrated that CHE could inhibit the migration and invasion of Hep3B cells in a dose-dependent manner with change of cell structure. RNA interference studies made a knockdown of matrix metalloproteinase (MMP)-2/9 respectively in Hep3B cells. And the results of wounding healing and transwell invasion assay with the treatment of small interfering RNA (siRNA) investigated that MMP-2/9 are positively associated with Hep3B cell metastasis. The results of enzyme-linked immunosorbent assay (ELISA), Western blotting and quantitative RT-PCR showed that CHE suppressed the expression of MMP-2/9 at both mRNA and protein levels. CHE also exhibited an inhibitory effect on the phosphorylation of Focal adhesion kinase (FAK), phosphatidylinositol 3-kinase (PI3K), Akt, mammalian target of rapamycin (mTOR), c-Jun N-terminal kinase (JNK), extracellular signal-regulated kinases (ERK) and p38. In summary, on Hep3B cells, CHE could change the cell cytoskeletal structures through reducing the expression of p-FAK and inhibit the metastasis of Hep3B cells by downregulating the expression of MMP-2/9 mainly through PI3K/Akt/mTOR signaling pathway.

Evolutionary dynamics of continuous strategy games on graphs and social networks under weak selection.

Understanding the emergence of cooperation among selfish individuals has been a long-standing puzzle, which has been studied by a variety of game models. Most previous studies presumed that interactions between individuals are discrete, but it seems unrealistic in real systems. Recently, there are increasing interests in studying game models with a continuous strategy space. Existing research work on continuous strategy games mainly focuses on well-mixed populations. Especially, little theoretical work has been conducted on their evolutionary dynamics in a structured population. In the previous work (Zhong et al., BioSystems, 2012), we showed that under strong selection, continuous and discrete strategies have significantly different equilibrium and game dynamics in spatially structured populations. In this paper, we further study evolutionary dynamics of continuous strategy games under weak selection in structured populations. By using the fixation probability based stochastic dynamics, we derive exact conditions of natural selection favoring cooperation for the death-birth updating scheme. We also present a network gain decomposition of the game equilibrium, which might provide a new view of the network reciprocity in a quantitative way. Finally, we make a detailed comparison between games using discrete and continuous strategies. As compared to the former, we find that for the latter (i) the same selection conditions are derived for the general 2×2 game; especially, the rule b/c>k in a simplified Prisoner's Dilemma is valid as well; however, (ii) for a coordination game, interestingly, the risk-dominant strategy is disfavored. Numerical simulations have also been conducted to validate our results.

How is the equilibrium of continuous strategy game different from that of discrete strategy game?

Cooperation in the prisoner's dilemma (PD) played on various networks has been explained by so-called network reciprocity. Most of the previous studies presumed that players can offer either cooperation (C) or defection (D). This discrete strategy seems unrealistic in the real world, since actual provisions might not be discrete, but rather continuous. This paper studies the differences between continuous and discrete strategies in two aspects under the condition that the payoff function of the former is a linear interpolation of the payoff matrix of the latter. The first part of this paper proves theoretically that for two-player games, continuous and discrete strategies have different equilibria and game dynamics in a well-mixed but finite population. The second part, conducting a series of numerical experiments, reveals that such differences become considerably large in the case of PD games on networks. Furthermore, it shows, using the Wilcoxon sign-rank test, that continuous and discrete strategy games are statistically significantly different in terms of equilibria. Intensive discussion by comparing these two kinds of games elucidates that describing a strategy as a real number blunts D strategy invasion to C clusters on a network in the early stage of evolution. Thus, network reciprocity is enhanced by the continuous strategy.

Motif difficulty (MD): a predictive measure of problem difficulty for evolutionary algorithms using network motifs.

One of the major challenges in the field of evolutionary algorithms (EAs) is to characterise which kinds of problems are easy and which are not. Researchers have been attracted to predict the behaviour of EAs in different domains. We introduce fitness landscape networks (FLNs) that are formed using operators satisfying specific conditions and define a new predictive measure that we call motif difficulty (MD) for comparison-based EAs. Because it is impractical to exhaustively search the whole network, we propose a sampling technique for calculating an approximate MD measure. Extensive experiments on binary search spaces are conducted to show both the advantages and limitations of MD. Multidimensional knapsack problems (MKPs) are also used to validate the performance of approximate MD on FLNs with different topologies. The effect of two representations, namely binary and permutation, on the difficulty of MKPs is analysed.

Local-global interaction and the emergence of scale-free networks with community structures.

Understanding complex networks in the real world is a nontrivial task. In the study of community structures we normally encounter several examples of these networks, which makes any statistical inferencing a challenging endeavor. Researchers resort to computer-generated networks that resemble networks encountered in the real world as a means to generate many networks with different sizes, while maintaining the real-world characteristics of interest. The generation of networks that resemble the real world turns out in itself to be a complex search problem. We present a new rewiring algorithm for the generation of networks with unique characteristics that combine the scale-free effects and community structures encountered in the real world. The algorithm is inspired by social interactions in the real world, whereby people tend to connect locally while occasionally they connect globally. This local-global coupling turns out to be a powerful characteristics that is required for our proposed rewiring algorithm to generate networks with community structures, power law distributions both in degree and in community size, positive assortative mixing by degree, and the rich-club phenomenon.

A multiagent evolutionary algorithm for combinatorial optimization problems.

Based on our previous works, multiagent systems and evolutionary algorithms (EAs) are integrated to form a new algorithm for combinatorial optimization problems (CmOPs), namely, MultiAgent EA for CmOPs (MAEA-CmOPs). In MAEA-CmOPs, all agents live in a latticelike environment, with each agent fixed on a lattice point. To increase energies, all agents compete with their neighbors, and they can also increase their own energies by making use of domain knowledge. Theoretical analyses show that MAEA-CmOPs converge to global optimum solutions. Since deceptive problems are the most difficult CmOPs for EAs, in the experiments, various deceptive problems with strong linkage, weak linkage, and overlapping linkage, and more difficult ones, namely, hierarchical problems with treelike structures, are used to validate the performance of MAEA-CmOPs. The results show that MAEA-CmOP outperforms the other algorithms and has a fast convergence rate. MAEA-CmOP is also used to solve large-scale deceptive and hierarchical problems with thousands of dimensions, and the experimental results show that MAEA-CmOP obtains a good performance and has a low computational cost, which the time complexity increases in a polynomial basis with the problem size.

An organizational evolutionary algorithm for numerical optimization.

Taking inspiration from the interacting process among organizations in human societies, this correspondence designs a kind of structured population and corresponding evolutionary operators to form a novel algorithm, Organizational Evolutionary Algorithm (OEA), for solving both unconstrained and constrained optimization problems. In OEA, a population consists of organizations, and an organization consists of individuals. All evolutionary operators are designed to simulate the interaction among organizations. In experiments, 15 unconstrained functions, 13 constrained functions, and 4 engineering design problems are used to validate the performance of OEA, and thorough comparisons are made between the OEA and the existing approaches. The results show that the OEA obtains good performances in both the solution quality and the computational cost. Moreover, for the constrained problems, the good performances are obtained by only incorporating two simple constraints handling techniques into the OEA. Furthermore, systematic analyses have been made on all parameters of the OEA. The results show that the OEA is quite robust and easy to use.

Comments on "the 1993 DIMACS graph coloring challenge" and "energy function-based approaches to graph coloring".

Since all graphs in the 1993 DIMACS graph coloring challenge are undirected, each edge should be only counted once. However, in some files each edge is counted once, whereas in others each edge is counted twice; so a systematical check on the DIMACS challenge is made to eliminate the inconsistencies. Besides, the experimental results of a previous paper by Blas et al. counted each violated edges twice and neglected the inconsistencies in the DIMACS challenge. So the correct experimental results of a previous paper by Blas et al are also given.

A multiagent evolutionary algorithm for constraint satisfaction problems.

With the intrinsic properties of constraint satisfaction problems (CSPs) in mind, we divide CSPs into two types, namely, permutation CSPs and nonpermutation CSPs. According to their characteristics, several behaviors are designed for agents by making use of the ability of agents to sense and act on the environment. These behaviors are controlled by means of evolution, so that the multiagent evolutionary algorithm for constraint satisfaction problems (MAEA-CSPs) results. To overcome the disadvantages of the general encoding methods, the minimum conflict encoding is also proposed. Theoretical analyzes show that MAEA-CSPs has a linear space complexity and converges to the global optimum. The first part of the experiments uses 250 benchmark binary CSPs and 79 graph coloring problems from the DIMACS challenge to test the performance of MAEA-CSPs for nonpermutation CSPs. MAEA-CSPs is compared with six well-defined algorithms and the effect of the parameters is analyzed systematically. The second part of the experiments uses a classical CSP, n-queen problems, and a more practical case, job-shop scheduling problems (JSPs), to test the performance of MAEA-CSPs for permutation CSPs. The scalability of MAEA-CSPs along n for n-queen problems is studied with great care. The results show that MAEA-CSPs achieves good performance when n increases from 10(4) to 10(7), and has a linear time complexity. Even for 10(7)-queen problems, MAEA-CSPs finds the solutions by only 150 seconds. For JSPs, 59 benchmark problems are used, and good performance is also obtained.

A multiagent genetic algorithm for global numerical optimization.

In this paper, multiagent systems and genetic algorithms are integrated to form a new algorithm, multiagent genetic algorithm (MAGA), for solving the global numerical optimization problem. An agent in MAGA represents a candidate solution to the optimization problem in hand. All agents live in a latticelike environment, with each agent fixed on a lattice-point. In order to increase energies, they compete or cooperate with their neighbors, and they can also use knowledge. Making use of these agent-agent interactions, MAGA realizes the purpose of minimizing the objective function value. Theoretical analyzes show that MAGA converges to the global optimum. In the first part of the experiments, ten benchmark functions are used to test the performance of MAGA, and the scalability of MAGA along the problem dimension is studied with great care. The results show that MAGA achieves a good performance when the dimensions are increased from 20-10,000. Moreover, even when the dimensions are increased to as high as 10,000, MAGA still can find high quality solutions at a low computational cost. Therefore, MAGA has good scalability and is a competent algorithm for solving high dimensional optimization problems. To the best of our knowledge, no researchers have ever optimized the functions with 10,000 dimensions by means of evolution. In the second part of the experiments, MAGA is applied to a practical case, the approximation of linear systems, with a satisfactory result.