Self-repair ability of evolved self-assembling systems in cellular automata

Self-repairing systems are those that are able to reconfigure themselves following disruptions to bring them back into a defined normal state. In this paper we explore the self-repair ability of some cellular automata-like systems, which differ from classical cellular automata by the introduction of a local diffusion process inspired by chemical signalling processes in biological development. The update rules in these systems are evolved using genetic programming to self-assemble towards a target pattern. In particular, we demonstrate that once the update rules have been evolved for self-assembly, many of those update rules also provide a self-repair ability without any additional evolutionary process aimed specifically at self-repair

Decelerating Spread of West Nile Virus by Percolation in a Heterogeneous Urban Landscape

Vector-borne diseases are emerging and re-emerging in urban environments throughout the world, presenting an increasing challenge to human health and a major obstacle to development. Currently, more than half of the global population is concentrated in urban environments, which are highly heterogeneous in the extent, degree, and distribution of environmental modifications. Because the prevalence of vector-borne pathogens is so closely coupled to the ecologies of vector and host species, this heterogeneity has the potential to significantly alter the dynamical systems through which pathogens propagate, and also thereby affect the epidemiological patterns of disease at multiple spatial scales. One such pattern is the speed of spread. Whereas standard models hold that pathogens spread as waves with constant or increasing speed, we hypothesized that heterogeneity in urban environments would cause decelerating travelling waves in incipient epidemics. To test this hypothesis, we analysed data on the spread of West Nile virus (WNV) in New York City (NYC), the 1999 epicentre of the North American pandemic, during annual epizootics from 2000–2008. These data show evidence of deceleration in all years studied, consistent with our hypothesis. To further explain these patterns, we developed a spatial model for vector-borne disease transmission in a heterogeneous environment. An emergent property of this model is that deceleration occurs only in the vicinity of a critical point. Geostatistical analysis suggests that NYC may be on the edge of this criticality. Together, these analyses provide the first evidence for the endogenous generation of decelerating travelling waves in an emerging infectious disease. Since the reported deceleration results from the heterogeneity of the environment through which the pathogen percolates, our findings suggest that targeting control at key sites could efficiently prevent pathogen spread to remote susceptible areas or even halt epidemics

Essential Role of Cyclophilin A for Hepatitis C Virus Replication and Virus Production and Possible Link to Polyprotein Cleavage Kinetics

Viruses are obligate intracellular parasites and therefore their replication completely depends on host cell factors. In case of the hepatitis C virus (HCV), a positive-strand RNA virus that in the majority of infections establishes persistence, cyclophilins are considered to play an important role in RNA replication. Subsequent to the observation that cyclosporines, known to sequester cyclophilins by direct binding, profoundly block HCV replication in cultured human hepatoma cells, conflicting results were obtained as to the particular cyclophilin (Cyp) required for viral RNA replication and the underlying possible mode of action. By using a set of cell lines with stable knock-down of CypA or CypB, we demonstrate in the present work that replication of subgenomic HCV replicons of different genotypes is reduced by CypA depletion up to 1,000-fold whereas knock-down of CypB had no effect. Inhibition of replication was rescued by over-expression of wild type CypA, but not by a mutant lacking isomerase activity. Replication of JFH1-derived full length genomes was even more sensitive to CypA depletion as compared to subgenomic replicons and virus production was completely blocked. These results argue that CypA may target an additional viral factor outside of the minimal replicase contributing to RNA amplification and assembly, presumably nonstructural protein 2. By selecting for resistance against the cyclosporine analogue DEBIO-025 that targets CypA in a dose-dependent manner, we identified two mutations (V2440A and V2440L) close to the cleavage site between nonstructural protein 5A and the RNA-dependent RNA polymerase in nonstructural protein 5B that slow down cleavage kinetics at this site and reduce CypA dependence of viral replication. Further amino acid substitutions at the same cleavage site accelerating processing increase CypA dependence. Our results thus identify an unexpected correlation between HCV polyprotein processing and CypA dependence of HCV replication

Understanding Influenza

Influenza, a serious illness of humans and domesticated animals, has been studied intensively for many years. It therefore provides an example of how much we can learn from detailed studies of an infectious disease and of how even the most intensive scientific research leaves further questions to answer. This introduction is written for researchers who have become interested in one of these unanswered questions, but who may not have previously worked on influenza. To investigate these questions, researchers must not only have a firm grasp of relevant methods and protocols; they must also be familiar with the basic details of our current understanding of influenza. This article therefore briefly covers the burden of disease that has driven influenza research, summarizes how our thinking about influenza has evolved over time, and sets out key features of influenza viruses by discussing how we classify them and what we understand of their replication. It does not aim to be comprehensive, as any researcher will read deeply into the specific areas that have grasped their interest. Instead, it aims to provide a general summary of how we came to think about influenza in the way we do now, in the hope that the reader’s own research will help us to understand it better

Probability Theory in Statistical Physics, Percolation, and Other Random Topics: The Work of C. Newman

In the introduction to this volume, we discuss some of the highlights of the research career of Chuck Newman. This introduction is divided into two main sections, the first covering Chuck's work in statistical mechanics and the second his work in percolation theory, continuum scaling limits, and related topics.Comment: 38 pages (including many references), introduction to Festschrift in honor of C.M. Newma