74 research outputs found

    Exploring the Effect of Crowd Management Measures on Passengers’ Behaviour at Metro Stations

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    To reduce problems of interaction at the platform train interface (PTI) platform edge doors (PEDs) and markings on the platform are used as door positions indicators. The common methods to study the effect of these measures are based on average values of density using Fruin’s Level of Service (LOS), however identification cannot be made of which part of the PTI is more congested. To solve this problem, a new method is proposed. The method included a conceptual model in which the PTI was discretised into 40 cm square cells to identify which part of the platform is more congested. Passengers’ behaviour was recorded considering two situations before the train arrives: i) passengers waiting in front of the doors; ii) passengers waiting beside the doors. Observation was done at existing stations at Metro de Santiago and London Underground. Results show that PEDs changed the behaviour of passengers as they were located beside the doors rather than in front of them. In addition, when markings were used on the platform, then this behaviour was reinforced. Therefore, it is recommended to use this method to better design the PTI rather than the LOS which is used to design the whole platform. Further research is needed to study the effect of PEDs on passengers with reduced mobility

    Evacuation Dynamics: Empirical Results, Modeling and Applications

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    This extensive review was written for the ``Encyclopedia of Complexity and System Science'' (Springer, 2008) and addresses a broad audience ranging from engineers to applied mathematicians, computer scientists and physicists. It provides an extensive overview of various aspects of pedestrian dynamics, focussing on evacuation processes. First the current status of empirical results is critically reviewed as it forms the basis for the calibration of models needed for quantitative predictions. Then various modeling approaches are discussed, focussing on cellular automata models. Finally, some specific applications to safety analysis in public buildings or public transport are presented.Comment: 57 pages, 19 figures; to appear in: ``Encyclopedia of Complexity and System Science'', B. Meyers (Ed.) (Springer, Berlin, 2008); for more information and a version with high quality figures, see <http://www.ped-net.org

    Prediction of lethal and synthetically lethal knock-outs in regulatory networks

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    The complex interactions involved in regulation of a cell's function are captured by its interaction graph. More often than not, detailed knowledge about enhancing or suppressive regulatory influences and cooperative effects is lacking and merely the presence or absence of directed interactions is known. Here we investigate to which extent such reduced information allows to forecast the effect of a knock-out or a combination of knock-outs. Specifically we ask in how far the lethality of eliminating nodes may be predicted by their network centrality, such as degree and betweenness, without knowing the function of the system. The function is taken as the ability to reproduce a fixed point under a discrete Boolean dynamics. We investigate two types of stochastically generated networks: fully random networks and structures grown with a mechanism of node duplication and subsequent divergence of interactions. On all networks we find that the out-degree is a good predictor of the lethality of a single node knock-out. For knock-outs of node pairs, the fraction of successors shared between the two knocked-out nodes (out-overlap) is a good predictor of synthetic lethality. Out-degree and out-overlap are locally defined and computationally simple centrality measures that provide a predictive power close to the optimal predictor.Comment: published version, 10 pages, 6 figures, 2 tables; supplement at http://www.bioinf.uni-leipzig.de/publications/supplements/11-01

    On the complexity of acyclic modules in automata networks

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    Modules were introduced as an extension of Boolean automata networks. They have inputs which are used in the computation said modules perform, and can be used to wire modules with each other. In the present paper we extend this new formalism and study the specific case of acyclic modules. These modules prove to be well described in their limit behavior by functions called output functions. We provide other results that offer an upper bound on the number of attractors in an acyclic module when wired recursively into an automata network, alongside a diversity of complexity results around the difficulty of deciding the existence of cycles depending on the number of inputs and the size of said cycle.Comment: 21 page

    Virtual Mutagenesis of the Yeast Cyclins Genetic Network Reveals Complex Dynamics of Transcriptional Control Networks

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    Study of genetic networks has moved from qualitative description of interactions between regulators and regulated genes to the analysis of the interaction dynamics. This paper focuses on the analysis of dynamics of one particular network – the yeast cyclins network. Using a dedicated mathematical model of gene expression and a procedure for computation of the parameters of the model from experimental data, a complete numerical model of the dynamics of the cyclins genetic network was attained. The model allowed for performing virtual experiments on the network and observing their influence on the expression dynamics of the genes downstream in the regulatory cascade. Results show that when the network structure is more complicated, and the regulatory interactions are indirect, results of gene deletion are highly unpredictable. As a consequence of quantitative behavior of the genes and their connections within the network, causal relationship between a regulator and target gene may not be discovered by gene deletion. Without including the dynamics of the system into the network, its functional properties cannot be studied and interpreted correctly

    Identification of a Topological Characteristic Responsible for the Biological Robustness of Regulatory Networks

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    Attribution of biological robustness to the specific structural properties of a regulatory network is an important yet unsolved problem in systems biology. It is widely believed that the topological characteristics of a biological control network largely determine its dynamic behavior, yet the actual mechanism is still poorly understood. Here, we define a novel structural feature of biological networks, termed ‘regulation entropy’, to quantitatively assess the influence of network topology on the robustness of the systems. Using the cell-cycle control networks of the budding yeast (Saccharomyces cerevisiae) and the fission yeast (Schizosaccharomyces pombe) as examples, we first demonstrate the correlation of this quantity with the dynamic stability of biological control networks, and then we establish a significant association between this quantity and the structural stability of the networks. And we further substantiate the generality of this approach with a broad spectrum of biological and random networks. We conclude that the regulation entropy is an effective order parameter in evaluating the robustness of biological control networks. Our work suggests a novel connection between the topological feature and the dynamic property of biological regulatory networks

    Detecting controlling nodes of boolean regulatory networks

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    Boolean models of regulatory networks are assumed to be tolerant to perturbations. That qualitatively implies that each function can only depend on a few nodes. Biologically motivated constraints further show that functions found in Boolean regulatory networks belong to certain classes of functions, for example, the unate functions. It turns out that these classes have specific properties in the Fourier domain. That motivates us to study the problem of detecting controlling nodes in classes of Boolean networks using spectral techniques. We consider networks with unbalanced functions and functions of an average sensitivity less than 23k, where k is the number of controlling variables for a function. Further, we consider the class of 1-low networks which include unate networks, linear threshold networks, and networks with nested canalyzing functions. We show that the application of spectral learning algorithms leads to both better time and sample complexity for the detection of controlling nodes compared with algorithms based on exhaustive search. For a particular algorithm, we state analytical upper bounds on the number of samples needed to find the controlling nodes of the Boolean functions. Further, improved algorithms for detecting controlling nodes in large-scale unate networks are given and numerically studied

    Modeling Stochasticity and Variability in Gene Regulatory Networks

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    Modeling stochasticity in gene regulatory networks is an important and complex problem in molecular systems biology. To elucidate intrinsic noise, several modeling strategies such as the Gillespie algorithm have been used successfully. This paper contributes an approach as an alternative to these classical settings. Within the discrete paradigm, where genes, proteins, and other molecular components of gene regulatory networks are modeled as discrete variables and are assigned as logical rules describing their regulation through interactions with other components. Stochasticity is modeled at the biological function level under the assumption that even if the expression levels of the input nodes of an update rule guarantee activation or degradation there is a probability that the process will not occur due to stochastic effects. This approach allows a finer analysis of discrete models and provides a natural setup for cell population simulations to study cell-to-cell variability. We applied our methods to two of the most studied regulatory networks, the outcome of lambda phage infection of bacteria and the p53-mdm2 complex.Comment: 23 pages, 8 figure

    A general co-expression network-based approach to gene expression analysis: comparison and applications

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    <p>Abstract</p> <p>Background</p> <p>Co-expression network-based approaches have become popular in analyzing microarray data, such as for detecting functional gene modules. However, co-expression networks are often constructed by ad hoc methods, and network-based analyses have not been shown to outperform the conventional cluster analyses, partially due to the lack of an unbiased evaluation metric.</p> <p>Results</p> <p>Here, we develop a general co-expression network-based approach for analyzing both genes and samples in microarray data. Our approach consists of a simple but robust rank-based network construction method, a parameter-free module discovery algorithm and a novel reference network-based metric for module evaluation. We report some interesting topological properties of rank-based co-expression networks that are very different from that of value-based networks in the literature. Using a large set of synthetic and real microarray data, we demonstrate the superior performance of our approach over several popular existing algorithms. Applications of our approach to yeast, Arabidopsis and human cancer microarray data reveal many interesting modules, including a fatal subtype of lymphoma and a gene module regulating yeast telomere integrity, which were missed by the existing methods.</p> <p>Conclusions</p> <p>We demonstrated that our novel approach is very effective in discovering the modular structures in microarray data, both for genes and for samples. As the method is essentially parameter-free, it may be applied to large data sets where the number of clusters is difficult to estimate. The method is also very general and can be applied to other types of data. A MATLAB implementation of our algorithm can be downloaded from <url>http://cs.utsa.edu/~jruan/Software.html</url>.</p

    Evolving Sensitivity Balances Boolean Networks

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    We investigate the sensitivity of Boolean Networks (BNs) to mutations. We are interested in Boolean Networks as a model of Gene Regulatory Networks (GRNs). We adopt Ribeiro and Kauffman’s Ergodic Set and use it to study the long term dynamics of a BN. We define the sensitivity of a BN to be the mean change in its Ergodic Set structure under all possible loss of interaction mutations. Insilico experiments were used to selectively evolve BNs for sensitivity to losing interactions. We find that maximum sensitivity was often achievable and resulted in the BNs becoming topologically balanced, i.e. they evolve towards network structures in which they have a similar number of inhibitory and excitatory interactions. In terms of the dynamics, the dominant sensitivity strategy that evolved was to build BNs with Ergodic Sets dominated by a single long limit cycle which is easily destabilised by mutations. We discuss the relevance of our findings in the context of Stem Cell Differentiation and propose a relationship between pluripotent stem cells and our evolved sensitive networks
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