WorldWideScience

Sample records for global metabolic network

  1. Global network reorganization during dynamic adaptations of Bacillus subtilis metabolism

    Buescher, Joerg Martin; Liebermeister, Wolfram; Jules, Matthieu

    2012-01-01

    Adaptation of cells to environmental changes requires dynamic interactions between metabolic and regulatory networks, but studies typically address only one or a few layers of regulation. For nutritional shifts between two preferred carbon sources of Bacillus subtilis, we combined statistical...

  2. Deletion of the Mitochondrial Chaperone TRAP-1 Uncovers Global Reprogramming of Metabolic Networks

    Sofia Lisanti

    2014-08-01

    Full Text Available Reprogramming of metabolic pathways contributes to human disease, especially cancer, but the regulators of this process are unknown. Here, we have generated a mouse knockout for the mitochondrial chaperone TRAP-1, a regulator of bioenergetics in tumors. TRAP-1−/− mice are viable and showed reduced incidence of age-associated pathologies, including obesity, inflammatory tissue degeneration, dysplasia, and spontaneous tumor formation. This was accompanied by global upregulation of oxidative phosphorylation and glycolysis transcriptomes, causing deregulated mitochondrial respiration, oxidative stress, impaired cell proliferation, and a switch to glycolytic metabolism in vivo. These data identify TRAP-1 as a central regulator of mitochondrial bioenergetics, and this pathway could contribute to metabolic rewiring in tumors.

  3. Global Networking.

    Lynch, Clifford

    1997-01-01

    Discusses the state of the Internet. Highlights include the magnitude of the infrastructure, costs, its increasing pace, constraints in international links, provision of network capacity to homes and small businesses, cable television modems, political and cultural problems, the digital library concept, search engines, the failure of personal…

  4. VRML metabolic network visualizer.

    Rojdestvenski, Igor

    2003-03-01

    A successful date collection visualization should satisfy a set of many requirements: unification of diverse data formats, support for serendipity research, support of hierarchical structures, algorithmizability, vast information density, Internet-readiness, and other. Recently, virtual reality has made significant progress in engineering, architectural design, entertainment and communication. We experiment with the possibility of using the immersive abstract three-dimensional visualizations of the metabolic networks. We present the trial Metabolic Network Visualizer software, which produces graphical representation of a metabolic network as a VRML world from a formal description written in a simple SGML-type scripting language.

  5. Extraction of elementary rate constants from global network analysis of E. coli central metabolism

    Broderick Gordon

    2008-05-01

    Full Text Available Abstract Background As computational performance steadily increases, so does interest in extending one-particle-per-molecule models to larger physiological problems. Such models however require elementary rate constants to calculate time-dependent rate coefficients under physiological conditions. Unfortunately, even when in vivo kinetic data is available, it is often in the form of aggregated rate laws (ARL that do not specify the required elementary rate constants corresponding to mass-action rate laws (MRL. There is therefore a need to develop a method which is capable of automatically transforming ARL kinetic information into more detailed MRL rate constants. Results By incorporating proteomic data related to enzyme abundance into an MRL modelling framework, here we present an efficient method operating at a global network level for extracting elementary rate constants from experiment-based aggregated rate law (ARL models. The method combines two techniques that can be used to overcome the difficult properties in parameterization. The first, a hybrid MRL/ARL modelling technique, is used to divide the parameter estimation problem into sub-problems, so that the parameters of the mass action rate laws for each enzyme are estimated in separate steps. This reduces the number of parameters that have to be optimized simultaneously. The second, a hybrid algebraic-numerical simulation and optimization approach, is used to render some rate constants identifiable, as well as to greatly narrow the bounds of the other rate constants that remain unidentifiable. This is done by incorporating equality constraints derived from the King-Altman and Cleland method into the simulated annealing algorithm. We apply these two techniques to estimate the rate constants of a model of E. coli glycolytic pathways. The simulation and statistical results show that our innovative method performs well in dealing with the issues of high computation cost, stiffness, local

  6. Extraction of elementary rate constants from global network analysis of E. coli central metabolism

    Zhao, Jiao; Ridgway, Douglas; Broderick, Gordon; Kovalenko, Andriy; Ellison, Michael

    2008-01-01

    Background As computational performance steadily increases, so does interest in extending one-particle-per-molecule models to larger physiological problems. Such models however require elementary rate constants to calculate time-dependent rate coefficients under physiological conditions. Unfortunately, even when in vivo kinetic data is available, it is often in the form of aggregated rate laws (ARL) that do not specify the required elementary rate constants corresponding to mass-action rate laws (MRL). There is therefore a need to develop a method which is capable of automatically transforming ARL kinetic information into more detailed MRL rate constants. Results By incorporating proteomic data related to enzyme abundance into an MRL modelling framework, here we present an efficient method operating at a global network level for extracting elementary rate constants from experiment-based aggregated rate law (ARL) models. The method combines two techniques that can be used to overcome the difficult properties in parameterization. The first, a hybrid MRL/ARL modelling technique, is used to divide the parameter estimation problem into sub-problems, so that the parameters of the mass action rate laws for each enzyme are estimated in separate steps. This reduces the number of parameters that have to be optimized simultaneously. The second, a hybrid algebraic-numerical simulation and optimization approach, is used to render some rate constants identifiable, as well as to greatly narrow the bounds of the other rate constants that remain unidentifiable. This is done by incorporating equality constraints derived from the King-Altman and Cleland method into the simulated annealing algorithm. We apply these two techniques to estimate the rate constants of a model of E. coli glycolytic pathways. The simulation and statistical results show that our innovative method performs well in dealing with the issues of high computation cost, stiffness, local minima and uncertainty

  7. Global Operations Networks

    In the current context of global economic liberalisation and technological advancements, industrial companies are less likely to generate value in the traditional vertically integrated chain. Instead, they are doing so by means of elaborate cross-border and cross-organisational networks. As a rule......, these networks are configured on a global basis and consist of diverse and interdependent affiliates (linked both through ownership and non-equity relationships), which are engaged in an exchange of goods, services and information. The Scandinavian context is no exception to this trend. Nevertheless......, international comparative studies providing comprehensive insights from it are still rare. With the objective of bridging this gap, Global Operations Networks (GONE) project (sponsored by the Danish Research Council) brought together numerous academic and industrial partners from Denmark, Sweden and Finland...

  8. Computer Networks and Globalization

    J. Magliaro

    2007-07-01

    Full Text Available Communication and information computer networks connect the world in ways that make globalization more natural and inequity more subtle. As educators, we look at these phenomena holistically analyzing them from the realist’s view, thus exploring tensions, (in equity and (injustice, and from the idealist’s view, thus embracing connectivity, convergence and development of a collective consciousness. In an increasingly market- driven world we find examples of openness and human generosity that are based on networks, specifically the Internet. After addressing open movements in publishing, software industry and education, we describe the possibility of a dialectic equilibrium between globalization and indigenousness in view of ecologically designed future smart networks

  9. Evolution of metabolic network organization

    Bonchev Danail

    2010-05-01

    Full Text Available Abstract Background Comparison of metabolic networks across species is a key to understanding how evolutionary pressures shape these networks. By selecting taxa representative of different lineages or lifestyles and using a comprehensive set of descriptors of the structure and complexity of their metabolic networks, one can highlight both qualitative and quantitative differences in the metabolic organization of species subject to distinct evolutionary paths or environmental constraints. Results We used a novel representation of metabolic networks, termed network of interacting pathways or NIP, to focus on the modular, high-level organization of the metabolic capabilities of the cell. Using machine learning techniques we identified the most relevant aspects of cellular organization that change under evolutionary pressures. We considered the transitions from prokarya to eukarya (with a focus on the transitions among the archaea, bacteria and eukarya, from unicellular to multicellular eukarya, from free living to host-associated bacteria, from anaerobic to aerobic, as well as the acquisition of cell motility or growth in an environment of various levels of salinity or temperature. Intuitively, we expect organisms with more complex lifestyles to have more complex and robust metabolic networks. Here we demonstrate for the first time that such organisms are not only characterized by larger, denser networks of metabolic pathways but also have more efficiently organized cross communications, as revealed by subtle changes in network topology. These changes are unevenly distributed among metabolic pathways, with specific categories of pathways being promoted to more central locations as an answer to environmental constraints. Conclusions Combining methods from graph theory and machine learning, we have shown here that evolutionary pressures not only affects gene and protein sequences, but also specific details of the complex wiring of functional modules

  10. Filling Knowledge Gaps in Biological Networks: integrating global approaches to understand H2 metabolism in Chlamydomonas reinhardtii - Final Report

    Posewitz, Matthew C

    2011-06-30

    The green alga Chlamydomonas reinhardtii (Chlamydomonas) has numerous genes encoding enzymes that function in fermentative pathways. Among these genes, are the [FeFe]-hydrogenases, pyruvate formate lyase, pyruvate ferredoxin oxidoreductase, acetate kinase, and phosphotransacetylase. We have systematically undertaken a series of targeted mutagenesis approaches to disrupt each of these key genes and omics techniques to characterize alterations in metabolic flux. Funds from DE-FG02-07ER64423 were specifically leveraged to generate mutants with disruptions in the genes encoding the [FeFe]-hydrogenases HYDA1 and HYDA2, pyruvate formate lyase (PFL1), and in bifunctional alcohol/aldehyde alcohol dehydrogenase (ADH1). Additionally funds were used to conduct global transcript profiling experiments of wildtype Chlamydomonas cells, as well as of the hydEF-1 mutant, which is unable to make H2 due to a lesion in the [FeFe]-hydrogenase biosynthetic pathway. In the wildtype cells, formate, acetate and ethanol are the dominant fermentation products with traces of CO2 and H2 also being produced. In the hydEF-1 mutant, succinate production is increased to offset the loss of protons as a terminal electron acceptor. In the pfl-1 mutant, lactate offsets the loss of formate production, and in the adh1-1 mutant glycerol is made instead of ethanol. To further probe the system, we generated a double mutant (pfl1-1 adh1) that is unable to synthesize both formate and ethanol. This strain, like the pfl1 mutants, secreted lactate, but also exhibited a significant increase in the levels of extracellular glycerol, acetate, and intracellular reduced sugars, and a decline in dark, fermentative H2 production. Whereas wild-type Chlamydomonas fermentation primarily produces formate and ethanol, the double mutant performs a complete rerouting of the glycolytic carbon to lactate and glycerol. Lastly, transcriptome data have been analysed for both the wildtype and hydEF-1, that correlate with our

  11. Network motif frequency vectors reveal evolving metabolic network organisation.

    Pearcy, Nicole; Crofts, Jonathan J; Chuzhanova, Nadia

    2015-01-01

    At the systems level many organisms of interest may be described by their patterns of interaction, and as such, are perhaps best characterised via network or graph models. Metabolic networks, in particular, are fundamental to the proper functioning of many important biological processes, and thus, have been widely studied over the past decade or so. Such investigations have revealed a number of shared topological features, such as a short characteristic path-length, large clustering coefficient and hierarchical modular structure. However, the extent to which evolutionary and functional properties of metabolism manifest via this underlying network architecture remains unclear. In this paper, we employ a novel graph embedding technique, based upon low-order network motifs, to compare metabolic network structure for 383 bacterial species categorised according to a number of biological features. In particular, we introduce a new global significance score which enables us to quantify important evolutionary relationships that exist between organisms and their physical environments. Using this new approach, we demonstrate a number of significant correlations between environmental factors, such as growth conditions and habitat variability, and network motif structure, providing evidence that organism adaptability leads to increased complexities in the resultant metabolic networks.

  12. Flux networks in metabolic graphs

    Warren, P B; Queiros, S M Duarte; Jones, J L

    2009-01-01

    A metabolic model can be represented as a bipartite graph comprising linked reaction and metabolite nodes. Here it is shown how a network of conserved fluxes can be assigned to the edges of such a graph by combining the reaction fluxes with a conserved metabolite property such as molecular weight. A similar flux network can be constructed by combining the primal and dual solutions to the linear programming problem that typically arises in constraint-based modelling. Such constructions may help with the visualization of flux distributions in complex metabolic networks. The analysis also explains the strong correlation observed between metabolite shadow prices (the dual linear programming variables) and conserved metabolite properties. The methods were applied to recent metabolic models for Escherichia coli, Saccharomyces cerevisiae and Methanosarcina barkeri. Detailed results are reported for E. coli; similar results were found for other organisms

  13. Noise effect in metabolic networks

    Zheng-Yan, Li; Zheng-Wei, Xie; Tong, Chen; Qi, Ouyang

    2009-01-01

    Constraint-based models such as flux balance analysis (FBA) are a powerful tool to study biological metabolic networks. Under the hypothesis that cells operate at an optimal growth rate as the result of evolution and natural selection, this model successfully predicts most cellular behaviours in growth rate. However, the model ignores the fact that cells can change their cellular metabolic states during evolution, leaving optimal metabolic states unstable. Here, we consider all the cellular processes that change metabolic states into a single term 'noise', and assume that cells change metabolic states by randomly walking in feasible solution space. By simulating a state of a cell randomly walking in the constrained solution space of metabolic networks, we found that in a noisy environment cells in optimal states tend to travel away from these points. On considering the competition between the noise effect and the growth effect in cell evolution, we found that there exists a trade-off between these two effects. As a result, the population of the cells contains different cellular metabolic states, and the population growth rate is at suboptimal states. (cross-disciplinary physics and related areas of science and technology)

  14. Reconstruction of the yeast protein-protein interaction network involved in nutrient sensing and global metabolic regulation

    Nandy, Subir Kumar; Jouhten, Paula; Nielsen, Jens

    2010-01-01

    proteins. Despite the value of BioGRID for studying protein-protein interactions, there is a need for manual curation of these interactions in order to remove false positives. RESULTS: Here we describe an annotated reconstruction of the protein-protein interactions around four key nutrient......) and for all the interactions between them (edges). The annotated information is readily available utilizing the functionalities of network modelling tools such as Cytoscape and CellDesigner. CONCLUSIONS: The reported fully annotated interaction model serves as a platform for integrated systems biology studies...

  15. Global Operations Networks in Motion

    Slepniov, Dmitrij; Jørgensen, Claus; Wæhrens, Brian Vejrum

    2009-01-01

    This paper addresses the phenomenon of global operations networks and how they change over time. The paper is based on the cases of three Danish companies and their global operations networks. It finds a number of common patterns highlighting some organisational effects and managerial challenges...... the companies face regarding rapid changes in their networks configurations and capabilities. The paper details the variables determining these changes and suggests how the on-going interplay between the focal organisation, its network partners, and their various contextual conditions can be approached....

  16. Global Synoptic Climatology Network (GSCN)

    National Oceanic and Atmospheric Administration, Department of Commerce — Dataset DSI-9290 is the result of a joint effort to create a Global Synoptic Climatology Network among the Meteorological Service of Canada (Downsview, Ontario and...

  17. Towards a global quantum network

    Simon, Christoph

    2017-11-01

    The creation of a global quantum network is now a realistic proposition thanks to developments in satellite and fibre links and quantum memory. Applications will range from secure communication and fundamental physics experiments to a future quantum internet.

  18. Logistical networking: a global storage network

    Beck, Micah; Moore, Terry

    2005-01-01

    The absence of an adequate distributed storage infrastructure for data buffering has become a significant impediment to the flow of work in the wide area, data intensive collaborations that are increasingly characteristic of leading edge research in several fields. One solution to this problem, pioneered under DOE's SciDAC program, is Logistical Networking, which provides a framework for a globally scalable, maximally interoperable storage network based on the Internet Backplane Protocol (IBP). This paper provides a brief overview of the Logistical Networking (LN) architecture, the middleware developed to exploit its value, and a few of the applications that some of research communities have made of it

  19. Managing Evolving Global Operations Networks

    Mykhaylenko, Alona; Wæhrens, Brian Vejrum; Johansen, John

    2015-01-01

    For many globally dispersed organisations, the home base (HB) is a historic locus of integrative and coordinating efforts that safeguard overall performance. However, the dynamism of global operations networks is increasingly pulling the centre of gravity away from the HB and dispersing it across...... the network, challenging the HB’s ability to sustain its centrality over time. To counteract this tendency, this paper addresses the gap in the literature regarding the development of the network management capability of the HB within the context of its network. Data was collected through a retrospective...... longitudinal case study of an intra-organisational operations network of one OEM and its three foreign subsidiaries. The findings suggest a row of strategic roles and corresponding managerial capabilities, which the HB needs to develop depending on the changing subsidiaries’ competencies and HB...

  20. Labour in Global Production Networks

    Lund-Thomsen, Peter; Nadvi, Khalid; Chan, Anita

    A critical challenge facing developing country producers is to meet international labour standards and codes of conduct in order to engage in global production networks. Evidence of gains for workers from compliance with such standards and codes remains limited and patchy. This paper focuses...... on the global football industry, a sector dominated by leading global brands who manage dispersed global production networks. It assesses the work conditions for football stitchers engaged in different forms of work organisation, factories, stitching centres, and home-based settings, in Pakistan, India......, and China. It draws on detailed qualitative primary field research with football stitching workers and producers in these three countries. The paper explains how, and why, work conditions of football stitchers differ across these locations through an analytical framework that interweaves both global...

  1. Global Dislocations, Network Solutions

    Pisani, Francis; Arquilla, John

    2004-01-01

    Globalization is essentially an attempt to foster universal commercial, social and political norms of behavior in a world where diversity—in all areas of interaction—has always ruled. Naturally, the great transformation called for by this vision of interconnectedness sparks tensions with existing institutions and practices. Yet there is nothing predetermined about the ways in which these tensions will be played out in the coming years; and by understanding the causes of potential difficulti...

  2. Regulation of metabolic networks by small molecule metabolites

    Kanehisa Minoru

    2007-03-01

    Full Text Available Abstract Background The ability to regulate metabolism is a fundamental process in living systems. We present an analysis of one of the mechanisms by which metabolic regulation occurs: enzyme inhibition and activation by small molecules. We look at the network properties of this regulatory system and the relationship between the chemical properties of regulatory molecules. Results We find that many features of the regulatory network, such as the degree and clustering coefficient, closely match those of the underlying metabolic network. While these global features are conserved across several organisms, we do find local differences between regulation in E. coli and H. sapiens which reflect their different lifestyles. Chemical structure appears to play an important role in determining a compounds suitability for use in regulation. Chemical structure also often determines how groups of similar compounds can regulate sets of enzymes. These groups of compounds and the enzymes they regulate form modules that mirror the modules and pathways of the underlying metabolic network. We also show how knowledge of chemical structure and regulation could be used to predict regulatory interactions for drugs. Conclusion The metabolic regulatory network shares many of the global properties of the metabolic network, but often varies at the level of individual compounds. Chemical structure is a key determinant in deciding how a compound is used in regulation and for defining modules within the regulatory system.

  3. Uncovering transcriptional regulation of metabolism by using metabolic network topology

    Patil, Kiran Raosaheb; Nielsen, Jens

    2005-01-01

    in the metabolic network that follow a common transcriptional response. Thus, the algorithm enables identification of so-called reporter metabolites (metabolites around which the most significant transcriptional changes occur) and a set of connected genes with significant and coordinated response to genetic......Cellular response to genetic and environmental perturbations is often reflected and/or mediated through changes in the metabolism, because the latter plays a key role in providing Gibbs free energy and precursors for biosynthesis. Such metabolic changes are often exerted through transcriptional...... therefore developed an algorithm that is based on hypothesis-driven data analysis to uncover the transcriptional regulatory architecture of metabolic networks. By using information on the metabolic network topology from genome-scale metabolic reconstruction, we show that it is possible to reveal patterns...

  4. Structuring evolution: biochemical networks and metabolic diversification in birds.

    Morrison, Erin S; Badyaev, Alexander V

    2016-08-25

    Recurrence and predictability of evolution are thought to reflect the correspondence between genomic and phenotypic dimensions of organisms, and the connectivity in deterministic networks within these dimensions. Direct examination of the correspondence between opportunities for diversification imbedded in such networks and realized diversity is illuminating, but is empirically challenging because both the deterministic networks and phenotypic diversity are modified in the course of evolution. Here we overcome this problem by directly comparing the structure of a "global" carotenoid network - comprising of all known enzymatic reactions among naturally occurring carotenoids - with the patterns of evolutionary diversification in carotenoid-producing metabolic networks utilized by birds. We found that phenotypic diversification in carotenoid networks across 250 species was closely associated with enzymatic connectivity of the underlying biochemical network - compounds with greater connectivity occurred the most frequently across species and were the hotspots of metabolic pathway diversification. In contrast, we found no evidence for diversification along the metabolic pathways, corroborating findings that the utilization of the global carotenoid network was not strongly influenced by history in avian evolution. The finding that the diversification in species-specific carotenoid networks is qualitatively predictable from the connectivity of the underlying enzymatic network points to significant structural determinism in phenotypic evolution.

  5. Language Choice & Global Learning Networks

    Dennis Sayers

    1995-05-01

    Full Text Available How can other languages be used in conjunction with English to further intercultural and multilingual learning when teachers and students participate in computer-based global learning networks? Two portraits are presented of multilingual activities in the Orillas and I*EARN learning networks, and are discussed as examples of the principal modalities of communication employed in networking projects between distant classes. Next, an important historical precedent --the social controversy which accompanied the introduction of telephone technology at the end of the last century-- is examined in terms of its implications for language choice in contemporary classroom telecomputing projects. Finally, recommendations are offered to guide decision making concerning the role of language choice in promoting collaborative critical inquiry.

  6. Modular co-evolution of metabolic networks

    Yu Zhong-Hao

    2007-08-01

    Full Text Available Abstract Background The architecture of biological networks has been reported to exhibit high level of modularity, and to some extent, topological modules of networks overlap with known functional modules. However, how the modular topology of the molecular network affects the evolution of its member proteins remains unclear. Results In this work, the functional and evolutionary modularity of Homo sapiens (H. sapiens metabolic network were investigated from a topological point of view. Network decomposition shows that the metabolic network is organized in a highly modular core-periphery way, in which the core modules are tightly linked together and perform basic metabolism functions, whereas the periphery modules only interact with few modules and accomplish relatively independent and specialized functions. Moreover, over half of the modules exhibit co-evolutionary feature and belong to specific evolutionary ages. Peripheral modules tend to evolve more cohesively and faster than core modules do. Conclusion The correlation between functional, evolutionary and topological modularity suggests that the evolutionary history and functional requirements of metabolic systems have been imprinted in the architecture of metabolic networks. Such systems level analysis could demonstrate how the evolution of genes may be placed in a genome-scale network context, giving a novel perspective on molecular evolution.

  7. Global action networks: agents for collective action

    Glasbergen, P.

    2010-01-01

    Global action networks (GANs) are civil society initiated multi-stakeholder arrangements that aim to fulfill a leadership role for systemic change in global governance for sustainable development. The paper develops a network approach to study some of these GANs as motivators of global collective

  8. Global health research needs global networking

    Ignaciuk, A.; Leemans, R.

    2012-01-01

    To meet the challenges arising from global environmental change on human health, co-developing common approaches and new alliances of science and society are necessary. The first steps towards defining cross-cutting, health-environment issues were developed by the Global Environmental Change and

  9. Hierarchical analysis of dependency in metabolic networks.

    Gagneur, Julien; Jackson, David B; Casari, Georg

    2003-05-22

    Elucidation of metabolic networks for an increasing number of organisms reveals that even small networks can contain thousands of reactions and chemical species. The intimate connectivity between components complicates their decomposition into biologically meaningful sub-networks. Moreover, traditional higher-order representations of metabolic networks as metabolic pathways, suffers from the lack of rigorous definition, yielding pathways of disparate content and size. We introduce a hierarchical representation that emphasizes the gross organization of metabolic networks in largely independent pathways and sub-systems at several levels of independence. The approach highlights the coupling of different pathways and the shared compounds responsible for those couplings. By assessing our results on Escherichia coli (E.coli metabolic reactions, Genetic Circuits Research Group, University of California, San Diego, http://gcrg.ucsd.edu/organisms/ecoli.html, 'model v 1.01. reactions') against accepted biochemical annotations, we provide the first systematic synopsis of an organism's metabolism. Comparison with operons of E.coli shows that low-level clusters are reflected in genome organization and gene regulation. Source code, data sets and supplementary information are available at http://www.mas.ecp.fr/labo/equipe/gagneur/hierarchy/hierarchy.html

  10. Control of fluxes in metabolic networks

    Basler, Georg; Nikoloski, Zoran; Larhlimi, Abdelhalim; Barabási, Albert-László; Liu, Yang-Yu

    2016-01-01

    Understanding the control of large-scale metabolic networks is central to biology and medicine. However, existing approaches either require specifying a cellular objective or can only be used for small networks. We introduce new coupling types describing the relations between reaction activities, and develop an efficient computational framework, which does not require any cellular objective for systematic studies of large-scale metabolism. We identify the driver reactions facilitating control of 23 metabolic networks from all kingdoms of life. We find that unicellular organisms require a smaller degree of control than multicellular organisms. Driver reactions are under complex cellular regulation in Escherichia coli, indicating their preeminent role in facilitating cellular control. In human cancer cells, driver reactions play pivotal roles in malignancy and represent potential therapeutic targets. The developed framework helps us gain insights into regulatory principles of diseases and facilitates design of engineering strategies at the interface of gene regulation, signaling, and metabolism. PMID:27197218

  11. Global tree network for computing structures enabling global processing operations

    Blumrich; Matthias A.; Chen, Dong; Coteus, Paul W.; Gara, Alan G.; Giampapa, Mark E.; Heidelberger, Philip; Hoenicke, Dirk; Steinmacher-Burow, Burkhard D.; Takken, Todd E.; Vranas, Pavlos M.

    2010-01-19

    A system and method for enabling high-speed, low-latency global tree network communications among processing nodes interconnected according to a tree network structure. The global tree network enables collective reduction operations to be performed during parallel algorithm operations executing in a computer structure having a plurality of the interconnected processing nodes. Router devices are included that interconnect the nodes of the tree via links to facilitate performance of low-latency global processing operations at nodes of the virtual tree and sub-tree structures. The global operations performed include one or more of: broadcast operations downstream from a root node to leaf nodes of a virtual tree, reduction operations upstream from leaf nodes to the root node in the virtual tree, and point-to-point message passing from any node to the root node. The global tree network is configurable to provide global barrier and interrupt functionality in asynchronous or synchronized manner, and, is physically and logically partitionable.

  12. Global Electricity Trade Network: Structures and Implications

    Ji, Ling; Jia, Xiaoping; Chiu, Anthony S. F.; Xu, Ming

    2016-01-01

    Nations increasingly trade electricity, and understanding the structure of the global power grid can help identify nations that are critical for its reliability. This study examines the global grid as a network with nations as nodes and international electricity trade as links. We analyze the structure of the global electricity trade network and find that the network consists of four sub-networks, and provide a detailed analysis of the largest network, Eurasia. Russia, China, Ukraine, and Azerbaijan have high betweenness measures in the Eurasian sub-network, indicating the degrees of centrality of the positions they hold. The analysis reveals that the Eurasian sub-network consists of seven communities based on the network structure. We find that the communities do not fully align with geographical proximity, and that the present international electricity trade in the Eurasian sub-network causes an approximately 11 million additional tons of CO2 emissions. PMID:27504825

  13. Final Report: Filling Knowledge Gaps in Biological Networks: Integrated Global Approaches to Understand H{sub 2} Metabolism in Chlamydomonas Reinhardtii

    Grossman, Arthur

    2012-05-01

    The major goal of our part of this project has been to generate mutants in fermentation metabolism and begin to decipher how lesions in the pathways associated with fermentation metabolism impact both H{sub 2} production and the production of other metabolites that accumulate as cells become anoxic. We are also trying to understand how metabolic pathways are regulated as O{sub 2} in the environment becomes depleted.

  14. The Global Epidemic of the Metabolic Syndrome.

    Saklayen, Mohammad G

    2018-02-26

    Metabolic syndrome, variously known also as syndrome X, insulin resistance, etc., is defined by WHO as a pathologic condition characterized by abdominal obesity, insulin resistance, hypertension, and hyperlipidemia. Though there is some variation in the definition by other health care organization, the differences are minor. With the successful conquest of communicable infectious diseases in most of the world, this new non-communicable disease (NCD) has become the major health hazard of modern world. Though it started in the Western world, with the spread of the Western lifestyle across the globe, it has become now a truly global problem. The prevalence of the metabolic syndrome is often more in the urban population of some developing countries than in its Western counterparts. The two basic forces spreading this malady are the increase in consumption of high calorie-low fiber fast food and the decrease in physical activity due to mechanized transportations and sedentary form of leisure time activities. The syndrome feeds into the spread of the diseases like type 2 diabetes, coronary diseases, stroke, and other disabilities. The total cost of the malady including the cost of health care and loss of potential economic activity is in trillions. The present trend is not sustainable unless a magic cure is found (unlikely) or concerted global/governmental/societal efforts are made to change the lifestyle that is promoting it. There are certainly some elements in the causation of the metabolic syndrome that cannot be changed but many are amenable for corrections and curtailments. For example, better urban planning to encourage active lifestyle, subsidizing consumption of whole grains and possible taxing high calorie snacks, restricting media advertisement of unhealthy food, etc. Revitalizing old fashion healthier lifestyle, promoting old-fashioned foods using healthy herbs rather than oil and sugar, and educating people about choosing healthy/wholesome food over junks

  15. Are we connected? : Ports in Global Networks

    R.A. Zuidwijk (Rob)

    2015-01-01

    markdownabstractAbstract Global supply chains are built on organizational, information, and logistics networks. Ports are connected via these networks and also need to connect these networks. Synchromodality is an innovative concept for container transportation, and the port plays an important

  16. Strategic Knowledge Networks for Global Education

    Peterson, J. Fiona

    2009-01-01

    The inherent opportunities for communication, collaboration and experiential learning in an online and global network create the impetus for the new network paradigm in higher education. A strategic knowledge network in education was designed and developed to build "Mode 2" knowledge capabilities; create new knowledge for innovative…

  17. Thermodynamics-based Metabolite Sensitivity Analysis in metabolic networks.

    Kiparissides, A; Hatzimanikatis, V

    2017-01-01

    The increasing availability of large metabolomics datasets enhances the need for computational methodologies that can organize the data in a way that can lead to the inference of meaningful relationships. Knowledge of the metabolic state of a cell and how it responds to various stimuli and extracellular conditions can offer significant insight in the regulatory functions and how to manipulate them. Constraint based methods, such as Flux Balance Analysis (FBA) and Thermodynamics-based flux analysis (TFA), are commonly used to estimate the flow of metabolites through genome-wide metabolic networks, making it possible to identify the ranges of flux values that are consistent with the studied physiological and thermodynamic conditions. However, unless key intracellular fluxes and metabolite concentrations are known, constraint-based models lead to underdetermined problem formulations. This lack of information propagates as uncertainty in the estimation of fluxes and basic reaction properties such as the determination of reaction directionalities. Therefore, knowledge of which metabolites, if measured, would contribute the most to reducing this uncertainty can significantly improve our ability to define the internal state of the cell. In the present work we combine constraint based modeling, Design of Experiments (DoE) and Global Sensitivity Analysis (GSA) into the Thermodynamics-based Metabolite Sensitivity Analysis (TMSA) method. TMSA ranks metabolites comprising a metabolic network based on their ability to constrain the gamut of possible solutions to a limited, thermodynamically consistent set of internal states. TMSA is modular and can be applied to a single reaction, a metabolic pathway or an entire metabolic network. This is, to our knowledge, the first attempt to use metabolic modeling in order to provide a significance ranking of metabolites to guide experimental measurements. Copyright © 2016 International Metabolic Engineering Society. Published by Elsevier

  18. Estimating the size of the solution space of metabolic networks

    Mulet Roberto

    2008-05-01

    Full Text Available Abstract Background Cellular metabolism is one of the most investigated system of biological interactions. While the topological nature of individual reactions and pathways in the network is quite well understood there is still a lack of comprehension regarding the global functional behavior of the system. In the last few years flux-balance analysis (FBA has been the most successful and widely used technique for studying metabolism at system level. This method strongly relies on the hypothesis that the organism maximizes an objective function. However only under very specific biological conditions (e.g. maximization of biomass for E. coli in reach nutrient medium the cell seems to obey such optimization law. A more refined analysis not assuming extremization remains an elusive task for large metabolic systems due to algorithmic limitations. Results In this work we propose a novel algorithmic strategy that provides an efficient characterization of the whole set of stable fluxes compatible with the metabolic constraints. Using a technique derived from the fields of statistical physics and information theory we designed a message-passing algorithm to estimate the size of the affine space containing all possible steady-state flux distributions of metabolic networks. The algorithm, based on the well known Bethe approximation, can be used to approximately compute the volume of a non full-dimensional convex polytope in high dimensions. We first compare the accuracy of the predictions with an exact algorithm on small random metabolic networks. We also verify that the predictions of the algorithm match closely those of Monte Carlo based methods in the case of the Red Blood Cell metabolic network. Then we test the effect of gene knock-outs on the size of the solution space in the case of E. coli central metabolism. Finally we analyze the statistical properties of the average fluxes of the reactions in the E. coli metabolic network. Conclusion We propose a

  19. Acquisition management of the Global Transportation Network

    2001-08-02

    This report discusses the acquisition management of the Global transportation Network by the U.S. Transportation Command. This report is one in a series of audit reports addressing DoD acquisition management of information technology systems. The Glo...

  20. The UNESCO Global Network of National Geoparks

    Mc Keever1, P.; Zouros, N.; Patzak, M.; Missotten, R.

    2009-12-01

    The UNESCO Global Network of National Geoparks was founded in 2004, following the model successfully established by the European Geoparks Network in 2000. It now comprises 63 members in 19 nations across the world. A Global Geopark is an area with geological heritage of international value but where that heritage is being used for the sustainable economic benefit if the local inhabitants, primarily through education and tourism. Supported by IUGS and IUCN, the aim of the Global Geoparks Network is to facilitate exchange and sharing between members to assist in the protection and conservation of the geological heritage of our planet but to do so in way where local communities can take ownership of these special places and where they can get some sustainable economic benefit from them. While allowing for the sustainable economic development of geoparks, the network explicitly forbids the destruction or sale of the geological value of a geopark. This paper outlines the ethos of the Global Geoparks Network and describes the typical activities of geoparks and how the network functions. Using two examples it also illustrates how members of the Global Geoparks Network provide good examples as tools not only for holistic nature conservation but also for economic development.

  1. Identification of metabolic system parameters using global optimization methods

    Gatzke Edward P

    2006-01-01

    Full Text Available Abstract Background The problem of estimating the parameters of dynamic models of complex biological systems from time series data is becoming increasingly important. Methods and results Particular consideration is given to metabolic systems that are formulated as Generalized Mass Action (GMA models. The estimation problem is posed as a global optimization task, for which novel techniques can be applied to determine the best set of parameter values given the measured responses of the biological system. The challenge is that this task is nonconvex. Nonetheless, deterministic optimization techniques can be used to find a global solution that best reconciles the model parameters and measurements. Specifically, the paper employs branch-and-bound principles to identify the best set of model parameters from observed time course data and illustrates this method with an existing model of the fermentation pathway in Saccharomyces cerevisiae. This is a relatively simple yet representative system with five dependent states and a total of 19 unknown parameters of which the values are to be determined. Conclusion The efficacy of the branch-and-reduce algorithm is illustrated by the S. cerevisiae example. The method described in this paper is likely to be widely applicable in the dynamic modeling of metabolic networks.

  2. Framework for network modularization and Bayesian network analysis to investigate the perturbed metabolic network

    Kim Hyun

    2011-12-01

    Full Text Available Abstract Background Genome-scale metabolic network models have contributed to elucidating biological phenomena, and predicting gene targets to engineer for biotechnological applications. With their increasing importance, their precise network characterization has also been crucial for better understanding of the cellular physiology. Results We herein introduce a framework for network modularization and Bayesian network analysis (FMB to investigate organism’s metabolism under perturbation. FMB reveals direction of influences among metabolic modules, in which reactions with similar or positively correlated flux variation patterns are clustered, in response to specific perturbation using metabolic flux data. With metabolic flux data calculated by constraints-based flux analysis under both control and perturbation conditions, FMB, in essence, reveals the effects of specific perturbations on the biological system through network modularization and Bayesian network analysis at metabolic modular level. As a demonstration, this framework was applied to the genetically perturbed Escherichia coli metabolism, which is a lpdA gene knockout mutant, using its genome-scale metabolic network model. Conclusions After all, it provides alternative scenarios of metabolic flux distributions in response to the perturbation, which are complementary to the data obtained from conventionally available genome-wide high-throughput techniques or metabolic flux analysis.

  3. Framework for network modularization and Bayesian network analysis to investigate the perturbed metabolic network.

    Kim, Hyun Uk; Kim, Tae Yong; Lee, Sang Yup

    2011-01-01

    Genome-scale metabolic network models have contributed to elucidating biological phenomena, and predicting gene targets to engineer for biotechnological applications. With their increasing importance, their precise network characterization has also been crucial for better understanding of the cellular physiology. We herein introduce a framework for network modularization and Bayesian network analysis (FMB) to investigate organism's metabolism under perturbation. FMB reveals direction of influences among metabolic modules, in which reactions with similar or positively correlated flux variation patterns are clustered, in response to specific perturbation using metabolic flux data. With metabolic flux data calculated by constraints-based flux analysis under both control and perturbation conditions, FMB, in essence, reveals the effects of specific perturbations on the biological system through network modularization and Bayesian network analysis at metabolic modular level. As a demonstration, this framework was applied to the genetically perturbed Escherichia coli metabolism, which is a lpdA gene knockout mutant, using its genome-scale metabolic network model. After all, it provides alternative scenarios of metabolic flux distributions in response to the perturbation, which are complementary to the data obtained from conventionally available genome-wide high-throughput techniques or metabolic flux analysis.

  4. The global structure of knowledge network

    Angelopoulos, Spyros; Lomi, Alessandro

    2017-01-01

    In this paper, we treat patent citations as knowledge networks connecting pieces of formalized knowledge and people, and focus on how ideas are connected, rather than how they are protected. We focus on the global structural properties of formalized knowledge network, and more specifically on the

  5. Networking the Global Maritime Partnership

    Galdorisi, George; Hszieh, Stephanie; McKearney, Terry

    2008-01-01

    The modern-day notion of a "Global Maritime Partnership," first introduced by then-CNO Admiral Michael Mullen at the 2005 International Seapower Symposium as "The 1000-Ship Navy," and later enshrined in the new U.S...

  6. GLOBAL CONVERGENCE FOR THE XOR BOOLEAN NETWORKS

    Ho, Juei-Ling

    2009-01-01

    Shih and Ho have proved a global convergent theorem for boolean network: if a map from $\\{0,1\\}^{n}$ to itself defines a boolean network has the conditions: (1) each column of the discrete Jacobian matrix of each element of $\\{0,1\\}^{n}$ is either a unit vector or a zero vector; (2) all the boolean eigenvalues of the discrete Jacobian matrix of this map evaluated at each element of $\\{0,1\\}^{n}$ are zero, then it has a unique fixed point and this boolean network is global convergent to the fi...

  7. The network of global corporate control.

    Vitali, Stefania; Glattfelder, James B; Battiston, Stefano

    2011-01-01

    The structure of the control network of transnational corporations affects global market competition and financial stability. So far, only small national samples were studied and there was no appropriate methodology to assess control globally. We present the first investigation of the architecture of the international ownership network, along with the computation of the control held by each global player. We find that transnational corporations form a giant bow-tie structure and that a large portion of control flows to a small tightly-knit core of financial institutions. This core can be seen as an economic "super-entity" that raises new important issues both for researchers and policy makers.

  8. Insights from the cold transcriptome and metabolome of Dendrobium officinale: global reprogramming of metabolic and gene regulation networks during cold acclimation

    Zhi-Gang Wu

    2016-11-01

    Full Text Available Plant cold acclimation (CA is a genetically complex phenomenon involving gene regulation and expression. Little is known about the cascading pattern of gene regulatroy network and the link between genes and metabolites during CA. Dendrobium officinale (DOKM is an important medicinal and ornamental plant and hypersensitive to low temperature. Here, we used the large scale metabolomic and transcriptomic technologies to reveal the response to CA in DOKM seedlings based on the physiological profile analyses. Lowering temperature from 4 oC to -2 oC resulted in significant increase(P<0.01)in antioxidant activities and electrolyte leakage during 24 h. The fitness CA piont of 0 oC and control (20 oC during 20 h were firstly obtained according to physiological analyses. Subsequently, massive transcriptome and metabolome reprogramming occurred during CA. The gene to metabolite network demonstrated that the CA associated processes are highly energy demanding through activating hydrolysis of sugars, amino acids catabolism and citrate cycle. The expression levels of 2,767 genes were significantly affected by CA, including 153-fold upregulation of CBF transcription factor, 56-fold upregulation of MAPKKK16 protein kinase. Moreover, the gene interaction and regulation network analysis revealed that the CA as an active process, was regulated at the transcriptional, post-transcriptional, translational and post-translational levels. Our findings highligted a comprehensive regulatory mechanism including cold signal transduction, transcriptional regulation and gene expression, which contributes a deeper understanding of the highly complex regulatory program during CA in DOKM. Some marker genes identified in DOKM seedlings will allow us to understand the role of each individual during CA by further functional analyses.

  9. Anthropomorphic Networks as Representatives of Global Consciousness

    Sergii Yahodzinskyi

    2018-02-01

    Full Text Available There has been analyzed a phenomenon of global consciousness, and its cultural and historical, civilizational dimensions have been substantiated. There has been demonstrated that the concept of planetary consciousness, global thinking, noosphere was described for the first time in the philosophy of cosmism. However, in modern conditions ideas of representatives of the naturalistic philosophical direction of cosmism have not lost their heuristic potential. They can be reconsidered in a new fashion within the context of emerging anthropomorphic (human dimension networks. There has been proved that global consciousness is a component of the social and cultural potential of global information networks defining vectors to prospects of humanity progress in the 21st century. Relying on methodology of the structural and functional analysis, the author arrives at a conclusion about global networks obtaining the status of representatives of global consciousness. This is the area of networks where all relevant information is concentrated – from statistical data to scientific and technical information. Access to these data is limited by human abilities and is realized in the form of discrete requests with using heuristic algorithms of information procession. A suggestion is introduced considering the fact that modern society being a self-organized system seeks to gain stable condition. Anthropomorphic networks are means of decreasing social entropy, which is growing as a result of any kind of human intervention into social processes. Thus, for the first time a human is challenged by their intellect, ability to create, discover and control.

  10. Development of the Global Measles Laboratory Network.

    Featherstone, David; Brown, David; Sanders, Ray

    2003-05-15

    The routine reporting of suspected measles cases and laboratory testing of samples from these cases is the backbone of measles surveillance. The Global Measles Laboratory Network (GMLN) has developed standards for laboratory confirmation of measles and provides training resources for staff of network laboratories, reference materials and expertise for the development and quality control of testing procedures, and accurate information for the Measles Mortality Reduction and Regional Elimination Initiative. The GMLN was developed along the lines of the successful Global Polio Laboratory Network, and much of the polio laboratory infrastructure was utilized for measles. The GMLN has developed as countries focus on measles control activities following successful eradication of polio. Currently more than 100 laboratories are part of the global network and follow standardized testing and reporting procedures. A comprehensive laboratory accreditation process will be introduced in 2002 with six quality assurance and performance indicators.

  11. Network configuration of global R&D networks

    Hansen, Zaza Nadja Lee; Srai, Jagjit Singh

    2011-01-01

    , network configuration of global R&D has tended to focus on strategic elements with limited attention given operational effectiveness, or to interfaces with downstream manufacturing operations. Within OM literature, the drivers of configuration of global networks within, engineering, production, supply...... to R&D networks emerged, e.g. product features were more prominent in R&D networks. Furthermore, the study has shown extensive interaction with other operations, including many downstream manufacturing operations. By extending the OM configuration concepts to the configuration of R&D networks......Companies are increasingly globalising their R&D activities, both within the firms and with external partners, with consequent implications for their interaction with manufacturing operations. Previous research in R&D networks has focused on coordination, governance and support elements. However...

  12. MANAGING GLOBAL OPERATIONS NETWORKS IN MOTION

    Slepniov, Dmitrij; Jørgensen, Claus; Sørensen, Brian Vejrum

    2008-01-01

    capabilities and intensified need for transfer, assimilation and augmentation of activities and know-how within the network. Based on these the paper highlights some organisational effects and managerial challenges the companies face regarding rapid changes in their networks configurations and capabilities.......Most industrial companies are, for reasons related to cost, market access or knowledge, working with some aspect of offshore operations. This may take form of captive operations or through outsourcing of activities overseas. With this trend, global operations networks are emerging resulting...... in corporate strategic repositioning, re-configurations of sites, and changes to the underlying capabilities. The paper is based on cases of 3 Danish companies and their global supply networks. These networks are not in a steady state, they evolve as a consequence of the ongoing co-evolution between the focal...

  13. Solidarity Action in Global Labor Networks

    Wad, Peter

    2014-01-01

    Globalization transforms workforces of transnational corporation from predominantly home countrydominated workforces into foreign-dominated, multinational workforces. Thus, the national grounding of trade unions as the key form of labor organizing is challenged by new multinational compositions...... and cross-border relocations of corporate employment affecting working conditions of employees and trade unions in local places. We assume that economic globalization is characterized by expanding global corporate network of vertically and horizontally integrated (equity-based) and disintegrated (nonequity......-based) value chains. We also assume that globalization can both impede and enable labor empowerment. Based on these premises the key question is, how can labor leverage effective power against management in global corporate networks? This question is split into two subquestions: a) How can labor theoretically...

  14. Resistance Genes in Global Crop Breeding Networks.

    Garrett, K A; Andersen, K F; Asche, F; Bowden, R L; Forbes, G A; Kulakow, P A; Zhou, B

    2017-10-01

    Resistance genes are a major tool for managing crop diseases. The networks of crop breeders who exchange resistance genes and deploy them in varieties help to determine the global landscape of resistance and epidemics, an important system for maintaining food security. These networks function as a complex adaptive system, with associated strengths and vulnerabilities, and implications for policies to support resistance gene deployment strategies. Extensions of epidemic network analysis can be used to evaluate the multilayer agricultural networks that support and influence crop breeding networks. Here, we evaluate the general structure of crop breeding networks for cassava, potato, rice, and wheat. All four are clustered due to phytosanitary and intellectual property regulations, and linked through CGIAR hubs. Cassava networks primarily include public breeding groups, whereas others are more mixed. These systems must adapt to global change in climate and land use, the emergence of new diseases, and disruptive breeding technologies. Research priorities to support policy include how best to maintain both diversity and redundancy in the roles played by individual crop breeding groups (public versus private and global versus local), and how best to manage connectivity to optimize resistance gene deployment while avoiding risks to the useful life of resistance genes. [Formula: see text] Copyright © 2017 The Author(s). This is an open access article distributed under the CC BY 4.0 International license .

  15. The global transmission network of HIV-1.

    Wertheim, Joel O; Leigh Brown, Andrew J; Hepler, N Lance; Mehta, Sanjay R; Richman, Douglas D; Smith, Davey M; Kosakovsky Pond, Sergei L

    2014-01-15

    Human immunodeficiency virus type 1 (HIV-1) is pandemic, but its contemporary global transmission network has not been characterized. A better understanding of the properties and dynamics of this network is essential for surveillance, prevention, and eventual eradication of HIV. Here, we apply a simple and computationally efficient network-based approach to all publicly available HIV polymerase sequences in the global database, revealing a contemporary picture of the spread of HIV-1 within and between countries. This approach automatically recovered well-characterized transmission clusters and extended other clusters thought to be contained within a single country across international borders. In addition, previously undescribed transmission clusters were discovered. Together, these clusters represent all known modes of HIV transmission. The extent of international linkage revealed by our comprehensive approach demonstrates the need to consider the global diversity of HIV, even when describing local epidemics. Finally, the speed of this method allows for near-real-time surveillance of the pandemic's progression.

  16. Networking the Global Maritime Partnership

    2016-04-13

    Strike, and Sea Basing) as “old wine in new bottles,” but with them Admiral Clark introduced a new term, “FORCEnet,” which referred to “an initiative...the primary reasons for the overwhelming combat power demonstrated in recent operations.18 C4ISR advances not only benefit so-called high-end...of the benefits of the adoption by coalition naval forces of a networked force structure. The report of AG-1 prompted leaders of the MAR in 2005 to

  17. A Network of Networks Perspective on Global Trade.

    Maluck, Julian; Donner, Reik V

    2015-01-01

    Mutually intertwined supply chains in contemporary economy result in a complex network of trade relationships with a highly non-trivial topology that varies with time. In order to understand the complex interrelationships among different countries and economic sectors, as well as their dynamics, a holistic view on the underlying structural properties of this network is necessary. This study employs multi-regional input-output data to decompose 186 national economies into 26 industry sectors and utilizes the approach of interdependent networks to analyze the substructure of the resulting international trade network for the years 1990-2011. The partition of the network into national economies is observed to be compatible with the notion of communities in the sense of complex network theory. By studying internal versus cross-subgraph contributions to established complex network metrics, new insights into the architecture of global trade are obtained, which allow to identify key elements of global economy. Specifically, financial services and business activities dominate domestic trade whereas electrical and machinery industries dominate foreign trade. In order to further specify each national sector's role individually, (cross-)clustering coefficients and cross-betweenness are obtained for different pairs of subgraphs. The corresponding analysis reveals that specific industrial sectors tend to favor distinct directionality patterns and that the cross-clustering coefficient for geographically close country pairs is remarkably high, indicating that spatial factors are still of paramount importance for the organization of trade patterns in modern economy. Regarding the evolution of the trade network's substructure, globalization is well-expressed by trends of several structural characteristics (e.g., link density and node strength) in the interacting network framework. Extreme events, such as the financial crisis 2008/2009, are manifested as anomalies superimposed to

  18. Global network centrality of university rankings

    Guo, Weisi; Del Vecchio, Marco; Pogrebna, Ganna

    2017-10-01

    Universities and higher education institutions form an integral part of the national infrastructure and prestige. As academic research benefits increasingly from international exchange and cooperation, many universities have increased investment in improving and enabling their global connectivity. Yet, the relationship of university performance and its global physical connectedness has not been explored in detail. We conduct, to our knowledge, the first large-scale data-driven analysis into whether there is a correlation between university relative ranking performance and its global connectivity via the air transport network. The results show that local access to global hubs (as measured by air transport network betweenness) strongly and positively correlates with the ranking growth (statistical significance in different models ranges between 5% and 1% level). We also found that the local airport's aggregate flight paths (degree) and capacity (weighted degree) has no effect on university ranking, further showing that global connectivity distance is more important than the capacity of flight connections. We also examined the effect of local city economic development as a confounding variable and no effect was observed suggesting that access to global transportation hubs outweighs economic performance as a determinant of university ranking. The impact of this research is that we have determined the importance of the centrality of global connectivity and, hence, established initial evidence for further exploring potential connections between university ranking and regional investment policies on improving global connectivity.

  19. Metabolic network prediction through pairwise rational kernels.

    Roche-Lima, Abiel; Domaratzki, Michael; Fristensky, Brian

    2014-09-26

    Metabolic networks are represented by the set of metabolic pathways. Metabolic pathways are a series of biochemical reactions, in which the product (output) from one reaction serves as the substrate (input) to another reaction. Many pathways remain incompletely characterized. One of the major challenges of computational biology is to obtain better models of metabolic pathways. Existing models are dependent on the annotation of the genes. This propagates error accumulation when the pathways are predicted by incorrectly annotated genes. Pairwise classification methods are supervised learning methods used to classify new pair of entities. Some of these classification methods, e.g., Pairwise Support Vector Machines (SVMs), use pairwise kernels. Pairwise kernels describe similarity measures between two pairs of entities. Using pairwise kernels to handle sequence data requires long processing times and large storage. Rational kernels are kernels based on weighted finite-state transducers that represent similarity measures between sequences or automata. They have been effectively used in problems that handle large amount of sequence information such as protein essentiality, natural language processing and machine translations. We create a new family of pairwise kernels using weighted finite-state transducers (called Pairwise Rational Kernel (PRK)) to predict metabolic pathways from a variety of biological data. PRKs take advantage of the simpler representations and faster algorithms of transducers. Because raw sequence data can be used, the predictor model avoids the errors introduced by incorrect gene annotations. We then developed several experiments with PRKs and Pairwise SVM to validate our methods using the metabolic network of Saccharomyces cerevisiae. As a result, when PRKs are used, our method executes faster in comparison with other pairwise kernels. Also, when we use PRKs combined with other simple kernels that include evolutionary information, the accuracy

  20. Genome-scale reconstruction of the Saccharomyces cerevisiae metabolic network

    Förster, Jochen; Famili, I.; Fu, P.

    2003-01-01

    The metabolic network in the yeast Saccharomyces cerevisiae was reconstructed using currently available genomic, biochemical, and physiological information. The metabolic reactions were compartmentalized between the cytosol and the mitochondria, and transport steps between the compartments...

  1. Integration of metabolomics data into metabolic networks.

    Töpfer, Nadine; Kleessen, Sabrina; Nikoloski, Zoran

    2015-01-01

    Metabolite levels together with their corresponding metabolic fluxes are integrative outcomes of biochemical transformations and regulatory processes and they can be used to characterize the response of biological systems to genetic and/or environmental changes. However, while changes in transcript or to some extent protein levels can usually be traced back to one or several responsible genes, changes in fluxes and particularly changes in metabolite levels do not follow such rationale and are often the outcome of complex interactions of several components. The increasing quality and coverage of metabolomics technologies have fostered the development of computational approaches for integrating metabolic read-outs with large-scale models to predict the physiological state of a system. Constraint-based approaches, relying on the stoichiometry of the considered reactions, provide a modeling framework amenable to analyses of large-scale systems and to the integration of high-throughput data. Here we review the existing approaches that integrate metabolomics data in variants of constrained-based approaches to refine model reconstructions, to constrain flux predictions in metabolic models, and to relate network structural properties to metabolite levels. Finally, we discuss the challenges and perspectives in the developments of constraint-based modeling approaches driven by metabolomics data.

  2. From genomes to in silico cells via metabolic networks

    Borodina, Irina; Nielsen, Jens

    2005-01-01

    Genome-scale metabolic models are the focal point of systems biology as they allow the collection of various data types in a form suitable for mathematical analysis. High-quality metabolic networks and metabolic networks with incorporated regulation have been successfully used for the analysis...... of phenotypes from phenotypic arrays and in gene-deletion studies. They have also been used for gene expression analysis guided by metabolic network structure, leading to the identification of commonly regulated genes. Thus, genome-scale metabolic modeling currently stands out as one of the most promising...

  3. Four Challenges That Global Health Networks Face

    Jeremy Shiffman

    2017-04-01

    Full Text Available Global health networks, webs of individuals and organizations with a shared concern for a particular condition, have proliferated over the past quarter century. They differ in their effectiveness, a factor that may help explain why resource allocations vary across health conditions and do not correspond closely with disease burden. Drawing on findings from recently concluded studies of eight global health networks—addressing alcohol harm, early childhood development (ECD, maternal mortality, neonatal mortality, pneumonia, surgically-treatable conditions, tobacco use, and tuberculosis—I identify four challenges that networks face in generating attention and resources for the conditions that concern them. The first is problem definition: generating consensus on what the problem is and how it should be addressed. The second is positioning: portraying the issue in ways that inspire external audiences to act. The third is coalition-building: forging alliances with these external actors, particularly ones outside the health sector. The fourth is governance: establishing institutions to facilitate collective action. Research indicates that global health networks that effectively tackle these challenges are more likely to garner support to address the conditions that concern them. In addition to the effectiveness of networks, I also consider their legitimacy, identifying reasons both to affirm and to question their right to exert power.

  4. Astroglial Metabolic Networks Sustain Hippocampal Synaptic Transmission

    Rouach, Nathalie; Koulakoff, Annette; Abudara, Veronica; Willecke, Klaus; Giaume, Christian

    2008-12-01

    Astrocytes provide metabolic substrates to neurons in an activity-dependent manner. However, the molecular mechanisms involved in this function, as well as its role in synaptic transmission, remain unclear. Here, we show that the gap-junction subunit proteins connexin 43 and 30 allow intercellular trafficking of glucose and its metabolites through astroglial networks. This trafficking is regulated by glutamatergic synaptic activity mediated by AMPA receptors. In the absence of extracellular glucose, the delivery of glucose or lactate to astrocytes sustains glutamatergic synaptic transmission and epileptiform activity only when they are connected by gap junctions. These results indicate that astroglial gap junctions provide an activity-dependent intercellular pathway for the delivery of energetic metabolites from blood vessels to distal neurons.

  5. Astroglial metabolic networks sustain hippocampal synaptic transmission.

    Rouach, Nathalie; Koulakoff, Annette; Abudara, Veronica; Willecke, Klaus; Giaume, Christian

    2008-12-05

    Astrocytes provide metabolic substrates to neurons in an activity-dependent manner. However, the molecular mechanisms involved in this function, as well as its role in synaptic transmission, remain unclear. Here, we show that the gap-junction subunit proteins connexin 43 and 30 allow intercellular trafficking of glucose and its metabolites through astroglial networks. This trafficking is regulated by glutamatergic synaptic activity mediated by AMPA receptors. In the absence of extracellular glucose, the delivery of glucose or lactate to astrocytes sustains glutamatergic synaptic transmission and epileptiform activity only when they are connected by gap junctions. These results indicate that astroglial gap junctions provide an activity-dependent intercellular pathway for the delivery of energetic metabolites from blood vessels to distal neurons.

  6. Metabolic networks of Cucurbita maxima phloem.

    Fiehn, Oliver

    2003-03-01

    Metabolomic analysis aims at a comprehensive characterization of biological samples. Yet, biologically meaningful interpretations are often limited by the poor spatial and temporal resolution of the acquired data sets. One way to remedy this is to limit the complexity of the cell types being studied. Cucurbita maxima Duch. vascular exudates provide an excellent material for metabolomics in this regard. Using automated mass spectral deconvolution, over 400 components have been detected in these exudates, but only 90 of them were tentatively identified. Many amino compounds were found in vascular exudates from leaf petioles at concentrations several orders of magnitude higher than in tissue disks from the same leaves, whereas hexoses and sucrose were found in far lower amounts. In order to find the expected impact of assimilation rates on sugar levels, total phloem composition of eight leaves from four plants was followed over 4.5 days. Surprisingly, no diurnal rhythm was found for any of the phloem metabolites that was statistically valid for all eight leaves. Instead, each leaf had its own distinct vascular exudate profile similar to leaves from the same plant, but clearly different from leaves harvested from plants at the same developmental stage. Thirty to forty per cent of all metabolite levels of individual leaves were different from the average of all metabolite profiles. Using metabolic co-regulation analysis, similarities and differences between the exudate profiles were more accurately characterized through network computation, specifically with respect to nitrogen metabolism.

  7. Global Interconnectedness - Local Authorities and Transnational Networking

    Hans Krause Hansen

    2006-09-01

    Full Text Available This article argues that, in their continuous and proclaimed efforts at "modernizing" themselves, public sector organizations, also at the sub-national level, increasingly envision the new media as an object of policy making and intervention. At the same time, this focus on the new media facilitates transborder networking, taking the shape of globalizing webs that connect the actors internationally through pro- cesses af mediation and with implications for relations af authority and modes of governance. As such, these webs both constitute and facilitate a form of everyday political globalization which is on the rise. Empirically, our account is based on studies of two local authorities, the cities of Vina del Mar in Chile and Bremen in Germany, as two of the transnational networks that connect them.

  8. Environmental versatility promotes modularity in genome-scale metabolic networks.

    Samal, Areejit; Wagner, Andreas; Martin, Olivier C

    2011-08-24

    The ubiquity of modules in biological networks may result from an evolutionary benefit of a modular organization. For instance, modularity may increase the rate of adaptive evolution, because modules can be easily combined into new arrangements that may benefit their carrier. Conversely, modularity may emerge as a by-product of some trait. We here ask whether this last scenario may play a role in genome-scale metabolic networks that need to sustain life in one or more chemical environments. For such networks, we define a network module as a maximal set of reactions that are fully coupled, i.e., whose fluxes can only vary in fixed proportions. This definition overcomes limitations of purely graph based analyses of metabolism by exploiting the functional links between reactions. We call a metabolic network viable in a given chemical environment if it can synthesize all of an organism's biomass compounds from nutrients in this environment. An organism's metabolism is highly versatile if it can sustain life in many different chemical environments. We here ask whether versatility affects the modularity of metabolic networks. Using recently developed techniques to randomly sample large numbers of viable metabolic networks from a vast space of metabolic networks, we use flux balance analysis to study in silico metabolic networks that differ in their versatility. We find that highly versatile networks are also highly modular. They contain more modules and more reactions that are organized into modules. Most or all reactions in a module are associated with the same biochemical pathways. Modules that arise in highly versatile networks generally involve reactions that process nutrients or closely related chemicals. We also observe that the metabolism of E. coli is significantly more modular than even our most versatile networks. Our work shows that modularity in metabolic networks can be a by-product of functional constraints, e.g., the need to sustain life in multiple

  9. Environmental versatility promotes modularity in genome-scale metabolic networks

    Wagner Andreas

    2011-08-01

    Full Text Available Abstract Background The ubiquity of modules in biological networks may result from an evolutionary benefit of a modular organization. For instance, modularity may increase the rate of adaptive evolution, because modules can be easily combined into new arrangements that may benefit their carrier. Conversely, modularity may emerge as a by-product of some trait. We here ask whether this last scenario may play a role in genome-scale metabolic networks that need to sustain life in one or more chemical environments. For such networks, we define a network module as a maximal set of reactions that are fully coupled, i.e., whose fluxes can only vary in fixed proportions. This definition overcomes limitations of purely graph based analyses of metabolism by exploiting the functional links between reactions. We call a metabolic network viable in a given chemical environment if it can synthesize all of an organism's biomass compounds from nutrients in this environment. An organism's metabolism is highly versatile if it can sustain life in many different chemical environments. We here ask whether versatility affects the modularity of metabolic networks. Results Using recently developed techniques to randomly sample large numbers of viable metabolic networks from a vast space of metabolic networks, we use flux balance analysis to study in silico metabolic networks that differ in their versatility. We find that highly versatile networks are also highly modular. They contain more modules and more reactions that are organized into modules. Most or all reactions in a module are associated with the same biochemical pathways. Modules that arise in highly versatile networks generally involve reactions that process nutrients or closely related chemicals. We also observe that the metabolism of E. coli is significantly more modular than even our most versatile networks. Conclusions Our work shows that modularity in metabolic networks can be a by-product of functional

  10. A Network of Networks Perspective on Global Trade

    Maluck, Julian; Donner, Reik V.

    2015-01-01

    Mutually intertwined supply chains in contemporary economy result in a complex network of trade relationships with a highly non-trivial topology that varies with time. In order to understand the complex interrelationships among different countries and economic sectors, as well as their dynamics, a holistic view on the underlying structural properties of this network is necessary. This study employs multi-regional input-output data to decompose 186 national economies into 26 industry sectors and utilizes the approach of interdependent networks to analyze the substructure of the resulting international trade network for the years 1990–2011. The partition of the network into national economies is observed to be compatible with the notion of communities in the sense of complex network theory. By studying internal versus cross-subgraph contributions to established complex network metrics, new insights into the architecture of global trade are obtained, which allow to identify key elements of global economy. Specifically, financial services and business activities dominate domestic trade whereas electrical and machinery industries dominate foreign trade. In order to further specify each national sector’s role individually, (cross-)clustering coefficients and cross-betweenness are obtained for different pairs of subgraphs. The corresponding analysis reveals that specific industrial sectors tend to favor distinct directionality patterns and that the cross-clustering coefficient for geographically close country pairs is remarkably high, indicating that spatial factors are still of paramount importance for the organization of trade patterns in modern economy. Regarding the evolution of the trade network’s substructure, globalization is well-expressed by trends of several structural characteristics (e.g., link density and node strength) in the interacting network framework. Extreme events, such as the financial crisis 2008/2009, are manifested as anomalies superimposed

  11. REMOTE OPERATIONS IN A GLOBAL ACCELERATOR NETWORK

    PEGGS, S.; SATOGATA, T.; AGARWAL, D.; RICE, D.

    2003-01-01

    The INTRODUCTION to this paper summarizes the history of the Global Accelerator Network (GAN) concept and the recent workshops that discussed the relationship between GAN and Remote Operations. The REMOTE OPERATIONS SCENARIOS section brings out the organizational philosophy embodied in GAN-like and to non-GAN-like scenarios. The set of major TOPICS RAISED AT THE WORKSHOPS are only partially resolved. COLLABORATION TOOLS are described and discussed, followed by examples of REMOTE ACCELERATOR CONTROL PROJECTS around the world

  12. Remote operations in a global accelerator network

    Peggs, Steve; Satogata, Todd; Agarwal, Deborah; Rice, David

    2003-01-01

    The INTRODUCTION to this paper summarizes the history of the Global Accelerator Network (GAN) concept and the recent workshops that discussed the relationship between GAN and Remote Operations. The REMOTE OPERATIONS SCENARIOS section brings out the organizational philosophy embodied in GAN-like and to non-GAN-like scenarios. The set of major TOPICS RAISED AT THE WORKSHOPS are only partially resolved. COLLABORATION TOOLS are described and discussed, followed by examples of REMOTE ACCELERATOR CONTROL PROJECTS around the world

  13. REMOTE OPERATIONS IN A GLOBAL ACCELERATOR NETWORK.

    PEGGS,S.; SATOGATA,T.; AGARWAL,D.; RICE,D.

    2003-05-12

    The INTRODUCTION to this paper summarizes the history of the Global Accelerator Network (GAN) concept and the recent workshops that discussed the relationship between GAN and Remote Operations. The REMOTE OPERATIONS SCENARIOS section brings out the organizational philosophy embodied in GAN-like and to non-GAN-like scenarios. The set of major TOPICS RAISED AT THE WORKSHOPS are only partially resolved. COLLABORATION TOOLS are described and discussed, followed by examples of REMOTE ACCELERATOR CONTROL PROJECTS around the world.

  14. The Global Alzheimer's Association Interactive Network.

    Toga, Arthur W; Neu, Scott C; Bhatt, Priya; Crawford, Karen L; Ashish, Naveen

    2016-01-01

    The Global Alzheimer's Association Interactive Network (GAAIN) is consolidating the efforts of independent Alzheimer's disease data repositories around the world with the goals of revealing more insights into the causes of Alzheimer's disease, improving treatments, and designing preventative measures that delay the onset of physical symptoms. We developed a system for federating these repositories that is reliant on the tenets that (1) its participants require incentives to join, (2) joining the network is not disruptive to existing repository systems, and (3) the data ownership rights of its members are protected. We are currently in various phases of recruitment with over 55 data repositories in North America, Europe, Asia, and Australia and can presently query >250,000 subjects using GAAIN's search interfaces. GAAIN's data sharing philosophy, which guided our architectural choices, is conducive to motivating membership in a voluntary data sharing network. Copyright © 2016 The Alzheimer's Association. Published by Elsevier Inc. All rights reserved.

  15. The Global Climatology Network Precipitation data

    Peterson, T.C.; Easterling, D.R.; Eischeid, J.K.

    1993-01-01

    Several years ago, in response to growing concern about global climate change, the US National Climatic Data Center and the Carbon Dioxide Information Analysis Center undertook an effort to create a baseline global land surface climate data set called the Global Historical Climatology Network (GHCN, Vose et al., 1992). GHCN was created by merging several large existing climate data sets into one data base. Fifteen separate data sets went into the creation of the GHCN version 1.0. GHCN version 1.0 was released in 1992. It has 7,533 precipitation stations, but the number of stations varies with time. A slight majority (55%) have records in excess of 50 years, and a significant proportion (13%) have records in excess of 100 years. The longest period of record for any given station is 291 years (1697--1987 for Kew, United Kingdom)

  16. The Importance of Transition Metals in the Expanding Network of Microbial Metabolism in the Archean Eon

    Moore, E. K.; Jelen, B. I.; Giovannelli, D.; Prabhu, A.; Raanan, H.; Falkowski, P. G.

    2017-12-01

    Deep time changes in Earth surface redox conditions, particularly due to global oxygenation, has impacted the availability of different metals and substrates that are central in biology. Oxidoreductase proteins are molecular nanomachines responsible for all biological electron transfer processes across the tree of life. These enzymes largely contain transition metals in their active sites. Microbial metabolic pathways form a global network of electron transfer, which expanded throughout the Archean eon. Older metabolisms (sulfur reduction, methanogenesis, anoxygenic photosynthesis) accessed negative redox potentials, while later evolving metabolisms (oxygenic photosynthesis, nitrification/denitrification, aerobic respiration) accessed positive redox potentials. The incorporation of different transition metals facilitated biological innovation and the expansion of the network of microbial metabolism. Network analysis was used to examine the connections between microbial taxa, metabolic pathways, crucial metallocofactors, and substrates in deep time by incorporating biosignatures preserved in the geologic record. Nitrogen fixation and aerobic respiration have the highest level of betweenness among metabolisms in the network, indicating that the oldest metabolisms are not the most central. Fe has by far the highest betweenness among metals. Clustering analysis largely separates High Metal Bacteria (HMB), Low Metal Bacteria (LMB), and Archaea showing that simple un-weighted links between taxa, metabolism, and metals have phylogenetic relevance. On average HMB have the highest betweenness among taxa, followed by Archaea and LMB. There is a correlation between the number of metallocofactors and metabolic pathways in representative bacterial taxa, but Archaea do not follow this trend. In many cases older and more recently evolved metabolisms were clustered together supporting previous findings that proliferation of metabolic pathways is not necessarily chronological.

  17. Genome-Scale Reconstruction of the Human Astrocyte Metabolic Network

    Mart?n-Jim?nez, Cynthia A.; Salazar-Barreto, Diego; Barreto, George E.; Gonz?lez, Janneth

    2017-01-01

    Astrocytes are the most abundant cells of the central nervous system; they have a predominant role in maintaining brain metabolism. In this sense, abnormal metabolic states have been found in different neuropathological diseases. Determination of metabolic states of astrocytes is difficult to model using current experimental approaches given the high number of reactions and metabolites present. Thus, genome-scale metabolic networks derived from transcriptomic data can be used as a framework t...

  18. The Global Environment Radiation Monitoring Network (GERMON)

    Zakheim, B.J.; Goellner, D.A.

    1994-01-01

    Following the Chernobyl accident in 1986, a group of experts from the World Health Organization (WHO) and the United Nations Environment Program (UNEP) met in France to discuss and develop the basic principles of a global environmental radiation monitoring network (GERMON). The basic functions of this network were to provide regular reports on environmental radiation levels and to be in a position to provide reliable and accurate radiation measurements on a quick and accurate radiation measurements on a quick turnaround basis in the event of a major radiation release. By 1992, although 58 countries had indicated an interest in becoming a part of the GERMON system, only 16 were providing data on a regular basis. This paper traces the history of GERMON from its inception in 1987 through its activities during 1993-4. It details the objectives of the network, describes functions, lists its participants, and presents obstacles in the current network. The paper examines the data requirements for radiological emergency preparedness and offers suggestions for the current system. The paper also describes the growing need for such a network. To add a domestic perspective, the authors present a summary of the environmental monitoring information system that was used by the NRC in 1986 in its analyses of the Chernobyl incident. Then we will use this 1986 experience to propose a method for the use of GERMON should a similar occasion arise in the future

  19. Connexin 43-Mediated Astroglial Metabolic Networks Contribute to the Regulation of the Sleep-Wake Cycle.

    Clasadonte, Jerome; Scemes, Eliana; Wang, Zhongya; Boison, Detlev; Haydon, Philip G

    2017-09-13

    Astrocytes produce and supply metabolic substrates to neurons through gap junction-mediated astroglial networks. However, the role of astroglial metabolic networks in behavior is unclear. Here, we demonstrate that perturbation of astroglial networks impairs the sleep-wake cycle. Using a conditional Cre-Lox system in mice, we show that knockout of the gap junction subunit connexin 43 in astrocytes throughout the brain causes excessive sleepiness and fragmented wakefulness during the nocturnal active phase. This astrocyte-specific genetic manipulation silenced the wake-promoting orexin neurons located in the lateral hypothalamic area (LHA) by impairing glucose and lactate trafficking through astrocytic networks. This global wakefulness instability was mimicked with viral delivery of Cre recombinase to astrocytes in the LHA and rescued by in vivo injections of lactate. Our findings propose a novel regulatory mechanism critical for maintaining normal daily cycle of wakefulness and involving astrocyte-neuron metabolic interactions. Copyright © 2017 Elsevier Inc. All rights reserved.

  20. Global Nuclear Safety and Security Network

    Guo Lingquan

    2013-01-01

    The objectives of the Regulatory Network are: - to contribute to the effectiveness of nuclear regulatory systems; - to contribute to continuous enhancements, and - to achieve and promote radiation and nuclear safety and security by: • Enhancing the effectiveness and efficiency of international cooperation in the regulation of nuclear and radiation safety of facilities and activities; • Enabling adequate access by regulators to relevant safety and security information; • Promoting dissemination of information on safety and security issues as well as information of good practices for addressing and resolving these issues; • Enabling synergies among different web based networks with a view to strengthening and enhancing the global nuclear safety framework and serving the specific needs of regulators and international organizations; • Providing additional information to the public on international regulatory cooperation in safety and security matters

  1. Building a Global Ocean Science Education Network

    Scowcroft, G. A.; Tuddenham, P. T.; Pizziconi, R.

    2016-02-01

    It is imperative for ocean science education to be closely linked to ocean science research. This is especially important for research that addresses global concerns that cross national boundaries, including climate related issues. The results of research on these critical topics must find its way to the public, educators, and students of all ages around the globe. To facilitate this, opportunities are needed for ocean scientists and educators to convene and identify priorities and strategies for ocean science education. On June 26 and 27, 2015 the first Global Ocean Science Education (GOSE) Workshop was convened in the United States at the University of Rhode Island Graduate School of Oceanography. The workshop, sponsored by the Consortium for Ocean Science Exploration and Engagement (COSEE) and the College of Exploration, had over 75 participants representing 15 nations. The workshop addressed critical global ocean science topics, current ocean science research and education priorities, advanced communication technologies, and leveraging international ocean research technologies. In addition, panels discussed elementary, secondary, undergraduate, graduate, and public education across the ocean basins with emphasis on opportunities for international collaboration. Special presentation topics included advancements in tropical cyclone forecasting, collaborations among Pacific Islands, ocean science for coastal resiliency, and trans-Atlantic collaboration. This presentation will focus on workshop outcomes as well as activities for growing a global ocean science education network. A summary of the workshop report will also be provided. The dates and location for the 2016 GOES Workshop will be announced. See http://www.coexploration.net/gose/index.html

  2. Network Fictions and the Global Unhomely

    Aris Mousoutzanis

    2016-04-01

    Full Text Available The paper suggests that the increasing proliferation of network fictions in literature, film, television and the internet may be interpreted through a theoretical framework that reconceptuallises the originally strictly psychoanalytic concept of the 'Unheimlich' (Freud’s idea of the ‘unhomely’ or ‘uncanny’ within the context of political, economic and cultural disources fo globalisation. ‘Network fictions’ are those texts consisting of multiple interlocking narratives set in various times and places that explore the interconnections of characters and events across different storylines: novels such as William Gibson’s 'Pattern Recognition' (2003, Hari Kunzro’s 'Transmission' (2005 and 'Gods Without Men' (2011, David Mitchell’s 'Cloud Atlas' (2004, or Rana Dasgupta’s 'Tokyo Cancelled' (2005 are some examples. My argument is that central to these fictions is a sense of a ‘global unhomely’. The sense of displacement, unhomeliness and global mobility that is conveyed in these fictions is fundamental to the experience of the 'Unheimlich'. In addition, the ability of the concept to convey a combined sense of the familiar and the strange is useful in exploring the ways in which these fictions engage with theoretical debates on globalisation that perceive the interaction between global flows and local cultures either in terms of homogenisation and uniformity or of heterogenisation and hybridity. Moreover, the repetitive temporality of the 'Unheimlich' is another distinctive aspect that allows a reading of the disjunctive, non-linear temporal structure of these fictions from this perspective. The ‘repetition compulsion’, however, that Freud considered to be an example of uncanniness was also theorised by him as a post-traumatic symptom, and this implicit association of uncanniness with post-traumatic experience also allows to interpret the persistent preoccupation of these fictions with suffering and disaster, as well as

  3. Horizontal and vertical growth of S. cerevisiae metabolic network.

    Grassi, Luigi

    2011-10-14

    BACKGROUND: The growth and development of a biological organism is reflected by its metabolic network, the evolution of which relies on the essential gene duplication mechanism. There are two current views about the evolution of metabolic networks. The retrograde model hypothesizes that a pathway evolves by recruiting novel enzymes in a direction opposite to the metabolic flow. The patchwork model is instead based on the assumption that the evolution is based on the exploitation of broad-specificity enzymes capable of catalysing a variety of metabolic reactions. RESULTS: We analysed a well-studied unicellular eukaryotic organism, S. cerevisiae, and studied the effect of the removal of paralogous gene products on its metabolic network. Our results, obtained using different paralog and network definitions, show that, after an initial period when gene duplication was indeed instrumental in expanding the metabolic space, the latter reached an equilibrium and subsequent gene duplications were used as a source of more specialized enzymes rather than as a source of novel reactions. We also show that the switch between the two evolutionary strategies in S. cerevisiae can be dated to about 350 million years ago. CONCLUSIONS: Our data, obtained through a novel analysis methodology, strongly supports the hypothesis that the patchwork model better explains the more recent evolution of the S. cerevisiae metabolic network. Interestingly, the effects of a patchwork strategy acting before the Euascomycete-Hemiascomycete divergence are still detectable today.

  4. Slave nodes and the controllability of metabolic networks

    Kim, Dong-Hee; Motter, Adilson E

    2009-01-01

    Recent work on synthetic rescues has shown that the targeted deletion of specific metabolic genes can often be used to rescue otherwise non-viable mutants. This raises a fundamental biophysical question: to what extent can the whole-cell behavior of a large metabolic network be controlled by constraining the flux of one or more reactions in the network? This touches upon the issue of the number of degrees of freedom contained by one such network. Using the metabolic network of Escherichia coli as a model system, here we address this question theoretically by exploring not only reaction deletions, but also a continuum of all possible reaction expression levels. We show that the behavior of the metabolic network can be largely manipulated by the pinned expression of a single reaction. In particular, a relevant fraction of the metabolic reactions exhibits canalizing interactions, in that the specification of one reaction flux determines cellular growth as well as the fluxes of most other reactions in optimal steady states. The activity of individual reactions can thus be used as surrogates to monitor and possibly control cellular growth and other whole-cell behaviors. In addition to its implications for the study of control processes, our methodology provides a new approach to study how the integrated dynamics of the entire metabolic network emerges from the coordinated behavior of its component parts.

  5. Does habitat variability really promote metabolic network modularity?

    Takemoto, Kazuhiro

    2013-01-01

    The hypothesis that variability in natural habitats promotes modular organization is widely accepted for cellular networks. However, results of some data analyses and theoretical studies have begun to cast doubt on the impact of habitat variability on modularity in metabolic networks. Therefore, we re-evaluated this hypothesis using statistical data analysis and current metabolic information. We were unable to conclude that an increase in modularity was the result of habitat variability. Although horizontal gene transfer was also considered because it may contribute for survival in a variety of environments, closely related to habitat variability, and is known to be positively correlated with network modularity, such a positive correlation was not concluded in the latest version of metabolic networks. Furthermore, we demonstrated that the previously observed increase in network modularity due to habitat variability and horizontal gene transfer was probably due to a lack of available data on metabolic reactions. Instead, we determined that modularity in metabolic networks is dependent on species growth conditions. These results may not entirely discount the impact of habitat variability and horizontal gene transfer. Rather, they highlight the need for a more suitable definition of habitat variability and a more careful examination of relationships of the network modularity with horizontal gene transfer, habitats, and environments.

  6. Sierra Stars Observatory Network: An Accessible Global Network

    Williams, Richard; Beshore, Edward

    2011-03-01

    The Sierra Stars Observatory Network (SSON) is a unique partnership among professional observatories that provides its users with affordable high-quality calibrated image data. SSON comprises observatories in the Northern and Southern Hemisphere and is in the process of expanding to a truly global network capable of covering the entire sky 24 hours a day in the near future. The goal of SSON is to serve the needs of science-based projects and programs. Colleges, universities, institutions, and individuals use SSON for their education and research projects. The mission of SSON is to promote and expand the use of its facilities among the thousands of colleges and schools worldwide that do not have access to professional-quality automated observatory systems to use for astronomy education and research. With appropriate leadership and guidance educators can use SSON to help teach astronomy and do meaningful scientific projects. The relatively small cost of using SSON for this type of work makes it affordable and accessible for educators to start using immediately. Remote observatory services like SSON need to evolve to better support education and research initiatives of colleges, institutions and individual investigators. To meet these needs, SSON is developing a sophisticated interactive scheduling system to integrate among the nodes of the observatory network. This will enable more dynamic observations, including immediate priority interrupts, acquiring moving objects using ephemeris data, and more.

  7. NASA's Contribution to Global Space Geodesy Networks

    Bosworth, John M.

    1999-01-01

    The NASA Space Geodesy program continues to be a major provider of space geodetic data for the international earth science community. NASA operates high performance Satellite Laser Ranging (SLR), Very Long Baseline Interferometry (VLBI) and Global Positioning System (GPS) ground receivers at well over 30 locations around the world and works in close cooperation with space geodetic observatories around the world. NASA has also always been at the forefront in the quest for technical improvement and innovation in the space geodesy technologies to make them even more productive, accurate and economical. This presentation will highlight the current status of NASA's networks; the plans for partnerships with international groups in the southern hemisphere to improve the geographic distribution of space geodesy sites and the status of the technological improvements in SLR and VLBI that will support the new scientific thrusts proposed by interdisciplinary earth scientists. In addition, the expanding role of the NASA Space geodesy data archive, the CDDIS will be described.

  8. The Role of Functional Interdependencies in Global Operations Networks

    Slepniov, Dmitrij; Wæhrens, Brian Vejrum

    2011-01-01

    The existing studies do not adequately address the complex interplay between co-evolving production, innovation and service networks. The widening geographical and cognitive gap between these networks means that managing their interfaces in global operations context is becoming strategically...

  9. Microalgal Metabolic Network Model Refinement through High-Throughput Functional Metabolic Profiling

    Chaiboonchoe, Amphun; Dohai, Bushra Saeed; Cai, Hong; Nelson, David R.; Jijakli, Kenan; Salehi-Ashtiani, Kourosh

    2014-01-01

    Metabolic modeling provides the means to define metabolic processes at a systems level; however, genome-scale metabolic models often remain incomplete in their description of metabolic networks and may include reactions that are experimentally unverified. This shortcoming is exacerbated in reconstructed models of newly isolated algal species, as there may be little to no biochemical evidence available for the metabolism of such isolates. The phenotype microarray (PM) technology (Biolog, Hayward, CA, USA) provides an efficient, high-throughput method to functionally define cellular metabolic activities in response to a large array of entry metabolites. The platform can experimentally verify many of the unverified reactions in a network model as well as identify missing or new reactions in the reconstructed metabolic model. The PM technology has been used for metabolic phenotyping of non-photosynthetic bacteria and fungi, but it has not been reported for the phenotyping of microalgae. Here, we introduce the use of PM assays in a systematic way to the study of microalgae, applying it specifically to the green microalgal model species Chlamydomonas reinhardtii. The results obtained in this study validate a number of existing annotated metabolic reactions and identify a number of novel and unexpected metabolites. The obtained information was used to expand and refine the existing COBRA-based C. reinhardtii metabolic network model iRC1080. Over 254 reactions were added to the network, and the effects of these additions on flux distribution within the network are described. The novel reactions include the support of metabolism by a number of d-amino acids, l-dipeptides, and l-tripeptides as nitrogen sources, as well as support of cellular respiration by cysteamine-S-phosphate as a phosphorus source. The protocol developed here can be used as a foundation to functionally profile other microalgae such as known microalgae mutants and novel isolates.

  10. Microalgal Metabolic Network Model Refinement through High-Throughput Functional Metabolic Profiling

    Chaiboonchoe, Amphun; Dohai, Bushra Saeed; Cai, Hong; Nelson, David R. [Division of Science and Math, New York University Abu Dhabi, Abu Dhabi (United Arab Emirates); Center for Genomics and Systems Biology (CGSB), New York University Abu Dhabi Institute, Abu Dhabi (United Arab Emirates); Jijakli, Kenan [Division of Science and Math, New York University Abu Dhabi, Abu Dhabi (United Arab Emirates); Center for Genomics and Systems Biology (CGSB), New York University Abu Dhabi Institute, Abu Dhabi (United Arab Emirates); Engineering Division, Biofinery, Manhattan, KS (United States); Salehi-Ashtiani, Kourosh, E-mail: ksa3@nyu.edu [Division of Science and Math, New York University Abu Dhabi, Abu Dhabi (United Arab Emirates); Center for Genomics and Systems Biology (CGSB), New York University Abu Dhabi Institute, Abu Dhabi (United Arab Emirates)

    2014-12-10

    Metabolic modeling provides the means to define metabolic processes at a systems level; however, genome-scale metabolic models often remain incomplete in their description of metabolic networks and may include reactions that are experimentally unverified. This shortcoming is exacerbated in reconstructed models of newly isolated algal species, as there may be little to no biochemical evidence available for the metabolism of such isolates. The phenotype microarray (PM) technology (Biolog, Hayward, CA, USA) provides an efficient, high-throughput method to functionally define cellular metabolic activities in response to a large array of entry metabolites. The platform can experimentally verify many of the unverified reactions in a network model as well as identify missing or new reactions in the reconstructed metabolic model. The PM technology has been used for metabolic phenotyping of non-photosynthetic bacteria and fungi, but it has not been reported for the phenotyping of microalgae. Here, we introduce the use of PM assays in a systematic way to the study of microalgae, applying it specifically to the green microalgal model species Chlamydomonas reinhardtii. The results obtained in this study validate a number of existing annotated metabolic reactions and identify a number of novel and unexpected metabolites. The obtained information was used to expand and refine the existing COBRA-based C. reinhardtii metabolic network model iRC1080. Over 254 reactions were added to the network, and the effects of these additions on flux distribution within the network are described. The novel reactions include the support of metabolism by a number of d-amino acids, l-dipeptides, and l-tripeptides as nitrogen sources, as well as support of cellular respiration by cysteamine-S-phosphate as a phosphorus source. The protocol developed here can be used as a foundation to functionally profile other microalgae such as known microalgae mutants and novel isolates.

  11. Sirtuins as regulators of the yeast metabolic network

    Markus eRalser

    2012-03-01

    Full Text Available There is growing evidence that the metabolic network is an integral regulator of cellularphysiology. Dynamic changes in metabolite concentrations, metabolic flux, or networktopology act as reporters of biological or environmental signals, and are required for the cellto trigger an appropriate biological reaction. Changes in the metabolic network are recognizedby specific sensory macromolecules and translated into a transcriptional or translationalresponse. The protein family of sirtuins, discovered more than 30 years ago as regulators ofsilent chromatin, seems to fulfill the role of a metabolic sensor during aging and conditions ofcaloric restriction. NAD+/NADH interconverting metabolic enzymes glyceraldehyde-3-phosphate dehydrogenase and alcohol dehydrogenase, as well as enzymes involved inNAD(H, synthesis provide or deprive NAD+ in close proximity to Sir2. This influence sirtuinactivity, and facilitates a dynamic response of the metabolic network to changes inmetabolism with effects on physiology and aging. The molecular network downstream Sir2,however, is complex. In just two orders, Sir2’s metabolism-related interactions span half ofthe yeast proteome, and are connected with virtually every physiological process. Thus,although it is fundamental to analyze single molecular mechanisms, it is at the same timecrucial to consider this genome-scale complexity when correlating single molecular eventswith phenotypes such as aging, cell growth, or stress resistance.

  12. Integration of metabolome data with metabolic networks reveals reporter reactions

    Çakir, Tunahan; Patil, Kiran Raosaheb; Önsan, Zeynep Ilsen

    2006-01-01

    Interpreting quantitative metabolome data is a difficult task owing to the high connectivity in metabolic networks and inherent interdependency between enzymatic regulation, metabolite levels and fluxes. Here we present a hypothesis-driven algorithm for the integration of such data with metabolic...... network topology. The algorithm thus enables identification of reporter reactions, which are reactions where there are significant coordinated changes in the level of surrounding metabolites following environmental/genetic perturbations. Applicability of the algorithm is demonstrated by using data from...... is measured. By combining the results with transcriptome data, we further show that it is possible to infer whether the reactions are hierarchically or metabolically regulated. Hereby, the reported approach represents an attempt to map different layers of regulation within metabolic networks through...

  13. Global synchronization of a class of delayed complex networks

    Li Ping; Yi Zhang; Zhang Lei

    2006-01-01

    Global synchronization of a class of complex networks with time-varying delays is investigated in this paper. Some sufficient conditions are derived. These conditions show that the synchronization of delayed complex networks can be determined by their topologies. In addition, these conditions are simply represented in terms of the networks coupling matrix and are easy to be checked. A typical example of complex networks with chaotic nodes is employed to illustrate the obtained global synchronization results

  14. GERMON. Global Environmental Radiation Monitoring Network

    1992-01-01

    Between 15-18 December 1987, a meeting of experts of WHO/UNEP met at Le Vesinet, France, to develop the basic principles of a global environmental radiation monitoring network (GERMON) which would have the function of reporting on a regular basis environmental radiation levels, and be positioned to provide rapid and reliable radiation measurements in the event of a major radiation release. To date, some 58 countries have indicated their willingness to become part of GERMON. About 40 of these have technical staff and equipment to meet the minimum requirements for joining the network, and about 30 have designated appropriate organizations within their country to serve as national Liaison Institutions for GERMON. Sixteen countries are now providing data on a regular basis to the CCC at SCPRI in Le Vesinet, France. Thirty-two countries responded to the request of WHO for readiness to take part in a IAEA radiation emergency exercise. The present meeting has been held in Montgomery, Alabama, USA at the National Air and Radiation Environmental Laboratory between 27 April 1992 and 30 April 1992, with the purpose of reviewing GERMON. One important topic considered was the implementation of GERMON in the Americas. Particular attention was given to the need for better coordination with IAEA in responding to the Convention on Early Notification, to the role of the CCC, to forms of data transmission, etc

  15. Community Health Global Network and Sustainable Development

    Rebekah Young

    2016-01-01

    Full Text Available With the achievements, failures and passing of the Millennium Development Goals (MDG, the world has turned its eyes to the Sustainable Development Goals (SDG, designed to foster sustainable social, economic and environmental development over the next 15 years.(1 Community-led initiatives are increasingly being recognised as playing a key role in realising sustainable community development and in the aspirations of universal healthcare.(2 In many parts of the world, faith-based organisations are some of the main players in community-led development and health care.(3 Community Health Global Network (CHGN creates links between organisations, with the purpose being to encourage communities to recognise their assets and abilities, identify shared concerns and discover solutions together, in order to define and lead their futures in sustainable ways.(4 CHGN has facilitated the development of collaborative groups of health and development initiatives called ‘Clusters’ in several countries including India, Bangladesh, Kenya, Tanzania, Zambia and Myanmar. In March 2016 these Clusters met together in an International Forum, to share learnings, experiences, challenges, achievements and to encourage one another. Discussions held throughout the forum suggest that the CHGN model is helping to promote effective, sustainable development and health care provision on both a local and a global scale.

  16. Construction of phylogenetic trees by kernel-based comparative analysis of metabolic networks.

    Oh, S June; Joung, Je-Gun; Chang, Jeong-Ho; Zhang, Byoung-Tak

    2006-06-06

    To infer the tree of life requires knowledge of the common characteristics of each species descended from a common ancestor as the measuring criteria and a method to calculate the distance between the resulting values of each measure. Conventional phylogenetic analysis based on genomic sequences provides information about the genetic relationships between different organisms. In contrast, comparative analysis of metabolic pathways in different organisms can yield insights into their functional relationships under different physiological conditions. However, evaluating the similarities or differences between metabolic networks is a computationally challenging problem, and systematic methods of doing this are desirable. Here we introduce a graph-kernel method for computing the similarity between metabolic networks in polynomial time, and use it to profile metabolic pathways and to construct phylogenetic trees. To compare the structures of metabolic networks in organisms, we adopted the exponential graph kernel, which is a kernel-based approach with a labeled graph that includes a label matrix and an adjacency matrix. To construct the phylogenetic trees, we used an unweighted pair-group method with arithmetic mean, i.e., a hierarchical clustering algorithm. We applied the kernel-based network profiling method in a comparative analysis of nine carbohydrate metabolic networks from 81 biological species encompassing Archaea, Eukaryota, and Eubacteria. The resulting phylogenetic hierarchies generally support the tripartite scheme of three domains rather than the two domains of prokaryotes and eukaryotes. By combining the kernel machines with metabolic information, the method infers the context of biosphere development that covers physiological events required for adaptation by genetic reconstruction. The results show that one may obtain a global view of the tree of life by comparing the metabolic pathway structures using meta-level information rather than sequence

  17. Construction of phylogenetic trees by kernel-based comparative analysis of metabolic networks

    Chang Jeong-Ho

    2006-06-01

    Full Text Available Abstract Background To infer the tree of life requires knowledge of the common characteristics of each species descended from a common ancestor as the measuring criteria and a method to calculate the distance between the resulting values of each measure. Conventional phylogenetic analysis based on genomic sequences provides information about the genetic relationships between different organisms. In contrast, comparative analysis of metabolic pathways in different organisms can yield insights into their functional relationships under different physiological conditions. However, evaluating the similarities or differences between metabolic networks is a computationally challenging problem, and systematic methods of doing this are desirable. Here we introduce a graph-kernel method for computing the similarity between metabolic networks in polynomial time, and use it to profile metabolic pathways and to construct phylogenetic trees. Results To compare the structures of metabolic networks in organisms, we adopted the exponential graph kernel, which is a kernel-based approach with a labeled graph that includes a label matrix and an adjacency matrix. To construct the phylogenetic trees, we used an unweighted pair-group method with arithmetic mean, i.e., a hierarchical clustering algorithm. We applied the kernel-based network profiling method in a comparative analysis of nine carbohydrate metabolic networks from 81 biological species encompassing Archaea, Eukaryota, and Eubacteria. The resulting phylogenetic hierarchies generally support the tripartite scheme of three domains rather than the two domains of prokaryotes and eukaryotes. Conclusion By combining the kernel machines with metabolic information, the method infers the context of biosphere development that covers physiological events required for adaptation by genetic reconstruction. The results show that one may obtain a global view of the tree of life by comparing the metabolic pathway

  18. Identification of Conserved Moieties in Metabolic Networks by Graph Theoretical Analysis of Atom Transition Networks

    Haraldsdóttir, Hulda S.; Fleming, Ronan M. T.

    2016-01-01

    Conserved moieties are groups of atoms that remain intact in all reactions of a metabolic network. Identification of conserved moieties gives insight into the structure and function of metabolic networks and facilitates metabolic modelling. All moiety conservation relations can be represented as nonnegative integer vectors in the left null space of the stoichiometric matrix corresponding to a biochemical network. Algorithms exist to compute such vectors based only on reaction stoichiometry but their computational complexity has limited their application to relatively small metabolic networks. Moreover, the vectors returned by existing algorithms do not, in general, represent conservation of a specific moiety with a defined atomic structure. Here, we show that identification of conserved moieties requires data on reaction atom mappings in addition to stoichiometry. We present a novel method to identify conserved moieties in metabolic networks by graph theoretical analysis of their underlying atom transition networks. Our method returns the exact group of atoms belonging to each conserved moiety as well as the corresponding vector in the left null space of the stoichiometric matrix. It can be implemented as a pipeline of polynomial time algorithms. Our implementation completes in under five minutes on a metabolic network with more than 4,000 mass balanced reactions. The scalability of the method enables extension of existing applications for moiety conservation relations to genome-scale metabolic networks. We also give examples of new applications made possible by elucidating the atomic structure of conserved moieties. PMID:27870845

  19. Pathway discovery in metabolic networks by subgraph extraction.

    Faust, Karoline; Dupont, Pierre; Callut, Jérôme; van Helden, Jacques

    2010-05-01

    Subgraph extraction is a powerful technique to predict pathways from biological networks and a set of query items (e.g. genes, proteins, compounds, etc.). It can be applied to a variety of different data types, such as gene expression, protein levels, operons or phylogenetic profiles. In this article, we investigate different approaches to extract relevant pathways from metabolic networks. Although these approaches have been adapted to metabolic networks, they are generic enough to be adjusted to other biological networks as well. We comparatively evaluated seven sub-network extraction approaches on 71 known metabolic pathways from Saccharomyces cerevisiae and a metabolic network obtained from MetaCyc. The best performing approach is a novel hybrid strategy, which combines a random walk-based reduction of the graph with a shortest paths-based algorithm, and which recovers the reference pathways with an accuracy of approximately 77%. Most of the presented algorithms are available as part of the network analysis tool set (NeAT). The kWalks method is released under the GPL3 license.

  20. Ensemble Kinetic Modeling of Metabolic Networks from Dynamic Metabolic Profiles

    Gengjie Jia

    2012-11-01

    Full Text Available Kinetic modeling of metabolic pathways has important applications in metabolic engineering, but significant challenges still remain. The difficulties faced vary from finding best-fit parameters in a highly multidimensional search space to incomplete parameter identifiability. To meet some of these challenges, an ensemble modeling method is developed for characterizing a subset of kinetic parameters that give statistically equivalent goodness-of-fit to time series concentration data. The method is based on the incremental identification approach, where the parameter estimation is done in a step-wise manner. Numerical efficacy is achieved by reducing the dimensionality of parameter space and using efficient random parameter exploration algorithms. The shift toward using model ensembles, instead of the traditional “best-fit” models, is necessary to directly account for model uncertainty during the application of such models. The performance of the ensemble modeling approach has been demonstrated in the modeling of a generic branched pathway and the trehalose pathway in Saccharomyces cerevisiae using generalized mass action (GMA kinetics.

  1. Global fluctuations of cerebral blood flow indicate a global brain network independent of systemic factors.

    Zhao, Li; Alsop, David C; Detre, John A; Dai, Weiying

    2017-01-01

    Global synchronization across specialized brain networks is a common feature of network models and in-vivo electrical measurements. Although the imaging of specialized brain networks with blood oxygenation sensitive resting state functional magnetic resonance imaging (rsfMRI) has enabled detailed study of regional networks, the study of globally correlated fluctuations with rsfMRI is confounded by spurious contributions to the global signal from systemic physiologic factors and other noise sources. Here we use an alternative rsfMRI method, arterial spin labeled perfusion MRI, to characterize global correlations and their relationship to correlations and anti-correlations between regional networks. Global fluctuations that cannot be explained by systemic factors dominate the fluctuations in cerebral blood flow. Power spectra of these fluctuations are band limited to below 0.05 Hz, similar to prior measurements of regional network fluctuations in the brain. Removal of these global fluctuations prior to measurement of regional networks reduces all regional network fluctuation amplitudes to below the global fluctuation amplitude and changes the strength and sign of inter network correlations. Our findings support large amplitude, globally synchronized activity across networks that require a reassessment of regional network amplitude and correlation measures.

  2. Preferential attachment in the evolution of metabolic networks

    Elofsson Arne

    2005-11-01

    Full Text Available Abstract Background Many biological networks show some characteristics of scale-free networks. Scale-free networks can evolve through preferential attachment where new nodes are preferentially attached to well connected nodes. In networks which have evolved through preferential attachment older nodes should have a higher average connectivity than younger nodes. Here we have investigated preferential attachment in the context of metabolic networks. Results The connectivities of the enzymes in the metabolic network of Escherichia coli were determined and representatives for these enzymes were located in 11 eukaryotes, 17 archaea and 46 bacteria. E. coli enzymes which have representatives in eukaryotes have a higher average connectivity while enzymes which are represented only in the prokaryotes, and especially the enzymes only present in βγ-proteobacteria, have lower connectivities than expected by chance. Interestingly, the enzymes which have been proposed as candidates for horizontal gene transfer have a higher average connectivity than the other enzymes. Furthermore, It was found that new edges are added to the highly connected enzymes at a faster rate than to enzymes with low connectivities which is consistent with preferential attachment. Conclusion Here, we have found indications of preferential attachment in the metabolic network of E. coli. A possible biological explanation for preferential attachment growth of metabolic networks is that novel enzymes created through gene duplication maintain some of the compounds involved in the original reaction, throughout its future evolution. In addition, we found that enzymes which are candidates for horizontal gene transfer have a higher average connectivity than other enzymes. This indicates that while new enzymes are attached preferentially to highly connected enzymes, these highly connected enzymes have sometimes been introduced into the E. coli genome by horizontal gene transfer. We speculate

  3. Signatures of arithmetic simplicity in metabolic network architecture.

    William J Riehl

    2010-04-01

    Full Text Available Metabolic networks perform some of the most fundamental functions in living cells, including energy transduction and building block biosynthesis. While these are the best characterized networks in living systems, understanding their evolutionary history and complex wiring constitutes one of the most fascinating open questions in biology, intimately related to the enigma of life's origin itself. Is the evolution of metabolism subject to general principles, beyond the unpredictable accumulation of multiple historical accidents? Here we search for such principles by applying to an artificial chemical universe some of the methodologies developed for the study of genome scale models of cellular metabolism. In particular, we use metabolic flux constraint-based models to exhaustively search for artificial chemistry pathways that can optimally perform an array of elementary metabolic functions. Despite the simplicity of the model employed, we find that the ensuing pathways display a surprisingly rich set of properties, including the existence of autocatalytic cycles and hierarchical modules, the appearance of universally preferable metabolites and reactions, and a logarithmic trend of pathway length as a function of input/output molecule size. Some of these properties can be derived analytically, borrowing methods previously used in cryptography. In addition, by mapping biochemical networks onto a simplified carbon atom reaction backbone, we find that properties similar to those predicted for the artificial chemistry hold also for real metabolic networks. These findings suggest that optimality principles and arithmetic simplicity might lie beneath some aspects of biochemical complexity.

  4. Multi-equilibrium property of metabolic networks: SSI module

    Chen Luonan

    2011-06-01

    Full Text Available Abstract Background Revealing the multi-equilibrium property of a metabolic network is a fundamental and important topic in systems biology. Due to the complexity of the metabolic network, it is generally a difficult task to study the problem as a whole from both analytical and numerical viewpoint. On the other hand, the structure-oriented modularization idea is a good choice to overcome such a difficulty, i.e. decomposing the network into several basic building blocks and then studying the whole network through investigating the dynamical characteristics of the basic building blocks and their interactions. Single substrate and single product with inhibition (SSI metabolic module is one type of the basic building blocks of metabolic networks, and its multi-equilibrium property has important influence on that of the whole metabolic networks. Results In this paper, we describe what the SSI metabolic module is, characterize the rates of the metabolic reactions by Hill kinetics and give a unified model for SSI modules by using a set of nonlinear ordinary differential equations with multi-variables. Specifically, a sufficient and necessary condition is first given to describe the injectivity of a class of nonlinear systems, and then, the sufficient condition is used to study the multi-equilibrium property of SSI modules. As a main theoretical result, for the SSI modules in which each reaction has no more than one inhibitor, a sufficient condition is derived to rule out multiple equilibria, i.e. the Jacobian matrix of its rate function is nonsingular everywhere. Conclusions In summary, we describe SSI modules and give a general modeling framework based on Hill kinetics, and provide a sufficient condition for ruling out multiple equilibria of a key type of SSI module.

  5. Integration of Genome Scale Metabolic Networks and Gene Regulation of Metabolic Enzymes With Physiologically Based Pharmacokinetics.

    Maldonado, Elaina M; Leoncikas, Vytautas; Fisher, Ciarán P; Moore, J Bernadette; Plant, Nick J; Kierzek, Andrzej M

    2017-11-01

    The scope of physiologically based pharmacokinetic (PBPK) modeling can be expanded by assimilation of the mechanistic models of intracellular processes from systems biology field. The genome scale metabolic networks (GSMNs) represent a whole set of metabolic enzymes expressed in human tissues. Dynamic models of the gene regulation of key drug metabolism enzymes are available. Here, we introduce GSMNs and review ongoing work on integration of PBPK, GSMNs, and metabolic gene regulation. We demonstrate example models. © 2017 The Authors CPT: Pharmacometrics & Systems Pharmacology published by Wiley Periodicals, Inc. on behalf of American Society for Clinical Pharmacology and Therapeutics.

  6. Global exponential stability for nonautonomous cellular neural networks with delays

    Zhang Qiang; Wei Xiaopeng; Xu Jin

    2006-01-01

    In this Letter, by utilizing Lyapunov functional method and Halanay inequalities, we analyze global exponential stability of nonautonomous cellular neural networks with delay. Several new sufficient conditions ensuring global exponential stability of the network are obtained. The results given here extend and improve the earlier publications. An example is given to demonstrate the effectiveness of the obtained results

  7. The Global Virus Network: Challenging chikungunya.

    McSweegan, Edward; Weaver, Scott C; Lecuit, Marc; Frieman, Matthew; Morrison, Thomas E; Hrynkow, Sharon

    2015-08-01

    The recent spread of chikungunya virus to the Western Hemisphere, together with the ongoing Ebola epidemic in West Africa, have highlighted the importance of international collaboration in the detection and management of disease outbreaks. In response to this need, the Global Virus Network (GVN) was formed in 2011. The GVN is a coalition of leading medical virologists in 34 affiliated laboratories in 24 countries, who collaborate to share their resources and expertise. The GVN supports research, promotes training for young scientists, serves as a technical resource for governments, businesses and international organizations, facilitates international scientific cooperation, and advocates for funding and evidence-based public policies. In response to the spread of chikungunya, the GVN formed a task force to identify research gaps and opportunities, including models of infection and disease, candidate vaccines and antivirals, epidemiology and vector control measures. Its members also serve as authoritative sources of information for the public, press, and policy-makers. This article forms part of a symposium in Antiviral Research on "Chikungunya discovers the New World". Published by Elsevier B.V.

  8. Global Analysis of Photosynthesis Transcriptional Regulatory Networks

    Imam, Saheed; Noguera, Daniel R.; Donohue, Timothy J.

    2014-01-01

    Photosynthesis is a crucial biological process that depends on the interplay of many components. This work analyzed the gene targets for 4 transcription factors: FnrL, PrrA, CrpK and MppG (RSP_2888), which are known or predicted to control photosynthesis in Rhodobacter sphaeroides. Chromatin immunoprecipitation followed by high-throughput sequencing (ChIP-seq) identified 52 operons under direct control of FnrL, illustrating its regulatory role in photosynthesis, iron homeostasis, nitrogen metabolism and regulation of sRNA synthesis. Using global gene expression analysis combined with ChIP-seq, we mapped the regulons of PrrA, CrpK and MppG. PrrA regulates ∼34 operons encoding mainly photosynthesis and electron transport functions, while CrpK, a previously uncharacterized Crp-family protein, regulates genes involved in photosynthesis and maintenance of iron homeostasis. Furthermore, CrpK and FnrL share similar DNA binding determinants, possibly explaining our observation of the ability of CrpK to partially compensate for the growth defects of a ΔFnrL mutant. We show that the Rrf2 family protein, MppG, plays an important role in photopigment biosynthesis, as part of an incoherent feed-forward loop with PrrA. Our results reveal a previously unrealized, high degree of combinatorial regulation of photosynthetic genes and significant cross-talk between their transcriptional regulators, while illustrating previously unidentified links between photosynthesis and the maintenance of iron homeostasis. PMID:25503406

  9. Global analysis of photosynthesis transcriptional regulatory networks.

    Saheed Imam

    2014-12-01

    Full Text Available Photosynthesis is a crucial biological process that depends on the interplay of many components. This work analyzed the gene targets for 4 transcription factors: FnrL, PrrA, CrpK and MppG (RSP_2888, which are known or predicted to control photosynthesis in Rhodobacter sphaeroides. Chromatin immunoprecipitation followed by high-throughput sequencing (ChIP-seq identified 52 operons under direct control of FnrL, illustrating its regulatory role in photosynthesis, iron homeostasis, nitrogen metabolism and regulation of sRNA synthesis. Using global gene expression analysis combined with ChIP-seq, we mapped the regulons of PrrA, CrpK and MppG. PrrA regulates ∼34 operons encoding mainly photosynthesis and electron transport functions, while CrpK, a previously uncharacterized Crp-family protein, regulates genes involved in photosynthesis and maintenance of iron homeostasis. Furthermore, CrpK and FnrL share similar DNA binding determinants, possibly explaining our observation of the ability of CrpK to partially compensate for the growth defects of a ΔFnrL mutant. We show that the Rrf2 family protein, MppG, plays an important role in photopigment biosynthesis, as part of an incoherent feed-forward loop with PrrA. Our results reveal a previously unrealized, high degree of combinatorial regulation of photosynthetic genes and significant cross-talk between their transcriptional regulators, while illustrating previously unidentified links between photosynthesis and the maintenance of iron homeostasis.

  10. From Local to Global Dilemmas in Social Networks

    Pinheiro, Fl?vio L.; Pacheco, Jorge M.; Santos, Francisco C.

    2012-01-01

    Social networks affect in such a fundamental way the dynamics of the population they support that the global, population-wide behavior that one observes often bears no relation to the individual processes it stems from. Up to now, linking the global networked dynamics to such individual mechanisms has remained elusive. Here we study the evolution of cooperation in networked populations and let individuals interact via a 2-person Prisoner's Dilemma ? a characteristic defection dominant social ...

  11. IMPLICATIONS OF SOCIAL RESPONSIBILITY DISCLOSURE ON GLOBAL PRODUCTION NETWORK

    Le Bo; Dan Shen; Jin Jun Bo

    2014-01-01

    This paper aims to discuss effectiveness of social responsibility disclosure in promoting global production network. Through a critical review on the theoretical development from supply chain to global production network, the global supply chain management of Apple Inc., as a case, is investigated, with focus on corporate and NGOs’ social disclosure on the environmental and labor rights' issues of its suppliers in China. The paper concludes that effectiveness of corporate social disclosure on...

  12. International collaboration in science: The global map and the network

    Leydesdorff, L.; Wagner, C.S.; Park, H.W.; Adams, J.

    2013-01-01

    The network of international co-authorship relations has been dominated by certain European nations and the USA, but this network is rapidly expanding at the global level. Between 40 and 50 countries appear in the center of the international network in 2011, and almost all (201) nations are nowadays

  13. Globalization: the evolution of enterprises in the global network competition

    Borghoff, Thomas; Welge, Martin K.

    2001-01-01

    The globalization of a company is embedded in the globalization of its task environment. This process can be described as a co-evolutionary process of a social system in its environment. A historical view of the globalization of competition seems to prove that it can be interpreted as an evolutionary process of differentiation and integration that is reinforced by the decreasing rigidity of boundaries. A liquefaction of competition" can be observed, in which an increasing number of autonomous...

  14. Metabolic Brain Network Analysis of Hypothyroidism Symptom Based on [18F]FDG-PET of Rats.

    Wan, Hongkai; Tan, Ziyu; Zheng, Qiang; Yu, Jing

    2018-03-12

    Recent researches have demonstrated the value of using 2-deoxy-2-[ 18 F]fluoro-D-glucose ([ 18 F]FDG) positron emission tomography (PET) imaging to reveal the hypothyroidism-related damages in local brain regions. However, the influence of hypothyroidism on the entire brain network is barely studied. This study focuses on the application of graph theory on analyzing functional brain networks of the hypothyroidism symptom. For both the hypothyroidism and the control groups of Wistar rats, the functional brain networks were constructed by thresholding the glucose metabolism correlation matrices of 58 brain regions. The network topological properties (including the small-world properties and the nodal centralities) were calculated and compared between the two groups. We found that the rat brains, like human brains, have typical properties of the small-world network in both the hypothyroidism and the control groups. However, the hypothyroidism group demonstrated lower global efficiency and decreased local cliquishness of the brain network, indicating hypothyroidism-related impairment to the brain network. The hypothyroidism group also has decreased nodal centrality in the left posterior hippocampus, the right hypothalamus, pituitary, pons, and medulla. This observation accorded with the hypothyroidism-related functional disorder of hypothalamus-pituitary-thyroid (HPT) feedback regulation mechanism. Our research quantitatively confirms that hypothyroidism hampers brain cognitive function by causing impairment to the brain network of glucose metabolism. This study reveals the feasibility and validity of applying graph theory method to preclinical [ 18 F]FDG-PET images and facilitates future study on human subjects.

  15. Environmental versatility promotes modularity in large scale metabolic networks

    Samal A.; Wagner Andreas; Martin O.C.

    2011-01-01

    Abstract Background The ubiquity of modules in biological networks may result from an evolutionary benefit of a modular organization. For instance, modularity may increase the rate of adaptive evolution, because modules can be easily combined into new arrangements that may benefit their carrier. Conversely, modularity may emerge as a by-product of some trait. We here ask whether this last scenario may play a role in genome-scale metabolic networks that need to sustain life in one or more chem...

  16. EGFR Signal-Network Reconstruction Demonstrates Metabolic Crosstalk in EMT.

    Kumari Sonal Choudhary

    2016-06-01

    Full Text Available Epithelial to mesenchymal transition (EMT is an important event during development and cancer metastasis. There is limited understanding of the metabolic alterations that give rise to and take place during EMT. Dysregulation of signalling pathways that impact metabolism, including epidermal growth factor receptor (EGFR, are however a hallmark of EMT and metastasis. In this study, we report the investigation into EGFR signalling and metabolic crosstalk of EMT through constraint-based modelling and analysis of the breast epithelial EMT cell model D492 and its mesenchymal counterpart D492M. We built an EGFR signalling network for EMT based on stoichiometric coefficients and constrained the network with gene expression data to build epithelial (EGFR_E and mesenchymal (EGFR_M networks. Metabolic alterations arising from differential expression of EGFR genes was derived from a literature review of AKT regulated metabolic genes. Signaling flux differences between EGFR_E and EGFR_M models subsequently allowed metabolism in D492 and D492M cells to be assessed. Higher flux within AKT pathway in the D492 cells compared to D492M suggested higher glycolytic activity in D492 that we confirmed experimentally through measurements of glucose uptake and lactate secretion rates. The signaling genes from the AKT, RAS/MAPK and CaM pathways were predicted to revert D492M to D492 phenotype. Follow-up analysis of EGFR signaling metabolic crosstalk in three additional breast epithelial cell lines highlighted variability in in vitro cell models of EMT. This study shows that the metabolic phenotype may be predicted by in silico analyses of gene expression data of EGFR signaling genes, but this phenomenon is cell-specific and does not follow a simple trend.

  17. EGFR Signal-Network Reconstruction Demonstrates Metabolic Crosstalk in EMT.

    Choudhary, Kumari Sonal; Rohatgi, Neha; Halldorsson, Skarphedinn; Briem, Eirikur; Gudjonsson, Thorarinn; Gudmundsson, Steinn; Rolfsson, Ottar

    2016-06-01

    Epithelial to mesenchymal transition (EMT) is an important event during development and cancer metastasis. There is limited understanding of the metabolic alterations that give rise to and take place during EMT. Dysregulation of signalling pathways that impact metabolism, including epidermal growth factor receptor (EGFR), are however a hallmark of EMT and metastasis. In this study, we report the investigation into EGFR signalling and metabolic crosstalk of EMT through constraint-based modelling and analysis of the breast epithelial EMT cell model D492 and its mesenchymal counterpart D492M. We built an EGFR signalling network for EMT based on stoichiometric coefficients and constrained the network with gene expression data to build epithelial (EGFR_E) and mesenchymal (EGFR_M) networks. Metabolic alterations arising from differential expression of EGFR genes was derived from a literature review of AKT regulated metabolic genes. Signaling flux differences between EGFR_E and EGFR_M models subsequently allowed metabolism in D492 and D492M cells to be assessed. Higher flux within AKT pathway in the D492 cells compared to D492M suggested higher glycolytic activity in D492 that we confirmed experimentally through measurements of glucose uptake and lactate secretion rates. The signaling genes from the AKT, RAS/MAPK and CaM pathways were predicted to revert D492M to D492 phenotype. Follow-up analysis of EGFR signaling metabolic crosstalk in three additional breast epithelial cell lines highlighted variability in in vitro cell models of EMT. This study shows that the metabolic phenotype may be predicted by in silico analyses of gene expression data of EGFR signaling genes, but this phenomenon is cell-specific and does not follow a simple trend.

  18. State Support: A Prerequisite for Global Health Network Effectiveness Comment on "Four Challenges that Global Health Networks Face".

    Marten, Robert; Smith, Richard D

    2017-07-24

    Shiffman recently summarized lessons for network effectiveness from an impressive collection of case-studies. However, in common with most global health governance analysis in recent years, Shiffman underplays the important role of states in these global networks. As the body which decides and signs international agreements, often provides the resourcing, and is responsible for implementing initiatives all contributing to the prioritization of certain issues over others, state recognition and support is a prerequisite to enabling and determining global health networks' success. The role of states deserves greater attention, analysis and consideration. We reflect upon the underappreciated role of the state within the current discourse on global health. We present the tobacco case study to illustrate the decisive role of states in determining progress for global health networks, and highlight how states use a legitimacy loop to gain legitimacy from and provide legitimacy to global health networks. Moving forward in assessing global health networks' effectiveness, further investigating state support as a determinant of success will be critical. Understanding how global health networks and states interact and evolve to shape and support their respective interests should be a focus for future research. © 2018 The Author(s); Published by Kerman University of Medical Sciences. This is an open-access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

  19. Predicting metabolic pathways by sub-network extraction.

    Faust, Karoline; van Helden, Jacques

    2012-01-01

    Various methods result in groups of functionally related genes obtained from genomes (operons, regulons, syntheny groups, and phylogenetic profiles), transcriptomes (co-expression groups) and proteomes (modules of interacting proteins). When such groups contain two or more enzyme-coding genes, graph analysis methods can be applied to extract a metabolic pathway that interconnects them. We describe here the way to use the Pathway extraction tool available on the NeAT Web server ( http://rsat.ulb.ac.be/neat/ ) to piece together the metabolic pathway from a group of associated, enzyme-coding genes. The tool identifies the reactions that can be catalyzed by the products of the query genes (seed reactions), and applies sub-graph extraction algorithms to extract from a metabolic network a sub-network that connects the seed reactions. This sub-network represents the predicted metabolic pathway. We describe here the pathway prediction process in a step-by-step way, give hints about the main parametric choices, and illustrate how this tool can be used to extract metabolic pathways from bacterial genomes, on the basis of two study cases: the isoleucine-valine operon in Escherichia coli and a predicted operon in Cupriavidus (Ralstonia) metallidurans.

  20. Metabolic networks in epilepsy by MR spectroscopic imaging.

    Pan, J W; Spencer, D D; Kuzniecky, R; Duckrow, R B; Hetherington, H; Spencer, S S

    2012-12-01

    The concept of an epileptic network has long been suggested from both animal and human studies of epilepsy. Based on the common observation that the MR spectroscopic imaging measure of NAA/Cr is sensitive to neuronal function and injury, we use this parameter to assess for the presence of a metabolic network in mesial temporal lobe epilepsy (MTLE) patients. A multivariate factor analysis is performed with controls and MTLE patients, using NAA/Cr measures from 12 loci: the bilateral hippocampi, thalami, basal ganglia, and insula. The factor analysis determines which and to what extent these loci are metabolically covarying. We extract two independent factors that explain the data's variability in control and MTLE patients. In controls, these factors characterize a 'thalamic' and 'dominant subcortical' function. The MTLE patients also exhibit a 'thalamic' factor, in addition to a second factor involving the ipsilateral insula and bilateral basal ganglia. These data suggest that MTLE patients demonstrate a metabolic network that involves the thalami, also seen in controls. The MTLE patients also display a second set of metabolically covarying regions that may be a manifestation of the epileptic network that characterizes limbic seizure propagation. © 2012 John Wiley & Sons A/S.

  1. Computing autocatalytic sets to unravel inconsistencies in metabolic network reconstructions

    Schmidt, R.; Waschina, S.; Boettger-Schmidt, D.

    2015-01-01

    , the method we report represents a powerful tool to identify inconsistencies in large-scale metabolic networks. AVAILABILITY AND IMPLEMENTATION: The method is available as source code on http://users.minet.uni-jena.de/ approximately m3kach/ASBIG/ASBIG.zip. CONTACT: christoph.kaleta@uni-jena.de SUPPLEMENTARY...... by inherent inconsistencies and gaps. RESULTS: Here we present a novel method to validate metabolic network reconstructions based on the concept of autocatalytic sets. Autocatalytic sets correspond to collections of metabolites that, besides enzymes and a growth medium, are required to produce all biomass...... components in a metabolic model. These autocatalytic sets are well-conserved across all domains of life, and their identification in specific genome-scale reconstructions allows us to draw conclusions about potential inconsistencies in these models. The method is capable of detecting inconsistencies, which...

  2. Blueprint for antimicrobial hit discovery targeting metabolic networks.

    Shen, Y; Liu, J; Estiu, G; Isin, B; Ahn, Y-Y; Lee, D-S; Barabási, A-L; Kapatral, V; Wiest, O; Oltvai, Z N

    2010-01-19

    Advances in genome analysis, network biology, and computational chemistry have the potential to revolutionize drug discovery by combining system-level identification of drug targets with the atomistic modeling of small molecules capable of modulating their activity. To demonstrate the effectiveness of such a discovery pipeline, we deduced common antibiotic targets in Escherichia coli and Staphylococcus aureus by identifying shared tissue-specific or uniformly essential metabolic reactions in their metabolic networks. We then predicted through virtual screening dozens of potential inhibitors for several enzymes of these reactions and showed experimentally that a subset of these inhibited both enzyme activities in vitro and bacterial cell viability. This blueprint is applicable for any sequenced organism with high-quality metabolic reconstruction and suggests a general strategy for strain-specific antiinfective therapy.

  3. Optimality principles in the regulation of metabolic networks.

    Berkhout, Jan; Bruggeman, Frank J; Teusink, Bas

    2012-08-29

    One of the challenging tasks in systems biology is to understand how molecular networks give rise to emergent functionality and whether universal design principles apply to molecular networks. To achieve this, the biophysical, evolutionary and physiological constraints that act on those networks need to be identified in addition to the characterisation of the molecular components and interactions. Then, the cellular "task" of the network-its function-should be identified. A network contributes to organismal fitness through its function. The premise is that the same functions are often implemented in different organisms by the same type of network; hence, the concept of design principles. In biology, due to the strong forces of selective pressure and natural selection, network functions can often be understood as the outcome of fitness optimisation. The hypothesis of fitness optimisation to understand the design of a network has proven to be a powerful strategy. Here, we outline the use of several optimisation principles applied to biological networks, with an emphasis on metabolic regulatory networks. We discuss the different objective functions and constraints that are considered and the kind of understanding that they provide.

  4. Global operations networks in motion: Managing configurations and capabilities

    Slepniov, Dmitrij; Wæhrens, Brian Vejrum; Jørgensen, Claus

    2010-01-01

    In the past, the ‘Made in the World’ label, although capturing what may lie ahead, seemed awkward and futuristic. Today, it has become a reality. An ample array of global products are built up of numerous components and modules manufactured by global networks of differentiated partners rather than...... within the boundaries of one national entity. The purpose of this paper is to contribute to bridging the empirical gap in the area of global operations networks and provide insights into how they change over time. The paper is based on the cases of three Danish companies and their global operations...

  5. Quantitative Tools for Dissection of Hydrogen-Producing Metabolic Networks-Final Report

    Rabinowitz, Joshua D.; Dismukes, G.Charles.; Rabitz, Herschel A.; Amador-Noguez, Daniel

    2012-10-19

    During this project we have pioneered the development of integrated experimental-computational technologies for the quantitative dissection of metabolism in hydrogen and biofuel producing microorganisms (i.e. C. acetobutylicum and various cyanobacteria species). The application of these new methodologies resulted in many significant advances in the understanding of the metabolic networks and metabolism of these organisms, and has provided new strategies to enhance their hydrogen or biofuel producing capabilities. As an example, using mass spectrometry, isotope tracers, and quantitative flux-modeling we mapped the metabolic network structure in C. acetobutylicum. This resulted in a comprehensive and quantitative understanding of central carbon metabolism that could not have been obtained using genomic data alone. We discovered that biofuel production in this bacterium, which only occurs during stationary phase, requires a global remodeling of central metabolism (involving large changes in metabolite concentrations and fluxes) that has the effect of redirecting resources (carbon and reducing power) from biomass production into solvent production. This new holistic, quantitative understanding of metabolism is now being used as the basis for metabolic engineering strategies to improve solvent production in this bacterium. In another example, making use of newly developed technologies for monitoring hydrogen and NAD(P)H levels in vivo, we dissected the metabolic pathways for photobiological hydrogen production by cyanobacteria Cyanothece sp. This investigation led to the identification of multiple targets for improving hydrogen production. Importantly, the quantitative tools and approaches that we have developed are broadly applicable and we are now using them to investigate other important biofuel producers, such as cellulolytic bacteria.

  6. State Support: A Prerequisite for Global Health Network Effectiveness

    Marten, Robert; Smith, Richard D.

    2018-01-01

    Shiffman recently summarized lessons for network effectiveness from an impressive collection of case-studies. However, in common with most global health governance analysis in recent years, Shiffman underplays the important role of states in these global networks. As the body which decides and signs international agreements, often provides the resourcing, and is responsible for implementing initiatives all contributing to the prioritization of certain issues over others, state recognition and support is a prerequisite to enabling and determining global health networks’ success. The role of states deserves greater attention, analysis and consideration. We reflect upon the underappreciated role of the state within the current discourse on global health. We present the tobacco case study to illustrate the decisive role of states in determining progress for global health networks, and highlight how states use a legitimacy loop to gain legitimacy from and provide legitimacy to global health networks. Moving forward in assessing global health networks’ effectiveness, further investigating state support as a determinant of success will be critical. Understanding how global health networks and states interact and evolve to shape and support their respective interests should be a focus for future research. PMID:29524958

  7. Novel global robust stability criterion for neural networks with delay

    Singh, Vimal

    2009-01-01

    A novel criterion for the global robust stability of Hopfield-type interval neural networks with delay is presented. An example illustrating the improvement of the present criterion over several recently reported criteria is given.

  8. Architectural Design for the Global Legal Information Network

    Kalpakis, Konstantinos

    1999-01-01

    In this report, we provide a summary of our activities regarding the goals, requirements analysis, design, and prototype implementation for the Global Legal Information Network, a joint effort between the Law Library of Congress and NASA.

  9. Global Historical Climatology Network - Daily (GHCN-Daily), Version 3

    National Oceanic and Atmospheric Administration, Department of Commerce — The Global Historical Climatology Network - Daily (GHCN-Daily) dataset integrates daily climate observations from approximately 30 different data sources. Version 3...

  10. Instantiating a Global Network Measurement Framework

    Tierney, Brian L.; Boote, Jeff; Boyd, Eric; Brown, Aaron; Grigoriev, Maxim; Metzger, Joe; Swany, Martin; Zekauskas, Matt; Zurawski, Jason

    2008-12-15

    perfSONAR is a web services-based infrastructure for collecting and publishing network performance monitoring. A primary goal of perfSONAR is making it easier to solve end-to-end performance problems on paths crossing several networks. It contains a set of services delivering performance measurements in a federated environment. These services act as an intermediate layer, between the performance measurement tools and the diagnostic or visualization applications. This layer is aimed at making and exchanging performance measurements across multiple networks and multiple user communities, using well-defined protocols. This paper summarizes the key perfSONAR components, and describes how they are deployed by the US-LHC community to monitor the networks distributing LHC data from CERN. All monitoring data described herein is publicly available, and we hope the availability of this data via a standard schema will inspire others to contribute to the effort by building network data analysis applications that use perfSONAR.

  11. Helping Behavior in Executives' Global Networks

    Miller, Stewart; Mors, Marie Louise; McDonald, Michael

    2014-01-01

    Drawing on research on helping behavior in networks at the upper echelons, we develop and test theory about helping behavior in senior executive networks. We examine the location and relational dependence of the network contact. Our results reveal that executives are more likely to perceive...... insiders in their network to be helpful, but geographic location has no effect on expectations of receiving help. With regards to relational dependence: executives who are more dependent on their contacts are more likely to perceive them to be helpful. We also look at whether perceived helpfulness affects...... an executive’s willingness to engage in risky new business development -- an important performance indicator - and indeed find that those executives that perceive their networks to be helpful are more likely to be willing to take risky decisions. We test these arguments using primary data on 1845 relationships...

  12. Parameter estimation in tree graph metabolic networks

    Laura Astola

    2016-09-01

    Full Text Available We study the glycosylation processes that convert initially toxic substrates to nutritionally valuable metabolites in the flavonoid biosynthesis pathway of tomato (Solanum lycopersicum seedlings. To estimate the reaction rates we use ordinary differential equations (ODEs to model the enzyme kinetics. A popular choice is to use a system of linear ODEs with constant kinetic rates or to use Michaelis–Menten kinetics. In reality, the catalytic rates, which are affected among other factors by kinetic constants and enzyme concentrations, are changing in time and with the approaches just mentioned, this phenomenon cannot be described. Another problem is that, in general these kinetic coefficients are not always identifiable. A third problem is that, it is not precisely known which enzymes are catalyzing the observed glycosylation processes. With several hundred potential gene candidates, experimental validation using purified target proteins is expensive and time consuming. We aim at reducing this task via mathematical modeling to allow for the pre-selection of most potential gene candidates. In this article we discuss a fast and relatively simple approach to estimate time varying kinetic rates, with three favorable properties: firstly, it allows for identifiable estimation of time dependent parameters in networks with a tree-like structure. Secondly, it is relatively fast compared to usually applied methods that estimate the model derivatives together with the network parameters. Thirdly, by combining the metabolite concentration data with a corresponding microarray data, it can help in detecting the genes related to the enzymatic processes. By comparing the estimated time dynamics of the catalytic rates with time series gene expression data we may assess potential candidate genes behind enzymatic reactions. As an example, we show how to apply this method to select prominent glycosyltransferase genes in tomato seedlings.

  13. Parameter estimation in tree graph metabolic networks.

    Astola, Laura; Stigter, Hans; Gomez Roldan, Maria Victoria; van Eeuwijk, Fred; Hall, Robert D; Groenenboom, Marian; Molenaar, Jaap J

    2016-01-01

    We study the glycosylation processes that convert initially toxic substrates to nutritionally valuable metabolites in the flavonoid biosynthesis pathway of tomato (Solanum lycopersicum) seedlings. To estimate the reaction rates we use ordinary differential equations (ODEs) to model the enzyme kinetics. A popular choice is to use a system of linear ODEs with constant kinetic rates or to use Michaelis-Menten kinetics. In reality, the catalytic rates, which are affected among other factors by kinetic constants and enzyme concentrations, are changing in time and with the approaches just mentioned, this phenomenon cannot be described. Another problem is that, in general these kinetic coefficients are not always identifiable. A third problem is that, it is not precisely known which enzymes are catalyzing the observed glycosylation processes. With several hundred potential gene candidates, experimental validation using purified target proteins is expensive and time consuming. We aim at reducing this task via mathematical modeling to allow for the pre-selection of most potential gene candidates. In this article we discuss a fast and relatively simple approach to estimate time varying kinetic rates, with three favorable properties: firstly, it allows for identifiable estimation of time dependent parameters in networks with a tree-like structure. Secondly, it is relatively fast compared to usually applied methods that estimate the model derivatives together with the network parameters. Thirdly, by combining the metabolite concentration data with a corresponding microarray data, it can help in detecting the genes related to the enzymatic processes. By comparing the estimated time dynamics of the catalytic rates with time series gene expression data we may assess potential candidate genes behind enzymatic reactions. As an example, we show how to apply this method to select prominent glycosyltransferase genes in tomato seedlings.

  14. Global metabolic profiling procedures for urine using UPLC-MS.

    Want, Elizabeth J; Wilson, Ian D; Gika, Helen; Theodoridis, Georgios; Plumb, Robert S; Shockcor, John; Holmes, Elaine; Nicholson, Jeremy K

    2010-06-01

    The production of 'global' metabolite profiles involves measuring low molecular-weight metabolites (sample preparation, stability/storage and the selection of chromatographic conditions that balance metabolome coverage, chromatographic resolution and throughput. We discuss quality control and metabolite identification, as well as provide details of multivariate data analysis approaches for analyzing such MS data. Using this protocol, the analysis of a sample set in 96-well plate format, would take ca. 30 h, including 1 h for system setup, 1-2 h for sample preparation, 24 h for UPLC-MS analysis and 1-2 h for initial data processing. The use of UPLC-MS for metabolic profiling in this way is not faster than the conventional HPLC-based methods but, because of improved chromatographic performance, provides superior metabolome coverage.

  15. Optimality Principles in the Regulation of Metabolic Networks

    Jan Berkhout

    2012-08-01

    Full Text Available One of the challenging tasks in systems biology is to understand how molecular networks give rise to emergent functionality and whether universal design principles apply to molecular networks. To achieve this, the biophysical, evolutionary and physiological constraints that act on those networks need to be identified in addition to the characterisation of the molecular components and interactions. Then, the cellular “task” of the network—its function—should be identified. A network contributes to organismal fitness through its function. The premise is that the same functions are often implemented in different organisms by the same type of network; hence, the concept of design principles. In biology, due to the strong forces of selective pressure and natural selection, network functions can often be understood as the outcome of fitness optimisation. The hypothesis of fitness optimisation to understand the design of a network has proven to be a powerful strategy. Here, we outline the use of several optimisation principles applied to biological networks, with an emphasis on metabolic regulatory networks. We discuss the different objective functions and constraints that are considered and the kind of understanding that they provide.

  16. Novel results for global robust stability of delayed neural networks

    Yucel, Eylem; Arik, Sabri

    2009-01-01

    This paper investigates the global robust convergence properties of continuous-time neural networks with discrete time delays. By employing suitable Lyapunov functionals, some sufficient conditions for the existence, uniqueness and global robust asymptotic stability of the equilibrium point are derived. The conditions can be easily verified as they can be expressed in terms of the network parameters only. Some numerical examples are also given to compare our results with previous robust stability results derived in the literature.

  17. Global asymptotic stability of delayed Cohen-Grossberg neural networks

    Wu Wei; Cui Baotong; Huang Min

    2007-01-01

    In this letter, the global asymptotic stability of a class of Cohen-Grossberg neural networks with time-varying delays is discussed. A new set of sufficient conditions for the neural networks are proposed to guarantee the global asymptotic convergence. Our criteria represent an extension of the existing results in literatures. An example is also presented to compare our results with the previous results

  18. Structure and evolution of the global seafood trade network

    Gephart, Jessica A.; Pace, Michael L.

    2015-12-01

    The food production system is increasingly global and seafood is among the most highly traded commodities. Global trade can improve food security by providing access to a greater variety of foods, increasing wealth, buffering against local supply shocks, and benefit the environment by increasing overall use efficiency for some resources. However, global trade can also expose countries to external supply shocks and degrade the environment by increasing resource demand and loosening feedbacks between consumers and the impacts of food production. As a result, changes in global food trade can have important implications for both food security and the environmental impacts of production. Measurements of globalization and the environmental impacts of food production require data on both total trade and the origin and destination of traded goods (the network structure). While the global trade network of agricultural and livestock products has previously been studied, seafood products have been excluded. This study describes the structure and evolution of the global seafood trade network, including metrics quantifying the globalization of seafood, shifts in bilateral trade flows, changes in centrality and comparisons of seafood to agricultural and industrial trade networks. From 1994 to 2012 the number of countries trading in the network remained relatively constant, while the number of trade partnerships increased by over 65%. Over this same period, the total quantity of seafood traded increased by 58% and the value increased 85% in real terms. These changes signify the increasing globalization of seafood products. Additionally, the trade patterns in the network indicate: increased influence of Thailand and China, strengthened intraregional trade, and increased exports from South America and Asia. In addition to characterizing these network changes, this study identifies data needs in order to connect seafood trade with environmental impacts and food security outcomes.

  19. Expanded flux variability analysis on metabolic network of Escherichia coli

    CHEN Tong; XIE ZhengWei; OUYANG Qi

    2009-01-01

    Flux balance analysis,based on the mass conservation law in a cellular organism,has been extensively employed to study the interplay between structures and functions of cellular metabolic networks.Consequently,the phenotypes of the metabolism can be well elucidated.In this paper,we introduce the Expanded Flux Variability Analysis (EFVA) to characterize the intrinsic nature of metabolic reactions,such as flexibility,modularity and essentiality,by exploring the trend of the range,the maximum and the minimum flux of reactions.We took the metabolic network of Escherichia coli as an example and analyzed the variability of reaction fluxes under different growth rate constraints.The average variability of all reactions decreases dramatically when the growth rate increases.Consider the noise effect on the metabolic system,we thus argue that the microorganism may practically grow under a suboptimal state.Besides,under the EFVA framework,the reactions are easily to be grouped into catabolic and anabolic groups.And the anabolic groups can be further assigned to specific biomass constitute.We also discovered the growth rate dependent essentiality of reactions.

  20. State Support: A Prerequisite for Global Health Network Effectiveness; Comment on “Four Challenges that Global Health Networks Face”

    Robert Marten

    2018-03-01

    Full Text Available Shiffman recently summarized lessons for network effectiveness from an impressive collection of case-studies. However, in common with most global health governance analysis in recent years, Shiffman underplays the important role of states in these global networks. As the body which decides and signs international agreements, often provides the resourcing, and is responsible for implementing initiatives all contributing to the prioritization of certain issues over others, state recognition and support is a prerequisite to enabling and determining global health networks’ success. The role of states deserves greater attention, analysis and consideration. We reflect upon the underappreciated role of the state within the current discourse on global health. We present the tobacco case study to illustrate the decisive role of states in determining progress for global health networks, and highlight how states use a legitimacy loop to gain legitimacy from and provide legitimacy to global health networks. Moving forward in assessing global health networks’ effectiveness, further investigating state support as a determinant of success will be critical. Understanding how global health networks and states interact and evolve to shape and support their respective interests should be a focus for future research.

  1. Core Support to Global Development Network (GND) - Phase II ...

    The Global Development Network (GDN) was launched by the World Bank in 1999 on the premise that good policy research, properly applied, can accelerate development and improve people's lives. Working mainly through regional networks, GDN supports economic and, increasingly, social science research in and on ...

  2. Metabolite coupling in genome-scale metabolic networks

    Palsson Bernhard Ø

    2006-03-01

    Full Text Available Abstract Background Biochemically detailed stoichiometric matrices have now been reconstructed for various bacteria, yeast, and for the human cardiac mitochondrion based on genomic and proteomic data. These networks have been manually curated based on legacy data and elementally and charge balanced. Comparative analysis of these well curated networks is now possible. Pairs of metabolites often appear together in several network reactions, linking them topologically. This co-occurrence of pairs of metabolites in metabolic reactions is termed herein "metabolite coupling." These metabolite pairs can be directly computed from the stoichiometric matrix, S. Metabolite coupling is derived from the matrix ŜŜT, whose off-diagonal elements indicate the number of reactions in which any two metabolites participate together, where Ŝ is the binary form of S. Results Metabolite coupling in the studied networks was found to be dominated by a relatively small group of highly interacting pairs of metabolites. As would be expected, metabolites with high individual metabolite connectivity also tended to be those with the highest metabolite coupling, as the most connected metabolites couple more often. For metabolite pairs that are not highly coupled, we show that the number of reactions a pair of metabolites shares across a metabolic network closely approximates a line on a log-log scale. We also show that the preferential coupling of two metabolites with each other is spread across the spectrum of metabolites and is not unique to the most connected metabolites. We provide a measure for determining which metabolite pairs couple more often than would be expected based on their individual connectivity in the network and show that these metabolites often derive their principal biological functions from existing in pairs. Thus, analysis of metabolite coupling provides information beyond that which is found from studying the individual connectivity of individual

  3. Global niche of marine anaerobic metabolisms expanded by particle microenvironments

    Bianchi, Daniele; Weber, Thomas S.; Kiko, Rainer; Deutsch, Curtis

    2018-04-01

    In ocean waters, anaerobic microbial respiration should be confined to the anoxic waters found in coastal regions and tropical oxygen minimum zones, where it is energetically favourable. However, recent molecular and geochemical evidence has pointed to a much broader distribution of denitrifying and sulfate-reducing microbes. Anaerobic metabolisms are thought to thrive in microenvironments that develop inside sinking organic aggregates, but the global distribution and geochemical significance of these microenvironments is poorly understood. Here, we develop a new size-resolved particle model to predict anaerobic respiration from aggregate properties and seawater chemistry. Constrained by observations of the size spectrum of sinking particles, the model predicts that denitrification and sulfate reduction can be sustained throughout vast, hypoxic expanses of the ocean, and could explain the trace metal enrichment observed in particles due to sulfide precipitation. Globally, the expansion of the anaerobic niche due to particle microenvironments doubles the rate of water column denitrification compared with estimates based on anoxic zones alone, and changes the sensitivity of the marine nitrogen cycle to deoxygenation in a warming climate.

  4. Global Daily Climatology Network: Kazakhstan subset

    National Oceanic and Atmospheric Administration, Department of Commerce — This dataset is a compilation of in situ daily meteorological observations for Kazakhstan within the framework of joint efforts to create Global Daily Climatology...

  5. Context-specific metabolic networks are consistent with experiments.

    Scott A Becker

    2008-05-01

    Full Text Available Reconstructions of cellular metabolism are publicly available for a variety of different microorganisms and some mammalian genomes. To date, these reconstructions are "genome-scale" and strive to include all reactions implied by the genome annotation, as well as those with direct experimental evidence. Clearly, many of the reactions in a genome-scale reconstruction will not be active under particular conditions or in a particular cell type. Methods to tailor these comprehensive genome-scale reconstructions into context-specific networks will aid predictive in silico modeling for a particular situation. We present a method called Gene Inactivity Moderated by Metabolism and Expression (GIMME to achieve this goal. The GIMME algorithm uses quantitative gene expression data and one or more presupposed metabolic objectives to produce the context-specific reconstruction that is most consistent with the available data. Furthermore, the algorithm provides a quantitative inconsistency score indicating how consistent a set of gene expression data is with a particular metabolic objective. We show that this algorithm produces results consistent with biological experiments and intuition for adaptive evolution of bacteria, rational design of metabolic engineering strains, and human skeletal muscle cells. This work represents progress towards producing constraint-based models of metabolism that are specific to the conditions where the expression profiling data is available.

  6. Three Eras in Global Tobacco Control: How Global Governance Processes Influenced Online Tobacco Control Networking.

    Wipfli, Heather; Chu, Kar-Hai; Lancaster, Molly; Valente, Thomas

    2016-01-01

    Online networks can serve as a platform to diffuse policy innovations and enhance global health governance. This study focuses on how shifts in global health governance may influence related online networks. We compare social network metrics (average degree centrality [AVGD], density [D] and clustering coefficient [CC]) of Globalink, an online network of tobacco control advocates, across three eras in global tobacco control governance; pre-Framework Convention on Tobacco Control (FCTC) policy transfer (1992-1998), global regime formation through the FCTC negotiations (1999-2005), and philanthropic funding through the Bloomberg Initiative (2006-2012). Prior to 1999, Globalink was driven by a handful of high-income countries (AVGD=1.908 D=0.030, CC=0.215). The FCTC negotiations (1999-2005) corresponded with a rapid uptick in the number of countries represented within Globalink and new members were most often brought into the network through relationships with regional neighbors (AVGD=2.824, D=0.021, CC=0.253). Between 2006 and 2012, the centrality of the US in the network increases significantly (AVGD=3.414, D=0.023, CC=0.310). The findings suggest that global institutionalization through WHO, as with the FCTC, can lead to the rapid growth of decentralized online networks. Alternatively, private initiatives, such as the Bloomberg Initiative, can lead to clustering in which a single source of information gains increasing influence over an online network.

  7. The CERN Global Network opens its doors to companies

    Francesco Poppi

    2010-01-01

    Six months after its launch, the CERN Global Network already has almost one thousand members. Today, it is opening its doors to companies from CERN's Member States. This will open up a variety of new professional and career opportunities to all the members and will enhance the networking capabilities of all parties involved.   Screenshot of the CERN Global Network website. A new item has recently appeared on the top menu of the Network's website: “Organisations”. This is the entry point for companies and, later, research institutes, wishing to join. “The CERN Global Network brings together hundreds of people who have worked at or with CERN and who have a wealth of skills and expertise. Thanks to the Network, the job opportunities made available by the companies will become visible to the wider community,” says Linda Orr-Easo, a member of the Knowledge and Technology Transfer Group and the CERN Global Network Manager. In addition to creating new career opp...

  8. Network analysis of metabolic enzyme evolution in Escherichia coli

    Kraulis Per

    2004-02-01

    Full Text Available Abstract Background The two most common models for the evolution of metabolism are the patchwork evolution model, where enzymes are thought to diverge from broad to narrow substrate specificity, and the retrograde evolution model, according to which enzymes evolve in response to substrate depletion. Analysis of the distribution of homologous enzyme pairs in the metabolic network can shed light on the respective importance of the two models. We here investigate the evolution of the metabolism in E. coli viewed as a single network using EcoCyc. Results Sequence comparison between all enzyme pairs was performed and the minimal path length (MPL between all enzyme pairs was determined. We find a strong over-representation of homologous enzymes at MPL 1. We show that the functionally similar and functionally undetermined enzyme pairs are responsible for most of the over-representation of homologous enzyme pairs at MPL 1. Conclusions The retrograde evolution model predicts that homologous enzymes pairs are at short metabolic distances from each other. In general agreement with previous studies we find that homologous enzymes occur close to each other in the network more often than expected by chance, which lends some support to the retrograde evolution model. However, we show that the homologous enzyme pairs which may have evolved through retrograde evolution, namely the pairs that are functionally dissimilar, show a weaker over-representation at MPL 1 than the functionally similar enzyme pairs. Our study indicates that, while the retrograde evolution model may have played a small part, the patchwork evolution model is the predominant process of metabolic enzyme evolution.

  9. Genetic networks of liver metabolism revealed by integration of metabolic and transcriptional profiling.

    Christine T Ferrara

    2008-03-01

    Full Text Available Although numerous quantitative trait loci (QTL influencing disease-related phenotypes have been detected through gene mapping and positional cloning, identification of the individual gene(s and molecular pathways leading to those phenotypes is often elusive. One way to improve understanding of genetic architecture is to classify phenotypes in greater depth by including transcriptional and metabolic profiling. In the current study, we have generated and analyzed mRNA expression and metabolic profiles in liver samples obtained in an F2 intercross between the diabetes-resistant C57BL/6 leptin(ob/ob and the diabetes-susceptible BTBR leptin(ob/ob mouse strains. This cross, which segregates for genotype and physiological traits, was previously used to identify several diabetes-related QTL. Our current investigation includes microarray analysis of over 40,000 probe sets, plus quantitative mass spectrometry-based measurements of sixty-seven intermediary metabolites in three different classes (amino acids, organic acids, and acyl-carnitines. We show that liver metabolites map to distinct genetic regions, thereby indicating that tissue metabolites are heritable. We also demonstrate that genomic analysis can be integrated with liver mRNA expression and metabolite profiling data to construct causal networks for control of specific metabolic processes in liver. As a proof of principle of the practical significance of this integrative approach, we illustrate the construction of a specific causal network that links gene expression and metabolic changes in the context of glutamate metabolism, and demonstrate its validity by showing that genes in the network respond to changes in glutamine and glutamate availability. Thus, the methods described here have the potential to reveal regulatory networks that contribute to chronic, complex, and highly prevalent diseases and conditions such as obesity and diabetes.

  10. Discovery of Boolean metabolic networks: integer linear programming based approach.

    Qiu, Yushan; Jiang, Hao; Ching, Wai-Ki; Cheng, Xiaoqing

    2018-04-11

    Traditional drug discovery methods focused on the efficacy of drugs rather than their toxicity. However, toxicity and/or lack of efficacy are produced when unintended targets are affected in metabolic networks. Thus, identification of biological targets which can be manipulated to produce the desired effect with minimum side-effects has become an important and challenging topic. Efficient computational methods are required to identify the drug targets while incurring minimal side-effects. In this paper, we propose a graph-based computational damage model that summarizes the impact of enzymes on compounds in metabolic networks. An efficient method based on Integer Linear Programming formalism is then developed to identify the optimal enzyme-combination so as to minimize the side-effects. The identified target enzymes for known successful drugs are then verified by comparing the results with those in the existing literature. Side-effects reduction plays a crucial role in the study of drug development. A graph-based computational damage model is proposed and the theoretical analysis states the captured problem is NP-completeness. The proposed approaches can therefore contribute to the discovery of drug targets. Our developed software is available at " http://hkumath.hku.hk/~wkc/APBC2018-metabolic-network.zip ".

  11. Second Law of Thermodynamics Applied to Metabolic Networks

    Nigam, R.; Liang, S.

    2003-01-01

    We present a simple algorithm based on linear programming, that combines Kirchoff's flux and potential laws and applies them to metabolic networks to predict thermodynamically feasible reaction fluxes. These law's represent mass conservation and energy feasibility that are widely used in electrical circuit analysis. Formulating the Kirchoff's potential law around a reaction loop in terms of the null space of the stoichiometric matrix leads to a simple representation of the law of entropy that can be readily incorporated into the traditional flux balance analysis without resorting to non-linear optimization. Our technique is new as it can easily check the fluxes got by applying flux balance analysis for thermodynamic feasibility and modify them if they are infeasible so that they satisfy the law of entropy. We illustrate our method by applying it to the network dealing with the central metabolism of Escherichia coli. Due to its simplicity this algorithm will be useful in studying large scale complex metabolic networks in the cell of different organisms.

  12. Global and local knowledge networks in innovation

    Lorentzen, Anne

    2006-01-01

    , of which global sources are considered most important to innovation, while the regional level basically provides a labour market. Firms are able to establish direct links to knowledge sources at all scales, and widely rely on ICT and their access to foreign customers. This questions the proximity...... hypothesis and the regional focus of industrial and regional innovation policies....

  13. Structure and dynamics of the global financial network

    Silva, Thiago Christiano; Rubens Stancato de Souza, Sergio; Tabak, Benjamin Miranda

    2016-01-01

    In this paper, we study the evolution of the network topology for the global financial market. We evaluate the level of diversification and participation of developed and emerging economies in cross-border exposures and find that the gross exposure network is dense, the vulnerability matrix is sparse, and the network’s fragility changes over time. Prior to the financial crisis in 2008, the network was relatively fragile, whereas it became more resilient afterwards, showing a reduction in financial institutions’ risk appetite. Our results suggest that financial regulators should track down the network evolution in their systemic risk assessment.

  14. Hydrogen based global renewable energy network

    Akai, Makoto [Mechanical Engineering Laboratory, AIST, MITI, Namiki, Tsukuba (Japan)

    1993-12-31

    In the last quarter of this century, global environmental problem has emerged as a major scientific, political and social issue. Specific Problems include: depletion of ozone layer by chlorofluorocarbons (CFCs), acid rain, destruction of tropical forests and desertification, pollution of the sea and global wanning due to the greenhouse effect by carbon dioxide and others. Among these problems, particular attention of the world has been focused on the global warming because it has direct linkage to energy consumption which our economic development depends on so far. On the other hand, the future program of The Sunshine Project for alternative energy technology R&D, The Moonlight Project for energy conservation technology R&D, and The Global Environmental Technology Program for environmental problem mitigating technology R&D which are Japan`s national projects being promoted by their Agency of Industrial Science and Technology (AIST) in the Ministry of International Trade and Industry have been reexamined in view of recent changes in the situations surrounding new energy technology. In this regard, The New Sunshine Program will be established by integrating these three activities to accelerate R&D in the field of energy and environmental technologies. In the reexamination, additional stress has been laid on the contribution to solving global environmental problem through development of clean renewable energies which constitute a major part of the {open_quotes}New Earth 21{close_quotes}, a comprehensive, long-term and international cooperative program proposed by MITI. The present paper discusses the results of feasibility study on hydrogen energy system leading to the concept of WE-NET following a brief summary on R&D status on solar and wind energy in Japan.

  15. Developmental changes in the metabolic network of snapdragon flowers.

    Joëlle K Muhlemann

    Full Text Available Evolutionary and reproductive success of angiosperms, the most diverse group of land plants, relies on visual and olfactory cues for pollinator attraction. Previous work has focused on elucidating the developmental regulation of pathways leading to the formation of pollinator-attracting secondary metabolites such as scent compounds and flower pigments. However, to date little is known about how flowers control their entire metabolic network to achieve the highly regulated production of metabolites attracting pollinators. Integrative analysis of transcripts and metabolites in snapdragon sepals and petals over flower development performed in this study revealed a profound developmental remodeling of gene expression and metabolite profiles in petals, but not in sepals. Genes up-regulated during petal development were enriched in functions related to secondary metabolism, fatty acid catabolism, and amino acid transport, whereas down-regulated genes were enriched in processes involved in cell growth, cell wall formation, and fatty acid biosynthesis. The levels of transcripts and metabolites in pathways leading to scent formation were coordinately up-regulated during petal development, implying transcriptional induction of metabolic pathways preceding scent formation. Developmental gene expression patterns in the pathways involved in scent production were different from those of glycolysis and the pentose phosphate pathway, highlighting distinct developmental regulation of secondary metabolism and primary metabolic pathways feeding into it.

  16. Globalizing Social Justice Education: The Case of The Global Solidarity Network Study e-Broad Program

    Harrison, Yvonne D.; Kostic, Kevin; Toton, Suzanne C.; Zurek, Jerome

    2010-01-01

    This paper documents the development, implementation, and evaluation of "The Global Solidarity Network Study e-Broad Program (GSNSeBP)", an online social justice educational program that is blended into an onsite academic course. This global electronic program, which was developed through a partnership between Catholic Relief Services (CRS) and…

  17. Reconstruction of the yeast Snf1 kinase regulatory network reveals its role as a global energy regulator

    Usaite, Renata; Jewett, Michael Christopher; Soberano de Oliveira, Ana Paula

    2009-01-01

    Highly conserved among eukaryotic cells, the AMP-activated kinase (AMPK) is a central regulator of carbon metabolism. To map the complete network of interactions around AMPK in yeast (Snf1) and to evaluate the role of its regulatory subunit Snf4, we measured global mRNA, protein and metabolite...

  18. Transcriptional regulation and steady-state modeling of metabolic networks

    Zelezniak, Aleksej

    Biological systems are characterized by a high degree of complexity wherein the individual components (e.g. proteins) are inter-linked in a way that leads to emergent behaviors that are difficult to decipher. Uncovering system complexity requires, at least, answers to the following three questions......: what are the components of the systems, how are the different components interconnected and how do these networks perform the functions that make the resulting system behavior? Modern analytical technologies allow us to unravel the constituents and interactions happening in a given system; however......, the third question is the ultimate challenge for systems biology. The work of this thesis systematically addresses this question in the context of metabolic networks, which are arguably the most well characterized cellular networks in terms of their constituting components and interactions among them...

  19. Evolution of the global virtual water trade network.

    Dalin, Carole; Konar, Megan; Hanasaki, Naota; Rinaldo, Andrea; Rodriguez-Iturbe, Ignacio

    2012-04-17

    Global freshwater resources are under increasing pressure from economic development, population growth, and climate change. The international trade of water-intensive products (e.g., agricultural commodities) or virtual water trade has been suggested as a way to save water globally. We focus on the virtual water trade network associated with international food trade built with annual trade data and annual modeled virtual water content. The evolution of this network from 1986 to 2007 is analyzed and linked to trade policies, socioeconomic circumstances, and agricultural efficiency. We find that the number of trade connections and the volume of water associated with global food trade more than doubled in 22 years. Despite this growth, constant organizational features were observed in the network. However, both regional and national virtual water trade patterns significantly changed. Indeed, Asia increased its virtual water imports by more than 170%, switching from North America to South America as its main partner, whereas North America oriented to a growing intraregional trade. A dramatic rise in China's virtual water imports is associated with its increased soy imports after a domestic policy shift in 2000. Significantly, this shift has led the global soy market to save water on a global scale, but it also relies on expanding soy production in Brazil, which contributes to deforestation in the Amazon. We find that the international food trade has led to enhanced savings in global water resources over time, indicating its growing efficiency in terms of global water use.

  20. Competition between global and local online social networks

    Kleineberg, Kaj-Kolja; Boguñá, Marián

    2016-04-01

    The overwhelming success of online social networks, the key actors in the Web 2.0 cosmos, has reshaped human interactions globally. To help understand the fundamental mechanisms which determine the fate of online social networks at the system level, we describe the digital world as a complex ecosystem of interacting networks. In this paper, we study the impact of heterogeneity in network fitnesses on the competition between an international network, such as Facebook, and local services. The higher fitness of international networks is induced by their ability to attract users from all over the world, which can then establish social interactions without the limitations of local networks. In other words, inter-country social ties lead to increased fitness of the international network. To study the competition between an international network and local ones, we construct a 1:1000 scale model of the digital world, consisting of the 80 countries with the most Internet users. Under certain conditions, this leads to the extinction of local networks; whereas under different conditions, local networks can persist and even dominate completely. In particular, our model suggests that, with the parameters that best reproduce the empirical overtake of Facebook, this overtake could have not taken place with a significant probability.

  1. Competition between global and local online social networks.

    Kleineberg, Kaj-Kolja; Boguñá, Marián

    2016-04-27

    The overwhelming success of online social networks, the key actors in the Web 2.0 cosmos, has reshaped human interactions globally. To help understand the fundamental mechanisms which determine the fate of online social networks at the system level, we describe the digital world as a complex ecosystem of interacting networks. In this paper, we study the impact of heterogeneity in network fitnesses on the competition between an international network, such as Facebook, and local services. The higher fitness of international networks is induced by their ability to attract users from all over the world, which can then establish social interactions without the limitations of local networks. In other words, inter-country social ties lead to increased fitness of the international network. To study the competition between an international network and local ones, we construct a 1:1000 scale model of the digital world, consisting of the 80 countries with the most Internet users. Under certain conditions, this leads to the extinction of local networks; whereas under different conditions, local networks can persist and even dominate completely. In particular, our model suggests that, with the parameters that best reproduce the empirical overtake of Facebook, this overtake could have not taken place with a significant probability.

  2. Genome scale metabolic network reconstruction of Spirochaeta cellobiosiphila

    Bharat Manna

    2017-10-01

    Full Text Available Substantial rise in the global energy demand is one of the biggest challenges in this century. Environmental pollution due to rapid depletion of the fossil fuel resources and its alarming impact on the climate change and Global Warming have motivated researchers to look for non-petroleum-based sustainable, eco-friendly, renewable, low-cost energy alternatives, such as biofuel. Lignocellulosic biomass is one of the most promising bio-resources with huge potential to contribute to this worldwide energy demand. However, the complex organization of the Cellulose, Hemicellulose and Lignin in the Lignocellulosic biomass requires extensive pre-treatment and enzymatic hydrolysis followed by fermentation, raising overall production cost of biofuel. This encourages researchers to design cost-effective approaches for the production of second generation biofuels. The products from enzymatic hydrolysis of cellulose are mostly glucose monomer or cellobiose unit that are subjected to fermentation. Spirochaeta genus is a well-known group of obligate or facultative anaerobes, living primarily on carbohydrate metabolism. Spirochaeta cellobiosiphila sp. is a facultative anaerobe under this genus, which uses a variety of monosaccharides and disaccharides as energy sources. However, most rapid growth occurs on cellobiose and fermentation yields significant amount of ethanol, acetate, CO2, H2 and small amounts of formate. It is predicted to be promising microbial machinery for industrial fermentation processes for biofuel production. The metabolic pathways that govern cellobiose metabolism in Spirochaeta cellobiosiphila are yet to be explored. The function annotation of the genome sequence of Spirochaeta cellobiosiphila is in progress. In this work we aim to map all the metabolic activities for reconstruction of genome-scale metabolic model of Spirochaeta cellobiosiphila.

  3. Bringing metabolic networks to life: integration of kinetic, metabolic, and proteomic data

    Klipp Edda

    2006-12-01

    Full Text Available Abstract Background Translating a known metabolic network into a dynamic model requires reasonable guesses of all enzyme parameters. In Bayesian parameter estimation, model parameters are described by a posterior probability distribution, which scores the potential parameter sets, showing how well each of them agrees with the data and with the prior assumptions made. Results We compute posterior distributions of kinetic parameters within a Bayesian framework, based on integration of kinetic, thermodynamic, metabolic, and proteomic data. The structure of the metabolic system (i.e., stoichiometries and enzyme regulation needs to be known, and the reactions are modelled by convenience kinetics with thermodynamically independent parameters. The parameter posterior is computed in two separate steps: a first posterior summarises the available data on enzyme kinetic parameters; an improved second posterior is obtained by integrating metabolic fluxes, concentrations, and enzyme concentrations for one or more steady states. The data can be heterogenous, incomplete, and uncertain, and the posterior is approximated by a multivariate log-normal distribution. We apply the method to a model of the threonine synthesis pathway: the integration of metabolic data has little effect on the marginal posterior distributions of individual model parameters. Nevertheless, it leads to strong correlations between the parameters in the joint posterior distribution, which greatly improve the model predictions by the following Monte-Carlo simulations. Conclusion We present a standardised method to translate metabolic networks into dynamic models. To determine the model parameters, evidence from various experimental data is combined and weighted using Bayesian parameter estimation. The resulting posterior parameter distribution describes a statistical ensemble of parameter sets; the parameter variances and correlations can account for missing knowledge, measurement

  4. Multinational Firms and the Management of Global Networks

    De Marchi, Valentina; Maria, Eleonora Di; Ponte, Stefano

    2014-01-01

    This paper aims at enriching the literature on international business (IB) studies to include insights from Global Value Chain (GVC) analysis to better explain how MNCs can orchestrate a global network organization. A first important contribution of the GVC literature is that it shifts the focus...... from single firms to their value chains, providing instruments to study how activities are split and organized among different firms at the industry level, and how MNCs can implement different governing mechanisms within a network-based setting. The GVC literature also highlights that retailers (as...... can manage their network relationships in a global scenario. Finally, through their focus on upgrading, GVC studies suggest that knowledge flows and innovation dynamics taking place within value chains are as important as those taking place within the MNC’s organizational border. We conclude...

  5. Global analytic treatment of terrestrial photogrammetric networks

    Mayoud, M

    1980-01-01

    In order to solve certain special CERN metrology problems, analytical terrestrial photogrammetry may have some advantages which are first discussed along with their drawbacks and limitations. In this application, it is necessary to carry out a rigorous and global adjustment of the observations and simultaneously process all the perspective ray bundles. The basic principles, the least squares solution and the stochastic analysis of the results are presented. However, for the CERN project, one wonders if the production of digital theodolites is going to reduce the advantages of the photogrammetric method. (12 refs).

  6. Networks of global bird invasion altered by regional trade ban.

    Reino, Luís; Figueira, Rui; Beja, Pedro; Araújo, Miguel B; Capinha, César; Strubbe, Diederik

    2017-11-01

    Wildlife trade is a major pathway for introduction of invasive species worldwide. However, how exactly wildlife trade influences invasion risk, beyond the transportation of individuals to novel areas, remains unknown. We analyze the global trade network of wild-caught birds from 1995 to 2011 as reported by CITES (Convention on International Trade in Endangered Species of Wild Fauna and Flora). We found that before the European Union ban on imports of wild-caught birds, declared in 2005, invasion risk was closely associated with numbers of imported birds, diversity of import sources, and degree of network centrality of importer countries. After the ban, fluxes of global bird trade declined sharply. However, new trade routes emerged, primarily toward the Nearctic, Afrotropical, and Indo-Malay regions. Although regional bans can curtail invasion risk globally, to be fully effective and prevent rerouting of trade flows, bans should be global.

  7. Network Design Guidance for the Global Special Operations Forces Network

    2014-12-01

    an introduction to the Network Design Continuum. 170 Robert M. Hayden, “ Moral Vision and Impaired Insight: The Imagining of Other Peoples...CEO and municipal president were of an abstract nature, about moral courage and political principles, which he felt it was the task of the UN to...the actions needled to improv e or rorrect peri:lrmance, relativ e to the goals of the syste m. Determin ing how a system shoukl WJrk and how dlanges

  8. Correlation and network topologies in global and local stock indices

    Nobi, A.; Lee, S.; Kim, D. H.

    2014-01-01

    the crises. A significant change in the network topologies was observed due to the financial crises in both markets. The Jaccard similarities identified the change in the market state due to a crisis in both markets. The dynamic change of the Jaccard index can be used as an indicator of systemic risk......We examined how the correlation and network structure of the global indices and local Korean indices have changed during years 2000-2012. The average correlations of the global indices increased with time, while the local indices showed a decreasing trend except for drastic changes during...... or precursors of the crisis. (C) 2014 Elsevier B.V. All rights reserved....

  9. Correlation and network topologies in global and local stock indices

    Nobi, Ashadun; Lee, Sungmin; Kim, Doo Hwan; Lee, Jae Woo

    2014-07-01

    We examined how the correlation and network structure of the global indices and local Korean indices have changed during years 2000-2012. The average correlations of the global indices increased with time, while the local indices showed a decreasing trend except for drastic changes during the crises. A significant change in the network topologies was observed due to the financial crises in both markets. The Jaccard similarities identified the change in the market state due to a crisis in both markets. The dynamic change of the Jaccard index can be used as an indicator of systemic risk or precursors of the crisis.

  10. Global robust stability of delayed recurrent neural networks

    Cao Jinde; Huang Deshuang; Qu Yuzhong

    2005-01-01

    This paper is concerned with the global robust stability of a class of delayed interval recurrent neural networks which contain time-invariant uncertain parameters whose values are unknown but bounded in given compact sets. A new sufficient condition is presented for the existence, uniqueness, and global robust stability of equilibria for interval neural networks with time delays by constructing Lyapunov functional and using matrix-norm inequality. An error is corrected in an earlier publication, and an example is given to show the effectiveness of the obtained results

  11. Network master planning for a global manufacturing company

    Heinz, Michael Pierre

    2006-01-01

    Production in global, intra-organisational networks is becoming more common. In this context, the allocation of production quantities to constrained manufacturing capacity is a challenging process. Due to a volatile environment it is argued to be impossible to achieve a ‘clean’ system design with dedicated resources which exactly meets future demand. Thus, recursive ‘Network Master Planning’ (NMP) becomes necessary. The aim of this research is to generate an understanding of th...

  12. Global robust exponential stability for interval neural networks with delay

    Cui Shihua; Zhao Tao; Guo Jie

    2009-01-01

    In this paper, new sufficient conditions for globally robust exponential stability of neural networks with either constant delays or time-varying delays are given. We show the sufficient conditions for the existence, uniqueness and global robust exponential stability of the equilibrium point by employing Lyapunov stability theory and linear matrix inequality (LMI) technique. Numerical examples are given to show the approval of our results.

  13. A global network for monitoring ocean acidification

    Celliers, Louis

    2012-10-01

    Full Text Available BASICally – It works! 15 Ma-Re Students Network – get involved! 15 A different kind of Carnival - Rio +20 dialogues 16 Science education—getting the message across 17 MCEN National Conference 2012 18 Mandela Day Celebrations 19 Kudos to Larry Hutchings 20...Ɵon:  How applicable is the ‘knowledge negoƟaƟon’ model for producing appropriate knowledge for coastal govern-ance in the context of a neo-liberal, develop-ing society in the process of transformaƟon?   The  main  objecƟve  of  the  research  is  the...

  14. Conducting network penetration and espionage in a global environment

    Middleton, Bruce

    2014-01-01

    When it's all said and done, penetration testing remains the most effective way to identify security vulnerabilities in computer networks. Conducting Network Penetration and Espionage in a Global Environment provides detailed guidance on how to perform effective penetration testing of computer networks-using free, open source, and commercially available tools, including Backtrack, Metasploit, Wireshark, Nmap, Netcat, and Nessus. It also considers exploits and other programs using Python, PERL, BASH, PHP, Ruby, and Windows PowerShell.The book taps into Bruce Middleton's decades of experience wi

  15. Enumeration of minimal stoichiometric precursor sets in metabolic networks.

    Andrade, Ricardo; Wannagat, Martin; Klein, Cecilia C; Acuña, Vicente; Marchetti-Spaccamela, Alberto; Milreu, Paulo V; Stougie, Leen; Sagot, Marie-France

    2016-01-01

    What an organism needs at least from its environment to produce a set of metabolites, e.g. target(s) of interest and/or biomass, has been called a minimal precursor set. Early approaches to enumerate all minimal precursor sets took into account only the topology of the metabolic network (topological precursor sets). Due to cycles and the stoichiometric values of the reactions, it is often not possible to produce the target(s) from a topological precursor set in the sense that there is no feasible flux. Although considering the stoichiometry makes the problem harder, it enables to obtain biologically reasonable precursor sets that we call stoichiometric. Recently a method to enumerate all minimal stoichiometric precursor sets was proposed in the literature. The relationship between topological and stoichiometric precursor sets had however not yet been studied. Such relationship between topological and stoichiometric precursor sets is highlighted. We also present two algorithms that enumerate all minimal stoichiometric precursor sets. The first one is of theoretical interest only and is based on the above mentioned relationship. The second approach solves a series of mixed integer linear programming problems. We compared the computed minimal precursor sets to experimentally obtained growth media of several Escherichia coli strains using genome-scale metabolic networks. The results show that the second approach efficiently enumerates minimal precursor sets taking stoichiometry into account, and allows for broad in silico studies of strains or species interactions that may help to understand e.g. pathotype and niche-specific metabolic capabilities. sasita is written in Java, uses cplex as LP solver and can be downloaded together with all networks and input files used in this paper at http://www.sasita.gforge.inria.fr.

  16. Development of global cortical networks in early infancy.

    Homae, Fumitaka; Watanabe, Hama; Otobe, Takayuki; Nakano, Tamami; Go, Tohshin; Konishi, Yukuo; Taga, Gentaro

    2010-04-07

    Human cognition and behaviors are subserved by global networks of neural mechanisms. Although the organization of the brain is a subject of interest, the process of development of global cortical networks in early infancy has not yet been clarified. In the present study, we explored developmental changes in these networks from several days to 6 months after birth by examining spontaneous fluctuations in brain activity, using multichannel near-infrared spectroscopy. We set up 94 measurement channels over the frontal, temporal, parietal, and occipital regions of the infant brain. The obtained signals showed complex time-series properties, which were characterized as 1/f fluctuations. To reveal the functional connectivity of the cortical networks, we calculated the temporal correlations of continuous signals between all the pairs of measurement channels. We found that the cortical network organization showed regional dependency and dynamic changes in the course of development. In the temporal, parietal, and occipital regions, connectivity increased between homologous regions in the two hemispheres and within hemispheres; in the frontal regions, it decreased progressively. Frontoposterior connectivity changed to a "U-shaped" pattern within 6 months: it decreases from the neonatal period to the age of 3 months and increases from the age of 3 months to the age of 6 months. We applied cluster analyses to the correlation coefficients and showed that the bilateral organization of the networks begins to emerge during the first 3 months of life. Our findings suggest that these developing networks, which form multiple clusters, are precursors of the functional cerebral architecture.

  17. The complex network of global cargo ship movements.

    Kaluza, Pablo; Kölzsch, Andrea; Gastner, Michael T; Blasius, Bernd

    2010-07-06

    Transportation networks play a crucial role in human mobility, the exchange of goods and the spread of invasive species. With 90 per cent of world trade carried by sea, the global network of merchant ships provides one of the most important modes of transportation. Here, we use information about the itineraries of 16 363 cargo ships during the year 2007 to construct a network of links between ports. We show that the network has several features that set it apart from other transportation networks. In particular, most ships can be classified into three categories: bulk dry carriers, container ships and oil tankers. These three categories do not only differ in the ships' physical characteristics, but also in their mobility patterns and networks. Container ships follow regularly repeating paths whereas bulk dry carriers and oil tankers move less predictably between ports. The network of all ship movements possesses a heavy-tailed distribution for the connectivity of ports and for the loads transported on the links with systematic differences between ship types. The data analysed in this paper improve current assumptions based on gravity models of ship movements, an important step towards understanding patterns of global trade and bioinvasion.

  18. Global synchronization of general delayed complex networks with stochastic disturbances

    Tu Li-Lan

    2011-01-01

    In this paper, global synchronization of general delayed complex networks with stochastic disturbances, which is a zero-mean real scalar Wiener process, is investigated. The networks under consideration are continuous-time networks with time-varying delay. Based on the stochastic Lyapunov stability theory, Ito's differential rule and the linear matrix inequality (LMI) optimization technique, several delay-dependent synchronous criteria are established, which guarantee the asymptotical mean-square synchronization of drive networks and response networks with stochastic disturbances. The criteria are expressed in terms of LMI, which can be easily solved using the Matlab LMI Control Toolbox. Finally, two examples show the effectiveness and feasibility of the proposed synchronous conditions. (general)

  19. Inferring transcriptional gene regulation network of starch metabolism in Arabidopsis thaliana leaves using graphical Gaussian model

    Ingkasuwan Papapit

    2012-08-01

    Full Text Available Abstract Background Starch serves as a temporal storage of carbohydrates in plant leaves during day/night cycles. To study transcriptional regulatory modules of this dynamic metabolic process, we conducted gene regulation network analysis based on small-sample inference of graphical Gaussian model (GGM. Results Time-series significant analysis was applied for Arabidopsis leaf transcriptome data to obtain a set of genes that are highly regulated under a diurnal cycle. A total of 1,480 diurnally regulated genes included 21 starch metabolic enzymes, 6 clock-associated genes, and 106 transcription factors (TF. A starch-clock-TF gene regulation network comprising 117 nodes and 266 edges was constructed by GGM from these 133 significant genes that are potentially related to the diurnal control of starch metabolism. From this network, we found that β-amylase 3 (b-amy3: At4g17090, which participates in starch degradation in chloroplast, is the most frequently connected gene (a hub gene. The robustness of gene-to-gene regulatory network was further analyzed by TF binding site prediction and by evaluating global co-expression of TFs and target starch metabolic enzymes. As a result, two TFs, indeterminate domain 5 (AtIDD5: At2g02070 and constans-like (COL: At2g21320, were identified as positive regulators of starch synthase 4 (SS4: At4g18240. The inference model of AtIDD5-dependent positive regulation of SS4 gene expression was experimentally supported by decreased SS4 mRNA accumulation in Atidd5 mutant plants during the light period of both short and long day conditions. COL was also shown to positively control SS4 mRNA accumulation. Furthermore, the knockout of AtIDD5 and COL led to deformation of chloroplast and its contained starch granules. This deformity also affected the number of starch granules per chloroplast, which increased significantly in both knockout mutant lines. Conclusions In this study, we utilized a systematic approach of microarray

  20. Linking high-resolution metabolic flux phenotypes and transcriptional regulation in yeast modulated by the global regulator Gcn4p

    Moxley, Joel F.; Jewett, Michael Christopher; Antoniewicz, Maciek R.

    2009-01-01

    . However, the potential of systems biology approaches is limited by difficulties in integrating metabolic measurements across the functional levels of the cell despite their being most closely linked to cellular phenotype. To address this limitation, we developed a model-based approach to correlate m......RNA and metabolic flux data that combines information from both interaction network models and flux determination models. We started by quantifying 5,764 mRNAs, 54 metabolites, and 83 experimental C-13-based reaction fluxes in continuous cultures of yeast under stress in the absence or presence of global regulator...... of metabolic flux (i.e., use of different reaction pathways) by transcriptional regulation and metabolite interaction density (i.e., level of pairwise metabolite-protein interactions) as a key biosynthetic control determinant. Furthermore, this model predicted flux rewiring in studies of follow...

  1. A Global Protein Kinase and Phosphatase Interaction Network in Yeast

    Breitkreutz, Ashton; Choi, Hyungwon; Sharom, Jeffrey R.; Boucher, Lorrie; Neduva, Victor; Larsen, Brett; Lin, Zhen-Yuan; Breitkreutz, Bobby-Joe; Stark, Chris; Liu, Guomin; Ahn, Jessica; Dewar-Darch, Danielle; Reguly, Teresa; Tang, Xiaojing; Almeida, Ricardo; Qin, Zhaohui Steve; Pawson, Tony; Gingras, Anne-Claude; Nesvizhskii, Alexey I.; Tyers, Mike

    2011-01-01

    The interactions of protein kinases and phosphatases with their regulatory subunits and substrates underpin cellular regulation. We identified a kinase and phosphatase interaction (KPI) network of 1844 interactions in budding yeast by mass spectrometric analysis of protein complexes. The KPI network contained many dense local regions of interactions that suggested new functions. Notably, the cell cycle phosphatase Cdc14 associated with multiple kinases that revealed roles for Cdc14 in mitogen-activated protein kinase signaling, the DNA damage response, and metabolism, whereas interactions of the target of rapamycin complex 1 (TORC1) uncovered new effector kinases in nitrogen and carbon metabolism. An extensive backbone of kinase-kinase interactions cross-connects the proteome and may serve to coordinate diverse cellular responses. PMID:20489023

  2. Prioritizing Candidate Disease Metabolites Based on Global Functional Relationships between Metabolites in the Context of Metabolic Pathways

    Yang, Haixiu; Xu, Yanjun; Han, Junwei; Li, Jing; Su, Fei; Zhang, Yunpeng; Zhang, Chunlong; Li, Dongguo; Li, Xia

    2014-01-01

    Identification of key metabolites for complex diseases is a challenging task in today's medicine and biology. A special disease is usually caused by the alteration of a series of functional related metabolites having a global influence on the metabolic network. Moreover, the metabolites in the same metabolic pathway are often associated with the same or similar disease. Based on these functional relationships between metabolites in the context of metabolic pathways, we here presented a pathway-based random walk method called PROFANCY for prioritization of candidate disease metabolites. Our strategy not only takes advantage of the global functional relationships between metabolites but also sufficiently exploits the functionally modular nature of metabolic networks. Our approach proved successful in prioritizing known metabolites for 71 diseases with an AUC value of 0.895. We also assessed the performance of PROFANCY on 16 disease classes and found that 4 classes achieved an AUC value over 0.95. To investigate the robustness of the PROFANCY, we repeated all the analyses in two metabolic networks and obtained similar results. Then we applied our approach to Alzheimer's disease (AD) and found that a top ranked candidate was potentially related to AD but had not been reported previously. Furthermore, our method was applicable to prioritize the metabolites from metabolomic profiles of prostate cancer. The PROFANCY could identify prostate cancer related-metabolites that are supported by literatures but not considered to be significantly differential by traditional differential analysis. We also developed a freely accessible web-based and R-based tool at http://bioinfo.hrbmu.edu.cn/PROFANCY. PMID:25153931

  3. Metabolic network model guided engineering ethylmalonyl-CoA pathway to improve ascomycin production in Streptomyces hygroscopicus var. ascomyceticus.

    Wang, Junhua; Wang, Cheng; Song, Kejing; Wen, Jianping

    2017-10-03

    Ascomycin is a 23-membered polyketide macrolide with high immunosuppressant and antifungal activity. As the lower production in bio-fermentation, global metabolic analysis is required to further explore its biosynthetic network and determine the key limiting steps for rationally engineering. To achieve this goal, an engineering approach guided by a metabolic network model was implemented to better understand ascomycin biosynthesis and improve its production. The metabolic conservation of Streptomyces species was first investigated by comparing the metabolic enzymes of Streptomyces coelicolor A3(2) with those of 31 Streptomyces strains, the results showed that more than 72% of the examined proteins had high sequence similarity with counterparts in every surveyed strain. And it was found that metabolic reactions are more highly conserved than the enzymes themselves because of its lower diversity of metabolic functions than that of genes. The main source of the observed metabolic differences was from the diversity of secondary metabolism. According to the high conservation of primary metabolic reactions in Streptomyces species, the metabolic network model of Streptomyces hygroscopicus var. ascomyceticus was constructed based on the latest reported metabolic model of S. coelicolor A3(2) and validated experimentally. By coupling with flux balance analysis and using minimization of metabolic adjustment algorithm, potential targets for ascomycin overproduction were predicted. Since several of the preferred targets were highly associated with ethylmalonyl-CoA biosynthesis, two target genes hcd (encoding 3-hydroxybutyryl-CoA dehydrogenase) and ccr (encoding crotonyl-CoA carboxylase/reductase) were selected for overexpression in S. hygroscopicus var. ascomyceticus FS35. Both the mutants HA-Hcd and HA-Ccr showed higher ascomycin titer, which was consistent with the model predictions. Furthermore, the combined effects of the two genes were evaluated and the strain HA

  4. Computers and networks in the age of globalization

    Bloch Rasmussen, Leif; Beardon, Colin; Munari, Silvio

    In modernity, an individual identity was constituted from civil society, while in a globalized network society, human identity, if it develops at all, must grow from communal resistance. A communal resistance to an abstract conceptualized world, where there is no possibility for perception and ex...

  5. Tracing the Slow Food Movement: local foodscapes and global networks

    Hendrikx, B.; Dormans, S.E.M.; Lagendijk, A.

    2012-01-01

    Over the last two decades alternative food practices have mushroomed across the globe. This proliferation has changed local food scapes, infusing localities with new ideas and ways of food production, circulation and consumption. It has also created global networks of innovation and

  6. Global and local targeted immunization in networks with community structure

    Yan, Shu; Tang, Shaoting; Pei, Sen; Zheng, Zhiming; Fang, Wenyi

    2015-01-01

    Immunization plays an important role in the field of epidemic spreading in complex networks. In previous studies, targeted immunization has been proved to be an effective strategy. However, when extended to networks with community structure, it is unknown whether the superior strategy is to vaccinate the nodes who have the most connections in the entire network (global strategy), or those in the original community where epidemic starts to spread (local strategy). In this work, by using both analytic approaches and simulations, we observe that the answer depends on the closeness between communities. If communities are tied closely, the global strategy is superior to the local strategy. Otherwise, the local targeted immunization is advantageous. The existence of a transitional value of closeness implies that we should adopt different strategies. Furthermore, we extend our investigation from two-community networks to multi-community networks. We consider the mode of community connection and the location of community where epidemic starts to spread. Both simulation results and theoretical predictions show that local strategy is a better option for immunization in most cases. But if the epidemic begins from a core community, global strategy is superior in some cases. (paper)

  7. Genome-scale reconstruction of the Streptococcus pyogenes M49 metabolic network reveals growth requirements and indicates potential drug targets

    Levering, J.; Fiedler, T.; Sieg, A.; van Grinsven, K.W.A.; Hering, S.; Veith, N.; Olivier, B.G.; Klett, L.; Hugenholtz, J.; Teusink, B.; Kreikemeyer, B.; Kummer, U.

    2016-01-01

    Genome-scale metabolic models comprise stoichiometric relations between metabolites, as well as associations between genes and metabolic reactions and facilitate the analysis of metabolism. We computationally reconstructed the metabolic network of the lactic acid bacterium Streptococcus pyogenes

  8. A simple model of global cascades on random networks

    Watts, Duncan J.

    2002-04-01

    The origin of large but rare cascades that are triggered by small initial shocks is a phenomenon that manifests itself as diversely as cultural fads, collective action, the diffusion of norms and innovations, and cascading failures in infrastructure and organizational networks. This paper presents a possible explanation of this phenomenon in terms of a sparse, random network of interacting agents whose decisions are determined by the actions of their neighbors according to a simple threshold rule. Two regimes are identified in which the network is susceptible to very large cascadesherein called global cascadesthat occur very rarely. When cascade propagation is limited by the connectivity of the network, a power law distribution of cascade sizes is observed, analogous to the cluster size distribution in standard percolation theory and avalanches in self-organized criticality. But when the network is highly connected, cascade propagation is limited instead by the local stability of the nodes themselves, and the size distribution of cascades is bimodal, implying a more extreme kind of instability that is correspondingly harder to anticipate. In the first regime, where the distribution of network neighbors is highly skewed, it is found that the most connected nodes are far more likely than average nodes to trigger cascades, but not in the second regime. Finally, it is shown that heterogeneity plays an ambiguous role in determining a system's stability: increasingly heterogeneous thresholds make the system more vulnerable to global cascades; but an increasingly heterogeneous degree distribution makes it less vulnerable.

  9. Global value chains: Building blocks and network dynamics

    Tsekeris, Theodore

    2017-12-01

    The paper employs measures and tools from complex network analysis to enhance the understanding and interpretation of structural characteristics pertaining to the Global Value Chains (GVCs) during the period 1995-2011. The analysis involves the country, sector and country-sector value chain networks to identify main drivers of structural change. The results indicate significant intertemporal changes, mirroring the increased globalization in terms of network size, strength and connectivity. They also demonstrate higher clustering and increased concentration of the most influential countries and country-sectors relative to all others in the GVC network, with the geographical dimension to prevail over the sectoral dimension in the formation of value chains. The regionalization and less hierarchical organization drive country-sector production sharing, while the sectoral value chain network has become more integrated and more competitive over time. The findings suggest that the impact of country-sector policies and/or shocks may vary with the own-group and network-wide influence of each country, take place in multiple geographical scales, as GVCs have a block structure, and involve time dynamics.

  10. A Global Network Alignment Method Using Discrete Particle Swarm Optimization.

    Huang, Jiaxiang; Gong, Maoguo; Ma, Lijia

    2016-10-19

    Molecular interactions data increase exponentially with the advance of biotechnology. This makes it possible and necessary to comparatively analyse the different data at a network level. Global network alignment is an important network comparison approach to identify conserved subnetworks and get insight into evolutionary relationship across species. Network alignment which is analogous to subgraph isomorphism is known to be an NP-hard problem. In this paper, we introduce a novel heuristic Particle-Swarm-Optimization based Network Aligner (PSONA), which optimizes a weighted global alignment model considering both protein sequence similarity and interaction conservations. The particle statuses and status updating rules are redefined in a discrete form by using permutation. A seed-and-extend strategy is employed to guide the searching for the superior alignment. The proposed initialization method "seeds" matches with high sequence similarity into the alignment, which guarantees the functional coherence of the mapping nodes. A greedy local search method is designed as the "extension" procedure to iteratively optimize the edge conservations. PSONA is compared with several state-of-art methods on ten network pairs combined by five species. The experimental results demonstrate that the proposed aligner can map the proteins with high functional coherence and can be used as a booster to effectively refine the well-studied aligners.

  11. Global dissipativity of continuous-time recurrent neural networks with time delay

    Liao Xiaoxin; Wang Jun

    2003-01-01

    This paper addresses the global dissipativity of a general class of continuous-time recurrent neural networks. First, the concepts of global dissipation and global exponential dissipation are defined and elaborated. Next, the sets of global dissipativity and global exponentially dissipativity are characterized using the parameters of recurrent neural network models. In particular, it is shown that the Hopfield network and cellular neural networks with or without time delays are dissipative systems

  12. Local and global responses in complex gene regulation networks

    Tsuchiya, Masa; Selvarajoo, Kumar; Piras, Vincent; Tomita, Masaru; Giuliani, Alessandro

    2009-04-01

    An exacerbated sensitivity to apparently minor stimuli and a general resilience of the entire system stay together side-by-side in biological systems. This apparent paradox can be explained by the consideration of biological systems as very strongly interconnected network systems. Some nodes of these networks, thanks to their peculiar location in the network architecture, are responsible for the sensitivity aspects, while the large degree of interconnection is at the basis of the resilience properties of the system. One relevant feature of the high degree of connectivity of gene regulation networks is the emergence of collective ordered phenomena influencing the entire genome and not only a specific portion of transcripts. The great majority of existing gene regulation models give the impression of purely local ‘hard-wired’ mechanisms disregarding the emergence of global ordered behavior encompassing thousands of genes while the general, genome wide, aspects are less known. Here we address, on a data analysis perspective, the discrimination between local and global scale regulations, this goal was achieved by means of the examination of two biological systems: innate immune response in macrophages and oscillating growth dynamics in yeast. Our aim was to reconcile the ‘hard-wired’ local view of gene regulation with a global continuous and scalable one borrowed from statistical physics. This reconciliation is based on the network paradigm in which the local ‘hard-wired’ activities correspond to the activation of specific crucial nodes in the regulation network, while the scalable continuous responses can be equated to the collective oscillations of the network after a perturbation.

  13. The relation between global migration and trade networks

    Sgrignoli, Paolo; Metulini, Rodolfo; Schiavo, Stefano; Riccaboni, Massimo

    2015-01-01

    In this paper we develop a methodology to analyze and compare multiple global networks, focusing our analysis on the relation between human migration and trade. First, we identify the subset of products for which the presence of a community of migrants significantly increases trade intensity, where to assure comparability across networks we apply a hypergeometric filter that lets us identify those links which intensity is significantly higher than expected. Next, proposing a new way to define country neighbors based on the most intense links in the trade network, we use spatial econometrics techniques to measure the effect of migration on international trade, while controlling for network interdependences. Overall, we find that migration significantly boosts trade across countries and we are able to identify product categories for which this effect is particularly strong.

  14. Global efficiency of local immunization on complex networks.

    Hébert-Dufresne, Laurent; Allard, Antoine; Young, Jean-Gabriel; Dubé, Louis J

    2013-01-01

    Epidemics occur in all shapes and forms: infections propagating in our sparse sexual networks, rumours and diseases spreading through our much denser social interactions, or viruses circulating on the Internet. With the advent of large databases and efficient analysis algorithms, these processes can be better predicted and controlled. In this study, we use different characteristics of network organization to identify the influential spreaders in 17 empirical networks of diverse nature using 2 epidemic models. We find that a judicious choice of local measures, based either on the network's connectivity at a microscopic scale or on its community structure at a mesoscopic scale, compares favorably to global measures, such as betweenness centrality, in terms of efficiency, practicality and robustness. We also develop an analytical framework that highlights a transition in the characteristic scale of different epidemic regimes. This allows to decide which local measure should govern immunization in a given scenario.

  15. Global efficiency of local immunization on complex networks

    Hébert-Dufresne, Laurent; Allard, Antoine; Young, Jean-Gabriel; Dubé, Louis J.

    2013-07-01

    Epidemics occur in all shapes and forms: infections propagating in our sparse sexual networks, rumours and diseases spreading through our much denser social interactions, or viruses circulating on the Internet. With the advent of large databases and efficient analysis algorithms, these processes can be better predicted and controlled. In this study, we use different characteristics of network organization to identify the influential spreaders in 17 empirical networks of diverse nature using 2 epidemic models. We find that a judicious choice of local measures, based either on the network's connectivity at a microscopic scale or on its community structure at a mesoscopic scale, compares favorably to global measures, such as betweenness centrality, in terms of efficiency, practicality and robustness. We also develop an analytical framework that highlights a transition in the characteristic scale of different epidemic regimes. This allows to decide which local measure should govern immunization in a given scenario.

  16. Quantitative analysis of proteome and lipidome dynamics reveals functional regulation of global lipid metabolism

    Casanovas, Albert; Sprenger, Richard R; Tarasov, Kirill

    2015-01-01

    Elucidating how and to what extent lipid metabolism is remodeled under changing conditions is essential for understanding cellular physiology. Here, we analyzed proteome and lipidome dynamics to investigate how regulation of lipid metabolism at the global scale supports remodeling of cellular...

  17. Exploring photosynthesis evolution by comparative analysis of metabolic networks between chloroplasts and photosynthetic bacteria

    Hou Jing

    2006-04-01

    Full Text Available Abstract Background Chloroplasts descended from cyanobacteria and have a drastically reduced genome following an endosymbiotic event. Many genes of the ancestral cyanobacterial genome have been transferred to the plant nuclear genome by horizontal gene transfer. However, a selective set of metabolism pathways is maintained in chloroplasts using both chloroplast genome encoded and nuclear genome encoded enzymes. As an organelle specialized for carrying out photosynthesis, does the chloroplast metabolic network have properties adapted for higher efficiency of photosynthesis? We compared metabolic network properties of chloroplasts and prokaryotic photosynthetic organisms, mostly cyanobacteria, based on metabolic maps derived from genome data to identify features of chloroplast network properties that are different from cyanobacteria and to analyze possible functional significance of those features. Results The properties of the entire metabolic network and the sub-network that consists of reactions directly connected to the Calvin Cycle have been analyzed using hypergraph representation. Results showed that the whole metabolic networks in chloroplast and cyanobacteria both possess small-world network properties. Although the number of compounds and reactions in chloroplasts is less than that in cyanobacteria, the chloroplast's metabolic network has longer average path length, a larger diameter, and is Calvin Cycle -centered, indicating an overall less-dense network structure with specific and local high density areas in chloroplasts. Moreover, chloroplast metabolic network exhibits a better modular organization than cyanobacterial ones. Enzymes involved in the same metabolic processes tend to cluster into the same module in chloroplasts. Conclusion In summary, the differences in metabolic network properties may reflect the evolutionary changes during endosymbiosis that led to the improvement of the photosynthesis efficiency in higher plants. Our

  18. Hegemonic transitions and global shifts in social metabolism: Implications for resource-rich countries. Introduction to the special section

    Muradian Sarache, R.P.; Walter, M.; Martinez-Alier, J.

    2012-01-01

    This introductory paper to the special section of Global Environmental Change entitled "Global transformations, social metabolism and the dynamics of socio-environmental conflicts" argues that the emergence of new global economic centers is inducing a major expansion in the global social metabolism

  19. Polycentrism in Global Health Governance Scholarship Comment on "Four Challenges That Global Health Networks Face".

    Tosun, Jale

    2017-05-23

    Drawing on an in-depth analysis of eight global health networks, a recent essay in this journal argued that global health networks face four challenges to their effectiveness: problem definition, positioning, coalition-building, and governance. While sharing the argument of the essay concerned, in this commentary, we argue that these analytical concepts can be used to explicate a concept that has implicitly been used in global health governance scholarship for quite a few years. While already prominent in the discussion of climate change governance, for instance, global health governance scholarship could make progress by looking at global health governance as being polycentric. Concisely, polycentric forms of governance mix scales, mechanisms, and actors. Drawing on the essay, we propose a polycentric approach to the study of global health governance that incorporates coalitionbuilding tactics, internal governance and global political priority as explanatory factors. © 2018 The Author(s); Published by Kerman University of Medical Sciences. This is an open-access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

  20. A state of the art of metabolic networks of unicellular microalgae and cyanobacteria for biofuel production.

    Baroukh, Caroline; Muñoz-Tamayo, Rafael; Steyer, Jean-Philippe; Bernard, Olivier

    2015-07-01

    The most promising and yet challenging application of microalgae and cyanobacteria is the production of renewable energy: biodiesel from microalgae triacylglycerols and bioethanol from cyanobacteria carbohydrates. A thorough understanding of microalgal and cyanobacterial metabolism is necessary to master and optimize biofuel production yields. To this end, systems biology and metabolic modeling have proven to be very efficient tools if supported by an accurate knowledge of the metabolic network. However, unlike heterotrophic microorganisms that utilize the same substrate for energy and as carbon source, microalgae and cyanobacteria require light for energy and inorganic carbon (CO2 or bicarbonate) as carbon source. This double specificity, together with the complex mechanisms of light capture, makes the representation of metabolic network nonstandard. Here, we review the existing metabolic networks of photoautotrophic microalgae and cyanobacteria. We highlight how these networks have been useful for gaining insight on photoautotrophic metabolism. Copyright © 2015 International Metabolic Engineering Society. Published by Elsevier Inc. All rights reserved.

  1. Global network structure of dominance hierarchy of ant workers.

    Shimoji, Hiroyuki; Abe, Masato S; Tsuji, Kazuki; Masuda, Naoki

    2014-10-06

    Dominance hierarchy among animals is widespread in various species and believed to serve to regulate resource allocation within an animal group. Unlike small groups, however, detection and quantification of linear hierarchy in large groups of animals are a difficult task. Here, we analyse aggression-based dominance hierarchies formed by worker ants in Diacamma sp. as large directed networks. We show that the observed dominance networks are perfect or approximate directed acyclic graphs, which are consistent with perfect linear hierarchy. The observed networks are also sparse and random but significantly different from networks generated through thinning of the perfect linear tournament (i.e. all individuals are linearly ranked and dominance relationship exists between every pair of individuals). These results pertain to global structure of the networks, which contrasts with the previous studies inspecting frequencies of different types of triads. In addition, the distribution of the out-degree (i.e. number of workers that the focal worker attacks), not in-degree (i.e. number of workers that attack the focal worker), of each observed network is right-skewed. Those having excessively large out-degrees are located near the top, but not the top, of the hierarchy. We also discuss evolutionary implications of the discovered properties of dominance networks. © 2014 The Author(s) Published by the Royal Society. All rights reserved.

  2. Global 4-H Network: Laying the Groundwork for Global Extension Opportunities

    Major, Jennifer; Miller, Rhonda

    2012-01-01

    A descriptive study examining 4-H programs in Africa, Asia, and Europe was conducted to provide understanding and direction in the establishment of a Global 4-H Network. Information regarding structure, organizational support, funding, and programming areas was gathered. Programs varied greatly by country, and many partnered with other 4-H…

  3. Global Horizontal Control Network of Shanghai Synchrotron Radiation Facility

    Yu Chenghao; Ke Ming; Du Hanwen; Yin Lixin; Zhao Zhentang; Dong Lan; Huang Kaixi

    2009-01-01

    As a national big scientific engineering, Shanghai Synchrotron Radiation Facility (SSRF) has rigid requirement to the components with sub-millimeter accuracy. In the process of survey and positioning global control network is a connecting link, which determines the position relationship between building and accelerator devices, and provides high accuracy datum to local control network. Within the designing process, building and devices are very restrict. While among observation, it's hard to be observed and abound with disadvantages. With continuous optimization and careful operation, super-high accuracy of 0.3 mm within 400 m circumference was achieved and slab's periodic movement could be seen through 3 times measurement. (authors)

  4. Spike propagation in driven chain networks with dominant global inhibition

    Chang Wonil; Jin, Dezhe Z.

    2009-01-01

    Spike propagation in chain networks is usually studied in the synfire regime, in which successive groups of neurons are synaptically activated sequentially through the unidirectional excitatory connections. Here we study the dynamics of chain networks with dominant global feedback inhibition that prevents the synfire activity. Neural activity is driven by suprathreshold external inputs. We analytically and numerically demonstrate that spike propagation along the chain is a unique dynamical attractor in a wide parameter regime. The strong inhibition permits a robust winner-take-all propagation in the case of multiple chains competing via the inhibition.

  5. Promoting Simulation Globally: Networking with Nursing Colleagues Across Five Continents.

    Alfes, Celeste M; Madigan, Elizabeth A

    Simulation education is gaining momentum internationally and may provide the opportunity to enhance clinical education while disseminating evidence-based practice standards for clinical simulation and learning. There is a need to develop a cohesive leadership group that fosters support, networking, and sharing of simulation resources globally. The Frances Payne Bolton School of Nursing at Case Western Reserve University has had the unique opportunity to establish academic exchange programs with schools of nursing across five continents. Although the joint and mutual simulation activities have been extensive, each international collaboration has also provided insight into the innovations developed by global partners.

  6. Global Asymptotic Stability of Switched Neural Networks with Delays

    Zhenyu Lu

    2015-01-01

    Full Text Available This paper investigates the global asymptotic stability of a class of switched neural networks with delays. Several new criteria ensuring global asymptotic stability in terms of linear matrix inequalities (LMIs are obtained via Lyapunov-Krasovskii functional. And here, we adopt the quadratic convex approach, which is different from the linear and reciprocal convex combinations that are extensively used in recent literature. In addition, the proposed results here are very easy to be verified and complemented. Finally, a numerical example is provided to illustrate the effectiveness of the results.

  7. Shifting Tides in Global Higher Education: Agency, Autonomy, and Governance in the Global Network. Global Studies in Education, Volume 9

    Witt, Mary Allison

    2011-01-01

    The increasing connection among higher education institutions worldwide is well documented. What is less understood is how this connectivity is enacted and manifested on specific levels of the global education network. This book details the planning process of a multi-institutional program in engineering between institutions in the US and…

  8. Integration of metabolic and gene regulatory networks modulates the C. elegans dietary response.

    Watson, Emma; MacNeil, Lesley T; Arda, H Efsun; Zhu, Lihua Julie; Walhout, Albertha J M

    2013-03-28

    Expression profiles are tailored according to dietary input. However, the networks that control dietary responses remain largely uncharacterized. Here, we combine forward and reverse genetic screens to delineate a network of 184 genes that affect the C. elegans dietary response to Comamonas DA1877 bacteria. We find that perturbation of a mitochondrial network composed of enzymes involved in amino acid metabolism and the TCA cycle affects the dietary response. In humans, mutations in the corresponding genes cause inborn diseases of amino acid metabolism, most of which are treated by dietary intervention. We identify several transcription factors (TFs) that mediate the changes in gene expression upon metabolic network perturbations. Altogether, our findings unveil a transcriptional response system that is poised to sense dietary cues and metabolic imbalances, illustrating extensive communication between metabolic networks in the mitochondria and gene regulatory networks in the nucleus. Copyright © 2013 Elsevier Inc. All rights reserved.

  9. Energetics of glucose metabolism: a phenomenological approach to metabolic network modeling.

    Diederichs, Frank

    2010-08-12

    A new formalism to describe metabolic fluxes as well as membrane transport processes was developed. The new flux equations are comparable to other phenomenological laws. Michaelis-Menten like expressions, as well as flux equations of nonequilibrium thermodynamics, can be regarded as special cases of these new equations. For metabolic network modeling, variable conductances and driving forces are required to enable pathway control and to allow a rapid response to perturbations. When applied to oxidative phosphorylation, results of simulations show that whole oxidative phosphorylation cannot be described as a two-flux-system according to nonequilibrium thermodynamics, although all coupled reactions per se fulfill the equations of this theory. Simulations show that activation of ATP-coupled load reactions plus glucose oxidation is brought about by an increase of only two different conductances: a [Ca(2+)] dependent increase of cytosolic load conductances, and an increase of phosphofructokinase conductance by [AMP], which in turn becomes increased through [ADP] generation by those load reactions. In ventricular myocytes, this feedback mechanism is sufficient to increase cellular power output and O(2) consumption several fold, without any appreciable impairment of energetic parameters. Glucose oxidation proceeds near maximal power output, since transformed input and output conductances are nearly equal, yielding an efficiency of about 0.5. This conductance matching is fulfilled also by glucose oxidation of β-cells. But, as a price for the metabolic mechanism of glucose recognition, β-cells have only a limited capability to increase their power output.

  10. Global Metabolic Reconstruction and Metabolic Gene Evolution in the Cattle Genome

    Kim, Woonsu; Park, Hyesun; Seo, Seongwon

    2016-01-01

    The sequence of cattle genome provided a valuable opportunity to systematically link genetic and metabolic traits of cattle. The objectives of this study were 1) to reconstruct genome-scale cattle-specific metabolic pathways based on the most recent and updated cattle genome build and 2) to identify duplicated metabolic genes in the cattle genome for better understanding of metabolic adaptations in cattle. A bioinformatic pipeline of an organism for amalgamating genomic annotations from multiple sources was updated. Using this, an amalgamated cattle genome database based on UMD_3.1, was created. The amalgamated cattle genome database is composed of a total of 33,292 genes: 19,123 consensus genes between NCBI and Ensembl databases, 8,410 and 5,493 genes only found in NCBI or Ensembl, respectively, and 266 genes from NCBI scaffolds. A metabolic reconstruction of the cattle genome and cattle pathway genome database (PGDB) was also developed using Pathway Tools, followed by an intensive manual curation. The manual curation filled or revised 68 pathway holes, deleted 36 metabolic pathways, and added 23 metabolic pathways. Consequently, the curated cattle PGDB contains 304 metabolic pathways, 2,460 reactions including 2,371 enzymatic reactions, and 4,012 enzymes. Furthermore, this study identified eight duplicated genes in 12 metabolic pathways in the cattle genome compared to human and mouse. Some of these duplicated genes are related with specific hormone biosynthesis and detoxifications. The updated genome-scale metabolic reconstruction is a useful tool for understanding biology and metabolic characteristics in cattle. There has been significant improvements in the quality of cattle genome annotations and the MetaCyc database. The duplicated metabolic genes in the cattle genome compared to human and mouse implies evolutionary changes in the cattle genome and provides a useful information for further research on understanding metabolic adaptations of cattle. PMID

  11. Collaboration tools for the global accelerator network: Workshop Report

    Agarwal, Deborah; Olson, Gary; Olson, Judy

    2002-01-01

    The concept of a ''Global Accelerator Network'' (GAN) has been put forward as a means for inter-regional collaboration in the operation of internationally constructed and operated frontier accelerator facilities. A workshop was held to allow representatives of the accelerator community and of the collaboratory development community to meet and discuss collaboration tools for the GAN environment. This workshop, called the Collaboration Tools for the Global Accelerator Network (GAN) Workshop, was held on August 26, 2002 at Lawrence Berkeley National Laboratory. The goal was to provide input about collaboration tools in general and to provide a strawman for the GAN collaborative tools environment. The participants at the workshop represented accelerator physicists, high-energy physicists, operations, technology tool developers, and social scientists that study scientific collaboration

  12. Collaboration tools for the global accelerator network Workshop Report

    Agarwal, D; Olson, J

    2002-01-01

    The concept of a ''Global Accelerator Network'' (GAN) has been put forward as a means for inter-regional collaboration in the operation of internationally constructed and operated frontier accelerator facilities. A workshop was held to allow representatives of the accelerator community and of the collaboratory development community to meet and discuss collaboration tools for the GAN environment. This workshop, called the Collaboration Tools for the Global Accelerator Network (GAN) Workshop, was held on August 26, 2002 at Lawrence Berkeley National Laboratory. The goal was to provide input about collaboration tools in general and to provide a strawman for the GAN collaborative tools environment. The participants at the workshop represented accelerator physicists, high-energy physicists, operations, technology tool developers, and social scientists that study scientific collaboration.

  13. Global research collaboration: Networks and partners in South East Asia

    Woolley, Richard; Robinson-Garcia, Nicolas; Costas, Rodrigo

    2017-01-01

    This is an empirical paper that addresses the role of bilateral and multilateral international co-authorships in the six leading science systems among the ASEAN group of countries (ASEAN6). The paper highlights the different ways that bilateral and multilateral co-authorships structure global networks and the collaborations of the ASEAN6. The paper looks at the influence of the collaboration styles of major collaborating countries of the ASEAN6, particularly the USA and Japan. It also highlig...

  14. Running a network on a shoestring: the Global Invasive Species Information Network

    Jarnevich, Catherine S.; Simpson, Annie; Graham, James J; Newman, Gregory J.; Bargeron, Chuck T.

    2015-01-01

    The Global Invasive Species Information Network (GISIN) was conceptualized in 2004 to aggregate and disseminate invasive species data in a standardized way. A decade later the GISIN community has implemented a data portal and three of six GISIN data aggregation models in the GISIN data exchange Protocol, including invasive species status information, resource URLs, and occurrence data. The portal is based on a protocol developed by representatives from 15 countries and 27 organizations of the global invasive species information management community. The GISIN has 19 data providers sharing 34,343 species status records, 1,693,073 occurrences, and 15,601 resource URLs. While the GISIN's goal is to be global, much of its data and funding are provided by the United States. Several initiatives use the GISIN as their information backbone, such as the Great Lakes Early Detection Network (GLEDN) and the North American Invasive Species Network (NAISN). Here we share several success stories and organizational challenges that remain.

  15. Tensor network decompositions in the presence of a global symmetry

    Singh, Sukhwinder; Pfeifer, Robert N. C.; Vidal, Guifre

    2010-01-01

    Tensor network decompositions offer an efficient description of certain many-body states of a lattice system and are the basis of a wealth of numerical simulation algorithms. We discuss how to incorporate a global symmetry, given by a compact, completely reducible group G, in tensor network decompositions and algorithms. This is achieved by considering tensors that are invariant under the action of the group G. Each symmetric tensor decomposes into two types of tensors: degeneracy tensors, containing all the degrees of freedom, and structural tensors, which only depend on the symmetry group. In numerical calculations, the use of symmetric tensors ensures the preservation of the symmetry, allows selection of a specific symmetry sector, and significantly reduces computational costs. On the other hand, the resulting tensor network can be interpreted as a superposition of exponentially many spin networks. Spin networks are used extensively in loop quantum gravity, where they represent states of quantum geometry. Our work highlights their importance in the context of tensor network algorithms as well, thus setting the stage for cross-fertilization between these two areas of research.

  16. Microbial diversity and metabolic networks in acid mine drainage habitats

    Celia eMendez-Garcia

    2015-05-01

    Full Text Available Acid mine drainage (AMD emplacements are low-complexity natural systems. Low-pH conditions appear to be the main factor underlying the limited diversity of the microbial populations thriving in these environments, although temperature, ionic composition, total organic carbon and dissolved oxygen are also considered to significantly influence their microbial life. This natural reduction in diversity driven by extreme conditions was reflected in several studies on the microbial populations inhabiting the various micro-environments present in such ecosystems. Early studies based on the physiology of the autochthonous microbiota and the growing success of omics technologies have enabled a better understanding of microbial ecology and function in low-pH mine outflows; however, complementary omics-derived data should be included to completely describe their microbial ecology. Furthermore, recent updates on the distribution of eukaryotes and ultra-micro-archaea demand their inclusion in the microbial characterisation of AMD systems. In this review, we present a complete overview of the bacterial, archaeal (including ultra-micro-archaeal and eukaryotic diversity in these ecosystems and include a thorough depiction of the metabolism and element cycling in AMD habitats. We also review different metabolic network structures at the organismal level, which is necessary to disentangle the role of each member of the AMD communities described thus far.

  17. A Bayesian approach to the evolution of metabolic networks on a phylogeny.

    Aziz Mithani

    2010-08-01

    Full Text Available The availability of genomes of many closely related bacteria with diverse metabolic capabilities offers the possibility of tracing metabolic evolution on a phylogeny relating the genomes to understand the evolutionary processes and constraints that affect the evolution of metabolic networks. Using simple (independent loss/gain of reactions or complex (incorporating dependencies among reactions stochastic models of metabolic evolution, it is possible to study how metabolic networks evolve over time. Here, we describe a model that takes the reaction neighborhood into account when modeling metabolic evolution. The model also allows estimation of the strength of the neighborhood effect during the course of evolution. We present Gibbs samplers for sampling networks at the internal node of a phylogeny and for estimating the parameters of evolution over a phylogeny without exploring the whole search space by iteratively sampling from the conditional distributions of the internal networks and parameters. The samplers are used to estimate the parameters of evolution of metabolic networks of bacteria in the genus Pseudomonas and to infer the metabolic networks of the ancestral pseudomonads. The results suggest that pathway maps that are conserved across the Pseudomonas phylogeny have a stronger neighborhood structure than those which have a variable distribution of reactions across the phylogeny, and that some Pseudomonas lineages are going through genome reduction resulting in the loss of a number of reactions from their metabolic networks.

  18. Approach on a global HTGR R and D network

    Lensa, W. von

    1997-01-01

    The present situation of nuclear power in general and of the innovative nuclear reactor systems in particular requires more comprehensive, coordinated R and D efforts on a broad international level to respond to today's requirements with respect to public and economic acceptance as well as to globalization trends and global environmental problems. HTGR technology development has already reached a high degree of maturity that will be complemented by the operation of the two new test reactors in Japan and China, representing technological milestones for the demonstration of HTGR safety characteristics and Nuclear Process Heat generation capabilities. It is proposed by the IAEA 'International Working Group on Gas-Cooled Reactors' to establish a 'Global HTGR R and D Network' on basic HTGR technology for the stable, long-term advancement of the specific HTGR features and as a basis for the future market introduction of this innovative reactor system. The background and the motivation for this approach are illustrated, as well as first proposals on the main objectives, the structure and the further procedures for the implementation of such a multinational working sharing R and D network. Modern telecooperation methods are foreseen as an interactive tool for effective communication and collaboration on a global scale. (author)

  19. Ecological network analysis on global virtual water trade.

    Yang, Zhifeng; Mao, Xufeng; Zhao, Xu; Chen, Bin

    2012-02-07

    Global water interdependencies are likely to increase with growing virtual water trade. To address the issues of the indirect effects of water trade through the global economic circulation, we use ecological network analysis (ENA) to shed insight into the complicated system interactions. A global model of virtual water flow among agriculture and livestock production trade in 1995-1999 is also built as the basis for network analysis. Control analysis is used to identify the quantitative control or dependency relations. The utility analysis provides more indicators for describing the mutual relationship between two regions/countries by imitating the interactions in the ecosystem and distinguishes the beneficiary and the contributor of virtual water trade system. Results show control and utility relations can well depict the mutual relation in trade system, and direct observable relations differ from integral ones with indirect interactions considered. This paper offers a new way to depict the interrelations between trade components and can serve as a meaningful start as we continue to use ENA in providing more valuable implications for freshwater study on a global scale.

  20. Global robust exponential stability analysis for interval recurrent neural networks

    Xu Shengyuan; Lam, James; Ho, Daniel W.C.; Zou Yun

    2004-01-01

    This Letter investigates the problem of robust global exponential stability analysis for interval recurrent neural networks (RNNs) via the linear matrix inequality (LMI) approach. The values of the time-invariant uncertain parameters are assumed to be bounded within given compact sets. An improved condition for the existence of a unique equilibrium point and its global exponential stability of RNNs with known parameters is proposed. Based on this, a sufficient condition for the global robust exponential stability for interval RNNs is obtained. Both of the conditions are expressed in terms of LMIs, which can be checked easily by various recently developed convex optimization algorithms. Examples are provided to demonstrate the reduced conservatism of the proposed exponential stability condition

  1. A consensus yeast metabolic network reconstruction obtained from a community approach to systems biology

    Herrgård, Markus J.; Swainston, Neil; Dobson, Paul; Dunn, Warwick B.; Arga, K. Yalçin; Arvas, Mikko; Blüthgen, Nils; Borger, Simon; Costenoble, Roeland; Heinemann, Matthias; Hucka, Michael; Novère, Nicolas Le; Li, Peter; Liebermeister, Wolfram; Mo, Monica L.; Oliveira, Ana Paula; Petranovic, Dina; Pettifer, Stephen; Simeonidis, Evangelos; Smallbone, Kieran; Spasić, Irena; Weichart, Dieter; Brent, Roger; Broomhead, David S.; Westerhoff, Hans V.; Kırdar, Betül; Penttilä, Merja; Klipp, Edda; Palsson, Bernhard Ø.; Sauer, Uwe; Oliver, Stephen G.; Mendes, Pedro; Nielsen, Jens; Kell, Douglas B.

    2008-01-01

    Genomic data allow the large-scale manual or semi-automated assembly of metabolic network reconstructions, which provide highly curated organism-specific knowledge bases. Although several genome-scale network reconstructions describe Saccharomyces cerevisiae metabolism, they differ in scope and

  2. Links that speak: The global language network and its association with global fame

    Ronen, Shahar; Gonçalves, Bruno; Hu, Kevin Z.; Vespignani, Alessandro; Pinker, Steven; Hidalgo, César A.

    2014-01-01

    Languages vary enormously in global importance because of historical, demographic, political, and technological forces. However, beyond simple measures of population and economic power, there has been no rigorous quantitative way to define the global influence of languages. Here we use the structure of the networks connecting multilingual speakers and translated texts, as expressed in book translations, multiple language editions of Wikipedia, and Twitter, to provide a concept of language importance that goes beyond simple economic or demographic measures. We find that the structure of these three global language networks (GLNs) is centered on English as a global hub and around a handful of intermediate hub languages, which include Spanish, German, French, Russian, Portuguese, and Chinese. We validate the measure of a language’s centrality in the three GLNs by showing that it exhibits a strong correlation with two independent measures of the number of famous people born in the countries associated with that language. These results suggest that the position of a language in the GLN contributes to the visibility of its speakers and the global popularity of the cultural content they produce. PMID:25512502

  3. Links that speak: the global language network and its association with global fame.

    Ronen, Shahar; Gonçalves, Bruno; Hu, Kevin Z; Vespignani, Alessandro; Pinker, Steven; Hidalgo, César A

    2014-12-30

    Languages vary enormously in global importance because of historical, demographic, political, and technological forces. However, beyond simple measures of population and economic power, there has been no rigorous quantitative way to define the global influence of languages. Here we use the structure of the networks connecting multilingual speakers and translated texts, as expressed in book translations, multiple language editions of Wikipedia, and Twitter, to provide a concept of language importance that goes beyond simple economic or demographic measures. We find that the structure of these three global language networks (GLNs) is centered on English as a global hub and around a handful of intermediate hub languages, which include Spanish, German, French, Russian, Portuguese, and Chinese. We validate the measure of a language's centrality in the three GLNs by showing that it exhibits a strong correlation with two independent measures of the number of famous people born in the countries associated with that language. These results suggest that the position of a language in the GLN contributes to the visibility of its speakers and the global popularity of the cultural content they produce.

  4. Coordinations between gene modules control the operation of plant amino acid metabolic networks

    Galili Gad

    2009-01-01

    Full Text Available Abstract Background Being sessile organisms, plants should adjust their metabolism to dynamic changes in their environment. Such adjustments need particular coordination in branched metabolic networks in which a given metabolite can be converted into multiple other metabolites via different enzymatic chains. In the present report, we developed a novel "Gene Coordination" bioinformatics approach and use it to elucidate adjustable transcriptional interactions of two branched amino acid metabolic networks in plants in response to environmental stresses, using publicly available microarray results. Results Using our "Gene Coordination" approach, we have identified in Arabidopsis plants two oppositely regulated groups of "highly coordinated" genes within the branched Asp-family network of Arabidopsis plants, which metabolizes the amino acids Lys, Met, Thr, Ile and Gly, as well as a single group of "highly coordinated" genes within the branched aromatic amino acid metabolic network, which metabolizes the amino acids Trp, Phe and Tyr. These genes possess highly coordinated adjustable negative and positive expression responses to various stress cues, which apparently regulate adjustable metabolic shifts between competing branches of these networks. We also provide evidence implying that these highly coordinated genes are central to impose intra- and inter-network interactions between the Asp-family and aromatic amino acid metabolic networks as well as differential system interactions with other growth promoting and stress-associated genome-wide genes. Conclusion Our novel Gene Coordination elucidates that branched amino acid metabolic networks in plants are regulated by specific groups of highly coordinated genes that possess adjustable intra-network, inter-network and genome-wide transcriptional interactions. We also hypothesize that such transcriptional interactions enable regulatory metabolic adjustments needed for adaptation to the stresses.

  5. SONG-China Project: A Global Automated Observation Network

    Yang, Z. Z.; Lu, X. M.; Tian, J. F.; Zhuang, C. G.; Wang, K.; Deng, L. C.

    2017-09-01

    Driven by advancements in technology and scientific objectives, data acquisition in observational astronomy has been changed greatly in recent years. Fully automated or even autonomous ground-based network of telescopes has now become a tendency for time-domain observational projects. The Stellar Observations Network Group (SONG) is an international collaboration with the participation and contribution of the Chinese astronomy community. The scientific goal of SONG is time-domain astrophysics such as asteroseismology and open cluster research. The SONG project aims to build a global network of 1 m telescopes equipped with high-precision and high-resolution spectrographs, and two-channel lucky-imaging cameras. It is the Chinese initiative to install a 50 cm binocular photometry telescope at each SONG node sharing the network platform and infrastructure. This work is focused on design and implementation in technology and methodology of SONG/50BiN, a typical ground-based network composed of multiple sites and a variety of instruments.

  6. Effects of local and global network connectivity on synergistic epidemics

    Broder-Rodgers, David; Pérez-Reche, Francisco J.; Taraskin, Sergei N.

    2015-12-01

    Epidemics in networks can be affected by cooperation in transmission of infection and also connectivity between nodes. An interplay between these two properties and their influence on epidemic spread are addressed in the paper. A particular type of cooperative effects (called synergy effects) is considered, where the transmission rate between a pair of nodes depends on the number of infected neighbors. The connectivity effects are studied by constructing networks of different topology, starting with lattices with only local connectivity and then with networks that have both local and global connectivity obtained by random bond-rewiring to nodes within a certain distance. The susceptible-infected-removed epidemics were found to exhibit several interesting effects: (i) for epidemics with strong constructive synergy spreading in networks with high local connectivity, the bond rewiring has a negative role in epidemic spread, i.e., it reduces invasion probability; (ii) in contrast, for epidemics with destructive or weak constructive synergy spreading on networks of arbitrary local connectivity, rewiring helps epidemics to spread; (iii) and, finally, rewiring always enhances the spread of epidemics, independent of synergy, if the local connectivity is low.

  7. Small-worldness and gender differences of large scale brain metabolic covariance networks in young adults: a FDG PET study of 400 subjects.

    Hu, Yuxiao; Xu, Qiang; Shen, Junkang; Li, Kai; Zhu, Hong; Zhang, Zhiqiang; Lu, Guangming

    2015-02-01

    Many studies have demonstrated the small-worldness of the human brain, and have revealed a sexual dimorphism in brain network properties. However, little is known about the gender effects on the topological organization of the brain metabolic covariance networks. To investigate the small-worldness and the gender differences in the topological architectures of human brain metabolic networks. FDG-PET data of 400 healthy right-handed subjects (200 women and 200 age-matched men) were involved in the present study. Metabolic networks of each gender were constructed by calculating the covariance of regional cerebral glucose metabolism (rCMglc) across subjects on the basis of AAL parcellation. Gender differences of network and nodal properties were investigated by using the graph theoretical approaches. Moreover, the gender-related difference of rCMglc in each brain region was tested for investigating the relationships between the hub regions and the brain regions showing significant gender-related differences in rCMglc. We found prominent small-world properties in the domain of metabolic networks in each gender. No significant gender difference in the global characteristics was found. Gender differences of nodal characteristic were observed in a few brain regions. We also found bilateral and lateralized distributions of network hubs in the females and males. Furthermore, we first reported that some hubs of a gender located in the brain regions showing weaker rCMglc in this gender than the other gender. The present study demonstrated that small-worldness was existed in metabolic networks, and revealed gender differences of organizational patterns in metabolic network. These results maybe provided insights into the understanding of the metabolic substrates underlying individual differences in cognition and behaviors. © The Foundation Acta Radiologica 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.

  8. The scaling structure of the global road network.

    Strano, Emanuele; Giometto, Andrea; Shai, Saray; Bertuzzo, Enrico; Mucha, Peter J; Rinaldo, Andrea

    2017-10-01

    Because of increasing global urbanization and its immediate consequences, including changes in patterns of food demand, circulation and land use, the next century will witness a major increase in the extent of paved roads built worldwide. To model the effects of this increase, it is crucial to understand whether possible self-organized patterns are inherent in the global road network structure. Here, we use the largest updated database comprising all major roads on the Earth, together with global urban and cropland inventories, to suggest that road length distributions within croplands are indistinguishable from urban ones, once rescaled to account for the difference in mean road length. Such similarity extends to road length distributions within urban or agricultural domains of a given area. We find two distinct regimes for the scaling of the mean road length with the associated area, holding in general at small and at large values of the latter. In suitably large urban and cropland domains, we find that mean and total road lengths increase linearly with their domain area, differently from earlier suggestions. Scaling regimes suggest that simple and universal mechanisms regulate urban and cropland road expansion at the global scale. As such, our findings bear implications for global road infrastructure growth based on land-use change and for planning policies sustaining urban expansions.

  9. Global patterns in lake ecosystem responses to warming based on the temperature dependence of metabolism.

    Kraemer, Benjamin M; Chandra, Sudeep; Dell, Anthony I; Dix, Margaret; Kuusisto, Esko; Livingstone, David M; Schladow, S Geoffrey; Silow, Eugene; Sitoki, Lewis M; Tamatamah, Rashid; McIntyre, Peter B

    2017-05-01

    Climate warming is expected to have large effects on ecosystems in part due to the temperature dependence of metabolism. The responses of metabolic rates to climate warming may be greatest in the tropics and at low elevations because mean temperatures are warmer there and metabolic rates respond exponentially to temperature (with exponents >1). However, if warming rates are sufficiently fast in higher latitude/elevation lakes, metabolic rate responses to warming may still be greater there even though metabolic rates respond exponentially to temperature. Thus, a wide range of global patterns in the magnitude of metabolic rate responses to warming could emerge depending on global patterns of temperature and warming rates. Here we use the Boltzmann-Arrhenius equation, published estimates of activation energy, and time series of temperature from 271 lakes to estimate long-term (1970-2010) changes in 64 metabolic processes in lakes. The estimated responses of metabolic processes to warming were usually greatest in tropical/low-elevation lakes even though surface temperatures in higher latitude/elevation lakes are warming faster. However, when the thermal sensitivity of a metabolic process is especially weak, higher latitude/elevation lakes had larger responses to warming in parallel with warming rates. Our results show that the sensitivity of a given response to temperature (as described by its activation energy) provides a simple heuristic for predicting whether tropical/low-elevation lakes will have larger or smaller metabolic responses to warming than higher latitude/elevation lakes. Overall, we conclude that the direct metabolic consequences of lake warming are likely to be felt most strongly at low latitudes and low elevations where metabolism-linked ecosystem services may be most affected. © 2016 John Wiley & Sons Ltd.

  10. Sustaining a Global Social Network: a quasi-experimental study.

    Benton, D C; Ferguson, S L

    2017-03-01

    To examine the longer term impact on the social network of participating nurses in the Global Nursing Leadership Institute (GNLI2013) through using differing frequencies of follow-up to assess impact on maintenance of network cohesion. Social network analysis is increasingly been used by nurse researchers, however, studies tend to use single point-in-time descriptive methods. This study utilizes a repeated measures, block group, control-intervention, quasi-experimental design. Twenty-eight nurse leaders, competitively selected through a double-blind peer review process, were allocated to five action learning-based learning groups. Network architecture, measures of cohesion and node degree frequency were all used to assess programme impact. The programme initiated and sustained connections between nurse leaders drawn from a geographically dispersed heterogeneous group. Modest inputs of two to three e-mails over a 6-month period seem sufficient to maintain connectivity as indicated by measures of network density, diameter and path length. Due to the teaching methodology used, the study sample was relatively small and the follow-up data collection took place after a relatively short time. Replication and further cohort data collection would be advantageous. In an era where many policy solutions are being debated and initiated at the global level, action learning leadership development that utilizes new technology follow-up appears to show significant impact and is worthy of wider application. The approach warrants further inquiry and testing as to its longer term effects on nursing's influence on policy formulation and implementation. © 2016 International Council of Nurses.

  11. Reconstruction and validation of RefRec: a global model for the yeast molecular interaction network.

    Tommi Aho

    2010-05-01

    Full Text Available Molecular interaction networks establish all cell biological processes. The networks are under intensive research that is facilitated by new high-throughput measurement techniques for the detection, quantification, and characterization of molecules and their physical interactions. For the common model organism yeast Saccharomyces cerevisiae, public databases store a significant part of the accumulated information and, on the way to better understanding of the cellular processes, there is a need to integrate this information into a consistent reconstruction of the molecular interaction network. This work presents and validates RefRec, the most comprehensive molecular interaction network reconstruction currently available for yeast. The reconstruction integrates protein synthesis pathways, a metabolic network, and a protein-protein interaction network from major biological databases. The core of the reconstruction is based on a reference object approach in which genes, transcripts, and proteins are identified using their primary sequences. This enables their unambiguous identification and non-redundant integration. The obtained total number of different molecular species and their connecting interactions is approximately 67,000. In order to demonstrate the capacity of RefRec for functional predictions, it was used for simulating the gene knockout damage propagation in the molecular interaction network in approximately 590,000 experimentally validated mutant strains. Based on the simulation results, a statistical classifier was subsequently able to correctly predict the viability of most of the strains. The results also showed that the usage of different types of molecular species in the reconstruction is important for accurate phenotype prediction. In general, the findings demonstrate the benefits of global reconstructions of molecular interaction networks. With all the molecular species and their physical interactions explicitly modeled, our

  12. Indications of marine bioinvasion from network theory. An analysis of the global cargo ship network

    Kölzsch, A.; Blasius, B.

    2011-01-01

    The transport of huge amounts of small aquatic organisms in the ballast tanks and at the hull of large cargo ships leads to ever increasing rates of marine bioinvasion. In this study, we apply a network theoretic approach to examine the introduction of invasive species into new ports by global

  13. Comprehensive Mapping of Pluripotent Stem Cell Metabolism Using Dynamic Genome-Scale Network Modeling

    Sriram Chandrasekaran

    2017-12-01

    Full Text Available Summary: Metabolism is an emerging stem cell hallmark tied to cell fate, pluripotency, and self-renewal, yet systems-level understanding of stem cell metabolism has been limited by the lack of genome-scale network models. Here, we develop a systems approach to integrate time-course metabolomics data with a computational model of metabolism to analyze the metabolic state of naive and primed murine pluripotent stem cells. Using this approach, we find that one-carbon metabolism involving phosphoglycerate dehydrogenase, folate synthesis, and nucleotide synthesis is a key pathway that differs between the two states, resulting in differential sensitivity to anti-folates. The model also predicts that the pluripotency factor Lin28 regulates this one-carbon metabolic pathway, which we validate using metabolomics data from Lin28-deficient cells. Moreover, we identify and validate metabolic reactions related to S-adenosyl-methionine production that can differentially impact histone methylation in naive and primed cells. Our network-based approach provides a framework for characterizing metabolic changes influencing pluripotency and cell fate. : Chandrasekaran et al. use computational modeling, metabolomics, and metabolic inhibitors to discover metabolic differences between various pluripotent stem cell states and infer their impact on stem cell fate decisions. Keywords: systems biology, stem cell biology, metabolism, genome-scale modeling, pluripotency, histone methylation, naive (ground state, primed state, cell fate, metabolic network

  14. Identifying the preferred subset of enzymatic profiles in nonlinear kinetic metabolic models via multiobjective global optimization and Pareto filters.

    Carlos Pozo

    Full Text Available Optimization models in metabolic engineering and systems biology focus typically on optimizing a unique criterion, usually the synthesis rate of a metabolite of interest or the rate of growth. Connectivity and non-linear regulatory effects, however, make it necessary to consider multiple objectives in order to identify useful strategies that balance out different metabolic issues. This is a fundamental aspect, as optimization of maximum yield in a given condition may involve unrealistic values in other key processes. Due to the difficulties associated with detailed non-linear models, analysis using stoichiometric descriptions and linear optimization methods have become rather popular in systems biology. However, despite being useful, these approaches fail in capturing the intrinsic nonlinear nature of the underlying metabolic systems and the regulatory signals involved. Targeting more complex biological systems requires the application of global optimization methods to non-linear representations. In this work we address the multi-objective global optimization of metabolic networks that are described by a special class of models based on the power-law formalism: the generalized mass action (GMA representation. Our goal is to develop global optimization methods capable of efficiently dealing with several biological criteria simultaneously. In order to overcome the numerical difficulties of dealing with multiple criteria in the optimization, we propose a heuristic approach based on the epsilon constraint method that reduces the computational burden of generating a set of Pareto optimal alternatives, each achieving a unique combination of objectives values. To facilitate the post-optimal analysis of these solutions and narrow down their number prior to being tested in the laboratory, we explore the use of Pareto filters that identify the preferred subset of enzymatic profiles. We demonstrate the usefulness of our approach by means of a case study

  15. Identifying the preferred subset of enzymatic profiles in nonlinear kinetic metabolic models via multiobjective global optimization and Pareto filters.

    Pozo, Carlos; Guillén-Gosálbez, Gonzalo; Sorribas, Albert; Jiménez, Laureano

    2012-01-01

    Optimization models in metabolic engineering and systems biology focus typically on optimizing a unique criterion, usually the synthesis rate of a metabolite of interest or the rate of growth. Connectivity and non-linear regulatory effects, however, make it necessary to consider multiple objectives in order to identify useful strategies that balance out different metabolic issues. This is a fundamental aspect, as optimization of maximum yield in a given condition may involve unrealistic values in other key processes. Due to the difficulties associated with detailed non-linear models, analysis using stoichiometric descriptions and linear optimization methods have become rather popular in systems biology. However, despite being useful, these approaches fail in capturing the intrinsic nonlinear nature of the underlying metabolic systems and the regulatory signals involved. Targeting more complex biological systems requires the application of global optimization methods to non-linear representations. In this work we address the multi-objective global optimization of metabolic networks that are described by a special class of models based on the power-law formalism: the generalized mass action (GMA) representation. Our goal is to develop global optimization methods capable of efficiently dealing with several biological criteria simultaneously. In order to overcome the numerical difficulties of dealing with multiple criteria in the optimization, we propose a heuristic approach based on the epsilon constraint method that reduces the computational burden of generating a set of Pareto optimal alternatives, each achieving a unique combination of objectives values. To facilitate the post-optimal analysis of these solutions and narrow down their number prior to being tested in the laboratory, we explore the use of Pareto filters that identify the preferred subset of enzymatic profiles. We demonstrate the usefulness of our approach by means of a case study that optimizes the

  16. Reconstruction of the yeast Snf1 kinase regulatory network reveals its role as a global energy regulator

    Usaite, Renata; Jewett, Michael C; Oliveira, Ana Paula; Yates, John R; Olsson, Lisbeth; Nielsen, Jens

    2009-01-01

    Highly conserved among eukaryotic cells, the AMP-activated kinase (AMPK) is a central regulator of carbon metabolism. To map the complete network of interactions around AMPK in yeast (Snf1) and to evaluate the role of its regulatory subunit Snf4, we measured global mRNA, protein and metabolite levels in wild type, Δsnf1, Δsnf4, and Δsnf1Δsnf4 knockout strains. Using four newly developed computational tools, including novel DOGMA sub-network analysis, we showed the benefits of three-level ome-data integration to uncover the global Snf1 kinase role in yeast. We for the first time identified Snf1's global regulation on gene and protein expression levels, and showed that yeast Snf1 has a far more extensive function in controlling energy metabolism than reported earlier. Additionally, we identified complementary roles of Snf1 and Snf4. Similar to the function of AMPK in humans, our findings showed that Snf1 is a low-energy checkpoint and that yeast can be used more extensively as a model system for studying the molecular mechanisms underlying the global regulation of AMPK in mammals, failure of which leads to metabolic diseases. PMID:19888214

  17. Modeling Cancer Metastasis using Global, Quantitative and Integrative Network Biology

    Schoof, Erwin; Erler, Janine

    understanding of molecular processes which are fundamental to tumorigenesis. In Article 1, we propose a novel framework for how cancer mutations can be studied by taking into account their effect at the protein network level. In Article 2, we demonstrate how global, quantitative data on phosphorylation dynamics...... can be generated using MS, and how this can be modeled using a computational framework for deciphering kinase-substrate dynamics. This framework is described in depth in Article 3, and covers the design of KinomeXplorer, which allows the prediction of kinases responsible for modulating observed...... phosphorylation dynamics in a given biological sample. In Chapter III, we move into Integrative Network Biology, where, by combining two fundamental technologies (MS & NGS), we can obtain more in-depth insights into the links between cellular phenotype and genotype. Article 4 describes the proof...

  18. Metabolic Network Topology Reveals Transcriptional Regulatory Signatures of Type 2 Diabetes

    Zelezniak, Aleksej; Pers, Tune Hannes; Pinho Soares, Simao Pedro

    2010-01-01

    mechanisms underlying these transcriptional changes and their impact on the cellular metabolic phenotype is a challenging task due to the complexity of transcriptional regulation and the highly interconnected nature of the metabolic network. In this study we integrate skeletal muscle gene expression datasets...... with human metabolic network reconstructions to identify key metabolic regulatory features of T2DM. These features include reporter metabolites—metabolites with significant collective transcriptional response in the associated enzyme-coding genes, and transcription factors with significant enrichment...... factor regulatory network connecting several parts of metabolism. The identified transcription factors include members of the CREB, NRF1 and PPAR family, among others, and represent regulatory targets for further experimental analysis. Overall, our results provide a holistic picture of key metabolic...

  19. Structure and relationships within global manufacturing virtual networks

    José Ramón Vilana

    2009-04-01

    Full Text Available Global Manufacturing Virtual Networks (GMVNs are dynamically changing organizations formed by Original Equipment Manufacturers (OEMs, Contract Manufacturers (CMs, turn-key and component suppliers, R+D centres and distributors. These networks establish a new type of vertical and horizontal relations between independent companies or even competitors where it is not needed to maintain internal manufacturing resources but to manage and share the network resources. The fluid relations that exist within the GMVNs allow them a very permeable organization easy to connect and disconnect from one to each other as well as to choose a set of partners with specific attributes. The result is a highly flexible system characterized by low barriers to entry and exit, geographic flexibility, low costs, rapid technological diffusion, high diversification through contract manufacturers and exceptional economies of scale. Anyhow, there are three major drawbacks in the GMVNs that should be considered at the beginning of this type of collaborations: 1 the risk of contract manufacturers to develop their own end-products in competition with their customers; 2 the technology transfer between competitors OEMs through other members of the GMVN and 3 the lose of process expertise by the OEMs the more they outsource manufacturing processes to the network.

  20. Coherent ambient infrasound recorded by the global IMS network

    Matoza, R. S.; Landes, M.; Le Pichon, A.; Ceranna, L.; Brown, D.

    2011-12-01

    The International Monitoring System (IMS) includes a global network of infrasound arrays, which is designed to detect atmospheric nuclear explosions anywhere on the planet. The infrasound network also has potential application in detection of natural hazards such as large volcanic explosions and severe weather. Ambient noise recorded by the network includes incoherent wind noise and coherent infrasound. We present a statistical analysis of coherent infrasound recorded by the IMS network. We have applied broadband (0.01 to 5 Hz) array processing systematically to the multi-year IMS historical dataset (2005-present) using an implementation of the Progressive Multi-Channel Correlation (PMCC) algorithm in log-frequency space. We show that IMS arrays consistently record coherent ambient infrasound across the broad frequency range from 0.01 to 5 Hz when wind-noise levels permit. Multi-year averaging of PMCC detection bulletins emphasizes continuous signals such as oceanic microbaroms, as well as persistent transient signals such as repetitive volcanic, surf, or anthropogenic activity (e.g., mining or industrial activity). While many of these continuous or repetitive signals are of interest in their own right, they may dominate IMS array detection bulletins and obscure or complicate detection of specific signals of interest. The new PMCC detection bulletins have numerous further applications, including in volcano and microbarom studies, and in IMS data quality assessment.

  1. Transformations of rural production landscapes in the global network society

    Swaffield, Simon; Primdahl, Jørgen

    2010-01-01

    The concept of the global network society provides a basis for examination of current trends and policy issues in rural landscape change across a range of developed countries. Drivers of change include the demand for food and fibre to support the growing urban populations in developing conutries......, the rationalization and centralisation of supply chains under the open market angenda, and the global integration of information and control systems. These dynamics frequently conflict with place specific socio-cultural values and environmental integrity. The regional and local institutions through which...... these dynamics are managed often express conflicting aims and means, despite clearly stated intentions of 'policy integration'. Comparative analysis has highlighted the way production landscapes continue to intensify, and clear indications are found that these landscapes are converging in character under...

  2. International earth science information network for global change decision making

    Autrey-Hunley, C.; Kuhn, W.R.; Kasischke, E.; Trichel, M.T.; Coppola, R.

    1991-01-01

    Effective environmental decision making depends upon the ability to predict physical changes in the environment, societal responses to these changes, and how both the physical changes and societal responses will be affected by changes in government regulations, public perceptions and the environment. Technological advances in remote sensing have provided a wealth of earth science data necessary to study global change problems; the Earth Observatory System will provide an unprecedented data source in the late 1990's. The Consortium for an International Earth Science Information Network (CIESIN) will combine earth science data (both satellite and ground-based) with data on the social sciences (e.g., economics, demographics, public health) to support informed policy decisions and to transfer knowledge on global change and its causes to the public.

  3. Virtual Global Accelerator Network (VGAN)(LCC-0083)

    Larsen, R

    2003-01-01

    The concept of a Global Accelerator Network (GAN) has been proposed by key members of ICFA as a cornerstone of a future International Linear Collider (LC). GAN would provide a tool for the participants of an international collaboration to participate in the actual running of the machine from different parts of the world. Some technical experts view the concept as technologically trivial, and instead point out the significant sociological, organizational and administrative problems that must be surmounted in creating a truly workable system. This note proposes that many real issues can be explored by building a simulator (VGAN) consisting of a virtual accelerator model, a global controls model, and a functioning human organizational model, a tool that would explore and resolve many real problems of GAN and the LC enterprise during the LC preliminary design and testing phase

  4. Discriminating response groups in metabolic and regulatory pathway networks.

    Van Hemert, John L; Dickerson, Julie A

    2012-04-01

    Analysis of omics experiments generates lists of entities (genes, metabolites, etc.) selected based on specific behavior, such as changes in response to stress or other signals. Functional interpretation of these lists often uses category enrichment tests using functional annotations like Gene Ontology terms and pathway membership. This approach does not consider the connected structure of biochemical pathways or the causal directionality of events. The Omics Response Group (ORG) method, described in this work, interprets omics lists in the context of metabolic pathway and regulatory networks using a statistical model for flow within the networks. Statistical results for all response groups are visualized in a novel Pathway Flow plot. The statistical tests are based on the Erlang distribution model under the assumption of independent and identically Exponential-distributed random walk flows through pathways. As a proof of concept, we applied our method to an Escherichia coli transcriptomics dataset where we confirmed common knowledge of the E.coli transcriptional response to Lipid A deprivation. The main response is related to osmotic stress, and we were also able to detect novel responses that are supported by the literature. We also applied our method to an Arabidopsis thaliana expression dataset from an abscisic acid study. In both cases, conventional pathway enrichment tests detected nothing, while our approach discovered biological processes beyond the original studies. We created a prototype for an interactive ORG web tool at http://ecoserver.vrac.iastate.edu/pathwayflow (source code is available from https://subversion.vrac.iastate.edu/Subversion/jlv/public/jlv/pathwayflow). The prototype is described along with additional figures and tables in Supplementary Material. julied@iastate.edu Supplementary data are available at Bioinformatics online.

  5. Estimation of the number of extreme pathways for metabolic networks

    Thiele Ines

    2007-09-01

    Full Text Available Abstract Background The set of extreme pathways (ExPa, {pi}, defines the convex basis vectors used for the mathematical characterization of the null space of the stoichiometric matrix for biochemical reaction networks. ExPa analysis has been used for a number of studies to determine properties of metabolic networks as well as to obtain insight into their physiological and functional states in silico. However, the number of ExPas, p = |{pi}|, grows with the size and complexity of the network being studied, and this poses a computational challenge. For this study, we investigated the relationship between the number of extreme pathways and simple network properties. Results We established an estimating function for the number of ExPas using these easily obtainable network measurements. In particular, it was found that log [p] had an exponential relationship with log⁡[∑i=1Rd−id+ici] MathType@MTEF@5@5@+=feaafiart1ev1aaatCvAUfKttLearuWrP9MDH5MBPbIqV92AaeXatLxBI9gBaebbnrfifHhDYfgasaacH8akY=wiFfYdH8Gipec8Eeeu0xXdbba9frFj0=OqFfea0dXdd9vqai=hGuQ8kuc9pgc9s8qqaq=dirpe0xb9q8qiLsFr0=vr0=vr0dc8meaabaqaciaacaGaaeqabaqabeGadaaakeaacyGGSbaBcqGGVbWBcqGGNbWzdaWadaqaamaaqadabaGaemizaq2aaSbaaSqaaiabgkHiTmaaBaaameaacqWGPbqAaeqaaaWcbeaakiabdsgaKnaaBaaaleaacqGHRaWkdaWgaaadbaGaemyAaKgabeaaaSqabaGccqWGJbWydaWgaaWcbaGaemyAaKgabeaaaeaacqWGPbqAcqGH9aqpcqaIXaqmaeaacqWGsbGua0GaeyyeIuoaaOGaay5waiaaw2faaaaa@4414@, where R = |Reff| is the number of active reactions in a network, d−i MathType@MTEF@5@5@+=feaafiart1ev1aaatCvAUfKttLearuWrP9MDH5MBPbIqV92AaeXatLxBI9gBaebbnrfifHhDYfgasaacH8akY=wiFfYdH8Gipec8Eeeu0xXdbba9frFj0=OqFfea0dXdd9vqai=hGuQ8kuc9pgc9s8qqaq=dirpe0xb9q8qiLsFr0=vr0=vr0dc8meaabaqaciaacaGaaeqabaqabeGadaaakeaacqWGKbazdaWgaaWcbaGaeyOeI0YaaSbaaWqaaiabdMgaPbqabaaaleqaaaaa@30A9@ and d+i MathType@MTEF@5@5@+=feaafiart1ev1aaatCvAUfKttLearuWrP9MDH5MBPbIqV92AaeXatLxBI9gBaebbnrfifHhDYfgasaacH8akY=wiFfYdH8Gipec8Eeeu0xXdbba9frFj0=OqFfea0dXdd9vqai=hGuQ8kuc9pgc9s8qqaq=dirpe0xb

  6. European network infrastructures of observatories for terrestrial Global Change research

    Vereecken, H.; Bogena, H.; Lehning, M.

    2009-04-01

    The earth's climate is significantly changing (e.g. IPCC, 2007) and thus directly affecting the terrestrial systems. The number and intensity hydrological extremes, such as floods and droughts, are continually increasing, resulting in major economical and social impacts. Furthermore, the land cover in Europe has been modified fundamentally by conversions for agriculture, forest and for other purposes such as industrialisation and urbanisation. Additionally, water resources are more than ever used for human development, especially as a key resource for agricultural and industrial activities. As a special case, the mountains of the world are of significant importance in terms of water resources supply, biodiversity, economy, agriculture, traffic and recreation but particularly vulnerable to environmental change. The Alps are unique because of the pronounced small scale variability they contain, the high population density they support and their central position in Europe. The Alps build a single coherent physical and natural environment, artificially cut by national borders. The scientific community and governmental bodies have responded to these environmental changes by performing dedicated experiments and by establishing environmental research networks to monitor, analyse and predict the impact of Global Change on different terrestrial systems of the Earths' environment. Several European network infrastructures for terrestrial Global Change research are presently immerging or upgrading, such as ICOS, ANAEE, LifeWatch or LTER-Europe. However, the strongest existing networks are still operating on a regional or national level and the historical growth of such networks resulted in a very heterogeneous landscape of observation networks. We propose therefore the establishment of two complementary networks: The NetwOrk of Hydrological observAtories, NOHA. NOHA aims to promote the sustainable management of water resources in Europe, to support the prediction of

  7. Efficient protein production by yeast requires global tuning of metabolism

    Huang, Mingtao; Bao, Jichen; Hallstrom, Bjorn M.

    2017-01-01

    The biotech industry relies on cell factories for production of pharmaceutical proteins, of which several are among the top-selling medicines. There is, therefore, considerable interest in improving the efficiency of protein production by cell factories. Protein secretion involves numerous...... intracellular processes with many underlying mechanisms still remaining unclear. Here, we use RNA-seq to study the genome-wide transcriptional response to protein secretion in mutant yeast strains. We find that many cellular processes have to be attuned to support efficient protein secretion. In particular...... that by tuning metabolism cells are able to efficiently secrete recombinant proteins. Our findings provide increased understanding of which cellular regulations and pathways are associated with efficient protein secretion....

  8. Computational solution to automatically map metabolite libraries in the context of genome scale metabolic networks

    Benjamin eMerlet

    2016-02-01

    Full Text Available This article describes a generic programmatic method for mapping chemical compound libraries on organism-specific metabolic networks from various databases (KEGG, BioCyc and flat file formats (SBML and Matlab files. We show how this pipeline was successfully applied to decipher the coverage of chemical libraries set up by two metabolomics facilities MetaboHub (French National infrastructure for metabolomics and fluxomics and Glasgow Polyomics on the metabolic networks available in the MetExplore web server. The present generic protocol is designed to formalize and reduce the volume of information transfer between the library and the network database. Matching of metabolites between libraries and metabolic networks is based on InChIs or InChIKeys and therefore requires that these identifiers are specified in both libraries and networks.In addition to providing covering statistics, this pipeline also allows the visualization of mapping results in the context of metabolic networks.In order to achieve this goal we tackled issues on programmatic interaction between two servers, improvement of metabolite annotation in metabolic networks and automatic loading of a mapping in genome scale metabolic network analysis tool MetExplore. It is important to note that this mapping can also be performed on a single or a selection of organisms of interest and is thus not limited to large facilities.

  9. Co-regulation of metabolic genes is better explained by flux coupling than by network distance.

    Richard A Notebaart

    2008-01-01

    Full Text Available To what extent can modes of gene regulation be explained by systems-level properties of metabolic networks? Prior studies on co-regulation of metabolic genes have mainly focused on graph-theoretical features of metabolic networks and demonstrated a decreasing level of co-expression with increasing network distance, a naïve, but widely used, topological index. Others have suggested that static graph representations can poorly capture dynamic functional associations, e.g., in the form of dependence of metabolic fluxes across genes in the network. Here, we systematically tested the relative importance of metabolic flux coupling and network position on gene co-regulation, using a genome-scale metabolic model of Escherichia coli. After validating the computational method with empirical data on flux correlations, we confirm that genes coupled by their enzymatic fluxes not only show similar expression patterns, but also share transcriptional regulators and frequently reside in the same operon. In contrast, we demonstrate that network distance per se has relatively minor influence on gene co-regulation. Moreover, the type of flux coupling can explain refined properties of the regulatory network that are ignored by simple graph-theoretical indices. Our results underline the importance of studying functional states of cellular networks to define physiologically relevant associations between genes and should stimulate future developments of novel functional genomic tools.

  10. A Computational Solution to Automatically Map Metabolite Libraries in the Context of Genome Scale Metabolic Networks.

    Merlet, Benjamin; Paulhe, Nils; Vinson, Florence; Frainay, Clément; Chazalviel, Maxime; Poupin, Nathalie; Gloaguen, Yoann; Giacomoni, Franck; Jourdan, Fabien

    2016-01-01

    This article describes a generic programmatic method for mapping chemical compound libraries on organism-specific metabolic networks from various databases (KEGG, BioCyc) and flat file formats (SBML and Matlab files). We show how this pipeline was successfully applied to decipher the coverage of chemical libraries set up by two metabolomics facilities MetaboHub (French National infrastructure for metabolomics and fluxomics) and Glasgow Polyomics (GP) on the metabolic networks available in the MetExplore web server. The present generic protocol is designed to formalize and reduce the volume of information transfer between the library and the network database. Matching of metabolites between libraries and metabolic networks is based on InChIs or InChIKeys and therefore requires that these identifiers are specified in both libraries and networks. In addition to providing covering statistics, this pipeline also allows the visualization of mapping results in the context of metabolic networks. In order to achieve this goal, we tackled issues on programmatic interaction between two servers, improvement of metabolite annotation in metabolic networks and automatic loading of a mapping in genome scale metabolic network analysis tool MetExplore. It is important to note that this mapping can also be performed on a single or a selection of organisms of interest and is thus not limited to large facilities.

  11. International Children's Palliative Care Network: A Global Action Network for Children With Life-Limiting Conditions.

    Marston, Joan; Boucher, Sue; Downing, Julia

    2018-02-01

    The International Children's Palliative Care Network (ICPCN) is a global network of individuals and organizations working together to reach the estimated 21 million children with life-limiting conditions and life-threatening illnesses. The drive to establish the ICPCN was born from the recognition of the gaps in service provision for children's palliative care and the need to collaborate, network, and share resources. Established in 2005 during a meeting in Seoul, South Korea, the ICPCN has developed over the years into an established network with a global membership. The history of the organization is described, including some of the key events since its inception. Working in collaboration with others, ICPCN has five key focus areas: Communication; Advocacy; Research; Education; and Strategic development, and is the only international charity working globally for the rights of children with palliative care needs. Activities in these areas are discussed, along with the inter-connection between the five areas. Without the ICPCN, palliative care for children would not have developed as far as it has over the years and the organization is committed to ongoing work in this area until all children requiring palliative care have access to quality services, wherever they live around the world. Copyright © 2017 American Academy of Hospice and Palliative Medicine. Published by Elsevier Inc. All rights reserved.

  12. Ensuring dynamic strategic fit of firms that compete globally in alliances and networks: proposing the Global SNA - Strategic Network Analysis - framework

    T. Diana L. Van Aduard de Macedo-Soares

    2011-02-01

    Full Text Available In order to sustain their competitive advantage in the current increasingly globalized and turbulent context, more and more firms are competing globally in alliances and networks that oblige them to adopt new managerial paradigms and tools. However, their strategic analyses rarely take into account the strategic implications of these alliances and networks, considering their global relational characteristics, admittedly because of a lack of adequate tools to do so. This paper contributes to research that seeks to fill this gap by proposing the Global Strategic Network Analysis - SNA - framework. Its purpose is to help firms that compete globally in alliances and networks to carry out their strategic assessments and decision-making with a view to ensuring dynamic strategic fit from both a global and relational perspective.

  13. European network for research in global change (ENRICH)

    Ghazi, A [European Commission, Bruxelles (Belgium). DG XII/JRC

    1996-12-31

    While approaching the beginning of the twenty first century, the scientific community is faced with the formidable tasks of monitoring and detecting, understanding and predicting changes in the Earth System and its interactions with human beings. A crucial challenge is to make scientific research results accessible and usable for those involved in the decision making process related to the concept of Sustainable Development. Major international scientific programmes under the umbrella of ICSU, such as the IGBP and WCRP, are dealing with these issues. Although there exist many well developed global change research programmes in several European countries and effective collaboration networks between research institutes, there is an urgent need for overall communication with a view to promoting wider international links ensuring complementarity, synergy and coherence. Recognizing the importance of promoting coherence in research and utilising research results for various European Union (EU) policies, the European Commissioner responsible for Science, Research and Development wrote in March 1992 to all the EU Research Ministers to propose an initiative in this domain. In a rapid response, a group of Senior Experts from the EU Member States was set up in April 1992. This Group established a Task Force to develop the concept of the European Network for Research In Global CHange (ENRICH) which was approved in July 1993

  14. Global information network on chemicals (GINC) and its Asian component

    Kaminuma, Tsuguchika; Nakata, Kotoko

    2003-01-01

    The Global Information Network on Chemicals (GINC) is an effort to build a global information network that links international, national, and other organizations working for the safe management of chemicals in order to exchange information and improve communications. The project was originally proposed in 1993 by one of the authors then at the National Institute of Health Sciences (NIHS) of Japan to the International Program on Chemical Safety (IPCS), which is a joint project of World Health Organization (WHO), International Labor Organization (ILO), and United Nations Environment Program (UNEP). The base support system was first implemented at NIHS using the Internet/World Wide Web (WWW) technology in 1995. The project was then endorsed by the Intergovernmental Forum on Chemical Safety (IFCS) and was adopted by the Inter-Organization Program for the Sound Management of Chemicals (IOMC). However, the base system (http://www.nihs.go.jp/GINC/index.html) has been developed and maintained solely by the NIHS group under the support of the Ministry of Health and Welfare (MHW), Japan. Asia, particularly East Asia and the Pacific region, was chosen as the feasibility study region for this project. During the period from December 1994 to July 2002, NIHS hosted eight meetings on this project held in Tokyo

  15. Re-Engineering Alzheimer Clinical Trials: Global Alzheimer's Platform Network.

    Cummings, J; Aisen, P; Barton, R; Bork, J; Doody, R; Dwyer, J; Egan, J C; Feldman, H; Lappin, D; Truyen, L; Salloway, S; Sperling, R; Vradenburg, G

    2016-06-01

    Alzheimer's disease (AD) drug development is costly, time-consuming, and inefficient. Trial site functions, trial design, and patient recruitment for trials all require improvement. The Global Alzheimer Platform (GAP) was initiated in response to these challenges. Four GAP work streams evolved in the US to address different trial challenges: 1) registry-to-cohort web-based recruitment; 2) clinical trial site activation and site network construction (GAP-NET); 3) adaptive proof-of-concept clinical trial design; and 4) finance and fund raising. GAP-NET proposes to establish a standardized network of continuously funded trial sites that are highly qualified to perform trials (with established clinical, biomarker, imaging capability; certified raters; sophisticated management system. GAP-NET will conduct trials for academic and biopharma industry partners using standardized instrument versions and administration. Collaboration with the Innovative Medicines Initiative (IMI) European Prevention of Alzheimer's Disease (EPAD) program, the Canadian Consortium on Neurodegeneration in Aging (CCNA) and other similar international initiatives will allow conduct of global trials. GAP-NET aims to increase trial efficiency and quality, decrease trial redundancy, accelerate cohort development and trial recruitment, and decrease trial costs. The value proposition for sites includes stable funding and uniform training and trial execution; the value to trial sponsors is decreased trial costs, reduced time to execute trials, and enhanced data quality. The value for patients and society is the more rapid availability of new treatments for AD.

  16. European network for research in global change (ENRICH)

    Ghazi, A. [European Commission, Bruxelles (Belgium). DG XII/JRC

    1995-12-31

    While approaching the beginning of the twenty first century, the scientific community is faced with the formidable tasks of monitoring and detecting, understanding and predicting changes in the Earth System and its interactions with human beings. A crucial challenge is to make scientific research results accessible and usable for those involved in the decision making process related to the concept of Sustainable Development. Major international scientific programmes under the umbrella of ICSU, such as the IGBP and WCRP, are dealing with these issues. Although there exist many well developed global change research programmes in several European countries and effective collaboration networks between research institutes, there is an urgent need for overall communication with a view to promoting wider international links ensuring complementarity, synergy and coherence. Recognizing the importance of promoting coherence in research and utilising research results for various European Union (EU) policies, the European Commissioner responsible for Science, Research and Development wrote in March 1992 to all the EU Research Ministers to propose an initiative in this domain. In a rapid response, a group of Senior Experts from the EU Member States was set up in April 1992. This Group established a Task Force to develop the concept of the European Network for Research In Global CHange (ENRICH) which was approved in July 1993

  17. The Worldviews Network: Transformative Global Change Education in Immersive Environments

    Hamilton, H.; Yu, K. C.; Gardiner, N.; McConville, D.; Connolly, R.; "Irving, Lindsay", L. S.

    2011-12-01

    own research to develop a library of immersive visualization stories and templates that explore ecological relationships across time at cosmic, global, and bioregional scales, with learning goals aligned to climate and earth science literacy principles. These experiential narratives are used to increase participants' awareness of global change issues as well as to engage them in dialogues and design processes focused on steps they can take within their own communities to systemically address these interconnected challenges. More than 600 digital planetariums in the U.S. collectively represent a pioneering opportunity for distributing Earth systems messages over large geographic areas. By placing the viewer-and Earth itself-within the context of the rest of the universe, digital planetariums can uniquely provide essential transcalar perspectives on the complex interdependencies of Earth's interacting physical and biological systems. The Worldviews Network is creating innovative, data-driven approaches for engaging the American public in dialogues about human-induced global changes.

  18. Limited Influence of Oxygen on the Evolution of Chemical Diversity in Metabolic Networks

    Kazuhiro Takemoto

    2013-10-01

    Full Text Available Oxygen is thought to promote species and biomolecule diversity. Previous studies have suggested that oxygen expands metabolic networks by acquiring metabolites with different chemical properties (higher hydrophobicity, for example. However, such conclusions are typically based on biased evaluation, and are therefore non-conclusive. Thus, we re-investigated the effect of oxygen on metabolic evolution using a phylogenetic comparative method and metadata analysis to reduce the bias as much as possible. Notably, we found no difference in metabolic network expansion between aerobes and anaerobes when evaluating phylogenetic relationships. Furthermore, we showed that previous studies have overestimated or underestimated the degrees of differences in the chemical properties (e.g., hydrophobicity between oxic and anoxic metabolites in metabolic networks of unicellular organisms; however, such overestimation was not observed when considering the metabolic networks of multicellular organisms. These findings indicate that the contribution of oxygen to increased chemical diversity in metabolic networks is lower than previously thought; rather, phylogenetic signals and cell-cell communication result in increased chemical diversity. However, this conclusion does not contradict the effect of oxygen on metabolic evolution; instead, it provides a deeper understanding of how oxygen contributes to metabolic evolution despite several limitations in data analysis methods.

  19. Metabolic Network Discovery by Top-Down and Bottom-Up Approaches and Paths for Reconciliation

    Çakır, Tunahan, E-mail: tcakir@gyte.edu.tr [Computational Systems Biology Group, Department of Bioengineering, Gebze Technical University (formerly known as Gebze Institute of Technology), Gebze (Turkey); Khatibipour, Mohammad Jafar [Computational Systems Biology Group, Department of Bioengineering, Gebze Technical University (formerly known as Gebze Institute of Technology), Gebze (Turkey); Department of Chemical Engineering, Gebze Technical University (formerly known as Gebze Institute of Technology), Gebze (Turkey)

    2014-12-03

    The primary focus in the network-centric analysis of cellular metabolism by systems biology approaches is to identify the active metabolic network for the condition of interest. Two major approaches are available for the discovery of the condition-specific metabolic networks. One approach starts from genome-scale metabolic networks, which cover all possible reactions known to occur in the related organism in a condition-independent manner, and applies methods such as the optimization-based Flux-Balance Analysis to elucidate the active network. The other approach starts from the condition-specific metabolome data, and processes the data with statistical or optimization-based methods to extract information content of the data such that the active network is inferred. These approaches, termed bottom-up and top-down, respectively, are currently employed independently. However, considering that both approaches have the same goal, they can both benefit from each other paving the way for the novel integrative analysis methods of metabolome data- and flux-analysis approaches in the post-genomic era. This study reviews the strengths of constraint-based analysis and network inference methods reported in the metabolic systems biology field; then elaborates on the potential paths to reconcile the two approaches to shed better light on how the metabolism functions.

  20. Metabolic Network Discovery by Top-Down and Bottom-Up Approaches and Paths for Reconciliation

    Çakır, Tunahan; Khatibipour, Mohammad Jafar

    2014-01-01

    The primary focus in the network-centric analysis of cellular metabolism by systems biology approaches is to identify the active metabolic network for the condition of interest. Two major approaches are available for the discovery of the condition-specific metabolic networks. One approach starts from genome-scale metabolic networks, which cover all possible reactions known to occur in the related organism in a condition-independent manner, and applies methods such as the optimization-based Flux-Balance Analysis to elucidate the active network. The other approach starts from the condition-specific metabolome data, and processes the data with statistical or optimization-based methods to extract information content of the data such that the active network is inferred. These approaches, termed bottom-up and top-down, respectively, are currently employed independently. However, considering that both approaches have the same goal, they can both benefit from each other paving the way for the novel integrative analysis methods of metabolome data- and flux-analysis approaches in the post-genomic era. This study reviews the strengths of constraint-based analysis and network inference methods reported in the metabolic systems biology field; then elaborates on the potential paths to reconcile the two approaches to shed better light on how the metabolism functions.

  1. Global Prioritization of Disease Candidate Metabolites Based on a Multi-omics Composite Network

    Yao, Qianlan; Xu, Yanjun; Yang, Haixiu; Shang, Desi; Zhang, Chunlong; Zhang, Yunpeng; Sun, Zeguo; Shi, Xinrui; Feng, Li; Han, Junwei; Su, Fei; Li, Chunquan; Li, Xia

    2015-01-01

    The identification of disease-related metabolites is important for a better understanding of metabolite pathological processes in order to improve human medicine. Metabolites, which are the terminal products of cellular regulatory process, can be affected by multi-omic processes. In this work, we propose a powerful method, MetPriCNet, to predict and prioritize disease candidate metabolites based on integrated multi-omics information. MetPriCNet prioritized candidate metabolites based on their global distance similarity with seed nodes in a composite network, which integrated multi-omics information from the genome, phenome, metabolome and interactome. After performing cross-validation on 87 phenotypes with a total of 602 metabolites, MetPriCNet achieved a high AUC value of up to 0.918. We also assessed the performance of MetPriCNet on 18 disease classes and found that 4 disease classes achieved an AUC value over 0.95. Notably, MetPriCNet can also predict disease metabolites without known disease metabolite knowledge. Some new high-risk metabolites of breast cancer were predicted, although there is a lack of known disease metabolite information. A predicted disease metabolic landscape was constructed and analyzed based on the results of MetPriCNet for 87 phenotypes to help us understand the genetic and metabolic mechanism of disease from a global view. PMID:26598063

  2. An integrated artificial neural networks approach for predicting global radiation

    Azadeh, A.; Maghsoudi, A.; Sohrabkhani, S.

    2009-01-01

    This article presents an integrated artificial neural network (ANN) approach for predicting solar global radiation by climatological variables. The integrated ANN trains and tests data with multi layer perceptron (MLP) approach which has the lowest mean absolute percentage error (MAPE). The proposed approach is particularly useful for locations where no available measurement equipment. Also, it considers all related climatological and meteorological parameters as input variables. To show the applicability and superiority of the integrated ANN approach, monthly data were collected for 6 years (1995-2000) in six nominal cities in Iran. Separate model for each city is considered and the quantity of solar global radiation in each city is calculated. Furthermore an integrated ANN model has been introduced for prediction of solar global radiation. The acquired results of the integrated model have shown high accuracy of about 94%. The results of the integrated model have been compared with traditional angstrom's model to show its considerable accuracy. Therefore, the proposed approach can be used as an efficient tool for prediction of solar radiation in the remote and rural locations with no direct measurement equipment.

  3. FLUXNET: A Global Network of Eddy-Covariance Flux Towers

    Cook, R. B.; Holladay, S. K.; Margle, S. M.; Olsen, L. M.; Gu, L.; Heinsch, F.; Baldocchi, D.

    2003-12-01

    The FLUXNET global network was established to aid in understanding the mechanisms controlling the exchanges of carbon dioxide, water vapor, and energy across a variety of terrestrial ecosystems. Flux tower data are also being used to validate ecosystem model outputs and to provide information for validating remote sensing based products, including surface temperature, reflectance, albedo, vegetation indices, leaf area index, photosynthetically active radiation, and photosynthesis derived from MODIS sensors on the Terra and Aqua satellites. The global FLUXNET database provides consistent and complete flux data to support global carbon cycle science. Currently FLUXNET consists of over 210 sites, with most flux towers operating continuously for 4 years or longer. Gap-filled data are available for 53 sites. The FLUXNET database contains carbon, water vapor, sensible heat, momentum, and radiation flux measurements with associated ancillary and value-added data products. Towers are located in temperate conifer and broadleaf forests, tropical and boreal forests, crops, grasslands, chaparral, wetlands, and tundra on five continents. Selected MODIS Land products in the immediate vicinity of the flux tower are subsetted and posted on the FLUXNET Web site for 169 flux-towers. The MODIS subsets are prepared in ASCII format for 8-day periods for an area 7 x 7 km around the tower.

  4. In Search of a Network Organization for Innovation: A Multilevel Analysis on Transnational Corporations' Global Innovation

    Hu, Yimei

    2013-01-01

    4 explores how transnational corporations perceive and design an internal network organization to facilitate global innovation. Based on a multiple case study of three Danish transnational corporations’ global R&D organization, this paper shows three types of network organization design...... explores how an SME develops a network organization consisting of both interfirm innovation networks and an internal network organization to facilitate its global innovation strategy. Regarding the intraorganizational network organization, market mechanism is adopted to optimize internal resource...... corporations perceive/design a network organization to facilitate their global innovation? • To what extent and how can we manage a network organization? Research focus of the dissertation is on transnational corporations’ network organization for innovation. The first research question aims to clarify...

  5. Solidarity Action in Global Labor Networks. Four Cases of Workplace Organizing at Foreign Affiliates in the Global South

    Peter Wad

    2014-03-01

    Full Text Available Globalization transforms workforces of transnational corporation from predominantly home countrydominated workforces into foreign-dominated, multinational workforces. Thus, the national grounding of trade unions as the key form of labor organizing is challenged by new multinational compositions and cross-border relocations of corporate employment affecting working conditions of employees and trade unions in local places. We assume that economic globalization is characterized by expanding global corporate network of vertically and horizontally integrated (equity-based and disintegrated (nonequity-based value chains. We also assume that globalization can both impede and enable labor empowerment. Based on these premises the key question is, how can labor leverage effective power against management in global corporate networks? This question is split into two subquestions: a How can labor theoretically reorganize from national unions and industrial relations institutions into global labor networks that allow prolabor improvement in global workplaces? b How and why has labor in a globalized economy secured the core International Labor Organization (ILO international labor right to organize companies and conduct collective bargaining? The Global Labor Network perspective is adopted as an analytical framework. Empirically, a comparative case methodology is applied comprising four more or less successful industrial disputes where labor achieved the right to organize and undertake collective bargaining. The disputes took place in affiliated factories of foreign transnational corporations located in Malaysia, the Philippines, Sri Lanka, and Turkey. The conclusion is that the combination of global labor capabilities and global labor strategizing must generate strategic labor power that adequately matches the weaknesses of the counterpart’s global corporate network in order to achieve prolabor outcomes. The most efficient solidarity action was leveraged

  6. Gap-filling analysis of the iJO1366 Escherichia coli metabolic network reconstruction for discovery of metabolic functions

    Orth Jeffrey D

    2012-05-01

    Full Text Available Abstract Background The iJO1366 reconstruction of the metabolic network of Escherichia coli is one of the most complete and accurate metabolic reconstructions available for any organism. Still, because our knowledge of even well-studied model organisms such as this one is incomplete, this network reconstruction contains gaps and possible errors. There are a total of 208 blocked metabolites in iJO1366, representing gaps in the network. Results A new model improvement workflow was developed to compare model based phenotypic predictions to experimental data to fill gaps and correct errors. A Keio Collection based dataset of E. coli gene essentiality was obtained from literature data and compared to model predictions. The SMILEY algorithm was then used to predict the most likely missing reactions in the reconstructed network, adding reactions from a KEGG based universal set of metabolic reactions. The feasibility of these putative reactions was determined by comparing updated versions of the model to the experimental dataset, and genes were predicted for the most feasible reactions. Conclusions Numerous improvements to the iJO1366 metabolic reconstruction were suggested by these analyses. Experiments were performed to verify several computational predictions, including a new mechanism for growth on myo-inositol. The other predictions made in this study should be experimentally verifiable by similar means. Validating all of the predictions made here represents a substantial but important undertaking.

  7. Impact of stoichiometry representation on simulation of genotype-phenotype relationships in metabolic networks

    Brochado, Ana Rita; Andrejev, Sergej; Maranas, Costas D.

    2012-01-01

    the formulation of the desired objective functions, by casting objective functions using metabolite turnovers rather than fluxes. By simulating perturbed metabolic networks, we demonstrate that the use of stoichiometry representation independent algorithms is fundamental for unambiguously linking modeling results...

  8. A global evolutionary and metabolic analysis of human obesity gene risk variants.

    Castillo, Joseph J; Hazlett, Zachary S; Orlando, Robert A; Garver, William S

    2017-09-05

    It is generally accepted that the selection of gene variants during human evolution optimized energy metabolism that now interacts with our obesogenic environment to increase the prevalence of obesity. The purpose of this study was to perform a global evolutionary and metabolic analysis of human obesity gene risk variants (110 human obesity genes with 127 nearest gene risk variants) identified using genome-wide association studies (GWAS) to enhance our knowledge of early and late genotypes. As a result of determining the mean frequency of these obesity gene risk variants in 13 available populations from around the world our results provide evidence for the early selection of ancestral risk variants (defined as selection before migration from Africa) and late selection of derived risk variants (defined as selection after migration from Africa). Our results also provide novel information for association of these obesity genes or encoded proteins with diverse metabolic pathways and other human diseases. The overall results indicate a significant differential evolutionary pattern for the selection of obesity gene ancestral and derived risk variants proposed to optimize energy metabolism in varying global environments and complex association with metabolic pathways and other human diseases. These results are consistent with obesity genes that encode proteins possessing a fundamental role in maintaining energy metabolism and survival during the course of human evolution. Copyright © 2017. Published by Elsevier B.V.

  9. Indications of marine bioinvasion from network theory. An analysis of the global cargo ship network

    Kölzsch, A.; Blasius, B.

    2011-12-01

    The transport of huge amounts of small aquatic organisms in the ballast tanks and at the hull of large cargo ships leads to ever increasing rates of marine bioinvasion. In this study, we apply a network theoretic approach to examine the introduction of invasive species into new ports by global shipping. This is the first stage of the invasion process where it is still possible to intervene with regulating measures. We compile a selection of widely used and newly developed network properties and apply these to analyse the structure and spread characteristics of the directed and weighted global cargo ship network (GCSN). Our results reveal that the GCSN is highly efficient, shows small world characteristics and is positive assortative, indicating that quick spread of invasive organisms between ports is likely. The GCSN shows strong community structure and contains two large communities, the Atlantic and Pacific trading groups. Ports that appear as connector hubs and are of high centralities are the Suez and Panama Canal, Singapore and Shanghai. Furthermore, from robustness analyses and the network's percolation behaviour, we evaluate differences of onboard and in-port ballast water treatment, set them into context with previous studies and advise bioinvasion management strategies.

  10. EGFR Signal-Network Reconstruction Demonstrates Metabolic Crosstalk in EMT

    Choudhary, Kumari Sonal; Rohatgi, Neha; Halldorsson, Skarphedinn; Briem, Eirikur; Gudjonsson, Thorarinn; Gudmundsson, Steinn; Rolfsson, Ottar

    2016-01-01

    Epithelial to mesenchymal transition (EMT) is an important event during development and cancer metastasis. There is limited understanding of the metabolic alterations that give rise to and take place during EMT. Dysregulation of signalling pathways that impact metabolism, including epidermal growth factor receptor (EGFR), are however a hallmark of EMT and metastasis. In this study, we report the investigation into EGFR signalling and metabolic crosstalk of EMT through constraint-based modelli...

  11. Improving the description of metabolic networks: the TCA cycle as example

    Stobbe, Miranda D.; Houten, Sander M.; van Kampen, Antoine H. C.; Wanders, Ronald J. A.; Moerland, Perry D.

    2012-01-01

    To collect the ever-increasing yet scattered knowledge on metabolism, multiple pathway databases like the Kyoto Encyclopedia of Genes and Genomes have been created. A complete and accurate description of the metabolic network for human and other organisms is essential to foster new biological

  12. A Status Report on the Global Research in Microbial Metabolic Engineering

    Joe, Min Ho; Lim, Sang Yong; Kim, Dong Ho

    2008-09-15

    Biotechnology industry is now a global 'Mega-Trend' and metabolic engineering technology has important role is this area. Therefore, many countries has made efforts in this field to produce top value added bio-products efficiently using microorganisms. It has been applied to increase the production of chemicals that are already produced by the host organism, to produce desired chemical substances from less expensive feedstock, and to generate products that are new to the host organism. Recent experimental advances, the so-called '-omics' technologies, mainly functional genomics, proteomics and metabolomics, have enabled wholesale generation of new genomic, transcriptomic, proteomic, and metabolomic data. This report provides the insights of the integrated view of metabolism generated by metabolic engineering for biotechnological applications of microbial metabolic engineering.

  13. A Status Report on the Global Research in Microbial Metabolic Engineering

    Joe, Min Ho; Lim, Sang Yong; Kim, Dong Ho

    2008-09-01

    Biotechnology industry is now a global 'Mega-Trend' and metabolic engineering technology has important role is this area. Therefore, many countries has made efforts in this field to produce top value added bio-products efficiently using microorganisms. It has been applied to increase the production of chemicals that are already produced by the host organism, to produce desired chemical substances from less expensive feedstock, and to generate products that are new to the host organism. Recent experimental advances, the so-called '-omics' technologies, mainly functional genomics, proteomics and metabolomics, have enabled wholesale generation of new genomic, transcriptomic, proteomic, and metabolomic data. This report provides the insights of the integrated view of metabolism generated by metabolic engineering for biotechnological applications of microbial metabolic engineering

  14. A Status Report on the Global Research in Microbial Metabolic Engineering

    Joe, Min Ho; Lim, Sang Yong; Kim, Dong Ho

    2008-09-15

    Biotechnology industry is now a global 'Mega-Trend' and metabolic engineering technology has important role is this area. Therefore, many countries has made efforts in this field to produce top value added bio-products efficiently using microorganisms. It has been applied to increase the production of chemicals that are already produced by the host organism, to produce desired chemical substances from less expensive feedstock, and to generate products that are new to the host organism. Recent experimental advances, the so-called '-omics' technologies, mainly functional genomics, proteomics and metabolomics, have enabled wholesale generation of new genomic, transcriptomic, proteomic, and metabolomic data. This report provides the insights of the integrated view of metabolism generated by metabolic engineering for biotechnological applications of microbial metabolic engineering.

  15. Toward the automated generation of genome-scale metabolic networks in the SEED.

    DeJongh, Matthew; Formsma, Kevin; Boillot, Paul; Gould, John; Rycenga, Matthew; Best, Aaron

    2007-04-26

    Current methods for the automated generation of genome-scale metabolic networks focus on genome annotation and preliminary biochemical reaction network assembly, but do not adequately address the process of identifying and filling gaps in the reaction network, and verifying that the network is suitable for systems level analysis. Thus, current methods are only sufficient for generating draft-quality networks, and refinement of the reaction network is still largely a manual, labor-intensive process. We have developed a method for generating genome-scale metabolic networks that produces substantially complete reaction networks, suitable for systems level analysis. Our method partitions the reaction space of central and intermediary metabolism into discrete, interconnected components that can be assembled and verified in isolation from each other, and then integrated and verified at the level of their interconnectivity. We have developed a database of components that are common across organisms, and have created tools for automatically assembling appropriate components for a particular organism based on the metabolic pathways encoded in the organism's genome. This focuses manual efforts on that portion of an organism's metabolism that is not yet represented in the database. We have demonstrated the efficacy of our method by reverse-engineering and automatically regenerating the reaction network from a published genome-scale metabolic model for Staphylococcus aureus. Additionally, we have verified that our method capitalizes on the database of common reaction network components created for S. aureus, by using these components to generate substantially complete reconstructions of the reaction networks from three other published metabolic models (Escherichia coli, Helicobacter pylori, and Lactococcus lactis). We have implemented our tools and database within the SEED, an open-source software environment for comparative genome annotation and analysis. Our method sets the

  16. Toward the automated generation of genome-scale metabolic networks in the SEED

    Gould John

    2007-04-01

    Full Text Available Abstract Background Current methods for the automated generation of genome-scale metabolic networks focus on genome annotation and preliminary biochemical reaction network assembly, but do not adequately address the process of identifying and filling gaps in the reaction network, and verifying that the network is suitable for systems level analysis. Thus, current methods are only sufficient for generating draft-quality networks, and refinement of the reaction network is still largely a manual, labor-intensive process. Results We have developed a method for generating genome-scale metabolic networks that produces substantially complete reaction networks, suitable for systems level analysis. Our method partitions the reaction space of central and intermediary metabolism into discrete, interconnected components that can be assembled and verified in isolation from each other, and then integrated and verified at the level of their interconnectivity. We have developed a database of components that are common across organisms, and have created tools for automatically assembling appropriate components for a particular organism based on the metabolic pathways encoded in the organism's genome. This focuses manual efforts on that portion of an organism's metabolism that is not yet represented in the database. We have demonstrated the efficacy of our method by reverse-engineering and automatically regenerating the reaction network from a published genome-scale metabolic model for Staphylococcus aureus. Additionally, we have verified that our method capitalizes on the database of common reaction network components created for S. aureus, by using these components to generate substantially complete reconstructions of the reaction networks from three other published metabolic models (Escherichia coli, Helicobacter pylori, and Lactococcus lactis. We have implemented our tools and database within the SEED, an open-source software environment for comparative

  17. Polycentrism in Global Health Governance Scholarship; Comment on “Four Challenges That Global Health Networks Face”

    Jale Tosun

    2018-01-01

    Full Text Available Drawing on an in-depth analysis of eight global health networks, a recent essay in this journal argued that global health networks face four challenges to their effectiveness: problem definition, positioning, coalition-building, and governance. While sharing the argument of the essay concerned, in this commentary, we argue that these analytical concepts can be used to explicate a concept that has implicitly been used in global health governance scholarship for quite a few years. While already prominent in the discussion of climate change governance, for instance, global health governance scholarship could make progress by looking at global health governance as being polycentric. Concisely, polycentric forms of governance mix scales, mechanisms, and actors. Drawing on the essay, we propose a polycentric approach to the study of global health governance that incorporates coalitionbuilding tactics, internal governance and global political priority as explanatory factors.

  18. Adaptive approach to global synchronization of directed networks with fast switching topologies

    Qin Buzhi; Lu Xinbiao

    2010-01-01

    Global synchronization of directed networks with switching topologies is investigated. It is found that if there exists at least one directed spanning tree in the network with the fixed time-average topology and the time-average topology is achieved sufficiently fast, the network will reach global synchronization for appreciate coupling strength. Furthermore, this appreciate coupling strength may be obtained by local adaptive approach. A sufficient condition about the global synchronization is given. Numerical simulations verify the effectiveness of the adaptive strategy.

  19. Accelerator Control and Global Networks State of the Art

    Gurd, D P

    2004-01-01

    As accelerators increase in size and complexity, demands upon their control systems increase correspondingly. Machine complexity is reflected in complexity of control system hardware and software and careful configuration management is essential. Model-based procedures and fast feedback based upon even faster beam instrumentation are often required. Managing machine protection systems with tens of thousands of inputs is another significant challenge. Increased use of commodity hardware and software introduces new issues of security and control. Large new facilities will increasingly be built by national (e.g. SNS) or international (e.g. a linear collider) collaborations. Building an integrated control system for an accelerator whose development is geographically widespread presents particular problems, not all of them technical. Recent discussions of a “Global Accelerator Network” include the possibility of multiple remote control rooms and no more night shifts. Based upon current experien...

  20. Secure and Efficient Anonymous Authentication Scheme in Global Mobility Networks

    Jun-Sub Kim

    2013-01-01

    Full Text Available In 2012, Mun et al. pointed out that Wu et al.’s scheme failed to achieve user anonymity and perfect forward secrecy and disclosed the passwords of legitimate users. And they proposed a new enhancement for anonymous authentication scheme. However, their proposed scheme has vulnerabilities that are susceptible to replay attack and man-in-the-middle attack. It also incurs a high overhead in the database. In this paper, we examine the vulnerabilities in the existing schemes and the computational overhead incurred in the database. We then propose a secure and efficient anonymous authentication scheme for roaming service in global mobility network. Our proposed scheme is secure against various attacks, provides mutual authentication and session key establishment, and incurs less computational overhead in the database than Mun et al.'s scheme.

  1. Structure versus time in the evolutionary diversification of avian carotenoid metabolic networks.

    Morrison, Erin S; Badyaev, Alexander V

    2018-05-01

    Historical associations of genes and proteins are thought to delineate pathways available to subsequent evolution; however, the effects of past functional involvements on contemporary evolution are rarely quantified. Here, we examined the extent to which the structure of a carotenoid enzymatic network persists in avian evolution. Specifically, we tested whether the evolution of carotenoid networks was most concordant with phylogenetically structured expansion from core reactions of common ancestors or with subsampling of biochemical pathway modules from an ancestral network. We compared structural and historical associations in 467 carotenoid networks of extant and ancestral species and uncovered the overwhelming effect of pre-existing metabolic network structure on carotenoid diversification over the last 50 million years of avian evolution. Over evolutionary time, birds repeatedly subsampled and recombined conserved biochemical modules, which likely maintained the overall structure of the carotenoid metabolic network during avian evolution. These findings explain the recurrent convergence of evolutionary distant species in carotenoid metabolism and weak phylogenetic signal in avian carotenoid evolution. Remarkable retention of an ancient metabolic structure throughout extensive and prolonged ecological diversification in avian carotenoid metabolism illustrates a fundamental requirement of organismal evolution - historical continuity of a deterministic network that links past and present functional associations of its components. © 2018 European Society For Evolutionary Biology. Journal of Evolutionary Biology © 2018 European Society For Evolutionary Biology.

  2. Stoichiometric network constraints on xylose metabolism by recombinant Saccharomyces cerevisiae

    Yong-Su Jin; Thomas W. Jeffries

    2004-01-01

    Metabolic pathway engineering is constrained by the thermodynamic and stoichiometric feasibility of enzymatic activities of introduced genes. Engineering of xylose metabolism in Saccharomyces cerevisiae has focused on introducing genes for the initial xylose assimilation steps from Pichia stipitis, a xylose-fermenting yeast, into S. cerevisiae, a yeast raditionally...

  3. Optimality principles in the regulation of metabolic networks

    Berkhout, J.; Bruggeman, F.J.; Teusink, B.

    2012-01-01

    One of the challenging tasks in systems biology is to understand how molecular networks give rise to emergent functionality and whether universal design principles apply to molecular networks. To achieve this, the biophysical, evolutionary and physiological constraints that act on those networks

  4. Local empathy provides global minimization of congestion in communication networks

    Meloni, Sandro; Gómez-Gardeñes, Jesús

    2010-11-01

    We present a mechanism to avoid congestion in complex networks based on a local knowledge of traffic conditions and the ability of routers to self-coordinate their dynamical behavior. In particular, routers make use of local information about traffic conditions to either reject or accept information packets from their neighbors. We show that when nodes are only aware of their own congestion state they self-organize into a hierarchical configuration that delays remarkably the onset of congestion although leading to a sharp first-order-like congestion transition. We also consider the case when nodes are aware of the congestion state of their neighbors. In this case, we show that empathy between nodes is strongly beneficial to the overall performance of the system and it is possible to achieve larger values for the critical load together with a smooth, second-order-like, transition. Finally, we show how local empathy minimize the impact of congestion as much as global minimization. Therefore, here we present an outstanding example of how local dynamical rules can optimize the system’s functioning up to the levels reached using global knowledge.

  5. Design concepts for a Global Telemetered Seismograph Network

    Peterson, Jon; Orsini, Nicholas A.

    1982-01-01

    This study represents a first step in developing an integrated, real-time global seismic data acquisition system a Global Telemetered Seismograph Network (GTSN). The principal objective of the GTSN will be to acquire reliable, high-quality, real-time seismic data for rapid location and analysis of seismic events. A secondary, but important, objective of the GTSN is to augment the existing off-line seismic data base available for research. The deployment of the GTSN will involve a variety of interrelated activities development of the data acquisition and receiving equipment, establishment of satellite and terrestrial communication links, site selection and preparation, training of station personnel, equipment installation, and establishment of support facilities. It is a complex program and the development of a sound management plan will be essential. The purpose of this study is not to fix design goals or dictate avenues of approach but to develop working concepts that may be used as a framework for program planning.The international exchange of seismic data has been an important factor in the progress that has been made during the past two decades in our understanding of earthquakes and global tectonics. The seismic data base available for analysis and research is derived principally from the Global Seismograph Network (GSN), which is funded and managed by the U.S. Geological Survey (USGS). The GSN comprises some 120 seismograph stations located in more than 60 countries of the world. Established during the 1960 s with the installation of the World-Wide Standardized Seismograph Network (WWSSN) , the GSN has been augmented in recent years by the installation of more advanced data systems, such as the Seismic Research Observatories (SRO), the modified High-Gain LongPeriod (ASRO) seismographs, and the digital WWSSN (DWWSSN). The SRO, ASRO, and DWWSSN stations have the common, distinctive feature of digital data recording, so they are known collectively as the Global

  6. Operating a global seismic network - perspectives from the USGS GSN

    Gee, L. S.; Derr, J. S.; Hutt, C. R.; Bolton, H.; Ford, D.; Gyure, G. S.; Storm, T.; Leith, W.

    2007-05-01

    The Global Seismographic Network (GSN) is a permanent digital network of state-of-the-art seismological and geophysical sensors connected by a global telecommunications network, serving as a multi-use scientific facility used for seismic monitoring for response applications, basic and applied research in solid earthquake geophysics, and earth science education. A joint program of the U.S. Geological Survey (USGS), the National Science Foundation, and Incorporated Research Institutions in Seismology (IRIS), the GSN provides near- uniform, worldwide monitoring of the Earth through 144 modern, globally distributed seismic stations. The USGS currently operates 90 GSN or GSN-affiliate stations. As a US government program, the USGS GSN is evaluated on several performance measures including data availability, data latency, and cost effectiveness. The USGS-component of the GSN, like the GSN as a whole, is in transition from a period of rapid growth to steady- state operations. The program faces challenges of aging equipment and increased operating costs at the same time that national and international earthquake and tsunami monitoring agencies place an increased reliance on GSN data. Data acquisition of the USGS GSN is based on the Quanterra Q680 datalogger, a workhorse system that is approaching twenty years in the field, often in harsh environments. An IRIS instrumentation committee recently selected the Quanterra Q330 HR as the "next generation" GSN data acquisition system, and the USGS will begin deploying the new equipment in the middle of 2007. These new systems will address many of the issues associated with the ageing Q680 while providing a platform for interoperability across the GSN.. In order to address the challenge of increasing operational costs, the USGS employs several tools. First, the USGS benefits from the contributions of local host institutions. The station operators are the first line of defense when a station experiences problems, changing boards

  7. Dead end metabolites--defining the known unknowns of the E. coli metabolic network.

    Amanda Mackie

    Full Text Available The EcoCyc database is an online scientific database which provides an integrated view of the metabolic and regulatory network of the bacterium Escherichia coli K-12 and facilitates computational exploration of this important model organism. We have analysed the occurrence of dead end metabolites within the database--these are metabolites which lack the requisite reactions (either metabolic or transport that would account for their production or consumption within the metabolic network. 127 dead end metabolites were identified from the 995 compounds that are contained within the EcoCyc metabolic network. Their presence reflects either a deficit in our representation of the network or in our knowledge of E. coli metabolism. Extensive literature searches resulted in the addition of 38 transport reactions and 3 metabolic reactions to the database and led to an improved representation of the pathway for Vitamin B12 salvage. 39 dead end metabolites were identified as components of reactions that are not physiologically relevant to E. coli K-12--these reactions are properties of purified enzymes in vitro that would not be expected to occur in vivo. Our analysis led to improvements in the software that underpins the database and to the program that finds dead end metabolites within EcoCyc. The remaining dead end metabolites in the EcoCyc database likely represent deficiencies in our knowledge of E. coli metabolism.

  8. Characterization of the Usage of the Serine Metabolic Network in Human Cancer

    Mahya Mehrmohamadi

    2014-11-01

    Full Text Available The serine, glycine, one-carbon (SGOC metabolic network is implicated in cancer pathogenesis, but its general functions are unknown. We carried out a computational reconstruction of the SGOC network and then characterized its expression across thousands of cancer tissues. Pathways including methylation and redox metabolism exhibited heterogeneous expression indicating a strong context dependency of their usage in tumors. From an analysis of coexpression, simultaneous up- or downregulation of nucleotide synthesis, NADPH, and glutathione synthesis was found to be a common occurrence in all cancers. Finally, we developed a method to trace the metabolic fate of serine using stable isotopes, high-resolution mass spectrometry, and a mathematical model. Although the expression of single genes didn’t appear indicative of flux, the collective expression of several genes in a given pathway allowed for successful flux prediction. Altogether, these findings identify expansive and heterogeneous functions for the SGOC metabolic network in human cancer.

  9. Construction and analysis of a genome-scale metabolic network for Bacillus licheniformis WX-02.

    Guo, Jing; Zhang, Hong; Wang, Cheng; Chang, Ji-Wei; Chen, Ling-Ling

    2016-05-01

    We constructed the genome-scale metabolic network of Bacillus licheniformis (B. licheniformis) WX-02 by combining genomic annotation, high-throughput phenotype microarray (PM) experiments and literature-based metabolic information. The accuracy of the metabolic network was assessed by an OmniLog PM experiment. The final metabolic model iWX1009 contains 1009 genes, 1141 metabolites and 1762 reactions, and the predicted metabolic phenotypes showed an agreement rate of 76.8% with experimental PM data. In addition, key metabolic features such as growth yield, utilization of different substrates and essential genes were identified by flux balance analysis. A total of 195 essential genes were predicted from LB medium, among which 149 were verified with the experimental essential gene set of B. subtilis 168. With the removal of 5 reactions from the network, pathways for poly-γ-glutamic acid (γ-PGA) synthesis were optimized and the γ-PGA yield reached 83.8 mmol/h. Furthermore, the important metabolites and pathways related to γ-PGA synthesis and bacterium growth were comprehensively analyzed. The present study provides valuable clues for exploring the metabolisms and metabolic regulation of γ-PGA synthesis in B. licheniformis WX-02. Copyright © 2016 Institut Pasteur. Published by Elsevier Masson SAS. All rights reserved.

  10. Global Optimization for Transport Network Expansion and Signal Setting

    Liu, Haoxiang; Wang, David Z. W.; Yue, Hao

    2015-01-01

    This paper proposes a model to address an urban transport planning problem involving combined network design and signal setting in a saturated network. Conventional transport planning models usually deal with the network design problem and signal setting problem separately. However, the fact that network capacity design and capacity allocation determined by network signal setting combine to govern the transport network performance requires the optimal transport planning to consider the two pr...

  11. SKYMONITOR: A Global Network for Sky Brightness Measurements

    Davis, Donald R.; Mckenna, D.; Pulvermacher, R.; Everett, M.

    2010-01-01

    We are implementing a global network to measure sky brightness at dark-sky critical sites with the goal of creating a multi-decade database. The heart of this project is the Night Sky Brightness Monitor (NSBM), an autonomous 2 channel photometer which measures night sky brightness in the visual wavelengths (Mckenna et al, AAS 2009). Sky brightness is measured every minute at two elevation angles typically zenith and 20 degrees to monitor brightness and transparency. The NSBM consists of two parts, a remote unit and a base station with an internet connection. Currently these devices use 2.4 Ghz transceivers with a range of 100 meters. The remote unit is battery powered with daytime recharging using a solar panel. Data received by the base unit is transmitted via email protocol to IDA offices in Tucson where it will be collected, archived and made available to the user community via a web interface. Two other versions of the NSBM are under development: one for radio sensitive areas using an optical fiber link and the second that reads data directly to a laptop for sites without internet access. NSBM units are currently undergoing field testing at two observatories. With support from the National Science Foundation, we will construct and install a total of 10 units at astronomical observatories. With additional funding, we will locate additional units at other sites such as National Parks, dark-sky preserves and other sites where dark sky preservation is crucial. We will present the current comparison with the National Park Service sky monitoring camera. We anticipate that the SKYMONITOR network will be functioning by the end of 2010.

  12. A general model for metabolic scaling in self-similar asymmetric networks.

    Alexander Byers Brummer

    2017-03-01

    Full Text Available How a particular attribute of an organism changes or scales with its body size is known as an allometry. Biological allometries, such as metabolic scaling, have been hypothesized to result from selection to maximize how vascular networks fill space yet minimize internal transport distances and resistances. The West, Brown, Enquist (WBE model argues that these two principles (space-filling and energy minimization are (i general principles underlying the evolution of the diversity of biological networks across plants and animals and (ii can be used to predict how the resulting geometry of biological networks then governs their allometric scaling. Perhaps the most central biological allometry is how metabolic rate scales with body size. A core assumption of the WBE model is that networks are symmetric with respect to their geometric properties. That is, any two given branches within the same generation in the network are assumed to have identical lengths and radii. However, biological networks are rarely if ever symmetric. An open question is: Does incorporating asymmetric branching change or influence the predictions of the WBE model? We derive a general network model that relaxes the symmetric assumption and define two classes of asymmetrically bifurcating networks. We show that asymmetric branching can be incorporated into the WBE model. This asymmetric version of the WBE model results in several theoretical predictions for the structure, physiology, and metabolism of organisms, specifically in the case for the cardiovascular system. We show how network asymmetry can now be incorporated in the many allometric scaling relationships via total network volume. Most importantly, we show that the 3/4 metabolic scaling exponent from Kleiber's Law can still be attained within many asymmetric networks.

  13. Identification of global oil trade patterns: An empirical research based on complex network theory

    Ji, Qiang; Zhang, Hai-Ying; Fan, Ying

    2014-01-01

    Highlights: • A global oil trade core network is analyzed using complex network theory. • The global oil export core network displays a scale-free behaviour. • The current global oil trade network can be divided into three trading blocs. • The global oil trade network presents a ‘robust and yet fragile’ characteristic. - Abstract: The Global oil trade pattern becomes increasingly complex, which has become one of the most important factors affecting every country’s energy strategy and economic development. In this paper, a global oil trade core network is constructed to analyze the overall features, regional characteristics and stability of the oil trade using complex network theory. The results indicate that the global oil export core network displays a scale-free behaviour, in which the trade position of nodes presents obvious heterogeneity and the ‘hub nodes’ play a ‘bridge’ role in the formation process of the trade network. The current global oil trade network can be divided into three trading blocs, including the ‘South America-West Africa-North America’ trading bloc, the ‘Middle East–Asian–Pacific region’ trading bloc, and ‘the former Soviet Union–North Africa–Europe’ trading bloc. Geopolitics and diplomatic relations are the two main reasons for this regional oil trade structure. Moreover, the global oil trade network presents a ‘robust but yet fragile’ characteristic, and the impacts of trade interruption always tend to spread throughout the whole network even if the occurrence of export disruptions is localised

  14. Isolated ionospheric disturbances as deduced from global GPS network

    E. L. Afraimovich

    2004-01-01

    Full Text Available We investigate an unusual class of medium-scale traveling ionospheric disturbances of the nonwave type, isolated ionospheric disturbances (IIDs that manifest themselves in total electron content (TEC variations in the form of single aperiodic negative TEC disturbances of a duration of about 10min (the total electron content spikes, TECS. The data were obtained using the technology of global detection of ionospheric disturbances using measurements of TEC variations from a global network of receivers of the GPS. For the first time, we present the TECS morphology for 170 days in 1998–2001. The total number of TEC series, with a duration of each series of about 2.3h (2h18m, exceeded 850000. It was found that TECS are observed in no more than 1–2% of the total number of TEC series mainly in the nighttime in the spring and autumn periods. The TECS amplitude exceeds the mean value of the "background" TEC variation amplitude by a factor of 5–10 as a minimum. TECS represent a local phenomenon with a typical radius of spatial correlation not larger than 500km. The IID-induced TEC variations are similar in their amplitude, form and duration to the TEC response to shock-acoustic waves (SAW generated during rocket launchings and earthquakes. However, the IID propagation velocity is less than the SAW velocity (800–1000m/s and are most likely to correspond to the velocity of background medium-scale acoustic-gravity waves, on the order of 100–200m/s. Key words. Ionosphere (ionospheric irregularities, instruments and techniques - Radio science (ionospheric propagation

  15. Complementary feeding: a Global Network cluster randomized controlled trial

    Pasha Omrana

    2011-01-01

    Full Text Available Abstract Background Inadequate and inappropriate complementary feeding are major factors contributing to excess morbidity and mortality in young children in low resource settings. Animal source foods in particular are cited as essential to achieve micronutrient requirements. The efficacy of the recommendation for regular meat consumption, however, has not been systematically evaluated. Methods/Design A cluster randomized efficacy trial was designed to test the hypothesis that 12 months of daily intake of beef added as a complementary food would result in greater linear growth velocity than a micronutrient fortified equi-caloric rice-soy cereal supplement. The study is being conducted in 4 sites of the Global Network for Women's and Children's Health Research located in Guatemala, Pakistan, Democratic Republic of the Congo (DRC and Zambia in communities with toddler stunting rates of at least 20%. Five clusters per country were randomized to each of the food arms, with 30 infants in each cluster. The daily meat or cereal supplement was delivered to the home by community coordinators, starting when the infants were 6 months of age and continuing through 18 months. All participating mothers received nutrition education messages to enhance complementary feeding practices delivered by study coordinators and through posters at the local health center. Outcome measures, obtained at 6, 9, 12, and 18 months by a separate assessment team, included anthropometry; dietary variety and diversity scores; biomarkers of iron, zinc and Vitamin B12 status (18 months; neurocognitive development (12 and 18 months; and incidence of infectious morbidity throughout the trial. The trial was supervised by a trial steering committee, and an independent data monitoring committee provided oversight for the safety and conduct of the trial. Discussion Findings from this trial will test the efficacy of daily intake of meat commencing at age 6 months and, if beneficial, will

  16. Metabolomics Approach Reveals Integrated Metabolic Network Associated with Serotonin Deficiency

    Weng, Rui; Shen, Sensen; Tian, Yonglu; Burton, Casey; Xu, Xinyuan; Liu, Yi; Chang, Cuilan; Bai, Yu; Liu, Huwei

    2015-07-01

    Serotonin is an important neurotransmitter that broadly participates in various biological processes. While serotonin deficiency has been associated with multiple pathological conditions such as depression, schizophrenia, Alzheimer’s disease and Parkinson’s disease, the serotonin-dependent mechanisms remain poorly understood. This study therefore aimed to identify novel biomarkers and metabolic pathways perturbed by serotonin deficiency using metabolomics approach in order to gain new metabolic insights into the serotonin deficiency-related molecular mechanisms. Serotonin deficiency was achieved through pharmacological inhibition of tryptophan hydroxylase (Tph) using p-chlorophenylalanine (pCPA) or genetic knockout of the neuronal specific Tph2 isoform. This dual approach improved specificity for the serotonin deficiency-associated biomarkers while minimizing nonspecific effects of pCPA treatment or Tph2 knockout (Tph2-/-). Non-targeted metabolic profiling and a targeted pCPA dose-response study identified 21 biomarkers in the pCPA-treated mice while 17 metabolites in the Tph2-/- mice were found to be significantly altered compared with the control mice. These newly identified biomarkers were associated with amino acid, energy, purine, lipid and gut microflora metabolisms. Oxidative stress was also found to be significantly increased in the serotonin deficient mice. These new biomarkers and the overall metabolic pathways may provide new understanding for the serotonin deficiency-associated mechanisms under multiple pathological states.

  17. Dynamic brain glucose metabolism identifies anti-correlated cortical-cerebellar networks at rest.

    Tomasi, Dardo G; Shokri-Kojori, Ehsan; Wiers, Corinde E; Kim, Sunny W; Demiral, Şukru B; Cabrera, Elizabeth A; Lindgren, Elsa; Miller, Gregg; Wang, Gene-Jack; Volkow, Nora D

    2017-12-01

    It remains unclear whether resting state functional magnetic resonance imaging (rfMRI) networks are associated with underlying synchrony in energy demand, as measured by dynamic 2-deoxy-2-[ 18 F]fluoroglucose (FDG) positron emission tomography (PET). We measured absolute glucose metabolism, temporal metabolic connectivity (t-MC) and rfMRI patterns in 53 healthy participants at rest. Twenty-two rfMRI networks emerged from group independent component analysis (gICA). In contrast, only two anti-correlated t-MC emerged from FDG-PET time series using gICA or seed-voxel correlations; one included frontal, parietal and temporal cortices, the other included the cerebellum and medial temporal regions. Whereas cerebellum, thalamus, globus pallidus and calcarine cortex arose as the strongest t-MC hubs, the precuneus and visual cortex arose as the strongest rfMRI hubs. The strength of the t-MC linearly increased with the metabolic rate of glucose suggesting that t-MC measures are strongly associated with the energy demand of the brain tissue, and could reflect regional differences in glucose metabolism, counterbalanced metabolic network demand, and/or differential time-varying delivery of FDG. The mismatch between metabolic and functional connectivity patterns computed as a function of time could reflect differences in the temporal characteristics of glucose metabolism as measured with PET-FDG and brain activation as measured with rfMRI.

  18. Validation of a metabolic network for Saccharomyces cerevisiae using mixed substrate studies.

    Vanrolleghem, P A; de Jong-Gubbels, P; van Gulik, W M; Pronk, J T; van Dijken, J P; Heijnen, S

    1996-01-01

    Setting up a metabolic network model for respiratory growth of Saccharomyces cerevisiae requires the estimation of only two (energetic) stoichiometric parameters: (1) the operational PO ratio and (2) a growth-related maintenance factor k. It is shown, both theoretically and practically, how chemostat cultivations with different mixtures of two substrates allow unique values to be given to these unknowns of the proposed metabolic model. For the yeast and model considered, an effective PO ratio of 1.09 mol of ATP/mol of O (95% confidence interval 1.07-1.11) and a k factor of 0.415 mol of ATP/C-mol of biomass (0.385-0.445) were obtained from biomass substrate yield data on glucose/ethanol mixtures. Symbolic manipulation software proved very valuable in this study as it supported the proof of theoretical identifiability and significantly reduced the necessary computations for parameter estimation. In the transition from 100% glucose to 100% ethanol in the feed, four metabolic regimes occur. Switching between these regimes is determined by cessation of an irreversible reaction and initiation of an alternative reaction. Metabolic network predictions of these metabolic switches compared well with activity measurements of key enzymes. As a second validation of the network, the biomass yield of S. cerevisiae on acetate was also compared to the network prediction. An excellent agreement was found for a network in which acetate transport was modeled with a proton symport, while passive diffusion of acetate gave significantly higher yield predictions.

  19. Optimal knockout strategies in genome-scale metabolic networks using particle swarm optimization.

    Nair, Govind; Jungreuthmayer, Christian; Zanghellini, Jürgen

    2017-02-01

    Knockout strategies, particularly the concept of constrained minimal cut sets (cMCSs), are an important part of the arsenal of tools used in manipulating metabolic networks. Given a specific design, cMCSs can be calculated even in genome-scale networks. We would however like to find not only the optimal intervention strategy for a given design but the best possible design too. Our solution (PSOMCS) is to use particle swarm optimization (PSO) along with the direct calculation of cMCSs from the stoichiometric matrix to obtain optimal designs satisfying multiple objectives. To illustrate the working of PSOMCS, we apply it to a toy network. Next we show its superiority by comparing its performance against other comparable methods on a medium sized E. coli core metabolic network. PSOMCS not only finds solutions comparable to previously published results but also it is orders of magnitude faster. Finally, we use PSOMCS to predict knockouts satisfying multiple objectives in a genome-scale metabolic model of E. coli and compare it with OptKnock and RobustKnock. PSOMCS finds competitive knockout strategies and designs compared to other current methods and is in some cases significantly faster. It can be used in identifying knockouts which will force optimal desired behaviors in large and genome scale metabolic networks. It will be even more useful as larger metabolic models of industrially relevant organisms become available.

  20. A mixed-integer linear programming approach to the reduction of genome-scale metabolic networks.

    Röhl, Annika; Bockmayr, Alexander

    2017-01-03

    Constraint-based analysis has become a widely used method to study metabolic networks. While some of the associated algorithms can be applied to genome-scale network reconstructions with several thousands of reactions, others are limited to small or medium-sized models. In 2015, Erdrich et al. introduced a method called NetworkReducer, which reduces large metabolic networks to smaller subnetworks, while preserving a set of biological requirements that can be specified by the user. Already in 2001, Burgard et al. developed a mixed-integer linear programming (MILP) approach for computing minimal reaction sets under a given growth requirement. Here we present an MILP approach for computing minimum subnetworks with the given properties. The minimality (with respect to the number of active reactions) is not guaranteed by NetworkReducer, while the method by Burgard et al. does not allow specifying the different biological requirements. Our procedure is about 5-10 times faster than NetworkReducer and can enumerate all minimum subnetworks in case there exist several ones. This allows identifying common reactions that are present in all subnetworks, and reactions appearing in alternative pathways. Applying complex analysis methods to genome-scale metabolic networks is often not possible in practice. Thus it may become necessary to reduce the size of the network while keeping important functionalities. We propose a MILP solution to this problem. Compared to previous work, our approach is more efficient and allows computing not only one, but even all minimum subnetworks satisfying the required properties.

  1. Observability of plant metabolic networks is reflected in the correlation of metabolic profiles

    Schwahn, Kevin; Küken, Anika; Kliebenstein, Daniel James

    2016-01-01

    to obtain information about the entire system. Yet, the extent to which the data profiles reflect the role of components in the observability of the system remains unexplored. Here we first identify the sensor metabolites in the model plant Arabidopsis (Arabidopsis thaliana) by employing state...... with in silico generated metabolic profiles from a medium-size kinetic model of plant central carbon metabolism. Altogether, due to the small number of identified sensors, our study implies that targeted metabolite analyses may provide the vast majority of relevant information about plant metabolic systems....

  2. Inferring influenza global transmission networks without complete phylogenetic information.

    Aris-Brosou, Stéphane

    2014-03-01

    Influenza is one of the most severe respiratory infections affecting humans throughout the world, yet the dynamics of its global transmission network are still contentious. Here, I describe a novel combination of phylogenetics, time series, and graph theory to analyze 14.25 years of data stratified in space and in time, focusing on the main target of the human immune response, the hemagglutinin gene. While bypassing the complete phylogenetic inference of huge data sets, the method still extracts information suggesting that waves of genetic or of nucleotide diversity circulate continuously around the globe for subtypes that undergo sustained transmission over several seasons, such as H3N2 and pandemic H1N1/09, while diversity of prepandemic H1N1 viruses had until 2009 a noncontinuous transmission pattern consistent with a source/sink model. Irrespective of the shift in the structure of H1N1 diversity circulation with the emergence of the pandemic H1N1/09 strain, US prevalence peaks during the winter months when genetic diversity is at its lowest. This suggests that a dominant strain is generally responsible for epidemics and that monitoring genetic and/or nucleotide diversity in real time could provide public health agencies with an indirect estimate of prevalence.

  3. Global Accelerator Network, Control Systems And Beam Diagnostics

    Raich, U

    2003-01-01

    Falling funds force all accelerator centers to look for new sources of financing and for the most efficient way of implementing new projects. This very often leads to collaborations between institutes scattered around the globe, a problem well known to big high energy physics experiments. The collaborations working on big detectors e.g. for LHC started thinking about detector acquisition and control systems which can be remotely used from their respective home institutes with minimal support on the spot. This idea was taken up by A. Wagner from DESY for the TESLA machine, who proposed the “Global Accelerator Network” (GAN) enabling users from around the world to run an accelerator remotely. Questions around this subject that immediately come to mind Is the GAN only relevant to big labs ? Or is it reasonable e.g. for operators or engineers in charge to do certain manipulations from home? Are our instruments ready for the GAN? Does the fact of being “GAN ready” increa...

  4. The Global Genome Biodiversity Network (GGBN) Data Standard specification

    Droege, G.; Barker, K.; Seberg, O.; Coddington, J.; Benson, E.; Berendsohn, W. G.; Bunk, B.; Butler, C.; Cawsey, E. M.; Deck, J.; Döring, M.; Flemons, P.; Gemeinholzer, B.; Güntsch, A.; Hollowell, T.; Kelbert, P.; Kostadinov, I.; Kottmann, R.; Lawlor, R. T.; Lyal, C.; Mackenzie-Dodds, J.; Meyer, C.; Mulcahy, D.; Nussbeck, S. Y.; O'Tuama, É.; Orrell, T.; Petersen, G.; Robertson, T.; Söhngen, C.; Whitacre, J.; Wieczorek, J.; Yilmaz, P.; Zetzsche, H.; Zhang, Y.; Zhou, X.

    2016-01-01

    Genomic samples of non-model organisms are becoming increasingly important in a broad range of studies from developmental biology, biodiversity analyses, to conservation. Genomic sample definition, description, quality, voucher information and metadata all need to be digitized and disseminated across scientific communities. This information needs to be concise and consistent in today’s ever-increasing bioinformatic era, for complementary data aggregators to easily map databases to one another. In order to facilitate exchange of information on genomic samples and their derived data, the Global Genome Biodiversity Network (GGBN) Data Standard is intended to provide a platform based on a documented agreement to promote the efficient sharing and usage of genomic sample material and associated specimen information in a consistent way. The new data standard presented here build upon existing standards commonly used within the community extending them with the capability to exchange data on tissue, environmental and DNA sample as well as sequences. The GGBN Data Standard will reveal and democratize the hidden contents of biodiversity biobanks, for the convenience of everyone in the wider biobanking community. Technical tools exist for data providers to easily map their databases to the standard. Database URL: http://terms.tdwg.org/wiki/GGBN_Data_Standard PMID:27694206

  5. Global Space Weather Observational Network: Challenges and China's Contribution

    Wang, C.

    2017-12-01

    To understand space weather physical processes and predict space weather accurately, global space-borne and ground-based space weather observational network, making simultaneous observations from the Sun to geo-space (magnetosphere, ionosphere and atmosphere), plays an essential role. In this talk, we will present the advances of the Chinese space weather science missions, including the ASO-S (Advanced Space-borne Solar Observatory), MIT (Magnetosphere - Ionosphere- Thermosphere Coupling Exploration), and the ESA-China joint space weather science mission SMILE (Solar wind - Magnetosphere - Ionosphere Link Explore), a new mission to image the magnetosphere. Compared to satellites, ground-based monitors are cheap, convenient, and provide continuous real-time data. We will also introduce the Chinese Meridian Project (CMP), a ground-based program fully utilizing the geographic location of the Chinese landmass to monitor the geo-space environment. CMP is just one arm of a larger program that Chinese scientists are proposing to the international community. The International Meridian Circle Program (IMCP) for space weather hopes to connect chains of ground-based monitors at the longitudinal meridians 120 deg E and 60 deg W. IMCP takes advantage of the fact that these meridians already have the most monitors of any on Earth, with monitors in Russia, Australia, Brazil, the United States, Canada, and other countries. This data will greatly enhance the ability of scientists to monitor and predict the space weather worldwide.

  6. Reconstruction and Analysis of Human Kidney-Specific Metabolic Network Based on Omics Data

    Ai-Di Zhang

    2013-01-01

    Full Text Available With the advent of the high-throughput data production, recent studies of tissue-specific metabolic networks have largely advanced our understanding of the metabolic basis of various physiological and pathological processes. However, for kidney, which plays an essential role in the body, the available kidney-specific model remains incomplete. This paper reports the reconstruction and characterization of the human kidney metabolic network based on transcriptome and proteome data. In silico simulations revealed that house-keeping genes were more essential than kidney-specific genes in maintaining kidney metabolism. Importantly, a total of 267 potential metabolic biomarkers for kidney-related diseases were successfully explored using this model. Furthermore, we found that the discrepancies in metabolic processes of different tissues are directly corresponding to tissue's functions. Finally, the phenotypes of the differentially expressed genes in diabetic kidney disease were characterized, suggesting that these genes may affect disease development through altering kidney metabolism. Thus, the human kidney-specific model constructed in this study may provide valuable information for the metabolism of kidney and offer excellent insights into complex kidney diseases.

  7. TIGER: Toolbox for integrating genome-scale metabolic models, expression data, and transcriptional regulatory networks

    Jensen Paul A

    2011-09-01

    Full Text Available Abstract Background Several methods have been developed for analyzing genome-scale models of metabolism and transcriptional regulation. Many of these methods, such as Flux Balance Analysis, use constrained optimization to predict relationships between metabolic flux and the genes that encode and regulate enzyme activity. Recently, mixed integer programming has been used to encode these gene-protein-reaction (GPR relationships into a single optimization problem, but these techniques are often of limited generality and lack a tool for automating the conversion of rules to a coupled regulatory/metabolic model. Results We present TIGER, a Toolbox for Integrating Genome-scale Metabolism, Expression, and Regulation. TIGER converts a series of generalized, Boolean or multilevel rules into a set of mixed integer inequalities. The package also includes implementations of existing algorithms to integrate high-throughput expression data with genome-scale models of metabolism and transcriptional regulation. We demonstrate how TIGER automates the coupling of a genome-scale metabolic model with GPR logic and models of transcriptional regulation, thereby serving as a platform for algorithm development and large-scale metabolic analysis. Additionally, we demonstrate how TIGER's algorithms can be used to identify inconsistencies and improve existing models of transcriptional regulation with examples from the reconstructed transcriptional regulatory network of Saccharomyces cerevisiae. Conclusion The TIGER package provides a consistent platform for algorithm development and extending existing genome-scale metabolic models with regulatory networks and high-throughput data.

  8. China's evolving role in global production networks: Implications for Trump's trade war

    Athukorala, Prema-chandra

    2017-01-01

    This paper examines China's evolving role in global production networks and its implications for assessing the potential impact of the "trade war" declared by President Trump. The analysis, which is based on a systematic disaggregation of trade based on global production sharing into components and final assembly, suggests that the Sino-US trade gap is a structural phenomenon driven by the pivotal role played by China within East Asia cantered production networks. The global competitiveness o...

  9. Linking metabolic QTLs with network and cis-eQTLs controlling biosynthetic pathways.

    Adam M Wentzell

    2007-09-01

    Full Text Available Phenotypic variation between individuals of a species is often under quantitative genetic control. Genomic analysis of gene expression polymorphisms between individuals is rapidly gaining popularity as a way to query the underlying mechanistic causes of variation between individuals. However, there is little direct evidence of a linkage between global gene expression polymorphisms and phenotypic consequences. In this report, we have mapped quantitative trait loci (QTLs-controlling glucosinolate content in a population of 403 Arabidopsis Bay x Sha recombinant inbred lines, 211 of which were previously used to identify expression QTLs controlling the transcript levels of biosynthetic genes. In a comparative study, we have directly tested two plant biosynthetic pathways for association between polymorphisms controlling biosynthetic gene transcripts and the resulting metabolites within the Arabidopsis Bay x Sha recombinant inbred line population. In this analysis, all loci controlling expression variation also affected the accumulation of the resulting metabolites. In addition, epistasis was detected more frequently for metabolic traits compared to transcript traits, even when both traits showed similar distributions. An analysis of candidate genes for QTL-controlling networks of transcripts and metabolites suggested that the controlling factors are a mix of enzymes and regulatory factors. This analysis showed that regulatory connections can feedback from metabolism to transcripts. Surprisingly, the most likely major regulator of both transcript level for nearly the entire pathway and aliphatic glucosinolate accumulation is variation in the last enzyme in the biosynthetic pathway, AOP2. This suggests that natural variation in transcripts may significantly impact phenotypic variation, but that natural variation in metabolites or their enzymatic loci can feed back to affect the transcripts.

  10. Chronic obstructive pulmonary disease candidate gene prioritization based on metabolic networks and functional information.

    Xinyan Wang

    Full Text Available Chronic obstructive pulmonary disease (COPD is a multi-factor disease, in which metabolic disturbances played important roles. In this paper, functional information was integrated into a COPD-related metabolic network to assess similarity between genes. Then a gene prioritization method was applied to the COPD-related metabolic network to prioritize COPD candidate genes. The gene prioritization method was superior to ToppGene and ToppNet in both literature validation and functional enrichment analysis. Top-ranked genes prioritized from the metabolic perspective with functional information could promote the better understanding about the molecular mechanism of this disease. Top 100 genes might be potential markers for diagnostic and effective therapies.

  11. Integration of Plant Metabolomics Data with Metabolic Networks: Progresses and Challenges.

    Töpfer, Nadine; Seaver, Samuel M D; Aharoni, Asaph

    2018-01-01

    In the last decade, plant genome-scale modeling has developed rapidly and modeling efforts have advanced from representing metabolic behavior of plant heterotrophic cell suspensions to studying the complex interplay of cell types, tissues, and organs. A crucial driving force for such developments is the availability and integration of "omics" data (e.g., transcriptomics, proteomics, and metabolomics) which enable the reconstruction, extraction, and application of context-specific metabolic networks. In this chapter, we demonstrate a workflow to integrate gas chromatography coupled to mass spectrometry (GC-MS)-based metabolomics data of tomato fruit pericarp (flesh) tissue, at five developmental stages, with a genome-scale reconstruction of tomato metabolism. This method allows for the extraction of context-specific networks reflecting changing activities of metabolic pathways throughout fruit development and maturation.

  12. Estimation of global network statistics from incomplete data.

    Catherine A Bliss

    Full Text Available Complex networks underlie an enormous variety of social, biological, physical, and virtual systems. A profound complication for the science of complex networks is that in most cases, observing all nodes and all network interactions is impossible. Previous work addressing the impacts of partial network data is surprisingly limited, focuses primarily on missing nodes, and suggests that network statistics derived from subsampled data are not suitable estimators for the same network statistics describing the overall network topology. We generate scaling methods to predict true network statistics, including the degree distribution, from only partial knowledge of nodes, links, or weights. Our methods are transparent and do not assume a known generating process for the network, thus enabling prediction of network statistics for a wide variety of applications. We validate analytical results on four simulated network classes and empirical data sets of various sizes. We perform subsampling experiments by varying proportions of sampled data and demonstrate that our scaling methods can provide very good estimates of true network statistics while acknowledging limits. Lastly, we apply our techniques to a set of rich and evolving large-scale social networks, Twitter reply networks. Based on 100 million tweets, we use our scaling techniques to propose a statistical characterization of the Twitter Interactome from September 2008 to November 2008. Our treatment allows us to find support for Dunbar's hypothesis in detecting an upper threshold for the number of active social contacts that individuals maintain over the course of one week.

  13. Global Talent Management in Multinational Corporations and the Role of Social Networks

    Ruel, Hubertus Johannes Maria; Bondarouk, Tatiana; Dresselhaus, Lena; Olivas-Lujan, M.R.; Bondarouk, T.V.

    2013-01-01

    Purpose — Current global business challenges and circumstances are responsible for the need for global talent management (GTM) within multinational corporations (MNCs). Social media and networks are becoming key channels for global communication and collaboration. For GTM in MNCs, an effective usage

  14. Thermodynamic analysis of regulation in metabolic networks using constraint-based modeling

    Mahadevan Radhakrishnan

    2010-05-01

    Full Text Available Abstract Background Geobacter sulfurreducens is a member of the Geobacter species, which are capable of oxidation of organic waste coupled to the reduction of heavy metals and electrode with applications in bioremediation and bioenergy generation. While the metabolism of this organism has been studied through the development of a stoichiometry based genome-scale metabolic model, the associated regulatory network has not yet been well studied. In this manuscript, we report on the implementation of a thermodynamics based metabolic flux model for Geobacter sulfurreducens. We use this updated model to identify reactions that are subject to regulatory control in the metabolic network of G. sulfurreducens using thermodynamic variability analysis. Findings As a first step, we have validated the regulatory sites and bottleneck reactions predicted by the thermodynamic flux analysis in E. coli by evaluating the expression ranges of the corresponding genes. We then identified ten reactions in the metabolic network of G. sulfurreducens that are predicted to be candidates for regulation. We then compared the free energy ranges for these reactions with the corresponding gene expression fold changes under conditions of different environmental and genetic perturbations and show that the model predictions of regulation are consistent with data. In addition, we also identify reactions that operate close to equilibrium and show that the experimentally determined exchange coefficient (a measure of reversibility is significant for these reactions. Conclusions Application of the thermodynamic constraints resulted in identification of potential bottleneck reactions not only from the central metabolism but also from the nucleotide and amino acid subsystems, thereby showing the highly coupled nature of the thermodynamic constraints. In addition, thermodynamic variability analysis serves as a valuable tool in estimating the ranges of ΔrG' of every reaction in the model

  15. Detection of driver metabolites in the human liver metabolic network using structural controllability analysis

    2014-01-01

    Background Abnormal states in human liver metabolism are major causes of human liver diseases ranging from hepatitis to hepatic tumor. The accumulation in relevant data makes it feasible to derive a large-scale human liver metabolic network (HLMN) and to discover important biological principles or drug-targets based on network analysis. Some studies have shown that interesting biological phenomenon and drug-targets could be discovered by applying structural controllability analysis (which is a newly prevailed concept in networks) to biological networks. The exploration on the connections between structural controllability theory and the HLMN could be used to uncover valuable information on the human liver metabolism from a fresh perspective. Results We applied structural controllability analysis to the HLMN and detected driver metabolites. The driver metabolites tend to have strong ability to influence the states of other metabolites and weak susceptibility to be influenced by the states of others. In addition, the metabolites were classified into three classes: critical, high-frequency and low-frequency driver metabolites. Among the identified 36 critical driver metabolites, 27 metabolites were found to be essential; the high-frequency driver metabolites tend to participate in different metabolic pathways, which are important in regulating the whole metabolic systems. Moreover, we explored some other possible connections between the structural controllability theory and the HLMN, and find that transport reactions and the environment play important roles in the human liver metabolism. Conclusion There are interesting connections between the structural controllability theory and the human liver metabolism: driver metabolites have essential biological functions; the crucial role of extracellular metabolites and transport reactions in controlling the HLMN highlights the importance of the environment in the health of human liver metabolism. PMID:24885538

  16. Enumeration of smallest intervention strategies in genome-scale metabolic networks.

    Axel von Kamp

    2014-01-01

    Full Text Available One ultimate goal of metabolic network modeling is the rational redesign of biochemical networks to optimize the production of certain compounds by cellular systems. Although several constraint-based optimization techniques have been developed for this purpose, methods for systematic enumeration of intervention strategies in genome-scale metabolic networks are still lacking. In principle, Minimal Cut Sets (MCSs; inclusion-minimal combinations of reaction or gene deletions that lead to the fulfilment of a given intervention goal provide an exhaustive enumeration approach. However, their disadvantage is the combinatorial explosion in larger networks and the requirement to compute first the elementary modes (EMs which itself is impractical in genome-scale networks. We present MCSEnumerator, a new method for effective enumeration of the smallest MCSs (with fewest interventions in genome-scale metabolic network models. For this we combine two approaches, namely (i the mapping of MCSs to EMs in a dual network, and (ii a modified algorithm by which shortest EMs can be effectively determined in large networks. In this way, we can identify the smallest MCSs by calculating the shortest EMs in the dual network. Realistic application examples demonstrate that our algorithm is able to list thousands of the most efficient intervention strategies in genome-scale networks for various intervention problems. For instance, for the first time we could enumerate all synthetic lethals in E.coli with combinations of up to 5 reactions. We also applied the new algorithm exemplarily to compute strain designs for growth-coupled synthesis of different products (ethanol, fumarate, serine by E.coli. We found numerous new engineering strategies partially requiring less knockouts and guaranteeing higher product yields (even without the assumption of optimal growth than reported previously. The strength of the presented approach is that smallest intervention strategies can be

  17. Development and analysis of an in vivo-compatible metabolic network of Mycobacterium tuberculosis

    Reifman Jaques

    2010-11-01

    Full Text Available Abstract Background During infection, Mycobacterium tuberculosis confronts a generally hostile and nutrient-poor in vivo host environment. Existing models and analyses of M. tuberculosis metabolic networks are able to reproduce experimentally measured cellular growth rates and identify genes required for growth in a range of different in vitro media. However, these models, under in vitro conditions, do not provide an adequate description of the metabolic processes required by the pathogen to infect and persist in a host. Results To better account for the metabolic activity of M. tuberculosis in the host environment, we developed a set of procedures to systematically modify an existing in vitro metabolic network by enhancing the agreement between calculated and in vivo-measured gene essentiality data. After our modifications, the new in vivo network contained 663 genes, 838 metabolites, and 1,049 reactions and had a significantly increased sensitivity (0.81 in predicted gene essentiality than the in vitro network (0.31. We verified the modifications generated from the purely computational analysis through a review of the literature and found, for example, that, as the analysis suggested, lipids are used as the main source for carbon metabolism and oxygen must be available for the pathogen under in vivo conditions. Moreover, we used the developed in vivo network to predict the effects of double-gene deletions on M. tuberculosis growth in the host environment, explore metabolic adaptations to life in an acidic environment, highlight the importance of different enzymes in the tricarboxylic acid-cycle under different limiting nutrient conditions, investigate the effects of inhibiting multiple reactions, and look at the importance of both aerobic and anaerobic cellular respiration during infection. Conclusions The network modifications we implemented suggest a distinctive set of metabolic conditions and requirements faced by M. tuberculosis during

  18. Visualization of Metabolic Interaction Networks in Microbial Communities Using VisANT 5.0.

    Brian R Granger

    2016-04-01

    Full Text Available The complexity of metabolic networks in microbial communities poses an unresolved visualization and interpretation challenge. We address this challenge in the newly expanded version of a software tool for the analysis of biological networks, VisANT 5.0. We focus in particular on facilitating the visual exploration of metabolic interaction between microbes in a community, e.g. as predicted by COMETS (Computation of Microbial Ecosystems in Time and Space, a dynamic stoichiometric modeling framework. Using VisANT's unique metagraph implementation, we show how one can use VisANT 5.0 to explore different time-dependent ecosystem-level metabolic networks. In particular, we analyze the metabolic interaction network between two bacteria previously shown to display an obligate cross-feeding interdependency. In addition, we illustrate how a putative minimal gut microbiome community could be represented in our framework, making it possible to highlight interactions across multiple coexisting species. We envisage that the "symbiotic layout" of VisANT can be employed as a general tool for the analysis of metabolism in complex microbial communities as well as heterogeneous human tissues. VisANT is freely available at: http://visant.bu.edu and COMETS at http://comets.bu.edu.

  19. Visualization of Metabolic Interaction Networks in Microbial Communities Using VisANT 5.0.

    Granger, Brian R; Chang, Yi-Chien; Wang, Yan; DeLisi, Charles; Segrè, Daniel; Hu, Zhenjun

    2016-04-01

    The complexity of metabolic networks in microbial communities poses an unresolved visualization and interpretation challenge. We address this challenge in the newly expanded version of a software tool for the analysis of biological networks, VisANT 5.0. We focus in particular on facilitating the visual exploration of metabolic interaction between microbes in a community, e.g. as predicted by COMETS (Computation of Microbial Ecosystems in Time and Space), a dynamic stoichiometric modeling framework. Using VisANT's unique metagraph implementation, we show how one can use VisANT 5.0 to explore different time-dependent ecosystem-level metabolic networks. In particular, we analyze the metabolic interaction network between two bacteria previously shown to display an obligate cross-feeding interdependency. In addition, we illustrate how a putative minimal gut microbiome community could be represented in our framework, making it possible to highlight interactions across multiple coexisting species. We envisage that the "symbiotic layout" of VisANT can be employed as a general tool for the analysis of metabolism in complex microbial communities as well as heterogeneous human tissues. VisANT is freely available at: http://visant.bu.edu and COMETS at http://comets.bu.edu.

  20. Local and global control of ecological and biological networks

    Alessandro Ferrarini

    2014-01-01

    Recently, I introduced a methodological framework so that ecological and biological networks can be controlled both from inside and outside by coupling network dynamics and evolutionary modelling. The endogenous control requires the network to be optimized at the beginning of its dynamics (by acting upon nodes, edges or both) so that it will then go inertially to the desired state. Instead, the exogenous control requires that exogenous controllers act upon the network at each time step. By th...

  1. FluxVisualizer, a Software to Visualize Fluxes through Metabolic Networks

    Tim Daniel Rose

    2018-04-01

    Full Text Available FluxVisualizer (Version 1.0, 2017, freely available at https://fluxvisualizer.ibgc.cnrs.fr is a software to visualize fluxes values on a scalable vector graphic (SVG representation of a metabolic network by colouring or increasing the width of reaction arrows of the SVG file. FluxVisualizer does not aim to draw metabolic networks but to use a customer’s SVG file allowing him to exploit his representation standards with a minimum of constraints. FluxVisualizer is especially suitable for small to medium size metabolic networks, where a visual representation of the fluxes makes sense. The flux distribution can either be an elementary flux mode (EFM, a flux balance analysis (FBA result or any other flux distribution. It allows the automatic visualization of a series of pathways of the same network as is needed for a set of EFMs. The software is coded in python3 and provides a graphical user interface (GUI and an application programming interface (API. All functionalities of the program can be used from the API and the GUI and allows advanced users to add their own functionalities. The software is able to work with various formats of flux distributions (Metatool, CellNetAnalyzer, COPASI and FAME export files as well as with Excel files. This simple software can save a lot of time when evaluating fluxes simulations on a metabolic network.

  2. The Global Network of Biofuel Sustainability Standards-setters

    Henriksen, Lasse Folke

    2015-01-01

    the relevance of incorporating in the current attributional conception of hybridity a network element, taking seriously the role of network structure in shaping regulatory fields. Social Network Analysis as an analytical tool holds great potential for further research into the structural features of hybrid...

  3. Conserved Metabolic Changes in Nondiabetic and Type 2 Diabetic Bariatric Surgery Patients: Global Metabolomic Pilot Study

    Konrad Sarosiek

    2016-01-01

    Full Text Available The goal of this study was to provide insight into the mechanism by which bariatric surgical procedures led to weight loss and improvement or resolution of diabetes. Global biochemical profiling was used to evaluate changes occurring in nondiabetic and type 2 diabetic (T2D patients experiencing either less extreme sleeve gastrectomy or a full gastric bypass. We were able to identify changes in metabolism that were affected by standard preoperation liquid weight loss diet as well as by bariatric surgery itself. Preoperation weight-loss diet was associated with a strong lipid metabolism signature largely related to the consumption of adipose reserves for energy production. Glucose usage shift away from glycolytic pyruvate production toward pentose phosphate pathway, via glucose-6-phosphate, appeared to be shared across all patients regardless of T2D status or bariatric surgery procedure. Our results suggested that bariatric surgery might promote antioxidant defense and insulin sensitivity through both increased heme synthesis and HO activity or expression. Changes in histidine and its metabolites following surgery might be an indication of altered gut microbiome ecology or liver function. This initial study provided broad understanding of how metabolism changed globally in morbidly obese nondiabetic and T2D patients following weight-loss surgery.

  4. Human-Centered Development of an Online Social Network for Metabolic Syndrome Management.

    Núñez-Nava, Jefersson; Orozco-Sánchez, Paola A; López, Diego M; Ceron, Jesus D; Alvarez-Rosero, Rosa E

    2016-01-01

    According to the International Diabetes Federation (IDF), a quarter of the world's population has Metabolic Syndrome (MS). To develop (and assess the users' degree of satisfaction of) an online social network for patients who suffer from Metabolic Syndrome, based on the recommendations and requirements of the Human-Centered Design. Following the recommendations of the ISO 9241-210 for Human-Centered Design (HCD), an online social network was designed to promote physical activity and healthy nutrition. In order to guarantee the active participation of the users during the development of the social network, a survey, an in-depth interview, a focal group, and usability tests were carried out with people suffering from MS. The study demonstrated how the different activities, recommendations, and requirements of the ISO 9241-210 are integrated into a traditional software development process. Early usability tests demonstrated that the user's acceptance and the effectiveness and efficiency of the social network are satisfactory.

  5. How Sustainable are Benefits from Global Production Networks? Malaysia's Upgrading Prospects in the Electronics Industry

    Dieter Ernst

    2003-01-01

    The paper introduces an operational definition of industrial upgrading (IU and documents the emergence of complex, multi-tier "networks of networks" which provide new opportunities for IU, but which also raise threshold requirements for participating in these networks. I highlight structural weaknesses of the Malaysian electronics industry that constrain its upgrading prospects; assess current policies that try to link cluster development and global network integration; discuss adjustments in...

  6. Impact of the topology of global macroeconomic network on the spreading of economic crises.

    Lee, Kyu-Min; Yang, Jae-Suk; Kim, Gunn; Lee, Jaesung; Goh, Kwang-Il; Kim, In-mook

    2011-03-31

    Throughout economic history, the global economy has experienced recurring crises. The persistent recurrence of such economic crises calls for an understanding of their generic features rather than treating them as singular events. The global economic system is a highly complex system and can best be viewed in terms of a network of interacting macroeconomic agents. In this regard, from the perspective of collective network dynamics, here we explore how the topology of the global macroeconomic network affects the patterns of spreading of economic crises. Using a simple toy model of crisis spreading, we demonstrate that an individual country's role in crisis spreading is not only dependent on its gross macroeconomic capacities, but also on its local and global connectivity profile in the context of the world economic network. We find that on one hand clustering of weak links at the regional scale can significantly aggravate the spread of crises, but on the other hand the current network structure at the global scale harbors higher tolerance of extreme crises compared to more "globalized" random networks. These results suggest that there can be a potential hidden cost in the ongoing globalization movement towards establishing less-constrained, trans-regional economic links between countries, by increasing vulnerability of the global economic system to extreme crises.

  7. Do all roads lead to Rome? A comparison of brain networks derived from inter-subject volumetric and metabolic covariance and moment-to-moment hemodynamic correlations in old individuals.

    Di, Xin; Gohel, Suril; Thielcke, Andre; Wehrl, Hans F; Biswal, Bharat B

    2017-11-01

    Relationships between spatially remote brain regions in human have typically been estimated by moment-to-moment correlations of blood-oxygen-level dependent signals in resting-state using functional MRI (fMRI). Recently, studies using subject-to-subject covariance of anatomical volumes, cortical thickness, and metabolic activity are becoming increasingly popular. However, question remains on whether these measures reflect the same inter-region connectivity and brain network organizations. In the current study, we systematically analyzed inter-subject volumetric covariance from anatomical MRI images, metabolic covariance from fluorodeoxyglucose positron emission tomography images from 193 healthy subjects, and resting-state moment-to-moment correlations from fMRI images of a subset of 44 subjects. The correlation matrices calculated from the three methods were found to be minimally correlated, with higher correlation in the range of 0.31, as well as limited proportion of overlapping connections. The volumetric network showed the highest global efficiency and lowest mean clustering coefficient, leaning toward random-like network, while the metabolic and resting-state networks conveyed properties more resembling small-world networks. Community structures of the volumetric and metabolic networks did not reflect known functional organizations, which could be observed in resting-state network. The current results suggested that inter-subject volumetric and metabolic covariance do not necessarily reflect the inter-regional relationships and network organizations as resting-state correlations, thus calling for cautions on interpreting results of inter-subject covariance networks.

  8. Modeling the Metabolism of Arabidopsis thaliana: Application of Network Decomposition and Network Reduction in the Context of Petri Nets

    Ina Koch

    2017-06-01

    Full Text Available Motivation:Arabidopsis thaliana is a well-established model system for the analysis of the basic physiological and metabolic pathways of plants. Nevertheless, the system is not yet fully understood, although many mechanisms are described, and information for many processes exists. However, the combination and interpretation of the large amount of biological data remain a big challenge, not only because data sets for metabolic paths are still incomplete. Moreover, they are often inconsistent, because they are coming from different experiments of various scales, regarding, for example, accuracy and/or significance. Here, theoretical modeling is powerful to formulate hypotheses for pathways and the dynamics of the metabolism, even if the biological data are incomplete. To develop reliable mathematical models they have to be proven for consistency. This is still a challenging task because many verification techniques fail already for middle-sized models. Consequently, new methods, like decomposition methods or reduction approaches, are developed to circumvent this problem.Methods: We present a new semi-quantitative mathematical model of the metabolism of Arabidopsis thaliana. We used the Petri net formalism to express the complex reaction system in a mathematically unique manner. To verify the model for correctness and consistency we applied concepts of network decomposition and network reduction such as transition invariants, common transition pairs, and invariant transition pairs.Results: We formulated the core metabolism of Arabidopsis thaliana based on recent knowledge from literature, including the Calvin cycle, glycolysis and citric acid cycle, glyoxylate cycle, urea cycle, sucrose synthesis, and the starch metabolism. By applying network decomposition and reduction techniques at steady-state conditions, we suggest a straightforward mathematical modeling process. We demonstrate that potential steady-state pathways exist, which provide the

  9. Network-based analysis of the sphingolipid metabolism in hypertension

    Fenger, Mogens; Linneberg, Allan; Jeppesen, Jørgen

    2015-01-01

    Common diseases like essential hypertension or diabetes mellitus are complex as they are polygenic in nature, such that each genetic variation only has a small influence on the disease. Genes operates in integrated networks providing the blue-print for all biological processes and conditional...

  10. Global exponential stability of fuzzy cellular neural networks with delays and reaction-diffusion terms

    Wang Jian; Lu Junguo

    2008-01-01

    In this paper, we study the global exponential stability of fuzzy cellular neural networks with delays and reaction-diffusion terms. By constructing a suitable Lyapunov functional and utilizing some inequality techniques, we obtain a sufficient condition for the uniqueness and global exponential stability of the equilibrium solution for a class of fuzzy cellular neural networks with delays and reaction-diffusion terms. The result imposes constraint conditions on the network parameters independently of the delay parameter. The result is also easy to check and plays an important role in the design and application of globally exponentially stable fuzzy neural circuits

  11. Flux Balance Analysis of Cyanobacterial Metabolism.The Metabolic Network of Synechocystis sp. PCC 6803

    Knoop, H.; Gründel, M.; Zilliges, Y.; Lehmann, R.; Hoffmann, S.; Lockau, W.; Steuer, Ralf

    2013-01-01

    Roč. 9, č. 6 (2013), e1003081-e1003081 ISSN 1553-7358 R&D Projects: GA MŠk(CZ) EE2.3.20.0256 Institutional support: RVO:67179843 Keywords : SP STRAIN PCC-6803 * SP ATCC 51142 * photoautotrophic metabolism * anacystis-nidulans * reconstructions * pathway * plants * models * growth Subject RIV: EI - Biotechnology ; Bionics Impact factor: 4.829, year: 2013

  12. Abnormal metabolic brain networks in Parkinson's disease from blackboard to bedside.

    Tang, Chris C; Eidelberg, David

    2010-01-01

    Metabolic imaging in the rest state has provided valuable information concerning the abnormalities of regional brain function that underlie idiopathic Parkinson's disease (PD). Moreover, network modeling procedures, such as spatial covariance analysis, have further allowed for the quantification of these changes at the systems level. In recent years, we have utilized this strategy to identify and validate three discrete metabolic networks in PD associated with the motor and cognitive manifestations of the disease. In this chapter, we will review and compare the specific functional topographies underlying parkinsonian akinesia/rigidity, tremor, and cognitive disturbance. While network activity progressed over time, the rate of change for each pattern was distinctive and paralleled the development of the corresponding clinical symptoms in early-stage patients. This approach is already showing great promise in identifying individuals with prodromal manifestations of PD and in assessing the rate of progression before clinical onset. Network modulation was found to correlate with the clinical effects of dopaminergic treatment and surgical interventions, such as subthalamic nucleus (STN) deep brain stimulation (DBS) and gene therapy. Abnormal metabolic networks have also been identified for atypical parkinsonian syndromes, such as multiple system atrophy (MSA) and progressive supranuclear palsy (PSP). Using multiple disease-related networks for PD, MSA, and PSP, we have developed a novel, fully automated algorithm for accurate classification at the single-patient level, even at early disease stages. Copyright © 2010 Elsevier B.V. All rights reserved.

  13. American cities, global networks: mapping the multiple geographies of globalization in the Americas

    Toly, N.J.; Bouteligier, S.; Smith, G.; Gibson, B.

    2012-01-01

    The mapping of advanced producer and financial service firms across global cities began to increase understanding of the role of cities in global governance, the presence and influence of cities in the shifting architecture of global political economy, and the role of globalization in shaping the

  14. Exploiting global information in complex network repair processes

    Tianyu WANG; Jun ZHANG; Sebastian WANDELT

    2017-01-01

    Robustness of complex networks has been studied for decades,with a particular focus on network attack.Research on network repair,on the other hand,has been conducted only very lately,given the even higher complexity and absence of an effective evaluation metric.A recently proposed network repair strategy is self-healing,which aims to repair networks for larger compo nents at a low cost only with local information.In this paper,we discuss the effectiveness and effi ciency of self-healing,which limits network repair to be a multi-objective optimization problem and makes it difficult to measure its optimality.This leads us to a new network repair evaluation metric.Since the time complexity of the computation is very high,we devise a greedy ranking strategy.Evaluations on both real-world and random networks show the effectiveness of our new metric and repair strategy.Our study contributes to optimal network repair algorithms and provides a gold standard for future studies on network repair.

  15. Global loss of bmal1 expression alters adipose tissue hormones, gene expression and glucose metabolism.

    David John Kennaway

    Full Text Available The close relationship between circadian rhythm disruption and poor metabolic status is becoming increasingly evident, but role of adipokines is poorly understood. Here we investigated adipocyte function and the metabolic status of mice with a global loss of the core clock gene Bmal1 fed either a normal or a high fat diet (22% by weight. Bmal1 null mice aged 2 months were killed across 24 hours and plasma adiponectin and leptin, and adipose tissue expression of Adipoq, Lep, Retn and Nampt mRNA measured. Glucose, insulin and pyruvate tolerance tests were conducted and the expression of liver glycolytic and gluconeogenic enzyme mRNA determined. Bmal1 null mice displayed a pattern of increased plasma adiponectin and plasma leptin concentrations on both control and high fat diets. Bmal1 null male and female mice displayed increased adiposity (1.8 fold and 2.3 fold respectively on the normal diet, but the high fat diet did not exaggerate these differences. Despite normal glucose and insulin tolerance, Bmal1 null mice had increased production of glucose from pyruvate, implying increased liver gluconeogenesis. The Bmal1 null mice had arrhythmic clock gene expression in epigonadal fat and liver, and loss of rhythmic transcription of a range of metabolic genes. Furthermore, the expression of epigonadal fat Adipoq, Retn, Nampt, AdipoR1 and AdipoR2 and liver Pfkfb3 mRNA were down-regulated. These results show for the first time that global loss of Bmal1, and the consequent arrhythmicity, results in compensatory changes in adipokines involved in the cellular control of glucose metabolism.

  16. Managerial capabilities of the home base in an intra-organisational global network

    Mykhaylenko, Alona

    of the HB change in the process of its global intra-organisational network evolution. In particular, the four papers constituting this thesis investigate how global intra-organisational networks evolve, how the types of network management capabilities of the HB change along with such network evolution....... This investigation was conducted through a retrospective longitudinal case study of one Danish original equipment manufacturer and its three subsidiaries in China, Slovakia, and the US. The findings, first of all, support, extend, and modify the revised Uppsala globalisation model with regard to the types...

  17. Metabolic Vascular Syndrome: New Insights into a Multidimensional Network of Risk Factors and Diseases.

    Scholz, Gerhard H; Hanefeld, Markolf

    2016-10-01

    Since 1981, we have used the term metabolic syndrome to describe an association of a dysregulation in lipid metabolism (high triglycerides, low high-density lipoprotein cholesterol, disturbed glucose homeostasis (enhanced fasting and/or prandial glucose), gout, and hypertension), with android obesity being based on a common soil (overnutrition, reduced physical activity, sociocultural factors, and genetic predisposition). We hypothesized that main traits of the syndrome occur early and are tightly connected with hyperinsulinemia/insulin resistance, procoagulation, and cardiovascular diseases. To establish a close link between the traits of the metabolic vascular syndrome, we focused our literature search on recent original work and comprehensive reviews dealing with the topics metabolic syndrome, visceral obesity, fatty liver, fat tissue inflammation, insulin resistance, atherogenic dyslipidemia, arterial hypertension, and type 2 diabetes mellitus. Recent research supports the concept that the metabolic vascular syndrome is a multidimensional and interactive network of risk factors and diseases based on individual genetic susceptibility and epigenetic changes where metabolic dysregulation/metabolic inflexibility in different organs and vascular dysfunction are early interconnected. The metabolic vascular syndrome is not only a risk factor constellation but rather a life-long abnormality of a closely connected interactive cluster of developing diseases which escalate each other and should continuously attract the attention of every clinician.

  18. Systems Nutrigenomics Reveals Brain Gene Networks Linking Metabolic and Brain Disorders.

    Meng, Qingying; Ying, Zhe; Noble, Emily; Zhao, Yuqi; Agrawal, Rahul; Mikhail, Andrew; Zhuang, Yumei; Tyagi, Ethika; Zhang, Qing; Lee, Jae-Hyung; Morselli, Marco; Orozco, Luz; Guo, Weilong; Kilts, Tina M; Zhu, Jun; Zhang, Bin; Pellegrini, Matteo; Xiao, Xinshu; Young, Marian F; Gomez-Pinilla, Fernando; Yang, Xia

    2016-05-01

    Nutrition plays a significant role in the increasing prevalence of metabolic and brain disorders. Here we employ systems nutrigenomics to scrutinize the genomic bases of nutrient-host interaction underlying disease predisposition or therapeutic potential. We conducted transcriptome and epigenome sequencing of hypothalamus (metabolic control) and hippocampus (cognitive processing) from a rodent model of fructose consumption, and identified significant reprogramming of DNA methylation, transcript abundance, alternative splicing, and gene networks governing cell metabolism, cell communication, inflammation, and neuronal signaling. These signals converged with genetic causal risks of metabolic, neurological, and psychiatric disorders revealed in humans. Gene network modeling uncovered the extracellular matrix genes Bgn and Fmod as main orchestrators of the effects of fructose, as validated using two knockout mouse models. We further demonstrate that an omega-3 fatty acid, DHA, reverses the genomic and network perturbations elicited by fructose, providing molecular support for nutritional interventions to counteract diet-induced metabolic and brain disorders. Our integrative approach complementing rodent and human studies supports the applicability of nutrigenomics principles to predict disease susceptibility and to guide personalized medicine. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

  19. From global agenda-setting to domestic implementation: successes and challenges of the global health network on tobacco control.

    Gneiting, Uwe

    2016-04-01

    Global policy attention to tobacco control has increased significantly since the 1990 s and culminated in the first international treaty negotiated under the auspices of the World Health Organization--the Framework Convention on Tobacco Control (FCTC). Although the political process that led to the creation of the FCTC has been extensively researched, the FCTC's progression from an aspirational treaty towards a global health governance framework with tangible policy effects within FCTC member countries has not been well-understood to date. This article analyses the role of the global health network of tobacco control advocates and scientists, which formed during the FCTC negotiations during the late 1990 s, in translating countries' commitment to the FCTC into domestic policy change. By comparing the network's influence around two central tobacco control interventions (smoke-free environments and taxation), the study identifies several scope conditions, which have shaped the network's effectiveness around the FCTC's implementation: the complexity of the policy issue and the relative importance of non-health expertise, the required scope of domestic political buy-in, the role of the general public as network allies, and the strength of policy opposition. These political factors had a greater influence on the network's success than the evidence base for the effectiveness of tobacco control interventions. The network's variable success points to a trade-off faced by global health networks between their need to maintain internal cohesion and their ability to form alliances with actors in their social environment. Published by Oxford University Press in association with The London School of Hygiene and Tropical Medicine © The Author 2015; all rights reserved.

  20. pbdd's global project and the educational research network of west

    IDRC'S PARTNERSHIP AND BUSINESS DEVELOPMENT DIVISION (PBDD) INITIATES, ... determines broad network strategic orientations and a regional scientific .... dissemination workshop of a transnational project on the integration of.

  1. Deciphering Fur transcriptional regulatory network highlights its complex role beyond iron metabolism in Escherichia coli

    Seo, Sang Woo; Kim, Donghyuk; Latif, Haythem

    2014-01-01

    The ferric uptake regulator (Fur) plays a critical role in the transcriptional regulation of iron metabolism. However, the full regulatory potential of Fur remains undefined. Here we comprehensively reconstruct the Fur transcriptional regulatory network in Escherichia coli K-12 MG1655 in response...

  2. Limitations of a metabolic network-based reverse ecology method for inferring host-pathogen interactions.

    Takemoto, Kazuhiro; Aie, Kazuki

    2017-05-25

    Host-pathogen interactions are important in a wide range of research fields. Given the importance of metabolic crosstalk between hosts and pathogens, a metabolic network-based reverse ecology method was proposed to infer these interactions. However, the validity of this method remains unclear because of the various explanations presented and the influence of potentially confounding factors that have thus far been neglected. We re-evaluated the importance of the reverse ecology method for evaluating host-pathogen interactions while statistically controlling for confounding effects using oxygen requirement, genome, metabolic network, and phylogeny data. Our data analyses showed that host-pathogen interactions were more strongly influenced by genome size, primary network parameters (e.g., number of edges), oxygen requirement, and phylogeny than the reserve ecology-based measures. These results indicate the limitations of the reverse ecology method; however, they do not discount the importance of adopting reverse ecology approaches altogether. Rather, we highlight the need for developing more suitable methods for inferring host-pathogen interactions and conducting more careful examinations of the relationships between metabolic networks and host-pathogen interactions.

  3. Random sampling of elementary flux modes in large-scale metabolic networks.

    Machado, Daniel; Soons, Zita; Patil, Kiran Raosaheb; Ferreira, Eugénio C; Rocha, Isabel

    2012-09-15

    The description of a metabolic network in terms of elementary (flux) modes (EMs) provides an important framework for metabolic pathway analysis. However, their application to large networks has been hampered by the combinatorial explosion in the number of modes. In this work, we develop a method for generating random samples of EMs without computing the whole set. Our algorithm is an adaptation of the canonical basis approach, where we add an additional filtering step which, at each iteration, selects a random subset of the new combinations of modes. In order to obtain an unbiased sample, all candidates are assigned the same probability of getting selected. This approach avoids the exponential growth of the number of modes during computation, thus generating a random sample of the complete set of EMs within reasonable time. We generated samples of different sizes for a metabolic network of Escherichia coli, and observed that they preserve several properties of the full EM set. It is also shown that EM sampling can be used for rational strain design. A well distributed sample, that is representative of the complete set of EMs, should be suitable to most EM-based methods for analysis and optimization of metabolic networks. Source code for a cross-platform implementation in Python is freely available at http://code.google.com/p/emsampler. dmachado@deb.uminho.pt Supplementary data are available at Bioinformatics online.

  4. The Theoretical Aspects of the Development of Global Production Networks and Value Chains: the New Paradigm of Globalization

    Cherkas Nataliia I.

    2018-03-01

    Full Text Available The article is aimed at systematizing the contemporary perceptions of the changing paradigms of globalization and international competition as a result of the spread of global networks and value chains. The development of global value chains (GVC occurred as a result of two distributions of globalization: (1 global competition is manifested at the level of sectors and companies (from the mid-nineteenth century (2 the concept of trade in tasks arises (at the end of XX century. The publication analyzes the impact of globalization on the international competitiveness of both the EU and the developing countries in the trade of final products and tasks. The model takes into consideration differences in wages, technology gap and trade costs, and provides for assessing the comparative advantages of individual sectors or segments of GVC. Features of the conception of global production networks have been identified as: «imports for production» and «imports for exports», which define international competitiveness on the basis of creation of the intrinsic value added. It is determined that the competitiveness of the economy is determined by the country’s positions in the GVC, and the increase in productivity of companies depends on their involvement in the segments (tasks with a high level of value added.

  5. Metabolic network modeling of microbial interactions in natural and engineered environmental systems

    Octavio ePerez-Garcia

    2016-05-01

    Full Text Available We review approaches to characterize metabolic interactions within microbial communities using Stoichiometric Metabolic Network (SMN models for applications in environmental and industrial biotechnology. SMN models are computational tools used to evaluate the metabolic engineering potential of various organisms. They have successfully been applied to design and optimize the microbial production of antibiotics, alcohols and amino acids by single strains. To date however, such models have been rarely applied to analyze and control the metabolism of more complex microbial communities. This is largely attributed to the diversity of microbial community functions, metabolisms and interactions. Here, we firstly review different types of microbial interaction and describe their relevance for natural and engineered environmental processes. Next, we provide a general description of the essential methods of the SMN modeling workflow including the steps of network reconstruction, simulation through Flux Balance Analysis (FBA, experimental data gathering, and model calibration. Then we broadly describe and compare four approaches to model microbial interactions using metabolic networks, i.e. i lumped networks, ii compartment per guild networks, iii bi-level optimization simulations and iv dynamic-SMN methods. These approaches can be used to integrate and analyze diverse microbial physiology, ecology and molecular community data. All of them (except the lumped approach are suitable for incorporating species abundance data but so far they have been used only to model simple communities of two to eight different species. Interactions based on substrate exchange and competition can be directly modeled using the above approaches. However, interactions based on metabolic feedbacks, such as product inhibition and synthropy require extensions to current models, incorporating gene regulation and compounding accumulation mechanisms. SMN models of microbial

  6. Alignment of global supply networks based on strategic groups of supply chains

    Nikos G. Moraitakis

    2017-09-01

    Full Text Available Background: From a supply chain perspective, often big differences exist between global raw material suppliers’ approaches to supply their respective local markets. The progressing complexity of large centrally managed global supply networks and their often-unknown upstream ramifications increase the likelihood of undetected bottlenecks and inefficiencies. It is therefore necessary to develop an approach to strategically master the upstream complexity of such networks from a holistic supply chain perspective in order to align regional competitive priorities and supply chain structures. The objective of this research is hence to develop an approach for the supply-chain-based alignment of complex global supply networks. Method: We review existing literature from the fields of supply chain and network management, strategic sourcing, and strategic management. Based on the literature review and theoretical and practical considerations we deduce a conceptual approach to consider upstream supply chain structures in supply network alignment initiatives. Results: On the basis of these considerations and current empirical literature we transfer strategic group theory to the supply network management context. The proposed approach introduces strategic groups of supply chains as a segmentation criterion for complex global supply networks which enables the network-wide alignment of competitive priorities. Conclusion: Supply-chain-based segmentation of global supply network structures can effectively reduce the complexity, firms face when aiming to strategically align their supply chains on a holistic level. The results of this research are applicable for certain types of global supply networks and can be used for network alignment and strategy development. The approach can furthermore generate insights useable for negotiation support with suppliers.

  7. Global efficiency of structural networks mediates cognitive control in Mild Cognitive Impairment

    Rok Berlot

    2016-12-01

    Full Text Available Background: Cognitive control has been linked to both the microstructure of individual tracts and the structure of whole-brain networks, but their relative contributions in health and disease remain unclear. Objective: To determine the contribution of both localised white matter tract damage and disruption of global network architecture to cognitive control, in older age and Mild Cognitive Impairment (MCI.Methods: 25 patients with MCI and 20 age, sex and intelligence-matched healthy volunteers were investigated with 3 Tesla structural magnetic resonance imaging (MRI. Cognitive control and episodic memory were evaluated with established tests. Structural network graphs were constructed from diffusion MRI-based whole-brain tractography. Their global measures were calculated using graph theory. Regression models utilized both global network metrics and microstructure of specific connections, known to be critical for each domain, to predict cognitive scores. Results: Global efficiency and the mean clustering coefficient of networks were reduced in MCI. Cognitive control was associated with global network topology. Episodic memory, in contrast, correlated with individual temporal tracts only. Relationships between cognitive control and network topology were attenuated by addition of single tract measures to regression models, consistent with a partial mediation effect. The mediation effect was stronger in MCI than healthy volunteers, explaining 23-36% of the effect of cingulum microstructure on cognitive control performance. Network clustering was a significant mediator in the relationship between tract microstructure and cognitive control in both groups. Conclusions: The status of critical connections and large-scale network topology are both important for maintenance of cognitive control in MCI. Mediation via large-scale networks is more important in patients with MCI than healthy volunteers. This effect is domain-specific, and true for cognitive

  8. Association of structural global brain network properties with intelligence in normal aging.

    Florian U Fischer

    Full Text Available Higher general intelligence attenuates age-associated cognitive decline and the risk of dementia. Thus, intelligence has been associated with cognitive reserve or resilience in normal aging. Neurophysiologically, intelligence is considered as a complex capacity that is dependent on a global cognitive network rather than isolated brain areas. An association of structural as well as functional brain network characteristics with intelligence has already been reported in young adults. We investigated the relationship between global structural brain network properties, general intelligence and age in a group of 43 cognitively healthy elderly, age 60-85 years. Individuals were assessed cross-sectionally using Wechsler Adult Intelligence Scale-Revised (WAIS-R and diffusion-tensor imaging. Structural brain networks were reconstructed individually using deterministic tractography, global network properties (global efficiency, mean shortest path length, and clustering coefficient were determined by graph theory and correlated to intelligence scores within both age groups. Network properties were significantly correlated to age, whereas no significant correlation to WAIS-R was observed. However, in a subgroup of 15 individuals aged 75 and above, the network properties were significantly correlated to WAIS-R. Our findings suggest that general intelligence and global properties of structural brain networks may not be generally associated in cognitively healthy elderly. However, we provide first evidence of an association between global structural brain network properties and general intelligence in advanced elderly. Intelligence might be affected by age-associated network deterioration only if a certain threshold of structural degeneration is exceeded. Thus, age-associated brain structural changes seem to be partially compensated by the network and the range of this compensation might be a surrogate of cognitive reserve or brain resilience.

  9. Association of Structural Global Brain Network Properties with Intelligence in Normal Aging

    Fischer, Florian U.; Wolf, Dominik; Scheurich, Armin; Fellgiebel, Andreas

    2014-01-01

    Higher general intelligence attenuates age-associated cognitive decline and the risk of dementia. Thus, intelligence has been associated with cognitive reserve or resilience in normal aging. Neurophysiologically, intelligence is considered as a complex capacity that is dependent on a global cognitive network rather than isolated brain areas. An association of structural as well as functional brain network characteristics with intelligence has already been reported in young adults. We investigated the relationship between global structural brain network properties, general intelligence and age in a group of 43 cognitively healthy elderly, age 60–85 years. Individuals were assessed cross-sectionally using Wechsler Adult Intelligence Scale-Revised (WAIS-R) and diffusion-tensor imaging. Structural brain networks were reconstructed individually using deterministic tractography, global network properties (global efficiency, mean shortest path length, and clustering coefficient) were determined by graph theory and correlated to intelligence scores within both age groups. Network properties were significantly correlated to age, whereas no significant correlation to WAIS-R was observed. However, in a subgroup of 15 individuals aged 75 and above, the network properties were significantly correlated to WAIS-R. Our findings suggest that general intelligence and global properties of structural brain networks may not be generally associated in cognitively healthy elderly. However, we provide first evidence of an association between global structural brain network properties and general intelligence in advanced elderly. Intelligence might be affected by age-associated network deterioration only if a certain threshold of structural degeneration is exceeded. Thus, age-associated brain structural changes seem to be partially compensated by the network and the range of this compensation might be a surrogate of cognitive reserve or brain resilience. PMID:24465994

  10. The evolution of enterprises in the global network competition

    Borghoff,Thomas; Welge,Martin K.

    2001-01-01

    The globalization of a company is embedded in the globalization of its task environment. This process can be described as a co-evolutionary process of a social system in its environment. A historical view of the globalization of competition seems to prove that it can be interpreted as an evolutionary process of differentiation and integration that is reinforced by the decreasing rigidity of boundaries. A liquefaction of competition" can be observed, in which an increasing number of autonomous...

  11. Dynamic Metabolic Footprinting Reveals the Key Components of Metabolic Network in Yeast Saccharomyces cerevisiae

    Chumnanpuen, Pramote; Hansen, Michael Adsetts Edberg; Smedsgaard, Jørn

    2014-01-01

    relies on analysis at a single time point. Using direct infusion-mass spectrometry (DI-MS), we could observe the dynamic metabolic footprinting in yeast S. cerevisiae BY4709 (wild type) cultured on 3 different C-sources (glucose, glycerol, and ethanol) and sampled along 10 time points with 5 biological...... replicates. In order to analyze the dynamic mass spectrometry data, we developed the novel analysis methods that allow us to perform correlation analysis to identify metabolites that significantly correlate over time during growth on the different carbon sources. Both positive and negative electrospray...... reconstructed an interaction map that provides information of how different metabolic pathways have correlated patterns during growth on the different carbon sources....

  12. Development of an internet based system for modeling biotin metabolism using Bayesian networks.

    Zhou, Jinglei; Wang, Dong; Schlegel, Vicki; Zempleni, Janos

    2011-11-01

    Biotin is an essential water-soluble vitamin crucial for maintaining normal body functions. The importance of biotin for human health has been under-appreciated but there is plenty of opportunity for future research with great importance for human health. Currently, carrying out predictions of biotin metabolism involves tedious manual manipulations. In this paper, we report the development of BiotinNet, an internet based program that uses Bayesian networks to integrate published data on various aspects of biotin metabolism. Users can provide a combination of values on the levels of biotin related metabolites to obtain the predictions on other metabolites that are not specified. As an inherent feature of Bayesian networks, the uncertainty of the prediction is also quantified and reported to the user. This program enables convenient in silico experiments regarding biotin metabolism, which can help researchers design future experiments while new data can be continuously incorporated. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

  13. Identifying all moiety conservation laws in genome-scale metabolic networks.

    De Martino, Andrea; De Martino, Daniele; Mulet, Roberto; Pagnani, Andrea

    2014-01-01

    The stoichiometry of a metabolic network gives rise to a set of conservation laws for the aggregate level of specific pools of metabolites, which, on one hand, pose dynamical constraints that cross-link the variations of metabolite concentrations and, on the other, provide key insight into a cell's metabolic production capabilities. When the conserved quantity identifies with a chemical moiety, extracting all such conservation laws from the stoichiometry amounts to finding all non-negative integer solutions of a linear system, a programming problem known to be NP-hard. We present an efficient strategy to compute the complete set of integer conservation laws of a genome-scale stoichiometric matrix, also providing a certificate for correctness and maximality of the solution. Our method is deployed for the analysis of moiety conservation relationships in two large-scale reconstructions of the metabolism of the bacterium E. coli, in six tissue-specific human metabolic networks, and, finally, in the human reactome as a whole, revealing that bacterial metabolism could be evolutionarily designed to cover broader production spectra than human metabolism. Convergence to the full set of moiety conservation laws in each case is achieved in extremely reduced computing times. In addition, we uncover a scaling relation that links the size of the independent pool basis to the number of metabolites, for which we present an analytical explanation.

  14. Identifying all moiety conservation laws in genome-scale metabolic networks.

    Andrea De Martino

    Full Text Available The stoichiometry of a metabolic network gives rise to a set of conservation laws for the aggregate level of specific pools of metabolites, which, on one hand, pose dynamical constraints that cross-link the variations of metabolite concentrations and, on the other, provide key insight into a cell's metabolic production capabilities. When the conserved quantity identifies with a chemical moiety, extracting all such conservation laws from the stoichiometry amounts to finding all non-negative integer solutions of a linear system, a programming problem known to be NP-hard. We present an efficient strategy to compute the complete set of integer conservation laws of a genome-scale stoichiometric matrix, also providing a certificate for correctness and maximality of the solution. Our method is deployed for the analysis of moiety conservation relationships in two large-scale reconstructions of the metabolism of the bacterium E. coli, in six tissue-specific human metabolic networks, and, finally, in the human reactome as a whole, revealing that bacterial metabolism could be evolutionarily designed to cover broader production spectra than human metabolism. Convergence to the full set of moiety conservation laws in each case is achieved in extremely reduced computing times. In addition, we uncover a scaling relation that links the size of the independent pool basis to the number of metabolites, for which we present an analytical explanation.

  15. THE GLOBAL MARITIME PORTS IN LOGISTICS CHAINS AND SUPPLY NETWORKS

    Henryk SALMONOWICZ

    2014-12-01

    Full Text Available This article applies to the new role of seaports in the global economy and logistics. The paper presents trends in the development of the world economy and the dynamics of global trade. Attention was drawn to the role of different modes of transport to use global trade, especially on transcontinental nature of sea and air transport. The influence of the processes taking place in the global economy on a new role of seaports in the mass movement of cargo between points of origin and reception.

  16. Global Networks: Emerging Constraints on Strategy (Defense Horizons, July 2004)

    Fonow, Bob

    2004-01-01

    .... This shift is problematic for U.S. national security, because the global telecommunications infrastructure is becoming an important strategic battlespace the physical battlefield of information warfare...

  17. Monthly Summaries of the Global Historical Climatology Network - Daily (GHCN-D)

    National Oceanic and Atmospheric Administration, Department of Commerce — Monthly Summaries of Global Historical Climatology Network (GHCN)-Daily is a dataset derived from GHCN-Daily. The data are produced by computing simple averages or...

  18. CTFS-ForestGEO: A worldwide network monitoring forests in an era of global change

    Anderson-Teixeira, K.J.; Davies, S.J.; Bennett, A.C.; Gonzalez-Akre, E.B.; Muller-Landau, H.C.; Wright, S.J.; Abu Salim, K.; Almeyda Zambrano, A.M.; Jansen, P.A.; Ouden, den J.

    2015-01-01

    Global change is impacting forests worldwide, threatening biodiversity and ecosystem services including climate regulation. Understanding how forests respond is critical to forest conservation and climate protection. This review describes an international network of 59 long-term forest dynamics

  19. The Talloires Network: A Global Coalition of Engaged Universities

    Hollister, Robert M.; Pollock, John P.; Gearan, Mark; Reid, Janice; Stroud, Susan; Babcock, Elizabeth

    2012-01-01

    This article describes and analyzes the origins, work to date, and future of the Talloires Network, an international association of institutions committed to strengthening the civic roles and social responsibilities of higher education. Included are reflections on the network's strategies for advancing civic engagement in higher education…

  20. Global Network : Integration and Harmonization of ICT Policy and ...

    IDRC has invested in the development of three regional networks focused on issues of inclusive information and communication technology (ICT) policy and regulation: Latin America - REDIS/DIRSI (103371), Asia - LIRNEAsia (103017). Africa - LINK Centre (101584). The three regional research networks were built as ...

  1. Data-driven integration of genome-scale regulatory and metabolic network models

    Imam, Saheed; Schäuble, Sascha; Brooks, Aaron N.; Baliga, Nitin S.; Price, Nathan D.

    2015-01-01

    Microbes are diverse and extremely versatile organisms that play vital roles in all ecological niches. Understanding and harnessing microbial systems will be key to the sustainability of our planet. One approach to improving our knowledge of microbial processes is through data-driven and mechanism-informed computational modeling. Individual models of biological networks (such as metabolism, transcription, and signaling) have played pivotal roles in driving microbial research through the years. These networks, however, are highly interconnected and function in concert—a fact that has led to the development of a variety of approaches aimed at simulating the integrated functions of two or more network types. Though the task of integrating these different models is fraught with new challenges, the large amounts of high-throughput data sets being generated, and algorithms being developed, means that the time is at hand for concerted efforts to build integrated regulatory-metabolic networks in a data-driven fashion. In this perspective, we review current approaches for constructing integrated regulatory-metabolic models and outline new strategies for future development of these network models for any microbial system. PMID:25999934

  2. Data-driven integration of genome-scale regulatory and metabolic network models

    Saheed eImam

    2015-05-01

    Full Text Available Microbes are diverse and extremely versatile organisms that play vital roles in all ecological niches. Understanding and harnessing microbial systems will be key to the sustainability of our planet. One approach to improving our knowledge of microbial processes is through data-driven and mechanism-informed computational modeling. Individual models of biological networks (such as metabolism, transcription and signaling have played pivotal roles in driving microbial research through the years. These networks, however, are highly interconnected and function in concert – a fact that has led to the development of a variety of approaches aimed at simulating the integrated functions of two or more network types. Though the task of integrating these different models is fraught with new challenges, the large amounts of high-throughput data sets being generated, and algorithms being developed, means that the time is at hand for concerted efforts to build integrated regulatory-metabolic networks in a data-driven fashion. In this perspective, we review current approaches for constructing integrated regulatory-metabolic models and outline new strategies for future development of these network models for any microbial system.

  3. Global asymptotical ω-periodicity of a fractional-order non-autonomous neural networks.

    Chen, Boshan; Chen, Jiejie

    2015-08-01

    We study the global asymptotic ω-periodicity for a fractional-order non-autonomous neural networks. Firstly, based on the Caputo fractional-order derivative it is shown that ω-periodic or autonomous fractional-order neural networks cannot generate exactly ω-periodic signals. Next, by using the contraction mapping principle we discuss the existence and uniqueness of S-asymptotically ω-periodic solution for a class of fractional-order non-autonomous neural networks. Then by using a fractional-order differential and integral inequality technique, we study global Mittag-Leffler stability and global asymptotical periodicity of the fractional-order non-autonomous neural networks, which shows that all paths of the networks, starting from arbitrary points and responding to persistent, nonconstant ω-periodic external inputs, asymptotically converge to the same nonconstant ω-periodic function that may be not a solution. Copyright © 2015 Elsevier Ltd. All rights reserved.

  4. Analysing the Outbound logistics process enhancements in Nokia-Siemens Networks Global Distribution Center

    Marjeta, Katri

    2011-01-01

    Marjeta, Katri. 2011. Analysing the outbound logistics process enhancements in Nokia-Siemens Networks Global Distribution Center. Master´s thesis. Kemi-Tornio University of Applied Sciences. Business and Culture. Pages 57. Due to confidentiality issues, this work has been modified from its original form. The aim of this Master Thesis work is to describe and analyze the outbound logistics process enhancement projects executed in Nokia-Siemens Networks Global Distribution Center after the N...

  5. Alignment of global supply networks based on strategic groups of supply chains

    Nikos G. Moraitakis; Jiazhen Huo; Hans-Christian Pfohl

    2017-01-01

    Background: From a supply chain perspective, often big differences exist between global raw material suppliers’ approaches to supply their respective local markets. The progressing complexity of large centrally managed global supply networks and their often-unknown upstream ramifications increase the likelihood of undetected bottlenecks and inefficiencies. It is therefore necessary to develop an approach to strategically master the upstream complexity of such networks from a holistic su...

  6. Global exponential stability of reaction-diffusion recurrent neural networks with time-varying delays

    Liang Jinling; Cao Jinde

    2003-01-01

    Employing general Halanay inequality, we analyze the global exponential stability of a class of reaction-diffusion recurrent neural networks with time-varying delays. Several new sufficient conditions are obtained to ensure existence, uniqueness and global exponential stability of the equilibrium point of delayed reaction-diffusion recurrent neural networks. The results extend and improve the earlier publications. In addition, an example is given to show the effectiveness of the obtained result

  7. Global exponential stability of mixed discrete and distributively delayed cellular neural network

    Yao Hong-Xing; Zhou Jia-Yan

    2011-01-01

    This paper concernes analysis for the global exponential stability of a class of recurrent neural networks with mixed discrete and distributed delays. It first proves the existence and uniqueness of the balance point, then by employing the Lyapunov—Krasovskii functional and Young inequality, it gives the sufficient condition of global exponential stability of cellular neural network with mixed discrete and distributed delays, in addition, the example is provided to illustrate the applicability of the result. (general)

  8. Global exponential stability for reaction-diffusion recurrent neural networks with multiple time varying delays

    Lou, X.; Cui, B.

    2008-01-01

    In this paper we consider the problem of exponential stability for recurrent neural networks with multiple time varying delays and reaction-diffusion terms. The activation functions are supposed to be bounded and globally Lipschitz continuous. By means of Lyapunov functional, sufficient conditions are derived, which guarantee global exponential stability of the delayed neural network. Finally, a numerical example is given to show the correctness of our analysis. (author)

  9. A network of tongues: African languages, multilingualism and global ...

    Some scholars have noted that globalization portends 'a global common language' that offers unprecedented possibilities for mutual understanding and thus enables us to find fresh opportunities for international co-operation. Yet, others have argued in favour of multilingualism, described as an alternative, fundamental ...

  10. Governance of global organic agro-food networks from Africa

    Glin, L.C.

    2014-01-01

    The increasing global concerns with regard to agro-food risks and the subsequent consumerist turn in the global food economy challenges the conventional chemical-intensive agricultural production. In fact, the post-war dominant agro-industrial development fostered the intensive use of chemical

  11. Molecular Networking As a Drug Discovery, Drug Metabolism, and Precision Medicine Strategy.

    Quinn, Robert A; Nothias, Louis-Felix; Vining, Oliver; Meehan, Michael; Esquenazi, Eduardo; Dorrestein, Pieter C

    2017-02-01

    Molecular networking is a tandem mass spectrometry (MS/MS) data organizational approach that has been recently introduced in the drug discovery, metabolomics, and medical fields. The chemistry of molecules dictates how they will be fragmented by MS/MS in the gas phase and, therefore, two related molecules are likely to display similar fragment ion spectra. Molecular networking organizes the MS/MS data as a relational spectral network thereby mapping the chemistry that was detected in an MS/MS-based metabolomics experiment. Although the wider utility of molecular networking is just beginning to be recognized, in this review we highlight the principles behind molecular networking and its use for the discovery of therapeutic leads, monitoring drug metabolism, clinical diagnostics, and emerging applications in precision medicine. Copyright © 2016. Published by Elsevier Ltd.

  12. SONG China project - participating in the global network

    Deng, Licai; Xin, Yu; Zhang, Xiaobin; Li, Yan; Jiang, Xiaojun; Wang, Guomin; Wang, Kun; Zhou, Jilin; Yan, Zhengzhou; Luo, Zhiquan

    2013-01-01

    SONG (Stellar Observations Network Goup) is a low-cost ground based international collaboration aimed at two cutting edge problems in contemporary astrophysics in the time-domain: 1) Direct diagnostics of the internal structure of stars and 2) looking for and studying extra solar planets, possibly in the habitable zone. The general plan is to set up a network of 1m telescopes uniformly distributed in geographic latitude (in both hemispheres). China jointed the collaboration (initiated by Danish astronomers) at the very beginning. In addition to SONG's original plan (http://song.phys.au.dk), the Chinese team proposed a parallel photometry subnet work in the northern hemisphere, namely 50BiN (50cm Binocular Network, previously known as mini-SONG), to enable a large field photometric capability for the network, therefore maximising the potential of the network platform. The network will be able to produce nearly continuous time series observations of a number of selected objects with high resolution spectroscopy (SONG) and accurate photometry (50BiN), and to produce ultra-high accuracy photometry in dense field to look for micro-lensing events caused by planetary systems. This project has great synergy with Chinese Astronomical activities in Antarctica (Dome A), and other similar networks (e.g. LCOGT). The plan and current status of the project are overviewed in this poster.

  13. A Transcript-Specific eIF3 Complex Mediates Global Translational Control of Energy Metabolism.

    Shah, Meera; Su, Dan; Scheliga, Judith S; Pluskal, Tomáš; Boronat, Susanna; Motamedchaboki, Khatereh; Campos, Alexandre Rosa; Qi, Feng; Hidalgo, Elena; Yanagida, Mitsuhiro; Wolf, Dieter A

    2016-08-16

    The multi-subunit eukaryotic translation initiation factor eIF3 is thought to assist in the recruitment of ribosomes to mRNA. The expression of eIF3 subunits is frequently disrupted in human cancers, but the specific roles of individual subunits in mRNA translation and cancer remain elusive. Using global transcriptomic, proteomic, and metabolomic profiling, we found a striking failure of Schizosaccharomyces pombe cells lacking eIF3e and eIF3d to synthesize components of the mitochondrial electron transport chain, leading to a defect in respiration, endogenous oxidative stress, and premature aging. Energy balance was maintained, however, by a switch to glycolysis with increased glucose uptake, upregulation of glycolytic enzymes, and strict dependence on a fermentable carbon source. This metabolic regulatory function appears to be conserved in human cells where eIF3e binds metabolic mRNAs and promotes their translation. Thus, via its eIF3d-eIF3e module, eIF3 orchestrates an mRNA-specific translational mechanism controlling energy metabolism that may be disrupted in cancer. Copyright © 2016 The Author(s). Published by Elsevier Inc. All rights reserved.

  14. A Transcript-Specific eIF3 Complex Mediates Global Translational Control of Energy Metabolism

    Meera Shah

    2016-08-01

    Full Text Available The multi-subunit eukaryotic translation initiation factor eIF3 is thought to assist in the recruitment of ribosomes to mRNA. The expression of eIF3 subunits is frequently disrupted in human cancers, but the specific roles of individual subunits in mRNA translation and cancer remain elusive. Using global transcriptomic, proteomic, and metabolomic profiling, we found a striking failure of Schizosaccharomyces pombe cells lacking eIF3e and eIF3d to synthesize components of the mitochondrial electron transport chain, leading to a defect in respiration, endogenous oxidative stress, and premature aging. Energy balance was maintained, however, by a switch to glycolysis with increased glucose uptake, upregulation of glycolytic enzymes, and strict dependence on a fermentable carbon source. This metabolic regulatory function appears to be conserved in human cells where eIF3e binds metabolic mRNAs and promotes their translation. Thus, via its eIF3d-eIF3e module, eIF3 orchestrates an mRNA-specific translational mechanism controlling energy metabolism that may be disrupted in cancer.

  15. Trade networks evolution under the conditions of stock market globalization

    Kopylova Olga Volodymyrivna

    2016-12-01

    Full Text Available The modern perception of the stock market in terms of information technologies rapid development and under the institutionalists influence has been significantly modified and becomes multifaceted. It was detected that the main function of the market is activated, information asymmetry is minimized and more advanced financial architecture space is formed through trade networks. Formation of the modern trade networks has started on the basis of the old infrastructure, that had the highest tendency to self-organization and adaptation. The proposed architecture of trade networks of the stock market has a very clear vector of subordination – from top to bottom and has a number of positive points.

  16. Compartmentalized metabolic network reconstruction of microbial communities to determine the effect of agricultural intervention on soils

    Álvarez-Yela, Astrid Catalina; Gómez-Cano, Fabio; Zambrano, María Mercedes; Husserl, Johana; Danies, Giovanna; Restrepo, Silvia; González-Barrios, Andrés Fernando

    2017-01-01

    Soil microbial communities are responsible for a wide range of ecological processes and have an important economic impact in agriculture. Determining the metabolic processes performed by microbial communities is crucial for understanding and managing ecosystem properties. Metagenomic approaches allow the elucidation of the main metabolic processes that determine the performance of microbial communities under different environmental conditions and perturbations. Here we present the first compartmentalized metabolic reconstruction at a metagenomics scale of a microbial ecosystem. This systematic approach conceives a meta-organism without boundaries between individual organisms and allows the in silico evaluation of the effect of agricultural intervention on soils at a metagenomics level. To characterize the microbial ecosystems, topological properties, taxonomic and metabolic profiles, as well as a Flux Balance Analysis (FBA) were considered. Furthermore, topological and optimization algorithms were implemented to carry out the curation of the models, to ensure the continuity of the fluxes between the metabolic pathways, and to confirm the metabolite exchange between subcellular compartments. The proposed models provide specific information about ecosystems that are generally overlooked in non-compartmentalized or non-curated networks, like the influence of transport reactions in the metabolic processes, especially the important effect on mitochondrial processes, as well as provide more accurate results of the fluxes used to optimize the metabolic processes within the microbial community. PMID:28767679

  17. Compartmentalized metabolic network reconstruction of microbial communities to determine the effect of agricultural intervention on soils.

    María Camila Alvarez-Silva

    Full Text Available Soil microbial communities are responsible for a wide range of ecological processes and have an important economic impact in agriculture. Determining the metabolic processes performed by microbial communities is crucial for understanding and managing ecosystem properties. Metagenomic approaches allow the elucidation of the main metabolic processes that determine the performance of microbial communities under different environmental conditions and perturbations. Here we present the first compartmentalized metabolic reconstruction at a metagenomics scale of a microbial ecosystem. This systematic approach conceives a meta-organism without boundaries between individual organisms and allows the in silico evaluation of the effect of agricultural intervention on soils at a metagenomics level. To characterize the microbial ecosystems, topological properties, taxonomic and metabolic profiles, as well as a Flux Balance Analysis (FBA were considered. Furthermore, topological and optimization algorithms were implemented to carry out the curation of the models, to ensure the continuity of the fluxes between the metabolic pathways, and to confirm the metabolite exchange between subcellular compartments. The proposed models provide specific information about ecosystems that are generally overlooked in non-compartmentalized or non-curated networks, like the influence of transport reactions in the metabolic processes, especially the important effect on mitochondrial processes, as well as provide more accurate results of the fluxes used to optimize the metabolic processes within the microbial community.

  18. Global exponential stability of BAM neural networks with time-varying delays and diffusion terms

    Wan Li; Zhou Qinghua

    2007-01-01

    The stability property of bidirectional associate memory (BAM) neural networks with time-varying delays and diffusion terms are considered. By using the method of variation parameter and inequality technique, the delay-independent sufficient conditions to guarantee the uniqueness and global exponential stability of the equilibrium solution of such networks are established

  19. Global exponential stability of BAM neural networks with time-varying delays and diffusion terms

    Wan, Li; Zhou, Qinghua

    2007-11-01

    The stability property of bidirectional associate memory (BAM) neural networks with time-varying delays and diffusion terms are considered. By using the method of variation parameter and inequality technique, the delay-independent sufficient conditions to guarantee the uniqueness and global exponential stability of the equilibrium solution of such networks are established.

  20. GA(2)LEN (Global Allergy and Asthma European Network) addresses the allergy and asthma 'epidemic'

    Bousquet, J.; Burney, P. G.; Zuberbier, T.; Cauwenberge, P. V.; Akdis, C. A.; Bindslev-Jensen, C.; Bonini, S.; Fokkens, W. J.; Kauffmann, F.; Kowalski, M. L.; Lodrup-Carlsen, K.; Mullol, J.; Nizankowska-Mogilnicka, E.; Papadopoulos, N.; Toskala, E.; Wickman, M.; Anto, J.; Auvergne, N.; Bachert, C.; Bousquet, P. J.; Brunekreef, B.; Canonica, G. W.; Carlsen, K. H.; Gjomarkaj, M.; Haahtela, T.; Howarth, P.; Lenzen, G.; Lotvall, J.; Radon, K.; Ring, J.; Salapatas, M.; Schünemann, H. J.; Szczecklik, A.; Todo-Bom, A.; Valovirta, E.; von Mutius, E.; Zock, J. P.

    2009-01-01

    Allergic diseases represent a major health problem in Europe. They are increasing in prevalence, severity and costs. The Global Allergy and Asthma European Network (GA(2)LEN), a Sixth EU Framework Program for Research and Technological Development (FP6) Network of Excellence, was created in 2005 as

  1. Abnormal metabolic network activity in REM sleep behavior disorder.

    Holtbernd, Florian; Gagnon, Jean-François; Postuma, Ron B; Ma, Yilong; Tang, Chris C; Feigin, Andrew; Dhawan, Vijay; Vendette, Mélanie; Soucy, Jean-Paul; Eidelberg, David; Montplaisir, Jacques

    2014-02-18

    To determine whether the Parkinson disease-related covariance pattern (PDRP) expression is abnormally increased in idiopathic REM sleep behavior disorder (RBD) and whether increased baseline activity is associated with greater individual risk of subsequent phenoconversion. For this cohort study, we recruited 2 groups of RBD and control subjects. Cohort 1 comprised 10 subjects with RBD (63.5 ± 9.4 years old) and 10 healthy volunteers (62.7 ± 8.6 years old) who underwent resting-state metabolic brain imaging with (18)F-fluorodeoxyglucose PET. Cohort 2 comprised 17 subjects with RBD (68.9 ± 4.8 years old) and 17 healthy volunteers (66.6 ± 6.0 years old) who underwent resting brain perfusion imaging with ethylcysteinate dimer SPECT. The latter group was followed clinically for 4.6 ± 2.5 years by investigators blinded to the imaging results. PDRP expression was measured in both RBD groups and compared with corresponding control values. PDRP expression was elevated in both groups of subjects with RBD (cohort 1: p abnormalities in subjects with idiopathic RBD are associated with a greater likelihood of subsequent phenoconversion to a progressive neurodegenerative syndrome.

  2. Globalization of Innovation and the Rise of Network Organization

    Hu, Yimei

    2016-01-01

    ’s innovation purposes. Such organizational structure is contrast with traditional hierarchical organizational structure, and featured with flexibility, market mechanism, internal trust, etc. Secondly, a network organization refers to various forms of interorganizational designs such as strategic alliances...

  3. Global patterns of interaction specialization in bird-flower networks

    Zanata, Thais B.; Dalsgaard, Bo; Passos, Fernando C.

    2017-01-01

    , such as plant species richness, asymmetry, latitude, insularity, topography, sampling methods and intensity. Results: Hummingbird–flower networks were more specialized than honeyeater–flower networks. Specifically, hummingbird–flower networks had a lower proportion of realized interactions (lower C), decreased...... in the interaction patterns with their floral resources. Location: Americas, Africa, Asia and Oceania/Australia. Methods: We compiled interaction networks between birds and floral resources for 79 hummingbird, nine sunbird and 33 honeyeater communities. Interaction specialization was quantified through connectance...... (C), complementary specialization (H2′), binary (QB) and weighted modularity (Q), with both observed and null-model corrected values. We compared interaction specialization among the three types of bird–flower communities, both independently and while controlling for potential confounding variables...

  4. The Global Public Health Intelligence Network and early warning outbreak detection: a Canadian contribution to global public health.

    Mykhalovskiy, Eric; Weir, Lorna

    2006-01-01

    The recent SARS epidemic has renewed widespread concerns about the global transmission of infectious diseases. In this commentary, we explore novel approaches to global infectious disease surveillance through a focus on an important Canadian contribution to the area--the Global Public Health Intelligence Network (GPHIN). GPHIN is a cutting-edge initiative that draws on the capacity of the Internet and newly available 24/7 global news coverage of health events to create a unique form of early warning outbreak detection. This commentary outlines the operation and development of GPHIN and compares it to ProMED-mail, another Internet-based approach to global health surveillance. We argue that GPHIN has created an important shift in the relationship of public health and news information. By exiting the pyramid of official reporting, GPHIN has created a new monitoring technique that has disrupted national boundaries of outbreak notification, while creating new possibilities for global outbreak response. By incorporating news within the emerging apparatus of global infectious disease surveillance, GPHIN has effectively responded to the global media's challenge to official country reporting of outbreak and enhanced the effectiveness and credibility of international public health.

  5. A new criterion for global robust stability of interval neural networks with discrete time delays

    Li Chuandong; Chen Jinyu; Huang Tingwen

    2007-01-01

    This paper further studies global robust stability of a class of interval neural networks with discrete time delays. By introducing an equivalent transformation of interval matrices, a new criterion on global robust stability is established. In comparison with the results reported in the literature, the proposed approach leads to results with less restrictive conditions. Numerical examples are also worked through to illustrate our results

  6. Power and Networks in Worldwide Knowledge Coordination: The Case of Global Science

    King, Roger

    2011-01-01

    The article considers the global governance of knowledge systems, exploring concepts of power, networks, standards (defined as normative practices), and structuration. The focus is on science as a form of predominantly private global governance, particularly the self-regulatory and collaborative processes stretching across time and space. These…

  7. The feasibility of implementing an ecological network in The Netherlands under conditions of global change

    Bakker, M.M.; Alam, S.J.; Dijk, van J.; Rounsevell, T.; Spek, T.; Brink, van den A.

    2015-01-01

    Context Both global change and policy reform will affect the implementation of the National Ecological Network (NEN) in the Netherlands. Global change refers to a combination of changing groundwater tables arising from climate change and improved economic prospects for farming. Policy reform refers

  8. The feasibility of implementing an ecological network in The Netherlands under conditions of global change

    Bakker, Martha; Alam, Shah Jamal; van Dijk, Jerry; Rounsevell, Mark; Spek, Teun; van den Brink, Adri

    2015-01-01

    Context: Both global change and policy reform will affect the implementation of the National Ecological Network (NEN) in the Netherlands. Global change refers to a combination of changing groundwater tables arising from climate change and improved economic prospects for farming. Policy reform refers

  9. Global Stability of Complex-Valued Genetic Regulatory Networks with Delays on Time Scales

    Wang Yajing

    2016-01-01

    Full Text Available In this paper, the global exponential stability of complex-valued genetic regulatory networks with delays is investigated. Besides presenting conditions guaranteeing the existence of a unique equilibrium pattern, its global exponential stability is discussed. Some numerical examples for different time scales.

  10. Beyond the network effect: towards an alternative understanding of global urban organizations

    James, P.; Verrest, H.; Gupta, J.; Pfeffer, K.; Verrest, H.; Ros-Tonen, M.

    2015-01-01

    Global organizations providing network relations for cities are bourgeoning. Organizations such as Metropolis, UN-Habitat, ICLEI - Local Governments for Sustainability, the Global Compact Cities Programme, and the C40, as well as City-to-City arrangements, have become increasingly important to

  11. Global Diffusion of Interactive Networks. The Impact of Culture

    Maitland, Carleen

    1998-01-01

    The Internet and other interactive networks are diffusing across the globe at rates that vary from country to country. Typically, economic and market structure variables are used to explain these differences. The addition of culture to these variables will provide a more robust understanding of the differences in Internet and interactive network diffusion. Existing analyses that identify culture as a predictor of diffusion do not adequately specificy the dimensions of culture and their imp...

  12. New Challenges for Urban History: Culture, Networks, Globalization

    Hietala, Marjatta

    2012-12-01

    Full Text Available Urban history is a very lively and dynamic research field, showing strict parallelism with the fast increasing of the urban population. Today, competitiveness is one of the key aims for cities in the globalized world. Factors such as accessibility and infrastructure, industry, human capital, innovation, and investment, green spaces, affordable housing, business support and quality of education are necessaries. However, the OECD recognizes three dilemmas in this strategic vision, concerning the spill over of metro-regions, the public strategic vision, and the relationship between economic dynamism and the liveable city. Today urban historians are facing some general challenges: comparative aspects are needed; also interdisciplinarity to develop cooperation between disciplines; and for maintaining the professional status of academic urban history. The expanding networks between towns and cities, and the meeting places as conferences and exhibitions are considered, as they are the multitudinous challenges and threats, especially for those cities suffering continuously of major natural and man-made disasters. Moreover, new amalgams of hazard are being created in metropolitan areas with overlapping natural, technological, biological and social risks, exposing more people and places, needing safety and security.

    La historia urbana es un campo de investigación muy vivo y dinámico, mostrando un paralelismo estricto con el rápido incremento de la población urbana. La competencia es hoy uno de los objetivos claves para las ciudades en el mundo globalizado. Factores tales como la accesibilidad y las infraestructuras, la industria, el capital humano, la innovación y la inversión, los espacios verdes, la vivienda accesible, el apoyo a los negocios y la calidad de la educación son necesarios. Sin embargo, la OCDE reconoce tres dilemas en esa visión estratégica, el desarrollo de las metrópolis, la visión estratégica pública y la relaci

  13. Combined metabolomic and correlation networks analyses reveal fumarase insufficiency altered amino acid metabolism.

    Hou, Entai; Li, Xian; Liu, Zerong; Zhang, Fuchang; Tian, Zhongmin

    2018-04-01

    Fumarase catalyzes the interconversion of fumarate and l-malate in the tricarboxylic acid cycle. Fumarase insufficiencies were associated with increased levels of fumarate, decreased levels of malate and exacerbated salt-induced hypertension. To gain insights into the metabolism profiles induced by fumarase insufficiency and identify key regulatory metabolites, we applied a GC-MS based metabolomics platform coupled with a network approach to analyze fumarase insufficient human umbilical vein endothelial cells (HUVEC) and negative controls. A total of 24 altered metabolites involved in seven metabolic pathways were identified as significantly altered, and enriched for the biological module of amino acids metabolism. In addition, Pearson correlation network analysis revealed that fumaric acid, l-malic acid, l-aspartic acid, glycine and l-glutamic acid were hub metabolites according to Pagerank based on their three centrality indices. Alanine aminotransferase and glutamate dehydrogenase activities increased significantly in fumarase deficiency HUVEC. These results confirmed that fumarase insufficiency altered amino acid metabolism. The combination of metabolomics and network methods would provide another perspective on expounding the molecular mechanism at metabolomics level. Copyright © 2017 John Wiley & Sons, Ltd.

  14. Network-level architecture and the evolutionary potential of underground metabolism.

    Notebaart, Richard A; Szappanos, Balázs; Kintses, Bálint; Pál, Ferenc; Györkei, Ádám; Bogos, Balázs; Lázár, Viktória; Spohn, Réka; Csörgő, Bálint; Wagner, Allon; Ruppin, Eytan; Pál, Csaba; Papp, Balázs

    2014-08-12

    A central unresolved issue in evolutionary biology is how metabolic innovations emerge. Low-level enzymatic side activities are frequent and can potentially be recruited for new biochemical functions. However, the role of such underground reactions in adaptation toward novel environments has remained largely unknown and out of reach of computational predictions, not least because these issues demand analyses at the level of the entire metabolic network. Here, we provide a comprehensive computational model of the underground metabolism in Escherichia coli. Most underground reactions are not isolated and 45% of them can be fully wired into the existing network and form novel pathways that produce key precursors for cell growth. This observation allowed us to conduct an integrated genome-wide in silico and experimental survey to characterize the evolutionary potential of E. coli to adapt to hundreds of nutrient conditions. We revealed that underground reactions allow growth in new environments when their activity is increased. We estimate that at least ∼20% of the underground reactions that can be connected to the existing network confer a fitness advantage under specific environments. Moreover, our results demonstrate that the genetic basis of evolutionary adaptations via underground metabolism is computationally predictable. The approach used here has potential for various application areas from bioengineering to medical genetics.

  15. Network Thermodynamic Curation of Human and Yeast Genome-Scale Metabolic Models

    Martínez, Verónica S.; Quek, Lake-Ee; Nielsen, Lars K.

    2014-01-01

    Genome-scale models are used for an ever-widening range of applications. Although there has been much focus on specifying the stoichiometric matrix, the predictive power of genome-scale models equally depends on reaction directions. Two-thirds of reactions in the two eukaryotic reconstructions Homo sapiens Recon 1 and Yeast 5 are specified as irreversible. However, these specifications are mainly based on biochemical textbooks or on their similarity to other organisms and are rarely underpinned by detailed thermodynamic analysis. In this study, a to our knowledge new workflow combining network-embedded thermodynamic and flux variability analysis was used to evaluate existing irreversibility constraints in Recon 1 and Yeast 5 and to identify new ones. A total of 27 and 16 new irreversible reactions were identified in Recon 1 and Yeast 5, respectively, whereas only four reactions were found with directions incorrectly specified against thermodynamics (three in Yeast 5 and one in Recon 1). The workflow further identified for both models several isolated internal loops that require further curation. The framework also highlighted the need for substrate channeling (in human) and ATP hydrolysis (in yeast) for the essential reaction catalyzed by phosphoribosylaminoimidazole carboxylase in purine metabolism. Finally, the framework highlighted differences in proline metabolism between yeast (cytosolic anabolism and mitochondrial catabolism) and humans (exclusively mitochondrial metabolism). We conclude that network-embedded thermodynamics facilitates the specification and validation of irreversibility constraints in compartmentalized metabolic models, at the same time providing further insight into network properties. PMID:25028891

  16. Global sensitivity analysis in stochastic simulators of uncertain reaction networks

    Navarro, Marí a; Le Maitre, Olivier; Knio, Omar

    2016-01-01

    sources are independent, and considers the Poisson processes in the random-time-change representation of the state dynamics as the fundamental objects governing the inherent stochasticity. A sampling algorithm is proposed to perform the global sensitivity

  17. Emerging global logistics networks : Implications for transport systems and policies

    Tavasszy, LA; Ruijgrok, CJ; Thissen, MJPM

    2003-01-01

    Logistics chains are constantly changing to facilitate increasingly global movements. In qualitative terms, long term trends in logistics services indicate a growing degree of product customization and an increased responsiveness in order delivery. These trends impact on the development of

  18. Adenylate Kinase and AMP Signaling Networks: Metabolic Monitoring, Signal Communication and Body Energy Sensing

    Andre Terzic

    2009-04-01

    Full Text Available Adenylate kinase and downstream AMP signaling is an integrated metabolic monitoring system which reads the cellular energy state in order to tune and report signals to metabolic sensors. A network of adenylate kinase isoforms (AK1-AK7 are distributed throughout intracellular compartments, interstitial space and body fluids to regulate energetic and metabolic signaling circuits, securing efficient cell energy economy, signal communication and stress response. The dynamics of adenylate kinase-catalyzed phosphotransfer regulates multiple intracellular and extracellular energy-dependent and nucleotide signaling processes, including excitation-contraction coupling, hormone secretion, cell and ciliary motility, nuclear transport, energetics of cell cycle, DNA synthesis and repair, and developmental programming. Metabolomic analyses indicate that cellular, interstitial and blood AMP levels are potential metabolic signals associated with vital functions including body energy sensing, sleep, hibernation and food intake. Either low or excess AMP signaling has been linked to human disease such as diabetes, obesity and hypertrophic cardiomyopathy. Recent studies indicate that derangements in adenylate kinase-mediated energetic signaling due to mutations in AK1, AK2 or AK7 isoforms are associated with hemolytic anemia, reticular dysgenesis and ciliary dyskinesia. Moreover, hormonal, food and antidiabetic drug actions are frequently coupled to alterations of cellular AMP levels and associated signaling. Thus, by monitoring energy state and generating and distributing AMP metabolic signals adenylate kinase represents a unique hub within the cellular homeostatic network.

  19. Genome-scale reconstruction of metabolic networks of Lactobacillus casei ATCC 334 and 12A.

    Elena Vinay-Lara

    Full Text Available Lactobacillus casei strains are widely used in industry and the utility of this organism in these industrial applications is strain dependent. Hence, tools capable of predicting strain specific phenotypes would have utility in the selection of strains for specific industrial processes. Genome-scale metabolic models can be utilized to better understand genotype-phenotype relationships and to compare different organisms. To assist in the selection and development of strains with enhanced industrial utility, genome-scale models for L. casei ATCC 334, a well characterized strain, and strain 12A, a corn silage isolate, were constructed. Draft models were generated from RAST genome annotations using the Model SEED database and refined by evaluating ATP generating cycles, mass-and-charge-balances of reactions, and growth phenotypes. After the validation process was finished, we compared the metabolic networks of these two strains to identify metabolic, genetic and ortholog differences that may lead to different phenotypic behaviors. We conclude that the metabolic capabilities of the two networks are highly similar. The L. casei ATCC 334 model accounts for 1,040 reactions, 959 metabolites and 548 genes, while the L. casei 12A model accounts for 1,076 reactions, 979 metabolites and 640 genes. The developed L. casei ATCC 334 and 12A metabolic models will enable better understanding of the physiology of these organisms and be valuable tools in the development and selection of strains with enhanced utility in a variety of industrial applications.

  20. Network organization is globally atypical in autism: A graph theory study of intrinsic functional connectivity.

    Keown, Christopher L; Datko, Michael C; Chen, Colleen P; Maximo, José Omar; Jahedi, Afrooz; Müller, Ralph-Axel

    2017-01-01

    Despite abundant evidence of brain network anomalies in autism spectrum disorder (ASD), findings have varied from broad functional underconnectivity to broad overconnectivity. Rather than pursuing overly simplifying general hypotheses ('under' vs. 'over'), we tested the hypothesis of atypical network distribution in ASD (i.e., participation of unusual loci in distributed functional networks). We used a selective high-quality data subset from the ABIDE datashare (including 111 ASD and 174 typically developing [TD] participants) and several graph theory metrics. Resting state functional MRI data were preprocessed and analyzed for detection of low-frequency intrinsic signal correlations. Groups were tightly matched for available demographics and head motion. As hypothesized, the Rand Index (reflecting how similar network organization was to a normative set of networks) was significantly lower in ASD than TD participants. This was accounted for by globally reduced cohesion and density, but increased dispersion of networks. While differences in hub architecture did not survive correction, rich club connectivity (among the hubs) was increased in the ASD group. Our findings support the model of reduced network integration (connectivity with networks) and differentiation (or segregation; based on connectivity outside network boundaries) in ASD. While the findings applied at the global level, they were not equally robust across all networks and in one case (greater cohesion within ventral attention network in ASD) even reversed.

  1. Global similarity and local divergence in human and mouse gene co-expression networks

    Koonin Eugene V

    2006-09-01

    Full Text Available Abstract Background A genome-wide comparative analysis of human and mouse gene expression patterns was performed in order to evaluate the evolutionary divergence of mammalian gene expression. Tissue-specific expression profiles were analyzed for 9,105 human-mouse orthologous gene pairs across 28 tissues. Expression profiles were resolved into species-specific coexpression networks, and the topological properties of the networks were compared between species. Results At the global level, the topological properties of the human and mouse gene coexpression networks are, essentially, identical. For instance, both networks have topologies with small-world and scale-free properties as well as closely similar average node degrees, clustering coefficients, and path lengths. However, the human and mouse coexpression networks are highly divergent at the local level: only a small fraction ( Conclusion The dissonance between global versus local network divergence suggests that the interspecies similarity of the global network properties is of limited biological significance, at best, and that the biologically relevant aspects of the architectures of gene coexpression are specific and particular, rather than universal. Nevertheless, there is substantial evolutionary conservation of the local network structure which is compatible with the notion that gene coexpression networks are subject to purifying selection.

  2. Differential network analysis reveals evolutionary complexity in secondary metabolism of Rauvolfia serpentina over Catharanthus roseus

    Shivalika Pathania

    2016-08-01

    Full Text Available Comparative co-expression analysis of multiple species using high-throughput data is an integrative approach to determine the uniformity as well as diversification in biological processes. Rauvolfia serpentina and Catharanthus roseus, both members of Apocyanacae family, are reported to have remedial properties against multiple diseases. Despite of sharing upstream of terpenoid indole alkaloid pathway, there is significant diversity in tissue-specific synthesis and accumulation of specialized metabolites in these plants. This led us to implement comparative co-expression network analysis to investigate the modules and genes responsible for differential tissue-specific expression as well as species-specific synthesis of metabolites. Towards these goals differential network analysis was implemented to identify candidate genes responsible for diversification of metabolites profile. Three genes were identified with significant difference in connectivity leading to differential regulatory behavior between these plants. These mechanisms may be responsible for diversification of secondary metabolism, and thereby for species-specific metabolite synthesis. The network robustness of R. serpentina, determined based on topological properties, was also complemented by comparison of gene-metabolite networks of both plants, and may have evolved to have complex metabolic mechanisms as compared to C. roseus under the influence of various stimuli. This study reveals evolution of complexity in secondary metabolism of Rauvolfia serpentina, and key genes that contribute towards diversification of specific metabolites.

  3. Differential Network Analysis Reveals Evolutionary Complexity in Secondary Metabolism of Rauvolfia serpentina over Catharanthus roseus.

    Pathania, Shivalika; Bagler, Ganesh; Ahuja, Paramvir S

    2016-01-01

    Comparative co-expression analysis of multiple species using high-throughput data is an integrative approach to determine the uniformity as well as diversification in biological processes. Rauvolfia serpentina and Catharanthus roseus, both members of Apocyanacae family, are reported to have remedial properties against multiple diseases. Despite of sharing upstream of terpenoid indole alkaloid pathway, there is significant diversity in tissue-specific synthesis and accumulation of specialized metabolites in these plants. This led us to implement comparative co-expression network analysis to investigate the modules and genes responsible for differential tissue-specific expression as well as species-specific synthesis of metabolites. Toward these goals differential network analysis was implemented to identify candidate genes responsible for diversification of metabolites profile. Three genes were identified with significant difference in connectivity leading to differential regulatory behavior between these plants. These genes may be responsible for diversification of secondary metabolism, and thereby for species-specific metabolite synthesis. The network robustness of R. serpentina, determined based on topological properties, was also complemented by comparison of gene-metabolite networks of both plants, and may have evolved to have complex metabolic mechanisms as compared to C. roseus under the influence of various stimuli. This study reveals evolution of complexity in secondary metabolism of R. serpentina, and key genes that contribute toward diversification of specific metabolites.

  4. Global asymptotic stability of Cohen-Grossberg neural networks with constant and variable delays

    Wu Wei; Cui Baotong; Huang Min

    2007-01-01

    Global asymptotic stability of Cohen-Grossberg neural networks with constant and variable delays is studied. Some sufficient conditions for the neural networks are proposed to guarantee the global asymptotic convergence by using different Lyapunov functionals. Our criteria represent an extension of the existing results in literatures. A comparison between our results and the previous results admits that our results establish a new set of stability criteria for delayed Cohen-Grossberg neural networks. Those conditions are less restrictive than those given in the earlier reference

  5. The role of “network of cities” in construction of global urban culture

    Baycan-Levent, Tüzin; Kundak, Seda; Gülümser, Aliye Ahu

    2004-01-01

    The globalization process has led to an increased interaction between cities and to a new urban system/network in which they need to be competitive and complementary at the same time. “Network of cities”, such as World Cities, Eurocities or Sister Cities are among the well known examples of interaction and cooperation of the cities at the regional and global level. The cities of different regions and countries tend to share their experiences and their cultures within these networks in order t...

  6. Globally exponential stability of neural network with constant and variable delays

    Zhao Weirui; Zhang Huanshui

    2006-01-01

    This Letter presents new sufficient conditions of globally exponential stability of neural networks with delays. We show that these results generalize recently published globally exponential stability results. In particular, several different globally exponential stability conditions in the literatures which were proved using different Lyapunov functionals are generalized and unified by using the same Lyapunov functional and the technique of inequality of integral. A comparison between our results and the previous results admits that our results establish a new set of stability criteria for delayed neural networks. Those conditions are less restrictive than those given in the earlier references

  7. A FDG-PET Study of Metabolic Networks in Apolipoprotein E ε4 Allele Carriers.

    Zhijun Yao

    Full Text Available Recently, some studies have applied the graph theory in brain network analysis in Alzheimer's disease (AD and Mild Cognitive Impairment (MCI. However, relatively little research has specifically explored the properties of the metabolic network in apolipoprotein E (APOE ε4 allele carriers. In our study, all the subjects, including ADs, MCIs and NCs (normal controls were divided into 165 APOE ε4 carriers and 165 APOE ε4 noncarriers. To establish the metabolic network for all brain regions except the cerebellum, cerebral glucose metabolism data obtained from FDG-PET (18F-fluorodeoxyglucose positron emission tomography were segmented into 90 areas with automated anatomical labeling (AAL template. Then, the properties of the networks were computed to explore the between-group differences. Our results suggested that both APOE ε4 carriers and noncarriers showed the small-world properties. Besides, compared with APOE ε4 noncarriers, the carriers showed a lower clustering coefficient. In addition, significant changes in 6 hub brain regions were found in between-group nodal centrality. Namely, compared with APOE ε4 noncarriers, significant decreases of the nodal centrality were found in left insula, right insula, right anterior cingulate, right paracingulate gyri, left cuneus, as well as significant increases in left paracentral lobule and left heschl gyrus in APOE ε4 carriers. Increased local short distance interregional correlations and disrupted long distance interregional correlations were found, which may support the point that the APOE ε4 carriers were more similar with AD or MCI in FDG uptake. In summary, the organization of metabolic network in APOE ε4 carriers indicated a less optimal pattern and APOE ε4 might be a risk factor for AD.

  8. E-njoy the first CERN Global Network e-vent!

    CERN Bulletin

    2010-01-01

    Empowered by the considerable interest it received after it was launched, the CERN Global Network takes off and organizes the first e-vent, which will be a special talk on science communication that will be held on 29 June at 4.30 p.m. in the Council Chamber. You can experience it live on the Global Network site and, if you are a Member, provide feedback. Stay linked!   On the CERN Global Network webpage, you will be able to choose the topic of the next e-vents. Seven weeks after its launch, about 600 people have already joined the CERN Global Network and six thematic groups have been created. The whole idea of joining the Network is to stay connected or reconnect with life at CERN where seminars, talks and discussions are undoubtedly a very important and much appreciated part of it. This is where the e-vents come into play. “The e-vents enable members of the Global Network to participate in selected events taking place at CERN, such as lectures or panel discussions. They will...

  9. Yeast 5 – an expanded reconstruction of the Saccharomyces cerevisiae metabolic network

    Heavner Benjamin D

    2012-06-01

    Full Text Available Abstract Background Efforts to improve the computational reconstruction of the Saccharomyces cerevisiae biochemical reaction network and to refine the stoichiometrically constrained metabolic models that can be derived from such a reconstruction have continued since the first stoichiometrically constrained yeast genome scale metabolic model was published in 2003. Continuing this ongoing process, we have constructed an update to the Yeast Consensus Reconstruction, Yeast 5. The Yeast Consensus Reconstruction is a product of efforts to forge a community-based reconstruction emphasizing standards compliance and biochemical accuracy via evidence-based selection of reactions. It draws upon models published by a variety of independent research groups as well as information obtained from biochemical databases and primary literature. Results Yeast 5 refines the biochemical reactions included in the reconstruction, particularly reactions involved in sphingolipid metabolism; updates gene-reaction annotations; and emphasizes the distinction between reconstruction and stoichiometrically constrained model. Although it was not a primary goal, this update also improves the accuracy of model prediction of viability and auxotrophy phenotypes and increases the number of epistatic interactions. This update maintains an emphasis on standards compliance, unambiguous metabolite naming, and computer-readable annotations available through a structured document format. Additionally, we have developed MATLAB scripts to evaluate the model’s predictive accuracy and to demonstrate basic model applications such as simulating aerobic and anaerobic growth. These scripts, which provide an independent tool for evaluating the performance of various stoichiometrically constrained yeast metabolic models using flux balance analysis, are included as Additional files 1, 2 and 3. Additional file 1 Function testYeastModel.m.m. Click here for file Additional file 2 Function model

  10. Habitat variability does not generally promote metabolic network modularity in flies and mammals.

    Takemoto, Kazuhiro

    2016-01-01

    The evolution of species habitat range is an important topic over a wide range of research fields. In higher organisms, habitat range evolution is generally associated with genetic events such as gene duplication. However, the specific factors that determine habitat variability remain unclear at higher levels of biological organization (e.g., biochemical networks). One widely accepted hypothesis developed from both theoretical and empirical analyses is that habitat variability promotes network modularity; however, this relationship has not yet been directly tested in higher organisms. Therefore, I investigated the relationship between habitat variability and metabolic network modularity using compound and enzymatic networks in flies and mammals. Contrary to expectation, there was no clear positive correlation between habitat variability and network modularity. As an exception, the network modularity increased with habitat variability in the enzymatic networks of flies. However, the observed association was likely an artifact, and the frequency of gene duplication appears to be the main factor contributing to network modularity. These findings raise the question of whether or not there is a general mechanism for habitat range expansion at a higher level (i.e., above the gene scale). This study suggests that the currently widely accepted hypothesis for habitat variability should be reconsidered. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  11. A global, multi-disciplinary, multi-sectorial initiative to combat leptospirosis: Global Leptospirosis Environmental Action Network (GLEAN).

    Durski, Kara N; Jancloes, Michel; Chowdhary, Tej; Bertherat, Eric

    2014-06-05

    Leptospirosis has emerged as a major public health problem in both animals and humans. The true burden of this epidemic and endemic disease is likely to be grossly under-estimated due to the non-specific clinical presentations of the disease and the difficulty of laboratory confirmation. The complexity that surrounds the transmission dynamics, particularly in epidemic situations, requires a coordinated, multi-disciplinary effort. Therefore, the Global Leptospirosis Environmental Action Network (GLEAN) was developed to improve global and local strategies of how to predict, prevent, detect, and intervene in leptospirosis outbreaks in order to prevent and control leptospirosis in high-risk populations.

  12. Novel Plasmodium falciparum metabolic network reconstruction identifies shifts associated with clinical antimalarial resistance.

    Carey, Maureen A; Papin, Jason A; Guler, Jennifer L

    2017-07-19

    Malaria remains a major public health burden and resistance has emerged to every antimalarial on the market, including the frontline drug, artemisinin. Our limited understanding of Plasmodium biology hinders the elucidation of resistance mechanisms. In this regard, systems biology approaches can facilitate the integration of existing experimental knowledge and further understanding of these mechanisms. Here, we developed a novel genome-scale metabolic network reconstruction, iPfal17, of the asexual blood-stage P. falciparum parasite to expand our understanding of metabolic changes that support resistance. We identified 11 metabolic tasks to evaluate iPfal17 performance. Flux balance analysis and simulation of gene knockouts and enzyme inhibition predict candidate drug targets unique to resistant parasites. Moreover, integration of clinical parasite transcriptomes into the iPfal17 reconstruction reveals patterns associated with antimalarial resistance. These results predict that artemisinin sensitive and resistant parasites differentially utilize scavenging and biosynthetic pathways for multiple essential metabolites, including folate and polyamines. Our findings are consistent with experimental literature, while generating novel hypotheses about artemisinin resistance and parasite biology. We detect evidence that resistant parasites maintain greater metabolic flexibility, perhaps representing an incomplete transition to the metabolic state most appropriate for nutrient-rich blood. Using this systems biology approach, we identify metabolic shifts that arise with or in support of the resistant phenotype. This perspective allows us to more productively analyze and interpret clinical expression data for the identification of candidate drug targets for the treatment of resistant parasites.

  13. MANAGING TRANSITION PROCESSES OF MANUFACTURING NETWORKS OF GLOBAL OPERATIONS

    Adeyemi, Oluseyi

    2012-01-01

    rather than the pure product. Incidentally, products and services are often inseparable and the sale of a product would lead to a relationship where services could be sold over an extended period of time (Levitt, 1983). Thereby, many manufacturers have sought growth through the increased sale of products......Western companies have now started to compete on the basis of value delivered by shifting their market focus from manufacturing to more product-service oriented systems. This is linked to the view that manufacturing companies are becoming more oriented to the use of the product-service offering......-services offerings. Localizing and globalizing these products-services offerings have inherent complexities which have been under researched. Facing the intense global competition, companies are seeking higher levels of efficiency and effectiveness by configuring their discrete value-added activities on a global...

  14. Comparative genomic reconstruction of transcriptional networks controlling central metabolism in the Shewanella genus

    Kovaleva Galina

    2011-06-01

    Full Text Available Abstract Background Genome-scale prediction of gene regulation and reconstruction of transcriptional regulatory networks in bacteria is one of the critical tasks of modern genomics. The Shewanella genus is comprised of metabolically versatile gamma-proteobacteria, whose lifestyles and natural environments are substantially different from Escherichia coli and other model bacterial species. The comparative genomics approaches and computational identification of regulatory sites are useful for the in silico reconstruction of transcriptional regulatory networks in bacteria. Results To explore conservation and variations in the Shewanella transcriptional networks we analyzed the repertoire of transcription factors and performed genomics-based reconstruction and comparative analysis of regulons in 16 Shewanella genomes. The inferred regulatory network includes 82 transcription factors and their DNA binding sites, 8 riboswitches and 6 translational attenuators. Forty five regulons were newly inferred from the genome context analysis, whereas others were propagated from previously characterized regulons in the Enterobacteria and Pseudomonas spp.. Multiple variations in regulatory strategies between the Shewanella spp. and E. coli include regulon contraction and expansion (as in the case of PdhR, HexR, FadR, numerous cases of recruiting non-orthologous regulators to control equivalent pathways (e.g. PsrA for fatty acid degradation and, conversely, orthologous regulators to control distinct pathways (e.g. TyrR, ArgR, Crp. Conclusions We tentatively defined the first reference collection of ~100 transcriptional regulons in 16 Shewanella genomes. The resulting regulatory network contains ~600 regulated genes per genome that are mostly involved in metabolism of carbohydrates, amino acids, fatty acids, vitamins, metals, and stress responses. Several reconstructed regulons including NagR for N-acetylglucosamine catabolism were experimentally validated in S

  15. Effects of global financial crisis on network structure in a local stock market

    Nobi, Ashadun; Maeng, Seong Eun; Ha, Gyeong Gyun; Lee, Jae Woo

    2014-08-01

    This study considers the effects of the 2008 global financial crisis on threshold networks of a local Korean financial market around the time of the crisis. Prices of individual stocks belonging to KOSPI 200 (Korea Composite Stock Price Index 200) are considered for three time periods, namely before, during, and after the crisis. Threshold networks are constructed from fully connected cross-correlation networks, and thresholds of cross-correlation coefficients are assigned to obtain threshold networks. At the high threshold, only one large cluster consisting of firms in the financial sector, heavy industry, and construction is observed during the crisis. However, before and after the crisis, there are several fragmented clusters belonging to various sectors. The power law of the degree distribution in threshold networks is observed within the limited range of thresholds. Threshold networks are fatter during the crisis than before or after the crisis. The clustering coefficient of the threshold network follows the power law in the scaling range.

  16. Global supply chain management/transportation : building a global network of scholars and educators : phase I

    2008-01-01

    During the project period two conferences--1st Symposium and Workshop in Global : Supply Chain (http://www.business.utoledo.edu/scm) at University of Toledo, Toledo, : OH, USA (October 6-7, 2007) and 2nd Symposium and Workshop in Global Supply : Chai...

  17. The Global Maritime Partnership: Networking Challenges and Opportunities

    2010-06-01

    The Victorians eagerly embraced the telegraph as something that was “faster and better” than waiting for newspapers to arrive via ship and... fashion . 31 While little quantitative work on network-centric operations has been done based on from-the-ground-up modeling and simulation, the United

  18. Determinant factors in dynamics of global manufacturing virtual networks

    José Ramón Vilana

    2011-04-01

    Full Text Available Purpose: The purpose of this work is to demonstrate the existence of a number of structural mechanisms that networks actors use to exert tacit power in the GMVNs. Design/methodology/approach: The analysis of the engine manufacturing aeronautical industry based on a quantitative approach with a binomial logistic model with a logit function. Findings and Originality/value: Original Equipment Manufacturers (OEMs exert a tacit power by occupying central positions in the network and having many structural holes. Suppliers, nevertheless, establish many strong and direct ties to increase trust with other network actors; while new actors establish, primarily, indirect ties to gain explicit knowledge. Research limitations/implications: Another similar works focused in other industrial segments like electronics, chemical o automotive would strengthen the findings of this work.Practical implications: The results of this work can facilitate, ex ante, the design of new GMVNs and increase drastically their efficiency.Originality/value: It classifies the internal operations of these organizations that, so far, were not analysed under this approach. Its conclusions can be used as a prescriptive model for other manufacturing networks.

  19. Global Networks: Emerging Constraints on Strategy (Defense Horizons, July 2004)

    2004-07-01

    great competitive disadvantage . In a very interesting development, several large Indian IT ser- vice companies have decided to tap into China. Gartner...telecommunications network design. These are not sweatshops . Working conditions at India’s IT develop- ment companies—whether managed directly by Western

  20. Networks of Practice in Science Education Research: A Global Context

    Martin, Sonya N.; Siry, Christina

    2011-01-01

    In this paper, we employ cultural sociology and Braj Kachru's model of World Englishes as theoretical and analytical tools for considering English as a form of capital necessary for widely disseminating research findings from local networks of practice to the greater science education research community. We present a brief analysis of recent…

  1. Ordinary differential equations and Boolean networks in application to modelling of 6-mercaptopurine metabolism.

    Lavrova, Anastasia I; Postnikov, Eugene B; Zyubin, Andrey Yu; Babak, Svetlana V

    2017-04-01

    We consider two approaches to modelling the cell metabolism of 6-mercaptopurine, one of the important chemotherapy drugs used for treating acute lymphocytic leukaemia: kinetic ordinary differential equations, and Boolean networks supplied with one controlling node, which takes continual values. We analyse their interplay with respect to taking into account ATP concentration as a key parameter of switching between different pathways. It is shown that the Boolean networks, which allow avoiding the complexity of general kinetic modelling, preserve the possibility of reproducing the principal switching mechanism.

  2. The Pan-University Network for Global Health: framework for collaboration and review of global health needs.

    Winchester, M S; BeLue, R; Oni, T; Wittwer-Backofen, U; Deobagkar, D; Onya, H; Samuels, T A; Matthews, S A; Stone, C; Airhihenbuwa, C

    2016-04-21

    In the current United Nations efforts to plan for post 2015-Millennium Development Goals, global partnership to address non-communicable diseases (NCDs) has become a critical goal to effectively respond to the complex global challenges of which inequity in health remains a persistent challenge. Building capacity in terms of well-equipped local researchers and service providers is a key to bridging the inequity in global health. Launched by Penn State University in 2014, the Pan University Network for Global Health responds to this need by bridging researchers at more than 10 universities across the globe. In this paper we outline our framework for international and interdisciplinary collaboration, as well the rationale for our research areas, including a review of these two themes. After its initial meeting, the network has established two central thematic priorities: 1) urbanization and health and 2) the intersection of infectious diseases and NCDs. The urban population in the global south will nearly double in 25 years (approx. 2 billion today to over 3.5 billion by 2040). Urban population growth will have a direct impact on global health, and this growth will be burdened with uneven development and the persistence of urban spatial inequality, including health disparities. The NCD burden, which includes conditions such as hypertension, stroke, and diabetes, is outstripping infectious disease in countries in the global south that are considered to be disproportionately burdened by infectious diseases. Addressing these two priorities demands an interdisciplinary and multi-institutional model to stimulate innovation and synergy that will influence the overall framing of research questions as well as the integration and coordination of research.

  3. Correlation and network analysis of global financial indices.

    Kumar, Sunil; Deo, Nivedita

    2012-08-01

    Random matrix theory (RMT) and network methods are applied to investigate the correlation and network properties of 20 financial indices. The results are compared before and during the financial crisis of 2008. In the RMT method, the components of eigenvectors corresponding to the second largest eigenvalue form two clusters of indices in the positive and negative directions. The components of these two clusters switch in opposite directions during the crisis. The network analysis uses the Fruchterman-Reingold layout to find clusters in the network of indices at different thresholds. At a threshold of 0.6, before the crisis, financial indices corresponding to the Americas, Europe, and Asia-Pacific form separate clusters. On the other hand, during the crisis at the same threshold, the American and European indices combine together to form a strongly linked cluster while the Asia-Pacific indices form a separate weakly linked cluster. If the value of the threshold is further increased to 0.9 then the European indices (France, Germany, and the United Kingdom) are found to be the most tightly linked indices. The structure of the minimum spanning tree of financial indices is more starlike before the crisis and it changes to become more chainlike during the crisis. The average linkage hierarchical clustering algorithm is used to find a clearer cluster structure in the network of financial indices. The cophenetic correlation coefficients are calculated and found to increase significantly, which indicates that the hierarchy increases during the financial crisis. These results show that there is substantial change in the structure of the organization of financial indices during a financial crisis.

  4. Integration of expression data in genome-scale metabolic network reconstructions

    Anna S. Blazier

    2012-08-01

    Full Text Available With the advent of high-throughput technologies, the field of systems biology has amassed an abundance of omics data, quantifying thousands of cellular components across a variety of scales, ranging from mRNA transcript levels to metabolite quantities. Methods are needed to not only integrate this omics data but to also use this data to heighten the predictive capabilities of computational models. Several recent studies have successfully demonstrated how flux balance analysis (FBA, a constraint-based modeling approach, can be used to integrate transcriptomic data into genome-scale metabolic network reconstructions to generate predictive computational models. In this review, we summarize such FBA-based methods for integrating expression data into genome-scale metabolic network reconstructions, highlighting their advantages as well as their limitations.

  5. Simultaneous Parameters Identifiability and Estimation of an E. coli Metabolic Network Model

    Kese Pontes Freitas Alberton

    2015-01-01

    Full Text Available This work proposes a procedure for simultaneous parameters identifiability and estimation in metabolic networks in order to overcome difficulties associated with lack of experimental data and large number of parameters, a common scenario in the modeling of such systems. As case study, the complex real problem of parameters identifiability of the Escherichia coli K-12 W3110 dynamic model was investigated, composed by 18 differential ordinary equations and 35 kinetic rates, containing 125 parameters. With the procedure, model fit was improved for most of the measured metabolites, achieving 58 parameters estimated, including 5 unknown initial conditions. The results indicate that simultaneous parameters identifiability and estimation approach in metabolic networks is appealing, since model fit to the most of measured metabolites was possible even when important measures of intracellular metabolites and good initial estimates of parameters are not available.

  6. Postmodern Educational Capitalism, Global Information Systems and New Media Networks

    Peters, Michael A.

    2012-01-01

    This article reinterprets Lyotard's argument in "The Postmodern Condition" as a basis for a radical political economy approach to knowledge capitalism focusing on post-industrialism in order to put the case that education and knowledge are increasingly becoming part of a globally integrated world capitalism (IWC) that is structured through…

  7. Global Brand Identity as a Network of Localized Meanings

    Gunawan, Elizabeth; van den Hoven, P.J.|info:eu-repo/dai/nl/070378096

    2017-01-01

    In this article, we develop a semiotic model to analyze advertisement localization. This model focuses on the mental representations that local audiences build of a “global” brand identity. We demonstrate how this model fills up gaps left by a popular marketing model for global advertising. We argue

  8. Building dynamic capabilities in large global advertising agency networks: managing the shift from mass communication to digital interactivity

    Suheimat, Wisam; Prætorius, Thim; Brambini-Pedersen, Jan Vang

    2018-01-01

    Interactive digital technologies result in significant managerial challenges for the largest global advertising agency networks. This paper, based on original data from in-depth case research in three of the largest global advertising networks, investigates how advertising agency networks manage...

  9. Global Exponential Stability of Periodic Oscillation for Nonautonomous BAM Neural Networks with Distributed Delay

    Hongli Liu

    2009-01-01

    Full Text Available We derive a new criterion for checking the global stability of periodic oscillation of bidirectional associative memory (BAM neural networks with periodic coefficients and distributed delay, and find that the criterion relies on the Lipschitz constants of the signal transmission functions, weights of the neural network, and delay kernels. The proposed model transforms the original interacting network into matrix analysis problem which is easy to check, thereby significantly reducing the computational complexity and making analysis of periodic oscillation for even large-scale networks.

  10. Metabolic network analysis-based identification of antimicrobial drug targets in category A bioterrorism agents.

    Yong-Yeol Ahn

    Full Text Available The 2001 anthrax mail attacks in the United States demonstrated the potential threat of bioterrorism, hence driving the need to develop sophisticated treatment and diagnostic protocols to counter biological warfare. Here, by performing flux balance analyses on the fully-annotated metabolic networks of multiple, whole genome-sequenced bacterial strains, we have identified a large number of metabolic enzymes as potential drug targets for each of the three Category A-designated bioterrorism agents including Bacillus anthracis, Francisella tularensis and Yersinia pestis. Nine metabolic enzymes- belonging to the coenzyme A, folate, phosphatidyl-ethanolamine and nucleic acid pathways common to all strains across the three distinct genera were identified as targets. Antimicrobial agents against some of these enzymes are available. Thus, a combination of cross species-specific antibiotics and common antimicrobials against shared targets may represent a useful combinatorial therapeutic approach against all Category A bioterrorism agents.

  11. Increasing galactose consumption by Saccharomyces cerevisiae through metabolic engineering of the GAL gene regulatory network

    Østergaard, Simon; Olsson, Lisbeth; Johnston, M.

    2000-01-01

    Increasing the flux through central carbon metabolism is difficult because of rigidity in regulatory structures, at both the genetic and the enzymatic levels. Here we describe metabolic engineering of a regulatory network to obtain a balanced increase in the activity of all the enzymes in the pat...... media. The improved galactose consumption of the gal mutants did not favor biomass formation, but rather caused excessive respiro-fermentative metabolism, with the ethanol production rate increasing linearly with glycolytic flux....... by eliminating three known negative regulators of the GAL system: Gale, Gal80, and Mig1. This led to a 41% increase in flux through the galactose utilization pathway compared with the wild-type strain. This is of significant interest within the field of biotechnology since galactose is present in many industrial...

  12. PPAR? population shift produces disease-related changes in molecular networks associated with metabolic syndrome

    Jurkowski, W; Roomp, K; Crespo, I; Schneider, J G; del Sol, A

    2011-01-01

    Peroxisome proliferator-activated receptor gamma (PPARγ) is a key regulator of adipocyte differentiation and has an important role in metabolic syndrome. Phosphorylation of the receptor's ligand-binding domain at serine 273 has been shown to change the expression of a large number of genes implicated in obesity. The difference in gene expression seen when comparing wild-type phosphorylated with mutant non-phosphorylated PPARγ may have important consequences for the cellular molecular network,...

  13. Metformin regulates global DNA methylation via mitochondrial one-carbon metabolism.

    Cuyàs, E; Fernández-Arroyo, S; Verdura, S; García, R Á-F; Stursa, J; Werner, L; Blanco-González, E; Montes-Bayón, M; Joven, J; Viollet, B; Neuzil, J; Menendez, J A

    2018-02-15

    The anti-diabetic biguanide metformin may exert health-promoting effects via metabolic regulation of the epigenome. Here we show that metformin promotes global DNA methylation in non-cancerous, cancer-prone and metastatic cancer cells by decreasing S-adenosylhomocysteine (SAH), a strong feedback inhibitor of S-adenosylmethionine (SAM)-dependent DNA methyltransferases, while promoting the accumulation of SAM, the universal methyl donor for cellular methylation. Using metformin and a mitochondria/complex I (mCI)-targeted analog of metformin (norMitoMet) in experimental pairs of wild-type and AMP-activated protein kinase (AMPK)-, serine hydroxymethyltransferase 2 (SHMT2)- and mCI-null cells, we provide evidence that metformin increases the SAM:SAH ratio-related methylation capacity by targeting the coupling between serine mitochondrial one-carbon flux and CI activity. By increasing the contribution of one-carbon units to the SAM from folate stores while decreasing SAH in response to AMPK-sensed energetic crisis, metformin can operate as a metabolo-epigenetic regulator capable of reprogramming one of the key conduits linking cellular metabolism to the DNA methylation machinery.

  14. Characterizing steady states of genome-scale metabolic networks in continuous cell cultures.

    Jorge Fernandez-de-Cossio-Diaz

    2017-11-01

    Full Text Available In the continuous mode of cell culture, a constant flow carrying fresh media replaces culture fluid, cells, nutrients and secreted metabolites. Here we present a model for continuous cell culture coupling intra-cellular metabolism to extracellular variables describing the state of the bioreactor, taking into account the growth capacity of the cell and the impact of toxic byproduct accumulation. We provide a method to determine the steady states of this system that is tractable for metabolic networks of arbitrary complexity. We demonstrate our approach in a toy model first, and then in a genome-scale metabolic network of the Chinese hamster ovary cell line, obtaining results that are in qualitative agreement with experimental observations. We derive a number of consequences from the model that are independent of parameter values. The ratio between cell density and dilution rate is an ideal control parameter to fix a steady state with desired metabolic properties. This conclusion is robust even in the presence of multi-stability, which is explained in our model by a negative feedback loop due to toxic byproduct accumulation. A complex landscape of steady states emerges from our simulations, including multiple metabolic switches, which also explain why cell-line and media benchmarks carried out in batch culture cannot be extrapolated to perfusion. On the other hand, we predict invariance laws between continuous cell cultures with different parameters. A practical consequence is that the chemostat is an ideal experimental model for large-scale high-density perfusion cultures, where the complex landscape of metabolic transitions is faithfully reproduced.

  15. Multiobjective flux balancing using the NISE method for metabolic network analysis.

    Oh, Young-Gyun; Lee, Dong-Yup; Lee, Sang Yup; Park, Sunwon

    2009-01-01

    Flux balance analysis (FBA) is well acknowledged as an analysis tool of metabolic networks in the framework of metabolic engineering. However, FBA has a limitation for solving a multiobjective optimization problem which considers multiple conflicting objectives. In this study, we propose a novel multiobjective flux balance analysis method, which adapts the noninferior set estimation (NISE) method (Solanki et al., 1993) for multiobjective linear programming (MOLP) problems. NISE method can generate an approximation of the Pareto curve for conflicting objectives without redundant iterations of single objective optimization. Furthermore, the flux distributions at each Pareto optimal solution can be obtained for understanding the internal flux changes in the metabolic network. The functionality of this approach is shown by applying it to a genome-scale in silico model of E. coli. Multiple objectives for the poly(3-hydroxybutyrate) [P(3HB)] production are considered simultaneously, and relationships among them are identified. The Pareto curve for maximizing succinic acid production vs. maximizing biomass production is used for the in silico analysis of various combinatorial knockout strains. This proposed method accelerates the strain improvement in the metabolic engineering by reducing computation time of obtaining the Pareto curve and analysis time of flux distribution at each Pareto optimal solution. (c) 2009 American Institute of Chemical Engineers Biotechnol. Prog., 2009.

  16. Metabolism

    ... Are More Common in People With Type 1 Diabetes Metabolic Syndrome Your Child's Weight Healthy Eating Endocrine System Blood Test: Basic Metabolic Panel (BMP) Activity: Endocrine System Growth Disorders Diabetes Center Thyroid Disorders Your Endocrine System Movie: Endocrine ...

  17. Dynamics on networks: the role of local dynamics and global networks on the emergence of hypersynchronous neural activity.

    Helmut Schmidt

    2014-11-01

    Full Text Available Graph theory has evolved into a useful tool for studying complex brain networks inferred from a variety of measures of neural activity, including fMRI, DTI, MEG and EEG. In the study of neurological disorders, recent work has discovered differences in the structure of graphs inferred from patient and control cohorts. However, most of these studies pursue a purely observational approach; identifying correlations between properties of graphs and the cohort which they describe, without consideration of the underlying mechanisms. To move beyond this necessitates the development of computational modeling approaches to appropriately interpret network interactions and the alterations in brain dynamics they permit, which in the field of complexity sciences is known as dynamics on networks. In this study we describe the development and application of this framework using modular networks of Kuramoto oscillators. We use this framework to understand functional networks inferred from resting state EEG recordings of a cohort of 35 adults with heterogeneous idiopathic generalized epilepsies and 40 healthy adult controls. Taking emergent synchrony across the global network as a proxy for seizures, our study finds that the critical strength of coupling required to synchronize the global network is significantly decreased for the epilepsy cohort for functional networks inferred from both theta (3-6 Hz and low-alpha (6-9 Hz bands. We further identify left frontal regions as a potential driver of seizure activity within these networks. We also explore the ability of our method to identify individuals with epilepsy, observing up to 80% predictive power through use of receiver operating characteristic analysis. Collectively these findings demonstrate that a computer model based analysis of routine clinical EEG provides significant additional information beyond standard clinical interpretation, which should ultimately enable a more appropriate mechanistic

  18. The impact of global signal regression on resting state correlations: are anti-correlated networks introduced?

    Murphy, Kevin; Birn, Rasmus M; Handwerker, Daniel A; Jones, Tyler B; Bandettini, Peter A

    2009-02-01

    Low-frequency fluctuations in fMRI signal have been used to map several consistent resting state networks in the brain. Using the posterior cingulate cortex as a seed region, functional connectivity analyses have found not only positive correlations in the default mode network but negative correlations in another resting state network related to attentional processes. The interpretation is that the human brain is intrinsically organized into dynamic, anti-correlated functional networks. Global variations of the BOLD signal are often considered nuisance effects and are commonly removed using a general linear model (GLM) technique. This global signal regression method has been shown to introduce negative activation measures in standard fMRI analyses. The topic of this paper is whether such a correction technique could be the cause of anti-correlated resting state networks in functional connectivity analyses. Here we show that, after global signal regression, correlation values to a seed voxel must sum to a negative value. Simulations also show that small phase differences between regions can lead to spurious negative correlation values. A combination breath holding and visual task demonstrates that the relative phase of global and local signals can affect connectivity measures and that, experimentally, global signal regression leads to bell-shaped correlation value distributions, centred on zero. Finally, analyses of negatively correlated networks in resting state data show that global signal regression is most likely the cause of anti-correlations. These results call into question the interpretation of negatively correlated regions in the brain when using global signal regression as an initial processing step.

  19. Network analytical tool for monitoring global food safety highlights China.

    Tamás Nepusz

    Full Text Available BACKGROUND: The Beijing Declaration on food safety and security was signed by over fifty countries with the aim of developing comprehensive programs for monitoring food safety and security on behalf of their citizens. Currently, comprehensive systems for food safety and security are absent in many countries, and the systems that are in place have been developed on different principles allowing poor opportunities for integration. METHODOLOGY/PRINCIPAL FINDINGS: We have developed a user-friendly analytical tool based on network approaches for instant customized analysis of food alert patterns in the European dataset from the Rapid Alert System for Food and Feed. Data taken from alert logs between January 2003-August 2008 were processed using network analysis to i capture complexity, ii analyze trends, and iii predict possible effects of interventions by identifying patterns of reporting activities between countries. The detector and transgressor relationships are readily identifiable between countries which are ranked using i Google's PageRank algorithm and ii the HITS algorithm of Kleinberg. The program identifies Iran, China and Turkey as the transgressors with the largest number of alerts. However, when characterized by impact, counting the transgressor index and the number of countries involved, China predominates as a transgressor country. CONCLUSIONS/SIGNIFICANCE: This study reports the first development of a network analysis approach to inform countries on their transgressor and detector profiles as a user-friendly aid for the adoption of the Beijing Declaration. The ability to instantly access the country-specific components of the several thousand annual reports will enable each country to identify the major transgressors and detectors within its trading network. Moreover, the tool can be used to monitor trading countries for improved detector/transgressor ratios.

  20. Reconfiguring global pharmaceutical value networks through targeted technology interventions

    Harrington, Tomas Seosamh; Phillips, MA; Srai, Jagjit Singh

    2016-01-01

    Targeting a series of advanced manufacturing technology (AMT) ‘interventions’ provides the potential for significant step changes across the pharmaceutical value chain, from early stage ‘system discovery’ and clinical trials, through to novel service supply models. This research explores future value network configurations which, when aligned with disruptive shifts in technology (process and digital), may enable alternative routes to medicines production and the delivery of additional value t...

  1. The Transition from Alliance Networks to Multilateral Alliances in the Global Airline Industry

    Sergio G. Lazzarini

    2008-01-01

    Full Text Available This study examines conditions in which alliance networks (informal webs of bilateral entanglements between firms may or may not evolve into multilateral alliances (broad, formal multiple-firm arrangements. I offer a theory to explain the formation of multilateral alliances based on both the resource profile and the structure of existing interfirm networks, and provide an initial test of that theory in the context of the global airline industry. Using data from 75 global airlines and their alliances, I propose a methodology to retrieve samples of alliance networks and then use regression analysis to assess how the resource profile and the structure of these networks influence their formalization into multilateral alliances. I find that multilateral alliances are more likely to emerge when alliance networks exhibit high resource diversity and network structure characterized by moderate density and high centralization. Apparently, while highly sparse networks reduce actors’ awareness of their potential joint collaboration, highly dense or embedded networks substitute for the need for formal controls accompanying multilateral agreements. The effect of centralization suggests that the formation of multilateral alliances tends to be triggered by leading actors directly connected to other network members.

  2. Vulnerability to shocks in the global seafood trade network

    Gephart, Jessica A.; Rovenskaya, Elena; Dieckmann, Ulf; Pace, Michael L.; Brännström, Åke

    2016-03-01

    Trade can allow countries to overcome local or regional losses (shocks) to their food supply, but reliance on international food trade also exposes countries to risks from external perturbations. Countries that are nutritionally or economically dependent on international trade of a commodity may be adversely affected by such shocks. While exposure to shocks has been studied in financial markets, communication networks, and some infrastructure systems, it has received less attention in food-trade networks. Here, we develop a forward shock-propagation model to quantify how trade flows are redistributed under a range of shock scenarios and assess the food-security outcomes by comparing changes in national fish supplies to indices of each country’s nutritional fish dependency. Shock propagation and distribution among regions are modeled on a network of historical bilateral seafood trade data from UN Comtrade using 205 reporting territories grouped into 18 regions. In our model exposure to shocks increases with total imports and the number of import partners. We find that Central and West Africa are the most vulnerable to shocks, with their vulnerability increasing when a willingness-to-pay proxy is included. These findings suggest that countries can reduce their overall vulnerability to shocks by reducing reliance on imports and diversifying food sources. As international seafood trade grows, identifying these types of potential risks and vulnerabilities is important to build a more resilient food system.

  3. Brain networks predict metabolism, diagnosis and prognosis at the bedside in disorders of consciousness.

    Chennu, Srivas; Annen, Jitka; Wannez, Sarah; Thibaut, Aurore; Chatelle, Camille; Cassol, Helena; Martens, Géraldine; Schnakers, Caroline; Gosseries, Olivia; Menon, David; Laureys, Steven

    2017-08-01

    Recent advances in functional neuroimaging have demonstrated novel potential for informing diagnosis and prognosis in the unresponsive wakeful syndrome and minimally conscious states. However, these technologies come with considerable expense and difficulty, limiting the possibility of wider clinical application in patients. Here, we show that high density electroencephalography, collected from 104 patients measured at rest, can provide valuable information about brain connectivity that correlates with behaviour and functional neuroimaging. Using graph theory, we visualize and quantify spectral connectivity estimated from electroencephalography as a dense brain network. Our findings demonstrate that key quantitative metrics of these networks correlate with the continuum of behavioural recovery in patients, ranging from those diagnosed as unresponsive, through those who have emerged from minimally conscious, to the fully conscious locked-in syndrome. In particular, a network metric indexing the presence of densely interconnected central hubs of connectivity discriminated behavioural consciousness with accuracy comparable to that achieved by expert assessment with positron emission tomography. We also show that this metric correlates strongly with brain metabolism. Further, with classification analysis, we predict the behavioural diagnosis, brain metabolism and 1-year clinical outcome of individual patients. Finally, we demonstrate that assessments of brain networks show robust connectivity in patients diagnosed as unresponsive by clinical consensus, but later rediagnosed as minimally conscious with the Coma Recovery Scale-Revised. Classification analysis of their brain network identified each of these misdiagnosed patients as minimally conscious, corroborating their behavioural diagnoses. If deployed at the bedside in the clinical context, such network measurements could complement systematic behavioural assessment and help reduce the high misdiagnosis rate reported

  4. The global health network on alcohol control: successes and limits of evidence-based advocacy.

    Schmitz, Hans Peter

    2016-04-01

    Global efforts to address alcohol harm have significantly increased since the mid-1990 s. By 2010, the World Health Organization (WHO) had adopted the non-binding Global Strategy to Reduce the Harmful Use of Alcohol. This study investigates the role of a global health network, anchored by the Global Alcohol Policy Alliance (GAPA), which has used scientific evidence on harm and effective interventions to advocate for greater global public health efforts to reduce alcohol harm. The study uses process-tracing methodology and expert interviews to evaluate the accomplishments and limitations of this network. The study documents how network members have not only contributed to greater global awareness about alcohol harm, but also advanced a public health approach to addressing this issue at the global level. Although the current network represents an expanding global coalition of like-minded individuals, it faces considerable challenges in advancing its cause towards successful implementation of effective alcohol control policies across many low- and middle-income countries (LMICs). The analysis reveals a need to transform the network into a formal coalition of regional and national organizations that represent a broader variety of constituents, including the medical community, consumer groups and development-focused non-governmental organizations. Considering the growing harm of alcohol abuse in LMICs and the availability of proven and cost-effective public health interventions, alcohol control represents an excellent 'buy' for donors interested in addressing non-communicable diseases. Alcohol control has broad beneficial effects for human development, including promoting road safety and reducing domestic violence and health care costs across a wide variety of illnesses caused by alcohol consumption. Published by Oxford University Press in association with The London School of Hygiene and Tropical Medicine © The Author 2015; all rights reserved.

  5. International trade network: fractal properties and globalization puzzle.

    Karpiarz, Mariusz; Fronczak, Piotr; Fronczak, Agata

    2014-12-12

    Globalization is one of the central concepts of our age. The common perception of the process is that, due to declining communication and transport costs, distance becomes less and less important. However, the distance coefficient in the gravity model of trade, which grows in time, indicates that the role of distance increases rather than decreases. This, in essence, captures the notion of the globalization puzzle. Here, we show that the fractality of the international trade system (ITS) provides a simple solution for the puzzle. We argue that the distance coefficient corresponds to the fractal dimension of ITS. We provide two independent methods, the box counting method and spatial choice model, which confirm this statement. Our results allow us to conclude that the previous approaches to solving the puzzle misinterpreted the meaning of the distance coefficient in the gravity model of trade.

  6. INTERACTIVE GLOBAL NETWORK FOR WEATHER DATA OBTAINING, EXCHANGE AND DISSEMINATION

    Ю.А. Авер’янова

    2012-12-01

    Full Text Available  The possibility to enhance the weather information provision of relevant customers is considered. It is based on the use of the complex global system for weather information obtaining, exchange and dissemination. The structural diagram of the system is proposed. The structural diagram is completed with addition connections that allow to pay strong attention on the most dangerous meteorological phenomena at the critical moment of flight. The proposed approach gives possibility to aircraft crew to select and use specified operative information and increase the probability for proper decision taking. The aircraft are used as the dynamic elements for data obtaining and exchange in the frame of the global system for weather information obtaining, exchange and dissemination.

  7. Future global SLR network evolution and its impact on the terrestrial reference frame

    Kehm, Alexander; Bloßfeld, Mathis; Pavlis, Erricos C.; Seitz, Florian

    2018-06-01

    Satellite laser ranging (SLR) is an important technique that contributes to the determination of terrestrial geodetic reference frames, especially to the realization of the origin and the scale of global networks. One of the major limiting factors of SLR-derived reference frame realizations is the datum accuracy which significantly suffers from the current global SLR station distribution. In this paper, the impact of a potential future development of the SLR network on the estimated datum parameters is investigated. The current status of the SLR network is compared to a simulated potential future network featuring additional stations improving the global network geometry. In addition, possible technical advancements resulting in a higher amount of observations are taken into account as well. As a result, we find that the network improvement causes a decrease in the scatter of the network translation parameters of up to 24%, and up to 20% for the scale, whereas the technological improvement causes a reduction in the scatter of up to 27% for the translations and up to 49% for the scale. The Earth orientation parameters benefit by up to 15% from both effects.

  8. A Space Operations Network Alternative: Using Globally Connected Research and Education Networks for Space-Based Science Operations

    Bradford, Robert N.

    2006-01-01

    Earth based networking in support of various space agency projects has been based on leased service/circuits which has a high associated cost. This cost is almost always taken from the science side resulting in less science. This is a proposal to use Research and Education Networks (RENs) worldwide to support space flight operations in general and space-based science operations in particular. The RENs were developed to support scientific and educational endeavors. They do not provide support for general Internet traffic. The connectivity and performance of the research and education networks is superb. The connectivity at Layer 3 (IP) virtually encompasses the globe. Most third world countries and all developed countries have their own research and education networks, which are connected globally. Performance of the RENs especially in the developed countries is exceptional. Bandwidth capacity currently exists and future expansion promises that this capacity will continue. REN performance statistics has always exceeded minimum requirements for spaceflight support. Research and Education networks are more loosely managed than a corporate network but are highly managed when compared to the commodity Internet. Management of RENs on an international level is accomplished by the International Network Operations Center at Indiana University at Indianapolis. With few exceptions, each regional and national REN has its own network ops center. The acceptable use policies (AUP), although differing by country, allows any scientific program or project the use of their networks. Once in compliance with the first RENs AUP, all others will accept that specific traffic including regional and transoceanic networks. RENs can support spaceflight related scientific programs and projects. Getting the science to the researcher is obviously key to any scientific project. RENs provide a pathway to virtually any college or university in the world, as well as many governmental institutes and

  9. Plasticity in habitat use determines metabolic response of fish to global warming in stratified lakes.

    Busch, Susan; Kirillin, Georgiy; Mehner, Thomas

    2012-09-01

    We used a coupled lake physics and bioenergetics-based foraging model to evaluate how the plasticity in habitat use modifies the seasonal metabolic response of two sympatric cold-water fishes (vendace and Fontane cisco, Coregonus spp.) under a global warming scenario for the year 2100. In different simulations, the vertically migrating species performed either a plastic strategy (behavioral thermoregulation) by shifting their population depth at night to maintain the temperatures occupied at current in-situ observations, or a fixed strategy (no thermoregulation) by keeping their occupied depths at night but facing modified temperatures. The lake physics model predicted higher temperatures above 20 m and lower temperatures below 20 m in response to warming. Using temperature-zooplankton relationships, the density of zooplankton prey was predicted to increase at the surface, but to decrease in hypolimnetic waters. Simulating the fixed strategy, growth was enhanced only for the deeper-living cisco due to the shift in thermal regime at about 20 m. In contrast, simulating the plastic strategy, individual growth of cisco and young vendace was predicted to increase compared to growth currently observed in the lake. Only growth rates of older vendace are reduced under future global warming scenarios irrespective of the behavioral strategy. However, performing behavioral thermoregulation would drive both species into the same depth layers, and hence will erode vertical microhabitat segregation and intensify inter-specific competition between the coexisting coregonids.

  10. Antimalarial drug targets in Plasmodium falciparum predicted by stage-specific metabolic network analysis

    Huthmacher Carola

    2010-08-01

    Full Text Available Abstract Background Despite enormous efforts to combat malaria the disease still afflicts up to half a billion people each year of which more than one million die. Currently no approved vaccine is available and resistances to antimalarials are widely spread. Hence, new antimalarial drugs are urgently needed. Results Here, we present a computational analysis of the metabolism of Plasmodium falciparum, the deadliest malaria pathogen. We assembled a compartmentalized metabolic model and predicted life cycle stage specific metabolism with the help of a flux balance approach that integrates gene expression data. Predicted metabolite exchanges between parasite and host were found to be in good accordance with experimental findings when the parasite's metabolic network was embedded into that of its host (erythrocyte. Knock-out simulations identified 307 indispensable metabolic reactions within the parasite. 35 out of 57 experimentally demonstrated essential enzymes were recovered and another 16 enzymes, if additionally the assumption was made that nutrient uptake from the host cell is limited and all reactions catalyzed by the inhibited enzyme are blocked. This predicted set of putative drug targets, shown to be enriched with true targets by a factor of at least 2.75, was further analyzed with respect to homology to human enzymes, functional similarity to therapeutic targets in other organisms and their predicted potency for prophylaxis and disease treatment. Conclusions The results suggest that the set of essential enzymes predicted by our flux balance approach represents a promising starting point for further drug development.

  11. XenoSite: accurately predicting CYP-mediated sites of metabolism with neural networks.

    Zaretzki, Jed; Matlock, Matthew; Swamidass, S Joshua

    2013-12-23

    Understanding how xenobiotic molecules are metabolized is important because it influences the safety, efficacy, and dose of medicines and how they can be modified to improve these properties. The cytochrome P450s (CYPs) are proteins responsible for metabolizing 90% of drugs on the market, and many computational methods can predict which atomic sites of a molecule--sites of metabolism (SOMs)--are modified during CYP-mediated metabolism. This study improves on prior methods of predicting CYP-mediated SOMs by using new descriptors and machine learning based on neural networks. The new method, XenoSite, is faster to train and more accurate by as much as 4% or 5% for some isozymes. Furthermore, some "incorrect" predictions made by XenoSite were subsequently validated as correct predictions by revaluation of the source literature. Moreover, XenoSite output is interpretable as a probability, which reflects both the confidence of the model that a particular atom is metabolized and the statistical likelihood that its prediction for that atom is correct.

  12. Cerebral energy metabolism and the brain's functional network architecture: an integrative review.

    Lord, Louis-David; Expert, Paul; Huckins, Jeremy F; Turkheimer, Federico E

    2013-09-01

    Recent functional magnetic resonance imaging (fMRI) studies have emphasized the contributions of synchronized activity in distributed brain networks to cognitive processes in both health and disease. The brain's 'functional connectivity' is typically estimated from correlations in the activity time series of anatomically remote areas, and postulated to reflect information flow between neuronal populations. Although the topological properties of functional brain networks have been studied extensively, considerably less is known regarding the neurophysiological and biochemical factors underlying the temporal coordination of large neuronal ensembles. In this review, we highlight the critical contributions of high-frequency electrical oscillations in the γ-band (30 to 100 Hz) to the emergence of functional brain networks. After describing the neurobiological substrates of γ-band dynamics, we specifically discuss the elevated energy requirements of high-frequency neural oscillations, which represent a mechanistic link between the functional connectivity of brain regions and their respective metabolic demands. Experimental evidence is presented for the high oxygen and glucose consumption, and strong mitochondrial performance required to support rhythmic cortical activity in the γ-band. Finally, the implications of mitochondrial impairments and deficits in glucose metabolism for cognition and behavior are discussed in the context of neuropsychiatric and neurodegenerative syndromes characterized by large-scale changes in the organization of functional brain networks.

  13. Global stability of a susceptible-infected-susceptible epidemic model on networks with individual awareness

    Li Ke-Zan; Xu Zhong-Pu; Zhu Guang-Hu; Ding Yong

    2014-01-01

    Recent research results indicate that individual awareness can play an important influence on epidemic spreading in networks. By local stability analysis, a significant conclusion is that the embedded awareness in an epidemic network can increase its epidemic threshold. In this paper, by using limit theory and dynamical system theory, we further give global stability analysis of a susceptible-infected-susceptible (SIS) epidemic model on networks with awareness. Results show that the obtained epidemic threshold is also a global stability condition for its endemic equilibrium, which implies the embedded awareness can enhance the epidemic threshold globally. Some numerical examples are presented to verify the theoretical results. (interdisciplinary physics and related areas of science and technology)

  14. Metal availability and the expanding network of microbial metabolisms in the Archaean eon

    Moore, Eli K.; Jelen, Benjamin I.; Giovannelli, Donato; Raanan, Hagai; Falkowski, Paul G.

    2017-09-01

    Life is based on energy gained by electron-transfer processes; these processes rely on oxidoreductase enzymes, which often contain transition metals in their structures. The availability of different metals and substrates has changed over the course of Earth's history as a result of secular changes in redox conditions, particularly global oxygenation. New metabolic pathways using different transition metals co-evolved alongside changing redox conditions. Sulfur reduction, sulfate reduction, methanogenesis and anoxygenic photosynthesis appeared between about 3.8 and 3.4 billion years ago. The oxidoreductases responsible for these metabolisms incorporated metals that were readily available in Archaean oceans, chiefly iron and iron-sulfur clusters. Oxygenic photosynthesis appeared between 3.2 and 2.5 billion years ago, as did methane oxidation, nitrogen fixation, nitrification and denitrification. These metabolisms rely on an expanded range of transition metals presumably made available by the build-up of molecular oxygen in soil crusts and marine microbial mats. The appropriation of copper in enzymes before the Great Oxidation Event is particularly important, as copper is key to nitrogen and methane cycling and was later incorporated into numerous aerobic metabolisms. We find that the diversity of metals used in oxidoreductases has increased through time, suggesting that surface redox potential and metal incorporation influenced the evolution of metabolism, biological electron transfer and microbial ecology.

  15. Experimental observation of chimera and cluster states in a minimal globally coupled network

    Hart, Joseph D. [Institute for Research in Electronics and Applied Physics, University of Maryland, College Park, Maryland 20742 (United States); Department of Physics, University of Maryland, College Park, Maryland 20742 (United States); Bansal, Kanika [Department of Mathematics, University at Buffalo, SUNY Buffalo, New York 14260 (United States); US Army Research Laboratory, Aberdeen Proving Ground, Maryland 21005 (United States); Murphy, Thomas E. [Institute for Research in Electronics and Applied Physics, University of Maryland, College Park, Maryland 20742 (United States); Department of Electrical and Computer Engineering, University of Maryland, College Park, Maryland 20742 (United States); Roy, Rajarshi [Institute for Research in Electronics and Applied Physics, University of Maryland, College Park, Maryland 20742 (United States); Department of Physics, University of Maryland, College Park, Maryland 20742 (United States); Institute for Physical Science and Technology, University of Maryland, College Park, Maryland 20742 (United States)

    2016-09-15

    A “chimera state” is a dynamical pattern that occurs in a network of coupled identical oscillators when the symmetry of the oscillator population is broken into synchronous and asynchronous parts. We report the experimental observation of chimera and cluster states in a network of four globally coupled chaotic opto-electronic oscillators. This is the minimal network that can support chimera states, and our study provides new insight into the fundamental mechanisms underlying their formation. We use a unified approach to determine the stability of all the observed partially synchronous patterns, highlighting the close relationship between chimera and cluster states as belonging to the broader phenomenon of partial synchronization. Our approach is general in terms of network size and connectivity. We also find that chimera states often appear in regions of multistability between global, cluster, and desynchronized states.

  16. Global asymptotic stability to a generalized Cohen-Grossberg BAM neural networks of neutral type delays.

    Zhang, Zhengqiu; Liu, Wenbin; Zhou, Dongming

    2012-01-01

    In this paper, we first discuss the existence of a unique equilibrium point of a generalized Cohen-Grossberg BAM neural networks of neutral type delays by means of the Homeomorphism theory and inequality technique. Then, by applying the existence result of an equilibrium point and constructing a Lyapunov functional, we study the global asymptotic stability of the equilibrium solution to the above Cohen-Grossberg BAM neural networks of neutral type. In our results, the hypothesis for boundedness in the existing paper, which discussed Cohen-Grossberg neural networks of neutral type on the activation functions, are removed. Finally, we give an example to demonstrate the validity of our global asymptotic stability result for the above neural networks. Copyright © 2011 Elsevier Ltd. All rights reserved.

  17. Coupling Strength and System Size Induce Firing Activity of Globally Coupled Neural Network

    Wei Duqu; Luo Xiaoshu; Zou Yanli

    2008-01-01

    We investigate how firing activity of globally coupled neural network depends on the coupling strength C and system size N. Network elements are described by space-clamped FitzHugh-Nagumo (SCFHN) neurons with the values of parameters at which no firing activity occurs. It is found that for a given appropriate coupling strength, there is an intermediate range of system size where the firing activity of globally coupled SCFHN neural network is induced and enhanced. On the other hand, for a given intermediate system size level, there exists an optimal value of coupling strength such that the intensity of firing activity reaches its maximum. These phenomena imply that the coupling strength and system size play a vital role in firing activity of neural network

  18. A method for estimation of elasticities in metabolic networks using steady state and dynamic metabolomics data and linlog kinetics

    Nikerel, I.E.; Van Winden, W.; Van Gulik, W.M.; Heijnen, J.J.

    2006-01-01

    Background: Dynamic modeling of metabolic reaction networks under in vivo conditions is a crucial step in order to obtain a better understanding of the (dis)functioning of living cells. So far dynamic metabolic models generally have been based on mechanistic rate equations which often contain so

  19. Network thermodynamic curation of human and yeast genome-scale metabolic models.

    Martínez, Verónica S; Quek, Lake-Ee; Nielsen, Lars K

    2014-07-15

    Genome-scale models are used for an ever-widening range of applications. Although there has been much focus on specifying the stoichiometric matrix, the predictive power of genome-scale models equally depends on reaction directions. Two-thirds of reactions in the two eukaryotic reconstructions Homo sapiens Recon 1 and Yeast 5 are specified as irreversible. However, these specifications are mainly based on biochemical textbooks or on their similarity to other organisms and are rarely underpinned by detailed thermodynamic analysis. In this study, a to our knowledge new workflow combining network-embedded thermodynamic and flux variability analysis was used to evaluate existing irreversibility constraints in Recon 1 and Yeast 5 and to identify new ones. A total of 27 and 16 new irreversible reactions were identified in Recon 1 and Yeast 5, respectively, whereas only four reactions were found with directions incorrectly specified against thermodynamics (three in Yeast 5 and one in Recon 1). The workflow further identified for both models several isolated internal loops that require further curation. The framework also highlighted the need for substrate channeling (in human) and ATP hydrolysis (in yeast) for the essential reaction catalyzed by phosphoribosylaminoimidazole carboxylase in purine metabolism. Finally, the framework highlighted differences in proline metabolism between yeast (cytosolic anabolism and mitochondrial catabolism) and humans (exclusively mitochondrial metabolism). We conclude that network-embedded thermodynamics facilitates the specification and validation of irreversibility constraints in compartmentalized metabolic models, at the same time providing further insight into network properties. Copyright © 2014 Biophysical Society. Published by Elsevier Inc. All rights reserved.

  20. Managing uncertainty in metabolic network structure and improving predictions using EnsembleFBA.

    Matthew B Biggs

    2017-03-01

    Full Text Available Genome-scale metabolic network reconstructions (GENREs are repositories of knowledge about the metabolic processes that occur in an organism. GENREs have been used to discover and interpret metabolic functions, and to engineer novel network structures. A major barrier preventing more widespread use of GENREs, particularly to study non-model organisms, is the extensive time required to produce a high-quality GENRE. Many automated approaches have been developed which reduce this time requirement, but automatically-reconstructed draft GENREs still require curation before useful predictions can be made. We present a novel approach to the analysis of GENREs which improves the predictive capabilities of draft GENREs by representing many alternative network structures, all equally consistent with available data, and generating predictions from this ensemble. This ensemble approach is compatible with many reconstruction methods. We refer to this new approach as Ensemble Flux Balance Analysis (EnsembleFBA. We validate EnsembleFBA by predicting growth and gene essentiality in the model organism Pseudomonas aeruginosa UCBPP-PA14. We demonstrate how EnsembleFBA can be included in a systems biology workflow by predicting essential genes in six Streptococcus species and mapping the essential genes to small molecule ligands from DrugBank. We found that some metabolic subsystems contributed disproportionately to the set of predicted essential reactions in a way that was unique to each Streptococcus species, leading to species-specific outcomes from small molecule interactions. Through our analyses of P. aeruginosa and six Streptococci, we show that ensembles increase the quality of predictions without drastically increasing reconstruction time, thus making GENRE approaches more practical for applications which require predictions for many non-model organisms. All of our functions and accompanying example code are available in an open online repository.

  1. Forced disappearance in an era of globalization: biopolitics, shadow networks, and imagined worlds.

    Rozema, Ralph

    2011-01-01

    In this article, I argue that the practice of forced disappearance of persons on the part of paramilitary groups has become linked to specific processes of globalization. Global flows related to biopolitics, global crime networks, and dehumanizing imaginations reproduced by mass media together constitute a driving force behind forced disappearances. Drawing on ethnographic fieldwork in the Colombian city of Medellín, I analyze how these global flows interact with local armed actors, helping create a climate conducive to forced disappearance. These mechanisms in Colombia show similarities to those in some African and Asian countries. Gaining insight into the mechanisms behind forced disappearance may help prevent it from occurring in the future. Enhancing social inclusion of residents, unraveling the transnational crime networks in which perpetrators are involved, and disseminating rehumanizing images of victims all contribute to curbing the practice of forced disappearance.

  2. CTFS-ForestGEO: a worldwide network monitoring forests in an era of global change

    Anderson-Teixeira, Kristina J. [Smithsonian Tropical Research Inst. (STRI), Panama (Panama). Center for Tropical Forest Science. Forest Global Earth Observatory; Smithsonian Conservation Biology Inst. (SCBI), Front Royal, VA (United States). National Zoological Park. Conservation Ecology Center; Davies, Stuart J. [Smithsonian Tropical Research Inst. (STRI), Panama (Panama). Center for Tropical Forest Science. Forest Global Earth Observatory; National Museum of Natural History, Washington, DC (United States). Dept. of Botany; Bennett, Amy C. [Smithsonian Conservation Biology Inst. (SCBI), Front Royal, VA (United States). National Zoological Park. Conservation Ecology Center; Gonzalez-Akre, Erika B. [Smithsonian Conservation Biology Inst. (SCBI), Front Royal, VA (United States). National Zoological Park. Conservation Ecology Center; Muller-Landau, Helene C. [Smithsonian Tropical Research Inst. (STRI), Panama (Panama). Center for Tropical Forest Science. Forest Global Earth Observatory; Joseph Wright, S. [Smithsonian Tropical Research Inst. (STRI), Panama (Panama). Center for Tropical Forest Science. Forest Global Earth Observatory; Abu Salim, Kamariah [Univ. of Brunei Darussalam, Bandar Seri Begawan (Brunei). Faculty of Science. Environmental and Life Sciences; Almeyda Zambrano, Angélica M. [Smithsonian Conservation Biology Inst. (SCBI), Front Royal, VA (United States). National Zoological Park. Conservation Ecology Center; Stanford Univ., CA (United States). Stanford Woods Inst. for the Environment; Univ. of Alabama, Tuscaloosa, AL (United States). Dept. of Geography; Alonso, Alfonso [Smithsonian Conservation Biology Inst., Washington, DC (United States). National Zoological Park. Center for Conservation Education and Sustainability; Baltzer, Jennifer L. [Wilfrid Laurier Univ., Waterloo, ON (Canada). Dept. of Biology; Basset, Yves [Smithsonian Tropical Research Inst. (STRI), Panama (Panama). Center for Tropical Forest Science. Forest Global Earth Observatory; Bourg, Norman A. [Smithsonian Conservation Biology Inst. (SCBI), Front Royal, VA (United States). National Zoological Park. Conservation Ecology Center; Broadbent, Eben N. [Smithsonian Conservation Biology Inst. (SCBI), Front Royal, VA (United States). National Zoological Park. Conservation Ecology Center; Stanford Univ., CA (United States). Stanford Woods Inst. for the Environment; Univ. of Alabama, Tuscaloosa, AL (United States). Dept. of Geography; Brockelman, Warren Y. [Mahidol Univ., Bangkok (Thailand). Dept. of Biology; Bunyavejchewin, Sarayudh [Dept. of National Parks, Wildlife and Plant Conservation, Bangkok (Thailand). Research Office; Burslem, David F. R. P. [Univ. of Aberdeen (United Kingdom). School of Biological Sciences; Butt, Nathalie [Univ. of Queensland, St. Lucia (Australia). School of Biological Sciences; Univ. of Oxford (United Kingdom). School of Geography and the Environment. Environmental Change Inst.; Cao, Min [Chinese Academy of Sciences (CAS), Kunming (China). Xishuangbanna Tropical Botanical Garden. Key Lab. of Tropical Forest Ecology; Cardenas, Dairon [Sinchi Amazonic Inst. of Scientific Research, Bogota (Colombia); Chuyong, George B. [Univ. of Buea (Cameroon). Dept. of Botany and Plant Physiology; Clay, Keith [Indiana Univ., Bloomington, IN (United States). Dept. of Biology; Cordell, Susan [USDA Forest Service, Hilo, HI (United States). Inst. of Pacific Islands Forestry; Dattaraja, Handanakere S. [Indian Inst. of Science, Bangalore (India). Centre for Ecological Sciences; Deng, Xiaobao [Chinese Academy of Sciences (CAS), Kunming (China). Xishuangbanna Tropical Botanical Garden. Key Lab. of Tropical Forest Ecology; Detto, Matteo [Smithsonian Tropical Research Inst. (STRI), Panama (Panama). Center for Tropical Forest Science. Forest Global Earth Observatory; Du, Xiaojun [Chinese Academy of Sciences (CAS), Beijing (China). Inst. of Botany; Duque, Alvaro [Univ. Nacional de Colombia, Medellin (Colombia). Dept. de Ciencias Forestales; Erikson, David L. [National Museum of Natural History, Washington, DC (United States). Dept. of Botany; Ewango, Corneille E. N. [Okapi Wildlife Reserve, Epulu (Democratic Republic of the Congo). Centre de Formation et de Recherche en Conservation Forestiere (CEFRECOF); Fischer, Gunter A. [Kadoorie Farm and Botanic Garden, Tai Po, Hong Kong (China); Fletcher, Christine [Forest Research Inst. Malaysia (FRIM), Selangor (Malaysia); Foster, Robin B. [The Field Museum, Chicago, IL (United States). Botany Dept.; Giardina, Christian P. [USDA Forest Service, Hilo, HI (United States). Inst. of Pacific Islands Forestry; Gilbert, Gregory S. [Smithsonian Tropical Research Inst. (STRI), Panama (Panama). Center for Tropical Forest Science. Forest Global Earth Observatory; Univ. of California, Santa Cruz, CA (United States). Environmental Studies Dept.; Gunatilleke, Nimal [Univ. of Peradeniya (Sri Lanka). Faculty of Science. Dept. of Botany; Gunatilleke, Savitri [Univ. of Peradeniya (Sri Lanka). Faculty of Science. Dept. of Botany; Hao, Zhanqing [Chinese Academy of Sciences (CAS), Shenyang (China). State Key Lab. of Forest and Soil Ecology. Inst. of Applied Ecology; Hargrove, William W. [USDA-Forest Service Station Headquarters, Asheville, NC (United States). Eastern Forest Environmental Threat Assessment Center; Hart, Terese B. [Lukuru Wildlife Research Foundation, Kinshasa (Democratic Republic of the Congo). Tshuapa-Lomami-Lualaba Project; Hau, Billy C. H. [Univ. of Hong Kong (China). School of Biological Sciences. Kadoorie Inst.; He, Fangliang [Univ. of Alberta, Edmonton, AB (Canada). Dept. of Renewable Resources; Hoffman, Forrest M. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States). Computational Earth Sciences Group; Howe, Robert W. [Univ. of Wisconsin, Green Bay, WI (United States). Dept. of Natural and Applied Sciences; Hubbell, Stephen P. [Smithsonian Tropical Research Inst. (STRI), Panama (Panama). Center for Tropical Forest Science. Forest Global Earth Observatory; Univ. of California, Los Angeles, CA (United States). Dept. of Ecology and Evolutionary Biology; Inman-Narahari, Faith M. [Univ. of Hawaii, Honolulu, HI (United States). College of Tropical Agriculture and Human Resources; Jansen, Patrick A. [Smithsonian Tropical Research Inst. (STRI), Panama (Panama). Center for Tropical Forest Science. Forest Global Earth Observatory; Wageningen Univ. (Netherlands). Resource Ecology Group; Jiang, Mingxi [Chinese Academy of Sciences (CAS), Wuhan (China). Wuhan Botanical Garden; Johnson, Daniel J. [Indiana Univ., Bloomington, IN (United States). Dept. of Biology; Kanzaki, Mamoru [Kyoto Univ. (Japan). Graduate School of Agriculture; Kassim, Abdul Rahman [Forest Research Inst. Malaysia (FRIM), Selangor (Malaysia); Kenfack, David [Smithsonian Tropical Research Inst. (STRI), Panama (Panama). Center for Tropical Forest Science. Forest Global Earth Observatory; National Museum of Natural History, Washington, DC (United States). Dept. of Botany; Kibet, Staline [National Museums of Kenya, Nairobi (Kenya); Univ. of Nairobi (Kenya). Land Resource Management and Agricultural Technology Dept.; Kinnaird, Margaret F. [Mpala Research Centre, Nanyuki (Kenya); Wildlife Conservation Society, New York, NY (United States). Global Conservation Programs; Korte, Lisa [Smithsonian Conservation Biology Inst., Washington, DC (United States). National Zoological Park. Center for Conservation Education and Sustainability; Kral, Kamil [Silva Tarouca Research Inst., Brno (Czech Republic). Dept. of Forest Ecology; Kumar, Jitendra [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States). Computational Earth Sciences Group; Larson, Andrew J. [Univ. of Montana, Missoula, MT (United States). College of Forestry and Conservation. Dept. of Forest Management; Li, Yide [Chinese Academy of Forestry, Guangzhou (China). Research Inst. of Tropical Forestry; Li, Xiankun [Chinese Academy of Sciences (CAS), Guilin (China). Guangxi Inst. of Botany; Liu, Shirong [Chinese Academy of Forestry, Beijing (China). Research Inst. of Forest Ecology, Environment and Protection; Lum, Shawn K. Y. [Nanyang Technological Univ. (Singapore). National Inst. of Education. Natural Sciences and Science Education Academic Group; Lutz, James A. [Utah State Univ., Logan, UT (United States). Wildland Resources Dept.; Ma, Keping [Chinese Academy of Sciences (CAS), Beijing (China). Inst. of Botany; Maddalena, Damian M. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States). Computational Earth Sciences Group; Makana, Jean-Remy [Wildlife Conservation Society, Brazzaville (Democratic Republic of the Congo); Malhi, Yadvinder [Univ. of Oxford (United Kingdom). School of Geography and the Environment. Environmental Change Inst.; Marthews, Toby [Univ. of Oxford (United Kingdom). School of Geography and the Environment. Environmental Change Inst.; Mat Serudin, Rafizah [Univ. of Brunei Darussalam, Bandar Seri Begawan (Brunei). Faculty of Science. Environmental and Life Sciences; McMahon, Sean M. [Smithsonian Tropical Research Inst. (STRI), Panama (Panama). Center for Tropical Forest Science. Forest Global Earth Observatory; Smithsonian Environmental Research Center, Edgewater, MD (United States). Forest Ecology Group; McShea, William J. [Smithsonian Conservation Biology Inst., Front Royal, VA (United States). National Zoological Park. Conservation Ecology Center; Memiaghe, Hervé R. [Inst. de Recherche en Ecologie Tropicale, Libreville (Gabon). Centre National de la Recherche Scientifique et Technologique; Mi, Xiangcheng [Chinese Academy of Sciences (CAS), Beijing (China). Inst. of Botany; Mizuno, Takashi [Kyoto Univ. (Japan). Graduate School of Agriculture; Morecroft, Michael [Natural England, Sheffield (United Kingdom); Myers, Jonathan A. [Washington Univ., St. Louis, MO (United States). Dept. of Biology; Novotny, Vojtech [New Guinea Binatang Research Centre, Madang (Papua New Guinea); Univ. of South Bohemia, Ceske Budejovice (Czech Republic). Academy of Sciences of the Czech Republic. Faculty of Science. Biology Centre; de Oliveira, Alexandre A. [Univ. of Sao Paulo (Brazil). Inst. of Biosciences. Ecology Dept.; Ong, Perry S. [Univ. of the Philippines Diliman, Quezon City (Philippines). Inst. of Biology; Orwig, David A. [Harvard Univ., Petersham, MA (United States). Harvard Forest; Ostertag, Rebecca [Univ. of Hawaii, Hilo, HI (United States). Dept. of Biology; den Ouden, Jan [Wageningen Univ. (Netherlands). Forest Ecology and Forest Management Group; Parker, Geoffrey G. [Smithsonian Environmental Research Center, Edgewater, MD (United States). Forest Ecology Group; Phillips, Richard P. [Indiana Univ., Bloomington, IN (United States). Dept. of Biology; Sack, Lawren [Univ. of California, Los Angeles, CA (United States). Dept. of Ecology and Evolutionary Biology; Sainge, Moses N. [Tropical Plant Exploration Group (TroPEG), Mundemba (Cameroon); Sang, Weiguo [Chinese Academy of Sciences (CAS), Beijing (China). Inst. of Botany; Sri-ngernyuang, Kriangsak [Maejo Univ., Chiang Mai (Thailand). Faculty of Architecture and Environmental Design; Sukumar, Raman [Indian Inst. of Science, Bangalore (India). Centre for Ecological Sciences; Sun, I-Fang [National Dong Hwa Univ., Hualian (Taiwan). Dept. of Natural Resources and Environmental Studies; Sungpalee, Witchaphart [Maejo Univ., Chiang Mai (Thailand). Faculty of Architecture and Environmental Design; Suresh, Hebbalalu Sathyanarayana [Indian Inst. of Science, Bangalore (India). Centre for Ecological Sciences; Tan, Sylvester [Sarawak Forest Dept., Kuching (Malaysia); Thomas, Sean C. [Univ. of Toronto, ON (Canada). Faculty of Forestry; Thomas, Duncan W. [Washington State Univ., Vancouver, WA (United States). School of Biological Sciences; Thompson, Jill [Centre for Ecology and Hydrology, Penicuik, Scotland (United Kingdom); Univ. of Puerto Rico Rio Pedras, San Juan (Puerto Rico). Dept. of Environmental Science. Inst. for Tropical Ecosystem Studies; Turner, Benjamin L. [Smithsonian Tropical Research Inst. (STRI), Panama (Panama). Center for Tropical Forest Science. Forest Global Earth Observatory; Uriarte, Maria [Columbia Univ., New York, NY (United States). Dept. of Ecology, Evolution and Environmental Biology; Valencia, Renato [Pontifical Catholic Univ. of Ecuador, Quito (Ecuador). Dept. of Biological Sciences; Vallejo, Marta I. [Inst. Alexander von Humboldt, Bogota (Colombia); Vicentini, Alberto [National Inst. of Amazonian Research (INPA), Manaus (Brazil); Vrška, Tomáš [Silva Tarouca Research Inst., Brno (Czech Republic). Dept. of Forest Ecology; Wang, Xihua [East China Normal Univ. (ECNU), Shanghai (China). School of Ecological and Environmental Sciences; Wang, Xugao [Lukuru Wildlife Research Foundation, Kinshasa (Democratic Republic of the Congo). Tshuapa-Lomami-Lualaba Project; Weiblen, George [Univ. of Minnesota, St. Paul, MN (United States). Dept. of Plant Biology; Wolf, Amy [Univ. of Wisconsin, Green Bay, WI (United States). Dept. of Biology. Dept. of Natural and Applied Sciences; Xu, Han [Chinese Academy of Forestry, Guangzhou (China). Research Inst. of Tropical Forestry; Yap, Sandra [Univ. of the Philippines Diliman, Quezon City (Philippines). Inst. of Biology; Zimmerman, Jess [Univ. of Puerto Rico Rio Piedras, San Juan (Puerto Rico). Dept. of Environmental Science. Inst. for Tropical Ecosystem Studies

    2014-09-25

    Global change is impacting forests worldwide, threatening biodiversity and ecosystem services, including climate regulation. Understanding how forests respond is critical to forest conservation and climate protection. This review describes an international network of 59 long-term forest dynamic research sites useful for characterizing forest responses to global change. The broad suite of measurements made at the CTFS-ForestGEO sites make it possible to investigate the complex ways in which global change is impacting forest dynamics. ongoing research across the network is yielding insights into how and why the forests are changing, and continued monitoring will provide vital contributions to understanding worldwide forest diversity and dynamics in a era of global change

  3. Global sensitivity analysis in stochastic simulators of uncertain reaction networks.

    Navarro Jimenez, M; Le Maître, O P; Knio, O M

    2016-12-28

    Stochastic models of chemical systems are often subjected to uncertainties in kinetic parameters in addition to the inherent random nature of their dynamics. Uncertainty quantification in such systems is generally achieved by means of sensitivity analyses in which one characterizes the variability with the uncertain kinetic parameters of the first statistical moments of model predictions. In this work, we propose an original global sensitivity analysis method where the parametric and inherent variability sources are both treated through Sobol's decomposition of the variance into contributions from arbitrary subset of uncertain parameters and stochastic reaction channels. The conceptual development only assumes that the inherent and parametric sources are independent, and considers the Poisson processes in the random-time-change representation of the state dynamics as the fundamental objects governing the inherent stochasticity. A sampling algorithm is proposed to perform the global sensitivity analysis, and to estimate the partial variances and sensitivity indices characterizing the importance of the various sources of variability and their interactions. The birth-death and Schlögl models are used to illustrate both the implementation of the algorithm and the richness of the proposed analysis method. The output of the proposed sensitivity analysis is also contrasted with a local derivative-based sensitivity analysis method classically used for this type of systems.

  4. Global sensitivity analysis in stochastic simulators of uncertain reaction networks

    Navarro, María

    2016-12-26

    Stochastic models of chemical systems are often subjected to uncertainties in kinetic parameters in addition to the inherent random nature of their dynamics. Uncertainty quantification in such systems is generally achieved by means of sensitivity analyses in which one characterizes the variability with the uncertain kinetic parameters of the first statistical moments of model predictions. In this work, we propose an original global sensitivity analysis method where the parametric and inherent variability sources are both treated through Sobol’s decomposition of the variance into contributions from arbitrary subset of uncertain parameters and stochastic reaction channels. The conceptual development only assumes that the inherent and parametric sources are independent, and considers the Poisson processes in the random-time-change representation of the state dynamics as the fundamental objects governing the inherent stochasticity. A sampling algorithm is proposed to perform the global sensitivity analysis, and to estimate the partial variances and sensitivity indices characterizing the importance of the various sources of variability and their interactions. The birth-death and Schlögl models are used to illustrate both the implementation of the algorithm and the richness of the proposed analysis method. The output of the proposed sensitivity analysis is also contrasted with a local derivative-based sensitivity analysis method classically used for this type of systems.

  5. Global stability of an SIR model with differential infectivity on complex networks

    Yuan, Xinpeng; Wang, Fang; Xue, Yakui; Liu, Maoxing

    2018-06-01

    In this paper, an SIR model with birth and death on complex networks is analyzed, where infected individuals are divided into m groups according to their infection and contact between human is treated as a scale-free social network. We obtain the basic reproduction number R0 as well as the effects of various immunization schemes. The results indicate that the disease-free equilibrium is locally and globally asymptotically stable in some conditions, otherwise disease-free equilibrium is unstable and exists an unique endemic equilibrium that is globally asymptotically stable. Our theoretical results are confirmed by numerical simulations and a promising way for infectious diseases control is suggested.

  6. Global existence of periodic solutions on a simplified BAM neural network model with delays

    Zheng Baodong; Zhang Yazhuo; Zhang Chunrui

    2008-01-01

    A simplified n-dimensional BAM neural network model with delays is considered. Some results of Hopf bifurcations occurring at the zero equilibrium as the delay increases are exhibited. Global existence of periodic solutions are established using a global Hopf bifurcation result of Wu [Wu J. Symmetric functional-differential equations and neural networks with memory. Trans Am Math Soc 1998;350:4799-838], and a Bendixson criterion for higher dimensional ordinary differential equations due to Li and Muldowney [Li MY, Muldowney J. On Bendixson's criterion. J Differ Equations 1994;106:27-39]. Finally, computer simulations are performed to illustrate the analytical results found

  7. Global stability of stochastic high-order neural networks with discrete and distributed delays

    Wang Zidong; Fang Jianan; Liu Xiaohui

    2008-01-01

    High-order neural networks can be considered as an expansion of Hopfield neural networks, and have stronger approximation property, faster convergence rate, greater storage capacity, and higher fault tolerance than lower-order neural networks. In this paper, the global asymptotic stability analysis problem is considered for a class of stochastic high-order neural networks with discrete and distributed time-delays. Based on an Lyapunov-Krasovskii functional and the stochastic stability analysis theory, several sufficient conditions are derived, which guarantee the global asymptotic convergence of the equilibrium point in the mean square. It is shown that the stochastic high-order delayed neural networks under consideration are globally asymptotically stable in the mean square if two linear matrix inequalities (LMIs) are feasible, where the feasibility of LMIs can be readily checked by the Matlab LMI toolbox. It is also shown that the main results in this paper cover some recently published works. A numerical example is given to demonstrate the usefulness of the proposed global stability criteria

  8. The Global Geodetic Observing System: Space Geodesy Networks for the Future

    Pearlman, Michael; Pavlis, Erricos; Ma, Chopo; Altamini, Zuheir; Noll, Carey; Stowers, David

    2011-01-01

    Ground-based networks of co-located space geodetic techniques (VLBI, SLR, GNSS. and DORIS) are the basis for the development and maintenance of the International Terrestrial Reference frame (ITRF), which is our metric of reference for measurements of global change, The Global Geodetic Observing System (GGOS) of the International Association of Geodesy (IAG) has established a task to develop a strategy to design, integrate and maintain the fundamental geodetic network and supporting infrastructure in a sustainable way to satisfy the long-term requirements for the reference frame. The GGOS goal is an origin definition at 1 mm or better and a temporal stability on the order of 0.1 mm/y, with similar numbers for the scale and orientation components. These goals are based on scientific requirements to address sea level rise with confidence, but other applications are not far behind. Recent studies including one by the US National Research Council has strongly stated the need and the urgency for the fundamental space geodesy network. Simulations are underway to examining accuracies for origin, scale and orientation of the resulting ITRF based on various network designs and system performance to determine the optimal global network to achieve this goal. To date these simulations indicate that 24 - 32 co-located stations are adequate to define the reference frame and a more dense GNSS and DORIS network will be required to distribute the reference frame to users anywhere on Earth. Stations in the new global network will require geologically stable sites with good weather, established infrastructure, and local support and personnel. GGOS wil seek groups that are interested in participation. GGOS intends to issues a Call for Participation of groups that would like to contribute in the network implementation and operation. Some examples of integrated stations currently in operation or under development will be presented. We will examine necessary conditions and challenges in

  9. On global exponential stability of high-order neural networks with time-varying delays

    Zhang Baoyong; Xu Shengyuan; Li Yongmin; Chu Yuming

    2007-01-01

    This Letter investigates the problem of stability analysis for a class of high-order neural networks with time-varying delays. The delays are bounded but not necessarily differentiable. Based on the Lyapunov stability theory together with the linear matrix inequality (LMI) approach and the use of Halanay inequality, sufficient conditions guaranteeing the global exponential stability of the equilibrium point of the considered neural networks are presented. Two numerical examples are provided to demonstrate the effectiveness of the proposed stability criteria

  10. On global exponential stability of high-order neural networks with time-varying delays

    Zhang Baoyong [School of Automation, Nanjing University of Science and Technology, Nanjing 210094, Jiangsu (China)]. E-mail: baoyongzhang@yahoo.com.cn; Xu Shengyuan [School of Automation, Nanjing University of Science and Technology, Nanjing 210094, Jiangsu (China)]. E-mail: syxu02@yahoo.com.cn; Li Yongmin [School of Automation, Nanjing University of Science and Technology, Nanjing 210094, Jiangsu (China) and Department of Mathematics, Huzhou Teacher' s College, Huzhou 313000, Zhejiang (China)]. E-mail: ymlwww@163.com; Chu Yuming [Department of Mathematics, Huzhou Teacher' s College, Huzhou 313000, Zhejiang (China)

    2007-06-18

    This Letter investigates the problem of stability analysis for a class of high-order neural networks with time-varying delays. The delays are bounded but not necessarily differentiable. Based on the Lyapunov stability theory together with the linear matrix inequality (LMI) approach and the use of Halanay inequality, sufficient conditions guaranteeing the global exponential stability of the equilibrium point of the considered neural networks are presented. Two numerical examples are provided to demonstrate the effectiveness of the proposed stability criteria.

  11. Global asymptotic stability of hybrid bidirectional associative memory neural networks with time delays

    Arik, Sabri

    2006-01-01

    This Letter presents a sufficient condition for the existence, uniqueness and global asymptotic stability of the equilibrium point for bidirectional associative memory (BAM) neural networks with distributed time delays. The results impose constraint conditions on the network parameters of neural system independently of the delay parameter, and they are applicable to all bounded continuous non-monotonic neuron activation functions. The results are also compared with the previous results derived in the literature

  12. Global exponential stability of BAM neural networks with delays and impulses

    Li Yongkun

    2005-01-01

    Sufficient conditions are obtained for the existence and global exponential stability of a unique equilibrium of a class of two-layer heteroassociative networks called bidirectional associative memory (BAM) networks with Lipschitzian activation functions without assuming their boundedness, monotonicity or differentiability and subjected to impulsive state displacements at fixed instants of time. An illustrative example is given to demonstrate the effectiveness of the obtained results

  13. Global robust stability of bidirectional associative memory neural networks with multiple time delays.

    Senan, Sibel; Arik, Sabri

    2007-10-01

    This correspondence presents a sufficient condition for the existence, uniqueness, and global robust asymptotic stability of the equilibrium point for bidirectional associative memory neural networks with discrete time delays. The results impose constraint conditions on the network parameters of the neural system independently of the delay parameter, and they are applicable to all bounded continuous nonmonotonic neuron activation functions. Some numerical examples are given to compare our results with the previous robust stability results derived in the literature.

  14. Global asymptotic stability of hybrid bidirectional associative memory neural networks with time delays

    Arik, Sabri

    2006-02-01

    This Letter presents a sufficient condition for the existence, uniqueness and global asymptotic stability of the equilibrium point for bidirectional associative memory (BAM) neural networks with distributed time delays. The results impose constraint conditions on the network parameters of neural system independently of the delay parameter, and they are applicable to all bounded continuous non-monotonic neuron activation functions. The results are also compared with the previous results derived in the literature.

  15. Software-Defined Radio Global System for Mobile Communications Transmitter Development for Heterogeneous Network Vulnerability Testing

    2013-12-01

    AbdelWahab, “ 2G / 3G Inter-RAT Handover Performance Analysis,” Second European Conference on Antennas and Propagation, pp. 1, 8, 11–16, Nov. 2007. [19] J...RADIO GLOBAL SYSTEM FOR MOBILE COMMUNICATIONS TRANSMITTER DEVELOPMENT FOR HETEROGENEOUS NETWORK VULNERABILITY TESTING by Carson C. McAbee... MOBILE COMMUNICATIONS TRANSMITTER DEVELOPMENT FOR HETEROGENEOUS NETWORK VULNERABILITY TESTING 5. FUNDING NUMBERS 6. AUTHOR(S) Carson C. McAbee

  16. Only (Dis-)Connect: Pentecostal Global Networking as Revelation and Concealment

    Coleman, Simon

    2013-01-01

    Contemporary forms of Pentecostalism, such as that of the Faith Movement, are often represented as inherently global, constituting a religion ‘made to travel’ and to missionize across the world. I argue that while much attention has been paid to proselytization as a catalyst in encouraging transnational activities among such Christians, more analysis is needed of how Pentecostalists represent each other in the construction of global imaginaries. The imagined and enacted networks that result a...

  17. Global Proteome Response to Deletion of Genes Related to Mercury Methylation and Dissimilatory Metal Reduction Reveals Changes in Respiratory Metabolism in Geobacter sulfurreducens PCA.

    Qian, Chen; Johs, Alexander; Chen, Hongmei; Mann, Benjamin F; Lu, Xia; Abraham, Paul E; Hettich, Robert L; Gu, Baohua

    2016-10-07

    Geobacter sulfurreducens PCA can reduce, sorb, and methylate mercury (Hg); however, the underlying biochemical mechanisms of these processes and interdependent metabolic pathways remain unknown. In this study, shotgun proteomics was used to compare global proteome profiles between wild-type G. sulfurreducens PCA and two mutant strains: a ΔhgcAB mutant, which is deficient in two genes known to be essential for Hg methylation and a ΔomcBESTZ mutant, which is deficient in five outer membrane c-type cytochromes and thus impaired in its ability for dissimilatory metal ion reduction. We were able to delineate the global response of G. sulfurreducens PCA in both mutants and identify cellular networks and metabolic pathways that were affected by the loss of these genes. Deletion of hgcAB increased the relative abundances of proteins implicated in extracellular electron transfer, including most of the c-type cytochromes, PilA-C, and OmpB, and is consistent with a previously observed increase in Hg reduction in the ΔhgcAB mutant. Deletion of omcBESTZ was found to significantly increase relative abundances of various methyltransferases, suggesting that a loss of dissimilatory reduction capacity results in elevated activity among one-carbon (C1) metabolic pathways and thus increased methylation. We show that G. sulfurreducens PCA encodes only the folate branch of the acetyl-CoA pathway, and proteins associated with the folate branch were found at lower abundance in the ΔhgcAB mutant strain than the wild type. This observation supports the hypothesis that the function of HgcA and HgcB is linked to C1 metabolism through the folate branch of the acetyl-CoA pathway by providing methyl groups required for Hg methylation.

  18. EnzDP: improved enzyme annotation for metabolic network reconstruction based on domain composition profiles.

    Nguyen, Nam-Ninh; Srihari, Sriganesh; Leong, Hon Wai; Chong, Ket-Fah

    2015-10-01

    Determining the entire complement of enzymes and their enzymatic functions is a fundamental step for reconstructing the metabolic network of cells. High quality enzyme annotation helps in enhancing metabolic networks reconstructed from the genome, especially by reducing gaps and increasing the enzyme coverage. Currently, structure-based and network-based approaches can only cover a limited number of enzyme families, and the accuracy of homology-based approaches can be further improved. Bottom-up homology-based approach improves the coverage by rebuilding Hidden Markov Model (HMM) profiles for all known enzymes. However, its clustering procedure relies firmly on BLAST similarity score, ignoring protein domains/patterns, and is sensitive to changes in cut-off thresholds. Here, we use functional domain architecture to score the association between domain families and enzyme families (Domain-Enzyme Association Scoring, DEAS). The DEAS score is used to calculate the similarity between proteins, which is then used in clustering procedure, instead of using sequence similarity score. We improve the enzyme annotation protocol using a stringent classification procedure, and by choosing optimal threshold settings and checking for active sites. Our analysis shows that our stringent protocol EnzDP can cover up to 90% of enzyme families available in Swiss-Prot. It achieves a high accuracy of 94.5% based on five-fold cross-validation. EnzDP outperforms existing methods across several testing scenarios. Thus, EnzDP serves as a reliable automated tool for enzyme annotation and metabolic network reconstruction. Available at: www.comp.nus.edu.sg/~nguyennn/EnzDP .

  19. Global alignment, coordination and collaboration in perinatal research: the Global Obstetrics Network (GONet) Initiative

    Mol, Ben Willem; Ruifrok, Anneloes Elisabeth

    2013-01-01

    Large clinical studies provide information and insight that are used to develop clinical guidelines. In view of the large sample sizes needed, many researchers have initiated multicenter studies. In some situations, the activities of these groups have led to networks, through which multiple trials

  20. Trends of the World Input and Output Network of Global Trade.

    Del Río-Chanona, Rita María; Grujić, Jelena; Jeldtoft Jensen, Henrik

    2017-01-01

    The international trade naturally maps onto a complex networks. Theoretical analysis of this network gives valuable insights about the global economic system. Although different economic data sets have been investigated from the network perspective, little attention has been paid to its dynamical behaviour. Here we take the World Input Output Data set, which has values of the annual transactions between 40 different countries of 35 different sectors for the period of 15 years, and infer the time interdependence between countries and sectors. As a measure of interdependence we use correlations between various time series of the network characteristics. First we form 15 primary networks for each year of the data we have, where nodes are countries and links are annual exports from one country to the other. Then we calculate the strengths (weighted degree) and PageRank of each country in each of the 15 networks for 15 different years. This leads to sets of time series and by calculating the correlations between these we form a secondary network where the links are the positive correlations between different countries or sectors. Furthermore, we also form a secondary network where the links are negative correlations in order to study the competition between countries and sectors. By analysing this secondary network we obtain a clearer picture of the mutual influences between countries. As one might expect, we find that political and geographical circumstances play an important role. However, the derived correlation network reveals surprising aspects which are hidden in the primary network. Sometimes countries which belong to the same community in the original network are found to be competitors in the secondary networks. E.g. Spain and Portugal are always in the same trade flow community, nevertheless secondary network analysis reveal that they exhibit contrary time evolution.

  1. Trends of the World Input and Output Network of Global Trade.

    Rita María Del Río-Chanona

    Full Text Available The international trade naturally maps onto a complex networks. Theoretical analysis of this network gives valuable insights about the global economic system. Although different economic data sets have been investigated from the network perspective, little attention has been paid to its dynamical behaviour. Here we take the World Input Output Data set, which has values of the annual transactions between 40 different countries of 35 different sectors for the period of 15 years, and infer the time interdependence between countries and sectors. As a measure of interdependence we use correlations between various time series of the network characteristics. First we form 15 primary networks for each year of the data we have, where nodes are countries and links are annual exports from one country to the other. Then we calculate the strengths (weighted degree and PageRank of each country in each of the 15 networks for 15 different years. This leads to sets of time series and by calculating the correlations between these we form a secondary network where the links are the positive correlations between different countries or sectors. Furthermore, we also form a secondary network where the links are negative correlations in order to study the competition between countries and sectors. By analysing this secondary network we obtain a clearer picture of the mutual influences between countries. As one might expect, we find that political and geographical circumstances play an important role. However, the derived correlation network reveals surprising aspects which are hidden in the primary network. Sometimes countries which belong to the same community in the original network are found to be competitors in the secondary networks. E.g. Spain and Portugal are always in the same trade flow community, nevertheless secondary network analysis reveal that they exhibit contrary time evolution.

  2. Global Logistic Network of Courier Services for the 21" Century

    Ratko Zelenika

    2006-09-01

    Full Text Available The development of logistics has contributed a lot to all thebranches of economy. A successful economic subject cannotexist without a well-developed logistic branch. In economicsthe organization of logistics is becoming a strategic element regardingthe policy making of enterprises. Logistics belongs to anarea that will play an important role in our lives; therefore, thedevelopment of a logistic system is of an exceptional significancefor the economy and also for the non-economic sphere ofactivities. So, modem logistics enables us to bring into line differentinterests in management of material current. Global organizersof logistic services are developing and specializing insome essential services, such as combining of cargo into assemblyconsignments and also their distribution. The biggest globaltenderers of logistic services are considered, DHL, TNT,FEDEX, UPS ...

  3. Network flexibility of the IRIDIUM (R) Global Mobile Satellite System

    Hutcheson, Jonathan; Laurin, Mala

    1995-01-01

    The IRIDIUM system is a global personal communications system supported by a constellation of 66 low earth orbit (LEO) satellites and a collection of earth-based 'gateway' switching installations. Like traditional wireless cellular systems, coverage is achieved by a grid of cells in which bandwidth is reused for spectral efficiency. Unlike any cellular system ever built, the moving cells can be shared by multiple switching facilities. Noteworthy features of the IRIDIUM system include inter-satellite links, a GSM-based telephony architecture, and a geographically controlled system access process. These features, working in concert, permit flexible and reliable administration of the worldwide service area by gateway operators. This paper will explore this unique concept.

  4. Metabolic Networks and Metabolites Underlie Associations Between Maternal Glucose During Pregnancy and Newborn Size at Birth.

    Scholtens, Denise M; Bain, James R; Reisetter, Anna C; Muehlbauer, Michael J; Nodzenski, Michael; Stevens, Robert D; Ilkayeva, Olga; Lowe, Lynn P; Metzger, Boyd E; Newgard, Christopher B; Lowe, William L

    2016-07-01

    Maternal metabolites and metabolic networks underlying associations between maternal glucose during pregnancy and newborn birth weight and adiposity demand fuller characterization. We performed targeted and nontargeted gas chromatography/mass spectrometry metabolomics on maternal serum collected at fasting and 1 h following glucose beverage consumption during an oral glucose tolerance test (OGTT) for 400 northern European mothers at ∼28 weeks' gestation in the Hyperglycemia and Adverse Pregnancy Outcome Study. Amino acids, fatty acids, acylcarnitines, and products of lipid metabolism decreased and triglycerides increased during the OGTT. Analyses of individual metabolites indicated limited maternal glucose associations at fasting, but broader associations, including amino acids, fatty acids, carbohydrates, and lipids, were found at 1 h. Network analyses modeling metabolite correlations provided context for individual metabolite associations and elucidated collective associations of multiple classes of metabolic fuels with newborn size and adiposity, including acylcarnitines, fatty acids, carbohydrates, and organic acids. Random forest analyses indicated an improved ability to predict newborn size outcomes by using maternal metabolomics data beyond traditional risk factors, including maternal glucose. Broad-scale association of fuel metabolites with maternal glucose is evident during pregnancy, with unique maternal metabolites potentially contributing specifically to newborn birth weight and adiposity. © 2016 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.

  5. U.S. Geological Survey Global Seismographic Network - Five-Year Plan 2006-2010

    Leith, William S.; Gee, Lind S.; Hutt, Charles R.

    2009-01-01

    The Global Seismographic Network provides data for earthquake alerting, tsunami warning, nuclear treaty verification, and Earth science research. The system consists of nearly 150 permanent digital stations, distributed across the globe, connected by a modern telecommunications network. It serves as a multi-use scientific facility and societal resource for monitoring, research, and education, by providing nearly uniform, worldwide monitoring of the Earth. The network was developed and is operated through a partnership among the National Science Foundation (http://www.nsf.gov), the Incorporated Research Institutions for Seismology (http://www.iris.edu/hq/programs/gsn), and the U.S. Geological Survey (http://earthquake.usgs.gov/gsn).

  6. Global exponential synchronization of inertial memristive neural networks with time-varying delay via nonlinear controller.

    Gong, Shuqing; Yang, Shaofu; Guo, Zhenyuan; Huang, Tingwen

    2018-06-01

    The paper is concerned with the synchronization problem of inertial memristive neural networks with time-varying delay. First, by choosing a proper variable substitution, inertial memristive neural networks described by second-order differential equations can be transformed into first-order differential equations. Then, a novel controller with a linear diffusive term and discontinuous sign term is designed. By using the controller, the sufficient conditions for assuring the global exponential synchronization of the derive and response neural networks are derived based on Lyapunov stability theory and some inequality techniques. Finally, several numerical simulations are provided to substantiate the effectiveness of the theoretical results. Copyright © 2018 Elsevier Ltd. All rights reserved.

  7. The Magic Pudding; Comment on “Four Challenges That Global Health Networks Face”

    Jill White

    2018-02-01

    Full Text Available This commentary reflects on the contribution of this editorial and its “Three Challenges That Global Health Networks Face” to the totality of the framework developed over the past decade by Shiffman and his collaborators. It reviews the earlier works to demonstrate that the whole is greater than the sum of the parts in providing a package of tools for analysis of network effectiveness. Additionally the assertion is made that the framework can be utilised in reverse to form a map for action planning for network activity around a potential health policy issue

  8. Global asymptotic stability analysis of bidirectional associative memory neural networks with distributed delays and impulse

    Huang Zaitang; Luo Xiaoshu; Yang Qigui

    2007-01-01

    Many systems existing in physics, chemistry, biology, engineering and information science can be characterized by impulsive dynamics caused by abrupt jumps at certain instants during the process. These complex dynamical behaviors can be model by impulsive differential system or impulsive neural networks. This paper formulates and studies a new model of impulsive bidirectional associative memory (BAM) networks with finite distributed delays. Several fundamental issues, such as global asymptotic stability and existence and uniqueness of such BAM neural networks with impulse and distributed delays, are established

  9. The existence and global attractivity of almost periodic sequence solution of discrete-time neural networks

    Huang Zhenkun; Wang Xinghua; Gao Feng

    2006-01-01

    In this Letter, we discuss discrete-time analogue of a continuous-time cellular neural network. Sufficient conditions are obtained for the existence of a unique almost periodic sequence solution which is globally attractive. Our results demonstrate dynamics of the formulated discrete-time analogue as mathematical models for the continuous-time cellular neural network in almost periodic case. Finally, a computer simulation illustrates the suitability of our discrete-time analogue as numerical algorithms in simulating the continuous-time cellular neural network conveniently

  10. Globally exponential stability condition of a class of neural networks with time-varying delays

    Liao, T.-L.; Yan, J.-J.; Cheng, C.-J.; Hwang, C.-C.

    2005-01-01

    In this Letter, the globally exponential stability for a class of neural networks including Hopfield neural networks and cellular neural networks with time-varying delays is investigated. Based on the Lyapunov stability method, a novel and less conservative exponential stability condition is derived. The condition is delay-dependent and easily applied only by checking the Hamiltonian matrix with no eigenvalues on the imaginary axis instead of directly solving an algebraic Riccati equation. Furthermore, the exponential stability degree is more easily assigned than those reported in the literature. Some examples are given to demonstrate validity and excellence of the presented stability condition herein

  11. Skeleton-Based Human Action Recognition With Global Context-Aware Attention LSTM Networks

    Liu, Jun; Wang, Gang; Duan, Ling-Yu; Abdiyeva, Kamila; Kot, Alex C.

    2018-04-01

    Human action recognition in 3D skeleton sequences has attracted a lot of research attention. Recently, Long Short-Term Memory (LSTM) networks have shown promising performance in this task due to their strengths in modeling the dependencies and dynamics in sequential data. As not all skeletal joints are informative for action recognition, and the irrelevant joints often bring noise which can degrade the performance, we need to pay more attention to the informative ones. However, the original LSTM network does not have explicit attention ability. In this paper, we propose a new class of LSTM network, Global Context-Aware Attention LSTM (GCA-LSTM), for skeleton based action recognition. This network is capable of selectively focusing on the informative joints in each frame of each skeleton sequence by using a global context memory cell. To further improve the attention capability of our network, we also introduce a recurrent attention mechanism, with which the attention performance of the network can be enhanced progressively. Moreover, we propose a stepwise training scheme in order to train our network effectively. Our approach achieves state-of-the-art performance on five challenging benchmark datasets for skeleton based action recognition.

  12. Global terrestrial water storage connectivity revealed using complex climate network analyses

    Sun, A. Y.; Chen, J.; Donges, J.

    2015-07-01

    Terrestrial water storage (TWS) exerts a key control in global water, energy, and biogeochemical cycles. Although certain causal relationship exists between precipitation and TWS, the latter quantity also reflects impacts of anthropogenic activities. Thus, quantification of the spatial patterns of TWS will not only help to understand feedbacks between climate dynamics and the hydrologic cycle, but also provide new insights and model calibration constraints for improving the current land surface models. This work is the first attempt to quantify the spatial connectivity of TWS using the complex network theory, which has received broad attention in the climate modeling community in recent years. Complex networks of TWS anomalies are built using two global TWS data sets, a remote sensing product that is obtained from the Gravity Recovery and Climate Experiment (GRACE) satellite mission, and a model-generated data set from the global land data assimilation system's NOAH model (GLDAS-NOAH). Both data sets have 1° × 1° grid resolutions and cover most global land areas except for permafrost regions. TWS networks are built by first quantifying pairwise correlation among all valid TWS anomaly time series, and then applying a cutoff threshold derived from the edge-density function to retain only the most important features in the network. Basinwise network connectivity maps are used to illuminate connectivity of individual river basins with other regions. The constructed network degree centrality maps show the TWS anomaly hotspots around the globe and the patterns are consistent with recent GRACE studies. Parallel analyses of networks constructed using the two data sets reveal that the GLDAS-NOAH model captures many of the spatial patterns shown by GRACE, although significant discrepancies exist in some regions. Thus, our results provide further measures for constraining the current land surface models, especially in data sparse regions.

  13. Forecasting hourly global solar radiation using hybrid k-means and nonlinear autoregressive neural network models

    Benmouiza, Khalil; Cheknane, Ali

    2013-01-01

    Highlights: • An unsupervised clustering algorithm with a neural network model was explored. • The forecasting results of solar radiation time series and the comparison of their performance was simulated. • A new method was proposed combining k-means algorithm and NAR network to provide better prediction results. - Abstract: In this paper, we review our work for forecasting hourly global horizontal solar radiation based on the combination of unsupervised k-means clustering algorithm and artificial neural networks (ANN). k-Means algorithm focused on extracting useful information from the data with the aim of modeling the time series behavior and find patterns of the input space by clustering the data. On the other hand, nonlinear autoregressive (NAR) neural networks are powerful computational models for modeling and forecasting nonlinear time series. Taking the advantage of both methods, a new method was proposed combining k-means algorithm and NAR network to provide better forecasting results

  14. Coherence resonance in globally coupled neuronal networks with different neuron numbers

    Ning Wei-Lian; Zhang Zheng-Zhen; Zeng Shang-You; Luo Xiao-Shu; Hu Jin-Lin; Zeng Shao-Wen; Qiu Yi; Wu Hui-Si

    2012-01-01

    Because a brain consists of tremendous neuronal networks with different neuron numbers ranging from tens to tens of thousands, we study the coherence resonance due to ion channel noises in globally coupled neuronal networks with different neuron numbers. We confirm that for all neuronal networks with different neuron numbers there exist the array enhanced coherence resonance and the optimal synaptic conductance to cause the maximal spiking coherence. Furthermoremore, the enhancement effects of coupling on spiking coherence and on optimal synaptic conductance are almost the same, regardless of the neuron numbers in the neuronal networks. Therefore for all the neuronal networks with different neuron numbers in the brain, relative weak synaptic conductance (0.1 mS/cm 2 ) is sufficient to induce the maximal spiking coherence and the best sub-threshold signal encoding. (interdisciplinary physics and related areas of science and technology)

  15. Mimoza: web-based semantic zooming and navigation in metabolic networks.

    Zhukova, Anna; Sherman, David J

    2015-02-26

    The complexity of genome-scale metabolic models makes them quite difficult for human users to read, since they contain thousands of reactions that must be included for accurate computer simulation. Interestingly, hidden similarities between groups of reactions can be discovered, and generalized to reveal higher-level patterns. The web-based navigation system Mimoza allows a human expert to explore metabolic network models in a semantically zoomable manner: The most general view represents the compartments of the model; the next view shows the generalized versions of reactions and metabolites in each compartment; and the most detailed view represents the initial network with the generalization-based layout (where similar metabolites and reactions are placed next to each other). It allows a human expert to grasp the general structure of the network and analyze it in a top-down manner Mimoza can be installed standalone, or used on-line at http://mimoza.bordeaux.inria.fr/ , or installed in a Galaxy server for use in workflows. Mimoza views can be embedded in web pages, or downloaded as COMBINE archives.

  16. Las Cumbres Observatory 1-Meter Global Science Telescope Network

    Pickles, Andrew; Dubberley, M.; Haldeman, B.; Haynes, R.; Posner, V.; Rosing, W.; staff, LCOGT

    2009-05-01

    We present the optical, mechanical and electronic design of the LCOGT 1-m telescope. These telescopes are planned to go in pairs to each of 6 sites worldwide, complementing 0.4m telescopes and 2-m telescopes at two existing sites. This science network is designed to provide continuously available photometric monitoring and spectroscopy of variable sources. The 1-m optical design is an f/8 quasi-RC system, with a doublet corrector and field flattener to provide good image quality out to 0.8 degrees. The field of view of the Fairchild 4K science CCD is 27 arcmin, with 0.39 arcsec pixels. The mechanical design includes a stiff C-ring equatorial mount and friction drive rollers, mounted on a triangular base that can be adjusted for latitude. Another friction drive is coupled at the Declination axis to the M1 mirror cell, that forms the main Optical Tube Assembly (OTA) structural element. The OTA design includes a stiff carbon fiber truss assembly, with offset vanes to an M2 drive that provides remote focus, tilt and collimation. The tube assembly weighs about 600 Kg, including Hextek mirrors, 4K science CCD, filter wheel, autoguiders and medium resolution spectrograph pick-off fiber. The telescopes will be housed in domes at existing observatory sites. They are designed to operate remotely and reliably under centralized control for automatic, optimized scheduling of observations with available hardware.

  17. Capturing the essence of a metabolic network: a flux balance analysis approach.

    Murabito, Ettore; Simeonidis, Evangelos; Smallbone, Kieran; Swinton, Jonathan

    2009-10-07

    As genome-scale metabolic reconstructions emerge, tools to manage their size and complexity will be increasingly important. Flux balance analysis (FBA) is a constraint-based approach widely used to study the metabolic capabilities of cellular or subcellular systems. FBA problems are highly underdetermined and many different phenotypes can satisfy any set of constraints through which the metabolic system is represented. Two of the main concerns in FBA are exploring the space of solutions for a given metabolic network and finding a specific phenotype which is representative for a given task such as maximal growth rate. Here, we introduce a recursive algorithm suitable for overcoming both of these concerns. The method proposed is able to find the alternate optimal patterns of active reactions of an FBA problem and identify the minimal subnetwork able to perform a specific task as optimally as the whole. Our method represents an alternative to and an extension of other approaches conceived for exploring the space of solutions of an FBA problem. It may also be particularly helpful in defining a scaffold of reactions upon which to build up a dynamic model, when the important pathways of the system have not yet been well-defined.

  18. Investigating host-pathogen behavior and their interaction using genome-scale metabolic network models.

    Sadhukhan, Priyanka P; Raghunathan, Anu

    2014-01-01

    Genome Scale Metabolic Modeling methods represent one way to compute whole cell function starting from the genome sequence of an organism and contribute towards understanding and predicting the genotype-phenotype relationship. About 80 models spanning all the kingdoms of life from archaea to eukaryotes have been built till date and used to interrogate cell phenotype under varying conditions. These models have been used to not only understand the flux distribution in evolutionary conserved pathways like glycolysis and the Krebs cycle but also in applications ranging from value added product formation in Escherichia coli to predicting inborn errors of Homo sapiens metabolism. This chapter describes a protocol that delineates the process of genome scale metabolic modeling for analysing host-pathogen behavior and interaction using flux balance analysis (FBA). The steps discussed in the process include (1) reconstruction of a metabolic network from the genome sequence, (2) its representation in a precise mathematical framework, (3) its translation to a model, and (4) the analysis using linear algebra and optimization. The methods for biological interpretations of computed cell phenotypes in the context of individual host and pathogen models and their integration are also discussed.

  19. PPARγ population shift produces disease-related changes in molecular networks associated with metabolic syndrome.

    Jurkowski, W; Roomp, K; Crespo, I; Schneider, J G; Del Sol, A

    2011-08-11

    Peroxisome proliferator-activated receptor gamma (PPARγ) is a key regulator of adipocyte differentiation and has an important role in metabolic syndrome. Phosphorylation of the receptor's ligand-binding domain at serine 273 has been shown to change the expression of a large number of genes implicated in obesity. The difference in gene expression seen when comparing wild-type phosphorylated with mutant non-phosphorylated PPARγ may have important consequences for the cellular molecular network, the state of which can be shifted from the healthy to a stable diseased state. We found that a group of differentially expressed genes are involved in bi-stable switches and form a core network, the state of which changes with disease progression. These findings support the idea that bi-stable switches may be a mechanism for locking the core gene network into a diseased state and for efficiently propagating perturbations to more distant regions of the network. A structural analysis of the PPARγ-RXRα dimer complex supports the hypothesis of a major structural change between the two states, and this may represent an important mechanism leading to the differential expression observed in the core network.

  20. Global Metabolic Stress of Isoeffort Continuous and High Intensity Interval Aerobic Exercise: A Comparative 1H NMR Metabonomic Study.

    Zafeiridis, Andreas; Chatziioannou, Anastasia Chrysovalantou; Sarivasiliou, Haralambos; Kyparos, Antonios; Nikolaidis, Michalis G; Vrabas, Ioannis S; Pechlivanis, Alexandros; Zoumpoulakis, Panagiotis; Baskakis, Constantinos; Dipla, Konstantina; Theodoridis, Georgios A

    2016-12-02

    The overall metabolic/energetic stress that occurs during an acute bout of exercise is proposed to be the main driving force for long-term training adaptations. Continuous and high-intensity interval exercise protocols (HIIE) are currently prescribed to acquire the muscular and metabolic benefits of aerobic training. We applied 1 H NMR-based metabonomics to compare the overall metabolic perturbation and activation of individual bioenergetic pathways of three popular aerobic exercises matched for effort/strain. Nine men performed continuous, long-interval (3 min), and short-interval (30 s) bouts of exercise under isoeffort conditions. Blood was collected before and after exercise. The multivariate PCA and OPLS-DA models showed a distinct separation of pre- and postexercise samples in three protocols. The two models did not discriminate the postexercise overall metabolic profiles of the three exercise types. Analysis focused on muscle bioenergetic pathways revealed an extensive upregulation of carbohydrate-lipid metabolism and the TCA cycle in all three protocols; there were only a few differences among protocols in the postexercise abundance of molecules when long-interval bouts were performed. In conclusion, continuous and HIIE exercise protocols, when performed with similar effort/strain, induce comparable global metabolic response/stress despite their marked differences in work-bout intensities. This study highlights the importance of NMR metabonomics in comprehensive monitoring of metabolic consequences of exercise training in the blood of athletes and exercising individuals.