WorldWideScience

Sample records for networks critical pathways

  1. Critical nodes in signalling pathways

    DEFF Research Database (Denmark)

    Taniguchi, Cullen M; Emanuelli, Brice; Kahn, C Ronald

    2006-01-01

    Physiologically important cell-signalling networks are complex, and contain several points of regulation, signal divergence and crosstalk with other signalling cascades. Here, we use the concept of 'critical nodes' to define the important junctions in these pathways and illustrate their unique role...... using insulin signalling as a model system....

  2. Social Networks as a Critical Pathway for Public Education in IYA2009

    Science.gov (United States)

    Plait, P.; Gay, P. L.

    2008-11-01

    Social networks are websites (or software that distributes media over the Internet) where users can share content to either a list of friends on that site or to anyone who surfs onto their page, and where those friends can interact and discuss the content. By linking to friends online, the users' personal content (pictures, songs, favorite movies, diaries, websites, and so on) is dynamically distributed, and can ``become viral,'' that is, get spread rapidly as more people see it and spread it themselves. Social networks are immensely popular around the planet, especially with teens, and by tapping into these networks IYA can excite and inspire a younger audience. IYA already has a small but growing presence on several of the larger social networks, and more are planned.

  3. Cybersecurity of Critical Control Networks

    Science.gov (United States)

    2015-07-14

    AFRL-OSR-VA-TR-2015-0173 CONGRESSIONAL) CYBERSECURITY OF CRITICAL CONTROL NETWORKS William Mahoney UNIVERSITY OF NEBRASKA Final Report 07/14/2015...Congressional) Cybersecurity of Critical Control Networks 5a. CONTRACT NUMBER 5b. GRANT NUMBER FA9550-10-1-0341 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR...FA9550-10-1-0341 Cybersecurity of Critical Control Networks Report Type Final Report Primary Contact E-mail wmahoney@unomaha.edu Primary

  4. Critical Branching Neural Networks

    Science.gov (United States)

    Kello, Christopher T.

    2013-01-01

    It is now well-established that intrinsic variations in human neural and behavioral activity tend to exhibit scaling laws in their fluctuations and distributions. The meaning of these scaling laws is an ongoing matter of debate between isolable causes versus pervasive causes. A spiking neural network model is presented that self-tunes to critical…

  5. Protecting Critical Infrastructure by Identifying Pathways of Exposure to Risk

    Directory of Open Access Journals (Sweden)

    Philip O’Neill

    2013-08-01

    Full Text Available Increasingly, our critical infrastructure is managed and controlled by computers and the information networks that connect them. Cyber-terrorists and other malicious actors understand the economic and social impact that a successful attack on these systems could have. While it is imperative that we defend against such attacks, it is equally imperative that we realize how best to react to them. This article presents the strongest-path method of analyzing all potential pathways of exposure to risk – no matter how indirect or circuitous they may be – in a network model of infrastructure and operations. The method makes direct use of expert knowledge about entities and dependency relationships without the need for any simulation or any other models. By using path analysis in a directed graph model of critical infrastructure, planners can model and assess the effects of a potential attack and develop resilient responses.

  6. Signaling Pathways Critical for Tooth Root Formation.

    Science.gov (United States)

    Wang, J; Feng, J Q

    2017-10-01

    Tooth is made of an enamel-covered crown and a cementum-covered root. Studies on crown dentin formation have been a major focus in tooth development for several decades. Interestingly, the population prevalence for genetic short root anomaly (SRA) with no apparent defects in crown is close to 1.3%. Furthermore, people with SRA itself are predisposed to root resorption during orthodontic treatment. The discovery of the unique role of Nfic (nuclear factor I C; a transcriptional factor) in controlling root but not crown dentin formation points to a new concept: tooth crown and root have different control mechanisms. Further genetic mechanism studies have identified more key molecules (including Osterix, β-catenin, and sonic hedgehog) that play a critical role in root formation. Extensive studies have also revealed the critical role of Hertwig's epithelial root sheath in tooth root formation. In addition, Wnt10a has recently been found to be linked to multirooted tooth furcation formation. These exciting findings not only fill the critical gaps in our understanding about tooth root formation but will aid future research regarding the identifying factors controlling tooth root size and the generation of a whole "bio-tooth" for therapeutic purposes. This review starts with human SRA and mainly focuses on recent progress on the roles of NFIC-dependent and NFIC-independent signaling pathways in tooth root formation. Finally, this review includes a list of the various Cre transgenic mouse lines used to achieve tooth root formation-related gene deletion or overexpression, as well as strengths and limitations of each line.

  7. Hiding Critical Targets in Smart Grid Networks

    Energy Technology Data Exchange (ETDEWEB)

    Bao, Wei [Univ. of Arkansas, Fayetteville, AR (United States); Li, Qinghua

    2017-10-23

    With the integration of advanced communication technologies, the power grid is expected to greatly enhance efficiency and reliability of future power systems. However, since most electrical devices in power grid substations are connected via communication networks, cyber security of these communication networks becomes a critical issue. Real-World incidents such as Stuxnet have shown the feasibility of compromising a device in the power grid network to further launch more sophisticated attacks. To deal with security attacks of this spirit, this paper aims to hide critical targets from compromised internal nodes and hence protect them from further attacks launched by those compromised nodes. In particular, we consider substation networks and propose to add carefully-controlled dummy traffic to a substation network to make critical target nodes indistinguishable from other nodes in network traffic patterns. This paper describes the design and evaluation of such a scheme. Evaluations show that the scheme can effectively protect critical nodes with acceptable communication cost.

  8. Historical emissions critical for mapping decarbonization pathways

    Science.gov (United States)

    Majkut, J.; Kopp, R. E.; Sarmiento, J. L.; Oppenheimer, M.

    2016-12-01

    Policymakers have set a goal of limiting temperature increase from human influence on the climate. This motivates the identification of decarbonization pathways to stabilize atmospheric concentrations of CO2. In this context, the future behavior of CO2 sources and sinks define the CO2 emissions necessary to meet warming thresholds with specified probabilities. We adopt a simple model of the atmosphere-land-ocean carbon balance to reflect uncertainty in how natural CO2 sinks will respond to increasing atmospheric CO2 and temperature. Bayesian inversion is used to estimate the probability distributions of selected parameters of the carbon model. Prior probability distributions are chosen to reflect the behavior of CMIP5 models. We then update these prior distributions by running historical simulations of the global carbon cycle and inverting with observationally-based inventories and fluxes of anthropogenic carbon in the ocean and atmosphere. The result is a best-estimate of historical CO2 sources and sinks and a model of how CO2 sources and sinks will vary in the future under various emissions scenarios, with uncertainty. By linking the carbon model to a simple climate model, we calculate emissions pathways and carbon budgets consistent with meeting specific temperature thresholds and identify key factors that contribute to remaining uncertainty. In particular, we show how the assumed history of CO2 emissions from land use change (LUC) critically impacts estimates of the strength of the land CO2 sink via CO2 fertilization. Different estimates of historical LUC emissions taken from the literature lead to significantly different parameterizations of the carbon system. High historical CO2 emissions from LUC lead to a more robust CO2 fertilization effect, significantly lower future atmospheric CO2 concentrations, and an increased amount of CO2 that can be emitted to satisfy temperature stabilization targets. Thus, in our model, historical LUC emissions have a

  9. Reaction network analysis in biochemical signaling pathways

    OpenAIRE

    Martinez-Forero, I. (Iván); Pelaez, A. (Antonio); Villoslada, P. (Pablo)

    2010-01-01

    The aim of this thesis is to improve the understanding of signaling pathways through a theoretical study of chemical reaction networks. The equilibirum solution to the equations derived from chemical networks will be analytically resolved using tools from algebraic geometry. The chapters are organized as follows: 1. An introduction to chemical dynamics in biological systems with a special emphasis on steady state analysis 2. Complete description of the chemical reaction network theor...

  10. Structural determinants of criticality in biological networks.

    Science.gov (United States)

    Valverde, Sergi; Ohse, Sebastian; Turalska, Malgorzata; West, Bruce J; Garcia-Ojalvo, Jordi

    2015-01-01

    Many adaptive evolutionary systems display spatial and temporal features, such as long-range correlations, typically associated with the critical point of a phase transition in statistical physics. Empirical and theoretical studies suggest that operating near criticality enhances the functionality of biological networks, such as brain and gene networks, in terms for instance of information processing, robustness, and evolvability. While previous studies have explained criticality with specific system features, we still lack a general theory of critical behavior in biological systems. Here we look at this problem from the complex systems perspective, since in principle all critical biological circuits have in common the fact that their internal organization can be described as a complex network. An important question is how self-similar structure influences self-similar dynamics. Modularity and heterogeneity, for instance, affect the location of critical points and can be used to tune the system toward criticality. We review and discuss recent studies on the criticality of neuronal and genetic networks, and discuss the implications of network theory when assessing the evolutionary features of criticality.

  11. Structural Determinants of Criticality in Biological Networks

    Directory of Open Access Journals (Sweden)

    Sergi eValverde

    2015-05-01

    Full Text Available Many adaptive evolutionary systems display spatial and temporal features, such as long-range correlations, typically associated with the critical point of a phase transition in statistical physics. Empirical and theoretical studies suggest that operating near criticality enhances the functionality of biological networks, such as brain and gene networks, in terms for instance of information processing, robustness and evolvability. While previous studies have explained criticality with specific system features, we still lack a general theory of critical behaviour in biological systems. Here we look at this problem from the complex systems perspective, since in principle all critical biological circuits have in common the fact that their internal organisation can be described as a complex network. An important question is how self-similar structure influences self-similar dynamics. Modularity and heterogeneity, for instance, affect the location of critical points and can be used to tune the system towards criticality. We review and discuss recent studies on the criticality of neuronal and genetic networks, and discuss the implications of network theory when assessing the evolutionary features of criticality.

  12. Pathways, Networks and Systems Medicine Conferences

    Energy Technology Data Exchange (ETDEWEB)

    Nadeau, Joseph H. [Pacific Northwest Research Institute

    2013-11-25

    The 6th Pathways, Networks and Systems Medicine Conference was held at the Minoa Palace Conference Center, Chania, Crete, Greece (16-21 June 2008). The Organizing Committee was composed of Joe Nadeau (CWRU, Cleveland), Rudi Balling (German Research Centre, Brauschweig), David Galas (Institute for Systems Biology, Seattle), Lee Hood (Institute for Systems Biology, Seattle), Diane Isonaka (Seattle), Fotis Kafatos (Imperial College, London), John Lambris (Univ. Pennsylvania, Philadelphia),Harris Lewin (Univ. of Indiana, Urbana-Champaign), Edison Liu (Genome Institute of Singapore, Singapore), and Shankar Subramaniam (Univ. California, San Diego). A total of 101 individuals from 21 countries participated in the conference: USA (48), Canada (5), France (5), Austria (4), Germany (3), Italy (3), UK (3), Greece (2), New Zealand (2), Singapore (2), Argentina (1), Australia (1), Cuba (1), Denmark (1), Japan (1), Mexico (1), Netherlands (1), Spain (1), Sweden (1), Switzerland (1). With respect to speakers, 29 were established faculty members and 13 were graduate students or postdoctoral fellows. With respect to gender representation, among speakers, 13 were female and 28 were male, and among all participants 43 were female and 58 were male. Program these included the following topics: Cancer Pathways and Networks (Day 1), Metabolic Disease Networks (Day 2), Day 3 ? Organs, Pathways and Stem Cells (Day 3), and Day 4 ? Inflammation, Immunity, Microbes and the Environment (Day 4). Proceedings of the Conference were not published.

  13. Using Proteomics To Elucidate Critical Signaling Pathways

    KAUST Repository

    Ahmed, Heba

    2012-11-01

    Despite important advances in the therapy of acute myeloid leukemia (AML) the majority of patients will die from their disease (Appelbaum, Rowe, Radich, & Dick, 2001). Characterization of the aberrant molecular pathways responsible for this malignancy provides a platform to discover alternative treatments to help alter the fate of patients. AML is characterized by a blockage in the differentiation of myeloid cells resulting in the accumulation of highly proliferating immature hematopoietic cells. Since treatments such as chemotherapy rarely destroy the leukemic cells entirely, differentiation induction therapy has become a very attractive treatment option. Interestingly, previous experiments have shown that ligation of CD44, a cell surface glycoprotein strongly expressed on all AML cells, with anti-CD44 monoclonal antibodies (mAbs) could reverse this block in differentiation of leukemic blasts regardless of the AML subtype. To expand the understanding of the cellular regulation and circuitry involved, we aim to apply quantitative phosphoproteomics to monitor dynamic changes in phosphorylation state in response to anti-CD44 treatment. Protein phosphorylation and dephosphorylation is a highly controlled biochemical process that responds to various intracellular and extracellular stimuli. As phosphorylation is a dynamic process, quantification of these phosphorylation events would be vastly insightful. The main objective of this project is to determine the differentiation-dependent phosphoproteome of AML cells upon treatment of cells with the anti-CD44 mAb.In these experiments, optimization of protein extraction, phosphopeptide enrichment and data processing and analysis has been achieved. The primary results show successful phosphoproteome extraction complemented with efficient phosphopeptide enrichment and informative data processing. Further quantification with stable isotope labeling techniques is anticipated to provide candidates for targeted therapy.

  14. Critical Signal Transduction Pathways in CLL

    Science.gov (United States)

    Ghosh, Asish K.; Kay, Neil E.

    2014-01-01

    Receptor tyrosine kinases (RTKs) are cell-surface transmembrane receptors that contain regulated kinase activity within their cytoplasmic domain and play a critical role in signal transduction in both normal and malignant cells. Besides B-cell receptor (BCR) signaling in CLL, multiple RTKs have been reported to be constitutively active in CLL B-cells resulting in enhanced survival and resistance to apoptosis of the leukemic cells induced by chemotherapeutic agents. In addition to increased plasma levels of various types of cytokines/growth factors in CLL, we and others have detected that CLL B-cells spontaneously produce multiple cytokines in vitro which may constitute an autocrine loop of RTK activation on the leukemic B-cells. Moreover, aberrant expression and activation of non-RTKs, for example Src/Syk kinases, induce resistance of the leukemic B-cells to therapy. Based on current available knowledge, we detailed the impact of aberrant activities of various RTKs/non-RTKs on CLL B-cell survival and the potential of using these signaling components as future therapeutic targets in CLL therapy. PMID:24014299

  15. Enabling software defined networking experiments in networked critical infrastructures

    Directory of Open Access Journals (Sweden)

    Béla Genge

    2014-05-01

    Full Text Available Nowadays, the fact that Networked Critical Infrastructures (NCI, e.g., power plants, water plants, oil and gas distribution infrastructures, and electricity grids, are targeted by significant cyber threats is well known. Nevertheless, recent research has shown that specific characteristics of NCI can be exploited in the enabling of more efficient mitigation techniques, while novel techniques from the field of IP networks can bring significant advantages. In this paper we explore the interconnection of NCI communication infrastructures with Software Defined Networking (SDN-enabled network topologies. SDN provides the means to create virtual networking services and to implement global networking decisions. It relies on OpenFlow to enable communication with remote devices and has been recently categorized as the “Next Big Technology”, which will revolutionize the way decisions are implemented in switches and routers. Therefore, the paper documents the first steps towards enabling an SDN-NCI and presents the impact of a Denial of Service experiment over traffic resulting from an XBee sensor network which is routed across an emulated SDN network.

  16. [Do critical pathways improve outcomes of patients with cardiac failure?].

    Science.gov (United States)

    Barbieri, Antonietta; Milan, Erika; Cattaneo, Maria Grazia; Faggian, Fabrizio; Panella, Massimiliano

    2011-01-01

    Cardiac failure represents an important public health problem and despite recent clinical, diagnostic and therapeutic advances, the incidence and prevalence of this syndrome show a steady increase. In view of this, the authors conducted a meta-analysis to evaluate the effect of critical pathways in the management of patients with cardiac failure when compared with standard care. The impact of critical pathways on the following outcomes were evaluated: hospital mortality, mortality at six months, mean length of hospital stay, direct costs, readmission rates at one, three and six months. The following databases were consulted: Medline, Embase, CINAHL, Cochrane Central Register of Controlled Trials and Cochrane Database of Systematic Reviews. The research was limited to articles published between January 1975 and June 2010. Methodological quality of studies was evaluated by the Jadad method (for RCTs, cRCT, CCT) and the New Castle Ottawa Scale for case-control and cohort studies. Data analysis was performed by using the statistical methods described in the Cochrane Collaboration guidelines. Meta-analyses were performed using RevMan software version 5. Eleven studies were included in the meta-analysis (5,460 patients). A lower mortality (hospital mortality and mortality at 6 months) was observed in the critical pathways group compared to the group treated with standard care. A positive impact of critical pathways was also observed in length of stay, direct costs, readmission after one, three and six months. Critical pathways can improve the quality of care provided to patients with cardiac failure. Further studies are needed to evaluate which mechanisms within the care pathways can truly improve the quality of care.

  17. Adverse Outcome Pathway Network Analyses: Techniques and benchmarking the AOPwiki

    Science.gov (United States)

    Abstract: As the community of toxicological researchers, risk assessors, and risk managers adopt the adverse outcome pathway (AOP) paradigm for organizing toxicological knowledge, the number and diversity of adverse outcome pathways and AOP networks are continuing to grow. This ...

  18. Critical size of ego communication networks

    Science.gov (United States)

    Wang, Qing; Gao, Jian; Zhou, Tao; Hu, Zheng; Tian, Hui

    2016-06-01

    With the help of information and communication technologies, studies on the overall social networks have been extensively reported recently. However, investigations on the directed Ego Communication Networks (ECNs) remain insufficient, where an ECN stands for a sub network composed of a centralized individual and his/her direct contacts. In this paper, the directed ECNs are built on the Call Detail Records (CDRs), which cover more than 7 million people of a provincial capital city in China for half a year. Results show that there is a critical size for ECN at about 150, above which the average emotional closeness between ego and alters drops, the balanced relationship between ego and network collapses, and the proportion of strong ties decreases. This paper not only demonstrate the significance of ECN size in affecting its properties, but also shows accordance with the “Dunbar's Number”. These results can be viewed as a cross-culture supportive evidence to the well-known Social Brain Hypothesis (SBH).

  19. Critical Transitions in Social Network Activity

    DEFF Research Database (Denmark)

    Kuehn, Christian; Martens, Erik Andreas; Romero, Daniel M

    2014-01-01

    for a priori unknown events in society are present in social networks is an exciting open problem, to which at present only highly speculative answers can be given. Here, we instead provide a first step towards tackling a simpler question by focusing on a priori known events and analyse a social media data set...... with a focus on classical variance and autocorrelation warning signs. Our results thus pertain to one absolutely fundamental question: Can the stochastic warning signs known from other areas also be detected in large-scale social media data? We answer this question affirmatively as we find that several...... a priori known events are preceded by variance and autocorrelation growth. Our findings thus clearly establish the necessary starting point to further investigate the relationship between abstract mathematical theory and various classes of critical transitions in social networks....

  20. Development of Network Analysis and Visualization System for KEGG Pathways

    Directory of Open Access Journals (Sweden)

    Dongmin Seo

    2015-07-01

    Full Text Available Big data refers to informationalization technology for extracting valuable information through the use and analysis of large-scale data and, based on that data, deriving plans for response or predicting changes. With the development of software and devices for next generation sequencing, a vast amount of bioinformatics data has been generated recently. Also, bioinformatics data based big-data technology is rising rapidly as a core technology by the bioinformatician, biologist and big-data scientist. KEGG pathway is bioinformatics data for understanding high-level functions and utilities of the biological system. However, KEGG pathway analysis requires a lot of time and effort because KEGG pathways are high volume and very diverse. In this paper, we proposed a network analysis and visualization system that crawl user interest KEGG pathways, construct a pathway network based on a hierarchy structure of pathways and visualize relations and interactions of pathways by clustering and selecting core pathways from the network. Finally, we construct a pathway network collected by starting with an Alzheimer’s disease pathway and show the results on clustering and selecting core pathways from the pathway network.

  1. Critical contaminant/critical pathway analysis - surface water transport for nonradioactive contaminants

    Energy Technology Data Exchange (ETDEWEB)

    Chen, Kuo-Fu

    1996-11-01

    The health risks for an individual exposed to contaminants released from SRS outfalls from 1989 to 1995 were estimated. The exposure pathways studied are ingestion of drinking water, ingestion of contaminated fish and dermal contact with contaminants in water while swimming. The estimated incremental risks for an individual developing cancer vary from 3.E-06 to 1.0E-05. The estimated total exposure chronic noncancer hazard indices vary from 6.E-02 to 1.E-01. The critical contaminants were ranked based on their cancer risks and chronic noncarcinogenic hazard quotients. For cancer risks, the critical contaminants released from SRS outfalls are arsenic, tetrachloroethylene, and benzene. For chronic noncarcinogenic risks, the critical contaminants released from srs outfalls are cadmium, arsenic, silver, chromium, mercury, selenium, nitrate, manganese, zinc, nickel, uranium, barium, copper, tetrachloroethylene, cyanide, and phenol. The critical pathways in decreasing risk order are ingestion of contaminated fish, ingestion of drinking water and dermal contact with contaminants in water while swimming.

  2. CRITICAL RADIONUCLIDE AND PATHWAY ANALYSIS FOR THE SAVANNAH RIVER SITE

    Energy Technology Data Exchange (ETDEWEB)

    Jannik, T.

    2011-08-30

    This report is an update to the analysis, Assessment of SRS Radiological Liquid and Airborne Contaminants and Pathways, that was performed in 1997. An electronic version of this large original report is included in the attached CD to this report. During the operational history (1954 to the present) of the Savannah River Site (SRS), many different radionuclides have been released to the environment from the various production facilities. However, as will be shown by this updated radiological critical contaminant/critical pathway analysis, only a small number of the released radionuclides have been significant contributors to potential doses and risks to offsite people. The analysis covers radiological releases to the atmosphere and to surface waters, the principal media that carry contaminants offsite. These releases potentially result in exposure to offsite people. The groundwater monitoring performed at the site shows that an estimated 5 to 10% of SRS has been contaminated by radionuclides, no evidence exists from the extensive monitoring performed that groundwater contaminated with these constituents has migrated off the site (SRS 2011). Therefore, with the notable exception of radiological source terms originating from shallow surface water migration into site streams, onsite groundwater was not considered as a potential exposure pathway to offsite people. In addition, in response to the Department of Energy's (DOE) Order 435.1, several Performance Assessments (WSRC 2008; LWO 2009; SRR 2010; SRR 2011) and a Comprehensive SRS Composite Analysis (SRNO 2010) have recently been completed at SRS. The critical radionuclides and pathways identified in these extensive reports are discussed and, where applicable, included in this analysis.

  3. graphite - a Bioconductor package to convert pathway topology to gene network

    Directory of Open Access Journals (Sweden)

    Sales Gabriele

    2012-01-01

    Full Text Available Abstract Background Gene set analysis is moving towards considering pathway topology as a crucial feature. Pathway elements are complex entities such as protein complexes, gene family members and chemical compounds. The conversion of pathway topology to a gene/protein networks (where nodes are a simple element like a gene/protein is a critical and challenging task that enables topology-based gene set analyses. Unfortunately, currently available R/Bioconductor packages provide pathway networks only from single databases. They do not propagate signals through chemical compounds and do not differentiate between complexes and gene families. Results Here we present graphite, a Bioconductor package addressing these issues. Pathway information from four different databases is interpreted following specific biologically-driven rules that allow the reconstruction of gene-gene networks taking into account protein complexes, gene families and sensibly removing chemical compounds from the final graphs. The resulting networks represent a uniform resource for pathway analyses. Indeed, graphite provides easy access to three recently proposed topological methods. The graphite package is available as part of the Bioconductor software suite. Conclusions graphite is an innovative package able to gather and make easily available the contents of the four major pathway databases. In the field of topological analysis graphite acts as a provider of biological information by reducing the pathway complexity considering the biological meaning of the pathway elements.

  4. Optimizing information processing in neuronal networks beyond critical states.

    Science.gov (United States)

    Ferraz, Mariana Sacrini Ayres; Melo-Silva, Hiago Lucas Cardeal; Kihara, Alexandre Hiroaki

    2017-01-01

    Critical dynamics have been postulated as an ideal regime for neuronal networks in the brain, considering optimal dynamic range and information processing. Herein, we focused on how information entropy encoded in spatiotemporal activity patterns may vary in critical networks. We employed branching process based models to investigate how entropy can be embedded in spatiotemporal patterns. We determined that the information capacity of critical networks may vary depending on the manipulation of microscopic parameters. Specifically, the mean number of connections governed the number of spatiotemporal patterns in the networks. These findings are compatible with those of the real neuronal networks observed in specific brain circuitries, where critical behavior is necessary for the optimal dynamic range response but the uncertainty provided by high entropy as coded by spatiotemporal patterns is not required. With this, we were able to reveal that information processing can be optimized in neuronal networks beyond critical states.

  5. Optimizing information processing in neuronal networks beyond critical states.

    Directory of Open Access Journals (Sweden)

    Mariana Sacrini Ayres Ferraz

    Full Text Available Critical dynamics have been postulated as an ideal regime for neuronal networks in the brain, considering optimal dynamic range and information processing. Herein, we focused on how information entropy encoded in spatiotemporal activity patterns may vary in critical networks. We employed branching process based models to investigate how entropy can be embedded in spatiotemporal patterns. We determined that the information capacity of critical networks may vary depending on the manipulation of microscopic parameters. Specifically, the mean number of connections governed the number of spatiotemporal patterns in the networks. These findings are compatible with those of the real neuronal networks observed in specific brain circuitries, where critical behavior is necessary for the optimal dynamic range response but the uncertainty provided by high entropy as coded by spatiotemporal patterns is not required. With this, we were able to reveal that information processing can be optimized in neuronal networks beyond critical states.

  6. Critical Choices: The United Nations, Networks, and the Future of ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    Critical Choices: The United Nations, Networks, and the Future of Global Governance. Book cover Critical Choices: The United Nations, Networks, and the Future of Global. Author(s):. Wolfgang H. Reinicke, Francis Deng, Jan Martin Witte, Thorsten Benner, Beth Whitaker, and John Gershman. Publisher(s):. IDRC. January 1 ...

  7. Critical Node Location in De Bruijn Networks

    Science.gov (United States)

    2016-10-01

    algorithms that are normally time- consuming perform exceptionally well on de Bruijn networks. This class of networks has yet to be considered from an... exceptionally well on de Bruijn networks. This class of networks has yet to be considered from an identifying code perspective, and a complete...Note that this provides only an upper bound on our t-prefixes - if we have repeated letters than we may have double -counted. Now we are ready to

  8. Signaling pathway networks mined from human pituitary adenoma proteomics data

    Directory of Open Access Journals (Sweden)

    Zhan Xianquan

    2010-04-01

    Full Text Available Abstract Background We obtained a series of pituitary adenoma proteomic expression data, including protein-mapping data (111 proteins, comparative proteomic data (56 differentially expressed proteins, and nitroproteomic data (17 nitroproteins. There is a pressing need to clarify the significant signaling pathway networks that derive from those proteins in order to clarify and to better understand the molecular basis of pituitary adenoma pathogenesis and to discover biomarkers. Here, we describe the significant signaling pathway networks that were mined from human pituitary adenoma proteomic data with the Ingenuity pathway analysis system. Methods The Ingenuity pathway analysis system was used to analyze signal pathway networks and canonical pathways from protein-mapping data, comparative proteomic data, adenoma nitroproteomic data, and control nitroproteomic data. A Fisher's exact test was used to test the statistical significance with a significance level of 0.05. Statistical significant results were rationalized within the pituitary adenoma biological system with literature-based bioinformatics analyses. Results For the protein-mapping data, the top pathway networks were related to cancer, cell death, and lipid metabolism; the top canonical toxicity pathways included acute-phase response, oxidative-stress response, oxidative stress, and cell-cycle G2/M transition regulation. For the comparative proteomic data, top pathway networks were related to cancer, endocrine system development and function, and lipid metabolism; the top canonical toxicity pathways included mitochondrial dysfunction, oxidative phosphorylation, oxidative-stress response, and ERK/MAPK signaling. The nitroproteomic data from a pituitary adenoma were related to cancer, cell death, lipid metabolism, and reproductive system disease, and the top canonical toxicity pathways mainly related to p38 MAPK signaling and cell-cycle G2/M transition regulation. Nitroproteins from a

  9. Social Network Analysis and Critical Realism

    DEFF Research Database (Denmark)

    Buch-Hansen, Hubert

    2014-01-01

    Social network analysis ( SNA) is an increasingly popular approach that provides researchers with highly developed tools to map and analyze complexes of social relations. Although a number of network scholars have explicated the assumptions that underpin SNA, the approach has yet to be discussed ...

  10. Pathways towards instability in financial networks

    Science.gov (United States)

    Bardoscia, Marco; Battiston, Stefano; Caccioli, Fabio; Caldarelli, Guido

    2017-02-01

    Following the financial crisis of 2007-2008, a deep analogy between the origins of instability in financial systems and complex ecosystems has been pointed out: in both cases, topological features of network structures influence how easily distress can spread within the system. However, in financial network models, the details of how financial institutions interact typically play a decisive role, and a general understanding of precisely how network topology creates instability remains lacking. Here we show how processes that are widely believed to stabilize the financial system, that is, market integration and diversification, can actually drive it towards instability, as they contribute to create cyclical structures which tend to amplify financial distress, thereby undermining systemic stability and making large crises more likely. This result holds irrespective of the details of how institutions interact, showing that policy-relevant analysis of the factors affecting financial stability can be carried out while abstracting away from such details.

  11. Reconstructing networks of pathways via significance analysis of their intersections

    Directory of Open Access Journals (Sweden)

    Francesconi Mirko

    2008-04-01

    Full Text Available Abstract Background Significance analysis at single gene level may suffer from the limited number of samples and experimental noise that can severely limit the power of the chosen statistical test. This problem is typically approached by applying post hoc corrections to control the false discovery rate, without taking into account prior biological knowledge. Pathway or gene ontology analysis can provide an alternative way to relax the significance threshold applied to single genes and may lead to a better biological interpretation. Results Here we propose a new analysis method based on the study of networks of pathways. These networks are reconstructed considering both the significance of single pathways (network nodes and the intersection between them (links. We apply this method for the reconstruction of networks of pathways to two gene expression datasets: the first one obtained from a c-Myc rat fibroblast cell line expressing a conditional Myc-estrogen receptor oncoprotein; the second one obtained from the comparison of Acute Myeloid Leukemia and Acute Lymphoblastic Leukemia derived from bone marrow samples. Conclusion Our method extends statistical models that have been recently adopted for the significance analysis of functional groups of genes to infer links between these groups. We show that groups of genes at the interface between different pathways can be considered as relevant even if the pathways they belong to are not significant by themselves.

  12. Migrant networks and pathways to child obesity in Mexico.

    Science.gov (United States)

    Creighton, Mathew J; Goldman, Noreen; Teruel, Graciela; Rubalcava, Luis

    2011-03-01

    The purpose of this paper is twofold: 1) to assess the link between migrant networks and becoming overweight or obese and 2) to explore the pathways by which migrant networks may contribute to the increasing overweight and obese population of children in Mexico. Using two waves of the Mexican Family Life Survey (MxFLS), we find that children and adolescents (ages 3 to 15) living in households with migrant networks are at an increased risk of becoming overweight or obese over the period of observation, relative to their peers with no migrant networks. Sedentary behavior and household-level measures of economic wellbeing explain some of the association between networks and changes in weight status, but the role of extended networks remains significant. Community-level characteristics related to migration do not account for any of the observed relationship between household-level networks and becoming overweight or obese. Copyright © 2010 Elsevier Ltd. All rights reserved.

  13. Consolidated Deep Actor Critic Networks (DRAFT)

    NARCIS (Netherlands)

    Van der Laan, T.A.

    2015-01-01

    The works [Volodymyr et al. Playing atari with deep reinforcement learning. arXiv preprint arXiv:1312.5602, 2013.] and [Volodymyr et al. Human-level control through deep reinforcement learning. Nature, 518(7540):529–533, 2015.] have demonstrated the power of combining deep neural networks with

  14. Sleep Scheduling in Critical Event Monitoring with Wireless Sensor Networks

    NARCIS (Netherlands)

    Guo, Peng; Jiang, Tao; Zhang, Qian; Zhang, Kui

    In this paper, we focus on the applications of wireless sensor networks (WSNs) for critical event monitoring, where normally there are only small number of packets need to be transmitted, while when urgent event occurs, the alarm should be broadcast to the entire network as soon as possible. During

  15. Migrant Networks and Pathways to Child Obesity in Mexico

    OpenAIRE

    Creighton, Mathew J.; Goldman, Noreen; Teruel, Graciela; Rubalcava, Luis

    2010-01-01

    The purpose of this paper is twofold: 1) to assess the link between migrant networks and becoming overweight or obese and 2) to explore the pathways by which migrant networks may contribute to the increasing overweight and obese population of children in Mexico. Using two waves of the Mexican Family Life Survey (MxFLS), we find that children and adolescents (ages 3 to 15) living in households with migrant networks are at an increased risk of becoming overweight or obese over the period of obs...

  16. Critical cooperation range to improve spatial network robustness.

    Directory of Open Access Journals (Sweden)

    Vitor H P Louzada

    Full Text Available A robust worldwide air-transportation network (WAN is one that minimizes the number of stranded passengers under a sequence of airport closures. Building on top of this realistic example, here we address how spatial network robustness can profit from cooperation between local actors. We swap a series of links within a certain distance, a cooperation range, while following typical constraints of spatially embedded networks. We find that the network robustness is only improved above a critical cooperation range. Such improvement can be described in the framework of a continuum transition, where the critical exponents depend on the spatial correlation of connected nodes. For the WAN we show that, except for Australia, all continental networks fall into the same universality class. Practical implications of this result are also discussed.

  17. Critical links and nonlocal rerouting in complex supply networks

    CERN Document Server

    Witthaut, Dirk; Zhang, Xiaozhu; Hallerberg, Sarah; Timme, Marc

    2015-01-01

    Link failures repeatedly induce large-scale outages in power grids and other supply networks. Yet, it is still not well understood, which links are particularly prone to inducing such outages. Here we analyze how the nature and location of each link impact the network's capability to maintain stable supply. We propose two criteria to identify critical links on the basis of the topology and the load distribution of the network prior to link failure. They are determined via a link's redundant capacity and a renormalized linear response theory we derive. These criteria outperform critical link prediction based on local measures such as loads. The results not only further our understanding of the physics of supply networks in general. As both criteria are available before any outage from the state of normal operation, they may also help real-time monitoring of grid operation, employing counter-measures and support network planning and design.

  18. Criticality predicts maximum irregularity in recurrent networks of excitatory nodes.

    Directory of Open Access Journals (Sweden)

    Yahya Karimipanah

    Full Text Available A rigorous understanding of brain dynamics and function requires a conceptual bridge between multiple levels of organization, including neural spiking and network-level population activity. Mounting evidence suggests that neural networks of cerebral cortex operate at a critical regime, which is defined as a transition point between two phases of short lasting and chaotic activity. However, despite the fact that criticality brings about certain functional advantages for information processing, its supporting evidence is still far from conclusive, as it has been mostly based on power law scaling of size and durations of cascades of activity. Moreover, to what degree such hypothesis could explain some fundamental features of neural activity is still largely unknown. One of the most prevalent features of cortical activity in vivo is known to be spike irregularity of spike trains, which is measured in terms of the coefficient of variation (CV larger than one. Here, using a minimal computational model of excitatory nodes, we show that irregular spiking (CV > 1 naturally emerges in a recurrent network operating at criticality. More importantly, we show that even at the presence of other sources of spike irregularity, being at criticality maximizes the mean coefficient of variation of neurons, thereby maximizing their spike irregularity. Furthermore, we also show that such a maximized irregularity results in maximum correlation between neuronal firing rates and their corresponding spike irregularity (measured in terms of CV. On the one hand, using a model in the universality class of directed percolation, we propose new hallmarks of criticality at single-unit level, which could be applicable to any network of excitable nodes. On the other hand, given the controversy of the neural criticality hypothesis, we discuss the limitation of this approach to neural systems and to what degree they support the criticality hypothesis in real neural networks. Finally

  19. The reactive oxygen species network pathways: an essential ...

    Indian Academy of Sciences (India)

    Home; Journals; Journal of Biosciences; Volume 31; Issue 3. The reactive oxygen species network pathways: an essential prerequisite for perception of pathogen attack and the acquired disease resistance in plants. Simeon O Kotchoni Emma W Gachomo. Review Volume 31 Issue 3 September 2006 pp 389-404 ...

  20. Metabolic network visualization eliminating node redundance and preserving metabolic pathways

    Directory of Open Access Journals (Sweden)

    Sagot Marie-France

    2007-07-01

    Full Text Available Abstract Background The tools that are available to draw and to manipulate the representations of metabolism are usually restricted to metabolic pathways. This limitation becomes problematic when studying processes that span several pathways. The various attempts that have been made to draw genome-scale metabolic networks are confronted with two shortcomings: 1- they do not use contextual information which leads to dense, hard to interpret drawings, 2- they impose to fit to very constrained standards, which implies, in particular, duplicating nodes making topological analysis considerably more difficult. Results We propose a method, called MetaViz, which enables to draw a genome-scale metabolic network and that also takes into account its structuration into pathways. This method consists in two steps: a clustering step which addresses the pathway overlapping problem and a drawing step which consists in drawing the clustered graph and each cluster. Conclusion The method we propose is original and addresses new drawing issues arising from the no-duplication constraint. We do not propose a single drawing but rather several alternative ways of presenting metabolism depending on the pathway on which one wishes to focus. We believe that this provides a valuable tool to explore the pathway structure of metabolism.

  1. Growth, collapse, and self-organized criticality in complex networks

    Science.gov (United States)

    Wang, Yafeng; Fan, Huawei; Lin, Weijie; Lai, Ying-Cheng; Wang, Xingang

    2016-04-01

    Network growth is ubiquitous in nature (e.g., biological networks) and technological systems (e.g., modern infrastructures). To understand how certain dynamical behaviors can or cannot persist as the underlying network grows is a problem of increasing importance in complex dynamical systems as well as sustainability science and engineering. We address the question of whether a complex network of nonlinear oscillators can maintain its synchronization stability as it expands. We find that a large scale avalanche over the entire network can be triggered in the sense that the individual nodal dynamics diverges from the synchronous state in a cascading manner within a relatively short time period. In particular, after an initial stage of linear growth, the network typically evolves into a critical state where the addition of a single new node can cause a group of nodes to lose synchronization, leading to synchronization collapse for the entire network. A statistical analysis reveals that the collapse size is approximately algebraically distributed, indicating the emergence of self-organized criticality. We demonstrate the generality of the phenomenon of synchronization collapse using a variety of complex network models, and uncover the underlying dynamical mechanism through an eigenvector analysis.

  2. Development of the Critical Care Pharmacotherapy Trials Network.

    Science.gov (United States)

    Bauer, Seth R; Abraham, Prasad E; Barletta, Jeffrey F; Brophy, Gretchen M; Erstad, Brian L; Gonzales, Jeffrey P; Haas, Curtis E; MacLaren, Robert; Mueller, Eric W; Olsen, Keith M; Lat, Ishaq

    2017-03-01

    The development of the Critical Care Pharmacotherapy Trials Network (CCPTN) as a model for practice-based pharmacotherapy research is described. The CCPTN was formed in 2010 as a collaborative research network dedicated to scientific investigation in the field of critical care pharmacotherapy. The CCPTN organizational structure is consistent with many professional pharmacy and interdisciplinary organizations and organized into 3 primary domains: executive committee, working committees, and network membership. The network membership consists of critical care investigators dedicated to the mission and vision of the CCPTN and is open to anyone expressing an interest in contributing to high-level research. Network member sites represent the breadth of U.S. critical care practice environments. In addition, network members include individuals with demonstrated expertise in patient safety, administration, research design, grantsmanship, database management, peer review, and scientific writing. In 2015, there were more than 100 site investigators from around the United States and Canada. Projects to date have yielded numerous abstracts, platform presentations, and peer-reviewed publications in high-impact journals. The CCPTN has expanded to form collaborations with researchers in the United Kingdom, Australia, and New Zealand. The CCPTN has identified new potential partnerships and field-based areas for inquiry. Numerous opportunities for continued growth and scientific inquiry in the field of critical care pharmacotherapy research exist for the CCPTN to foster in the coming years. The CCPTN has been a successful model for practice-based pharmacotherapy research and assists its members in expanding critical care pharmacotherapy knowledge. Copyright © 2017 by the American Society of Health-System Pharmacists, Inc. All rights reserved.

  3. Using Critical Systems thinking to Improve Student Performance in Networking

    OpenAIRE

    Albertus G. Joubert; Roelien Goede

    2012-01-01

    This paper explores how Critical Systems Thinking and Action Research can be used to improve student performance in Networking. When describing a system from a systems thinking perspective, the following aspects can be identified: the total system performance, the systems environment, the resources, the components and the management of the system. Following the history of system thinking we observe three emerged methodologies namely, hard systems, soft systems, and critical systems. This pape...

  4. Deciphering Signaling Pathway Networks to Understand the Molecular Mechanisms of Metformin Action.

    Science.gov (United States)

    Sun, Jingchun; Zhao, Min; Jia, Peilin; Wang, Lily; Wu, Yonghui; Iverson, Carissa; Zhou, Yubo; Bowton, Erica; Roden, Dan M; Denny, Joshua C; Aldrich, Melinda C; Xu, Hua; Zhao, Zhongming

    2015-06-01

    A drug exerts its effects typically through a signal transduction cascade, which is non-linear and involves intertwined networks of multiple signaling pathways. Construction of such a signaling pathway network (SPNetwork) can enable identification of novel drug targets and deep understanding of drug action. However, it is challenging to synopsize critical components of these interwoven pathways into one network. To tackle this issue, we developed a novel computational framework, the Drug-specific Signaling Pathway Network (DSPathNet). The DSPathNet amalgamates the prior drug knowledge and drug-induced gene expression via random walk algorithms. Using the drug metformin, we illustrated this framework and obtained one metformin-specific SPNetwork containing 477 nodes and 1,366 edges. To evaluate this network, we performed the gene set enrichment analysis using the disease genes of type 2 diabetes (T2D) and cancer, one T2D genome-wide association study (GWAS) dataset, three cancer GWAS datasets, and one GWAS dataset of cancer patients with T2D on metformin. The results showed that the metformin network was significantly enriched with disease genes for both T2D and cancer, and that the network also included genes that may be associated with metformin-associated cancer survival. Furthermore, from the metformin SPNetwork and common genes to T2D and cancer, we generated a subnetwork to highlight the molecule crosstalk between T2D and cancer. The follow-up network analyses and literature mining revealed that seven genes (CDKN1A, ESR1, MAX, MYC, PPARGC1A, SP1, and STK11) and one novel MYC-centered pathway with CDKN1A, SP1, and STK11 might play important roles in metformin's antidiabetic and anticancer effects. Some results are supported by previous studies. In summary, our study 1) develops a novel framework to construct drug-specific signal transduction networks; 2) provides insights into the molecular mode of metformin; 3) serves a model for exploring signaling pathways

  5. Deciphering Signaling Pathway Networks to Understand the Molecular Mechanisms of Metformin Action

    Science.gov (United States)

    Sun, Jingchun; Zhao, Min; Jia, Peilin; Wang, Lily; Wu, Yonghui; Iverson, Carissa; Zhou, Yubo; Bowton, Erica; Roden, Dan M.; Denny, Joshua C.; Aldrich, Melinda C.; Xu, Hua; Zhao, Zhongming

    2015-01-01

    A drug exerts its effects typically through a signal transduction cascade, which is non-linear and involves intertwined networks of multiple signaling pathways. Construction of such a signaling pathway network (SPNetwork) can enable identification of novel drug targets and deep understanding of drug action. However, it is challenging to synopsize critical components of these interwoven pathways into one network. To tackle this issue, we developed a novel computational framework, the Drug-specific Signaling Pathway Network (DSPathNet). The DSPathNet amalgamates the prior drug knowledge and drug-induced gene expression via random walk algorithms. Using the drug metformin, we illustrated this framework and obtained one metformin-specific SPNetwork containing 477 nodes and 1,366 edges. To evaluate this network, we performed the gene set enrichment analysis using the disease genes of type 2 diabetes (T2D) and cancer, one T2D genome-wide association study (GWAS) dataset, three cancer GWAS datasets, and one GWAS dataset of cancer patients with T2D on metformin. The results showed that the metformin network was significantly enriched with disease genes for both T2D and cancer, and that the network also included genes that may be associated with metformin-associated cancer survival. Furthermore, from the metformin SPNetwork and common genes to T2D and cancer, we generated a subnetwork to highlight the molecule crosstalk between T2D and cancer. The follow-up network analyses and literature mining revealed that seven genes (CDKN1A, ESR1, MAX, MYC, PPARGC1A, SP1, and STK11) and one novel MYC-centered pathway with CDKN1A, SP1, and STK11 might play important roles in metformin’s antidiabetic and anticancer effects. Some results are supported by previous studies. In summary, our study 1) develops a novel framework to construct drug-specific signal transduction networks; 2) provides insights into the molecular mode of metformin; 3) serves a model for exploring signaling pathways

  6. Neural Network Based Intrusion Detection System for Critical Infrastructures

    Energy Technology Data Exchange (ETDEWEB)

    Todd Vollmer; Ondrej Linda; Milos Manic

    2009-07-01

    Resiliency and security in control systems such as SCADA and Nuclear plant’s in today’s world of hackers and malware are a relevant concern. Computer systems used within critical infrastructures to control physical functions are not immune to the threat of cyber attacks and may be potentially vulnerable. Tailoring an intrusion detection system to the specifics of critical infrastructures can significantly improve the security of such systems. The IDS-NNM – Intrusion Detection System using Neural Network based Modeling, is presented in this paper. The main contributions of this work are: 1) the use and analyses of real network data (data recorded from an existing critical infrastructure); 2) the development of a specific window based feature extraction technique; 3) the construction of training dataset using randomly generated intrusion vectors; 4) the use of a combination of two neural network learning algorithms – the Error-Back Propagation and Levenberg-Marquardt, for normal behavior modeling. The presented algorithm was evaluated on previously unseen network data. The IDS-NNM algorithm proved to be capable of capturing all intrusion attempts presented in the network communication while not generating any false alerts.

  7. Mathematical Teaching Strategies: Pathways to Critical Thinking and Metacognition

    Science.gov (United States)

    Su, Hui Fang Huang; Ricci, Frederick A.; Mnatsakanian, Mamikon

    2016-01-01

    A teacher that emphasizes reasoning, logic and validity gives their students access to mathematics as an effective way of practicing critical thinking. All students have the ability to enhance and expand their critical thinking when learning mathematics. Students can develop this ability when confronting mathematical problems, identifying possible…

  8. Critical dynamics in genetic regulatory networks: examples from four kingdoms.

    Directory of Open Access Journals (Sweden)

    Enrique Balleza

    2008-06-01

    Full Text Available The coordinated expression of the different genes in an organism is essential to sustain functionality under the random external perturbations to which the organism might be subjected. To cope with such external variability, the global dynamics of the genetic network must possess two central properties. (a It must be robust enough as to guarantee stability under a broad range of external conditions, and (b it must be flexible enough to recognize and integrate specific external signals that may help the organism to change and adapt to different environments. This compromise between robustness and adaptability has been observed in dynamical systems operating at the brink of a phase transition between order and chaos. Such systems are termed critical. Thus, criticality, a precise, measurable, and well characterized property of dynamical systems, makes it possible for robustness and adaptability to coexist in living organisms. In this work we investigate the dynamical properties of the gene transcription networks reported for S. cerevisiae, E. coli, and B. subtilis, as well as the network of segment polarity genes of D. melanogaster, and the network of flower development of A. thaliana. We use hundreds of microarray experiments to infer the nature of the regulatory interactions among genes, and implement these data into the Boolean models of the genetic networks. Our results show that, to the best of the current experimental data available, the five networks under study indeed operate close to criticality. The generality of this result suggests that criticality at the genetic level might constitute a fundamental evolutionary mechanism that generates the great diversity of dynamically robust living forms that we observe around us.

  9. Acoustic quasi-lossless transmission in arbitrary pathway of network

    CERN Document Server

    Dai, Hongqing; Xia, Baizhan; Yu, Dejie

    2016-01-01

    Acoustic metamaterials have exhibited extraordinary possibilities to manipulate the propagation of the sound wave. Up to now, it is still a challenge to control the propagation of the sound wave in an arbitrary pathway of a network. Here, we design a symmetry breaking cross-shape metamaterial comprised of Helmholtz resonant cells and a square column. The square column is eccentrically arranged. The sound wave can quasi-lossless transmit through channels along the eccentric direction with compressed spaces, which breaks through the general transmission phenomenon. This exotic propagation characteristic is verified by the band structure and the mode of the metamaterial. Two acoustic networks, including a 2x2 network and an 8x8 network, show that the sound wave can quasi-lossless propagate along various arbitrary pathways, such as the Great Wall shape, the stair step shape and the serpentine shape, by reconfiguring eccentric directions. This ability opens up a new venue to route the sound wave and exhibits promi...

  10. Mixed Criticality Scheduling for Industrial Wireless Sensor Networks

    Directory of Open Access Journals (Sweden)

    Xi Jin

    2016-08-01

    Full Text Available Wireless sensor networks (WSNs have been widely used in industrial systems. Their real-time performance and reliability are fundamental to industrial production. Many works have studied the two aspects, but only focus on single criticality WSNs. Mixed criticality requirements exist in many advanced applications in which different data flows have different levels of importance (or criticality. In this paper, first, we propose a scheduling algorithm, which guarantees the real-time performance and reliability requirements of data flows with different levels of criticality. The algorithm supports centralized optimization and adaptive adjustment. It is able to improve both the scheduling performance and flexibility. Then, we provide the schedulability test through rigorous theoretical analysis. We conduct extensive simulations, and the results demonstrate that the proposed scheduling algorithm and analysis significantly outperform existing ones.

  11. Optimal Dynamical Range of Excitable Networks at Criticality

    CERN Document Server

    Kinouchi, Osame

    2006-01-01

    A recurrent idea in the study of complex systems is that optimal information processing is to be found near bifurcation points or phase transitions. However, this heuristic hypothesis has few (if any) concrete realizations where a standard and biologically relevant quantity is optimized at criticality. Here we give a clear example of such a phenomenon: a network of excitable elements has its sensitivity and dynamic range maximized at the critical point of a non-equilibrium phase transition. Our results are compatible with the essential role of gap junctions in olfactory glomeruli and retinal ganglionar cell output. Synchronization and global oscillations also appear in the network dynamics. We propose that the main functional role of electrical coupling is to provide an enhancement of dynamic range, therefore allowing the coding of information spanning several orders of magnitude. The mechanism could provide a microscopic neural basis for psychophysical laws.

  12. The critical pathway for deceased donation : reportable uniformity in the approach to deceased donation

    NARCIS (Netherlands)

    Dominguez-Gil, Beatriz; Delmonico, Francis L.; Shaheen, Faissal A. M.; Matesanz, Rafael; O'Connor, Kevin; Minina, Marina; Muller, Elmi; Young, Kimberly; Manyalich, Marti; Chapman, Jeremy; Kirste, Guenter; Al-Mousawi, Mustafa; Coene, Leen; Garcia, Valter Duro; Gautier, Serguei; Hasegawa, Tomonori; Jha, Vivekanand; Kwek, Tong Kiat; Chen, Zhonghua Klaus; Loty, Bernard; Costa, Alessandro Nanni; Nathan, Howard M.; Ploeg, Rutger; Reznik, Oleg; Rosendale, John D.; Tibell, Annika; Tsoulfas, George; Vathsala, Anantharaman; Noel, Luc

    P>The critical pathway of deceased donation provides a systematic approach to the organ donation process, considering both donation after cardiac death than donation after brain death. The pathway provides a tool for assessing the potential of deceased donation and for the prospective identification

  13. Critical Infrastructure Surveillance Using SecureWireless Sensor Networks

    Directory of Open Access Journals (Sweden)

    Michael Niedermeier

    2015-11-01

    Full Text Available In this work, a secure wireless sensor network (WSN for the surveillance, monitoring and protection of critical infrastructures was developed. To guarantee the security of the system, the main focus was the implementation of a unique security concept, which includes both security on the communication level, as well as mechanisms that ensure the functional safety during its operation. While there are many theoretical approaches in various subdomains of WSNs—like network structures, communication protocols and security concepts—the construction, implementation and real-life application of these devices is still rare. This work deals with these aforementioned aspects, including all phases from concept-generation to operation of a secure wireless sensor network. While the key focus of this paper lies on the security and safety features of the WSN, the detection, localization and classification capabilities resulting from the interaction of the nodes’ different sensor types are also described.

  14. The Critical Role of Metabolic Pathways in Aging

    Science.gov (United States)

    Barzilai, Nir; Huffman, Derek M.; Muzumdar, Radhika H.; Bartke, Andrzej

    2012-01-01

    Aging is characterized by a deterioration in the maintenance of homeostatic processes over time, leading to functional decline and increased risk for disease and death. The aging process is characterized metabolically by insulin resistance, changes in body composition, and physiological declines in growth hormone (GH), insulin-like growth factor-1 (IGF-1), and sex steroids. Some interventions designed to address features of aging, such as caloric restriction or visceral fat depletion, have succeeded in improving insulin action and life span in rodents. Meanwhile, pharmacologic interventions and hormonal perturbations have increased the life span of several mammalian species without necessarily addressing features of age-related metabolic decline. These interventions include inhibition of the mammalian target of rapamycin and lifetime deficiency in GH/IGF-1 signaling. However, strategies to treat aging in humans, such as hormone replacement, have mostly failed to achieve their desired response. We will briefly discuss recent advances in our understanding of the complex role of metabolic pathways in the aging process and highlight important paradoxes that have emerged from these discoveries. Although life span has been the major outcome of interest in the laboratory, a special focus is made in this study on healthspan, as improved quality of life is the goal when translated to humans. PMID:22618766

  15. An Analysis for the Use of Research and Education Networks and Commercial Network Vendors in Support of Space Based Mission Critical and Non-Critical Networking

    Science.gov (United States)

    Bradford, Robert N.

    2002-01-01

    Currently, and in the past, dedicated communication circuits and "network services" with very stringent performance requirements are being used to support manned and unmanned mission critical ground operations at GSFC, JSC, MSFC, KSC and other NASA facilities. Because of the evolution of network technology, it is time to investigate using other approaches to providing mission services for space ground operations. The current NASA approach is not in keeping with the evolution of network technologies. In the past decade various research and education networks dedicated to scientific and educational endeavors have emerged, as well as commercial networking providers, that employ advanced networking technologies. These technologies have significantly changed networking in recent years. Significant advances in network routing techniques, various topologies and equipment have made commercial networks very stable and virtually error free. Advances in Dense Wave Division Multiplexing will provide tremendous amounts of bandwidth for the future. The question is: Do these networks, which are controlled and managed centrally, provide a level of service that equals the stringent NASA performance requirements. If they do, what are the implication(s) of using them for critical space based ground operations as they are, without adding high cost contractual performance requirements? A second question is the feasibility of applying the emerging grid technology in space operations. Is it feasible to develop a Space Operations Grid and/or a Space Science Grid? Since these network's connectivity is substantial, both nationally and internationally, development of these sorts of grids may be feasible. The concept of research and education networks has evolved to the international community as well. Currently there are international RENs connecting the US in Chicago to and from Europe, South America, Asia and the Pacific rim, Russia and Canada. And most countries in these areas have their

  16. Emergence of Critical Behavior in β-Cell Network

    Science.gov (United States)

    Westacott, Matthew; Hraha, Thomas; McClatchey, Mason; Pozzoli, Marina; Benninger, Richard

    2014-03-01

    The β-cell is a cell type located in the Islet of Langerhans, a micro-organ of the pancreas which maintains glucose homeostasis through secretion of insulin. An electrophysiological process governing insulin release occurs through initial uptake of blood glucose and generation of ATP which inhibits the ATP sensitive potassium channel (K-ATP) causing membrane depolarization (activation). Neighboring β-cells are electrically coupled through gap junctions which allow passage of cationic molecules, creating a network of coupled electrical oscillators. Cells exhibiting hyperpolzarized (inactive) membrane potential affect behavior of neighboring cells by electrically suppressing their depolarization. Here we observe critical behavior between global active-inactive states by increasing the number of inactive elements with the K-ATP inhibitor Diazoxide and a tunable ATP insensitive transgenic mouse model. We show this behavior occurs due to from cell-cell coupling as mice lacking β-cell gap junctions show no critical behavior. Also, a computational β-cell model was expanded to construct a coupled β-cell network and we show this model replicates the critical behavior seen in-vitro.While electrical activity of single β-cells is well studied these data highlight a newly defined characteristic of their emergent multicellular behavior within the Islet of Langerhans and may elucidate pathophysiology of Diabetes due to mutations in the K-ATP channel.

  17. Identification of Pathways Critical to Quorum Sensing and Virulence Induction

    Energy Technology Data Exchange (ETDEWEB)

    Ognibene, Ted J. [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States); Young, N. [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States); Holtz-Morris, A. [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States); Daley, P. [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States)

    2009-02-27

    Quorum sensing is a mode of intercellular communication between bacteria that allows them to collectively regulate behavior such as virulence, sporulation, motility and biofilm formation. It is mediated by bacterially synthesized, diffusible, signaling molecules (autoinducers) that increase in concentration as a bacterial population expands until a critical threshold concentration is reached. However, in most bacterial species that produce autoinducer molecules, the physiologic concentration of these molecules is unknown. Moreover, many bacterial species, including Y. pestis, produce an array of quorum sensing molecules and the physiologic concentration of each individual type of autoinducer molecule is not known. There is a need to accurately and precisely quantitate these molecules, as it may be that different types of autoinducer molecules have different effects on virulence in the bacterium. We focused our efforts on the construction of a platform to identify and quantitate autoinducer molecules using FTICR, 14C isotope labeling and accelerator mass spectrometry (AMS). Specifically, we focused on autoinducer-1 type molecules, acylhomoserine lactone (HSL), derived from S-adenosylmethionine (SAM).

  18. Making Wireless Networks Secure for NASA Mission Critical Applications Using Virtual Private Network (VPN) Technology

    Science.gov (United States)

    Nichols, Kelvin F.; Best, Susan; Schneider, Larry

    2004-01-01

    With so many security issues involved with wireless networks, the technology has not been fully utilized in the area of mission critical applications. These applications would include the areas of telemetry, commanding, voice and video. Wireless networking would allow payload operators the mobility to take computers outside of the control room to their off ices and anywhere else in the facility that the wireless network was extended. But the risk is too great of having someone sit just inside of your wireless network coverage and intercept enough of your network traffic to steal proprietary data from a payload experiment or worse yet hack back into your system and do even greater harm by issuing harmful commands. Wired Equivalent Privacy (WEP) is improving but has a ways to go before it can be trusted to protect mission critical data. Today s hackers are becoming more aggressive and innovative, and in order to take advantage of the benefits that wireless networking offer, appropriate security measures need to be in place that will thwart hackers. The Virtual Private Network (VPN) offers a solution to the security problems that have kept wireless networks from being used for mission critical applications. VPN provides a level of encryption that will ensure that data is protected while it is being transmitted over a wireless local area network (LAN). The VPN allows a user to authenticate to the site that the user needs to access. Once this authentication has taken place the network traffic between that site and the user is encapsulated in VPN packets with the Triple Data Encryption Standard (3DES). 3DES is an encryption standard that uses a single secret key to encrypt and decrypt data. The length of the encryption key is 168 bits as opposed to its predecessor DES that has a 56-bit encryption key. Even though 3DES is the common encryption standard for today, the Advance Encryption Standard (AES), which provides even better encryption at a lower cycle cost is growing

  19. Controlling self-organized criticality in complex networks

    CERN Document Server

    Cajueiro, Daniel O

    2013-01-01

    A control scheme to reduce the size of avalanches of the Bak-Tang-Wiesenfeld model on complex networks is proposed. Three network types are considered: those proposed by Erd\\H{o}s-Renyi, Goh-Kahng-Kim, and a real network representing the main connections of the electrical power grid of the western United States. The control scheme is based on the idea of triggering avalanches in the highest degree nodes that are near to become critical. We show that this strategy works in the sense that the dissipation of mass occurs most locally avoiding larger avalanches. We also compare this strategy with a random strategy where the nodes are chosen randomly. Although the random control has some ability to reduce the probability of large avalanches, its performance is much worse than the one based on the choice of the highest degree nodes. Finally, we argue that the ability of the proposed control scheme is related to its ability to reduce the concentration of mass on the network.

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

    Directory of Open Access Journals (Sweden)

    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

  1. Metabolic pathway of non-alcoholic fatty liver disease: Network properties and robustness

    OpenAIRE

    WenJun Zhang

    2017-01-01

    Nonalcoholic fatty liver disease (NAFLD) is a systematic and complex disease involving various cytokines/metabolites. In present article, we use methodology of network biology to analyze network properties of NAFLD metabolic pathway. It is found that the metabolic pathway of NAFLD is not a typical complex network with power-law degree distribution, p(x)=x^(-4.4275), x>=5. There is only one connected component in the metabolic pathway. The calculated cut cytokines/metabolites of the metabolic ...

  2. Network Randomization and Dynamic Defense for Critical Infrastructure Systems

    Energy Technology Data Exchange (ETDEWEB)

    Chavez, Adrian R. [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Martin, Mitchell Tyler [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Hamlet, Jason [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Stout, William M.S. [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Lee, Erik [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States)

    2015-04-01

    Critical Infrastructure control systems continue to foster predictable communication paths, static configurations, and unpatched systems that allow easy access to our nation's most critical assets. This makes them attractive targets for cyber intrusion. We seek to address these attack vectors by automatically randomizing network settings, randomizing applications on the end devices themselves, and dynamically defending these systems against active attacks. Applying these protective measures will convert control systems into moving targets that proactively defend themselves against attack. Sandia National Laboratories has led this effort by gathering operational and technical requirements from Tennessee Valley Authority (TVA) and performing research and development to create a proof-of-concept solution. Our proof-of-concept has been tested in a laboratory environment with over 300 nodes. The vision of this project is to enhance control system security by converting existing control systems into moving targets and building these security measures into future systems while meeting the unique constraints that control systems face.

  3. Mergeomics: a web server for identifying pathological pathways, networks, and key regulators via multidimensional data integration.

    Science.gov (United States)

    Arneson, Douglas; Bhattacharya, Anindya; Shu, Le; Mäkinen, Ville-Petteri; Yang, Xia

    2016-09-09

    Human diseases are commonly the result of multidimensional changes at molecular, cellular, and systemic levels. Recent advances in genomic technologies have enabled an outpour of omics datasets that capture these changes. However, separate analyses of these various data only provide fragmented understanding and do not capture the holistic view of disease mechanisms. To meet the urgent needs for tools that effectively integrate multiple types of omics data to derive biological insights, we have developed Mergeomics, a computational pipeline that integrates multidimensional disease association data with functional genomics and molecular networks to retrieve biological pathways, gene networks, and central regulators critical for disease development. To make the Mergeomics pipeline available to a wider research community, we have implemented an online, user-friendly web server ( http://mergeomics. idre.ucla.edu/ ). The web server features a modular implementation of the Mergeomics pipeline with detailed tutorials. Additionally, it provides curated genomic resources including tissue-specific expression quantitative trait loci, ENCODE functional annotations, biological pathways, and molecular networks, and offers interactive visualization of analytical results. Multiple computational tools including Marker Dependency Filtering (MDF), Marker Set Enrichment Analysis (MSEA), Meta-MSEA, and Weighted Key Driver Analysis (wKDA) can be used separately or in flexible combinations. User-defined summary-level genomic association datasets (e.g., genetic, transcriptomic, epigenomic) related to a particular disease or phenotype can be uploaded and computed real-time to yield biologically interpretable results, which can be viewed online and downloaded for later use. Our Mergeomics web server offers researchers flexible and user-friendly tools to facilitate integration of multidimensional data into holistic views of disease mechanisms in the form of tissue-specific key regulators

  4. Nano hydroxyapatite-blasted titanium surface affects pre-osteoblast morphology by modulating critical intracellular pathways.

    Science.gov (United States)

    Bezerra, Fábio; Ferreira, Marcel R; Fontes, Giselle N; da Costa Fernandes, Célio Jr; Andia, Denise C; Cruz, Nilson C; da Silva, Rodrigo A; Zambuzzi, Willian F

    2017-08-01

    Although, intracellular signaling pathways are proposed to predict the quality of cell-surface relationship, this study addressed pre-osteoblast behavior in response to nano hydroxyapatite (HA)-blasted titanium (Ti) surface by exploring critical intracellular pathways and pre-osteoblast morphological change. Physicochemical properties were evaluated by atomic force microscopy (AFM) and wettability considering water contact angle of three differently texturized Ti surfaces: Machined (Mac), Dual acid-etching (DAE), and nano hydroxyapatite-blasted (nHA). The results revealed critical differences in surface topography, impacting the water contact angle and later the osteoblast performance. In order to evaluate the effect of those topographical characteristics on biological responses, we have seeded pre-osteoblast cells on the Ti discs for up to 4 h and subjected the cultures to biological analysis. First, we have observed pre-osteoblasts morphological changes resulting from the interaction with the Ti texturized surfaces whereas the cells cultured on nHA presented a more advanced spreading process when compared with the cells cultured on the other surfaces. These results argued us for analyzing the molecular machinery and thus, we have shown that nHA promoted a lower Bax/Bcl2 ratio, suggesting an interesting anti-apoptotic effect, maybe explained by the fact that HA is a natural element present in bone composition. Thereafter, we investigated the potential effect of those surfaces on promoting pre-osteoblast adhesion and survival signaling by performing crystal violet and immunoblotting approaches, respectively. Our results showed that nHA promoted a higher pre-osteoblast adhesion supported by up-modulating FAK and Src activations, both signaling transducers involved during eukaryotic cell adhesion. Also, we have shown Ras-Erk stimulation by the all evaluated surfaces. Finally, we showed that all Ti-texturing surfaces were able to promote osteoblast differentiation

  5. Genome-wide analysis of a Wnt1-regulated transcriptional network implicates neurodegenerative pathways.

    Science.gov (United States)

    Wexler, Eric M; Rosen, Ezra; Lu, Daning; Osborn, Gregory E; Martin, Elizabeth; Raybould, Helen; Geschwind, Daniel H

    2011-10-04

    Wnt proteins are critical to mammalian brain development and function. The canonical Wnt signaling pathway involves the stabilization and nuclear translocation of β-catenin; however, Wnt also signals through alternative, noncanonical pathways. To gain a systems-level, genome-wide view of Wnt signaling, we analyzed Wnt1-stimulated changes in gene expression by transcriptional microarray analysis in cultured human neural progenitor (hNP) cells at multiple time points over a 72-hour time course. We observed a widespread oscillatory-like pattern of changes in gene expression, involving components of both the canonical and the noncanonical Wnt signaling pathways. A higher-order, systems-level analysis that combined independent component analysis, waveform analysis, and mutual information-based network construction revealed effects on pathways related to cell death and neurodegenerative disease. Wnt effectors were tightly clustered with presenilin1 (PSEN1) and granulin (GRN), which cause dominantly inherited forms of Alzheimer's disease and frontotemporal dementia (FTD), respectively. We further explored a potential link between Wnt1 and GRN and found that Wnt1 decreased GRN expression by hNPs. Conversely, GRN knockdown increased WNT1 expression, demonstrating that Wnt and GRN reciprocally regulate each other. Finally, we provided in vivo validation of the in vitro findings by analyzing gene expression data from individuals with FTD. These unbiased and genome-wide analyses provide evidence for a connection between Wnt signaling and the transcriptional regulation of neurodegenerative disease genes.

  6. Critical Radionuclide and Pathway Analysis for the Savannah River Site, 2016 Update

    Energy Technology Data Exchange (ETDEWEB)

    Jannik, Tim [Savannah River Site (SRS), Aiken, SC (United States). Savannah River National Lab. (SRNL); Hartman, Larry [Savannah River Site (SRS), Aiken, SC (United States). Savannah River National Lab. (SRNL)

    2016-09-08

    During the operational history of Savannah River Site, many different radionuclides have been released from site facilities. However, as shown in this analysis, only a relatively small number of the released radionuclides have been significant contributors to doses to the offsite public. This report is an update to the 2011 analysis, Critical Radionuclide and Pathway Analysis for the Savannah River Site. SRS-based Performance Assessments for E-Area, Saltstone, F-Tank Farm, H-Tank Farm, and a Comprehensive SRS Composite Analysis have been completed. The critical radionuclides and pathways identified in those extensive reports are also detailed and included in this analysis.

  7. Using consensus bayesian network to model the reactive oxygen species regulatory pathway.

    Directory of Open Access Journals (Sweden)

    Liangdong Hu

    Full Text Available Bayesian network is one of the most successful graph models for representing the reactive oxygen species regulatory pathway. With the increasing number of microarray measurements, it is possible to construct the bayesian network from microarray data directly. Although large numbers of bayesian network learning algorithms have been developed, when applying them to learn bayesian networks from microarray data, the accuracies are low due to that the databases they used to learn bayesian networks contain too few microarray data. In this paper, we propose a consensus bayesian network which is constructed by combining bayesian networks from relevant literatures and bayesian networks learned from microarray data. It would have a higher accuracy than the bayesian networks learned from one database. In the experiment, we validated the bayesian network combination algorithm on several classic machine learning databases and used the consensus bayesian network to model the Escherichia coli's ROS pathway.

  8. Using consensus bayesian network to model the reactive oxygen species regulatory pathway.

    Science.gov (United States)

    Hu, Liangdong; Wang, Limin

    2013-01-01

    Bayesian network is one of the most successful graph models for representing the reactive oxygen species regulatory pathway. With the increasing number of microarray measurements, it is possible to construct the bayesian network from microarray data directly. Although large numbers of bayesian network learning algorithms have been developed, when applying them to learn bayesian networks from microarray data, the accuracies are low due to that the databases they used to learn bayesian networks contain too few microarray data. In this paper, we propose a consensus bayesian network which is constructed by combining bayesian networks from relevant literatures and bayesian networks learned from microarray data. It would have a higher accuracy than the bayesian networks learned from one database. In the experiment, we validated the bayesian network combination algorithm on several classic machine learning databases and used the consensus bayesian network to model the Escherichia coli's ROS pathway.

  9. Elongation factor P mediates a novel post-transcriptional regulatory pathway critical for bacterial virulence

    DEFF Research Database (Denmark)

    Zou, S Betty; Roy, Hervé; Ibba, Michael

    2012-01-01

    of the pathogen to respond to external cues are typically attenuating. Here we discuss our recent discovery of a novel post-transcriptional regulatory pathway critical for Salmonella virulence and stress resistance. The enzymes PoxA and YjeK coordinately attach a unique beta-amino acid onto a highly conserved...

  10. Optimal Workflow Scheduling in Critical Infrastructure Systems with Neural Networks

    Directory of Open Access Journals (Sweden)

    S. Vukmirović

    2012-04-01

    Full Text Available Critical infrastructure systems (CISs, such as power grids, transportation systems, communication networks and water systems are the backbone of a country’s national security and industrial prosperity. These CISs execute large numbers of workflows with very high resource requirements that can span through different systems and last for a long time. The proper functioning and synchronization of these workflows is essential since humanity’s well-being is connected to it. Because of this, the challenge of ensuring availability and reliability of these services in the face of a broad range of operating conditions is very complicated. This paper proposes an architecture which dynamically executes a scheduling algorithm using feedback about the current status of CIS nodes. Different artificial neural networks (ANNs were created in order to solve the scheduling problem. Their performances were compared and as the main result of this paper, an optimal ANN architecture for workflow scheduling in CISs is proposed. A case study is shown for a meter data management system with measurements from a power distribution management system in Serbia. Performance tests show that significant improvement of the overall execution time can be achieved by ANNs.

  11. Network dynamics in nociceptive pathways assessed by the neuronal avalanche model

    Directory of Open Access Journals (Sweden)

    Wu José

    2012-04-01

    Full Text Available Abstract Background Traditional electroencephalography provides a critical assessment of pain responses. The perception of pain, however, may involve a series of signal transmission pathways in higher cortical function. Recent studies have shown that a mathematical method, the neuronal avalanche model, may be applied to evaluate higher-order network dynamics. The neuronal avalanche is a cascade of neuronal activity, the size distribution of which can be approximated by a power law relationship manifested by the slope of a straight line (i.e., the α value. We investigated whether the neuronal avalanche could be a useful index for nociceptive assessment. Findings Neuronal activity was recorded with a 4 × 8 multichannel electrode array in the primary somatosensory cortex (S1 and anterior cingulate cortex (ACC. Under light anesthesia, peripheral pinch stimulation increased the slope of the α value in both the ACC and S1, whereas brush stimulation increased the α value only in the S1. The increase in α values was blocked in both regions under deep anesthesia. The increase in α values in the ACC induced by peripheral pinch stimulation was blocked by medial thalamic lesion, but the increase in α values in the S1 induced by brush and pinch stimulation was not affected. Conclusions The neuronal avalanche model shows a critical state in the cortical network for noxious-related signal processing. The α value may provide an index of brain network activity that distinguishes the responses to somatic stimuli from the control state. These network dynamics may be valuable for the evaluation of acute nociceptive processes and may be applied to chronic pathological pain conditions.

  12. Bayesian network model for identification of pathways by integrating protein interaction with genetic interaction data.

    Science.gov (United States)

    Fu, Changhe; Deng, Su; Jin, Guangxu; Wang, Xinxin; Yu, Zu-Guo

    2017-09-21

    Molecular interaction data at proteomic and genetic levels provide physical and functional insights into a molecular biosystem and are helpful for the construction of pathway structures complementarily. Despite advances in inferring biological pathways using genetic interaction data, there still exists weakness in developed models, such as, activity pathway networks (APN), when integrating the data from proteomic and genetic levels. It is necessary to develop new methods to infer pathway structure by both of interaction data. We utilized probabilistic graphical model to develop a new method that integrates genetic interaction and protein interaction data and infers exquisitely detailed pathway structure. We modeled the pathway network as Bayesian network and applied this model to infer pathways for the coherent subsets of the global genetic interaction profiles, and the available data set of endoplasmic reticulum genes. The protein interaction data were derived from the BioGRID database. Our method can accurately reconstruct known cellular pathway structures, including SWR complex, ER-Associated Degradation (ERAD) pathway, N-Glycan biosynthesis pathway, Elongator complex, Retromer complex, and Urmylation pathway. By comparing N-Glycan biosynthesis pathway and Urmylation pathway identified from our approach with that from APN, we found that our method is able to overcome its weakness (certain edges are inexplicable). According to underlying protein interaction network, we defined a simple scoring function that only adopts genetic interaction information to avoid the balance difficulty in the APN. Using the effective stochastic simulation algorithm, the performance of our proposed method is significantly high. We developed a new method based on Bayesian network to infer detailed pathway structures from interaction data at proteomic and genetic levels. The results indicate that the developed method performs better in predicting signaling pathways than previously

  13. Pandora, a pathway and network discovery approach based on common biological evidence.

    Science.gov (United States)

    Zhang, Kelvin Xi; Ouellette, B F Francis

    2010-02-15

    Many biological phenomena involve extensive interactions between many of the biological pathways present in cells. However, extraction of all the inherent biological pathways remains a major challenge in systems biology. With the advent of high-throughput functional genomic techniques, it is now possible to infer biological pathways and pathway organization in a systematic way by integrating disparate biological information. Here, we propose a novel integrated approach that uses network topology to predict biological pathways. We integrated four types of biological evidence (protein-protein interaction, genetic interaction, domain-domain interaction and semantic similarity of Gene Ontology terms) to generate a functionally associated network. This network was then used to develop a new pathway finding algorithm to predict biological pathways in yeast. Our approach discovered 195 biological pathways and 31 functionally redundant pathway pairs in yeast. By comparing our identified pathways to three public pathway databases (KEGG, BioCyc and Reactome), we observed that our approach achieves a maximum positive predictive value of 12.8% and improves on other predictive approaches. This study allows us to reconstruct biological pathways and delineates cellular machinery in a systematic view.

  14. Rahnuma: hypergraph-based tool for metabolic pathway prediction and network comparison.

    Science.gov (United States)

    Mithani, Aziz; Preston, Gail M; Hein, Jotun

    2009-07-15

    We present a tool called Rahnuma for prediction and analysis of metabolic pathways and comparison of metabolic networks. Rahnuma represents metabolic networks as hypergraphs and computes all possible pathways between two or more metabolites. It provides an intuitive way to answer biological ques- tions focusing on differences between organisms or the evolution of different species by allowing pathway-based metabolic network comparisons at an organism as well as at a phylogenetic level. Rahnuma is available online at http://portal.stats.ox.ac.uk:8080/rahnuma/.

  15. KeyPathwayMiner - De-novo network enrichment by combining multiple OMICS data and biological networks

    DEFF Research Database (Denmark)

    Baumbach, Jan; Alcaraz, Nicolas; Pauling, Josch K.

    We tackle the problem of de-novo pathway extraction. Given a biological network and a set of case-control studies, KeyPathwayMiner efficiently extracts and visualizes all maximal connected sub-networks that contain mainly genes that are dysregulated, e.g., differentially expressed, in most cases...... problems and designed a set of algorithms to tackle the combinatorial explosion of the search space. During the presentation we will demonstrate how to: Import and process the data, set the parameters for the two models, compute and visualize the key pathways, judge and statistically evaluate the results...

  16. Construction of an miRNA-Regulated Pathway Network Reveals Candidate Biomarkers for Postmenopausal Osteoporosis

    Directory of Open Access Journals (Sweden)

    Min Shao

    2017-01-01

    Full Text Available We aimed to identify risk pathways for postmenopausal osteoporosis (PMOP via establishing an microRNAs- (miRNA- regulated pathway network (MRPN. Firstly, we identified differential pathways through calculating gene- and pathway-level statistics based on the accumulated normal samples using the individual pathway aberrance score (iPAS. Significant pathways based on differentially expressed genes (DEGs using DAVID were extracted, followed by identifying the common pathways between iPAS and DAVID methods. Next, miRNAs prediction was implemented via calculating TargetScore values with precomputed input (log fold change (FC, TargetScan context score (TSCS, and probabilities of conserved targeting (PCT. An MRPN construction was constructed using the common genes in the common pathways and the predicted miRNAs. Using false discovery rate (FDR < 0.05, 279 differential pathways were identified. Using the criteria of FDR < 0.05 and log⁡FC≥2, 39 DEGs were retrieved, and these DEGs were enriched in 64 significant pathways identified by DAVID. Overall, 27 pathways were the common ones between two methods. Importantly, MAPK signaling pathway and PI3K-Akt signaling pathway were the first and second significantly enriched ones, respectively. These 27 common pathways separated PMOP from controls with the accuracy of 0.912. MAPK signaling pathway and PI3K/Akt signaling pathway might play crucial roles in PMOP.

  17. Retrospective Assessment of the Implementation of Critical Pathway in Stroke Patients in a Single University Hospital

    OpenAIRE

    Kim, Jin Hoan; Byun, Ha Young; Son, Seungnam; Lee, Joong Hoon; Yoon, Chul Ho; Lee, Eun Shin; Shin, Heesuk; Oh, Min-Kyun

    2014-01-01

    Objective To evaluate the effects of the implementation of critical pathway (CP) in stroke patients treated at a single university hospital. Methods A retrospective medical review collected data from 497 patients who had suffered acute stroke in the rehabilitation center. Stroke outcomes were compared between before and after the implementation of CP based on factors including demographic factors, stroke characteristics, pre-existing medical conditions, medical complications, functional state...

  18. Identifying the Critical Links in Road Transportation Networks: Centrality-based approach utilizing structural properties

    Energy Technology Data Exchange (ETDEWEB)

    Chinthavali, Supriya [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States)

    2016-04-01

    Surface transportation road networks share structural properties similar to other complex networks (e.g., social networks, information networks, biological networks, and so on). This research investigates the structural properties of road networks for any possible correlation with the traffic characteristics such as link flows those determined independently. Additionally, we define a criticality index for the links of the road network that identifies the relative importance in the network. We tested our hypotheses with two sample road networks. Results show that, correlation exists between the link flows and centrality measures of a link of the road (dual graph approach is followed) and the criticality index is found to be effective for one test network to identify the vulnerable nodes.

  19. Characterization of critical network components of coupled oscillators

    Science.gov (United States)

    Holifield, Gregory A.

    This dissertation analyzes the fundamental limits for the determination of the network structure of loosely coupled oscillators based on observing the behavior of the network, specifically, node synchronization. The determination of the requisite characteristics and underlying behaviors necessary for the application of a theoretical mechanism for determining the underlying network topology in a network of loosely coupled natural oscillators are the desired outcome. To that end, this effort defines an analytical framework where key components of networks of coupled oscillators are isolated in order to determine the relationships between the various components. The relationship between the number of nodes in a network, the number of connections in the network, the number of connections of a given node, the distribution of the phases of the network, and the resolution of measurement of the components of the network, and system noise is investigated.

  20. FNV: light-weight flash-based network and pathway viewer.

    Science.gov (United States)

    Dannenfelser, Ruth; Lachmann, Alexander; Szenk, Mariola; Ma'ayan, Avi

    2011-04-15

    Network diagrams are commonly used to visualize biochemical pathways by displaying the relationships between genes, proteins, mRNAs, microRNAs, metabolites, regulatory DNA elements, diseases, viruses and drugs. While there are several currently available web-based pathway viewers, there is still room for improvement. To this end, we have developed a flash-based network viewer (FNV) for the visualization of small to moderately sized biological networks and pathways. Written in Adobe ActionScript 3.0, the viewer accepts simple Extensible Markup Language (XML) formatted input files to display pathways in vector graphics on any web-page providing flexible layout options, interactivity with the user through tool tips, hyperlinks and the ability to rearrange nodes on the screen. FNV was utilized as a component in several web-based systems, namely Genes2Networks, Lists2Networks, KEA, ChEA and PathwayGenerator. In addition, FVN can be used to embed pathways inside pdf files for the communication of pathways in soft publication materials. FNV is available for use and download along with the supporting documentation and sample networks at http://www.maayanlab.net/FNV. avi.maayan@mssm.edu.

  1. Metabolic pathway of non-alcoholic fatty liver disease: Network properties and robustness

    Directory of Open Access Journals (Sweden)

    WenJun Zhang

    2017-03-01

    Full Text Available Nonalcoholic fatty liver disease (NAFLD is a systematic and complex disease involving various cytokines/metabolites. In present article, we use methodology of network biology to analyze network properties of NAFLD metabolic pathway. It is found that the metabolic pathway of NAFLD is not a typical complex network with power-law degree distribution, p(x=x^(-4.4275, x>=5. There is only one connected component in the metabolic pathway. The calculated cut cytokines/metabolites of the metabolic pathway are SREBP-1c, ChREBP, ObR, AMPK, IRE1alpha, ROS, PERK, elF2alpha, ATF4, CHOP, Bim, CASP8, Bid, CxII, Lipogenic enzymes, XBP1, and FFAs. The most important cytokine/metabolite for possible network robustness is FFAs, seconded by TNF-alpha. It is concluded that FFAs is the most important cytokine/metabolite in the metabolic pathway, seconded by ROS. FFAs, LEP, ACDC, CYP2E1, and Glucose are the only cytokines/metabolites that affect others without influences from other cytokines/metabolites. Finally, the IDs matrix for identifying possible sub-networks/modules is given. However, jointly combining the results of connectedness analysis and sub-networks/modules identification, we hold that there are not significant sub-networks/modules in the pathway.

  2. Characterization of biomarkers in stroke based on ego-networks and pathways.

    Science.gov (United States)

    Li, Haixia; Guo, Qianqian

    2017-12-01

    To explore potential biomarkers in stroke based on ego-networks and pathways. EgoNet method was applied to search for the underlying biomarkers in stroke using transcription profiling of E-GEOD-58294 and protein-protein interaction (PPI) data. Eight ego-genes were identified from PPI network according to the degree characteristics at the criteria of top 5% ranked z-sore and degree >1. Eight candidate ego-networks with classification accuracy ≥0.9 were selected. After performed randomization test, seven significant ego-networks with adjusted p value ego-networks to search for the significant pathways. Finally, two significant pathways were identified, and six of seven ego-networks were enriched to "3'-UTR-mediated translational regulation" pathway, indicating that this pathway performs an important role in the development of stroke. Seven ego-networks were constructed using EgoNet and two significant enriched by pathways were identified. These may provide new insights into the potential biomarkers for the development of stroke.

  3. A Critical Agency Network Model for Building an Integrated Outreach Program

    Science.gov (United States)

    Kiyama, Judy Marquez; Lee, Jenny J.; Rhoades, Gary

    2012-01-01

    This study considers a distinct case of a college outreach program that integrates student affairs staff, academic administrators, and faculty across campus. The authors find that social networks and critical agency help to understand the integration of these various professionals and offer a critical agency network model of enacting change.…

  4. Critical Pathways for Post-Emergency Outpatient Diagnosis and Treatment: Tools to Improve the Value of Emergency Care

    Science.gov (United States)

    Schuur, Jeremiah D.; Baugh, Christopher W.; Hess, Erik P.; Hilton, Joshua A.; Pines, Jesse M.; Asplin, Brent R.

    2013-01-01

    The decision to admit a patient to the hospital after an emergency department (ED) visit is expensive, frequently not evidence-based, and variable. Outpatient critical pathways are a promising approach to reduce hospital admission after emergency care. Critical pathways exist to risk-stratify patients for potentially serious diagnoses (e.g. acute myocardial infarction) or evaluate response to therapy (e.g. community acquired pneumonia) within a short time period (i.e. less than 36 hours), to determine if further hospital-based acute care is needed. Yet, such pathways are variably used while many patients are admitted for conditions for which they could be treated as outpatients. In this article, the authors propose a model of post-ED critical pathways, describe their role in emergency care, list common diagnoses that are amenable to critical pathways in the outpatient setting, and propose a research agenda to address barriers and solutions to increase the use of outpatient critical pathways. If emergency providers are to routinely conduct rapid evaluations in outpatient or observation settings, they must have several conditions at their disposal: 1) evidence-based tools to accurately risk-stratify patients for protocolized care, 2) systems of care that reliably facilitate workup in the outpatient setting, and 3) a medical environment conducive to non-inpatient pathways, with aligned risks and incentives among patients, providers, and payers. Increased use of critical pathways after emergency care is a potential way to improve the value of emergency care. PMID:21676050

  5. Prediction Approach of Critical Node Based on Multiple Attribute Decision Making for Opportunistic Sensor Networks

    Directory of Open Access Journals (Sweden)

    Qifan Chen

    2016-01-01

    Full Text Available Predicting critical nodes of Opportunistic Sensor Network (OSN can help us not only to improve network performance but also to decrease the cost in network maintenance. However, existing ways of predicting critical nodes in static network are not suitable for OSN. In this paper, the conceptions of critical nodes, region contribution, and cut-vertex in multiregion OSN are defined. We propose an approach to predict critical node for OSN, which is based on multiple attribute decision making (MADM. It takes RC to present the dependence of regions on Ferry nodes. TOPSIS algorithm is employed to find out Ferry node with maximum comprehensive contribution, which is a critical node. The experimental results show that, in different scenarios, this approach can predict the critical nodes of OSN better.

  6. Critical behavior of the contact process in annealed scale-free networks

    OpenAIRE

    Noh, Jae Dong; Park, Hyunggyu

    2008-01-01

    Critical behavior of the contact process is studied in annealed scale-free networks by mapping it on the random walk problem. We obtain the analytic results for the critical scaling, using the event-driven dynamics approach. These results are confirmed by numerical simulations. The disorder fluctuation induced by the sampling disorder in annealed networks is also explored. Finally, we discuss over the discrepancy of the finite-size-scaling theory in annealed and quenched networks in spirit of...

  7. Life after the Liverpool Care Pathway (LCP): a qualitative study of critical care practitioners delivering end-of-life care.

    Science.gov (United States)

    Ramasamy Venkatasalu, Munikumar; Whiting, Dean; Cairnduff, Karen

    2015-09-01

    To explore the experiences, challenges and practices of critical care practitioners since the discontinuation of the Liverpool Care Pathway in critical care settings. The Liverpool Care Pathway was widely used with an aim to improve communication and care for dying individuals and their relatives. However, widespread media criticism prompted a review, which resulted in the discontinuation of the Liverpool Care Pathway across all UK clinical settings. A qualitative study. The study was carried out in two large acute hospitals in England. Semi-structured interviews were conducted with 14 critical care practitioners, 6 months after discontinuation of the Liverpool Care Pathway. Transcribed verbatim data were analysed using framework analysis. Three key themes emerged: 'lessons learned', 'uncertainties and ambivalences' and 'the future'. Critical care practitioners reported that life after the Liverpool Care Pathway in critical care settings often involved various clinical ambivalences, uncertainties and inconsistencies in the delivery of end-of-life care, especially for less experienced practitioners. Critical care practitioners had 'become accustomed' to the components of the Liverpool Care Pathway, which still guide them in principle to ensure quality end-of-life care. The Liverpool Care Pathway's structured format was perceived to be a useful clinical tool, but was also criticized as a 'tick-box exercise' and for lacking in family involvement. This study posits two key conclusions. Despite experienced critical care practitioners being able to deliver quality end-of-life care without using the Liverpool Care Pathway, junior nursing and medical staff need clear guidelines and support from experienced mentors in practice. Evidence-based guidelines related to family involvement in end-of-life care planning in critical care settings are also needed to avoid future controversies. © 2015 John Wiley & Sons Ltd.

  8. A networked pathway to the PhD: The African-Norwegian case of ...

    African Journals Online (AJOL)

    How do PhD students become socialised into the professional world of academic work? This article pays attention to a 'networked' support pathway towards a PhD. The network constitutes an international research collaboration through a programme called Productive Learning Cultures (PLC) (2002-2011) between Norway ...

  9. Finding pathway-modulating genes from a novel Ontology Fingerprint-derived gene network.

    Science.gov (United States)

    Qin, Tingting; Matmati, Nabil; Tsoi, Lam C; Mohanty, Bidyut K; Gao, Nan; Tang, Jijun; Lawson, Andrew B; Hannun, Yusuf A; Zheng, W Jim

    2014-10-01

    To enhance our knowledge regarding biological pathway regulation, we took an integrated approach, using the biomedical literature, ontologies, network analyses and experimental investigation to infer novel genes that could modulate biological pathways. We first constructed a novel gene network via a pairwise comparison of all yeast genes' Ontology Fingerprints--a set of Gene Ontology terms overrepresented in the PubMed abstracts linked to a gene along with those terms' corresponding enrichment P-values. The network was further refined using a Bayesian hierarchical model to identify novel genes that could potentially influence the pathway activities. We applied this method to the sphingolipid pathway in yeast and found that many top-ranked genes indeed displayed altered sphingolipid pathway functions, initially measured by their sensitivity to myriocin, an inhibitor of de novo sphingolipid biosynthesis. Further experiments confirmed the modulation of the sphingolipid pathway by one of these genes, PFA4, encoding a palmitoyl transferase. Comparative analysis showed that few of these novel genes could be discovered by other existing methods. Our novel gene network provides a unique and comprehensive resource to study pathway modulations and systems biology in general. © The Author(s) 2014. Published by Oxford University Press on behalf of Nucleic Acids Research.

  10. Modeling the resilience of critical infrastructure: the role of network dependencies.

    Science.gov (United States)

    Guidotti, Roberto; Chmielewski, Hana; Unnikrishnan, Vipin; Gardoni, Paolo; McAllister, Therese; van de Lindt, John

    2016-01-01

    Water and wastewater network, electric power network, transportation network, communication network, and information technology network are among the critical infrastructure in our communities; their disruption during and after hazard events greatly affects communities' well-being, economic security, social welfare, and public health. In addition, a disruption in one network may cause disruption to other networks and lead to their reduced functionality. This paper presents a unified theoretical methodology for the modeling of dependent/interdependent infrastructure networks and incorporates it in a six-step probabilistic procedure to assess their resilience. Both the methodology and the procedure are general, can be applied to any infrastructure network and hazard, and can model different types of dependencies between networks. As an illustration, the paper models the direct effects of seismic events on the functionality of a potable water distribution network and the cascading effects of the damage of the electric power network (EPN) on the potable water distribution network (WN). The results quantify the loss of functionality and delay in the recovery process due to dependency of the WN on the EPN. The results show the importance of capturing the dependency between networks in modeling the resilience of critical infrastructure.

  11. Extending pathways and processes using molecular interaction networks to analyse cancer genome data

    Directory of Open Access Journals (Sweden)

    Krasnogor Natalio

    2010-12-01

    Full Text Available Abstract Background Cellular processes and pathways, whose deregulation may contribute to the development of cancers, are often represented as cascades of proteins transmitting a signal from the cell surface to the nucleus. However, recent functional genomic experiments have identified thousands of interactions for the signalling canonical proteins, challenging the traditional view of pathways as independent functional entities. Combining information from pathway databases and interaction networks obtained from functional genomic experiments is therefore a promising strategy to obtain more robust pathway and process representations, facilitating the study of cancer-related pathways. Results We present a methodology for extending pre-defined protein sets representing cellular pathways and processes by mapping them onto a protein-protein interaction network, and extending them to include densely interconnected interaction partners. The added proteins display distinctive network topological features and molecular function annotations, and can be proposed as putative new components, and/or as regulators of the communication between the different cellular processes. Finally, these extended pathways and processes are used to analyse their enrichment in pancreatic mutated genes. Significant associations between mutated genes and certain processes are identified, enabling an analysis of the influence of previously non-annotated cancer mutated genes. Conclusions The proposed method for extending cellular pathways helps to explain the functions of cancer mutated genes by exploiting the synergies of canonical knowledge and large-scale interaction data.

  12. Stochastic robustness and relative stability of multiple pathways in biological networks

    CERN Document Server

    Guo, Yongyi; Qian, Min; Ge, Hao

    2015-01-01

    Multiple dynamic pathways always exist in biological networks, but their robustness against internal fluctuations and relative stability have not been well recognized and carefully analyzed yet. Here we try to address these issues through an illustrative example, namely the Siah-1/beta-catenin/p14/19 ARF loop of protein p53 dynamics. Its deterministic Boolean network model predicts that two parallel pathways with comparable magnitudes of attractive basins should exist after the protein p53 is activated when a cell becomes harmfully disturbed. Once the low but non-neglectable intrinsic fluctuations are incorporated into the model, we show that a phase transition phenomenon is emerged: in one parameter region the probability weights of the normal pathway, reported in experimental literature, are comparable with the other pathway which is seemingly abnormal with the unknown functions, whereas, in some other parameter regions, the probability weight of the abnormal pathway can even dominate and become globally at...

  13. Network analysis of the MVA and MEP pathways for isoprenoid synthesis.

    Science.gov (United States)

    Vranová, Eva; Coman, Diana; Gruissem, Wilhelm

    2013-01-01

    Isoprenoid biosynthesis is essential for all living organisms, and isoprenoids are also of industrial and agricultural interest. All isoprenoids are derived from prenyl diphosphate (prenyl-PP) precursors. Unlike isoprenoid biosynthesis in other living organisms, prenyl-PP, as the precursor of all isoprenoids in plants, is synthesized by two independent pathways: the mevalonate (MVA) pathway in the cytoplasm and the 2-C-methyl-D-erythritol 4-phosphate (MEP) pathway in plastids. This review focuses on progress in our understanding of how the precursors for isoprenoid biosynthesis are synthesized in the two subcellular compartments, how the underlying pathway gene networks are organized and regulated, and how network perturbations impact each pathway and plant development. Because of the wealth of data on isoprenoid biosynthesis, we emphasize research in Arabidopsis thaliana and compare the synthesis of isoprenoid precursor molecules in this model plant with their synthesis in other prokaryotic and eukaryotic organisms.

  14. Definition of critical periods for Hedgehog pathway antagonist-induced holoprosencephaly, cleft lip, and cleft palate.

    Directory of Open Access Journals (Sweden)

    Galen W Heyne

    Full Text Available The Hedgehog (Hh signaling pathway mediates multiple spatiotemporally-specific aspects of brain and face development. Genetic and chemical disruptions of the pathway are known to result in an array of structural malformations, including holoprosencephaly (HPE, clefts of the lip with or without cleft palate (CL/P, and clefts of the secondary palate only (CPO. Here, we examined patterns of dysmorphology caused by acute, stage-specific Hh signaling inhibition. Timed-pregnant wildtype C57BL/6J mice were administered a single dose of the potent pathway antagonist vismodegib at discrete time points between gestational day (GD 7.0 and 10.0, an interval approximately corresponding to the 15th to 24th days of human gestation. The resultant pattern of facial and brain dysmorphology was dependent upon stage of exposure. Insult between GD7.0 and GD8.25 resulted in HPE, with peak incidence following exposure at GD7.5. Unilateral clefts of the lip extending into the primary palate were also observed, with peak incidence following exposure at GD8.875. Insult between GD9.0 and GD10.0 resulted in CPO and forelimb abnormalities. We have previously demonstrated that Hh antagonist-induced cleft lip results from deficiency of the medial nasal process and show here that CPO is associated with reduced growth of the maxillary-derived palatal shelves. By defining the critical periods for the induction of HPE, CL/P, and CPO with fine temporal resolution, these results provide a mechanism by which Hh pathway disruption can result in "non-syndromic" orofacial clefting, or HPE with or without co-occurring clefts. This study also establishes a novel and tractable mouse model of human craniofacial malformations using a single dose of a commercially available and pathway-specific drug.

  15. The reactive oxygen species network pathways: an essential ...

    Indian Academy of Sciences (India)

    Madhu

    Recent studies suggest that cross-talk between salicylic acid (SA)-, jasmonic acid (JA)-, and ethylene-dependent signalling pathways regulates plant responses to both biotic and abiotic stress factors. Treating cell cultures with H2O2 alone induces defence responses and cell death (Levine et al 1994; Solomon et al 1999).

  16. Networks and Inter-Organizational Learning: A Critical Review.

    Science.gov (United States)

    Beeby, Mick; Booth, Charles

    2000-01-01

    Reviews literature on knowledge management and organizational learning; highlights the significance of networks, alliances, and interorganizational relationships. Refines a model of organizational learning to account for different levels: individual, interdepartmental, team, organizational, and interorganizational learning. (Contains 62…

  17. Implementing critical pathways and a multidisciplinary team approach to cardiovascular disease management.

    Science.gov (United States)

    Peterson, Eric D; Albert, Nancy M; Amin, Alpesh; Patterson, J Herbert; Fonarow, Gregg C

    2008-09-08

    According to several medical registries, there is a need to improve the care of post-myocardial infarction (MI) patients, especially those with left ventricular dysfunction (LVD) and heart failure. This can potentially be achieved by implementing disease management programs, which include critical pathways, patient education, and multidisciplinary hospital teams. Currently, algorithms for critical pathways, including discharge processes, are lacking for post-MI LVD patients. Such schemes can increase the use of evidence-based medicines proved to reduce mortality. Educational programs are aimed at increasing patients' awareness of their condition, promoting medication compliance, and encouraging the adoption of healthy behaviors; such programs have been shown to be effective in improving outcomes of post-MI LVD patients. Reductions in all-cause hospitalizations and medical costs as well as improved survival rates have been observed when a multidisciplinary team (a nurse, a pharmacist, and a hospitalist) is engaged in patient care. In addition, the use of the "pay for performance" method, which can be advantageous for patients, physicians, and hospitals, may potentially improve the care of post-MI patients with LVD.

  18. [Applications of elementary mode analysis in biological network and pathway analysis].

    Science.gov (United States)

    Zhao, Quanyu; Yu, Shuiyan; Shi, Jiping

    2013-06-01

    Elementary mode analysis is the widely applied tool in metabolic pathway analysis. Studies based on elementary mode analysis (EMA) were performed for both metabolic network and signal transduction network. Its analytical objective is from cell to bioreactor, and even ecological system. EMA is available to describe biological behaviors by steady state and dynamic models. Not only microorganism metabolism but also human health could be evaluated by EMA. The algorithms and software for calculating elementary mode (EM) were analyzed. The applications of EMA are reviewed such as special metabolic pathway and robustness of metabolic network, metabolic flux decomposition, metabolic flux analysis at steady state, dynamic model and bioprocess simulation, network structure and regulation, strain design and signal transduction network. Solving combinatorial explosion, exploring the relations between EM and metabolic regulation, and improving the algorithm efficiency of strain design are important issues of EMA in future.

  19. Inferring hidden causal relations between pathway members using reduced Google matrix of directed biological networks

    Science.gov (United States)

    2018-01-01

    Signaling pathways represent parts of the global biological molecular network which connects them into a seamless whole through complex direct and indirect (hidden) crosstalk whose structure can change during development or in pathological conditions. We suggest a novel methodology, called Googlomics, for the structural analysis of directed biological networks using spectral analysis of their Google matrices, using parallels with quantum scattering theory, developed for nuclear and mesoscopic physics and quantum chaos. We introduce analytical “reduced Google matrix” method for the analysis of biological network structure. The method allows inferring hidden causal relations between the members of a signaling pathway or a functionally related group of genes. We investigate how the structure of hidden causal relations can be reprogrammed as a result of changes in the transcriptional network layer during cancerogenesis. The suggested Googlomics approach rigorously characterizes complex systemic changes in the wiring of large causal biological networks in a computationally efficient way. PMID:29370181

  20. Estimating the per-capita contribution of habitats and pathways in a migratory network: A modelling approach

    Science.gov (United States)

    Wiederholt, Ruscena; Mattsson, Brady J.; Thogmartin, Wayne E.; Runge, Michael C.; Diffendorfer, Jay E.; Erickson, Richard A.; Federico, Paula; Lopez-Hoffman, Laura; Fryxell, John; Norris, D. Ryan; Sample, Christine

    2017-01-01

    Every year, migratory species undertake seasonal movements along different pathways between discrete regions and habitats. The ability to assess the relative demographic contributions of these different habitats and pathways to the species’ overall population dynamics is critical for understanding the ecology of migratory species, and also has practical applications for management and conservation. Metrics for assessing habitat contributions have been well-developed for metapopulations, but an equivalent metric is not currently available for migratory populations. Here, we develop a framework for estimating the demographic contributions of the discrete habitats and pathways used by migratory species throughout the annual cycle by estimating the per capita contribution of cohorts using these locations. Our framework accounts for seasonal movements between multiple breeding and non-breeding habitats and for both resident and migratory cohorts. We illustrate our framework using a hypothetical migratory network of four habitats, which allows us to better understand how variations in habitat quality affect per capita contributions. Results indicate that per capita contributions for any habitat or pathway are dependent on habitat-specific survival probabilities in all other areas used as part of the migratory circuit, and that contribution metrics are spatially linked (e.g. reduced survival in one habitat also decreases the contribution metric for other habitats). Our framework expands existing theory on the dynamics of spatiotemporally structured populations by developing a generalized approach to estimate the habitat- and pathway-specific contributions of species migrating between multiple breeding and multiple non-breeding habitats for a range of life histories or migratory strategies. Most importantly, it provides a means of prioritizing conservation efforts towards those migratory pathways and habitats that are most critical for the population viability of

  1. Acute coronary syndrome critical pathway: chest PAIN caremap: a qualitative research study--provider-level intervention.

    Science.gov (United States)

    Saint-Jacques, Henock; Burroughs, Valentine J; Watkowska, Justyna; Valcarcel, Michelle; Moreno, Pedro; Maw, Myo

    2005-09-01

    Recently published data on healthcare performance continue to show a substantial gap between evidence-based guidelines and management of patients in real-world settings. This article describes an operational model that will be used to test whether a critical pathway applied in a secondary care-level institution may improve the process of care related to acute coronary syndromes (ACS). We have developed the pathway for management of all patients who present to our emergency department with a chief complaint of acute chest pain. Based on individual immediate ischemic event risk, patients are categorized according to a prespecified algorithm under the acronym of "PAIN" (P-Priority risk, A-Advanced risk, I-Intermediate risk, and N-Negative/low risk) as prespecified in an algorithm. Along with the algorithm come 2 detailed order sets, 1 for ST-elevation ACS and another for non ST-elevation ACS. The pathway, together with the 2 order sets, are color-coded with the "PAIN" acronym (P-red, A-yellow, I-yellow, N-green) that will guide patient management according to his or her risk stratification. These colors, similar to the road traffic light code, have been chosen as an easy reference for the provider about the sequential risk level of patients with ACS. This experimental model intends, with its unique structured approach, to increase awareness and improve adherence to the published American Heart Association/American College of Cardiology guidelines for the management of ACS.

  2. Evaluating empirical contact networks as potential transmission pathways for infectious diseases

    Science.gov (United States)

    Enns, Eva A.; Picasso, Catalina; Packer, Craig; Craft, Meggan E.

    2016-01-01

    Networks are often used to incorporate heterogeneity in contact patterns in mathematical models of pathogen spread. However, few tools exist to evaluate whether potential transmission pathways in a population are adequately represented by an observed contact network. Here, we describe a novel permutation-based approach, the network k-test, to determine whether the pattern of cases within the observed contact network are likely to have resulted from transmission processes in the network, indicating that the network represents potential transmission pathways between nodes. Using simulated data of pathogen spread, we compare the power of this approach to other commonly used analytical methods. We test the robustness of this technique across common sampling constraints, including undetected cases, unobserved individuals and missing interaction data. We also demonstrate the application of this technique in two case studies of livestock and wildlife networks. We show that the power of the k-test to correctly identify the epidemiologic relevance of contact networks is substantially greater than other methods, even when 50% of contact or case data are missing. We further demonstrate that the impact of missing data on network analysis depends on the structure of the network and the type of missing data. PMID:27488249

  3. Green pathways: Metabolic network analysis of plant systems.

    Science.gov (United States)

    Dersch, Lisa Maria; Beckers, Veronique; Wittmann, Christoph

    2016-03-01

    Metabolic engineering of plants with enhanced crop yield and value-added compositional traits is particularly challenging as they probably exhibit the highest metabolic network complexity of all living organisms. Therefore, approaches of plant metabolic network analysis, which can provide systems-level understanding of plant physiology, appear valuable as guidance for plant metabolic engineers. Strongly supported by the sequencing of plant genomes, a number of different experimental and computational methods have emerged in recent years to study plant systems at various levels: from heterotrophic cell cultures to autotrophic entire plants. The present review presents a state-of-the-art toolbox for plant metabolic network analysis. Among the described approaches are different in silico modeling techniques, including flux balance analysis, elementary flux mode analysis and kinetic flux profiling, as well as different variants of experiments with plant systems which use radioactive and stable isotopes to determine in vivo plant metabolic fluxes. The fundamental principles of these techniques, the required data input and the obtained flux information are enriched by technical advices, specific to plants. In addition, pioneering and high-impacting findings of plant metabolic network analysis highlight the potential of the field. Copyright © 2015 International Metabolic Engineering Society. Published by Elsevier Inc. All rights reserved.

  4. Notch, Wnt, and Hedgehog Pathways in Rhabdomyosarcoma: From Single Pathways to an Integrated Network

    Directory of Open Access Journals (Sweden)

    Josep Roma

    2012-01-01

    Full Text Available Rhabdomyosarcoma (RMS is the most common type of soft tissue sarcoma in children. Regarding histopathological criteria, RMS can be divided into 2 main subtypes: embryonal and alveolar. These subtypes differ considerably in their clinical phenotype and molecular features. Abnormal regulation or mutation of signalling pathways that regulate normal embryonic development such as Notch, Hedgehog, and Wnt is a recurrent feature in tumorigenesis. Herein, the general features of each of the three pathways, their implication in cancer and particularly in RMS are reviewed. Finally, the cross-talking among these three pathways and the possibility of better understanding of the horizontal communication among them, leading to the development of more potent therapeutic approaches, are discussed.

  5. SYNER-G buildings, lifelines, transportation networks and critical facilities

    CERN Document Server

    Pitilakis, K; Kaynia, AM

    2014-01-01

    This volume collates serviceable fragility functions from an international selection of seismic risk probability research, developing and adapting them to a European context to improve damage forecasts for buildings, infrastructure, and critical facilities.

  6. Creating and analyzing pathway and protein interaction compendia for modelling signal transduction networks

    Directory of Open Access Journals (Sweden)

    Kirouac Daniel C

    2012-05-01

    Full Text Available Abstract Background Understanding the information-processing capabilities of signal transduction networks, how those networks are disrupted in disease, and rationally designing therapies to manipulate diseased states require systematic and accurate reconstruction of network topology. Data on networks central to human physiology, such as the inflammatory signalling networks analyzed here, are found in a multiplicity of on-line resources of pathway and interactome databases (Cancer CellMap, GeneGo, KEGG, NCI-Pathway Interactome Database (NCI-PID, PANTHER, Reactome, I2D, and STRING. We sought to determine whether these databases contain overlapping information and whether they can be used to construct high reliability prior knowledge networks for subsequent modeling of experimental data. Results We have assembled an ensemble network from multiple on-line sources representing a significant portion of all machine-readable and reconcilable human knowledge on proteins and protein interactions involved in inflammation. This ensemble network has many features expected of complex signalling networks assembled from high-throughput data: a power law distribution of both node degree and edge annotations, and topological features of a “bow tie” architecture in which diverse pathways converge on a highly conserved set of enzymatic cascades focused around PI3K/AKT, MAPK/ERK, JAK/STAT, NFκB, and apoptotic signaling. Individual pathways exhibit “fuzzy” modularity that is statistically significant but still involving a majority of “cross-talk” interactions. However, we find that the most widely used pathway databases are highly inconsistent with respect to the actual constituents and interactions in this network. Using a set of growth factor signalling networks as examples (epidermal growth factor, transforming growth factor-beta, tumor necrosis factor, and wingless, we find a multiplicity of network topologies in which receptors couple to downstream

  7. Ventral aspect of the visual form pathway is not critical for the perception of biological motion

    Science.gov (United States)

    Gilaie-Dotan, Sharon; Saygin, Ayse Pinar; Lorenzi, Lauren J.; Rees, Geraint; Behrmann, Marlene

    2015-01-01

    Identifying the movements of those around us is fundamental for many daily activities, such as recognizing actions, detecting predators, and interacting with others socially. A key question concerns the neurobiological substrates underlying biological motion perception. Although the ventral “form” visual cortex is standardly activated by biologically moving stimuli, whether these activations are functionally critical for biological motion perception or are epiphenomenal remains unknown. To address this question, we examined whether focal damage to regions of the ventral visual cortex, resulting in significant deficits in form perception, adversely affects biological motion perception. Six patients with damage to the ventral cortex were tested with sensitive point-light display paradigms. All patients were able to recognize unmasked point-light displays and their perceptual thresholds were not significantly different from those of three different control groups, one of which comprised brain-damaged patients with spared ventral cortex (n > 50). Importantly, these six patients performed significantly better than patients with damage to regions critical for biological motion perception. To assess the necessary contribution of different regions in the ventral pathway to biological motion perception, we complement the behavioral findings with a fine-grained comparison between the lesion location and extent, and the cortical regions standardly implicated in biological motion processing. This analysis revealed that the ventral aspects of the form pathway (e.g., fusiform regions, ventral extrastriate body area) are not critical for biological motion perception. We hypothesize that the role of these ventral regions is to provide enhanced multiview/posture representations of the moving person rather than to represent biological motion perception per se. PMID:25583504

  8. From pathways to networks: connecting dots by establishing protein-protein interaction networks in signaling pathways using affinity purification and mass spectrometry.

    Science.gov (United States)

    Li, Xu; Wang, Wenqi; Chen, Junjie

    2015-01-01

    Signal transductions are the basis of biological activities in all living organisms. Studying the signaling pathways, especially under physiological conditions, has become one of the most important facets of modern biological research. During the last decade, MS has been used extensively in biological research and is proven to be effective in addressing important biological questions. Here, we review the current progress in the understanding of signaling networks using MS approaches. We will focus on studies of protein-protein interactions that use affinity purification followed by MS approach. We discuss obstacles to affinity purification, data processing, functional validation, and identification of transient interactions and provide potential solutions for pathway-specific proteomics analysis, which we hope one day will lead to a comprehensive understanding of signaling networks in humans. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  9. Canalizing Kauffman Networks: Nonergodicity and Its Effect on Their Critical Behavior

    OpenAIRE

    Moreira, André Auto; Nunes Amaral, Luís A.

    2005-01-01

    Boolean networks have been used to study numerous phenomena, including gene regulation, neural networks, social interactions, and biological evolution. Here, we propose a general method for determining the critical behavior of Boolean systems built from arbitrary ensembles of Boolean functions. In particular, we solve the critical condition for systems of units operating according to canalizing functions and present strong numerical evidence that our approach correctly predicts the phase tran...

  10. Canalizing Kauffman networks: non-ergodicity and its effect on their critical behavior

    OpenAIRE

    Moreira, Andre A.; Amaral, Luis A. N.

    2005-01-01

    Boolean Networks have been used to study numerous phenomena, including gene regulation, neural networks, social interactions, and biological evolution. Here, we propose a general method for determining the critical behavior of Boolean systems built from arbitrary ensembles of Boolean functions. In particular, we solve the critical condition for systems of units operating according to canalizing functions and present strong numerical evidence that our approach correctly predicts the phase tran...

  11. Pathway switching explains the sharp response characteristic of hypoxia response network.

    Directory of Open Access Journals (Sweden)

    Yihai Yu

    2007-08-01

    Full Text Available Hypoxia induces the expression of genes that alter metabolism through the hypoxia-inducible factor (HIF. A theoretical model based on differential equations of the hypoxia response network has been previously proposed in which a sharp response to changes in oxygen concentration was observed but not quantitatively explained. That model consisted of reactions involving 23 molecular species among which the concentrations of HIF and oxygen were linked through a complex set of reactions. In this paper, we analyze this previous model using a combination of mathematical tools to draw out the key components of the network and explain quantitatively how they contribute to the sharp oxygen response. We find that the switch-like behavior is due to pathway-switching wherein HIF degrades rapidly under normoxia in one pathway, while the other pathway accumulates HIF to trigger downstream genes under hypoxia. The analytic technique is potentially useful in studying larger biomedical networks.

  12. Sustained activity in hierarchical modular neural networks: self-organized criticality and oscillations

    Directory of Open Access Journals (Sweden)

    Sheng-Jun Wang

    2011-06-01

    Full Text Available Cerebral cortical brain networks possess a number of conspicuous features of structure and dynamics. First, these networks have an intricate, non-random organization. They are structured in a hierarchical modular fashion, from large-scale regions of the whole brain, via cortical areas and area subcompartments organized as structural and functional maps to cortical columns, and finally circuits made up of individual neurons. Second, the networks display self-organized sustained activity, which is persistent in the absence of external stimuli. At the systems level, such activity is characterized by complex rhythmical oscillations over a broadband background, while at the cellular level, neuronal discharges have been observed to display avalanches, indicating that cortical networks are at the state of self-organized criticality. We explored the relationship between hierarchical neural network organization and sustained dynamics using large-scale network modeling. It was shown that sparse random networks with balanced excitation and inhibition can sustain neural activity without external stimulation. We find that a hierarchical modular architecture can generate sustained activity better than random networks. Moreover, the system can simultaneously support rhythmical oscillations and self-organized criticality, which are not present in the respective random networks. The underlying mechanism is that each dense module cannot sustain activity on its own, but displays self-organized criticality in the presence of weak perturbations. The hierarchical modular networks provide the coupling among subsystems with self-organized criticality. These results imply that the hierarchical modular architecture of cortical networks plays an important role in shaping the ongoing spontaneous activity of the brain, potentially allowing the system to take advantage of both the sensitivityof critical state and predictability and timing of oscillations for efficient

  13. Model Criticism of Bayesian Networks with Latent Variables.

    Science.gov (United States)

    Williamson, David M.; Mislevy, Robert J.; Almond, Russell G.

    This study investigated statistical methods for identifying errors in Bayesian networks (BN) with latent variables, as found in intelligent cognitive assessments. BN, commonly used in artificial intelligence systems, are promising mechanisms for scoring constructed-response examinations. The success of an intelligent assessment or tutoring system…

  14. Assessing Security-Critical Energy-Efficient Sensor Networks

    NARCIS (Netherlands)

    Law, Y.W.; Dulman, S.O.; Etalle, Sandro; Havinga, Paul J.M.

    In the EYES project (http://eyes.eu.org), we are investigating self-organizing, collaborative, energy-efficient sensor networks. This study is devoted to the security aspects of the project. Our contribution is three-fold: firstly, we present a survey, where we discuss the dominant issues of

  15. Evaluating Action Learning: A Critical Realist Complex Network Theory Approach

    Science.gov (United States)

    Burgoyne, John G.

    2010-01-01

    This largely theoretical paper will argue the case for the usefulness of applying network and complex adaptive systems theory to an understanding of action learning and the challenge it is evaluating. This approach, it will be argued, is particularly helpful in the context of improving capability in dealing with wicked problems spread around…

  16. Identification of gene networks and pathways associated with Guillain-Barre syndrome.

    Directory of Open Access Journals (Sweden)

    Kuo-Hsuan Chang

    Full Text Available BACKGROUND: The underlying change of gene network expression of Guillain-Barré syndrome (GBS remains elusive. We sought to identify GBS-associated gene networks and signaling pathways by analyzing the transcriptional profile of leukocytes in the patients with GBS. METHODS AND FINDINGS: Quantitative global gene expression microarray analysis of peripheral blood leukocytes was performed on 7 patients with GBS and 7 healthy controls. Gene expression profiles were compared between patients and controls after standardization. The set of genes that significantly correlated with GBS was further analyzed by Ingenuity Pathways Analyses. 256 genes and 18 gene networks were significantly associated with GBS (fold change ≥2, P<0.05. FOS, PTGS2, HMGB2 and MMP9 are the top four of 246 significantly up-regulated genes. The most significant disease and altered biological function genes associated with GBS were those involved in inflammatory response, infectious disease, and respiratory disease. Cell death, cellular development and cellular movement were the top significant molecular and cellular functions involved in GBS. Hematological system development and function, immune cell trafficking and organismal survival were the most significant GBS-associated function in physiological development and system category. Several hub genes, such as MMP9, PTGS2 and CREB1 were identified in the associated gene networks. Canonical pathway analysis showed that GnRH, corticotrophin-releasing hormone and ERK/MAPK signaling were the most significant pathways in the up-regulated gene set in GBS. CONCLUSIONS: This study reveals the gene networks and canonical pathways associated with GBS. These data provide not only networks between the genes for understanding the pathogenic properties of GBS but also map significant pathways for the future development of novel therapeutic strategies.

  17. Critical thresholds and dynamical network states in a neural architecture for cognitive tasks

    NARCIS (Netherlands)

    de Vries, Pieter

    2017-01-01

    Cognitive tasks are represented in a network, in which: - Nodes correspond to cell-assemblies with a critical threshold, which enables explanation of various psychological phenomena, like priming. - Dynamical network states (excitation loops) can propagate in specific, task-dependent ways ranging

  18. Biologically meaningful update rules increase the critical connectivity of generalized kauffman networks

    OpenAIRE

    Wittmann, Dominik M.; Marr, Carsten; Theis, Fabian J

    2010-01-01

    Abstract We generalize random Boolean networks by softening the hard binary discretization into multiple discrete states. These multistate networks are generic models of gene regulatory networks, where each gene is known to assume a finite number of functionally different expression levels. We analytically determine the critical connectivity that separates the biologically unfavorable frozen and chaotic regimes. This connectivity is inversely proportional to a parameter which measu...

  19. Gene expression, signal transduction pathways and functional networks associated with growth of sporadic vestibular schwannomas

    DEFF Research Database (Denmark)

    Sass, Hjalte C.R.; Borup, Rehannah; Alanin, Mikkel

    2017-01-01

    The objective of this study was to determine global gene expression in relation to Vestibular schwannomas (VS) growth rate and to identify signal transduction pathways and functional molecular networks associated with growth. Repeated magnetic resonance imaging (MRI) prior to surgery determined...... and analyzed by dChip software. Differential gene expression was defined as a 1.5-fold difference between fast and slow growing tumors (>... of signal transduction pathways and functional molecular networks associated with tumor growth. In total 109 genes were deregulated in relation to tumor growth rate. Genes associated with apoptosis, growth and cell proliferation were deregulated. Gene ontology included regulation of the cell cycle, cell...

  20. HIF-VEGF pathways are critical for chronic otitis media in Junbo and Jeff mouse mutants.

    Directory of Open Access Journals (Sweden)

    Michael T Cheeseman

    2011-10-01

    Full Text Available Otitis media with effusion (OME is the commonest cause of hearing loss in children, yet the underlying genetic pathways and mechanisms involved are incompletely understood. Ventilation of the middle ear with tympanostomy tubes is the commonest surgical procedure in children and the best treatment for chronic OME, but the mechanism by which they work remains uncertain. As hypoxia is a common feature of inflamed microenvironments, moderation of hypoxia may be a significant contributory mechanism. We have investigated the occurrence of hypoxia and hypoxia-inducible factor (HIF mediated responses in Junbo and Jeff mouse mutant models, which develop spontaneous chronic otitis media. We found that Jeff and Junbo mice labeled in vivo with pimonidazole showed cellular hypoxia in inflammatory cells in the bulla lumen, and in Junbo the middle ear mucosa was also hypoxic. The bulla fluid inflammatory cell numbers were greater and the upregulation of inflammatory gene networks were more pronounced in Junbo than Jeff. Hif-1α gene expression was elevated in bulla fluid inflammatory cells, and there was upregulation of its target genes including Vegfa in Junbo and Jeff. We therefore investigated the effects in Junbo of small-molecule inhibitors of VEGFR signaling (PTK787, SU-11248, and BAY 43-9006 and destabilizing HIF by inhibiting its chaperone HSP90 with 17-DMAG. We found that both classes of inhibitor significantly reduced hearing loss and the occurrence of bulla fluid and that VEGFR inhibitors moderated angiogenesis and lymphangiogenesis in the inflamed middle ear mucosa. The effectiveness of HSP90 and VEGFR signaling inhibitors in suppressing OM in the Junbo model implicates HIF-mediated VEGF as playing a pivotal role in OM pathogenesis. Our analysis of the Junbo and Jeff mutants highlights the role of hypoxia and HIF-mediated pathways, and we conclude that targeting molecules in HIF-VEGF signaling pathways has therapeutic potential in the treatment of

  1. The association of the kynurenine pathway of tryptophan metabolism with acute brain dysfunction during critical illness*.

    Science.gov (United States)

    Adams Wilson, Jessica R; Morandi, Alessandro; Girard, Timothy D; Thompson, Jennifer L; Boomershine, Chad S; Shintani, Ayumi K; Ely, E Wesley; Pandharipande, Pratik P

    2012-03-01

    Plasma tryptophan levels are associated with delirium in critically ill patients. Although tryptophan has been linked to the pathogenesis of other neurocognitive diseases through metabolism to neurotoxins via the kynurenine pathway, a role for kynurenine pathway activity in intensive care unit brain dysfunction (delirium and coma) remains unknown. This study examined the association between kynurenine pathway activity as determined by plasma kynurenine concentrations and kynurenine/tryptophan ratios and presence or absence of acute brain dysfunction (defined as delirium/coma-free days) in intensive care unit patients. This was a prospective cohort study that utilized patient data and blood samples from the Maximizing Efficacy of Targeted Sedation and Reducing Neurologic Dysfunction trial, which compared sedation with dexmedetomidine vs. lorazepam in mechanically ventilated patients. Baseline plasma kynurenine and tryptophan concentrations were measured using high-performance liquid chromatography with or without tandem mass spectrometry. Delirium was assessed daily using the Confusion Assessment Method for the Intensive Care Unit. Linear regression examined associations between kynurenine pathway activity and delirium/coma-free days after adjusting for sedative exposure, age, and severity of illness. Among 84 patients studied, median age was 60 yrs and Acute Physiology and Chronic Health Evaluation II score was 28.5. Elevated plasma kynurenine and kynurenine/tryptophan ratio were both independently associated with significantly fewer delirium/coma-free days (i.e., fewer days without acute brain dysfunction). Specifically, patients with plasma kynurenine or kynurenine/tryptophan ratios at the 75th percentile of our population had an average of 1.8 (95% confidence interval 0.6-3.1) and 2.1 (95% confidence interval 1.0-3.2) fewer delirium/coma-free days than those patients with values at the 25th percentile (p = .006 and p < .001, respectively). Increased kynurenine

  2. Non-Markovian State-Dependent Networks in Critical Loading

    Science.gov (United States)

    2015-02-04

    detail in Section 5.) State-dependent features are present in congestion control protocols in communication networks, such as TCP (see Refs...information if it does not display a currently valid OMB control number. PLEASE DO NOT RETURN YOUR FORM TO THE ABOVE ADDRESS. Colorado State University - Ft...Puhalskii FIGURE 1 The tandem queue. the workload and investigate the effect of controlling the arrival rate. We will adopt a similar model. We

  3. The origin of the criticality in meme popularity distribution on complex networks

    OpenAIRE

    Yup Kim; Seokjong Park; Soon-Hyung Yook

    2016-01-01

    Previous studies showed that the meme popularity distribution is described by a heavy-tailed distribution or a power-law, which is a characteristic feature of the criticality. Here, we study the origin of the criticality on non-growing and growing networks based on the competition induced criticality model. From the direct Mote Carlo simulations and the exact mapping into the position dependent biased random walk (PDBRW), we find that the meme popularity distribution satisfies a very robust p...

  4. Cross tissue trait-pathway network reveals the importance of oxidative stress and inflammation pathways in obesity-induced diabetes in mouse.

    Directory of Open Access Journals (Sweden)

    Shouguo Gao

    Full Text Available Complex disorders often involve dysfunctions in multiple tissue organs. Elucidating the communication among them is important to understanding disease pathophysiology. In this study we integrate multiple tissue gene expression and quantitative trait measurements of an obesity-induced diabetes mouse model, with databases of molecular interaction networks, to construct a cross tissue trait-pathway network. The animals belong to two strains of mice (BTBR or B6, of two obesity status (obese or lean, and at two different ages (4 weeks and 10 weeks. Only 10 week obese BTBR animals are diabetic. The expression data was first utilized to determine the state of every pathway in each tissue, which is subsequently utilized to construct a pathway co-expression network and to define trait-relevant and trait-linking pathways. Among the six tissues profiled, the adipose contains the largest number of trait-linking pathways. Among the eight traits measured, the body weight and plasma insulin level possess the most number of relevant and linking pathways. Topological analysis of the trait-pathway network revealed that the glycolysis/gluconeogenesis pathway in liver and the insulin signaling pathway in muscle are of top importance to the information flow in the network, with the highest degrees and betweenness centralities. Interestingly, pathways related to metabolism and oxidative stress actively interact with many other pathways in all animals, whereas, among the 10 week animals, the inflammation pathways were preferentially interactive in the diabetic ones only. In summary, our method offers a systems approach to delineate disease trait relevant intra- and cross tissue pathway interactions, and provides insights to the molecular basis of the obesity-induced diabetes.

  5. Bruno Latour, actor-networks, and the critique of critical sociology

    Directory of Open Access Journals (Sweden)

    Spasić Ivana

    2007-01-01

    Full Text Available The paper analyzes the theoretical opus of Bruno Latour and his treatment of the concept of critique. In the first section "actor-network theory" is presented through its key notions (actant, network, translation, associations together with Latour’s theory of modernity. In the second section various aspects of the relation between Latour and critique are discussed - first his own criticism of others (standard sociology and especially "critical", i.e. Bourdieu’s sociology, then the criticisms aimed at his work, to conclude with the political ambivalences of Latour’s attempt to develop an "acritical" social theory. .

  6. MPINet: Metabolite Pathway Identification via Coupling of Global Metabolite Network Structure and Metabolomic Profile

    Directory of Open Access Journals (Sweden)

    Feng Li

    2014-01-01

    Full Text Available High-throughput metabolomics technology, such as gas chromatography mass spectrometry, allows the analysis of hundreds of metabolites. Understanding that these metabolites dominate the study condition from biological pathway perspective is still a significant challenge. Pathway identification is an invaluable aid to address this issue and, thus, is urgently needed. In this study, we developed a network-based metabolite pathway identification method, MPINet, which considers the global importance of metabolites and the unique character of metabolomic profile. Through integrating the global metabolite functional network structure and the character of metabolomic profile, MPINet provides a more accurate metabolomic pathway analysis. This integrative strategy simultaneously captures the global nonequivalence of metabolites in a pathway and the bias from metabolomic experimental technology. We then applied MPINet to four different types of metabolite datasets. In the analysis of metastatic prostate cancer dataset, we demonstrated the effectiveness of MPINet. With the analysis of the two type 2 diabetes datasets, we show that MPINet has the potentiality for identifying novel pathways related with disease and is reliable for analyzing metabolomic data. Finally, we extensively applied MPINet to identify drug sensitivity related pathways. These results suggest MPINet’s effectiveness and reliability for analyzing metabolomic data across multiple different application fields.

  7. Decentralized control of transmission rates in energy-critical wireless networks

    KAUST Repository

    Xia, Li

    2013-06-01

    In this paper, we discuss the decentralized optimization of delay and energy consumption in a multi-hop wireless network. The goal is to minimize the energy consumption of energy-critical nodes and the overall packet transmission delay of the network. The transmission rates of energy-critical nodes are adjustable according to the local information of nodes, i.e., the length of packets queued. The multi-hop network is modeled as a queueing network.We prove that the system performance is monotone w.r.t. (with respect to) the transmission rate, thus the “bang-bang” control is an optimal control. We also prove that there exists a threshold type control policy which is optimal. We propose a decentralized algorithm to control transmission rates of these energy-critical nodes. Some simulation experiments are conducted to demonstrate the effectiveness of our approach.

  8. Adaptive learning in tracking control based on the dual critic network design.

    Science.gov (United States)

    Ni, Zhen; He, Haibo; Wen, Jinyu

    2013-06-01

    In this paper, we present a new adaptive dynamic programming approach by integrating a reference network that provides an internal goal representation to help the systems learning and optimization. Specifically, we build the reference network on top of the critic network to form a dual critic network design that contains the detailed internal goal representation to help approximate the value function. This internal goal signal, working as the reinforcement signal for the critic network in our design, is adaptively generated by the reference network and can also be adjusted automatically. In this way, we provide an alternative choice rather than crafting the reinforcement signal manually from prior knowledge. In this paper, we adopt the online action-dependent heuristic dynamic programming (ADHDP) design and provide the detailed design of the dual critic network structure. Detailed Lyapunov stability analysis for our proposed approach is presented to support the proposed structure from a theoretical point of view. Furthermore, we also develop a virtual reality platform to demonstrate the real-time simulation of our approach under different disturbance situations. The overall adaptive learning performance has been tested on two tracking control benchmarks with a tracking filter. For comparative studies, we also present the tracking performance with the typical ADHDP, and the simulation results justify the improved performance with our approach.

  9. Analysis of critical operating conditions for LV distribution networks with microgrids

    Science.gov (United States)

    Zehir, M. A.; Batman, A.; Sonmez, M. A.; Font, A.; Tsiamitros, D.; Stimoniaris, D.; Kollatou, T.; Bagriyanik, M.; Ozdemir, A.; Dialynas, E.

    2016-11-01

    Increase in the penetration of Distributed Generation (DG) in distribution networks, raises the risk of voltage limit violations while contributing to line losses. Especially in low voltage (LV) distribution networks (secondary distribution networks), impacts of active power flows on the bus voltages and on the network losses are more dominant. As network operators must meet regulatory limitations, they have to take into account the most critical operating conditions in their systems. In this study, it is aimed to present the impact of the worst operation cases of LV distribution networks comprising microgrids. Simulation studies are performed on a field data-based virtual test-bed. The simulations are repeated for several cases consisting different microgrid points of connection with different network loading and microgrid supply/demand conditions.

  10. HPIminer: A text mining system for building and visualizing human protein interaction networks and pathways.

    Science.gov (United States)

    Subramani, Suresh; Kalpana, Raja; Monickaraj, Pankaj Moses; Natarajan, Jeyakumar

    2015-04-01

    The knowledge on protein-protein interactions (PPI) and their related pathways are equally important to understand the biological functions of the living cell. Such information on human proteins is highly desirable to understand the mechanism of several diseases such as cancer, diabetes, and Alzheimer's disease. Because much of that information is buried in biomedical literature, an automated text mining system for visualizing human PPI and pathways is highly desirable. In this paper, we present HPIminer, a text mining system for visualizing human protein interactions and pathways from biomedical literature. HPIminer extracts human PPI information and PPI pairs from biomedical literature, and visualize their associated interactions, networks and pathways using two curated databases HPRD and KEGG. To our knowledge, HPIminer is the first system to build interaction networks from literature as well as curated databases. Further, the new interactions mined only from literature and not reported earlier in databases are highlighted as new. A comparative study with other similar tools shows that the resultant network is more informative and provides additional information on interacting proteins and their associated networks. Copyright © 2015 Elsevier Inc. All rights reserved.

  11. Hidden protein folding pathways in free-energy landscapes uncovered by network analysis.

    Science.gov (United States)

    Yin, Yanping; Maisuradze, Gia G; Liwo, Adam; Scheraga, Harold A

    2012-04-10

    A network analysis is used to uncover hidden folding pathways in free-energy landscapes usually defined in terms of such arbitrary order parameters as root-mean-square deviation from the native structure, radius of gyration, etc. The analysis has been applied to molecular dynamics (MD) trajectories of the B-domain of staphylococcal protein A, generated with the coarse-grained united-residue (UNRES) force field in a broad range of temperatures (270K ≤ T ≤ 325K). Thousands of folding pathways have been identified at each temperature. Out of these many folding pathways, several most probable ones were selected for investigation of the conformational transitions during protein folding. Unlike other conformational space network (CSN) methods, a node in the CSN variant implemented in this work is defined according to the nativelikeness class of the structure, which defines the similarity of segments of the compared structures in terms of secondary-structure, contact-pattern, and local geometry, as well as the overall geometric similarity of the conformation under consideration to that of the reference (experimental) structure. Our previous findings, regarding the folding model and conformations found at the folding-transition temperature for protein A (Maisuradze et al., J. Am. Chem. Soc. 132, 9444, 2010), were confirmed by the conformational space network analysis. In the methodology and in the analysis of the results, the shortest path identified by using the shortest-path algorithm corresponds to the most probable folding pathway in the conformational space network.

  12. Critical controllability in proteome-wide protein interaction network integrating transcriptome

    Science.gov (United States)

    Ishitsuka, Masayuki; Akutsu, Tatsuya; Nacher, Jose C.

    2016-04-01

    Recently, the number of essential gene entries has considerably increased. However, little is known about the relationships between essential genes and their functional roles in critical network control at both the structural (protein interaction network) and dynamic (transcriptional) levels, in part because the large size of the network prevents extensive computational analysis. Here, we present an algorithm that identifies the critical control set of nodes by reducing the computational time by 180 times and by expanding the computable network size up to 25 times, from 1,000 to 25,000 nodes. The developed algorithm allows a critical controllability analysis of large integrated systems composed of a transcriptome- and proteome-wide protein interaction network for the first time. The data-driven analysis captures a direct triad association of the structural controllability of genes, lethality and dynamic synchronization of co-expression. We believe that the identified optimized critical network control subsets may be of interest as drug targets; thus, they may be useful for drug design and development.

  13. Social Network Assessments and Interventions for Health Behavior Change: A Critical Review.

    Science.gov (United States)

    Latkin, Carl A; Knowlton, Amy R

    2015-01-01

    Social networks provide a powerful approach for health behavior change. This article documents how social network interventions have been successfully used for a range of health behaviors, including HIV risk practices, smoking, exercise, dieting, family planning, bullying, and mental health. We review the literature that suggests the relationship between health behaviors and social network attributes demonstrates a high degree of specificity. The article then examines hypothesized social influence mechanisms including social norms, modeling, and social rewards and the factors of social identity and social rewards that can be employed to sustain social network interventions. Areas of future research avenues are highlighted, including the need to examine and to adjust analytically for contamination and social diffusion, social influence versus differential affiliation, and network change. Use and integration of mhealth and face-to-face networks for promoting health behavior change are also critical research areas.

  14. Social Network Assessments and Interventions for Health Behavior Change: A Critical Review

    Science.gov (United States)

    Latkin, Carl A.; Knowlton, Amy R.

    2016-01-01

    Social networks provide a powerful approach for health behavior change. This article documents how social network interventions have been successfully utilized for a range of health behaviors including HIV risk practices, smoking, exercise, dieting, family planning, bullying, and mental health. We review the literature that suggests relationship between health behaviors and social network attributes demonstrate a high degree of specificity. The article then examines hypothesized social influence mechanisms including social norms, modeling, and social rewards and the factors of social identity and social rewards that can be employed to sustain social network interventions. Areas of future research avenues are highlighted, including the need to examine and analytically adjust for contamination and social diffusion, social influence versus differential affiliation, and network change. Use and integration of mhealth and face-to-face networks for promoting health behavior change are also critical research areas. PMID:26332926

  15. Critical pollutant emissions from the Indian telecom network

    Science.gov (United States)

    Sahu, S. K.; Schultz, M. G.; Beig, G.

    2015-02-01

    In recent years, India developed the world's 2nd largest telecom network based largely on mobile phone connections. The energy demand of the telecom sector especially in rural areas is mainly fueled by diesel combustion in mid-size generators due to either lack of grid power or unstable provision of electricity. This study quantifies the magnitude of emissions from the Indian telecom sector and presents a gridded inventory for the year 2011 with a spatial distribution derived on the provincial level including information on urban versus rural telecom installations. The estimated total NOx, PM, CO, BC, SO2, HC and CO2 emissions are found to be 295 ± 196 Gg/yr, 155 ± 108 Gg/yr, 61 ± 41 Gg/yr, 28 ± 18 Gg/yr, 114 ± 12 Gg/yr 19.50 ± 13 Gg/yr and 27.9 ± 12 million tons/yr, respectively. The future development of emissions from this sector will depend on the rate of electrification and possible market saturation. Air quality in rural areas of India could be improved by replacing diesel generators with renewable energy sources or electricity from the grid.

  16. Association between mutations of critical pathway genes and survival outcomes according to the tumor location in colorectal cancer.

    Science.gov (United States)

    Lee, Dae-Won; Han, Sae-Won; Cha, Yongjun; Bae, Jeong Mo; Kim, Hwang-Phill; Lyu, Jaemyun; Han, Hyojun; Kim, Hyoki; Jang, Hoon; Bang, Duhee; Huh, Iksoo; Park, Taesung; Won, Jae-Kyung; Jeong, Seung-Yong; Park, Kyu Joo; Kang, Gyeong Hoon; Kim, Tae-You

    2017-09-15

    Colorectal cancer (CRC) develops through the alteration of several critical pathways. This study was aimed at evaluating the influence of critical pathways on survival outcomes for patients with CRC. Targeted next-generation sequencing of 40 genes included in the 5 critical pathways of CRC (WNT, P53, RTK-RAS, phosphatidylinositol-4,5-bisphosphate 3-kinase [PI3K], and transforming growth factor β [TGF-β]) was performed for 516 patients with stage III or high-risk stage II CRC treated with surgery followed by adjuvant fluoropyrimidine and oxaliplatin chemotherapy. The associations between critical pathway mutations and relapse-free survival (RFS) and overall survival were analyzed. The associations were further analyzed according to the tumor location. The mutation rates for the WNT, P53, RTK-RAS, PI3K, and TGF-β pathways were 84.5%, 69.0%, 60.7%, 30.0%, and 28.9%, respectively. A mutation in the PI3K pathway was associated with longer RFS (adjusted hazard ratio [HR], 0.59; 95% confidence interval [CI], 0.36-0.99), whereas a mutation in the RTK-RAS pathway was associated with shorter RFS (adjusted HR, 1.60; 95% CI, 1.01-2.52). Proximal tumors showed a higher mutation rate than distal tumors, and the mutation profile was different according to the tumor location. The mutation rates of Kirsten rat sarcoma viral oncogene homolog (KRAS), phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit α (PIK3CA), and B-Raf proto-oncogene serine/threonine kinase (BRAF) were higher in proximal tumors, and the mutation rates of adenomatous polyposis coli (APC), tumor protein 53 (TP53), and neuroblastoma RAS viral oncogene homolog (NRAS) were higher in distal tumors. The better RFS with the PI3K pathway mutation was significant only for proximal tumors, and the worse RFS with the RTK-RAS pathway mutation was significant only for distal tumors. A PI3K pathway mutation was associated with better RFS for CRC patients treated with adjuvant chemotherapy, and an RTK

  17. A Method to Evaluate Critical Factors for Successful Implementation of Clinical Pathways.

    Science.gov (United States)

    Dong, W; Huang, Z

    2015-01-01

    Clinical pathways (CPs) have been viewed as a multidisciplinary tool to improve the quality and efficiency of evidence-based care. Despite widespread enthusiasm for CPs, research has shown that many CP initiatives are unsuccessful. To this end, this study provides a methodology to evaluate critical success factors (CSFs) that can aid healthcare organizations to achieve successful CP implementation. This study presents a new approach to evaluate CP implementation CSFs, with the aims being: (1) to identify CSFs for implementation of CPs through a comprehensive literature review and interviews with collaborative experts; (2) to use a filed study data with a robust fuzzy DEMATEL (the decision making trial and evaluation laboratory) approach to visualize the structure of complicated causal relationships between CSFs and obtain the influence level of these factors. The filed study data is provided by ten clinical experts of a Chinese hospital. 23 identified CSF factors which are initially identified through a review of the literature and interviews with collaborative experts. Then, a number of direct and indirect relationships are derived from the data such that different perceptions can be integrated into a compromised cause and effect model of CP implementation. The results indicate that the proposed approach can systematically evaluate CSFs and realize the importance of each factor such that the most common causes of failure of CP implementation could be eliminated or avoided. Therefore, the tool proposed would help healthcare organizations to manage CP implementation in a more effective and proactive way.

  18. Critical Analysis of the Melanogenic Pathway in Insects and Higher Animals

    Directory of Open Access Journals (Sweden)

    Manickam Sugumaran

    2016-10-01

    Full Text Available Animals synthesize melanin pigments for the coloration of their skin and use it for their protection from harmful solar radiation. Insects use melanins even more ingeniously than mammals and employ them for exoskeletal pigmentation, cuticular hardening, wound healing and innate immune responses. In this review, we discuss the biochemistry of melanogenesis process occurring in higher animals and insects. A special attention is given to number of aspects that are not previously brought to light: (1 the molecular mechanism of dopachrome conversion that leads to the production of two different dihydroxyindoles; (2 the role of catecholamine derivatives other than dopa in melanin production in animals; (3 the critical parts played by various biosynthetic enzymes associated with insect melanogenesis; and (4 the presence of a number of important gaps in both melanogenic and sclerotinogenic pathways. Additionally, importance of the melanogenic process in insect physiology especially in the sclerotization of their exoskeleton, wound healing reactions and innate immune responses is highlighted. The comparative biochemistry of melanization with sclerotization is also discussed.

  19. Retrospective assessment of the implementation of critical pathway in stroke patients in a single university hospital.

    Science.gov (United States)

    Kim, Jin Hoan; Byun, Ha Young; Son, Seungnam; Lee, Joong Hoon; Yoon, Chul Ho; Lee, Eun Shin; Shin, Heesuk; Oh, Min-Kyun

    2014-10-01

    To evaluate the effects of the implementation of critical pathway (CP) in stroke patients treated at a single university hospital. A retrospective medical review collected data from 497 patients who had suffered acute stroke in the rehabilitation center. Stroke outcomes were compared between before and after the implementation of CP based on factors including demographic factors, stroke characteristics, pre-existing medical conditions, medical complications, functional states, and length of stay (LOS). After the implementation of CP, the patients showed significantly higher stage for upper proximal (p=0.008) and lower extremity (p=0.001) on Brunnstrom stage and significantly lower scores for modified Rankin Scale (p=0.003) at transfer. For those with pre-existing medical conditions, there were significantly increased osteoarthritis (p=0.002) and valvular heart disease (p=0.011). Regarding medical complications during acute inpatient rehabilitation, there were significantly decreased shoulder pain (p=0.001) and dysphagia (p=0.017), and significantly increased gastrointestinal symptoms (p=0.001). Functional gain and efficiency of stroke patients during rehabilitation center hospitalization did not significantly change after implementation of CP. But, shorter LOS of total hospitalization, pre-rehabilitation center hospitalization, and rehabilitation center hospitalization were evident. After the implementation of CP, patients less often developed complications and displayed no changes in functional gain and efficiency. They had shorter LOS of total hospitalization, pre-rehabilitation center hospitalization and rehabilitation center hospitalization.

  20. Pathway-Consensus Approach to Metabolic Network Reconstruction for Pseudomonas putida KT2440 by Systematic Comparison of Published Models.

    Directory of Open Access Journals (Sweden)

    Qianqian Yuan

    Full Text Available Over 100 genome-scale metabolic networks (GSMNs have been published in recent years and widely used for phenotype prediction and pathway design. However, GSMNs for a specific organism reconstructed by different research groups usually produce inconsistent simulation results, which makes it difficult to use the GSMNs for precise optimal pathway design. Therefore, it is necessary to compare and identify the discrepancies among networks and build a consensus metabolic network for an organism. Here we proposed a process for systematic comparison of metabolic networks at pathway level. We compared four published GSMNs of Pseudomonas putida KT2440 and identified the discrepancies leading to inconsistent pathway calculation results. The mistakes in the models were corrected based on information from literature so that all the calculated synthesis and uptake pathways were the same. Subsequently we built a pathway-consensus model and then further updated it with the latest genome annotation information to obtain modelPpuQY1140 for P. putida KT2440, which includes 1140 genes, 1171 reactions and 1104 metabolites. We found that even small errors in a GSMN could have great impacts on the calculated optimal pathways and thus may lead to incorrect pathway design strategies. Careful investigation of the calculated pathways during the metabolic network reconstruction process is essential for building proper GSMNs for pathway design.

  1. Modeling the altered expression levels of genes on signaling pathways in tumors as causal bayesian networks.

    Science.gov (United States)

    Neapolitan, Richard; Xue, Diyang; Jiang, Xia

    2014-01-01

    This paper concerns a study indicating that the expression levels of genes in signaling pathways can be modeled using a causal Bayesian network (BN) that is altered in tumorous tissue. These results open up promising areas of future research that can help identify driver genes and therapeutic targets. So, it is most appropriate for the cancer informatics community. Our central hypothesis is that the expression levels of genes that code for proteins on a signal transduction network (STP) are causally related and that this causal structure is altered when the STP is involved in cancer. To test this hypothesis, we analyzed 5 STPs associated with breast cancer, 7 STPs associated with other cancers, and 10 randomly chosen pathways, using a breast cancer gene expression level dataset containing 529 cases and 61 controls. We identified all the genes related to each of the 22 pathways and developed separate gene expression datasets for each pathway. We obtained significant results indicating that the causal structure of the expression levels of genes coding for proteins on STPs, which are believed to be implicated in both breast cancer and in all cancers, is more altered in the cases relative to the controls than the causal structure of the randomly chosen pathways.

  2. Fault tolerance in protein interaction networks: stable bipartite subgraphs and redundant pathways.

    Directory of Open Access Journals (Sweden)

    Arthur Brady

    Full Text Available As increasing amounts of high-throughput data for the yeast interactome become available, more system-wide properties are uncovered. One interesting question concerns the fault tolerance of protein interaction networks: whether there exist alternative pathways that can perform some required function if a gene essential to the main mechanism is defective, absent or suppressed. A signature pattern for redundant pathways is the BPM (between-pathway model motif, introduced by Kelley and Ideker. Past methods proposed to search the yeast interactome for BPM motifs have had several important limitations. First, they have been driven heuristically by local greedy searches, which can lead to the inclusion of extra genes that may not belong in the motif; second, they have been validated solely by functional coherence of the putative pathways using GO enrichment, making it difficult to evaluate putative BPMs in the absence of already known biological annotation. We introduce stable bipartite subgraphs, and show they form a clean and efficient way of generating meaningful BPMs which naturally discard extra genes included by local greedy methods. We show by GO enrichment measures that our BPM set outperforms previous work, covering more known complexes and functional pathways. Perhaps most importantly, since our BPMs are initially generated by examining the genetic-interaction network only, the location of edges in the protein-protein physical interaction network can then be used to statistically validate each candidate BPM, even with sparse GO annotation (or none at all. We uncover some interesting biological examples of previously unknown putative redundant pathways in such areas as vesicle-mediated transport and DNA repair.

  3. DMPD: IRAK1: a critical signaling mediator of innate immunity. [Dynamic Macrophage Pathway CSML Database

    Lifescience Database Archive (English)

    Full Text Available 17890055 IRAK1: a critical signaling mediator of innate immunity. Gottipati S, Rao ...IRAK1: a critical signaling mediator of innate immunity. PubmedID 17890055 Title IRAK1: a critical signaling media

  4. Mapping Systemic Risk: Critical Degree and Failures Distribution in Financial Networks.

    Science.gov (United States)

    Smerlak, Matteo; Stoll, Brady; Gupta, Agam; Magdanz, James S

    2015-01-01

    The financial crisis illustrated the need for a functional understanding of systemic risk in strongly interconnected financial structures. Dynamic processes on complex networks being intrinsically difficult to model analytically, most recent studies of this problem have relied on numerical simulations. Here we report analytical results in a network model of interbank lending based on directly relevant financial parameters, such as interest rates and leverage ratios. We obtain a closed-form formula for the "critical degree" (the number of creditors per bank below which an individual shock can propagate throughout the network), and relate failures distributions to network topologies, in particular scalefree ones. Our criterion for the onset of contagion turns out to be isomorphic to the condition for cooperation to evolve on graphs and social networks, as recently formulated in evolutionary game theory. This remarkable connection supports recent calls for a methodological rapprochement between finance and ecology.

  5. Mapping Systemic Risk: Critical Degree and Failures Distribution in Financial Networks

    Science.gov (United States)

    Smerlak, Matteo; Stoll, Brady; Gupta, Agam; Magdanz, James S.

    2015-01-01

    The financial crisis illustrated the need for a functional understanding of systemic risk in strongly interconnected financial structures. Dynamic processes on complex networks being intrinsically difficult to model analytically, most recent studies of this problem have relied on numerical simulations. Here we report analytical results in a network model of interbank lending based on directly relevant financial parameters, such as interest rates and leverage ratios. We obtain a closed-form formula for the “critical degree” (the number of creditors per bank below which an individual shock can propagate throughout the network), and relate failures distributions to network topologies, in particular scalefree ones. Our criterion for the onset of contagion turns out to be isomorphic to the condition for cooperation to evolve on graphs and social networks, as recently formulated in evolutionary game theory. This remarkable connection supports recent calls for a methodological rapprochement between finance and ecology. PMID:26207631

  6. Critical pathways of change in fruit export regions at desert margin (Chile)

    DEFF Research Database (Denmark)

    Frederiksen, Peter

    field surveys, semi-structured interviews, and library investigations. The main result is that no single variable could explain the pathways. Pathways were found to be explained by the functioning of the regional dynamic system. Pathways were found to vary in type, cause, relation and space-time. Global...... scales (formation of the Andes to the colonization) constrained the pathways. Historical tendencies (land and water reforms, land and water markets and others) influenced but did not determine pathways because of the increasing openness to teleconnections. Emergent properties were identified in some...

  7. Critical biological pathways for chronic psychosocial stress and research opportunities to advance the consideration of stress in chemical risk assessment.

    Science.gov (United States)

    McEwen, Bruce S; Tucker, Pamela

    2011-12-01

    Emerging evidence suggests that psychosocial stress and toxicants may interact to modify health risks. Stress-toxicant interactions could be important in chemical risk assessment, but these interactions are poorly understood and additional research is necessary to advance their application. Environmental health research can increase knowledge of these interactions by exploring hypotheses on allostatic load, which measures the cumulative impacts of stress across multiple physiological pathways, using knowledge about physiological pathways for stress-related health effects, and evidence of common target pathways for both stress and toxicants. In this article, critical physiological pathways for stress-related health effects are discussed, with specific attention to allostatic load and stress-toxicant interactions, concluding with research suggestions for potential applications of such research in chemical risk assessment.

  8. Transnational issue-specific expert networking: A pathway to local policy change.

    Science.gov (United States)

    O'Brien, Cheryl

    2015-12-01

    This article reports on key findings from a study of subnational governments in Mexico and Nigeria (O'Brien, 2013). With empirical richness of the case study method and small-n statistical analysis across the subnational units for each country, this study asks: How can we push the needle toward more progressive policy change on violence against women in developing and democratizing contexts? This study finds that issue-specific expert networking is a civic pathway to subnational policy responsiveness in Mexico and Nigeria. The dynamics of this pathway illuminate local-global political connections, and this study shows how issue-specific expert networking is important for the diffusion of an international norm and policies on violence against women. Copyright © 2015 Elsevier Ltd. All rights reserved.

  9. Learning the Art of Networking: A Critical Skill for Enhancing Social Capital and Career Success

    Science.gov (United States)

    de Janasz, Suzanne C.; Forret, Monica L.

    2008-01-01

    In this era of boundaryless careers, with individuals making frequent career moves and needing to get up-to-speed quickly, networking is seen as a critical competency. Developing and maintaining relationships with others for the purpose of mutual benefit can help individuals search for and secure employment opportunities, gain access to needed…

  10. Critical Social Network Analysis in Community Colleges: Peer Effects and Credit Attainment

    Science.gov (United States)

    González Canché, Manuel S.; Rios-Aguilar, Cecilia

    2014-01-01

    This chapter discusses the importance of conducting critical social network analysis (CSNA) in higher education. To illustrate the benefits of CSNA, the authors use existing institutional data to examine peer effects in community colleges. The chapter ends with a discussion of the implications of using a CSNA approach to measure inequities in…

  11. Intramural Purkinje cell network of sheep ventricles as the terminal pathway of conduction system.

    Science.gov (United States)

    Ryu, Shonosuke; Yamamoto, Shoji; Andersen, Clark R; Nakazawa, Kiyoshi; Miyake, Fumihiko; James, Thomas N

    2009-01-01

    To identify the anatomical basis for cardiac electrical signal conduction, particularly seeking the intramural terminals of conduction pathway within the ventricles, sheep hearts were examined compared with human hearts utilizing the characteristic morphology of Purkinje cells as a histological marker. In 15 sheep and five human autopsies of noncardiac death, prevalence of Purkinje or Purkinje-type cells were histologically examined in the atrioventricular node, its distal conduction pathway, the interventricular septum, and the right- and left-ventricular free walls. Myocardial tissue cleavages were examined in the transmural sections (along cardiac base-to-apex axis) obtained from the septum and ventricular free walls. Serial histological sections through virtually the entirety of the septum in selected sheep were used as the basis of a three-dimensional reconstruction of the conduction pathway, particularly of the intramural Purkinje cell network. Purkinje cells were found within the mural myocardium of sheep ventricles whereas no intramural Purkinje-type cell was detected within the human ventricles. In the sheep septum, every intramural Purkinje cell composed a three-dimensional network throughout the mural myocardium, which proximally connected to the subendocardial extension of the bundle branches and distally formed an occasional junction with ordinary working myocytes. The Purkinje-cell network may participate in the ventricular excitation as the terminal conduction pathway. Individual connections among the Purkinje cells contain the links of through-wall orientation which would benefit the signal conduction crossing the architectural barriers by cleavages in sheep hearts. The myocardial architectural changes found in diseased hearts could disrupt the network links including those with transmural orientation. Anat Rec, 2009. (c) 2008 Wiley-Liss, Inc.

  12. Critical pathways for the management of preeclampsia and severe preeclampsia in institutionalised health care settings

    Directory of Open Access Journals (Sweden)

    Daftari Ashi

    2003-10-01

    Full Text Available Abstract Background Preeclampsia is a complex disease in which several providers should interact continuously and in a coordinated manner to provide proper health care. However, standardizing criteria to treat patients with preeclampsia is problematical and severe flaws have been observed in the management of the disease. This paper describes a set of critical pathways (CPs designed to provide uniform criteria for clinical decision-making at different levels of care of pregnant patients with preeclampsia or severe preeclampsia. Methods Clinicians and researchers from different countries participated in the construction of the CPs. The CPs were developed using the following steps: a Definition of the conceptual framework; b Identification of potential users: primary care physicians and maternal and child health nurses in ambulatory settings; ob/gyn and intensive care physicians in secondary and tertiary care levels. c Structural development. Results The CPs address the following care processes: 1. Screening for preeclampsia, risk assessment and classification according to the level of risk. 2. Management of preeclampsia at primary care clinics. 3. Evaluation and management of preeclampsia at secondary and tertiary care hospitals: 4. Criteria for clinical decision-making between conservative management and expedited delivery of patients with severe preeclampsia. Conclusion Since preeclampsia continues to be one of the primary causes of maternal deaths and morbidity worldwide, the expected impact of these CPs is the contribution to improving health care quality in both developed and developing countries. The CPs are designed to be applied in a complex health care system, where different physicians and health providers at different levels of care should interact continuously and in a coordinated manner to provide care to all preeclamptic women. Although the CPs were developed using evidence-based criteria, they could require careful evaluation and

  13. Systems level analysis and identification of pathways and networks associated with liver fibrosis.

    Directory of Open Access Journals (Sweden)

    Mohamed Diwan M AbdulHameed

    Full Text Available Toxic liver injury causes necrosis and fibrosis, which may lead to cirrhosis and liver failure. Despite recent progress in understanding the mechanism of liver fibrosis, our knowledge of the molecular-level details of this disease is still incomplete. The elucidation of networks and pathways associated with liver fibrosis can provide insight into the underlying molecular mechanisms of the disease, as well as identify potential diagnostic or prognostic biomarkers. Towards this end, we analyzed rat gene expression data from a range of chemical exposures that produced observable periportal liver fibrosis as documented in DrugMatrix, a publicly available toxicogenomics database. We identified genes relevant to liver fibrosis using standard differential expression and co-expression analyses, and then used these genes in pathway enrichment and protein-protein interaction (PPI network analyses. We identified a PPI network module associated with liver fibrosis that includes known liver fibrosis-relevant genes, such as tissue inhibitor of metalloproteinase-1, galectin-3, connective tissue growth factor, and lipocalin-2. We also identified several new genes, such as perilipin-3, legumain, and myocilin, which were associated with liver fibrosis. We further analyzed the expression pattern of the genes in the PPI network module across a wide range of 640 chemical exposure conditions in DrugMatrix and identified early indications of liver fibrosis for carbon tetrachloride and lipopolysaccharide exposures. Although it is well known that carbon tetrachloride and lipopolysaccharide can cause liver fibrosis, our network analysis was able to link these compounds to potential fibrotic damage before histopathological changes associated with liver fibrosis appeared. These results demonstrated that our approach is capable of identifying early-stage indicators of liver fibrosis and underscore its potential to aid in predictive toxicity, biomarker identification, and to

  14. Network modularity reveals critical scales for connectivity in ecology and evolution

    Science.gov (United States)

    Fletcher, Robert J.; Revell, Andre; Reichert, Brian E.; Kitchens, Wiley M.; Dixon, J.; Austin, James D.

    2013-01-01

    For nearly a century, biologists have emphasized the profound importance of spatial scale for ecology, evolution and conservation. Nonetheless, objectively identifying critical scales has proven incredibly challenging. Here we extend new techniques from physics and social sciences that estimate modularity on networks to identify critical scales for movement and gene flow in animals. Using four species that vary widely in dispersal ability and include both mark-recapture and population genetic data, we identify significant modularity in three species, two of which cannot be explained by geographic distance alone. Importantly, the inclusion of modularity in connectivity and population viability assessments alters conclusions regarding patch importance to connectivity and suggests higher metapopulation viability than when ignoring this hidden spatial scale. We argue that network modularity reveals critical meso-scales that are probably common in populations, providing a powerful means of identifying fundamental scales for biology and for conservation strategies aimed at recovering imperilled species.

  15. Network modularity reveals critical scales for connectivity in ecology and evolution.

    Science.gov (United States)

    Fletcher, Robert J; Revell, Andre; Reichert, Brian E; Kitchens, Wiley M; Dixon, Jeremy D; Austin, James D

    2013-01-01

    For nearly a century, biologists have emphasized the profound importance of spatial scale for ecology, evolution and conservation. Nonetheless, objectively identifying critical scales has proven incredibly challenging. Here we extend new techniques from physics and social sciences that estimate modularity on networks to identify critical scales for movement and gene flow in animals. Using four species that vary widely in dispersal ability and include both mark-recapture and population genetic data, we identify significant modularity in three species, two of which cannot be explained by geographic distance alone. Importantly, the inclusion of modularity in connectivity and population viability assessments alters conclusions regarding patch importance to connectivity and suggests higher metapopulation viability than when ignoring this hidden spatial scale. We argue that network modularity reveals critical meso-scales that are probably common in populations, providing a powerful means of identifying fundamental scales for biology and for conservation strategies aimed at recovering imperilled species.

  16. A SLM2 Feedback Pathway Controls Cortical Network Activity and Mouse Behavior

    Directory of Open Access Journals (Sweden)

    Ingrid Ehrmann

    2016-12-01

    Full Text Available The brain is made up of trillions of synaptic connections that together form neural networks needed for normal brain function and behavior. SLM2 is a member of a conserved family of RNA binding proteins, including Sam68 and SLM1, that control splicing of Neurexin1-3 pre-mRNAs. Whether SLM2 affects neural network activity is unknown. Here, we find that SLM2 levels are maintained by a homeostatic feedback control pathway that predates the divergence of SLM2 and Sam68. SLM2 also controls the splicing of Tomosyn2, LysoPLD/ATX, Dgkb, Kif21a, and Cask, each of which are important for synapse function. Cortical neural network activity dependent on synaptic connections between SLM2-expressing-pyramidal neurons and interneurons is decreased in Slm2-null mice. Additionally, these mice are anxious and have a decreased ability to recognize novel objects. Our data reveal a pathway of SLM2 homeostatic auto-regulation controlling brain network activity and behavior.

  17. Inference of biological pathway from gene expression profiles by time delay boolean networks.

    Directory of Open Access Journals (Sweden)

    Tung-Hung Chueh

    Full Text Available One great challenge of genomic research is to efficiently and accurately identify complex gene regulatory networks. The development of high-throughput technologies provides numerous experimental data such as DNA sequences, protein sequence, and RNA expression profiles makes it possible to study interactions and regulations among genes or other substance in an organism. However, it is crucial to make inference of genetic regulatory networks from gene expression profiles and protein interaction data for systems biology. This study will develop a new approach to reconstruct time delay boolean networks as a tool for exploring biological pathways. In the inference strategy, we will compare all pairs of input genes in those basic relationships by their corresponding p-scores for every output gene. Then, we will combine those consistent relationships to reveal the most probable relationship and reconstruct the genetic network. Specifically, we will prove that O(log n state transition pairs are sufficient and necessary to reconstruct the time delay boolean network of n nodes with high accuracy if the number of input genes to each gene is bounded. We also have implemented this method on simulated and empirical yeast gene expression data sets. The test results show that this proposed method is extensible for realistic networks.

  18. Effective identification of conserved pathways in biological networks using hidden Markov models.

    Directory of Open Access Journals (Sweden)

    Xiaoning Qian

    2009-12-01

    Full Text Available The advent of various high-throughput experimental techniques for measuring molecular interactions has enabled the systematic study of biological interactions on a global scale. Since biological processes are carried out by elaborate collaborations of numerous molecules that give rise to a complex network of molecular interactions, comparative analysis of these biological networks can bring important insights into the functional organization and regulatory mechanisms of biological systems.In this paper, we present an effective framework for identifying common interaction patterns in the biological networks of different organisms based on hidden Markov models (HMMs. Given two or more networks, our method efficiently finds the top matching paths in the respective networks, where the matching paths may contain a flexible number of consecutive insertions and deletions.Based on several protein-protein interaction (PPI networks obtained from the Database of Interacting Proteins (DIP and other public databases, we demonstrate that our method is able to detect biologically significant pathways that are conserved across different organisms. Our algorithm has a polynomial complexity that grows linearly with the size of the aligned paths. This enables the search for very long paths with more than 10 nodes within a few minutes on a desktop computer. The software program that implements this algorithm is available upon request from the authors.

  19. The origin of the criticality in meme popularity distribution on complex networks

    Science.gov (United States)

    Kim, Yup; Park, Seokjong; Yook, Soon-Hyung

    2016-03-01

    Previous studies showed that the meme popularity distribution is described by a heavy-tailed distribution or a power-law, which is a characteristic feature of the criticality. Here, we study the origin of the criticality on non-growing and growing networks based on the competition induced criticality model. From the direct Mote Carlo simulations and the exact mapping into the position dependent biased random walk (PDBRW), we find that the meme popularity distribution satisfies a very robust power- law with exponent α = 3/2 if there is an innovation process. On the other hand, if there is no innovation, then we find that the meme popularity distribution is bounded and highly skewed for early transient time periods, while it satisfies a power-law with exponent α ≠ 3/2 for intermediate time periods. The exact mapping into PDBRW clearly shows that the balance between the creation of new memes by the innovation process and the extinction of old memes is the key factor for the criticality. We confirm that the balance for the criticality sustains for relatively small innovation rate. Therefore, the innovation processes with significantly influential memes should be the simple and fundamental processes which cause the critical distribution of the meme popularity in real social networks.

  20. Towards a Bio-inspired Security Framework for Mission-Critical Wireless Sensor Networks

    Science.gov (United States)

    Ren, Wei; Song, Jun; Ma, Zhao; Huang, Shiyong

    Mission-critical wireless sensor networks (WSNs) have been found in numerous promising applications in civil and military fields. However, the functionality of WSNs extensively relies on its security capability for detecting and defending sophisticated adversaries, such as Sybil, worm hole and mobile adversaries. In this paper, we propose a bio-inspired security framework to provide intelligence-enabled security mechanisms. This scheme is composed of a middleware, multiple agents and mobile agents. The agents monitor the network packets, host activities, make decisions and launch corresponding responses. Middleware performs an infrastructure for the communication between various agents and corresponding mobility. Certain cognitive models and intelligent algorithms such as Layered Reference Model of Brain and Self-Organizing Neural Network with Competitive Learning are explored in the context of sensor networks that have resource constraints. The security framework and implementation are also described in details.

  1. DMPD: Toll like receptors and autoimmunity: a critical appraisal. [Dynamic Macrophage Pathway CSML Database

    Lifescience Database Archive (English)

    Full Text Available 17959357 Toll like receptors and autoimmunity: a critical appraisal. Papadimitraki ...ml) Show Toll like receptors and autoimmunity: a critical appraisal. PubmedID 17959357 Title Toll like receptors and autoimmuni

  2. Critical Nodes Identification of Power Systems Based on Controllability of Complex Networks

    Directory of Open Access Journals (Sweden)

    Yu-Shuai Li

    2015-09-01

    Full Text Available This paper proposes a new method for assessing the vulnerability of power systems based on the controllability theories of complex networks. A novel controllability index is established, taking into consideration the full controllability of the power systems, for identifying critical nodes. The network controllability model is used to calculate the minimum number of driver nodes (ND, which can solve the computable problems of the controllability of power systems. The proposed approach firstly applies the network controllability theories to research the power systems' vulnerability, which can not only effectively reveal the important nodes but also maintain full control of the power systems. Meanwhile, the method can also overcome the limitation of the hypothesis that the weight of each link or transmission line must be known compared with the existing literature. In addition, the power system is considered as a directed network and the power system model is also redefined. The proposed methodology is then used to identify critical nodes of the IEEE 118 and 300 bus system. The results show that the failure of the critical nodes can clearly increase ND and lead a significant driver node shift. Thus, the rationality and validity are verified.

  3. Determining Associations between Human Diseases and non-coding RNAs with Critical Roles in Network Control

    Science.gov (United States)

    Kagami, Haruna; Akutsu, Tatsuya; Maegawa, Shingo; Hosokawa, Hiroshi; Nacher, Jose C.

    2015-10-01

    Deciphering the association between life molecules and human diseases is currently an important task in systems biology. Research over the past decade has unveiled that the human genome is almost entirely transcribed, producing a vast number of non-protein-coding RNAs (ncRNAs) with potential regulatory functions. More recent findings suggest that many diseases may not be exclusively linked to mutations in protein-coding genes. The combination of these arguments poses the question of whether ncRNAs that play a critical role in network control are also enriched with disease-associated ncRNAs. To address this question, we mapped the available annotated information of more than 350 human disorders to the largest collection of human ncRNA-protein interactions, which define a bipartite network of almost 93,000 interactions. Using a novel algorithmic-based controllability framework applied to the constructed bipartite network, we found that ncRNAs engaged in critical network control are also statistically linked to human disorders (P-value of P = 9.8 × 10-109). Taken together, these findings suggest that the addition of those genes that encode optimized subsets of ncRNAs engaged in critical control within the pool of candidate genes could aid disease gene prioritization studies.

  4. Social networks and secondary health conditions: the critical secondary team for individuals with spinal cord injury.

    Science.gov (United States)

    Guilcher, Sara J T; Casciaro, Tiziana; Lemieux-Charles, Louise; Craven, Catharine; McColl, Mary Ann; Jaglal, Susan B

    2012-09-01

    To describe the structure of informal networks for individuals with spinal cord injury (SCI) living in the community, to understand the quality of relationship of informal networks, and to understand the role of informal networks in the prevention and management of secondary health conditions (SHCs). Mixed-method descriptive study. Ontario, Canada Participants: Community-dwelling adults with an SCI living in Ontario Interventions/methods: The Arizona Social Support Interview Survey was used to measure social networks. Participants were asked the following open-ended questions: (1) What have been your experiences with your health care in the community? (2) What have been your experiences with care related to prevention and/or management of SHCs?, (3)What has been the role of your informal social networks (friends/family) related to SHCs? Fourteen key informant interviews were conducted (6 men, 8 women). The overall median for available informal networks was 11.0 persons (range 3-19). The informal network engaged in the following roles: (1) advice/validating concerns; (2) knowledge brokers; (3) advocacy; (4) preventing SHCs; (5) assisting with finances; and (6) managing SHCs. Participants described their informal networks as a "secondary team"; a critical and essential force in dealing with SHCs. While networks are smaller for persons with SCI compared with the general population, these ties seems to be strong, which is essential when the roles involve a level of trust, certainty, tacit knowledge, and flexibility. These informal networks serve as essential key players in filling the gaps that exist within the formal health care system.

  5. Targeting the human cancer pathway protein interaction network by structural genomics.

    Science.gov (United States)

    Huang, Yuanpeng Janet; Hang, Dehua; Lu, Long Jason; Tong, Liang; Gerstein, Mark B; Montelione, Gaetano T

    2008-10-01

    Structural genomics provides an important approach for characterizing and understanding systems biology. As a step toward better integrating protein three-dimensional (3D) structural information in cancer systems biology, we have constructed a Human Cancer Pathway Protein Interaction Network (HCPIN) by analysis of several classical cancer-associated signaling pathways and their physical protein-protein interactions. Many well known cancer-associated proteins play central roles as "hubs" or "bottlenecks" in the HCPIN. At least half of HCPIN proteins are either directly associated with or interact with multiple signaling pathways. Although some 45% of residues in these proteins are in sequence segments that meet criteria sufficient for approximate homology modeling (Basic Local Alignment Search Tool (BLAST) E-value structurally covered using high accuracy homology modeling criteria (i.e. BLAST E-value structures. The HCPIN Website provides a comprehensive description of this biomedically important multipathway network together with experimental and homology models of HCPIN proteins useful for cancer biology research. To complement and enrich cancer systems biology, the Northeast Structural Genomics Consortium is targeting >1000 human proteins and protein domains from the HCPIN for sample production and 3D structure determination. The long range goal of this effort is to provide a comprehensive 3D structure-function database for human cancer-associated proteins and protein complexes in the context of their interaction networks. The network-based target selection (BioNet) approach described here is an example of a general strategy for targeting co-functioning proteins by structural genomics projects.

  6. Targeting the Human Cancer Pathway Protein Interaction Network by Structural Genomics*

    Science.gov (United States)

    Huang, Yuanpeng Janet; Hang, Dehua; Lu, Long Jason; Tong, Liang; Gerstein, Mark B.; Montelione, Gaetano T.

    2008-01-01

    Structural genomics provides an important approach for characterizing and understanding systems biology. As a step toward better integrating protein three-dimensional (3D) structural information in cancer systems biology, we have constructed a Human Cancer Pathway Protein Interaction Network (HCPIN) by analysis of several classical cancer-associated signaling pathways and their physical protein-protein interactions. Many well known cancer-associated proteins play central roles as “hubs” or “bottlenecks” in the HCPIN. At least half of HCPIN proteins are either directly associated with or interact with multiple signaling pathways. Although some 45% of residues in these proteins are in sequence segments that meet criteria sufficient for approximate homology modeling (Basic Local Alignment Search Tool (BLAST) E-value structurally covered using high accuracy homology modeling criteria (i.e. BLAST E-value structures. The HCPIN Website provides a comprehensive description of this biomedically important multipathway network together with experimental and homology models of HCPIN proteins useful for cancer biology research. To complement and enrich cancer systems biology, the Northeast Structural Genomics Consortium is targeting >1000 human proteins and protein domains from the HCPIN for sample production and 3D structure determination. The long range goal of this effort is to provide a comprehensive 3D structure-function database for human cancer-associated proteins and protein complexes in the context of their interaction networks. The network-based target selection (BioNet) approach described here is an example of a general strategy for targeting co-functioning proteins by structural genomics projects. PMID:18487680

  7. Efficient identification of critical residues based only on protein structure by network analysis.

    Directory of Open Access Journals (Sweden)

    Michael P Cusack

    Full Text Available Despite the increasing number of published protein structures, and the fact that each protein's function relies on its three-dimensional structure, there is limited access to automatic programs used for the identification of critical residues from the protein structure, compared with those based on protein sequence. Here we present a new algorithm based on network analysis applied exclusively on protein structures to identify critical residues. Our results show that this method identifies critical residues for protein function with high reliability and improves automatic sequence-based approaches and previous network-based approaches. The reliability of the method depends on the conformational diversity screened for the protein of interest. We have designed a web site to give access to this software at http://bis.ifc.unam.mx/jamming/. In summary, a new method is presented that relates critical residues for protein function with the most traversed residues in networks derived from protein structures. A unique feature of the method is the inclusion of the conformational diversity of proteins in the prediction, thus reproducing a basic feature of the structure/function relationship of proteins.

  8. Identification of genes and signaling pathways associated with diabetic neuropathy using a weighted correlation network analysis

    Science.gov (United States)

    Li, Ya; Ma, Weiguo; Xie, Chuanqing; Zhang, Min; Yin, Xiaohong; Wang, Fenfen; Xu, Jie; Shi, Bingyin

    2016-01-01

    Abstract Background: The molecular mechanisms behind diabetic neuropathy remains to be investigated. Methods: This is a secondary study on microarray dataset (GSE24290) downloaded from Gene Expression Omnibus (GEO) at the National Center for Biotechnology Information (NCBI), which included 18 nerve tissue samples of progressing diabetic neuropathy (fibers loss ≥500 fibers/mm2) and 17 nerve tissue samples of nonprogressing diabetic neuropathy (fibers loss ≤100 fibers/mm2). Differentially expressed genes (DEGs) were screened between progressing and nonprogressing diabetic neuropathy. With the DEGs obtained, a weighted gene coexpression network analysis was conducted to identify gene clusters associated with diabetic neuropathy. Diabetes-related microRNAs (miRNAs) and their target genes were predicted and mapped to the genes in the gene clusters identified. Consequently, a miRNA–gene network was constructed, for which gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis was performed. Potential drugs for treatment of diabetic neuropathy were also predicted. Results: Total 370 upregulated and 379 downregulated DEGs were screened between nonprogressing and progressing diabetic neuropathy. Has-miR-377, has-miR-216a, and has-miR-217 were associated with diabetes. Inflammation was the most significant GO term. The peroxisome proliferator-activated receptor (PPAR) pathway and the adenosine monophosphate (AMP)-activated protein kinase (AMPK) signaling pathway were significantly KEGG pathways significantly enriched with PPAR gamma (PPARG), stearoyl-CoA desaturase (SCD), cluster of differentiation 36 (CD36), and phosphoenolpyruvate carboxykinase 1 (PCK1). Conclusion: The study suggests that PPARG, SCD, CD36, PCK1, AMPK pathway, and PPAR pathway may be involved in progression of diabetic neuropathy. PMID:27893688

  9. Optimizing mission critical data dissemination in massive IoT networks

    KAUST Repository

    Farooq, Muhammad Junaid

    2017-06-29

    Mission critical data dissemination in massive Internet of things (IoT) networks imposes constraints on the message transfer delay between devices. Due to low power and communication range of IoT devices, data is foreseen to be relayed over multiple device-to-device (D2D) links before reaching the destination. The coexistence of a massive number of IoT devices poses a challenge in maximizing the successful transmission capacity of the overall network alongside reducing the multi-hop transmission delay in order to support mission critical applications. There is a delicate interplay between the carrier sensing threshold of the contention based medium access protocol and the choice of packet forwarding strategy selected at each hop by the devices. The fundamental problem in optimizing the performance of such networks is to balance the tradeoff between conflicting performance objectives such as the spatial frequency reuse, transmission quality, and packet progress towards the destination. In this paper, we use a stochastic geometry approach to quantify the performance of multi-hop massive IoT networks in terms of the spatial frequency reuse and the transmission quality under different packet forwarding schemes. We also develop a comprehensive performance metric that can be used to optimize the system to achieve the best performance. The results can be used to select the best forwarding scheme and tune the carrier sensing threshold to optimize the performance of the network according to the delay constraints and transmission quality requirements.

  10. Two critical brain networks for generation and combination of remote associations.

    Science.gov (United States)

    Bendetowicz, David; Urbanski, Marika; Garcin, Béatrice; Foulon, Chris; Levy, Richard; Bréchemier, Marie-Laure; Rosso, Charlotte; Thiebaut de Schotten, Michel; Volle, Emmanuelle

    2018-01-01

    Recent functional imaging findings in humans indicate that creativity relies on spontaneous and controlled processes, possibly supported by the default mode and the fronto-parietal control networks, respectively. Here, we examined the ability to generate and combine remote semantic associations, in relation to creative abilities, in patients with focal frontal lesions. Voxel-based lesion-deficit mapping, disconnection-deficit mapping and network-based lesion-deficit approaches revealed critical prefrontal nodes and connections for distinct mechanisms related to creative cognition. Damage to the right medial prefrontal region, or its potential disrupting effect on the default mode network, affected the ability to generate remote ideas, likely by altering the organization of semantic associations. Damage to the left rostrolateral prefrontal region and its connections, or its potential disrupting effect on the left fronto-parietal control network, spared the ability to generate remote ideas but impaired the ability to appropriately combine remote ideas. Hence, the current findings suggest that damage to specific nodes within the default mode and fronto-parietal control networks led to a critical loss of verbal creative abilities by altering distinct cognitive mechanisms. © The Author (2017). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  11. Brain Organization into Resting State Networks Emerges at Criticality on a Model of the Human Connectome

    Science.gov (United States)

    Haimovici, Ariel; Tagliazucchi, Enzo; Balenzuela, Pablo; Chialvo, Dante R.

    2013-04-01

    The relation between large-scale brain structure and function is an outstanding open problem in neuroscience. We approach this problem by studying the dynamical regime under which realistic spatiotemporal patterns of brain activity emerge from the empirically derived network of human brain neuroanatomical connections. The results show that critical dynamics unfolding on the structural connectivity of the human brain allow the recovery of many key experimental findings obtained from functional magnetic resonance imaging, such as divergence of the correlation length, the anomalous scaling of correlation fluctuations, and the emergence of large-scale resting state networks.

  12. Adaptive Critic Neural Network-Based Terminal Area Energy Management and Approach and Landing Guidance

    Science.gov (United States)

    Grantham, Katie

    2003-01-01

    Reusable Launch Vehicles (RLVs) have different mission requirements than the Space Shuttle, which is used for benchmark guidance design. Therefore, alternative Terminal Area Energy Management (TAEM) and Approach and Landing (A/L) Guidance schemes can be examined in the interest of cost reduction. A neural network based solution for a finite horizon trajectory optimization problem is presented in this paper. In this approach the optimal trajectory of the vehicle is produced by adaptive critic based neural networks, which were trained off-line to maintain a gradual glideslope.

  13. Drug use Discrimination Predicts Formation of High-Risk Social Networks: Examining Social Pathways of Discrimination.

    Science.gov (United States)

    Crawford, Natalie D; Ford, Chandra; Rudolph, Abby; Kim, BoRin; Lewis, Crystal M

    2017-09-01

    Experiences of discrimination, or social marginalization and ostracism, may lead to the formation of social networks characterized by inequality. For example, those who experience discrimination may be more likely to develop drug use and sexual partnerships with others who are at increased risk for HIV compared to those without experiences of discrimination. This is critical as engaging in risk behaviors with others who are more likely to be HIV positive can increase one's risk of HIV. We used log-binomial regression models to examine the relationship between drug use, racial and incarceration discrimination with changes in the composition of one's risk network among 502 persons who use drugs. We examined both absolute and proportional changes with respect to sex partners, drug use partners, and injecting partners, after accounting for individual risk behaviors. At baseline, participants were predominately male (70%), black or Latino (91%), un-married (85%), and used crack (64%). Among those followed-up (67%), having experienced discrimination due to drug use was significantly related to increases in the absolute number of sex networks and drug networks over time. No types of discrimination were related to changes in the proportion of high-risk network members. Discrimination may increase one's risk of HIV acquisition by leading them to preferentially form risk relationships with higher-risk individuals, thereby perpetuating racial and ethnic inequities in HIV. Future social network studies and behavioral interventions should consider whether social discrimination plays a role in HIV transmission.

  14. Methodologies for the modeling and simulation of biochemical networks, illustrated for signal transduction pathways: a primer.

    Science.gov (United States)

    ElKalaawy, Nesma; Wassal, Amr

    2015-03-01

    Biochemical networks depict the chemical interactions that take place among elements of living cells. They aim to elucidate how cellular behavior and functional properties of the cell emerge from the relationships between its components, i.e. molecules. Biochemical networks are largely characterized by dynamic behavior, and exhibit high degrees of complexity. Hence, the interest in such networks is growing and they have been the target of several recent modeling efforts. Signal transduction pathways (STPs) constitute a class of biochemical networks that receive, process, and respond to stimuli from the environment, as well as stimuli that are internal to the organism. An STP consists of a chain of intracellular signaling processes that ultimately result in generating different cellular responses. This primer presents the methodologies used for the modeling and simulation of biochemical networks, illustrated for STPs. These methodologies range from qualitative to quantitative, and include structural as well as dynamic analysis techniques. We describe the different methodologies, outline their underlying assumptions, and provide an assessment of their advantages and disadvantages. Moreover, publicly and/or commercially available implementations of these methodologies are listed as appropriate. In particular, this primer aims to provide a clear introduction and comprehensive coverage of biochemical modeling and simulation methodologies for the non-expert, with specific focus on relevant literature of STPs. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  15. Distinct configurations of protein complexes and biochemical pathways revealed by epistatic interaction network motifs

    LENUS (Irish Health Repository)

    Casey, Fergal

    2011-08-22

    Abstract Background Gene and protein interactions are commonly represented as networks, with the genes or proteins comprising the nodes and the relationship between them as edges. Motifs, or small local configurations of edges and nodes that arise repeatedly, can be used to simplify the interpretation of networks. Results We examined triplet motifs in a network of quantitative epistatic genetic relationships, and found a non-random distribution of particular motif classes. Individual motif classes were found to be associated with different functional properties, suggestive of an underlying biological significance. These associations were apparent not only for motif classes, but for individual positions within the motifs. As expected, NNN (all negative) motifs were strongly associated with previously reported genetic (i.e. synthetic lethal) interactions, while PPP (all positive) motifs were associated with protein complexes. The two other motif classes (NNP: a positive interaction spanned by two negative interactions, and NPP: a negative spanned by two positives) showed very distinct functional associations, with physical interactions dominating for the former but alternative enrichments, typical of biochemical pathways, dominating for the latter. Conclusion We present a model showing how NNP motifs can be used to recognize supportive relationships between protein complexes, while NPP motifs often identify opposing or regulatory behaviour between a gene and an associated pathway. The ability to use motifs to point toward underlying biological organizational themes is likely to be increasingly important as more extensive epistasis mapping projects in higher organisms begin.

  16. Quantifying nitrous oxide production pathways in wastewater treatment systems using isotope technology - A critical review.

    Science.gov (United States)

    Duan, Haoran; Ye, Liu; Erler, Dirk; Ni, Bing-Jie; Yuan, Zhiguo

    2017-10-01

    Nitrous oxide (N2O) is an important greenhouse gas and an ozone-depleting substance which can be emitted from wastewater treatment systems (WWTS) causing significant environmental impacts. Understanding the N2O production pathways and their contribution to total emissions is the key to effective mitigation. Isotope technology is a promising method that has been applied to WWTS for quantifying the N2O production pathways. Within the scope of WWTS, this article reviews the current status of different isotope approaches, including both natural abundance and labelled isotope approaches, to N2O production pathways quantification. It identifies the limitations and potential problems with these approaches, as well as improvement opportunities. We conclude that, while the capabilities of isotope technology have been largely recognized, the quantification of N2O production pathways with isotope technology in WWTS require further improvement, particularly in relation to its accuracy and reliability. Copyright © 2017 Elsevier Ltd. All rights reserved.

  17. Unavailability of critical SCADA communication links interconnecting a power grid and a Telco network

    Energy Technology Data Exchange (ETDEWEB)

    Bobbio, A. [Dipartimento di Informatica, Universita del Piemonte Orientale, Viale Michel 11, 15121 Alessandria (Italy); Bonanni, G.; Ciancamerla, E. [ENEA - CRE Casaccia, Via Anguillarese 301, 00060 Roma (Italy); Clemente, R. [Telecom Italia Mobile, Via Isonzo112, 10141 Torino (Italy); Iacomini, A. [ACEA, Pl. Ostiense 2, 00154 Roma (Italy); Minichino, M., E-mail: minichino@casaccia.enea.i [ENEA - CRE Casaccia, Via Anguillarese 301, 00060 Roma (Italy); Scarlatti, A. [ACEA, Pl. Ostiense 2, 00154 Roma (Italy); Terruggia, R. [Dipartimento di Informatica, Universita del Piemonte Orientale, Viale Michel 11, 15121 Alessandria (Italy); Zendri, E. [ACEA, Pl. Ostiense 2, 00154 Roma (Italy)

    2010-12-15

    The availability of power supply to power grid customers depends upon the availability of services of supervision, control and data acquisition (SCADA) system, which constitutes the nervous system of a power grid. In turn, SCADA services depend on the availability of the interconnected networks supporting such services. We propose a service oriented stochastic modelling methodology to investigate the availability of large interconnected networks, based on the hierarchical application of different modelling formalisms to different parts of the networks. Interconnected networks are decomposed according to the specific services delivered until the failure and repair mechanisms of the decomposed elementary blocks can be identified. We represent each network by a convenient stochastic modelling formalism, able to capture the main technological issues and to cope with realistic assumptions about failure and recovery mechanisms. This procedure confines the application of the more intensive computational techniques to those subsystems that actually require it. The paper concentrates on an actual failure scenario, occurred in Rome in January 2004 that involved the outage of critical SCADA communication links, interconnecting a power grid and a Telco network.

  18. Optimal Information Representation and Criticality in an Adaptive Sensory Recurrent Neuronal Network.

    Directory of Open Access Journals (Sweden)

    Oren Shriki

    2016-02-01

    Full Text Available Recurrent connections play an important role in cortical function, yet their exact contribution to the network computation remains unknown. The principles guiding the long-term evolution of these connections are poorly understood as well. Therefore, gaining insight into their computational role and into the mechanism shaping their pattern would be of great importance. To that end, we studied the learning dynamics and emergent recurrent connectivity in a sensory network model based on a first-principle information theoretic approach. As a test case, we applied this framework to a model of a hypercolumn in the visual cortex and found that the evolved connections between orientation columns have a "Mexican hat" profile, consistent with empirical data and previous modeling work. Furthermore, we found that optimal information representation is achieved when the network operates near a critical point in its dynamics. Neuronal networks working near such a phase transition are most sensitive to their inputs and are thus optimal in terms of information representation. Nevertheless, a mild change in the pattern of interactions may cause such networks to undergo a transition into a different regime of behavior in which the network activity is dominated by its internal recurrent dynamics and does not reflect the objective input. We discuss several mechanisms by which the pattern of interactions can be driven into this supercritical regime and relate them to various neurological and neuropsychiatric phenomena.

  19. Pathway-based network analysis of myeloma tumors: monoclonal gammopathy of unknown significance, smoldering multiple myeloma, and multiple myeloma.

    Science.gov (United States)

    Dong, L; Chen, C Y; Ning, B; Xu, D L; Gao, J H; Wang, L L; Yan, S Y; Cheng, S

    2015-08-14

    Although many studies have been carried out on monoclonal gammopathy of unknown significances (MGUS), smoldering multiple myeloma (SMM), and multiple myeloma (MM), their classification and underlying pathogenesis are far from elucidated. To discover the relationships among MGUS, SMM, and MM at the transcriptome level, differentially expressed genes in MGUS, SMM, and MM were identified by the rank product method, and then co-expression networks were constructed by integrating the data. Finally, a pathway-network was constructed based on Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis, and the relationships between the pathways were identified. The results indicated that there were 55, 78, and 138 pathways involved in the myeloma tumor developmental stages of MGUS, SMM, and MM, respectively. The biological processes identified therein were found to have a close relationship with the immune system. Processes and pathways related to the abnormal activity of DNA and RNA were also present in SMM and MM. Six common pathways were found in the whole process of myeloma tumor development. Nine pathways were shown to participate in the progression of MGUS to SMM, and prostate cancer was the sole pathway that was involved only in MGUS and MM. Pathway-network analysis might provide a new indicator for the developmental stage diagnosis of myeloma tumors.

  20. Cooperative FRET: Comparison between Interacting and Independent FRET Pathways in a Light Harvesting Network

    Science.gov (United States)

    Cunningham, Paul; Spillmann, Christopher; Buckhout-White, Susan; Melinger, Joseph; Ancona, Mario; Goldman, Ellen; Medintz, Igor

    Light harvesting antennae use Förster Resonance Energy Transfer (FRET) between dyes to funnel energy to a reaction center. Inhomogenities in dipole orientation in distributions of static dyes reduce FRET efficiencies, via the large multiplicity of unfavorable orientations. Multiple FRET pathways may compensate for inhomogeneities. We examine multi-step FRET in a series of dye-labeled DNA rail scaffolds where the degree of interaction between two parallel rails was adjusted via their separation. We find that interacting pathways outperform simply redundant independent pathways. For one FRET step, addition of a second donor yields an unexpected increase in FRET efficiency. Monte-Carlo simulations show that suppression of inefficient FRET pathways causes this increase. As the number of donors increases, the FRET efficiency of a static distribution approaches the dynamic limit, where dyes are free to reorient. This suppression is optimal when the rails are close enough to allow fast homo-FRET between them. However, at close separations H-like aggregate formation can lead to energy sinks. These are important considerations when designing light harvesting networks and may aid in the understanding of incoherent hopping transport in other systems.

  1. Linking Biosynthetic Gene Clusters to their Metabolites via Pathway-Targeted Molecular Networking

    Science.gov (United States)

    Trautman, Eric P.; Crawford, Jason M.

    2016-01-01

    The connection of microbial biosynthetic gene clusters to the small molecule metabolites they encode is central to the discovery and characterization of new metabolic pathways with ecological and pharmacological potential. With increasing microbial genome sequence information being deposited into publicly available databases, it is clear that microbes have the coding capacity for many more biologically active small molecules than previously realized. Of increasing interest are the small molecules encoded by the human microbiome, as these metabolites likely mediate a variety of currently uncharacterized human-microbe interactions that influence health and disease. In this mini-review, we describe the ongoing biosynthetic, structural, and functional characterizations of the genotoxic colibactin pathway in gut bacteria as a thematic example of linking biosynthetic gene clusters to their metabolites. We also highlight other natural products that are produced through analogous biosynthetic logic and comment on some current disconnects between bioinformatics predictions and experimental structural characterizations. Lastly, we describe the use of pathway-targeted molecular networking as a tool to characterize secondary metabolic pathways within complex metabolomes and to aid in downstream metabolite structural elucidation efforts. PMID:26456470

  2. Application of R to investigate common gene regulatory network pathway among bipolar disorder and associate diseases

    Directory of Open Access Journals (Sweden)

    Nahida Habib

    2016-12-01

    Full Text Available Depression, Major Depression or mental disorder creates severe diseases. Mental illness such as Unipolar Major Depression, Bipolar Disorder, Dysthymia, Schizophrenia, Cardiovascular Diseases (Hypertension, Coronary Heart Disease, Stroke etc., are known as Major Depression. Several studies have revealed the possibilities about the association among Bipolar Disorder, Schizophrenia, Coronary Heart Diseases and Stroke with each other. The current study aimed to investigate the relationships between genetic variants in the above four diseases and to create a common pathway or PPI network. The associated genes of each disease are collected from different gene database with verification using R. After performing some preprocessing, mining and operations using R on collected genes, seven (7 common associated genes are discovered on selected four diseases (SZ, BD, CHD and Stroke. In each of the iteration, the numbers of collected genes are reduced up to 51%, 36%, 10%, 2% and finally less than 1% respectively. Moreover, common pathway on selected diseases has been investigated in this research.

  3. Phase transitions and self-organized criticality in networks of stochastic spiking neurons

    Science.gov (United States)

    Brochini, Ludmila; de Andrade Costa, Ariadne; Abadi, Miguel; Roque, Antônio C.; Stolfi, Jorge; Kinouchi, Osame

    2016-11-01

    Phase transitions and critical behavior are crucial issues both in theoretical and experimental neuroscience. We report analytic and computational results about phase transitions and self-organized criticality (SOC) in networks with general stochastic neurons. The stochastic neuron has a firing probability given by a smooth monotonic function Φ(V) of the membrane potential V, rather than a sharp firing threshold. We find that such networks can operate in several dynamic regimes (phases) depending on the average synaptic weight and the shape of the firing function Φ. In particular, we encounter both continuous and discontinuous phase transitions to absorbing states. At the continuous transition critical boundary, neuronal avalanches occur whose distributions of size and duration are given by power laws, as observed in biological neural networks. We also propose and test a new mechanism to produce SOC: the use of dynamic neuronal gains - a form of short-term plasticity probably located at the axon initial segment (AIS) - instead of depressing synapses at the dendrites (as previously studied in the literature). The new self-organization mechanism produces a slightly supercritical state, that we called SOSC, in accord to some intuitions of Alan Turing.

  4. A glutamatergic network mediates lithium response in bipolar disorder as defined by epigenome pathway analysis.

    Science.gov (United States)

    Higgins, Gerald A; Allyn-Feuer, Ari; Barbour, Edward; Athey, Brian D

    2015-01-01

    A regulatory network in the human brain mediating lithium response in bipolar patients was revealed by analysis of functional SNPs from genome-wide association studies (GWAS) and published gene association studies, followed by epigenome mapping. An initial set of 23,312 SNPs in linkage disequilibrium with lead SNPs, and sub-threshold GWAS SNPs rescued by pathway analysis, were studied in the same populations. These were assessed using our workflow and annotation by the epigenome roadmap consortium. Twenty-seven percent of 802 SNPs that were associated with lithium response (13 published studies gene association studies and two GWAS) were shared in common with 1281 SNPs from 18 GWAS examining psychiatric disorders and adverse events associated with lithium treatment. Nineteen SNPs were annotated as active regulatory elements such as enhancers and promoters in a tissue-specific manner. They were located within noncoding regions of ten genes: ANK3, ARNTL, CACNA1C, CACNG2, CDKN1A, CREB1, GRIA2, GSK3B, NR1D1 and SLC1A2. Following gene set enrichment and pathway analysis, these genes were found to be significantly associated (p = 10(-27); Fisher exact test) with an AMPA2 glutamate receptor network in human brain. Our workflow results showed concordance with annotation of regulatory elements from the epigenome roadmap. Analysis of cognate mRNA and enhancer RNA exhibited patterns consistent with an integrated pathway in human brain. This pharmacoepigenomic regulatory pathway is located in the same brain regions that exhibit tissue volume loss in bipolar disorder. Although in silico analysis requires biological validation, the approach provides value for identification of candidate variants that may be used in pharmacogenomic testing to identify bipolar patients likely to respond to lithium.

  5. Critical Action as a Pathway to Social Mobility among Marginalized Youth

    Science.gov (United States)

    Rapa, Luke J.; Diemer, Matthew A.; Bañales, Josefina

    2018-01-01

    Marginalized youth's development occurs in contexts rife with racialized, gendered, and socioeconomic social identity threats and barriers to social mobility. An emergent line of inquiry suggests critical action--a component of critical consciousness, defined as engaging in individual or collective social action to produce social change--may…

  6. Evaluating protein-protein interaction (PPI) networks for diseases pathway, target discovery, and drug-design using 'in silico pharmacology'.

    Science.gov (United States)

    Chakraborty, Chiranjib; Doss C, George Priya; Chen, Luonan; Zhu, Hailong

    2014-01-01

    In silico pharmacology is a promising field in the current state-of drug discovery. This area exploits "protein-protein Interaction (PPI) network analysis for drug discovery using the drug "target class". To document the current status, we have discussed in this article how this an integrated system of PPI networks contribute to understand the disease pathways, present state-of-the-art drug target discovery and drug discovery process. This review article enhances our knowledge on conventional drug discovery and current drug discovery using in silico techniques, best "target class", universal architecture of PPI networks, the present scenario of disease pathways and protein-protein interaction networks as well as the method to comprehend the PPI networks. Taken all together, ultimately a snapshot has been discussed to be familiar with how PPI network architecture can used to validate a drug target. At the conclusion, we have illustrated the future directions of PPI in target discovery and drug-design.

  7. Heading in the right direction: thermodynamics-based network analysis and pathway engineering.

    Science.gov (United States)

    Ataman, Meric; Hatzimanikatis, Vassily

    2015-12-01

    Thermodynamics-based network analysis through the introduction of thermodynamic constraints in metabolic models allows a deeper analysis of metabolism and guides pathway engineering. The number and the areas of applications of thermodynamics-based network analysis methods have been increasing in the last ten years. We review recent applications of these methods and we identify the areas that such analysis can contribute significantly, and the needs for future developments. We find that organisms with multiple compartments and extremophiles present challenges for modeling and thermodynamics-based flux analysis. The evolution of current and new methods must also address the issues of the multiple alternatives in flux directionalities and the uncertainties and partial information from analytical methods. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

  8. Correlations induced by depressing synapses in critically self-organized networks with quenched dynamics

    Science.gov (United States)

    Campos, João Guilherme Ferreira; Costa, Ariadne de Andrade; Copelli, Mauro; Kinouchi, Osame

    2017-04-01

    In a recent work, mean-field analysis and computer simulations were employed to analyze critical self-organization in networks of excitable cellular automata where randomly chosen synapses in the network were depressed after each spike (the so-called annealed dynamics). Calculations agree with simulations of the annealed version, showing that the nominal branching ratio σ converges to unity in the thermodynamic limit, as expected of a self-organized critical system. However, the question remains whether the same results apply to the biological case where only the synapses of firing neurons are depressed (the so-called quenched dynamics). We show that simulations of the quenched model yield significant deviations from σ =1 due to spatial correlations. However, the model is shown to be critical, as the largest eigenvalue of the synaptic matrix approaches unity in the thermodynamic limit, that is, λc=1 . We also study the finite size effects near the critical state as a function of the parameters of the synaptic dynamics.

  9. Adaptive critic autopilot design of bank-to-turn missiles using fuzzy basis function networks.

    Science.gov (United States)

    Lin, Chuan-Kai

    2005-04-01

    A new adaptive critic autopilot design for bank-to-turn missiles is presented. In this paper, the architecture of adaptive critic learning scheme contains a fuzzy-basis-function-network based associative search element (ASE), which is employed to approximate nonlinear and complex functions of bank-to-turn missiles, and an adaptive critic element (ACE) generating the reinforcement signal to tune the associative search element. In the design of the adaptive critic autopilot, the control law receives signals from a fixed gain controller, an ASE and an adaptive robust element, which can eliminate approximation errors and disturbances. Traditional adaptive critic reinforcement learning is the problem faced by an agent that must learn behavior through trial-and-error interactions with a dynamic environment, however, the proposed tuning algorithm can significantly shorten the learning time by online tuning all parameters of fuzzy basis functions and weights of ASE and ACE. Moreover, the weight updating law derived from the Lyapunov stability theory is capable of guaranteeing both tracking performance and stability. Computer simulation results confirm the effectiveness of the proposed adaptive critic autopilot.

  10. Digital poetry and critical discourse: a network of self-references?

    Directory of Open Access Journals (Sweden)

    Seiça, Álvaro

    2016-03-01

    Full Text Available This article emerges from macroanalysis of several works of critical writing in the field of digital poetry, which have been documented in the ELMCIP Knowledge Base. The problems addressed in this context are the self-referentiality exhibited by authors who are both practitioners and theoreticians, and the need for a wider selection of digital poems in critical discourse. The dataset consists of monographs and Ph.D. dissertations on digital poetry (1995-2015, which have been exported into visualization software. Macro and network analyses enable new debate concerning the outlined problems and new findings. My findings suggest that criticism in this domain is chiefly endogenous and that a limited number of poems is being canonized. Therefore, a meta-discourse perspective can pave the way for an external view of the field, concerning its epistemology and evolution. The dataset is available online for download and can be tested and reconsidered by other researchers.

  11. Crossing Educational Boundaries: Text, Technology, and Dialogue as a Critical Pathway

    Science.gov (United States)

    Abnet, LaNae; Nichols, Joe D.; Moss, Glenda

    2008-01-01

    Can the perceived boundary between professor and student be crossed? Can technology be used as a pathway to cross that boundary? These questions were answered as a result of a project initiated to meet the requirements in creating an honors option for an undergraduate educational psychology course. In constructing the course requirements, the…

  12. Proceedings of the International Symposium on Topological Aspects of Critical Systems and Networks

    Science.gov (United States)

    Yakubo, Kousuke; Amitsuka, Hiroshi; Ishikawa, Goo; Machino, Kazuo; Nakagaki, Toshiyuki; Tanda, Satoshi; Yamada, Hideto; Kichiji, Nozomi

    2007-07-01

    I. General properties of networks. Physics of network security / Y.-C. Lai, X. Wand and C. H. Lai. Multi-state interacting particle systems on scale-free networks / N. Masuda and N. Konno. Homotopy Reduction of Complex Networks 18 / Y. Hiraoka and T. Ichinomiya. Analysis of the Susceptible-Infected-Susceptible Model on Complex Network / T. Ichinomiya -- II. Complexity in social science. Innovation and Development in a Random Lattice / J. Lahtinen. Long-tailed distributions in biological systems: revisit to Lognormals / N. Kobayashi ... [et al.]. Two-class structure of income distribution in the USA:exponential bulk and power-law tail / V. M. Yakovenko and A. Christian Silva. Power Law distributions in two community currencies / N. Kichiji and M. Nishibe -- III. Patterns in biological objects. Stoichiometric network analysis of nonlinear phenomena in rection mechanism for TWC converters / M. Marek ... [et al.]. Collective movement and morphogenesis of epithelial cells / H. Haga and K. Kawabata. Indecisive behavior of amoeba crossing an environmental barrier / S. Takagi ... [et al.]. Effects of amount of food on path selection in the transport network of an amoeboid organism / T. Nakagaki ... [et al.]. Light scattering study in double network gels / M. Fukunaya ... [et al.].Blood flow velocity in the choroid in punctate inner choroidopathy and Vogt-Koyanagi-Harada disease; amd multifractal analysis of choroidal blood flow in age-related macular degeneration / K. Yoshida ... [et al.]. Topological analysis of placental arteries: correlation with neonatal growth / H. Yamada and K. Yakubo -- IV. Criticality in pure and applied physics. Droplets in Disordered Metallic Quantum Critical Systems / A. H. Castro Neto and B. A. Jones. Importance of static disorder and inhomogeneous cooperative dynamics in heavy-fermion metals / O. O. Bernal. Competition between spin glass and Antiferromagnetic phases in heavy fermion materials / S. Sullow. Emergent Phases via Fermi surface

  13. Pathway and network-based strategies to translate genetic discoveries into effective therapies.

    Science.gov (United States)

    Greene, Casey S; Voight, Benjamin F

    2016-10-01

    One way to design a drug is to attempt to phenocopy a genetic variant that is known to have the desired effect. In general, drugs that are supported by genetic associations progress further in the development pipeline. However, the number of associations that are candidates for development into drugs is limited because many associations are in non-coding regions or difficult to target genes. Approaches that overlay information from pathway databases or biological networks can expand the potential target list. In cases where the initial variant is not targetable or there is no variant with the desired effect, this may reveal new means to target a disease. In this review, we discuss recent examples in the domain of pathway and network-based drug repositioning from genetic associations. We highlight important caveats and challenges for the field, and we discuss opportunities for further development. © The Author (2016). Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  14. AID/APOBEC-network reconstruction identifies pathways associated with survival in ovarian cancer.

    Science.gov (United States)

    Svoboda, Martin; Meshcheryakova, Anastasia; Heinze, Georg; Jaritz, Markus; Pils, Dietmar; Castillo-Tong, Dan Cacsire; Hager, Gudrun; Thalhammer, Theresia; Jensen-Jarolim, Erika; Birner, Peter; Braicu, Ioana; Sehouli, Jalid; Lambrechts, Sandrina; Vergote, Ignace; Mahner, Sven; Zimmermann, Philip; Zeillinger, Robert; Mechtcheriakova, Diana

    2016-08-16

    Building up of pathway-/disease-relevant signatures provides a persuasive tool for understanding the functional relevance of gene alterations and gene network associations in multifactorial human diseases. Ovarian cancer is a highly complex heterogeneous malignancy in respect of tumor anatomy, tumor microenvironment including pro-/antitumor immunity and inflammation; still, it is generally treated as single disease. Thus, further approaches to investigate novel aspects of ovarian cancer pathogenesis aiming to provide a personalized strategy to clinical decision making are of high priority. Herein we assessed the contribution of the AID/APOBEC family and their associated genes given the remarkable ability of AID and APOBECs to edit DNA/RNA, and as such, providing tools for genetic and epigenetic alterations potentially leading to reprogramming of tumor cells, stroma and immune cells. We structured the study by three consecutive analytical modules, which include the multigene-based expression profiling in a cohort of patients with primary serous ovarian cancer using a self-created AID/APOBEC-associated gene signature, building up of multivariable survival models with high predictive accuracy and nomination of top-ranked candidate/target genes according to their prognostic impact, and systems biology-based reconstruction of the AID/APOBEC-driven disease-relevant mechanisms using transcriptomics data from ovarian cancer samples. We demonstrated that inclusion of the AID/APOBEC signature-based variables significantly improves the clinicopathological variables-based survival prognostication allowing significant patient stratification. Furthermore, several of the profiling-derived variables such as ID3, PTPRC/CD45, AID, APOBEC3G, and ID2 exceed the prognostic impact of some clinicopathological variables. We next extended the signature-/modeling-based knowledge by extracting top genes co-regulated with target molecules in ovarian cancer tissues and dissected potential

  15. Critical phenomena and noise-induced phase transitions in neuronal networks

    Science.gov (United States)

    Lee, K.-E.; Lopes, M. A.; Mendes, J. F. F.; Goltsev, A. V.

    2014-01-01

    We study numerically and analytically first- and second-order phase transitions in neuronal networks stimulated by shot noise (a flow of random spikes bombarding neurons). Using an exactly solvable cortical model of neuronal networks on classical random networks, we find critical phenomena accompanying the transitions and their dependence on the shot noise intensity. We show that a pattern of spontaneous neuronal activity near a critical point of a phase transition is a characteristic property that can be used to identify the bifurcation mechanism of the transition. We demonstrate that bursts and avalanches are precursors of a first-order phase transition, paroxysmal-like spikes of activity precede a second-order phase transition caused by a saddle-node bifurcation, while irregular spindle oscillations represent spontaneous activity near a second-order phase transition caused by a supercritical Hopf bifurcation. Our most interesting result is the observation of the paroxysmal-like spikes. We show that a paroxysmal-like spike is a single nonlinear event that appears instantly from a low background activity with a rapid onset, reaches a large amplitude, and ends up with an abrupt return to lower activity. These spikes are similar to single paroxysmal spikes and sharp waves observed in electroencephalographic (EEG) measurements. Our analysis shows that above the saddle-node bifurcation, sustained network oscillations appear with a large amplitude but a small frequency in contrast to network oscillations near the Hopf bifurcation that have a small amplitude but a large frequency. We discuss an amazing similarity between excitability of the cortical model stimulated by shot noise and excitability of the Morris-Lecar neuron stimulated by an applied current.

  16. Critical phenomena and noise-induced phase transitions in neuronal networks.

    Science.gov (United States)

    Lee, K-E; Lopes, M A; Mendes, J F F; Goltsev, A V

    2014-01-01

    We study numerically and analytically first- and second-order phase transitions in neuronal networks stimulated by shot noise (a flow of random spikes bombarding neurons). Using an exactly solvable cortical model of neuronal networks on classical random networks, we find critical phenomena accompanying the transitions and their dependence on the shot noise intensity. We show that a pattern of spontaneous neuronal activity near a critical point of a phase transition is a characteristic property that can be used to identify the bifurcation mechanism of the transition. We demonstrate that bursts and avalanches are precursors of a first-order phase transition, paroxysmal-like spikes of activity precede a second-order phase transition caused by a saddle-node bifurcation, while irregular spindle oscillations represent spontaneous activity near a second-order phase transition caused by a supercritical Hopf bifurcation. Our most interesting result is the observation of the paroxysmal-like spikes. We show that a paroxysmal-like spike is a single nonlinear event that appears instantly from a low background activity with a rapid onset, reaches a large amplitude, and ends up with an abrupt return to lower activity. These spikes are similar to single paroxysmal spikes and sharp waves observed in electroencephalographic (EEG) measurements. Our analysis shows that above the saddle-node bifurcation, sustained network oscillations appear with a large amplitude but a small frequency in contrast to network oscillations near the Hopf bifurcation that have a small amplitude but a large frequency. We discuss an amazing similarity between excitability of the cortical model stimulated by shot noise and excitability of the Morris-Lecar neuron stimulated by an applied current.

  17. Critical importance of the de novo pyrimidine biosynthesis pathway for Trypanosoma cruzi growth in the mammalian host cell cytoplasm

    Energy Technology Data Exchange (ETDEWEB)

    Hashimoto, Muneaki, E-mail: muneaki@juntendo.ac.jp [Department of Molecular and Cellular Parasitology, Juntendo University School of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo 113-8421 (Japan); Morales, Jorge; Fukai, Yoshihisa; Suzuki, Shigeo; Takamiya, Shinzaburo; Tsubouchi, Akiko; Inoue, Syou [Department of Molecular and Cellular Parasitology, Juntendo University School of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo 113-8421 (Japan); Inoue, Masayuki [Graduate School of Pharmaceutical Sciences, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033 (Japan); Kita, Kiyoshi [Department of Biomedical Chemistry, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033 (Japan); Harada, Shigeharu [Department of Applied Biology, Graduate School of Science and Technology, Kyoto Institute of Technology, Sakyo-ku, Kyoto 606-8585 (Japan); Tanaka, Akiko [Systems and Structural Biology Center, RIKEN, Tsurumi, Yokohama 230-0045 (Japan); Aoki, Takashi [Department of Molecular and Cellular Parasitology, Juntendo University School of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo 113-8421 (Japan); Nara, Takeshi, E-mail: tnara@juntendo.ac.jp [Department of Molecular and Cellular Parasitology, Juntendo University School of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo 113-8421 (Japan)

    2012-01-20

    Highlights: Black-Right-Pointing-Pointer We established Trypanosoma cruzi lacking the gene for carbamoyl phosphate synthetase II. Black-Right-Pointing-Pointer Disruption of the cpsII gene significantly reduced the growth of epimastigotes. Black-Right-Pointing-Pointer In particular, the CPSII-null mutant severely retarded intracellular growth. Black-Right-Pointing-Pointer The de novo pyrimidine pathway is critical for the parasite growth in the host cell. -- Abstract: The intracellular parasitic protist Trypanosoma cruzi is the causative agent of Chagas disease in Latin America. In general, pyrimidine nucleotides are supplied by both de novo biosynthesis and salvage pathways. While epimastigotes-an insect form-possess both activities, amastigotes-an intracellular replicating form of T. cruzi-are unable to mediate the uptake of pyrimidine. However, the requirement of de novo pyrimidine biosynthesis for parasite growth and survival has not yet been elucidated. Carbamoyl-phosphate synthetase II (CPSII) is the first and rate-limiting enzyme of the de novo biosynthetic pathway, and increased CPSII activity is associated with the rapid proliferation of tumor cells. In the present study, we showed that disruption of the T. cruzicpsII gene significantly reduced parasite growth. In particular, the growth of amastigotes lacking the cpsII gene was severely suppressed. Thus, the de novo pyrimidine pathway is important for proliferation of T. cruzi in the host cell cytoplasm and represents a promising target for chemotherapy against Chagas disease.

  18. Regulatory network of secondary metabolism in Brassica rapa: insight into the glucosinolate pathway.

    Science.gov (United States)

    Pino Del Carpio, Dunia; Basnet, Ram Kumar; Arends, Danny; Lin, Ke; De Vos, Ric C H; Muth, Dorota; Kodde, Jan; Boutilier, Kim; Bucher, Johan; Wang, Xiaowu; Jansen, Ritsert; Bonnema, Guusje

    2014-01-01

    Brassica rapa studies towards metabolic variation have largely been focused on the profiling of the diversity of metabolic compounds in specific crop types or regional varieties, but none aimed to identify genes with regulatory function in metabolite composition. Here we followed a genetical genomics approach to identify regulatory genes for six biosynthetic pathways of health-related phytochemicals, i.e carotenoids, tocopherols, folates, glucosinolates, flavonoids and phenylpropanoids. Leaves from six weeks-old plants of a Brassica rapa doubled haploid population, consisting of 92 genotypes, were profiled for their secondary metabolite composition, using both targeted and LC-MS-based untargeted metabolomics approaches. Furthermore, the same population was profiled for transcript variation using a microarray containing EST sequences mainly derived from three Brassica species: B. napus, B. rapa and B. oleracea. The biochemical pathway analysis was based on the network analyses of both metabolite QTLs (mQTLs) and transcript QTLs (eQTLs). Co-localization of mQTLs and eQTLs lead to the identification of candidate regulatory genes involved in the biosynthesis of carotenoids, tocopherols and glucosinolates. We subsequently focused on the well-characterized glucosinolate pathway and revealed two hotspots of co-localization of eQTLs with mQTLs in linkage groups A03 and A09. Our results indicate that such a large-scale genetical genomics approach combining transcriptomics and metabolomics data can provide new insights into the genetic regulation of metabolite composition of Brassica vegetables.

  19. Exploring the Causal Pathway From Telomere Length to Coronary Heart Disease: A Network Mendelian Randomization Study.

    Science.gov (United States)

    Zhan, Yiqiang; Karlsson, Ida K; Karlsson, Robert; Tillander, Annika; Reynolds, Chandra A; Pedersen, Nancy L; Hägg, Sara

    2017-07-21

    Observational studies have found shorter leukocyte telomere length (TL) to be a risk factor for coronary heart disease (CHD), and recently the association was suggested to be causal. However, the relationship between TL and common metabolic risk factors for CHD is not well understood. Whether these risk factors could explain pathways from TL to CHD warrants further attention. To examine whether metabolic risk factors for CHD mediate the causal pathway from short TL to increased risk of CHD using a network Mendelian randomization design. Summary statistics from several genome-wide association studies were used in a 2-sample Mendelian randomization study design. Network Mendelian randomization analysis-an approach using genetic variants as the instrumental variables for both the exposure and mediator to infer causality-was performed to examine the causal association between telomeres and CHD and metabolic risk factors. Summary statistics from the ENGAGE Telomere Consortium were used (n=37 684) as a TL genetic instrument, CARDIoGRAMplusC4D Consortium data were used (case=22 233 and control=64 762) for CHD, and other consortia data were used for metabolic traits (fasting insulin, triglyceride, total cholesterol, low-density lipoprotein cholesterol, fasting glucose, diabetes mellitus, glycohemoglobin, body mass index, waist circumference, and waist:hip ratio). One-unit increase of genetically determined TL was associated with -0.07 (95% confidence interval, -0.01 to -0.12; P=0.01) lower log-transformed fasting insulin (pmol/L) and 21% lower odds (95% confidence interval, 3-35; P=0.02) of CHD. Higher genetically determined log-transformed fasting insulin level was associated with higher CHD risk (odds ratio, 1.86; 95% confidence interval, 1.01-3.41; P=0.04). Overall, our findings support a role of insulin as a mediator on the causal pathway from shorter telomeres to CHD pathogenesis. © 2017 American Heart Association, Inc.

  20. A direct descending pathway informing locomotor networks about tactile sensor movement.

    Science.gov (United States)

    Ache, Jan M; Haupt, S Shuichi; Dürr, Volker

    2015-03-04

    Much like visually impaired humans use a white-cane, nocturnal insects and mammals use antennae or whiskers for near-range orientation. Stick insects, for example, rely heavily on antennal tactile cues to find footholds and detect obstacles. Antennal contacts can even induce aimed reaching movements. Because tactile sensors are essentially one-dimensional, they must be moved to probe the surrounding space. Sensor movement is thus an essential cue for tactile sensing, which needs to be integrated by thoracic networks for generating appropriate adaptive leg movements. Based on single and double recordings, we describe a descending neural pathway comprising three identified ON- and OFF-type neurons that convey complementary, unambiguous, and short-latency information about antennal movement to thoracic networks in the stick insect. The neurons are sensitive to the velocity of antennal movements across the entire range covered by natural movements, regardless of movement direction and joint angle. Intriguingly, none of them originates from the brain. Instead, they descend from the gnathal ganglion and receive input from antennal mechanoreceptors in this lower region of the CNS. From there, they convey information about antennal movement to the thorax. One of the descending neurons, which is additionally sensitive to substrate vibration, feeds this information back to the brain via an ascending branch. We conclude that descending interneurons with complementary tuning characteristics, gains, input and output regions convey detailed information about antennal movement to thoracic networks. This pathway bypasses higher processing centers in the brain and thus constitutes a shortcut between tactile sensors on the head and the thorax. Copyright © 2015 the authors 0270-6474/15/354081-11$15.00/0.

  1. Comparative pathway and network analysis of brain transcriptome changes during adult aging and in Parkinson's disease.

    Science.gov (United States)

    Glaab, Enrico; Schneider, Reinhard

    2015-02-01

    Aging is considered as one of the main factors promoting the risk for Parkinson's disease (PD), and common mechanisms of dopamine neuron degeneration in aging and PD have been proposed in recent years. Here, we use a statistical meta-analysis of human brain transcriptomics data to investigate potential mechanistic relationships between adult brain aging and PD pathogenesis at the pathway and network level. The analyses identify statistically significant shared pathway and network alterations in aging and PD and an enrichment in PD-associated sequence variants from genome-wide association studies among the jointly deregulated genes. We find robust discriminative patterns for groups of functionally related genes with potential applications as combined risk biomarkers to detect aging- and PD-linked oxidative stress, e.g., a consistent over-expression of metallothioneins matching with findings in previous independent studies. Interestingly, analyzing the regulatory network and mouse knockout expression data for NR4A2, a transcription factor previously associated with rare mutations in PD and here found as the most significantly under-expressed gene in PD among the jointly altered genes, suggests that aging-related NR4A2 expression changes may increase PD risk via downstream effects similar to disease-linked mutations and to expression changes in sporadic PD. Overall, the analyses suggest mechanistic explanations for the age-dependence of PD risk and reveal significant and robust shared process alterations with potential applications in biomarker development for pre-symptomatic risk assessment or early stage diagnosis. Copyright © 2014. Published by Elsevier Inc.

  2. Hub nodes in the network of human Mitogen-Activated Protein Kinase (MAPK pathways: Characteristics and potential as drug targets

    Directory of Open Access Journals (Sweden)

    V.K. MD Aksam

    2017-01-01

    Full Text Available Proteins involved in the cross-talk between ERK1/2, ERK5, JNK, and P38 signalling pathways integrate the network of Mitogen-Activated Protein Kinase (MAPK pathways. Graph theory-based approach is used to construct the network of MAPK pathways, and to observe the network organisational principles. Connectivity pattern reveals rich-club among the hubs, enabling structural ordering. A positive correlation between the degree of the nodes and percentage of essential protein showed hubs are central to the network architecture and function. Furthermore, attributes like connectivity, inter/intra-pathway class, position in the pathway, protein type and subcellular localization of the essential and non-essential proteins are characterizing complex functional roles. Shared properties of 34 cancerous essential proteins lack to be drug targets. We identified the seven nodes overlapping properties of the hub, essential and causing side effects on targeting them. We exploit the strategy of cancerous, non-hub and non-essential proteins as potential drug targets and identified 4EBP1, BAD, CHOP10, GADD45, HSP27, MKP1, RNPK, MLTKa/b, cPLA2, eEF2K and elF4E. We have illustrated the implication of targeting hub nodes and proposed network-based drug targets which would cause less side effect.

  3. Significant Deregulated Pathways in Diabetes Type II Complications Identified through Expression Based Network Biology

    Science.gov (United States)

    Ukil, Sanchaita; Sinha, Meenakshee; Varshney, Lavneesh; Agrawal, Shipra

    Type 2 Diabetes is a complex multifactorial disease, which alters several signaling cascades giving rise to serious complications. It is one of the major risk factors for cardiovascular diseases. The present research work describes an integrated functional network biology approach to identify pathways that get transcriptionally altered and lead to complex complications thereby amplifying the phenotypic effect of the impaired disease state. We have identified two sub-network modules, which could be activated under abnormal circumstances in diabetes. Present work describes key proteins such as P85A and SRC serving as important nodes to mediate alternate signaling routes during diseased condition. P85A has been shown to be an important link between stress responsive MAPK and CVD markers involved in fibrosis. MAPK8 has been shown to interact with P85A and further activate CTGF through VEGF signaling. We have traced a novel and unique route correlating inflammation and fibrosis by considering P85A as a key mediator of signals. The next sub-network module shows SRC as a junction for various signaling processes, which results in interaction between NF-kB and beta catenin to cause cell death. The powerful interaction between these important genes in response to transcriptionally altered lipid metabolism and impaired inflammatory response via SRC causes apoptosis of cells. The crosstalk between inflammation, lipid homeostasis and stress, and their serious effects downstream have been explained in the present analyses.

  4. A pathway-based network analysis of hypertension-related genes

    Science.gov (United States)

    Wang, Huan; Hu, Jing-Bo; Xu, Chuan-Yun; Zhang, De-Hai; Yan, Qian; Xu, Ming; Cao, Ke-Fei; Zhang, Xu-Sheng

    2016-02-01

    Complex network approach has become an effective way to describe interrelationships among large amounts of biological data, which is especially useful in finding core functions and global behavior of biological systems. Hypertension is a complex disease caused by many reasons including genetic, physiological, psychological and even social factors. In this paper, based on the information of biological pathways, we construct a network model of hypertension-related genes of the salt-sensitive rat to explore the interrelationship between genes. Statistical and topological characteristics show that the network has the small-world but not scale-free property, and exhibits a modular structure, revealing compact and complex connections among these genes. By the threshold of integrated centrality larger than 0.71, seven key hub genes are found: Jun, Rps6kb1, Cycs, Creb312, Cdk4, Actg1 and RT1-Da. These genes should play an important role in hypertension, suggesting that the treatment of hypertension should focus on the combination of drugs on multiple genes.

  5. Interoperable Medical Instrument Networking and Access System with Security Considerations for Critical Care

    Directory of Open Access Journals (Sweden)

    Deniz Gurkan

    2010-01-01

    Full Text Available The recent influx of electronic medical records in the health care field, coupled with the need of providing continuous care to patients in the critical care environment, has driven the need for interoperability of medical devices. Open standards are needed to support flexible processes and interoperability of medical devices, especially in intensive care units. In this paper, we present an interoperable networking and access architecture based on the CAN protocol. Predictability of the delay of medical data reports is a desirable attribute that can be realized using a tightly-coupled system architecture. Our simulations on network architecture demonstrate that a bounded delay for event reports offers predictability. In addition, we address security issues related to the storage of electronic medical records. We present a set of open source tools and tests to identify the security breaches, and appropriate measures that can be implemented to be compliant with the HIPAA rules.

  6. Minimal-Intrusion Traffic Monitoring And Analysis In Mission-Critical Communication Networks

    Directory of Open Access Journals (Sweden)

    Alberto Domingo Ajenjo

    2003-10-01

    Full Text Available A good knowledge of expected and actual traffic patterns is an essential tool for network planning, design and operation in deployed, mission-critical applications. This paper describes those needs, and explains the Traffic Monitoring and Analysis Platform (TMAP concept, as developed in support of NATO deployed military headquarters Communications and Information Systems. It shows how a TMAP was deployed to a real NATO exercise, to prove the concept and baseline the traffic needs per application, per user community and per time of day. Then, it analyses the obtained results and derives conclusions on how to integrate traffic monitoring and analysis platforms in future deployments.

  7. Designing a network of critical zone observatories to explore the living skin of the terrestrial Earth

    Directory of Open Access Journals (Sweden)

    S. L. Brantley

    2017-12-01

    Full Text Available The critical zone (CZ, the dynamic living skin of the Earth, extends from the top of the vegetative canopy through the soil and down to fresh bedrock and the bottom of the groundwater. All humans live in and depend on the CZ. This zone has three co-evolving surfaces: the top of the vegetative canopy, the ground surface, and a deep subsurface below which Earth's materials are unweathered. The network of nine CZ observatories supported by the US National Science Foundation has made advances in three broad areas of CZ research relating to the co-evolving surfaces. First, monitoring has revealed how natural and anthropogenic inputs at the vegetation canopy and ground surface cause subsurface responses in water, regolith structure, minerals, and biotic activity to considerable depths. This response, in turn, impacts aboveground biota and climate. Second, drilling and geophysical imaging now reveal how the deep subsurface of the CZ varies across landscapes, which in turn influences aboveground ecosystems. Third, several new mechanistic models now provide quantitative predictions of the spatial structure of the subsurface of the CZ.Many countries fund critical zone observatories (CZOs to measure the fluxes of solutes, water, energy, gases, and sediments in the CZ and some relate these observations to the histories of those fluxes recorded in landforms, biota, soils, sediments, and rocks. Each US observatory has succeeded in (i synthesizing research across disciplines into convergent approaches; (ii providing long-term measurements to compare across sites; (iii testing and developing models; (iv collecting and measuring baseline data for comparison to catastrophic events; (v stimulating new process-based hypotheses; (vi catalyzing development of new techniques and instrumentation; (vii informing the public about the CZ; (viii mentoring students and teaching about emerging multidisciplinary CZ science; and (ix discovering new insights about the CZ. Many

  8. Designing a network of critical zone observatories to explore the living skin of the terrestrial Earth

    Science.gov (United States)

    Brantley, Susan L.; McDowell, William H.; Dietrich, William E.; White, Timothy S.; Kumar, Praveen; Anderson, Suzanne P.; Chorover, Jon; Lohse, Kathleen Ann; Bales, Roger C.; Richter, Daniel D.; Grant, Gordon; Gaillardet, Jérôme

    2017-12-01

    The critical zone (CZ), the dynamic living skin of the Earth, extends from the top of the vegetative canopy through the soil and down to fresh bedrock and the bottom of the groundwater. All humans live in and depend on the CZ. This zone has three co-evolving surfaces: the top of the vegetative canopy, the ground surface, and a deep subsurface below which Earth's materials are unweathered. The network of nine CZ observatories supported by the US National Science Foundation has made advances in three broad areas of CZ research relating to the co-evolving surfaces. First, monitoring has revealed how natural and anthropogenic inputs at the vegetation canopy and ground surface cause subsurface responses in water, regolith structure, minerals, and biotic activity to considerable depths. This response, in turn, impacts aboveground biota and climate. Second, drilling and geophysical imaging now reveal how the deep subsurface of the CZ varies across landscapes, which in turn influences aboveground ecosystems. Third, several new mechanistic models now provide quantitative predictions of the spatial structure of the subsurface of the CZ.Many countries fund critical zone observatories (CZOs) to measure the fluxes of solutes, water, energy, gases, and sediments in the CZ and some relate these observations to the histories of those fluxes recorded in landforms, biota, soils, sediments, and rocks. Each US observatory has succeeded in (i) synthesizing research across disciplines into convergent approaches; (ii) providing long-term measurements to compare across sites; (iii) testing and developing models; (iv) collecting and measuring baseline data for comparison to catastrophic events; (v) stimulating new process-based hypotheses; (vi) catalyzing development of new techniques and instrumentation; (vii) informing the public about the CZ; (viii) mentoring students and teaching about emerging multidisciplinary CZ science; and (ix) discovering new insights about the CZ. Many of these

  9. A novel critical infrastructure resilience assessment approach using dynamic Bayesian networks

    Science.gov (United States)

    Cai, Baoping; Xie, Min; Liu, Yonghong; Liu, Yiliu; Ji, Renjie; Feng, Qiang

    2017-10-01

    The word resilience originally originates from the Latin word "resiliere", which means to "bounce back". The concept has been used in various fields, such as ecology, economics, psychology, and society, with different definitions. In the field of critical infrastructure, although some resilience metrics are proposed, they are totally different from each other, which are determined by the performances of the objects of evaluation. Here we bridge the gap by developing a universal critical infrastructure resilience metric from the perspective of reliability engineering. A dynamic Bayesian networks-based assessment approach is proposed to calculate the resilience value. A series, parallel and voting system is used to demonstrate the application of the developed resilience metric and assessment approach.

  10. Failure Diagnosis and Prognosis of Rolling - Element Bearings using Artificial Neural Networks: A Critical Overview

    Science.gov (United States)

    Rao, B. K. N.; Srinivasa Pai, P.; Nagabhushana, T. N.

    2012-05-01

    Rolling - Element Bearings are extensively used in almost all global industries. Any critical failures in these vitally important components would not only affect the overall systems performance but also its reliability, safety, availability and cost-effectiveness. Proactive strategies do exist to minimise impending failures in real time and at a minimum cost. Continuous innovative developments are taking place in the field of Artificial Neural Networks (ANNs) technology. Significant research and development are taking place in many universities, private and public organizations and a wealth of published literature is available highlighting the potential benefits of employing ANNs in intelligently monitoring, diagnosing, prognosing and managing rolling-element bearing failures. This paper attempts to critically review the recent trends in this topical area of interest.

  11. Optimal system size for complex dynamics in random neural networks near criticality

    Energy Technology Data Exchange (ETDEWEB)

    Wainrib, Gilles, E-mail: wainrib@math.univ-paris13.fr [Laboratoire Analyse Géométrie et Applications, Université Paris XIII, Villetaneuse (France); García del Molino, Luis Carlos, E-mail: garciadelmolino@ijm.univ-paris-diderot.fr [Institute Jacques Monod, Université Paris VII, Paris (France)

    2013-12-15

    In this article, we consider a model of dynamical agents coupled through a random connectivity matrix, as introduced by Sompolinsky et al. [Phys. Rev. Lett. 61(3), 259–262 (1988)] in the context of random neural networks. When system size is infinite, it is known that increasing the disorder parameter induces a phase transition leading to chaotic dynamics. We observe and investigate here a novel phenomenon in the sub-critical regime for finite size systems: the probability of observing complex dynamics is maximal for an intermediate system size when the disorder is close enough to criticality. We give a more general explanation of this type of system size resonance in the framework of extreme values theory for eigenvalues of random matrices.

  12. MicroRNA mediated network motifs in autoimmune diseases and its crosstalk between genes, functions and pathways.

    Science.gov (United States)

    Prabahar, Archana; Natarajan, Jeyakumar

    2017-01-01

    Autoimmune diseases (AIDs) are incurable but suppressible diseases whose molecular mechanisms are yet to be elucidated. In this work, we selected five systemic autoimmune diseases such as Rheumatoid Arthritis (RA), Type 1 Diabetes (T1D), Inflammatory Bowel Disease (IBD), Autoimmune Thyroid Disease (ATD) and Systemic Lupus Erythematosus (SLE). Heterogeneous data such as miRNA, transcription factor (TF), target genes and protein-protein interactions involved in these AIDs were integrated to understand their roles at different functional levels of miRNA such as transcription initiation, gene regulatory network formation and post transcriptional regulation. To understand the functional characteristics of these complex biological networks, they can be simplified as network motifs (sub networks) and motif-motif interacting pairs (MMIs). The network motif patterns and motif-motif interacting pairs that occur for the selected five diseases were identified. To further understand the functional association between AIDs, functions and pathways were determined using gene set enrichment analysis and five selected immune signaling pathways (ISPs). The crosstalk within AIDs and between the immune signaling pathways (ISPs) could provide novel insights in deciphering disease mechanisms. This study represents the first investigation of miRNA-TF regulatory network for AIDs and its association with ISPs using sub-network motifs. Copyright © 2016 Elsevier B.V. All rights reserved.

  13. Neurobiologically realistic determinants of self-organized criticality in networks of spiking neurons.

    Directory of Open Access Journals (Sweden)

    Mikail Rubinov

    2011-06-01

    Full Text Available Self-organized criticality refers to the spontaneous emergence of self-similar dynamics in complex systems poised between order and randomness. The presence of self-organized critical dynamics in the brain is theoretically appealing and is supported by recent neurophysiological studies. Despite this, the neurobiological determinants of these dynamics have not been previously sought. Here, we systematically examined the influence of such determinants in hierarchically modular networks of leaky integrate-and-fire neurons with spike-timing-dependent synaptic plasticity and axonal conduction delays. We characterized emergent dynamics in our networks by distributions of active neuronal ensemble modules (neuronal avalanches and rigorously assessed these distributions for power-law scaling. We found that spike-timing-dependent synaptic plasticity enabled a rapid phase transition from random subcritical dynamics to ordered supercritical dynamics. Importantly, modular connectivity and low wiring cost broadened this transition, and enabled a regime indicative of self-organized criticality. The regime only occurred when modular connectivity, low wiring cost and synaptic plasticity were simultaneously present, and the regime was most evident when between-module connection density scaled as a power-law. The regime was robust to variations in other neurobiologically relevant parameters and favored systems with low external drive and strong internal interactions. Increases in system size and connectivity facilitated internal interactions, permitting reductions in external drive and facilitating convergence of postsynaptic-response magnitude and synaptic-plasticity learning rate parameter values towards neurobiologically realistic levels. We hence infer a novel association between self-organized critical neuronal dynamics and several neurobiologically realistic features of structural connectivity. The central role of these features in our model may reflect

  14. Thermodynamic analysis of computed pathways integrated into the metabolic networks of E. coli and Synechocystis reveals contrasting expansion potential.

    Science.gov (United States)

    Asplund-Samuelsson, Johannes; Janasch, Markus; Hudson, Elton P

    2017-12-23

    Introducing biosynthetic pathways into an organism is both reliant on and challenged by endogenous biochemistry. Here we compared the expansion potential of the metabolic network in the photoautotroph Synechocystis with that of the heterotroph E. coli using the novel workflow POPPY (Prospecting Optimal Pathways with PYthon). First, E. coli and Synechocystis metabolomic and fluxomic data were combined with metabolic models to identify thermodynamic constraints on metabolite concentrations (NET analysis). Then, thousands of automatically constructed pathways were placed within each network and subjected to a network-embedded variant of the max-min driving force analysis (NEM). We found that the networks had different capabilities for imparting thermodynamic driving forces toward certain compounds. Key metabolites were constrained differently in Synechocystis due to opposing flux directions in glycolysis and carbon fixation, the forked tri-carboxylic acid cycle, and photorespiration. Furthermore, the lysine biosynthesis pathway in Synechocystis was identified as thermodynamically constrained, impacting both endogenous and heterologous reactions through low 2-oxoglutarate levels. Our study also identified important yet poorly covered areas in existing metabolomics data and provides a reference for future thermodynamics-based engineering in Synechocystis and beyond. The POPPY methodology represents a step in making optimal pathway-host matches, which is likely to become important as the practical range of host organisms is diversified. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

  15. Network model explains why cancer cells use inefficient pathway to produce energy

    Science.gov (United States)

    Lee, Joo Sang; Marko, John; Motter, Adilson

    2012-02-01

    The Warburg effect---the use of the (energetically inefficient) fermentative pathway as opposed to (energetically efficient) respiration even in the presence of oxygen---is a common property of cancer metabolism. Here, we propose that the Warburg effect is in fact a consequence of a trade-off between the benefit of rapid growth and the cost for protein synthesis. Using genome-scale metabolic networks, we have modeled the cellular resources for protein synthesis as a growth defect that increases with enzyme concentration. Based on our model, we demonstrate that the cost of protein production during rapid growth drives the cell to rely on fermentation to produce ATP. We also identify an intimate link between extensive fermentation and rapid biosynthesis. Our findings emphasize the importance of protein synthesis as a limiting factor on cell proliferation and provide a novel mathematical framework to analyze cancer metabolism.

  16. Selective breakdown of metallic pathways in double-walled carbon nanotube networks.

    Science.gov (United States)

    Ng, Allen L; Sun, Yong; Powell, Lyndsey; Sun, Chuan-Fu; Chen, Chien-Fu; Lee, Cheng S; Wang, YuHuang

    2015-01-07

    Covalently functionalized, semiconducting double-walled carbon nanotubes exhibit remarkable properties and can outperform their single-walled carbon nanotube counterparts. In order to harness their potential for electronic applications, metallic double-walled carbon nanotubes must be separated from the semiconductors. However, the inner wall is inaccessible to current separation techniques which rely on the surface properties. Here, the first approach to address this challenge through electrical breakdown of metallic double-walled carbon nanotubes, both inner and outer walls, within networks of mixed electronic types is described. The intact semiconductors demonstrate a ∼62% retention of the ON-state conductance in thin film transistors in response to covalent functionalization. The selective elimination of the metallic pathways improves the ON/OFF ratio, by more than 360 times, to as high as 40 700, while simultaneously retaining high ON-state conductance. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  17. Activation of critical, host-induced, metabolic and stress pathways marks neutrophil entry into cystic fibrosis lungs.

    Science.gov (United States)

    Makam, Megha; Diaz, Daisy; Laval, Julie; Gernez, Yael; Conrad, Carol K; Dunn, Colleen E; Davies, Zoe A; Moss, Richard B; Herzenberg, Leonore A; Herzenberg, Leonard A; Tirouvanziam, Rabindra

    2009-04-07

    Cystic fibrosis (CF) patients undergo progressive airway destruction caused in part by chronic neutrophilic inflammation. While opportunistic pathogens infecting CF airways can cause inflammation, we hypothesized that host-derived metabolic and stress signals would also play a role in this process. We show that neutrophils that have entered CF airways have increased phosphorylation of the eukaryotic initiation factor 4E and its partner the 4E-binding protein 1; 2 key effectors in the growth factor- and amino acid-regulated mammalian target of rapamycin (mTOR) pathway. Furthermore CF airway neutrophils display increased phosphorylation of the cAMP response element binding protein (CREB), a major transcriptional coactivator in stress signaling cascades. These active intracellular pathways are associated with increased surface expression of critical adaptor molecules, including the growth factor receptor CD114 and the receptor for advanced glycation end-products (RAGE), a CREB inducer and sensor for host-derived damage-associated molecular patterns (DAMPs). Most CF airway fluids lack any detectable soluble RAGE, an inhibitory decoy receptor for DAMPs. Concomitantly, CF airway fluids displayed high and consequently unopposed levels of S100A12; a potent mucosa- and neutrophil-derived DAMP. CF airway neutrophils also show increased surface levels of 2 critical CREB targets, the purine-recycling enzyme CD39 and the multifunctional, mTOR-inducing CXCR4 receptor. This coordinated set of events occurs in all patients, even in the context of minimal airway inflammation and well-preserved lung function. Taken together, our data demonstrate an early and sustained activation of host-responsive metabolic and stress pathways upon neutrophil entry into CF airways, suggesting potential targets for therapeutic modulation.

  18. Effects of Interactive Function Forms and Refractoryperiod in a Self-Organized Critical Model Based on Neural Networks

    Institute of Scientific and Technical Information of China (English)

    ZHOU Li-Ming; CHEN Tian-Lun

    2004-01-01

    Based on the standard self-organizing map neural network model and an integrate-and-tire mechanism, we investigate the effect of the nonlinear interactive function on the self-organized criticality in our model. Based on these we also investigate the effect of the refractoryperiod on the self-organized criticality of the system.

  19. Constructing Integrated Networks for Identifying New Secondary Metabolic Pathway Regulators in Grapevine: Recent Applications and Future Opportunities.

    Science.gov (United States)

    Wong, Darren C J; Matus, José Tomás

    2017-01-01

    Representing large biological data as networks is becoming increasingly adopted for predicting gene function while elucidating the multifaceted organization of life processes. In grapevine ( Vitis vinifera L.), network analyses have been mostly adopted to contribute to the understanding of the regulatory mechanisms that control berry composition. Whereas, some studies have used gene co-expression networks to find common pathways and putative targets for transcription factors related to development and metabolism, others have defined networks of primary and secondary metabolites for characterizing the main metabolic differences between cultivars throughout fruit ripening. Lately, proteomic-related networks and those integrating genome-wide analyses of promoter regulatory elements have also been generated. The integration of all these data in multilayered networks allows building complex maps of molecular regulation and interaction. This perspective article describes the currently available network data and related resources for grapevine. With the aim of illustrating data integration approaches into network construction and analysis in grapevine, we searched for berry-specific regulators of the phenylpropanoid pathway. We generated a composite network consisting of overlaying maps of co-expression between structural and transcription factor genes, integrated with the presence of promoter cis -binding elements, microRNAs, and long non-coding RNAs (lncRNA). This approach revealed new uncharacterized transcription factors together with several microRNAs potentially regulating different steps of the phenylpropanoid pathway, and one particular lncRNA compromising the expression of nine stilbene synthase (STS) genes located in chromosome 10. Application of network-based approaches into multi-omics data will continue providing supplementary resources to address important questions regarding grapevine fruit quality and composition.

  20. Expression patterns of genes critical for BMP signaling pathway in developing human primary tooth germs.

    Science.gov (United States)

    Dong, Xiuqing; Shen, Bin; Ruan, Ningsheng; Guan, Zhen; Zhang, Yanding; Chen, YiPing; Hu, Xuefeng

    2014-12-01

    The developing murine tooth has been used as an excellent model system to study the molecular mechanism of organ development and regeneration. While the expression patterns of numerous regulatory genes have been examined and their roles have begun to be revealed in the developing murine tooth, little is known about gene expression and function in human tooth development. In order to unveil the molecular mechanisms that regulate human tooth morphogenesis, we examined the expression patterns of the major BMP signaling pathway molecules in the developing human tooth germ at the cap and bell stages by in situ hybridization, immunohistochemistry, and real-time RT-PCR. Expression of BMP ligands and antagonist, including BMP2, BMP3, BMP4, BMP7, and NOOGGIN, exhibited uniform patterns in the tooth germs of incisor and molar at the cap and bell stages with stronger expression in the inner dental epithelium than that in the dental mesenchyme. Both type I and type II BMP receptors were present in widespread expression pattern in the whole-enamel organ and the dental mesenchyme with the strongest expression in inner dental epithelium at the cap and bell stages. SMAD4 and SMAD1/5/8 showed an expression pattern similar to that of BMP ligands with more intensive signals in the inner dental epithelium. Despite some unique and distinct patterns as compared to the mouse, the intensive expression of BMP signaling pathway molecules in the developing human tooth strongly suggests conserved functions of BMP signaling during human odontogenesis, such as in mediating tissue interactions and regulating differentiation and organization of odontogenic tissues. Our results provide an important set of documents for studying molecular regulatory mechanisms underlying tooth development and regeneration in humans.

  1. Rational Extension of the Ribosome Biogenesis Pathway Using Network-Guided Genetics

    Science.gov (United States)

    Li, Zhihua; Lee, Insuk; Moradi, Emily; Hung, Nai-Jung; Johnson, Arlen W.; Marcotte, Edward M.

    2009-01-01

    Biogenesis of ribosomes is an essential cellular process conserved across all eukaryotes and is known to require >170 genes for the assembly, modification, and trafficking of ribosome components through multiple cellular compartments. Despite intensive study, this pathway likely involves many additional genes. Here, we employ network-guided genetics—an approach for associating candidate genes with biological processes that capitalizes on recent advances in functional genomic and proteomic studies—to computationally identify additional ribosomal biogenesis genes. We experimentally evaluated >100 candidate yeast genes in a battery of assays, confirming involvement of at least 15 new genes, including previously uncharacterized genes (YDL063C, YIL091C, YOR287C, YOR006C/TSR3, YOL022C/TSR4). We associate the new genes with specific aspects of ribosomal subunit maturation, ribosomal particle association, and ribosomal subunit nuclear export, and we identify genes specifically required for the processing of 5S, 7S, 20S, 27S, and 35S rRNAs. These results reveal new connections between ribosome biogenesis and mRNA splicing and add >10% new genes—most with human orthologs—to the biogenesis pathway, significantly extending our understanding of a universally conserved eukaryotic process. PMID:19806183

  2. Rational extension of the ribosome biogenesis pathway using network-guided genetics.

    Directory of Open Access Journals (Sweden)

    Zhihua Li

    2009-10-01

    Full Text Available Biogenesis of ribosomes is an essential cellular process conserved across all eukaryotes and is known to require >170 genes for the assembly, modification, and trafficking of ribosome components through multiple cellular compartments. Despite intensive study, this pathway likely involves many additional genes. Here, we employ network-guided genetics-an approach for associating candidate genes with biological processes that capitalizes on recent advances in functional genomic and proteomic studies-to computationally identify additional ribosomal biogenesis genes. We experimentally evaluated >100 candidate yeast genes in a battery of assays, confirming involvement of at least 15 new genes, including previously uncharacterized genes (YDL063C, YIL091C, YOR287C, YOR006C/TSR3, YOL022C/TSR4. We associate the new genes with specific aspects of ribosomal subunit maturation, ribosomal particle association, and ribosomal subunit nuclear export, and we identify genes specifically required for the processing of 5S, 7S, 20S, 27S, and 35S rRNAs. These results reveal new connections between ribosome biogenesis and mRNA splicing and add >10% new genes-most with human orthologs-to the biogenesis pathway, significantly extending our understanding of a universally conserved eukaryotic process.

  3. Wnt-signalling pathways and microRNAs network in carcinogenesis: experimental and bioinformatics approaches.

    Science.gov (United States)

    Onyido, Emenike K; Sweeney, Eloise; Nateri, Abdolrahman Shams

    2016-09-02

    Over the past few years, microRNAs (miRNAs) have not only emerged as integral regulators of gene expression at the post-transcriptional level but also respond to signalling molecules to affect cell function(s). miRNAs crosstalk with a variety of the key cellular signalling networks such as Wnt, transforming growth factor-β and Notch, control stem cell activity in maintaining tissue homeostasis, while if dysregulated contributes to the initiation and progression of cancer. Herein, we overview the molecular mechanism(s) underlying the crosstalk between Wnt-signalling components (canonical and non-canonical) and miRNAs, as well as changes in the miRNA/Wnt-signalling components observed in the different forms of cancer. Furthermore, the fundamental understanding of miRNA-mediated regulation of Wnt-signalling pathway and vice versa has been significantly improved by high-throughput genomics and bioinformatics technologies. Whilst, these approaches have identified a number of specific miRNA(s) that function as oncogenes or tumour suppressors, additional analyses will be necessary to fully unravel the links among conserved cellular signalling pathways and miRNAs and their potential associated components in cancer, thereby creating therapeutic avenues against tumours. Hence, we also discuss the current challenges associated with Wnt-signalling/miRNAs complex and the analysis using the biomedical experimental and bioinformatics approaches.

  4. Network-Based Identification of Adaptive Pathways in Evolved Ethanol-Tolerant Bacterial Populations.

    Science.gov (United States)

    Swings, Toon; Weytjens, Bram; Schalck, Thomas; Bonte, Camille; Verstraeten, Natalie; Michiels, Jan; Marchal, Kathleen

    2017-11-01

    Efficient production of ethanol for use as a renewable fuel requires organisms with a high level of ethanol tolerance. However, this trait is complex and increased tolerance therefore requires mutations in multiple genes and pathways. Here, we use experimental evolution for a system-level analysis of adaptation of Escherichia coli to high ethanol stress. As adaptation to extreme stress often results in complex mutational data sets consisting of both causal and noncausal passenger mutations, identifying the true adaptive mutations in these settings is not trivial. Therefore, we developed a novel method named IAMBEE (Identification of Adaptive Mutations in Bacterial Evolution Experiments). IAMBEE exploits the temporal profile of the acquisition of mutations during evolution in combination with the functional implications of each mutation at the protein level. These data are mapped to a genome-wide interaction network to search for adaptive mutations at the level of pathways. The 16 evolved populations in our data set together harbored 2,286 mutated genes with 4,470 unique mutations. Analysis by IAMBEE significantly reduced this number and resulted in identification of 90 mutated genes and 345 unique mutations that are most likely to be adaptive. Moreover, IAMBEE not only enabled the identification of previously known pathways involved in ethanol tolerance, but also identified novel systems such as the AcrAB-TolC efflux pump and fatty acids biosynthesis and even allowed to gain insight into the temporal profile of adaptation to ethanol stress. Furthermore, this method offers a solid framework for identifying the molecular underpinnings of other complex traits as well. © The Author 2017. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.

  5. Neuroplasticity pathways and protein-interaction networks are modulated by vortioxetine in rodents.

    Science.gov (United States)

    Waller, Jessica A; Nygaard, Sara Holm; Li, Yan; du Jardin, Kristian Gaarn; Tamm, Joseph A; Abdourahman, Aicha; Elfving, Betina; Pehrson, Alan L; Sánchez, Connie; Wernersson, Rasmus

    2017-08-04

    The identification of biomarkers that predict susceptibility to major depressive disorder and treatment response to antidepressants is a major challenge. Vortioxetine is a novel multimodal antidepressant that possesses pro-cognitive properties and differentiates from other conventional antidepressants on various cognitive and plasticity measures. The aim of the present study was to identify biological systems rather than single biomarkers that may underlie vortioxetine's treatment effects. We show that the biological systems regulated by vortioxetine are overlapping between mouse and rat in response to distinct treatment regimens and in different brain regions. Furthermore, analysis of complexes of physically-interacting proteins reveal that biomarkers involved in transcriptional regulation, neurodevelopment, neuroplasticity, and endocytosis are modulated by vortioxetine. A subsequent qPCR study examining the expression of targets in the protein-protein interactome space in response to chronic vortioxetine treatment over a range of doses provides further biological validation that vortioxetine engages neuroplasticity networks. Thus, the same biology is regulated in different species and sexes, different brain regions, and in response to distinct routes of administration and regimens. A recurring theme, based on the present study as well as previous findings, is that networks related to synaptic plasticity, synaptic transmission, signal transduction, and neurodevelopment are modulated in response to vortioxetine treatment. Regulation of these signaling pathways by vortioxetine may underlie vortioxetine's cognitive-enhancing properties.

  6. Boundary Detection Method for Large-Scale Coverage Holes in Wireless Sensor Network Based on Minimum Critical Threshold Constraint

    Directory of Open Access Journals (Sweden)

    Rong Jing

    2014-01-01

    Full Text Available The existing coverage hole boundary detection methods cannot detect large-scale coverage hole boundary in wireless sensor network quickly and efficiently. Aiming at this problem, a boundary detection method for large-scale coverage holes in wireless sensor network based on minimum critical threshold constraint is proposed. Firstly, the optimization problem of minimum critical threshold is highlighted, and its formulaic description is constructed according to probabilistic sensing model. On the basis of this, the distributed gradient information is used to approximately solve the optimization problem. After that, local-scale rough boundary detection algorithm incorporating the minimum critical threshold and its iterative thinning algorithm are proposed according to blocking flow theory. The experimental results show that the proposed method has low computational complexity and network overhead when detecting large-scale coverage hole boundary in wireless sensor network.

  7. Towards Resilient Critical Infrastructures: Application of Type-2 Fuzzy Logic in Embedded Network Security Cyber Sensor

    Energy Technology Data Exchange (ETDEWEB)

    Ondrej Linda; Todd Vollmer; Jim Alves-Foss; Milos Manic

    2011-08-01

    Resiliency and cyber security of modern critical infrastructures is becoming increasingly important with the growing number of threats in the cyber-environment. This paper proposes an extension to a previously developed fuzzy logic based anomaly detection network security cyber sensor via incorporating Type-2 Fuzzy Logic (T2 FL). In general, fuzzy logic provides a framework for system modeling in linguistic form capable of coping with imprecise and vague meanings of words. T2 FL is an extension of Type-1 FL which proved to be successful in modeling and minimizing the effects of various kinds of dynamic uncertainties. In this paper, T2 FL provides a basis for robust anomaly detection and cyber security state awareness. In addition, the proposed algorithm was specifically developed to comply with the constrained computational requirements of low-cost embedded network security cyber sensors. The performance of the system was evaluated on a set of network data recorded from an experimental cyber-security test-bed.

  8. Effective connectivity of ascending and descending frontalthalamic pathways during sustained attention: Complex brain network interactions in adolescence.

    Science.gov (United States)

    Jagtap, Pranav; Diwadkar, Vaibhav A

    2016-07-01

    Frontal-thalamic interactions are crucial for bottom-up gating and top-down control, yet have not been well studied from brain network perspectives. We applied network modeling of fMRI signals [dynamic causal modeling (DCM)] to investigate frontal-thalamic interactions during an attention task with parametrically varying levels of demand. fMRI was collected while subjects participated in a sustained continuous performance task with low and high attention demands. 162 competing model architectures were employed in DCM to evaluate hypotheses on bilateral frontal-thalamic connections and their modulation by attention demand, selected at a second level using Bayesian model selection. The model architecture evinced significant contextual modulation by attention of ascending (thalamus → dPFC) and descending (dPFC → thalamus) pathways. However, modulation of these pathways was asymmetric: while positive modulation of the ascending pathway was comparable across attention demand, modulation of the descending pathway was significantly greater when attention demands were increased. Increased modulation of the (dPFC → thalamus) pathway in response to increased attention demand constitutes novel evidence of attention-related gain in the connectivity of the descending attention pathway. By comparison demand-independent modulation of the ascending (thalamus → dPFC) pathway suggests unbiased thalamic inputs to the cortex in the context of the paradigm. Hum Brain Mapp 37:2557-2570, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  9. Effective connectivity of ascending and descending frontal-thalamic pathways during sustained attention: Complex brain network interactions in adolescence

    Science.gov (United States)

    Jagtap, Pranav; Diwadkar, Vaibhav A.

    2016-01-01

    Frontal-thalamic interactions are crucial for bottom-up gating and top-down control, yet have not been well studied from brain network perspectives. We applied network modeling of fMRI signals (Dynamic Causal Modeling; DCM) to investigate frontal-thalamic interactions during an attention task with parametrically varying levels of demand. fMRI was collected while subjects participated in a sustained continuous performance task with low and high attention demands. 162 competing model architectures were employed in DCM to evaluate hypotheses on bilateral frontal-thalamic connections and their modulation by attention demand, selected at a second level using Bayesian Model Selection. The model architecture evinced significant contextual modulation by attention of ascending (thalamus → dPFC) and descending (dPFC → thalamus) pathways. However, modulation of these pathways was asymmetric: While positive modulation of the ascending pathway was comparable across attention demand, modulation of the descending pathway was significantly greater when attention demands were increased. Increased modulation of the (dPFC → thalamus) pathway in response to increased attention demand constitutes novel evidence of attention-related gain in the connectivity of the descending attention pathway. By comparison demand-independent modulation of the ascending (thalamus → dPFC) pathway suggests unbiased thalamic inputs to the cortex in the context of the paradigm. PMID:27145923

  10. The Anterior Insular Cortex→Central Amygdala Glutamatergic Pathway Is Critical to Relapse after Contingency Management.

    Science.gov (United States)

    Venniro, Marco; Caprioli, Daniele; Zhang, Michelle; Whitaker, Leslie R; Zhang, Shiliang; Warren, Brandon L; Cifani, Carlo; Marchant, Nathan J; Yizhar, Ofer; Bossert, Jennifer M; Chiamulera, Cristiano; Morales, Marisela; Shaham, Yavin

    2017-10-11

    Despite decades of research on neurobiological mechanisms of psychostimulant addiction, the only effective treatment for many addicts is contingency management, a behavioral treatment that uses alternative non-drug reward to maintain abstinence. However, when contingency management is discontinued, most addicts relapse to drug use. The brain mechanisms underlying relapse after cessation of contingency management are largely unknown, and, until recently, an animal model of this human condition did not exist. Here we used a novel rat model, in which the availability of a mutually exclusive palatable food maintains prolonged voluntary abstinence from intravenous methamphetamine self-administration, to demonstrate that the activation of monosynaptic glutamatergic projections from anterior insular cortex to central amygdala is critical to relapse after the cessation of contingency management. We identified the anterior insular cortex-to-central amygdala projection as a new addiction- and motivation-related projection and a potential target for relapse prevention. Published by Elsevier Inc.

  11. Mobile Ad Hoc Networks in Bandwidth-Demanding Mission-Critical Applications: Practical Implementation Insights

    KAUST Repository

    Bader, Ahmed

    2016-09-28

    There has been recently a growing trend of using live video feeds in mission-critical applications. Real-time video streaming from front-end personnel or mobile agents is believed to substantially improve situational awareness in mission-critical operations such as disaster relief, law enforcement, and emergency response. Mobile Ad Hoc Networks (MANET) is a natural contender in such contexts. However, classical MANET routing schemes fall short in terms of scalability, bandwidth and latency; all three metrics being quite essential for mission-critical applications. As such, autonomous cooperative routing (ACR) has gained traction as the most viable MANET proposition. Nonetheless, ACR is also associated with a few implementation challenges. If they go unaddressed, will deem ACR practically useless. In this paper, efficient and low-complexity remedies to those issues are presented, analyzed, and validated. The validation is based on field experiments carried out using software-defined radio (SDR) platforms. Compared to classical MANET routing schemes, ACR was shown to offer up to 2X better throughput, more than 4X reduction in end-to-end latency, while observing a given target of transport rate normalized to energy consumption.

  12. Pathways and pipelines: Self-reported critical experiences for expert and novice geologists

    Science.gov (United States)

    LaDue, N.; Pacheco, H. A.

    2011-12-01

    The recruitment and retention of geology students has received attention due to pressure from industry to replenish an aging workforce nearing retirement (Gonzales and Keane, 2010). Thorough, qualitative studies have been conducted using critical incident methodology to understand what experiences cause various groups of people to choose careers in the geosciences or geoscience degree programs (Levine et al., 2007; Houlton, 2010). This study both builds upon earlier studies and provides new insights about capacity building in the geosciences. Individuals who have been successfully pipelined into the geosciences ranging from upper-level undergraduates to decades-long professionals, were selected for an expert-novice study about field mapping. All of the 38 participants have field-mapping experience and were selected to achieve a balance of age, gender and experience in the sample and secondarily based on geographic diversity. Participants were asked how they became interested in geology as the last question of an interview about the other tasks during the study. Participants were surficially probed, in contrast to in-depth interviews conducted using critical incident methods. Remarkably, though the interview question was unstructured and open ended, the three persistent themes that emerged are consistent with previous studies of women geologists (Holmes and O'Connell, 2003), under-represented minorities (Levine et al., 2007), and undergraduate geoscience majors (Houlton, 2010): Role or influence of academic experience, influence of and/or connections with people and connections with Earth. Additionally, individual participant comments are well aligned the proposed framework by Kraft et al. (2011) for engaging geoscience students through the affective domain. We suggest that future studies should examine whether these findings are consistent across geologists from sub-domains that are less field-based and involve primarily modeling, or other computer- and lab

  13. OZCAR: the French network of Critical Zone Observatories: principles and scientific objectives

    Science.gov (United States)

    Braud, Isabelle; Gaillardet, Jérôme; Hankard, Fatim; Le Borgne, Tanguy; Nord, Guillaume; Six, Delphine; Galy, Catherine; Laggoun-Défarge, Fatima; Tallec, Tiphaine; Pauwels, Hélène

    2017-04-01

    This contribution aims at presenting the principles that underlined the creation of the OZCAR research infrastructure, gathering various Critical Zone Observatories in France, and the scientific questions that drives the observation settings. The Critical Zone includes the fine zone between the lower atmosphere at the top of the canopy down to the bedrock-soil interface. This lithosphere-atmosphere boundary is critical for the availability of life-sustaining resources and critical for humanity because this is the zone where we live, where we build our cities, from which we extract our food and our water and where we release most of our wastes. This is the fragile zone on which the natural ecosystem relies because this is where nutrients are being released from the rocks. OZCAR is a distributed research infrastructure gathering instrumented sites and catchments on continental surfaces all dedicated to the observation and monitoring of the different compartments of the Critical Zone at the national scale. All these observatories (more that 40) were all built up on specific questions (acid deposition, flood prediction, urban hydrology…), some of them more than 50 years ago, but they have all in common to be highly instrumented, permanently funded as infrastructures. They all share the same overarching goal of understanding and predicting the Critical Zone in a changing world. OZCAR gathers instrumented catchments, hydrogeological sites, peatlands, glacier and permafrost regions and a spatial observatory under the common umbrella of understanding water and biogeochemical cycles and the associated fluxes of energy by using natural gradients and experimentation. Based on the collaboration with Southern Countries, OZCAR's sites have a global coverage including tropical areas and high mountainous regions in the Andes and the Himalaya. OZCAR benefits from a French investments project called CRITEX (Innovative equipment for the critical zone, https://www.critex.fr/critex-3

  14. Gene networks and toxicity pathways induced by acute cadmium exposure in adult largemouth bass (Micropterus salmoides)

    Energy Technology Data Exchange (ETDEWEB)

    Mehinto, Alvine C., E-mail: alvinam@sccwrp.org [Southern California Coastal Water Research Project, Costa Mesa, CA 92626 (United States); Department of Physiological Sciences and Center for Environmental and Human Toxicology, University of Florida, Gainesville, FL 32611 (United States); Prucha, Melinda S. [Department of Human Genetics, Yerkes National Primate Research Center, Emory University, Atlanta, GA 30322 (United States); Department of Physiological Sciences and Center for Environmental and Human Toxicology, University of Florida, Gainesville, FL 32611 (United States); Colli-Dula, Reyna C.; Kroll, Kevin J.; Lavelle, Candice M.; Barber, David S. [Department of Physiological Sciences and Center for Environmental and Human Toxicology, University of Florida, Gainesville, FL 32611 (United States); Vulpe, Christopher D. [Department of Nutritional Sciences and Toxicology, University of California, Berkeley, CA 94720 (United States); Denslow, Nancy D. [Department of Physiological Sciences and Center for Environmental and Human Toxicology, University of Florida, Gainesville, FL 32611 (United States)

    2014-07-01

    Highlights: • Low-level acute cadmium exposure elicited tissue-specific gene expression changes. • Molecular initiating events included oxidative stress and disruption of DNA repair. • Metallothionein, a marker of metal exposure, was not significantly affected. • We report effects of cadmium on cholesterol metabolism and steroid synthesis. • Diabetic complications and impaired reproduction are potential adverse outcomes. - Abstract: Cadmium is a heavy metal that can accumulate to toxic levels in the environment leading to detrimental effects in animals and humans including kidney, liver and lung injuries. Using a transcriptomics approach, genes and cellular pathways affected by a low dose of cadmium were investigated. Adult largemouth bass were intraperitoneally injected with 20 μg/kg of cadmium chloride (mean exposure level – 2.6 μg of cadmium per fish) and microarray analyses were conducted in the liver and testis 48 h after injection. Transcriptomic profiles identified in response to cadmium exposure were tissue-specific with the most differential expression changes found in the liver tissues, which also contained much higher levels of cadmium than the testis. Acute exposure to a low dose of cadmium induced oxidative stress response and oxidative damage pathways in the liver. The mRNA levels of antioxidants such as catalase increased and numerous transcripts related to DNA damage and DNA repair were significantly altered. Hepatic mRNA levels of metallothionein, a molecular marker of metal exposure, did not increase significantly after 48 h exposure. Carbohydrate metabolic pathways were also disrupted with hepatic transcripts such as UDP-glucose, pyrophosphorylase 2, and sorbitol dehydrogenase highly induced. Both tissues exhibited a disruption of steroid signaling pathways. In the testis, estrogen receptor beta and transcripts linked to cholesterol metabolism were suppressed. On the contrary, genes involved in cholesterol metabolism were highly

  15. A Systems Biology Analysis Unfolds the Molecular Pathways and Networks of Two Proteobacteria in Spaceflight and Simulated Microgravity Conditions

    Science.gov (United States)

    Roy, Raktim; Phani Shilpa, P.; Bagh, Sangram

    2016-09-01

    Bacteria are important organisms for space missions due to their increased pathogenesis in microgravity that poses risks to the health of astronauts and for projected synthetic biology applications at the space station. We understand little about the effect, at the molecular systems level, of microgravity on bacteria, despite their significant incidence. In this study, we proposed a systems biology pipeline and performed an analysis on published gene expression data sets from multiple seminal studies on Pseudomonas aeruginosa and Salmonella enterica serovar Typhimurium under spaceflight and simulated microgravity conditions. By applying gene set enrichment analysis on the global gene expression data, we directly identified a large number of new, statistically significant cellular and metabolic pathways involved in response to microgravity. Alteration of metabolic pathways in microgravity has rarely been reported before, whereas in this analysis metabolic pathways are prevalent. Several of those pathways were found to be common across studies and species, indicating a common cellular response in microgravity. We clustered genes based on their expression patterns using consensus non-negative matrix factorization. The genes from different mathematically stable clusters showed protein-protein association networks with distinct biological functions, suggesting the plausible functional or regulatory network motifs in response to microgravity. The newly identified pathways and networks showed connection with increased survival of pathogens within macrophages, virulence, and antibiotic resistance in microgravity. Our work establishes a systems biology pipeline and provides an integrated insight into the effect of microgravity at the molecular systems level.

  16. Barriers, pathways and processes for uptake, translocation and accumulation of nanomaterials in plants--Critical review.

    Science.gov (United States)

    Schwab, Fabienne; Zhai, Guangshu; Kern, Meaghan; Turner, Amalia; Schnoor, Jerald L; Wiesner, Mark R

    2016-01-01

    Uptake, transport and toxicity of engineered nanomaterials (ENMs) into plant cells are complex processes that are currently still not well understood. Parts of this problem are the multifaceted plant anatomy, and analytical challenges to visualize and quantify ENMs in plants. We critically reviewed the currently known ENM uptake, translocation, and accumulation processes in plants. A vast number of studies showed uptake, clogging, or translocation in the apoplast of plants, most notably of nanoparticles with diameters much larger than the commonly assumed size exclusion limit of the cell walls of ∼5-20 nm. Plants that tended to translocate less ENMs were those with low transpiration, drought-tolerance, tough cell wall architecture, and tall growth. In the absence of toxicity, accumulation was often linearly proportional to exposure concentration. Further important factors strongly affecting ENM internalization are the cell wall composition, mucilage, symbiotic microorganisms (mycorrhiza), the absence of a cuticle (submerged plants) and stomata aperture. Mostly unexplored are the roles of root hairs, leaf repellency, pit membrane porosity, xylem segmentation, wounding, lateral roots, nodes, the Casparian band, hydathodes, lenticels and trichomes. The next steps towards a realistic risk assessment of nanoparticles in plants are to measure ENM uptake rates, the size exclusion limit of the apoplast and to unravel plant physiological features favoring uptake.

  17. Target inhibition networks: predicting selective combinations of druggable targets to block cancer survival pathways.

    Directory of Open Access Journals (Sweden)

    Jing Tang

    Full Text Available A recent trend in drug development is to identify drug combinations or multi-target agents that effectively modify multiple nodes of disease-associated networks. Such polypharmacological effects may reduce the risk of emerging drug resistance by means of attacking the disease networks through synergistic and synthetic lethal interactions. However, due to the exponentially increasing number of potential drug and target combinations, systematic approaches are needed for prioritizing the most potent multi-target alternatives on a global network level. We took a functional systems pharmacology approach toward the identification of selective target combinations for specific cancer cells by combining large-scale screening data on drug treatment efficacies and drug-target binding affinities. Our model-based prediction approach, named TIMMA, takes advantage of the polypharmacological effects of drugs and infers combinatorial drug efficacies through system-level target inhibition networks. Case studies in MCF-7 and MDA-MB-231 breast cancer and BxPC-3 pancreatic cancer cells demonstrated how the target inhibition modeling allows systematic exploration of functional interactions between drugs and their targets to maximally inhibit multiple survival pathways in a given cancer type. The TIMMA prediction results were experimentally validated by means of systematic siRNA-mediated silencing of the selected targets and their pairwise combinations, showing increased ability to identify not only such druggable kinase targets that are essential for cancer survival either individually or in combination, but also synergistic interactions indicative of non-additive drug efficacies. These system-level analyses were enabled by a novel model construction method utilizing maximization and minimization rules, as well as a model selection algorithm based on sequential forward floating search. Compared with an existing computational solution, TIMMA showed both enhanced

  18. Expression-based network biology identifies alteration in key regulatory pathways of type 2 diabetes and associated risk/complications.

    Directory of Open Access Journals (Sweden)

    Urmi Sengupta

    Full Text Available Type 2 diabetes mellitus (T2D is a multifactorial and genetically heterogeneous disease which leads to impaired glucose homeostasis and insulin resistance. The advanced form of disease causes acute cardiovascular, renal, neurological and microvascular complications. Thus there is a constant need to discover new and efficient treatment against the disease by seeking to uncover various novel alternate signalling mechanisms that can lead to diabetes and its associated complications. The present study allows detection of molecular targets by unravelling their role in altered biological pathways during diabetes and its associated risk factors and complications. We have used an integrated functional networks concept by merging co-expression network and interaction network to detect the transcriptionally altered pathways and regulations involved in the disease. Our analysis reports four novel significant networks which could lead to the development of diabetes and other associated dysfunctions. (a The first network illustrates the up regulation of TGFBRII facilitating oxidative stress and causing the expression of early transcription genes via MAPK pathway leading to cardiovascular and kidney related complications. (b The second network demonstrates novel interactions between GAPDH and inflammatory and proliferation candidate genes i.e., SUMO4 and EGFR indicating a new link between obesity and diabetes. (c The third network portrays unique interactions PTPN1 with EGFR and CAV1 which could lead to an impaired vascular function in diabetic nephropathy condition. (d Lastly, from our fourth network we have inferred that the interaction of beta-catenin with CDH5 and TGFBR1 through Smad molecules could contribute to endothelial dysfunction. A probability of emergence of kidney complication might be suggested in T2D condition. An experimental investigation on this aspect may further provide more decisive observation in drug target identification and better

  19. Integrated miRNA-risk gene-pathway pair network analysis provides prognostic biomarkers for gastric cancer

    Directory of Open Access Journals (Sweden)

    Cai H

    2016-05-01

    Full Text Available Hui Cai,1 Jiping Xu,2 Yifang Han,3 Zhengmao Lu,1 Ting Han,1 Yibo Ding,4 Liye Ma1 1Department of General Surgery, Changhai Hospital, Second Military Medical University, Shanghai, 2Department of Medical Administration, Changhai Hospital, Second Military Medical University, Shanghai, 3Department of Epidemiology, Research Institute for Medicine of Nanjing Command, Nanjing, 4Department of Epidemiology, Changhai Hospital, Second Military Medical University, Shanghai, People’s Republic of China Purpose: This study aimed to identify molecular prognostic biomarkers for gastric cancer. Methods: mRNA and miRNA expression profiles of eligible gastric cancer and control samples were downloaded from Gene Expression Omnibus to screen the differentially expressed genes (DEGs and differentially expressed miRNAs (DEmiRs, using MetaDE and limma packages, respectively. Target genes of the DEmiRs were also collected from both predictive and experimentally validated target databases of miRNAs. The overlapping genes between selected targets and DEGs were identified as risk genes, followed by functional enrichment analysis. Human pathways and their corresponding genes were downloaded from the Kyoto Encyclopedia of Genes and Genomes (KEGG database for the expression analysis of each pathway in gastric cancer samples. Next, co-pathway pairs were selected according to the Pearson correlation coefficients. Finally, the co-pathway pairs, miRNA–target pairs, and risk gene–pathway pairs were merged into a complex interaction network, the most important nodes (miRNAs/target genes/co-pathway pairs of which were selected by calculating their degrees.Results: Totally, 1,260 DEGs and 144 DEmiRs were identified. There were 336 risk genes found in the 9,572 miRNA–target pairs. Judging from the pathway expression files, 45 co-pathway pairs were screened out. There were 1,389 interactive pairs and 480 nodes in the integrated network. Among all nodes in the network, focal

  20. A Systems Biology Analysis Unfolds the Molecular Pathways and Networks of Two Proteobacteria in Spaceflight and Simulated Microgravity Conditions.

    Science.gov (United States)

    Roy, Raktim; Shilpa, P Phani; Bagh, Sangram

    2016-09-01

    Bacteria are important organisms for space missions due to their increased pathogenesis in microgravity that poses risks to the health of astronauts and for projected synthetic biology applications at the space station. We understand little about the effect, at the molecular systems level, of microgravity on bacteria, despite their significant incidence. In this study, we proposed a systems biology pipeline and performed an analysis on published gene expression data sets from multiple seminal studies on Pseudomonas aeruginosa and Salmonella enterica serovar Typhimurium under spaceflight and simulated microgravity conditions. By applying gene set enrichment analysis on the global gene expression data, we directly identified a large number of new, statistically significant cellular and metabolic pathways involved in response to microgravity. Alteration of metabolic pathways in microgravity has rarely been reported before, whereas in this analysis metabolic pathways are prevalent. Several of those pathways were found to be common across studies and species, indicating a common cellular response in microgravity. We clustered genes based on their expression patterns using consensus non-negative matrix factorization. The genes from different mathematically stable clusters showed protein-protein association networks with distinct biological functions, suggesting the plausible functional or regulatory network motifs in response to microgravity. The newly identified pathways and networks showed connection with increased survival of pathogens within macrophages, virulence, and antibiotic resistance in microgravity. Our work establishes a systems biology pipeline and provides an integrated insight into the effect of microgravity at the molecular systems level. Systems biology-Microgravity-Pathways and networks-Bacteria. Astrobiology 16, 677-689.

  1. Pathway Detection from Protein Interaction Networks and Gene Expression Data Using Color-Coding Methods and A* Search Algorithms

    Directory of Open Access Journals (Sweden)

    Cheng-Yu Yeh

    2012-01-01

    Full Text Available With the large availability of protein interaction networks and microarray data supported, to identify the linear paths that have biological significance in search of a potential pathway is a challenge issue. We proposed a color-coding method based on the characteristics of biological network topology and applied heuristic search to speed up color-coding method. In the experiments, we tested our methods by applying to two datasets: yeast and human prostate cancer networks and gene expression data set. The comparisons of our method with other existing methods on known yeast MAPK pathways in terms of precision and recall show that we can find maximum number of the proteins and perform comparably well. On the other hand, our method is more efficient than previous ones and detects the paths of length 10 within 40 seconds using CPU Intel 1.73GHz and 1GB main memory running under windows operating system.

  2. Networks of Power and Privilege: A Critical Discourse Analysis of the US Next Generation Science Standards

    Science.gov (United States)

    Satchithananthamoorthy, Hindurika

    Science holds significant power in shaping many of our everyday choices. Thus, it is important for science education to foster the development of scientific literacy for all students, so that they can navigate science-related issues in their daily lives. This study carries out a critical discourse analysis of the US Next Generation Science Standards (NGSS) through an actor network theory framework to explore how the NGSS document is shaping the discourse of science education. The findings of this study show that the NGSS delivers a highly technocratic document that leaves little room for democratic engagement. It seems to place an emphasis on science education that is necessary for entry into STEM fields. The NGSS appears to have co-opted the notion of a "science for all" approach to push a neoliberal agenda of science education that serves to fuel the economic market and privileges a select few.

  3. Developing Critical Thinking Skills through Interactive Radio Programs (IRPs: Building Online Knowledge Networks In Distance Education

    Directory of Open Access Journals (Sweden)

    Gulsun KURUBACAK

    2005-07-01

    Full Text Available ABSTRACT In considering how best to optimize distance education systems, economy (cost effectiveness and efficiency, technology (communication technologies and equity (gender, accessibility, minority, language, religion etc. are vital issues in any distance education systems. Moreover, how end-users, distance learners, can equally share and exchange knowledge and resources for educational purposes, how they can promote their higher-order thinking skills as well as how they can cope with the limitations they have (such as time, age, gender, language etc. are major concerns in distance education milieus. Kurubacak strongly emphasize that interactive radio programs, as a forgotten educational media, with a little cost can effectively integrate in any distance education systems. Therefore, the main purpose of this paper is to focus on interactive radio programs to build critical and creative knowledge networks among diverse learners in the distance education systems of developing countries.

  4. Fracture network, fluid pathways and paleostress at the Tolhuaca geothermal field

    Science.gov (United States)

    Pérez-Flores, Pamela; Veloso, Eugenio; Cembrano, José; Sánchez-Alfaro, Pablo; Lizama, Martín; Arancibia, Gloria

    2017-03-01

    In this study, we examine the fracture network of the Tolhuaca geothermal system located in the Southern Andean volcanic zone that may have acted as a pathway for migration and ascent of deep-seated fluids under the far/local stress field conditions of the area. We collected the orientation, slip-data and mineralogical content of faults and veins recovered on a ca. 1000 m deep borehole (Tol-1) located in the NW-flank of the Tolhuaca volcano. Tol-1 is a non-oriented, vertical borehole that recovered relatively young (50°) dips. The EW-striking veins are compatible with the calculated local stress field whereas NE-striking veins are compatible with the regional stress field, the morphological elongation of volcanic centers, alignments of flank vents and dikes orientation. Our results demonstrate that the paleomagnetic methodology proved to be reliable and it is useful to re-orient vertical boreholes such as Tol-1. Furthermore, our data show that the bulk transpressional regional stress field has local variations to a tensional stress field within the NE-striking fault zone belonging to the Liquiñe-Ofqui Fault System, favoring the activation of both NW- and NE-striking pre-existent discontinuities, especially the latter which are favorably oriented to open under the prevailing stress field. The vertical σ1 and NS-trending subhorizontal σ3 calculated in the TGS promote the activation of EW-striking extensional veins and both NE and NW-striking hybrid faults, constituting a complex fluid pathway geometry of at least one kilometer depth.

  5. Unravelling the architecture and dynamics of tropane alkaloid biosynthesis pathways using metabolite correlation networks.

    Science.gov (United States)

    Nguyen, Thi-Kieu-Oanh; Jamali, Arash; Lanoue, Arnaud; Gontier, Eric; Dauwe, Rebecca

    2015-08-01

    The tropane alkaloid spectrum in Solanaceae is highly variable within and between species. Little is known about the topology and the coordination of the biosynthetic pathways leading to the variety of tropine and pseudotropine derived esters in the alkaloid spectrum, or about the metabolic dynamics induced by tropane alkaloid biosynthesis stimulating conditions. A good understanding of the metabolism, including all ramifications, is however necessary for the development of strategies to increase the abundance of pharmacologically interesting compounds such as hyoscyamine and scopolamine. The present study explores the tropane alkaloid metabolic pathways in an untargeted approach involving a correlation-based network analysis. Using GC-MS metabolite profiling, the variation and co-variation among tropane alkaloids and primary metabolites was monitored in 60 Datura innoxia Mill. individuals, of which half were exposed to tropane alkaloid biosynthesis stimulating conditions by co-culture with Agrobacterium rhizogenes. Considerable variation was evident in the relative proportions of the tropane alkaloids. Remodeling of the tropane alkaloid spectrum under co-culture with A. rhizogenes involved a specific and strong increase of hyoscyamine production and revealed that the accumulation of hyoscyamine, 3-tigloyloxy-6,7-epoxytropane, and 3-methylbutyryloxytropane was controlled independently of the majority of tropane alkaloids. Based on correlations between metabolites, we propose a biosynthetic origin of hygrine, the order of esterification of certain di-oxygenated tropanes, and that the rate of acetoxylation contributes to control of hyoscyamine production. Overall, this study shows that the biosynthesis of tropane alkaloids may be far more complex and finely controlled than previously expected. Copyright © 2015 Elsevier Ltd. All rights reserved.

  6. Stormwater management network effectiveness and implications for urban watershed function: A critical review

    Science.gov (United States)

    Jefferson, Anne J.; Bhaskar, Aditi S.; Hopkins, Kristina G.; Fanelli, Rosemary; Avellaneda, Pedro M.; McMillan, Sara K.

    2017-01-01

    Deleterious effects of urban stormwater are widely recognized. In several countries, regulations have been put into place to improve the conditions of receiving water bodies, but planning and engineering of stormwater control is typically carried out at smaller scales. Quantifying cumulative effectiveness of many stormwater control measures on a watershed scale is critical to understanding how small-scale practices translate to urban river health. We review 100 empirical and modelling studies of stormwater management effectiveness at the watershed scale in diverse physiographic settings. Effects of networks with stormwater control measures (SCMs) that promote infiltration and harvest have been more intensively studied than have detention-based SCM networks. Studies of peak flows and flow volumes are common, whereas baseflow, groundwater recharge, and evapotranspiration have received comparatively little attention. Export of nutrients and suspended sediments have been the primary water quality focus in the United States, whereas metals, particularly those associated with sediments, have received greater attention in Europe and Australia. Often, quantifying cumulative effects of stormwater management is complicated by needing to separate its signal from the signal of urbanization itself, innate watershed characteristics that lead to a range of hydrologic and water quality responses, and the varying functions of multiple types of SCMs. Biases in geographic distribution of study areas, and size and impervious surface cover of watersheds studied also limit our understanding of responses. We propose hysteretic trajectories for how watershed function responds to increasing imperviousness and stormwater management. Even where impervious area is treated with SCMs, watershed function may not be restored to its predevelopment condition because of the lack of treatment of all stormwater generated from impervious surfaces; non-additive effects of individual SCMs; and

  7. Critical tipping point distinguishing two types of transitions in modular network structures.

    Science.gov (United States)

    Shai, Saray; Kenett, Dror Y; Kenett, Yoed N; Faust, Miriam; Dobson, Simon; Havlin, Shlomo

    2015-12-01

    Modularity is a key organizing principle in real-world large-scale complex networks. The relatively sparse interactions between modules are critical to the functionality of the system and are often the first to fail. We model such failures as site percolation targeting interconnected nodes, those connecting between modules. We find, using percolation theory and simulations, that they lead to a "tipping point" between two distinct regimes. In one regime, removal of interconnected nodes fragments the modules internally and causes the system to collapse. In contrast, in the other regime, while only attacking a small fraction of nodes, the modules remain but become disconnected, breaking the entire system. We show that networks with broader degree distribution might be highly vulnerable to such attacks since only few nodes are needed to interconnect the modules, consequently putting the entire system at high risk. Our model has the potential to shed light on many real-world phenomena, and we briefly consider its implications on recent advances in the understanding of several neurocognitive processes and diseases.

  8. Critical space-time networks and geometric phase transitions from frustrated edge antiferromagnetism.

    Science.gov (United States)

    Trugenberger, Carlo A

    2015-12-01

    Recently I proposed a simple dynamical network model for discrete space-time that self-organizes as a graph with Hausdorff dimension d(H)=4. The model has a geometric quantum phase transition with disorder parameter (d(H)-d(s)), where d(s) is the spectral dimension of the dynamical graph. Self-organization in this network model is based on a competition between a ferromagnetic Ising model for vertices and an antiferromagnetic Ising model for edges. In this paper I solve a toy version of this model defined on a bipartite graph in the mean-field approximation. I show that the geometric phase transition corresponds exactly to the antiferromagnetic transition for edges, the dimensional disorder parameter of the former being mapped to the staggered magnetization order parameter of the latter. The model has a critical point with long-range correlations between edges, where a continuum random geometry can be defined, exactly as in Kazakov's famed 2D random lattice Ising model but now in any number of dimensions.

  9. Sub-critical crack growth in silicate glasses: Role of network topology

    Science.gov (United States)

    Smedskjaer, Morten M.; Bauchy, Mathieu

    2015-10-01

    The presence of water in the surrounding atmosphere can cause sub-critical crack growth (SCCG) in glasses, a phenomenon known as fatigue or stress corrosion. Here, to facilitate the compositional design of more fatigue-resistant glasses, we investigate the composition dependence of SCCG by studying fourteen silicate glasses. The fatigue curves (V-KI) have been obtained by indentation experiments through measurements of the crack length as a function of post-indentation fatigue duration. Interestingly, we find that the fatigue resistance parameter N is generally improved by increasing the alumina content and is thereby found to exhibit a fairly linear dependence on the measured Vickers hardness HV for a wide range of N and HV values. This finding highlights the important role of network topology in governing the SCCG in silicate glasses, since hardness has been shown to scale linearly with the number of atomic constraints. Our results therefore suggest that glasses showing under-constrained flexible networks, which feature floppy internal modes of deformation, are more readily attacked by water molecules, thus promoting stress corrosion and reducing the fatigue resistance.

  10. Group B streptococcal infection of the choriodecidua induces dysfunction of the cytokeratin network in amniotic epithelium: a pathway to membrane weakening.

    Directory of Open Access Journals (Sweden)

    Jeroen P Vanderhoeven

    2014-03-01

    Full Text Available Early events leading to intrauterine infection remain poorly defined, but may hold the key to preventing preterm delivery. To determine molecular pathways within fetal membranes (chorioamnion associated with early choriodecidual infection that may progress to preterm premature rupture of membranes (PPROM, we examined the effects of a Group B Streptococcus (GBS choriodecidual infection on chorioamnion in a nonhuman primate model. Ten chronically catheterized pregnant monkeys (Macaca nemestrina at 118-125 days gestation (term = 172 days received choriodecidual inoculation of either GBS (n = 5 or saline (n = 5. Cesarean section was performed in the first week after GBS or saline inoculation. RNA extracted from chorioamnion (inoculation site was profiled by microarray. Single gene, Gene Set, and Ingenuity Pathway Analysis results were validated using qRT-PCR (chorioamnion, Luminex (amniotic fluid, AF, immunohistochemistry, and transmission electron microscopy (TEM. Despite uterine quiescence in most cases, significant elevations of AF cytokines (TNF-α, IL-8, IL-1β, IL-6 were detected in GBS versus controls (p2-fold change, p<0.05. Remarkably, GBS exposure was associated with significantly downregulated expression of multiple cytokeratin (CK and other cytoskeletal genes critical for maintenance of tissue tensile strength. Immunofluorescence revealed highly significant changes in the CK network within amniocytes with dense CK aggregates and retraction from the cell periphery (all p = 0.006. In human pregnancies affected by PPROM, there was further evidence of CK network retraction with significantly shorter amniocyte foot processes (p = 0.002. These results suggest early choriodecidual infection results in decreased cellular membrane integrity and tensile strength via dysfunction of CK networks. Downregulation of CK expression and perturbations in the amniotic epithelial cell intermediate filament network occur after GBS

  11. Identification of significant pathways in gastric cancer based on protein-protein interaction networks and cluster analysis

    Directory of Open Access Journals (Sweden)

    Kongwang Hu

    2012-01-01

    Full Text Available Gastric cancer is one of the most common and lethal cancers worldwide. However, despite its clinical importance, the regulatory mechanisms involved in the aggressiveness of this cancer are still poorly understood. A better understanding of the biology, genetics and molecular mechanisms of gastric cancer would be useful in developing novel targeted approaches for treating this disease. In this study we used protein-protein interaction networks and cluster analysis to comprehensively investigate the cellular pathways involved in gastric cancer. A primary immunodeficiency pathway, focal adhesion, ECM-receptor interactions and the metabolism of xenobiotics by cytochrome P450 were identified as four important pathways associated with the progression of gastric cancer. The genes in these pathways, e.g., ZAP70, IGLL1, CD79A, COL6A3, COL3A1, COL1A1, CYP2C18 and CYP2C9, may be considered as potential therapeutic targets for gastric cancer.

  12. Integrated control of wind farms, FACTS devices and the power network using neural networks and adaptive critic designs

    Science.gov (United States)

    Qiao, Wei

    Worldwide concern about the environmental problems and a possible energy crisis has led to increasing interest in clean and renewable energy generation. Among various renewable energy sources, wind power is the most rapidly growing one. Therefore, how to provide efficient, reliable, and high-performance wind power generation and distribution has become an important and practical issue in the power industry. In addition, because of the new constraints placed by the environmental and economical factors, the trend of power system planning and operation is toward maximum utilization of the existing infrastructure with tight system operating and stability margins. This trend, together with the increased penetration of renewable energy sources, will bring new challenges to power system operation, control, stability and reliability which require innovative solutions. Flexible ac transmission system (FACTS) devices, through their fast, flexible, and effective control capability, provide one possible solution to these challenges. To fully utilize the capability of individual power system components, e.g., wind turbine generators (WTGs) and FACTS devices, their control systems must be suitably designed with high reliability. Moreover, in order to optimize local as well as system-wide performance and stability of the power system, real-time local and wide-area coordinated control is becoming an important issue. Power systems containing conventional synchronous generators, WTGs, and FACTS devices are large-scale, nonlinear, nonstationary, stochastic and complex systems distributed over large geographic areas. Traditional mathematical tools and system control techniques have limitations to control such complex systems to achieve an optimal performance. Intelligent and bio-inspired techniques, such as swarm intelligence, neural networks, and adaptive critic designs, are emerging as promising alternative technologies for power system control and performance optimization. This

  13. Generate networks with power-law and exponential-law distributed degrees: with applications in link prediction of tumor pathways

    Directory of Open Access Journals (Sweden)

    WenJun Zhang

    2016-03-01

    Full Text Available In present study I proposed a method for generating biological networks based on power-law (p(x=x^(-a and exponential-law (p(x=e^(-ax distribution functions. Given the parameter of power-law or exponential-law distribution function, a, the algorithm generates an expected frequency distribution according to the given parameter, thereafter creates an adjacency matrix in which (practical frequency distribution of node degrees matches the expected frequency distribution. The results showed that power-law distribution function performs much better than exponential-law distribution function in generating networks. Using the revised algorithm, tumor related networks (pathways are simulated and predicted. The results prove that the algorithm is overall effective in predicting network links (14.6%-21.2%of correctly predicted links against 0.1%-3.4% of that for random assignments. Matlab codes of the algorithms are given also.

  14. Social networks on both sides of the transition point A research commentary on "Critical mass and willingness to pay for social networks" by J. Christopher Westland

    NARCIS (Netherlands)

    Smith-David, Julie

    2010-01-01

    Westland's article provides an excellent foundational understanding of the percolation theory and how it can be applied to understand achieving "critical mass" in social networks. This commentary introduces extensions to the percolation theory that have been developed while studying sea ice, and

  15. Developmental transcriptomic analyses for mechanistic insights into critical pathways involved in embryogenesis of pelagic mahi-mahi (Coryphaena hippurus.

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    Elvis Genbo Xu

    Full Text Available Mahi-mahi (Coryphaena hippurus is a commercially and ecologically important species of fish occurring in tropical and temperate waters worldwide. Understanding early life events is crucial for predicting effects of environmental stress, which is largely restricted by a lack of genetic resources regarding expression of early developmental genes and regulation of pathways. The need for anchoring developmental stages to transcriptional activities is highlighted by increasing evidence on the impacts of recurrent worldwide oil spills in this sensitive species during early development. By means of high throughput sequencing, we characterized the developmental transcriptome of mahi-mahi at three critical developmental stages, from pharyngula embryonic stage (24 hpf to 48 hpf yolk-sac larva (transition 1, and to 96 hpf free-swimming larva (transition 2. With comparative analysis by multiple bioinformatic tools, a larger number of significantly altered genes and more diverse gene ontology terms were observed during transition 2 than transition 1. Cellular and tissue development terms were more significantly enriched in transition 1, while metabolism related terms were more enriched in transition 2, indicating a switch progressing from general embryonic development to metabolism during the two transitions. Special focus was given on the most significant common canonical pathways (e.g. calcium signaling, glutamate receptor signaling, cAMP response element-binding protein signaling, cardiac β-adrenergic signaling, etc. and expression of developmental genes (e.g. collagens, myosin, notch, glutamate metabotropic receptor etc., which were associated with morphological changes of nervous, muscular, and cardiovascular system. These data will provide an important basis for understanding embryonic development and identifying molecular mechanisms of abnormal development in fish species.

  16. Several Critical Cell Types, Tissues, and Pathways Are Implicated in Genome-Wide Association Studies for Systemic Lupus Erythematosus

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    Lu Liu

    2016-06-01

    Full Text Available We aimed to elucidate the cell types, tissues, and pathways influenced by common variants in systemic lupus erythematosus (SLE. We applied a nonparameter enrichment statistical approach, termed SNPsea, in 181 single nucleotide polymorphisms (SNPs that have been identified to be associated with the risk of SLE through genome-wide association studies (GWAS in Eastern Asian and Caucasian populations, to manipulate the critical cell types, tissues, and pathways. In the two most significant cells’ findings (B lymphocytes and CD14+ monocytes, we subjected the GWAS association evidence in the Han Chinese population to an enrichment test of expression quantitative trait locus (QTL sites and DNase I hypersensitivity, respectively. In both Eastern Asian and Caucasian populations, we observed that the expression level of SLE GWAS implicated genes was significantly elevated in xeroderma pigentosum B cells (P ≤ 1.00 × 10−6, CD14+ monocytes (P ≤ 2.74 × 10−4 and CD19+ B cells (P ≤ 2.00 × 10−6, and plasmacytoid dendritic cells (pDCs (P ≤ 9.00 × 10−6. We revealed that the SLE GWAS-associated variants were more likely to reside in expression QTL in B lymphocytes (q1/q0 = 2.15, P = 1.23 × 10−44 and DNase I hypersensitivity sites (DHSs in CD14+ monocytes (q1/q0 = 1.41, P = 0.08. We observed the common variants affected the risk of SLE mostly through by regulating multiple immune system processes and immune response signaling. This study sheds light on several immune cells and responses, as well as the regulatory effect of common variants in the pathogenesis of SLE.

  17. Modeling most likely pathways for smuggling radioactive and special nuclear materials on a worldwide multi-modal transportation network

    Energy Technology Data Exchange (ETDEWEB)

    Saeger, Kevin J [Los Alamos National Laboratory; Cuellar, Leticia [Los Alamos National Laboratory

    2010-10-28

    Nuclear weapons proliferation is an existing and growing worldwide problem. To help with devising strategies and supporting decisions to interdict the transport of nuclear material, we developed the Pathway Analysis, Threat Response and Interdiction Options Tool (PATRIOT) that provides an analytical approach for evaluating the probability that an adversary smuggling radioactive or special nuclear material will be detected during transit. We incorporate a global, multi-modal transportation network, explicit representation of designed and serendipitous detection opportunities, and multiple threat devices, material types, and shielding levels. This paper presents the general structure of PATRIOT, all focuses on the theoretical framework used to model the reliabilities of all network components that are used to predict the most likely pathways to the target.

  18. Modeling most likely pathways for smuggling radioactive and special nuclear materials on a worldwide multimodal transportation network

    Energy Technology Data Exchange (ETDEWEB)

    Saeger, Kevin J [Los Alamos National Laboratory; Cuellar, Leticia [Los Alamos National Laboratory

    2010-01-01

    Nuclear weapons proliferation is an existing and growing worldwide problem. To help with devising strategies and supporting decisions to interdict the transport of nuclear material, we developed the Pathway Analysis, Threat Response and Interdiction Options Tool (PATRIOT) that provides an analytical approach for evaluating the probability that an adversary smuggling radioactive or special nuclear material will be detected during transit. We incorporate a global, multi-modal transportation network, explicit representation of designed and serendipitous detection opportunities, and multiple threat devices, material types, and shielding levels. This paper presents the general structure of PATRIOT, and focuses on the theoretical framework used to model the reliabilities of all network components that are used to predict the most likely pathways to the target.

  19. Reply to the first systematic response by the Global Footprint Network to criticism: A real debate finally?

    NARCIS (Netherlands)

    van den Bergh, J.C.J.M.; Grazi, F.

    2015-01-01

    Abstract We respond to a reaction of the Global Footprint Network/GFN on our 8-point criticism of the ecological footprint. We also refer to, and comment on, an associated debate in this journal between Giampietro and Saltelli (2014a, 2014b), on the one hand, and Goldfinger et al. (2014), on the

  20. Pathway-based network modeling finds hidden genes in shRNA screen for regulators of acute lymphoblastic leukemia.

    Science.gov (United States)

    Wilson, Jennifer L; Dalin, Simona; Gosline, Sara; Hemann, Michael; Fraenkel, Ernest; Lauffenburger, Douglas A

    2016-07-11

    Data integration stands to improve interpretation of RNAi screens which, as a result of off-target effects, typically yield numerous gene hits of which only a few validate. These off-target effects can result from seed matches to unintended gene targets (reagent-based) or cellular pathways, which can compensate for gene perturbations (biology-based). We focus on the biology-based effects and use network modeling tools to discover pathways de novo around RNAi hits. By looking at hits in a functional context, we can uncover novel biology not identified from any individual 'omics measurement. We leverage multiple 'omic measurements using the Simultaneous Analysis of Multiple Networks (SAMNet) computational framework to model a genome scale shRNA screen investigating Acute Lymphoblastic Leukemia (ALL) progression in vivo. Our network model is enriched for cellular processes associated with hematopoietic differentiation and homeostasis even though none of the individual 'omic sets showed this enrichment. The model identifies genes associated with the TGF-beta pathway and predicts a role in ALL progression for many genes without this functional annotation. We further experimentally validate the hidden genes - Wwp1, a ubiquitin ligase, and Hgs, a multi-vesicular body associated protein - for their role in ALL progression. Our ALL pathway model includes genes with roles in multiple types of leukemia and roles in hematological development. We identify a tumor suppressor role for Wwp1 in ALL progression. This work demonstrates that network integration approaches can compensate for off-target effects, and that these methods can uncover novel biology retroactively on existing screening data. We anticipate that this framework will be valuable to multiple functional genomic technologies - siRNA, shRNA, and CRISPR - generally, and will improve the utility of functional genomic studies.

  1. Catchment organisation, free energy dynamics and network control on critical zone water flows

    Science.gov (United States)

    Zehe, E.; Ehret, U.; Kleidon, A.; Jackisch, C.; Scherer, U.; Blume, T.

    2012-04-01

    as that these flow structures organize and dominate flows of water, dissolved matter and sediments during rainfall driven conditions at various scales: - Surface connected vertical flow structures of anecic worm burrows or soil cracks organize and dominated vertical flows at the plot scale - this is usually referred to as preferential flow; - Rill networks at the soil surface organise and dominate hillslope scale overland flow response and sediment yields; - Subsurface pipe networks at the bedrock interface organize and dominate hillslope scale lateral subsurface water and tracer flows; - The river net organizes and dominates flows of water, dissolved matter and sediments to the catchment outlet and finally across continental gradients to the sea. Fundamental progress with respect to the parameterization of hydrological models, subscale flow networks and to understand the adaptation of hydro-geo ecosystems to change could be achieved by discovering principles that govern the organization of catchments flow networks in particular at least during steady state conditions. This insight has inspired various scientists to suggest principles for organization of ecosystems, landscapes and flow networks; as Bejans constructural law, Minimum Energy Expenditure , Maximum Entropy Production. In line with these studies we suggest that a thermodynamic/energetic treatment of the catchment is might be a key for understanding the underlying principles that govern organisation of flow and transport. Our approach is to employ a) physically based hydrological model that address at least all the relevant hydrological processes in the critical zone in a coupled way, behavioural representations of the observed organisation of flow structures and textural elements, that are consistent with observations in two well investigated research catchments and have been tested against distributed observations of soil moisture and catchment scale discharge; to simulate the full concert of hydrological

  2. Avalanches in self-organized critical neural networks: a minimal model for the neural SOC universality class.

    Directory of Open Access Journals (Sweden)

    Matthias Rybarsch

    Full Text Available The brain keeps its overall dynamics in a corridor of intermediate activity and it has been a long standing question what possible mechanism could achieve this task. Mechanisms from the field of statistical physics have long been suggesting that this homeostasis of brain activity could occur even without a central regulator, via self-organization on the level of neurons and their interactions, alone. Such physical mechanisms from the class of self-organized criticality exhibit characteristic dynamical signatures, similar to seismic activity related to earthquakes. Measurements of cortex rest activity showed first signs of dynamical signatures potentially pointing to self-organized critical dynamics in the brain. Indeed, recent more accurate measurements allowed for a detailed comparison with scaling theory of non-equilibrium critical phenomena, proving the existence of criticality in cortex dynamics. We here compare this new evaluation of cortex activity data to the predictions of the earliest physics spin model of self-organized critical neural networks. We find that the model matches with the recent experimental data and its interpretation in terms of dynamical signatures for criticality in the brain. The combination of signatures for criticality, power law distributions of avalanche sizes and durations, as well as a specific scaling relationship between anomalous exponents, defines a universality class characteristic of the particular critical phenomenon observed in the neural experiments. Thus the model is a candidate for a minimal model of a self-organized critical adaptive network for the universality class of neural criticality. As a prototype model, it provides the background for models that may include more biological details, yet share the same universality class characteristic of the homeostasis of activity in the brain.

  3. The TCA Pathway is an Important Player in the Regulatory Network Governing Vibrio alginolyticus Adhesion Under Adversity.

    Science.gov (United States)

    Huang, Lixing; Huang, Li; Yan, Qingpi; Qin, Yingxue; Ma, Ying; Lin, Mao; Xu, Xiaojin; Zheng, Jiang

    2016-01-01

    Adhesion is a critical step in the initial stage of Vibrio alginolyticus infection; therefore, it is important to understand the underlying mechanisms governing the adhesion of V. alginolyticus and determine if environmental factors have any effect. A greater understanding of this process may assist in developing preventive measures for reducing infection. In our previous research, we presented the first RNA-seq data from V. alginolyticus cultured under stress conditions that resulted in reduced adhesion. Based on the RNA-seq data, we found that the Tricarboxylic acid cycle (TCA pathway) might be closely related to adhesion. Environmental interactions with the TCA pathway might alter adhesion. To validate this, bioinformatics analysis, quantitative Real-Time PCR (qPCR), RNAi, and in vitro adhesion assays were performed, while V. alginolyticus was treated with various stresses including temperature, pH, salinity, and starvation. The expression of genes involved in the TCA pathway was confirmed by qPCR, which reinforced the reliability of the sequencing data. Silencing of these genes was capable of reducing the adhesion ability of V. alginolyticus. Adhesion of V. alginolyticus is influenced substantially by environmental factors and the TCA pathway is sensitive to some environmental stresses, especially changes in pH and starvation. Our results indicated that (1) the TCA pathway plays a key role in V. alginolyticus adhesion: (2) the TCA pathway is sensitive to environmental stresses.

  4. The TCA pathway is an important player in the regulatory network governing Vibrio alginolyticus adhesion under adversity

    Directory of Open Access Journals (Sweden)

    Lixing eHuang

    2016-02-01

    Full Text Available Adhesion is a critical step in the initial stage of Vibrio alginolyticus infection; therefore, it is important to understand the underlying mechanisms governing the adhesion of V. alginolyticus and determine if environmental factors have any effect. A greater understanding of this process may assist in developing preventive measures for reducing infection. In our previous research, we presented the first RNA-seq data from V. alginolyticus cultured under stress conditions that resulted in reduced adhesion. Based on the RNA-seq data, we found that the Tricarboxylic acid cycle (TCA pathway might be closely related to adhesion. Environmental interactions with the TCA pathway might alter adhesion. To validate this, bioinformatics analysis, qPCR, RNAi and in vitro adhesion assays were performed, while V. alginolyticus was treated with various stresses including temperature, pH, salinity and starvation. The expression of genes involved in the TCA pathway was confirmed by qPCR, which reinforced the reliability of the sequencing data. Silencing of these genes was capable of reducing the adhesion ability of V. alginolyticus. Adhesion of V. alginolyticus is influenced substantially by environmental factors and the TCA pathway is sensitive to some environmental stresses, especially changes in pH and starvation. Our results indicated that 1 the TCA pathway plays a key role in V. alginolyticus adhesion: 2 the TCA pathway is sensitive to environmental stresses.

  5. Pathway Processor: A Tool for Integrating Whole-Genome Expression Results into Metabolic Networks

    Science.gov (United States)

    Grosu, Paul; Townsend, Jeffrey P.; Hartl, Daniel L.; Cavalieri, Duccio

    2002-01-01

    We have developed a new tool to visualize expression data on metabolic pathways and to evaluate which metabolic pathways are most affected by transcriptional changes in whole-genome expression experiments. Using the Fisher Exact Test, the method scores biochemical pathways according to the probability that as many or more genes in a pathway would be significantly altered in a given experiment by chance alone. This method has been validated on diauxic shift experiments and reproduces well known effects of carbon source on yeast metabolism. The analysis is implemented with Pathway Analyzer, one of the tools of Pathway Processor, a new statistical package for the analysis of whole-genome expression data. Results from multiple experiments can be compared, reducing the analysis from the full set of individual genes to a limited number of pathways of interest. The pathways are visualized with OpenDX, an open-source visualization software package, and the relationship between genes in the pathways can be examined in detail using Expression Mapper, the second program of the package. This program features a graphical output displaying differences in expression on metabolic charts of the biochemical pathways to which the open reading frames are assigned. [Supplementary materials are available at http://www.cgr.harvard.edu/cavalieri/pp.html and http://www.genome.org.] PMID:12097350

  6. Tumor necrosis factor-α regulates distinct molecular pathways and gene networks in cultured skeletal muscle cells.

    Directory of Open Access Journals (Sweden)

    Shephali Bhatnagar

    2010-10-01

    Full Text Available Skeletal muscle wasting is a debilitating consequence of large number of disease states and conditions. Tumor necrosis factor-α (TNF-α is one of the most important muscle-wasting cytokine, elevated levels of which cause significant muscular abnormalities. However, the underpinning molecular mechanisms by which TNF-α causes skeletal muscle wasting are less well-understood.We have used microarray, quantitative real-time PCR (QRT-PCR, Western blot, and bioinformatics tools to study the effects of TNF-α on various molecular pathways and gene networks in C2C12 cells (a mouse myoblastic cell line. Microarray analyses of C2C12 myotubes treated with TNF-α (10 ng/ml for 18h showed differential expression of a number of genes involved in distinct molecular pathways. The genes involved in nuclear factor-kappa B (NF-kappaB signaling, 26s proteasome pathway, Notch1 signaling, and chemokine networks are the most important ones affected by TNF-α. The expression of some of the genes in microarray dataset showed good correlation in independent QRT-PCR and Western blot assays. Analysis of TNF-treated myotubes showed that TNF-α augments the activity of both canonical and alternative NF-κB signaling pathways in myotubes. Bioinformatics analyses of microarray dataset revealed that TNF-α affects the activity of several important pathways including those involved in oxidative stress, hepatic fibrosis, mitochondrial dysfunction, cholesterol biosynthesis, and TGF-β signaling. Furthermore, TNF-α was found to affect the gene networks related to drug metabolism, cell cycle, cancer, neurological disease, organismal injury, and abnormalities in myotubes.TNF-α regulates the expression of multiple genes involved in various toxic pathways which may be responsible for TNF-induced muscle loss in catabolic conditions. Our study suggests that TNF-α activates both canonical and alternative NF-κB signaling pathways in a time-dependent manner in skeletal muscle cells

  7. Identification of candidate flavonoid pathway genes using transcriptome correlation network analysis in ripe strawberry (Fragaria × ananassa) fruits.

    Science.gov (United States)

    Pillet, Jeremy; Yu, Hao-Wei; Chambers, Alan H; Whitaker, Vance M; Folta, Kevin M

    2015-08-01

    New modulators of the strawberry flavonoid pathway were identified through correlation network analysis. The transcriptomes of red, ripe fruit from two parental lines and 14 of their progeny were compared, and uncharacterized transcripts matching the expression patterns of known flavonoid-pathway genes were identified. Fifteen transcripts corresponded with putative transcription factors, and several of these were examined experimentally using transient expression in developing fruits. The results suggest that two of the newly-identified regulators likely contribute to discrete nodes of the flavonoid pathway. One increases only LEUCOANTHOCYANIDIN REDUCTASE (LAR) and FLAVONOL 3'-HYDROXYLASE (F3'H) transcript accumulation upon overexpression. Another affects LAR and FLAVONOL SYNTHASE (FLS) after overexpression. The third putative transcription factor appears to be a universal regulator of flavonoid-pathway genes, as many pathway transcripts decrease in abundance when this gene is silenced. This report demonstrates that such systems-level approaches may be especially powerful when connected to an effective transient expression system, helping to provide rapid and strong evidence of gene function in key fruit-ripening processes. © The Author 2015. Published by Oxford University Press on behalf of the Society for Experimental Biology.

  8. Deciphering ascorbic acid regulatory pathways in ripening tomato fruit using a weighted gene correlation network analysis approach.

    Science.gov (United States)

    Gao, Chao; Ju, Zheng; Li, Shan; Zuo, Jinhua; Fu, Daqi; Tian, Huiqin; Luo, Yunbo; Zhu, Benzhong

    2013-11-01

    Genotype is generally determined by the co-expression of diverse genes and multiple regulatory pathways in plants. Gene co-expression analysis combining with physiological trait data provides very important information about the gene function and regulatory mechanism. L-Ascorbic acid (AsA), which is an essential nutrient component for human health and plant metabolism, plays key roles in diverse biological processes such as cell cycle, cell expansion, stress resistance, hormone synthesis, and signaling. Here, we applied a weighted gene correlation network analysis approach based on gene expression values and AsA content data in ripening tomato (Solanum lycopersicum L.) fruit with different AsA content levels, which leads to identification of AsA relevant modules and vital genes in AsA regulatory pathways. Twenty-four modules were compartmentalized according to gene expression profiling. Among these modules, one negatively related module containing genes involved in redox processes and one positively related module enriched with genes involved in AsA biosynthetic and recycling pathways were further analyzed. The present work herein indicates that redox pathways as well as hormone-signal pathways are closely correlated with AsA accumulation in ripening tomato fruit, and allowed us to prioritize candidate genes for follow-up studies to dissect this interplay at the biochemical and molecular level. © 2013 Institute of Botany, Chinese Academy of Sciences.

  9. Exposing the role of exposure : Identifying and evaluating critical links in public transport networks

    NARCIS (Netherlands)

    Cats, O.; Yap, M.; Van Oort, N.

    2015-01-01

    Network vulnerability depends on the probability that adverse events occur and on the impacts of such disruptions on network functionality. Most studies on transport network vulnerability have only analysed vulnerability in terms of the reduction in performance indicators given that a disruption

  10. Application of the network robustness index to identifying critical road-network links in Chittenden County, Vermont.

    Science.gov (United States)

    2010-06-01

    The purpose of this project is to conduct a pilot application of the Network : Robustness Index (NRI) for the Chittenden County Regional Transportation Model. : Using the results, improvements to the method to increase its effectiveness for more : wi...

  11. Correction: An integrated anti-arrhythmic target network of compound Chinese medicine Wenxin Keli revealed by combined machine learning and molecular pathway analysis.

    Science.gov (United States)

    Wang, Taiyi; Lu, Ming; Du, Qunqun; Yao, Xi; Zhang, Peng; Chen, Xiaonan; Xie, Weiwei; Li, Zheng; Ma, Yuling; Zhu, Yan

    2017-09-26

    Correction for 'An integrated anti-arrhythmic target network of a Chinese medicine compound, Wenxin Keli, revealed by combined machine learning and molecular pathway analysis' by Taiyi Wang et al., Mol. BioSyst., 2017, 13, 1018-1030.

  12. Distinct muscle apoptotic pathways are activated in muscles with different fiber types in a rat model of critical illness myopathy.

    Science.gov (United States)

    Barnes, Benjamin T; Confides, Amy L; Rich, Mark M; Dupont-Versteegden, Esther E

    2015-06-01

    Critical illness myopathy (CIM) is associated with severe muscle atrophy and fatigue in affected patients. Apoptotic signaling is involved in atrophy and is elevated in muscles from patients with CIM. In this study we investigated underlying mechanisms of apoptosis-related pathways in muscles with different fiber type composition in a rat model of CIM using denervation and glucocorticoid administration (denervation and steroid-induced myopathy, DSIM). Soleus and tibialis anterior (TA) muscles showed severe muscle atrophy (40-60% of control muscle weight) and significant apoptosis in interstitial as well as myofiber nuclei that was similar between the two muscles with DSIM. Caspase-3 and -8 activities, but not caspase-9 and -12, were elevated in TA and not in soleus muscle, while the caspase-independent proteins endonuclease G (EndoG) and apoptosis inducing factor (AIF) were not changed in abundance nor differentially localized in either muscle. Anti-apoptotic proteins HSP70, -27, and apoptosis repressor with a caspase recruitment domain (ARC) were elevated in soleus compared to TA muscle and ARC was significantly decreased with induction of DSIM in soleus. Results indicate that apoptosis is a significant process associated with DSIM in both soleus and TA muscles, and that apoptosis-associated processes are differentially regulated in muscles of different function and fiber type undergoing atrophy due to DSIM. We conclude that interventions combating apoptosis with CIM may need to be directed towards inhibiting caspase-dependent as well as -independent mechanisms to be able to affect muscles of all fiber types.

  13. The lectin pathway of complement activation is a critical component of the innate immune response to pneumococcal infection

    DEFF Research Database (Denmark)

    Ali, Youssif M; Lynch, Nicholas J; Haleem, Kashif S

    2012-01-01

    The complement system plays a key role in host defense against pneumococcal infection. Three different pathways, the classical, alternative and lectin pathways, mediate complement activation. While there is limited information available on the roles of the classical and the alternative activation......-binding lectin associated serine protease-2 (MASP-2) and shown that this mouse strain is unable to form the lectin pathway specific C3 and C5 convertases. Here we report that MASP-2 deficient mice (which can still activate complement via the classical pathway and the alternative pathway) are highly susceptible...... to pneumococcal infection and fail to opsonize Streptococcus pneumoniae in the none-immune host. This defect in complement opsonisation severely compromises pathogen clearance in the lectin pathway deficient host. Using sera from mice and humans with defined complement deficiencies, we demonstrate that mouse...

  14. Use of Microarray Datasets to generate Caco-2-dedicated Networks and to identify Reporter Genes of Specific Pathway Activity.

    Science.gov (United States)

    Venkatasubramanian, Prashanna Balaji; Toydemir, Gamze; de Wit, Nicole; Saccenti, Edoardo; Martins Dos Santos, Vitor A P; van Baarlen, Peter; Wells, Jerry M; Suarez-Diez, Maria; Mes, Jurriaan J

    2017-07-28

    Intestinal epithelial cells, like Caco-2, are commonly used to study the interaction between food, other luminal factors and the host, often supported by microarray analysis to study the changes in gene expression as a result of the exposure. However, no compiled dataset for Caco-2 has ever been initiated and Caco-2-dedicated gene expression networks are barely available. Here, 341 Caco-2-specific microarray samples were collected from public databases and from in-house experiments pertaining to Caco-2 cells exposed to pathogens, probiotics and several food compounds. Using these datasets, a gene functional association network specific for Caco-2 was generated containing 8937 nodes 129711 edges. Two in silico methods, a modified version of biclustering and the new Differential Expression Correlation Analysis, were developed to identify Caco-2-specific gene targets within a pathway of interest. These methods were subsequently applied to the AhR and Nrf2 signalling pathways and altered expression of the predicted target genes was validated by qPCR in Caco-2 cells exposed to coffee extracts, known to activate both AhR and Nrf2 pathways. The datasets and in silico method(s) to identify and predict responsive target genes can be used to more efficiently design experiments to study Caco-2/intestinal epithelial-relevant biological processes.

  15. Pathway mapping and development of disease-specific biomarkers: protein-based network biomarkers

    Science.gov (United States)

    Chen, Hao; Zhu, Zhitu; Zhu, Yichun; Wang, Jian; Mei, Yunqing; Cheng, Yunfeng

    2015-01-01

    It is known that a disease is rarely a consequence of an abnormality of a single gene, but reflects the interactions of various processes in a complex network. Annotated molecular networks offer new opportunities to understand diseases within a systems biology framework and provide an excellent substrate for network-based identification of biomarkers. The network biomarkers and dynamic network biomarkers (DNBs) represent new types of biomarkers with protein–protein or gene–gene interactions that can be monitored and evaluated at different stages and time-points during development of disease. Clinical bioinformatics as a new way to combine clinical measurements and signs with human tissue-generated bioinformatics is crucial to translate biomarkers into clinical application, validate the disease specificity, and understand the role of biomarkers in clinical settings. In this article, the recent advances and developments on network biomarkers and DNBs are comprehensively reviewed. How network biomarkers help a better understanding of molecular mechanism of diseases, the advantages and constraints of network biomarkers for clinical application, clinical bioinformatics as a bridge to the development of diseases-specific, stage-specific, severity-specific and therapy predictive biomarkers, and the potentials of network biomarkers are also discussed. PMID:25560835

  16. Pathway mapping and development of disease-specific biomarkers: protein-based network biomarkers.

    Science.gov (United States)

    Chen, Hao; Zhu, Zhitu; Zhu, Yichun; Wang, Jian; Mei, Yunqing; Cheng, Yunfeng

    2015-02-01

    It is known that a disease is rarely a consequence of an abnormality of a single gene, but reflects the interactions of various processes in a complex network. Annotated molecular networks offer new opportunities to understand diseases within a systems biology framework and provide an excellent substrate for network-based identification of biomarkers. The network biomarkers and dynamic network biomarkers (DNBs) represent new types of biomarkers with protein-protein or gene-gene interactions that can be monitored and evaluated at different stages and time-points during development of disease. Clinical bioinformatics as a new way to combine clinical measurements and signs with human tissue-generated bioinformatics is crucial to translate biomarkers into clinical application, validate the disease specificity, and understand the role of biomarkers in clinical settings. In this article, the recent advances and developments on network biomarkers and DNBs are comprehensively reviewed. How network biomarkers help a better understanding of molecular mechanism of diseases, the advantages and constraints of network biomarkers for clinical application, clinical bioinformatics as a bridge to the development of diseases-specific, stage-specific, severity-specific and therapy predictive biomarkers, and the potentials of network biomarkers are also discussed. © 2015 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.

  17. Robust Selection Algorithm (RSA for Multi-Omic Biomarker Discovery; Integration with Functional Network Analysis to Identify miRNA Regulated Pathways in Multiple Cancers.

    Directory of Open Access Journals (Sweden)

    Vasudha Sehgal

    Full Text Available MicroRNAs (miRNAs play a crucial role in the maintenance of cellular homeostasis by regulating the expression of their target genes. As such, the dysregulation of miRNA expression has been frequently linked to cancer. With rapidly accumulating molecular data linked to patient outcome, the need for identification of robust multi-omic molecular markers is critical in order to provide clinical impact. While previous bioinformatic tools have been developed to identify potential biomarkers in cancer, these methods do not allow for rapid classification of oncogenes versus tumor suppressors taking into account robust differential expression, cutoffs, p-values and non-normality of the data. Here, we propose a methodology, Robust Selection Algorithm (RSA that addresses these important problems in big data omics analysis. The robustness of the survival analysis is ensured by identification of optimal cutoff values of omics expression, strengthened by p-value computed through intensive random resampling taking into account any non-normality in the data and integration into multi-omic functional networks. Here we have analyzed pan-cancer miRNA patient data to identify functional pathways involved in cancer progression that are associated with selected miRNA identified by RSA. Our approach demonstrates the way in which existing survival analysis techniques can be integrated with a functional network analysis framework to efficiently identify promising biomarkers and novel therapeutic candidates across diseases.

  18. Robust Selection Algorithm (RSA) for Multi-Omic Biomarker Discovery; Integration with Functional Network Analysis to Identify miRNA Regulated Pathways in Multiple Cancers.

    Science.gov (United States)

    Sehgal, Vasudha; Seviour, Elena G; Moss, Tyler J; Mills, Gordon B; Azencott, Robert; Ram, Prahlad T

    2015-01-01

    MicroRNAs (miRNAs) play a crucial role in the maintenance of cellular homeostasis by regulating the expression of their target genes. As such, the dysregulation of miRNA expression has been frequently linked to cancer. With rapidly accumulating molecular data linked to patient outcome, the need for identification of robust multi-omic molecular markers is critical in order to provide clinical impact. While previous bioinformatic tools have been developed to identify potential biomarkers in cancer, these methods do not allow for rapid classification of oncogenes versus tumor suppressors taking into account robust differential expression, cutoffs, p-values and non-normality of the data. Here, we propose a methodology, Robust Selection Algorithm (RSA) that addresses these important problems in big data omics analysis. The robustness of the survival analysis is ensured by identification of optimal cutoff values of omics expression, strengthened by p-value computed through intensive random resampling taking into account any non-normality in the data and integration into multi-omic functional networks. Here we have analyzed pan-cancer miRNA patient data to identify functional pathways involved in cancer progression that are associated with selected miRNA identified by RSA. Our approach demonstrates the way in which existing survival analysis techniques can be integrated with a functional network analysis framework to efficiently identify promising biomarkers and novel therapeutic candidates across diseases.

  19. Boolean network approach to negative feedback loops of the p53 pathways: synchronized dynamics and stochastic limit cycles.

    Science.gov (United States)

    Ge, Hao; Qian, Min

    2009-01-01

    Deterministic and stochastic Boolean network models are built for the dynamics of negative feedback loops of the p53 pathways. It is shown that the main function of the negative feedback in the p53 pathways is to keep p53 at a low steady state level, and each sequence of protein states in the negative feedback loops, is globally attracted to a closed cycle of the p53 dynamics after being perturbed by outside signal (e.g., DNA damage). Our theoretical and numerical studies show that both the biological stationary state and the biological oscillation after being perturbed are stable for a wide range of noise level. Applying the mathematical circulation theory of Markov chains, we investigate their stochastic synchronized dynamics and by comparing the network dynamics of the stochastic model with its corresponding deterministic network counterpart, a dominant circulation in the stochastic model is the natural generalization of the deterministic limit cycle in the deterministic system. Moreover, the period of the main peak in the power spectrum, which is in common use to characterize the synchronized dynamics, perfectly corresponds to the number of states in the main cycle with dominant circulation. Such a large separation in the magnitude of the circulations--between a dominant, main cycle and the rest--gives rise to the stochastic synchronization phenomenon.

  20. Regulatory MicroRNA Networks: Complex Patterns of Target Pathways for Disease-related and Housekeeping MicroRNAs

    Directory of Open Access Journals (Sweden)

    Sachli Zafari

    2015-06-01

    Full Text Available Blood-based microRNA (miRNA signatures as biomarkers have been reported for various pathologies, including cancer, neurological disorders, cardiovascular diseases, and also infections. The regulatory mechanism behind respective miRNA patterns is only partially understood. Moreover, “preserved” miRNAs, i.e., miRNAs that are not dysregulated in any disease, and their biological impact have been explored to a very limited extent. We set out to systematically determine their role in regulatory networks by defining groups of highly-dysregulated miRNAs that contribute to a disease signature as opposed to preserved housekeeping miRNAs. We further determined preferential targets and pathways of both dysregulated and preserved miRNAs by computing multi-layer networks, which were compared between housekeeping and dysregulated miRNAs. Of 848 miRNAs examined across 1049 blood samples, 8 potential housekeepers showed very limited expression variations, while 20 miRNAs showed highly-dysregulated expression throughout the investigated blood samples. Our approach provides important insights into miRNAs and their role in regulatory networks. The methodology can be applied to systematically investigate the differences in target genes and pathways of arbitrary miRNA sets.

  1. Anti-social networking: crowdsourcing and the cyber defence of national critical infrastructures.

    Science.gov (United States)

    Johnson, Chris W

    2014-01-01

    We identify four roles that social networking plays in the 'attribution problem', which obscures whether or not cyber-attacks were state-sponsored. First, social networks motivate individuals to participate in Distributed Denial of Service attacks by providing malware and identifying potential targets. Second, attackers use an individual's social network to focus attacks, through spear phishing. Recipients are more likely to open infected attachments when they come from a trusted source. Third, social networking infrastructures create disposable architectures to coordinate attacks through command and control servers. The ubiquitous nature of these architectures makes it difficult to determine who owns and operates the servers. Finally, governments recruit anti-social criminal networks to launch attacks on third-party infrastructures using botnets. The closing sections identify a roadmap to increase resilience against the 'dark side' of social networking.

  2. Phytochrome and retrograde signalling pathways coverage to antogonistically regulate a light-induced transcription network

    Science.gov (United States)

    Plastid-to-nucleus retrograde signals emitted by dysfunctional chloroplasts impact photomorphogenic development, but the molecular link between retrograde and photosensory-receptor signaling has remained undefined. Here, we show that the phytochrome (phy) and retrograde signaling pathways converge a...

  3. DMPD: Bruton's tyrosine kinase (Btk)-the critical tyrosine kinase in LPS signalling? [Dynamic Macrophage Pathway CSML Database

    Lifescience Database Archive (English)

    Full Text Available 15081522 Bruton's tyrosine kinase (Btk)-the critical tyrosine kinase in LPS signall...ruton's tyrosine kinase (Btk)-the critical tyrosine kinase in LPS signalling? PubmedID 15081522 Title Bruton...'s tyrosine kinase (Btk)-the critical tyrosine kinase in LPS signalling? Authors

  4. Tracing Pathways to Higher Education for Refugees: The Role of Virtual Support Networks and Mobile Phones for Women in Refugee Camps

    Science.gov (United States)

    Dahya, Negin; Dryden-Peterson, Sarah

    2017-01-01

    In this paper, we explore the role of online social networks in the cultivation of pathways to higher education for refugees, particularly for women. We compare supports garnered in local and offline settings to those accrued through online social networks and examine the differences between women and men. The paper draws on complementary original…

  5. The reverse cholesterol transport pathway improves understanding of genetic networks for fat deposition and muscle growth in beef cattle.

    Directory of Open Access Journals (Sweden)

    Tyler F Daniels

    Full Text Available In the present study, thirteen genes involved in the reverse cholesterol transport (RCT pathway were investigated for their associations with three fat depositions, eight fatty acid compositions and two growth-related phenotypes in a Wagyu x Limousin reference population, including 6 F(1 bulls, 113 F(1 dams, and 246 F(2 progeny. A total of 37 amplicons were used to screen single nucleotide polymorphisms (SNPs on 6 F(1 bulls. Among 36 SNPs detected in 11 of these 13 genes, 19 were selected for genotyping by the Sequenom assay design on all F(2 progeny. Single-marker analysis revealed seven SNPs in ATP binding cassette A1, apolipoproteins A1, B and E, phospholipid transfer protein and paraoxinase 1 genes significantly associated with nine phenotypes (P<0.05. Previously, we reported genetic networks associated with 19 complex phenotypes based on a total of 138 genetic polymorphisms derived from 71 known functional genes. Therefore, after Bonferroni correction, these significant (adjusted P<0.05 and suggestive (adjusted P<0.10 associations were then used to identify genetic networks related to the RCT pathway. Multiple-marker analysis suggested possible genetic networks involving the RCT pathway for kidney-pelvic-heart fat percentage, rib-eye area, and subcutaneous fat depth phenotypes with markers derived from paraoxinase 1, apolipoproteins A1 and E, respectively. The present study confirmed that genes involved in cholesterol homeostasis are useful targets for investigating obesity in humans as well as for improving meat quality phenotypes in a livestock production.

  6. Proteomics-based network analysis characterizes biological processes and pathways activated by preconditioned mesenchymal stem cells in cardiac repair mechanisms.

    Science.gov (United States)

    Di Silvestre, Dario; Brambilla, Francesca; Scardoni, Giovanni; Brunetti, Pietro; Motta, Sara; Matteucci, Marco; Laudanna, Carlo; Recchia, Fabio A; Lionetti, Vincenzo; Mauri, Pierluigi

    2017-05-01

    We have demonstrated that intramyocardial delivery of human mesenchymal stem cells preconditioned with a hyaluronan mixed ester of butyric and retinoic acid (MSCp+) is more effective in preventing the decay of regional myocardial contractility in a swine model of myocardial infarction (MI). However, the understanding of the role of MSCp+ in proteomic remodeling of cardiac infarcted tissue is not complete. We therefore sought to perform a comprehensive analysis of the proteome of infarct remote (RZ) and border zone (BZ) of pigs treated with MSCp+ or unconditioned stem cells. Heart tissues were analyzed by MudPIT and differentially expressed proteins were selected by a label-free approach based on spectral counting. Protein profiles were evaluated by using PPI networks and their topological analysis. The proteomic remodeling was largely prevented in MSCp+ group. Extracellular proteins involved in fibrosis were down-regulated, while energetic pathways were globally up-regulated. Cardioprotectant pathways involved in the production of keto acid metabolites were also activated. Additionally, we found that new hub proteins support the cardioprotective phenotype characterizing the left ventricular BZ treated with MSCp+. In fact, the up-regulation of angiogenic proteins NCL and RAC1 can be explained by the increase of capillary density induced by MSCp+. Our results show that angiogenic pathways appear to be uniquely positioned to integrate signaling with energetic pathways involving cardiac repair. Our findings prompt the use of proteomics-based network analysis to optimize new approaches preventing the post-ischemic proteomic remodeling that may underlie the limited self-repair ability of adult heart. Copyright © 2017 Elsevier B.V. All rights reserved.

  7. A critical analysis of the implementation of social networking as an e-recruitment tool within a security enterprise

    Directory of Open Access Journals (Sweden)

    Anthony Lewis

    2015-12-01

    Full Text Available Many enterprises are operating in complex and competitive environments, and changes in the internal and external environment have prompted them to engage in better ways of doing business. In order to respond to these changes, and survive in today’s volatile business environment, enterprises need to change their strategies. Human Resource departments are under pressure to keep operating costs low whilst also ensuring they are attracting, recruiting, and retaining talent within the enterprise. To achieve this, an increasing number of enterprises have adopted social networking into their recruitment strategy. This research aims to critically analyze the implementation of social networking as an e-recruitment tool within a Security Enterprise. The research key objective is to examine the importance of attracting Generation Y through the use of social networking sites and also to develop an understanding of the advantages and disadvantages of using social networking as an e-recruitment tool. The research also looks at contemporary examples of enterprises that have implemented social networking into their recruitment strategy. A further objective of the research is to gain an understanding of the attitudes and perceptions of the use of social networking as an e-recruitment tool. To achieve this, the research has taken a mixed-methods approach whilst focusing on an interpretivist stance. Data was gathered through an interview with the HR Manager at the Security Enterprise and a questionnaire was distributed to 22 employees within the enterprise and 84 respondents on social networking sites. The overall attitudes and perceptions of respondents showed that social networking can be effectively used as an e-recruitment tool as long as a traditional recruitment method is also used.

  8. Social networking with a brain: a critical review of academic sites

    Directory of Open Access Journals (Sweden)

    Kim Leeder

    2008-12-01

    Full Text Available Social networking may have started out as a way for students to keep track of their friends, but it has expanded in just about every direction. These days, you can find at least one related social networking site on just about any general topic, including music, photography, television, books, shopping, and bookmarking. But it isn’t [...

  9. Dose and Time Dependencies in Stress Pathway Responses during Chemical Exposure: Novel Insights from Gene Regulatory Networks

    Directory of Open Access Journals (Sweden)

    Terezinha M. Souza

    2017-10-01

    Full Text Available Perturbation of biological networks is often observed during exposure to xenobiotics, and the identification of disturbed processes, their dynamic traits, and dose–response relationships are some of the current challenges for elucidating the mechanisms determining adverse outcomes. In this scenario, reverse engineering of gene regulatory networks (GRNs from expression data may provide a system-level snapshot embedded within accurate molecular events. Here, we investigate the composition of GRNs inferred from groups of chemicals with two distinct outcomes, namely carcinogenicity [azathioprine (AZA and cyclophosphamide (CYC] and drug-induced liver injury (DILI; diclofenac, nitrofurantoin, and propylthiouracil, and a non-carcinogenic/non-DILI group (aspirin, diazepam, and omeprazole. For this, we analyzed publicly available exposed in vitro human data, taking into account dose and time dependencies. Dose–Time Network Identification (DTNI was applied to gene sets from exposed primary human hepatocytes using four stress pathways, namely endoplasmic reticulum (ER, NF-κB, NRF2, and TP53. Inferred GRNs suggested case specificity, varying in interactions, starting nodes, and target genes across groups. DILI and carcinogenic compounds were shown to directly affect all pathway-based GRNs, while non-DILI/non-carcinogenic chemicals only affected NF-κB. NF-κB-based GRNs clearly illustrated group-specific disturbances, with the cancer-related casein kinase CSNK2A1 being a target gene only in the carcinogenic group, and opposite regulation of NF-κB subunits being observed in DILI and non-DILI/non-carcinogenic groups. Target genes in NRF2-based GRNs shared by DILI and carcinogenic compounds suggested markers of hepatotoxicity. Finally, we indicate several of these group-specific interactions as potentially novel. In summary, our reversed-engineered GRNs are capable of revealing dose dependent, chemical-specific mechanisms of action in stress

  10. Identification of cell proliferation, immune response and cell migration as critical pathways in a prognostic signature for HER2+:ERα- breast cancer.

    Directory of Open Access Journals (Sweden)

    Jeffrey C Liu

    Full Text Available Multi-gene prognostic signatures derived from primary tumor biopsies can guide clinicians in designing an appropriate course of treatment. Identifying genes and pathways most essential to a signature performance may facilitate clinical application, provide insights into cancer progression, and uncover potentially new therapeutic targets. We previously developed a 17-gene prognostic signature (HTICS for HER2+:ERα- breast cancer patients, using genes that are differentially expressed in tumor initiating cells (TICs versus non-TICs from MMTV-Her2/neu mammary tumors. Here we probed the pathways and genes that underlie the prognostic power of HTICS.We used Leave-One Out, Data Combination Test, Gene Set Enrichment Analysis (GSEA, Correlation and Substitution analyses together with Receiver Operating Characteristic (ROC and Kaplan-Meier survival analysis to identify critical biological pathways within HTICS. Publically available cohorts with gene expression and clinical outcome were used to assess prognosis. NanoString technology was used to detect gene expression in formalin-fixed paraffin embedded (FFPE tissues.We show that three major biological pathways: cell proliferation, immune response, and cell migration, drive the prognostic power of HTICS, which is further tuned by Homeostatic and Glycan metabolic signalling. A 6-gene minimal Core that retained a significant prognostic power, albeit less than HTICS, also comprised the proliferation/immune/migration pathways. Finally, we developed NanoString probes that could detect expression of HTICS genes and their substitutions in FFPE samples.Our results demonstrate that the prognostic power of a signature is driven by the biological processes it monitors, identify cell proliferation, immune response and cell migration as critical pathways for HER2+:ERα- cancer progression, and defines substitutes and Core genes that should facilitate clinical application of HTICS.

  11. Satisfying needs through Social Networking Sites: A pathway towards problematic Internet use for socially anxious people?

    National Research Council Canada - National Science Library

    Casale, Silvia; Fioravanti, Giulia

    2015-01-01

    Introduction: Following the theoretical frameworks of the dual-factor model of Facebook use and the Self Determination Theory, the present study hypothesizes that the satisfaction of unmet needs through Social Networking Sites (SNSs...

  12. Social network as a determinant of pathway to mental health service ...

    African Journals Online (AJOL)

    14,15] and the perceived or actual reactions of ... of perceived support. Both network and support can act as coping resources.[20,21] While some ..... disability and service utilisation. Overview of the. Australian National Mental Health Survey.

  13. Hydrogen-Bonded Networks Along and Bifurcation of the E-Pathway in Quinol: Fumarate Reductase

    Energy Technology Data Exchange (ETDEWEB)

    Herzog, Elena; Gu, Wei; Juhnke, Hanno D.; Haas, Alexander H.; Mantele, Werner; Simon, Jorg; Helms, Volkhard H.; Lancaster , C. Roy D.

    2012-09-19

    The E-pathway of transmembrane proton transfer has been demonstrated previously to be essential for catalysis by the diheme-containing quinol:fumarate reductase (QFR) of Wolinella succinogenes. Two constituents of this pathway, Glu- C180 and heme bD ring C (bD-C-) propionate, have been validated experimentally. Here, we identify further constituents of the E-pathway by analysis of molecular dynamics simulations. The redox state of heme groups has a crucial effect on the connectivity patterns of mobile internal water molecules that can transiently support proton transfer from the bD-C-propionate to Glu-C180. The short H-bonding paths formed in the reduced states can lead to high proton conduction rates and thus provide a plausible explanation for the required opening of the E-pathway in reduced QFR. We found evidence that the bD-C-propionate group is the previously postulated branching point connecting proton transfer to the E-pathway from the quinol-oxidation site via interactions with the heme bD ligand His-C44. An essential functional role of His-C44 is supported experimentally by site-directed mutagenesis resulting in its replacement with Glu. Although the H44E variant enzyme retains both heme groups, it is unable to catalyze quinol oxidation. All results obtained are relevant to the QFR enzymes from the human pathogens Campylobacter jejuni and Helicobacter pylori.

  14. Modelling pathways to Rubisco degradation: a structural equation network modelling approach.

    Directory of Open Access Journals (Sweden)

    Catherine Tétard-Jones

    Full Text Available 'Omics analysis (transcriptomics, proteomics quantifies changes in gene/protein expression, providing a snapshot of changes in biochemical pathways over time. Although tools such as modelling that are needed to investigate the relationships between genes/proteins already exist, they are rarely utilised. We consider the potential for using Structural Equation Modelling to investigate protein-protein interactions in a proposed Rubisco protein degradation pathway using previously published data from 2D electrophoresis and mass spectrometry proteome analysis. These informed the development of a prior model that hypothesised a pathway of Rubisco Large Subunit and Small Subunit degradation, producing both primary and secondary degradation products. While some of the putative pathways were confirmed by the modelling approach, the model also demonstrated features that had not been originally hypothesised. We used Bayesian analysis based on Markov Chain Monte Carlo simulation to generate output statistics suggesting that the model had replicated the variation in the observed data due to protein-protein interactions. This study represents an early step in the development of approaches that seek to enable the full utilisation of information regarding the dynamics of biochemical pathways contained within proteomics data. As these approaches gain attention, they will guide the design and conduct of experiments that enable 'Omics modelling to become a common place practice within molecular biology.

  15. NeAT: a toolbox for the analysis of biological networks, clusters, classes and pathways

    Science.gov (United States)

    Brohée, Sylvain; Faust, Karoline; Lima-Mendez, Gipsi; Sand, Olivier; Janky, Rekin's; Vanderstocken, Gilles; Deville, Yves; van Helden, Jacques

    2008-01-01

    The network analysis tools (NeAT) (http://rsat.ulb.ac.be/neat/) provide a user-friendly web access to a collection of modular tools for the analysis of networks (graphs) and clusters (e.g. microarray clusters, functional classes, etc.). A first set of tools supports basic operations on graphs (comparison between two graphs, neighborhood of a set of input nodes, path finding and graph randomization). Another set of programs makes the connection between networks and clusters (graph-based clustering, cliques discovery and mapping of clusters onto a network). The toolbox also includes programs for detecting significant intersections between clusters/classes (e.g. clusters of co-expression versus functional classes of genes). NeAT are designed to cope with large datasets and provide a flexible toolbox for analyzing biological networks stored in various databases (protein interactions, regulation and metabolism) or obtained from high-throughput experiments (two-hybrid, mass-spectrometry and microarrays). The web interface interconnects the programs in predefined analysis flows, enabling to address a series of questions about networks of interest. Each tool can also be used separately by entering custom data for a specific analysis. NeAT can also be used as web services (SOAP/WSDL interface), in order to design programmatic workflows and integrate them with other available resources. PMID:18524799

  16. Find_tfSBP: find thermodynamics-feasible and smallest balanced pathways with high yield from large-scale metabolic networks.

    Science.gov (United States)

    Xu, Zixiang; Sun, Jibin; Wu, Qiaqing; Zhu, Dunming

    2017-12-11

    Biologically meaningful metabolic pathways are important references in the design of industrial bacterium. At present, constraint-based method is the only way to model and simulate a genome-scale metabolic network under steady-state criteria. Due to the inadequate assumption of the relationship in gene-enzyme-reaction as one-to-one unique association, computational difficulty or ignoring the yield from substrate to product, previous pathway finding approaches can't be effectively applied to find out the high yield pathways that are mass balanced in stoichiometry. In addition, the shortest pathways may not be the pathways with high yield. At the same time, a pathway, which exists in stoichiometry, may not be feasible in thermodynamics. By using mixed integer programming strategy, we put forward an algorithm to identify all the smallest balanced pathways which convert the source compound to the target compound in large-scale metabolic networks. The resulting pathways by our method can finely satisfy the stoichiometric constraints and non-decomposability condition. Especially, the functions of high yield and thermodynamics feasibility have been considered in our approach. This tool is tailored to direct the metabolic engineering practice to enlarge the metabolic potentials of industrial strains by integrating the extensive metabolic network information built from systems biology dataset.

  17. Fast alarm broadcasting in critical event monitoring using wireless sensor networks

    NARCIS (Netherlands)

    Zhang, Kui; Meratnia, Nirvana; Havinga, Paul J.M.; Guo, Peng; Beutel, Jan

    In mission-critical applications such as battlefield reconnaissance or industrial safety and security, a large number of sensor nodes are deployed in a large area to detect and report event related information to the end-users. When a critical event in the monitoring region is detected by a node,

  18. Innate immune sensing 2.0 - from linear activation pathways to fine tuned and regulated innate immune networks.

    Science.gov (United States)

    Volz, Thomas; Kaesler, Susanne; Biedermann, Tilo

    2012-01-01

    The innate immune system is based on pathogen recognition receptors that bind conserved microbial molecular structures, so called pathogen-associated molecular patterns (PAMPs). The characterization of the innate immune system was long based on a linear step-wise concept of recognition, activation pathways and effector defense mechanisms. Only more recently it was recognized that the innate immune system needs regulatory elements, sideways and crosstalks that allows it to fine tune and adapt its response. Thus, it is an emerging field within innate immunity research to try to understand how the immune outcome of innate immune sensing is regulated and why immune responses can be substantially different, even though the same PAMPs may have been 'sensed' at the surface organs such as the skin. Only the expansion of the innate immune system from 'pure' linear activation pathways to fine tuned and regulated innate immune networks allows us to integrate the generation of gradually accentuated and qualitatively different effector and tolerogenic immune responses. This article provides a review of the basic concepts and players of the innate immune system and will present some of the newer data defining the innate immune networks effectively regulating the immune homoeostasis and immune effector mechanisms with special focus on the skin as one of the organs involved in regulating the immune interface between the environment and the organism. © 2011 John Wiley & Sons A/S.

  19. Estimating Network Kinetics of the MAPK/ERK Pathway Using Biochemical Data

    NARCIS (Netherlands)

    Purutcuoglu, Vilda; Wit, Ernst

    2012-01-01

    The MAPK/ERK pathway is a major signal transduction system which regulates many fundamental cellular processes including the growth control and the cell death. As a result of these roles, it has a crucial importance in cancer as well as normal developmental processes. Therefore, it has been

  20. A Network Approach to Psychosis : Pathways Between Childhood Trauma and Psychotic Symptoms

    NARCIS (Netherlands)

    Isvoranu, Adela-Maria; van Borkulo, Claudia D.; Boyette, Lindy-Lou; Wigman, Johanna T. W.; Vinkers, Christiaan H.; Borsboom, Denny

    2017-01-01

    Childhood trauma (CT) has been identified as a potential risk factor for the onset of psychotic disorders. However, to date, there is limited consensus with respect to which symptoms may ensue after exposure to trauma in early life, and whether specific pathways may account for these associations.

  1. A critical review on the applications of artificial neural networks in winemaking technology.

    Science.gov (United States)

    Moldes, O A; Mejuto, J C; Rial-Otero, R; Simal-Gandara, J

    2017-09-02

    Since their development in 1943, artificial neural networks were extended into applications in many fields. Last twenty years have brought their introduction into winery, where they were applied following four basic purposes: authenticity assurance systems, electronic sensory devices, production optimization methods, and artificial vision in image treatment tools, with successful and promising results. This work reviews the most significant approaches for neural networks in winemaking technologies with the aim of producing a clear and useful review document.

  2. Identification of critical regulatory genes in cancer signaling network using controllability analysis

    Science.gov (United States)

    Ravindran, Vandana; Sunitha, V.; Bagler, Ganesh

    2017-05-01

    Cancer is characterized by a complex web of regulatory mechanisms which makes it difficult to identify features that are central to its control. Molecular integrative models of cancer, generated with the help of data from experimental assays, facilitate use of control theory to probe for ways of controlling the state of such a complex dynamic network. We modeled the human cancer signaling network as a directed graph and analyzed it for its controllability, identification of driver nodes and their characterization. We identified the driver nodes using the maximum matching algorithm and classified them as backbone, peripheral and ordinary based on their role in regulatory interactions and control of the network. We found that the backbone driver nodes were key to driving the regulatory network into cancer phenotype (via mutations) as well as for steering into healthy phenotype (as drug targets). This implies that while backbone genes could lead to cancer by virtue of mutations, they are also therapeutic targets of cancer. Further, based on their impact on the size of the set of driver nodes, genes were characterized as indispensable, dispensable and neutral. Indispensable nodes within backbone of the network emerged as central to regulatory mechanisms of control of cancer. In addition to probing the cancer signaling network from the perspective of control, our findings suggest that indispensable backbone driver nodes could be potentially leveraged as therapeutic targets. This study also illustrates the application of structural controllability for studying the mechanisms underlying the regulation of complex diseases.

  3. Critical forces for actin filament buckling and force transmission influence transport in actomyosin networks

    Science.gov (United States)

    Stam, Samantha; Gardel, Margaret

    Viscoelastic networks of biopolymers coordinate the motion of intracellular objects during transport. These networks have nonlinear mechanical properties due to events such as filament buckling or breaking of cross-links. The influence of such nonlinear properties on the time and length scales of transport is not understood. Here, we use in vitro networks of actin and the motor protein myosin II to clarify how intracellular forces regulate active diffusion. We observe two transitions in the mean-squared displacement of cross-linked actin with increasing motor concentration. The first is a sharp transition from initially subdiffusive to diffusive-like motion that requires filament buckling but does not cause net contraction of the network. Further increase of the motor density produces a second transition to network rupture and ballistic actin transport. This corresponds with an increase in the correlation of motion and thus may be caused when forces propagate far enough for global motion. We conclude that filament buckling and overall network contraction require different amounts of force and produce distinct transport properties. These nonlinear transitions may act as mechanical switches that can be turned on to produce observed motion within cells.

  4. The effect of alcohol on the differential expression of cluster of differentiation 14 gene, associated pathways, and genetic network.

    Directory of Open Access Journals (Sweden)

    Diana X Zhou

    Full Text Available Alcohol consumption affects human health in part by compromising the immune system. In this study, we examined the expression of the Cd14 (cluster of differentiation 14 gene, which is involved in the immune system through a proinflammatory cascade. Expression was evaluated in BXD mice treated with saline or acute 1.8 g/kg i.p. ethanol (12.5% v/v. Hippocampal gene expression data were generated to examine differential expression and to perform systems genetics analyses. The Cd14 gene expression showed significant changes among the BXD strains after ethanol treatment, and eQTL mapping revealed that Cd14 is a cis-regulated gene. We also identified eighteen ethanol-related phenotypes correlated with Cd14 expression related to either ethanol responses or ethanol consumption. Pathway analysis was performed to identify possible biological pathways involved in the response to ethanol and Cd14. We also constructed a genetic network for Cd14 using the top 20 correlated genes and present several genes possibly involved in Cd14 and ethanol responses based on differential gene expression. In conclusion, we found Cd14, along with several other genes and pathways, to be involved in ethanol responses in the hippocampus, such as increased susceptibility to lipopolysaccharides and neuroinflammation.

  5. A temporal shift in regulatory networks and pathways in the bovine small intestine during Cooperia oncophora infection.

    Science.gov (United States)

    Li, Robert W; Gasbarre, Louis C

    2009-06-01

    Cooperia oncophora is an important parasitic nematode of cattle with a wide distribution in temperate areas. Twenty Holstein nematode-naïve bull calves were experimentally infected with approximately 100,000 infective L3s and infection was allowed to progress for 7, 14, 28, 42 days, respectively. This experiment was conducted to identify putative recognition and inflammatory pathways in the host-parasite relationship. Gene expression profiles of the small intestine were compared using a high-density bovine 60 mer oligo microarray. A total of 310 genes were differentially expressed during the course of infection. The pathways and regulatory networks significantly impacted by the infection were analysed. A total of 22 canonical pathways and nine regulatory networks were significantly affected during infection. During the early phase of the infection (7 days p.i.), parasites suppressed the acute phase response and the complement system of the host. At 14 days p.i., three out of the six pathways impacted were related with retinoid X receptor (RXR) functions. At 28 days p.i., the effects on RXR were less evident. The host response shifted to lipid metabolism and signalling, especially eicosanoid production and signalling, suggesting that eicosanoid-mediated inflammation might be a major host defence mechanism. By 42 days p.i., the pathways impacted involved glycosphingolipid biosynthesis and transforming growth factor beta (TGFbeta signalling. The expression of cadherin-like 26 (CDH26) was strongly up-regulated starting at 14 days p.i. and peaked at 28 days p.i. The extent of its expression is positively correlated with the infiltration of eosinophils (R=0.82) and coincides with the number of adult parasites in the tissue. CDH26 demonstrated an expression profile similar to two other cell adhesion molecules involved in recognition of carbohydrates on foreign organisms, collectin and galectin, suggesting that it may serve as a pattern recognition molecule for C

  6. Temporal network based analysis of cell specific vein graft transcriptome defines key pathways and hub genes in implantation injury.

    Directory of Open Access Journals (Sweden)

    Manoj Bhasin

    Full Text Available Vein graft failure occurs between 1 and 6 months after implantation due to obstructive intimal hyperplasia, related in part to implantation injury. The cell-specific and temporal response of the transcriptome to vein graft implantation injury was determined by transcriptional profiling of laser capture microdissected endothelial cells (EC and medial smooth muscle cells (SMC from canine vein grafts, 2 hours (H to 30 days (D following surgery. Our results demonstrate a robust genomic response beginning at 2 H, peaking at 12-24 H, declining by 7 D, and resolving by 30 D. Gene ontology and pathway analyses of differentially expressed genes indicated that implantation injury affects inflammatory and immune responses, apoptosis, mitosis, and extracellular matrix reorganization in both cell types. Through backpropagation an integrated network was built, starting with genes differentially expressed at 30 D, followed by adding upstream interactive genes from each prior time-point. This identified significant enrichment of IL-6, IL-8, NF-κB, dendritic cell maturation, glucocorticoid receptor, and Triggering Receptor Expressed on Myeloid Cells (TREM-1 signaling, as well as PPARα activation pathways in graft EC and SMC. Interactive network-based analyses identified IL-6, IL-8, IL-1α, and Insulin Receptor (INSR as focus hub genes within these pathways. Real-time PCR was used for the validation of two of these genes: IL-6 and IL-8, in addition to Collagen 11A1 (COL11A1, a cornerstone of the backpropagation. In conclusion, these results establish causality relationships clarifying the pathogenesis of vein graft implantation injury, and identifying novel targets for its prevention.

  7. The Mla pathway is critical for Pseudomonas aeruginosa resistance to outer membrane permeabilization and host innate immune clearance.

    Science.gov (United States)

    Munguia, Jason; LaRock, Doris L; Tsunemoto, Hannah; Olson, Joshua; Cornax, Ingrid; Pogliano, Joseph; Nizet, Victor

    2017-10-01

    Pseudomonas aeruginosa is an important opportunistic pathogen that has become a serious problem due to increased rates of antibiotic resistance. Due to this along with a dearth in novel antibiotic development, especially against Gram-negative pathogens, new therapeutic strategies are needed to prevent a post-antibiotic era. Here, we describe the importance of the vacJ/Mla pathway in resisting bactericidal actions of the host innate immune response. P. aeruginosa tn5 transposon mutants in genes from the VacJ/Mla pathway showed increased susceptibility to killing by the host cathelicidin antimicrobial peptide, LL-37, when compared to the wild-type parent strain. The P. aeruginosa vacJ - mutant demonstrated increased membrane permeability upon damage as well as sensitivity to killing in the presence of the detergent sodium dodecyl sulfate and the divalent cation chelator EDTA. When exposed to human whole blood and serum complement, the vacJ - mutant was killed more rapidly when compared to the wild-type parent strain and complemented mutant. Finally, in an in vivo mouse lung infection model, infection with the vacJ - mutant resulted in reduced mortality, lower bacterial burden, and reduced lung damage when compared to the wild-type strain. This study highlights the potential in therapeutically targeting the VacJ/Mla pathway in sensitizing P. aeruginosa to killing by the host innate immune response. • The Mla pathway regulates outer membrane dynamics in human pathogen Pseudomonas aeruginosa (PA). • Disruption of Mla pathway gene vacJ sensitizes PA to host cathelicidin antimicrobial peptide LL-37. • Loss of vacJ expression renders PA more sensitive to human whole blood and serum killing. • Loss of vacJ expression reduces PA survival and virulence in a murine lung infection model. • The Mla pathway merits exploration as a pharmacologic target to sensitize PA to host innate immunity.

  8. The interaction of social networks and child obesity prevention program effects: the pathways trial.

    Science.gov (United States)

    Shin, Hee-Sung; Valente, Thomas W; Riggs, Nathaniel R; Huh, Jimi; Spruijt-Metz, Donna; Chou, Chih-Ping; Ann Pentz, Mary

    2014-06-01

    Social network analysis was used to examine whether peer influence from one's social networks moderates obesity prevention program effects on obesity-related behaviors: healthful and unhealthful. Participants included 557 children residing in Southern California. The survey assessed health-promoting behaviors (i.e., physical activity at school, physical activity outside of school, and fruit and vegetable intake), as well as unhealthful behaviors (high-calorie, low-nutrient intake and sedentary activity), and peer exposure calculated from social network nominations as indicators of peer influence. Multilevel models were conducted separately on outcomes predicted by program participation, peer exposure, and program participation by peer exposure. Results indicated that peer exposure was positively associated with one's own healthful and unhealthful behaviors. Program participation effects were moderated by peer influence, but only when unhealthful peer influence was present. Results suggest that peer influence can diminish or amplify prevention programs Future interventions should consider peer-led components to promote healthful influence of peers on healthful and unhealthful behaviors, and programs should be mindful that their effects are moderated by social networks. Copyright © 2014 The Obesity Society.

  9. Behavioral and Physiological Neural Network Analyses: A Common Pathway toward Pattern Recognition and Prediction

    Science.gov (United States)

    Ninness, Chris; Lauter, Judy L.; Coffee, Michael; Clary, Logan; Kelly, Elizabeth; Rumph, Marilyn; Rumph, Robin; Kyle, Betty; Ninness, Sharon K.

    2012-01-01

    Using 3 diversified datasets, we explored the pattern-recognition ability of the Self-Organizing Map (SOM) artificial neural network as applied to diversified nonlinear data distributions in the areas of behavioral and physiological research. Experiment 1 employed a dataset obtained from the UCI Machine Learning Repository. Data for this study…

  10. Systems Level Analysis and Identification of Pathways and Networks Associated with Liver Fibrosis

    Science.gov (United States)

    2014-11-07

    Kamal Kumar1, Danielle L. Ippolito2, John A. Lewis2, Jonathan D. Stallings2, Anders Wallqvist1* 1 Department of Defense Biotechnology High Performance...Coordinated modular functionality and prognostic potential of a heart failure biomarker-driven interaction network. BMC Syst Biol 4: 60. 32. Azuaje FJ, Dewey FE

  11. Social network as a determinant of pathway to mental health service ...

    African Journals Online (AJOL)

    The presence of some social network and social support structures were significantly associated with the use of general medical and specialty psychiatric services for patients with schizophrenia (P = 0.03), schizoaffective disorder (P = 0.02), bipolar I disorder (P = 0.01), but not with major depression and symptoms of ...

  12. A CRITICAL ANALYSIS OF THE CONTRIBUTIONS MADE BY BRAZILIAN THESES ON THE TOPIC OF NETWORKS

    Directory of Open Access Journals (Sweden)

    Eduardo Jorge Branco Vieira Barcelos

    2015-03-01

    Full Text Available Research into Management Networks is not a dominant paradigm, which leaves it open for discussions on its statements, models and theories. This paper analyzes the contributions made by Brazilian theses on networks in the area of management, from 2004 to 2013. For this purpose, criteria that define contribution are used, for both national and international literature, resulting in a chart of 12 originality and 8 significance indicators. 23 theses were identified as dealing with the subject of networks. Content analysis was employed on explicit contributing texts and a search of the keywords for each of the 20 indicators. As the subject of networks presents multifaceted concepts, research methodologies and management models, it is beneficial to discuss and develop new approaches and contributions were expected at all three levels. The results indicate, however, that theoretical contributions were practically non-existent, methodological contributions were limited, focusing on improvements, and managerial contributions were most common, especially when focused on local networks. The results and analysis show that more research and a deeper discussion on this subject are needed. These could include coordinators and supervisors due to the pre-paradigmatic nature of the topic.

  13. Satisfying needs through Social Networking Sites: A pathway towards problematic Internet use for socially anxious people?

    Directory of Open Access Journals (Sweden)

    Silvia Casale

    2015-06-01

    Conclusions: The present results extend our understanding of the development of problematic use of Internet communicative services, based on the framework of the dual factor model of Facebook use and the Self Determination Theory. The fulfillment of an unmet need for self-presentation (i.e. the desire to create a positive impression of one's self in others through SNSs could be one of the possible pathways to GPIU for socially anxious males.

  14. Virtualization of open-source secure web services to support data exchange in a pediatric critical care research network.

    Science.gov (United States)

    Frey, Lewis J; Sward, Katherine A; Newth, Christopher J L; Khemani, Robinder G; Cryer, Martin E; Thelen, Julie L; Enriquez, Rene; Shaoyu, Su; Pollack, Murray M; Harrison, Rick E; Meert, Kathleen L; Berg, Robert A; Wessel, David L; Shanley, Thomas P; Dalton, Heidi; Carcillo, Joseph; Jenkins, Tammara L; Dean, J Michael

    2015-11-01

    To examine the feasibility of deploying a virtual web service for sharing data within a research network, and to evaluate the impact on data consistency and quality. Virtual machines (VMs) encapsulated an open-source, semantically and syntactically interoperable secure web service infrastructure along with a shadow database. The VMs were deployed to 8 Collaborative Pediatric Critical Care Research Network Clinical Centers. Virtual web services could be deployed in hours. The interoperability of the web services reduced format misalignment from 56% to 1% and demonstrated that 99% of the data consistently transferred using the data dictionary and 1% needed human curation. Use of virtualized open-source secure web service technology could enable direct electronic abstraction of data from hospital databases for research purposes. © The Author 2015. Published by Oxford University Press on behalf of the American Medical Informatics Association. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  15. Optimization of the Critical Diameter and Average Path Length of Social Networks

    Directory of Open Access Journals (Sweden)

    Haifeng Du

    2017-01-01

    Full Text Available Optimizing average path length (APL by adding shortcut edges has been widely discussed in connection with social networks, but the relationship between network diameter and APL is generally ignored in the dynamic optimization of APL. In this paper, we analyze this relationship and transform the problem of optimizing APL into the problem of decreasing diameter to 2. We propose a mathematic model based on a memetic algorithm. Experimental results show that our algorithm can efficiently solve this problem as well as optimize APL.

  16. NLRP3 inflammasome pathway has a critical role in the host immunity against clinically relevant Acinetobacter baumannii pulmonary infection.

    Science.gov (United States)

    Dikshit, N; Kale, S D; Khameneh, H J; Balamuralidhar, V; Tang, C Y; Kumar, P; Lim, T P; Tan, T T; Kwa, A L; Mortellaro, A; Sukumaran, B

    2018-01-01

    The opportunistic Gram-negative bacterium Acinetobacter baumannii (AB) is a leading cause of life-threatening nosocomial pneumonia. Outbreaks of multidrug resistant (MDR)-AB belonging to international clones (ICs) I and II with limited treatment options are major global health threats. However, the pathogenesis mechanisms of various AB clonal groups are understudied. Although inflammation-associated interleukin-1β (IL-1β) levels and IL-1 receptor antagonist polymorphisms were previously implicated in MDR-AB-related pneumonia in patients, whether inflammasomes has any role in the host defense and/or pathogenesis of clinically relevant A. baumannii infection is unknown. Using a sublethal mouse pneumonia model, we demonstrate that an extensively drug-resistant clinical isolate (ICII) of A. baumannii exhibits reduced/delayed early pulmonary neutrophil recruitment, higher lung persistence, and, most importantly, elicits enhanced IL-1β/IL-18 production and lung damage through NLRP3 inflammasome, in comparison with A. baumannii-type strain. A. baumannii infection-induced IL-1β/IL-18 production is entirely dependent on NLRP3-ASC-caspase-1/caspase-11 pathway. Using Nlrp3 -/- mice infection models, we further show that while NLRP3 inflammasome pathway contributes to host defense against A. baumannii clinical isolate, it is dispensable for protection against A. baumannii-type strain. Our study reveals a novel differential role for NLRP3 inflammasome pathway in the immunity against clinically relevant A. baumannii infections, and highlights inflammasome pathway as a potential immunomodulatory target.

  17. Exploring critical uncertainties in pathway assessments of human-assisted introductions of alien forest species in Canada

    Science.gov (United States)

    Denys Yemshanov; Frank H. Koch; Mark J. Ducey; Marty Siltanen; Kirsty Wilson; Klaus Koehler

    2013-01-01

    Long-distance introductions of alien species are often driven by socioeconomic factors, such that conventional “biological” invasion models may not be capable of estimating spread fully and reliably. In this study, we demonstrate a new technique for assessing and reconstructing human-mediated pathways of alien forest species entries to major settlements in Canada via...

  18. A Small Morris-Lecar Neuron Network Gets Close to Critical Only in the Small-World Regimen

    Directory of Open Access Journals (Sweden)

    Juan Luis Cabrera

    2013-01-01

    Full Text Available Spontaneous emergence of neuronal activity avalanches characterized by power-law distributions is known to occur in different types of nervous tissues suggesting that nervous systems may operate at a critical regime. Here, we explore the possible relation of this dynamical state with the underlying topology in a small-size network of interconnected Morris-Lecar neurons. Studying numerically different topological configurations, we find that, very close to the efficient small-world situation, the system self-organizes near to a critical branching process with observable distributions in the proximity of a power law with exponents similar to those reported in the experimental literature. Therefore, we conclude that the observed scaling is intimately related only with the small-world topology.

  19. Pathways to Care for Critically Ill or Injured Children: A Cohort Study from First Presentation to Healthcare Services through to Admission to Intensive Care or Death.

    Directory of Open Access Journals (Sweden)

    Peter Hodkinson

    Full Text Available Critically ill or injured children require prompt identification, rapid referral and quality emergency management. We undertook a study to evaluate the care pathway of critically ill or injured children to identify preventable failures in the care provided.A year-long cohort study of critically ill and injured children was performed in Cape Town, South Africa, from first presentation to healthcare services until paediatric intensive care unit (PICU admission or emergency department death, using expert panel review of medical records and caregiver interview. Main outcomes were expert assessment of overall quality of care; avoidability of severity of illness and PICU admission or death and the identification of modifiable factors.The study enrolled 282 children, 252 emergency PICU admissions, and 30 deaths. Global quality of care was graded good in 10% of cases, with half having at least one major impact modifiable factor. Key modifiable factors related to access to care and identification of the critically ill, assessment of severity, inadequate resuscitation, and delays in decision making and referral. Children were transferred with median time from first presentation to PICU admission of 12.3 hours. There was potentially avoidable severity of illness in 185 (74% of children, and death prior to PICU admission was avoidable in 17/30 (56.7% of children.The study presents a novel methodology, examining quality of care across an entire system, and highlighting the complexity of the pathway and the modifiable events amenable to interventions, that could reduce mortality and morbidity, and optimize utilization of scarce critical care resources; as well as demonstrating the importance of continuity and quality of care.

  20. MicroRNA and transcription factor mediated regulatory network analysis reveals critical regulators and regulatory modules in myocardial infarction.

    Directory of Open Access Journals (Sweden)

    Guangde Zhang

    Full Text Available Myocardial infarction (MI is a severe coronary artery disease and a leading cause of mortality and morbidity worldwide. However, the molecular mechanisms of MI have yet to be fully elucidated. In this study, we compiled MI-related genes, MI-related microRNAs (miRNAs and known human transcription factors (TFs, and we then identified 1,232 feed-forward loops (FFLs among these miRNAs, TFs and their co-regulated target genes through integrating target prediction. By merging these FFLs, the first miRNA and TF mediated regulatory network for MI was constructed, from which four regulators (SP1, ESR1, miR-21-5p and miR-155-5p and three regulatory modules that might play crucial roles in MI were then identified. Furthermore, based on the miRNA and TF mediated regulatory network and literature survey, we proposed a pathway model for miR-21-5p, the miR-29 family and SP1 to demonstrate their potential co-regulatory mechanisms in cardiac fibrosis, apoptosis and angiogenesis. The majority of the regulatory relations in the model were confirmed by previous studies, which demonstrated the reliability and validity of this miRNA and TF mediated regulatory network. Our study will aid in deciphering the complex regulatory mechanisms involved in MI and provide putative therapeutic targets for MI.

  1. Progressing Knowledge in Alternative and Local Food Networks: Critical Reflections and a Research Agenda

    Science.gov (United States)

    Tregear, Angela

    2011-01-01

    In the now extensive literature on alternative food networks (AFNs) (e.g. farmers' markets, community supported agriculture, box schemes), a body of work has pointed to socio-economic problems with such systems, which run counter to headline claims in the literature. This paper argues that rather than being a reflection of inherent complexities in…

  2. Data of the interacting protein networks and nucleotide metabolism pathways related to NDK and NT5

    Directory of Open Access Journals (Sweden)

    Dan Zhang

    2016-12-01

    Full Text Available The data presented in this article are related to the research article entitled “Antibacterial mechanism of daptomycin antibiotic against Staphylococcus aureus based on a quantitative bacterial proteome analysis” (Ma et al., 2016 [1]. Nucleoside diphosphate kinase (NDK and 5′-nucleotidase (NT5 are two proteins related to bacterial growth. Here, a bioinformatics analysis was presented to explore NDK and NT5-invovled in the interacting protein network and purine metabolism.

  3. Neuroplasticity pathways and protein-interaction networks are modulated by vortioxetine in rodents

    DEFF Research Database (Denmark)

    Waller, Jessica A.; Nygaard, Sara Holm; Li, Yan

    2017-01-01

    species and sexes, different brain regions, and in response to distinct routes of administration and regimens. Conclusions: A recurring theme, based on the present study as well as previous findings, is that networks related to synaptic plasticity, synaptic transmission, signal transduction...... antidepressants on various cognitive and plasticity measures. The aim of the present study was to identify biological systems rather than single biomarkers that may underlie vortioxetine's treatment effects. Results: We show that the biological systems regulated by vortioxetine are overlapping between mouse...

  4. An integrated anti-arrhythmic target network of a Chinese medicine compound, Wenxin Keli, revealed by combined machine learning and molecular pathway analysis.

    Science.gov (United States)

    Wang, Taiyi; Lu, Ming; Du, Qunqun; Yao, Xi; Zhang, Peng; Chen, Xiaonan; Xie, Weiwei; Li, Zheng; Ma, Yuling; Zhu, Yan

    2017-05-02

    Wenxin Keli (WK), a Chinese patent medicine, is known to be effective against cardiac arrhythmias and heart failure. Although a number of electrophysiological findings regarding its therapeutic effect have been reported, the active components and system-level characterizations of the component-target interactions of WK have yet to be elucidated. In the current study, we present the first report of a new protective effect of WK on suppressing anti-arrhythmic-agent-induced arrhythmias. In a model of isolated guinea pig hearts, rapid perfusion of quinidine altered the heart rate and prolonged the Q-T interval. Pretreatment with WK significantly prevented quinidine-induced arrhythmias. To explain the therapeutic and protective effects of WK, we constructed an integrated multi-target pharmacological mechanism prediction workflow in combination with machine learning and molecular pathway analysis. This workflow had the ability to predict and rank the probability of each compound interacting with 1715 target proteins simultaneously. The ROC value statistics showed that 97.786% of the values for target prediction were larger than 0.8. We applied this model to carry out target prediction and network analysis for the identified components of 5 herbs in WK. Using the 124 potential anti-arrhythmic components and the 30 corresponding protein targets obtained, an integrative anti-arrhythmic molecular mechanism of WK was proposed. Emerging drug/target networks suggested ion channel and intracellular calcium and autonomic nervous and hormonal regulation had critical roles in WK-mediated anti-arrhythmic activity. A validation of the proposed mechanisms was achieved by demonstrating that calaxin, one of the WK components from Gansong, dose-dependently blocked its predicted target Ca V 1.2 channel in an electrophysiological assay.

  5. Applying a Space-Based Security Recovery Scheme for Critical Homeland Security Cyberinfrastructure Utilizing the NASA Tracking and Data Relay (TDRS) Based Space Network

    Science.gov (United States)

    Shaw, Harry C.; McLaughlin, Brian; Stocklin, Frank; Fortin, Andre; Israel, David; Dissanayake, Asoka; Gilliand, Denise; LaFontaine, Richard; Broomandan, Richard; Hyunh, Nancy

    2015-01-01

    Protection of the national infrastructure is a high priority for cybersecurity of the homeland. Critical infrastructure such as the national power grid, commercial financial networks, and communications networks have been successfully invaded and re-invaded from foreign and domestic attackers. The ability to re-establish authentication and confidentiality of the network participants via secure channels that have not been compromised would be an important countermeasure to compromise of our critical network infrastructure. This paper describes a concept of operations by which the NASA Tracking and Data Relay (TDRS) constellation of spacecraft in conjunction with the White Sands Complex (WSC) Ground Station host a security recovery system for re-establishing secure network communications in the event of a national or regional cyberattack. Users would perform security and network restoral functions via a Broadcast Satellite Service (BSS) from the TDRS constellation. The BSS enrollment only requires that each network location have a receive antenna and satellite receiver. This would be no more complex than setting up a DIRECTTV-like receiver at each network location with separate network connectivity. A GEO BSS would allow a mass re-enrollment of network nodes (up to nationwide) simultaneously depending upon downlink characteristics. This paper details the spectrum requirements, link budget, notional assets and communications requirements for the scheme. It describes the architecture of such a system and the manner in which it leverages off of the existing secure infrastructure which is already in place and managed by the NASAGSFC Space Network Project.

  6. Mental retardation and associated neurological dysfunctions in Down syndrome: a consequence of dysregulation in critical chromosome 21 genes and associated molecular pathways.

    Science.gov (United States)

    Rachidi, Mohammed; Lopes, Carmela

    2008-05-01

    Down syndrome (DS), affecting 1/700 live births, is the major genetic cause of mental retardation (MR), a cognitive disorder with hard impact on public health. DS brain is characterized by a reduced cerebellar volume and number of granular cells, defective cortical lamination and reduced cortical neurons, malformed dendritic trees and spines, and abnormal synapses. These neurological alterations, also found in trisomic mouse models, result from gene-dosage effects of Human Chromosome 21 (HC21) on the expression of critical developmental genes. HC21 sequencing, mouse ortholog gene identification and DS mouse model generation lead to determine HC21 gene functions and the effects of protein-dosage alterations in neurodevelopmental and metabolic pathways in DS individuals. Trisomic brain transcriptome of DS patients and trisomic mouse models identified some molecular changes determined by gene-overdosage and associated dysregulation of some disomic gene expression in DS brains. These transcriptional variations cause developmental alterations in neural patterning and signal transduction pathways that may lead to defective neuronal circuits responsible for the pathogenesis of MR in DS. Recently, the first altered molecular pathway responsible of some DS phenotypes, including neurological and cognitive disorders has been identified. In this pathway, two critical HC21 genes (DYRK1A and DSCR1) act synergistically to control the phosphorylation levels of NFATc and NFATc-regulated gene expression. Interestingly, the NFATc mice show neurological dysfunctions similar to those seen in DS patients and trisomic mouse models. Treatment of DS mouse model Ts65Dn with GABA(A) antagonists allowed post-drug rescue of cognitive defects, indicating a hopeful direction in clinical therapies for MR in children with DS.

  7. Delay-Tolerant, Low-Power Protocols for Large Security-Critical Wireless Sensor Networks

    Directory of Open Access Journals (Sweden)

    Claudio S. Malavenda

    2012-01-01

    Full Text Available This paper reports the analysis, implementation, and experimental testing of a delay-tolerant and energy-aware protocol for a wireless sensor node, oriented to security applications. The solution proposed takes advantages from different domains considering as a guideline the low power consumption and facing the problems of seamless and lossy connectivity offered by the wireless medium along with very limited resources offered by a wireless network node. The paper is organized as follows: first we give an overview on delay-tolerant wireless sensor networking (DTN; then we perform a simulation-based comparative analysis of state-of-the-art DTN approaches and illustrate the improvement offered by the proposed protocol; finally we present experimental data gathered from the implementation of the proposed protocol on a proprietary hardware node.

  8. Reaction-diffusion-like formalism for plastic neural networks reveals dissipative solitons at criticality

    Science.gov (United States)

    Grytskyy, Dmytro; Diesmann, Markus; Helias, Moritz

    2016-06-01

    Self-organized structures in networks with spike-timing dependent synaptic plasticity (STDP) are likely to play a central role for information processing in the brain. In the present study we derive a reaction-diffusion-like formalism for plastic feed-forward networks of nonlinear rate-based model neurons with a correlation sensitive learning rule inspired by and being qualitatively similar to STDP. After obtaining equations that describe the change of the spatial shape of the signal from layer to layer, we derive a criterion for the nonlinearity necessary to obtain stable dynamics for arbitrary input. We classify the possible scenarios of signal evolution and find that close to the transition to the unstable regime metastable solutions appear. The form of these dissipative solitons is determined analytically and the evolution and interaction of several such coexistent objects is investigated.

  9. A Bayesian Network-Based Approach to Selection of Intervention Points in the Mitogen-Activated Protein Kinase Plant Defense Response Pathway.

    Science.gov (United States)

    Venkat, Priya S; Narayanan, Krishna R; Datta, Aniruddha

    2017-04-01

    An important problem in computational biology is the identification of potential points of intervention that can lead to modified network behavior in a genetic regulatory network. We consider the problem of deducing the effect of individual genes on the behavior of the network in a statistical framework. In this article, we make use of biological information from the literature to develop a Bayesian network and introduce a method to estimate parameters of this network using data that are relevant to the biological phenomena under study. Then, we give a novel approach to select significant nodes in the network using a decision-theoretic approach. The proposed method is applied to the analysis of the mitogen-activated protein kinase pathway in the plant defense response to pathogens. Results from applying the method to experimental data show that the proposed approach is effective in selecting genes that play crucial roles in the biological phenomenon being studied.

  10. Critical hydraulic gradient for nonlinear flow through rock fracture networks: The roles of aperture, surface roughness, and number of intersections

    Science.gov (United States)

    Liu, Richeng; Li, Bo; Jiang, Yujing

    2016-02-01

    Transition of fluid flow from the linear to the nonlinear regime has been confirmed in single rock fractures when the Reynolds number (Re) exceeds some critical values, yet the criterion for such a transition in discrete fracture networks (DFNs) has received little attention. This study conducted flow tests on crossed fracture models with a single intersection and performed numerical simulations on fluid flow through DFNs of various geometric characteristics. The roles of aperture, surface roughness, and number of intersections of fractures on the variation of the critical hydraulic gradient (Jc) for the onset of nonlinear flow through DFNs were systematically investigated. The results showed that the relationship between hydraulic gradient (J) and flow rate can be well quantified by Forchheimer's law; when J drops below Jc, it reduces to the widely used cubic law, by diminishing the nonlinear term. Larger apertures, rougher fracture surfaces, and a greater number of intersections in a DFN would result in the onset of nonlinear flow at a lower Jc. Mathematical expressions of Jc and the coefficients involved in Forchheimer's law were developed based on multi-variable regressions of simulation results, which can help to choose proper governing equations when solving problems associated with fluid flow in fracture networks.

  11. Critical conducting networks in disordered solids: ac universality from topological arguments

    DEFF Research Database (Denmark)

    Milovanov, A.V.; Juul Rasmussen, Jens

    2001-01-01

    This paper advocates an unconventional description of charge transport processes in disordered solids, which brings together the ideas of fractal geometry, percolation theory, and topology of manifolds. We demonstrate that the basic features of ac conductivity in disordered materials as seen...... in various experiments are reproduced with remarkable accuracy by the conduction properties of percolating fractal networks near the threshold of percolation. The universal character of ac conductivity in three embedding dimensions is discussed in connection with the available experimental data. An important...

  12. Social Network Sites as ESL/EFL Learning and Teaching Tools: A Critical Review

    Directory of Open Access Journals (Sweden)

    Sulaiman Alnujaidi

    2017-03-01

    Full Text Available This study analyzed the educational and instructional implications of Social Network Sites (SNS in the ESL/EFL teaching and learning context. SNS's definition, types, classifications, features, positive and negative aspects, their educational implications as well as their limitations and challenges in the ESL/EFL classroom settings are identified and discussed in order to better utilize and integrate their innovative aspects into the language teaching and learning practices.

  13. Networks and Pathways in Preparing for Careers in Industrial R&D

    Science.gov (United States)

    Young, Mary H.

    1998-03-01

    A discussion of the skills not typically learned in academic course work but important to a young scientist embarking on a technical career in "Research and Development" will be presented. These include skills relating to "networking" with other scientists and other people intersected with along a career path. Examples and the specific context for the discussion will come from experiences in a central research laboratory for a large industrial company engaged in an unusually wide range of technically-based businesses - defense electronics, telecommunications, and automotive electronics.

  14. ER network homeostasis is critical for plant endosome streaming and endocytosis

    Science.gov (United States)

    Stefano, Giovanni; Renna, Luciana; Lai, YaShiuan; Slabaugh, Erin; Mannino, Nicole; Buono, Rafael A; Otegui, Marisa S; Brandizzi, Federica

    2015-01-01

    Eukaryotic cells internalize cargo at the plasma membrane via endocytosis, a vital process that is accomplished through a complex network of endosomal organelles. In mammalian cells, the ER is in close association with endosomes and regulates their fission. Nonetheless, the physiological role of such interaction on endocytosis is yet unexplored. Here, we probed the existence of ER–endosome association in plant cells and assayed its physiological role in endocytosis. Through live-cell imaging and electron microscopy studies, we established that endosomes are extensively associated with the plant ER, supporting conservation of interaction between heterotypic organelles in evolutionarily distant kingdoms. Furthermore, by analyzing ER–endosome dynamics in genetic backgrounds with defects in ER structure and movement, we also established that the ER network integrity is necessary for homeostasis of the distribution and streaming of various endosome populations as well as for efficient endocytosis. These results support a novel model that endocytosis homeostasis depends on a spatiotemporal control of the endosome dynamics dictated by the ER membrane network. PMID:27462431

  15. Deep sequencing and in silico analyses identify MYB-regulated gene networks and signaling pathways in pancreatic cancer.

    Science.gov (United States)

    Azim, Shafquat; Zubair, Haseeb; Srivastava, Sanjeev K; Bhardwaj, Arun; Zubair, Asif; Ahmad, Aamir; Singh, Seema; Khushman, Moh'd; Singh, Ajay P

    2016-06-29

    We have recently demonstrated that the transcription factor MYB can modulate several cancer-associated phenotypes in pancreatic cancer. In order to understand the molecular basis of these MYB-associated changes, we conducted deep-sequencing of transcriptome of MYB-overexpressing and -silenced pancreatic cancer cells, followed by in silico pathway analysis. We identified significant modulation of 774 genes upon MYB-silencing (p MYB-silenced pancreatic cancer cells exhibiting suppression of EGFR and NF-κB. Decreased expression of EGFR and RELA was validated by both qPCR and immunoblotting and they were both shown to be under direct transcriptional control of MYB. These observations were further confirmed in a converse approach wherein MYB was overexpressed ectopically in a MYB-null pancreatic cancer cell line. Our findings thus suggest that MYB potentially regulates growth and genomic stability of pancreatic cancer cells via targeting complex gene networks and signaling pathways. Further in-depth functional studies are warranted to fully understand MYB signaling in pancreatic cancer.

  16. Variances handling method of clinical pathways based on T-S fuzzy neural networks with novel hybrid learning algorithm.

    Science.gov (United States)

    Du, Gang; Jiang, Zhibin; Diao, Xiaodi; Ye, Yan; Yao, Yang

    2012-06-01

    Clinical pathways' variances present complex, fuzzy, uncertain and high-risk characteristics. They could cause complicating diseases or even endanger patients' life if not handled effectively. In order to improve the accuracy and efficiency of variances handling by Takagi-Sugeno (T-S) fuzzy neural networks (FNNs), a new variances handling method for clinical pathways (CPs) is proposed in this study, which is based on T-S FNNs with novel hybrid learning algorithm. And the optimal structure and parameters can be achieved simultaneously by integrating the random cooperative decomposing particle swarm optimization algorithm (RCDPSO) and discrete binary version of PSO (DPSO) algorithm. Finally, a case study on liver poisoning of osteosarcoma preoperative chemotherapy CP is used to validate the proposed method. The result demonstrates that T-S FNNs based on the proposed algorithm achieves superior performances in efficiency, precision, and generalization ability to standard T-S FNNs, Mamdani FNNs and T-S FNNs based on other algorithms (CPSO and PSO) for variances handling of CPs.

  17. VSNL1 Co-expression networks in aging include calcium signaling, synaptic plasticity, and Alzheimer’s disease pathways

    Directory of Open Access Journals (Sweden)

    C W Lin

    2015-03-01

    Full Text Available The Visinin-like 1 (VSNL1 gene encodes Visinin-like protein 1, a peripheral biomarker for Alzheimer disease (AD. Little is known, however, about normal VSNL1 expression in brain and the biologic networks in which it participates. Frontal cortex gray matter from 209 subjects without neurodegenerative or psychiatric illness, ranging in age from 16–91, were processed on Affymetrix GeneChip 1.1 ST and Human SNP Array 6.0. VSNL1 expression was unaffected by age and sex, and not significantly associated with SNPs in cis or trans. VSNL1 was significantly co-expressed with genes in pathways for Calcium Signaling, AD, Long Term Potentiation, Long Term Depression, and Trafficking of AMPA Receptors. The association with AD was driven, in part, by correlation with amyloid precursor protein (APP expression. These findings provide an unbiased link between VSNL1 and molecular mechanisms of AD, including pathways implicated in synaptic pathology in AD. Whether APP may drive increased VSNL1 expression, VSNL1 drives increased APP expression, or both are downstream of common pathogenic regulators will need to be evaluated in model systems.

  18. CSGene: a literature-based database for cell senescence genes and its application to identify critical cell aging pathways and associated diseases.

    Science.gov (United States)

    Zhao, M; Chen, L; Qu, H

    2016-01-14

    Cell senescence is a cellular process in which normal diploid cells cease to replicate and is a major driving force for human cancers and aging-associated diseases. Recent studies on cell senescence have identified many new genetic components and pathways that control cell aging. However, there is no comprehensive resource for cell senescence that integrates various genetic studies and relationships with cell senescence, and the risk associated with complex diseases such as cancer is still unexplored. We have developed the first literature-based gene resource for exploring cell senescence genes, CSGene. We complied 504 experimentally verified genes from public data resources and published literature. Pathway analyses highlighted the prominent roles of cell senescence genes in the control of rRNA gene transcription and unusual rDNA repeat that constitute a center for the stability of the whole genome. We also found a strong association of cell senescence with HIV-1 infection and viral carcinogenesis that are mainly related to promoter/enhancer binding and chromatin modification processes. Moreover, pan-cancer mutation and network analysis also identified common cell aging mechanisms in cancers and uncovered a highly modular network structure. These results highlight the utility of CSGene for elucidating the complex cellular events of cell senescence.

  19. Development of an artificial neural network to predict critical heat flux based on the look up tables

    Energy Technology Data Exchange (ETDEWEB)

    Terng, Nilton; Carajilescov, Pedro, E-mail: Nil.terng@gmail.com, E-mail: pedro.carajilescov@ufabc.edu.br [Universidade Federal do ABC (UFABC), Santo Andre, SP (Brazil). Centro de Engenharia, Modelagem e Ciencias Sociais

    2015-07-01

    The critical heat flux (CHF) is one of the principal thermal hydraulic limits of PWR type nuclear reactors. The present work consists in the development of an artificial neural network (ANN) to estimate the CHF, based on Look Up Table CHF data, published by Groeneveld (2006). Three parameters were considered in the development of the ANN: the pressure in the range of 1 to 21 MPa, the mass flux in the range of 50 to 8000 kg m{sup -2} s{sup -1} and the thermodynamic quality in the range of - 0.5 to 0.9. The ANN model considered was a multi feed forward net, which have two feedforward ANN. The first one, called main neural network, is used to calculate the result of CHF, and the second, denominated spacenet, is responsible to modify the main neural network according to the input. Comparing the ANN predictions with the data of the Look Up Table, it was observed an average of the ratio of 0.993 and a root mean square error of 13.3%. With the developed ANN, a parametric study of CHF was performed to observe the influence of each parameter in the CHF. It was possible to note that the CHF decreases with the increase of pressure and thermodynamic quality, while CHF increases with the mass flow rate, as expected. However, some erratic trends were also observed which can be attributed to either unknown aspect of the CHF phenomenon or uncertainties in the data. (author)

  20. Altered protein networks and cellular pathways in severe west nile disease in mice.

    Directory of Open Access Journals (Sweden)

    Christophe Fraisier

    Full Text Available BACKGROUND: The recent West Nile virus (WNV outbreaks in developed countries, including Europe and the United States, have been associated with significantly higher neuropathology incidence and mortality rate than previously documented. The changing epidemiology, the constant risk of (re-emergence of more virulent WNV strains, and the lack of effective human antiviral therapy or vaccines makes understanding the pathogenesis of severe disease a priority. Thus, to gain insight into the pathophysiological processes in severe WNV infection, a kinetic analysis of protein expression profiles in the brain of WNV-infected mice was conducted using samples prior to and after the onset of clinical symptoms. METHODOLOGY/PRINCIPAL FINDINGS: To this end, 2D-DIGE and gel-free iTRAQ labeling approaches were combined, followed by protein identification by mass spectrometry. Using these quantitative proteomic approaches, a set of 148 proteins with modified abundance was identified. The bioinformatics analysis (Ingenuity Pathway Analysis of each protein dataset originating from the different time-point comparisons revealed that four major functions were altered during the course of WNV-infection in mouse brain tissue: i modification of cytoskeleton maintenance associated with virus circulation; ii deregulation of the protein ubiquitination pathway; iii modulation of the inflammatory response; and iv alteration of neurological development and neuronal cell death. The differential regulation of selected host protein candidates as being representative of these biological processes were validated by western blotting using an original fluorescence-based method. CONCLUSION/SIGNIFICANCE: This study provides novel insights into the in vivo kinetic host reactions against WNV infection and the pathophysiologic processes involved, according to clinical symptoms. This work offers useful clues for anti-viral research and further evaluation of early biomarkers for the diagnosis

  1. The Integration of Epistasis Network and Functional Interactions in a GWAS Implicates RXR Pathway Genes in the Immune Response to Smallpox Vaccine.

    Directory of Open Access Journals (Sweden)

    Brett A McKinney

    Full Text Available Although many diseases and traits show large heritability, few genetic variants have been found to strongly separate phenotype groups by genotype. Complex regulatory networks of variants and expression of multiple genes lead to small individual-variant effects and difficulty replicating the effect of any single variant in an affected pathway. Interaction network modeling of GWAS identifies effects ignored by univariate models, but population differences may still cause specific genes to not replicate. Integrative network models may help detect indirect effects of variants in the underlying biological pathway. In this study, we used gene-level functional interaction information from the Integrative Multi-species Prediction (IMP tool to reveal important genes associated with a complex phenotype through evidence from epistasis networks and pathway enrichment. We test this method for augmenting variant-based network analyses with functional interactions by applying it to a smallpox vaccine immune response GWAS. The integrative analysis spotlights the role of genes related to retinoid X receptor alpha (RXRA, which has been implicated in a previous epistasis network analysis of smallpox vaccine.

  2. Gene network inference and biochemical assessment delineates GPCR pathways and CREB targets in small intestinal neuroendocrine neoplasia.

    Directory of Open Access Journals (Sweden)

    Ignat Drozdov

    Full Text Available Small intestinal (SI neuroendocrine tumors (NET are increasing in incidence, however little is known about their biology. High throughput techniques such as inference of gene regulatory networks from microarray experiments can objectively define signaling machinery in this disease. Genome-wide co-expression analysis was used to infer gene relevance network in SI-NETs. The network was confirmed to be non-random, scale-free, and highly modular. Functional analysis of gene co-expression modules revealed processes including 'Nervous system development', 'Immune response', and 'Cell-cycle'. Importantly, gene network topology and differential expression analysis identified over-expression of the GPCR signaling regulators, the cAMP synthetase, ADCY2, and the protein kinase A, PRKAR1A. Seven CREB response element (CRE transcripts associated with proliferation and secretion: BEX1, BICD1, CHGB, CPE, GABRB3, SCG2 and SCG3 as well as ADCY2 and PRKAR1A were measured in an independent SI dataset (n = 10 NETs; n = 8 normal preparations. All were up-regulated (p<0.035 with the exception of SCG3 which was not differently expressed. Forskolin (a direct cAMP activator, 10(-5 M significantly stimulated transcription of pCREB and 3/7 CREB targets, isoproterenol (a selective ß-adrenergic receptor agonist and cAMP activator, 10(-5 M stimulated pCREB and 4/7 targets while BIM-53061 (a dopamine D(2 and Serotonin [5-HT(2] receptor agonist, 10(-6 M stimulated 100% of targets as well as pCREB; CRE transcription correlated with the levels of cAMP accumulation and PKA activity; BIM-53061 stimulated the highest levels of cAMP and PKA (2.8-fold and 2.5-fold vs. 1.8-2-fold for isoproterenol and forskolin. Gene network inference and graph topology analysis in SI NETs suggests that SI NETs express neural GPCRs that activate different CRE targets associated with proliferation and secretion. In vitro studies, in a model NET cell system, confirmed that transcriptional

  3. Dissecting the Gene Network of Dietary Restriction to Identify Evolutionarily Conserved Pathways and New Functional Genes

    Science.gov (United States)

    Wuttke, Daniel; Connor, Richard; Vora, Chintan; Craig, Thomas; Li, Yang; Wood, Shona; Vasieva, Olga; Shmookler Reis, Robert; Tang, Fusheng; de Magalhães, João Pedro

    2012-01-01

    Dietary restriction (DR), limiting nutrient intake from diet without causing malnutrition, delays the aging process and extends lifespan in multiple organisms. The conserved life-extending effect of DR suggests the involvement of fundamental mechanisms, although these remain a subject of debate. To help decipher the life-extending mechanisms of DR, we first compiled a list of genes that if genetically altered disrupt or prevent the life-extending effects of DR. We called these DR–essential genes and identified more than 100 in model organisms such as yeast, worms, flies, and mice. In order for other researchers to benefit from this first curated list of genes essential for DR, we established an online database called GenDR (http://genomics.senescence.info/diet/). To dissect the interactions of DR–essential genes and discover the underlying lifespan-extending mechanisms, we then used a variety of network and systems biology approaches to analyze the gene network of DR. We show that DR–essential genes are more conserved at the molecular level and have more molecular interactions than expected by chance. Furthermore, we employed a guilt-by-association method to predict novel DR–essential genes. In budding yeast, we predicted nine genes related to vacuolar functions; we show experimentally that mutations deleting eight of those genes prevent the life-extending effects of DR. Three of these mutants (OPT2, FRE6, and RCR2) had extended lifespan under ad libitum, indicating that the lack of further longevity under DR is not caused by a general compromise of fitness. These results demonstrate how network analyses of DR using GenDR can be used to make phenotypically relevant predictions. Moreover, gene-regulatory circuits reveal that the DR–induced transcriptional signature in yeast involves nutrient-sensing, stress responses and meiotic transcription factors. Finally, comparing the influence of gene expression changes during DR on the interactomes of multiple

  4. Distinct kinetic pathways generate organogel networks with contrasting fractality and thixotropic properties.

    Science.gov (United States)

    Huang, Xiao; Raghavan, Srinivasa R; Terech, Pierre; Weiss, Richard G

    2006-11-29

    The kinetics of the isothermal transformation of sols, comprised of a low molecular-mass organogelator (LMOG) and an organic liquid, to their organogel phases have been followed by circular dichroism (CD), fluorescence, small angle neutron scattering (SANS), and rheological methods. The thixotropic properties (in the sense that severe shearing followed by rest lead to reestablishment of viscoelasticity) of the gels have been examined as well by rheological measurements. The compositions of the samples were either 5alpha-cholestan-3beta-yl N-(2-naphthyl) carbamate (CNC) in an n-alkane (n-octane or n-dodecane) or 3beta-cholesteryl N-(2-naphthyl) carbamate (CeNC) in ethyl acetate. Values of Df, the mass fractal dimension of the microcrystalline self-assembled fibrillar networks (SAFINs) in the gels, have been extracted from the kinetic data using a model developed by Dickinson (J. Chem. Soc., Faraday Trans. 1997, 93, 111). The Df values, 1.1-1.3 for the CeNC gels and 1.3-1.4 or 1.6-1.8 (depending on the temperature of incubation of the sol phase) for CNC gels, are consistent with the gel network structures observed by optical microscopy. In addition, comparison of the temperature dependence of both n (the Avrami component) and K (the Avrami "rate constant") for CeNC/ethyl acetate gelation with those reported previously for gelation of CNC/n-alkane sols demonstrate that the very small change of a single bond in CNC to a double bond in CeNC causes significant differences in their gelation abilities and gel properties. The rheological measurements on CNC/n-alkane gels with spherulitic SAFIN units, formed by incubation of their sols at or =30 degrees C, leading to fiberlike SAFIN units, remain liquidlike after shearing regardless of the periods they are at rest. The time-dependent viscoelastic properties of the gel networks are treated according to a stretched exponential model. The observations from these studies provide detailed insights into the mechanisms of formation

  5. Aurora Kinase A is critical for the Nkx6.1 mediated β-cell proliferation pathway

    OpenAIRE

    Hobson, Amanda; Draney, Carrie; Stratford, Andrew; Becker, Thomas C.; Lu, Danhong; Arlotto, Michelle; Jeffery S. Tessem

    2015-01-01

    Type 1 and type 2 diabetes are ultimately characterized by depleted β-cell mass. Characterization of the molecular pathways that control β-cell proliferation could be harnessed to restore these cells. The homeobox β-cell transcription factor Nkx6.1 induces β-cell proliferation by activating the orphan nuclear receptors Nr4a1 and Nr4a3. Here, we demonstrate that Nkx6.1 localizes to the promoter of the mitotic kinase AURKA (Aurora Kinase A) and induces its expression. Adenovirus mediated overex...

  6. B cells as a critical node in the microbiota-host immune system network.

    Science.gov (United States)

    Slack, Emma; Balmer, Maria L; Macpherson, Andrew J

    2014-07-01

    Mutualism with our intestinal microbiota is a prerequisite for healthy existence. This requires physical separation of the majority of the microbiota from the host (by secreted antimicrobials, mucus, and the intestinal epithelium) and active immune control of the low numbers of microbes that overcome these physical and chemical barriers, even in healthy individuals. In this review, we address how B-cell responses to members of the intestinal microbiota form a robust network with mucus, epithelial integrity, follicular helper T cells, innate immunity, and gut-associated lymphoid tissues to maintain host-microbiota mutualism. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  7. Network Mendelian randomization: using genetic variants as instrumental variables to investigate mediation in causal pathways.

    Science.gov (United States)

    Burgess, Stephen; Daniel, Rhian M; Butterworth, Adam S; Thompson, Simon G

    2015-04-01

    Mendelian randomization uses genetic variants, assumed to be instrumental variables for a particular exposure, to estimate the causal effect of that exposure on an outcome. If the instrumental variable criteria are satisfied, the resulting estimator is consistent even in the presence of unmeasured confounding and reverse causation. We extend the Mendelian randomization paradigm to investigate more complex networks of relationships between variables, in particular where some of the effect of an exposure on the outcome may operate through an intermediate variable (a mediator). If instrumental variables for the exposure and mediator are available, direct and indirect effects of the exposure on the outcome can be estimated, for example using either a regression-based method or structural equation models. The direction of effect between the exposure and a possible mediator can also be assessed. Methods are illustrated in an applied example considering causal relationships between body mass index, C-reactive protein and uric acid. These estimators are consistent in the presence of unmeasured confounding if, in addition to the instrumental variable assumptions, the effects of both the exposure on the mediator and the mediator on the outcome are homogeneous across individuals and linear without interactions. Nevertheless, a simulation study demonstrates that even considerable heterogeneity in these effects does not lead to bias in the estimates. These methods can be used to estimate direct and indirect causal effects in a mediation setting, and have potential for the investigation of more complex networks between multiple interrelated exposures and disease outcomes. © The Author 2014. Published by Oxford University Press on behalf of the International Epidemiological Association.

  8. A critical pathway for the management of elderly inpatients with malnutrition: effects on serum insulin-like growth factor-I.

    Science.gov (United States)

    Trombetti, A; Cheseaux, J; Herrmann, F R; Rizzoli, R

    2013-11-01

    Several guidelines recommend systematic screening for malnutrition in elderly inpatients for early dietary intakes assessment and treatment, but data demonstrating the efficacy of such interventions are scarce. The aim of this study was to evaluate a critical medical pathway for the detection and management of malnutrition in elderly inpatients. In a 3-month prospective controlled study, 694 recently admitted inpatients were assigned to an intervention group (critical medical pathway; n=465) or a standard care control group (n=229). Nutritional status was assessed at the time of admission with a Mini Nutritional Assessment. A renutrition program tailored to the initial dietary assessment results was applied in the intervention group. The efficacy of the program was verified by measuring the evolution of serum insulin-like growth factor 1 (IGF-I) between admission and 3 weeks later. In the intervention group at baseline, 23% were malnourished, 51% were at risk and 26% were eunourished. Serum IGF-I increased in the intervention group (from 84±45 μg/l to 95±50 μg/l, Pelderly inpatients were associated with an increase in serum IGF-I. It remains to be determined whether such variations are clinically relevant.

  9. Module-based functional pathway enrichment analysis of a protein-protein interaction network to study the effects of intestinal microbiota depletion in mice.

    Science.gov (United States)

    Jia, Zhen-Yi; Xia, Yang; Tong, Danian; Yao, Jing; Chen, Hong-Qi; Yang, Jun

    2014-06-01

    Complex communities of microorganisms play important roles in human health, and alterations in the intestinal microbiota may induce intestinal inflammation and numerous diseases. The purpose of this study was to identify the key genes and processes affected by depletion of the intestinal microbiota in a murine model. The Affymetrix microarray dataset GSE22648 was downloaded from the Gene Expression Omnibus database, and differentially expressed genes (DEGs) were identified using the limma package in R. A protein-protein interaction (PPI) network was constructed for the DEGs using the Cytoscape software, and the network was divided into several modules using the MCODE plugin. Furthermore, the modules were functionally annotated using the PiNGO plugin, and DEG-related pathways were retrieved and analyzed using the GenMAPP software. A total of 53 DEGs were identified, of which 26 were upregulated and 27 were downregulated. The PPI network of these DEGs comprised 3 modules. The most significant module-related DEGs were the cytochrome P450 (CYP) 4B1 isozyme gene (CYP4B1) in module 1, CYP4F14 in module 2 and the tachykinin precursor 1 gene (TAC1) in module 3. The majority of enriched pathways of module 1 and 2 were oxidation reduction pathways (metabolism of xenobiotics by CYPs) and lipid metabolism-related pathways, including linoleic acid and arachidonic acid metabolism. The neuropeptide signaling pathway was the most significantly enriched functional pathway of module 3. In conclusion, our findings strongly suggest that intestinal microbiota depletion affects cellular metabolism and oxidation reduction pathways. In addition, this is the first time, to the best of our knowledge, that the neuropeptide signaling pathway is reported to be affected by intestinal microbiota depletion in mice. The present study provides a list of candidate genes and processes related to the interaction of microbiota with the intestinal tract.

  10. Automated generation of patient-tailored electronic care pathways by translating computer-interpretable guidelines into hierarchical task networks.

    Science.gov (United States)

    González-Ferrer, Arturo; ten Teije, Annette; Fdez-Olivares, Juan; Milian, Krystyna

    2013-02-01

    This paper describes a methodology which enables computer-aided support for the planning, visualization and execution of personalized patient treatments in a specific healthcare process, taking into account complex temporal constraints and the allocation of institutional resources. To this end, a translation from a time-annotated computer-interpretable guideline (CIG) model of a clinical protocol into a temporal hierarchical task network (HTN) planning domain is presented. The proposed method uses a knowledge-driven reasoning process to translate knowledge previously described in a CIG into a corresponding HTN Planning and Scheduling domain, taking advantage of HTNs known ability to (i) dynamically cope with temporal and resource constraints, and (ii) automatically generate customized plans. The proposed method, focusing on the representation of temporal knowledge and based on the identification of workflow and temporal patterns in a CIG, makes it possible to automatically generate time-annotated and resource-based care pathways tailored to the needs of any possible patient profile. The proposed translation is illustrated through a case study based on a 70 pages long clinical protocol to manage Hodgkin's disease, developed by the Spanish Society of Pediatric Oncology. We show that an HTN planning domain can be generated from the corresponding specification of the protocol in the Asbru language, providing a running example of this translation. Furthermore, the correctness of the translation is checked and also the management of ten different types of temporal patterns represented in the protocol. By interpreting the automatically generated domain with a state-of-art HTN planner, a time-annotated care pathway is automatically obtained, customized for the patient's and institutional needs. The generated care pathway can then be used by clinicians to plan and manage the patients long-term care. The described methodology makes it possible to automatically generate

  11. A care pathway analysis of tuberculosis patients in benin: Highlights on direct costs and critical stages for an evidence-based decision-making.

    Directory of Open Access Journals (Sweden)

    Samia Laokri

    Full Text Available BACKGROUND: Free tuberculosis control fail to protect patients from substantial medical and non-medical expenditure, thus a greater degree of disaggregation of patient cost is needed to fully capture their context and inform policymaking. METHODS: A retrospective cross-sectional study was conducted on a convenience sample of six health districts of Southern Benin. From August 2008 to February 2009, we recruited all smear-positive pulmonary tuberculosis patients treated under the national strategy in the selected districts. Direct out-of-pocket costs associated with tuberculosis, time delays, and care-seeking pattern were collected from symptom onset to end of treatment. RESULTS: Population description and outcome data were reported for 245 patients of whom 153 completed their care pathway. For them, the median overall direct cost was USD 183 per patient. Payments to traditional healers, self-medication drugs, travel, and food expenditures contributed largely to this cost burden. Patient, provider, and treatment delays were also reported. Pre-diagnosis and intensive treatment stages were the most critical stages, with median expenditure of USD 43 per patient and accounting for 38% and 29% of the overall direct cost, respectively. However, financial barriers differed depending on whether the patient lived in urban or rural areas. CONCLUSIONS: This study delivers new evidence about bottlenecks encountered during the TB care pathway. Financial barriers to accessing the free-of-charge tuberculosis control strategy in Benin remain substantial for low-income households. Irregular time delays and hidden costs, often generated by multiple visits to various care providers, impair appropriate patient pathways. Particular attention should be paid to pre-diagnosis and intensive treatment. Cost assessment and combined targeted interventions embodied by a patient-centered approach on the specific critical stages would likely deliver better program outcomes.

  12. A care pathway analysis of tuberculosis patients in benin: Highlights on direct costs and critical stages for an evidence-based decision-making.

    Science.gov (United States)

    Laokri, Samia; Amoussouhui, Arnaud; Ouendo, Edgard M; Hounnankan, Athanase Cossi; Anagonou, Séverin; Gninafon, Martin; Kassa, Ferdinand; Tawo, Léon; Dujardin, Bruno

    2014-01-01

    Free tuberculosis control fail to protect patients from substantial medical and non-medical expenditure, thus a greater degree of disaggregation of patient cost is needed to fully capture their context and inform policymaking. A retrospective cross-sectional study was conducted on a convenience sample of six health districts of Southern Benin. From August 2008 to February 2009, we recruited all smear-positive pulmonary tuberculosis patients treated under the national strategy in the selected districts. Direct out-of-pocket costs associated with tuberculosis, time delays, and care-seeking pattern were collected from symptom onset to end of treatment. Population description and outcome data were reported for 245 patients of whom 153 completed their care pathway. For them, the median overall direct cost was USD 183 per patient. Payments to traditional healers, self-medication drugs, travel, and food expenditures contributed largely to this cost burden. Patient, provider, and treatment delays were also reported. Pre-diagnosis and intensive treatment stages were the most critical stages, with median expenditure of USD 43 per patient and accounting for 38% and 29% of the overall direct cost, respectively. However, financial barriers differed depending on whether the patient lived in urban or rural areas. This study delivers new evidence about bottlenecks encountered during the TB care pathway. Financial barriers to accessing the free-of-charge tuberculosis control strategy in Benin remain substantial for low-income households. Irregular time delays and hidden costs, often generated by multiple visits to various care providers, impair appropriate patient pathways. Particular attention should be paid to pre-diagnosis and intensive treatment. Cost assessment and combined targeted interventions embodied by a patient-centered approach on the specific critical stages would likely deliver better program outcomes.

  13. Effects of chemical inhibition of N-WASP, a critical regulator of actin polymerization on aqueous humor outflow through the conventional pathway.

    Science.gov (United States)

    Inoue, Toshihiro; Pattabiraman, Padmanabhan P; Epstein, David L; Vasantha Rao, P

    2010-02-01

    The integrity of actin cytoskeletal organization in aqueous humor outflow pathway is thought to play a critical role in modulation of aqueous humor outflow through the trabecular meshwork. Our understanding of the regulation of actin cytoskeletal dynamics in outflow pathway, however, is very limited. To explore the potential importance of Neural Wiskott-Aldrich syndrome protein (N-WASP), a critical regulator of actin polymerization/nucleation in aqueous humor outflow pathway, the effects of Wiskostatin, a selective pharmacological inhibitor of N-WASP, on aqueous humor outflow facility were evaluated using enucleated porcine eyes and a constant pressure perfusion system. Further, drug induced effects on actin cytoskeletal organization, cell adhesions, myosin II phosphorylation, matrix metalloproteinase (MMP) activity, and cytoskeletal protein profile in porcine trabecular meshwork (TM) cells were determined by immunofluorescence, zymography, and mass spectrometry. Aqueous humor outflow facility was increased significantly and progressively in the Wiskostatin perfused porcine eyes. The Wiskostatin perfused eyes appear to exhibit increased giant vacuoles in the inner wall of aqueous plexi and deformation of aqueous plexi. The Wiskostatin treated TM cells demonstrated extensive vacuoles in their cytosol, and both actin stress fibers and focal adhesions were decreased in a reversible manner. The drug-treated TM cells also revealed decreased myosin II and actin in the cytoskeletal enriched triton insoluble fraction but did not affect myosin II phosphorylation or MMP-2 activity. These data demonstrate that the chemical inhibition of N-WASP increases aqueous humor outflow facility in association with decreased actomyosin interaction and cell adhesive interactions revealing the importance of N-WASP in homeostasis of aqueous humor outflow. Copyright 2009 Elsevier Ltd. All rights reserved.

  14. A Network Approach of Gene Co-expression in the Zea mays/Aspergillus flavus Pathosystem to Map Host/Pathogen Interaction Pathways.

    Science.gov (United States)

    Musungu, Bryan M; Bhatnagar, Deepak; Brown, Robert L; Payne, Gary A; OBrian, Greg; Fakhoury, Ahmad M; Geisler, Matt

    2016-01-01

    A gene co-expression network (GEN) was generated using a dual RNA-seq study with the fungal pathogen Aspergillus flavus and its plant host Zea mays during the initial 3 days of infection. The analysis deciphered novel pathways and mapped genes of interest in both organisms during the infection. This network revealed a high degree of connectivity in many of the previously recognized pathways in Z. mays such as jasmonic acid, ethylene, and reactive oxygen species (ROS). For the pathogen A. flavus, a link between aflatoxin production and vesicular transport was identified within the network. There was significant interspecies correlation of expression between Z. mays and A. flavus for a subset of 104 Z. mays, and 1942 A. flavus genes. This resulted in an interspecies subnetwork enriched in multiple Z. mays genes involved in the production of ROS. In addition to the ROS from Z. mays, there was enrichment in the vesicular transport pathways and the aflatoxin pathway for A. flavus. Included in these genes, a key aflatoxin cluster regulator, AflS, was found to be co-regulated with multiple Z. mays ROS producing genes within the network, suggesting AflS may be monitoring host ROS levels. The entire GEN for both host and pathogen, and the subset of interspecies correlations, is presented as a tool for hypothesis generation and discovery for events in the early stages of fungal infection of Z. mays by A. flavus.

  15. A Network Approach of Gene Co-expression in the Zea mays/Aspergillus flavus Pathosystem to Map Host/Pathogen Interaction Pathways

    Science.gov (United States)

    Musungu, Bryan M.; Bhatnagar, Deepak; Brown, Robert L.; Payne, Gary A.; OBrian, Greg; Fakhoury, Ahmad M.; Geisler, Matt

    2016-01-01

    A gene co-expression network (GEN) was generated using a dual RNA-seq study with the fungal pathogen Aspergillus flavus and its plant host Zea mays during the initial 3 days of infection. The analysis deciphered novel pathways and mapped genes of interest in both organisms during the infection. This network revealed a high degree of connectivity in many of the previously recognized pathways in Z. mays such as jasmonic acid, ethylene, and reactive oxygen species (ROS). For the pathogen A. flavus, a link between aflatoxin production and vesicular transport was identified within the network. There was significant interspecies correlation of expression between Z. mays and A. flavus for a subset of 104 Z. mays, and 1942 A. flavus genes. This resulted in an interspecies subnetwork enriched in multiple Z. mays genes involved in the production of ROS. In addition to the ROS from Z. mays, there was enrichment in the vesicular transport pathways and the aflatoxin pathway for A. flavus. Included in these genes, a key aflatoxin cluster regulator, AflS, was found to be co-regulated with multiple Z. mays ROS producing genes within the network, suggesting AflS may be monitoring host ROS levels. The entire GEN for both host and pathogen, and the subset of interspecies correlations, is presented as a tool for hypothesis generation and discovery for events in the early stages of fungal infection of Z. mays by A. flavus. PMID:27917194

  16. Safety and security profiles of industry networks used in safety- critical applications

    Directory of Open Access Journals (Sweden)

    Mária FRANEKOVÁ

    2008-01-01

    Full Text Available The author describes the mechanisms of safety and security profiles of industry and communication networks used within safety – related applications in technological and information levels of process control recommended according to standards IEC 61784-3,4. Nowadays the number of vendors of the safety – related communication technologies who guarantees besides the standard communication, the communication amongst the safety – related equipment according to IEC 61508 is increasing. Also the number of safety – related products is increasing, e. g. safety Fieldbus, safety PLC, safety curtains, safety laser scanners, safety buttons, safety relays and other. According to world survey the safety Fieldbus denoted the highest growth from all manufactured safety products.The main part of this paper is the description of the safety-related Fieldbus communication system, which has to guaranty Safety Integrity Level.

  17. Gene co-expression network analysis for identifying modules and functionally enriched pathways in SCA2.

    Science.gov (United States)

    Pflieger, Lance T; Dansithong, Warunee; Paul, Sharan; Scoles, Daniel R; Figueroa, Karla P; Meera, Pratap; Otis, Thomas S; Facelli, Julio C; Pulst, Stefan M

    2017-08-15

    Spinocerebellar ataxia type 2 (SCA2) is an autosomal dominant neurodegenerative disease caused by CAG repeat expansion in the ATXN2 gene. The repeat resides in an encoded region of the gene resulting in polyglutamine (polyQ) expansion which has been assumed to result in gain of function, predominantly, for the ATXN2 protein. We evaluated temporal cerebellar expression profiles by RNA sequencing of ATXN2Q127 mice versus wild-type (WT) littermates. ATXN2Q127 mice are characterized by a progressive motor phenotype onset, and have progressive cerebellar molecular and neurophysiological (Purkinje cell firing frequency) phenotypes. Our analysis revealed previously uncharacterized early and progressive abnormal patterning of cerebellar gene expression. Weighted Gene Coexpression Network Analysis revealed four gene modules that were significantly correlated with disease status, composed primarily of genes associated with GTPase signaling, calcium signaling and cell death. Of these genes, few overlapped with differentially expressed cerebellar genes that we identified in Atxn2-/- knockout mice versus WT littermates, suggesting that loss-of-function is not a significant component of disease pathology. We conclude that SCA2 is a disease characterized by gain of function for ATXN2. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  18. [Critical factors affecting nurse use of in-hospital employee communication networks].

    Science.gov (United States)

    Yu, Shu-Chin; Hou, Ying-Hui

    2011-10-01

    Level of concealment/suppression of true feelings in the course of carrying out nursing duties relates positively to risk of emotional exhaustion and burnout. Therefore, nurses need channels to release and reduce emotional stressors. We surveyed nurse use of an In-Hospital Employee Communication Network (IECN) to identify its efficacy as well as factors that influence nurse IECN use. This paper also provides research suggestions to help further reduce emotional exhaustion and burnout in nurses. We chose a region hospital as our case hospital and received Institution Review Board (IRB) approval for this study. A stratified sampling approach that reflected the ratio of staff in each department was used to distribute the questionnaires at the case hospital. 80 questionnaires were sent out with a response rate of 80%. All returned questionnaires were qualified as valid responses. IECN users numbered three times more than non-users. Nearly sixty percent of non-users did not use IECN due to, "lack of interest in the IECN." About half of the users have more than four years' experience with IECN. Primary motivations for using the IECN were entertainment, learning, and emotional relaxation, e.g., expressing emotions (43.8%) and emotional support (31.3%). IECN may be improved by enriching content to increase readability. Hospital managers should pay attention to network content and give timely feedback to improve nurse communication and effectively relieve emotional stresses to reduce risks of emotional exhaustion and burnout. Increasing opportunities for nurses to obtain new knowledge through information sharing via IECN can achieve a win-win situation for both the hospital and its employees.

  19. A critical review of the Mediterranean sea turtle rescue network: a web looking for a weaver

    Directory of Open Access Journals (Sweden)

    Judith Ullmann

    2015-06-01

    Full Text Available A key issue in conservation biology is recognizing and bridging the gap between scientific results and specific action. We examine sea turtles—charismatic yet endangered flagship species—in the Mediterranean, a sea with historically high levels of exploitation and 22 coastal nations. We take sea turtle rescue facilities as a visible measure for implemented conservation action. Our study yielded 34 confirmed sea turtle rescue centers, 8 first-aid stations, and 7 informal rescue institutions currently in operation. Juxtaposing these facilities to known sea turtle distribution and threat hotspots reveals a clear disconnect. Only 14 of the 22 coastal countries had centers, with clear gaps in the Middle East and Africa. Moreover, the information flow between centers is apparently limited. The populations of the two species nesting in the Mediterranean, the loggerhead Caretta caretta and the green turtle Chelonia mydas, are far below historical levels and face a range of anthropogenic threats at sea and on land. Sea turtle rescue centers are acknowledged to reduce mortality in bycatch hotspots, provide a wealth of scientific data, and raise public awareness. The proposal for a Mediterranean-wide rescue network as published by the Regional Activity Centre for Specially Protected Areas a decade ago has not materialized in its envisioned scope. We discuss the efficiency, gaps, and needs for a rescue network and call for establishing additional rescue centers and an accompanying common online database to connect existing centers. This would provide better information on the number and types of rescue facilities on a Mediterranean scale, improve communication between these facilities, enhance standardization of procedures, yield large-scale data on the number of treated turtles and their injuries, and thus provide valuable input for targeted conservation measures.

  20. A critical consideration of the role of social networks in the Arab spring

    Directory of Open Access Journals (Sweden)

    Kragović Branislava B.

    2013-01-01

    Full Text Available Mass media play a role in social changes by influencing the public opinion during phases of preparation, implementation and justification of performed changes. Social changes in the global age, especially those of greater scope, are hardly imaginable without the role of mass media. Mass media as an instrument of influence over public opinion is used in both cases - when a change goes from 'down' or from 'up'. With regards to the changes initiated by the power holders, the means of impact usually used are classic mass media-newspapers, radio, television, and more often, Internet. However, in cases when the initiators of changes are on lower levels of social hierarchy, the first choice is Internet due to its accessibility and decentralized structure. Internet had demonstrated its influence on social changes earlier, but that influence was especially visible during the 'Arab spring'. The 'Arab spring' is a collective name for a wave of protests and changes which sparked in Tunisia in December 2010 and spilled over to other countries of the northern Africa and Near East. Egypt, Syria, Bahrain, Sudan, Libya, Morocco, Yemen, Algeria are some of them. Due to their prominent role in dissemination of information, the Tunisian episode of the 'Arab spring' is called Facebook revolution or Internet revolution, which clearly indicates which media and social networks had played key role in change of government in Tunisia. Mobile phone, being media of interpersonal communication, have also played significant role in case of Tunisia, the same role mass media had in changes of real-socialist systems. Development of new technologies and their application in field of communication means have revolutionized the communication process. Naturally, television has also played its role in the 'Arab spring'. Bearing in mind that national media services are mostly controlled by the governing elite, the news on rebellion in Tunisia were spread through global media

  1. Curcumin-Induced Apoptosis in Human Hepatocellular Carcinoma J5 Cells: Critical Role of Ca+2-Dependent Pathway

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    Wei-Hsun Wang

    2012-01-01

    Full Text Available The antitumor effects of curcumin, a natural biologically active compound extracted from rhizomes of Curcuma longa, have been studied in many cancer cell types including human hepatocellular carcinoma (HCC. Here, we investigated the effects of Ca2+ on curcumin-induced apoptosis in human HCC J5 cells. The abrogation of mitochondrial membrane potential (ΔΨm, the increase of reactive oxygen species (ROS production, and calcium release were demonstrated with flow cytometry as early as 15 minutes after curcumin treatment. In addition, an increase level of cytochrome c in the cytoplasm which led to DNA fragmentation was observed. To verify the role of Ca2+ in curcumin-induced apoptosis, 1,2-bis(o-aminophenoxyethane-N,N,N′,N′-tetraacetic acid (BAPTA, an intracellular calcium chelator, was applied. Cell viability was increased, but ΔΨm, ROS production, activation of caspase 3, and cell death were decreased in J5 cells pretreated with BAPTA for 2 h followed by the treatment of 25 μM curcumin. These results suggest that the curcumin-induced apoptosis in human HCC J5 cells is via mitochondria-dependent pathway and is closely related to the level of intracellular accumulation of calcium.

  2. Reverse engineering of modified genes by Bayesian network analysis defines molecular determinants critical to the development of glioblastoma.

    Directory of Open Access Journals (Sweden)

    Brian W Kunkle

    Full Text Available In this study we have identified key genes that are critical in development of astrocytic tumors. Meta-analysis of microarray studies which compared normal tissue to astrocytoma revealed a set of 646 differentially expressed genes in the majority of astrocytoma. Reverse engineering of these 646 genes using Bayesian network analysis produced a gene network for each grade of astrocytoma (Grade I-IV, and 'key genes' within each grade were identified. Genes found to be most influential to development of the highest grade of astrocytoma, Glioblastoma multiforme were: COL4A1, EGFR, BTF3, MPP2, RAB31, CDK4, CD99, ANXA2, TOP2A, and SERBP1. All of these genes were up-regulated, except MPP2 (down regulated. These 10 genes were able to predict tumor status with 96-100% confidence when using logistic regression, cross validation, and the support vector machine analysis. Markov genes interact with NFkβ, ERK, MAPK, VEGF, growth hormone and collagen to produce a network whose top biological functions are cancer, neurological disease, and cellular movement. Three of the 10 genes - EGFR, COL4A1, and CDK4, in particular, seemed to be potential 'hubs of activity'. Modified expression of these 10 Markov Blanket genes increases lifetime risk of developing glioblastoma compared to the normal population. The glioblastoma risk estimates were dramatically increased with joint effects of 4 or more than 4 Markov Blanket genes. Joint interaction effects of 4, 5, 6, 7, 8, 9 or 10 Markov Blanket genes produced 9, 13, 20.9, 26.7, 52.8, 53.2, 78.1 or 85.9%, respectively, increase in lifetime risk of developing glioblastoma compared to normal population. In summary, it appears that modified expression of several 'key genes' may be required for the development of glioblastoma. Further studies are needed to validate these 'key genes' as useful tools for early detection and novel therapeutic options for these tumors.

  3. SMAD4 loss enables EGF, TGFβ1 and S100A8/A9 induced activation of critical pathways to invasion in human pancreatic adenocarcinoma cells.

    Science.gov (United States)

    Moz, Stefania; Basso, Daniela; Bozzato, Dania; Galozzi, Paola; Navaglia, Filippo; Negm, Ola H; Arrigoni, Giorgio; Zambon, Carlo-Federico; Padoan, Andrea; Tighe, Paddy; Todd, Ian; Franchin, Cinzia; Pedrazzoli, Sergio; Punzi, Leonardo; Plebani, Mario

    2016-10-25

    Epidermal Growth Factor (EGF) receptor overexpression, KRAS, TP53, CDKN2A and SMAD4 mutations characterize pancreatic ductal adenocarcinoma. This mutational landscape might influence cancer cells response to EGF, Transforming Growth Factor β1 (TGFβ1) and stromal inflammatory calcium binding proteins S100A8/A9. We investigated whether chronic exposure to EGF modifies in a SMAD4-dependent manner pancreatic cancer cell signalling, proliferation and invasion in response to EGF, TGFβ1 and S100A8/A9. BxPC3, homozigously deleted (HD) for SMAD4, and BxPC3-SMAD4+ cells were or not stimulated with EGF (100 ng/mL) for three days. EGF pre-treated and non pretreated cells were stimulated with a single dose of EGF (100 ng/mL), TGFβ1 (0,02 ng/mL), S100A8/A9 (10 nM). Signalling pathways (Reverse Phase Protein Array and western blot), cell migration (Matrigel) and cell proliferation (XTT) were evaluated. SMAD4 HD constitutively activated ERK and Wnt/β-catenin, while inhibiting PI3K/AKT pathways. These effects were antagonized by chronic EGF, which increased p-BAD (anti-apoptotic) in response to combined TGFβ1 and S100A8/A9 stimulation. SMAD4 HD underlied the inhibition of NF-κB and PI3K/AKT in response to TGFβ1 and S100A8/A9, which also induced cell migration. Chronic EGF exposure enhanced cell migration of both BxPC3 and BxPC3-SMAD4+, rendering the cells less sensitive to the other inflammatory stimuli. In conclusion, SMAD4 HD is associated with the constitutive activation of the ERK and Wnt/β-catenin signalling pathways, and favors the EGF-induced activation of multiple signalling pathways critical to cancer proliferation and invasion. TGFβ1 and S100A8/A9 mainly inhibit NF-κB and PI3K/AKT pathways and, when combined, sinergize with EGF in enhancing anti-apoptotic p-BAD in a SMAD4-dependent manner.

  4. Excessive Time on Social Networking Sites and Disordered Eating Behaviors Among Undergraduate Students: Appearance and Weight Esteem as Mediating Pathways.

    Science.gov (United States)

    Murray, Marisa; Maras, Danijela; Goldfield, Gary S

    2016-12-01

    Social networking sites (SNS) are a popular form of communication among undergraduate students. Body image concerns and disordered eating behaviors are also quite prevalent among this population. Maladaptive use of SNS has been associated with disordered eating behaviors; however, the mechanisms remain unclear. The present study examined if body image concerns (e.g., appearance and weight esteem) mediate the relationship between excessive time spent on SNS and disordered eating behaviors (restrained and emotional eating). The sample included 383 (70.2 percent female) undergraduate students (mean age = 23.08 years, standard deviation = 3.09) who completed self-report questionnaires related to SNS engagement, body image, disordered eating behaviors, and demographics. Parallel multiple mediation and moderated mediation analyses revealed that lower weight and appearance esteem mediated the relationship between excessive time on SNS and restrained eating for males and females, whereas appearance esteem mediated the relationship between excessive time on SNS and emotional eating for females only. The study adds to the literature by highlighting mediational pathways and gender differences. Intervention research is needed to determine if teaching undergraduate students more adaptive ways of using SNS or reducing exposure to SNS reduces body dissatisfaction and disordered eating in this high-risk population.

  5. BMP and TGF-β pathway mediators are critical upstream regulators of Wnt signaling during midbrain dopamine differentiation in human pluripotent stem cells.

    Science.gov (United States)

    Cai, Jingli; Schleidt, Stephanie; Pelta-Heller, Joshua; Hutchings, Danielle; Cannarsa, Gregory; Iacovitti, Lorraine

    2013-04-01

    Although many laboratories currently use small molecule inhibitors of the BMP (Dorsomorphin/DM) and TGF-β (SB431542/SB) signaling pathways in protocols to generate midbrain dopamine (mDA) neurons from hES and hiPS cells, until now, these substances have not been thought to play a role in the mDA differentiation process. We report here that the transient inhibition of constitutive BMP (pSMADs 1, 5, 8) signaling, either alone or in combination with TGF-β inhibition (pSMADs 2, 3), is critically important in the upstream regulation of Wnt1-Lmx1a signaling in mDA progenitors. We postulate that the mechanism via which DM or DM/SB mediates these effects involves the up-regulation in SMAD-interacting protein 1 (SIP1), which results in greater repression of the Wnt antagonist, secreted frizzled related protein 1 (Sfrp1) in stem cells. Accordingly, knockdown of SIP1 reverses the inductive effects of DM/SB on mDA differentiation while Sfrp1 knockdown/inhibition mimics DM/SB. The rise in Wnt1-Lmx1a levels in SMAD-inhibited cultures is, however, accompanied by a reciprocal down-regulation in SHH-Foxa2 levels leading to the generation of few TH+ neurons that co-express Foxa2. If however, exogenous SHH/FGF8 is added along with SMAD inhibitors, equilibrium in these two important pathways is achieved such that authentic (Lmx1a+Foxa2+TH+) mDA neuron differentiation is promoted while alternate cell fates are suppressed in stem cell cultures. These data indicate that activators/inhibitors of BMP and TGF-β signaling play a critical upstream regulatory role in the mDA differentiation process in human pluripotent stem cells. Copyright © 2013 Elsevier Inc. All rights reserved.

  6. Anti-inflammatory mechanism of galangin in lipopolysaccharide-stimulated microglia: Critical role of PPAR-γ signaling pathway.

    Science.gov (United States)

    Choi, Min-Ji; Lee, Eun-Jung; Park, Jin-Sun; Kim, Su-Nam; Park, Eun-Mi; Kim, Hee-Sun

    2017-11-15

    Since microglia-associated neuroinflammation plays a pivotal role in the progression of neurodegenerative diseases, controlling microglial activation has been suggested as a potential therapeutic strategy. Here, we investigated the anti-inflammatory effects of galangin (3,5,7-trihydroxyflavone) in microglia and analyzed the underlying molecular mechanisms. Galangin inhibited the expression of inducible nitric oxide synthase (iNOS) and pro-inflammatory cytokines and enhanced the expression of anti-inflammatory interleukin (IL)-10 in lipopolysaccharide (LPS)-stimulated BV2 microglia. Galangin also suppressed microglial activation and the expression of pro-inflammatory markers in LPS-injected mouse brains. The results of mechanistic studies have shown that galangin inhibited LPS-induced phosphorylation of p38 mitogen activated protein kinase (MAPK), c-Jun N-terminal kinase (JNK), phosphatidylinositol 3-kinase (PI3K)/Akt, and nuclear factor (NF)-κB activity. On the contrary, galangin increased the activity of transcription factors, such as nuclear factor-E2-related factor 2 (Nrf2), cAMP response element-binding protein (CREB), and peroxisome proliferator-activated receptor (PPAR)-γ, known to play an anti-inflammatory role. In addition, galangin showed antioxidant effects by suppressing the expression of NADPH oxidase subunits p47phox and gp91phox, and by enhancing hemeoxygenase-1. We then investigated whether PPAR-γ was involved in the anti-inflammatory function of galangin. Pretreatment with a PPAR-γ antagonist or siRNA significantly blocked galangin-mediated upregulation of IL-10 and attenuated the inhibition of tumor necrosis factor (TNF)-α, nitric oxide (NO), and IL-6 in LPS-stimulated microglia. Moreover, the PPAR-γ antagonist reversed the effects of galangin on NF-κB, Nrf2, and CREB. Altogether, our data suggest that PPAR-γ plays a key role in mediating the anti-inflammatory effects of galangin by modulating the NF-κB and Nrf2/CREB signaling pathways

  7. A novel protein, Rsf1/Pxd1, is critical for the single-strand annealing pathway of double-strand break repair in Schizosaccharomyces pombe.

    Science.gov (United States)

    Wang, Hanqian; Zhang, Zhanlu; Zhang, Lan; Zhang, Qiuxue; Zhang, Liang; Zhao, Yangmin; Wang, Weibu; Fan, Yunliu; Wang, Lei

    2015-06-01

    The process of single-strand annealing (SSA) repairs DNA double-strand breaks that are flanked by direct repeat sequences through the coordinated actions of a series of proteins implicated in recombination, mismatch repair and nucleotide excision repair (NER). Many of the molecular and mechanistic insights gained in SSA repair have principally come from studies in the budding yeast Saccharomyces cerevisiae. However, there is little molecular understanding of the SSA pathway in the fission yeast Schizosaccharomyces pombe. To further our understanding of this important process, we established a new chromosome-based SSA assay in fission yeast. Our genetic analyses showed that, although many homologous components participate in SSA repair in these species indicating that some evolutionary conservation, Saw1 and Slx4 are not principal agents in the SSA repair pathway in fission yeast. This is in marked contrast to the function of Saw1 and Slx4 in budding yeast. Additionally, a novel genus-specific protein, Rsf1/Pxd1, physically interacts with Rad16, Swi10 and Saw1 in vitro and in vivo. We find that Rsf1/Pxd1 is not required for NER and demonstrate that, in fission yeast, Rsf1/Pxd1, but not Saw1, plays a critical role in SSA recombination. © 2015 John Wiley & Sons Ltd.

  8. Identification of hydrologic and geochemical pathways using high frequency sampling, REE aqueous sampling and soil characterization at Koiliaris Critical Zone Observatory, Crete

    Energy Technology Data Exchange (ETDEWEB)

    Moraetis, Daniel, E-mail: moraetis@mred.tuc.gr [Department of Environmental Engineering, Technical University of Crete, 73100 Chania (Greece); Stamati, Fotini; Kotronakis, Manolis; Fragia, Tasoula; Paranychnianakis, Nikolaos; Nikolaidis, Nikolaos P. [Department of Environmental Engineering, Technical University of Crete, 73100 Chania (Greece)

    2011-06-15

    Highlights: > Identification of hydrological and geochemical pathways within a complex watershed. > Water increased N-NO{sub 3} concentration and E.C. values during flash flood events. > Soil degradation and impact on water infiltration within the Koiliaris watershed. > Analysis of Rare Earth Elements in water bodies for identification of karstic water. - Abstract: Koiliaris River watershed is a Critical Zone Observatory that represents severely degraded soils due to intensive agricultural activities and biophysical factors. It has typical Mediterranean soils under the imminent threat of desertification which is expected to intensify due to projected climate change. High frequency hydro-chemical monitoring with targeted sampling for Rare Earth Elements (REE) analysis of different water bodies and geochemical characterization of soils were used for the identification of hydrologic and geochemical pathways. The high frequency monitoring of water chemical data highlighted the chemical alterations of water in Koiliaris River during flash flood events. Soil physical and chemical characterization surveys were used to identify erodibility patterns within the watershed and the influence of soils on surface and ground water chemistry. The methodology presented can be used to identify the impacts of degraded soils to surface and ground water quality as well as in the design of methods to minimize the impacts of land use practices.

  9. The cholesterol-dependent cytolysin signature motif: a critical element in the allosteric pathway that couples membrane binding to pore assembly.

    Directory of Open Access Journals (Sweden)

    Kelley J Dowd

    Full Text Available The cholesterol-dependent cytolysins (CDCs constitute a family of pore-forming toxins that contribute to the pathogenesis of a large number of Gram-positive bacterial pathogens.The most highly conserved region in the primary structure of the CDCs is the signature undecapeptide sequence (ECTGLAWEWWR. The CDC pore forming mechanism is highly sensitive to changes in its structure, yet its contribution to the molecular mechanism of the CDCs has remained enigmatic. Using a combination of fluorescence spectroscopic methods we provide evidence that shows the undecapeptide motif of the archetype CDC, perfringolysin O (PFO, is a key structural element in the allosteric coupling of the cholesterol-mediated membrane binding in domain 4 (D4 to distal structural changes in domain 3 (D3 that are required for the formation of the oligomeric pore complex. Loss of the undecapeptide function prevents all measurable D3 structural transitions, the intermolecular interaction of membrane bound monomers and the assembly of the oligomeric pore complex. We further show that this pathway does not exist in intermedilysin (ILY, a CDC that exhibits a divergent undecapeptide and that has evolved to use human CD59 rather than cholesterol as its receptor. These studies show for the first time that the undecapeptide of the cholesterol-binding CDCs forms a critical element of the allosteric pathway that controls the assembly of the pore complex.

  10. Incorporation of Spatial Interactions in Location Networks to Identify Critical Geo-Referenced Routes for Assessing Disease Control Measures on a Large-Scale Campus

    Directory of Open Access Journals (Sweden)

    Tzai-Hung Wen

    2015-04-01

    Full Text Available Respiratory diseases mainly spread through interpersonal contact. Class suspension is the most direct strategy to prevent the spread of disease through elementary or secondary schools by blocking the contact network. However, as university students usually attend courses in different buildings, the daily contact patterns on a university campus are complicated, and once disease clusters have occurred, suspending classes is far from an efficient strategy to control disease spread. The purpose of this study is to propose a methodological framework for generating campus location networks from a routine administration database, analyzing the community structure of the network, and identifying the critical links and nodes for blocking respiratory disease transmission. The data comes from the student enrollment records of a major comprehensive university in Taiwan. We combined the social network analysis and spatial interaction model to establish a geo-referenced community structure among the classroom buildings. We also identified the critical links among the communities that were acting as contact bridges and explored the changes in the location network after the sequential removal of the high-risk buildings. Instead of conducting a questionnaire survey, the study established a standard procedure for constructing a location network on a large-scale campus from a routine curriculum database. We also present how a location network structure at a campus could function to target the high-risk buildings as the bridges connecting communities for blocking disease transmission.

  11. A Microsoft-Excel-based tool for running and critically appraising network meta-analyses--an overview and application of NetMetaXL.

    Science.gov (United States)

    Brown, Stephen; Hutton, Brian; Clifford, Tammy; Coyle, Doug; Grima, Daniel; Wells, George; Cameron, Chris

    2014-09-29

    The use of network meta-analysis has increased dramatically in recent years. WinBUGS, a freely available Bayesian software package, has been the most widely used software package to conduct network meta-analyses. However, the learning curve for WinBUGS can be daunting, especially for new users. Furthermore, critical appraisal of network meta-analyses conducted in WinBUGS can be challenging given its limited data manipulation capabilities and the fact that generation of graphical output from network meta-analyses often relies on different software packages than the analyses themselves. We developed a freely available Microsoft-Excel-based tool called NetMetaXL, programmed in Visual Basic for Applications, which provides an interface for conducting a Bayesian network meta-analysis using WinBUGS from within Microsoft Excel. . This tool allows the user to easily prepare and enter data, set model assumptions, and run the network meta-analysis, with results being automatically displayed in an Excel spreadsheet. It also contains macros that use NetMetaXL's interface to generate evidence network diagrams, forest plots, league tables of pairwise comparisons, probability plots (rankograms), and inconsistency plots within Microsoft Excel. All figures generated are publication quality, thereby increasing the efficiency of knowledge transfer and manuscript preparation. We demonstrate the application of NetMetaXL using data from a network meta-analysis published previously which compares combined resynchronization and implantable defibrillator therapy in left ventricular dysfunction. We replicate results from the previous publication while demonstrating result summaries generated by the software. Use of the freely available NetMetaXL successfully demonstrated its ability to make running network meta-analyses more accessible to novice WinBUGS users by allowing analyses to be conducted entirely within Microsoft Excel. NetMetaXL also allows for more efficient and transparent

  12. Daily visual stimulation in the critical period enhances multiple aspects of vision through BDNF-mediated pathways in the mouse retina.

    Science.gov (United States)

    Mui, Amanda M; Yang, Victoria; Aung, Moe H; Fu, Jieming; Adekunle, Adewumi N; Prall, Brian C; Sidhu, Curran S; Park, Han Na; Boatright, Jeffrey H; Iuvone, P Michael; Pardue, Machelle T

    2018-01-01

    Visual experience during the critical period modulates visual development such that deprivation causes visual impairments while stimulation induces enhancements. This study aimed to determine whether visual stimulation in the form of daily optomotor response (OMR) testing during the mouse critical period (1) improves aspects of visual function, (2) involves retinal mechanisms and (3) is mediated by brain derived neurotrophic factor (BDNF) and dopamine (DA) signaling pathways. We tested spatial frequency thresholds in C57BL/6J mice daily from postnatal days 16 to 23 (P16 to P23) using OMR testing. Daily OMR-treated mice were compared to littermate controls that were placed in the OMR chamber without moving gratings. Contrast sensitivity thresholds, electroretinograms (ERGs), visual evoked potentials, and pattern ERGs were acquired at P21. To determine the role of BDNF signaling, a TrkB receptor antagonist (ANA-12) was systemically injected 2 hours prior to OMR testing in another cohort of mice. BDNF immunohistochemistry was performed on retina and brain sections. Retinal DA levels were measured using high-performance liquid chromatography. Daily OMR testing enhanced spatial frequency thresholds and contrast sensitivity compared to controls. OMR-treated mice also had improved rod-driven ERG oscillatory potential response times, greater BDNF immunoreactivity in the retinal ganglion cell layer, and increased retinal DA content compared to controls. VEPs and pattern ERGs were unchanged. Systemic delivery of ANA-12 attenuated OMR-induced visual enhancements. Daily OMR testing during the critical period leads to general visual function improvements accompanied by increased DA and BDNF in the retina, with this process being requisitely mediated by TrkB activation. These results suggest that novel combination therapies involving visual stimulation and using both behavioral and molecular approaches may benefit degenerative retinal diseases or amblyopia.

  13. How Effective Are Clinical Pathways With and Without Online Peer-Review? An Analysis of Bone Metastases Pathway in a Large, Integrated National Cancer Institute-Designated Comprehensive Cancer Center Network

    Energy Technology Data Exchange (ETDEWEB)

    Beriwal, Sushil, E-mail: beriwals@upmc.edu [Department of Radiation Oncology, University of Pittsburgh Cancer Institute, Pittsburgh, PA (United States); Rajagopalan, Malolan S.; Flickinger, John C.; Rakfal, Susan M. [Department of Radiation Oncology, University of Pittsburgh Cancer Institute, Pittsburgh, PA (United States); Rodgers, Edwin [Via Oncology, Pittsburgh, PA (United States); Heron, Dwight E. [Department of Radiation Oncology, University of Pittsburgh Cancer Institute, Pittsburgh, PA (United States)

    2012-07-15

    Purpose: Clinical pathways are an important tool used to manage the quality in health care by standardizing processes. This study evaluated the impact of the implementation of a peer-reviewed clinical pathway in a large, integrated National Cancer Institute-Designated Comprehensive Cancer Center Network. Methods: In 2003, we implemented a clinical pathway for the management of bone metastases with palliative radiation therapy. In 2009, we required the entry of management decisions into an online tool that records pathway choices. The pathway specified 1 or 5 fractions for symptomatic bone metastases with the option of 10-14 fractions for certain clinical situations. The data were obtained from 13 integrated sites (3 central academic, 10 community locations) from 2003 through 2010. Results: In this study, 7905 sites were treated with 64% of courses delivered in community practice and 36% in academic locations. Academic practices were more likely than community practices to treat with 1-5 fractions (63% vs. 23%; p < 0.0001). The number of delivered fractions decreased gradually from 2003 to 2010 for both academic and community practices (p < 0.0001); however, greater numbers of fractions were selected more often in community practices (p < 0.0001). Using multivariate logistic regression, we found that a significantly greater selection of 1-5 fractions developed after implementation online pathway monitoring (2009) with an odds ratio of 1.2 (confidence interval, 1.1-1.4) for community and 1.3 (confidence interval, 1.1-1.6) for academic practices. The mean number of fractions also decreased after online peer review from 6.3 to 6.0 for academic (p = 0.07) and 9.4 to 9.0 for community practices (p < 0.0001). Conclusion: This is one of the first studies to examine the efficacy of a clinical pathway for radiation oncology in an integrated cancer network. Clinical pathway implementation appears to be effective in changing patterns of care, particularly with online clinical

  14. Reverse Engineering of Modified Genes by Bayesian Network Analysis Defines Molecular Determinants Critical to the Development of Glioblastoma

    Science.gov (United States)

    Kunkle, Brian W.; Yoo, Changwon; Roy, Deodutta

    2013-01-01

    In this study we have identified key genes that are critical in development of astrocytic tumors. Meta-analysis of microarray studies which compared normal tissue to astrocytoma revealed a set of 646 differentially expressed genes in the majority of astrocytoma. Reverse engineering of these 646 genes using Bayesian network analysis produced a gene network for each grade of astrocytoma (Grade I–IV), and ‘key genes’ within each grade were identified. Genes found to be most influential to development of the highest grade of astrocytoma, Glioblastoma multiforme were: COL4A1, EGFR, BTF3, MPP2, RAB31, CDK4, CD99, ANXA2, TOP2A, and SERBP1. All of these genes were up-regulated, except MPP2 (down regulated). These 10 genes were able to predict tumor status with 96–100% confidence when using logistic regression, cross validation, and the support vector machine analysis. Markov genes interact with NFkβ, ERK, MAPK, VEGF, growth hormone and collagen to produce a network whose top biological functions are cancer, neurological disease, and cellular movement. Three of the 10 genes - EGFR, COL4A1, and CDK4, in particular, seemed to be potential ‘hubs of activity’. Modified expression of these 10 Markov Blanket genes increases lifetime risk of developing glioblastoma compared to the normal population. The glioblastoma risk estimates were dramatically increased with joint effects of 4 or more than 4 Markov Blanket genes. Joint interaction effects of 4, 5, 6, 7, 8, 9 or 10 Markov Blanket genes produced 9, 13, 20.9, 26.7, 52.8, 53.2, 78.1 or 85.9%, respectively, increase in lifetime risk of developing glioblastoma compared to normal population. In summary, it appears that modified expression of several ‘key genes’ may be required for the development of glioblastoma. Further studies are needed to validate these ‘key genes’ as useful tools for early detection and novel therapeutic options for these tumors. PMID:23737970

  15. Echocardiography practice, training and accreditation in the intensive care: document for the World Interactive Network Focused on Critical Ultrasound (WINFOCUS

    Directory of Open Access Journals (Sweden)

    Catena Emanuele

    2008-10-01

    Full Text Available Abstract Echocardiography is increasingly used in the management of the critically ill patient as a non-invasive diagnostic and monitoring tool. Whilst in few countries specialized national training schemes for intensive care unit (ICU echocardiography have been developed, specific guidelines for ICU physicians wishing to incorporate echocardiography into their clinical practice are lacking. Further, existing echocardiography accreditation does not reflect the requirements of the ICU practitioner. The WINFOCUS (World Interactive Network Focused On Critical UltraSound ECHO-ICU Group drew up a document aimed at providing guidance to individual physicians, trainers and the relevant societies of the requirements for the development of skills in echocardiography in the ICU setting. The document is based on recommendations published by the Royal College of Radiologists, British Society of Echocardiography, European Association of Echocardiography and American Society of Echocardiography, together with international input from established practitioners of ICU echocardiography. The recommendations contained in this document are concerned with theoretical basis of ultrasonography, the practical aspects of building an ICU-based echocardiography service as well as the key components of standard adult TTE and TEE studies to be performed on the ICU. Specific issues regarding echocardiography in different ICU clinical scenarios are then described. Obtaining competence in ICU echocardiography may be achieved in different ways – either through completion of an appropriate fellowship/training scheme, or, where not available, via a staged approach designed to train the practitioner to a level at which they can achieve accreditation. Here, peri-resuscitation focused echocardiography represents the entry level – obtainable through established courses followed by mentored practice. Next, a competence-based modular training programme is proposed: theoretical

  16. Multi-objective genetic algorithm for the automated planning of a wireless sensor network to monitor a critical facility

    Science.gov (United States)

    Jourdan, Damien B.; de Weck, Olivier L.

    2004-09-01

    This paper examines the optimal placement of nodes for a Wireless Sensor Network (WSN) designed to monitor a critical facility in a hostile region. The sensors are dropped from an aircraft, and they must be connected (directly or via hops) to a High Energy Communication Node (HECN), which serves as a relay from the ground to a satellite or a high-altitude aircraft. The sensors are assumed to have fixed communication and sensing ranges. The facility is modeled as circular and served by two roads. This simple model is used to benchmark the performance of the optimizer (a Multi-Objective Genetic Algorithm, or MOGA) in creating WSN designs that provide clear assessments of movements in and out of the facility, while minimizing both the likelihood of sensors being discovered and the number of sensors to be dropped. The algorithm is also tested on two other scenarios; in the first one the WSN must detect movements in and out of a circular area, and in the second one it must cover uniformly a square region. The MOGA is shown again to perform well on those scenarios, which shows its flexibility and possible application to more complex mission scenarios with multiple and diverse targets of observation.

  17. Development of the heated length to diameter correction factor on critical heat flux using the artificial neural networks

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Yong Ho; Baek, Won Pil; Chang, Soon Heung [Korea Advanced Institute of Science and Technology, Taejon (Korea, Republic of); Chun, Tae Hyun [Korea Atomic Energy Research Institute, Taejon (Korea, Republic of)

    1998-12-31

    With using artificial neural networks (ANNs), an analytical study related to the heated length effect on critical heat flux (CHF) has been carried out to make an improvement of the CHF prediction accuracy based on local condition correlations or table. It has been carried out to suggest a feasible criterion of the threshold length-to-diameter (L/D) value in which heated length could affect CHF. And within the criterion, a L/D correction factor has been developed through conventional regression. In order to validate the developed L/D correction factor, CHF experiments for various heated lengths have been carried out under low and intermediate pressure conditions. The developed threshold L/D correlation provides a new feasible criterion of L/D threshold value. The developed correction factor gives a reasonable accuracy for the original database, showing the error of -2.18% for average and 27.75% for RMS, and promising results for new experimental data. 7 refs., 12 figs., 1 tab. (Author)

  18. Defining the critical material attributes of lactose monohydrate in carrier based dry powder inhaler formulations using artificial neural networks.

    Science.gov (United States)

    Kinnunen, Hanne; Hebbink, Gerald; Peters, Harry; Shur, Jagdeep; Price, Robert

    2014-08-01

    The study aimed to establish a function-based relationship between the physical and bulk properties of pre-blended mixtures of fine and coarse lactose grades with the in vitro performance of an adhesive active pharmaceutical ingredient (API). Different grades of micronised and milled lactose (Lactohale (LH) LH300, LH230, LH210 and Sorbolac 400) were pre-blended with coarse grades of lactose (LH100, LH206 and Respitose SV010) at concentrations of 2.5, 5, 10 and 20 wt.%. The bulk and rheological properties and particle size distributions were characterised. The pre-blends were formulated with micronised budesonide and in vitro performance in a Cyclohaler device tested using a next-generation impactor (NGI) at 90 l/min. Correlations between the lactose properties and in vitro performance were established using linear regression and artificial neural network (ANN) analyses. The addition of milled and micronised lactose fines with the coarse lactose had a significant influence on physical and rheological properties of the bulk lactose. Formulations of the different pre-blends with budesonide directly influenced in vitro performance attributes including fine particle fraction, mass median aerodynamic diameter and pre-separator deposition. While linear regression suggested a number of physical and bulk properties may influence in vitro performance, ANN analysis suggested the critical parameters in describing in vitro deposition patterns were the relative concentrations of lactose fines % dry powder inhaler formulation design.

  19. Prevention of alcohol-heightened aggression by CRF-R1 antagonists in mice: critical role for DRN-PFC serotonin pathway.

    Science.gov (United States)

    Quadros, Isabel M; Hwa, Lara S; Shimamoto, Akiko; Carlson, Julia; DeBold, Joseph F; Miczek, Klaus A

    2014-11-01

    Alcohol can escalate aggressive behavior in a significant subgroup of rodents, humans, and nonhuman primates. The present study investigated whether blockade of corticotropin-releasing factor receptor type 1 (CRF-R1) could prevent the emergence of alcohol-heightened aggression in mice. The serotonin (5-HT) pathway from the dorsal raphe nucleus (DRN) to the medial prefrontal cortex (mPFC) by CRF-R1 was investigated as a possible target for the prevention of alcohol-heightened aggressive behavior. Male CFW mice that reliably exhibited aggressive behaviors after consuming 1 g/kg of alcohol received systemic or intra-DRN administration of CRF-R1 antagonists, CP-154,526 or MTIP, before a confrontation with a male conspecific. Blockade of DRN CRF-R1 receptors with both antagonists significantly reduced only alcohol-heightened aggression, whereas systemic administration reduced both alcohol-heightened and species-typical aggression. Next, a 5-HT1A agonist, 8-OH-DPAT, was coadministered with CP-154,526 into the DRN to temporarily disrupt 5-HT activity. This manipulation abolished the antiaggressive effects of intra-DRN CP-154,526. In the mPFC, in vivo microdialysis revealed that extracellular 5-HT levels were increased in mice that consumed alcohol and were then injected with CP-154,526, both systemically or intra-DRN. Neither alcohol nor CP-154,526 alone affected 5-HT release in the mPFC. The present results suggest the DRN as a critical site for CRF-R1 to modulate alcohol-heightened aggression via action on the serotonergic DRN-PFC pathway.

  20. CUZD1 is a critical mediator of the JAK/STAT5 signaling pathway that controls mammary gland development during pregnancy.

    Directory of Open Access Journals (Sweden)

    Janelle Mapes

    2017-03-01

    Full Text Available In the mammary gland, genetic circuits controlled by estrogen, progesterone, and prolactin, act in concert with pathways regulated by members of the epidermal growth factor family to orchestrate growth and morphogenesis during puberty, pregnancy and lactation. However, the precise mechanisms underlying the crosstalk between the hormonal and growth factor pathways remain poorly understood. We have identified the CUB and zona pellucida-like domain-containing protein 1 (CUZD1, expressed in mammary ductal and alveolar epithelium, as a novel mediator of mammary gland proliferation and differentiation during pregnancy and lactation. Cuzd1-null mice exhibited a striking impairment in mammary ductal branching and alveolar development during pregnancy, resulting in a subsequent defect in lactation. Gene expression profiling of mammary epithelium revealed that CUZD1 regulates the expression of a subset of the EGF family growth factors, epiregulin, neuregulin-1, and epigen, which act in an autocrine fashion to activate ErbB1 and ErbB4 receptors. Proteomic studies further revealed that CUZD1 interacts with a complex containing JAK1/JAK2 and STAT5, downstream transducers of prolactin signaling in the mammary gland. In the absence of CUZD1, STAT5 phosphorylation in the mammary epithelium during alveologenesis was abolished. Conversely, elevated expression of Cuzd1 in mammary epithelial cells stimulated prolactin-induced phosphorylation and nuclear translocation of STAT5. Chromatin immunoprecipitation confirmed co-occupancy of phosphorylated STAT5 and CUZD1 in the regulatory regions of epiregulin, a potential regulator of epithelial proliferation, and whey acidic protein, a marker of epithelial differentiation. Collectively, these findings suggest that CUZD1 plays a critical role in prolactin-induced JAK/STAT5 signaling that controls the expression of key STAT5 target genes involved in mammary epithelial proliferation and differentiation during alveolar

  1. DMPD: The interferon signaling network and transcription factor C/EBP-beta. [Dynamic Macrophage Pathway CSML Database

    Lifescience Database Archive (English)

    Full Text Available 18163952 The interferon signaling network and transcription factor C/EBP-beta. Li H... The interferon signaling network and transcription factor C/EBP-beta. PubmedID 18163952 Title The interfero...n signaling network and transcription factor C/EBP-beta. Authors Li H, Gade P, Xi

  2. DMPD: Toll-like receptor (TLR)-based networks regulate neutrophilic inflammation inrespiratory disease. [Dynamic Macrophage Pathway CSML Database

    Lifescience Database Archive (English)

    Full Text Available 18031251 Toll-like receptor (TLR)-based networks regulate neutrophilic inflammation...l) (.csml) Show Toll-like receptor (TLR)-based networks regulate neutrophilic inflammation inrespiratory dis...ease. PubmedID 18031251 Title Toll-like receptor (TLR)-based networks regulate neutrophilic inflammation

  3. Protein design for pathway engineering

    Energy Technology Data Exchange (ETDEWEB)

    Eriksen, DT; Lian, JZ; Zhao, HM

    2014-02-01

    Design and construction of biochemical pathways has increased the complexity of biosynthetically-produced compounds when compared to single enzyme biocatalysis. However, the coordination of multiple enzymes can introduce a complicated set of obstacles to overcome in order to achieve a high titer and yield of the desired compound. Metabolic engineering has made great strides in developing tools to optimize the flux through a target pathway, but the inherent characteristics of a particular enzyme within the pathway can still limit the productivity. Thus, judicious protein design is critical for metabolic and pathway engineering. This review will describe various strategies and examples of applying protein design to pathway engineering to optimize the flux through the pathway. The proteins can be engineered for altered substrate specificity/selectivity, increased catalytic activity, reduced mass transfer limitations through specific protein localization, and reduced substrate/product inhibition. Protein engineering can also be expanded to design biosensors to enable high through-put screening and to customize cell signaling networks. These strategies have successfully engineered pathways for significantly increased productivity of the desired product or in the production of novel compounds. (C) 2013 Elsevier Inc. All rights reserved.

  4. Protein Design for Pathway Engineering

    Science.gov (United States)

    Eriksen, Dawn T.; Lian, Jiazhang; Zhao, Huimin

    2013-01-01

    Design and construction of biochemical pathways has increased the complexity of biosynthetically-produced compounds when compared to single enzyme biocatalysis. However, the coordination of multiple enzymes can introduce a complicated set of obstacles to overcome in order to achieve a high titer and yield of the desired compound. Metabolic engineering has made great strides in developing tools to optimize the flux through a target pathway, but the inherent characteristics of a particular enzyme within the pathway can still limit the productivity. Thus, judicious protein design is critical for metabolic and pathway engineering. This review will describe various strategies and examples of applying protein design to pathway engineering to optimize the flux through the pathway. The proteins can be engineered for altered substrate specificity/selectivity, increased catalytic activity, reduced mass transfer limitations through specific protein localization, and reduced substrate/product inhibition. Protein engineering can also be expanded to design biosensors to enable high through-put screening and to customize cell signaling networks. These strategies have successfully engineered pathways for significantly increased productivity of the desired product or in the production of novel compounds. PMID:23558037

  5. Pathway collages: personalized multi-pathway diagrams.

    Science.gov (United States)

    Paley, Suzanne; O'Maille, Paul E; Weaver, Daniel; Karp, Peter D

    2016-12-13

    Metabolic pathway diagrams are a classical way of visualizing a linked cascade of biochemical reactions. However, to understand some biochemical situations, viewing a single pathway is insufficient, whereas viewing the entire metabolic network results in information overload. How do we enable scientists to rapidly construct personalized multi-pathway diagrams that depict a desired collection of interacting pathways that emphasize particular pathway interactions? We define software for constructing personalized multi-pathway diagrams called pathway-collages using a combination of manual and automatic layouts. The user specifies a set of pathways of interest for the collage from a Pathway/Genome Database. Layouts for the individual pathways are generated by the Pathway Tools software, and are sent to a Javascript Pathway Collage application implemented using Cytoscape.js. That application allows the user to re-position pathways; define connections between pathways; change visual style parameters; and paint metabolomics, gene expression, and reaction flux data onto the collage to obtain a desired multi-pathway diagram. We demonstrate the use of pathway collages in two application areas: a metabolomics study of pathogen drug response, and an Escherichia coli metabolic model. Pathway collages enable facile construction of personalized multi-pathway diagrams.

  6. Critical pathway for the management of acute heart failure at the Veterans Affairs San Diego Healthcare System: transforming performance measures into cardiac care.

    Science.gov (United States)

    Gardetto, Nancy J; Greaney, Karen; Arai, Lisa; Brenner, April; Carroll, Karen C; Howerton, Nancy M; Lee, Melinda; Pada, Laureen; Tseng, Marilynne; Maisel, Alan S

    2008-09-01

    Acute decompensated heart failure (ADHF) is a major public health problem and leading cause for hospitalization in people 65 years and older. Admission rates for ADHF, accounted for more than 1 million heart failure (HF) hospitalizations in 2004, and more than 6.5 million inpatient hospital days. Despite significant advances in HF management, including pharmacotherapy and devices; and extensive collaborative efforts of the American College of Cardiology, and American Heart Association to disseminate evidence-based practice guidelines for management of chronic HF in adults; 3 patients continue to present to the emergency departments in ADHF. The hospital treatment of HF frequently does not follow published guidelines, potentially contributing to the high morbidity, mortality, and economic cost of this disorder. This highlights an ongoing need for development of quality improvement programs that focus on delivering reliable, evidence-based care for patients with ADHF. Consequently, the development of clinical pathways has the potential to reduce the current variability in care, enhance guideline adherence, and improve outcomes for patients. The Veterans Affairs San Diego Healthcare System (VASDHCS) formed a multidisciplinary HF performance improvement team. The team set forth on the task of developing standard order sets for patients with ADHF. After analyzing local care processes, reviewing evidence of best care practices, and defining appropriate goals to satisfy the multidimensional needs of HF patient; the team developed a computerized pathway in a user-friendly format that is simple, yet comprehensive; and focuses on early stages of HF evaluation and treatment for patients presenting to the emergency department. Successful strategies to improve care for HF patients need to assist health care providers with rapid recognition and early aggressive treatment, while creating a reliable process that ensures continuity of care. This critical pathway for management of

  7. Critical percolation phase and thermal Berezinskii-Kosterlitz-Thouless transition in a scale-free network with short-range and long-range random bonds.

    Science.gov (United States)

    Berker, A Nihat; Hinczewski, Michael; Netz, Roland R

    2009-10-01

    Percolation in a scale-free hierarchical network is solved exactly by renormalization-group theory in terms of the different probabilities of short-range and long-range bonds. A phase of critical percolation, with algebraic [Berezinskii-Kosterlitz-Thouless (BKT)] geometric order, occurs in the phase diagram in addition to the ordinary (compact) percolating phase and the nonpercolating phase. It is found that no connection exists between, on the one hand, the onset of this geometric BKT behavior and, on the other hand, the onsets of the highly clustered small-world character of the network and of the thermal BKT transition of the Ising model on this network. Nevertheless, both geometric and thermal BKT behaviors have inverted characters, occurring where disorder is expected, namely, at low bond probability and high temperature, respectively. This may be a general property of long-range networks.

  8. PRL-3 engages the focal adhesion pathway in triple-negative breast cancer cells to alter actin structure and substrate adhesion properties critical for cell migration and invasion.

    Science.gov (United States)

    Gari, Hamid H; DeGala, Gregory D; Ray, Rahul; Lucia, M Scott; Lambert, James R

    2016-10-01

    Triple-negative breast cancers (TNBCs) are among the most aggressive cancers characterized by a high propensity to invade, metastasize and relapse. We previously reported that the TNBC-specific inhibitor, AMPI-109, significantly impairs the ability of TNBC cells to migrate and invade by reducing levels of the metastasis-promoting phosphatase, PRL-3. Here, we examined the mechanisms by which AMPI-109 and loss of PRL-3 impede cell migration and invasion. AMPI-109 treatment or knock down of PRL-3 expression were associated with deactivation of Src and ERK signaling and concomitant downregulation of RhoA and Rac1/2/3 GTPase protein levels. These cellular changes led to rearranged filamentous actin networks necessary for cell migration and invasion. Conversely, overexpression of PRL-3 promoted TNBC cell invasion by upregulating matrix metalloproteinase 10, which resulted in increased TNBC cell adherence to, and degradation of, the major basement membrane component laminin. Our data demonstrate that PRL-3 engages the focal adhesion pathway in TNBC cells as a key mechanism for promoting TNBC cell migration and invasion. Collectively, these data suggest that blocking PRL-3 activity may be an effective method for reducing the metastatic potential of TNBC cells. Copyright © 2016 The Author(s). Published by Elsevier Ireland Ltd.. All rights reserved.

  9. Early Brain Response to Low-Dose Radiation Exposure Involves Molecular Networks and Pathways Associated with Cognitive Functions, Advanced Aging and Alzheimer's Disease

    Energy Technology Data Exchange (ETDEWEB)

    Lowe, Xiu R; Bhattacharya, Sanchita; Marchetti, Francesco; Wyrobek, Andrew J.

    2008-06-06

    Understanding the cognitive and behavioral consequences of brain exposures to low-dose ionizing radiation has broad relevance for health risks from medical radiation diagnostic procedures, radiotherapy, environmental nuclear contamination, as well as earth orbit and space missions. Analyses of transcriptome profiles of murine brain tissue after whole-body radiation showed that low-dose exposures (10 cGy) induced genes not affected by high dose (2 Gy), and low-dose genes were associated with unique pathways and functions. The low-dose response had two major components: pathways that are consistently seen across tissues, and pathways that were brain tissue specific. Low-dose genes clustered into a saturated network (p < 10{sup -53}) containing mostly down-regulated genes involving ion channels, long-term potentiation and depression, vascular damage, etc. We identified 9 neural signaling pathways that showed a high degree of concordance in their transcriptional response in mouse brain tissue after low-dose radiation, in the aging human brain (unirradiated), and in brain tissue from patients with Alzheimer's disease. Mice exposed to high-dose radiation did not show these effects and associations. Our findings indicate that the molecular response of the mouse brain within a few hours after low-dose irradiation involves the down-regulation of neural pathways associated with cognitive dysfunctions that are also down regulated in normal human aging and Alzheimer's disease.

  10. A Space for Critical Research on Education Policy: ECER Paper Sessions and the "Policy Studies and Politics of Education" Network

    Science.gov (United States)

    Rasmussen, Palle

    2014-01-01

    The activities of the European Educational Research Association (EERA) and the yearly European Conference on Educational Research (ECER) are mainly organised in standing networks. Through the example of the Policy Studies and Politics of Education network, this article takes a closer look at network activity and the ways in which it contributes to…

  11. Evaluation of critical pathways, radionuclides, and remedial measures for reducing the radiological dose to returning populations at a former nuclear test site

    Energy Technology Data Exchange (ETDEWEB)

    Robison, W. L., LLNL

    1997-11-01

    Bikini Island, the major residence island at Bikini Atoll, was contaminated with radioactive fallout as a result of the BRAVO test conducted on March 1, 1954. We have identified the critical radionuclides and supplied radiological data needed to develop dose estimates for all possible exposure pathways. These estimates show that the major dose to returning populations would result from ingestion of cesium-137 (137 Cs) in locally grown terrestrial foods where the predicted population average effective dose exceeds current federal guidelines. Consequently, we designed several long-term field experiments to develop and evaluate methods to reduce the 137 Cs content in locally grown foods.This paper gives a general outline of the remediation experiments with a more detailed description of a preferred combined option. Our comparative evaluation on various remedial methods show that the combined option--potassium treatment of the entire islands with limited excavation of soil in village an d housing areas--will be effective in reducing the dose to about 10% of pretreatment levels, and offers very significant benefits with respect to adverse environmental impacts as well as savings in overall costs, time, and required expert resources.

  12. Ultraperformance liquid chromatography-mass spectrometry based comprehensive metabolomics combined with pattern recognition and network analysis methods for characterization of metabolites and metabolic pathways from biological data sets.

    Science.gov (United States)

    Zhang, Ai-hua; Sun, Hui; Han, Ying; Yan, Guang-li; Yuan, Ye; Song, Gao-chen; Yuan, Xiao-xia; Xie, Ning; Wang, Xi-jun

    2013-08-06

    Metabolomics is the study of metabolic changes in biological systems and provides the small molecule fingerprints related to the disease. Extracting biomedical information from large metabolomics data sets by multivariate data analysis is of considerable complexity. Therefore, more efficient and optimizing metabolomics data processing technologies are needed to improve mass spectrometry applications in biomarker discovery. Here, we report the findings of urine metabolomic investigation of hepatitis C virus (HCV) patients by high-throughput ultraperformance liquid chromatography-mass spectrometry (UPLC-MS) coupled with pattern recognition methods (principal component analysis, partial least-squares, and OPLS-DA) and network pharmacology. A total of 20 urinary differential metabolites (13 upregulated and 7 downregulated) were identified and contributed to HCV progress, involve several key metabolic pathways such as taurine and hypotaurine metabolism, glycine, serine and threonine metabolism, histidine metabolism, arginine and proline metabolism, and so forth. Metabolites identified through metabolic profiling may facilitate the development of more accurate marker algorithms to better monitor disease progression. Network analysis validated close contact between these metabolites and implied the importance of the metabolic pathways. Mapping altered metabolites to KEGG pathways identified alterations in a variety of biological processes mediated through complex networks. These findings may be promising to yield a valuable and noninvasive tool that insights into the pathophysiology of HCV and to advance the early diagnosis and monitor the progression of disease. Overall, this investigation illustrates the power of the UPLC-MS platform combined with the pattern recognition and network analysis methods that can engender new insights into HCV pathobiology.

  13. Stochastic causality, criticality, and non-locality in brain networks. Comment on "Foundational perspectives on causality in large-scale brain networks" by M. Mannino and S.L. Bressler

    Science.gov (United States)

    Kozma, Robert; Hu, Sanqing

    2015-12-01

    For millennia, causality served as a powerful guiding principle to our understanding of natural processes, including the functioning of our body, mind, and brain. The target paper presents an impressive vista of the field of causality in brain networks, starting from philosophical issues, expanding on neuroscience effects, and addressing broad engineering and societal aspects as well. The authors conclude that the concept of stochastic causality is more suited to characterize the experimentally observed complex dynamical processes in large-scale brain networks, rather than the more traditional view of deterministic causality. We strongly support this conclusion and provide two additional examples that may enhance and complement this review: (i) a generalization of the Wiener-Granger Causality (WGC) to fit better the complexity of brain networks; (ii) employment of criticality as a key concept highly relevant to interpreting causality and non-locality in large-scale brain networks.

  14. Critical-state dynamics of avalanches and oscillations jointly emerge from balanced excitation/inhibition in neuronal networks

    NARCIS (Netherlands)

    Poil, S.S.; Hardstone, R.E.; Mansvelder, H.D.; Linkenkaer-Hansen, K.

    2012-01-01

    Criticality has gained widespread interest in neuroscience as an attractive framework for understanding the character and functional implications of variability in brain activity. The metastability of critical systems maximizes their dynamic range, storage capacity, and computational power.

  15. Connecting Social Networks with Ecosystem Services for Watershed Governance: a Social-Ecological Network Perspective Highlights the Critical Role of Bridging Organizations

    Directory of Open Access Journals (Sweden)

    Kaitlyn J. Rathwell

    2012-06-01

    Full Text Available In many densely settled agricultural watersheds, water quality is a point of conflict between amenity and agricultural activities because of the varied demands and impacts on shared water resources. Successful governance of these watersheds requires coordination among different activities. Recent research has highlighted the role that social networks between management entities can play to facilitate cross-scale interaction in watershed governance. For example, bridging organizations can be positioned in social networks to bridge local initiatives done by single municipalities across whole watersheds. To better understand the role of social networks in social-ecological system dynamics, we combine a social network analysis of the water quality management networks held by local governments with a social-ecological analysis of variation in water management and ecosystem services across the Montérégie, an agricultural landscape near Montréal, Québec, Canada. We analyze municipal water management networks by using one-mode networks to represent direct collaboration between municipalities, and two-mode networks to capture how bridging organizations indirectly connect municipalities. We find that municipalities do not collaborate directly with one another but instead are connected via bridging organizations that span the water quality management network. We also discovered that more connected municipalities engaged in more water management activities. However, bridging organizations preferentially connected with municipalities that used more tourism related ecosystem services rather than those that used more agricultural ecosystem services. Many agricultural municipalities were relatively isolated, despite being the main producers of water quality problems. In combination, these findings suggest that further strengthening the water management network in the Montérégie will contribute to improving water quality in the region. However, such

  16. Capacity building for critical care training delivery: Development and evaluation of the Network for Improving Critical care Skills Training (NICST) programme in Sri Lanka.

    Science.gov (United States)

    Stephens, Tim; De Silva, A Pubudu; Beane, Abi; Welch, John; Sigera, Chathurani; De Alwis, Sunil; Athapattu, Priyantha; Dharmagunawardene, Dilantha; Peiris, Lalitha; Siriwardana, Somalatha; Abeynayaka, Ashoka; Jayasinghe, Kosala Saroj Amarasena; Mahipala, Palitha G; Dondorp, Arjen; Haniffa, Rashan

    2017-04-01

    To deliver and evaluate a short critical care nurse training course whilst simultaneously building local training capacity. A multi-modal short course for critical care nursing skills was delivered in seven training blocks, from 06/2013-11/2014. Each training block included a Train the Trainer programme. The project was evaluated using Kirkpatrick's Hierarchy of Learning. There was a graded hand over of responsibility for course delivery from overseas to local faculty between 2013 and 2014. Sri Lanka. Participant learning assessed through pre/post course Multi-Choice Questionnaires. A total of 584 nurses and 29 faculty were trained. Participant feedback was consistently positive and each course demonstrated a significant increase (p≤0.0001) in MCQ scores. There was no significant difference MCQ scores (p=0.186) between overseas faculty led and local faculty led courses. In a relatively short period, training with good educational outcomes was delivered to nearly 25% of the critical care nursing population in Sri Lanka whilst simultaneously building a local faculty of trainers. Through use of a structured Train the Trainer programme, course outcomes were maintained following the handover of training responsibility to Sri Lankan faculty. The focus on local capacity building increases the possibility of long term course sustainability. Copyright © 2016 Elsevier Ltd. All rights reserved.

  17. Letter to the editor: Generation of self organized critical connectivity network map (SOCCNM of randomly situated water bodies during flooding process

    Directory of Open Access Journals (Sweden)

    B. S. Daya Sagar

    2001-01-01

    Full Text Available This letter presents a brief framework based on nonlinear morphological transformations to generate a self organized critical connectivity network map (SOCCNM in 2-dimensional space. This simple and elegant framework is implemented on a section that contains a few simulated water bodies to generate SOCCNM. This is based on a postulate that the randomly situated surface water bodies of various sizes and shapes self organize during flooding process.

  18. The evolutionary pathway to obligate scavenging in Gyps vultures

    NARCIS (Netherlands)

    Dermody, B.; Tanner, C.J.; Jackson, A.L.

    2011-01-01

    The evolutionary pathway to obligate scavenging in Gyps vultures remains unclear. We propose that communal roosting plays a central role in setting up the information transfer network critical for obligate scavengers in ephemeral environments and that the formation of a flotilla-like foraging group

  19. A Microsoft-Excel-based tool for running and critically appraising network meta-analyses—an overview and application of NetMetaXL

    Science.gov (United States)

    2014-01-01

    Background The use of network meta-analysis has increased dramatically in recent years. WinBUGS, a freely available Bayesian software package, has been the most widely used software package to conduct network meta-analyses. However, the learning curve for WinBUGS can be daunting, especially for new users. Furthermore, critical appraisal of network meta-analyses conducted in WinBUGS can be challenging given its limited data manipulation capabilities and the fact that generation of graphical output from network meta-analyses often relies on different software packages than the analyses themselves. Methods We developed a freely available Microsoft-Excel-based tool called NetMetaXL, programmed in Visual Basic for Applications, which provides an interface for conducting a Bayesian network meta-analysis using WinBUGS from within Microsoft Excel. . This tool allows the user to easily prepare and enter data, set model assumptions, and run the network meta-analysis, with results being automatically displayed in an Excel spreadsheet. It also contains macros that use NetMetaXL’s interface to generate evidence network diagrams, forest plots, league tables of pairwise comparisons, probability plots (rankograms), and inconsistency plots within Microsoft Excel. All figures generated are publication quality, thereby increasing the efficiency of knowledge transfer and manuscript preparation. Results We demonstrate the application of NetMetaXL using data from a network meta-analysis published previously which compares combined resynchronization and implantable defibrillator therapy in left ventricular dysfunction. We replicate results from the previous publication while demonstrating result summaries generated by the software. Conclusions Use of the freely available NetMetaXL successfully demonstrated its ability to make running network meta-analyses more accessible to novice WinBUGS users by allowing analyses to be conducted entirely within Microsoft Excel. NetMetaXL also allows

  20. A protein–protein interaction network linking the energy-sensor kinase SnRK1 to multiple signaling pathways in Arabidopsis thaliana

    Directory of Open Access Journals (Sweden)

    Madlen Nietzsche

    2016-04-01

    Full Text Available In plants, the sucrose non-fermenting (SNF1-related protein kinase 1 (SnRK1 represents a central integrator of low energy signaling and acclimation towards many environmental stress responses. Although SnRK1 acts as a convergent point for many different environmental and metabolic signals to control growth and development, it is currently unknown how these many different signals could be translated into a cell-type or stimulus specific response since many components of SnRK1-regulated signaling pathways remain unidentified. Recently, we have demonstrated that proteins containing a domain of unknown function (DUF 581 interact with the catalytic α subunits of SnRK1 (AKIN10/11 from Arabidopsis thaliana and could potentially act as mediators conferring tissue- and stimulus-type specific differences in SnRK1 regulation. To further extend the SnRK1 signaling network in plants, we systematically screened for novel DUF581 interaction partners using the yeast two-hybrid system. A deep and exhaustive screening identified 17 interacting partners for 10 of the DUF581 proteins tested. Many of these novel interaction partners are implicated in cellular processes previously associated with SnRK1 signaling. Furthermore, we mined publicly available interaction data to identify additional DUF581 interacting proteins. A protein–protein interaction network resulting from our studies suggests connections between SnRK1 signaling and other central signaling pathways involved in growth regulation and environmental responses. These include TOR and MAP-kinase signaling as well as hormonal pathways. The resulting protein–protein interaction network promises to be effective in generating hypotheses to study the precise mechanisms SnRK1 signaling on a functional level.

  1. Critical role of ROR-γt in a new thymic pathway leading to IL-17-producing invariant NKT cell differentiation.

    Science.gov (United States)

    Michel, Marie-Laure; Mendes-da-Cruz, Daniella; Keller, Alexandre Castro; Lochner, Matthias; Schneider, Elke; Dy, Michel; Eberl, Gérard; Leite-de-Moraes, Maria C

    2008-12-16

    Invariant natural killer T (iNKT) cells constitute a subpopulation of T cells that recognize glycolipids presented by CD1d molecules. They are characterized by their prompt production of interleukin-4 (IL-4) and interferon-gamma (IFN-gamma), which enables them to modulate diverse immune responses. Recently, we enlarged this concept by identifying a distinct IL-17-producing iNKT cell subset, named iNKT17 cells. The mechanisms leading to the acquisition of this new iNKT cell activity are unknown. Herein we show that IL-17-producing iNKT cells are already present in the thymus, predominantly among a subset regarded so far as an immature stage of thymic iNKT cell development, the CD1d tetramer(pos)CD44(pos)NK1.1(neg)CD4(neg) cells. Using EGFP reporter mice, we demonstrate that the transcription factor ROR-gammat is critical for the thymic differentiation of this subset because only ROR-gammat(pos) iNKT cells are capable of massively secreting IL-17. Moreover, IL-17-producing CD1d tetramer(pos)CD44(pos)NK1.1(neg)CD4(neg) thymic iNKT cells have reached a mature differentiation stage because they fail to generate other cell subsets in fetal thymic organ culture. Conversely, thymic ROR-gammat(neg) iNKT cell precursors give rise to progeny, but acquire neither ROR-gammat expression nor the ability to secrete IL-17. In conclusion, our findings demonstrate an alternative thymic pathway leading to the development of iNKT17 cells that requires ROR-gammat expression.

  2. Ensuring Patient Safety by using Colored Petri Net Simulation in the Design of Heterogeneous, Multi-Vendor, Integrated, Life-Critical Wireless (802.x) Patient Care Device Networks.

    Science.gov (United States)

    Sloane, Elliot; Gehlot, Vijay

    2005-01-01

    Hospitals and manufacturers are designing and deploying the IEEE 802.x wireless technologies in medical devices to promote patient mobility and flexible facility use. There is little information, however, on the reliability or ultimate safety of connecting multiple wireless life-critical medical devices from multiple vendors using commercial 802.11a, 802.11b, 802.11g or pre-802.11n devices. It is believed that 802.11-type devices can introduce unintended life-threatening risks unless delivery of critical patient alarms to central monitoring systems and/or clinical personnel is assured by proper use of 802.11e Quality of Service (QoS) methods. Petri net tools can be used to simulate all possible states and transitions between devices and/or systems in a wireless device network, and can identify failure modes in advance. Colored Petri Net (CPN) tools are ideal, in fact, as they allow tracking and controlling each message in a network based on pre-selected criteria. This paper describes a research project using CPN to simulate and validate alarm integrity in a small multi-modality wireless patient monitoring system. A 20-monitor wireless patient monitoring network is created in two versions: one with non-prioritized 802.x CSM protocols and the second with simulated Quality of Service (QoS) capabilities similar to 802.11e (i.e., the second network allows message priority management.) In the standard 802.x network, dangerous heart arrhythmia and pulse oximetry alarms could not be reliably and rapidly communicated, but the second network's QoS priority management reduced that risk significantly.

  3. Utilizing Social Networks in Times of Crisis: Understanding, Exploring and Analyzing Critical Incident Management at Institutions of Higher Education

    Science.gov (United States)

    Asselin, Martha Jo

    2012-01-01

    With the rising number of major crises on college campuses today (Security on Campus Inc., 2009), institutions of higher education can benefit from understanding of how social networks may be used in times of emergency. What is currently known about the usage of social networks is not integral to the current practices of crisis management that are…

  4. A robust network of double-strand break repair pathways governs genome integrity during C. elegans development.

    Science.gov (United States)

    Pontier, Daphne B; Tijsterman, Marcel

    2009-08-25

    To preserve genomic integrity, various mechanisms have evolved to repair DNA double-strand breaks (DSBs). Depending on cell type or cell cycle phase, DSBs can be repaired error-free, by homologous recombination, or with concomitant loss of sequence information, via nonhomologous end-joining (NHEJ) or single-strand annealing (SSA). Here, we created a transgenic reporter system in C. elegans to investigate the relative contribution of these pathways in somatic cells during animal development. Although all three canonical pathways contribute to repair in the soma, in their combined absence, animals develop without growth delay and chromosomal breaks are still efficiently repaired. This residual repair, which we call alternative end-joining, dominates DSB repair only in the absence of NHEJ and resembles SSA, but acts independent of the SSA nuclease XPF and repair proteins from other pathways. The dynamic interplay between repair pathways might be developmentally regulated, because it was lost from terminally differentiated cells in adult animals. Our results demonstrate profound versatility in DSB repair pathways for somatic cells of C. elegans, which are thus extremely fit to deal with chromosomal breaks.

  5. Effective connectivity of ascending and descending frontal-thalamic pathways during sustained attention: Complex brain network interactions in adolescence

    OpenAIRE

    Jagtap, Pranav; Diwadkar, Vaibhav A.

    2016-01-01

    Frontal-thalamic interactions are crucial for bottom-up gating and top-down control, yet have not been well studied from brain network perspectives. We applied network modeling of fMRI signals (Dynamic Causal Modeling; DCM) to investigate frontal-thalamic interactions during an attention task with parametrically varying levels of demand. fMRI was collected while subjects participated in a sustained continuous performance task with low and high attention demands. 162 competing model architectu...

  6. DMPD: Glucocorticoids and the innate immune system: crosstalk with the toll-likereceptor signaling network. [Dynamic Macrophage Pathway CSML Database

    Lifescience Database Archive (English)

    Full Text Available 17576036 Glucocorticoids and the innate immune system: crosstalk with the toll-like...07 May 13. (.png) (.svg) (.html) (.csml) Show Glucocorticoids and the innate immune system: crosstalk with t...he toll-likereceptor signaling network. PubmedID 17576036 Title Glucocorticoids and the innate immune syst...em: crosstalk with the toll-likereceptor signaling network. Authors Chinenov Y, Rog

  7. Managing the critical zone to obtain and sustain multiple benefits from working landscapes: The value of partnerships between LTAR and NSF CZO networks

    Science.gov (United States)

    Lohse, K. A.; Seyfried, M. S.; Pierson, F. B.

    2015-12-01

    The Critical Zone Observatories add value to earth system science and society by addressing research gaps to understand the critical zone, the surface skin of the earth that extends from the top of the tree canopy to the lower limits of the groundwater. The Critical Zone (CZ) sustains life on earth and provides food, shelter, forage, and fuel and other services to human well-being. This Zone is also where most of human activities take place and thus subject to change and degradation. Managing the critical zone to obtain and sustain these services will require initiatives, policies and incentives that maintain and enhance this zone. The Critical Zone Observatories are seeking to address major gaps in understanding how earth surface evolves over time and how it will respond to future changes. Many of these gaps in our understanding occur at the interface between disciplines, across space and deep time scales, and multiple dimensions. For example, the Reynolds Creek CZO seeks to understand the role of soil environmental variables such as soil moisture and depth that vary across complex terrain in governing soil carbon storage and turnover in a semi-arid environment. For this reason, soil samples are being collected to depth of bedrock. Other networks and agencies such as the new LTAR and NEON are quantifying soil carbon at more shallow depths that will likely capture the variability in near surface soil carbon that is more sensitive to management and climate changes but may underestimate the total stores of carbon on the landscape. The CZOs also provide a platform to conduct interdisciplinary to transdisciplinary science by integrating across geological, soil, hydrologic, ecological, and social sciences to understand the critical zone. The emergence of the CZO Network and the LTAR network brings the opportunity to standardize methods and test hypotheses and ask questions across broad environmental conditions and gradients that could not be achieved with single

  8. Conservation of the critically endangered eastern Australian population of the grey nurse shark (Carcharias taurus) through cross-jurisdictional management of a network of marine-protected areas.

    Science.gov (United States)

    Lynch, Tim P; Harcourt, Robert; Edgar, Graham; Barrett, Neville

    2013-12-01

    Between 2001 and 2009, 26 marine-protected areas (MPA) were established on the east Australian seaboard, at least in part, to manage human interactions with a critically endangered population of grey nurse shark, Carcharias taurus. This network is spread across six MPA systems and includes all 19 sites outlined in the National Recovery Plan for C. taurus, though five sites remain open to some forms of fishing. The reserve network has complex cross-jurisdictional management, as the sharks occur in waters controlled by the Australian states of New South Wales (NSW) and Queensland, as well as by the Commonwealth (Federal) government. Jurisdiction is further complicated by fisheries and conservation departments both engaging in management activities within each state. This has resulted in protected area types that include IUCN category II equivalent zones in NSW, Queensland, and Commonwealth marine parks that either overlay or complement another large scaled network of protected sites called critical habitats. Across the network, seven and eight rule permutations for diving and fishing, respectively, are applied to this population of sharks. Besides sites identified by the recovery plan, additional sites have been protected as part of the general development of MPA networks. A case study at one of these sites, which historically was known to be occupied by C. taurus but had been abandoned, appears to shows re-establishment of an aggregation of juvenile and sub-adult sharks. Concurrent with the re-establishment of the aggregation, a local dive operator increased seasonal dive visitation rates at the site fourfold. As a precautionary measure, protection of abandoned sites, which includes nursery and gestating female habitats are options that may assist recovery of the east coast population of C. taurus.

  9. Reconstruction of the gene regulatory network involved in the sonic hedgehog pathway with a potential role in early development of the mouse brain.

    Directory of Open Access Journals (Sweden)

    Jinhua Liu

    2014-10-01

    Full Text Available The Sonic hedgehog (Shh signaling pathway is crucial for pattern formation in early central nervous system development. By systematically analyzing high-throughput in situ hybridization data of E11.5 mouse brain, we found that Shh and its receptor Ptch1 define two adjacent mutually exclusive gene expression domains: Shh+Ptch1- and Shh-Ptch1+. These two domains are associated respectively with Foxa2 and Gata3, two transcription factors that play key roles in specifying them. Gata3 ChIP-seq experiments and RNA-seq assays on Gata3-knockdown cells revealed that Gata3 up-regulates the genes that are enriched in the Shh-Ptch1+ domain. Important Gata3 targets include Slit2 and Slit3, which are involved in the process of axon guidance, as well as Slc18a1, Th and Qdpr, which are associated with neurotransmitter synthesis and release. By contrast, Foxa2 both up-regulates the genes expressed in the Shh+Ptch1- domain and down-regulates the genes characteristic of the Shh-Ptch1+ domain. From these and other data, we were able to reconstruct a gene regulatory network governing both domains. Our work provides the first genome-wide characterization of the gene regulatory network involved in the Shh pathway that underlies pattern formation in the early mouse brain.

  10. Pulsed laser validation of recovery mechanisms of critical SEE`s in an artificial neural network system

    Energy Technology Data Exchange (ETDEWEB)

    Buchner, S. [SFA Inc/NRL, Washington, DC (United States); Olmos, M.; Cheynet, P.; Velazco, R. [TIMA Lab., Grenoble (France); McMorrow, D.; Melinger, J. [Naval Research Lab., Washington, DC (United States); Ecoffet, R. [CNES-CT/AQ/CB, Toulouse (France); Muller, J.D. [CEA-DAM/FRIF/DCRE/SEIM, Bruyeres-le-Chatel (France)

    1998-06-01

    A pulsed laser was used to inject errors into an electronic system consisting of a number of different integrated circuits functioning as a digital version of an artificial neutral network. The results confirm that the system as a whole can operate autonomously in the radiation environment of space. Additional work was done to characterize the effects of the upsets on the output of the artificial neural network.

  11. Social networks and the resilience of rural communities in the Global South: a critical review and conceptual reflections

    Directory of Open Access Journals (Sweden)

    Till Rockenbauch

    2017-03-01

    Full Text Available In the last decades, a growing scholarship has outlined the crucial role of social networks as a source of resilience. However, with regard to the Global South, the role of social networks for the resilience of rural communities remains an under-researched and underconceptualized issue, because research remains scattered between different strands and has rarely been integrated from a resilience perspective. To provide common ground for the exchange between disciplines and to identify steps towards a more comprehensive social network perspective on the resilience of rural communities in the Global South, we present a systematic review of contemporary case studies from three strands of research: (i natural resource management, (ii agricultural innovation, and (iii social support. Although studies in each strand have their own particular strengths and weaknesses in addressing aspects of the resilience of rural communities in the Global South, they all share a static view of the outcomes of social networks, tend to emphasize structure over agency, and neglect spatial dimensions of social relations. To address these challenges, we propose a translocal social network perspective on resilience that views rural communities as being embedded in social networks that connect people and facilitate the flow of resources, information, and knowledge between places.

  12. The reverse cholesterol transport pathway improves understanding of genetic networks for fat deposition and muscle growth in beef cattle

    Science.gov (United States)

    In the present study, thirteen genes involved in the reverse cholesterol transport (RCT) pathway were investigated for their associations with three fat depositions, eight fatty acid compositions and two growth-related phenotypes in a Wagyu x Limousin reference population, including 6 F1 bulls, 113 ...

  13. Self-organized nanocrack networks: a pathway to enlarge catalytic surface area in sputtered ceramic thin films, showcased for photocatalytic TiO2

    Science.gov (United States)

    Henkel, B.; Vahl, A.; Aktas, O. C.; Strunskus, T.; Faupel, F.

    2018-01-01

    Sputter deposited photocatalytic thin films offer high adherence and mechanical stability, but typically are outperformed in their photocatalytic properties by colloidal TiO2 nanostructures, which in turn typically suffer from problematic removal. Here we report on thermally controlled nanocrack formation as a feasible and batch applicable approach to enhance the photocatalytic performance of well adhering, reactively sputtered TiO2 thin films. Networks of nanoscopic cracks were induced into tailored columnar TiO2 thin films by thermal annealing. These deep trenches are separating small bundles of TiO2 columns, adding their flanks to the overall catalytically active surface area. The variation of thin film thickness reveals a critical layer thickness for initial nanocrack network formation, which was found to be about 400 nm in case of TiO2. The columnar morphology of the as deposited TiO2 layer with weak bonds between respective columns and with strong bonds to the substrate is of crucial importance for the formation of nanocrack networks. A beneficial effect of nanocracking on the photocatalytic performance was experimentally observed. It was correlated by a simple geometric model for explaining the positive impact of the crack induced enlargement of active surface area on photocatalytic efficiency. The presented method of nanocrack network formation is principally not limited to TiO2 and is therefore seen as a promising candidate for utilizing increased surface area by controlled crack formation in ceramic thin films in general.

  14. Novel functional view of the crocidolite asbestos-treated A549 human lung epithelial transcriptome reveals an intricate network of pathways with opposing functions

    Directory of Open Access Journals (Sweden)

    Stevens John R

    2008-08-01

    Full Text Available Abstract Background Although exposure to asbestos is now regulated, patients continue to be diagnosed with mesothelioma, asbestosis, fibrosis and lung carcinoma because of the long latent period between exposure and clinical disease. Asbestosis is observed in approximately 200,000 patients annually and asbestos-related deaths are estimated at 4,000 annually1. Although advances have been made using single gene/gene product or pathway studies, the complexity of the response to asbestos and the many unanswered questions suggested the need for a systems biology approach. The objective of this study was to generate a comprehensive view of the transcriptional changes induced by crocidolite asbestos in A549 human lung epithelial cells. Results A statistically robust, comprehensive data set documenting the crocidolite-induced changes in the A549 transcriptome was collected. A systems biology approach involving global observations from gene ontological analyses coupled with functional network analyses was used to explore the effects of crocidolite in the context of known molecular interactions. The analyses uniquely document a transcriptome with function-based networks in cell death, cancer, cell cycle, cellular growth, proliferation, and gene expression. These functional modules show signs of a complex interplay between signaling pathways consisting of both novel and previously described asbestos-related genes/gene products. These networks allowed for the identification of novel, putative crocidolite-related genes, leading to several new hypotheses regarding genes that are important for the asbestos response. The global analysis revealed a transcriptome that bears signatures of both apoptosis/cell death and cell survival/proliferation. Conclusion Our analyses demonstrate the power of combining a statistically robust, comprehensive dataset and a functional network genomics approach to 1 identify and explore relationships between genes of known importance

  15. Local industry in global networks : changing competitiveness, corporate strategies and pathways of development in Singapore and Malaysia's garment industry

    NARCIS (Netherlands)

    Smakman, Floortje

    2004-01-01

    The garment industry in Singapore and Malaysia has been incorporated into global production networks and commodity chains - driven by large US and European garment companies - since the 1960s and 1970s respectively. The industry was an intricate part of the export led industrialisation strategies

  16. Cell-type deconvolution with immune pathways identifies gene networks of host defense and immunopathology in leprosy

    Science.gov (United States)

    Inkeles, Megan S.; Teles, Rosane M.B.; Pouldar, Delila; Andrade, Priscila R.; Madigan, Cressida A.; Ambrose, Mike; Sarno, Euzenir N.; Rea, Thomas H.; Ochoa, Maria T.; Iruela-Arispe, M. Luisa; Swindell, William R.; Ottenhoff, Tom H.M.; Geluk, Annemieke; Bloom, Barry R.

    2016-01-01

    Transcriptome profiles derived from the site of human disease have led to the identification of genes that contribute to pathogenesis, yet the complex mixture of cell types in these lesions has been an obstacle for defining specific mechanisms. Leprosy provides an outstanding model to study host defense and pathogenesis in a human infectious disease, given its clinical spectrum, which interrelates with the host immunologic and pathologic responses. Here, we investigated gene expression profiles derived from skin lesions for each clinical subtype of leprosy, analyzing gene coexpression modules by cell-type deconvolution. In lesions from tuberculoid leprosy patients, those with the self-limited form of the disease, dendritic cells were linked with MMP12 as part of a tissue remodeling network that contributes to granuloma formation. In lesions from lepromatous leprosy patients, those with disseminated disease, macrophages were linked with a gene network that programs phagocytosis. In erythema nodosum leprosum, neutrophil and endothelial cell gene networks were identified as part of the vasculitis that results in tissue injury. The present integrated computational approach provides a systems approach toward identifying cell-defined functional networks that contribute to host defense and immunopathology at the site of human infectious disease. PMID:27699251

  17. Systems level analysis of systemic sclerosis shows a network of immune and profibrotic pathways connected with genetic polymorphisms.

    Directory of Open Access Journals (Sweden)

    J Matthew Mahoney

    2015-01-01

    Full Text Available Systemic sclerosis (SSc is a rare systemic autoimmune disease characterized by skin and organ fibrosis. The pathogenesis of SSc and its progression are poorly understood. The SSc intrinsic gene expression subsets (inflammatory, fibroproliferative, normal-like, and limited are observed in multiple clinical cohorts of patients with SSc. Analysis of longitudinal skin biopsies suggests that a patient's subset assignment is stable over 6-12 months. Genetically, SSc is multi-factorial with many genetic risk loci for SSc generally and for specific clinical manifestations. Here we identify the genes consistently associated with the intrinsic subsets across three independent cohorts, show the relationship between these genes using a gene-gene interaction network, and place the genetic risk loci in the context of the intrinsic subsets. To identify gene expression modules common to three independent datasets from three different clinical centers, we developed a consensus clustering procedure based on mutual information of partitions, an information theory concept, and performed a meta-analysis of these genome-wide gene expression datasets. We created a gene-gene interaction network of the conserved molecular features across the intrinsic subsets and analyzed their connections with SSc-associated genetic polymorphisms. The network is composed of distinct, but interconnected, components related to interferon activation, M2 macrophages, adaptive immunity, extracellular matrix remodeling, and cell proliferation. The network shows extensive connections between the inflammatory- and fibroproliferative-specific genes. The network also shows connections between these subset-specific genes and 30 SSc-associated polymorphic genes including STAT4, BLK, IRF7, NOTCH4, PLAUR, CSK, IRAK1, and several human leukocyte antigen (HLA genes. Our analyses suggest that the gene expression changes underlying the SSc subsets may be long-lived, but mechanistically interconnected

  18. Comparison of pharmacological and non-pharmacological interventions to prevent delirium in critically ill patients: a protocol for a systematic review incorporating network meta-analyses.

    Science.gov (United States)

    Burry, L D; Hutton, B; Guenette, M; Williamson, D; Mehta, S; Egerod, I; Kanji, S; Adhikari, N K; Moher, D; Martin, C M; Rose, L

    2016-09-08

    Delirium is characterized by acute changes in mental status including inattention, disorganized thinking, and altered level of consciousness, and is highly prevalent in critically ill adults. Delirium has adverse consequences for both patients and the healthcare system; however, at this time, no effective treatment exists. The identification of effective prevention strategies is therefore a clinical and research imperative. An important limitation of previous reviews of delirium prevention is that interventions were considered in isolation and only direct evidence was used. Our systematic review will synthesize all existing data using network meta-analysis, a powerful statistical approach that enables synthesis of both direct and indirect evidence. We will search Ovid MEDLINE, CINAHL, Embase, PsycINFO, and Web of Science from 1980 to March 2016. We will search the PROSPERO registry for protocols and the Cochrane Library for published systematic reviews. We will examine reference lists of pertinent reviews and search grey literature and the International Clinical Trials Registry Platform for unpublished studies and ongoing trials. We will include randomized and quasi-randomized trials of critically ill adults evaluating any pharmacological, non-pharmacological, or multi-component intervention for delirium prevention, administered in or prior to (i.e., peri-operatively) transfer to the ICU. Two authors will independently screen search results and extract data from eligible studies. Risk of bias assessments will be completed on all included studies. To inform our network meta-analysis, we will first conduct conventional pair-wise meta-analyses for primary and secondary outcomes using random-effects models. We will generate our network meta-analysis using a Bayesian framework, assuming a common heterogeneity parameter across all comparisons, and accounting for correlations in multi-arm studies. We will perform analyses using WinBUGS software. This systematic review

  19. An in silico assessment of gene function and organization of the phenylpropanoid pathway metabolic networks in Arabidopsis thaliana and limitations thereof

    Science.gov (United States)

    Costa, Michael A.; Collins, R. Eric; Anterola, Aldwin M.; Cochrane, Fiona C.; Davin, Laurence B.; Lewis, Norman G.

    2003-01-01

    The Arabidopsis genome sequencing in 2000 gave to science the first blueprint of a vascular plant. Its successful completion also prompted the US National Science Foundation to launch the Arabidopsis 2010 initiative, the goal of which is to identify the function of each gene by 2010. In this study, an exhaustive analysis of The Institute for Genomic Research (TIGR) and The Arabidopsis Information Resource (TAIR) databases, together with all currently compiled EST sequence data, was carried out in order to determine to what extent the various metabolic networks from phenylalanine ammonia lyase (PAL) to the monolignols were organized and/or could be predicted. In these databases, there are some 65 genes which have been annotated as encoding putative enzymatic steps in monolignol biosynthesis, although many of them have only very low homology to monolignol pathway genes of known function in other plant systems. Our detailed analysis revealed that presently only 13 genes (two PALs, a cinnamate-4-hydroxylase, a p-coumarate-3-hydroxylase, a ferulate-5-hydroxylase, three 4-coumarate-CoA ligases, a cinnamic acid O-methyl transferase, two cinnamoyl-CoA reductases) and two cinnamyl alcohol dehydrogenases can be classified as having a bona fide (definitive) function; the remaining 52 genes currently have undetermined physiological roles. The EST database entries for this particular set of genes also provided little new insight into how the monolignol pathway was organized in the different tissues and organs, this being perhaps a consequence of both limitations in how tissue samples were collected and in the incomplete nature of the EST collections. This analysis thus underscores the fact that even with genomic sequencing, presumed to provide the entire suite of putative genes in the monolignol-forming pathway, a very large effort needs to be conducted to establish actual catalytic roles (including enzyme versatility), as well as the physiological function(s) for each member

  20. Simulating an Impact of Road Network Improvements on the Performance of Transportation Systems under Critical Load: Agent-based Approach

    NARCIS (Netherlands)

    Milevich, D.; Melnikov, V.; Karbovskii, V.; Krzhizhanovskaya, V.

    2016-01-01

    In this paper, we analyze the impact of planned road network development on the dynamics of the automobile transportation system during the departure of visitors after the semifinal match of the 2018 FIFA World Cup, which will take place in the newly built stadium on Krestovsky Island. To perform

  1. Extracting the field-effect mobilities of random semiconducting single-walled carbon nanotube networks: A critical comparison of methods

    Science.gov (United States)

    Schießl, Stefan P.; Rother, Marcel; Lüttgens, Jan; Zaumseil, Jana

    2017-11-01

    The field-effect mobility is an important figure of merit for semiconductors such as random networks of single-walled carbon nanotubes (SWNTs). However, owing to their network properties and quantum capacitance, the standard models for field-effect transistors cannot be applied without modifications. Several different methods are used to determine the mobility with often very different results. We fabricated and characterized field-effect transistors with different polymer-sorted, semiconducting SWNT network densities ranging from low (≈6 μm-1) to densely packed quasi-monolayers (≈26 μm-1) with a maximum on-conductance of 0.24 μS μm-1 and compared four different techniques to evaluate the field-effect mobility. We demonstrate the limits and requirements for each method with regard to device layout and carrier accumulation. We find that techniques that take into account the measured capacitance on the active device give the most reliable mobility values. Finally, we compare our experimental results to a random-resistor-network model.

  2. Modeling Flow in Naturally Fractured Reservoirs : Effect of Fracture Aperture Distribution on Critical Sub-Network for Flow

    NARCIS (Netherlands)

    Gong, J.; Rossen, W.R.

    2014-01-01

    Fracture network connectivity and aperture (or conductivity) distribution are two crucial features controlling the flow behavior of fractured formations. The effect of connectivity on flow properties is well documented. We focus here on the influence of fracture aperture distribution. We model a

  3. The Killing Fields on TV: A Critical Analysis of Network Coverage of Cambodia under the Khmer Rouge.

    Science.gov (United States)

    Smith, Ted J., III; Grassmick, David E.

    In an effort to determine the nature of American network television news coverage of the Khmer Rouge rule in Cambodia, a study examined the television evening news from April 16, 1975, the date on which the Lon Nol government first offered to capitulate to the Khmer Rouge, through January 8, 1979, when news of the fall of Phnom Penh to the…

  4. Reconstruction of pathway modification induced by nicotinamide using multi-omic network analyses in triple negative breast cancer

    OpenAIRE

    Kim, Ji Young; Lee, Hyebin; Woo, Jongmin; Yue, Wang; Kim, Kwangsoo; Choi, Seongmin; Jang, Ja-June; Kim, Youngsoo; Park, In Ae; Han, Dohyun; Ryu, Han Suk

    2017-01-01

    Triple negative breast cancer (TNBC) is characterized by an aggressive biological behavior in the absence of a specific target agent. Nicotinamide has recently been proven to be a novel therapeutic agent for skin tumors in an ONTRAC trial. We performed combinatory transcriptomic and in-depth proteomic analyses to characterize the network of molecular interactions in TNBC cells treated with nicotinamide. The multi-omic profiles revealed that nicotinamide drives significant functional alteratio...

  5. Organizational Networks

    DEFF Research Database (Denmark)

    Grande, Bård; Sørensen, Ole Henning

    1998-01-01

    The paper focuses on the concept of organizational networks. Four different uses of the concept of organizational network are identified and critically discussed. Special focus is placed on how information and communication technologies as communication mediators and cognitive pictures influence...

  6. Ranking of critical species to preserve the functionality of mutualistic networks using the k-core decomposition.

    Science.gov (United States)

    García-Algarra, Javier; Pastor, Juan Manuel; Iriondo, José María; Galeano, Javier

    2017-01-01

    Network analysis has become a relevant approach to analyze cascading species extinctions resulting from perturbations on mutualistic interactions as a result of environmental change. In this context, it is essential to be able to point out key species, whose stability would prevent cascading extinctions, and the consequent loss of ecosystem function. In this study, we aim to explain how the k-core decomposition sheds light on the understanding the robustness of bipartite mutualistic networks. We defined three k-magnitudes based on the k-core decomposition: k-radius, k-degree, and k-risk. The first one, k-radius, quantifies the distance from a node to the innermost shell of the partner guild, while k-degree provides a measure of centrality in the k-shell based decomposition. k-risk is a way to measure the vulnerability of a network to the loss of a particular species. Using these magnitudes we analyzed 89 mutualistic networks involving plant pollinators or seed dispersers. Two static extinction procedures were implemented in which k-degree and k-risk were compared against other commonly used ranking indexes, as for example MusRank, explained in detail in Material and Methods. When extinctions take place in both guilds, k-risk is the best ranking index if the goal is to identify the key species to preserve the giant component. When species are removed only in the primary class and cascading extinctions are measured in the secondary class, the most effective ranking index to identify the key species to preserve the giant component is k-degree. However, MusRank index was more effective when the goal is to identify the key species to preserve the greatest species richness in the second class. The k-core decomposition offers a new topological view of the structure of mutualistic networks. The new k-radius, k-degree and k-risk magnitudes take advantage of its properties and provide new insight into the structure of mutualistic networks. The k-risk and k-degree ranking

  7. Ranking of critical species to preserve the functionality of mutualistic networks using the k-core decomposition

    Directory of Open Access Journals (Sweden)

    Javier García-Algarra

    2017-05-01

    Full Text Available Background Network analysis has become a relevant approach to analyze cascading species extinctions resulting from perturbations on mutualistic interactions as a result of environmental change. In this context, it is essential to be able to point out key species, whose stability would prevent cascading extinctions, and the consequent loss of ecosystem function. In this study, we aim to explain how the k-core decomposition sheds light on the understanding the robustness of bipartite mutualistic networks. Methods We defined three k-magnitudes based on the k-core decomposition: k-radius, k-degree, and k-risk. The first one, k-radius, quantifies the distance from a node to the innermost shell of the partner guild, while k-degree provides a measure of centrality in the k-shell based decomposition. k-risk is a way to measure the vulnerability of a network to the loss of a particular species. Using these magnitudes we analyzed 89 mutualistic networks involving plant pollinators or seed dispersers. Two static extinction procedures were implemented in which k-degree and k-risk were compared against other commonly used ranking indexes, as for example MusRank, explained in detail in Material and Methods. Results When extinctions take place in both guilds, k-risk is the best ranking index if the goal is to identify the key species to preserve the giant component. When species are removed only in the primary class and cascading extinctions are measured in the secondary class, the most effective ranking index to identify the key species to preserve the giant component is k-degree. However, MusRank index was more effective when the goal is to identify the key species to preserve the greatest species richness in the second class. Discussion The k-core decomposition offers a new topological view of the structure of mutualistic networks. The new k-radius, k-degree and k-risk magnitudes take advantage of its properties and provide new insight into the structure of

  8. Many-body localization and new critical phenomena in regular random graphs and constrained Erd\\H{o}s-Renyi networks

    CERN Document Server

    Avetisov, V; Nechaev, S; Valba, O

    2016-01-01

    We consider from the localization perspective the new critical behavior discovered recently for the regular random graphs (RRG) and constrained Erd\\H{o}s-Renyi networks (CERN). The diagonal disorder for standard models, we replace by the fugacity $\\mu$ of triads in the RRG and CERN. At some critical value of $\\mu$ the network decays into the maximally possible number of almost full graphs, and the adjacency matrix acquires the two-gapped structure. We find that the eigenvalue statistics corresponds to delocalized states in the central zone, and to the localized states in the side one. The mobility edge lies between zones. We apply these findings to the many-body localization assuming the approximation of the hierarchical structure of the Fock space (for some interacting many-body system) by the RGG and by CERN with some vertex degree. We allow the 3-cycles in the Fock space and identify particles in the many-body system above the phase transition with clusters in the RRG. We discuss the controversial issue of...

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

    Science.gov (United States)

    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

  10. Competências críticas ao desenvolvimento de mapas cognitivos de redes interorganizacionais Critical capabilities for the development of cognitive maps of inter-organizational networks

    Directory of Open Access Journals (Sweden)

    José Osvaldo de Sordi

    2009-10-01

    Full Text Available Este artigo identifica alguns dos conhecimentos e habilidades requeridos para a compreensão e abstração de redes interorganizacionais por intermédio de diagramas de rede. Para tanto, realizou-se um exercício prático junto a 102 alunos da área de administração. No exercício, foi pedido o desenvolvimento de um diagrama de rede a partir da transcrição de falas de atores centrais de uma rede do cultivo de uva. Na fase de pré-análise das respostas, os pesquisadores identificaram aspectos críticos para abstração de redes interorganizacionais, reflexão que auxiliou a definir os códigos requeridos para exploração do material por meio de análise de conteúdo: abstração de organizações com mesma função na rede; abstração de macroprocessos que compõem a rede; abstração do ator central da rede. Além de apurar a grande dificuldade dos alunos para compreender e abstrair redes interorganizacionais, o exercício auxiliou na identificação de algumas competências críticas para tal, como: conhecimentos e habilidades referentes a entidades e seus relacionamentos, como os alcançados pela prática das técnicas de construção de modelo entidade-relacionamento; conhecimentos e habilidades de processos de negócio, em especial de atividades de decomposição e síntese de processos.This article identifies the knowledge and skills required for understanding and abstracting inter-organizational network through network diagrams. A practical exercise was applied to 102 business administration students asking them to draw a network diagram based on the transcripts of the statements of central actors in a viniculture network. The pre-analysis of the answers revealed critical aspects for inter-organizational network abstraction. This reflection helped define the required codes to explore the material through content analysis: abstraction of organizations with same function in the network; abstraction of the network's macro

  11. The development of Sustainability Graduate Community (SGC) as a learning pathway for sustainability education - a framework for engineering programmes in Malaysia Technical Universities Network (MTUN)

    Science.gov (United States)

    Johan, Kartina; Mohd Turan, Faiz

    2016-11-01

    ‘Environmental and sustainability’ is one of the Program Outcome (PO) designated by the Board of Engineers Malaysia (BEM) as one of the accreditation program requirement. However, to-date the implementation of sustainability elements in engineering programme in the technical universities in Malaysia is within individual faculty's curriculum plan and lack of university-level structured learning pathway, which enable all students to have access to an education in sustainability across all disciplines. Sustainability Graduate Community (SGC) is a framework designed to provide a learning pathway in the curriculum of engineering programs to inculcate sustainability education among engineering graduates. This paper aims to study the required attributes in Sustainability Graduate Community (SGC) framework to produce graduates who are not just engineers but also skilful in sustainability competencies using Global Project Management (GPM) P5 Standard for Sustainability. The development of the conceptual framework is to provide a constructive teaching and learning plan for educators and policy makers to work on together in developing the Sustainability Graduates (SG), the new kind of graduates from Malaysia Technical Universities Network (MTUN) in Malaysia who are literate in sustainability practices. The framework also support the call for developing holistic students based on Malaysian Education Blueprint (Higher Education) and address the gap between the statuses of engineering qualification to the expected competencies from industries in Malaysia in particular by achieving the SG attributes outlined in the framework

  12. DMPD: Critical role of toll-like receptors and nucleotide oligomerisation domain inthe regulation of health and disease. [Dynamic Macrophage Pathway CSML Database

    Lifescience Database Archive (English)

    Full Text Available and nucleotide oligomerisation domain inthe regulation of health and disease. Pu...bmedID 17535871 Title Critical role of toll-like receptors and nucleotide oligomerisation domain inthe regulation of health...17535871 Critical role of toll-like receptors and nucleotide oligomerisation domain inthe regulation of heal...th and disease. Mitchell JA, Paul-Clark MJ, Clarke GW, McMaster SK, Cartwright N. J

  13. 3D-stacked carbon composites employing networked electrical intra-pathways for direct-printable, extremely stretchable conductors.

    Science.gov (United States)

    Chae, Changju; Seo, Yeong-Hui; Jo, Yejin; Kim, Ki Woong; Song, Wooseok; An, Ki-Seok; Choi, Sungho; Choi, Youngmin; Lee, Sun Sook; Jeong, Sunho

    2015-02-25

    The newly designed materials for stretchable conductors meeting the demands for both electrical and mechanical stability upon morphological elongation have recently been of paramount interest in the applications of stretchable, wearable electronics. To date, carbon nanotube-elastomeric polymer mixtures have been mainly developed; however, the method of preparing such CNT-polymer mixtures as stretchable conductors has been limited to an ionic liquid-mediated approach. In this study, we suggest a simple wet-chemical method for producing newly designed, three-dimensionally stacked carbon composite materials that facilitate the stable morphological elongation up to a strain of 300% with normalized conductivity variation of only 0.34 under a strain of 300%. Through a comparative study with other control samples, it is demonstrated that the intraconnected electrical pathways in hierarchically structured composite materials enable the generation of highly stretchable conductors. Their direct patternability is also evaluated by printing on demand using a programmable disperser without the use of prepatterned masks.

  14. The role of the Parkinson's disease gene PARK9 in essential cellular pathways and the manganese homeostasis network in yeast.

    Directory of Open Access Journals (Sweden)

    Alessandra Chesi

    Full Text Available YPK9 (Yeast PARK9; also known as YOR291W is a non-essential yeast gene predicted by sequence to encode a transmembrane P-type transport ATPase. However, its substrate specificity is unknown. Mutations in the human homolog of YPK9, ATP13A2/PARK9, have been linked to genetic forms of early onset parkinsonism. We previously described a strong genetic interaction between Ypk9 and another Parkinson's disease (PD protein α-synuclein in multiple model systems, and a role for Ypk9 in manganese detoxification in yeast. In humans, environmental exposure to toxic levels of manganese causes a syndrome similar to PD and is thus an environmental risk factor for the disease. How manganese contributes to neurodegeneration is poorly understood. Here we describe multiple genome-wide screens in yeast aimed at defining the cellular function of Ypk9 and the mechanisms by which it protects cells from manganese toxicity. In physiological conditions, we found that Ypk9 genetically interacts with essential genes involved in cellular trafficking and the cell cycle. Deletion of Ypk9 sensitizes yeast cells to exposure to excess manganese. Using a library of non-essential gene deletions, we screened for additional genes involved in tolerance to excess manganese exposure, discovering several novel pathways involved in manganese homeostasis. We defined the dependence of the deletion strain phenotypes in the presence of manganese on Ypk9, and found that Ypk9 deletion modifies the manganese tolerance of only a subset of strains. These results confirm a role for Ypk9 in manganese homeostasis and illuminates cellular pathways and biological processes in which Ypk9 likely functions.

  15. A Systems Biology Approach to Reveal Putative Host-Derived Biomarkers of Periodontitis by Network Topology Characterization of MMP-REDOX/NO and Apoptosis Integrated Pathways.

    Science.gov (United States)

    Zeidán-Chuliá, Fares; Gürsoy, Mervi; Neves de Oliveira, Ben-Hur; Özdemir, Vural; Könönen, Eija; Gürsoy, Ulvi K

    2015-01-01

    Periodontitis, a formidable global health burden, is a common chronic disease that destroys tooth-supporting tissues. Biomarkers of the early phase of this progressive disease are of utmost importance for global health. In this context, saliva represents a non-invasive biosample. By using systems biology tools, we aimed to (1) identify an integrated interactome between matrix metalloproteinase (MMP)-REDOX/nitric oxide (NO) and apoptosis upstream pathways of periodontal inflammation, and (2) characterize the attendant topological network properties to uncover putative biomarkers to be tested in saliva from patients with periodontitis. Hence, we first generated a protein-protein network model of interactions ("BIOMARK" interactome) by using the STRING 10 database, a search tool for the retrieval of interacting genes/proteins, with "Experiments" and "Databases" as input options and a confidence score of 0.400. Second, we determined the centrality values (closeness, stress, degree or connectivity, and betweenness) for the "BIOMARK" members by using the Cytoscape software. We found Ubiquitin C (UBC), Jun proto-oncogene (JUN), and matrix metalloproteinase-14 (MMP14) as the most central hub- and non-hub-bottlenecks among the 211 genes/proteins of the whole interactome. We conclude that UBC, JUN, and MMP14 are likely an optimal candidate group of host-derived biomarkers, in combination with oral pathogenic bacteria-derived proteins, for detecting periodontitis at its early phase by using salivary samples from patients. These findings therefore have broader relevance for systems medicine in global health as well.

  16. Ultrastructural localization of extracellular matrix proteins of the lymph node cortex: evidence supporting the reticular network as a pathway for lymphocyte migration

    Directory of Open Access Journals (Sweden)

    Sobocinski Gregg P

    2010-08-01

    Full Text Available Abstract Background The lymph node (LN is a crossroads of blood and lymphatic vessels allowing circulating lymphocytes to efficiently recognize foreign molecules displayed on antigen presenting cells. Increasing evidence indicates that after crossing high endothelial venules, lymphocytes migrate within the node along the reticular network (RN, a scaffold of fibers enwrapped by fibroblastic reticular cells (FRC. Light microscopy has shown that the RN contains specific extracellular matrix (ECM proteins, which are putative molecular "footholds" for migration, and are known ligands for lymphocyte integrin adhesion receptors. Results To investigate whether ECM proteins of the RN are present on the outer surface of the FRC and are thus accessible to migrating lymphocytes, ultrastructural immunohistochemical staining of cynomolgus monkey LN was performed using antibodies to human ECM proteins that were successfully employed at the light microscopic level. The fibrillar collagens I and III were observed primarily within the reticular network fibers themselves. In contrast, the matrix proteins laminin, fibronectin, collagen IV, and tenascin were observed within the reticular fibers and also on the outer membrane surface of the FRC. Conclusions These findings suggest a molecular basis for how the RN functions as a pathway for lymphocyte migration within the lymph node.

  17. Probabilistic low-rank factorization accelerates tensor network simulations of critical quantum many-body ground states

    Science.gov (United States)

    Kohn, Lucas; Tschirsich, Ferdinand; Keck, Maximilian; Plenio, Martin B.; Tamascelli, Dario; Montangero, Simone

    2018-01-01

    We provide evidence that randomized low-rank factorization is a powerful tool for the determination of the ground-state properties of low-dimensional lattice Hamiltonians through tensor network techniques. In particular, we show that randomized matrix factorization outperforms truncated singular value decomposition based on state-of-the-art deterministic routines in time-evolving block decimation (TEBD)- and density matrix renormalization group (DMRG)-style simulations, even when the system under study gets close to a phase transition: We report linear speedups in the bond or local dimension of up to 24 times in quasi-two-dimensional cylindrical systems.

  18. Mechanistically Distinct Pathways of Divergent Regulatory DNA Creation Contribute to Evolution of Human-Specific Genomic Regulatory Networks Driving Phenotypic Divergence of Homo sapiens.

    Science.gov (United States)

    Glinsky, Gennadi V

    2016-09-19

    Thousands of candidate human-specific regulatory sequences (HSRS) have been identified, supporting the hypothesis that unique to human phenotypes result from human-specific alterations of genomic regulatory networks. Collectively, a compendium of multiple diverse families of HSRS that are functionally and structurally divergent from Great Apes could be defined as the backbone of human-specific genomic regulatory networks. Here, the conservation patterns analysis of 18,364 candidate HSRS was carried out requiring that 100% of bases must remap during the alignments of human, chimpanzee, and bonobo sequences. A total of 5,535 candidate HSRS were identified that are: (i) highly conserved in Great Apes; (ii) evolved by the exaptation of highly conserved ancestral DNA; (iii) defined by either the acceleration of mutation rates on the human lineage or the functional divergence from non-human primates. The exaptation of highly conserved ancestral DNA pathway seems mechanistically distinct from the evolution of regulatory DNA segments driven by the species-specific expansion of transposable elements. Genome-wide proximity placement analysis of HSRS revealed that a small fraction of topologically associating domains (TADs) contain more than half of HSRS from four distinct families. TADs that are enriched for HSRS and termed rapidly evolving in humans TADs (revTADs) comprise 0.8-10.3% of 3,127 TADs in the hESC genome. RevTADs manifest distinct correlation patterns between placements of human accelerated regions, human-specific transcription factor-binding sites, and recombination rates. There is a significant enrichment within revTAD boundaries of hESC-enhancers, primate-specific CTCF-binding sites, human-specific RNAPII-binding sites, hCONDELs, and H3K4me3 peaks with human-specific enrichment at TSS in prefrontal cortex neurons (P Homo sapiens is driven by the evolution of human-specific genomic regulatory networks via at least two mechanistically distinct pathways of

  19. Designing pathways

    DEFF Research Database (Denmark)

    2010-01-01

    The theoretical background in this chapter is organizational studies and especially theories about design and design processes in organizations. The concept of design is defined as a particular kind of work aimed at making arrangements in order to change existing situations into desired ones....... The illustrative case example is the introduction of clinical pathways in a psychiatric department. The contribution to a general core of design research is the development of the concept of design work and a critical discussion of the role of technological rules in design work....

  20. Critical analysis of laboratory measurements and monitoring system of water-pipe network corrosion-case study.

    Directory of Open Access Journals (Sweden)

    Agata Jazdzewska

    2016-06-01

    Full Text Available Case study of corrosion failure of urban water supply system caused by environmental factors was presented. Nowadays corrosion monitoring of water distribution systems is an object of major concern. There is possibility of application broad range of techniques like gravimetric and electrochemical. Both kinds of techniques can be applied in laboratory and field conditions. In many cases researches limit the case analysis to measurements in laboratory conditions. Presented work contain critical analysis of results obtained in laboratory and field conditions based on corrosion monitoring of three pipelines systems failure in Krakow.

  1. Prevention of Alcohol-Heightened Aggression by CRF-R1 Antagonists in Mice: Critical Role for DRN-PFC Serotonin Pathway

    OpenAIRE

    Quadros, Isabel M.; Hwa, Lara S.; Shimamoto, Akiko; Carlson, Julia; DeBold, Joseph F.; Miczek, Klaus A.

    2014-01-01

    Alcohol can escalate aggressive behavior in a significant subgroup of rodents, humans, and nonhuman primates. The present study investigated whether blockade of corticotropin-releasing factor receptor type 1 (CRF-R1) could prevent the emergence of alcohol-heightened aggression in mice. The serotonin (5-HT) pathway from the dorsal raphe nucleus (DRN) to the medial prefrontal cortex (mPFC) by CRF-R1 was investigated as a possible target for the prevention of alcohol-heightened aggressive behavi...

  2. Critical analysis of protein signaling networks involved in the regulation of plant secondary metabolism: focus on anthocyanins.

    Science.gov (United States)

    Bulgakov, Victor P; Avramenko, Tatiana V; Tsitsiashvili, Gurami Sh

    2017-09-01

    Anthocyanin biosynthesis in Arabidopsis is a convenient and relatively simple model for investigating the basic principles of secondary metabolism regulation. In recent years, many publications have described links between anthocyanin biosynthesis and general defense reactions in plants as well as photomorphogenesis and hormonal signaling. These relationships are complex, and they cannot be understood intuitively. Upon observing the lacuna in the Arabidopsis interactome (an interaction map of the factors involved in the regulation of Arabidopsis secondary metabolism is not available), we attempted to connect various cellular processes that affect anthocyanin biosynthesis. In this review, we revealed the main signaling protein modules that regulate anthocyanin biosynthesis. To our knowledge, this is the first reconstruction of a network of proteins involved in plant secondary metabolism.

  3. Soil processes and functions across an international network of Critical Zone Observatories: Introduction to experimental methods and initial results

    Science.gov (United States)

    Banwart, Steven; Menon, Manoj; Bernasconi, Stefano M.; Bloem, Jaap; Blum, Winfried E. H.; Souza, Danielle Maia de; Davidsdotir, Brynhildur; Duffy, Christopher; Lair, Georg J.; Kram, Pavel; Lamacova, Anna; Lundin, Lars; Nikolaidis, Nikolaos P.; Novak, Martin; Panagos, Panos; Ragnarsdottir, Kristin Vala; Reynolds, Brian; Robinson, David; Rousseva, Svetla; de Ruiter, Peter; van Gaans, Pauline; Weng, Liping; White, Tim; Zhang, Bin

    2012-11-01

    Growth in human population and demand for wealth creates ever-increasing pressure on global soils, leading to soil losses and degradation worldwide. Critical Zone science studies the impact linkages between these pressures, the resulting environmental state of soils, and potential interventions to protect soil and reverse degradation. New research on soil processes is being driven by the scientific hypothesis that soil processes can be described along a life cycle of soil development. This begins with formation of new soil from parent material, development of the soil profile, and potential loss of the developed soil functions and the soil itself under overly intensive anthropogenic land use, thus closing the cycle. Four Critical Zone Observatories in Europe have been selected focusing research at sites that represent key stages along the hypothetical soil life cycle; incipient soil formation, productive use of soil for farming and forestry, and decline of soil due to longstanding intensive agriculture. Initial results from the research show that soil develops important biogeochemical properties on the time scale of decades and that soil carbon and the development of favourable soil structure takes place over similar time scales. A new mathematical model of soil aggregate formation and degradation predicts that set-aside land at the most degraded site studied can develop substantially improved soil structure with the accumulation of soil carbon over a period of several years. Further results demonstrate the rapid dynamics of soil carbon; how quickly it can be lost, and also demonstrate how data from the CZOs can be used to determine parameter values for models at catchment scale. A structure for a new integrated Critical Zone model is proposed that combines process descriptions of carbon and nutrient flows, a simplified description of the soil food web, and reactive transport; all coupled with a dynamic model for soil structure and soil aggregation. This approach

  4. Organizational Networks

    DEFF Research Database (Denmark)

    Sørensen, Ole Henning; Grande, Bård

    1996-01-01

    The paper focuses on the concept of organizational networks. Four different uses of the concept are identified and critically discussed.......The paper focuses on the concept of organizational networks. Four different uses of the concept are identified and critically discussed....

  5. Pathways for diffusion in the potential energy landscape of the network glass former SiO2

    Science.gov (United States)

    Niblett, S. P.; Biedermann, M.; Wales, D. J.; de Souza, V. K.

    2017-10-01

    We study the dynamical behaviour of a computer model for viscous silica, the archetypal strong glass former, and compare its diffusion mechanism with earlier studies of a fragile binary Lennard-Jones liquid. Three different methods of analysis are employed. First, the temperature and time scale dependence of the diffusion constant is analysed. Negative correlation of particle displacements influences transport properties in silica as well as in fragile liquids. We suggest that the difference between Arrhenius and super-Arrhenius diffusive behaviour results from competition between the correlation time scale and the caging time scale. Second, we analyse the dynamics using a geometrical definition of cage-breaking transitions that was proposed previously for fragile glass formers. We find that this definition accurately captures the bond rearrangement mechanisms that control transport in open network liquids, and reproduces the diffusion constants accurately at low temperatures. As the same method is applicable to both strong and fragile glass formers, we can compare correlation time scales in these two types of systems. We compare the time spent in chains of correlated cage breaks with the characteristic caging time and find that correlations in the fragile binary Lennard-Jones system persist for an order of magnitude longer than those in the strong silica system. We investigate the origin of the correlation behaviour by sampling the potential energy landscape for silica and comparing it with the binary Lennard-Jones model. We find no qualitative difference between the landscapes, but several metrics suggest that the landscape of the fragile liquid is rougher and more frustrated. Metabasins in silica are smaller than those in binary Lennard-Jones and contain fewer high-barrier processes. This difference probably leads to the observed separation of correlation and caging time scales.

  6. Transcription Adaptation during In Vitro Adipogenesis and Osteogenesis of Porcine Mesenchymal Stem Cells: Dynamics of Pathways, Biological Processes, Up-Stream Regulators, and Gene Networks.

    Science.gov (United States)

    Bionaz, Massimo; Monaco, Elisa; Wheeler, Matthew B

    2015-01-01

    The importance of mesenchymal stem cells (MSC) for bone regeneration is growing. Among MSC the bone marrow-derived stem cells (BMSC) are considered the gold standard in tissue engineering and regenerative medicine; however, the adipose-derived stem cells (ASC) have very similar properties and some advantages to be considered a good alternative to BMSC. The molecular mechanisms driving adipogenesis are relatively well-known but mechanisms driving osteogenesis are poorly known, particularly in pig. In the present study we have used transcriptome analysis to unravel pathways and biological functions driving in vitro adipogenesis and osteogenesis in BMSC and ASC. The analysis was performed using the novel Dynamic Impact Approach and functional enrichment analysis. In addition, a k-mean cluster analysis in association with enrichment analysis, networks reconstruction, and transcription factors overlapping analysis were performed in order to uncover the coordination of biological functions underlining differentiations. Analysis indicated a larger and more coordinated transcriptomic adaptation during adipogenesis compared to osteogenesis, with a larger induction of metabolism, particularly lipid synthesis (mostly triglycerides), and a larger use of amino acids for synthesis of feed-forward adipogenic compounds, larger cell signaling, lower cell-to-cell interactions, particularly for the cytoskeleton organization and cell junctions, and lower cell proliferation. The coordination of adipogenesis was mostly driven by Peroxisome Proliferator-activated Receptors together with other known adipogenic transcription factors. Only a few pathways and functions were more induced during osteogenesis compared to adipogenesis and some were more inhibited during osteogenesis, such as cholesterol and protein synthesis. Up-stream transcription factor analysis indicated activation of several lipid-related transcription regulators (e.g., PPARs and CEBPα) during adipogenesis but osteogenesis

  7. C/EBPγ Is a Critical Regulator of Cellular Stress Response Networks through Heterodimerization with ATF4

    Science.gov (United States)

    Huggins, Christopher J.; Mayekar, Manasi K.; Martin, Nancy; Saylor, Karen L.; Gonit, Mesfin; Jailwala, Parthav; Kasoji, Manjula; Haines, Diana C.; Quiñones, Octavio A.

    2015-01-01

    The integrated stress response (ISR) controls cellular adaptations to nutrient deprivation, redox imbalances, and endoplasmic reticulum (ER) stress. ISR genes are upregulated in stressed cells, primarily by the bZIP transcription factor ATF4 through its recruitment to cis-regulatory C/EBP:ATF response elements (CAREs) together with a dimeric partner of uncertain identity. Here, we show that C/EBPγ:ATF4 heterodimers, but not C/EBPβ:ATF4 dimers, are the predominant CARE-binding species in stressed cells. C/EBPγ and ATF4 associate with genomic CAREs in a mutually dependent manner and coregulate many ISR genes. In contrast, the C/EBP family members C/EBPβ and C/EBP homologous protein (CHOP) were largely dispensable for induction of stress genes. Cebpg−/− mouse embryonic fibroblasts (MEFs) proliferate poorly and exhibit oxidative stress due to reduced glutathione levels and impaired expression of several glutathione biosynthesis pathway genes. Cebpg−/− mice (C57BL/6 background) display reduced body size and microphthalmia, similar to ATF4-null animals. In addition, C/EBPγ-deficient newborns die from atelectasis and respiratory failure, which can be mitigated by in utero exposure to the antioxidant, N-acetyl-cysteine. Cebpg−/− mice on a mixed strain background showed improved viability but, upon aging, developed significantly fewer malignant solid tumors than WT animals. Our findings identify C/EBPγ as a novel antioxidant regulator and an obligatory ATF4 partner that controls redox homeostasis in normal and cancerous cells. PMID:26667036

  8. Corrected and Republished from: BCL11A is a critical component of a transcriptional network that activates RAG expression and VDJ recombination.

    Science.gov (United States)

    Lee, Baeck-Seung; Lee, Bum-Kyu; Iyer, Vishwanath R; Sleckman, Barry P; Shaffer, Arthur L; Ippolito, Gregory C; Tucker, Haley O; Dekker, Joseph D

    2017-10-16

    Recombination activating gene 1 (RAG1) and RAG2 are critical enzymes for initiating variable-diversity-joining (VDJ) segment recombination, an essential process for antigen receptor expression and lymphocyte development. The BCL11A transcription factor is required for B cell and Plasmacytoid dendritic cell (pDC) development, but its molecular function(s) in early B cell fate specification and commitment are unknown. We show here that the major B cell isoform, BCL11A-XL, binds directly to the RAG1 promoter as well as directly to regulatory regions of transcription factors previously implicated in both B cell and pDC development to activate RAG1 and RAG2 transcription in pro- and pre-B cells. We employ BCL11A over-expression with recombination substrates to demonstrate direct consequences of BCL11A/RAG modulation on V(D)J recombination. We conclude that BCL11A is a critical component of a transcriptional network that regulates B cell fate by controlling V(D)J recombination. Copyright © 2017 American Society for Microbiology.

  9. Clinical accuracy of RIFLE and Acute Kidney Injury Network (AKIN) criteria for predicting hospital mortality in critically ill patients with multi-organ dysfunction syndrome.

    Science.gov (United States)

    Ratanarat, Ranistha; Skulratanasak, Peenida; Tangkawattanakul, Nattakarn; Hantaweepant, Chattree

    2013-02-01

    The Acute Dialysis Quality Initiative (ADQI) group developed RIFLE criteria and the Acute Kidney Injury Network published AKIN classification that modified form RIFLE criteria. The authors aimed to compare the ability of RIFLE and AKIN criteria to measure the incidence of acute kidney injury (AKI) and to predict clinical outcomes in critically illpatients. A retrospective cohort study, in Siriraj Hospital, Bangkok. The critically ill patients admitted to medical intensive care unit (ICU) during January 2006-December 2008 were classified according to the maximum RIFLE and AKIN classification reached during their hospital stay Demographic data, hospital mortality, hospital length of stay, need of renal replacement therapy was collected. Three hundred patients were included in this study, AKI occurred in 200 (66.7%) patients: Risk 12.7%, Injury 20.7%, Failure 33.3% defined by RIFLE criteria. According to AKIN criteria, AKI occurred 230 (76.7%) patients: stage 1 16%, stage 2 13.3% and stage 3 47.3%. AKIN classification was diagnosed AKI, approximately 10% more than RIFLE (p < 0.001). The hospital mortality was 51.7% and the mortality in patients with AKI was significantly higher than patients without AKI (p < 0.001). The predictive ability using the AUC-ROC showed poor discrimination for the prediction of mortality of both RIFLE and AKIN: 0.63 and 0.69, respectively. However, AKIN showed superior prediction of mortality than RIFLE (p = 0.003). The APACHE II had the best discriminative accuracy for mortality (AUC = 0.80), followed by the SAPS3 scores (AUC = 0.77) and SAPS2 (AUC = 0.76). AKIN criteria improved sensitivity for detection of AKI and its discrimination for prediction of in-hospital mortality was better than that of RIFLE criteria. However, APACHE II had the best discriminative value for prediction of mortality in the critically ill patients.

  10. Artificial neural network-based exploration of gene-nutrient interactions in folate and xenobiotic metabolic pathways that modulate susceptibility to breast cancer.

    Science.gov (United States)

    Naushad, Shaik Mohammad; Ramaiah, M Janaki; Pavithrakumari, Manickam; Jayapriya, Jaganathan; Hussain, Tajamul; Alrokayan, Salman A; Gottumukkala, Suryanarayana Raju; Digumarti, Raghunadharao; Kutala, Vijay Kumar

    2016-04-15

    In the current study, an artificial neural network (ANN)-based breast cancer prediction model was developed from the data of folate and xenobiotic pathway genetic polymorphisms along with the nutritional and demographic variables to investigate how micronutrients modulate susceptibility to breast cancer. The developed ANN model explained 94.2% variability in breast cancer prediction. Fixed effect models of folate (400 μg/day) and B12 (6 μg/day) showed 33.3% and 11.3% risk reduction, respectively. Multifactor dimensionality reduction analysis showed the following interactions in responders to folate: RFC1 G80A × MTHFR C677T (primary), COMT H108L × CYP1A1 m2 (secondary), MTR A2756G (tertiary). The interactions among responders to B12 were RFC1G80A × cSHMT C1420T and CYP1A1 m2 × CYP1A1 m4. ANN simulations revealed that increased folate might restore ER and PR expression and reduce the promoter CpG island methylation of extra cellular superoxide dismutase and BRCA1. Dietary intake of folate appears to confer protection against breast cancer through its modulating effects on ER and PR expression and methylation of EC-SOD and BRCA1. Copyright © 2016 Elsevier B.V. All rights reserved.

  11. Low Dose Radiation Response Curves, Networks and Pathways in Human Lymphoblastoid Cells Exposed from 1 to 10 cGy of Acute Gamma Radiation

    Energy Technology Data Exchange (ETDEWEB)

    Wyrobek, A. J.; Manohar, C. F.; Nelson, D. O.; Furtado, M. R.; Bhattacharya, M. S.; Marchetti, F.; Coleman, M.A.

    2011-04-18

    We investigated the low dose dependency of the transcriptional response of human cells to characterize the shape and biological functions associated with the dose response curve and to identify common and conserved functions of low dose expressed genes across cells and tissues. Human lymphoblastoid (HL) cells from two unrelated individuals were exposed to graded doses of radiation spanning the range of 1-10 cGy were analyzed by transcriptome profiling, qPCR and bioinformatics, in comparison to sham irradiated samples. A set of {approx}80 genes showed consistent responses in both cell lines; these genes were associated with homeostasis mechanisms (e.g., membrane signaling, molecule transport), subcellular locations (e.g., Golgi, and endoplasmic reticulum), and involved diverse signal transduction pathways. The majority of radiation-modulated genes had plateau-like responses across 1-10 cGy, some with suggestive evidence that transcription was modulated at doses below 1 cGy. MYC, FOS and TP53 were the major network nodes of the low-dose response in HL cells. Comparison our low dose expression findings in HL cells with those of prior studies in mouse brain after whole body exposure, in human keratinocyte cultures, and in endothelial cells cultures, indicates that certain components of the low dose radiation response are broadly conserved across cell types and tissues, independent of proliferation status.

  12. A Critical Review of Surveys Emphasizing on Routing in Wireless Sensor Networks-An Anatomization under General Survey Design Framework.

    Science.gov (United States)

    Rehan, Waqas; Fischer, Stefan; Rehan, Maaz

    2017-07-26

    A large number of routing-related surveys are published so far for Wireless Sensor Networks (WSNs) that exhibit either complete or partial emphasis on routing in WSNs. These surveys classify and discuss the relevant routing protocols published mainly in the fields of classical, energy efficient, secure, hierarchical, geographic, intelligent, Quality of Service (QoS)-based and multipath WSNs. However, to the best of our knowledge, no study is presented so far which may clearly categorize the routing-related survey literature for WSNs.To fill this gap, an effort is made in this paper for presenting an in-depth review of already published routing-related survey literature in WSNs. Our review initially proposes a generalized survey design model and afterwards analyzes the routing-related survey literature in the light of the devised General Survey Design Framework (GSDF). Such an analysis describes the design soundness of the published routing-related surveys. Therefore, our review puts forth an original classification based on the frequency-of-survey-publication and taxonomizes the corresponding routing-related fields into high, medium and low focused areas of survey publication in WSNs. Furthermore, the surveys belonging to each main category are sub-categorized into various sub-classes and briefly discussed according to their design characteristics. On the one hand, this review is useful for beginners who may easily explore the already published routing-related survey literature in WSNs in a single document and investigate it by spending less effort. On the other hand, it is useful for expert researchers who may explore the trends and frequency of writing surveys in different areas of routing in WSNs. The experts may explore those areas of routing which are either neglected or least focused or lack in design soundness as per general survey design framework. In the end, insights and future research directions are outlined and a reasonable conclusion is put forth

  13. Antimicrobials for the treatment of drug-resistant Acinetobacter baumannii pneumonia in critically ill patients: a systemic review and Bayesian network meta-analysis.

    Science.gov (United States)

    Jung, Su Young; Lee, Seung Hee; Lee, Soo Young; Yang, Seungwon; Noh, Hayeon; Chung, Eun Kyoung; Lee, Jangik I

    2017-12-20

    . This Bayesian network meta-analysis demonstrated the comparative effectiveness of fifteen antimicrobial treatments for drug-resistant A. baumannii pneumonia in critically ill patients. For survival benefit, SUL appears to be the best treatment followed by HD SUL, FOS + IV COL, IH COL + IV COL, HD TIG, and IV COL therapy, in numerical order.

  14. Affective and neural reactivity to criticism in individuals high and low on perceived criticism.

    Directory of Open Access Journals (Sweden)

    Jill M Hooley

    Full Text Available People who have remitted from depression are at increased risk for relapse if they rate their relatives as being critical of them on a simple self-report measure of Perceived Criticism (PC. To explore neural mechanisms associated with this we used functional magnetic resonance imaging (fMRI to examine how people with different levels of PC responded to hearing criticism from their own mothers. To maximize variability in affective reactivity, depressed, recovered depressed, and healthy control participants (n = 33 were classified as high or low in PC based on a median split. They were then exposed to personally-relevant critical and praising comments from their mothers. Perceived Criticism levels were unrelated to depression status and to negative mood change after hearing criticism. However, compared to low PC participants, those who scored high on PC showed differential activation in a network of regions associated with emotion reactivity and regulation, including increased amygdala activity and decreased reactions in prefrontal regulatory regions when they heard criticism. This was not the case for praise. Criticism may be a risk factor for relapse because it helps to "train" pathways characteristic of depressive information processing. The Perceived Criticism measure may help identify people who are more susceptible to this vulnerability.

  15. Critical role of the neural pathway from the intermediate medial mesopallium to the intermediate hyperpallium apicale in filial imprinting of domestic chicks (Gallus gallus domesticus).

    Science.gov (United States)

    Aoki, N; Yamaguchi, S; Kitajima, T; Takehara, A; Katagiri-Nakagawa, S; Matsui, R; Watanabe, D; Matsushima, T; Homma, K J

    2015-11-12

    Filial imprinting in precocial birds is a useful model for studying early learning and cognitive development, as it is characterized by a well-defined sensitive or critical period. We recently showed that the thyroid hormone 3,5,3'-triiodothyronine (T3) determines the onset of the sensitive period. Moreover, exogenous injection of T3 into the intermediate medial mesopallium (IMM) region (analogous to the associative cortex in mammals) enables imprinting even on post-hatch day 4 or 6 when the sensitive period has been terminated. However, the neural mechanisms downstream from T3 action in the IMM region remain elusive. Here, we analyzed the functional involvement of the intermediate hyperpallium apicale (IMHA) in T3 action. Bilateral excitotoxic ablation of the IMHA prevented imprinting in newly hatched chicks, and also suppressed the recovery of the sensitive period by systemic intra-venous or localized intra-IMM injection of T3 in day-4 chicks. In contrast to the effect in the IMM, direct injection of T3 into the IMHA did not enable imprinting in day-4 chicks. Moreover, bilateral ablation of IMHA after imprinting training impaired recall. These results suggest that the IMHA is critical for memory acquisition downstream following T3 action in the IMM and further, that it receives and retains information stored in the IMM for recall. Furthermore, both an avian adeno-associated viral construct containing an anterograde tracer (wheat-germ agglutinin) and a retrograde tracer (cholera toxin subunit B) revealed neural connections from the IMM to the IMHA. Taken together, our findings suggest that hierarchical processes from the primary area (IMM) to the secondary area (IMHA) are required for imprinting. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

  16. The Critical Role of Redox Homeostasis in Shikonin-Induced HL-60 Cell Differentiation via Unique Modulation of the Nrf2/ARE Pathway

    Directory of Open Access Journals (Sweden)

    Bo Zhang

    2012-01-01

    Full Text Available Among various cancer cell lines, the leukemia cell line HL-60 was most sensitive to Shikonin, with evidence showing both the prooxidative activities and proapoptotic effects of micromolar concentrations of Shikonin. However, the mechanism involved in the cytotoxicity of Shikonin in the submicromolar range has not been fully characterized. Using biochemical and free radical biological experiments in vitro, we identified the prodifferentiated profiles of Shikonin and evaluated the redox homeostasis during HL-60 differentiation. The data showed a strong dose-response relationship between Shikonin exposure and the characteristics of HL-60 differentiation in terms of morphology changes, nitroblue tetrazolium (NBT reductive activity, and the expression level of surface antigens CD11b/CD14. During drug exposure, intercellular redox homeostasis changes towards oxidation are necessary to support Shikonin-induced differentiation, which was proven by additional enzymatic and non-enzymatic redox modulators. A statistically significant and dose-dependent increase (P<0.05 was recorded with regard to the unique expression levels of the Nrf2/ARE downstream target genes in HL-60 cells undergoing late differentiation, which were restored with further antioxidants employed with the Shikonin treatment. Our research demonstrated that Shikonin is a differentiation-inducing agent, and its mechanisms involve the Nrf2/ARE pathway to modulate the intercellular redox homeostasis, thus facilitating differentiation.

  17. A network of networks.

    Science.gov (United States)

    Iedema, Rick; Verma, Raj; Wutzke, Sonia; Lyons, Nigel; McCaughan, Brian

    2017-04-10

    from network members than participation in a single network, as it involves health service professionals and consumers in a multi-network dynamic. This dynamic requires deliberations and collaborations to be flexible, and it increasingly positions members as "strategic hybrids" - people who have moved on from singular taken-as-given stances and identities, towards hybrid positionings and flexible perspectives. Originality/value This paper is novel in that it identifies a critical feature of health service reform and large system transformation: network governance is empowered through the dynamic co-location of and collaboration among healthcare networks, particularly when complemented with "enabler" teams of people specialising in programme implementation and evaluation.

  18. Application of adverse outcome pathways (AOPs) in human health and ecotoxicology capturing divergent consequences of conserved molecular initiating events via AOP networks

    Science.gov (United States)

    The adverse outcome pathway (AOP) framework was developed to help organize and disseminate existing knowledge concerning the means through which specific perturbations of biological pathways can lead to adverse outcomes considered relevant to risk-based regulatory decision-making...

  19. Application of Adverse Outcome Pathways (AOPs) in Human Health and Ecotoxicology Capturing Divergent Consequences of Conserved Molecular Initiating Events via AOP Networks (Presentation)

    Science.gov (United States)

    The adverse outcome pathway (AOP) framework was developed to help organize and disseminate existing knowledge concerning the means through which specific perturbations of biological pathways can lead to adverse outcomes considered relevant to risk-based regulatory decision-making...

  20. Inversion of Schlumberger resistivity sounding data from the critically dynamic Koyna region using the Hybrid Monte Carlo-based neural network approach

    Directory of Open Access Journals (Sweden)

    S. Maiti

    2011-03-01

    Full Text Available Koyna region is well-known for its triggered seismic activities since the hazardous earthquake of M=6.3 occurred around the Koyna reservoir on 10 December 1967. Understanding the shallow distribution of resistivity pattern in such a seismically critical area is vital for mapping faults, fractures and lineaments. However, deducing true resistivity distribution from the apparent resistivity data lacks precise information due to intrinsic non-linearity in the data structures. Here we present a new technique based on the Bayesian neural network (BNN theory using the concept of Hybrid Monte Carlo (HMC/Markov Chain Monte Carlo (MCMC simulation scheme. The new method is applied to invert one and two-dimensional Direct Current (DC vertical electrical sounding (VES data acquired around the Koyna region in India. Prior to apply the method on actual resistivity data, the new method was tested for simulating synthetic signal. In this approach the objective/cost function is optimized following the Hybrid Monte Carlo (HMC/Markov Chain Monte Carlo (MCMC sampling based algorithm and each trajectory was updated by approximating the Hamiltonian differential equations through a leapfrog discretization scheme. The stability of the new inversion technique was tested in presence of correlated red noise and uncertainty of the result was estimated using the BNN code. The estimated true resistivity distribution was compared with the results of singular value decomposition (SVD-based conventional resistivity inversion results. Comparative results based on the HMC-based Bayesian Neural Network are in good agreement with the existing model results, however in some cases, it also provides more detail and precise results, which appears to be justified with local geological and structural details. The new BNN approach based on HMC is faster and proved to be a promising inversion scheme to interpret complex and non-linear resistivity problems. The HMC-based BNN results

  1. Transcription Adaptation during In Vitro Adipogenesis and Osteogenesis of Porcine Mesenchymal Stem Cells: Dynamics of Pathways, Biological Processes, Up-Stream Regulators, and Gene Networks.

    Directory of Open Access Journals (Sweden)

    Massimo Bionaz

    Full Text Available The importance of mesenchymal stem cells (MSC for bone regeneration is growing. Among MSC the bone marrow-derived stem cells (BMSC are considered the gold standard in tissue engineering and regenerative medicine; however, the adipose-derived stem cells (ASC have very similar properties and some advantages to be considered a good alternative to BMSC. The molecular mechanisms driving adipogenesis are relatively well-known but mechanisms driving osteogenesis are poorly known, particularly in pig. In the present study we have used transcriptome analysis to unravel pathways and biological functions driving in vitro adipogenesis and osteogenesis in BMSC and ASC. The analysis was performed using the novel Dynamic Impact Approach and functional enrichment analysis. In addition, a k-mean cluster analysis in association with enrichment analysis, networks reconstruction, and transcription factors overlapping analysis were performed in order to uncover the coordination of biological functions underlining differentiations. Analysis indicated a larger and more coordinated transcriptomic adaptation during adipogenesis compared to osteogenesis, with a larger induction of metabolism, particularly lipid synthesis (mostly triglycerides, and a larger use of amino acids for synthesis of feed-forward adipogenic compounds, larger cell signaling, lower cell-to-cell interactions, particularly for the cytoskeleton organization and cell junctions, and lower cell proliferation. The coordination of adipogenesis was mostly driven by Peroxisome Proliferator-activated Receptors together with other known adipogenic transcription factors. Only a few pathways and functions were more induced during osteogenesis compared to adipogenesis and some were more inhibited during osteogenesis, such as cholesterol and protein synthesis. Up-stream transcription factor analysis indicated activation of several lipid-related transcription regulators (e.g., PPARs and CEBPα during adipogenesis

  2. Activation of the Nrf2 Signaling Pathway Involving KLF9 Plays a Critical Role in Allicin Resisting Against Arsenic Trioxide-Induced Hepatotoxicity in Rats.

    Science.gov (United States)

    Yang, Daqian; Lv, Zhanjun; Zhang, Haili; Liu, Biying; Jiang, Huijie; Tan, Xiao; Lu, Jingjing; Baiyun, Ruiqi; Zhang, Zhigang

    2017-03-01

    Arsenic trioxide (As 2 O 3 ) is both the most prevalent, naturally occurring inorganic arsenical threatening human health and an efficient therapeutic for acute promyelocytic leukemia. Regretfully, As 2 O 3 -treated cancer patients often suffer from hepatotoxicity. While effective antioxidant and anticarcinogenic actions of allicin have previously been demonstrated, studies indicating how allicin affects As 2 O 3 -induced hepatotoxicity and arsenic accumulation are lacking. Our study, for the first time, elaborates potential details of the hepatoprotective mechanisms of allicin against As 2 O 3 -induced liver injury. Wistar rats were administrated allicin (30 mg/kg) 1 h before As 2 O 3 (3 mg/kg) by daily gavage for 2 weeks. Our results indicate that allicin ameliorated As 2 O 3 -induced liver dysfunction, oxidative stress, and arsenic accumulation in the liver. Meanwhile, allicin decreased NF-κB level and upregulated expression of proteins reduced by As 2 O 3 including nuclear factor erythroid 2-related factor 2 (Nrf2), heme oxygenase 1, nicotinamide adenine dinucleotide phosphate:quinone oxidoreductase 1, and Krüppel-like factor 9 (KLF9). In addition, allicin promoted B cell lymphoma-extra large expression and suppressed B cell lymphoma-2-associated X protein levels regulated by As 2 O 3 . However, neither allicin nor As 2 O 3 affected cytochrome P450 2E1 mRNA expression. In conclusion, allicin attenuated As 2 O 3 -induced hepatotoxicity by activating the Nrf2 signaling pathway involving KLF9 to inhibit oxidative stress and apoptosis. Our findings elucidate a detailed mechanism by which allicin provides protection against As 2 O 3 -induced liver injury and support its potential role as an adjunctive therapy for patients suffering from chronic arsenic exposure.

  3. Putting the pieces together: high-performance LC-MS/MS provides network-, pathway-, and protein-level perspectives in Populus.

    Science.gov (United States)

    Abraham, Paul; Giannone, Richard J; Adams, Rachel M; Kalluri, Udaya; Tuskan, Gerald A; Hettich, Robert L

    2013-01-01

    High-performance mass spectrometry (MS)-based proteomics enabled the construction of a detailed proteome atlas for Populus, a woody perennial plant model organism. Optimization of experimental procedures and implementation of current state-of-the-art instrumentation afforded the most detailed look into the predicted proteome space of Populus, offering varying proteome perspectives: (1) network-wide, (2) pathway-specific, and (3) protein-level viewpoints. Together, enhanced protein retrieval through a detergent-based lysis approach and maximized peptide sampling via the dual-pressure linear ion trap mass spectrometer (LTQ Velos), have resulted in the identification of 63,056 tryptic peptides. The technological advancements, specifically spectral-acquisition and sequencing speed, afforded the deepest look into the Populus proteome, with peptide abundances spanning 6 orders of magnitude and mapping to ∼25% of the predicted proteome space. In total, tryptic peptides mapped to 11,689 protein assignments across four organ-types: mature (fully expanded, leaf plastichronic index (LPI) 10-12) leaf, young (juvenile, LPI 4-6) leaf, root, and stem. To resolve protein ambiguity, identified proteins were grouped by sequence similarity (≥ 90%), thereby reducing the protein assignments into 7538 protein groups. In addition, this large-scale data set features the first systems-wide survey of protein expression across different Populus organs. As a demonstration of the precision and comprehensiveness of the semiquantitative analysis, we were able to contrast two stages of leaf development, mature versus young leaf. Statistical comparison through ANOVA analysis revealed 1432 protein groups that exhibited statistically significant (p ≤ 0.01) differences in protein abundance. Experimental validation of the metabolic circuitry expected in mature leaf (characterized by photosynthesis and carbon fixation) compared with young leaf (characterized by rapid growth and moderate

  4. Putting the Pieces Together: High-performance LC-MS/MS Provides Network-, Pathway-, and Protein-level Perspectives in Populus*

    Science.gov (United States)

    Abraham, Paul; Giannone, Richard J.; Adams, Rachel M.; Kalluri, Udaya; Tuskan, Gerald A.; Hettich, Robert L.

    2013-01-01

    High-performance mass spectrometry (MS)-based proteomics enabled the construction of a detailed proteome atlas for Populus, a woody perennial plant model organism. Optimization of experimental procedures and implementation of current state-of-the-art instrumentation afforded the most detailed look into the predicted proteome space of Populus, offering varying proteome perspectives: (1) network-wide, (2) pathway-specific, and (3) protein-level viewpoints. Together, enhanced protein retrieval through a detergent-based lysis approach and maximized peptide sampling via the dual-pressure linear ion trap mass spectrometer (LTQ Velos), have resulted in the identification of 63,056 tryptic peptides. The technological advancements, specifically spectral-acquisition and sequencing speed, afforded the deepest look into the Populus proteome, with peptide abundances spanning 6 orders of magnitude and mapping to ∼25% of the predicted proteome space. In total, tryptic peptides mapped to 11,689 protein assignments across four organ-types: mature (fully expanded, leaf plastichronic index (LPI) 10–12) leaf, young (juvenile, LPI 4–6) leaf, root, and stem. To resolve protein ambiguity, identified proteins were grouped by sequence similarity (≥ 90%), thereby reducing the protein assignments into 7538 protein groups. In addition, this large-scale data set features the first systems-wide survey of protein expression across different Populus organs. As a demonstration of the precision and comprehensiveness of the semiquantitative analysis, we were able to contrast two stages of leaf development, mature versus young leaf. Statistical comparison through ANOVA analysis revealed 1432 protein groups that exhibited statistically significant (p ≤ 0.01) differences in protein abundance. Experimental validation of the metabolic circuitry expected in mature leaf (characterized by photosynthesis and carbon fixation) compared with young leaf (characterized by rapid growth and moderate

  5. Intelligent ensemble T-S fuzzy neural networks with RCDPSO_DM optimization for effective handling of complex clinical pathway variances.

    Science.gov (United States)

    Du, Gang; Jiang, Zhibin; Diao, Xiaodi; Yao, Yang

    2013-07-01

    Takagi-Sugeno (T-S) fuzzy neural networks (FNNs) can be used to handle complex, fuzzy, uncertain clinical pathway (CP) variances. However, there are many drawbacks, such as slow training rate, propensity to become trapped in a local minimum and poor ability to perform a global search. In order to improve overall performance of variance handling by T-S FNNs, a new CP variance handling method is proposed in this study. It is based on random cooperative decomposing particle swarm optimization with double mutation mechanism (RCDPSO_DM) for T-S FNNs. Moreover, the proposed integrated learning algorithm, combining the RCDPSO_DM algorithm with a Kalman filtering algorithm, is applied to optimize antecedent and consequent parameters of constructed T-S FNNs. Then, a multi-swarm cooperative immigrating particle swarm algorithm ensemble method is used for intelligent ensemble T-S FNNs with RCDPSO_DM optimization to further improve stability and accuracy of CP variance handling. Finally, two case studies on liver and kidney poisoning variances in osteosarcoma preoperative chemotherapy are used to validate the proposed method. The result demonstrates that intelligent ensemble T-S FNNs based on the RCDPSO_DM achieves superior performances, in terms of stability, efficiency, precision and generalizability, over PSO ensemble of all T-S FNNs with RCDPSO_DM optimization, single T-S FNNs with RCDPSO_DM optimization, standard T-S FNNs, standard Mamdani FNNs and T-S FNNs based on other algorithms (cooperative particle swarm optimization and particle swarm optimization) for CP variance handling. Therefore, it makes CP variance handling more effective. Copyright © 2013 Elsevier Ltd. All rights reserved.

  6. Using Patient Pathway Analysis to Design Patient-centered Referral Networks for Diagnosis and Treatment of Tuberculosis: The Case of the Philippines.

    Science.gov (United States)

    Garfin, Celine; Mantala, Mariquita; Yadav, Rajendra; Hanson, Christy L; Osberg, Mike; Hymoff, Aaron; Makayova, Julia

    2017-11-06

    Tuberculosis (TB) is the 8th leading cause of death in the Philippines. A recent prevalence survey found that there were nearly 70% more cases of tuberculosis than previously estimated. Given these new data, the National TB Program (NTP), operating through a decentralized health system, identified about 58% of the estimated new drug-sensitive (DS) TB patients in 2016. However, the NTP only identified and commenced treatment for around 17% of estimated new drug-resistant patients. In order to reach the remaining 42% of drug-sensitive patients and 83% of drug-resistant patients, it is necessary to develop a better understanding of where patients seek care. National and regional patient pathway analyses (PPAs) were undertaken using existing national survey and NTP data. The PPA assessed the alignment between patient care seeking and the availability of TB diagnostic and treatment services. Systemic referral networks from the community-level Barangay Health Stations (BHSs) to diagnostic facilities have enabled more efficient detection of drug-sensitive tuberculosis in the public sector. Approximately 36% of patients initiated care in the private sector, where there is limited coverage of appropriate diagnostic technologies. Important differences in the alignment between care seeking patterns and diagnostic and treatment availability were found between regions. The PPA identified opportunities for strengthening access to care for all forms of tuberculosis and for accelerating the time to diagnosis by aligning services to where patients initiate care. Geographic variations in care seeking may guide prioritization of some regions for intensified engagement with the private sector.

  7. Pathways of Lipid Metabolism in Marine Algae, Co-Expression Network, Bottlenecks and Candidate Genes for Enhanced Production of EPA and DHA in Species of Chromista

    Directory of Open Access Journals (Sweden)

    Alice Mühlroth

    2013-11-01

    Full Text Available The importance of n-3 long chain polyunsaturated fatty acids (LC-PUFAs for human health has received more focus the last decades, and the global consumption of n-3 LC-PUFA has increased. Seafood, the natural n-3 LC-PUFA source, is harvested beyond a sustainable capacity, and it is therefore imperative to develop alternative n-3 LC-PUFA sources for both eicosapentaenoic acid (EPA, 20:5n-3 and docosahexaenoic acid (DHA, 22:6n-3. Genera of algae such as Nannochloropsis, Schizochytrium, Isochrysis and Phaedactylum within the kingdom Chromista have received attention due to their ability to produce n-3 LC-PUFAs. Knowledge of LC-PUFA synthesis and its regulation in algae at the molecular level is fragmentary and represents a bottleneck for attempts to enhance the n-3 LC-PUFA levels for industrial production. In the present review, Phaeodactylum tricornutum has been used to exemplify the synthesis and compartmentalization of n-3 LC-PUFAs. Based on recent transcriptome data a co-expression network of 106 genes involved in lipid metabolism has been created. Together with recent molecular biological and metabolic studies, a model pathway for n-3 LC-PUFA synthesis in P. tricornutum has been proposed, and is compared to industrialized species of Chromista. Limitations of the n-3 LC-PUFA synthesis by enzymes such as thioesterases, elongases, acyl-CoA synthetases and acyltransferases are discussed and metabolic bottlenecks are hypothesized such as the supply of the acetyl-CoA and NADPH. A future industrialization will depend on optimization of chemical compositions and increased biomass production, which can be achieved by exploitation of the physiological potential, by selective breeding and by genetic engineering.

  8. Exploring resistance pathways for first-generation NS3/4A protease inhibitors boceprevir and telaprevir using Bayesian network learning.

    Science.gov (United States)

    Cuypers, Lize; Libin, Pieter; Schrooten, Yoeri; Theys, Kristof; Di Maio, Velia Chiara; Cento, Valeria; Lunar, Maja M; Nevens, Frederik; Poljak, Mario; Ceccherini-Silberstein, Francesca; Nowé, Ann; Van Laethem, Kristel; Vandamme, Anne-Mieke

    2017-09-01

    Resistance-associated variants (RAVs) have been shown to influence treatment response to direct-acting antivirals (DAAs) and first generation NS3/4A protease inhibitors (PIs) in particular. Interpretation of hepatitis C virus (HCV) genotypic drug resistance remains a challenge, especially in patients who previously failed DAA therapy and need to be retreated with a second DAA based regimen. Bayesian network (BN) learning on HCV sequence data from patients treated with DAAs could provide insight in resistance pathways against PIs for HCV subtypes 1a and 1b, in a similar way as applied before for HIV. The publicly available 'Rega-BN' tool chain was developed to study associative analyses for various pathogens. Our first analysis, comparing sequences from PI-naïve and PI-experienced patients, determined that NS3 substitutions R155K and V36M arise with PI-exposure in HCV1a infected patients, and were defined as major and minor resistance-associated variants respectively. NS3 variant 174H was newly identified as potentially related to PI resistance. In a second analysis, NS3 sequences from PI-naïve patients who cleared the virus during PI therapy and from PI-naïve patients who failed PI therapy were compared, showing that NS3 baseline variant 67S predisposes to treatment-failure and variant 72I to treatment success. This approach has the potential to better characterize the role of more RAVs, if sufficient therapy annotated sequence data becomes available in curated public databases. In addition, polymorphisms present in baseline sequences that predispose patients to therapy failure can be identified using this approach. Copyright © 2017 Elsevier B.V. All rights reserved.

  9. Designing a Care Pathway Model – A Case Study of the Outpatient Total Hip Arthroplasty Care Pathway

    Directory of Open Access Journals (Sweden)

    Robin I. Oosterholt

    2017-03-01

    Full Text Available Introduction: Although the clinical attributes of total hip arthroplasty (THA care pathways have been thoroughly researched, a detailed understanding of the equally important organisational attributes is still lacking. The aim of this article is to contribute with a model of the outpatient THA care pathway that depicts how the care team should be organised to enable patient discharge on the day of surgery. Theory: The outpatient THA care pathway enables patients to be discharged on the day of surgery, short- ening the length of stay and intensifying the provision and organisation of care. We utilise visual care modelling to construct a visual design of the organisation of the care pathway. Methods: An embedded case study was conducted of the outpatient THA care pathway at a teaching hospital in the Netherlands. The data were collected using a visual care modelling toolkit in 16 semi- structured interviews. Problems and inefficiencies in the care pathway were identified and addressed in the iterative design process. Results: The results are two visual models of the most critical phases of the outpatient THA care pathway: diagnosis & preparation (1 and mobilisation & discharge (4. The results show the care team composition, critical value exchanges, and sequence that enable patient discharge on the day of surgery. Conclusion: The design addressed existing problems and is an optimisation of the case hospital’s pathway. The network of actors consists of the patient (1, radiologist (1, anaesthetist (1, nurse specialist (1, pharmacist (1, orthopaedic surgeon (1,4, physiotherapist (1,4, nurse (4, doctor (4 and patient applica- tion (1,4. The critical value exchanges include patient preparation (mental and practical, patient education, aligned care team, efficient sequence of value exchanges, early patient mobilisation, flexible availability of the physiotherapist, functional discharge criteria, joint decision making and availability of the care team.

  10. What is the potential for social networks and support to enhance future telehealth interventions for people with a diagnosis of schizophrenia: a critical interpretive synthesis.

    Science.gov (United States)

    Daker-White, Gavin; Rogers, Anne

    2013-11-01

    Digital technologies are increasingly directed at improved monitoring, management and treatment of mental health. However, their potential contribution to social networks and self-management support for people diagnosed with a serious mental illness has rarely been considered. This review and meta-synthesis aimed to examine the processes of engagement and perceived relevance and appropriateness of telehealth interventions for people with a diagnosis of schizophrenia. The review addresses three key questions. How is the use of digital communications technologies framed in the professional psychiatric literature? How might the recognised benefits of telehealth translate to people with a diagnosis of schizophrenia? What is the user perspective concerning Internet information and communication technologies? A critical interpretive synthesis (CIS) of published findings from quantitative and qualitative studies of telehealth interventions for people with a diagnosis of schizophrenia. Most studies were of an exploratory nature. The professional discourse about the use of different technologies was overlain by concerns with surveillance and control, focusing on the Internet as a potential site of risk and danger. The critical synthesis of findings showed that the key focus of the available studies was on the delivery of existing traditional approaches (e.g. improving medications adherence, provision of medical information about the condition, symptom monitoring and cognitive behavioural therapy). Even though it was clear that the Internet has considerable potential in terms of accessing and utilising lay support, the potential of communication technologies in mobilising of resources for personal self-management or peer support was a relatively absent or hidden a focus of the available studies. Based on an interpretive synthesis of available studies, people with a diagnosis of schizophrenia or psychosis use the Internet primarily for the purposes of disclosure and

  11. What is the potential for social networks and support to enhance future telehealth interventions for people with a diagnosis of schizophrenia: a critical interpretive synthesis

    Science.gov (United States)

    2013-01-01

    Background Digital technologies are increasingly directed at improved monitoring, management and treatment of mental health. However, their potential contribution to social networks and self-management support for people diagnosed with a serious mental illness has rarely been considered. This review and meta-synthesis aimed to examine the processes of engagement and perceived relevance and appropriateness of telehealth interventions for people with a diagnosis of schizophrenia. The review addresses three key questions. How is the use of digital communications technologies framed in the professional psychiatric literature? How might the recognised benefits of telehealth translate to people with a diagnosis of schizophrenia? What is the user perspective concerning Internet information and communication technologies? Methods A critical interpretive synthesis (CIS) of published findings from quantitative and qualitative studies of telehealth interventions for people with a diagnosis of schizophrenia. Results Most studies were of an exploratory nature. The professional discourse about the use of different technologies was overlain by concerns with surveillance and control, focusing on the Internet as a potential site of risk and danger. The critical synthesis of findings showed that the key focus of the available studies was on the delivery of existing traditional approaches (e.g. improving medications adherence, provision of medical information about the condition, symptom monitoring and cognitive behavioural therapy). Even though it was clear that the Internet has considerable potential in terms of accessing and utilising lay support, the potential of communication technologies in mobilising of resources for personal self-management or peer support was a relatively absent or hidden a focus of the available studies. Conclusions Based on an interpretive synthesis of available studies, people with a diagnosis of schizophrenia or psychosis use the Internet primarily for

  12. CriticalEd

    DEFF Research Database (Denmark)

    Kjellberg, Caspar Mølholt; Meredith, David

    2014-01-01

    The best text method is commonly applied among music scholars engaged in producing critical editions. In this method, a comment list is compiled, consisting of variant readings and editorial emendations. This list is maintained by inserting the comments into a document as the changes are made...... such as Sibelius or Finale. It was hypothesized that it would be possible to develop a Sibelius plug-in, written in Manuscript 6, that would improve the critical editing work flow, but it was found that the capabilities of this scripting language were insufficient. Instead, a 3-part system was designed and built...