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Sample records for approaches identify syk

  1. [Syk inhibitors].

    Science.gov (United States)

    Kimura, Yukihiro; Chihara, Kazuyasu; Takeuchi, Kenji; Sada, Kiyonao

    2013-07-01

    Non-receptor type of protein-tyrosine kinase Syk (spleen tyrosine kinase) was isolated in the University of Fukui in 1991. Syk is known to be essential for the various physiological functions, especially in hematopoietic lineage cells. Moreover, ectopic expression of Syk by epigenetic changes is reported to cause retinoblastoma. Recently, novel Syk inhibitors were developed and its usefulness has been evaluated in the treatment of allergic rhinitis, rheumatoid arthritis, and idiopathic thrombocytopenic purpura. In this review, we will summarize the history, structure, and function of Syk, and then describe the novel Syk inhibitors and their current status. Furthermore, we will introduce our findings of the adaptor protein 3BP2 (c-Abl SH3 domain-binding protein-2), as a novel target of Syk.

  2. Syk inhibitors.

    Science.gov (United States)

    Chihara, Kazuyasu; Kimura, Yukihiro; Honjo, Chisato; Takeuchi, Kenji; Sada, Kiyonao

    2013-01-01

    Non-receptor type of protein-tyrosine kinase Syk (spleen tyrosine kinase) was isolated in University of Fukui in 1991. Syk is most highly expressed by haemopoietic cells and known to play crucial roles in the signal transduction through various immunoreceptors of the adaptive immune response. However, recent reports demonstrate that Syk also mediates other biological functions, such as innate immune response, osteoclast maturation, platelet activation and cellular adhesion. Moreover, ectopic expression of Syk by epigenetic changes is reported to cause retinoblastoma. Because of its critical roles on the cellular functions, the development of Syk inhibitors for clinical use has been desired. Although many candidate compounds were produced, none of them had progressed to clinical trials. However, novel Syk inhibitors were finally developed and its usefulness has been evaluated in the treatment of allergic rhinitis, rheumatoid arthritis and idiopathic thrombocytopenic purpura. In this review, we will summarize the history, structure and function of Syk, and then the novel Syk inhibitors and their current status. In addition, we will introduce our research focused on the functions of Syk on Dectin-1-mediated mast cell activation.

  3. Molecular mechanism of the Syk activation switch.

    Science.gov (United States)

    Tsang, Emily; Giannetti, Anthony M; Shaw, David; Dinh, Marie; Tse, Joyce K Y; Gandhi, Shaan; Ho, Hoangdung; Wang, Sandra; Papp, Eva; Bradshaw, J Michael

    2008-11-21

    Many immune signaling pathways require activation of the Syk tyrosine kinase to link ligation of surface receptors to changes in gene expression. Despite the central role of Syk in these pathways, the Syk activation process remains poorly understood. In this work we quantitatively characterized the molecular mechanism of Syk activation in vitro using a real time fluorescence kinase assay, mutagenesis, and other biochemical techniques. We found that dephosphorylated full-length Syk demonstrates a low initial rate of substrate phosphorylation that increases during the kinase reaction due to autophosphorylation. The initial rate of Syk activity was strongly increased by either pre-autophosphorylation or binding of phosphorylated immune tyrosine activation motif peptides, and each of these factors independently fully activated Syk. Deletion mutagenesis was used to identify regions of Syk important for regulation, and residues 340-356 of the SH2 kinase linker region were identified to be important for suppression of activity before activation. Comparison of the activation processes of Syk and Zap-70 revealed that Syk is more readily activated by autophosphorylation than Zap-70, although both kinases are rapidly activated by Src family kinases. We also studied Syk activity in B cell lysates and found endogenous Syk is also activated by phosphorylation and immune tyrosine activation motif binding. Together these experiments show that Syk functions as an "OR-gate" type of molecular switch. This mechanism of switch-like activation helps explain how Syk is both rapidly activated after receptor binding but also sustains activity over time to facilitate longer term changes in gene expression.

  4. A Combined Experimental and Computational Study of Vam3, a Derivative of Resveratrol, and Syk Interaction

    Directory of Open Access Journals (Sweden)

    Ming Jiang

    2014-09-01

    Full Text Available Spleen tyrosine kinase (Syk plays an indispensable role through preliminary extracellular antigen-induced crosslinking of Fc receptor (FcR in the pathogenesis of autoimmune disorders, such as rheumatoid arthritis. In this study, we identify Vam3, a dimeric derivative of resveratrol isolated from grapes, as an ATP-competitive inhibitor of Syk with an IC50 of 62.95 nM in an in vitro kinase assay. Moreover, docking and molecular dynamics simulation approaches were performed to get more detailed information about the binding mode of Vam3 and Syk. The results show that 11b-OH on ring-C and 4b-OH on ring-D could form two hydrogen bonds with Glu449 and Phe382 of Syk, respectively. In addition, arene-cation interaction between ring-D of Vam3 and Lys402 of Syk was also observed. These results indicate that ring-C and D play an essential role in Vam3–Syk interaction. Our studies may be helpful in the structural optimization of Vam3, and also aid the design of novel Syk inhibitors in the future.

  5. Syk Tyrosine Kinase Acts as a Pancreatic Adenocarcinoma Tumor Suppressor by Regulating Cellular Growth and Invasion

    OpenAIRE

    Layton, Tracy; Stalens, Cristel; Gunderson, Felizza; Goodison, Steve; Silletti, Steve

    2009-01-01

    We have identified the nonreceptor tyrosine kinase syk as a marker of differentiation/tumor suppressor in pancreatic ductal adenocarcinoma (PDAC). Syk expression is lost in poorly differentiated PDAC cells in vitro and in situ, and stable reexpression of syk in endogenously syk-negative Panc1 (Panc1/syk) cells retarded their growth in vitro and in vivo and reduced anchorage-independent growth in vitro. Panc1/syk cells exhibited a more differentiated morphology and down-regulated cyclin D1, ak...

  6. Depletion of STAT5 blocks TEL–SYK-induced APMF-type leukemia with myelofibrosis and myelodysplasia in mice

    International Nuclear Information System (INIS)

    Sprissler, C; Belenki, D; Maurer, H; Aumann, K; Pfeifer, D; Klein, C; Müller, T A; Kissel, S; Hülsdünker, J; Alexandrovski, J; Brummer, T; Jumaa, H; Duyster, J; Dierks, C

    2014-01-01

    The spleen tyrosine kinase (SYK) was identified as an oncogenic driver in a broad spectrum of hematologic malignancies. The in vivo comparison of three SYK containing oncogenes, SYK wt , TEL–SYK and IL-2-inducible T-cell kinase (ITK)-SYK revealed a general myeloexpansion and the establishment of three different hematologic (pre)diseases. SYK wt enhanced the myeloid and T-cell compartment, without leukemia/lymphoma development. ITK–SYK caused lethal T-cell lymphomas and the cytoplasmic TEL–SYK fusion induced an acute panmyelosis with myelofibrosis-type acute myeloid leukemia (AML) with up to 50% immature megakaryoblasts infiltrating bone marrow, spleen and liver, additional MPN features (myelofibrosis and granulocyte expansion) and MDS stigmata with megakaryocytic and erythroid dysplasia. LKS cells were reduced and all subsets (LT/ST/MPP) showed reduced proliferation rates. SYK inhibitor treatment (R788) of diseased TEL–SYK mice reduced leukocytosis, spleen and liver infiltration, enhanced the hematocrit and prolonged survival time, but could not significantly reduce myelofibrosis. Stat5 was identified as a major downstream mediator of TEL–SYK in vitro as well as in vivo. Consequently, targeted deletion of Stat5 in vivo completely abrogated TEL–SYK-induced AML and myelofibrosis development, proving Stat5 as a major driver of SYK-induced transformation. Our experiments highlight the important role of SYK in AML and myelofibrosis and prove SYK and STAT5 inhibitors as potent treatment options for those diseases

  7. Quantum ergodicity in the SYK model

    Science.gov (United States)

    Altland, Alexander; Bagrets, Dmitry

    2018-05-01

    We present a replica path integral approach describing the quantum chaotic dynamics of the SYK model at large time scales. The theory leads to the identification of non-ergodic collective modes which relax and eventually give way to an ergodic long time regime (describable by random matrix theory). These modes, which play a role conceptually similar to the diffusion modes of dirty metals, carry quantum numbers which we identify as the generators of the Clifford algebra: each of the 2N different products that can be formed from N Majorana operators defines one effective mode. The competition between a decay rate quickly growing in the order of the product and a density of modes exponentially growing in the same parameter explains the characteristics of the system's approach to the ergodic long time regime. We probe this dynamics through various spectral correlation functions and obtain favorable agreement with existing numerical data.

  8. Chaos and random matrices in supersymmetric SYK

    Science.gov (United States)

    Hunter-Jones, Nicholas; Liu, Junyu

    2018-05-01

    We use random matrix theory to explore late-time chaos in supersymmetric quantum mechanical systems. Motivated by the recent study of supersymmetric SYK models and their random matrix classification, we consider the Wishart-Laguerre unitary ensemble and compute the spectral form factors and frame potentials to quantify chaos and randomness. Compared to the Gaussian ensembles, we observe the absence of a dip regime in the form factor and a slower approach to Haar-random dynamics. We find agreement between our random matrix analysis and predictions from the supersymmetric SYK model, and discuss the implications for supersymmetric chaotic systems.

  9. The Syk kinase SmTK4 of Schistosoma mansoni is involved in the regulation of spermatogenesis and oogenesis.

    Directory of Open Access Journals (Sweden)

    Svenja Beckmann

    2010-02-01

    Full Text Available The signal transduction protein SmTK4 from Schistosoma mansoni belongs to the family of Syk kinases. In vertebrates, Syk kinases are known to play specialized roles in signaling pathways in cells of the hematopoietic system. Although Syk kinases were identified in some invertebrates, their role in this group of animals has not yet been elucidated. Since SmTK4 is the first Syk kinase from a parasitic helminth, shown to be predominantly expressed in the testes and ovary of adult worms, we investigated its function. To unravel signaling cascades in which SmTK4 is involved, yeast two-/three-hybrid library screenings were performed with either the tandem SH2-domain, or with the linker region including the tyrosine kinase domain of SmTK4. Besides the Src kinase SmTK3 we identified a new Src kinase (SmTK6 acting upstream of SmTK4 and a MAPK-activating protein, as well as mapmodulin acting downstream. Their identities and colocalization studies pointed to a role of SmTK4 in a signaling cascade regulating the proliferation and/or differentiation of cells in the gonads of schistosomes. To confirm this decisive role we performed biochemical and molecular approaches to knock down SmTK4 combined with a novel protocol for confocal laser scanning microscopy for morphological analyses. Using the Syk kinase-specific inhibitor Piceatannol or by RNAi treatment of adult schistosomes in vitro, corresponding phenotypes were detected in the testes and ovary. In the Xenopus oocyte system it was finally confirmed that Piceatannol suppressed the activity of the catalytic kinase domain of SmTK4. Our findings demonstrate a pivotal role of SmTK4 in gametogenesis, a new function for Syk kinases in eukaryotes.

  10. Reconstruction and signal propagation analysis of the Syk signaling network in breast cancer cells.

    Directory of Open Access Journals (Sweden)

    Aurélien Naldi

    2017-03-01

    Full Text Available The ability to build in-depth cell signaling networks from vast experimental data is a key objective of computational biology. The spleen tyrosine kinase (Syk protein, a well-characterized key player in immune cell signaling, was surprisingly first shown by our group to exhibit an onco-suppressive function in mammary epithelial cells and corroborated by many other studies, but the molecular mechanisms of this function remain largely unsolved. Based on existing proteomic data, we report here the generation of an interaction-based network of signaling pathways controlled by Syk in breast cancer cells. Pathway enrichment of the Syk targets previously identified by quantitative phospho-proteomics indicated that Syk is engaged in cell adhesion, motility, growth and death. Using the components and interactions of these pathways, we bootstrapped the reconstruction of a comprehensive network covering Syk signaling in breast cancer cells. To generate in silico hypotheses on Syk signaling propagation, we developed a method allowing to rank paths between Syk and its targets. We first annotated the network according to experimental datasets. We then combined shortest path computation with random walk processes to estimate the importance of individual interactions and selected biologically relevant pathways in the network. Molecular and cell biology experiments allowed to distinguish candidate mechanisms that underlie the impact of Syk on the regulation of cortactin and ezrin, both involved in actin-mediated cell adhesion and motility. The Syk network was further completed with the results of our biological validation experiments. The resulting Syk signaling sub-networks can be explored via an online visualization platform.

  11. Differential Requirements for Src-Family Kinases in SYK or ZAP70-Mediated SLP-76 Phosphorylation in Lymphocytes

    Directory of Open Access Journals (Sweden)

    Frank Fasbender

    2017-07-01

    Full Text Available In a synthetic biology approach using Schneider (S2 cells, we show that SLP-76 is directly phosphorylated at tyrosines Y113 and Y128 by SYK in the presence of ITAM-containing adapters such as CD3ζ, DAP12, or FcεRγ. This phosphorylation was dependent on at least one functional ITAM and a functional SH2 domain within SYK. Inhibition of Src-kinases by inhibitors PP1 and PP2 did not reduce SLP-76 phosphorylation in S2 cells, suggesting an ITAM and SYK dependent, but Src-kinase independent signaling pathway. This direct ITAM/SYK/SLP-76 signaling pathway therefore differs from previously described ITAM signaling. However, the SYK-family kinase ZAP70 required the additional co-expression of the Src-family kinases Fyn or Lck to efficiently phosphorylate SLP-76 in S2 cells. This difference in Src-family kinase dependency of SYK versus ZAP70-mediated ITAM-based signaling was further demonstrated in human lymphocytes. ITAM signaling in ZAP70-expressing T cells was dependent on the activity of Src-family kinases. In contrast, Src-family kinases were partially dispensable for ITAM signaling in SYK-expressing B cells or in natural killer cells, which express SYK and ZAP70. This demonstrates that SYK can signal using a Src-kinase independent ITAM-based signaling pathway, which may be involved in calibrating the threshold for lymphocyte activation.

  12. Spleen tyrosine kinase (Syk), a novel target of curcumin, is required for B lymphoma growth.

    Science.gov (United States)

    Gururajan, Murali; Dasu, Trivikram; Shahidain, Seif; Jennings, C Darrell; Robertson, Darrell A; Rangnekar, Vivek M; Bondada, Subbarao

    2007-01-01

    Curcumin (diferuloylmethane), a component of dietary spice turmeric (Curcuma longa), has been shown in recent studies to have therapeutic potential in the treatment of cancer, diabetes, arthritis, and osteoporosis. We investigated the ability of curcumin to modulate the growth of B lymphomas. Curcumin inhibited the growth of both murine and human B lymphoma in vitro and murine B lymphoma in vivo. We also demonstrate that curcumin-mediated growth inhibition of B lymphoma is through inhibition of the survival kinase Akt and its key target Bad. However, in vitro kinase assays show that Akt is not a direct target of curcumin. We identified a novel target for curcumin in B lymphoma viz spleen tyrosine kinase (Syk). Syk is constitutively activated in primary tumors and B lymphoma cell lines and curcumin down-modulates Syk activity accompanied by down-regulation of Akt activation. Moreover, we show that overexpression of Akt, a target of Syk, or Bcl-x(L), a target of Akt can overcome curcumin-induced apoptosis of B lymphoma cells. These observations suggest a novel growth promoting role for Syk in lymphoma cells.

  13. Higher dimensional generalizations of the SYK model

    Energy Technology Data Exchange (ETDEWEB)

    Berkooz, Micha [Department of Particle Physics and Astrophysics, Weizmann Institute of Science,Rehovot 7610001 (Israel); Narayan, Prithvi [International Centre for Theoretical Sciences, Hesaraghatta,Bengaluru North, 560 089 (India); Rozali, Moshe [Department of Physics and Astronomy, University of British Columbia,Vancouver, BC V6T 1Z1 (Canada); Simón, Joan [School of Mathematics and Maxwell Institute for Mathematical Sciences, University of Edinburgh,King’s Buildings, Edinburgh EH9 3FD (United Kingdom)

    2017-01-31

    We discuss a 1+1 dimensional generalization of the Sachdev-Ye-Kitaev model. The model contains N Majorana fermions at each lattice site with a nearest-neighbour hopping term. The SYK random interaction is restricted to low momentum fermions of definite chirality within each lattice site. This gives rise to an ordinary 1+1 field theory above some energy scale and a low energy SYK-like behavior. We exhibit a class of low-pass filters which give rise to a rich variety of hyperscaling behaviour in the IR. We also discuss another set of generalizations which describes probing an SYK system with an external fermion, together with the new scaling behavior they exhibit in the IR.

  14. A supersymmetric SYK-like tensor model

    Energy Technology Data Exchange (ETDEWEB)

    Peng, Cheng; Spradlin, Marcus; Volovich, Anastasia [Department of Physics, Brown University,Providence, RI, 02912 (United States)

    2017-05-11

    We consider a supersymmetric SYK-like model without quenched disorder that is built by coupling two kinds of fermionic N=1 tensor-valued superfields, “quarks” and “mesons”. We prove that the model has a well-defined large-N limit in which the (s)quark 2-point functions are dominated by mesonic “melon” diagrams. We sum these diagrams to obtain the Schwinger-Dyson equations and show that in the IR, the solution agrees with that of the supersymmetric SYK model.

  15. Vector models and generalized SYK models

    Energy Technology Data Exchange (ETDEWEB)

    Peng, Cheng [Department of Physics, Brown University,Providence RI 02912 (United States)

    2017-05-23

    We consider the relation between SYK-like models and vector models by studying a toy model where a tensor field is coupled with a vector field. By integrating out the tensor field, the toy model reduces to the Gross-Neveu model in 1 dimension. On the other hand, a certain perturbation can be turned on and the toy model flows to an SYK-like model at low energy. A chaotic-nonchaotic phase transition occurs as the sign of the perturbation is altered. We further study similar models that possess chaos and enhanced reparameterization symmetries.

  16. A supersymmetric SYK-like tensor model

    International Nuclear Information System (INIS)

    Peng, Cheng; Spradlin, Marcus; Volovich, Anastasia

    2017-01-01

    We consider a supersymmetric SYK-like model without quenched disorder that is built by coupling two kinds of fermionic N=1 tensor-valued superfields, “quarks” and “mesons”. We prove that the model has a well-defined large-N limit in which the (s)quark 2-point functions are dominated by mesonic “melon” diagrams. We sum these diagrams to obtain the Schwinger-Dyson equations and show that in the IR, the solution agrees with that of the supersymmetric SYK model.

  17. Functional Roles of Syk in Macrophage-Mediated Inflammatory Responses

    Science.gov (United States)

    Yi, Young-Su; Son, Young-Jin; Ryou, Chongsuk; Sung, Gi-Ho; Kim, Jong-Hoon; Cho, Jae Youl

    2014-01-01

    Inflammation is a series of complex biological responses to protect the host from pathogen invasion. Chronic inflammation is considered a major cause of diseases, such as various types of inflammatory/autoimmune diseases and cancers. Spleen tyrosine kinase (Syk) was initially found to be highly expressed in hematopoietic cells and has been known to play crucial roles in adaptive immune responses. However, recent studies have reported that Syk is also involved in other biological functions, especially in innate immune responses. Although Syk has been extensively studied in adaptive immune responses, numerous studies have recently presented evidence that Syk has critical functions in macrophage-mediated inflammatory responses and is closely related to innate immune response. This review describes the characteristics of Syk-mediated signaling pathways, summarizes the recent findings supporting the crucial roles of Syk in macrophage-mediated inflammatory responses and diseases, and discusses Syk-targeted drug development for the therapy of inflammatory diseases. PMID:25045209

  18. Functional Roles of Syk in Macrophage-Mediated Inflammatory Responses

    Directory of Open Access Journals (Sweden)

    Young-Su Yi

    2014-01-01

    Full Text Available Inflammation is a series of complex biological responses to protect the host from pathogen invasion. Chronic inflammation is considered a major cause of diseases, such as various types of inflammatory/autoimmune diseases and cancers. Spleen tyrosine kinase (Syk was initially found to be highly expressed in hematopoietic cells and has been known to play crucial roles in adaptive immune responses. However, recent studies have reported that Syk is also involved in other biological functions, especially in innate immune responses. Although Syk has been extensively studied in adaptive immune responses, numerous studies have recently presented evidence that Syk has critical functions in macrophage-mediated inflammatory responses and is closely related to innate immune response. This review describes the characteristics of Syk-mediated signaling pathways, summarizes the recent findings supporting the crucial roles of Syk in macrophage-mediated inflammatory responses and diseases, and discusses Syk-targeted drug development for the therapy of inflammatory diseases.

  19. Regulation of Discrete Functional Responses by Syk and Src Family Tyrosine Kinases in Human Neutrophils

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    Thornin Ear

    2017-01-01

    Full Text Available Neutrophils play a critical role in innate immunity and also influence adaptive immune responses. This occurs in good part through their production of inflammatory and immunomodulatory cytokines, in conjunction with their prolonged survival at inflamed foci. While a picture of the signaling machinery underlying these neutrophil responses is now emerging, much remains to be uncovered. In this study, we report that neutrophils constitutively express various Src family isoforms (STKs, as well as Syk, and that inhibition of these protein tyrosine kinases selectively hinders inflammatory cytokine generation by acting posttranscriptionally. Accordingly, STK or Syk inhibition decreases the phosphorylation of signaling intermediates (e.g., eIF-4E, S6K, and MNK1 involved in translational control. By contrast, delayed apoptosis appears to be independent of either STKs or Syk. Our data therefore significantly extend our understanding of which neutrophil responses are governed by STKs and Syk and pinpoint some signaling intermediates that are likely involved. In view of the foremost role of neutrophils in several chronic inflammatory conditions, our findings identify potential molecular targets that could be exploited for future therapeutic intervention.

  20. Modification by covalent reaction or oxidation of cysteine residues in the tandem-SH2 domains of ZAP-70 and Syk can block phosphopeptide binding.

    Science.gov (United States)

    Visperas, Patrick R; Winger, Jonathan A; Horton, Timothy M; Shah, Neel H; Aum, Diane J; Tao, Alyssa; Barros, Tiago; Yan, Qingrong; Wilson, Christopher G; Arkin, Michelle R; Weiss, Arthur; Kuriyan, John

    2015-01-01

    Zeta-chain associated protein of 70 kDa (ZAP-70) and spleen tyrosine kinase (Syk) are non-receptor tyrosine kinases that are essential for T-cell and B-cell antigen receptor signalling respectively. They are recruited, via their tandem-SH2 (Src-homology domain 2) domains, to doubly phosphorylated immunoreceptor tyrosine-based activation motifs (ITAMs) on invariant chains of immune antigen receptors. Because of their critical roles in immune signalling, ZAP-70 and Syk are targets for the development of drugs for autoimmune diseases. We show that three thiol-reactive small molecules can prevent the tandem-SH2 domains of ZAP-70 and Syk from binding to phosphorylated ITAMs. We identify a specific cysteine residue in the phosphotyrosine-binding pocket of each protein (Cys39 in ZAP-70, Cys206 in Syk) that is necessary for inhibition by two of these compounds. We also find that ITAM binding to ZAP-70 and Syk is sensitive to the presence of H2O2 and these two cysteine residues are also necessary for inhibition by H2O2. Our findings suggest a mechanism by which the reactive oxygen species generated during responses to antigen could attenuate signalling through these kinases and may also inform the development of ZAP-70 and Syk inhibitors that bind covalently to their SH2 domains.

  1. DMPD: Complement-mediated phagocytosis--the role of Syk. [Dynamic Macrophage Pathway CSML Database

    Lifescience Database Archive (English)

    Full Text Available 16754322 Complement-mediated phagocytosis--the role of Syk. Tohyama Y, Yamamura H. ...IUBMB Life. 2006 May-Jun;58(5-6):304-8. (.png) (.svg) (.html) (.csml) Show Complement-mediated phagocytosis-...-the role of Syk. PubmedID 16754322 Title Complement-mediated phagocytosis--the role of Syk. Authors Tohyama

  2. Distributed design approach in persistent identifiers systems

    Science.gov (United States)

    Golodoniuc, Pavel; Car, Nicholas; Klump, Jens

    2017-04-01

    The need to identify both digital and physical objects is ubiquitous in our society. Past and present persistent identifier (PID) systems, of which there is a great variety in terms of technical and social implementations, have evolved with the advent of the Internet, which has allowed for globally unique and globally resolvable identifiers. PID systems have catered for identifier uniqueness, integrity, persistence, and trustworthiness, regardless of the identifier's application domain, the scope of which has expanded significantly in the past two decades. Since many PID systems have been largely conceived and developed by small communities, or even a single organisation, they have faced challenges in gaining widespread adoption and, most importantly, the ability to survive change of technology. This has left a legacy of identifiers that still exist and are being used but which have lost their resolution service. We believe that one of the causes of once successful PID systems fading is their reliance on a centralised technical infrastructure or a governing authority. Golodoniuc et al. (2016) proposed an approach to the development of PID systems that combines the use of (a) the Handle system, as a distributed system for the registration and first-degree resolution of persistent identifiers, and (b) the PID Service (Golodoniuc et al., 2015), to enable fine-grained resolution to different information object representations. The proposed approach solved the problem of guaranteed first-degree resolution of identifiers, but left fine-grained resolution and information delivery under the control of a single authoritative source, posing risk to the long-term availability of information resources. Herein, we develop these approaches further and explore the potential of large-scale decentralisation at all levels: (i) persistent identifiers and information resources registration; (ii) identifier resolution; and (iii) data delivery. To achieve large-scale decentralisation

  3. Diffusion in higher dimensional SYK model with complex fermions

    Science.gov (United States)

    Cai, Wenhe; Ge, Xian-Hui; Yang, Guo-Hong

    2018-01-01

    We construct a new higher dimensional SYK model with complex fermions on bipartite lattices. As an extension of the original zero-dimensional SYK model, we focus on the one-dimension case, and similar Hamiltonian can be obtained in higher dimensions. This model has a conserved U(1) fermion number Q and a conjugate chemical potential μ. We evaluate the thermal and charge diffusion constants via large q expansion at low temperature limit. The results show that the diffusivity depends on the ratio of free Majorana fermions to Majorana fermions with SYK interactions. The transport properties and the butterfly velocity are accordingly calculated at low temperature. The specific heat and the thermal conductivity are proportional to the temperature. The electrical resistivity also has a linear temperature dependence term.

  4. syk kinase activation by a src kinase-initiated activation loop phosphorylation chain reaction

    Science.gov (United States)

    El-Hillal, O.; Kurosaki, T.; Yamamura, H.; Kinet, J.-P.; Scharenberg, A. M.

    1997-01-01

    Activation of the syk tyrosine kinase occurs almost immediately following engagement of many types of antigen receptors, including Fc receptors, but the mechanism through which syk is activated is currently unclear. Here we demonstrate that Fc receptor-induced syk activation occurs as the result of phosphorylation of the syk activation loop by both src family kinases and other molecules of activated syk, suggesting that syk activation occurs as the result of a src kinase-initiated activation loop phosphorylation chain reaction. This type of activation mechanism predicts that syk activation would exhibit exponential kinetics, providing a potential explanation for its rapid and robust activation by even weak antigen receptor stimuli. We propose that a similar mechanism may be responsible for generating rapid activation of other cytoplasmic tyrosine kinases, such as those of the Bruton tyrosine kinase/tec family, as well. PMID:9050880

  5. Subthreshold Desensitization of Human Basophils Re-capitulates the Loss of syk and FcεRI expression Characterized by Other Methods of Desensitization

    Science.gov (United States)

    MacGlashan, Donald

    2012-01-01

    Background Clinical desensitization of patients to drugs involves progressive exposure to escalating doses of drug over a period of 24 hours. In prior studies, this method was recapitulated in vitro to also demonstrate loss of mast cell or basophil responsiveness. However, most signaling studies of human basophils have identified changes in signaling by using other methods of inducing cellular desensitization. Objective This study examined two well-described endpoints of basophil desensitization, loss of syk or FcεRI expression, under conditions of subthreshold desensitization. Methods The loss of FceRI and syk was examined in human basophils. Results It was shown that both loss of syk and FcεRI/IgE occurred during an escalating series of stimulation (anti-IgE Ab) and that expression loss occurred despite the presence of little histamine release. If basophils were first cultured for 3 days in 10 ng/ml IL-3, the concentration-dependence of histamine release shifted to 100 fold lower concentrations of stimulus. However, loss of syk did not show any change in its EC50 while loss of FcεRI also shifted 100 fold. From the perspective of early signal element activation, the marked shift in the EC50 for histamine release was not accompanied by similar shifts in the EC50s for several signaling elements. The EC50s for phospho-Src, phospho-SHIP1, phospho-Syk, or phospho-Cbl did not change while the EC50s for phospho-Erk and the cytosolic calcium response did shift 100 fold. Conclusions These studies show that under normal conditions, subthreshold desensitization leads to loss of two critical signaling molecules (FcεRI and syk) but under at least one condition, treatment with IL-3, it is possible to markedly blunt the loss of syk, but not FcεRI, while executing a proper subthreshold titration. These data also suggest that IL-3 modifies only the sensitivity of signaling elements that are downstream of syk activation. PMID:22702505

  6. Expression of Tyrosine Kinase Syk in Breast Cancer and Their Clinical Significance

    Institute of Scientific and Technical Information of China (English)

    DINGYong-bin; WUZheng-yan; WANGShui; FANPing; ZHAXiao-ming; ZHENGWei; LIUXiao-an

    2004-01-01

    To evaluate the effects of the Syk mRNA expression in human breast cancer on tummor growth and metastasis, and the correlalion of the Syk gene expression with ER, PR, 1)53, and HER2/neu. Methods: Using se~i-RT-PCR,specimens from 40 breast cancer palients( tumor 1issues,adjacent normal tissues),and 15 filmmdenoma were detected for the expression of the Syk gene and level of Syk mRNA. Meanwhile, Eli, PR, P53, llER2/neu were detected in 40 tumor tissues from breast cancer with immunohistoch~mical staining. Resu/ts:Expression of the Syk gene was detected in all normal breast 1issues. Unlike normal breast tissue, 31 out of 40 breast cancer tissues did not show any detectable Syk mRNA expression,and there were significant differences in two groups(P <0.05).The level of Syk mRNA in the primary breast cancer 1issues was significantly lower than that in the adjacent non-cancerous breast tissues and benign fibroadenonm breast tissues( P < 0.05). Furthermore, only two breast cancer tissues in 18 pa ",tights with lymph node metastasis had the Syk mRNA expression. The Syk mRNA expression was negatively correlated to lymph nodemetastasis,HER2/neuproteinexpression(P<0.05). Conc/us/on.. The expression of the Syk gene may play an important role in suppressing growth and metastasis of breast cancer.

  7. Identifying bully victims: definitional versus behavioral approaches.

    Science.gov (United States)

    Green, Jennifer Greif; Felix, Erika D; Sharkey, Jill D; Furlong, Michael J; Kras, Jennifer E

    2013-06-01

    Schools frequently assess bullying and the Olweus Bully/Victimization Questionnaire (BVQ; Olweus, 1996) is the most widely adopted tool for this purpose. The BVQ is a self-report survey that uses a definitional measurement method--describing "bullying" as involving repeated, intentional aggression in a relationship where there is an imbalance of power and then asking respondents to indicate how frequently they experienced this type of victimization. Few studies have examined BVQ validity and whether this definitional method truly identifies the repetition and power differential that distinguish bullying from other forms of peer victimization. This study examined the concurrent validity of the BVQ definitional question among 435 students reporting peer victimization. BVQ definitional responses were compared with responses to a behavioral measure that did not use the term "bullying" but, instead, included items that asked about its defining characteristics (repetition, intentionality, power imbalance). Concordance between the two approaches was moderate, with an area under the receiver operating curve of .72. BVQ responses were more strongly associated with students indicating repeated victimization and multiple forms of victimization, than with power imbalance in their relationship with the bully. Findings indicate that the BVQ is a valid measure of repeated victimization and a broad range of victimization experiences but may not detect the more subtle and complex power imbalances that distinguish bullying from other forms of peer victimization. PsycINFO Database Record (c) 2013 APA, all rights reserved.

  8. Nontranscriptional regulation of SYK by the coactivator OCA-B is required at multiple stages of B cell development.

    Science.gov (United States)

    Siegel, Rachael; Kim, Unkyu; Patke, Alina; Yu, Xin; Ren, Xiaodi; Tarakhovsky, Alexander; Roeder, Robert G

    2006-05-19

    OCA-B was originally identified as a nuclear transcriptional coactivator that is essential for antigen-driven immune responses. The later identification of a membrane bound, myristoylated form of OCA-B suggested additional, unique functions in B cell signaling pathways. This study has shown that OCA-B also functions in the pre-B1-to-pre-B2 cell transition and, most surprisingly, that it directly interacts with SYK, a tyrosine kinase critical for pre-BCR and BCR signaling. This unprecedented type of interaction-a transcriptional coactivator with a signaling kinase-occurs in the cytoplasm and directly regulates SYK stability. This study indicates that OCA-B is required for pre-BCR and BCR signaling at multiple stages of B cell development through its nontranscriptional regulation of SYK. Combined with the deregulation of OCA-B target genes, this may help explain the multitude of defects observed in B cell development and immune responses of Oca-b-/- mice.

  9. Syk and IRAK1 Contribute to Immunopharmacological Activities of Anthraquinone-2-carboxlic Acid

    Directory of Open Access Journals (Sweden)

    Jae Gwang Park

    2016-06-01

    Full Text Available Anthraquinone-2-carboxlic acid (9,10-dihydro-9,10-dioxo-2-anthracenecarboxylic acid, AQCA was identified as one of the major anthraquinones in Brazilian taheebo. Since there was no report explaining its immunopharmacological actions, in this study, we aimed to investigate the molecular mechanism of AQCA-mediated anti-inflammatory activity using reporter gene assays, kinase assays, immunoblot analyses, and overexpression strategies with lipopolysaccharide (LPS-treated macrophages. AQCA was found to suppress the release of nitric oxide (NO and prostaglandin (PG E2 from LPS-treated peritoneal macrophages without displaying any toxic side effects. Molecular analysis revealed that AQCA was able to inhibit the activation of the nuclear factor (NF-κB and activator protein (AP-1 pathways by direct suppression of upstream signaling enzymes including interleukin-1 receptor-associated kinase 1 (IRAK1 and spleen tyrosine kinase (Syk. Therefore, our data strongly suggest that AQCA-mediated suppression of inflammatory responses could be managed by a direct interference of signaling cascades including IRAK and Syk, linked to the activation of NF-κB and AP-1.

  10. Syk and IRAK1 Contribute to Immunopharmacological Activities of Anthraquinone-2-carboxlic Acid.

    Science.gov (United States)

    Park, Jae Gwang; Son, Young-Jin; Kim, Mi-Yeon; Cho, Jae Youl

    2016-06-22

    Anthraquinone-2-carboxlic acid (9,10-dihydro-9,10-dioxo-2-anthracenecarboxylic acid, AQCA) was identified as one of the major anthraquinones in Brazilian taheebo. Since there was no report explaining its immunopharmacological actions, in this study, we aimed to investigate the molecular mechanism of AQCA-mediated anti-inflammatory activity using reporter gene assays, kinase assays, immunoblot analyses, and overexpression strategies with lipopolysaccharide (LPS)-treated macrophages. AQCA was found to suppress the release of nitric oxide (NO) and prostaglandin (PG) E₂ from LPS-treated peritoneal macrophages without displaying any toxic side effects. Molecular analysis revealed that AQCA was able to inhibit the activation of the nuclear factor (NF)-κB and activator protein (AP)-1 pathways by direct suppression of upstream signaling enzymes including interleukin-1 receptor-associated kinase 1 (IRAK1) and spleen tyrosine kinase (Syk). Therefore, our data strongly suggest that AQCA-mediated suppression of inflammatory responses could be managed by a direct interference of signaling cascades including IRAK and Syk, linked to the activation of NF-κB and AP-1.

  11. Differential recognition of syk-binding sites by each of the two phosphotyrosine-binding pockets of the Vav SH2 domain.

    Science.gov (United States)

    Chen, Chih-Hong; Piraner, Dan; Gorenstein, Nina M; Geahlen, Robert L; Beth Post, Carol

    2013-11-01

    The association of spleen tyrosine kinase (Syk), a central tyrosine kinase in B cell signaling, with Vav SH2 domain is controlled by phosphorylation of two closely spaced tyrosines in Syk linker B: Y342 and Y346. Previous studies established both singly phosphorylated and doubly phosphorylated forms play a role in signaling. The structure of the doubly phosphorylated form identified a new recognition of phosphotyrosine whereby two phosphotyrosines bind simultaneously to the Vav SH2 domain, one in the canonical pTyr pocket and one in the specificity pocket on the opposite side of the central β-sheet. It is unknown if the specificity pocket can bind phosphotyrosine independent of phosphotyrosine binding the pTyr pocket. To address this gap in knowledge, we determined the structure of the complex between Vav1 SH2 and a peptide (SykLB-YpY) modeling the singly phosphorylated-Y346 form of Syk with unphosphorylated Y342. The nuclear magnetic resonance (NMR) data conclusively establish that recognition of phosphotyrosine is swapped between the two pockets; phosphorylated pY346 binds the specificity pocket of Vav1 SH2, and unphosphorylated Y342 occupies what is normally the pTyr binding pocket. Nearly identical changes in chemical shifts occurred upon binding all three forms of singly and doubly phosphorylated peptides; however, somewhat smaller shift perturbations for SykLB-YpY from residues in regions of high internal mobility suggest that internal motions are coupled to binding affinity. The differential recognition that includes this swapped binding of phosphotyrosine to the specificity pocket of Vav SH2 increases the repertoire of possible phosphotyrosine binding by SH2 domains in regulating protein-protein interactions in cellular signaling. Copyright © 2013 Wiley Periodicals, Inc.

  12. Identifying MMORPG Bots: A Traffic Analysis Approach

    Science.gov (United States)

    Chen, Kuan-Ta; Jiang, Jhih-Wei; Huang, Polly; Chu, Hao-Hua; Lei, Chin-Laung; Chen, Wen-Chin

    2008-12-01

    Massively multiplayer online role playing games (MMORPGs) have become extremely popular among network gamers. Despite their success, one of MMORPG's greatest challenges is the increasing use of game bots, that is, autoplaying game clients. The use of game bots is considered unsportsmanlike and is therefore forbidden. To keep games in order, game police, played by actual human players, often patrol game zones and question suspicious players. This practice, however, is labor-intensive and ineffective. To address this problem, we analyze the traffic generated by human players versus game bots and propose general solutions to identify game bots. Taking Ragnarok Online as our subject, we study the traffic generated by human players and game bots. We find that their traffic is distinguishable by 1) the regularity in the release time of client commands, 2) the trend and magnitude of traffic burstiness in multiple time scales, and 3) the sensitivity to different network conditions. Based on these findings, we propose four strategies and two ensemble schemes to identify bots. Finally, we discuss the robustness of the proposed methods against countermeasures of bot developers, and consider a number of possible ways to manage the increasingly serious bot problem.

  13. Identifying MMORPG Bots: A Traffic Analysis Approach

    Directory of Open Access Journals (Sweden)

    Wen-Chin Chen

    2008-11-01

    Full Text Available Massively multiplayer online role playing games (MMORPGs have become extremely popular among network gamers. Despite their success, one of MMORPG's greatest challenges is the increasing use of game bots, that is, autoplaying game clients. The use of game bots is considered unsportsmanlike and is therefore forbidden. To keep games in order, game police, played by actual human players, often patrol game zones and question suspicious players. This practice, however, is labor-intensive and ineffective. To address this problem, we analyze the traffic generated by human players versus game bots and propose general solutions to identify game bots. Taking Ragnarok Online as our subject, we study the traffic generated by human players and game bots. We find that their traffic is distinguishable by 1 the regularity in the release time of client commands, 2 the trend and magnitude of traffic burstiness in multiple time scales, and 3 the sensitivity to different network conditions. Based on these findings, we propose four strategies and two ensemble schemes to identify bots. Finally, we discuss the robustness of the proposed methods against countermeasures of bot developers, and consider a number of possible ways to manage the increasingly serious bot problem.

  14. Protein flexibility and ligand rigidity : a thermodynamic and kinetic study of ITAM-based ligand binding to Syk tandem SH2

    NARCIS (Netherlands)

    de Mol, Nico J; Catalina, M Isabel; Dekker, Frank J; Fischer, Marcel J E; Heck, Albert J R; Liskamp, Rob M J; Dekker, Frank

    2005-01-01

    The Syk tandem Src homology 2 domain (Syk tSH2) constitutes a flexible protein module involved in the regulation of Syk kinase activity. The Syk tSH2 domain is assumed to function by adapting the distance between its two SH2 domains upon bivalent binding to diphosphotyrosine ligands. A thermodynamic

  15. An approach to identify urban groundwater recharge

    Directory of Open Access Journals (Sweden)

    E. Vázquez-Suñé

    2010-10-01

    Full Text Available Evaluating the proportion in which waters from different origins are mixed in a given water sample is relevant for many hydrogeological problems, such as quantifying total recharge, assessing groundwater pollution risks, or managing water resources. Our work is motivated by urban hydrogeology, where waters with different chemical signature can be identified (losses from water supply and sewage networks, infiltration from surface runoff and other water bodies, lateral aquifers inflows, .... The relative contribution of different sources to total recharge can be quantified by means of solute mass balances, but application is hindered by the large number of potential origins. Hence, the need to incorporate data from a large number of conservative species, the uncertainty in sources concentrations and measurement errors. We present a methodology to compute mixing ratios and end-members composition, which consists of (i Identification of potential recharge sources, (ii Selection of tracers, (iii Characterization of the hydrochemical composition of potential recharge sources and mixed water samples, and (iv Computation of mixing ratios and reevaluation of end-members. The analysis performed in a data set from samples of the Barcelona city aquifers suggests that the main contributors to total recharge are the water supply network losses (22%, the sewage network losses (30%, rainfall, concentrated in the non-urbanized areas (17%, from runoff infiltration (20%, and the Besòs River (11%. Regarding species, halogens (chloride, fluoride and bromide, sulfate, total nitrogen, and stable isotopes (18O, 2H, and 34S behaved quite conservatively. Boron, residual alkalinity, EDTA and Zn did not. Yet, including these species in the computations did not affect significantly the proportion estimations.

  16. Involvement of Syk kinase in TNF-induced nitric oxide production by airway epithelial cells

    International Nuclear Information System (INIS)

    Ulanova, Marina; Marcet-Palacios, Marcelo; Munoz, Samira; Asfaha, Samuel; Kim, Moo-Kyung; Schreiber, Alan D.; Befus, A. Dean

    2006-01-01

    We have recently found that Syk is widely expressed in lung epithelial cells (EC) and participates in β1 integrin signaling. In this study, we assessed the role of Syk in regulation of NO production. Stimulation of human bronchial EC line HS-24 by TNF caused an increased expression of inducible nitric oxide synthase (iNOS). Inhibition of Syk using siRNA or piceatannol down-regulated the iNOS expression and reduced NO production. This effect occurred in EC simultaneously stimulated via β1 integrins, suggesting that TNF and β1 integrins provide co-stimulatory signals. Inhibition of Syk down-regulated TNF-induced p38 and p44/42 MAPK phosphorylation and nuclear translocation of p65 NF-κB. Thus, TNF-induced activation of pro-inflammatory signaling in EC leading to enhanced expression of iNOS and NO production was dependent on Syk. Syk-mediated signaling regulates NO production at least partly via activating the MAPK cascade. Understanding the role of Syk in airway EC may help in developing new therapeutic tools for inflammatory lung disorders

  17. Shiga Toxin Increases Formation of Clathrin-Coated Pits through Syk Kinase

    DEFF Research Database (Denmark)

    Utskarpen, Audrun; Massol, Ramiro; van Deurs, Bo

    2010-01-01

    Clathrin-dependent endocytosis is a main entry mechanism for the glycolipid-binding Shiga toxin (Stx), although clathrin-independent pathways are also involved. Binding of Stx to its receptor Gb3 not only is essential for Stx retrograde transport to the endoplasmic reticulum and toxicity but also...... activates signaling through the tyrosine kinase Syk. We previously described that Syk activity is important for Stx entry, but it remained unclear how this kinase modulates endocytosis of Stx. Here we characterized the effects of Stx and Syk on clathrin-coated pit formation. We found that acute treatment...

  18. Tumor suppressor function of Syk in human MCF10A in vitro and normal mouse mammary epithelium in vivo.

    Directory of Open Access Journals (Sweden)

    You Me Sung

    2009-10-01

    Full Text Available The normal function of Syk in epithelium of the developing or adult breast is not known, however, Syk suppresses tumor growth, invasion, and metastasis in breast cancer cells. Here, we demonstrate that in the mouse mammary gland, loss of one Syk allele profoundly increases proliferation and ductal branching and invasion of epithelial cells through the mammary fat pad during puberty. Mammary carcinomas develop by one year. Syk also suppresses proliferation and invasion in vitro. siRNA or shRNA knockdown of Syk in MCF10A breast epithelial cells dramatically increased proliferation, anchorage independent growth, cellular motility, and invasion, with formation of functional, extracellular matrix-degrading invadopodia. Morphological and gene microarray analysis following Syk knockdown revealed a loss of luminal and differentiated epithelial features with epithelial to mesenchymal transition and a gain in invadopodial cell surface markers CD44, CD49F, and MMP14. These results support the role of Syk in limiting proliferation and invasion of epithelial cells during normal morphogenesis, and emphasize the critical role of Syk as a tumor suppressor for breast cancer. The question of breast cancer risk following systemic anti-Syk therapy is raised since only partial loss of Syk was sufficient to induce mammary carcinomas.

  19. Aspirin Augments IgE-Mediated Histamine Release from Human Peripheral Basophils via Syk Kinase Activation

    Directory of Open Access Journals (Sweden)

    Hiroaki Matsuo

    2013-01-01

    Conclusions: Aspirin enhanced histamine release from basophils via increased Syk kinase activation, and that the augmentation of histamine release by NSAIDs or FAs may be one possible cause of worsening symptoms in patients with chronic urticaria and FDEIA.

  20. Complement receptor-3 negatively regulates the phagocytosis of degenerated myelin through tyrosine kinase Syk and cofilin

    Directory of Open Access Journals (Sweden)

    Hadas Smadar

    2012-07-01

    Full Text Available Abstract Background Intact myelin, which normally surrounds axons, breaks down in Wallerian degeneration following axonal injury and during neurodegenerative diseases such as multiple sclerosis. Clearance of degenerated myelin by phagocytosis is essential since myelin impedes repair and exacerbates damage. CR3 (complement receptor-3 is a principal phagocytic receptor in myelin phagocytosis. We studied how tyrosine kinase Syk (spleen tyrosine kinase and cofilin control phagocytosis of degenerated myelin by CR3 in microglia and macrophages. Syk is a non-receptor tyrosine kinase that CR3 recruits to convey cellular functions. Cofilin is an actin-depolymerizing protein that controls F-actin (filamentous actin remodeling (i.e., disassembly and reassembly by shifting between active unphosphorylated and inactive phosphorylated states. Results Syk was continuously activated during prolonged phagocytosis. Phagocytosis increased when Syk activity and expression were reduced, suggesting that normally Syk down regulates CR3-mediated myelin phagocytosis. Levels of inactive p-cofilin (phosphorylated cofilin decreased transiently during prolonged phagocytosis. In contrast, p-cofilin levels decreased continuously when Syk activity and expression were continuously reduced, suggesting that normally Syk advances the inactive state of cofilin. Observations also revealed inverse relationships between levels of phagocytosis and levels of inactive p-cofilin, suggesting that active unphosphorylated cofilin advances phagocytosis. Active cofilin could advance phagocytosis by promoting F-actin remodeling, which supports the production of membrane protrusions (e.g., filopodia, which, as we also revealed, are instrumental in myelin phagocytosis. Conclusions CR3 both activates and downregulates myelin phagocytosis at the same time. Activation was previously documented. We presently demonstrate that downregulation is mediated through Syk, which advances the inactive

  1. GCN5 regulates the activation of PI3K/Akt survival pathway in B cells exposed to oxidative stress via controlling gene expressions of Syk and Btk.

    Science.gov (United States)

    Kikuchi, Hidehiko; Kuribayashi, Futoshi; Takami, Yasunari; Imajoh-Ohmi, Shinobu; Nakayama, Tatsuo

    2011-02-25

    Histone acetyltransferase(s) (HATs) are involved in the acetylation of core histones, which is an important event for transcription regulation through alterations in the chromatin structure in eukaryotes. General control non-depressible 5 (GCN5) was first identified as a global coactivator and transcription-related HAT. Here we report that GCN5 regulates the activation of phosphatidylinositol 3-kinase (PI3K)/acutely transforming retrovirus AKT8 in rodent T cell lymphoma (Akt) survival pathway in B cells exposed to oxidative stress via controlling gene expressions of spleen tyrosine kinase (Syk) and Bruton's tyrosine kinase (Btk). The GCN5-deficiency remarkably caused apoptotic cell death by treatment with exogenous hydrogen peroxide (H(2)O(2)) in chicken DT40 cells. In GCN5-deficient DT40 cells, gene expressions of Syk and Btk, which are involved in activation of PI3K/Akt survival pathway in DT40 cells exposed to exogenous H(2)O(2), were remarkably decreased compared with those in wild type DT40 cells. In addition, phosphorylation of Akt in H(2)O(2)-treated GCN5-deficient cells was remarkably suppressed as compared to that of DT40. Chromatin immunoprecipitation assay revealed that GCN5 binds to proximal 5'-upstream regions of Syk and Btk genes in vivo. These results suggest that GCN5 takes part in transcriptional regulations of the Syk and Btk genes, and plays a key role in epigenetic regulation of PI3K/Akt survival pathway in B cells exposed to reactive oxygen species such as H(2)O(2). Copyright © 2011 Elsevier Inc. All rights reserved.

  2. Dectin-1-mediated signaling leads to characteristic gene expressions and cytokine secretion via spleen tyrosine kinase (Syk) in rat mast cells.

    Science.gov (United States)

    Kimura, Yukihiro; Chihara, Kazuyasu; Honjoh, Chisato; Takeuchi, Kenji; Yamauchi, Shota; Yoshiki, Hatsumi; Fujieda, Shigeharu; Sada, Kiyonao

    2014-11-07

    Dectin-1 recognizes β-glucan and plays important roles for the antifungal immunity through the activation of spleen tyrosine kinase (Syk) in dendritic cells or macrophages. Recently, expression of Dectin-1 was also identified in human and mouse mast cells, although its physiological roles were largely unknown. In this report, rat mast cell line RBL-2H3 was analyzed to investigate the molecular mechanism of Dectin-1-mediated activation and responses of mast cells. Treatment of cells with Dectin-1-specific agonist curdlan induced tyrosine phosphorylation of cellular proteins and the interaction of Dectin-1 with the Src homology 2 domain of Syk. These responses depended on tyrosine phosphorylation of the hemi-immunoreceptor tyrosine-based activation motif in the cytoplasmic tail of Dectin-1, whereas they were independent of the γ-subunit of high-affinity IgE receptor. DNA microarray and real-time PCR analyses showed that Dectin-1-mediated signaling stimulated gene expression of transcription factor Nfkbiz and inflammatory cytokines, such as monocyte chemoattractant protein-1, IL-3, IL-4, IL-13, and tumor necrosis factor (TNF)-α. The response was abrogated by pretreatment with Syk inhibitor R406. These results suggest that Syk is critical for Dectin-1-mediated activation of mast cells, although the signaling differs from that triggered by FcϵRI activation. In addition, these gene expressions induced by curdlan stimulation were specifically observed in mast cells, suggesting that Dectin-1-mediated signaling of mast cells offers new insight into the antifungal immunity. © 2014 by The American Society for Biochemistry and Molecular Biology, Inc.

  3. Modulation of BCR Signaling by the Induced Dimerization of Receptor-Associated SYK

    Directory of Open Access Journals (Sweden)

    Mark L. Westbroek

    2017-12-01

    Full Text Available Clustering of the B cell antigen receptor (BCR by polyvalent antigens is transmitted through the SYK tyrosine kinase to the activation of multiple intracellular pathways that determine the physiological consequences of receptor engagement. To explore factors that modulate the quantity and quality of signals sent by the crosslinked BCR, we developed a novel chemical mediator of dimerization to induce clustering of receptor-associated SYK. To accomplish this, we fused SYK with E. coli dihydrofolate reductase (eDHFR, which binds the small molecule trimethoprim (TMP with high affinity and selectivity and synthesized a dimer of TMP with a flexible linker. The TMP dimer is able to induce the aggregation of eDHFR-linked SYK in live cells. The induced dimerization of SYK bound to the BCR differentially regulates the activation of downstream transcription factors, promoting the activation of Nuclear Factor of Activated T cells (NFAT without affecting the activation of NFκB. The dimerization of SYK enhances the duration but not the amplitude of calcium mobilization by enhancing the extent and duration of its interaction with the crosslinked BCR at the plasma membrane.

  4. Sesquiterpene dimmer (DSF-27) inhibits the release of neuroinflammatory mediators from microglia by targeting spleen tyrosine kinase (Syk) and Janus kinase 2 (Jak2): Two major non-receptor tyrosine signaling proteins involved in inflammatory events

    Energy Technology Data Exchange (ETDEWEB)

    Zeng, Ke-Wu [State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University Health Science Center, Beijing 100191 (China); Wang, Shu [State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University Health Science Center, Beijing 100191 (China); Department of Medicinal Chemistry and Pharmaceutical Analysis, Logistics College of Chinese People' s Armed Police Forces, Tianjin 300162 (China); Dong, Xin; Jiang, Yong; Jin, Hong-Wei [State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University Health Science Center, Beijing 100191 (China); Tu, Peng-Fei, E-mail: pengfeitu@vip.163.com [State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University Health Science Center, Beijing 100191 (China)

    2014-03-15

    Non-receptor protein tyrosine kinases (NRPTKs)-dependent inflammatory signal transduction cascades play key roles in immunoregulation. However, drug intervention through NRPTKs-involved immunoregulation mechanism in microglia (the major immune cells of the central nervous system) has not been widely investigated. A main aim of the present study is to elucidate the contribution of two major NRPTKs (Syk and Jak2) in neuroinflammation suppression by a bioactive sesquiterpene dimmer (DSF-27). We found that LPS-stimulated BV-2 cells activated Syk and further initiated Akt/NF-κB inflammatory pathway. This Syk-dependent Akt/NF-κB inflammatory pathway can be effectively ameliorated by DSF-27. Moreover, Jak2 was activated by LPS, which was followed by transcriptional factor Stat3 activation. The Jak2/Stat3 signal was suppressed by DSF-27 through inhibition of Jak2 and Stat3 phosphorylation, promotion of Jak/Stat3 inhibitory factors PIAS3 expression, and down-regulation of ERK and p38 MAPK phosphorylation. Furthermore, DSF-27 protected cortical and mesencephalic dopaminergic neurons against neuroinflammatory injury. Taken together, our findings indicate NRPTK signaling pathways including Syk/NF-κB and Jak2/Stat3 cascades are potential anti-neuroinflammatory targets in microglia, and may also set the basis for the use of sesquiterpene dimmer as a therapeutic approach for neuroinflammation via interruption of these pathways. - Highlights: • Sesquiterpene dimmer DSF-27 inhibits inflammatory mediators' production in microglia. • Syk-dependent Akt/NF-κB pathway is important for DSF-27's anti-inflammation activity. • Jak2/Stat3 pathway is important for DSF-27's anti-inflammation activity. • Jak2/Stat3 signaling pathway is partly regulated by ERK and p38 MAPKs and PIAS3. • DSF-27 protects neurons against microglia-mediated neuroinflammatory injury.

  5. Hierarchy of protein tyrosine kinases in interleukin-2 (IL-2) signaling: activation of syk depends on Jak3; however, neither Syk nor Lck is required for IL-2-mediated STAT activation.

    Science.gov (United States)

    Zhou, Y J; Magnuson, K S; Cheng, T P; Gadina, M; Frucht, D M; Galon, J; Candotti, F; Geahlen, R L; Changelian, P S; O'Shea, J J

    2000-06-01

    Interleukin-2 (IL-2) activates several different families of tyrosine kinases, but precisely how these kinases interact is not completely understood. We therefore investigated the functional relationships among Jak3, Lck, and Syk in IL-2 signaling. We first observed that in the absence of Jak3, both Lck and Syk had the capacity to phosphorylate Stat3 and Stat5a. However, neither supported IL-2-induced STAT activation, nor did dominant negative alleles of these kinases inhibit. Moreover, pharmacological abrogation of Lck activity did not inhibit IL-2-mediated phosphorylation of Jak3 and Stat5a. Importantly, ligand-dependent Syk activation was dependent on the presence of catalytically active Jak3, whereas Lck activation was not. Interestingly, Syk functioned as a direct substrate of Jak1 but not Jak3. Additionally, Jak3 phosphorylated Jak1, whereas the reverse was not the case. Taken together, our data support a model in which Lck functions in parallel with Jak3, while Syk functions as a downstream element of Jaks in IL-2 signaling. Jak3 may regulate Syk catalytic activity indirectly via Jak1. However, IL-2-mediated Jak3/Stat activation is not dependent on Lck or Syk. While the essential roles of Jak1 and Jak3 in signaling by gammac-utilizing cytokines are clear, it will be important to dissect the exact contributions of Lck and Syk in mediating the effects of IL-2 and related cytokines.

  6. Phosphatidylinositol-3-kinase-dependent phosphorylation of SLP-76 by the lymphoma-associated ITK-SYK fusion-protein

    International Nuclear Information System (INIS)

    Hussain, Alamdar; Faryal, Rani; Nore, Beston F.; Mohamed, Abdalla J.; Smith, C.I. Edvard

    2009-01-01

    Recurrent chromosomal translocations have long been implicated in various types of lymphomas and other malignancies. Novel recurrent t(5;9)(q33;q22) has been recently discovered in un-specified peripheral T-cell lymphoma. To elucidate the role of this translocation, the corresponding fusion construct encoding the N-terminal portion of the ITK kinase and the C-terminal catalytic region of the SYK kinase was generated. We herein show that the ITK-SYK fusion-protein is constitutively active. Moreover, we demonstrate that ITK-SYK is phosphorylated on key tyrosine residues and is capable of potently phosphorylating the related adapter proteins BLNK and SLP-76. In transiently transfected cells, SYK was phosphorylated at Y352 but not detectably at the activation-loop tyrosines Y525/Y526. In contrast, ITK-SYK was phosphorylated both at Y212 and the activation-loop tyrosines Y385/Y386, corresponding to Y352 and Y525/Y526 in SYK, respectively. In resting primary lymphocytes, ITK-SYK predominantly localizes to the cell surface. In addition, we demonstrate that following stimulation, the ITK-SYK fusion-protein in cell lines translocates to the cell membrane and, moreover, that this phenomenon as well as SLP-76 phosphorylation are blocked upon phosphatidylinositol-3-kinase (PI3-kinase) inhibition.

  7. 'Omics' approaches in tomato aimed at identifying candidate genes ...

    African Journals Online (AJOL)

    adriana

    2013-12-04

    Dec 4, 2013 ... approaches could be combined in order to identify candidate genes for the genetic control of ascorbic ..... applied to other traits under the complex control of many ... Engineering increased vitamin C levels in ... Chem. Biol. 13:532–538. Giovannucci E, Rimm EB, Liu Y, Stampfer MJ, Willett WC (2002). A.

  8. A Computer Vision Approach to Identify Einstein Rings and Arcs

    Science.gov (United States)

    Lee, Chien-Hsiu

    2017-03-01

    Einstein rings are rare gems of strong lensing phenomena; the ring images can be used to probe the underlying lens gravitational potential at every position angles, tightly constraining the lens mass profile. In addition, the magnified images also enable us to probe high-z galaxies with enhanced resolution and signal-to-noise ratios. However, only a handful of Einstein rings have been reported, either from serendipitous discoveries or or visual inspections of hundred thousands of massive galaxies or galaxy clusters. In the era of large sky surveys, an automated approach to identify ring pattern in the big data to come is in high demand. Here, we present an Einstein ring recognition approach based on computer vision techniques. The workhorse is the circle Hough transform that recognise circular patterns or arcs in the images. We propose a two-tier approach by first pre-selecting massive galaxies associated with multiple blue objects as possible lens, than use Hough transform to identify circular pattern. As a proof-of-concept, we apply our approach to SDSS, with a high completeness, albeit with low purity. We also apply our approach to other lenses in DES, HSC-SSP, and UltraVISTA survey, illustrating the versatility of our approach.

  9. A statistical approach to identify candidate cues for nestmate recognition

    DEFF Research Database (Denmark)

    van Zweden, Jelle; Pontieri, Luigi; Pedersen, Jes Søe

    2014-01-01

    normalization, centroid,and distance calculation is most diagnostic to discriminate between NMR cues andother compounds. We find that using a “global centroid” instead of a “colony centroid”significantly improves the analysis. One reason may be that this new approach, unlikeprevious ones, provides...... than forF. exsecta, possibly due to less than ideal datasets. Nonetheless, some compound setsperformed better than others, showing that this approach can be used to identify candidatecompounds to be tested in bio-assays, and eventually crack the sophisticated code thatgoverns nestmate recognition....

  10. An Objective Approach to Identify Spectral Distinctiveness for Hearing Impairment

    Directory of Open Access Journals (Sweden)

    Yeou-Jiunn Chen

    2013-01-01

    Full Text Available To facilitate the process of developing speech perception, speech-language pathologists have to teach a subject with hearing loss the differences between two syllables by manually enhancing acoustic cues of speech. However, this process is time consuming and difficult. Thus, this study proposes an objective approach to automatically identify the regions of spectral distinctiveness between two syllables, which is used for speech-perception training. To accurately represent the characteristics of speech, mel-frequency cepstrum coefficients are selected as analytical parameters. The mismatch between two syllables in time domain is handled by dynamic time warping. Further, a filter bank is adopted to estimate the components in different frequency bands, which are also represented as mel-frequency cepstrum coefficients. The spectral distinctiveness in different frequency bands is then easily estimated by using Euclidean metrics. Finally, a morphological gradient operator is applied to automatically identify the regions of spectral distinctiveness. To evaluate the proposed approach, the identified regions are manipulated and then the manipulated syllables are measured by a close-set based speech-perception test. The experimental results demonstrated that the identified regions of spectral distinctiveness are very useful in speech perception, which indeed can help speech-language pathologists in speech-perception training.

  11. Distinctive functions of Syk N-terminal and C-terminal SH2 domains in the signaling cascade elicited by oxidative stress in B cells.

    Science.gov (United States)

    Ding, J; Takano, T; Hermann, P; Gao, S; Han, W; Noda, C; Yanagi, S; Yamamura, H

    2000-05-01

    Syk plays a crucial role in the transduction of oxidative stress signaling. In this paper, we investigated the roles of Src homology 2 (SH2) domains of Syk in oxidative stress signaling, using Syk-negative DT40 cells expressing the N- or C-terminal SH2 domain mutant [mSH2(N) or mSH2(C)] of Syk. Tyrosine phosphorylation of Syk in cells expressing mSH2(N) Syk after H(2)O(2) treatment was higher than that in cells expressing wild-type Syk or mSH2(C) Syk. The tyrosine phosphorylation of wild-type Syk and mSH2(C) Syk, but not that of mSH2(N), was sensitive to PP2, a specific inhibitor of Src-family protein-tyrosine kinase. In oxidative stress, the C-terminal SH2 domain of Syk was demonstrated to be required for induction of tyrosine phosphorylation of cellular proteins, phospholipase C (PLC)-gamma2 phosphorylation, inositol 1,4, 5-triphosphate (IP(3)) generation, Ca(2)(+) release from intracellular stores, and c-Jun N-terminal kinase activation. In contrast, in mSH2(N) Syk-expressing cells, tyrosine phosphorylation of intracellular proteins including PLC-gamma2 was markedly induced in oxidative stress. The enhanced phosphorylation of mSH2(N) Syk and PLC-gamma2, however, did not link to Ca(2)(+) mobilization from intracellular pools and IP(3) generation. Thus, the N- and C-terminal SH2 domains of Syk possess distinctive functions in oxidative stress signaling.

  12. A Sensitivity Analysis Approach to Identify Key Environmental Performance Factors

    Directory of Open Access Journals (Sweden)

    Xi Yu

    2014-01-01

    Full Text Available Life cycle assessment (LCA is widely used in design phase to reduce the product’s environmental impacts through the whole product life cycle (PLC during the last two decades. The traditional LCA is restricted to assessing the environmental impacts of a product and the results cannot reflect the effects of changes within the life cycle. In order to improve the quality of ecodesign, it is a growing need to develop an approach which can reflect the changes between the design parameters and product’s environmental impacts. A sensitivity analysis approach based on LCA and ecodesign is proposed in this paper. The key environmental performance factors which have significant influence on the products’ environmental impacts can be identified by analyzing the relationship between environmental impacts and the design parameters. Users without much environmental knowledge can use this approach to determine which design parameter should be first considered when (redesigning a product. A printed circuit board (PCB case study is conducted; eight design parameters are chosen to be analyzed by our approach. The result shows that the carbon dioxide emission during the PCB manufacture is highly sensitive to the area of PCB panel.

  13. Identifying technology innovations for marginalized smallholders-A conceptual approach.

    Science.gov (United States)

    Malek, Mohammad Abdul; Gatzweiler, Franz W; Von Braun, Joachim

    2017-05-01

    This paper adds a contribution in the existing literature in terms of theoretical and conceptual background for the identification of idle potentials of marginal rural areas and people by means of technological and institutional innovations. The approach follows ex-ante assessment for identifying suitable technology and institutional innovations for marginalized smallholders in marginal areas-divided into three main parts (mapping, surveying and evaluating) and several steps. Finally, it contributes to the inclusion of marginalized smallholders by an improved way of understanding the interactions between technology needs, farming systems, ecological resources and poverty characteristics in the different segments of the poor, and to link these insights with productivity enhancing technologies.

  14. An Efficient Approach for Identifying Stable Lobes with Discretization Method

    Directory of Open Access Journals (Sweden)

    Baohai Wu

    2013-01-01

    Full Text Available This paper presents a new approach for quick identification of chatter stability lobes with discretization method. Firstly, three different kinds of stability regions are defined: absolute stable region, valid region, and invalid region. Secondly, while identifying the chatter stability lobes, three different regions within the chatter stability lobes are identified with relatively large time intervals. Thirdly, stability boundary within the valid regions is finely calculated to get exact chatter stability lobes. The proposed method only needs to test a small portion of spindle speed and cutting depth set; about 89% computation time is savedcompared with full discretization method. It spends only about10 minutes to get exact chatter stability lobes. Since, based on discretization method, the proposed method can be used for different immersion cutting including low immersion cutting process, the proposed method can be directly implemented in the workshop to promote machining parameters selection efficiency.

  15. Peptidomimetic ligands for the tandem SH2 domain of Syk kinase

    NARCIS (Netherlands)

    Kuil, J.

    2009-01-01

    The Spleen tyrosine kinase (Syk) protein functions as a switch in a number of receptor signaling cascades. One of these cascades is the high affinity IgE receptor (Fc?RI) signaling pathway. Fc?RI consists of an ?-, ?- and two ?-chains. The ?- and ?-chains have intracellular an Immunoreceptor

  16. Novel approaches to identify protective malaria vaccine candidates

    Directory of Open Access Journals (Sweden)

    Wan Ni eChia

    2014-11-01

    Full Text Available Efforts to develop vaccines against malaria have been the focus of substantial research activities for decades. Several categories of candidate vaccines are currently being developed for protection against malaria, based on antigens corresponding to the pre-erythrocytic, blood-stage or sexual stages of the parasite. Long lasting sterile protection from Plasmodium falciparum sporozoite challenge has been observed in human following vaccination with whole parasite formulations, clearly demonstrating that a protective immune response targeting predominantly the pre-erythrocytic stages can develop against malaria. However, most of vaccine candidates currently being investigated, which are mostly subunits vaccines, have not been able to induce substantial (>50% protection thus far. This is due to the fact that the antigens responsible for protection against the different parasite stages are still yet to be known and relevant correlates of protection have remained elusive. For a vaccine to be developed in a timely manner, novel approaches are required. In this article, we review the novel approaches that have been developed to identify the antigens for the development of an effective malaria vaccine.

  17. Identifying biomarkers for asthma diagnosis using targeted metabolomics approaches.

    Science.gov (United States)

    Checkley, William; Deza, Maria P; Klawitter, Jost; Romero, Karina M; Klawitter, Jelena; Pollard, Suzanne L; Wise, Robert A; Christians, Uwe; Hansel, Nadia N

    2016-12-01

    The diagnosis of asthma in children is challenging and relies on a combination of clinical factors and biomarkers including methacholine challenge, lung function, bronchodilator responsiveness, and presence of airway inflammation. No single test is diagnostic. We sought to identify a pattern of inflammatory biomarkers that was unique to asthma using a targeted metabolomics approach combined with data science methods. We conducted a nested case-control study of 100 children living in a peri-urban community in Lima, Peru. We defined cases as children with current asthma, and controls as children with no prior history of asthma and normal lung function. We further categorized enrollment following a factorial design to enroll equal numbers of children as either overweight or not. We obtained a fasting venous blood sample to characterize a comprehensive panel of targeted markers using a metabolomics approach based on high performance liquid chromatography-mass spectrometry. A statistical comparison of targeted metabolites between children with asthma (n = 50) and healthy controls (n = 49) revealed distinct patterns in relative concentrations of several metabolites: children with asthma had approximately 40-50% lower relative concentrations of ascorbic acid, 2-isopropylmalic acid, shikimate-3-phosphate, and 6-phospho-d-gluconate when compared to children without asthma, and 70% lower relative concentrations of reduced glutathione (all p  13 077 normalized counts/second and betaine ≤ 16 47 121 normalized counts/second). By using a metabolomics approach applied to serum, we were able to discriminate between children with and without asthma by revealing different metabolic patterns. These results suggest that serum metabolomics may represent a diagnostic tool for asthma and may be helpful for distinguishing asthma phenotypes. Copyright © 2016 Elsevier Ltd. All rights reserved.

  18. A tripartite approach identifies the major sunflower seed albumins.

    Science.gov (United States)

    Jayasena, Achala S; Franke, Bastian; Rosengren, Johan; Mylne, Joshua S

    2016-03-01

    We have used a combination of genomic, transcriptomic, and proteomic approaches to identify the napin-type albumin genes in sunflower and define their contributions to the seed albumin pool. Seed protein content is determined by the expression of what are typically large gene families. A major class of seed storage proteins is the napin-type, water soluble albumins. In this work we provide a comprehensive analysis of the napin-type albumin content of the common sunflower (Helianthus annuus) by analyzing a draft genome, a transcriptome and performing a proteomic analysis of the seed albumin fraction. We show that although sunflower contains at least 26 genes for napin-type albumins, only 15 of these are present at the mRNA level. We found protein evidence for 11 of these but the albumin content of mature seeds is dominated by the encoded products of just three genes. So despite high genetic redundancy for albumins, only a small sub-set of this gene family contributes to total seed albumin content. The three genes identified as producing the majority of sunflower seed albumin are potential future candidates for manipulation through genetics and breeding.

  19. Integrative biology approach identifies cytokine targeting strategies for psoriasis.

    Science.gov (United States)

    Perera, Gayathri K; Ainali, Chrysanthi; Semenova, Ekaterina; Hundhausen, Christian; Barinaga, Guillermo; Kassen, Deepika; Williams, Andrew E; Mirza, Muddassar M; Balazs, Mercedesz; Wang, Xiaoting; Rodriguez, Robert Sanchez; Alendar, Andrej; Barker, Jonathan; Tsoka, Sophia; Ouyang, Wenjun; Nestle, Frank O

    2014-02-12

    Cytokines are critical checkpoints of inflammation. The treatment of human autoimmune disease has been revolutionized by targeting inflammatory cytokines as key drivers of disease pathogenesis. Despite this, there exist numerous pitfalls when translating preclinical data into the clinic. We developed an integrative biology approach combining human disease transcriptome data sets with clinically relevant in vivo models in an attempt to bridge this translational gap. We chose interleukin-22 (IL-22) as a model cytokine because of its potentially important proinflammatory role in epithelial tissues. Injection of IL-22 into normal human skin grafts produced marked inflammatory skin changes resembling human psoriasis. Injection of anti-IL-22 monoclonal antibody in a human xenotransplant model of psoriasis, developed specifically to test potential therapeutic candidates, efficiently blocked skin inflammation. Bioinformatic analysis integrating both the IL-22 and anti-IL-22 cytokine transcriptomes and mapping them onto a psoriasis disease gene coexpression network identified key cytokine-dependent hub genes. Using knockout mice and small-molecule blockade, we show that one of these hub genes, the so far unexplored serine/threonine kinase PIM1, is a critical checkpoint for human skin inflammation and potential future therapeutic target in psoriasis. Using in silico integration of human data sets and biological models, we were able to identify a new target in the treatment of psoriasis.

  20. Dual Role of the Tyrosine Kinase Syk in Regulation of Toll-Like Receptor Signaling in Plasmacytoid Dendritic Cells.

    Directory of Open Access Journals (Sweden)

    Besma Aouar

    Full Text Available Crosslinking of regulatory immunoreceptors (RR, such as BDCA-2 (CD303 or ILT7 (CD85g, of plasmacytoid dendritic cells (pDCs efficiently suppresses production of type-I interferon (IFN-α/β and other cytokines in response to Toll-like receptor (TLR 7/9 ligands. This cytokine-inhibitory pathway is mediated by spleen tyrosine kinase (Syk associated with the ITAM-containing adapter of RR. Here we demonstrate by pharmacological targeting of Syk that in addition to the negative regulation of TLR7/9 signaling via RR, Syk also positively regulates the TLR7/9 pathway in human pDCs. Novel highly specific Syk inhibitor AB8779 suppressed IFN-α, TNF-α and IL-6 production induced by TLR7/9 agonists in primary pDCs and in the pDC cell line GEN2.2. Triggering of TLR9 or RR signaling induced a differential kinetics of phosphorylation at Y352 and Y525/526 of Syk and a differential sensitivity to AB8779. Consistent with the different roles of Syk in TLR7/9 and RR signaling, a concentration of AB8779 insufficient to block TLR7/9 signaling still released the block of IFN-α production triggered via the RR pathway, including that induced by hepatitis B and C viruses. Thus, pharmacological targeting of Syk partially restored the main pDC function-IFN-α production. Opposing roles of Syk in TLR7/9 and RR pathways may regulate the innate immune response to weaken inflammation reaction.

  1. Identifying perinatal risk factors for infant maltreatment: an ecological approach

    Directory of Open Access Journals (Sweden)

    Hallisey Elaine J

    2006-12-01

    Full Text Available Abstract Background Child maltreatment and its consequences are a persistent problem throughout the world. Public health workers, human services officials, and others are interested in new and efficient ways to determine which geographic areas to target for intervention programs and resources. To improve assessment efforts, selected perinatal factors were examined, both individually and in various combinations, to determine if they are associated with increased risk of infant maltreatment. State of Georgia birth records and abuse and neglect data were analyzed using an area-based, ecological approach with the census tract as a surrogate for the community. Cartographic visualization suggested some correlation exists between risk factors and child maltreatment, so bivariate and multivariate regression were performed. The presence of spatial autocorrelation precluded the use of traditional ordinary least squares regression, therefore a spatial regression model coupled with maximum likelihood estimation was employed. Results Results indicate that all individual factors or their combinations are significantly associated with increased risk of infant maltreatment. The set of perinatal risk factors that best predicts infant maltreatment rates are: mother smoked during pregnancy, families with three or more siblings, maternal age less than 20 years, births to unmarried mothers, Medicaid beneficiaries, and inadequate prenatal care. Conclusion This model enables public health to take a proactive stance, to reasonably predict areas where poor outcomes are likely to occur, and to therefore more efficiently allocate resources. U.S. states that routinely collect the variables the National Center for Health Statistics (NCHS defines for birth certificates can easily identify areas that are at high risk for infant maltreatment. The authors recommend that agencies charged with reducing child maltreatment target communities that demonstrate the perinatal risks

  2. Developing an instrument to identify MBChB students' approaches ...

    African Journals Online (AJOL)

    The constructs of deep, surface and achieving approaches to learning are well defined in the literature and amply supported by research. Quality learning results from a deep approach to learning, and a deep-achieving approach to learning is regarded as the most adaptive approach institutionally. It is therefore felt that ...

  3. Reverse Vaccinology: An Approach for Identifying Leptospiral Vaccine Candidates

    Directory of Open Access Journals (Sweden)

    Odir A. Dellagostin

    2017-01-01

    Full Text Available Leptospirosis is a major public health problem with an incidence of over one million human cases each year. It is a globally distributed, zoonotic disease and is associated with significant economic losses in farm animals. Leptospirosis is caused by pathogenic Leptospira spp. that can infect a wide range of domestic and wild animals. Given the inability to control the cycle of transmission among animals and humans, there is an urgent demand for a new vaccine. Inactivated whole-cell vaccines (bacterins are routinely used in livestock and domestic animals, however, protection is serovar-restricted and short-term only. To overcome these limitations, efforts have focused on the development of recombinant vaccines, with partial success. Reverse vaccinology (RV has been successfully applied to many infectious diseases. A growing number of leptospiral genome sequences are now available in public databases, providing an opportunity to search for prospective vaccine antigens using RV. Several promising leptospiral antigens were identified using this approach, although only a few have been characterized and evaluated in animal models. In this review, we summarize the use of RV for leptospirosis and discuss the need for potential improvements for the successful development of a new vaccine towards reducing the burden of human and animal leptospirosis.

  4. CR3 and Dectin-1 Collaborate in Macrophage Cytokine Response through Association on Lipid Rafts and Activation of Syk-JNK-AP-1 Pathway.

    Directory of Open Access Journals (Sweden)

    Juin-Hua Huang

    2015-07-01

    Full Text Available Collaboration between heterogeneous pattern recognition receptors (PRRs leading to synergistic coordination of immune response is important for the host to fight against invading pathogens. Although complement receptor 3 (CR3 and Dectin-1 are major PRRs to detect fungi, crosstalk between these two receptors in antifungal immunity is largely undefined. Here we took advantage of Histoplasma capsulatum which is known to interact with both CR3 and Dectin-1 and specific particulate ligands to study the collaboration of CR3 and Dectin-1 in macrophage cytokine response. By employing Micro-Western Array (MWA, genetic approach, and pharmacological inhibitors, we demonstrated that CR3 and Dectin-1 act collaboratively to trigger macrophage TNF and IL-6 response through signaling integration at Syk kinase, allowing subsequent enhanced activation of Syk-JNK-AP-1 pathway. Upon engagement, CR3 and Dectin-1 colocalize and form clusters on lipid raft microdomains which serve as a platform facilitating their cooperation in signaling activation and cytokine production. Furthermore, in vivo studies showed that CR3 and Dectin-1 cooperatively participate in host defense against disseminated histoplasmosis and instruct adaptive immune response. Taken together, our findings define the mechanism of receptor crosstalk between CR3 and Dectin-1 and demonstrate the importance of their collaboration in host defense against fungal infection.

  5. Identifying predictors of physics item difficulty: A linear regression approach

    Science.gov (United States)

    Mesic, Vanes; Muratovic, Hasnija

    2011-06-01

    Large-scale assessments of student achievement in physics are often approached with an intention to discriminate students based on the attained level of their physics competencies. Therefore, for purposes of test design, it is important that items display an acceptable discriminatory behavior. To that end, it is recommended to avoid extraordinary difficult and very easy items. Knowing the factors that influence physics item difficulty makes it possible to model the item difficulty even before the first pilot study is conducted. Thus, by identifying predictors of physics item difficulty, we can improve the test-design process. Furthermore, we get additional qualitative feedback regarding the basic aspects of student cognitive achievement in physics that are directly responsible for the obtained, quantitative test results. In this study, we conducted a secondary analysis of data that came from two large-scale assessments of student physics achievement at the end of compulsory education in Bosnia and Herzegovina. Foremost, we explored the concept of “physics competence” and performed a content analysis of 123 physics items that were included within the above-mentioned assessments. Thereafter, an item database was created. Items were described by variables which reflect some basic cognitive aspects of physics competence. For each of the assessments, Rasch item difficulties were calculated in separate analyses. In order to make the item difficulties from different assessments comparable, a virtual test equating procedure had to be implemented. Finally, a regression model of physics item difficulty was created. It has been shown that 61.2% of item difficulty variance can be explained by factors which reflect the automaticity, complexity, and modality of the knowledge structure that is relevant for generating the most probable correct solution, as well as by the divergence of required thinking and interference effects between intuitive and formal physics knowledge

  6. Identifying predictors of physics item difficulty: A linear regression approach

    Directory of Open Access Journals (Sweden)

    Hasnija Muratovic

    2011-06-01

    Full Text Available Large-scale assessments of student achievement in physics are often approached with an intention to discriminate students based on the attained level of their physics competencies. Therefore, for purposes of test design, it is important that items display an acceptable discriminatory behavior. To that end, it is recommended to avoid extraordinary difficult and very easy items. Knowing the factors that influence physics item difficulty makes it possible to model the item difficulty even before the first pilot study is conducted. Thus, by identifying predictors of physics item difficulty, we can improve the test-design process. Furthermore, we get additional qualitative feedback regarding the basic aspects of student cognitive achievement in physics that are directly responsible for the obtained, quantitative test results. In this study, we conducted a secondary analysis of data that came from two large-scale assessments of student physics achievement at the end of compulsory education in Bosnia and Herzegovina. Foremost, we explored the concept of “physics competence” and performed a content analysis of 123 physics items that were included within the above-mentioned assessments. Thereafter, an item database was created. Items were described by variables which reflect some basic cognitive aspects of physics competence. For each of the assessments, Rasch item difficulties were calculated in separate analyses. In order to make the item difficulties from different assessments comparable, a virtual test equating procedure had to be implemented. Finally, a regression model of physics item difficulty was created. It has been shown that 61.2% of item difficulty variance can be explained by factors which reflect the automaticity, complexity, and modality of the knowledge structure that is relevant for generating the most probable correct solution, as well as by the divergence of required thinking and interference effects between intuitive and formal

  7. Carboxamide Spleen Tyrosine Kinase (Syk) Inhibitors: Leveraging Ground State Interactions To Accelerate Optimization

    Energy Technology Data Exchange (ETDEWEB)

    Ellis, J. Michael; Altman, Michael D.; Cash, Brandon; Haidle, Andrew M.; Kubiak, Rachel L.; Maddess, Matthew L.; Yan, Youwei; Northrup, Alan B. (Merck)

    2016-12-08

    Optimization of a series of highly potent and kinome selective carbon-linked carboxamide spleen tyrosine kinase (Syk) inhibitors with favorable drug-like properties is described. A pervasive Ames liability in an analogous nitrogen-linked carboxamide series was obviated by replacement with a carbon-linked moiety. Initial efforts lacked on-target potency, likely due to strain induced between the hinge binding amide and solvent front heterocycle. Consideration of ground state and bound state energetics allowed rapid realization of improved solvent front substituents affording subnanomolar Syk potency and high kinome selectivity. These molecules were also devoid of mutagenicity risk as assessed via the Ames test using the TA97a Salmonella strain.

  8. 2PI effective action for the SYK model and tensor field theories

    Science.gov (United States)

    Benedetti, Dario; Gurau, Razvan

    2018-05-01

    We discuss the two-particle irreducible (2PI) effective action for the SYK model and for tensor field theories. For the SYK model the 2PI effective action reproduces the bilocal reformulation of the model without using replicas. In general tensor field theories the 2PI formalism is the only way to obtain a bilocal reformulation of the theory, and as such is a precious instrument for the identification of soft modes and for possible holographic interpretations. We compute the 2PI action for several models, and push it up to fourth order in the 1 /N expansion for the model proposed by Witten in [1], uncovering a one-loop structure in terms of an auxiliary bilocal action.

  9. Identifying Similarities in Cognitive Subtest Functional Requirements: An Empirical Approach

    Science.gov (United States)

    Frisby, Craig L.; Parkin, Jason R.

    2007-01-01

    In the cognitive test interpretation literature, a Rational/Intuitive, Indirect Empirical, or Combined approach is typically used to construct conceptual taxonomies of the functional (behavioral) similarities between subtests. To address shortcomings of these approaches, the functional requirements for 49 subtests from six individually…

  10. DNA enrichment approaches to identify unauthorized genetically modified organisms (GMOs).

    Science.gov (United States)

    Arulandhu, Alfred J; van Dijk, Jeroen P; Dobnik, David; Holst-Jensen, Arne; Shi, Jianxin; Zel, Jana; Kok, Esther J

    2016-07-01

    With the increased global production of different genetically modified (GM) plant varieties, chances increase that unauthorized GM organisms (UGMOs) may enter the food chain. At the same time, the detection of UGMOs is a challenging task because of the limited sequence information that will generally be available. PCR-based methods are available to detect and quantify known UGMOs in specific cases. If this approach is not feasible, DNA enrichment of the unknown adjacent sequences of known GMO elements is one way to detect the presence of UGMOs in a food or feed product. These enrichment approaches are also known as chromosome walking or gene walking (GW). In recent years, enrichment approaches have been coupled with next generation sequencing (NGS) analysis and implemented in, amongst others, the medical and microbiological fields. The present review will provide an overview of these approaches and an evaluation of their applicability in the identification of UGMOs in complex food or feed samples.

  11. IDENTIFYING DEMENTIA IN ELDERLY POPULATION : A CAMP APPROACH

    OpenAIRE

    Anand P; Chaukimath; Srikanth; Koli

    2015-01-01

    BACKGROUND: Dementia is an emerging medico social problem affecting elderly, and poses a challenge to clinician and caregivers. It is usually identified in late stage where management becomes difficult. AIM: The aim of camp was to identify dementia in elderly population participating in screening camp. MATERIAL AND METHODS : The geriatric clinic and department of psychiatry jointly organised screening camp to detect dementia in elderly for five days in Sept...

  12. IDENTIFYING DEMENTIA IN ELDERLY POPULATION : A CAMP APPROACH

    Directory of Open Access Journals (Sweden)

    Anand P

    2015-06-01

    Full Text Available BACKGROUND: Dementia is an emerging medico social problem affecting elderly, and poses a challenge to clinician and caregivers. It is usually identified in late stage where management becomes difficult. AIM: The aim of camp was to identify dementia in elderly population participating in screening camp. MATERIAL AND METHODS : The geriatric clinic and department of psychiatry jointly organised screening camp to detect dementia in elderly for five days in September 2014 to commemorate world Alzheimer’s day. The invitation regarding camp was sent to all senio r citizen forums and also published in leading Kannada daily newspaper. Mini Mental Status Examination and Diagnostic and Statistical Manual of Mental Disorders, 4 th edition criteria (DSM IV was used to identify dementia. RESULTS: Elderly male participate d in camp in more number than females and dementia was identified in 36% elderly with education less than 9 th standard. Dementia was found in 18% in our study population. CONCLUSION: The camp help identify elderly suffering from dementia and also created a wareness about it. Hypertension and diabetes mellitus were common co morbidity in study population. Our study suggested organising screening camp will help identify elderly living with dementia.

  13. Identifying Meaningful Behaviors for Social Competence: A Contextual Approach.

    Science.gov (United States)

    Warnes, Emily D.; Sheridan, Susan M.; Geske, Jenenne; Warnes, William A.

    An exploratory study was conducted which assessed behaviors that characterize social competence in the 2nd and 5th grades. A contextual approach was used to gather information from 2nd and 5th grade children and their parents and teachers regarding the behaviors they perceived to be important for getting along well with peers. Data were gathered…

  14. Key role of integrin α(IIb)β (3) signaling to Syk kinase in tissue factor-induced thrombin generation.

    Science.gov (United States)

    van der Meijden, Paola E J; Feijge, Marion A H; Swieringa, Frauke; Gilio, Karen; Nergiz-Unal, Reyhan; Hamulyák, Karly; Heemskerk, Johan W M

    2012-10-01

    The fibrin(ogen) receptor, integrin α(IIb)β(3), has a well-established role in platelet spreading, aggregation and clot retraction. How α(IIb)β(3) contributes to platelet-dependent coagulation is less well resolved. Here, we demonstrate that the potent suppressing effect of clinically used α(IIb)β(3) blockers on tissue factor-induced thrombin generation is linked to diminished platelet Ca(2+) responses and phosphatidylserine (PS) exposure. The same blockers suppress these responses in platelets stimulated with collagen and thrombin receptor agonists, whereas added fibrinogen potentiates these responses. In platelets spreading on fibrinogen, outside-in α(IIb)β(3) signaling similarly enhances thrombin-induced Ca(2+) rises and PS exposure. These responses are reduced in α(IIb)β(3)-deficient platelets from patients with Glanzmann's thrombasthenia. Furthermore, the contribution of α(IIb)β(3) to tissue factor-induced platelet Ca(2+) rises, PS exposure and thrombin generation in plasma are fully dependent on Syk kinase activity. Tyrosine phosphorylation analysis confirms a key role of Syk activation, which is largely but not exclusively dependent on α(IIb)β(3) activation. It is concluded that the majority of tissue factor-induced procoagulant activity of platelets relies on Syk activation and ensuing Ca(2+) signal generation, and furthermore that a considerable part of Syk activation relies on α(IIb)β(3) signaling. These results hence point to a novel role of Syk in integrin-dependent thrombin generation.

  15. Tiered High-Throughput Screening Approach to Identify ...

    Science.gov (United States)

    High-throughput screening (HTS) for potential thyroid–disrupting chemicals requires a system of assays to capture multiple molecular-initiating events (MIEs) that converge on perturbed thyroid hormone (TH) homeostasis. Screening for MIEs specific to TH-disrupting pathways is limited in the US EPA ToxCast screening assay portfolio. To fill one critical screening gap, the Amplex UltraRed-thyroperoxidase (AUR-TPO) assay was developed to identify chemicals that inhibit TPO, as decreased TPO activity reduces TH synthesis. The ToxCast Phase I and II chemical libraries, comprised of 1,074 unique chemicals, were initially screened using a single, high concentration to identify potential TPO inhibitors. Chemicals positive in the single concentration screen were retested in concentration-response. Due to high false positive rates typically observed with loss-of-signal assays such as AUR-TPO, we also employed two additional assays in parallel to identify possible sources of nonspecific assay signal loss, enabling stratification of roughly 300 putative TPO inhibitors based upon selective AUR-TPO activity. A cell-free luciferase inhibition assay was used to identify nonspecific enzyme inhibition among the putative TPO inhibitors, and a cytotoxicity assay using a human cell line was used to estimate the cellular tolerance limit. Additionally, the TPO inhibition activities of 150 chemicals were compared between the AUR-TPO and an orthogonal peroxidase oxidation assay using

  16. A novel scientific approach in identifying talents among female ...

    African Journals Online (AJOL)

    This study determine the most significant physical fitness and anthro-energy intake components in identifying the talents among female adolescent field hockey players. 45 players from Terengganu sport academy were assessed in physical fitness and anthro-energy intake measurements. The first rotated PCAs presented 8 ...

  17. Identifying the "Truly Disadvantaged": A Comprehensive Biosocial Approach

    Science.gov (United States)

    Barnes, J. C.; Beaver, Kevin M.; Connolly, Eric J.; Schwartz, Joseph A.

    2016-01-01

    There has been significant interest in examining the developmental factors that predispose individuals to chronic criminal offending. This body of research has identified some social-environmental risk factors as potentially important. At the same time, the research producing these results has generally failed to employ genetically sensitive…

  18. Identifying the Determinants of Chronic Absenteeism: A Bioecological Systems Approach

    Science.gov (United States)

    Gottfried, Michael A.; Gee, Kevin A.

    2017-01-01

    Background/Context: Chronic school absenteeism is a pervasive problem across the US; in early education, it is most rampant in kindergarten and its consequences are particularly detrimental, often leading to poorer academic, behavioral and developmental outcomes later in life. Though prior empirical research has identified a broad range of…

  19. Antibody-mediated platelet phagocytosis by human macrophages is inhibited by siRNA specific for sequences in the SH2 tyrosine kinase, Syk.

    Science.gov (United States)

    Lu, Ying; Wang, Weiming; Mao, Huiming; Hu, Hai; Wu, Yanling; Chen, Bing-Guan; Liu, Zhongmin

    2011-01-01

    Immune thrombocytopenia depends upon Fc receptor-mediated phagocytosis that involves signaling through the SH2 tyrosine kinase, Syk. We designed small interfering (siRNA) sequences complementary to Syk coding regions to decrease the expression of Syk in the human macrophage cell line, THP-1. To evaluate the functional effect of siRNA on phagocytosis, we developed a new in vitro assay for antibody-mediated platelet ingestion by THP-1 cells. Incubation of THP-1 cells at 37°C with fluorescence-labeled platelets and anti-platelet antibody promoted ingestion of platelets that could be quantitated by flow cytometry. Transfection of THP-1 cells with Syk-specific siRNA resulted in a reduction in the amount of FcγRII-associated Syk protein. Coincident with decreased Syk expression, we observed inhibition of antibody-mediated platelet ingestion. These results confirm a key role for Syk in antibody-mediated phagocytosis and suggest Syk-specific siRNA as a possible therapeutic candidate for immune thrombocytopenia. Copyright © 2011 Elsevier Inc. All rights reserved.

  20. Photostimulated luminescence (PSL): A new approach to identifying irradiated foods

    International Nuclear Information System (INIS)

    Sanderson, D.C.W.

    1991-01-01

    PSL, and particularly Anti-Stokes luminescence is a highly specific indicator of energy storage in systems which have been exposed to ionising radiation. The preliminary work illustrated here demonstrates the radiation response of food analogues and the manner in which the phenomenon complements existing tests for irradiated herbs and spices. There appears to be considerable potential for further extension of this approach to a wider range of foods and food components. 5 figs

  1. A Lexical Approach to Identifying Dimensions of Organizational Culture

    Science.gov (United States)

    Chapman, Derek S.; Reeves, Paige; Chapin, Michelle

    2018-01-01

    A comprehensive measure of organizational culture was developed using a lexical approach, a method typically employed within the study of personality. 1761 adjectives were narrowed down and factor analyzed, which resulted in the identification of a nine factor solution to organizational culture, including the dimensions of: Innovative, Dominant, Pace, Friendly, Prestigious, Trendy, Corporate Social Responsibility, Traditional, and Diverse. Comprised of 135 adjectives most frequently used in describing organizational culture by current employees of several hundred organizations, the Lexical Organizational Culture Scale (LOCS) was found to predict employee commitment, job satisfaction, job search behaviors, and subjective fit better than earlier scales of organizational culture. PMID:29922200

  2. Multimodal approach to identifying malingered posttraumatic stress disorder: a review.

    Science.gov (United States)

    Ali, Shahid; Jabeen, Shagufta; Alam, Farzana

    2015-01-01

    The primary aim of this article is to aid clinicians in differentiating true posttraumatic stress disorder from malingered posttraumatic stress disorder. Posttraumatic stress disorder and malingering are defined, and prevalence rates are explored. Similarities and differences in diagnostic criteria between the fourth and fifth editions of the Diagnostic and Statistical Manual of Mental Disorders are described for posttraumatic stress disorder. Possible motivations for malingering posttraumatic stress disorder are discussed, and common characteristics of malingered posttraumatic stress disorder are described. A multimodal approach is described for evaluating posttraumatic stress disorder, including interview techniques, collection of collateral data, and psychometric and physiologic testing, that should allow clinicians to distinguish between those patients who are truly suffering from posttraumatic disorder and those who are malingering the illness.

  3. Identifying Pathogenicity Islands in Bacterial Pathogenomics Using Computational Approaches

    Directory of Open Access Journals (Sweden)

    Dongsheng Che

    2014-01-01

    Full Text Available High-throughput sequencing technologies have made it possible to study bacteria through analyzing their genome sequences. For instance, comparative genome sequence analyses can reveal the phenomenon such as gene loss, gene gain, or gene exchange in a genome. By analyzing pathogenic bacterial genomes, we can discover that pathogenic genomic regions in many pathogenic bacteria are horizontally transferred from other bacteria, and these regions are also known as pathogenicity islands (PAIs. PAIs have some detectable properties, such as having different genomic signatures than the rest of the host genomes, and containing mobility genes so that they can be integrated into the host genome. In this review, we will discuss various pathogenicity island-associated features and current computational approaches for the identification of PAIs. Existing pathogenicity island databases and related computational resources will also be discussed, so that researchers may find it to be useful for the studies of bacterial evolution and pathogenicity mechanisms.

  4. Omics Approach to Identify Factors Involved in Brassica Disease Resistance.

    Science.gov (United States)

    Francisco, Marta; Soengas, Pilar; Velasco, Pablo; Bhadauria, Vijai; Cartea, Maria E; Rodríguez, Victor M

    2016-01-01

    Understanding plant's defense mechanisms and their response to biotic stresses is of fundamental meaning for the development of resistant crop varieties and more productive agriculture. The Brassica genus involves a large variety of economically important species and cultivars used as vegetable source, oilseeds, forage and ornamental. Damage caused by pathogens attack affects negatively various aspects of plant growth, development, and crop productivity. Over the last few decades, advances in plant physiology, genetics, and molecular biology have greatly improved our understanding of plant responses to biotic stress conditions. In this regard, various 'omics' technologies enable qualitative and quantitative monitoring of the abundance of various biological molecules in a high-throughput manner, and thus allow determination of their variation between different biological states on a genomic scale. In this review, we have described advances in 'omic' tools (genomics, transcriptomics, proteomics and metabolomics) in the view of conventional and modern approaches being used to elucidate the molecular mechanisms that underlie Brassica disease resistance.

  5. Human Development in Romania: A Comparative Approach to Identifying Shortcomings

    Directory of Open Access Journals (Sweden)

    Robert STEFAN

    2017-12-01

    Full Text Available Following the research carried out by the economist Mahbub ul Haq, derived from the studies of Amartya Sen on human capabilities, in 1990, the United Nations Development Programme (UNDP published its first Human Development Report. It introduced the notion that development of a country is not merely equal to economic growth, but has the ultimate purpose of enriching human life by expanding people’s choices. Thus, Human Development seeks to reveal the fundamental role of human life: that of reaching its full potential. Even after 28 years since the fall of communism, the political environment in Romania continues to be unsopportive of proper development. This study seeks to identify the shortcomings of the primary dimensions of Human Development in Romania and hopefully make a firm and rhetorical call to action.

  6. Computational approaches to identify functional genetic variants in cancer genomes

    DEFF Research Database (Denmark)

    Gonzalez-Perez, Abel; Mustonen, Ville; Reva, Boris

    2013-01-01

    The International Cancer Genome Consortium (ICGC) aims to catalog genomic abnormalities in tumors from 50 different cancer types. Genome sequencing reveals hundreds to thousands of somatic mutations in each tumor but only a minority of these drive tumor progression. We present the result of discu......The International Cancer Genome Consortium (ICGC) aims to catalog genomic abnormalities in tumors from 50 different cancer types. Genome sequencing reveals hundreds to thousands of somatic mutations in each tumor but only a minority of these drive tumor progression. We present the result...... of discussions within the ICGC on how to address the challenge of identifying mutations that contribute to oncogenesis, tumor maintenance or response to therapy, and recommend computational techniques to annotate somatic variants and predict their impact on cancer phenotype....

  7. An Integrative data mining approach to identifying Adverse ...

    Science.gov (United States)

    The Adverse Outcome Pathway (AOP) framework is a tool for making biological connections and summarizing key information across different levels of biological organization to connect biological perturbations at the molecular level to adverse outcomes for an individual or population. Computational approaches to explore and determine these connections can accelerate the assembly of AOPs. By leveraging the wealth of publicly available data covering chemical effects on biological systems, computationally-predicted AOPs (cpAOPs) were assembled via data mining of high-throughput screening (HTS) in vitro data, in vivo data and other disease phenotype information. Frequent Itemset Mining (FIM) was used to find associations between the gene targets of ToxCast HTS assays and disease data from Comparative Toxicogenomics Database (CTD) by using the chemicals as the common aggregators between datasets. The method was also used to map gene expression data to disease data from CTD. A cpAOP network was defined by considering genes and diseases as nodes and FIM associations as edges. This network contained 18,283 gene to disease associations for the ToxCast data and 110,253 for CTD gene expression. Two case studies show the value of the cpAOP network by extracting subnetworks focused either on fatty liver disease or the Aryl Hydrocarbon Receptor (AHR). The subnetwork surrounding fatty liver disease included many genes known to play a role in this disease. When querying the cpAOP

  8. Newer Approaches to Identify Potential Untoward Effects in Functional Foods.

    Science.gov (United States)

    Marone, Palma Ann; Birkenbach, Victoria L; Hayes, A Wallace

    2016-01-01

    Globalization has greatly accelerated the numbers and variety of food and beverage products available worldwide. The exchange among greater numbers of countries, manufacturers, and products in the United States and worldwide has necessitated enhanced quality measures for nutritional products for larger populations increasingly reliant on functionality. These functional foods, those that provide benefit beyond basic nutrition, are increasingly being used for their potential to alleviate food insufficiency while enhancing quality and longevity of life. In the United States alone, a steady import increase of greater than 15% per year or 24 million shipments, over 70% products of which are food related, is regulated under the Food and Drug Administration (FDA). This unparalleled growth has resulted in the need for faster, cheaper, and better safety and efficacy screening methods in the form of harmonized guidelines and recommendations for product standardization. In an effort to meet this need, the in vitro toxicology testing market has similarly grown with an anticipatory 15% increase between 2010 and 2015 of US$1.3 to US$2.7 billion. Although traditionally occupying a small fraction of the market behind pharmaceuticals and cosmetic/household products, the scope of functional food testing, including additives/supplements, ingredients, residues, contact/processing, and contaminants, is potentially expansive. Similarly, as functional food testing has progressed, so has the need to identify potential adverse factors that threaten the safety and quality of these products. © The Author(s) 2015.

  9. A consequence index approach to identifying radiological sabotage targets

    International Nuclear Information System (INIS)

    Altman, W.D.; Hockert, J.W.

    1988-01-01

    One of the threats to concern to facilities using significant quantities of radioactive material is radiological sabotage. Both the Department of Energy (DOE) and the U.S. Nuclear Regulatory Commission have issued guidance to facilities for radiological sabotage protection. At those facilities where the inventories of radioactive materials change frequently, there is an operational need for a technically defensible method of determining whether or not the inventory of radioactive material at a given facility poses a potential radiological sabotage risk. In order to determine quickly whether a building is a potential radiological sabotage target, Lawrence Livermore National Loaboratory (LLNL) has developed a radiological sabotage consequence index that provides a conservative estimate of the maximum potential off-site consequences of a radiological sabotage attempt involving the facility. This radiological sabotage consequence index can be used by safeguards and security staff to rapidly determine whether a change in building operations poses a potential radiological sabotage risk. In those cases where such a potential risk is identified, a more detailed radiological sabotage vulnerability analysis can be performed

  10. Bioinformatics approaches for identifying new therapeutic bioactive peptides in food

    Directory of Open Access Journals (Sweden)

    Nora Khaldi

    2012-10-01

    Full Text Available ABSTRACT:The traditional methods for mining foods for bioactive peptides are tedious and long. Similar to the drug industry, the length of time to identify and deliver a commercial health ingredient that reduces disease symptoms can take anything between 5 to 10 years. Reducing this time and effort is crucial in order to create new commercially viable products with clear and important health benefits. In the past few years, bioinformatics, the science that brings together fast computational biology, and efficient genome mining, is appearing as the long awaited solution to this problem. By quickly mining food genomes for characteristics of certain food therapeutic ingredients, researchers can potentially find new ones in a matter of a few weeks. Yet, surprisingly, very little success has been achieved so far using bioinformatics in mining for food bioactives.The absence of food specific bioinformatic mining tools, the slow integration of both experimental mining and bioinformatics, and the important difference between different experimental platforms are some of the reasons for the slow progress of bioinformatics in the field of functional food and more specifically in bioactive peptide discovery.In this paper I discuss some methods that could be easily translated, using a rational peptide bioinformatics design, to food bioactive peptide mining. I highlight the need for an integrated food peptide database. I also discuss how to better integrate experimental work with bioinformatics in order to improve the mining of food for bioactive peptides, therefore achieving a higher success rates.

  11. Identifying problematic concepts in SNOMED CT using a lexical approach.

    Science.gov (United States)

    Agrawal, Ankur; Perl, Yehoshua; Elhanan, Gai

    2013-01-01

    SNOMED CT (SCT) has been endorsed as a premier clinical terminology by many organizations with a perceived use within electronic health records and clinical information systems. However, there are indications that, at the moment, SCT is not optimally structured for its intended use by healthcare practitioners. A study is conducted to investigate the extent of inconsistencies among the concepts in SCT. A group auditing technique to improve the quality of SCT is introduced that can help identify problematic concepts with a high probability. Positional similarity sets are defined, which are groups of concepts that are lexically similar and the position of the differing word in the fully specified name of the concepts of a set that correspond to each other. A manual auditing of a sample of such sets found 38% of the sets exhibiting one or more inconsistent concepts. Group auditing techniques such as this can thus be very helpful to assure the quality of SCT, which will help expedite its adoption as a reference terminology for clinical purposes.

  12. A landscape ecology approach identifies important drivers of urban biodiversity.

    Science.gov (United States)

    Turrini, Tabea; Knop, Eva

    2015-04-01

    Cities are growing rapidly worldwide, yet a mechanistic understanding of the impact of urbanization on biodiversity is lacking. We assessed the impact of urbanization on arthropod diversity (species richness and evenness) and abundance in a study of six cities and nearby intensively managed agricultural areas. Within the urban ecosystem, we disentangled the relative importance of two key landscape factors affecting biodiversity, namely the amount of vegetated area and patch isolation. To do so, we a priori selected sites that independently varied in the amount of vegetated area in the surrounding landscape at the 500-m scale and patch isolation at the 100-m scale, and we hold local patch characteristics constant. As indicator groups, we used bugs, beetles, leafhoppers, and spiders. Compared to intensively managed agricultural ecosystems, urban ecosystems supported a higher abundance of most indicator groups, a higher number of bug species, and a lower evenness of bug and beetle species. Within cities, a high amount of vegetated area increased species richness and abundance of most arthropod groups, whereas evenness showed no clear pattern. Patch isolation played only a limited role in urban ecosystems, which contrasts findings from agro-ecological studies. Our results show that urban areas can harbor a similar arthropod diversity and abundance compared to intensively managed agricultural ecosystems. Further, negative consequences of urbanization on arthropod diversity can be mitigated by providing sufficient vegetated space in the urban area, while patch connectivity is less important in an urban context. This highlights the need for applying a landscape ecological approach to understand the mechanisms shaping urban biodiversity and underlines the potential of appropriate urban planning for mitigating biodiversity loss. © 2015 John Wiley & Sons Ltd.

  13. Syk/Src Pathway-Targeted Inhibition of Skin Inflammatory Responses by Carnosic Acid

    Directory of Open Access Journals (Sweden)

    Jueun Oh

    2012-01-01

    Full Text Available Carnosic acid (CA is a diterpene compound exhibiting antioxidative, anticancer, anti-angiogenic, anti-inflammatory, anti-metabolic disorder, and hepatoprotective and neuroprotective activities. In this study, the effect of CA on various skin inflammatory responses and its inhibitory mechanism were examined. CA strongly suppressed the production of IL-6, IL-8, and MCP-1 from keratinocyte HaCaT cells stimulated with sodium lauryl sulfate (SLS and retinoic acid (RA. In addition, CA blocked the release of nitric oxide (NO, tumor necrosis factor (TNF-α, and prostaglandin E2 (PGE2 from RAW264.7 cells activated by the toll-like receptor (TLR-2 ligands, Gram-positive bacterium-derived peptidoglycan (PGN and pam3CSK, and the TLR4 ligand, Gram-negative bacterium-derived lipopolysaccharide (LPS. CA arrested the growth of dermatitis-inducing Gram-positive and Gram-negative microorganisms such Propionibacterium acnes, Pseudomonas aeruginosa, and Staphylococcus aureus. CA also blocked the nuclear translocation of nuclear factor (NF-κB and its upstream signaling including Syk/Src, phosphoinositide 3-kinase (PI3K, Akt, inhibitor of κBα (IκBα kinase (IKK, and IκBα for NF-κB activation. Kinase assays revealed that Syk could be direct enzymatic target of CA in its anti-inflammatory action. Therefore, our data strongly suggest the potential of CA as an anti-inflammatory drug against skin inflammatory responses with Src/NF-κB inhibitory properties.

  14. Band 3 Erythrocyte Membrane Protein Acts as Redox Stress Sensor Leading to Its Phosphorylation by p72 Syk

    Directory of Open Access Journals (Sweden)

    Antonella Pantaleo

    2016-01-01

    Full Text Available In erythrocytes, the regulation of the redox sensitive Tyr phosphorylation of band 3 and its functions are still partially defined. A role of band 3 oxidation in regulating its own phosphorylation has been previously suggested. The current study provides evidences to support this hypothesis: (i in intact erythrocytes, at 2 mM concentration of GSH, band 3 oxidation, and phosphorylation, Syk translocation to the membrane and Syk phosphorylation responded to the same micromolar concentrations of oxidants showing identical temporal variations; (ii the Cys residues located in the band 3 cytoplasmic domain are 20-fold more reactive than GSH; (iii disulfide linked band 3 cytoplasmic domain docks Syk kinase; (iv protein Tyr phosphatases are poorly inhibited at oxidant concentrations leading to massive band 3 oxidation and phosphorylation. We also observed that hemichromes binding to band 3 determined its irreversible oxidation and phosphorylation, progressive hemolysis, and serine hyperphosphorylation of different cytoskeleton proteins. Syk inhibitor suppressed the phosphorylation of band 3 also preventing serine phosphorylation changes and hemolysis. Our data suggest that band 3 acts as redox sensor regulating its own phosphorylation and that hemichromes leading to the protracted phosphorylation of band 3 may trigger a cascade of events finally leading to hemolysis.

  15. Nonredundant roles of Src-family kinases and Syk in the initiation of B-cell antigen receptor signaling

    Czech Academy of Sciences Publication Activity Database

    Štěpánek, Ondřej; Dráber, Peter; Drobek, Aleš; Hořejší, Václav; Brdička, Tomáš

    2013-01-01

    Roč. 190, č. 4 (2013), s. 1807-1818 ISSN 0022-1767 R&D Projects: GA ČR(CZ) GBP302/12/G101; GA ČR GAP302/12/1712 Institutional support: RVO:68378050 Keywords : BCR signaling * Src family kinases * Syk Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 5.362, year: 2013

  16. Phosphorylation of the Grb2- and phosphatidylinositol 3-kinase p85-binding p36/38 by Syk in Lck-negative T cells.

    Science.gov (United States)

    von Willebrand, M; Williams, S; Tailor, P; Mustelin, T

    1998-06-01

    Activation of the mitogen-activated protein kinase (MAPK) pathway by the T-cell antigen receptor (TCR) in T cells involves a positive role for phosphatidylinositol 3-kinase (PI3K) activity. We recently reported that over-expression of the Syk protein tyrosine kinase in the Lck-negative JCaM1 cells enabled the TCR to induce a normal activation of the Erk2 MAPK and enhanced transcription of a reporter gene driven by the nuclear factor of activated T cells and AP-1. Because this system allows us to analyse the targets for Syk in receptor-mediated signalling, we examined the role of PI3K in signalling events between the TCR-regulated Syk and the downstream activation of Erk2. We report that inhibition of PI3K by wortmannin or an inhibitory p85 construct, p85deltaiSH2, reduced the TCR-induced Syk-dependent activation of Erk2, as well as the appearance of phospho-Erk and phospho-Mek. At the same time, expression of Syk resulted in the activation-dependent phosphorylation of three proteins that bound to the src homology 2 (SH2) domains of PI3K p85. The strongest of these bands had an apparent molecular mass of 36-38 kDa on SDS gels, and it was quantitatively removed from the lysates by adsorption to a fusion protein containing the SH2 domain of Grb2. The appearance of this band was Syk dependent, and it was seen only upon triggering of the TCR complex. Thus, p36/38 was phosphorylated by Syk or a Syk-regulated kinase, and this protein may provide a link to the recruitment and activation of PI3K, as well as to the Ras-MAPK pathway, in TCR-triggered T cells.

  17. ZAP-70 and p72syk are signaling response elements through MHC class II molecules

    DEFF Research Database (Denmark)

    Kanner, S B; Grosmaire, L S; Blake, J

    1995-01-01

    Ligation of major histocompatibility complex (MHC) class II antigens expressed on antigen-activated human CD4+ T-lymphocytes induces early signal transduction events including the activation of tyrosine kinases, the tyrosine phosphorylation of phospholipase-C gamma 1 and the mobilization...... of intracellular calcium. Similar responses have been observed in B-cells following stimulation of MHC class II molecules, including the increased production of intracellular cAMP. In this report, we demonstrate that the ZAP-70 tyrosine kinase is a responsive signaling element following cross-linking of HLA...... by herbimycin A. MHC class II ligation on B-lymphocytes resulted in cell death, which was both qualitatively distinct from Fas-induced apoptosis and partially protected by herbimycin A pretreatment. Thus, ligation of MHC class II molecules expressed on human lymphocytes stimulates the ZAP-70/p72syk family...

  18. In Vivo RNA Interference Screening Identifies a Leukemia-Specific Dependence on Integrin Beta 3 Signaling

    Science.gov (United States)

    Miller, Peter G.; Al-Shahrour, Fatima; Hartwell, Kimberly A.; Chu, Lisa P.; Järås, Marcus; Puram, Rishi V.; Puissant, Alexandre; Callahan, Kevin P.; Ashton, John; McConkey, Marie E.; Poveromo, Luke P.; Cowley, Glenn S.; Kharas, Michael G.; Labelle, Myriam; Shterental, Sebastian; Fujisaki, Joji; Silberstein, Lev; Alexe, Gabriela; Al-Hajj, Muhammad A.; Shelton, Christopher A.; Armstrong, Scott A.; Root, David E.; Scadden, David T.; Hynes, Richard O.; Mukherjee, Siddhartha; Stegmaier, Kimberly; Jordan, Craig T.; Ebert, Benjamin L.

    2013-01-01

    SUMMARY We used an in vivo short hairpin RNA (shRNA) screening approach to identify genes that are essential for MLL-AF9 acute myeloid leukemia (AML). We found that Integrin Beta 3 (Itgb3) is essential for murine leukemia cells in vivo, and for human leukemia cells in xenotransplantation studies. In leukemia cells, Itgb3 knockdown impaired homing, downregulated LSC transcriptional programs, and induced differentiation via the intracellular kinase, Syk. In contrast, loss of Itgb3 in normal HSPCs did not affect engraftment, reconstitution, or differentiation. Finally, we confirmed that Itgb3 is dispensable for normal hematopoiesis and required for leukemogenesis using an Itgb3 knockout mouse model. Our results establish the significance of the Itgb3 signaling pathway as a potential therapeutic target in AML. PMID:23770013

  19. Identifying inhibitory compounds in lignocellulosic biomass hydrolysates using an exometabolomics approach

    NARCIS (Netherlands)

    Zha, Y.; Westerhuis, J.A.; Muilwijk, B.; Overkamp, K.M.; Nijmeijer, B.M.; Coulier, L.; Smilde, A.K.; Punt, P.J.

    2014-01-01

    Background: Inhibitors are formed that reduce the fermentation performance of fermenting yeast during the pretreatment process of lignocellulosic biomass. An exometabolomics approach was applied to systematically identify inhibitors in lignocellulosic biomass hydrolysates.Results: We studied the

  20. Identifying inhibitory compounds in lignocellulosic biomass hydrolysates using an exometabolomics approach

    NARCIS (Netherlands)

    Zha, Y.; Westerhuis, J.A.; Muilwijk, B.; Overkamp, K.M.; Nijmeijer, B.M.; Coulier, L.; Smilde, A.K.; Punt, P.J.

    2014-01-01

    BACKGROUND: Inhibitors are formed that reduce the fermentation performance of fermenting yeast during the pretreatment process of lignocellulosic biomass. An exometabolomics approach was applied to systematically identify inhibitors in lignocellulosic biomass hydrolysates. RESULTS: We studied the

  1. Gene-based Association Approach Identify Genes Across Stress Traits in Fruit Flies

    DEFF Research Database (Denmark)

    Rohde, Palle Duun; Edwards, Stefan McKinnon; Sarup, Pernille Merete

    Identification of genes explaining variation in quantitative traits or genetic risk factors of human diseases requires both good phenotypic- and genotypic data, but also efficient statistical methods. Genome-wide association studies may reveal association between phenotypic variation and variation...... approach grouping variants accordingly to gene position, thus lowering the number of statistical tests performed and increasing the probability of identifying genes with small to moderate effects. Using this approach we identify numerous genes associated with different types of stresses in Drosophila...... melanogaster, but also identify common genes that affects the stress traits....

  2. The node-weighted Steiner tree approach to identify elements of cancer-related signaling pathways.

    Science.gov (United States)

    Sun, Yahui; Ma, Chenkai; Halgamuge, Saman

    2017-12-28

    Cancer constitutes a momentous health burden in our society. Critical information on cancer may be hidden in its signaling pathways. However, even though a large amount of money has been spent on cancer research, some critical information on cancer-related signaling pathways still remains elusive. Hence, new works towards a complete understanding of cancer-related signaling pathways will greatly benefit the prevention, diagnosis, and treatment of cancer. We propose the node-weighted Steiner tree approach to identify important elements of cancer-related signaling pathways at the level of proteins. This new approach has advantages over previous approaches since it is fast in processing large protein-protein interaction networks. We apply this new approach to identify important elements of two well-known cancer-related signaling pathways: PI3K/Akt and MAPK. First, we generate a node-weighted protein-protein interaction network using protein and signaling pathway data. Second, we modify and use two preprocessing techniques and a state-of-the-art Steiner tree algorithm to identify a subnetwork in the generated network. Third, we propose two new metrics to select important elements from this subnetwork. On a commonly used personal computer, this new approach takes less than 2 s to identify the important elements of PI3K/Akt and MAPK signaling pathways in a large node-weighted protein-protein interaction network with 16,843 vertices and 1,736,922 edges. We further analyze and demonstrate the significance of these identified elements to cancer signal transduction by exploring previously reported experimental evidences. Our node-weighted Steiner tree approach is shown to be both fast and effective to identify important elements of cancer-related signaling pathways. Furthermore, it may provide new perspectives into the identification of signaling pathways for other human diseases.

  3. A discrete wavelet spectrum approach for identifying non-monotonic trends in hydroclimate data

    Science.gov (United States)

    Sang, Yan-Fang; Sun, Fubao; Singh, Vijay P.; Xie, Ping; Sun, Jian

    2018-01-01

    The hydroclimatic process is changing non-monotonically and identifying its trends is a great challenge. Building on the discrete wavelet transform theory, we developed a discrete wavelet spectrum (DWS) approach for identifying non-monotonic trends in hydroclimate time series and evaluating their statistical significance. After validating the DWS approach using two typical synthetic time series, we examined annual temperature and potential evaporation over China from 1961-2013 and found that the DWS approach detected both the warming and the warming hiatus in temperature, and the reversed changes in potential evaporation. Further, the identified non-monotonic trends showed stable significance when the time series was longer than 30 years or so (i.e. the widely defined climate timescale). The significance of trends in potential evaporation measured at 150 stations in China, with an obvious non-monotonic trend, was underestimated and was not detected by the Mann-Kendall test. Comparatively, the DWS approach overcame the problem and detected those significant non-monotonic trends at 380 stations, which helped understand and interpret the spatiotemporal variability in the hydroclimatic process. Our results suggest that non-monotonic trends of hydroclimate time series and their significance should be carefully identified, and the DWS approach proposed has the potential for wide use in the hydrological and climate sciences.

  4. A discrete wavelet spectrum approach for identifying non-monotonic trends in hydroclimate data

    Directory of Open Access Journals (Sweden)

    Y.-F. Sang

    2018-01-01

    Full Text Available The hydroclimatic process is changing non-monotonically and identifying its trends is a great challenge. Building on the discrete wavelet transform theory, we developed a discrete wavelet spectrum (DWS approach for identifying non-monotonic trends in hydroclimate time series and evaluating their statistical significance. After validating the DWS approach using two typical synthetic time series, we examined annual temperature and potential evaporation over China from 1961–2013 and found that the DWS approach detected both the warming and the warming hiatus in temperature, and the reversed changes in potential evaporation. Further, the identified non-monotonic trends showed stable significance when the time series was longer than 30 years or so (i.e. the widely defined climate timescale. The significance of trends in potential evaporation measured at 150 stations in China, with an obvious non-monotonic trend, was underestimated and was not detected by the Mann–Kendall test. Comparatively, the DWS approach overcame the problem and detected those significant non-monotonic trends at 380 stations, which helped understand and interpret the spatiotemporal variability in the hydroclimatic process. Our results suggest that non-monotonic trends of hydroclimate time series and their significance should be carefully identified, and the DWS approach proposed has the potential for wide use in the hydrological and climate sciences.

  5. Candidate gene linkage approach to identify DNA variants that predispose to preterm birth

    DEFF Research Database (Denmark)

    Bream, Elise N A; Leppellere, Cara R; Cooper, Margaret E

    2013-01-01

    Background:The aim of this study was to identify genetic variants contributing to preterm birth (PTB) using a linkage candidate gene approach.Methods:We studied 99 single-nucleotide polymorphisms (SNPs) for 33 genes in 257 families with PTBs segregating. Nonparametric and parametric analyses were...... through the infant and/or the mother in the etiology of PTB....

  6. The Baby TALK Model: An Innovative Approach to Identifying High-Risk Children and Families

    Science.gov (United States)

    Villalpando, Aimee Hilado; Leow, Christine; Hornstein, John

    2012-01-01

    This research report examines the Baby TALK model, an innovative early childhood intervention approach used to identify, recruit, and serve young children who are at-risk for developmental delays, mental health needs, and/or school failure, and their families. The report begins with a description of the model. This description is followed by an…

  7. Identifying Core Mobile Learning Faculty Competencies Based Integrated Approach: A Delphi Study

    Science.gov (United States)

    Elbarbary, Rafik Said

    2015-01-01

    This study is based on the integrated approach as a concept framework to identify, categorize, and rank a key component of mobile learning core competencies for Egyptian faculty members in higher education. The field investigation framework used four rounds Delphi technique to determine the importance rate of each component of core competencies…

  8. Identifying bioaccumulative halogenated organic compounds using a nontargeted analytical approach: seabirds as sentinels.

    Directory of Open Access Journals (Sweden)

    Christopher J Millow

    Full Text Available Persistent organic pollutants (POPs are typically monitored via targeted mass spectrometry, which potentially identifies only a fraction of the contaminants actually present in environmental samples. With new anthropogenic compounds continuously introduced to the environment, novel and proactive approaches that provide a comprehensive alternative to targeted methods are needed in order to more completely characterize the diversity of known and unknown compounds likely to cause adverse effects. Nontargeted mass spectrometry attempts to extensively screen for compounds, providing a feasible approach for identifying contaminants that warrant future monitoring. We employed a nontargeted analytical method using comprehensive two-dimensional gas chromatography coupled to time-of-flight mass spectrometry (GC×GC/TOF-MS to characterize halogenated organic compounds (HOCs in California Black skimmer (Rynchops niger eggs. Our study identified 111 HOCs; 84 of these compounds were regularly detected via targeted approaches, while 27 were classified as typically unmonitored or unknown. Typically unmonitored compounds of note in bird eggs included tris(4-chlorophenylmethane (TCPM, tris(4-chlorophenylmethanol (TCPMOH, triclosan, permethrin, heptachloro-1'-methyl-1,2'-bipyrrole (MBP, as well as four halogenated unknown compounds that could not be identified through database searching or the literature. The presence of these compounds in Black skimmer eggs suggests they are persistent, bioaccumulative, potentially biomagnifying, and maternally transferring. Our results highlight the utility and importance of employing nontargeted analytical tools to assess true contaminant burdens in organisms, as well as to demonstrate the value in using environmental sentinels to proactively identify novel contaminants.

  9. Identifying seizure onset zone from electrocorticographic recordings: A machine learning approach based on phase locking value.

    Science.gov (United States)

    Elahian, Bahareh; Yeasin, Mohammed; Mudigoudar, Basanagoud; Wheless, James W; Babajani-Feremi, Abbas

    2017-10-01

    Using a novel technique based on phase locking value (PLV), we investigated the potential for features extracted from electrocorticographic (ECoG) recordings to serve as biomarkers to identify the seizure onset zone (SOZ). We computed the PLV between the phase of the amplitude of high gamma activity (80-150Hz) and the phase of lower frequency rhythms (4-30Hz) from ECoG recordings obtained from 10 patients with epilepsy (21 seizures). We extracted five features from the PLV and used a machine learning approach based on logistic regression to build a model that classifies electrodes as SOZ or non-SOZ. More than 96% of electrodes identified as the SOZ by our algorithm were within the resected area in six seizure-free patients. In four non-seizure-free patients, more than 31% of the identified SOZ electrodes by our algorithm were outside the resected area. In addition, we observed that the seizure outcome in non-seizure-free patients correlated with the number of non-resected SOZ electrodes identified by our algorithm. This machine learning approach, based on features extracted from the PLV, effectively identified electrodes within the SOZ. The approach has the potential to assist clinicians in surgical decision-making when pre-surgical intracranial recordings are utilized. Copyright © 2017 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.

  10. Quantitative and qualitative approaches to identifying migration chronology in a continental migrant.

    Directory of Open Access Journals (Sweden)

    William S Beatty

    Full Text Available The degree to which extrinsic factors influence migration chronology in North American waterfowl has not been quantified, particularly for dabbling ducks. Previous studies have examined waterfowl migration using various methods, however, quantitative approaches to define avian migration chronology over broad spatio-temporal scales are limited, and the implications for using different approaches have not been assessed. We used movement data from 19 female adult mallards (Anas platyrhynchos equipped with solar-powered global positioning system satellite transmitters to evaluate two individual level approaches for quantifying migration chronology. The first approach defined migration based on individual movements among geopolitical boundaries (state, provincial, international, whereas the second method modeled net displacement as a function of time using nonlinear models. Differences in migration chronologies identified by each of the approaches were examined with analysis of variance. The geopolitical method identified mean autumn migration midpoints at 15 November 2010 and 13 November 2011, whereas the net displacement method identified midpoints at 15 November 2010 and 14 November 2011. The mean midpoints for spring migration were 3 April 2011 and 20 March 2012 using the geopolitical method and 31 March 2011 and 22 March 2012 using the net displacement method. The duration, initiation date, midpoint, and termination date for both autumn and spring migration did not differ between the two individual level approaches. Although we did not detect differences in migration parameters between the different approaches, the net displacement metric offers broad potential to address questions in movement ecology for migrating species. Ultimately, an objective definition of migration chronology will allow researchers to obtain a comprehensive understanding of the extrinsic factors that drive migration at the individual and population levels. As a result

  11. Quantitative and qualitative approaches to identifying migration chronology in a continental migrant

    Science.gov (United States)

    Beatty, William S.; Kesler, Dylan C.; Webb, Elisabeth B.; Raedeke, Andrew H.; Naylor, Luke W.; Humburg, Dale D.

    2013-01-01

    The degree to which extrinsic factors influence migration chronology in North American waterfowl has not been quantified, particularly for dabbling ducks. Previous studies have examined waterfowl migration using various methods, however, quantitative approaches to define avian migration chronology over broad spatio-temporal scales are limited, and the implications for using different approaches have not been assessed. We used movement data from 19 female adult mallards (Anas platyrhynchos) equipped with solar-powered global positioning system satellite transmitters to evaluate two individual level approaches for quantifying migration chronology. The first approach defined migration based on individual movements among geopolitical boundaries (state, provincial, international), whereas the second method modeled net displacement as a function of time using nonlinear models. Differences in migration chronologies identified by each of the approaches were examined with analysis of variance. The geopolitical method identified mean autumn migration midpoints at 15 November 2010 and 13 November 2011, whereas the net displacement method identified midpoints at 15 November 2010 and 14 November 2011. The mean midpoints for spring migration were 3 April 2011 and 20 March 2012 using the geopolitical method and 31 March 2011 and 22 March 2012 using the net displacement method. The duration, initiation date, midpoint, and termination date for both autumn and spring migration did not differ between the two individual level approaches. Although we did not detect differences in migration parameters between the different approaches, the net displacement metric offers broad potential to address questions in movement ecology for migrating species. Ultimately, an objective definition of migration chronology will allow researchers to obtain a comprehensive understanding of the extrinsic factors that drive migration at the individual and population levels. As a result, targeted

  12. A comparison of approaches for finding minimum identifying codes on graphs

    Science.gov (United States)

    Horan, Victoria; Adachi, Steve; Bak, Stanley

    2016-05-01

    In order to formulate mathematical conjectures likely to be true, a number of base cases must be determined. However, many combinatorial problems are NP-hard and the computational complexity makes this research approach difficult using a standard brute force approach on a typical computer. One sample problem explored is that of finding a minimum identifying code. To work around the computational issues, a variety of methods are explored and consist of a parallel computing approach using MATLAB, an adiabatic quantum optimization approach using a D-Wave quantum annealing processor, and lastly using satisfiability modulo theory (SMT) and corresponding SMT solvers. Each of these methods requires the problem to be formulated in a unique manner. In this paper, we address the challenges of computing solutions to this NP-hard problem with respect to each of these methods.

  13. A model-based approach to identify binding sites in CLIP-Seq data.

    Directory of Open Access Journals (Sweden)

    Tao Wang

    Full Text Available Cross-linking immunoprecipitation coupled with high-throughput sequencing (CLIP-Seq has made it possible to identify the targeting sites of RNA-binding proteins in various cell culture systems and tissue types on a genome-wide scale. Here we present a novel model-based approach (MiClip to identify high-confidence protein-RNA binding sites from CLIP-seq datasets. This approach assigns a probability score for each potential binding site to help prioritize subsequent validation experiments. The MiClip algorithm has been tested in both HITS-CLIP and PAR-CLIP datasets. In the HITS-CLIP dataset, the signal/noise ratios of miRNA seed motif enrichment produced by the MiClip approach are between 17% and 301% higher than those by the ad hoc method for the top 10 most enriched miRNAs. In the PAR-CLIP dataset, the MiClip approach can identify ∼50% more validated binding targets than the original ad hoc method and two recently published methods. To facilitate the application of the algorithm, we have released an R package, MiClip (http://cran.r-project.org/web/packages/MiClip/index.html, and a public web-based graphical user interface software (http://galaxy.qbrc.org/tool_runner?tool_id=mi_clip for customized analysis.

  14. Alternative approaches for identifying acute systemic toxicity: Moving from research to regulatory testing.

    Science.gov (United States)

    Hamm, Jon; Sullivan, Kristie; Clippinger, Amy J; Strickland, Judy; Bell, Shannon; Bhhatarai, Barun; Blaauboer, Bas; Casey, Warren; Dorman, David; Forsby, Anna; Garcia-Reyero, Natàlia; Gehen, Sean; Graepel, Rabea; Hotchkiss, Jon; Lowit, Anna; Matheson, Joanna; Reaves, Elissa; Scarano, Louis; Sprankle, Catherine; Tunkel, Jay; Wilson, Dan; Xia, Menghang; Zhu, Hao; Allen, David

    2017-06-01

    Acute systemic toxicity testing provides the basis for hazard labeling and risk management of chemicals. A number of international efforts have been directed at identifying non-animal alternatives for in vivo acute systemic toxicity tests. A September 2015 workshop, Alternative Approaches for Identifying Acute Systemic Toxicity: Moving from Research to Regulatory Testing, reviewed the state-of-the-science of non-animal alternatives for this testing and explored ways to facilitate implementation of alternatives. Workshop attendees included representatives from international regulatory agencies, academia, nongovernmental organizations, and industry. Resources identified as necessary for meaningful progress in implementing alternatives included compiling and making available high-quality reference data, training on use and interpretation of in vitro and in silico approaches, and global harmonization of testing requirements. Attendees particularly noted the need to characterize variability in reference data to evaluate new approaches. They also noted the importance of understanding the mechanisms of acute toxicity, which could be facilitated by the development of adverse outcome pathways. Workshop breakout groups explored different approaches to reducing or replacing animal use for acute toxicity testing, with each group crafting a roadmap and strategy to accomplish near-term progress. The workshop steering committee has organized efforts to implement the recommendations of the workshop participants. Copyright © 2017 Elsevier Ltd. All rights reserved.

  15. Protein tyrosine kinases p53/56lyn and p72syk in MHC class I-mediated signal transduction in B lymphoma cells

    DEFF Research Database (Denmark)

    Pedersen, Anders Elm; Bregenholt, S; Skov, S

    1998-01-01

    syk are among the tyrosine-phosphorylated proteins. The kinetics of phosphorylation of these kinases after MHC-I crosslinking differ from the kinetics observed after crosslinking of the B cell antigen receptor (BCR). Additional experiments were performed with chicken lyn- and syk-negative DT40 B cells...... mobilization of intracellular free calcium compared with MHC-I crosslinking of wild-type DT40 cells. Thus, expression of BCR at the cell surface is likely to be important for the signal cascade initiated by MHC-I crosslinking. Our data suggest that signal transduction initiated through ligation of the MHC...

  16. Identifying prognostic features by bottom-up approach and correlating to drug repositioning.

    Directory of Open Access Journals (Sweden)

    Wei Li

    Full Text Available Traditionally top-down method was used to identify prognostic features in cancer research. That is to say, differentially expressed genes usually in cancer versus normal were identified to see if they possess survival prediction power. The problem is that prognostic features identified from one set of patient samples can rarely be transferred to other datasets. We apply bottom-up approach in this study: survival correlated or clinical stage correlated genes were selected first and prioritized by their network topology additionally, then a small set of features can be used as a prognostic signature.Gene expression profiles of a cohort of 221 hepatocellular carcinoma (HCC patients were used as a training set, 'bottom-up' approach was applied to discover gene-expression signatures associated with survival in both tumor and adjacent non-tumor tissues, and compared with 'top-down' approach. The results were validated in a second cohort of 82 patients which was used as a testing set.Two sets of gene signatures separately identified in tumor and adjacent non-tumor tissues by bottom-up approach were developed in the training cohort. These two signatures were associated with overall survival times of HCC patients and the robustness of each was validated in the testing set, and each predictive performance was better than gene expression signatures reported previously. Moreover, genes in these two prognosis signature gave some indications for drug-repositioning on HCC. Some approved drugs targeting these markers have the alternative indications on hepatocellular carcinoma.Using the bottom-up approach, we have developed two prognostic gene signatures with a limited number of genes that associated with overall survival times of patients with HCC. Furthermore, prognostic markers in these two signatures have the potential to be therapeutic targets.

  17. Three novel approaches to structural identifiability analysis in mixed-effects models.

    Science.gov (United States)

    Janzén, David L I; Jirstrand, Mats; Chappell, Michael J; Evans, Neil D

    2016-05-06

    Structural identifiability is a concept that considers whether the structure of a model together with a set of input-output relations uniquely determines the model parameters. In the mathematical modelling of biological systems, structural identifiability is an important concept since biological interpretations are typically made from the parameter estimates. For a system defined by ordinary differential equations, several methods have been developed to analyse whether the model is structurally identifiable or otherwise. Another well-used modelling framework, which is particularly useful when the experimental data are sparsely sampled and the population variance is of interest, is mixed-effects modelling. However, established identifiability analysis techniques for ordinary differential equations are not directly applicable to such models. In this paper, we present and apply three different methods that can be used to study structural identifiability in mixed-effects models. The first method, called the repeated measurement approach, is based on applying a set of previously established statistical theorems. The second method, called the augmented system approach, is based on augmenting the mixed-effects model to an extended state-space form. The third method, called the Laplace transform mixed-effects extension, is based on considering the moment invariants of the systems transfer function as functions of random variables. To illustrate, compare and contrast the application of the three methods, they are applied to a set of mixed-effects models. Three structural identifiability analysis methods applicable to mixed-effects models have been presented in this paper. As method development of structural identifiability techniques for mixed-effects models has been given very little attention, despite mixed-effects models being widely used, the methods presented in this paper provides a way of handling structural identifiability in mixed-effects models previously not

  18. A Systematic Approach to Determining the Identifiability of Multistage Carcinogenesis Models.

    Science.gov (United States)

    Brouwer, Andrew F; Meza, Rafael; Eisenberg, Marisa C

    2017-07-01

    Multistage clonal expansion (MSCE) models of carcinogenesis are continuous-time Markov process models often used to relate cancer incidence to biological mechanism. Identifiability analysis determines what model parameter combinations can, theoretically, be estimated from given data. We use a systematic approach, based on differential algebra methods traditionally used for deterministic ordinary differential equation (ODE) models, to determine identifiable combinations for a generalized subclass of MSCE models with any number of preinitation stages and one clonal expansion. Additionally, we determine the identifiable combinations of the generalized MSCE model with up to four clonal expansion stages, and conjecture the results for any number of clonal expansion stages. The results improve upon previous work in a number of ways and provide a framework to find the identifiable combinations for further variations on the MSCE models. Finally, our approach, which takes advantage of the Kolmogorov backward equations for the probability generating functions of the Markov process, demonstrates that identifiability methods used in engineering and mathematics for systems of ODEs can be applied to continuous-time Markov processes. © 2016 Society for Risk Analysis.

  19. Online-Based Approaches to Identify Real Journals and Publishers from Hijacked Ones.

    Science.gov (United States)

    Asadi, Amin; Rahbar, Nader; Asadi, Meisam; Asadi, Fahime; Khalili Paji, Kokab

    2017-02-01

    The aim of the present paper was to introduce some online-based approaches to evaluate scientific journals and publishers and to differentiate them from the hijacked ones, regardless of their disciplines. With the advent of open-access journals, many hijacked journals and publishers have deceitfully assumed the mantle of authenticity in order to take advantage of researchers and students. Although these hijacked journals and publishers can be identified through checking their advertisement techniques and their websites, these ways do not always result in their identification. There exist certain online-based approaches, such as using Master Journal List provided by Thomson Reuters, and Scopus database, and using the DOI of a paper, to certify the realness of a journal or publisher. It is indispensable that inexperienced students and researchers know these methods so as to identify hijacked journals and publishers with a higher level of probability.

  20. Maximal Predictability Approach for Identifying the Right Descriptors for Electrocatalytic Reactions.

    Science.gov (United States)

    Krishnamurthy, Dilip; Sumaria, Vaidish; Viswanathan, Venkatasubramanian

    2018-02-01

    Density functional theory (DFT) calculations are being routinely used to identify new material candidates that approach activity near fundamental limits imposed by thermodynamics or scaling relations. DFT calculations are associated with inherent uncertainty, which limits the ability to delineate materials (distinguishability) that possess high activity. Development of error-estimation capabilities in DFT has enabled uncertainty propagation through activity-prediction models. In this work, we demonstrate an approach to propagating uncertainty through thermodynamic activity models leading to a probability distribution of the computed activity and thereby its expectation value. A new metric, prediction efficiency, is defined, which provides a quantitative measure of the ability to distinguish activity of materials and can be used to identify the optimal descriptor(s) ΔG opt . We demonstrate the framework for four important electrochemical reactions: hydrogen evolution, chlorine evolution, oxygen reduction and oxygen evolution. Future studies could utilize expected activity and prediction efficiency to significantly improve the prediction accuracy of highly active material candidates.

  1. Constructing New Theory for Identifying Students with Emotional Disturbance: A Constructivist Approach to Grounded Theory

    OpenAIRE

    Dori Barnett

    2012-01-01

    A grounded theory study that examined how practitioners in a county alternative and correctional education setting identify youth with emotional and behavioral difficulties for special education services provides an exemplar for a constructivist approach to grounded theory methodology. Discussion focuses on how a constructivist orientation to grounded theory methodology informed research decisions, shaped the development of the emergent grounded theory, and prompted a way of thinking about da...

  2. An Approach to Identify and Characterize a Subunit Candidate Shigella Vaccine Antigen.

    Science.gov (United States)

    Pore, Debasis; Chakrabarti, Manoj K

    2016-01-01

    Shigellosis remains a serious issue throughout the developing countries, particularly in children under the age of 5. Numerous strategies have been tested to develop vaccines targeting shigellosis; unfortunately despite several years of extensive research, no safe, effective, and inexpensive vaccine against shigellosis is available so far. Here, we illustrate in detail an approach to identify and establish immunogenic outer membrane proteins from Shigella flexneri 2a as subunit vaccine candidates.

  3. A new approach to hazardous materials transportation risk analysis: decision modeling to identify critical variables.

    Science.gov (United States)

    Clark, Renee M; Besterfield-Sacre, Mary E

    2009-03-01

    We take a novel approach to analyzing hazardous materials transportation risk in this research. Previous studies analyzed this risk from an operations research (OR) or quantitative risk assessment (QRA) perspective by minimizing or calculating risk along a transport route. Further, even though the majority of incidents occur when containers are unloaded, the research has not focused on transportation-related activities, including container loading and unloading. In this work, we developed a decision model of a hazardous materials release during unloading using actual data and an exploratory data modeling approach. Previous studies have had a theoretical perspective in terms of identifying and advancing the key variables related to this risk, and there has not been a focus on probability and statistics-based approaches for doing this. Our decision model empirically identifies the critical variables using an exploratory methodology for a large, highly categorical database involving latent class analysis (LCA), loglinear modeling, and Bayesian networking. Our model identified the most influential variables and countermeasures for two consequences of a hazmat incident, dollar loss and release quantity, and is one of the first models to do this. The most influential variables were found to be related to the failure of the container. In addition to analyzing hazmat risk, our methodology can be used to develop data-driven models for strategic decision making in other domains involving risk.

  4. A Systematic Approach to Identify Promising New Items for Small to Medium Enterprises: A Case Study

    Directory of Open Access Journals (Sweden)

    Sukjae Jeong

    2016-11-01

    Full Text Available Despite the growing importance of identifying new business items for small and medium enterprises (SMEs, most previous studies focus on conglomerates. The paucity of empirical studies has also led to limited real-life applications. Hence, this study proposes a systematic approach to find new business items (NBIs that help the prospective SMEs develop, evaluate, and select viable business items to survive the competitive environment. The proposed approach comprises two stages: (1 the classification of diversification of SMEs; and (2 the searching and screening of business items. In the first stage, SMEs are allocated to five groups, based on their internal technological competency and external market conditions. In the second stage, based on the types of SMEs identified in the first stage, a set of alternative business items is derived by combining the results of portfolio analysis and benchmarking analysis. After deriving new business items, a market and technology-driven matrix analysis is utilized to screen suitable business items, and the Bruce Merrifield-Ohe (BMO method is used to categorize and identify prospective items based on market attractiveness and internal capability. To illustrate the applicability of the proposed approach, a case study is presented.

  5. Integrated systems approach identifies risk regulatory pathways and key regulators in coronary artery disease.

    Science.gov (United States)

    Zhang, Yan; Liu, Dianming; Wang, Lihong; Wang, Shuyuan; Yu, Xuexin; Dai, Enyu; Liu, Xinyi; Luo, Shanshun; Jiang, Wei

    2015-12-01

    Coronary artery disease (CAD) is the most common type of heart disease. However, the molecular mechanisms of CAD remain elusive. Regulatory pathways are known to play crucial roles in many pathogenic processes. Thus, inferring risk regulatory pathways is an important step toward elucidating the mechanisms underlying CAD. With advances in high-throughput data, we developed an integrated systems approach to identify CAD risk regulatory pathways and key regulators. Firstly, a CAD-related core subnetwork was identified from a curated transcription factor (TF) and microRNA (miRNA) regulatory network based on a random walk algorithm. Secondly, candidate risk regulatory pathways were extracted from the subnetwork by applying a breadth-first search (BFS) algorithm. Then, risk regulatory pathways were prioritized based on multiple CAD-associated data sources. Finally, we also proposed a new measure to prioritize upstream regulators. We inferred that phosphatase and tensin homolog (PTEN) may be a key regulator in the dysregulation of risk regulatory pathways. This study takes a closer step than the identification of disease subnetworks or modules. From the risk regulatory pathways, we could understand the flow of regulatory information in the initiation and progression of the disease. Our approach helps to uncover its potential etiology. We developed an integrated systems approach to identify risk regulatory pathways. We proposed a new measure to prioritize the key regulators in CAD. PTEN may be a key regulator in dysregulation of the risk regulatory pathways.

  6. An approach to identify issues affecting ERP implementation in Indian SMEs

    Directory of Open Access Journals (Sweden)

    Rana Basu

    2012-06-01

    Full Text Available Purpose: The purpose of this paper is to present the findings of a study which is based on the results of a comprehensive compilation of literature and subsequent analysis of ERP implementation success issues in context to Indian Small and Medium scale Enterprises (SME’s. This paper attempts to explore the existing literature and highlight those issues on ERP implementation and further to this the researchers applied TOPSIS (Technique for order preference by similarity to ideal solution method to prioritize issues affecting successful implementation of ERP. Design/methodology/approach: Based on the literature review certain issues leading to successful ERP implementation have been identified and to identify key issues Pareto Analysis (80-20 Rule have been applied. Further to extraction of key issues a survey based on TOPSIS was carried out in Indian small and medium scale enterprises. Findings: Based on review of literature 25 issues have been identified and further Pareto analysis has been done to extract key issues which is further prioritized by applying Topsis method. Research limitations/implications: Beside those identified issues there may be other issues that need to be explored. There is scope to enhance this study by taking into consideration different type of industries and by extending number of respondents. Practical implications: By identifying key issues for SMEs, managers can better prioritize issues to make implementation process smooth without disruption. ERP vendors can take inputs from this study to change their implementation approach while targeting small scale enterprises. Originality/value: There is no published literature available which followed a similar approach in identification of the critical issues affecting ERP in small and mid-sized companies in India or in any developing economy.

  7. Identifying Key Performance Indicators for Holistic Hospital Management with a Modified DEMATEL Approach.

    Science.gov (United States)

    Si, Sheng-Li; You, Xiao-Yue; Liu, Hu-Chen; Huang, Jia

    2017-08-19

    Performance analysis is an important way for hospitals to achieve higher efficiency and effectiveness in providing services to their customers. The performance of the healthcare system can be measured by many indicators, but it is difficult to improve them simultaneously due to the limited resources. A feasible way is to identify the central and influential indicators to improve healthcare performance in a stepwise manner. In this paper, we propose a hybrid multiple criteria decision making (MCDM) approach to identify key performance indicators (KPIs) for holistic hospital management. First, through integrating evidential reasoning approach and interval 2-tuple linguistic variables, various assessments of performance indicators provided by healthcare experts are modeled. Then, the decision making trial and evaluation laboratory (DEMATEL) technique is adopted to build an interactive network and visualize the causal relationships between the performance indicators. Finally, an empirical case study is provided to demonstrate the proposed approach for improving the efficiency of healthcare management. The results show that "accidents/adverse events", "nosocomial infection", ''incidents/errors", "number of operations/procedures" are significant influential indicators. Also, the indicators of "length of stay", "bed occupancy" and "financial measures" play important roles in performance evaluation of the healthcare organization. The proposed decision making approach could be considered as a reference for healthcare administrators to enhance the performance of their healthcare institutions.

  8. A physarum-inspired prize-collecting steiner tree approach to identify subnetworks for drug repositioning.

    Science.gov (United States)

    Sun, Yahui; Hameed, Pathima Nusrath; Verspoor, Karin; Halgamuge, Saman

    2016-12-05

    Drug repositioning can reduce the time, costs and risks of drug development by identifying new therapeutic effects for known drugs. It is challenging to reposition drugs as pharmacological data is large and complex. Subnetwork identification has already been used to simplify the visualization and interpretation of biological data, but it has not been applied to drug repositioning so far. In this paper, we fill this gap by proposing a new Physarum-inspired Prize-Collecting Steiner Tree algorithm to identify subnetworks for drug repositioning. Drug Similarity Networks (DSN) are generated using the chemical, therapeutic, protein, and phenotype features of drugs. In DSNs, vertex prizes and edge costs represent the similarities and dissimilarities between drugs respectively, and terminals represent drugs in the cardiovascular class, as defined in the Anatomical Therapeutic Chemical classification system. A new Physarum-inspired Prize-Collecting Steiner Tree algorithm is proposed in this paper to identify subnetworks. We apply both the proposed algorithm and the widely-used GW algorithm to identify subnetworks in our 18 generated DSNs. In these DSNs, our proposed algorithm identifies subnetworks with an average Rand Index of 81.1%, while the GW algorithm can only identify subnetworks with an average Rand Index of 64.1%. We select 9 subnetworks with high Rand Index to find drug repositioning opportunities. 10 frequently occurring drugs in these subnetworks are identified as candidates to be repositioned for cardiovascular diseases. We find evidence to support previous discoveries that nitroglycerin, theophylline and acarbose may be able to be repositioned for cardiovascular diseases. Moreover, we identify seven previously unknown drug candidates that also may interact with the biological cardiovascular system. These discoveries show our proposed Prize-Collecting Steiner Tree approach as a promising strategy for drug repositioning.

  9. An information-theoretic approach to assess practical identifiability of parametric dynamical systems.

    Science.gov (United States)

    Pant, Sanjay; Lombardi, Damiano

    2015-10-01

    A new approach for assessing parameter identifiability of dynamical systems in a Bayesian setting is presented. The concept of Shannon entropy is employed to measure the inherent uncertainty in the parameters. The expected reduction in this uncertainty is seen as the amount of information one expects to gain about the parameters due to the availability of noisy measurements of the dynamical system. Such expected information gain is interpreted in terms of the variance of a hypothetical measurement device that can measure the parameters directly, and is related to practical identifiability of the parameters. If the individual parameters are unidentifiable, correlation between parameter combinations is assessed through conditional mutual information to determine which sets of parameters can be identified together. The information theoretic quantities of entropy and information are evaluated numerically through a combination of Monte Carlo and k-nearest neighbour methods in a non-parametric fashion. Unlike many methods to evaluate identifiability proposed in the literature, the proposed approach takes the measurement-noise into account and is not restricted to any particular noise-structure. Whilst computationally intensive for large dynamical systems, it is easily parallelisable and is non-intrusive as it does not necessitate re-writing of the numerical solvers of the dynamical system. The application of such an approach is presented for a variety of dynamical systems--ranging from systems governed by ordinary differential equations to partial differential equations--and, where possible, validated against results previously published in the literature. Copyright © 2015 Elsevier Inc. All rights reserved.

  10. Identifying best-fitting inputs in health-economic model calibration: a Pareto frontier approach.

    Science.gov (United States)

    Enns, Eva A; Cipriano, Lauren E; Simons, Cyrena T; Kong, Chung Yin

    2015-02-01

    To identify best-fitting input sets using model calibration, individual calibration target fits are often combined into a single goodness-of-fit (GOF) measure using a set of weights. Decisions in the calibration process, such as which weights to use, influence which sets of model inputs are identified as best-fitting, potentially leading to different health economic conclusions. We present an alternative approach to identifying best-fitting input sets based on the concept of Pareto-optimality. A set of model inputs is on the Pareto frontier if no other input set simultaneously fits all calibration targets as well or better. We demonstrate the Pareto frontier approach in the calibration of 2 models: a simple, illustrative Markov model and a previously published cost-effectiveness model of transcatheter aortic valve replacement (TAVR). For each model, we compare the input sets on the Pareto frontier to an equal number of best-fitting input sets according to 2 possible weighted-sum GOF scoring systems, and we compare the health economic conclusions arising from these different definitions of best-fitting. For the simple model, outcomes evaluated over the best-fitting input sets according to the 2 weighted-sum GOF schemes were virtually nonoverlapping on the cost-effectiveness plane and resulted in very different incremental cost-effectiveness ratios ($79,300 [95% CI 72,500-87,600] v. $139,700 [95% CI 79,900-182,800] per quality-adjusted life-year [QALY] gained). Input sets on the Pareto frontier spanned both regions ($79,000 [95% CI 64,900-156,200] per QALY gained). The TAVR model yielded similar results. Choices in generating a summary GOF score may result in different health economic conclusions. The Pareto frontier approach eliminates the need to make these choices by using an intuitive and transparent notion of optimality as the basis for identifying best-fitting input sets. © The Author(s) 2014.

  11. Molecular mechanism of strict substrate specificity of an extradiol dioxygenase, DesB, derived from Sphingobium sp. SYK-6.

    Directory of Open Access Journals (Sweden)

    Keisuke Sugimoto

    Full Text Available DesB, which is derived from Sphingobium sp. SYK-6, is a type II extradiol dioxygenase that catalyzes a ring opening reaction of gallate. While typical extradiol dioxygenases show broad substrate specificity, DesB has strict substrate specificity for gallate. The substrate specificity of DesB seems to be required for the efficient growth of S. sp. SYK-6 using lignin-derived aromatic compounds. Since direct coordination of hydroxyl groups of the substrate to the non-heme iron in the active site is a critical step for the catalytic reaction of the extradiol dioxygenases, the mechanism of the substrate recognition and coordination of DesB was analyzed by biochemical and crystallographic methods. Our study demonstrated that the direct coordination between the non-heme iron and hydroxyl groups of the substrate requires a large shift of the Fe (II ion in the active site. Mutational analysis revealed that His124 and His192 in the active site are essential to the catalytic reaction of DesB. His124, which interacts with OH (4 of the bound gallate, seems to contribute to proper positioning of the substrate in the active site. His192, which is located close to OH (3 of the gallate, is likely to serve as the catalytic base. Glu377' interacts with OH (5 of the gallate and seems to play a critical role in the substrate specificity. Our biochemical and structural study showed the substrate recognition and catalytic mechanisms of DesB.

  12. Meliae cortex extract exhibits anti-allergic activity through the inhibition of Syk kinase in mast cells

    International Nuclear Information System (INIS)

    Lee, Jun Ho; Ko, Na Young; Kim, Nam Wook; Mun, Se Hwan; Kim, Jie Wan; Her, Erk; Kim, Bo Kyung; Seo, Dong Wan; Chang, Hyun Wook; Moon, Tae Chul; Han, Jeung Whan; Kim, Young Mi; Choi, Wahn Soo

    2007-01-01

    The anti-allergic action of various Oriental medicinal herbs was investigated using in vitro and in vivo experimental models. Of these extracts, the ethanol extract of Meliae cortex (MC) exhibited the most potent activity in mast cells; its IC 50 values were 29 ± 1.5 μg/ml for antigen stimulation and 57 ± 3.4 μg/ml for thapsigargin stimulation. It inhibited compound-48/80-induced systemic anaphylaxis by 52.9% at a dose of 300 mg/kg in mice; it also inhibited the expression of the proinflammatory mediator TNF-α. With regard to its mechanism of action, MC suppressed the activating phosphorylation of Syk, a key enzyme in mast-cell signaling processes and that of Akt in a dose-dependent manner. It also inhibited the MAP kinase ERK1/2, which is critical for the production of inflammatory cytokines in mast cells, as indicated by the suppression of the activating phosphorylation of ERK1/2. Taken together, these results suggest that the anti-allergic activity of MC may be due to the inhibition of histamine secretion and cytokine expression through the Syk inhibition in mast cells

  13. Screening and syndromic approaches to identify gonorrhea and chlamydial infection among women.

    Science.gov (United States)

    Sloan, N L; Winikoff, B; Haberland, N; Coggins, C; Elias, C

    2000-03-01

    The standard diagnostic tools to identify sexually transmitted infections are often expensive and have laboratory and infrastructure requirements that make them unavailable to family planning and primary health-care clinics in developing countries. Therefore, inexpensive, accessible tools that rely on symptoms, signs, and/or risk factors have been developed to identify and treat reproductive tract infections without the need for laboratory diagnostics. Studies were reviewed that used standard diagnostic tests to identify gonorrhea and cervical chlamydial infection among women and that provided adequate information about the usefulness of the tools for screening. Aggregation of the studies' results suggest that risk factors, algorithms, and risk scoring for syndromic management are poor indicators of gonorrhea and chlamydial infection in samples of both low and high prevalence and, consequently, are not effective mechanisms with which to identify or manage these conditions. The development and evaluation of other approaches to identify gonorrhea and chlamydial infections, including inexpensive and simple laboratory screening tools, periodic universal treatment, and other alternatives must be given priority.

  14. A Novel Approach to Identifying Trajectories of Mobility Change in Older Adults.

    Directory of Open Access Journals (Sweden)

    Rachel E Ward

    Full Text Available To validate trajectories of late-life mobility change using a novel approach designed to overcome the constraints of modest sample size and few follow-up time points.Using clinical reasoning and distribution-based methodology, we identified trajectories of mobility change (Late Life Function and Disability Instrument across 2 years in 391 participants age ≥65 years from a prospective cohort study designed to identify modifiable impairments predictive of mobility in late-life. We validated our approach using model fit indices and comparing baseline mobility-related factors between trajectories.Model fit indices confirmed that the optimal number of trajectories were between 4 and 6. Mobility-related factors varied across trajectories with the most unfavorable values in poor mobility trajectories and the most favorable in high mobility trajectories. These factors included leg strength, trunk extension endurance, knee flexion range of motion, limb velocity, physical performance measures, and the number and prevalence of medical conditions including osteoarthritis and back pain.Our findings support the validity of this approach and may facilitate the investigation of a broader scope of research questions within aging populations of varied sizes and traits.

  15. A multi-indicator approach for identifying shoreline sewage pollution hotspots adjacent to coral reefs.

    Science.gov (United States)

    Abaya, Leilani M; Wiegner, Tracy N; Colbert, Steven L; Beets, James P; Carlson, Kaile'a M; Kramer, K Lindsey; Most, Rebecca; Couch, Courtney S

    2018-04-01

    Sewage pollution is contributing to the global decline of coral reefs. Identifying locations where it is entering waters near reefs is therefore a management priority. Our study documented shoreline sewage pollution hotspots in a coastal community with a fringing coral reef (Puakō, Hawai'i) using dye tracer studies, sewage indicator measurements, and a pollution scoring tool. Sewage reached shoreline waters within 9 h to 3 d. Fecal indicator bacteria concentrations were high and variable, and δ 15 N macroalgal values were indicative of sewage at many stations. Shoreline nutrient concentrations were two times higher than those in upland groundwater. Pollution hotspots were identified with a scoring tool using three sewage indicators. It confirmed known locations of sewage pollution from dye tracer studies. Our study highlights the need for a multi-indicator approach and scoring tool to identify sewage pollution hotspots. This approach will be useful for other coastal communities grappling with sewage pollution. Copyright © 2018 Elsevier Ltd. All rights reserved.

  16. Association of C-Type Lectin Mincle with FcεRIβγ Subunits Leads to Functional Activation of RBL-2H3 Cells through Syk.

    Science.gov (United States)

    Honjoh, Chisato; Chihara, Kazuyasu; Yoshiki, Hatsumi; Yamauchi, Shota; Takeuchi, Kenji; Kato, Yuji; Hida, Yukio; Ishizuka, Tamotsu; Sada, Kiyonao

    2017-04-10

    Macrophage-inducible C-type lectin (Mincle) interacts with the γ-subunit of high-affinity IgE receptor (FcεRIγ) and activates Syk by recognizing its specific ligand, trehalose-6,6'-dimycolate, a glycolipid produced by Mycobacterium tuberculosis. It has been suggested that mast cells participate in the immune defense against pathogenic microbes including M. tuberculosis, although the functions are still uncertain. In this study, we examined the Mincle-mediated signaling pathway and cellular responses using RBL-2H3 cells. Mincle formed a protein complex with not only FcεRIγ but also FcεRIβ in a stable cell line expressing myc-tagged Mincle. In addition, engagement of Mincle increased the levels of protein tyrosine phosphorylation and ERK phosphorylation. A pull-down assay demonstrated that cross-linking of Mincle induced binding of FcεRIβγ subunits to the Src homology 2 domain of Syk. Pharmacological and genetic studies indicated that activation of Syk was critical for Mincle-mediated activation of phospholipase Cγ2, leading to the activation of ERK and nuclear factor of activated T cells. Moreover, engagement of Mincle efficiently induced up-regulation of characteristic mast cell genes in addition to degranulation. Taken together, our present results suggest that mast cells contribute to Mincle-mediated immunity through Syk activation triggered by association with the FcεRIβγ complex.

  17. Amino propynyl benzoic acid building block in rigid spacers of divalent ligands binding to the Syk SH2 domains with equally high affinity as the natural ligand

    NARCIS (Netherlands)

    Dekker, Frank J; de Mol, Nico J; Fischer, Marcel J E; Liskamp, Rob M J; Dekker, Frank

    2003-01-01

    The construction of rigid spacers composed of amino propynyl benzoic acid building blocks is described. These spacers were used to link two phosphopeptide ligand sites towards obtaining divalent ligands with a high affinity for Syk tandem SH2 domains, which are important in signal transduction. The

  18. Binding of a diphosphorylated-ITAM peptide to spleen tyrosine kinase (Syk) induces distal conformational changes : a hydrogen exchange mass spectrometry study

    NARCIS (Netherlands)

    Catalina, M Isabel; Fischer, Marcel J E; Liskamp, Rob M J; Heck, Albert J R; Dekker, Frank

    Structural flexibility plays a crucial role in protein function. To assess whether specific structural changes are associated with the binding of an immunoreceptor tyrosine-based activation motif (ITAM) to the tandem Src homology-2 domains (tSH2) of the spleen tyrosine kinase [EC 2.7.7.112] (Syk),

  19. Improving accuracy for identifying related PubMed queries by an integrated approach.

    Science.gov (United States)

    Lu, Zhiyong; Wilbur, W John

    2009-10-01

    PubMed is the most widely used tool for searching biomedical literature online. As with many other online search tools, a user often types a series of multiple related queries before retrieving satisfactory results to fulfill a single information need. Meanwhile, it is also a common phenomenon to see a user type queries on unrelated topics in a single session. In order to study PubMed users' search strategies, it is necessary to be able to automatically separate unrelated queries and group together related queries. Here, we report a novel approach combining both lexical and contextual analyses for segmenting PubMed query sessions and identifying related queries and compare its performance with the previous approach based solely on concept mapping. We experimented with our integrated approach on sample data consisting of 1539 pairs of consecutive user queries in 351 user sessions. The prediction results of 1396 pairs agreed with the gold-standard annotations, achieving an overall accuracy of 90.7%. This demonstrates that our approach is significantly better than the previously published method. By applying this approach to a one day query log of PubMed, we found that a significant proportion of information needs involved more than one PubMed query, and that most of the consecutive queries for the same information need are lexically related. Finally, the proposed PubMed distance is shown to be an accurate and meaningful measure for determining the contextual similarity between biological terms. The integrated approach can play a critical role in handling real-world PubMed query log data as is demonstrated in our experiments.

  20. Master Logic Diagram: An Approach to Identify Initiating Events of HTGRs

    Science.gov (United States)

    Purba, J. H.

    2018-02-01

    Initiating events of a nuclear power plant being evaluated need to be firstly identified prior to applying probabilistic safety assessment on that plant. Various types of master logic diagrams (MLDs) have been proposedforsearching initiating events of the next generation of nuclear power plants, which have limited data and operating experiences. Those MLDs are different in the number of steps or levels and different in the basis for developing them. This study proposed another type of MLD approach to find high temperature gas cooled reactor (HTGR) initiating events. It consists of five functional steps starting from the top event representing the final objective of the safety functions to the basic event representing the goal of the MLD development, which is an initiating event. The application of the proposed approach to search for two HTGR initiating events, i.e. power turbine generator trip and loss of offsite power, is provided. The results confirmed that the proposed MLD is feasiblefor finding HTGR initiating events.

  1. A multicriteria approach to identify investment opportunities for the exploitation of the clean development mechanism

    International Nuclear Information System (INIS)

    Diakoulaki, D.; Georgiou, P.; Tourkolias, C.; Georgopoulou, E.; Lalas, D.; Mirasgedis, S.; Sarafidis, Y.

    2007-01-01

    The aim of the present paper is to investigate the prospects for the exploitation of the Kyoto Protocol's Clean Development Mechanism (CDM) in Greece. The paper is addressing 3 questions: in which country, what kind of investment, with which economic and environmental return? The proposed approach is based on a multicriteria analysis for identifying priority countries and interesting investment opportunities in each priority country. These opportunities are then evaluated through a conventional financial analysis in order to assess their economic and environmental attractiveness. To this purpose, the IRR of a typical project in each investment category is calculated by taking into account country-specific parameters, such as baseline emission factors, load factors, costs, energy prices etc. The results reveal substantial differences in the economic and environmental return of different types of projects in different host-countries and show that for the full exploitation of the CDM a multifaceted approach to decision-making is necessary

  2. Interpretative approaches to identifying sources of hydrocarbons in complex contaminated environments

    International Nuclear Information System (INIS)

    Sauer, T.C.; Brown, J.S.; Boehm, P.D.

    1993-01-01

    Recent advances in analytical instrumental hardware and software have permitted the use of more sophisticated approaches in identifying or fingerprinting sources of hydrocarbons in complex matrix environments. In natural resource damage assessments and contaminated site investigations of both terrestrial and aquatic environments, chemical fingerprinting has become an important interpretative tool. The alkyl homologues of the major polycyclic and heterocyclic aromatic hydrocarbons (e.g., phenanthrenes/anthracenes, dibenzothiophenes, chrysenes) have been found to the most valuable hydrocarbons in differentiating hydrocarbon sources, but there are other hydrocarbon analytes, such as the chemical biomarkers steranes and triterpanes, and alkyl homologues of benzene, and chemical methodologies, such as scanning UV fluorescence, that have been found to be useful in certain environments. This presentation will focus on recent data interpretative approaches for hydrocarbon source identification assessments. Selection of appropriate targets analytes and data quality requirements will be discussed and example cases including the Arabian Gulf War oil spill results will be presented

  3. Identifying reports of randomized controlled trials (RCTs) via a hybrid machine learning and crowdsourcing approach.

    Science.gov (United States)

    Wallace, Byron C; Noel-Storr, Anna; Marshall, Iain J; Cohen, Aaron M; Smalheiser, Neil R; Thomas, James

    2017-11-01

    Identifying all published reports of randomized controlled trials (RCTs) is an important aim, but it requires extensive manual effort to separate RCTs from non-RCTs, even using current machine learning (ML) approaches. We aimed to make this process more efficient via a hybrid approach using both crowdsourcing and ML. We trained a classifier to discriminate between citations that describe RCTs and those that do not. We then adopted a simple strategy of automatically excluding citations deemed very unlikely to be RCTs by the classifier and deferring to crowdworkers otherwise. Combining ML and crowdsourcing provides a highly sensitive RCT identification strategy (our estimates suggest 95%-99% recall) with substantially less effort (we observed a reduction of around 60%-80%) than relying on manual screening alone. Hybrid crowd-ML strategies warrant further exploration for biomedical curation/annotation tasks. © The Author 2017. Published by Oxford University Press on behalf of the American Medical Informatics Association.

  4. Identifying western yellow-billed cuckoo breeding habitat with a dual modelling approach

    Science.gov (United States)

    Johnson, Matthew J.; Hatten, James R.; Holmes, Jennifer A.; Shafroth, Patrick B.

    2017-01-01

    The western population of the yellow-billed cuckoo (Coccyzus americanus) was recently listed as threatened under the federal Endangered Species Act. Yellow-billed cuckoo conservation efforts require the identification of features and area requirements associated with high quality, riparian forest habitat at spatial scales that range from nest microhabitat to landscape, as well as lower-suitability areas that can be enhanced or restored. Spatially explicit models inform conservation efforts by increasing ecological understanding of a target species, especially at landscape scales. Previous yellow-billed cuckoo modelling efforts derived plant-community maps from aerial photography, an expensive and oftentimes inconsistent approach. Satellite models can remotely map vegetation features (e.g., vegetation density, heterogeneity in vegetation density or structure) across large areas with near perfect repeatability, but they usually cannot identify plant communities. We used aerial photos and satellite imagery, and a hierarchical spatial scale approach, to identify yellow-billed cuckoo breeding habitat along the Lower Colorado River and its tributaries. Aerial-photo and satellite models identified several key features associated with yellow-billed cuckoo breeding locations: (1) a 4.5 ha core area of dense cottonwood-willow vegetation, (2) a large native, heterogeneously dense forest (72 ha) around the core area, and (3) moderately rough topography. The odds of yellow-billed cuckoo occurrence decreased rapidly as the amount of tamarisk cover increased or when cottonwood-willow vegetation was limited. We achieved model accuracies of 75–80% in the project area the following year after updating the imagery and location data. The two model types had very similar probability maps, largely predicting the same areas as high quality habitat. While each model provided unique information, a dual-modelling approach provided a more complete picture of yellow-billed cuckoo habitat

  5. A multi-criteria decision making approach to identify a vaccine formulation.

    Science.gov (United States)

    Dewé, Walthère; Durand, Christelle; Marion, Sandie; Oostvogels, Lidia; Devaster, Jeanne-Marie; Fourneau, Marc

    2016-01-01

    This article illustrates the use of a multi-criteria decision making approach, based on desirability functions, to identify an appropriate adjuvant composition for an influenza vaccine to be used in elderly. The proposed adjuvant system contained two main elements: monophosphoryl lipid and α-tocopherol with squalene in an oil/water emulsion. The objective was to elicit a stronger immune response while maintaining an acceptable reactogenicity and safety profile. The study design, the statistical models, the choice of the desirability functions, the computation of the overall desirability index, and the assessment of the robustness of the ranking are all detailed in this manuscript.

  6. Constructing New Theory for Identifying Students with Emotional Disturbance: A Constructivist Approach to Grounded Theory

    Directory of Open Access Journals (Sweden)

    Dori Barnett

    2012-06-01

    Full Text Available A grounded theory study that examined how practitioners in a county alternative and correctional education setting identify youth with emotional and behavioral difficulties for special education services provides an exemplar for a constructivist approach to grounded theory methodology. Discussion focuses on how a constructivist orientation to grounded theory methodology informed research decisions, shaped the development of the emergent grounded theory, and prompted a way of thinking about data collection and analysis. Implications for future research directions and policy and practice in the field of special and alternative education are discussed.

  7. Identifying approaches for assessing methodological and reporting quality of systematic reviews

    DEFF Research Database (Denmark)

    Pussegoda, Kusala; Turner, Lucy; Garritty, Chantelle

    2017-01-01

    there are potential gaps in research best-practice guidance materials. The aims of this study are to identify reports assessing the methodological quality (MQ) and/or reporting quality (RQ) of a cohort of SRs and to assess their number, general characteristics, and approaches to 'quality' assessment over time......BACKGROUND: The methodological quality and completeness of reporting of the systematic reviews (SRs) is fundamental to optimal implementation of evidence-based health care and the reduction of research waste. Methods exist to appraise SRs yet little is known about how they are used in SRs or where...... or reporting guidelines used as proxy to assess RQ were used in 80% (61/76) of identified reports. These included two reporting guidelines (PRISMA and QUOROM) and five quality assessment tools (AMSTAR, R-AMSTAR, OQAQ, Mulrow, Sacks) and GRADE criteria. The remaining 24% (18/76) of reports developed their own...

  8. Identifying Mother-Child Interaction Styles Using a Person-Centered Approach.

    Science.gov (United States)

    Nelson, Jackie A; O'Brien, Marion; Grimm, Kevin J; Leerkes, Esther M

    2014-05-01

    Parent-child conflict in the context of a supportive relationship has been discussed as a potentially constructive interaction pattern; the current study is the first to test this using a holistic analytic approach. Interaction styles, defined as mother-child conflict in the context of maternal sensitivity, were identified and described with demographic and stress-related characteristics of families. Longitudinal associations were tested between interaction styles and children's later social competence. Participants included 814 partnered mothers with a first-grade child. Latent profile analysis identified agreeable , dynamic , and disconnected interaction styles. Mothers' intimacy with a partner, depressive symptoms, and authoritarian childrearing beliefs, along with children's later conflict with a best friend and externalizing problems, were associated with group membership. Notably, the dynamic style, characterized by high sensitivity and high conflict, included families who experienced psychological and relational stressors. Findings are discussed with regard to how family stressors shape parent-child interaction patterns.

  9. 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.

  10. Identifying barriers to and facilitators of tuberculosis contact investigation in Kampala, Uganda: a behavioral approach.

    Science.gov (United States)

    Ayakaka, Irene; Ackerman, Sara; Ggita, Joseph M; Kajubi, Phoebe; Dowdy, David; Haberer, Jessica E; Fair, Elizabeth; Hopewell, Philip; Handley, Margaret A; Cattamanchi, Adithya; Katamba, Achilles; Davis, J Lucian

    2017-03-09

    The World Health Organization recommends routine household tuberculosis contact investigation in high-burden countries but adoption has been limited. We sought to identify barriers to and facilitators of TB contact investigation during its introduction in Kampala, Uganda. We collected cross-sectional qualitative data through focus group discussions and interviews with stakeholders, addressing three core activities of contact investigation: arranging household screening visits through index TB patients, visiting households to screen contacts and refer them to clinics, and evaluating at-risk contacts coming to clinics. We analyzed the data using a validated theory of behavior change, the Capability, Opportunity, and Motivation determine Behavior (COM-B) model, and sought to identify targeted interventions using the related Behavior Change Wheel implementation framework. We led seven focus-group discussions with 61 health-care workers, two with 21 lay health workers (LHWs), and one with four household contacts of newly diagnosed TB patients. We, in addition, performed 32 interviews with household contacts from 14 households of newly diagnosed TB patients. Commonly noted barriers included stigma, limited knowledge about TB among contacts, insufficient time and space in clinics for counselling, mistrust of health-center staff among index patients and contacts, and high travel costs for LHWs and contacts. The most important facilitators identified were the personalized and enabling services provided by LHWs. We identified education, persuasion, enablement, modeling of health-positive behaviors, incentivization, and restructuring of the service environment as relevant intervention functions with potential to alleviate barriers to and enhance facilitators of TB contact investigation. The use of a behavioral theory and a validated implementation framework provided a comprehensive approach for systematically identifying barriers to and facilitators of TB contact

  11. An innovative and integrated approach based on DNA walking to identify unauthorised GMOs.

    Science.gov (United States)

    Fraiture, Marie-Alice; Herman, Philippe; Taverniers, Isabel; De Loose, Marc; Deforce, Dieter; Roosens, Nancy H

    2014-03-15

    In the coming years, the frequency of unauthorised genetically modified organisms (GMOs) being present in the European food and feed chain will increase significantly. Therefore, we have developed a strategy to identify unauthorised GMOs containing a pCAMBIA family vector, frequently present in transgenic plants. This integrated approach is performed in two successive steps on Bt rice grains. First, the potential presence of unauthorised GMOs is assessed by the qPCR SYBR®Green technology targeting the terminator 35S pCAMBIA element. Second, its presence is confirmed via the characterisation of the junction between the transgenic cassette and the rice genome. To this end, a DNA walking strategy is applied using a first reverse primer followed by two semi-nested PCR rounds using primers that are each time nested to the previous reverse primer. This approach allows to rapidly identify the transgene flanking region and can easily be implemented by the enforcement laboratories. Copyright © 2013 The Authors. Published by Elsevier Ltd.. All rights reserved.

  12. Accurately identifying patients who are excellent candidates or unsuitable for a medication: a novel approach

    Directory of Open Access Journals (Sweden)

    South C

    2017-12-01

    Full Text Available Charles South,1–3 A John Rush,4,* Thomas J Carmody,1–3 Manish K Jha,1,2 Madhukar H Trivedi1,2,*1Center for Depression Research and Clinical Care, 2Department of Psychiatry, 3Department of Clinical Sciences, University of Texas Southwestern Medical Center, Dallas, TX, USA; 4Department of Psychiatry and Behavioral Sciences, Duke-National University of Singapore, Singapore; Duke Medical School, Durham, NC, USA*These authors contributed equally to this work Objective: The objective of the study was to determine whether a unique analytic approach – as a proof of concept – could identify individual depressed outpatients (using 30 baseline clinical and demographic variables who are very likely (75% certain to not benefit (NB or to remit (R, accepting that without sufficient certainty, no prediction (NP would be made.Methods: Patients from the Combining Medications to Enhance Depression Outcomes trial treated with escitalopram (S-CIT + placebo (n=212 or S-CIT + bupropion-SR (n=206 were analyzed separately to assess replicability. For each treatment, the elastic net was used to identify subsets of predictive baseline measures for R and NB, separately. Two different equations that estimate the likelihood of remission and no benefit were developed for each patient. The ratio of these two numbers characterized likely outcomes for each patient.Results: The two treatment cells had comparable rates of remission (40% and no benefit (22%. In S-CIT + bupropion-SR, 11 were predicted NB of which 82% were correct; 26 were predicted R – 85% correct (169 had NP. For S-CIT + placebo, 13 were predicted NB – 69% correct; 44 were predicted R – 75% correct (155 were NP. Overall, 94/418 (22% patients were identified with a meaningful degree of certainty (69%–85% correct. Different variable sets with some overlap were predictive of remission and no benefit within and across treatments, despite comparable outcomes.Conclusion: In two separate analyses with two

  13. A Systematic Approach to Identify Sources of Abnormal Interior Noise for a High-Speed Train

    Directory of Open Access Journals (Sweden)

    Jie Zhang

    2018-01-01

    Full Text Available A systematic approach to identify sources of abnormal interior noise occurring in a high-speed train is presented and applied in this paper to resolve a particular noise issue. This approach is developed based on a number of previous dealings with similar noise problems. The particular noise issue occurs in a Chinese high-speed train. It is measured that there is a difference of 7 dB(A in overall Sound Pressure Level (SPL between two nominally identical VIP cabins at 250 km/h. The systematic approach is applied to identify the root cause of the 7 dB(A difference. Well planned measurements are performed in both the VIP cabins. Sound pressure contributions, either in terms of frequency band or in terms of facing area, are analyzed. Order analysis is also carried out. Based on these analyses, it is found that the problematic frequency is the sleeper passing frequency of the train, and an area on the roof contributes the most. In order to determine what causes that area to be the main contributor without disassembling the structure of the roof, measured noise and vibration data for different train speeds are further analyzed. It is then reasoned that roof is the main contributor caused by sound pressure behind the panel. Up to this point, panels of the roof are removed, revealing that a hole of 300 cm2 for running cables is presented behind the red area without proper sound insulation. This study can provide a basis for abnormal interior noise analysis and control of high-speed trains.

  14. Identifying functional reorganization of spelling networks: an individual peak probability comparison approach

    Science.gov (United States)

    Purcell, Jeremy J.; Rapp, Brenda

    2013-01-01

    Previous research has shown that damage to the neural substrates of orthographic processing can lead to functional reorganization during reading (Tsapkini et al., 2011); in this research we ask if the same is true for spelling. To examine the functional reorganization of spelling networks we present a novel three-stage Individual Peak Probability Comparison (IPPC) analysis approach for comparing the activation patterns obtained during fMRI of spelling in a single brain-damaged individual with dysgraphia to those obtained in a set of non-impaired control participants. The first analysis stage characterizes the convergence in activations across non-impaired control participants by applying a technique typically used for characterizing activations across studies: Activation Likelihood Estimate (ALE) (Turkeltaub et al., 2002). This method was used to identify locations that have a high likelihood of yielding activation peaks in the non-impaired participants. The second stage provides a characterization of the degree to which the brain-damaged individual's activations correspond to the group pattern identified in Stage 1. This involves performing a Mahalanobis distance statistics analysis (Tsapkini et al., 2011) that compares each of a control group's peak activation locations to the nearest peak generated by the brain-damaged individual. The third stage evaluates the extent to which the brain-damaged individual's peaks are atypical relative to the range of individual variation among the control participants. This IPPC analysis allows for a quantifiable, statistically sound method for comparing an individual's activation pattern to the patterns observed in a control group and, thus, provides a valuable tool for identifying functional reorganization in a brain-damaged individual with impaired spelling. Furthermore, this approach can be applied more generally to compare any individual's activation pattern with that of a set of other individuals. PMID:24399981

  15. A Multiomics Approach to Identify Genes Associated with Childhood Asthma Risk and Morbidity.

    Science.gov (United States)

    Forno, Erick; Wang, Ting; Yan, Qi; Brehm, John; Acosta-Perez, Edna; Colon-Semidey, Angel; Alvarez, Maria; Boutaoui, Nadia; Cloutier, Michelle M; Alcorn, John F; Canino, Glorisa; Chen, Wei; Celedón, Juan C

    2017-10-01

    Childhood asthma is a complex disease. In this study, we aim to identify genes associated with childhood asthma through a multiomics "vertical" approach that integrates multiple analytical steps using linear and logistic regression models. In a case-control study of childhood asthma in Puerto Ricans (n = 1,127), we used adjusted linear or logistic regression models to evaluate associations between several analytical steps of omics data, including genome-wide (GW) genotype data, GW methylation, GW expression profiling, cytokine levels, asthma-intermediate phenotypes, and asthma status. At each point, only the top genes/single-nucleotide polymorphisms/probes/cytokines were carried forward for subsequent analysis. In step 1, asthma modified the gene expression-protein level association for 1,645 genes; pathway analysis showed an enrichment of these genes in the cytokine signaling system (n = 269 genes). In steps 2-3, expression levels of 40 genes were associated with intermediate phenotypes (asthma onset age, forced expiratory volume in 1 second, exacerbations, eosinophil counts, and skin test reactivity); of those, methylation of seven genes was also associated with asthma. Of these seven candidate genes, IL5RA was also significant in analytical steps 4-8. We then measured plasma IL-5 receptor α levels, which were associated with asthma age of onset and moderate-severe exacerbations. In addition, in silico database analysis showed that several of our identified IL5RA single-nucleotide polymorphisms are associated with transcription factors related to asthma and atopy. This approach integrates several analytical steps and is able to identify biologically relevant asthma-related genes, such as IL5RA. It differs from other methods that rely on complex statistical models with various assumptions.

  16. Calibrated photostimulated luminescence is an effective approach to identify irradiated orange during storage

    International Nuclear Information System (INIS)

    Jo, Yunhee; Sanyal, Bhaskar; Chung, Namhyeok; Lee, Hyun-Gyu; Park, Yunji; Park, Hae-Jun; Kwon, Joong-Ho

    2015-01-01

    Photostimulated luminescence (PSL) has been employed as a fast screening method for various irradiated foods. In this study the potential use of PSL was evaluated to identify oranges irradiated with gamma ray, electron beam and X-ray (0–2 kGy) and stored under different conditions for 6 weeks. The effects of light conditions (natural light, artificial light, and dark) and storage temperatures (4 and 20 °C) on PSL photon counts (PCs) during post-irradiation periods were studied. Non-irradiated samples always showed negative values of PCs, while irradiated oranges exhibited intermediate results after first PSL measurements. However, the irradiated samples had much higher PCs. The PCs of all the samples declined as the storage time increased. Calibrated second PSL measurements showed PSL ratio <10 for the irradiated samples after 3 weeks of irradiation confirming their irradiation status in all the storage conditions. Calibrated PSL and sample storage in dark at 4 °C were found out to be most suitable approaches to identify irradiated oranges during storage. - Highlights: • Photostimulatedluminescence (PSL) was studied to identify irradiated orange for quarantine application. • PSL detection efficiency was compared amonggamma,electron, and X irradiation during shelf-life of oranges • PSL properties of samples were characterized by standard samples • Calibrated PSL gave a clear verdict on irradiation extending potential of PSL technique

  17. Structured methodology review identified seven (RETREAT) criteria for selecting qualitative evidence synthesis approaches.

    Science.gov (United States)

    Booth, Andrew; Noyes, Jane; Flemming, Kate; Gerhardus, Ansgar; Wahlster, Philip; van der Wilt, Gert Jan; Mozygemba, Kati; Refolo, Pietro; Sacchini, Dario; Tummers, Marcia; Rehfuess, Eva

    2018-07-01

    To compare and contrast different methods of qualitative evidence synthesis (QES) against criteria identified from the literature and to map their attributes to inform selection of the most appropriate QES method to answer research questions addressed by qualitative research. Electronic databases, citation searching, and a study register were used to identify studies reporting QES methods. Attributes compiled from 26 methodological papers (2001-2014) were used as a framework for data extraction. Data were extracted into summary tables by one reviewer and then considered within the author team. We identified seven considerations determining choice of methods from the methodological literature, encapsulated within the mnemonic Review question-Epistemology-Time/Timescale-Resources-Expertise-Audience and purpose-Type of data. We mapped 15 different published QES methods against these seven criteria. The final framework focuses on stand-alone QES methods but may also hold potential when integrating quantitative and qualitative data. These findings offer a contemporary perspective as a conceptual basis for future empirical investigation of the advantages and disadvantages of different methods of QES. It is hoped that this will inform appropriate selection of QES approaches. Copyright © 2018 Elsevier Inc. All rights reserved.

  18. Matrine Is Identified as a Novel Macropinocytosis Inducer by a Network Target Approach

    Directory of Open Access Journals (Sweden)

    Bo Zhang

    2018-01-01

    Full Text Available Comprehensively understanding pharmacological functions of natural products is a key issue to be addressed for the discovery of new drugs. Unlike some single-target drugs, natural products always exert diverse therapeutic effects through acting on a “network” that consists of multiple targets, making it necessary to develop a systematic approach, e.g., network pharmacology, to reveal pharmacological functions of natural products and infer their mechanisms of action. In this work, to identify the “network target” of a natural product, we perform a functional analysis of matrine, a marketed drug in China extracted from a medical herb Ku-Shen (Radix Sophorae Flavescentis. Here, the network target of matrine was firstly predicted by drugCIPHER, a genome-wide target prediction method. Based on the network target of matrine, we performed a functional gene set enrichment analysis to computationally identify the potential pharmacological functions of matrine, most of which are supported by the literature evidence, including neurotoxicity and neuropharmacological activities of matrine. Furthermore, computational results demonstrated that matrine has the potential for the induction of macropinocytosis and the regulation of ATP metabolism. Our experimental data revealed that the large vesicles induced by matrine are consistent with the typical characteristics of macropinosome. Our verification results also suggested that matrine could decrease cellular ATP level. These findings demonstrated the availability and effectiveness of the network target strategy for identifying the comprehensive pharmacological functions of natural products.

  19. Aspergillus Cell Wall Chitin Induces Anti- and Proinflammatory Cytokines in Human PBMCs via the Fc-γ Receptor/Syk/PI3K Pathway

    Science.gov (United States)

    Becker, K. L.; Aimanianda, V.; Wang, X.; Gresnigt, M. S.; Ammerdorffer, A.; Jacobs, C. W.; Gazendam, R. P.; Joosten, L. A. B.; Netea, M. G.

    2016-01-01

    ABSTRACT Chitin is an important cell wall component of Aspergillus fumigatus conidia, of which hundreds are inhaled on a daily basis. Previous studies have shown that chitin has both anti- and proinflammatory properties; however the exact mechanisms determining the inflammatory signature of chitin are poorly understood, especially in human immune cells. Human peripheral blood mononuclear cells were isolated from healthy volunteers and stimulated with chitin from Aspergillus fumigatus. Transcription and production of the proinflammatory cytokine interleukin-1β (IL-1β) and the anti-inflammatory cytokine IL-1 receptor antagonist (IL-1Ra) were measured from the cell culture supernatant by quantitative PCR (qPCR) or enzyme-linked immunosorbent assay (ELISA), respectively. Chitin induced an anti-inflammatory signature characterized by the production of IL-1Ra in the presence of human serum, which was abrogated in immunoglobulin-depleted serum. Fc-γ-receptor-dependent recognition and phagocytosis of IgG-opsonized chitin was identified as a novel IL-1Ra-inducing mechanism by chitin. IL-1Ra production induced by chitin was dependent on Syk kinase and phosphatidylinositol 3-kinase (PI3K) activation. In contrast, costimulation of chitin with the pattern recognition receptor (PRR) ligands lipopolysaccharide, Pam3Cys, or muramyl dipeptide, but not β-glucan, had synergistic effects on the induction of proinflammatory cytokines by human peripheral blood mononuclear cells (PBMCs). In conclusion, chitin can have both pro- and anti-inflammatory properties, depending on the presence of pathogen-associated molecular patterns and immunoglobulins, thus explaining the various inflammatory signatures reported for chitin. PMID:27247234

  20. An integrative -omics approach to identify functional sub-networks in human colorectal cancer.

    Directory of Open Access Journals (Sweden)

    Rod K Nibbe

    2010-01-01

    Full Text Available Emerging evidence indicates that gene products implicated in human cancers often cluster together in "hot spots" in protein-protein interaction (PPI networks. Additionally, small sub-networks within PPI networks that demonstrate synergistic differential expression with respect to tumorigenic phenotypes were recently shown to be more accurate classifiers of disease progression when compared to single targets identified by traditional approaches. However, many of these studies rely exclusively on mRNA expression data, a useful but limited measure of cellular activity. Proteomic profiling experiments provide information at the post-translational level, yet they generally screen only a limited fraction of the proteome. Here, we demonstrate that integration of these complementary data sources with a "proteomics-first" approach can enhance the discovery of candidate sub-networks in cancer that are well-suited for mechanistic validation in disease. We propose that small changes in the mRNA expression of multiple genes in the neighborhood of a protein-hub can be synergistically associated with significant changes in the activity of that protein and its network neighbors. Further, we hypothesize that proteomic targets with significant fold change between phenotype and control may be used to "seed" a search for small PPI sub-networks that are functionally associated with these targets. To test this hypothesis, we select proteomic targets having significant expression changes in human colorectal cancer (CRC from two independent 2-D gel-based screens. Then, we use random walk based models of network crosstalk and develop novel reference models to identify sub-networks that are statistically significant in terms of their functional association with these proteomic targets. Subsequently, using an information-theoretic measure, we evaluate synergistic changes in the activity of identified sub-networks based on genome-wide screens of mRNA expression in CRC

  1. An affinity pull-down approach to identify the plant cyclic nucleotide interactome

    KAUST Repository

    Donaldson, Lara Elizabeth; Meier, Stuart Kurt

    2013-01-01

    Cyclic nucleotides (CNs) are intracellular second messengers that play an important role in mediating physiological responses to environmental and developmental signals, in species ranging from bacteria to humans. In response to these signals, CNs are synthesized by nucleotidyl cyclases and then act by binding to and altering the activity of downstream target proteins known as cyclic nucleotide-binding proteins (CNBPs). A number of CNBPs have been identified across kingdoms including transcription factors, protein kinases, phosphodiesterases, and channels, all of which harbor conserved CN-binding domains. In plants however, few CNBPs have been identified as homology searches fail to return plant sequences with significant matches to known CNBPs. Recently, affinity pull-down techniques have been successfully used to identify CNBPs in animals and have provided new insights into CN signaling. The application of these techniques to plants has not yet been extensively explored and offers an alternative approach toward the unbiased discovery of novel CNBP candidates in plants. Here, an affinity pull-down technique for the identification of the plant CN interactome is presented. In summary, the method involves an extraction of plant proteins which is incubated with a CN-bait, followed by a series of increasingly stringent elutions that eliminates proteins in a sequential manner according to their affinity to the bait. The eluted and bait-bound proteins are separated by one-dimensional gel electrophoresis, excised, and digested with trypsin after which the resultant peptides are identified by mass spectrometry - techniques that are commonplace in proteomics experiments. The discovery of plant CNBPs promises to provide valuable insight into the mechanism of CN signal transduction in plants. © Springer Science+Business Media New York 2013.

  2. Identifying key performance indicators for nursing and midwifery care using a consensus approach.

    Science.gov (United States)

    McCance, Tanya; Telford, Lorna; Wilson, Julie; Macleod, Olive; Dowd, Audrey

    2012-04-01

    The aim of this study was to gain consensus on key performance indicators that are appropriate and relevant for nursing and midwifery practice in the current policy context. There is continuing demand to demonstrate effectiveness and efficiency in health and social care and to communicate this at boardroom level. Whilst there is substantial literature on the use of clinical indicators and nursing metrics, there is less evidence relating to indicators that reflect the patient experience. A consensus approach was used to identify relevant key performance indicators. A nominal group technique was used comprising two stages: a workshop involving all grades of nursing and midwifery staff in two HSC trusts in Northern Ireland (n = 50); followed by a regional Consensus Conference (n = 80). During the workshop, potential key performance indicators were identified. This was used as the basis for the Consensus Conference, which involved two rounds of consensus. Analysis was based on aggregated scores that were then ranked. Stage one identified 38 potential indicators and stage two prioritised the eight top-ranked indicators as a core set for nursing and midwifery. The relevance and appropriateness of these indicators were confirmed with nurses and midwives working in a range of settings and from the perspective of service users. The eight indicators identified do not conform to the majority of other nursing metrics generally reported in the literature. Furthermore, they are strategically aligned to work on the patient experience and are reflective of the fundamentals of nursing and midwifery practice, with the focus on person-centred care. Nurses and midwives have a significant contribution to make in determining the extent to which these indicators are achieved in practice. Furthermore, measurement of such indicators provides an opportunity to evidence of the unique impact of nursing/midwifery care on the patient experience. © 2011 Blackwell Publishing Ltd.

  3. An affinity pull-down approach to identify the plant cyclic nucleotide interactome

    KAUST Repository

    Donaldson, Lara Elizabeth

    2013-09-03

    Cyclic nucleotides (CNs) are intracellular second messengers that play an important role in mediating physiological responses to environmental and developmental signals, in species ranging from bacteria to humans. In response to these signals, CNs are synthesized by nucleotidyl cyclases and then act by binding to and altering the activity of downstream target proteins known as cyclic nucleotide-binding proteins (CNBPs). A number of CNBPs have been identified across kingdoms including transcription factors, protein kinases, phosphodiesterases, and channels, all of which harbor conserved CN-binding domains. In plants however, few CNBPs have been identified as homology searches fail to return plant sequences with significant matches to known CNBPs. Recently, affinity pull-down techniques have been successfully used to identify CNBPs in animals and have provided new insights into CN signaling. The application of these techniques to plants has not yet been extensively explored and offers an alternative approach toward the unbiased discovery of novel CNBP candidates in plants. Here, an affinity pull-down technique for the identification of the plant CN interactome is presented. In summary, the method involves an extraction of plant proteins which is incubated with a CN-bait, followed by a series of increasingly stringent elutions that eliminates proteins in a sequential manner according to their affinity to the bait. The eluted and bait-bound proteins are separated by one-dimensional gel electrophoresis, excised, and digested with trypsin after which the resultant peptides are identified by mass spectrometry - techniques that are commonplace in proteomics experiments. The discovery of plant CNBPs promises to provide valuable insight into the mechanism of CN signal transduction in plants. © Springer Science+Business Media New York 2013.

  4. Novel VEGFR-2 kinase inhibitor identified by the back-to-front approach

    Science.gov (United States)

    Sanphanya, Kingkan; Phowichit, Suwadee; Wattanapitayakul, Suvara K.; Fokin, Valery V.; Vajragupta, Opa

    2013-01-01

    Novel lead was developed as VEGFR-2 inhibitor by the back-to-front approach. Docking experiment guided that the 3-chloromethylphenylurea motif occupied the back pocket of the VEGFR-2 kinase. The attempt to enhance the binding affinity of 1 was made by expanding structure to access the front pocket using triazole as linker. A library of 1,4-(disubsituted)-1H-1,2,3-triazoles were screened in silico and one lead compound (VH02) was identified with enzymatic IC50 against VEGFR-2 of 0.56 μM. VH02 showed antiangiogenic effect by inhibiting the tube formation of HUVEC cells (EA.hy926) at 0.3 μM which was 13 times lower than its cytotoxic dose. The enzymatic and cellular activities suggested the potential of VH02 as a lead for further optimization. PMID:23562241

  5. Identifying niche-mediated regulatory factors of stem cell phenotypic state: a systems biology approach.

    Science.gov (United States)

    Ravichandran, Srikanth; Del Sol, Antonio

    2017-02-01

    Understanding how the cellular niche controls the stem cell phenotype is often hampered due to the complexity of variegated niche composition, its dynamics, and nonlinear stem cell-niche interactions. Here, we propose a systems biology view that considers stem cell-niche interactions as a many-body problem amenable to simplification by the concept of mean field approximation. This enables approximation of the niche effect on stem cells as a constant field that induces sustained activation/inhibition of specific stem cell signaling pathways in all stem cells within heterogeneous populations exhibiting the same phenotype (niche determinants). This view offers a new basis for the development of single cell-based computational approaches for identifying niche determinants, which has potential applications in regenerative medicine and tissue engineering. © 2017 The Authors. FEBS Letters published by John Wiley & Sons Ltd on behalf of Federation of European Biochemical Societies.

  6. Metabolomic approach to identifying bioactive compounds in berries: advances toward fruit nutritional enhancement.

    Science.gov (United States)

    Stewart, Derek; McDougall, Gordon J; Sungurtas, Julie; Verrall, Susan; Graham, Julie; Martinussen, Inger

    2007-06-01

    Plant polyphenolics continue to be the focus of attention with regard to their putative impact on human health. An increasing and ageing human population means that the focus on nutrition and nutritional enhancement or optimisation of our foodstuffs is paramount. Using the raspberry as a model, we have shown how modern metabolic profiling approaches can be used to identify the changes in the level of beneficial polyphenolics in fruit breeding segregating populations and how the level of these components is determined by genetic and/or environmental control. Interestingly, the vitamin C content appeared to be significantly influenced by environment (growth conditions) whilst the content of the polyphenols such as cyanidin, pelargonidin and quercetin glycosides appeared much more tightly regulated, suggesting a rigorous genetic control. Preliminary metabolic profiling showed that the fruit polyphenolic profiles divided into two gross groups segregating on the basis of relative levels of cyanidin-3-sophoroside and cyanidin-3-rutinoside, compounds implicated as conferring human health benefits.

  7. Identifying the critical financial ratios for stocks evaluation: A fuzzy delphi approach

    Science.gov (United States)

    Mokhtar, Mazura; Shuib, Adibah; Mohamad, Daud

    2014-12-01

    Stocks evaluation has always been an interesting and challenging problem for both researchers and practitioners. Generally, the evaluation can be made based on a set of financial ratios. Nevertheless, there are a variety of financial ratios that can be considered and if all ratios in the set are placed into the evaluation process, data collection would be more difficult and time consuming. Thus, the objective of this paper is to identify the most important financial ratios upon which to focus in order to evaluate the stock's performance. For this purpose, a survey was carried out using an approach which is based on an expert judgement, namely the Fuzzy Delphi Method (FDM). The results of this study indicated that return on equity, return on assets, net profit margin, operating profit margin, earnings per share and debt to equity are the most important ratios.

  8. Identifying Personal Goals of Patients With Long Term Condition: A Service Design Thinking Approach.

    Science.gov (United States)

    Lee, Eunji; Gammon, Deede

    2017-01-01

    Care for patients with long term conditions is often characterized as fragmented and ineffective, and fails to engage the resources of patients and their families in the care process. Information and communication technology can potentially help bridge the gap between patients' lives and resources and services provided by professionals. However, there is little attention on how to identify and incorporate the patients' individual needs, values, preferences and care goals into the digitally driven care settings. We conducted a case study with healthcare professionals and patients participated applying a service design thinking approach. The participants could elaborate some personal goals of patients with long term condition which can potentially be incorporated in digitally driven care plans using examples from their own experiences.

  9. A Complementary Bioinformatics Approach to Identify Potential Plant Cell Wall Glycosyltransferase-Encoding Genes

    DEFF Research Database (Denmark)

    Egelund, Jack; Skjøt, Michael; Geshi, Naomi

    2004-01-01

    Plant cell wall (CW) synthesizing enzymes can be divided into the glycan (i.e. cellulose and callose) synthases, which are multimembrane spanning proteins located at the plasma membrane, and the glycosyltransferases (GTs), which are Golgi localized single membrane spanning proteins, believed....... Although much is known with regard to composition and fine structures of the plant CW, only a handful of CW biosynthetic GT genes-all classified in the CAZy system-have been characterized. In an effort to identify CW GTs that have not yet been classified in the CAZy database, a simple bioinformatics...... approach was adopted. First, the entire Arabidopsis proteome was run through the Transmembrane Hidden Markov Model 2.0 server and proteins containing one or, more rarely, two transmembrane domains within the N-terminal 150 amino acids were collected. Second, these sequences were submitted...

  10. A new simplex chemometric approach to identify olive oil blends with potentially high traceability.

    Science.gov (United States)

    Semmar, N; Laroussi-Mezghani, S; Grati-Kamoun, N; Hammami, M; Artaud, J

    2016-10-01

    Olive oil blends (OOBs) are complex matrices combining different cultivars at variable proportions. Although qualitative determinations of OOBs have been subjected to several chemometric works, quantitative evaluations of their contents remain poorly developed because of traceability difficulties concerning co-occurring cultivars. Around this question, we recently published an original simplex approach helping to develop predictive models of the proportions of co-occurring cultivars from chemical profiles of resulting blends (Semmar & Artaud, 2015). Beyond predictive model construction and validation, this paper presents an extension based on prediction errors' analysis to statistically define the blends with the highest predictability among all the possible ones that can be made by mixing cultivars at different proportions. This provides an interesting way to identify a priori labeled commercial products with potentially high traceability taking into account the natural chemical variability of different constitutive cultivars. Copyright © 2016 Elsevier Ltd. All rights reserved.

  11. Market potential of nanoremediation in Europe - Market drivers and interventions identified in a deliberative scenario approach.

    Science.gov (United States)

    Bartke, Stephan; Hagemann, Nina; Harries, Nicola; Hauck, Jennifer; Bardos, Paul

    2018-04-01

    A deliberate expert-based scenario approach is applied to better understand the likely determinants of the evolution of the market for nanoparticles use in remediation in Europe until 2025. An initial set of factors had been obtained from a literature review and was complemented by a workshop and key-informant interviews. In further expert engaging formats - focus groups, workshops, conferences, surveys - this initial set of factors was condensed and engaged experts scored the factors regarding their importance for being likely to influence the market development. An interaction matrix was obtained identifying the factors being most active in shaping the market development in Europe by 2025, namely "Science-Policy-Interface" and "Validated information on nanoparticle application potential". Based on these, potential scenarios were determined and development of factors discussed. Conclusions are offered on achievable interventions to enhance nanoremediation deployment. Copyright © 2017 Elsevier B.V. All rights reserved.

  12. Xtalk: a path-based approach for identifying crosstalk between signaling pathways

    Science.gov (United States)

    Tegge, Allison N.; Sharp, Nicholas; Murali, T. M.

    2016-01-01

    Motivation: Cells communicate with their environment via signal transduction pathways. On occasion, the activation of one pathway can produce an effect downstream of another pathway, a phenomenon known as crosstalk. Existing computational methods to discover such pathway pairs rely on simple overlap statistics. Results: We present Xtalk, a path-based approach for identifying pairs of pathways that may crosstalk. Xtalk computes the statistical significance of the average length of multiple short paths that connect receptors in one pathway to the transcription factors in another. By design, Xtalk reports the precise interactions and mechanisms that support the identified crosstalk. We applied Xtalk to signaling pathways in the KEGG and NCI-PID databases. We manually curated a gold standard set of 132 crosstalking pathway pairs and a set of 140 pairs that did not crosstalk, for which Xtalk achieved an area under the receiver operator characteristic curve of 0.65, a 12% improvement over the closest competing approach. The area under the receiver operator characteristic curve varied with the pathway, suggesting that crosstalk should be evaluated on a pathway-by-pathway level. We also analyzed an extended set of 658 pathway pairs in KEGG and to a set of more than 7000 pathway pairs in NCI-PID. For the top-ranking pairs, we found substantial support in the literature (81% for KEGG and 78% for NCI-PID). We provide examples of networks computed by Xtalk that accurately recovered known mechanisms of crosstalk. Availability and implementation: The XTALK software is available at http://bioinformatics.cs.vt.edu/~murali/software. Crosstalk networks are available at http://graphspace.org/graphs?tags=2015-bioinformatics-xtalk. Contact: ategge@vt.edu, murali@cs.vt.edu Supplementary information: Supplementary data are available at Bioinformatics online. PMID:26400040

  13. Identifying Green Infrastructure from Social Media and Crowdsourcing- An Image Based Machine-Learning Approach.

    Science.gov (United States)

    Rai, A.; Minsker, B. S.

    2016-12-01

    In this work we introduce a novel dataset GRID: GReen Infrastructure Detection Dataset and a framework for identifying urban green storm water infrastructure (GI) designs (wetlands/ponds, urban trees, and rain gardens/bioswales) from social media and satellite aerial images using computer vision and machine learning methods. Along with the hydrologic benefits of GI, such as reducing runoff volumes and urban heat islands, GI also provides important socio-economic benefits such as stress recovery and community cohesion. However, GI is installed by many different parties and cities typically do not know where GI is located, making study of its impacts or siting new GI difficult. We use object recognition learning methods (template matching, sliding window approach, and Random Hough Forest method) and supervised machine learning algorithms (e.g., support vector machines) as initial screening approaches to detect potential GI sites, which can then be investigated in more detail using on-site surveys. Training data were collected from GPS locations of Flickr and Instagram image postings and Amazon Mechanical Turk identification of each GI type. Sliding window method outperformed other methods and achieved an average F measure, which is combined metric for precision and recall performance measure of 0.78.

  14. OPTICAL CROSS-CORRELATION FILTERS: AN ECONOMICAL APPROACH FOR IDENTIFYING SNe Ia AND ESTIMATING THEIR REDSHIFTS

    International Nuclear Information System (INIS)

    Scolnic, Daniel M.; Riess, Adam G.; Huber, Mark E.; Rest, Armin; Stubbs, Christoper W.; Tonry, John L.

    2009-01-01

    Large photometric surveys of transient phenomena, such as Panoramic Survey Telescope and Rapid Response System and Large Synoptic Survey Telescope, will locate thousands to millions of Type Ia supernova (SN Ia) candidates per year, a rate prohibitive for acquiring spectroscopy to determine each candidate's type and redshift. In response, we have developed an economical approach to identifying SNe Ia and their redshifts using an uncommon type of optical filter which has multiple, discontinuous passbands on a single substrate. Observation of a supernova through a specially designed pair of these 'cross-correlation filters' measures the approximate amplitude and phase of the cross-correlation between the spectrum and a SN Ia template, a quantity typically used to determine the redshift and type of a high-redshift SN Ia. Simulating the use of these filters, we obtain a sample of SNe Ia which is ∼98% pure with individual redshifts measured to σ z = 0.01 precision. The advantages of this approach over standard broadband photometric methods are that it is insensitive to reddening, independent of the color data used for subsequent distance determinations which reduce selection or interpretation bias, and because it makes use of the spectral features its reliability is greater. A great advantage over long-slit spectroscopy comes from increased throughput, enhanced multiplexing, and reduced setup time resulting in a net gain in speed of up to ∼30 times. This approach is also insensitive to host galaxy contamination. Prototype filters were built and successfully used on Magellan with LDSS-3 to characterize three SuperNova Legacy Survey candidates. We discuss how these filters can provide critical information for the upcoming photometric supernova surveys.

  15. A statistical approach for identifying the ionospheric footprint of magnetospheric boundaries from SuperDARN observations

    Directory of Open Access Journals (Sweden)

    G. Lointier

    2008-02-01

    Full Text Available Identifying and tracking the projection of magnetospheric regions on the high-latitude ionosphere is of primary importance for studying the Solar Wind-Magnetosphere-Ionosphere system and for space weather applications. By its unique spatial coverage and temporal resolution, the Super Dual Auroral Radar Network (SuperDARN provides key parameters, such as the Doppler spectral width, which allows the monitoring of the ionospheric footprint of some magnetospheric boundaries in near real-time. In this study, we present the first results of a statistical approach for monitoring these magnetospheric boundaries. The singular value decomposition is used as a data reduction tool to describe the backscattered echoes with a small set of parameters. One of these is strongly correlated with the Doppler spectral width, and can thus be used as a proxy for it. Based on this, we propose a Bayesian classifier for identifying the spectral width boundary, which is classically associated with the Polar Cap boundary. The results are in good agreement with previous studies. Two advantages of the method are: the possibility to apply it in near real-time, and its capacity to select the appropriate threshold level for the boundary detection.

  16. Integrative screening approach identifies regulators of polyploidization and targets for acute megakaryocytic leukemia

    Science.gov (United States)

    Wen, Qiang; Goldenson, Benjamin; Silver, Serena J.; Schenone, Monica; Dancik, Vladimir; Huang, Zan; Wang, Ling-Zhi; Lewis, Timothy; An, W. Frank; Li, Xiaoyu; Bray, Mark-Anthony; Thiollier, Clarisse; Diebold, Lauren; Gilles, Laure; Vokes, Martha S.; Moore, Christopher B.; Bliss-Moreau, Meghan; VerPlank, Lynn; Tolliday, Nicola J.; Mishra, Rama; Vemula, Sasidhar; Shi, Jianjian; Wei, Lei; Kapur, Reuben; Lopez, Cécile K.; Gerby, Bastien; Ballerini, Paola; Pflumio, Francoise; Gilliland, D. Gary; Goldberg, Liat; Birger, Yehudit; Izraeli, Shai; Gamis, Alan S.; Smith, Franklin O.; Woods, William G.; Taub, Jeffrey; Scherer, Christina A.; Bradner, James; Goh, Boon-Cher; Mercher, Thomas; Carpenter, Anne E.; Gould, Robert J.; Clemons, Paul A.; Carr, Steven A.; Root, David E.; Schreiber, Stuart L.; Stern, Andrew M.; Crispino, John D.

    2012-01-01

    Summary The mechanism by which cells decide to skip mitosis to become polyploid is largely undefined. Here we used a high-content image-based screen to identify small-molecule probes that induce polyploidization of megakaryocytic leukemia cells and serve as perturbagens to help understand this process. We found that dimethylfasudil (diMF, H-1152P) selectively increased polyploidization, mature cell-surface marker expression, and apoptosis of malignant megakaryocytes. A broadly applicable, highly integrated target identification approach employing proteomic and shRNA screening revealed that a major target of diMF is Aurora A kinase (AURKA), which has not been studied extensively in megakaryocytes. Moreover, we discovered that MLN8237 (Alisertib), a selective inhibitor of AURKA, induced polyploidization and expression of mature megakaryocyte markers in AMKL blasts and displayed potent anti-AMKL activity in vivo. This research provides the rationale to support clinical trials of MLN8237 and other inducers of polyploidization in AMKL. Finally, we have identified five networks of kinases that regulate the switch to polyploidy. PMID:22863010

  17. Modelling Creativity: Identifying Key Components through a Corpus-Based Approach.

    Science.gov (United States)

    Jordanous, Anna; Keller, Bill

    2016-01-01

    Creativity is a complex, multi-faceted concept encompassing a variety of related aspects, abilities, properties and behaviours. If we wish to study creativity scientifically, then a tractable and well-articulated model of creativity is required. Such a model would be of great value to researchers investigating the nature of creativity and in particular, those concerned with the evaluation of creative practice. This paper describes a unique approach to developing a suitable model of how creative behaviour emerges that is based on the words people use to describe the concept. Using techniques from the field of statistical natural language processing, we identify a collection of fourteen key components of creativity through an analysis of a corpus of academic papers on the topic. Words are identified which appear significantly often in connection with discussions of the concept. Using a measure of lexical similarity to help cluster these words, a number of distinct themes emerge, which collectively contribute to a comprehensive and multi-perspective model of creativity. The components provide an ontology of creativity: a set of building blocks which can be used to model creative practice in a variety of domains. The components have been employed in two case studies to evaluate the creativity of computational systems and have proven useful in articulating achievements of this work and directions for further research.

  18. Calibrated photostimulated luminescence is an effective approach to identify irradiated orange during storage

    Science.gov (United States)

    Jo, Yunhee; Sanyal, Bhaskar; Chung, Namhyeok; Lee, Hyun-Gyu; Park, Yunji; Park, Hae-Jun; Kwon, Joong-Ho

    2015-06-01

    Photostimulated luminescence (PSL) has been employed as a fast screening method for various irradiated foods. In this study the potential use of PSL was evaluated to identify oranges irradiated with gamma ray, electron beam and X-ray (0-2 kGy) and stored under different conditions for 6 weeks. The effects of light conditions (natural light, artificial light, and dark) and storage temperatures (4 and 20 °C) on PSL photon counts (PCs) during post-irradiation periods were studied. Non-irradiated samples always showed negative values of PCs, while irradiated oranges exhibited intermediate results after first PSL measurements. However, the irradiated samples had much higher PCs. The PCs of all the samples declined as the storage time increased. Calibrated second PSL measurements showed PSL ratio <10 for the irradiated samples after 3 weeks of irradiation confirming their irradiation status in all the storage conditions. Calibrated PSL and sample storage in dark at 4 °C were found out to be most suitable approaches to identify irradiated oranges during storage.

  19. Clustering approaches to identifying gene expression patterns from DNA microarray data.

    Science.gov (United States)

    Do, Jin Hwan; Choi, Dong-Kug

    2008-04-30

    The analysis of microarray data is essential for large amounts of gene expression data. In this review we focus on clustering techniques. The biological rationale for this approach is the fact that many co-expressed genes are co-regulated, and identifying co-expressed genes could aid in functional annotation of novel genes, de novo identification of transcription factor binding sites and elucidation of complex biological pathways. Co-expressed genes are usually identified in microarray experiments by clustering techniques. There are many such methods, and the results obtained even for the same datasets may vary considerably depending on the algorithms and metrics for dissimilarity measures used, as well as on user-selectable parameters such as desired number of clusters and initial values. Therefore, biologists who want to interpret microarray data should be aware of the weakness and strengths of the clustering methods used. In this review, we survey the basic principles of clustering of DNA microarray data from crisp clustering algorithms such as hierarchical clustering, K-means and self-organizing maps, to complex clustering algorithms like fuzzy clustering.

  20. Identifying barriers to chronic disease reporting in Chicago Public Schools: a mixed-methods approach.

    Science.gov (United States)

    Rivkina, Victoria; Tapke, David E; Cardenas, Lilliana D; Harvey-Gintoft, Blair; Whyte, Stephanie A; Gupta, Ruchi S

    2014-12-06

    Chronic disease among school-aged children is a public health concern, particularly for asthma and food allergy. In Chicago Public Schools (CPS), rates of asthma and food allergy among students are underreported. The aim of this study was to determine the barriers to chronic disease reporting as experienced by CPS parents and school nurses. A mixed-methods approach included focus groups and key informant interviews with parents and school nurses, and a cross-sectional survey was completed by parents. Qualitative data analysis was performed and survey data were analyzed to determine the significant demographic and knowledge variables associated with successfully completing the reporting process. The three main barriers identified were 1) a lack of parental process knowledge; 2) limited communication from schools; and 3) insufficient availability of school nurses. Parents were significantly more likely to successfully complete the reporting process if they knew about special accommodations for chronic diseases, understood the need for physician verification, and/or knew the school nurse. These findings suggest that increasing parental knowledge of the reporting process will allow schools to better identify and manage their students' chronic conditions. A parent-focused intervention informed by these results has been completed.

  1. A Neural Network Approach for Identifying Particle Pitch Angle Distributions in Van Allen Probes Data

    Science.gov (United States)

    Souza, V. M.; Vieira, L. E. A.; Medeiros, C.; Da Silva, L. A.; Alves, L. R.; Koga, D.; Sibeck, D. G.; Walsh, B. M.; Kanekal, S. G.; Jauer, P. R.; hide

    2016-01-01

    Analysis of particle pitch angle distributions (PADs) has been used as a means to comprehend a multitude of different physical mechanisms that lead to flux variations in the Van Allen belts and also to particle precipitation into the upper atmosphere. In this work we developed a neural network-based data clustering methodology that automatically identifies distinct PAD types in an unsupervised way using particle flux data. One can promptly identify and locate three well-known PAD types in both time and radial distance, namely, 90deg peaked, butterfly, and flattop distributions. In order to illustrate the applicability of our methodology, we used relativistic electron flux data from the whole month of November 2014, acquired from the Relativistic Electron-Proton Telescope instrument on board the Van Allen Probes, but it is emphasized that our approach can also be used with multiplatform spacecraft data. Our PAD classification results are in reasonably good agreement with those obtained by standard statistical fitting algorithms. The proposed methodology has a potential use for Van Allen belt's monitoring.

  2. Learn the Lagrangian: A Vector-Valued RKHS Approach to Identifying Lagrangian Systems.

    Science.gov (United States)

    Cheng, Ching-An; Huang, Han-Pang

    2016-12-01

    We study the modeling of Lagrangian systems with multiple degrees of freedom. Based on system dynamics, canonical parametric models require ad hoc derivations and sometimes simplification for a computable solution; on the other hand, due to the lack of prior knowledge in the system's structure, modern nonparametric models in machine learning face the curse of dimensionality, especially in learning large systems. In this paper, we bridge this gap by unifying the theories of Lagrangian systems and vector-valued reproducing kernel Hilbert space. We reformulate Lagrangian systems with kernels that embed the governing Euler-Lagrange equation-the Lagrangian kernels-and show that these kernels span a subspace capturing the Lagrangian's projection as inverse dynamics. By such property, our model uses only inputs and outputs as in machine learning and inherits the structured form as in system dynamics, thereby removing the need for the mundane derivations for new systems as well as the generalization problem in learning from scratches. In effect, it learns the system's Lagrangian, a simpler task than directly learning the dynamics. To demonstrate, we applied the proposed kernel to identify the robot inverse dynamics in simulations and experiments. Our results present a competitive novel approach to identifying Lagrangian systems, despite using only inputs and outputs.

  3. Shortest-path network analysis is a useful approach toward identifying genetic determinants of longevity.

    Directory of Open Access Journals (Sweden)

    J R Managbanag

    Full Text Available BACKGROUND: Identification of genes that modulate longevity is a major focus of aging-related research and an area of intense public interest. In addition to facilitating an improved understanding of the basic mechanisms of aging, such genes represent potential targets for therapeutic intervention in multiple age-associated diseases, including cancer, heart disease, diabetes, and neurodegenerative disorders. To date, however, targeted efforts at identifying longevity-associated genes have been limited by a lack of predictive power, and useful algorithms for candidate gene-identification have also been lacking. METHODOLOGY/PRINCIPAL FINDINGS: We have utilized a shortest-path network analysis to identify novel genes that modulate longevity in Saccharomyces cerevisiae. Based on a set of previously reported genes associated with increased life span, we applied a shortest-path network algorithm to a pre-existing protein-protein interaction dataset in order to construct a shortest-path longevity network. To validate this network, the replicative aging potential of 88 single-gene deletion strains corresponding to predicted components of the shortest-path longevity network was determined. Here we report that the single-gene deletion strains identified by our shortest-path longevity analysis are significantly enriched for mutations conferring either increased or decreased replicative life span, relative to a randomly selected set of 564 single-gene deletion strains or to the current data set available for the entire haploid deletion collection. Further, we report the identification of previously unknown longevity genes, several of which function in a conserved longevity pathway believed to mediate life span extension in response to dietary restriction. CONCLUSIONS/SIGNIFICANCE: This work demonstrates that shortest-path network analysis is a useful approach toward identifying genetic determinants of longevity and represents the first application of

  4. A comprehensive approach to identifying repurposed drugs to treat SCN8A epilepsy.

    Science.gov (United States)

    Atkin, Talia A; Maher, Chani M; Gerlach, Aaron C; Gay, Bryant C; Antonio, Brett M; Santos, Sonia C; Padilla, Karen M; Rader, JulieAnn; Krafte, Douglas S; Fox, Matthew A; Stewart, Gregory R; Petrovski, Slavé; Devinsky, Orrin; Might, Matthew; Petrou, Steven; Goldstein, David B

    2018-04-01

    Many previous studies of drug repurposing have relied on literature review followed by evaluation of a limited number of candidate compounds. Here, we demonstrate the feasibility of a more comprehensive approach using high-throughput screening to identify inhibitors of a gain-of-function mutation in the SCN8A gene associated with severe pediatric epilepsy. We developed cellular models expressing wild-type or an R1872Q mutation in the Na v 1.6 sodium channel encoded by SCN8A. Voltage clamp experiments in HEK-293 cells expressing the SCN8A R1872Q mutation demonstrated a leftward shift in sodium channel activation as well as delayed inactivation; both changes are consistent with a gain-of-function mutation. We next developed a fluorescence-based, sodium flux assay and used it to assess an extensive library of approved drugs, including a panel of antiepileptic drugs, for inhibitory activity in the mutated cell line. Lead candidates were evaluated in follow-on studies to generate concentration-response curves for inhibiting sodium influx. Select compounds of clinical interest were evaluated by electrophysiology to further characterize drug effects on wild-type and mutant sodium channel functions. The screen identified 90 drugs that significantly inhibited sodium influx in the R1872Q cell line. Four drugs of potential clinical interest-amitriptyline, carvedilol, nilvadipine, and carbamazepine-were further investigated and demonstrated concentration-dependent inhibition of sodium channel currents. A comprehensive drug repurposing screen identified potential new candidates for the treatment of epilepsy caused by the R1872Q mutation in the SCN8A gene. Wiley Periodicals, Inc. © 2018 International League Against Epilepsy.

  5. SU-E-J-212: Identifying Bones From MRI: A Dictionary Learnign and Sparse Regression Approach

    International Nuclear Information System (INIS)

    Ruan, D; Yang, Y; Cao, M; Hu, P; Low, D

    2014-01-01

    Purpose: To develop an efficient and robust scheme to identify bony anatomy based on MRI-only simulation images. Methods: MRI offers important soft tissue contrast and functional information, yet its lack of correlation to electron-density has placed it as an auxiliary modality to CT in radiotherapy simulation and adaptation. An effective scheme to identify bony anatomy is an important first step towards MR-only simulation/treatment paradigm and would satisfy most practical purposes. We utilize a UTE acquisition sequence to achieve visibility of the bone. By contrast to manual + bulk or registration-to identify bones, we propose a novel learning-based approach for improved robustness to MR artefacts and environmental changes. Specifically, local information is encoded with MR image patch, and the corresponding label is extracted (during training) from simulation CT aligned to the UTE. Within each class (bone vs. nonbone), an overcomplete dictionary is learned so that typical patches within the proper class can be represented as a sparse combination of the dictionary entries. For testing, an acquired UTE-MRI is divided to patches using a sliding scheme, where each patch is sparsely regressed against both bone and nonbone dictionaries, and subsequently claimed to be associated with the class with the smaller residual. Results: The proposed method has been applied to the pilot site of brain imaging and it has showed general good performance, with dice similarity coefficient of greater than 0.9 in a crossvalidation study using 4 datasets. Importantly, it is robust towards consistent foreign objects (e.g., headset) and the artefacts relates to Gibbs and field heterogeneity. Conclusion: A learning perspective has been developed for inferring bone structures based on UTE MRI. The imaging setting is subject to minimal motion effects and the post-processing is efficient. The improved efficiency and robustness enables a first translation to MR-only routine. The scheme

  6. An Immunohistochemical Approach to Identify the Sex of Young Marine Turtles.

    Science.gov (United States)

    Tezak, Boris M; Guthrie, Kathleen; Wyneken, Jeanette

    2017-08-01

    Marine turtles exhibit temperature-dependent sex determination (TSD). During critical periods of embryonic development, the nest's thermal environment directs whether an embryo will develop as a male or female. At warmer sand temperatures, nests tend to produce female-biased sex ratios. The rapid increase of global temperature highlights the need for a clear assessment of its effects on sea turtle sex ratios. However, estimating hatchling sex ratios at rookeries remains imprecise due to the lack of sexual dimorphism in young marine turtles. We rely mainly upon laparoscopic procedures to verify hatchling sex; however, in some species, morphological sex can be ambiguous even at the histological level. Recent studies using immunohistochemical (IHC) techniques identified that embryonic snapping turtle (Chelydra serpentina) ovaries overexpressed a particular cold-induced RNA-binding protein in comparison to testes. This feature allows the identification of females vs. males. We modified this technique to successfully identify the sexes of loggerhead sea turtle (Caretta caretta) hatchlings, and independently confirmed the results by standard histological and laparoscopic methods that reliably identify sex in this species. We next tested the CIRBP IHC method on gonad samples from leatherback turtles (Dermochelys coriacea). Leatherbacks display delayed gonad differentiation, when compared to other sea turtles, making hatchling gonads difficult to sex using standard H&E stain histology. The IHC approach was successful in both C. caretta and D. coriacea samples, offering a much-needed tool to establish baseline hatchling sex ratios, particularly for assessing impacts of climate change effects on leatherback turtle hatchlings and sea turtle demographics. Anat Rec, 300:1512-1518, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

  7. SU-E-J-212: Identifying Bones From MRI: A Dictionary Learnign and Sparse Regression Approach

    Energy Technology Data Exchange (ETDEWEB)

    Ruan, D; Yang, Y; Cao, M; Hu, P; Low, D [UCLA, Los Angeles, CA (United States)

    2014-06-01

    Purpose: To develop an efficient and robust scheme to identify bony anatomy based on MRI-only simulation images. Methods: MRI offers important soft tissue contrast and functional information, yet its lack of correlation to electron-density has placed it as an auxiliary modality to CT in radiotherapy simulation and adaptation. An effective scheme to identify bony anatomy is an important first step towards MR-only simulation/treatment paradigm and would satisfy most practical purposes. We utilize a UTE acquisition sequence to achieve visibility of the bone. By contrast to manual + bulk or registration-to identify bones, we propose a novel learning-based approach for improved robustness to MR artefacts and environmental changes. Specifically, local information is encoded with MR image patch, and the corresponding label is extracted (during training) from simulation CT aligned to the UTE. Within each class (bone vs. nonbone), an overcomplete dictionary is learned so that typical patches within the proper class can be represented as a sparse combination of the dictionary entries. For testing, an acquired UTE-MRI is divided to patches using a sliding scheme, where each patch is sparsely regressed against both bone and nonbone dictionaries, and subsequently claimed to be associated with the class with the smaller residual. Results: The proposed method has been applied to the pilot site of brain imaging and it has showed general good performance, with dice similarity coefficient of greater than 0.9 in a crossvalidation study using 4 datasets. Importantly, it is robust towards consistent foreign objects (e.g., headset) and the artefacts relates to Gibbs and field heterogeneity. Conclusion: A learning perspective has been developed for inferring bone structures based on UTE MRI. The imaging setting is subject to minimal motion effects and the post-processing is efficient. The improved efficiency and robustness enables a first translation to MR-only routine. The scheme

  8. A novel approach identifying hybrid sterility QTL on the autosomes of Drosophila simulans and D. mauritiana.

    Science.gov (United States)

    Dickman, Christopher T D; Moehring, Amanda J

    2013-01-01

    When species interbreed, the hybrid offspring that are produced are often sterile. If only one hybrid sex is sterile, it is almost always the heterogametic (XY or ZW) sex. Taking this trend into account, the predominant model used to explain the genetic basis of F1 sterility involves a deleterious interaction between recessive sex-linked loci from one species and dominant autosomal loci from the other species. This model is difficult to evaluate, however, as only a handful of loci influencing interspecies hybrid sterility have been identified, and their autosomal genetic interactors have remained elusive. One hindrance to their identification has been the overwhelming effect of the sex chromosome in mapping studies, which could 'mask' the ability to accurately map autosomal factors. Here, we use a novel approach employing attached-X chromosomes to create reciprocal backcross interspecies hybrid males that have a non-recombinant sex chromosome and recombinant autosomes. The heritable variation in phenotype is thus solely caused by differences in the autosomes, thereby allowing us to accurately identify the number and location of autosomal sterility loci. In one direction of backcross, all males were sterile, indicating that sterility could be entirely induced by the sex chromosome complement in these males. In the other direction, we identified nine quantitative trait loci that account for a surprisingly large amount (56%) of the autosome-induced phenotypic variance in sterility, with a large contribution of autosome-autosome epistatic interactions. These loci are capable of acting dominantly, and thus could contribute to F1 hybrid sterility.

  9. A novel approach identifying hybrid sterility QTL on the autosomes of Drosophila simulans and D. mauritiana.

    Directory of Open Access Journals (Sweden)

    Christopher T D Dickman

    Full Text Available When species interbreed, the hybrid offspring that are produced are often sterile. If only one hybrid sex is sterile, it is almost always the heterogametic (XY or ZW sex. Taking this trend into account, the predominant model used to explain the genetic basis of F1 sterility involves a deleterious interaction between recessive sex-linked loci from one species and dominant autosomal loci from the other species. This model is difficult to evaluate, however, as only a handful of loci influencing interspecies hybrid sterility have been identified, and their autosomal genetic interactors have remained elusive. One hindrance to their identification has been the overwhelming effect of the sex chromosome in mapping studies, which could 'mask' the ability to accurately map autosomal factors. Here, we use a novel approach employing attached-X chromosomes to create reciprocal backcross interspecies hybrid males that have a non-recombinant sex chromosome and recombinant autosomes. The heritable variation in phenotype is thus solely caused by differences in the autosomes, thereby allowing us to accurately identify the number and location of autosomal sterility loci. In one direction of backcross, all males were sterile, indicating that sterility could be entirely induced by the sex chromosome complement in these males. In the other direction, we identified nine quantitative trait loci that account for a surprisingly large amount (56% of the autosome-induced phenotypic variance in sterility, with a large contribution of autosome-autosome epistatic interactions. These loci are capable of acting dominantly, and thus could contribute to F1 hybrid sterility.

  10. A Machine Learning Approach to Identifying Placebo Responders in Late-Life Depression Trials.

    Science.gov (United States)

    Zilcha-Mano, Sigal; Roose, Steven P; Brown, Patrick J; Rutherford, Bret R

    2018-01-11

    Despite efforts to identify characteristics associated with medication-placebo differences in antidepressant trials, few consistent findings have emerged to guide participant selection in drug development settings and differential therapeutics in clinical practice. Limitations in the methodologies used, particularly searching for a single moderator while treating all other variables as noise, may partially explain the failure to generate consistent results. The present study tested whether interactions between pretreatment patient characteristics, rather than a single-variable solution, may better predict who is most likely to benefit from placebo versus medication. Data were analyzed from 174 patients aged 75 years and older with unipolar depression who were randomly assigned to citalopram or placebo. Model-based recursive partitioning analysis was conducted to identify the most robust significant moderators of placebo versus citalopram response. The greatest signal detection between medication and placebo in favor of medication was among patients with fewer years of education (≤12) who suffered from a longer duration of depression since their first episode (>3.47 years) (B = 2.53, t(32) = 3.01, p = 0.004). Compared with medication, placebo had the greatest response for those who were more educated (>12 years), to the point where placebo almost outperformed medication (B = -0.57, t(96) = -1.90, p = 0.06). Machine learning approaches capable of evaluating the contributions of multiple predictor variables may be a promising methodology for identifying placebo versus medication responders. Duration of depression and education should be considered in the efforts to modulate placebo magnitude in drug development settings and in clinical practice. Copyright © 2018 American Association for Geriatric Psychiatry. Published by Elsevier Inc. All rights reserved.

  11. Fingerprints of zones in boreholes. An approach to identify the characteristics of structures

    Energy Technology Data Exchange (ETDEWEB)

    Straeng, Thomas; Waenstedt, Stefan; Tiren, Sven (GEOSIGMA AB (Sweden))

    2010-11-15

    The classification of geophysical borehole data in order to identify and characterize structures, which intercepts the borehole, is an important part of 3D modelling of the structural pattern of the bedrock. The objective of this study is to test a statistical approach, cluster analysis, on site data in order to see if it is possible to classify complex data set, geological and geophysical borehole data, in order to identify borehole intersects with increased brittle deformation, i.e. brittle deformation zones. The base data used in the study have been provided and delivered by SKB and consist of borehole logging data from the cored borehole KFM03A. The statistical method chosen for this study, cluster analysis using K-means method, groups data into a pre-defined number of clusters with the goal to minimize the variance of data within the group and to maximize the variance between the clusters. The idea is that data can and should be grouped into two categories, two clusters -corresponding to homogeneous bedrock (matrix) in one cluster and open fractures in the other cluster. The analysis also includes a repetition of the cluster analysis, with a stepwise refined data set to see whether strongly accentuated features could be identified. The results show that the use of K-mean Cluster analysis will present clusters that could represent the spatial distribution of bedrock matrix and the location of fractures respectively down the borehole. The results were compared with fracture frequency data (from core mapping) and also with the geological Single Hole Interpretation of KFM03A performed by SKB. The fracture zones identified in the Single Hole Interpretation process are all indicated in the cluster analysis results. The cluster analysis revealed eight additional possible zones. A majority of these are smaller than 5 metres (section width in the borehole) but they are still pronounced in the analysis. Based on the geophysical data, these sections should be taken into

  12. Identifying typical patterns of vulnerability: A 5-step approach based on cluster analysis

    Science.gov (United States)

    Sietz, Diana; Lüdeke, Matthias; Kok, Marcel; Lucas, Paul; Carsten, Walther; Janssen, Peter

    2013-04-01

    Specific processes that shape the vulnerability of socio-ecological systems to climate, market and other stresses derive from diverse background conditions. Within the multitude of vulnerability-creating mechanisms, distinct processes recur in various regions inspiring research on typical patterns of vulnerability. The vulnerability patterns display typical combinations of the natural and socio-economic properties that shape a systems' vulnerability to particular stresses. Based on the identification of a limited number of vulnerability patterns, pattern analysis provides an efficient approach to improving our understanding of vulnerability and decision-making for vulnerability reduction. However, current pattern analyses often miss explicit descriptions of their methods and pay insufficient attention to the validity of their groupings. Therefore, the question arises as to how do we identify typical vulnerability patterns in order to enhance our understanding of a systems' vulnerability to stresses? A cluster-based pattern recognition applied at global and local levels is scrutinised with a focus on an applicable methodology and practicable insights. Taking the example of drylands, this presentation demonstrates the conditions necessary to identify typical vulnerability patterns. They are summarised in five methodological steps comprising the elicitation of relevant cause-effect hypotheses and the quantitative indication of mechanisms as well as an evaluation of robustness, a validation and a ranking of the identified patterns. Reflecting scale-dependent opportunities, a global study is able to support decision-making with insights into the up-scaling of interventions when available funds are limited. In contrast, local investigations encourage an outcome-based validation. This constitutes a crucial step in establishing the credibility of the patterns and hence their suitability for informing extension services and individual decisions. In this respect, working at

  13. The metabolomic approach identifies a biological signature of low-dose chronic exposure to Cesium 137

    International Nuclear Information System (INIS)

    Grison, S.; Grandcolas, L.; Martin, J.C.

    2012-01-01

    Reports have described apparent biological effects of 137 Cs (the most persistent dispersed radionuclide) irradiation in people living in Chernobyl-contaminated territory. The sensitive analytical technology described here should now help assess the relation of this contamination to the observed effects. A rat model chronically exposed to 137 Cs through drinking water was developed to identify biomarkers of radiation-induced metabolic disorders, and the biological impact was evaluated by a metabolomic approach that allowed us to detect several hundred metabolites in biofluids and assess their association with disease states. After collection of plasma and urine from contaminated and non-contaminated rats at the end of the 9-months contamination period, analysis with a liquid chromatography coupled to mass spectrometry (LC-MS) system detected 742 features in urine and 1309 in plasma. Biostatistical discriminant analysis extracted a subset of 26 metabolite signals (2 urinary, 4 plasma non-polar, and 19 plasma polar metabolites) that in combination were able to predict from 68 up to 94% of the contaminated rats, depending on the prediction method used, with a misclassification rate as low as 5.3%. The difference in this metabolic score between the contaminated and non-contaminated rats was highly significant (P=0.019 after ANOVA cross-validation). In conclusion, our proof-of-principle study demonstrated for the first time the usefulness of a metabolomic approach for addressing biological effects of chronic low-dose contamination. We can conclude that a metabolomic signature discriminated 137 Cs-contaminated from control animals in our model. Further validation is nevertheless required together with full annotation of the metabolic indicators. (author)

  14. Probing the dynamics of identified neurons with a data-driven modeling approach.

    Directory of Open Access Journals (Sweden)

    Thomas Nowotny

    2008-07-01

    Full Text Available In controlling animal behavior the nervous system has to perform within the operational limits set by the requirements of each specific behavior. The implications for the corresponding range of suitable network, single neuron, and ion channel properties have remained elusive. In this article we approach the question of how well-constrained properties of neuronal systems may be on the neuronal level. We used large data sets of the activity of isolated invertebrate identified cells and built an accurate conductance-based model for this cell type using customized automated parameter estimation techniques. By direct inspection of the data we found that the variability of the neurons is larger when they are isolated from the circuit than when in the intact system. Furthermore, the responses of the neurons to perturbations appear to be more consistent than their autonomous behavior under stationary conditions. In the developed model, the constraints on different parameters that enforce appropriate model dynamics vary widely from some very tightly controlled parameters to others that are almost arbitrary. The model also allows predictions for the effect of blocking selected ionic currents and to prove that the origin of irregular dynamics in the neuron model is proper chaoticity and that this chaoticity is typical in an appropriate sense. Our results indicate that data driven models are useful tools for the in-depth analysis of neuronal dynamics. The better consistency of responses to perturbations, in the real neurons as well as in the model, suggests a paradigm shift away from measuring autonomous dynamics alone towards protocols of controlled perturbations. Our predictions for the impact of channel blockers on the neuronal dynamics and the proof of chaoticity underscore the wide scope of our approach.

  15. Determining the optimal approach to identifying individuals with chronic obstructive pulmonary disease: The DOC study.

    Science.gov (United States)

    Ronaldson, Sarah J; Dyson, Lisa; Clark, Laura; Hewitt, Catherine E; Torgerson, David J; Cooper, Brendan G; Kearney, Matt; Laughey, William; Raghunath, Raghu; Steele, Lisa; Rhodes, Rebecca; Adamson, Joy

    2018-06-01

    Early identification of chronic obstructive pulmonary disease (COPD) results in patients receiving appropriate management for their condition at an earlier stage in their disease. The determining the optimal approach to identifying individuals with chronic obstructive pulmonary disease (DOC) study was a case-finding study to enhance early identification of COPD in primary care, which evaluated the diagnostic accuracy of a series of simple lung function tests and symptom-based case-finding questionnaires. Current smokers aged 35 or more were invited to undertake a series of case-finding tools, which comprised lung function tests (specifically, spirometry, microspirometry, peak flow meter, and WheezoMeter) and several case-finding questionnaires. The effectiveness of these tests, individually or in combination, to identify small airways obstruction was evaluated against the gold standard of spirometry, with the quality of spirometry tests assessed by independent overreaders. The study was conducted with general practices in the Yorkshire and Humberside area, in the UK. Six hundred eighty-one individuals met the inclusion criteria, with 444 participants completing their study appointments. A total of 216 (49%) with good-quality spirometry readings were included in the analysis. The most effective case-finding tools were found to be the peak flow meter alone, the peak flow meter plus WheezoMeter, and microspirometry alone. In addition to the main analysis, where the severity of airflow obstruction was based on fixed ratios and percent of predicted values, sensitivity analyses were conducted by using lower limit of normal values. This research informs the choice of test for COPD identification; case-finding by use of the peak flow meter or microspirometer could be used routinely in primary care for suspected COPD patients. Only those testing positive to these tests would move on to full spirometry, thereby reducing unnecessary spirometric testing. © 2018 John Wiley

  16. Coalitional game theory as a promising approach to identify candidate autism genes.

    Science.gov (United States)

    Gupta, Anika; Sun, Min Woo; Paskov, Kelley Marie; Stockham, Nate Tyler; Jung, Jae-Yoon; Wall, Dennis Paul

    2018-01-01

    Despite mounting evidence for the strong role of genetics in the phenotypic manifestation of Autism Spectrum Disorder (ASD), the specific genes responsible for the variable forms of ASD remain undefined. ASD may be best explained by a combinatorial genetic model with varying epistatic interactions across many small effect mutations. Coalitional or cooperative game theory is a technique that studies the combined effects of groups of players, known as coalitions, seeking to identify players who tend to improve the performance--the relationship to a specific disease phenotype--of any coalition they join. This method has been previously shown to boost biologically informative signal in gene expression data but to-date has not been applied to the search for cooperative mutations among putative ASD genes. We describe our approach to highlight genes relevant to ASD using coalitional game theory on alteration data of 1,965 fully sequenced genomes from 756 multiplex families. Alterations were encoded into binary matrices for ASD (case) and unaffected (control) samples, indicating likely gene-disrupting, inherited mutations in altered genes. To determine individual gene contributions given an ASD phenotype, a "player" metric, referred to as the Shapley value, was calculated for each gene in the case and control cohorts. Sixty seven genes were found to have significantly elevated player scores and likely represent significant contributors to the genetic coordination underlying ASD. Using network and cross-study analysis, we found that these genes are involved in biological pathways known to be affected in the autism cases and that a subset directly interact with several genes known to have strong associations to autism. These findings suggest that coalitional game theory can be applied to large-scale genomic data to identify hidden yet influential players in complex polygenic disorders such as autism.

  17. MrTADFinder: A network modularity based approach to identify topologically associating domains in multiple resolutions.

    Directory of Open Access Journals (Sweden)

    Koon-Kiu Yan

    2017-07-01

    Full Text Available Genome-wide proximity ligation based assays such as Hi-C have revealed that eukaryotic genomes are organized into structural units called topologically associating domains (TADs. From a visual examination of the chromosomal contact map, however, it is clear that the organization of the domains is not simple or obvious. Instead, TADs exhibit various length scales and, in many cases, a nested arrangement. Here, by exploiting the resemblance between TADs in a chromosomal contact map and densely connected modules in a network, we formulate TAD identification as a network optimization problem and propose an algorithm, MrTADFinder, to identify TADs from intra-chromosomal contact maps. MrTADFinder is based on the network-science concept of modularity. A key component of it is deriving an appropriate background model for contacts in a random chain, by numerically solving a set of matrix equations. The background model preserves the observed coverage of each genomic bin as well as the distance dependence of the contact frequency for any pair of bins exhibited by the empirical map. Also, by introducing a tunable resolution parameter, MrTADFinder provides a self-consistent approach for identifying TADs at different length scales, hence the acronym "Mr" standing for Multiple Resolutions. We then apply MrTADFinder to various Hi-C datasets. The identified domain boundaries are marked by characteristic signatures in chromatin marks and transcription factors (TF that are consistent with earlier work. Moreover, by calling TADs at different length scales, we observe that boundary signatures change with resolution, with different chromatin features having different characteristic length scales. Furthermore, we report an enrichment of HOT (high-occupancy target regions near TAD boundaries and investigate the role of different TFs in determining boundaries at various resolutions. To further explore the interplay between TADs and epigenetic marks, as tumor mutational

  18. Identifying diffused nitrate sources in a stream in an agricultural field using a dual isotopic approach

    International Nuclear Information System (INIS)

    Ding, Jingtao; Xi, Beidou; Gao, Rutai; He, Liansheng; Liu, Hongliang; Dai, Xuanli; Yu, Yijun

    2014-01-01

    Nitrate (NO 3 − ) pollution is a severe problem in aquatic systems in Taihu Lake Basin in China. A dual isotope approach (δ 15 N-NO 3 − and δ 18 O-NO 3 − ) was applied to identify diffused NO 3 − inputs in a stream in an agricultural field at the basin in 2013. The site-specific isotopic characteristics of five NO 3 − sources (atmospheric deposition, AD; NO 3 − derived from soil organic matter nitrification, NS; NO 3 − derived from chemical fertilizer nitrification, NF; groundwater, GW; and manure and sewage, M and S) were identified. NO 3 − concentrations in the stream during the rainy season [mean ± standard deviation (SD) = 2.5 ± 0.4 mg/L] were lower than those during the dry season (mean ± SD = 4.0 ± 0.5 mg/L), whereas the δ 18 O-NO 3 − values during the rainy season (mean ± SD = + 12.3 ± 3.6‰) were higher than those during the dry season (mean ± SD = + 0.9 ± 1.9‰). Both chemical and isotopic characteristics indicated that mixing with atmospheric NO 3 − resulted in the high δ 18 O values during the rainy season, whereas NS and M and S were the dominant NO 3 − sources during the dry season. A Bayesian model was used to determine the contribution of each NO 3 − source to total stream NO 3 − . Results showed that reduced N nitrification in soil zones (including soil organic matter and fertilizer) was the main NO 3 − source throughout the year. M and S contributed more NO 3 − during the dry season (22.4%) than during the rainy season (17.8%). AD generated substantial amounts of NO 3 − in May (18.4%), June (29.8%), and July (24.5%). With the assessment of temporal variation of diffused NO 3 − sources in agricultural field, improved agricultural management practices can be implemented to protect the water resource and avoid further water quality deterioration in Taihu Lake Basin. - Highlights: • The isotopic characteristics of potential NO 3 − sources were identified. • Mixing with atmospheric NO 3 − resulted

  19. New approaches for identifying and testing potential new anti-asthma agents.

    Science.gov (United States)

    Licari, Amelia; Castagnoli, Riccardo; Brambilla, Ilaria; Marseglia, Alessia; Tosca, Maria Angela; Marseglia, Gian Luigi; Ciprandi, Giorgio

    2018-01-01

    Asthma is a chronic disease with significant heterogeneity in clinical features, disease severity, pattern of underlying disease mechanisms, and responsiveness to specific treatments. While the majority of asthmatic patients are controlled by standard pharmacological strategies, a significant subgroup has limited therapeutic options representing a major unmet need. Ongoing asthma research aims to better characterize distinct clinical phenotypes, molecular endotypes, associated reliable biomarkers, and also to develop a series of new effective targeted treatment modalities. Areas covered: The expanding knowledge on the pathogenetic mechanisms of asthma has allowed researchers to investigate a range of new treatment options matched to patient profiles. The aim of this review is to provide a comprehensive and updated overview of the currently available, new and developing approaches for identifying and testing potential treatment options for asthma management. Expert opinion: Future therapeutic strategies for asthma require the identification of reliable biomarkers that can help with diagnosis and endotyping, in order to determine the most effective drug for the right patient phenotype. Furthermore, in addition to the identification of clinical and inflammatory phenotypes, it is expected that a better understanding of the mechanisms of airway remodeling will likely optimize asthma targeted treatment.

  20. Identifying Meaning Components in the Translation of Medical Terms from English into Indonesian: A Semantic Approach

    Directory of Open Access Journals (Sweden)

    I Gusti Agung Sri Rwa Jayantini

    2017-10-01

    Full Text Available This paper focuses on identifying meaning components in the translation of English medical terms into Indonesian. The data used in this study are the English medical term disorder and its Indonesian equivalent penyakit (disease. The two terms are purposively chosen as the data of the present study, which is a comparative research on the lexical meaning investigation in two different languages. The investigation involving a particular term in one language and its equivalent in the other language is worth doing since the lexicons in every language have their own specific concepts that may be synonymous, yet they are not always interchangeable in all contexts. The analysis into meaning components is called decomposition by means of several semantic theories to analyse the meaning of a lexical item (Löbner 2013. Here, the meaning components of the two compared terms are demonstrated through a semantic approach, particularly Natural Semantic Metalanguage (NSM supported by the investigation on their synonyms and how the terms are used in different contexts. The results show that the meaning components of a particular term in one language like the English term disorder are not always found in the Indonesian term penyakit, or, conversely, some of the meaning components of the Indonesian term do not always exist in the English term.

  1. Parallel approach to identifying the well-test interpretation model using a neurocomputer

    Science.gov (United States)

    May, Edward A., Jr.; Dagli, Cihan H.

    1996-03-01

    The well test is one of the primary diagnostic and predictive tools used in the analysis of oil and gas wells. In these tests, a pressure recording device is placed in the well and the pressure response is recorded over time under controlled flow conditions. The interpreted results are indicators of the well's ability to flow and the damage done to the formation surrounding the wellbore during drilling and completion. The results are used for many purposes, including reservoir modeling (simulation) and economic forecasting. The first step in the analysis is the identification of the Well-Test Interpretation (WTI) model, which determines the appropriate solution method. Mis-identification of the WTI model occurs due to noise and non-ideal reservoir conditions. Previous studies have shown that a feed-forward neural network using the backpropagation algorithm can be used to identify the WTI model. One of the drawbacks to this approach is, however, training time, which can run into days of CPU time on personal computers. In this paper a similar neural network is applied using both a personal computer and a neurocomputer. Input data processing, network design, and performance are discussed and compared. The results show that the neurocomputer greatly eases the burden of training and allows the network to outperform a similar network running on a personal computer.

  2. Pharmacy patronage: identifying key factors in the decision making process using the determinant attribute approach.

    Science.gov (United States)

    Franic, Duska M; Haddock, Sarah M; Tucker, Leslie Tootle; Wooten, Nathan

    2008-01-01

    To use the determinant attribute approach, a research method commonly used in marketing to identify the wants of various consumer groups, to evaluate consumer pharmacy choice when having a prescription order filled in different pharmacy settings. Cross sectional. Community independent, grocery store, community chain, and discount store pharmacies in Georgia between April 2005 and April 2006. Convenience sample of adult pharmacy consumers (n = 175). Survey measuring consumer preferences on 26 attributes encompassing general pharmacy site features (16 items), pharmacist characteristics (5 items), and pharmacy staff characteristics (5 items). 26 potential determinant attributes for pharmacy selection. 175 consumers were surveyed at community independent (n = 81), grocery store (n = 44), community chain (n = 27), or discount store (n = 23) pharmacy settings. The attributes of pharmacists and staff at all four pharmacy settings were shown to affect pharmacy patronage motives, although consumers frequenting non-community independent pharmacies were also motivated by secondary convenience factors, e.g., hours of operation, and prescription coverage. Most consumers do not perceive pharmacies as merely prescription-distribution centers that vary only by convenience. Prescriptions are not just another economic good. Pharmacy personnel influence pharmacy selection; therefore, optimal staff selection and training is likely the greatest asset and most important investment for ensuring pharmacy success.

  3. Identifying medication error chains from critical incident reports: a new analytic approach.

    Science.gov (United States)

    Huckels-Baumgart, Saskia; Manser, Tanja

    2014-10-01

    Research into the distribution of medication errors usually focuses on isolated stages within the medication use process. Our study aimed to provide a novel process-oriented approach to medication incident analysis focusing on medication error chains. Our study was conducted across a 900-bed teaching hospital in Switzerland. All reported 1,591 medication errors 2009-2012 were categorized using the Medication Error Index NCC MERP and the WHO Classification for Patient Safety Methodology. In order to identify medication error chains, each reported medication incident was allocated to the relevant stage of the hospital medication use process. Only 25.8% of the reported medication errors were detected before they propagated through the medication use process. The majority of medication errors (74.2%) formed an error chain encompassing two or more stages. The most frequent error chain comprised preparation up to and including medication administration (45.2%). "Non-consideration of documentation/prescribing" during the drug preparation was the most frequent contributor for "wrong dose" during the administration of medication. Medication error chains provide important insights for detecting and stopping medication errors before they reach the patient. Existing and new safety barriers need to be extended to interrupt error chains and to improve patient safety. © 2014, The American College of Clinical Pharmacology.

  4. Omics Approaches for Identifying Physiological Adaptations to Genome Instability in Aging.

    Science.gov (United States)

    Edifizi, Diletta; Schumacher, Björn

    2017-11-04

    DNA damage causally contributes to aging and age-related diseases. The declining functioning of tissues and organs during aging can lead to the increased risk of succumbing to aging-associated diseases. Congenital syndromes that are caused by heritable mutations in DNA repair pathways lead to cancer susceptibility and accelerated aging, thus underlining the importance of genome maintenance for withstanding aging. High-throughput mass-spectrometry-based approaches have recently contributed to identifying signalling response networks and gaining a more comprehensive understanding of the physiological adaptations occurring upon unrepaired DNA damage. The insulin-like signalling pathway has been implicated in a DNA damage response (DDR) network that includes epidermal growth factor (EGF)-, AMP-activated protein kinases (AMPK)- and the target of rapamycin (TOR)-like signalling pathways, which are known regulators of growth, metabolism, and stress responses. The same pathways, together with the autophagy-mediated proteostatic response and the decline in energy metabolism have also been found to be similarly regulated during natural aging, suggesting striking parallels in the physiological adaptation upon persistent DNA damage due to DNA repair defects and long-term low-level DNA damage accumulation occurring during natural aging. These insights will be an important starting point to study the interplay between signalling networks involved in progeroid syndromes that are caused by DNA repair deficiencies and to gain new understanding of the consequences of DNA damage in the aging process.

  5. Assessment of a Novel Approach to Identify Trichiasis Cases Using Community Treatment Assistants in Tanzania.

    Science.gov (United States)

    Greene, Gregory S; West, Sheila K; Mkocha, Harran; Munoz, Beatriz; Merbs, Shannath L

    2015-12-01

    Simple surgical intervention advocated by the World Health Organization can alleviate trachomatous trichiasis (TT) and prevent subsequent blindness. A large backlog of TT cases remain unidentified and untreated. To increase identification and referral of TT cases, a novel approach using standard screening questions, a card, and simple training for Community Treatment Assistants (CTAs) to use during Mass Drug Administration (MDA) was developed and evaluated in Kongwa District, a trachoma-endemic area of central Tanzania. A community randomized trial was conducted in 36 communities during MDA. CTAs in intervention villages received an additional half-day of training and a TT screening card in addition to the training received by CTAs in villages assigned to usual care. All MDA participants 15 years and older were screened for TT, and senior TT graders confirmed case status by evaluating all screened-positive cases. A random sample of those screened negative for TT and those who did not present at MDA were also evaluated by the master graders. Intervention CTAs identified 5.6 times as many cases (n = 50) as those assigned to usual care (n = 9, p card significantly increased the ability of CTAs to recognize and refer TT cases during MDA; however, further efforts are needed to improve case detection and reduce the number of false positive cases.

  6. Mixed Integer Linear Programming based machine learning approach identifies regulators of telomerase in yeast.

    Science.gov (United States)

    Poos, Alexandra M; Maicher, André; Dieckmann, Anna K; Oswald, Marcus; Eils, Roland; Kupiec, Martin; Luke, Brian; König, Rainer

    2016-06-02

    Understanding telomere length maintenance mechanisms is central in cancer biology as their dysregulation is one of the hallmarks for immortalization of cancer cells. Important for this well-balanced control is the transcriptional regulation of the telomerase genes. We integrated Mixed Integer Linear Programming models into a comparative machine learning based approach to identify regulatory interactions that best explain the discrepancy of telomerase transcript levels in yeast mutants with deleted regulators showing aberrant telomere length, when compared to mutants with normal telomere length. We uncover novel regulators of telomerase expression, several of which affect histone levels or modifications. In particular, our results point to the transcription factors Sum1, Hst1 and Srb2 as being important for the regulation of EST1 transcription, and we validated the effect of Sum1 experimentally. We compiled our machine learning method leading to a user friendly package for R which can straightforwardly be applied to similar problems integrating gene regulator binding information and expression profiles of samples of e.g. different phenotypes, diseases or treatments. © The Author(s) 2016. Published by Oxford University Press on behalf of Nucleic Acids Research.

  7. Omics Approaches for Identifying Physiological Adaptations to Genome Instability in Aging

    Directory of Open Access Journals (Sweden)

    Diletta Edifizi

    2017-11-01

    Full Text Available DNA damage causally contributes to aging and age-related diseases. The declining functioning of tissues and organs during aging can lead to the increased risk of succumbing to aging-associated diseases. Congenital syndromes that are caused by heritable mutations in DNA repair pathways lead to cancer susceptibility and accelerated aging, thus underlining the importance of genome maintenance for withstanding aging. High-throughput mass-spectrometry-based approaches have recently contributed to identifying signalling response networks and gaining a more comprehensive understanding of the physiological adaptations occurring upon unrepaired DNA damage. The insulin-like signalling pathway has been implicated in a DNA damage response (DDR network that includes epidermal growth factor (EGF-, AMP-activated protein kinases (AMPK- and the target of rapamycin (TOR-like signalling pathways, which are known regulators of growth, metabolism, and stress responses. The same pathways, together with the autophagy-mediated proteostatic response and the decline in energy metabolism have also been found to be similarly regulated during natural aging, suggesting striking parallels in the physiological adaptation upon persistent DNA damage due to DNA repair defects and long-term low-level DNA damage accumulation occurring during natural aging. These insights will be an important starting point to study the interplay between signalling networks involved in progeroid syndromes that are caused by DNA repair deficiencies and to gain new understanding of the consequences of DNA damage in the aging process.

  8. Prevalence and characteristics of asthma–COPD overlap syndrome identified by a stepwise approach

    Directory of Open Access Journals (Sweden)

    Inoue H

    2017-06-01

    Full Text Available Hiromasa Inoue,1 Takahide Nagase,2 Satoshi Morita,3 Atsushi Yoshida,4 Tatsunori Jinnai,4 Masakazu Ichinose5 1Department of Pulmonary Medicine, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima, 2Department of Respiratory Medicine, Graduate School of Medicine, The University of Tokyo, Tokyo, 3Department of Biomedical Statistics and Bioinformatics, Kyoto University Graduate School of Medicine, Kyoto, 4Medical Department, AstraZeneca K.K., Osaka, 5Department of Respiratory Medicine, Tohoku University Graduate School of Medicine, Sendai, Japan Background and objective: There is increasing recognition of asthma–COPD overlap syndrome (ACOS, which shares some features of both asthma and COPD; however, the prevalence and characteristics of ACOS are not well understood. The aim of this study was to investigate the prevalence of ACOS among patients with COPD and its characteristics using a stepwise approach as stated in the recent report of the Global Initiative for Asthma (GINA and the Global Initiative for Chronic Obstructive Lung Disease (GOLD. Methods: This multicenter, cross-sectional, observational study enrolled outpatients who were receiving medical treatment for COPD. Clinical data, including spirometry results, were retrieved from medical records. For symptom assessment, patients were asked to complete the Clinical COPD questionnaire and the modified British Medical Research Council questionnaire. Results: Of the 1,008 patients analyzed, 167 (16.6% had syndromic features of ACOS. Of the total number of patients, 93 and 42 (9.2% and 4.2% also had a predefined clinical variability of ≥12%/≥200 mL and ≥12%/≥400 mL in forced expiratory volume in 1 second (FEV1, respectively, and therefore were identified as having ACOS. Conversely, the number of patients who had either syndromic or spirometric feature of ACOS was 595 (59.0%, ≥12%/≥200 mL FEV1 clinical variability, and 328 patients (32.5%, ≥12%/≥400 m

  9. Syk-dependent tyrosine phosphorylation of 3BP2 is required for optimal FcRγ-mediated phagocytosis and chemokine expression in U937 cells.

    Science.gov (United States)

    Chihara, Kazuyasu; Kato, Yuji; Yoshiki, Hatsumi; Takeuchi, Kenji; Fujieda, Shigeharu; Sada, Kiyonao

    2017-09-13

    The adaptor protein c-Abl SH3 domain binding protein-2 (3BP2) is tyrosine phosphorylated by Syk in response to cross-linking of antigen receptors, which in turn activates various immune responses. Recently, a study using the mouse model of cherubism, a dominant inherited disorder caused by mutations in the gene encoding 3BP2, showed that 3BP2 is involved in the regulation of phagocytosis mediated by Fc receptor for IgG (FcγR) in macrophages. However, the molecular mechanisms underlying 3BP2-mediated regulation of phagocytosis and the physiological relevance of 3BP2 tyrosine phosphorylation remains elusive. In this study, we established various gene knockout U937 cell lines using the CRISPR/Cas9 system and found that 3BP2 is rapidly tyrosine phosphorylated by Syk in response to cross-linking of FcγRI. Depletion of 3BP2 caused significant reduction in the Fc receptor γ chain (FcRγ)-mediated phagocytosis in addition to the FcγRI-mediated induction of chemokine mRNA for IL-8, CCL3L3 and CCL4L2. Syk-dependent tyrosine phosphorylation of 3BP2 was required for overcoming these defects. Finally, we found that the PH and SH2 domains play important roles on FcγRI-mediated tyrosine phosphorylation of 3BP2 in HL-60 cells. Taken together, these results indicate that Syk-dependent tyrosine phosphorylation of 3BP2 is required for optimal FcRγ-mediated phagocytosis and chemokine expression.

  10. A Spatial Approach to Identify Slum Areas in East Wara Sub-Districts, South Sulawesi

    Science.gov (United States)

    Anurogo, W.; Lubis, M. Z.; Pamungkas, D. S.; Hartono; Ibrahim, F. M.

    2017-12-01

    Spatial approach is one of the main approaches of geography, its analysis emphasizes the existence of space that serves to accommodate human activities. The dynamic development of the city area brings many impacts to the urban community’s own life patterns. The development of the city center which is the center of economic activity becomes the attraction for the community that can bring influence to the high flow of labor both from within the city itself and from outside the city area, thus causing the high flow of urbanization. Urbanization has caused an explosion in urban population and one implication is the occurrence of labor-clumping in major cities in Indonesia. Another impact of the high urbanization flow of cities is the problem of urban settlements. The more populations that come in the city, the worse the quality of the existing settlements in the city if not managed properly. This study aims to determine the location of slum areas in East Wara Sub-Districts using remote sensing technology tools and Geographic Information System (GIS). Parameters used to identify slum areas partially extracted using remote sensing data and for parameters that cannot be extracted using remote sensing data, information obtained from field surveys with information retrieval based on reference data. Analysis results for slum settlements taken from the parameters indicate that the East Wara Sub-District has the largest slum areas located in Pontap village. The village of Pontap has two classes of slums that are very shabby and slums. Slum classes are also in Surutangga Village. The result of the analysis shows that the slum settlement area has 46,324 Ha, which is only located in Pontap Village, whereas for the slum class are found in some villages of Pontap and Surutangga Urban Village, there are 37.797 Ha area. The class of slum settlement areas has the largest proportion of the area among other classes in East Wara Subdistrict. The class of slum settlement areas has an

  11. The GOES-R/JPSS Approach for Identifying Hazardous Low Clouds: Overview and Operational Impacts

    Science.gov (United States)

    Calvert, Corey; Pavolonis, Michael; Lindstrom, Scott; Gravelle, Chad; Terborg, Amanda

    2017-04-01

    Low ceiling and visibility is a weather hazard that nearly every forecaster, in nearly every National Weather Service (NWS) Weather Forecast Office (WFO), must regularly address. In addition, national forecast centers such as the Aviation Weather Center (AWC), Alaska Aviation Weather Unit (AAWU) and the Ocean Prediction Center (OPC) are responsible for issuing low ceiling and visibility related products. As such, reliable methods for detecting and characterizing hazardous low clouds are needed. Traditionally, hazardous areas of Fog/Low Stratus (FLS) are identified using a simple stand-alone satellite product that is constructed by subtracting the 3.9 and 11 μm brightness temperatures. However, the 3.9-11 μm brightness temperature difference (BTD) has several major limitations. In an effort to address the limitations of the BTD product, the GOES-R Algorithm Working Group (AWG) developed an approach that fuses satellite, Numerical Weather Prediction (NWP) model, Sea Surface Temperature (SST) analyses, and other data sets (e.g. digital surface elevation maps, surface emissivity maps, and surface type maps) to determine the probability that hazardous low clouds are present using a naïve Bayesian classifier. In addition, recent research has focused on blending geostationary (e.g. GOES-R) and low earth orbit (e.g. JPSS) satellite data to further improve the products. The FLS algorithm has adopted an enterprise approach in that it can utilize satellite data from a variety of current and future operational sensors and NWP data from a variety of models. The FLS products are available in AWIPS/N-AWIPS/AWIPS-II and have been evaluated within NWS operations over the last four years as part of the Satellite Proving Ground. Forecaster feedback has been predominantly positive and references to these products within Area Forecast Discussions (AFD's) indicate that the products are influencing operational forecasts. At the request of the NWS, the FLS products are currently being

  12. Outbreaks source: A new mathematical approach to identify their possible location

    Science.gov (United States)

    Buscema, Massimo; Grossi, Enzo; Breda, Marco; Jefferson, Tom

    2009-11-01

    Classical epidemiology has generally relied on the description and explanation of the occurrence of infectious diseases in relation to time occurrence of events rather than to place of occurrence. In recent times, computer generated dot maps have facilitated the modeling of the spread of infectious epidemic diseases either with classical statistics approaches or with artificial “intelligent systems”. Few attempts, however, have been made so far to identify the origin of the epidemic spread rather than its evolution by mathematical topology methods. We report on the use of a new artificial intelligence method (the H-PST Algorithm) and we compare this new technique with other well known algorithms to identify the source of three examples of infectious disease outbreaks derived from literature. The H-PST algorithm is a new system able to project a distances matrix of points (events) into a bi-dimensional space, with the generation of a new point, named hidden unit. This new hidden unit deforms the original Euclidean space and transforms it into a new space (cognitive space). The cost function of this transformation is the minimization of the differences between the original distance matrix among the assigned points and the distance matrix of the same points projected into the bi-dimensional map (or any different set of constraints). For many reasons we will discuss, the position of the hidden unit shows to target the outbreak source in many epidemics much better than the other classic algorithms specifically targeted for this task. Compared with main algorithms known in the location theory, the hidden unit was within yards of the outbreak source in the first example (the 2007 epidemic of Chikungunya fever in Italy). The hidden unit was located in the river between the two village epicentres of the spread exactly where the index case was living. Equally in the second (the 1967 foot and mouth disease epidemic in England), and the third (1854 London Cholera epidemic

  13. Identifying Country-Specific Cultures of Physics Education: A differential item functioning approach

    Science.gov (United States)

    Mesic, Vanes

    2012-11-01

    In international large-scale assessments of educational outcomes, student achievement is often represented by unidimensional constructs. This approach allows for drawing general conclusions about country rankings with respect to the given achievement measure, but it typically does not provide specific diagnostic information which is necessary for systematic comparisons and improvements of educational systems. Useful information could be obtained by exploring the differences in national profiles of student achievement between low-achieving and high-achieving countries. In this study, we aimed to identify the relative weaknesses and strengths of eighth graders' physics achievement in Bosnia and Herzegovina in comparison to the achievement of their peers from Slovenia. For this purpose, we ran a secondary analysis of Trends in International Mathematics and Science Study (TIMSS) 2007 data. The student sample consisted of 4,220 students from Bosnia and Herzegovina and 4,043 students from Slovenia. After analysing the cognitive demands of TIMSS 2007 physics items, the correspondent differential item functioning (DIF)/differential group functioning contrasts were estimated. Approximately 40% of items exhibited large DIF contrasts, indicating significant differences between cultures of physics education in Bosnia and Herzegovina and Slovenia. The relative strength of students from Bosnia and Herzegovina showed to be mainly associated with the topic area 'Electricity and magnetism'. Classes of items which required the knowledge of experimental method, counterintuitive thinking, proportional reasoning and/or the use of complex knowledge structures proved to be differentially easier for students from Slovenia. In the light of the presented results, the common practice of ranking countries with respect to universally established cognitive categories seems to be potentially misleading.

  14. A spatial modeling approach to identify potential butternut restoration sites in Mammoth Cave National Park

    Science.gov (United States)

    Thompson, L.M.; Van Manen, F.T.; Schlarbaum, S.E.; DePoy, M.

    2006-01-01

    Incorporation of disease resistance is nearly complete for several important North American hardwood species threatened by exotic fungal diseases. The next important step toward species restoration would be to develop reliable tools to delineate ideal restoration sites on a landscape scale. We integrated spatial modeling and remote sensing techniques to delineate potential restoration sites for Butternut (Juglans cinerea L.) trees, a hardwood species being decimated by an exotic fungus, in Mammoth Cave National Park (MCNP), Kentucky. We first developed a multivariate habitat model to determine optimum Butternut habitats within MCNP. Habitat characteristics of 54 known Butternut locations were used in combination with eight topographic and land use data layers to calculate an index of habitat suitability based on Mahalanobis distance (D2). We used a bootstrapping technique to test the reliability of model predictions. Based on a threshold value for the D2 statistic, 75.9% of the Butternut locations were correctly classified, indicating that the habitat model performed well. Because Butternut seedlings require extensive amounts of sunlight to become established, we used canopy cover data to refine our delineation of favorable areas for Butternut restoration. Areas with the most favorable conditions to establish Butternut seedlings were limited to 291.6 ha. Our study provides a useful reference on the amount and location of favorable Butternut habitat in MCNP and can be used to identify priority areas for future Butternut restoration. Given the availability of relevant habitat layers and accurate location records, our approach can be applied to other tree species and areas. ?? 2006 Society for Ecological Restoration International.

  15. Identifying and prioritizing barriers to implementation of smart energy city projects in Europe: An empirical approach

    International Nuclear Information System (INIS)

    Mosannenzadeh, Farnaz; Di Nucci, Maria Rosaria; Vettorato, Daniele

    2017-01-01

    Successful implementation of smart energy city projects in Europe is crucial for a sustainable transition of urban energy systems and the improvement of quality of life for citizens. We aim to develop a systematic classification and analysis of the barriers hindering successful implementation of smart energy city projects. Through an empirical approach, we investigated 43 communities implementing smart and sustainable energy city projects under the Sixth and Seventh Framework Programmes of the European Union. Validated through literature review, we identified 35 barriers categorized in policy, administrative, legal, financial, market, environmental, technical, social, and information-and-awareness dimensions. We prioritized these barriers, using a novel multi-dimensional methodology that simultaneously analyses barriers based on frequency, level of impact, causal relationship among barriers, origin, and scale. The results indicate that the key barriers are lacking or fragmented political support on the long term at the policy level, and lack of good cooperation and acceptance among project partners, insufficient external financial support, lack of skilled and trained personnel, and fragmented ownership at the project level. The outcome of the research should aid policy-makers to better understand and prioritize implementation barriers to develop effective action and policy interventions towards more successful implementation of smart energy city projects. - Highlights: • A solid empirical study on the implementation of European smart energy city projects. • We found 35 barriers in nine dimensions; e.g. policy, legal, financial, and social. • We suggested a new multi-dimensional methodology to prioritize barriers. • Lacking or fragmented political support on the long term is a key barrier. • We provided insights for action for project coordinators and policy makers.

  16. Assessment of a Novel Approach to Identify Trichiasis Cases Using Community Treatment Assistants in Tanzania.

    Directory of Open Access Journals (Sweden)

    Gregory S Greene

    2015-12-01

    Full Text Available Simple surgical intervention advocated by the World Health Organization can alleviate trachomatous trichiasis (TT and prevent subsequent blindness. A large backlog of TT cases remain unidentified and untreated. To increase identification and referral of TT cases, a novel approach using standard screening questions, a card, and simple training for Community Treatment Assistants (CTAs to use during Mass Drug Administration (MDA was developed and evaluated in Kongwa District, a trachoma-endemic area of central Tanzania.A community randomized trial was conducted in 36 communities during MDA. CTAs in intervention villages received an additional half-day of training and a TT screening card in addition to the training received by CTAs in villages assigned to usual care. All MDA participants 15 years and older were screened for TT, and senior TT graders confirmed case status by evaluating all screened-positive cases. A random sample of those screened negative for TT and those who did not present at MDA were also evaluated by the master graders. Intervention CTAs identified 5.6 times as many cases (n = 50 as those assigned to usual care (n = 9, p < 0.05. While specificity was above 90% for both groups, the sensitivity for the novel screening tool was 31.2% compared to 5.6% for the usual care group (p < 0.05.CTAs appear to be viable resources for the identification of TT cases. Additional training and use of a TT screening card significantly increased the ability of CTAs to recognize and refer TT cases during MDA; however, further efforts are needed to improve case detection and reduce the number of false positive cases.

  17. Predicting Fish Growth Potential and Identifying Water Quality Constraints: A Spatially-Explicit Bioenergetics Approach

    Science.gov (United States)

    Budy, Phaedra; Baker, Matthew; Dahle, Samuel K.

    2011-10-01

    Anthropogenic impairment of water bodies represents a global environmental concern, yet few attempts have successfully linked fish performance to thermal habitat suitability and fewer have distinguished co-varying water quality constraints. We interfaced fish bioenergetics, field measurements, and Thermal Remote Imaging to generate a spatially-explicit, high-resolution surface of fish growth potential, and next employed a structured hypothesis to detect relationships among measures of fish performance and co-varying water quality constraints. Our thermal surface of fish performance captured the amount and spatial-temporal arrangement of thermally-suitable habitat for three focal species in an extremely heterogeneous reservoir, but interpretation of this pattern was initially confounded by seasonal covariation of water residence time and water quality. Subsequent path analysis revealed that in terms of seasonal patterns in growth potential, catfish and walleye responded to temperature, positively and negatively, respectively; crappie and walleye responded to eutrophy (negatively). At the high eutrophy levels observed in this system, some desired fishes appear to suffer from excessive cultural eutrophication within the context of elevated temperatures whereas others appear to be largely unaffected or even enhanced. Our overall findings do not lead to the conclusion that this system is degraded by pollution; however, they do highlight the need to use a sensitive focal species in the process of determining allowable nutrient loading and as integrators of habitat suitability across multiple spatial and temporal scales. We provide an integrated approach useful for quantifying fish growth potential and identifying water quality constraints on fish performance at spatial scales appropriate for whole-system management.

  18. A side-effect free method for identifying cancer drug targets.

    Science.gov (United States)

    Ashraf, Md Izhar; Ong, Seng-Kai; Mujawar, Shama; Pawar, Shrikant; More, Pallavi; Paul, Somnath; Lahiri, Chandrajit

    2018-04-27

    Identifying effective drug targets, with little or no side effects, remains an ever challenging task. A potential pitfall of failing to uncover the correct drug targets, due to side effect of pleiotropic genes, might lead the potential drugs to be illicit and withdrawn. Simplifying disease complexity, for the investigation of the mechanistic aspects and identification of effective drug targets, have been done through several approaches of protein interactome analysis. Of these, centrality measures have always gained importance in identifying candidate drug targets. Here, we put forward an integrated method of analysing a complex network of cancer and depict the importance of k-core, functional connectivity and centrality (KFC) for identifying effective drug targets. Essentially, we have extracted the proteins involved in the pathways leading to cancer from the pathway databases which enlist real experimental datasets. The interactions between these proteins were mapped to build an interactome. Integrative analyses of the interactome enabled us to unearth plausible reasons for drugs being rendered withdrawn, thereby giving future scope to pharmaceutical industries to potentially avoid them (e.g. ESR1, HDAC2, F2, PLG, PPARA, RXRA, etc). Based upon our KFC criteria, we have shortlisted ten proteins (GRB2, FYN, PIK3R1, CBL, JAK2, LCK, LYN, SYK, JAK1 and SOCS3) as effective candidates for drug development.

  19. Identifying the Return on Investment for Army Migration to a Modular Open Systems Approach for Future and Legacy Systems

    Science.gov (United States)

    2017-04-05

    Identifying the Return on Investment for Army Migration to a Modular Open Systems Approach for Future and Legacy Systems Phillip Minor...Authorization Act (NDAA) of 2015, cites the modular open systems approach (MOSA) as both a business and technical strategy to reduce the cost of system ...access the service over the network. Combine the advances cited above with the emergence of systems developed using the modular open systems approach

  20. A multivariate and stochastic approach to identify key variables to rank dairy farms on profitability.

    Science.gov (United States)

    Atzori, A S; Tedeschi, L O; Cannas, A

    2013-05-01

    The economic efficiency of dairy farms is the main goal of farmers. The objective of this work was to use routinely available information at the dairy farm level to develop an index of profitability to rank dairy farms and to assist the decision-making process of farmers to increase the economic efficiency of the entire system. A stochastic modeling approach was used to study the relationships between inputs and profitability (i.e., income over feed cost; IOFC) of dairy cattle farms. The IOFC was calculated as: milk revenue + value of male calves + culling revenue - herd feed costs. Two databases were created. The first one was a development database, which was created from technical and economic variables collected in 135 dairy farms. The second one was a synthetic database (sDB) created from 5,000 synthetic dairy farms using the Monte Carlo technique and based on the characteristics of the development database data. The sDB was used to develop a ranking index as follows: (1) principal component analysis (PCA), excluding IOFC, was used to identify principal components (sPC); and (2) coefficient estimates of a multiple regression of the IOFC on the sPC were obtained. Then, the eigenvectors of the sPC were used to compute the principal component values for the original 135 dairy farms that were used with the multiple regression coefficient estimates to predict IOFC (dRI; ranking index from development database). The dRI was used to rank the original 135 dairy farms. The PCA explained 77.6% of the sDB variability and 4 sPC were selected. The sPC were associated with herd profile, milk quality and payment, poor management, and reproduction based on the significant variables of the sPC. The mean IOFC in the sDB was 0.1377 ± 0.0162 euros per liter of milk (€/L). The dRI explained 81% of the variability of the IOFC calculated for the 135 original farms. When the number of farms below and above 1 standard deviation (SD) of the dRI were calculated, we found that 21

  1. Comparison of methodological approaches to identify economic activity regularities in transition economy

    Directory of Open Access Journals (Sweden)

    Jitka Poměnková

    2011-01-01

    Full Text Available Presented paper focuses on consideration and evaluation of methodical approaches to analyze cyclical structure character of economic activity in transition economy. As a starting point, work in time domain is applied, which is followed in frequency domain approach. Both approaches are viewed from methodical as well as application point of view and their advantage and disadvantage are discussed. Consequently, time-frequency domain approach is added and applied on real data. On the basis of obtained results recommendation is formulated. All discussed methodical approaches are also considered from the perspective of capability to evaluate behaving of business cycle in time of global economic crisis before/after year 2008. The empirical part of the paper deals with data of gross domestic product in the Czech Republic in 1996/Q1–2010/Q2.

  2. Identifying Creatively Gifted Students: Necessity of a Multi-Method Approach

    Science.gov (United States)

    Ambrose, Laura; Machek, Greg R.

    2015-01-01

    The process of identifying students as creatively gifted provides numerous challenges for educators. Although many schools assess for creativity in identifying students for gifted and talented services, the relationship between creativity and giftedness is often not fully understood. This article reviews commonly used methods of creativity…

  3. A systems genetics approach identifies genes and pathways for type 2 diabetes in human islets

    DEFF Research Database (Denmark)

    Taneera, Jalal; Lang, Stefan; Sharma, Amitabh

    2012-01-01

    Close to 50 genetic loci have been associated with type 2 diabetes (T2D), but they explain only 15% of the heritability. In an attempt to identify additional T2D genes, we analyzed global gene expression in human islets from 63 donors. Using 48 genes located near T2D risk variants, we identified ...

  4. Identifying target groups for environmentally sustainable transport: assessment of different segmentation approaches

    DEFF Research Database (Denmark)

    Haustein, Sonja; Hunecke, Marcel

    2013-01-01

    Recently, the use of attitude-based market segmentation to promote environmentally sustainable transport has significantly increased. The segmentation of the population into meaningful groups sharing similar attitudes and preferences provides valuable information about how green measures should...... and behavioural segmentations are compared regarding marketing criteria. Although none of the different approaches can claim absolute superiority, attitudinal approaches show advantages in providing startingpoints for interventions to reduce car use....

  5. A New Approach for Identifying Ionospheric Gradients in the Context of the Gagan System

    Science.gov (United States)

    Kudala, Ravi Chandra

    The Indian Space Research Organization and the Airports Authority of India are jointly implementing the Global Positioning System (GPS) aided GEO Augmented Navigation (GAGAN) system in order to meet the following required navigation performance (RNP) parameters: integrity, continuity, accuracy, and availability (for aircraft operations). Such a system provides the user with orbit, clock, and ionospheric corrections in addition to ranging signals via the geostationary earth orbit satellite (GEOSAT). The equatorial ionization anomaly (EIA), due to rapid non-uniform electron-ion recombination that persists on the Indian subcontinent, causes ionospheric gradients. Ionospheric gradients represent the most severe threat to high-integrity differential GNSS systems such as GAGAN. In order to ensure integrity under conditions of an ionospheric storm, the following three objectives must be met: careful monitoring, error bounding, and sophisticated storm-front modeling. The first objective is met by continuously tracking data due to storms, and, on quiet days, determining precise estimates of the threat parameters from reference monitoring stations. The second objective is met by quantifying the above estimates of threat parameters due to storms through maximum and minimum typical thresholds. In the context GAGAN, this work proposes a new method for identifying ionospheric gradients, in addition to determining an appropriate upper bound, in order to sufficiently understand error during storm days. Initially, carrier phase data of the GAGAN network from Indian TEC stations for both storm and quiet days was used for estimating ionospheric spatial and temporal gradients (the vertical ionospheric gradient (σVIG) and the rate of the TEC index (ROTI), respectively) in multiple viewing directions. Along similar lines, using the carrier to noise ratio (C/N0) for the same data, the carrier to noise ratio index (σCNRI) was derived. Subsequently, the one-toone relationship between

  6. Development of Novel Random Network Theory-Based Approaches to Identify Network Interactions among Nitrifying Bacteria

    Energy Technology Data Exchange (ETDEWEB)

    Shi, Cindy

    2015-07-17

    The interactions among different microbial populations in a community could play more important roles in determining ecosystem functioning than species numbers and their abundances, but very little is known about such network interactions at a community level. The goal of this project is to develop novel framework approaches and associated software tools to characterize the network interactions in microbial communities based on high throughput, large scale high-throughput metagenomics data and apply these approaches to understand the impacts of environmental changes (e.g., climate change, contamination) on network interactions among different nitrifying populations and associated microbial communities.

  7. A Contextual Approach to the Assessment of Social Skills: Identifying Meaningful Behaviors for Social Competence

    Science.gov (United States)

    Warnes, Emily D.; Sheridan, Susan M.; Geske, Jenenne; Warnes, William A.

    2005-01-01

    An exploratory study was conducted which assessed behaviors that characterize social competence in the second and fifth grades. A contextual approach was used to gather information from second- and fifth-grade children and their parents and teachers regarding the behaviors they perceived to be important for getting along well with peers. Data were…

  8. A probabilistic approach to identify putative drug targets in biochemical networks.

    NARCIS (Netherlands)

    Murabito, E.; Smalbone, K.; Swinton, J.; Westerhoff, H.V.; Steuer, R.

    2011-01-01

    Network-based drug design holds great promise in clinical research as a way to overcome the limitations of traditional approaches in the development of drugs with high efficacy and low toxicity. This novel strategy aims to study how a biochemical network as a whole, rather than its individual

  9. Identifying multiple outliers in linear regression: robust fit and clustering approach

    International Nuclear Information System (INIS)

    Robiah Adnan; Mohd Nor Mohamad; Halim Setan

    2001-01-01

    This research provides a clustering based approach for determining potential candidates for outliers. This is modification of the method proposed by Serbert et. al (1988). It is based on using the single linkage clustering algorithm to group the standardized predicted and residual values of data set fit by least trimmed of squares (LTS). (Author)

  10. Identify too big to fail banks and capital insurance: An equilibrium approach

    OpenAIRE

    Katerina Ivanov

    2017-01-01

    The objective of this paper is develop a rational expectation equilibrium model of capital insurance to identify too big to fail banks. The main results of this model include (1) too big to fail banks can be identified explicitly by a systemic risk measure, loss betas, of all banks in the entire financial sector; (2) the too big to fail feature can be largely justified by a high level of loss beta; (3) the capital insurance proposal benefits market participants and reduces the systemic risk; ...

  11. A Transcriptomic Approach to Identify Novel Drug Efflux Pumps in Bacteria.

    Science.gov (United States)

    Li, Liping; Tetu, Sasha G; Paulsen, Ian T; Hassan, Karl A

    2018-01-01

    The core genomes of most bacterial species include a large number of genes encoding putative efflux pumps. The functional roles of most of these pumps are unknown, however, they are often under tight regulatory control and expressed in response to their substrates. Therefore, one way to identify pumps that function in antimicrobial resistance is to examine the transcriptional responses of efflux pump genes to antimicrobial shock. By conducting complete transcriptomic experiments following antimicrobial shock treatments, it may be possible to identify novel drug efflux pumps encoded in bacterial genomes. In this chapter we describe a complete workflow for conducting transcriptomic analyses by RNA sequencing, to determine transcriptional changes in bacteria responding to antimicrobials.

  12. A User Centered Innovation Approach Identifying Key User Values for the E-Newspaper

    OpenAIRE

    Carina Ihlström Eriksson; Jesper Svensson

    2009-01-01

    We have studied the pre-adoption phase of the e-newspaper, i.e. a newspaper published with e-paper technology. The research question of this article is: In what way can a user centered innovation process contribute to identifying key values in mobile innovations? The aim of this article is threefold: firstly, to identify key values for the e-newspaper, secondly, to examine the intention to adopt a new possible innovation and thirdly, to explore user centered design processes ability to captur...

  13. Particle Swarm Based Approach of a Real-Time Discrete Neural Identifier for Linear Induction Motors

    Directory of Open Access Journals (Sweden)

    Alma Y. Alanis

    2013-01-01

    Full Text Available This paper focusses on a discrete-time neural identifier applied to a linear induction motor (LIM model, whose model is assumed to be unknown. This neural identifier is robust in presence of external and internal uncertainties. The proposed scheme is based on a discrete-time recurrent high-order neural network (RHONN trained with a novel algorithm based on extended Kalman filter (EKF and particle swarm optimization (PSO, using an online series-parallel con…figuration. Real-time results are included in order to illustrate the applicability of the proposed scheme.

  14. Identifying Ghanaian Pre-Service Teachers' Readiness for Computer Use: A Technology Acceptance Model Approach

    Science.gov (United States)

    Gyamfi, Stephen Adu

    2016-01-01

    This study extends the technology acceptance model to identify factors that influence technology acceptance among pre-service teachers in Ghana. Data from 380 usable questionnaires were tested against the research model. Utilising the extended technology acceptance model (TAM) as a research framework, the study found that: pre-service teachers'…

  15. An interdisciplinary approach to identify adaptation strategies that enhance flood resilience and urban liveability

    DEFF Research Database (Denmark)

    Rogers, B. C.; Bertram, N.; Gunn, Alex

    This paper provides guidance on how to identify and design the most suitable climate adaptation strategies for enhancing the liveability and flood resilience of urban catchments. It presents findings from a case study of Elwood, a coastal Melbourne suburb regularly affected by flooding. The resea...

  16. Identifying Onboarding Heuristics for Free-to-Play Mobile Games: A Mixed Methods Approach

    DEFF Research Database (Denmark)

    Thomsen, Line Ebdrup; Weigert Petersen, Falko; Mirza-Babaei, Pejman

    2016-01-01

    The onboarding phase of Free-to-Play mobile games, covering the first few minutes of play, typically sees a substantial retention rate amongst players. It is therefore crucial to the success of these games that the onboarding phase promotes engagement to the widest degree possible. In this paper ...... of puzzle games, base builders and arcade games, and utilize different onboarding phase design approaches. Results showcase how heuristics can be used to design engaging onboarding phases in mobile games....

  17. A Guttman-Based Approach to Identifying Cumulativeness Applied to Chimpanzee Culture

    OpenAIRE

    Graber, RB; de Cock, DR; Burton, ML

    2012-01-01

    Human culture appears to build on itself-that is, to be to some extent cumulative. Whether this property is shared by culture in the common chimpanzee is controversial. The question previously has been approached, qualitatively (and inconclusively), by debating whether any chimpanzee culture traits have resulted from individuals building on one another's work ("ratcheting"). The fact that the chimpanzees at different sites have distinctive repertoires of traits affords a different avenue of a...

  18. Provocative Endoscopy to Identify Bleeding Site in Upper Gastrointestinal Bleeding: A Novel Approach in Transarterial Embolization.

    Science.gov (United States)

    Kamo, Minobu; Fuwa, Sokun; Fukuda, Katsuyuki; Fujita, Yoshiyuki; Kurihara, Yasuyuki

    2016-07-01

    This report describes a novel approach to endoscopically induce bleeding by removing a clot from the bleeding site during angiography for upper gastrointestinal (UGI) hemorrhage. This procedure enabled accurate identification of the bleeding site, allowing for successful targeted embolization despite a negative initial angiogram. Provocative endoscopy may be a feasible and useful option for angiography of obscure bleeding sites in patients with UGI arterial hemorrhage. Copyright © 2016 SIR. Published by Elsevier Inc. All rights reserved.

  19. An integrated approach to identify the origin of PM10 exceedances.

    Science.gov (United States)

    Amodio, M; Andriani, E; de Gennaro, G; Demarinis Loiotile, A; Di Gilio, A; Placentino, M C

    2012-09-01

    This study was aimed to the development of an integrated approach for the characterization of particulate matter (PM) pollution events in the South of Italy. PM(10) and PM(2.5) daily samples were collected from June to November 2008 at an urban background site located in Bari (Puglia Region, South of Italy). Meteorological data, particle size distributions and atmospheric dispersion conditions were also monitored in order to provide information concerning the different features of PM sources. The collected data allowed suggesting four indicators to characterize different PM(10) exceedances. PM(2.5)/PM(10) ratio, natural radioactivity, aerosol maps and back-trajectory analysis and particle distributions were considered in order to evaluate the contribution of local anthropogenic sources and to determine the different origins of intrusive air mass coming from long-range transport, such as African dust outbreaks and aerosol particles from Central and Eastern Europe. The obtained results were confirmed by applying principal component analysis to the number particle concentration dataset and by the chemical characterization of the samples (PM(10) and PM(2.5)). The integrated approach for PM study suggested in this paper can be useful to support the air quality managers for the development of cost-effective control strategies and the application of more suitable risk management approaches.

  20. Surveying Libraries to Identify Best Practices for a Menu Approach for Library Instruction Requests

    Directory of Open Access Journals (Sweden)

    Candice Benjes-Small

    2009-11-01

    Full Text Available A challenging situation has developed in regards to library instruction. With increases in both the quantity of information and the variety of information technologies being made available to researchers, the information literacy landscape is getting more complex. Simultaneously, the time allotted for library instruction is remaining essentially the same. In order to market the breadth of content available for library instruction sessions and to promote collaboration between librarians and teaching faculty in order to create optimal instruction sessions an 'a la carte menu' approach to library instruction requests was adopted by Radford University in 2004. Since the late 1990s a number of community colleges and universities have included some type of menu in their instruction request forms or documentation and the authors desired to understand what approach these institutions had taken and whether they were effective in marketing instruction and improving communication between library instructors and teaching faculty. They analyzed forty-seven adaptations of the menu available on the web and surveyed the librarians who created them. In this article the authors present the findings of the web analysis and the survey, and recommendations are given for using the menu approach to library instruction requests.

  1. Combining phenotypic and proteomic approaches to identify membrane targets in a ‘triple negative’ breast cancer cell type

    Directory of Open Access Journals (Sweden)

    Rust Steven

    2013-02-01

    Full Text Available Abstract Background The continued discovery of therapeutic antibodies, which address unmet medical needs, requires the continued discovery of tractable antibody targets. Multiple protein-level target discovery approaches are available and these can be used in combination to extensively survey relevant cell membranomes. In this study, the MDA-MB-231 cell line was selected for membranome survey as it is a ‘triple negative’ breast cancer cell line, which represents a cancer subtype that is aggressive and has few treatment options. Methods The MDA-MB-231 breast carcinoma cell line was used to explore three membranome target discovery approaches, which were used in parallel to cross-validate the significance of identified antigens. A proteomic approach, which used membrane protein enrichment followed by protein identification by mass spectrometry, was used alongside two phenotypic antibody screening approaches. The first phenotypic screening approach was based on hybridoma technology and the second was based on phage display technology. Antibodies isolated by the phenotypic approaches were tested for cell specificity as well as internalisation and the targets identified were compared to each other as well as those identified by the proteomic approach. An anti-CD73 antibody derived from the phage display-based phenotypic approach was tested for binding to other ‘triple negative’ breast cancer cell lines and tested for tumour growth inhibitory activity in a MDA-MB-231 xenograft model. Results All of the approaches identified multiple cell surface markers, including integrins, CD44, EGFR, CD71, galectin-3, CD73 and BCAM, some of which had been previously confirmed as being tractable to antibody therapy. In total, 40 cell surface markers were identified for further study. In addition to cell surface marker identification, the phenotypic antibody screening approaches provided reagent antibodies for target validation studies. This is illustrated

  2. Identify too big to fail banks and capital insurance: An equilibrium approach

    Directory of Open Access Journals (Sweden)

    Katerina Ivanov

    2017-09-01

    Full Text Available The objective of this paper is develop a rational expectation equilibrium model of capital insurance to identify too big to fail banks. The main results of this model include (1 too big to fail banks can be identified explicitly by a systemic risk measure, loss betas, of all banks in the entire financial sector; (2 the too big to fail feature can be largely justified by a high level of loss beta; (3 the capital insurance proposal benefits market participants and reduces the systemic risk; (4 the implicit guarantee subsidy can be estimated endogenously; and lastly, (5 the capital insurance proposal can be used to resolve the moral hazard issue. We implement this model and document that the too big to fail issue has been considerably reduced in the pro-crisis period. As a result, the capital insurance proposal could be a useful macro-regulation innovation policy tool

  3. Astronomy and big data a data clustering approach to identifying uncertain galaxy morphology

    CERN Document Server

    Edwards, Kieran Jay

    2014-01-01

    With the onset of massive cosmological data collection through media such as the Sloan Digital Sky Survey (SDSS), galaxy classification has been accomplished for the most part with the help of citizen science communities like Galaxy Zoo. Seeking the wisdom of the crowd for such Big Data processing has proved extremely beneficial. However, an analysis of one of the Galaxy Zoo morphological classification data sets has shown that a significant majority of all classified galaxies are labelled as “Uncertain”. This book reports on how to use data mining, more specifically clustering, to identify galaxies that the public has shown some degree of uncertainty for as to whether they belong to one morphology type or another. The book shows the importance of transitions between different data mining techniques in an insightful workflow. It demonstrates that Clustering enables to identify discriminating features in the analysed data sets, adopting a novel feature selection algorithms called Incremental Feature Select...

  4. A GIS Approach to Identifying Socially and Medically Vulnerable Older Adult Populations in South Florida.

    Science.gov (United States)

    Hames, Elizabeth; Stoler, Justin; Emrich, Christopher T; Tewary, Sweta; Pandya, Naushira

    2017-11-10

    We define, map, and analyze geodemographic patterns of socially and medically vulnerable older adults within the tri-county region of South Florida. We apply principal components analysis (PCA) to a set of previously identified indicators of social and medical vulnerability at the census tract level. We create and map age-stratified vulnerability scores using a geographic information system (GIS), and use spatial analysis techniques to identify patterns and interactions between social and medical vulnerability. Key factors contributing to social vulnerability in areas with higher numbers of older adults include age, large household size, and Hispanic ethnicity. Medical vulnerability in these same areas is driven by disease burden, access to emergency cardiac services, availability of nursing home and hospice beds, access to home health care, and available mental health services. Age-dependent areas of social vulnerability emerge in Broward County, whereas age-dependent areas of medical vulnerability emerge in Palm Beach County. Older-adult social and medical vulnerability interact differently throughout the study area. Spatial analysis of older adult social and medical vulnerability using PCA and GIS can help identify age-dependent pockets of vulnerability that are not easily identifiable in a populationwide analysis; improve our understanding of the dynamic spatial organization of health care, health care needs, access to care, and outcomes; and ultimately serve as a tool for health care planning. © The Author 2016. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  5. An International Approach to identify the root causes of Childhood Leukemia

    International Nuclear Information System (INIS)

    Laurier, Dominique

    2015-01-01

    Living near a nuclear site is one of the risk factors studied for childhood leukemia. The IRSN and BfS brought together scientists from several disciplines under the aegis of the European Association MelodiGLO to take stock of the existing epidemiological studies, their contributions and their limitations as well as to identify the analysis and research avenues to provide more robust answers. (author)

  6. Identifying predictors, moderators, and mediators of antidepressant response in major depressive disorder: neuroimaging approaches.

    Science.gov (United States)

    Phillips, Mary L; Chase, Henry W; Sheline, Yvette I; Etkin, Amit; Almeida, Jorge R C; Deckersbach, Thilo; Trivedi, Madhukar H

    2015-02-01

    Despite significant advances in neuroscience and treatment development, no widely accepted biomarkers are available to inform diagnostics or identify preferred treatments for individuals with major depressive disorder. In this critical review, the authors examine the extent to which multimodal neuroimaging techniques can identify biomarkers reflecting key pathophysiologic processes in depression and whether such biomarkers may act as predictors, moderators, and mediators of treatment response that might facilitate development of personalized treatments based on a better understanding of these processes. The authors first highlight the most consistent findings from neuroimaging studies using different techniques in depression, including structural and functional abnormalities in two parallel neural circuits: serotonergically modulated implicit emotion regulation circuitry, centered on the amygdala and different regions in the medial prefrontal cortex; and dopaminergically modulated reward neural circuitry, centered on the ventral striatum and medial prefrontal cortex. They then describe key findings from the relatively small number of studies indicating that specific measures of regional function and, to a lesser extent, structure in these neural circuits predict treatment response in depression. Limitations of existing studies include small sample sizes, use of only one neuroimaging modality, and a focus on identifying predictors rather than moderators and mediators of differential treatment response. By addressing these limitations and, most importantly, capitalizing on the benefits of multimodal neuroimaging, future studies can yield moderators and mediators of treatment response in depression to facilitate significant improvements in shorter- and longer-term clinical and functional outcomes.

  7. Identifying Predictors, Moderators, and Mediators of Antidepressant Response in Major Depressive Disorder: Neuroimaging Approaches

    Science.gov (United States)

    Phillips, Mary L.; Chase, Henry W.; Sheline, Yvette I.; Etkin, Amit; Almeida, Jorge R.C.; Deckersbach, Thilo; Trivedi, Madhukar H.

    2015-01-01

    Objective Despite significant advances in neuroscience and treatment development, no widely accepted biomarkers are available to inform diagnostics or identify preferred treatments for individuals with major depressive disorder. Method In this critical review, the authors examine the extent to which multimodal neuroimaging techniques can identify biomarkers reflecting key pathophysiologic processes in depression and whether such biomarkers may act as predictors, moderators, and mediators of treatment response that might facilitate development of personalized treatments based on a better understanding of these processes. Results The authors first highlight the most consistent findings from neuroimaging studies using different techniques in depression, including structural and functional abnormalities in two parallel neural circuits: serotonergically modulated implicit emotion regulation circuitry, centered on the amygdala and different regions in the medial prefrontal cortex; and dopaminergically modulated reward neural circuitry, centered on the ventral striatum and medial prefrontal cortex. They then describe key findings from the relatively small number of studies indicating that specific measures of regional function and, to a lesser extent, structure in these neural circuits predict treatment response in depression. Conclusions Limitations of existing studies include small sample sizes, use of only one neuroimaging modality, and a focus on identifying predictors rather than moderators and mediators of differential treatment response. By addressing these limitations and, most importantly, capitalizing on the benefits of multimodal neuroimaging, future studies can yield moderators and mediators of treatment response in depression to facilitate significant improvements in shorter- and longer-term clinical and functional outcomes. PMID:25640931

  8. A target based approach identifies genomic predictors of breast cancer patient response to chemotherapy

    Directory of Open Access Journals (Sweden)

    Hallett Robin M

    2012-05-01

    Full Text Available Abstract Background The efficacy of chemotherapy regimens in breast cancer patients is variable and unpredictable. Whether individual patients either achieve long-term remission or suffer recurrence after therapy may be dictated by intrinsic properties of their breast tumors including genetic lesions and consequent aberrant transcriptional programs. Global gene expression profiling provides a powerful tool to identify such tumor-intrinsic transcriptional programs, whose analyses provide insight into the underlying biology of individual patient tumors. For example, multi-gene expression signatures have been identified that can predict the likelihood of disease reccurrence, and thus guide patient prognosis. Whereas such prognostic signatures are being introduced in the clinical setting, similar signatures that predict sensitivity or resistance to chemotherapy are not currently clinically available. Methods We used gene expression profiling to identify genes that were co-expressed with genes whose transcripts encode the protein targets of commonly used chemotherapeutic agents. Results Here, we present target based expression indices that predict breast tumor response to anthracycline and taxane based chemotherapy. Indeed, these signatures were independently predictive of chemotherapy response after adjusting for standard clinic-pathological variables such as age, grade, and estrogen receptor status in a cohort of 488 breast cancer patients treated with adriamycin and taxotere/taxol. Conclusions Importantly, our findings suggest the practicality of developing target based indices that predict response to therapeutics, as well as highlight the possibility of using gene signatures to guide the use of chemotherapy during treatment of breast cancer patients.

  9. Improving probabilistic prediction of daily streamflow by identifying Pareto optimal approaches for modelling heteroscedastic residual errors

    Science.gov (United States)

    David, McInerney; Mark, Thyer; Dmitri, Kavetski; George, Kuczera

    2017-04-01

    This study provides guidance to hydrological researchers which enables them to provide probabilistic predictions of daily streamflow with the best reliability and precision for different catchment types (e.g. high/low degree of ephemerality). Reliable and precise probabilistic prediction of daily catchment-scale streamflow requires statistical characterization of residual errors of hydrological models. It is commonly known that hydrological model residual errors are heteroscedastic, i.e. there is a pattern of larger errors in higher streamflow predictions. Although multiple approaches exist for representing this heteroscedasticity, few studies have undertaken a comprehensive evaluation and comparison of these approaches. This study fills this research gap by evaluating 8 common residual error schemes, including standard and weighted least squares, the Box-Cox transformation (with fixed and calibrated power parameter, lambda) and the log-sinh transformation. Case studies include 17 perennial and 6 ephemeral catchments in Australia and USA, and two lumped hydrological models. We find the choice of heteroscedastic error modelling approach significantly impacts on predictive performance, though no single scheme simultaneously optimizes all performance metrics. The set of Pareto optimal schemes, reflecting performance trade-offs, comprises Box-Cox schemes with lambda of 0.2 and 0.5, and the log scheme (lambda=0, perennial catchments only). These schemes significantly outperform even the average-performing remaining schemes (e.g., across ephemeral catchments, median precision tightens from 105% to 40% of observed streamflow, and median biases decrease from 25% to 4%). Theoretical interpretations of empirical results highlight the importance of capturing the skew/kurtosis of raw residuals and reproducing zero flows. Recommendations for researchers and practitioners seeking robust residual error schemes for practical work are provided.

  10. Research Resource: A Dual Proteomic Approach Identifies Regulated Islet Proteins During β-Cell Mass Expansion In Vivo

    DEFF Research Database (Denmark)

    Horn, Signe; Kirkegaard, Jeannette S.; Hoelper, Soraya

    2016-01-01

    to be up regulated as a response to pregnancy. These included several proteins, not previously associated with pregnancy-induced islet expansion, such as CLIC1, STMN1, MCM6, PPIB, NEDD4, and HLTF. Confirming the validity of our approach, we also identified proteins encoded by genes known to be associated...

  11. Integrated Pathway-Based Approach Identifies Association between Genomic Regions at CTCF and CACNB2 and Schizophrenia

    NARCIS (Netherlands)

    Juraeva, Dilafruz; Haenisch, Britta; Zapatka, Marc; Frank, Josef; Witt, Stephanie H.; Mühleisen, Thomas W.; Treutlein, Jens; Strohmaier, Jana; Meier, Sandra; Degenhardt, Franziska; Giegling, Ina; Ripke, Stephan; Leber, Markus; Lange, Christoph; Schulze, Thomas G.; Mössner, Rainald; Nenadic, Igor; Sauer, Heinrich; Rujescu, Dan; Maier, Wolfgang; Børglum, Anders; Ophoff, Roel; Cichon, Sven; Nöthen, Markus M.; Rietschel, Marcella; Mattheisen, Manuel; Brors, Benedikt; Kahn, René S.; Cahn, Wiepke; Linszen, Don H.; de Haan, Lieuwe; van Os, Jim; Krabbendam, Lydia; Myin-Germeys, Inez; Wiersma, Durk; Bruggeman, Richard; Mors, O.; Børglum, A. D.; Mortensen, P. B.; Pedersen, C. B.; Demontis, D.; Grove, J.; Mattheisen, M.; Hougaard, D. M.

    2014-01-01

    In the present study, an integrated hierarchical approach was applied to: (1) identify pathways associated with susceptibility to schizophrenia; (2) detect genes that may be potentially affected in these pathways since they contain an associated polymorphism; and (3) annotate the functional

  12. 78 FR 20672 - Literature Review ApproachIdentifying Research Needs for Assessing Safe Use of High Intakes of...

    Science.gov (United States)

    2013-04-05

    ... DEPARTMENT OF HEALTH AND HUMAN SERVICES National Institutes of Health Literature Review Approach... Needs for Assessing Safe Use of High Intakes of Folic Acid,'' for review of the pertinent literature... folate and folic acid, screening of the literature was undertaken to identify the potential adverse...

  13. Exome-first approach identified a novel gloss deletion associated with Lowe syndrome.

    Science.gov (United States)

    Watanabe, Miki; Nakagawa, Ryuji; Kohmoto, Tomohiro; Naruto, Takuya; Suga, Ken-Ichi; Goji, Aya; Horikawa, Hideaki; Masuda, Kiyoshi; Kagami, Shoji; Imoto, Issei

    2016-01-01

    Lowe syndrome (LS) is an X-linked disorder affecting the eyes, nervous system and kidneys, typically caused by missense or nonsense/frameshift OCRL mutations. We report a 6-month-old male clinically suspected to have LS, but without the Fanconi-type renal dysfunction. Using a targeted-exome sequencing-first approach, LS was diagnosed by the identification of a deletion involving 1.7 Mb at Xq25-q26.1, encompassing the entire OCRL gene and neighboring loci.

  14. [The general methodological approaches identifying strategic positions in developing healthy lifestyle of population].

    Science.gov (United States)

    Dorofeev, S B; Babenko, A I

    2017-01-01

    The article deals with analysis of national and international publications concerning methodological aspects of elaborating systematic approach to healthy life-style of population. This scope of inquiry plays a key role in development of human capital. The costs related to healthy life-style are to be considered as personal investment into future income due to physical incrementation of human capital. The definitions of healthy life-style, its categories and supportive factors are to be considered in the process of development of strategies and programs of healthy lifestyle. The implementation of particular strategies entails application of comprehensive information and educational programs meant for various categories of population. Therefore, different motivation techniques are to be considered for children, adolescents, able-bodied population, the elderly. This approach is to be resulted in establishing particular responsibility for national government, territorial administrations, health care administrations, employers and population itself. The necessity of complex legislative measures is emphasized. The recent social hygienic studies were focused mostly on particular aspects of development of healthy life-style of population. Hence, the demand for long term exploration of development of organizational and functional models implementing medical preventive measures on the basis of comprehensive information analysis using statistical, sociological and professional expertise.

  15. Integrating modelling and phenotyping approaches to identify and screen complex traits - Illustration for transpiration efficiency in cereals.

    Science.gov (United States)

    Chenu, K; van Oosterom, E J; McLean, G; Deifel, K S; Fletcher, A; Geetika, G; Tirfessa, A; Mace, E S; Jordan, D R; Sulman, R; Hammer, G L

    2018-02-21

    Following advances in genetics, genomics, and phenotyping, trait selection in breeding is limited by our ability to understand interactions within the plants and with their environments, and to target traits of most relevance for the target population of environments. We propose an integrated approach that combines insights from crop modelling, physiology, genetics, and breeding to identify traits valuable for yield gain in the target population of environments, develop relevant high-throughput phenotyping platforms, and identify genetic controls and their values in production environments. This paper uses transpiration efficiency (biomass produced per unit of water used) as an example of a complex trait of interest to illustrate how the approach can guide modelling, phenotyping, and selection in a breeding program. We believe that this approach, by integrating insights from diverse disciplines, can increase the resource use efficiency of breeding programs for improving yield gains in target populations of environments.

  16. Identifying "social smoking" U.S. young adults using an empirically-driven approach.

    Science.gov (United States)

    Villanti, Andrea C; Johnson, Amanda L; Rath, Jessica M; Williams, Valerie; Vallone, Donna M; Abrams, David B; Hedeker, Donald; Mermelstein, Robin J

    2017-07-01

    The phenomenon of "social smoking" emerged in the past decade as an important area of research, largely due to its high prevalence in young adults. The purpose of this study was to identify classes of young adult ever smokers based on measures of social and contextual influences on tobacco use. Latent class models were developed using social smoking measures, and not the frequency or quantity of tobacco use. Data come from a national sample of young adult ever smokers aged 18-24 (Truth Initiative Young Adult Cohort Study, N=1564). The optimal models identified three latent classes: Class 1 - nonsmokers (52%); Class 2 - social smokers (18%); and Class 3 - smokers (30%). Nearly 60% of the "social smoker" class self-identified as a social smoker, 30% as an ex-smoker/tried smoking, and 12% as a non-smoker. The "social smoker" class was most likely to report using tobacco mainly or only with others. Past 30-day cigarette use was highest in the "smoker" class. Hookah use was highest in the "social smoker" class. Other tobacco and e-cigarette use was similar in the "social smoker" and "smoker" classes. Past 30-day tobacco and e-cigarette use was present for all products in the "non-smoker" class. Young adult social smokers emerge empirically as a sizable, distinct class from other smokers, even without accounting for tobacco use frequency or intensity. The prevalence of hookah use in "social smokers" indicates a group for which the social aspect of tobacco use could drive experimentation and progression to regular use. Copyright © 2017 Elsevier Ltd. All rights reserved.

  17. Using a Systematic Approach to Identifying Organizational Factors in Root Cause Analysis

    International Nuclear Information System (INIS)

    Gallogly, Kay Wilde

    2011-01-01

    This presentation set the scene for the second discussion session. In her presentation, the author observed that: - Investigators do not see the connection between the analysis tools available and the identification of HOF. Most investigators use the tools in a cursory manner and so do not derive the full benefits of the tools. Some tools are used for presentation purposes as opposed to being used for analytical purposes e.g. event and causal factors charts. In some cases, the report will indicate that specific analytical tools were used in the investigation but the analysis is not in the body of the report. - Some investigators are documenting HOF causes but do not recognize them as such. This indicates a lack of understanding of HOF. - Others investigators focus on technical issues because of their own comfort level. - The culture of the Organisation will affect the depth of the investigation and therefore the use of the analytical tools to pursue HOF issues. - The author contends that if analysis tools are applied systematically to gather factually based data, then HOF issues can be identified. The use of factual information (without judgement and subjectivity) is important to maintain the credibility of the investigation especially when HOF issues are identified. - Systematic use of tools assists in better communication of the issues to foster greater understanding and acceptance by senior management. - Barrier Analysis, Change Analysis, and TWIN (Task Demands, Work Environment, Individual Capabilities, and Human Nature) all offer the opportunity to identify HOF issues if the analyst pursues this line of investigation. It was illustrated that many elements of the TWIN Error Precursors are themselves Organisational in nature. - The TWIN model applied to the Anatomy of an Event will help to distinguish those which are Organisational issues (Latent Organisational Weaknesses, Error Precursors and Flawed Defences) and those which are human factors (Active Errors

  18. Domestic Violence and Pregnancy: A CBPR Coalition Approach to Identifying Needs and Informing Policy.

    Science.gov (United States)

    Bright, Candace Forbes; Bagley, Braden; Pulliam, Ivie; Newton, Amy Swetha

    2018-01-01

    Community engagement-the collaborative process of addressing issues that impact the well-being of a community-is a strategic effort to address community issues. The Gulf States Health Policy Center (GS-HPC) formed the Hattiesburg Area Health Coalition (HAHC) in November 2014 for the purpose of addressing policies impacting the health of Forrest and Lamar counties in Mississippi. To chronicle the community-based participatory research (CBPR) process used by HAHC's identification of infant and maternal health as a policy area, domestic violence in pregnancy as a priority area within infant and maternal health, and a community action plan (CAP) regarding this priority area. HAHC reviewed data and identified infant and maternal health as a priority area. They then conducted a policy scan of local prenatal health care to determine the policy area of domestic violence in pregnancy. HAHC developed a CAP identifying three goals with regard to domestic violence and pregnancy that together informed policy. Changes included the development of materials specific to resources available in the area. The materials and recommended changes will first be implemented by Southeast Mississippi Rural Health Initiative (SeMRHI) through a screening question for all pregnant patients, and the adoption of policies for providing information and referrals. The lack of community-level data was a challenge to HAHC in identifying focus and priority areas, but this was overcome by shared leadership and community engagement. After completion of the CAP, 100% of expecting mothers receiving prenatal care in the area will be screened for domestic violence.

  19. Identifying the determinants of South Africa's extensive and intensive trade margins: A gravity model approach

    OpenAIRE

    Matthee, Marianne; Santana-Gallego, Maria

    2017-01-01

    Background: The significance of the paper is twofold. Firstly, it adds to the small but growing body of literature focusing on the decomposition of South Africa’s export growth. Secondly, it identifies the determinants of the intensive and extensive margins of South Africa’s exports – a topic that (as far as the authors are concerned) has not been explored before. Aim: This paper aims to investigate a wide range of market access determinants that affect South Africa’s export growth along ...

  20. Identifying the greatest team and captain—A complex network approach to cricket matches

    Science.gov (United States)

    Mukherjee, Satyam

    2012-12-01

    We consider all Test matches played between 1877 and 2010 and One Day International (ODI) matches played between 1971 and 2010. We form directed and weighted networks of teams and also of their captains. The success of a team (or captain) is determined by the ‘quality’ of the wins, not simply by the number of wins. We apply the diffusion-based PageRank algorithm to the networks to assess the importance of the wins, and rank the respective teams and captains. Our analysis identifies Australia as the best team in both forms of cricket, Test and ODI. Steve Waugh is identified as the best captain in Test cricket and Ricky Ponting is the best captain in the ODI format. We also compare our ranking scheme with an existing ranking scheme, the Reliance ICC ranking. Our method does not depend on ‘external’ criteria in the ranking of teams (captains). The purpose of this paper is to introduce a revised ranking of cricket teams and to quantify the success of the captains.

  1. A Proteomic Approach Identifies Candidate Early Biomarkers to Predict Severe Dengue in Children.

    Directory of Open Access Journals (Sweden)

    Dang My Nhi

    2016-02-01

    Full Text Available Severe dengue with severe plasma leakage (SD-SPL is the most frequent of dengue severe form. Plasma biomarkers for early predictive diagnosis of SD-SPL are required in the primary clinics for the prevention of dengue death.Among 63 confirmed dengue pediatric patients recruited, hospital based longitudinal study detected six SD-SPL and ten dengue with warning sign (DWS. To identify the specific proteins increased or decreased in the SD-SPL plasma obtained 6-48 hours before the shock compared with the DWS, the isobaric tags for relative and absolute quantification (iTRAQ technology was performed using four patients each group. Validation was undertaken in 6 SD-SPL and 10 DWS patients.Nineteen plasma proteins exhibited significantly different relative concentrations (p<0.05, with five over-expressed and fourteen under-expressed in SD-SPL compared with DWS. The individual protein was classified to either blood coagulation, vascular regulation, cellular transport-related processes or immune response. The immunoblot quantification showed angiotensinogen and antithrombin III significantly increased in SD-SPL whole plasma of early stage compared with DWS subjects. Even using this small number of samples, antithrombin III predicted SD-SPL before shock occurrence with accuracy.Proteins identified here may serve as candidate predictive markers to diagnose SD-SPL for timely clinical management. Since the number of subjects are small, so further studies are needed to confirm all these biomarkers.

  2. A model-based approach for identifying signatures of ancient balancing selection in genetic data.

    Science.gov (United States)

    DeGiorgio, Michael; Lohmueller, Kirk E; Nielsen, Rasmus

    2014-08-01

    While much effort has focused on detecting positive and negative directional selection in the human genome, relatively little work has been devoted to balancing selection. This lack of attention is likely due to the paucity of sophisticated methods for identifying sites under balancing selection. Here we develop two composite likelihood ratio tests for detecting balancing selection. Using simulations, we show that these methods outperform competing methods under a variety of assumptions and demographic models. We apply the new methods to whole-genome human data, and find a number of previously-identified loci with strong evidence of balancing selection, including several HLA genes. Additionally, we find evidence for many novel candidates, the strongest of which is FANK1, an imprinted gene that suppresses apoptosis, is expressed during meiosis in males, and displays marginal signs of segregation distortion. We hypothesize that balancing selection acts on this locus to stabilize the segregation distortion and negative fitness effects of the distorter allele. Thus, our methods are able to reproduce many previously-hypothesized signals of balancing selection, as well as discover novel interesting candidates.

  3. A model-based approach for identifying signatures of ancient balancing selection in genetic data.

    Directory of Open Access Journals (Sweden)

    Michael DeGiorgio

    2014-08-01

    Full Text Available While much effort has focused on detecting positive and negative directional selection in the human genome, relatively little work has been devoted to balancing selection. This lack of attention is likely due to the paucity of sophisticated methods for identifying sites under balancing selection. Here we develop two composite likelihood ratio tests for detecting balancing selection. Using simulations, we show that these methods outperform competing methods under a variety of assumptions and demographic models. We apply the new methods to whole-genome human data, and find a number of previously-identified loci with strong evidence of balancing selection, including several HLA genes. Additionally, we find evidence for many novel candidates, the strongest of which is FANK1, an imprinted gene that suppresses apoptosis, is expressed during meiosis in males, and displays marginal signs of segregation distortion. We hypothesize that balancing selection acts on this locus to stabilize the segregation distortion and negative fitness effects of the distorter allele. Thus, our methods are able to reproduce many previously-hypothesized signals of balancing selection, as well as discover novel interesting candidates.

  4. Genetic Susceptibility to Vitiligo: GWAS Approaches for Identifying Vitiligo Susceptibility Genes and Loci

    Science.gov (United States)

    Shen, Changbing; Gao, Jing; Sheng, Yujun; Dou, Jinfa; Zhou, Fusheng; Zheng, Xiaodong; Ko, Randy; Tang, Xianfa; Zhu, Caihong; Yin, Xianyong; Sun, Liangdan; Cui, Yong; Zhang, Xuejun

    2016-01-01

    Vitiligo is an autoimmune disease with a strong genetic component, characterized by areas of depigmented skin resulting from loss of epidermal melanocytes. Genetic factors are known to play key roles in vitiligo through discoveries in association studies and family studies. Previously, vitiligo susceptibility genes were mainly revealed through linkage analysis and candidate gene studies. Recently, our understanding of the genetic basis of vitiligo has been rapidly advancing through genome-wide association study (GWAS). More than 40 robust susceptible loci have been identified and confirmed to be associated with vitiligo by using GWAS. Most of these associated genes participate in important pathways involved in the pathogenesis of vitiligo. Many susceptible loci with unknown functions in the pathogenesis of vitiligo have also been identified, indicating that additional molecular mechanisms may contribute to the risk of developing vitiligo. In this review, we summarize the key loci that are of genome-wide significance, which have been shown to influence vitiligo risk. These genetic loci may help build the foundation for genetic diagnosis and personalize treatment for patients with vitiligo in the future. However, substantial additional studies, including gene-targeted and functional studies, are required to confirm the causality of the genetic variants and their biological relevance in the development of vitiligo. PMID:26870082

  5. A Systematic Approach to Identify Candidate Transcription Factors that Control Cell Identity

    Directory of Open Access Journals (Sweden)

    Ana C. D’Alessio

    2015-11-01

    Full Text Available Hundreds of transcription factors (TFs are expressed in each cell type, but cell identity can be induced through the activity of just a small number of core TFs. Systematic identification of these core TFs for a wide variety of cell types is currently lacking and would establish a foundation for understanding the transcriptional control of cell identity in development, disease, and cell-based therapy. Here, we describe a computational approach that generates an atlas of candidate core TFs for a broad spectrum of human cells. The potential impact of the atlas was demonstrated via cellular reprogramming efforts where candidate core TFs proved capable of converting human fibroblasts to retinal pigment epithelial-like cells. These results suggest that candidate core TFs from the atlas will prove a useful starting point for studying transcriptional control of cell identity and reprogramming in many human cell types.

  6. Identifying the optimal supply temperature in district heating networks - A modelling approach

    DEFF Research Database (Denmark)

    Mohammadi, Soma; Bojesen, Carsten

    2014-01-01

    of this study is to develop a model for thermo-hydraulic calculation of low temperature DH system. The modelling is performed with emphasis on transient heat transfer in pipe networks. The pseudo-dynamic approach is adopted to model the District Heating Network [DHN] behaviour which estimates the temperature...... dynamically while the flow and pressure are calculated on the basis of steady state conditions. The implicit finite element method is applied to simulate the transient temperature behaviour in the network. Pipe network heat losses, pressure drop in the network and return temperature to the plant...... are calculated in the developed model. The model will serve eventually as a basis to find out the optimal supply temperature in an existing DHN in later work. The modelling results are used as decision support for existing DHN; proposing possible modifications to operate at optimal supply temperature....

  7. Identifying Silence Climate in Organizations in the Framework of Contemporary Management Approaches

    Directory of Open Access Journals (Sweden)

    Mustafa Emre Civelek

    2015-10-01

    Full Text Available Dynamic competition conditions in present day, bring about the consequence for businesses to face varied problems with each passing day. At this point, current management approaches include studies that would shed light on the new problems of businesses. Organizational Silence, a concept that has recently been being voiced in business world, has come up in such context. Organizational silence could be expressed as the employee behavior of keeping silent about certain negativities due to various reasons in an organization. Since knowledge sharing in modern organizations is of capital importance in terms of responding hastily to the changes in a competitive environment, spread of this behavior of employees to organization culture and climate presents a threat of indifference. In this study, the concept of Organizational Silence is defined and the effects of conceived silence climate on management of organizations are discussed.

  8. Identifying Silence Climate in Organizations in the Framework of Contemporary Management Approaches

    Directory of Open Access Journals (Sweden)

    Mustafa Emre Civelek

    2015-12-01

    Full Text Available Dynamic competition conditions in present day bring about the consequence for businesses to face varied problems with each passing day. At this point, current management approaches include studies that would shed light on the new problems of businesses. Organizational Silence, a concept that has recently been being voiced in business world, has come up in such context. Organizational silence could be expressed as the employee behavior of keeping silent about certain negativities due to various reasons in an organization. Since knowledge sharing in modern organizations is of capital importance in terms of responding hastily to the changes in a competitive environment, spread of this behavior of employees to organization culture and climate presents a threat of indifference. In this study, the concept of Organizational Silence is defined and the effects of conceived silence climate on management of organizations are discussed.

  9. Improving probabilistic prediction of daily streamflow by identifying Pareto optimal approaches for modeling heteroscedastic residual errors

    Science.gov (United States)

    McInerney, David; Thyer, Mark; Kavetski, Dmitri; Lerat, Julien; Kuczera, George

    2017-03-01

    Reliable and precise probabilistic prediction of daily catchment-scale streamflow requires statistical characterization of residual errors of hydrological models. This study focuses on approaches for representing error heteroscedasticity with respect to simulated streamflow, i.e., the pattern of larger errors in higher streamflow predictions. We evaluate eight common residual error schemes, including standard and weighted least squares, the Box-Cox transformation (with fixed and calibrated power parameter λ) and the log-sinh transformation. Case studies include 17 perennial and 6 ephemeral catchments in Australia and the United States, and two lumped hydrological models. Performance is quantified using predictive reliability, precision, and volumetric bias metrics. We find the choice of heteroscedastic error modeling approach significantly impacts on predictive performance, though no single scheme simultaneously optimizes all performance metrics. The set of Pareto optimal schemes, reflecting performance trade-offs, comprises Box-Cox schemes with λ of 0.2 and 0.5, and the log scheme (λ = 0, perennial catchments only). These schemes significantly outperform even the average-performing remaining schemes (e.g., across ephemeral catchments, median precision tightens from 105% to 40% of observed streamflow, and median biases decrease from 25% to 4%). Theoretical interpretations of empirical results highlight the importance of capturing the skew/kurtosis of raw residuals and reproducing zero flows. Paradoxically, calibration of λ is often counterproductive: in perennial catchments, it tends to overfit low flows at the expense of abysmal precision in high flows. The log-sinh transformation is dominated by the simpler Pareto optimal schemes listed above. Recommendations for researchers and practitioners seeking robust residual error schemes for practical work are provided.

  10. Identifying dominant controls on hydrologic parameter transfer from gauged to ungauged catchments: a comparative hydrology approach

    Science.gov (United States)

    Singh, R.; Archfield, S.A.; Wagener, T.

    2014-01-01

    Daily streamflow information is critical for solving various hydrologic problems, though observations of continuous streamflow for model calibration are available at only a small fraction of the world’s rivers. One approach to estimate daily streamflow at an ungauged location is to transfer rainfall–runoff model parameters calibrated at a gauged (donor) catchment to an ungauged (receiver) catchment of interest. Central to this approach is the selection of a hydrologically similar donor. No single metric or set of metrics of hydrologic similarity have been demonstrated to consistently select a suitable donor catchment. We design an experiment to diagnose the dominant controls on successful hydrologic model parameter transfer. We calibrate a lumped rainfall–runoff model to 83 stream gauges across the United States. All locations are USGS reference gauges with minimal human influence. Parameter sets from the calibrated models are then transferred to each of the other catchments and the performance of the transferred parameters is assessed. This transfer experiment is carried out both at the scale of the entire US and then for six geographic regions. We use classification and regression tree (CART) analysis to determine the relationship between catchment similarity and performance of transferred parameters. Similarity is defined using physical/climatic catchment characteristics, as well as streamflow response characteristics (signatures such as baseflow index and runoff ratio). Across the entire US, successful parameter transfer is governed by similarity in elevation and climate, and high similarity in streamflow signatures. Controls vary for different geographic regions though. Geology followed by drainage, topography and climate constitute the dominant similarity metrics in forested eastern mountains and plateaus, whereas agricultural land use relates most strongly with successful parameter transfer in the humid plains.

  11. Identifying seminal papers in the Australasian Journal on Ageing 1982-2011: a Delphi consensus approach.

    Science.gov (United States)

    Parkinson, Lynne; Richardson, Kristy; Sims, Jane; Wells, Yvonne; Naganathan, Vasi; Brooke, Elizabeth; Lindley, Richard

    2013-10-01

    The aim of this study was to identify seminal Australasian Journal on Ageing papers published over 30 years through a Delphi consensus process. The main data collection was a three-round Delphi consensus study with 38 past and current members of the Australasian Journal on Ageing Editorial Board, Editorial Team and Management Committee. Three papers were agreed as top-ranking. One of the top-ranking articles was also highly cited. One article was published in the 1990 s, two in 2001. While it is difficult to judge how well the top-ranking papers represent seminal papers arising over 30 years, these papers do represent three different research strengths in Australasia, they do span three different disciplines, and they do reflect some of the diversity that characterises ageing research in Australasia over 30 years. © 2013 ACOTA.

  12. An improved approach to identify irradiated dog feed by electron paramagnetic resonance study and thermoluminescence measurements

    Energy Technology Data Exchange (ETDEWEB)

    Sanyal, Bhaskar, E-mail: bhaskar_sanyal@rediffmail.co [Food Technology Division, Bhabha Atomic Research Centre, Mumbai-400 085 (India); Chawla, S.P.; Sharma, Arun [Food Technology Division, Bhabha Atomic Research Centre, Mumbai-400 085 (India)

    2011-05-15

    In the present study, probably for the first time, a detailed analysis of the radiation induced radical species and thermoluminescence measurements of irradiated dog feed are reported. The EPR spectrum of non-irradiated ready-to-eat dog feed was characterized by singlet g=2.0047{+-}0.0003. Irradiated samples exhibited a complex EPR spectrum. During high power (50.0 mW) EPR spectroscopy, a visible change in the shape of the EPR spectrum was observed and characterized by EPR spectrum simulation technique. An axially symmetric anisotropic signal with g{sub ||}=2.0028 and g{sub perpendicular}=1.9976 was identified. However, a negligible change in the matrix of irradiated edible dog chew was observed using EPR spectroscopy. Therefore, thermoluminescence study of the isolated minerals from dog chew was carried out. The composition of the poly-minerals was studied using SEM and EDX analysis and a complete verdict on identification of irradiation is proposed.

  13. An improved approach to identify irradiated dog feed by electron paramagnetic resonance study and thermoluminescence measurements

    International Nuclear Information System (INIS)

    Sanyal, Bhaskar; Chawla, S.P.; Sharma, Arun

    2011-01-01

    In the present study, probably for the first time, a detailed analysis of the radiation induced radical species and thermoluminescence measurements of irradiated dog feed are reported. The EPR spectrum of non-irradiated ready-to-eat dog feed was characterized by singlet g=2.0047±0.0003. Irradiated samples exhibited a complex EPR spectrum. During high power (50.0 mW) EPR spectroscopy, a visible change in the shape of the EPR spectrum was observed and characterized by EPR spectrum simulation technique. An axially symmetric anisotropic signal with g || =2.0028 and g perpendicular =1.9976 was identified. However, a negligible change in the matrix of irradiated edible dog chew was observed using EPR spectroscopy. Therefore, thermoluminescence study of the isolated minerals from dog chew was carried out. The composition of the poly-minerals was studied using SEM and EDX analysis and a complete verdict on identification of irradiation is proposed.

  14. One Health approach to identify research needs in bovine and human babesioses: workshop report

    Directory of Open Access Journals (Sweden)

    McElwain Terry F

    2010-04-01

    Full Text Available Abstract Background Babesia are emerging health threats to humans and animals in the United States. A collaborative effort of multiple disciplines to attain optimal health for people, animals and our environment, otherwise known as the One Health concept, was taken during a research workshop held in April 2009 to identify gaps in scientific knowledge regarding babesioses. The impetus for this analysis was the increased risk for outbreaks of bovine babesiosis, also known as Texas cattle fever, associated with the re-infestation of the U.S. by cattle fever ticks. Results The involvement of wildlife in the ecology of cattle fever ticks jeopardizes the ability of state and federal agencies to keep the national herd free of Texas cattle fever. Similarly, there has been a progressive increase in the number of cases of human babesiosis over the past 25 years due to an increase in the white-tailed deer population. Human babesiosis due to cattle-associated Babesia divergens and Babesia divergens-like organisms have begun to appear in residents of the United States. Research needs for human and bovine babesioses were identified and are presented herein. Conclusions The translation of this research is expected to provide veterinary and public health systems with the tools to mitigate the impact of bovine and human babesioses. However, economic, political, and social commitments are urgently required, including increased national funding for animal and human Babesia research, to prevent the re-establishment of cattle fever ticks and the increasing problem of human babesiosis in the United States.

  15. TU-H-206-01: An Automated Approach for Identifying Geometric Distortions in Gamma Cameras

    Energy Technology Data Exchange (ETDEWEB)

    Mann, S; Nelson, J [Clinical Imaging Physics Group and Carl E. Ravin Advanced Imaging Laboratories, Department of Radiology, Duke University Medical Center, Durham, North Carolina 27705 and Medical Physics Graduate Program, Duke University, Durham, North Carolina 27705 (United States); Samei, E [Clinical Imaging Physics Group and Carl E. Ravin Advanced Imaging Laboratories, Department of Radiology, Duke University Medical Center, Durham, North Carolina 27705 and Departments of Physics, Electrical and Computer Engineering, and Biomedical Engineering, and Medical Physics Graduate Program, Duke University, Durham, North Carolina 27705 (United States)

    2016-06-15

    Purpose: To develop a clinically-deployable, automated process for detecting artifacts in routine nuclear medicine (NM) quality assurance (QA) bar phantom images. Methods: An artifact detection algorithm was created to analyze bar phantom images as part of an ongoing QA program. A low noise, high resolution reference image was acquired from an x-ray of the bar phantom with a Philips Digital Diagnost system utilizing image stitching. NM bar images, acquired for 5 million counts over a 512×512 matrix, were registered to the template image by maximizing mutual information (MI). The MI index was used as an initial test for artifacts; low values indicate an overall presence of distortions regardless of their spatial location. Images with low MI scores were further analyzed for bar linearity, periodicity, alignment, and compression to locate differences with respect to the template. Findings from each test were spatially correlated and locations failing multiple tests were flagged as potential artifacts requiring additional visual analysis. The algorithm was initially deployed for GE Discovery 670 and Infinia Hawkeye gamma cameras. Results: The algorithm successfully identified clinically relevant artifacts from both systems previously unnoticed by technologists performing the QA. Average MI indices for artifact-free images are 0.55. Images with MI indices < 0.50 have shown 100% sensitivity and specificity for artifact detection when compared with a thorough visual analysis. Correlation of geometric tests confirms the ability to spatially locate the most likely image regions containing an artifact regardless of initial phantom orientation. Conclusion: The algorithm shows the potential to detect gamma camera artifacts that may be missed by routine technologist inspections. Detection and subsequent correction of artifacts ensures maximum image quality and may help to identify failing hardware before it impacts clinical workflow. Going forward, the algorithm is being

  16. A molecular systems approach to modelling human skin pigmentation: identifying underlying pathways and critical components.

    Science.gov (United States)

    Raghunath, Arathi; Sambarey, Awanti; Sharma, Neha; Mahadevan, Usha; Chandra, Nagasuma

    2015-04-29

    Ultraviolet radiations (UV) serve as an environmental stress for human skin, and result in melanogenesis, with the pigment melanin having protective effects against UV induced damage. This involves a dynamic and complex regulation of various biological processes that results in the expression of melanin in the outer most layers of the epidermis, where it can exert its protective effect. A comprehensive understanding of the underlying cross talk among different signalling molecules and cell types is only possible through a systems perspective. Increasing incidences of both melanoma and non-melanoma skin cancers necessitate the need to better comprehend UV mediated effects on skin pigmentation at a systems level, so as to ultimately evolve knowledge-based strategies for efficient protection and prevention of skin diseases. A network model for UV-mediated skin pigmentation in the epidermis was constructed and subjected to shortest path analysis. Virtual knock-outs were carried out to identify essential signalling components. We describe a network model for UV-mediated skin pigmentation in the epidermis. The model consists of 265 components (nodes) and 429 directed interactions among them, capturing the manner in which one component influences the other and channels information. Through shortest path analysis, we identify novel signalling pathways relevant to pigmentation. Virtual knock-outs or perturbations of specific nodes in the network have led to the identification of alternate modes of signalling as well as enabled determining essential nodes in the process. The model presented provides a comprehensive picture of UV mediated signalling manifesting in human skin pigmentation. A systems perspective helps provide a holistic purview of interconnections and complexity in the processes leading to pigmentation. The model described here is extensive yet amenable to expansion as new data is gathered. Through this study, we provide a list of important proteins essential

  17. An open simulation approach to identify chances and limitations for vulnerable road user (VRU) active safety.

    Science.gov (United States)

    Seiniger, Patrick; Bartels, Oliver; Pastor, Claus; Wisch, Marcus

    2013-01-01

    It is commonly agreed that active safety will have a significant impact on reducing accident figures for pedestrians and probably also bicyclists. However, chances and limitations for active safety systems have only been derived based on accident data and the current state of the art, based on proprietary simulation models. The objective of this article is to investigate these chances and limitations by developing an open simulation model. This article introduces a simulation model, incorporating accident kinematics, driving dynamics, driver reaction times, pedestrian dynamics, performance parameters of different autonomous emergency braking (AEB) generations, as well as legal and logical limitations. The level of detail for available pedestrian accident data is limited. Relevant variables, especially timing of the pedestrian appearance and the pedestrian's moving speed, are estimated using assumptions. The model in this article uses the fact that a pedestrian and a vehicle in an accident must have been in the same spot at the same time and defines the impact position as a relevant accident parameter, which is usually available from accident data. The calculations done within the model identify the possible timing available for braking by an AEB system as well as the possible speed reduction for different accident scenarios as well as for different system configurations. The simulation model identifies the lateral impact position of the pedestrian as a significant parameter for system performance, and the system layout is designed to brake when the accident becomes unavoidable by the vehicle driver. Scenarios with a pedestrian running from behind an obstruction are the most demanding scenarios and will very likely never be avoidable for all vehicle speeds due to physical limits. Scenarios with an unobstructed person walking will very likely be treatable for a wide speed range for next generation AEB systems.

  18. PREDICT-PD: An online approach to prospectively identify risk indicators of Parkinson's disease.

    Science.gov (United States)

    Noyce, Alastair J; R'Bibo, Lea; Peress, Luisa; Bestwick, Jonathan P; Adams-Carr, Kerala L; Mencacci, Niccolo E; Hawkes, Christopher H; Masters, Joseph M; Wood, Nicholas; Hardy, John; Giovannoni, Gavin; Lees, Andrew J; Schrag, Anette

    2017-02-01

    A number of early features can precede the diagnosis of Parkinson's disease (PD). To test an online, evidence-based algorithm to identify risk indicators of PD in the UK population. Participants aged 60 to 80 years without PD completed an online survey and keyboard-tapping task annually over 3 years, and underwent smell tests and genotyping for glucocerebrosidase (GBA) and leucine-rich repeat kinase 2 (LRRK2) mutations. Risk scores were calculated based on the results of a systematic review of risk factors and early features of PD, and individuals were grouped into higher (above 15th centile), medium, and lower risk groups (below 85th centile). Previously defined indicators of increased risk of PD ("intermediate markers"), including smell loss, rapid eye movement-sleep behavior disorder, and finger-tapping speed, and incident PD were used as outcomes. The correlation of risk scores with intermediate markers and movement of individuals between risk groups was assessed each year and prospectively. Exploratory Cox regression analyses with incident PD as the dependent variable were performed. A total of 1323 participants were recruited at baseline and >79% completed assessments each year. Annual risk scores were correlated with intermediate markers of PD each year and baseline scores were correlated with intermediate markers during follow-up (all P values < 0.001). Incident PD diagnoses during follow-up were significantly associated with baseline risk score (hazard ratio = 4.39, P = .045). GBA variants or G2019S LRRK2 mutations were found in 47 participants, and the predictive power for incident PD was improved by the addition of genetic variants to risk scores. The online PREDICT-PD algorithm is a unique and simple method to identify indicators of PD risk. © 2017 The Authors. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society. © 2016 International Parkinson and Movement Disorder

  19. A macroepigenetic approach to identify factors responsible for the autism epidemic in the United States

    Directory of Open Access Journals (Sweden)

    Dufault Renee

    2012-04-01

    Full Text Available Abstract The number of children ages 6 to 21 in the United States receiving special education services under the autism disability category increased 91% between 2005 to 2010 while the number of children receiving special education services overall declined by 5%. The demand for special education services continues to rise in disability categories associated with pervasive developmental disorders. Neurodevelopment can be adversely impacted when gene expression is altered by dietary transcription factors, such as zinc insufficiency or deficiency, or by exposure to toxic substances found in our environment, such as mercury or organophosphate pesticides. Gene expression patterns differ geographically between populations and within populations. Gene variants of paraoxonase-1 are associated with autism in North America, but not in Italy, indicating regional specificity in gene-environment interactions. In the current review, we utilize a novel macroepigenetic approach to compare variations in diet and toxic substance exposure between these two geographical populations to determine the likely factors responsible for the autism epidemic in the United States.

  20. Fingerprint-Based Machine Learning Approach to Identify Potent and Selective 5-HT2BR Ligands

    Directory of Open Access Journals (Sweden)

    Krzysztof Rataj

    2018-05-01

    Full Text Available The identification of subtype-selective GPCR (G-protein coupled receptor ligands is a challenging task. In this study, we developed a computational protocol to find compounds with 5-HT2BR versus 5-HT1BR selectivity. Our approach employs the hierarchical combination of machine learning methods, docking, and multiple scoring methods. First, we applied machine learning tools to filter a large database of druglike compounds by the new Neighbouring Substructures Fingerprint (NSFP. This two-dimensional fingerprint contains information on the connectivity of the substructural features of a compound. Preselected subsets of the database were then subjected to docking calculations. The main indicators of compounds’ selectivity were their different interactions with the secondary binding pockets of both target proteins, while binding modes within the orthosteric binding pocket were preserved. The combined methodology of ligand-based and structure-based methods was validated prospectively, resulting in the identification of hits with nanomolar affinity and ten-fold to ten thousand-fold selectivities.

  1. Biomechanical approaches to identify and quantify injury mechanisms and risk factors in women's artistic gymnastics.

    Science.gov (United States)

    Bradshaw, Elizabeth J; Hume, Patria A

    2012-09-01

    Targeted injury prevention strategies, based on biomechanical analyses, have the potential to help reduce the incidence and severity of gymnastics injuries. This review outlines the potential benefits of biomechanics research to contribute to injury prevention strategies for women's artistic gymnastics by identification of mechanisms of injury and quantification of the effects of injury risk factors. One hundred and twenty-three articles were retained for review after searching electronic databases using key words, including 'gymnastic', 'biomech*', and 'inj*', and delimiting by language and relevance to the paper aim. Impact load can be measured biomechanically by the use of instrumented equipment (e.g. beatboard), instrumentation on the gymnast (accelerometers), or by landings on force plates. We need further information on injury mechanisms and risk factors in gymnastics and practical methods of monitoring training loads. We have not yet shown, beyond a theoretical approach, how biomechanical analysis of gymnastics can help reduce injury risk through injury prevention interventions. Given the high magnitude of impact load, both acute and accumulative, coaches should monitor impact loads per training session, taking into consideration training quality and quantity such as the control of rotation and the height from which the landings are executed.

  2. Identifying endogenous neural stem cells in the adult brain in vitro and in vivo: novel approaches.

    Science.gov (United States)

    Rueger, Maria Adele; Androutsellis-Theotokis, Andreas

    2013-01-01

    In the 1960s, Joseph Altman reported that the adult mammalian brain is capable of generating new neurons. Today it is understood that some of these neurons are derived from uncommitted cells in the subventricular zone lining the lateral ventricles, and the dentate gyrus of the hippocampus. The first area generates new neuroblasts which migrate to the olfactory bulb, whereas hippocampal neurogenesis seems to play roles in particular types of learning and memory. A part of these uncommitted (immature) cells is able to divide and their progeny can generate all three major cell types of the nervous system: neurons, astrocytes, and oligodendrocytes; these properties define such cells as neural stem cells. Although the roles of these cells are not yet clear, it is accepted that they affect functions including olfaction and learning/memory. Experiments with insults to the central nervous system also show that neural stem cells are quickly mobilized due to injury and in various disorders by proliferating, and migrating to injury sites. This suggests a role of endogenous neural stem cells in disease. New pools of stem cells are being discovered, suggesting an even more important role for these cells. To understand these cells and to coax them to contribute to tissue repair it would be very useful to be able to image them in the living organism. Here we discuss advances in imaging approaches as well as new concepts that emerge from stem cell biology with emphasis on the interface between imaging and stem cells.

  3. An Integrated Bioinformatics and Computational Biology Approach Identifies New BH3-Only Protein Candidates.

    Science.gov (United States)

    Hawley, Robert G; Chen, Yuzhong; Riz, Irene; Zeng, Chen

    2012-05-04

    In this study, we utilized an integrated bioinformatics and computational biology approach in search of new BH3-only proteins belonging to the BCL2 family of apoptotic regulators. The BH3 (BCL2 homology 3) domain mediates specific binding interactions among various BCL2 family members. It is composed of an amphipathic α-helical region of approximately 13 residues that has only a few amino acids that are highly conserved across all members. Using a generalized motif, we performed a genome-wide search for novel BH3-containing proteins in the NCBI Consensus Coding Sequence (CCDS) database. In addition to known pro-apoptotic BH3-only proteins, 197 proteins were recovered that satisfied the search criteria. These were categorized according to α-helical content and predictive binding to BCL-xL (encoded by BCL2L1) and MCL-1, two representative anti-apoptotic BCL2 family members, using position-specific scoring matrix models. Notably, the list is enriched for proteins associated with autophagy as well as a broad spectrum of cellular stress responses such as endoplasmic reticulum stress, oxidative stress, antiviral defense, and the DNA damage response. Several potential novel BH3-containing proteins are highlighted. In particular, the analysis strongly suggests that the apoptosis inhibitor and DNA damage response regulator, AVEN, which was originally isolated as a BCL-xL-interacting protein, is a functional BH3-only protein representing a distinct subclass of BCL2 family members.

  4. How to Identify the Most Powerful Node in Complex Networks? A Novel Entropy Centrality Approach

    Directory of Open Access Journals (Sweden)

    Tong Qiao

    2017-11-01

    Full Text Available Centrality is one of the most studied concepts in network analysis. Despite an abundance of methods for measuring centrality in social networks has been proposed, each approach exclusively characterizes limited parts of what it implies for an actor to be “vital” to the network. In this paper, a novel mechanism is proposed to quantitatively measure centrality using the re-defined entropy centrality model, which is based on decompositions of a graph into subgraphs and analysis on the entropy of neighbor nodes. By design, the re-defined entropy centrality which describes associations among node pairs and captures the process of influence propagation can be interpreted explained as a measure of actor potential for communication activity. We evaluate the efficiency of the proposed model by using four real-world datasets with varied sizes and densities and three artificial networks constructed by models including Barabasi-Albert, Erdos-Renyi and Watts-Stroggatz. The four datasets are Zachary’s karate club, USAir97, Collaboration network and Email network URV respectively. Extensive experimental results prove the effectiveness of the proposed method.

  5. A Novel Entropy-Based Centrality Approach for Identifying Vital Nodes in Weighted Networks

    Directory of Open Access Journals (Sweden)

    Tong Qiao

    2018-04-01

    Full Text Available Measuring centrality has recently attracted increasing attention, with algorithms ranging from those that simply calculate the number of immediate neighbors and the shortest paths to those that are complicated iterative refinement processes and objective dynamical approaches. Indeed, vital nodes identification allows us to understand the roles that different nodes play in the structure of a network. However, quantifying centrality in complex networks with various topological structures is not an easy task. In this paper, we introduce a novel definition of entropy-based centrality, which can be applicable to weighted directed networks. By design, the total power of a node is divided into two parts, including its local power and its indirect power. The local power can be obtained by integrating the structural entropy, which reveals the communication activity and popularity of each node, and the interaction frequency entropy, which indicates its accessibility. In addition, the process of influence propagation can be captured by the two-hop subnetworks, resulting in the indirect power. In order to evaluate the performance of the entropy-based centrality, we use four weighted real-world networks with various instance sizes, degree distributions, and densities. Correspondingly, these networks are adolescent health, Bible, United States (US airports, and Hep-th, respectively. Extensive analytical results demonstrate that the entropy-based centrality outperforms degree centrality, betweenness centrality, closeness centrality, and the Eigenvector centrality.

  6. Experimental approaches to identify cellular G-quadruplex structures and functions.

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    Di Antonio, Marco; Rodriguez, Raphaël; Balasubramanian, Shankar

    2012-05-01

    Guanine-rich nucleic acids can fold into non-canonical DNA secondary structures called G-quadruplexes. The formation of these structures can interfere with the biology that is crucial to sustain cellular homeostases and metabolism via mechanisms that include transcription, translation, splicing, telomere maintenance and DNA recombination. Thus, due to their implication in several biological processes and possible role promoting genomic instability, G-quadruplex forming sequences have emerged as potential therapeutic targets. There has been a growing interest in the development of synthetic molecules and biomolecules for sensing G-quadruplex structures in cellular DNA. In this review, we summarise and discuss recent methods developed for cellular imaging of G-quadruplexes, and the application of experimental genomic approaches to detect G-quadruplexes throughout genomic DNA. In particular, we will discuss the use of engineered small molecules and natural proteins to enable pull-down, ChIP-Seq, ChIP-chip and fluorescence imaging of G-quadruplex structures in cellular DNA. Copyright © 2012 Elsevier Inc. All rights reserved.

  7. A bioinformatics approach for identifying transgene insertion sites using whole genome sequencing data.

    Science.gov (United States)

    Park, Doori; Park, Su-Hyun; Ban, Yong Wook; Kim, Youn Shic; Park, Kyoung-Cheul; Kim, Nam-Soo; Kim, Ju-Kon; Choi, Ik-Young

    2017-08-15

    Genetically modified crops (GM crops) have been developed to improve the agricultural traits of modern crop cultivars. Safety assessments of GM crops are of paramount importance in research at developmental stages and before releasing transgenic plants into the marketplace. Sequencing technology is developing rapidly, with higher output and labor efficiencies, and will eventually replace existing methods for the molecular characterization of genetically modified organisms. To detect the transgenic insertion locations in the three GM rice gnomes, Illumina sequencing reads are mapped and classified to the rice genome and plasmid sequence. The both mapped reads are classified to characterize the junction site between plant and transgene sequence by sequence alignment. Herein, we present a next generation sequencing (NGS)-based molecular characterization method, using transgenic rice plants SNU-Bt9-5, SNU-Bt9-30, and SNU-Bt9-109. Specifically, using bioinformatics tools, we detected the precise insertion locations and copy numbers of transfer DNA, genetic rearrangements, and the absence of backbone sequences, which were equivalent to results obtained from Southern blot analyses. NGS methods have been suggested as an effective means of characterizing and detecting transgenic insertion locations in genomes. Our results demonstrate the use of a combination of NGS technology and bioinformatics approaches that offers cost- and time-effective methods for assessing the safety of transgenic plants.

  8. Multi-omics approach identifies molecular mechanisms of plant-fungus mycorrhizal interaction

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    Peter E Larsen

    2016-01-01

    Full Text Available In mycorrhizal symbiosis, plant roots form close, mutually beneficial interactions with soil fungi. Before this mycorrhizal interaction can be established however, plant roots must be capable of detecting potential beneficial fungal partners and initiating the gene expression patterns necessary to begin symbiosis. To predict a plant root – mycorrhizal fungi sensor systems, we analyzed in vitro experiments of Populus tremuloides (aspen tree and Laccaria bicolor (mycorrhizal fungi interaction and leveraged over 200 previously published transcriptomic experimental data sets, 159 experimentally validated plant transcription factor binding motifs, and more than 120-thousand experimentally validated protein-protein interactions to generate models of pre-mycorrhizal sensor systems in aspen root. These sensor mechanisms link extracellular signaling molecules with gene regulation through a network comprised of membrane receptors, signal cascade proteins, transcription factors, and transcription factor biding DNA motifs. Modeling predicted four pre-mycorrhizal sensor complexes in aspen that interact with fifteen transcription factors to regulate the expression of 1184 genes in response to extracellular signals synthesized by Laccaria. Predicted extracellular signaling molecules include common signaling molecules such as phenylpropanoids, salicylate, and, jasmonic acid. This multi-omic computational modeling approach for predicting the complex sensory networks yielded specific, testable biological hypotheses for mycorrhizal interaction signaling compounds, sensor complexes, and mechanisms of gene regulation.

  9. Identifying determinants of medication adherence following myocardial infarction using the Theoretical Domains Framework and the Health Action Process Approach.

    Science.gov (United States)

    Presseau, Justin; Schwalm, J D; Grimshaw, Jeremy M; Witteman, Holly O; Natarajan, Madhu K; Linklater, Stefanie; Sullivan, Katrina; Ivers, Noah M

    2017-10-01

    Despite evidence-based recommendations, adherence with secondary prevention medications post-myocardial infarction (MI) remains low. Taking medication requires behaviour change, and using behavioural theories to identify what factors determine adherence could help to develop novel adherence interventions. Compare the utility of different behaviour theory-based approaches for identifying modifiable determinants of medication adherence post-MI that could be targeted by interventions. Two studies were conducted with patients 0-2, 3-12, 13-24 or 25-36 weeks post-MI. Study 1: 24 patients were interviewed about barriers and facilitators to medication adherence. Interviews were conducted and coded using the Theoretical Domains Framework. Study 2: 201 patients answered a telephone questionnaire assessing Health Action Process Approach constructs to predict intention and medication adherence (MMAS-8). Study 1: domains identified: Beliefs about Consequences, Memory/Attention/Decision Processes, Behavioural Regulation, Social Influences and Social Identity. Study 2: 64, 59, 42 and 58% reported high adherence at 0-2, 3-12, 13-24 and 25-36 weeks. Social Support and Action Planning predicted adherence at all time points, though the relationship between Action Planning and adherence decreased over time. Using two behaviour theory-based approaches provided complimentary findings and identified modifiable factors that could be targeted to help translate Intention into action to improve medication adherence post-MI.

  10. Proteomics approach to identify unique xylem sap proteins in Pierce's disease-tolerant Vitis species.

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    Basha, Sheikh M; Mazhar, Hifza; Vasanthaiah, Hemanth K N

    2010-03-01

    Pierce's disease (PD) is a destructive bacterial disease of grapes caused by Xylella fastidiosa which is xylem-confined. The tolerance level to this disease varies among Vitis species. Our research was aimed at identifying unique xylem sap proteins present in PD-tolerant Vitis species. The results showed wide variation in the xylem sap protein composition, where a set of polypeptides with pI between 4.5 and 4.7 and M(r) of 31 kDa were present in abundant amount in muscadine (Vitis rotundifolia, PD-tolerant), in reduced levels in Florida hybrid bunch (Vitis spp., PD-tolerant) and absent in bunch grapes (Vitis vinifera, PD-susceptible). Liquid chromatography/mass spectrometry/mass spectrometry analysis of these proteins revealed their similarity to beta-1, 3-glucanase, peroxidase, and a subunit of oxygen-evolving enhancer protein 1, which are known to play role in defense and oxygen generation. In addition, the amount of free amino acids and soluble sugars was found to be significantly lower in xylem sap of muscadine genotypes compared to V. vinifera genotypes, indicating that the higher nutritional value of bunch grape sap may be more suitable for Xylella growth. These data suggest that the presence of these unique proteins in xylem sap is vital for PD tolerance in muscadine and Florida hybrid bunch grapes.

  11. Ab initio Thermodynamic Approach to Identify Mixed Solid Sorbents for CO2 Capture Technology

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    Yuhua eDuan

    2015-10-01

    Full Text Available Because the current technologies for capturing CO2 are still too energy intensive, new materials must be developed that can capture CO2 reversibly with acceptable energy costs. At a given CO2 pressure, the turnover temperature (Tt of the reaction of an individual solid that can capture CO2 is fixed. Such Tt may be outside the operating temperature range (ΔTo for a practical capture technology. To adjust Tt to fit the practical ΔTo, in this study, three scenarios of mixing schemes are explored by combining thermodynamic database mining with first principles density functional theory and phonon lattice dynamics calculations. Our calculated results demonstrate that by mixing different types of solids, it’s possible to shift Tt to the range of practical operating temperature conditions. According to the requirements imposed by the pre- and post- combustion technologies and based on our calculated thermodynamic properties for the CO2 capture reactions by the mixed solids of interest, we were able to identify the mixing ratios of two or more solids to form new sorbent materials for which lower capture energy costs are expected at the desired pressure and temperature conditions.

  12. General Practice Clinical Data Help Identify Dementia Hotspots: A Novel Geospatial Analysis Approach.

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    Bagheri, Nasser; Wangdi, Kinley; Cherbuin, Nicolas; Anstey, Kaarin J

    2018-01-01

    We have a poor understanding of whether dementia clusters geographically, how this occurs, and how dementia may relate to socio-demographic factors. To shed light on these important questions, this study aimed to compute a dementia risk score for individuals to assess spatial variation of dementia risk, identify significant clusters (hotspots), and explore their association with socioeconomic status. We used clinical records from 16 general practices (468 Statistical Area level 1 s, N = 14,746) from the city of west Adelaide, Australia for the duration of 1 January 2012 to 31 December 2014. Dementia risk was estimated using The Australian National University-Alzheimer's Disease Risk Index. Hotspot analyses were applied to examine potential clusters in dementia risk at small area level. Significant hotspots were observed in eastern and southern areas while coldspots were observed in the western area within the study perimeter. Additionally, significant hotspots were observed in low socio-economic communities. We found dementia risk scores increased with age, sex (female), high cholesterol, no physical activity, living alone (widow, divorced, separated, or never married), and co-morbidities such as diabetes and depression. Similarly, smoking was associated with a lower dementia risk score. The identification of dementia risk clusters may provide insight into possible geographical variations in risk factors for dementia and quantify these risks at the community level. As such, this research may enable policy makers to tailor early prevention strategies to the correct individuals within their precise locations.

  13. An improved approach to identify irradiated spices using electronic nose, FTIR, and EPR spectroscopy.

    Science.gov (United States)

    Sanyal, Bhaskar; Ahn, Jae-Jun; Maeng, Jeong-Hwan; Kyung, Hyun-Kyu; Lim, Ha-Kyeong; Sharma, Arun; Kwon, Joong-Ho

    2014-09-01

    Changes in cumin and chili powder from India resulting from electron-beam irradiation were investigated using 3 analytical methods: electronic nose (E-nose), Fourier transform infrared (FTIR) spectroscopy, and electron paramagnetic resonance (EPR) spectroscopy. The spices had been exposed to 6 to 14 kGy doses recommended for microbial decontamination. E-nose measured a clear difference in flavor patterns of the irradiated spices in comparison with the nonirradiated samples. Principal component analysis further showed a dose-dependent variation. FTIR spectra of the samples showed strong absorption bands at 3425, 3007 to 2854, and 1746 cm(-1). However, both nonirradiated and irradiated spice samples had comparable patterns without any noteworthy changes in functional groups. EPR spectroscopy of the irradiated samples showed a radiation-specific triplet signal at g = 2.006 with a hyper-fine coupling constant of 3 mT confirming the results obtained with the E-nose technique. Thus, E-nose was found to be a potential tool to identify irradiated spices. © 2014 Institute of Food Technologists®

  14. Identifying and Classifying Mobile Business Models Based on Meta-Synthesis Approach

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    Porrandokht Niroomand

    2012-03-01

    Full Text Available The appearance of mobile has provided unique opportunities and fields through the development and creation of businesses and has been able to create the new job opportunities. The current research tries to familiarize entrepreneures who are running the businesses especially in the area of mobile services with business models. These business models can familiarize them for implementing the new ideas and designs since they can enter to business market. Searching in many papers shows that there are no propitiated papers and researches that can identify, categorize and analyze the mobile business models. Consequently, this paper involves innovation. The first part of this paper presents the review about the concepts and theories about the different mobile generations, the mobile commerce and business models. Afterwards, 92 models are compared, interpreted, translated and combined using 33 papers, books based on two different criteria that are expert criterion and kind of product criterion. In the classification of models according to models that are presented by experts, the models are classified based on criteria such as business fields, business partners, the rate of dynamism, the kind of activity, the focus areas, the mobile generations, transparency, the type of operator activities, marketing and advertisements. The models that are classified based on the kind of product have been analyzed and classified at four different areas of mobile commerce including the content production, technology (software and hardware, network and synthetic.

  15. Identifying Associations Between Brain Imaging Phenotypes and Genetic Factors via A Novel Structured SCCA Approach.

    Science.gov (United States)

    Du, Lei; Zhang, Tuo; Liu, Kefei; Yan, Jingwen; Yao, Xiaohui; Risacher, Shannon L; Saykin, Andrew J; Han, Junwei; Guo, Lei; Shen, Li

    2017-06-01

    Brain imaging genetics attracts more and more attention since it can reveal associations between genetic factors and the structures or functions of human brain. Sparse canonical correlation analysis (SCCA) is a powerful bi-multivariate association identification technique in imaging genetics. There have been many SCCA methods which could capture different types of structured imaging genetic relationships. These methods either use the group lasso to recover the group structure, or employ the graph/network guided fused lasso to find out the network structure. However, the group lasso methods have limitation in generalization because of the incomplete or unavailable prior knowledge in real world. The graph/network guided methods are sensitive to the sign of the sample correlation which may be incorrectly estimated. We introduce a new SCCA model using a novel graph guided pairwise group lasso penalty, and propose an efficient optimization algorithm. The proposed method has a strong upper bound for the grouping effect for both positively and negatively correlated variables. We show that our method performs better than or equally to two state-of-the-art SCCA methods on both synthetic and real neuroimaging genetics data. In particular, our method identifies stronger canonical correlations and captures better canonical loading profiles, showing its promise for revealing biologically meaningful imaging genetic associations.

  16. Hidden Markov model approach for identifying the modular framework of the protein backbone.

    Science.gov (United States)

    Camproux, A C; Tuffery, P; Chevrolat, J P; Boisvieux, J F; Hazout, S

    1999-12-01

    The hidden Markov model (HMM) was used to identify recurrent short 3D structural building blocks (SBBs) describing protein backbones, independently of any a priori knowledge. Polypeptide chains are decomposed into a series of short segments defined by their inter-alpha-carbon distances. Basically, the model takes into account the sequentiality of the observed segments and assumes that each one corresponds to one of several possible SBBs. Fitting the model to a database of non-redundant proteins allowed us to decode proteins in terms of 12 distinct SBBs with different roles in protein structure. Some SBBs correspond to classical regular secondary structures. Others correspond to a significant subdivision of their bounding regions previously considered to be a single pattern. The major contribution of the HMM is that this model implicitly takes into account the sequential connections between SBBs and thus describes the most probable pathways by which the blocks are connected to form the framework of the protein structures. Validation of the SBBs code was performed by extracting SBB series repeated in recoding proteins and examining their structural similarities. Preliminary results on the sequence specificity of SBBs suggest promising perspectives for the prediction of SBBs or series of SBBs from the protein sequences.

  17. A systems approach identifies networks and genes linking sleep and stress: implications for neuropsychiatric disorders.

    Science.gov (United States)

    Jiang, Peng; Scarpa, Joseph R; Fitzpatrick, Karrie; Losic, Bojan; Gao, Vance D; Hao, Ke; Summa, Keith C; Yang, He S; Zhang, Bin; Allada, Ravi; Vitaterna, Martha H; Turek, Fred W; Kasarskis, Andrew

    2015-05-05

    Sleep dysfunction and stress susceptibility are comorbid complex traits that often precede and predispose patients to a variety of neuropsychiatric diseases. Here, we demonstrate multilevel organizations of genetic landscape, candidate genes, and molecular networks associated with 328 stress and sleep traits in a chronically stressed population of 338 (C57BL/6J × A/J) F2 mice. We constructed striatal gene co-expression networks, revealing functionally and cell-type-specific gene co-regulations important for stress and sleep. Using a composite ranking system, we identified network modules most relevant for 15 independent phenotypic categories, highlighting a mitochondria/synaptic module that links sleep and stress. The key network regulators of this module are overrepresented with genes implicated in neuropsychiatric diseases. Our work suggests that the interplay among sleep, stress, and neuropathology emerges from genetic influences on gene expression and their collective organization through complex molecular networks, providing a framework for interrogating the mechanisms underlying sleep, stress susceptibility, and related neuropsychiatric disorders. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

  18. A stepwise approach to identify intellectual disabilities in the criminal justice system

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    Valentina Cabral Iversen

    2010-07-01

    Full Text Available A significant proportion of the prison inmates have an IQ level corresponding to intellectual disability (ID or borderline ID. These persons are rarely identified and subsequently not offered any compensation for their learning and comprehension deficits. The purpose of this study was to explore and help providing methods for better identification of ID at an early stage during criminal proceedings. 143 randomly selected prisoners serving sentences in prisons were assessed using The Wechsler Abbreviated Scale of Intelligence (WASI and the Hayes Ability Screening Index (HASI while a semi-structured interview was carried out to obtain data on health as well as social and criminological issues. A total of 10.8% (n = 15 of the participants showed an IQ below 70. From previous analyses of the semistructured interview, a checklist was extracted and found to have good predictive validity on ID (AUC= 93%. The resulting identification referred 32% (n= 46 of the sample for comprehensive assessment. Within this group, all participants with an IQ below70 were included. Identification through this checklist, the screening and a full assessment is essential in improving the quality of the services.

  19. Identifying overrepresented concepts in gene lists from literature: a statistical approach based on Poisson mixture model

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    Zhai Chengxiang

    2010-05-01

    Full Text Available Abstract Background Large-scale genomic studies often identify large gene lists, for example, the genes sharing the same expression patterns. The interpretation of these gene lists is generally achieved by extracting concepts overrepresented in the gene lists. This analysis often depends on manual annotation of genes based on controlled vocabularies, in particular, Gene Ontology (GO. However, the annotation of genes is a labor-intensive process; and the vocabularies are generally incomplete, leaving some important biological domains inadequately covered. Results We propose a statistical method that uses the primary literature, i.e. free-text, as the source to perform overrepresentation analysis. The method is based on a statistical framework of mixture model and addresses the methodological flaws in several existing programs. We implemented this method within a literature mining system, BeeSpace, taking advantage of its analysis environment and added features that facilitate the interactive analysis of gene sets. Through experimentation with several datasets, we showed that our program can effectively summarize the important conceptual themes of large gene sets, even when traditional GO-based analysis does not yield informative results. Conclusions We conclude that the current work will provide biologists with a tool that effectively complements the existing ones for overrepresentation analysis from genomic experiments. Our program, Genelist Analyzer, is freely available at: http://workerbee.igb.uiuc.edu:8080/BeeSpace/Search.jsp

  20. A zone-based approach to identifying urban land uses using nationally-available data

    Science.gov (United States)

    Falcone, James A.

    Accurate identification of urban land use is essential for many applications in environmental study, ecological assessment, and urban planning, among other fields. However, because physical surfaces of land cover types are not necessarily related to their use and economic function, differentiating among thematically-detailed urban land uses (single-family residential, multi-family residential, commercial, industrial, etc.) using remotely-sensed imagery is a challenging task, particularly over large areas. Because the process requires an interpretation of tone/color, size, shape, pattern, and neighborhood association elements within a scene, it has traditionally been accomplished via manual interpretation of aerial photography or high-resolution satellite imagery. Although success has been achieved for localized areas using various automated techniques based on high-spatial or high-spectral resolution data, few detailed (Anderson Level II equivalent or greater) urban land use mapping products have successfully been created via automated means for broad (multi-county or larger) areas, and no such product exists today for the United States. In this study I argue that by employing a zone-based approach it is feasible to map thematically-detailed urban land use classes over large areas using appropriate combinations of non-image based predictor data which are nationally and publicly available. The approach presented here uses U.S. Census block groups as the basic unit of geography, and predicts the percent of each of ten land use types---nine of them urban---for each block group based on a number of data sources, to include census data, nationally-available point locations of features from the USGS Geographic Names Information System, historical land cover, and metrics which characterize spatial pattern, context (e.g. distance to city centers or other features), and measures of spatial autocorrelation. The method was demonstrated over a four-county area surrounding the

  1. Identifying applicants suitable to a career in nursing: a value-based approach to undergraduate selection.

    Science.gov (United States)

    Traynor, Marian; Galanouli, Despina; Roberts, Martin; Leonard, Lawrence; Gale, Thomas

    2017-06-01

    The aim of this study was to complement existing evidence on the suitability of Multiple Mini Interviews as a potential tool for the selection of nursing candidates on to a BSc (Hons) nursing programme. This study aimed to trial the Multiple Mini Interview approach to recruitment with a group of first year nursing students (already selected using traditional interviews). Cross-sectional validation study. This paper reports on the evaluation of the participants' detailed scores from the Multiple Mini Interview stations; their original interview scores and their end of year results. This study took place in March 2015. Scores from the seven Multiple Mini Interview stations were analysed to show the internal structure, reliability and generalizability of the stations. Original selection scores from interviews and in-course assessment were correlated with the MMI scores and variation by students' age, gender and disability status was explored. Reliability of the Multiple Mini Interview score was moderate (G = 0·52). The Multiple Mini Interview score provided better differentiation between more able students than did the original interview score but neither score was correlated with the module results. Multiple Mini Interview scores were positively associated with students' age but not their gender or disability status. The Multiple Mini Interview reported in this study offers a selection process that is based on the values and personal attributes regarded as desirable for a career in nursing and does not necessarily predict academic success. Its moderate reliability indicates the need for further improvement but it is capable of discriminating between candidates and shows little evidence of bias. © 2016 John Wiley & Sons Ltd.

  2. A Proteomics Approach to Identify New Putative Cardiac Intercalated Disk Proteins.

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    Siddarth Soni

    Full Text Available Synchronous beating of the heart is dependent on the efficient functioning of the cardiac intercalated disk (ID. The ID is composed of a complex protein network enabling electrical continuity and chemical communication between individual cardiomyocytes. Recently, several different studies have shed light on increasingly prevalent cardiac diseases involving the ID. Insufficient knowledge of its composition makes it difficult to study these disease mechanisms in more detail and therefore here we aim expand the ID proteome. Here, using a combination of general membrane enrichment, in-depth quantitative proteomics and an intracellular location driven bioinformatics approach, we aim to discover new putative ID proteins in rat ventricular tissue.General membrane isolation, enriched amongst others also with ID proteins as based on presence of the established markers connexin-43 and n-cadherin, was performed using centrifugation. By mass spectrometry, we quantitatively evaluated the level of 3455 proteins in the enriched membrane fraction (EMF and its counterpart, the soluble cytoplasmic fraction. These data were stringently filtered to generate a final set of 97 enriched, putative ID proteins. These included Cx43 and n-cadherin, but also many interesting novel candidates. We selected 4 candidates (Flotillin-2 (FLOT2, Nexilin (NEXN, Popeye-domain-containg-protein 2 (POPDC2 and thioredoxin-related-transmembrane-protein 2 (TMX2 and confirmed their co-localization with n-cadherin in the ID of human and rat heart cryo-sections, and isolated dog cardiomyocytes.The presented proteomics dataset of putative new ID proteins is a valuable resource for future research into this important molecular intersection of the heart.

  3. Identifying natural compounds as multi-target-directed ligands against Alzheimer's disease: an in silico approach.

    Science.gov (United States)

    Ambure, Pravin; Bhat, Jyotsna; Puzyn, Tomasz; Roy, Kunal

    2018-04-23

    Alzheimer's disease (AD) is a multi-factorial disease, which can be simply outlined as an irreversible and progressive neurodegenerative disorder with an unclear root cause. It is a major cause of dementia in old aged people. In the present study, utilizing the structural and biological activity information of ligands for five important and mostly studied vital targets (i.e. cyclin-dependant kinase 5, β-secretase, monoamine oxidase B, glycogen synthase kinase 3β, acetylcholinesterase) that are believed to be effective against AD, we have developed five classification models using linear discriminant analysis (LDA) technique. Considering the importance of data curation, we have given more attention towards the chemical and biological data curation, which is a difficult task especially in case of big data-sets. Thus, to ease the curation process we have designed Konstanz Information Miner (KNIME) workflows, which are made available at http://teqip.jdvu.ac.in/QSAR_Tools/ . The developed models were appropriately validated based on the predictions for experiment derived data from test sets, as well as true external set compounds including known multi-target compounds. The domain of applicability for each classification model was checked based on a confidence estimation approach. Further, these validated models were employed for screening of natural compounds collected from the InterBioScreen natural database ( https://www.ibscreen.com/natural-compounds ). Further, the natural compounds that were categorized as 'actives' in at least two classification models out of five developed models were considered as multi-target leads, and these compounds were further screened using the drug-like filter, molecular docking technique and then thoroughly analyzed using molecular dynamics studies. Finally, the most potential multi-target natural compounds against AD are suggested.

  4. Antibiotic Resistances in Livestock: A Comparative Approach to Identify an Appropriate Regression Model for Count Data

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    Anke Hüls

    2017-05-01

    Full Text Available Antimicrobial resistance in livestock is a matter of general concern. To develop hygiene measures and methods for resistance prevention and control, epidemiological studies on a population level are needed to detect factors associated with antimicrobial resistance in livestock holdings. In general, regression models are used to describe these relationships between environmental factors and resistance outcome. Besides the study design, the correlation structures of the different outcomes of antibiotic resistance and structural zero measurements on the resistance outcome as well as on the exposure side are challenges for the epidemiological model building process. The use of appropriate regression models that acknowledge these complexities is essential to assure valid epidemiological interpretations. The aims of this paper are (i to explain the model building process comparing several competing models for count data (negative binomial model, quasi-Poisson model, zero-inflated model, and hurdle model and (ii to compare these models using data from a cross-sectional study on antibiotic resistance in animal husbandry. These goals are essential to evaluate which model is most suitable to identify potential prevention measures. The dataset used as an example in our analyses was generated initially to study the prevalence and associated factors for the appearance of cefotaxime-resistant Escherichia coli in 48 German fattening pig farms. For each farm, the outcome was the count of samples with resistant bacteria. There was almost no overdispersion and only moderate evidence of excess zeros in the data. Our analyses show that it is essential to evaluate regression models in studies analyzing the relationship between environmental factors and antibiotic resistances in livestock. After model comparison based on evaluation of model predictions, Akaike information criterion, and Pearson residuals, here the hurdle model was judged to be the most appropriate

  5. Harmonization of clinical laboratories in Africa: a multidisciplinary approach to identify innovative and sustainable technical solutions.

    Science.gov (United States)

    Putoto, Giovanni; Cortese, Antonella; Pecorari, Ilaria; Musi, Roberto; Nunziata, Enrico

    2015-06-01

    In an effective and efficient health system, laboratory medicine should play a critical role. This is not the case in Africa, where there is a lack of demand for diagnostic exams due to mistrust of health laboratory performance. Doctors with Africa CUAMM (Collegio Universitario Aspiranti Medici Missionari) is a non-profit organization, working mainly in sub-Saharan Africa (Angola, Ethiopia, Mozambique, Sierra Leone, South Sudan, Tanzania and Uganda) to help and sustain local health systems. Doctors with Africa CUAMM has advocated the need for a harmonized model for health laboratories to assess and evaluate the performance of the facilities in which they operate. In order to develop a harmonized model for African health laboratories, previous attempts at strengthening them through standardization were taken into consideration and reviewed. A survey with four Italian clinicians experienced in the field was then performed to try and understand the actual needs of health facilities. Finally a market survey was conducted to find new technologies able to update the resulting model. Comparison of actual laboratories with the developed standard - which represents the best setting any African health laboratory could aim for - allowed shortcomings in expected services to be identified and interventions subsequently prioritized. The most appropriate equipment was proposed to perform the envisaged techniques. The suitability of appliances was evaluated in consideration of recognized international recommendations, reported experiences in the field, and the availability of innovative solutions that can be performed on site in rural areas, but require minimal sample preparation and little technical expertise. The present work has developed a new, up-to-date, harmonized model for African health laboratories. The authors suggest lists of procedures to challenge the major African health problems - HIV/AIDS, malaria, tubercolosis (TB) - at each level of pyramidal health system. This

  6. An Evolutionary Genomic Approach to Identify Genes Involved in Human Birth Timing

    Science.gov (United States)

    Orabona, Guilherme; Morgan, Thomas; Haataja, Ritva; Hallman, Mikko; Puttonen, Hilkka; Menon, Ramkumar; Kuczynski, Edward; Norwitz, Errol; Snegovskikh, Victoria; Palotie, Aarno; Fellman, Vineta; DeFranco, Emily A.; Chaudhari, Bimal P.; McGregor, Tracy L.; McElroy, Jude J.; Oetjens, Matthew T.; Teramo, Kari; Borecki, Ingrid; Fay, Justin; Muglia, Louis

    2011-01-01

    Coordination of fetal maturation with birth timing is essential for mammalian reproduction. In humans, preterm birth is a disorder of profound global health significance. The signals initiating parturition in humans have remained elusive, due to divergence in physiological mechanisms between humans and model organisms typically studied. Because of relatively large human head size and narrow birth canal cross-sectional area compared to other primates, we hypothesized that genes involved in parturition would display accelerated evolution along the human and/or higher primate phylogenetic lineages to decrease the length of gestation and promote delivery of a smaller fetus that transits the birth canal more readily. Further, we tested whether current variation in such accelerated genes contributes to preterm birth risk. Evidence from allometric scaling of gestational age suggests human gestation has been shortened relative to other primates. Consistent with our hypothesis, many genes involved in reproduction show human acceleration in their coding or adjacent noncoding regions. We screened >8,400 SNPs in 150 human accelerated genes in 165 Finnish preterm and 163 control mothers for association with preterm birth. In this cohort, the most significant association was in FSHR, and 8 of the 10 most significant SNPs were in this gene. Further evidence for association of a linkage disequilibrium block of SNPs in FSHR, rs11686474, rs11680730, rs12473870, and rs1247381 was found in African Americans. By considering human acceleration, we identified a novel gene that may be associated with preterm birth, FSHR. We anticipate other human accelerated genes will similarly be associated with preterm birth risk and elucidate essential pathways for human parturition. PMID:21533219

  7. Molecular subtypes of osteosarcoma identified by reducing tumor heterogeneity through an interspecies comparative approach

    Science.gov (United States)

    Scott, Milcah C.; Sarver, Aaron L.; Gavin, Katherine J.; Thayanithy, Venugopal; Getzy, David M.; Newman, Robert A.; Cutter, Gary R.; Lindblad-Toh, Kerstin; Kisseberth, William C.; Hunter, Lawrence E.; Subramanian, Subbaya; Breen, Matthew; Modiano, Jaime F.

    2011-01-01

    The heterogeneous and chaotic nature of osteosarcoma has confounded accurate molecular classification, prognosis, and prediction for this tumor. The occurrence of spontaneous osteosarcoma is largely confined to humans and dogs. While the clinical features are remarkably similar in both species, the organization of dogs into defined breeds provides a more homogeneous genetic background that may increase the likelihood to uncover molecular subtypes for this complex disease. We thus hypothesized that molecular profiles derived from canine osteosarcoma would aid in molecular subclassification of this disease when applied to humans. To test the hypothesis, we performed genome wide gene expression profiling in a cohort of dogs with osteosarcoma, primarily from high-risk breeds. To further reduce inter-sample heterogeneity, we assessed tumor-intrinsic properties through use of an extensive panel of osteosarcoma-derived cell lines. We observed strong differential gene expression that segregated samples into two groups with differential survival probabilities. Groupings were characterized by the inversely correlated expression of genes associated with G2/M transition and DNA damage checkpoint and microenvironment-interaction categories. This signature was preserved in data from whole tumor samples of three independent dog osteosarcoma cohorts, with stratification into the two expected groups. Significantly, this restricted signature partially overlapped a previously defined, predictive signature for soft tissue sarcomas, and it unmasked orthologous molecular subtypes and their corresponding natural histories in five independent data sets from human patients with osteosarcoma. Our results indicate that the narrower genetic diversity of dogs can be utilized to group complex human osteosarcoma into biologically and clinically relevant molecular subtypes. This in turn may enhance prognosis and prediction, and identify relevant therapeutic targets. PMID:21621658

  8. The hierarchy-by-interval approach to identifying important models that need improvement in severe-accident simulation codes

    International Nuclear Information System (INIS)

    Heames, T.J.; Khatib-Rahbar, M.; Kelly, J.E.

    1995-01-01

    The hierarchy-by-interval (HBI) methodology was developed to determine an appropriate phenomena identification and ranking table for an independent peer review of severe-accident computer codes. The methodology is described, and the results of a specific code review are presented. Use of this systematic and structured approach ensures that important code models that need improvement are identified and prioritized, which allows code sponsors to more effectively direct limited resources in future code development. In addition, critical phenomenological areas that need more fundamental work, such as experimentation, are identified

  9. Macrophage polarisation: an immunohistochemical approach for identifying M1 and M2 macrophages.

    Directory of Open Access Journals (Sweden)

    Mário Henrique M Barros

    Full Text Available Macrophage polarization is increasingly recognised as an important pathogenetic factor in inflammatory and neoplastic diseases. Proinflammatory M1 macrophages promote T helper (Th 1 responses and show tumoricidal activity. M2 macrophages contribute to tissue repair and promote Th2 responses. CD68 and CD163 are used to identify macrophages in tissue sections. However, characterisation of polarised macrophages in situ has remained difficult. Macrophage polarisation is regulated by transcription factors, pSTAT1 and RBP-J for M1, and CMAF for M2. We reasoned that double-labelling immunohistochemistry for the detection of macrophage markers together with transcription factors may be suitable to characterise macrophage polarisation in situ. To test this hypothesis, we have studied conditions associated with Th1- and Th2-predominant immune responses: infectious mononucleosis and Crohn's disease for Th1 and allergic nasal polyps, oxyuriasis, wound healing and foreign body granulomas for predominant Th2 response. In all situations, CD163+ cells usually outnumbered CD68+ cells. Moreover, CD163+ cells, usually considered as M2 macrophages, co-expressing pSTAT1 and RBP-J were found in all conditions examined. The numbers of putative M1 macrophages were higher in Th1- than in Th2-associated diseases, while more M2 macrophages were seen in Th2- than in Th1 related disorders. In most Th1-related diseases, the balance of M1 over M2 cells was shifted towards M1 cells, while the reverse was observed for Th2-related conditions. Hierarchical cluster analysis revealed two distinct clusters: cluster I included Th1 diseases together with cases with high numbers of CD163+pSTAT1+, CD68+pSTAT1+, CD163+RBP-J+ and CD68+RBP-J+ macrophages; cluster II comprised Th2 conditions together with cases displaying high numbers of CD163+CMAF+ and CD68+CMAF+ macrophages. These results suggest that the detection of pSTAT1, RBP-J, and CMAF in the context of CD68 or CD163 expression is a

  10. Macrophage polarisation: an immunohistochemical approach for identifying M1 and M2 macrophages.

    Science.gov (United States)

    Barros, Mário Henrique M; Hauck, Franziska; Dreyer, Johannes H; Kempkes, Bettina; Niedobitek, Gerald

    2013-01-01

    Macrophage polarization is increasingly recognised as an important pathogenetic factor in inflammatory and neoplastic diseases. Proinflammatory M1 macrophages promote T helper (Th) 1 responses and show tumoricidal activity. M2 macrophages contribute to tissue repair and promote Th2 responses. CD68 and CD163 are used to identify macrophages in tissue sections. However, characterisation of polarised macrophages in situ has remained difficult. Macrophage polarisation is regulated by transcription factors, pSTAT1 and RBP-J for M1, and CMAF for M2. We reasoned that double-labelling immunohistochemistry for the detection of macrophage markers together with transcription factors may be suitable to characterise macrophage polarisation in situ. To test this hypothesis, we have studied conditions associated with Th1- and Th2-predominant immune responses: infectious mononucleosis and Crohn's disease for Th1 and allergic nasal polyps, oxyuriasis, wound healing and foreign body granulomas for predominant Th2 response. In all situations, CD163+ cells usually outnumbered CD68+ cells. Moreover, CD163+ cells, usually considered as M2 macrophages, co-expressing pSTAT1 and RBP-J were found in all conditions examined. The numbers of putative M1 macrophages were higher in Th1- than in Th2-associated diseases, while more M2 macrophages were seen in Th2- than in Th1 related disorders. In most Th1-related diseases, the balance of M1 over M2 cells was shifted towards M1 cells, while the reverse was observed for Th2-related conditions. Hierarchical cluster analysis revealed two distinct clusters: cluster I included Th1 diseases together with cases with high numbers of CD163+pSTAT1+, CD68+pSTAT1+, CD163+RBP-J+ and CD68+RBP-J+ macrophages; cluster II comprised Th2 conditions together with cases displaying high numbers of CD163+CMAF+ and CD68+CMAF+ macrophages. These results suggest that the detection of pSTAT1, RBP-J, and CMAF in the context of CD68 or CD163 expression is a suitable tool for

  11. Identifying Opportunities for Decision Support Systems in Support of Regional Resource Use Planning: An Approach Through Soft Systems Methodology.

    Science.gov (United States)

    Zhu; Dale

    2000-10-01

    / Regional resource use planning relies on key regional stakeholder groups using and having equitable access to appropriate social, economic, and environmental information and assessment tools. Decision support systems (DSS) can improve stakeholder access to such information and analysis tools. Regional resource use planning, however, is a complex process involving multiple issues, multiple assessment criteria, multiple stakeholders, and multiple values. There is a need for an approach to DSS development that can assist in understanding and modeling complex problem situations in regional resource use so that areas where DSSs could provide effective support can be identified, and the user requirements can be well established. This paper presents an approach based on the soft systems methodology for identifying DSS opportunities for regional resource use planning, taking the Central Highlands Region of Queensland, Australia, as a case study.

  12. Can children identify and achieve goals for intervention? A randomized trial comparing two goal-setting approaches.

    Science.gov (United States)

    Vroland-Nordstrand, Kristina; Eliasson, Ann-Christin; Jacobsson, Helén; Johansson, Ulla; Krumlinde-Sundholm, Lena

    2016-06-01

    The efficacy of two different goal-setting approaches (children's self-identified goals and goals identified by parents) were compared on a goal-directed, task-oriented intervention. In this assessor-blinded parallel randomized trial, 34 children with disabilities (13 males, 21 females; mean age 9y, SD 1y 4mo) were randomized using concealed allocation to one of two 8-week, goal-directed, task-oriented intervention groups with different goal-setting approaches: (1) children's self-identified goals (n=18) using the Perceived Efficacy and Goal-Setting System, or (2) goals identified by parents (n=16) using the Canadian Occupational Performance Measure (COPM). Participants were recruited through eight paediatric rehabilitation centres and randomized between October 2011 and May 2013. The primary outcome measure was the Goal Attainment Scaling and the secondary measure, the COPM performance scale (COPM-P). Data were collected pre- and post-intervention and at the 5-month follow-up. There was no evidence of a difference in mean characteristics at baseline between groups. There was evidence of an increase in mean goal attainment (mean T score) in both groups after intervention (child-goal group: estimated mean difference [EMD] 27.84, 95% CI 22.93-32.76; parent-goal group: EMD 21.42, 95% CI 16.16-26.67). There was no evidence of a difference in the mean T scores post-intervention between the two groups (EMD 6.42, 95% CI -0.80 to 13.65). These results were sustained at the 5-month follow-up. Children's self-identified goals are achievable to the same extent as parent-identified goals and remain stable over time. Thus children can be trusted to identify their own goals for intervention, thereby influencing their involvement in their intervention programmes. © 2015 Mac Keith Press.

  13. Peptidomic approach identifies cruzioseptins, a new family of potent antimicrobial peptides in the splendid leaf frog, Cruziohyla calcarifer

    OpenAIRE

    Proaño Bolaños, Carolina; Zhou, Mei; Wang, Lei; Luis, Coloma; Chen, Tianbao; Shaw, Christopher

    2016-01-01

    Phyllomedusine frogs are an extraordinary source of biologically active peptides. At least 8 families of antimicrobial peptides have been reported in this frog clade, the dermaseptins being the most diverse. By a peptidomic approach, integrating molecular cloning, Edman degradation sequencing and tandem mass spectrometry, a new family of antimicrobial peptides has been identified in Cruziohyla calcarifer. These 15 novel antimicrobial peptides of 20–32 residues in length are named cruzioseptin...

  14. Evaluation of multiple approaches to identify genome-wide polymorphisms in closely related genotypes of sweet cherry (Prunus avium L.

    Directory of Open Access Journals (Sweden)

    Seanna Hewitt

    Full Text Available Identification of genetic polymorphisms and subsequent development of molecular markers is important for marker assisted breeding of superior cultivars of economically important species. Sweet cherry (Prunus avium L. is an economically important non-climacteric tree fruit crop in the Rosaceae family and has undergone a genetic bottleneck due to breeding, resulting in limited genetic diversity in the germplasm that is utilized for breeding new cultivars. Therefore, it is critical to recognize the best platforms for identifying genome-wide polymorphisms that can help identify, and consequently preserve, the diversity in a genetically constrained species. For the identification of polymorphisms in five closely related genotypes of sweet cherry, a gel-based approach (TRAP, reduced representation sequencing (TRAPseq, a 6k cherry SNParray, and whole genome sequencing (WGS approaches were evaluated in the identification of genome-wide polymorphisms in sweet cherry cultivars. All platforms facilitated detection of polymorphisms among the genotypes with variable efficiency. In assessing multiple SNP detection platforms, this study has demonstrated that a combination of appropriate approaches is necessary for efficient polymorphism identification, especially between closely related cultivars of a species. The information generated in this study provides a valuable resource for future genetic and genomic studies in sweet cherry, and the insights gained from the evaluation of multiple approaches can be utilized for other closely related species with limited genetic diversity in the breeding germplasm. Keywords: Polymorphisms, Prunus avium, Next-generation sequencing, Target region amplification polymorphism (TRAP, Genetic diversity, SNParray, Reduced representation sequencing, Whole genome sequencing (WGS

  15. A hybrid life cycle and multi-criteria decision analysis approach for identifying sustainable development strategies of Beijing's taxi fleet

    International Nuclear Information System (INIS)

    Cai, Yanpeng; Applegate, Scott; Yue, Wencong; Cai, Jianying; Wang, Xuan; Liu, Gengyuan; Li, Chunhui

    2017-01-01

    To identify and evaluate sustainable strategies of taxi fleet in Beijing in terms of economic, policy, and environmental implications, a hybrid approach was developed through incorporating multi-criteria decision analysis (MCDA) methods within a general life-cycle analysis (LCA) framework. The approach can (a) help comprehensive evaluate environmental impacts of multiple types of vehicles, (b) facilitate analysis of environmental, economic and policy features of such vehicles, and (c) identify desirable taxi fleet development strategies for the city. The developed approach represented an improvement of the decision-making capability for taxi implementation based on multiple available technologies and their performance that can be specifically tailored to Beijing. The results demonstrated that the proposed approach could comprehensively reflect multiple implications of strategies for the taxi fleet in Beijing to reduce air pollution in the city. The results also indicated that the electric vehicle powered with the year 2020 electricity projections would be the ideal solution, outranking the other alternatives. The conventional vehicle ranked the lowest among the alternatives. The plug-in hybrid vehicle powered by 2020 electricity projects ranked the third, followed by the plug-in hybrid vehicle ranking the fourth, and the hybrid vehicle ranking the fifth. - Highlights: • An hybrid approach was proposed for evaluating sustainable strategies of Beijing's taxi fleet. • This approach was based on the combination of multi-criteria decision analysis methods and life-cycle assessment. • Environmental, economic and policy performances of multiple strategies were compared. • Detailed responses of taxi drivers and local residents were interviewed. • The electric vehicle would be the ideal solution for Beijing Taxi fleet.

  16. An ontological approach to identifying cases of chronic kidney disease from routine primary care data: a cross-sectional study.

    Science.gov (United States)

    Cole, Nicholas I; Liyanage, Harshana; Suckling, Rebecca J; Swift, Pauline A; Gallagher, Hugh; Byford, Rachel; Williams, John; Kumar, Shankar; de Lusignan, Simon

    2018-04-10

    Accurately identifying cases of chronic kidney disease (CKD) from primary care data facilitates the management of patients, and is vital for surveillance and research purposes. Ontologies provide a systematic and transparent basis for clinical case definition and can be used to identify clinical codes relevant to all aspects of CKD care and its diagnosis. We used routinely collected primary care data from the Royal College of General Practitioners Research and Surveillance Centre. A domain ontology was created and presented in Ontology Web Language (OWL). The identification and staging of CKD was then carried out using two parallel approaches: (1) clinical coding consistent with a diagnosis of CKD; (2) laboratory-confirmed CKD, based on estimated glomerular filtration rate (eGFR) or the presence of proteinuria. The study cohort comprised of 1.2 million individuals aged 18 years and over. 78,153 (6.4%) of the population had CKD on the basis of an eGFR of < 60 mL/min/1.73m 2 , and a further 7366 (0.6%) individuals were identified as having CKD due to proteinuria. 19,504 (1.6%) individuals without laboratory-confirmed CKD had a clinical code consistent with the diagnosis. In addition, a subset of codes allowed for 1348 (0.1%) individuals receiving renal replacement therapy to be identified. Finding cases of CKD from primary care data using an ontological approach may have greater sensitivity than less comprehensive methods, particularly for identifying those receiving renal replacement therapy or with CKD stages 1 or 2. However, the possibility of inaccurate coding may limit the specificity of this method.

  17. High throughput sequencing and proteomics to identify immunogenic proteins of a new pathogen: the dirty genome approach.

    Science.gov (United States)

    Greub, Gilbert; Kebbi-Beghdadi, Carole; Bertelli, Claire; Collyn, François; Riederer, Beat M; Yersin, Camille; Croxatto, Antony; Raoult, Didier

    2009-12-23

    With the availability of new generation sequencing technologies, bacterial genome projects have undergone a major boost. Still, chromosome completion needs a costly and time-consuming gap closure, especially when containing highly repetitive elements. However, incomplete genome data may be sufficiently informative to derive the pursued information. For emerging pathogens, i.e. newly identified pathogens, lack of release of genome data during gap closure stage is clearly medically counterproductive. We thus investigated the feasibility of a dirty genome approach, i.e. the release of unfinished genome sequences to develop serological diagnostic tools. We showed that almost the whole genome sequence of the emerging pathogen Parachlamydia acanthamoebae was retrieved even with relatively short reads from Genome Sequencer 20 and Solexa. The bacterial proteome was analyzed to select immunogenic proteins, which were then expressed and used to elaborate the first steps of an ELISA. This work constitutes the proof of principle for a dirty genome approach, i.e. the use of unfinished genome sequences of pathogenic bacteria, coupled with proteomics to rapidly identify new immunogenic proteins useful to develop in the future specific diagnostic tests such as ELISA, immunohistochemistry and direct antigen detection. Although applied here to an emerging pathogen, this combined dirty genome sequencing/proteomic approach may be used for any pathogen for which better diagnostics are needed. These genome sequences may also be very useful to develop DNA based diagnostic tests. All these diagnostic tools will allow further evaluations of the pathogenic potential of this obligate intracellular bacterium.

  18. Who’s Who at the Border? A rights-based approach to identifying human trafficking at international borders

    Directory of Open Access Journals (Sweden)

    Marika McAdam

    2013-09-01

    Full Text Available International borders are widely touted as bastions in the fight against trafficking in persons. This article acknowledges the important role border officials play in preventing human trafficking, but calls for expectations to be tempered by deference to the conceptual complexity of cross-border trafficking and the migration processes involved. The fact that many trafficked victims begin their journeys as irregular or smuggled migrants highlights the challenge posed to border officials in identifying trafficked persons among the people they encounter. Indicators of trafficking generally relate to the exploitation phase, leaving border officials with little guidance as to how persons vulnerable to trafficking can be accurately identified before any exploitation has occurred. Ultimately, this paper advocates a pragmatic rights-based approach in designating anti-trafficking functions to border officials. A rights-based approach to border control acknowledges the core work of border officials as being to uphold border integrity, while ensuring that their performance of this role does not jeopardise the rights of those they intercept nor result in missed opportunities for specialists to identify trafficked persons and other vulnerable people among them.

  19. Approaches to identifying reservoir heterogeneity and reserve growth opportunities from subsurface data: The Oficina Formation, Budare field, Venezuela

    Energy Technology Data Exchange (ETDEWEB)

    Hamilton, D.S.; Raeuchle, S.K.; Holtz, M.H. [Bureau of Economic Geology, Austin, TX (United States)] [and others

    1997-08-01

    We applied an integrated geologic, geophysical, and engineering approach devised to identify heterogeneities in the subsurface that might lead to reserve growth opportunities in our analysis of the Oficina Formation at Budare field, Venezuela. The approach involves 4 key steps: (1) Determine geologic reservoir architecture; (2) Investigate trends in reservoir fluid flow; (3) Integrate fluid flow trends with reservoir architecture; and (4) Estimate original oil-in-place, residual oil saturation, and remaining mobile oil, to identify opportunities for reserve growth. There are three main oil-producing reservoirs in the Oficina Formation that were deposited in a bed-load fluvial system, an incised valley-fill, and a barrier-strandplain system. Reservoir continuity is complex because, in addition to lateral facies variability, the major Oficina depositional systems were internally subdivided by high-frequency stratigraphic surfaces. These surfaces define times of intermittent lacustrine and marine flooding events that punctuated the fluvial and marginal marine sedimentation, respectively. Syn and post depositional faulting further disrupted reservoir continuity. Trends in fluid flow established from initial fluid levels, response to recompletion workovers, and pressure depletion data demonstrated barriers to lateral and vertical fluid flow caused by a combination of reservoir facies pinchout, flooding shale markers, and the faults. Considerable reserve growth potential exists at Budare field because the reservoir units are highly compartment by the depositional heterogeneity and structural complexity. Numerous reserve growth opportunities were identified in attics updip of existing production, in untapped or incompletely drained compartments, and in field extensions.

  20. A novel baiting microcosm approach used to identify the bacterial community associated with Penicillium bilaii hyphae in soil.

    Directory of Open Access Journals (Sweden)

    Behnoushsadat Ghodsalavi

    Full Text Available It is important to identify and recover bacteria associating with fungi under natural soil conditions to enable eco-physiological studies, and to facilitate the use of bacterial-fungal consortia in environmental biotechnology. We have developed a novel type of baiting microcosm, where fungal hyphae interact with bacteria under close-to-natural soil conditions; an advantage compared to model systems that determine fungal influences on bacterial communities in laboratory media. In the current approach, the hyphae are placed on a solid support, which enables the recovery of hyphae with associated bacteria in contrast to model systems that compare bulk soil and mycosphere soil. We used the baiting microcosm approach to determine, for the first time, the composition of the bacterial community associating in the soil with hyphae of the phosphate-solubilizer, Penicillium bilaii. By applying a cultivation-independent 16S rRNA gene-targeted amplicon sequencing approach, we found a hypha-associated bacterial community with low diversity compared to the bulk soil community and exhibiting massive dominance of Burkholderia OTUs. Burkholderia is known be abundant in soil environments affected by fungi, but the discovery of this massive dominance among bacteria firmly associating with hyphae in soil is novel and made possible by the current bait approach.

  1. A novel baiting microcosm approach used to identify the bacterial community associated with Penicillium bilaii hyphae in soil

    DEFF Research Database (Denmark)

    Ghodsalavi, Behnoushsadat; Svenningsen, Nanna Bygvraa; Hao, Xiuli

    2017-01-01

    It is important to identify and recover bacteria associating with fungi under natural soil conditions to enable eco-physiological studies, and to facilitate the use of bacterial-fungal consortia in environmental biotechnology. We have developed a novel type of baiting microcosm, where fungal hyphae...... interact with bacteria under close-to-natural soil conditions; an advantage compared to model systems that determine fungal influences on bacterial communities in laboratory media. In the current approach, the hyphae are placed on a solid support, which enables the recovery of hyphae with associated...... bacteria in contrast to model systems that compare bulk soil and mycosphere soil. We used the baiting microcosm approach to determine, for the first time, the composition of the bacterial community associating in the soil with hyphae of the phosphate-solubilizer, Penicillium bilaii. By applying...

  2. Genome-wide local ancestry approach identifies genes and variants associated with chemotherapeutic susceptibility in African Americans.

    Directory of Open Access Journals (Sweden)

    Heather E Wheeler

    Full Text Available Chemotherapeutic agents are used in the treatment of many cancers, yet variable resistance and toxicities among individuals limit successful outcomes. Several studies have indicated outcome differences associated with ancestry among patients with various cancer types. Using both traditional SNP-based and newly developed gene-based genome-wide approaches, we investigated the genetics of chemotherapeutic susceptibility in lymphoblastoid cell lines derived from 83 African Americans, a population for which there is a disparity in the number of genome-wide studies performed. To account for population structure in this admixed population, we incorporated local ancestry information into our association model. We tested over 2 million SNPs and identified 325, 176, 240, and 190 SNPs that were suggestively associated with cytarabine-, 5'-deoxyfluorouridine (5'-DFUR-, carboplatin-, and cisplatin-induced cytotoxicity, respectively (p≤10(-4. Importantly, some of these variants are found only in populations of African descent. We also show that cisplatin-susceptibility SNPs are enriched for carboplatin-susceptibility SNPs. Using a gene-based genome-wide association approach, we identified 26, 11, 20, and 41 suggestive candidate genes for association with cytarabine-, 5'-DFUR-, carboplatin-, and cisplatin-induced cytotoxicity, respectively (p≤10(-3. Fourteen of these genes showed evidence of association with their respective chemotherapeutic phenotypes in the Yoruba from Ibadan, Nigeria (p<0.05, including TP53I11, COPS5 and GAS8, which are known to be involved in tumorigenesis. Although our results require further study, we have identified variants and genes associated with chemotherapeutic susceptibility in African Americans by using an approach that incorporates local ancestry information.

  3. Identifying the most informative variables for decision-making problems – a survey of recent approaches and accompanying problems

    Czech Academy of Sciences Publication Activity Database

    Pudil, Pavel; Somol, Petr

    2008-01-01

    Roč. 16, č. 4 (2008), s. 37-55 ISSN 0572-3043 R&D Projects: GA MŠk 1M0572 Grant - others:GA MŠk(CZ) 2C06019 Institutional research plan: CEZ:AV0Z10750506 Keywords : variable selection * decision making Subject RIV: BD - Theory of Information http://library.utia.cas.cz/separaty/2008/RO/pudil-identifying%20the%20most%20informative%20variables%20for%20decision- making %20problems%20a%20survey%20of%20recent%20approaches%20and%20accompanying%20problems.pdf

  4. Comparison of two model approaches in the Zambezi river basin with regard to model reliability and identifiability

    Directory of Open Access Journals (Sweden)

    H. C. Winsemius

    2006-01-01

    Full Text Available Variations of water stocks in the upper Zambezi river basin have been determined by 2 different hydrological modelling approaches. The purpose was to provide preliminary terrestrial storage estimates in the upper Zambezi, which will be compared with estimates derived from the Gravity Recovery And Climate Experiment (GRACE in a future study. The first modelling approach is GIS-based, distributed and conceptual (STREAM. The second approach uses Lumped Elementary Watersheds identified and modelled conceptually (LEW. The STREAM model structure has been assessed using GLUE (Generalized Likelihood Uncertainty Estimation a posteriori to determine parameter identifiability. The LEW approach could, in addition, be tested for model structure, because computational efforts of LEW are low. Both models are threshold models, where the non-linear behaviour of the Zambezi river basin is explained by a combination of thresholds and linear reservoirs. The models were forced by time series of gauged and interpolated rainfall. Where available, runoff station data was used to calibrate the models. Ungauged watersheds were generally given the same parameter sets as their neighbouring calibrated watersheds. It appeared that the LEW model structure could be improved by applying GLUE iteratively. Eventually, it led to better identifiability of parameters and consequently a better model structure than the STREAM model. Hence, the final model structure obtained better represents the true hydrology. After calibration, both models show a comparable efficiency in representing discharge. However the LEW model shows a far greater storage amplitude than the STREAM model. This emphasizes the storage uncertainty related to hydrological modelling in data-scarce environments such as the Zambezi river basin. It underlines the need and potential for independent observations of terrestrial storage to enhance our understanding and modelling capacity of the hydrological processes. GRACE

  5. An Integrated Approach to Change the Outcome Part II: Targeted Neuromuscular Training Techniques to Reduce Identified ACL Injury Risk Factors

    Science.gov (United States)

    Myer, Gregory D.; Ford, Kevin R.; Brent, Jensen L.; Hewett, Timothy E.

    2014-01-01

    Prior reports indicate that female athletes who demonstrate high knee abduction moments (KAMs) during landing are more responsive to neuromuscular training designed to reduce KAM. Identification of female athletes who demonstrate high KAM, which accurately identifies those at risk for noncontact anterior cruciate ligament (ACL) injury, may be ideal for targeted neuromuscular training. Specific neuromuscular training targeted to the underlying biomechanical components that increase KAM may provide the most efficient and effective training strategy to reduce noncontact ACL injury risk. The purpose of the current commentary is to provide an integrative approach to identify and target mechanistic underpinnings to increased ACL injury in female athletes. Specific neuromuscular training techniques will be presented that address individual algorithm components related to high knee load landing patterns. If these integrated techniques are employed on a widespread basis, prevention strategies for noncontact ACL injury among young female athletes may prove both more effective and efficient. PMID:22580980

  6. The HepTestContest: a global innovation contest to identify approaches to hepatitis B and C testing.

    Science.gov (United States)

    Tucker, Joseph D; Meyers, Kathrine; Best, John; Kaplan, Karyn; Pendse, Razia; Fenton, Kevin A; Andrieux-Meyer, Isabelle; Figueroa, Carmen; Goicochea, Pedro; Gore, Charles; Ishizaki, Azumi; Khwairakpam, Giten; Miller, Veronica; Mozalevskis, Antons; Ninburg, Michael; Ocama, Ponsiano; Peeling, Rosanna; Walsh, Nick; Colombo, Massimo G; Easterbrook, Philippa

    2017-11-01

    Innovation contests are a novel approach to elicit good ideas and innovative practices in various areas of public health. There remains limited published literature on approaches to deliver hepatitis testing. The purpose of this innovation contest was to identify examples of different hepatitis B and C approaches to support countries in their scale-up of hepatitis testing and to supplement development of formal recommendations on service delivery in the 2017 World Health Organization hepatitis B and C testing guidelines. This contest involved four steps: 1) establishment of a multisectoral steering committee to coordinate a call for contest entries; 2) dissemination of the call for entries through diverse media (Facebook, Twitter, YouTube, email listservs, academic journals); 3) independent ranking of submissions by a panel of judges according to pre-specified criteria (clarity of testing model, innovation, effectiveness, next steps) using a 1-10 scale; 4) recognition of highly ranked entries through presentation at international conferences, commendation certificate, and inclusion as a case study in the WHO 2017 testing guidelines. The innovation contest received 64 entries from 27 countries and took a total of 4 months to complete. Sixteen entries were directly included in the WHO testing guidelines. The entries covered testing in different populations, including primary care patients (n = 5), people who inject drugs (PWID) (n = 4), pregnant women (n = 4), general populations (n = 4), high-risk groups (n = 3), relatives of people living with hepatitis B and C (n = 2), migrants (n = 2), incarcerated individuals (n = 2), workers (n = 2), and emergency department patients (n = 2). A variety of different testing delivery approaches were employed, including integrated HIV-hepatitis testing (n = 12); integrated testing with harm reduction and addiction services (n = 9); use of electronic medical records to support targeted testing (n = 8

  7. The HepTestContest: a global innovation contest to identify approaches to hepatitis B and C testing

    Directory of Open Access Journals (Sweden)

    Joseph D. Tucker

    2017-11-01

    Full Text Available Abstract Background Innovation contests are a novel approach to elicit good ideas and innovative practices in various areas of public health. There remains limited published literature on approaches to deliver hepatitis testing. The purpose of this innovation contest was to identify examples of different hepatitis B and C approaches to support countries in their scale-up of hepatitis testing and to supplement development of formal recommendations on service delivery in the 2017 World Health Organization hepatitis B and C testing guidelines. Methods This contest involved four steps: 1 establishment of a multisectoral steering committee to coordinate a call for contest entries; 2 dissemination of the call for entries through diverse media (Facebook, Twitter, YouTube, email listservs, academic journals; 3 independent ranking of submissions by a panel of judges according to pre-specified criteria (clarity of testing model, innovation, effectiveness, next steps using a 1-10 scale; 4 recognition of highly ranked entries through presentation at international conferences, commendation certificate, and inclusion as a case study in the WHO 2017 testing guidelines. Results The innovation contest received 64 entries from 27 countries and took a total of 4 months to complete. Sixteen entries were directly included in the WHO testing guidelines. The entries covered testing in different populations, including primary care patients (n = 5, people who inject drugs (PWID (n = 4, pregnant women (n = 4, general populations (n = 4, high-risk groups (n = 3, relatives of people living with hepatitis B and C (n = 2, migrants (n = 2, incarcerated individuals (n = 2, workers (n = 2, and emergency department patients (n = 2. A variety of different testing delivery approaches were employed, including integrated HIV-hepatitis testing (n = 12; integrated testing with harm reduction and addiction services (n = 9; use of electronic medical records to

  8. Giant hub Src and Syk tyrosine kinase thermodynamic profiles recapitulate evolution

    Science.gov (United States)

    Phillips, J. C.

    2017-10-01

    Thermodynamic scaling theory, previously applied mainly to small proteins, here analyzes quantitative evolution of the titled functional network giant hub enzymes. The broad domain structure identified homologically is confirmed hydropathically using amino acid sequences only. The most surprising results concern the evolution of the tyrosine kinase globular surface roughness from avians to mammals, which is first order, compared to the evolution within mammals from rodents to humans, which is second order. The mystery of the unique amide terminal region of proto oncogene tyrosine protein kinase is resolved by the discovery there of a rare hydroneutral septad targeting cluster, which is paralleled by an equally rare octad catalytic cluster in tyrosine kinase in humans and a few other species (cat and dog). These results, which go far towards explaining why these proteins are among the largest giant hubs in protein interaction networks, use no adjustable parameters.

  9. A data-driven approach to identify controls on global fire activity from satellite and climate observations (SOFIA V1

    Directory of Open Access Journals (Sweden)

    M. Forkel

    2017-12-01

    Full Text Available Vegetation fires affect human infrastructures, ecosystems, global vegetation distribution, and atmospheric composition. However, the climatic, environmental, and socioeconomic factors that control global fire activity in vegetation are only poorly understood, and in various complexities and formulations are represented in global process-oriented vegetation-fire models. Data-driven model approaches such as machine learning algorithms have successfully been used to identify and better understand controlling factors for fire activity. However, such machine learning models cannot be easily adapted or even implemented within process-oriented global vegetation-fire models. To overcome this gap between machine learning-based approaches and process-oriented global fire models, we introduce a new flexible data-driven fire modelling approach here (Satellite Observations to predict FIre Activity, SOFIA approach version 1. SOFIA models can use several predictor variables and functional relationships to estimate burned area that can be easily adapted with more complex process-oriented vegetation-fire models. We created an ensemble of SOFIA models to test the importance of several predictor variables. SOFIA models result in the highest performance in predicting burned area if they account for a direct restriction of fire activity under wet conditions and if they include a land cover-dependent restriction or allowance of fire activity by vegetation density and biomass. The use of vegetation optical depth data from microwave satellite observations, a proxy for vegetation biomass and water content, reaches higher model performance than commonly used vegetation variables from optical sensors. We further analyse spatial patterns of the sensitivity between anthropogenic, climate, and vegetation predictor variables and burned area. We finally discuss how multiple observational datasets on climate, hydrological, vegetation, and socioeconomic variables together with

  10. A data-driven approach to identify controls on global fire activity from satellite and climate observations (SOFIA V1)

    Science.gov (United States)

    Forkel, Matthias; Dorigo, Wouter; Lasslop, Gitta; Teubner, Irene; Chuvieco, Emilio; Thonicke, Kirsten

    2017-12-01

    Vegetation fires affect human infrastructures, ecosystems, global vegetation distribution, and atmospheric composition. However, the climatic, environmental, and socioeconomic factors that control global fire activity in vegetation are only poorly understood, and in various complexities and formulations are represented in global process-oriented vegetation-fire models. Data-driven model approaches such as machine learning algorithms have successfully been used to identify and better understand controlling factors for fire activity. However, such machine learning models cannot be easily adapted or even implemented within process-oriented global vegetation-fire models. To overcome this gap between machine learning-based approaches and process-oriented global fire models, we introduce a new flexible data-driven fire modelling approach here (Satellite Observations to predict FIre Activity, SOFIA approach version 1). SOFIA models can use several predictor variables and functional relationships to estimate burned area that can be easily adapted with more complex process-oriented vegetation-fire models. We created an ensemble of SOFIA models to test the importance of several predictor variables. SOFIA models result in the highest performance in predicting burned area if they account for a direct restriction of fire activity under wet conditions and if they include a land cover-dependent restriction or allowance of fire activity by vegetation density and biomass. The use of vegetation optical depth data from microwave satellite observations, a proxy for vegetation biomass and water content, reaches higher model performance than commonly used vegetation variables from optical sensors. We further analyse spatial patterns of the sensitivity between anthropogenic, climate, and vegetation predictor variables and burned area. We finally discuss how multiple observational datasets on climate, hydrological, vegetation, and socioeconomic variables together with data

  11. Systematic Correlation Matrix Evaluation (SCoMaE) - a bottom-up, science-led approach to identifying indicators

    Science.gov (United States)

    Mengis, Nadine; Keller, David P.; Oschlies, Andreas

    2018-01-01

    This study introduces the Systematic Correlation Matrix Evaluation (SCoMaE) method, a bottom-up approach which combines expert judgment and statistical information to systematically select transparent, nonredundant indicators for a comprehensive assessment of the state of the Earth system. The methods consists of two basic steps: (1) the calculation of a correlation matrix among variables relevant for a given research question and (2) the systematic evaluation of the matrix, to identify clusters of variables with similar behavior and respective mutually independent indicators. Optional further analysis steps include (3) the interpretation of the identified clusters, enabling a learning effect from the selection of indicators, (4) testing the robustness of identified clusters with respect to changes in forcing or boundary conditions, (5) enabling a comparative assessment of varying scenarios by constructing and evaluating a common correlation matrix, and (6) the inclusion of expert judgment, for example, to prescribe indicators, to allow for considerations other than statistical consistency. The example application of the SCoMaE method to Earth system model output forced by different CO2 emission scenarios reveals the necessity of reevaluating indicators identified in a historical scenario simulation for an accurate assessment of an intermediate-high, as well as a business-as-usual, climate change scenario simulation. This necessity arises from changes in prevailing correlations in the Earth system under varying climate forcing. For a comparative assessment of the three climate change scenarios, we construct and evaluate a common correlation matrix, in which we identify robust correlations between variables across the three considered scenarios.

  12. A Systems Genetic Approach to Identify Low Dose Radiation-Induced Lymphoma Susceptibility/DOE2013FinalReport

    Energy Technology Data Exchange (ETDEWEB)

    Balmain, Allan [University of California, San Francisco; Song, Ihn Young [University of California, San Francisco

    2013-05-15

    The ultimate goal of this project is to identify the combinations of genetic variants that confer an individual's susceptibility to the effects of low dose (0.1 Gy) gamma-radiation, in particular with regard to tumor development. In contrast to the known effects of high dose radiation in cancer induction, the responses to low dose radiation (defined as 0.1 Gy or less) are much less well understood, and have been proposed to involve a protective anti-tumor effect in some in vivo scientific models. These conflicting results confound attempts to develop predictive models of the risk of exposure to low dose radiation, particularly when combined with the strong effects of inherited genetic variants on both radiation effects and cancer susceptibility. We have used a Systems Genetics approach in mice that combines genetic background analysis with responses to low and high dose radiation, in order to develop insights that will allow us to reconcile these disparate observations. Using this comprehensive approach we have analyzed normal tissue gene expression (in this case the skin and thymus), together with the changes that take place in this gene expression architecture a) in response to low or high- dose radiation and b) during tumor development. Additionally, we have demonstrated that using our expression analysis approach in our genetically heterogeneous/defined radiation-induced tumor mouse models can uniquely identify genes and pathways relevant to human T-ALL, and uncover interactions between common genetic variants of genes which may lead to tumor susceptibility.

  13. Identifying postpartum intervention approaches to reduce cardiometabolic risk among American Indian women with prior gestational diabetes, Oklahoma, 2012-2013.

    Science.gov (United States)

    Jones, Emily J; Peercy, Michael; Woods, J Cedric; Parker, Stephany P; Jackson, Teresa; Mata, Sara A; McCage, Shondra; Levkoff, Sue E; Nicklas, Jacinda M; Seely, Ellen W

    2015-04-02

    Innovative approaches are needed to reduce cardiometabolic risk among American Indian women with a history of gestational diabetes. We assessed beliefs of Oklahoma American Indian women about preventing type 2 diabetes and cardiovascular disease after having gestational diabetes. We also assessed barriers and facilitators to healthy lifestyle changes postpartum and intervention approaches that facilitate participation in a postpartum lifestyle program. In partnership with a tribal health system, we conducted a mixed-method study with American Indian women aged 19 to 45 years who had prior gestational diabetes, using questionnaires, focus groups, and individual interviews. Questionnaires were used to identify women's cardiometabolic risk perceptions and feasibility and acceptability of Internet or mobile phone technology for delivery of a postpartum lifestyle modification program. Focus groups and individual interviews were conducted to identify key perspectives and preferences related to a potential program. Participants were 26 women, all of whom completed surveys; 11 women participated in focus group sessions, and 15 participated in individual interviews. Most women believed they would inevitably develop diabetes, cardiovascular disease, or both; however, they were optimistic that they could delay onset with lifestyle change. Most women expressed enthusiasm for a family focused, technology-based intervention that emphasizes the importance of delaying disease onset, provides motivation, and promotes accountability while accommodating women's competing priorities. Our findings suggest that an intervention that uses the Internet, text messaging, or both and that emphasizes the benefits of delaying disease onset should be tested as a novel, culturally relevant approach to reducing rates of diabetes and cardiovascular disease in this high-risk population.

  14. A data-driven modeling approach to identify disease-specific multi-organ networks driving physiological dysregulation.

    Directory of Open Access Journals (Sweden)

    Warren D Anderson

    2017-07-01

    Full Text Available Multiple physiological systems interact throughout the development of a complex disease. Knowledge of the dynamics and connectivity of interactions across physiological systems could facilitate the prevention or mitigation of organ damage underlying complex diseases, many of which are currently refractory to available therapeutics (e.g., hypertension. We studied the regulatory interactions operating within and across organs throughout disease development by integrating in vivo analysis of gene expression dynamics with a reverse engineering approach to infer data-driven dynamic network models of multi-organ gene regulatory influences. We obtained experimental data on the expression of 22 genes across five organs, over a time span that encompassed the development of autonomic nervous system dysfunction and hypertension. We pursued a unique approach for identification of continuous-time models that jointly described the dynamics and structure of multi-organ networks by estimating a sparse subset of ∼12,000 possible gene regulatory interactions. Our analyses revealed that an autonomic dysfunction-specific multi-organ sequence of gene expression activation patterns was associated with a distinct gene regulatory network. We analyzed the model structures for adaptation motifs, and identified disease-specific network motifs involving genes that exhibited aberrant temporal dynamics. Bioinformatic analyses identified disease-specific single nucleotide variants within or near transcription factor binding sites upstream of key genes implicated in maintaining physiological homeostasis. Our approach illustrates a novel framework for investigating the pathogenesis through model-based analysis of multi-organ system dynamics and network properties. Our results yielded novel candidate molecular targets driving the development of cardiovascular disease, metabolic syndrome, and immune dysfunction.

  15. High throughput sequencing and proteomics to identify immunogenic proteins of a new pathogen: the dirty genome approach.

    Directory of Open Access Journals (Sweden)

    Gilbert Greub

    Full Text Available BACKGROUND: With the availability of new generation sequencing technologies, bacterial genome projects have undergone a major boost. Still, chromosome completion needs a costly and time-consuming gap closure, especially when containing highly repetitive elements. However, incomplete genome data may be sufficiently informative to derive the pursued information. For emerging pathogens, i.e. newly identified pathogens, lack of release of genome data during gap closure stage is clearly medically counterproductive. METHODS/PRINCIPAL FINDINGS: We thus investigated the feasibility of a dirty genome approach, i.e. the release of unfinished genome sequences to develop serological diagnostic tools. We showed that almost the whole genome sequence of the emerging pathogen Parachlamydia acanthamoebae was retrieved even with relatively short reads from Genome Sequencer 20 and Solexa. The bacterial proteome was analyzed to select immunogenic proteins, which were then expressed and used to elaborate the first steps of an ELISA. CONCLUSIONS/SIGNIFICANCE: This work constitutes the proof of principle for a dirty genome approach, i.e. the use of unfinished genome sequences of pathogenic bacteria, coupled with proteomics to rapidly identify new immunogenic proteins useful to develop in the future specific diagnostic tests such as ELISA, immunohistochemistry and direct antigen detection. Although applied here to an emerging pathogen, this combined dirty genome sequencing/proteomic approach may be used for any pathogen for which better diagnostics are needed. These genome sequences may also be very useful to develop DNA based diagnostic tests. All these diagnostic tools will allow further evaluations of the pathogenic potential of this obligate intracellular bacterium.

  16. An Approach to Evaluate Comprehensive Plan and Identify Priority Lands for Future Land Use Development to Conserve More Ecological Values

    Directory of Open Access Journals (Sweden)

    Long Zhou

    2018-01-01

    Full Text Available Urbanization has significant impacts on the regional environmental quality through altering natural lands, converting them to urban built-up areas. One common strategy applied by urban planners to manage urbanization and preserve natural resources is to make a comprehensive plan and concentrate future land use in certain areas. However, in practice, planners used to make future land use planning mainly based on their subjective interpretations with limited ecological supporting evidence and analysis. Here, we propose a new approach composed of ecological modelling and land use zoning in the spatial matrix to evaluate the comprehensive plan and identify priority lands for sustainable land use planning. We use the city of Corvallis, OR, as the test bed to demonstrate this new approach. The results indicate that the Corvallis Comprehensive Plan 1998–2020 featured with compact development is not performing efficiently in conserving ecological values, and the land use plan featured with mixed-use spreading development generated by the proposed approach meets the city’s land demands for urban growth, and conserves 103% more ecological value of retaining storm water nitrogen, 270% more ecological value of retaining storm water phosphorus and 19% more ecological value in storing carbon in the whole watershed. This study indicates that if planned with scientific analysis and evidence, spreading urban development does not necessarily result in less sustainable urban environment than the compact development recommended in smart growth.

  17. Novel colchicine-site binders with a cyclohexanedione scaffold identified through a ligand-based virtual screening approach.

    Science.gov (United States)

    Canela, María-Dolores; Pérez-Pérez, María-Jesús; Noppen, Sam; Sáez-Calvo, Gonzalo; Díaz, J Fernando; Camarasa, María-José; Liekens, Sandra; Priego, Eva-María

    2014-05-22

    Vascular disrupting agents (VDAs) constitute an innovative anticancer therapy that targets the tumor endothelium, leading to tumor necrosis. Our approach for the identification of new VDAs has relied on a ligand 3-D shape similarity virtual screening (VS) approach using the ROCS program as the VS tool and as query colchicine and TN-16, which both bind the α,β-tubulin dimer. One of the hits identified, using TN-16 as query, has been explored by the synthesis of its structural analogues, leading to 2-(1-((2-methoxyphenyl)amino)ethylidene)-5-phenylcyclohexane-1,3-dione (compound 16c) with an IC50 = 0.09 ± 0.01 μM in HMEC-1 and BAEC, being 100-fold more potent than the initial hit. Compound 16c caused cell cycle arrest in the G2/M phase and interacted with the colchicine-binding site in tubulin, as confirmed by a competition assay with N,N'-ethylenebis(iodoacetamide) and by fluorescence spectroscopy. Moreover, 16c destroyed an established endothelial tubular network at 1 μM and inhibited the migration and invasion of human breast carcinoma cells at 0.4 μM. In conclusion, our approach has led to a new chemotype of promising antiproliferative compounds with antimitotic and potential VDA properties.

  18. In silico analysis of SNPs of SYK gene Involved in Oral Cancer

    Directory of Open Access Journals (Sweden)

    Sarita Swain

    2017-12-01

    Full Text Available Oral cancer is the sixth most common cancer in the world. Oral cancer is the cancer of the oral cavity and pharynx, including cancer of the lip, tongue, salivary glands, gum, floor and other areas of the mouth. The aim of the study is to identify SNPs using dbSNP and predict the effect of mutation using Predict SNP. The association of genes is done by STRING. The disease and drugs associated with the genes are obtained from Webgestalt. The prediction of binding site is done by CASTp. The interaction of ligand and protein is done by using Autodock and Visualised through Discovery studio, pymol, Ligplot. From this report we found that oral cancer differs from person to person based on their genes and genetic interactions and expressions which recommend the clinicians to go for personalized medicine rather that generalized medicine for the patients with oral cancer. Seeking the importance of genetic background of oral cancer patients further studies can be done by mining of non-synonymous SNPs associated with genes for causing oral cancer.

  19. A risk assessment approach to identifying constituents in oilfield produced water for treatment prior to beneficial use.

    Science.gov (United States)

    Horner, Jennifer E; Castle, James W; Rodgers, John H

    2011-05-01

    A risk assessment approach incorporating exposure pathways and calculated risk quotients was applied to identifying constituents requiring treatment prior to beneficial use of oilfield produced water (OPW). In this study, risk quotients are ratios of constituent concentrations in soil or water to guideline concentrations for no adverse effects to receptors. The risk assessment approach is illustrated by an example of an oilfield water produced from non-marine geologic strata of a rift basin in sub-Saharan Africa. The OPW studied has the following characteristics: 704-1370 mg L(-1) total dissolved solids (TDS), 45-48 mg L(-1) chloride, and 103.8 mg L(-1) oil and grease. Exposure pathways of constituents in OPW used for irrigation include: ingestion of plant tissue, ingestion and direct contact of irrigated soil by livestock, inhalation of aerosols or volatilized constituents, and ingestion of OPW directly by livestock. Applying risk quotient methods for constituents in soil and water, constituents of concern (COCs) identified for irrigation and livestock watering using the OPW studied include: iron (Fe), manganese (Mn), nickel (Ni), zinc (Zn), and oil and grease. Approximately 165,000 barrels d(-1) (26,233 m(3) d(-1)) of OPW from the study site are available for use. Identification of COCs and consideration of water quantity allows for development of reliable treatment design criteria to ensure effective and consistent treatment is achieved to meet guideline levels required for irrigation, livestock watering, or other uses. This study illustrates the utility of risk assessment for identifying the COCs in OPW for treatment, the level of treatment required, and viable options for use of the treated water. Copyright © 2011 Elsevier Inc. All rights reserved.

  20. New probiotic strains for inflammatory bowel disease management identified by combining in vitro and in vivo approaches.

    Science.gov (United States)

    Alard, J; Peucelle, V; Boutillier, D; Breton, J; Kuylle, S; Pot, B; Holowacz, S; Grangette, C

    2018-02-27

    Alterations in the gut microbiota composition play a key role in the development of chronic diseases such as inflammatory bowel disease (IBD). The potential use of probiotics therefore gained attention, although outcomes were sometimes conflicting and results largely strain-dependent. The present study aimed to identify new probiotic strains that have a high potential for the management of this type of pathologies. Strains were selected from a large collection by combining different in vitro and in vivo approaches, addressing both anti-inflammatory potential and ability to improve the gut barrier function. We identified six strains with an interesting anti-inflammatory profile on peripheral blood mononuclear cells and with the ability to restore the gut barrier using a gut permeability model based on Caco-2 cells sensitized with hydrogen peroxide. The in vivo evaluation in two 2,4,6-trinitrobenzene sulfonic acid-induced murine models of colitis highlighted that some of the strains exhibited beneficial activities against acute colitis while others improved chronic colitis. Bifidobacterium bifidum PI22, the strain that exhibited the most protective capacities against acute colitis was only slightly efficacious against chronic colitis, while Bifidobacterium lactis LA804 which was less efficacious in the acute model was the most protective against chronic colitis. Lactobacillus helveticus PI5 was not anti-inflammatory in vitro but the best in strengthening the epithelial barrier and as such able to significantly dampen murine acute colitis. Interestingly, Lactobacillus salivarius LA307 protected mice significantly against both types of colitis. This work provides crucial clues for selecting the best strains for more efficacious therapeutic approaches in the management of chronic inflammatory diseases. The strategy employed allowed us to identify four strains with different characteristics and a high potential for the management of inflammatory diseases, such as IBD.

  1. Identifying designatable units for intraspecific conservation prioritization: a hierarchical approach applied to the lake whitefish species complex (Coregonus spp.).

    Science.gov (United States)

    Mee, Jonathan A; Bernatchez, Louis; Reist, Jim D; Rogers, Sean M; Taylor, Eric B

    2015-06-01

    The concept of the designatable unit (DU) affords a practical approach to identifying diversity below the species level for conservation prioritization. However, its suitability for defining conservation units in ecologically diverse, geographically widespread and taxonomically challenging species complexes has not been broadly evaluated. The lake whitefish species complex (Coregonus spp.) is geographically widespread in the Northern Hemisphere, and it contains a great deal of variability in ecology and evolutionary legacy within and among populations, as well as a great deal of taxonomic ambiguity. Here, we employ a set of hierarchical criteria to identify DUs within the Canadian distribution of the lake whitefish species complex. We identified 36 DUs based on (i) reproductive isolation, (ii) phylogeographic groupings, (iii) local adaptation and (iv) biogeographic regions. The identification of DUs is required for clear discussion regarding the conservation prioritization of lake whitefish populations. We suggest conservation priorities among lake whitefish DUs based on biological consequences of extinction, risk of extinction and distinctiveness. Our results exemplify the need for extensive genetic and biogeographic analyses for any species with broad geographic distributions and the need for detailed evaluation of evolutionary history and adaptive ecological divergence when defining intraspecific conservation units.

  2. Identifying Risk Factors for Drug Use in an Iranian Treatment Sample: A Prediction Approach Using Decision Trees.

    Science.gov (United States)

    Amirabadizadeh, Alireza; Nezami, Hossein; Vaughn, Michael G; Nakhaee, Samaneh; Mehrpour, Omid

    2018-05-12

    Substance abuse exacts considerable social and health care burdens throughout the world. The aim of this study was to create a prediction model to better identify risk factors for drug use. A prospective cross-sectional study was conducted in South Khorasan Province, Iran. Of the total of 678 eligible subjects, 70% (n: 474) were randomly selected to provide a training set for constructing decision tree and multiple logistic regression (MLR) models. The remaining 30% (n: 204) were employed in a holdout sample to test the performance of the decision tree and MLR models. Predictive performance of different models was analyzed by the receiver operating characteristic (ROC) curve using the testing set. Independent variables were selected from demographic characteristics and history of drug use. For the decision tree model, the sensitivity and specificity for identifying people at risk for drug abuse were 66% and 75%, respectively, while the MLR model was somewhat less effective at 60% and 73%. Key independent variables in the analyses included first substance experience, age at first drug use, age, place of residence, history of cigarette use, and occupational and marital status. While study findings are exploratory and lack generalizability they do suggest that the decision tree model holds promise as an effective classification approach for identifying risk factors for drug use. Convergent with prior research in Western contexts is that age of drug use initiation was a critical factor predicting a substance use disorder.

  3. Assessment Approach for Identifying Compatibility of Restoration Projects with Geomorphic and Flooding Processes in Gravel Bed Rivers.

    Science.gov (United States)

    DeVries, Paul; Aldrich, Robert

    2015-08-01

    A critical requirement for a successful river restoration project in a dynamic gravel bed river is that it be compatible with natural hydraulic and sediment transport processes operating at the reach scale. The potential for failure is greater at locations where the influence of natural processes is inconsistent with intended project function and performance. We present an approach using practical GIS, hydrologic, hydraulic, and sediment transport analyses to identify locations where specific restoration project types have the greatest likelihood of working as intended because their function and design are matched with flooding and morphologic processes. The key premise is to identify whether a specific river analysis segment (length ~1-10 bankfull widths) within a longer reach is geomorphically active or inactive in the context of vertical and lateral stabilities, and hydrologically active for floodplain connectivity. Analyses involve empirical channel geometry relations, aerial photographic time series, LiDAR data, HEC-RAS hydraulic modeling, and a time-integrated sediment transport budget to evaluate trapping efficiency within each segment. The analysis segments are defined by HEC-RAS model cross sections. The results have been used effectively to identify feasible projects in a variety of alluvial gravel bed river reaches with lengths between 11 and 80 km and 2-year flood magnitudes between ~350 and 1330 m(3)/s. Projects constructed based on the results have all performed as planned. In addition, the results provide key criteria for formulating erosion and flood management plans.

  4. Assessment Approach for Identifying Compatibility of Restoration Projects with Geomorphic and Flooding Processes in Gravel Bed Rivers

    Science.gov (United States)

    DeVries, Paul; Aldrich, Robert

    2015-08-01

    A critical requirement for a successful river restoration project in a dynamic gravel bed river is that it be compatible with natural hydraulic and sediment transport processes operating at the reach scale. The potential for failure is greater at locations where the influence of natural processes is inconsistent with intended project function and performance. We present an approach using practical GIS, hydrologic, hydraulic, and sediment transport analyses to identify locations where specific restoration project types have the greatest likelihood of working as intended because their function and design are matched with flooding and morphologic processes. The key premise is to identify whether a specific river analysis segment (length ~1-10 bankfull widths) within a longer reach is geomorphically active or inactive in the context of vertical and lateral stabilities, and hydrologically active for floodplain connectivity. Analyses involve empirical channel geometry relations, aerial photographic time series, LiDAR data, HEC-RAS hydraulic modeling, and a time-integrated sediment transport budget to evaluate trapping efficiency within each segment. The analysis segments are defined by HEC-RAS model cross sections. The results have been used effectively to identify feasible projects in a variety of alluvial gravel bed river reaches with lengths between 11 and 80 km and 2-year flood magnitudes between ~350 and 1330 m3/s. Projects constructed based on the results have all performed as planned. In addition, the results provide key criteria for formulating erosion and flood management plans.

  5. An integrated chemical biology approach identifies specific vulnerability of Ewing's sarcoma to combined inhibition of Aurora kinases A and B.

    Science.gov (United States)

    Winter, Georg E; Rix, Uwe; Lissat, Andrej; Stukalov, Alexey; Müllner, Markus K; Bennett, Keiryn L; Colinge, Jacques; Nijman, Sebastian M; Kubicek, Stefan; Kovar, Heinrich; Kontny, Udo; Superti-Furga, Giulio

    2011-10-01

    Ewing's sarcoma is a pediatric cancer of the bone that is characterized by the expression of the chimeric transcription factor EWS-FLI1 that confers a highly malignant phenotype and results from the chromosomal translocation t(11;22)(q24;q12). Poor overall survival and pronounced long-term side effects associated with traditional chemotherapy necessitate the development of novel, targeted, therapeutic strategies. We therefore conducted a focused viability screen with 200 small molecule kinase inhibitors in 2 different Ewing's sarcoma cell lines. This resulted in the identification of several potential molecular intervention points. Most notably, tozasertib (VX-680, MK-0457) displayed unique nanomolar efficacy, which extended to other cell lines, but was specific for Ewing's sarcoma. Furthermore, tozasertib showed strong synergies with the chemotherapeutic drugs etoposide and doxorubicin, the current standard agents for Ewing's sarcoma. To identify the relevant targets underlying the specific vulnerability toward tozasertib, we determined its cellular target profile by chemical proteomics. We identified 20 known and unknown serine/threonine and tyrosine protein kinase targets. Additional target deconvolution and functional validation by RNAi showed simultaneous inhibition of Aurora kinases A and B to be responsible for the observed tozasertib sensitivity, thereby revealing a new mechanism for targeting Ewing's sarcoma. We further corroborated our cellular observations with xenograft mouse models. In summary, the multilayered chemical biology approach presented here identified a specific vulnerability of Ewing's sarcoma to concomitant inhibition of Aurora kinases A and B by tozasertib and danusertib, which has the potential to become a new therapeutic option.

  6. A Network Biology Approach Identifies Molecular Cross-Talk between Normal Prostate Epithelial and Prostate Carcinoma Cells.

    Directory of Open Access Journals (Sweden)

    Victor Trevino

    2016-04-01

    Full Text Available The advent of functional genomics has enabled the genome-wide characterization of the molecular state of cells and tissues, virtually at every level of biological organization. The difficulty in organizing and mining this unprecedented amount of information has stimulated the development of computational methods designed to infer the underlying structure of regulatory networks from observational data. These important developments had a profound impact in biological sciences since they triggered the development of a novel data-driven investigative approach. In cancer research, this strategy has been particularly successful. It has contributed to the identification of novel biomarkers, to a better characterization of disease heterogeneity and to a more in depth understanding of cancer pathophysiology. However, so far these approaches have not explicitly addressed the challenge of identifying networks representing the interaction of different cell types in a complex tissue. Since these interactions represent an essential part of the biology of both diseased and healthy tissues, it is of paramount importance that this challenge is addressed. Here we report the definition of a network reverse engineering strategy designed to infer directional signals linking adjacent cell types within a complex tissue. The application of this inference strategy to prostate cancer genome-wide expression profiling data validated the approach and revealed that normal epithelial cells exert an anti-tumour activity on prostate carcinoma cells. Moreover, by using a Bayesian hierarchical model integrating genetics and gene expression data and combining this with survival analysis, we show that the expression of putative cell communication genes related to focal adhesion and secretion is affected by epistatic gene copy number variation and it is predictive of patient survival. Ultimately, this study represents a generalizable approach to the challenge of deciphering cell

  7. A Combined Raindrop Aggregate Destruction Test-Settling Tube (RADT-ST Approach to Identify the Settling Velocity of Sediment

    Directory of Open Access Journals (Sweden)

    Liangang Xiao

    2015-10-01

    Full Text Available The use of sediment settling velocity based on mineral grain size distribution in erosion models ignores the effects of aggregation on settling velocity. The alternative approach, wet-sieved aggregate size distribution, on the other hand, cannot represent all destructive processes that eroded soils may experience under impacting raindrops. Therefore, without considering raindrop impact, both methods may lead to biased predictions of the redistribution of sediment and associated substances across landscapes. Rainfall simulation is an effective way to simulate natural raindrop impact under controlled laboratory conditions. However, very few methods have been developed to integrate rainfall simulation with the settling velocity of eroded sediment. This study aims to develop a new proxy, based on rainfall simulation, in order to identify the actual settling velocity distribution of aggregated sediment. A combined Raindrop Aggregate Destruction Test-Settling Tube (RADT-ST approach was developed to (1 simulate aggregate destruction under a series of simulated rainfalls; and (2 measure the actual settling velocity distribution of destroyed aggregates. Mean Weight Settling Velocity (MWSV of aggregates was used to investigate settling behaviors of different soils as rainfall kinetic energy increased. The results show the settling velocity of silt-rich raindrop impacted aggregates is likely to be underestimated by at least six times if based on mineral grain size distribution. The RADT-ST designed in this study effectively captures the effects of aggregation on settling behavior. The settling velocity distribution should be regarded as an evolving, rather than steady state parameter during erosion events. The combined RADT-ST approach is able to generate the quasi-natural sediment under controlled simulated rainfall conditions and is adequately sensitive to measure actual settling velocities of differently aggregated soils. This combined approach provides

  8. A Network Biology Approach Identifies Molecular Cross-Talk between Normal Prostate Epithelial and Prostate Carcinoma Cells.

    Science.gov (United States)

    Trevino, Victor; Cassese, Alberto; Nagy, Zsuzsanna; Zhuang, Xiaodong; Herbert, John; Antczak, Philipp; Clarke, Kim; Davies, Nicholas; Rahman, Ayesha; Campbell, Moray J; Guindani, Michele; Bicknell, Roy; Vannucci, Marina; Falciani, Francesco

    2016-04-01

    The advent of functional genomics has enabled the genome-wide characterization of the molecular state of cells and tissues, virtually at every level of biological organization. The difficulty in organizing and mining this unprecedented amount of information has stimulated the development of computational methods designed to infer the underlying structure of regulatory networks from observational data. These important developments had a profound impact in biological sciences since they triggered the development of a novel data-driven investigative approach. In cancer research, this strategy has been particularly successful. It has contributed to the identification of novel biomarkers, to a better characterization of disease heterogeneity and to a more in depth understanding of cancer pathophysiology. However, so far these approaches have not explicitly addressed the challenge of identifying networks representing the interaction of different cell types in a complex tissue. Since these interactions represent an essential part of the biology of both diseased and healthy tissues, it is of paramount importance that this challenge is addressed. Here we report the definition of a network reverse engineering strategy designed to infer directional signals linking adjacent cell types within a complex tissue. The application of this inference strategy to prostate cancer genome-wide expression profiling data validated the approach and revealed that normal epithelial cells exert an anti-tumour activity on prostate carcinoma cells. Moreover, by using a Bayesian hierarchical model integrating genetics and gene expression data and combining this with survival analysis, we show that the expression of putative cell communication genes related to focal adhesion and secretion is affected by epistatic gene copy number variation and it is predictive of patient survival. Ultimately, this study represents a generalizable approach to the challenge of deciphering cell communication networks

  9. Using 50 years of soil radiocarbon data to identify optimal approaches for estimating soil carbon residence times

    Science.gov (United States)

    Baisden, W. T.; Canessa, S.

    2013-01-01

    In 1959, Athol Rafter began a substantial programme of systematically monitoring the flow of 14C produced by atmospheric thermonuclear tests through organic matter in New Zealand soils under stable land use. A database of ∼500 soil radiocarbon measurements spanning 50 years has now been compiled, and is used here to identify optimal approaches for soil C-cycle studies. Our results confirm the potential of 14C to determine residence times, by estimating the amount of ‘bomb 14C’ incorporated. High-resolution time series confirm this approach is appropriate, and emphasise that residence times can be calculated routinely with two or more time points as little as 10 years apart. This approach is generally robust to the key assumptions that can create large errors when single time-point 14C measurements are modelled. The three most critical assumptions relate to: (1) the distribution of turnover times, and particularly the proportion of old C (‘passive fraction’), (2) the lag time between photosynthesis and C entering the modelled pool, (3) changes in the rates of C input. When carrying out approaches using robust assumptions on time-series samples, multiple soil layers can be aggregated using a mixing equation. Where good archived samples are available, AMS measurements can develop useful understanding for calibrating models of the soil C cycle at regional to continental scales with sample numbers on the order of hundreds rather than thousands. Sample preparation laboratories and AMS facilities can play an important role in coordinating the efficient delivery of robust calculated residence times for soil carbon.

  10. Using 50 years of soil radiocarbon data to identify optimal approaches for estimating soil carbon residence times

    International Nuclear Information System (INIS)

    Baisden, W.T.; Canessa, S.

    2013-01-01

    In 1959, Athol Rafter began a substantial programme of systematically monitoring the flow of 14 C produced by atmospheric thermonuclear tests through organic matter in New Zealand soils under stable land use. A database of ∼500 soil radiocarbon measurements spanning 50 years has now been compiled, and is used here to identify optimal approaches for soil C-cycle studies. Our results confirm the potential of 14 C to determine residence times, by estimating the amount of ‘bomb 14 C’ incorporated. High-resolution time series confirm this approach is appropriate, and emphasise that residence times can be calculated routinely with two or more time points as little as 10 years apart. This approach is generally robust to the key assumptions that can create large errors when single time-point 14 C measurements are modelled. The three most critical assumptions relate to: (1) the distribution of turnover times, and particularly the proportion of old C (‘passive fraction’), (2) the lag time between photosynthesis and C entering the modelled pool, (3) changes in the rates of C input. When carrying out approaches using robust assumptions on time-series samples, multiple soil layers can be aggregated using a mixing equation. Where good archived samples are available, AMS measurements can develop useful understanding for calibrating models of the soil C cycle at regional to continental scales with sample numbers on the order of hundreds rather than thousands. Sample preparation laboratories and AMS facilities can play an important role in coordinating the efficient delivery of robust calculated residence times for soil carbon.

  11. Using 50 years of soil radiocarbon data to identify optimal approaches for estimating soil carbon residence times

    Energy Technology Data Exchange (ETDEWEB)

    Baisden, W.T., E-mail: t.baisden@gns.cri.nz [National Isotope Centre, GNS Science, P.O. Box 31312, Lower Hutt (New Zealand); Canessa, S. [National Isotope Centre, GNS Science, P.O. Box 31312, Lower Hutt (New Zealand)

    2013-01-15

    In 1959, Athol Rafter began a substantial programme of systematically monitoring the flow of {sup 14}C produced by atmospheric thermonuclear tests through organic matter in New Zealand soils under stable land use. A database of {approx}500 soil radiocarbon measurements spanning 50 years has now been compiled, and is used here to identify optimal approaches for soil C-cycle studies. Our results confirm the potential of {sup 14}C to determine residence times, by estimating the amount of 'bomb {sup 14}C' incorporated. High-resolution time series confirm this approach is appropriate, and emphasise that residence times can be calculated routinely with two or more time points as little as 10 years apart. This approach is generally robust to the key assumptions that can create large errors when single time-point {sup 14}C measurements are modelled. The three most critical assumptions relate to: (1) the distribution of turnover times, and particularly the proportion of old C ('passive fraction'), (2) the lag time between photosynthesis and C entering the modelled pool, (3) changes in the rates of C input. When carrying out approaches using robust assumptions on time-series samples, multiple soil layers can be aggregated using a mixing equation. Where good archived samples are available, AMS measurements can develop useful understanding for calibrating models of the soil C cycle at regional to continental scales with sample numbers on the order of hundreds rather than thousands. Sample preparation laboratories and AMS facilities can play an important role in coordinating the efficient delivery of robust calculated residence times for soil carbon.

  12. A hybrid approach identifies metabolic signatures of high-producers for chinese hamster ovary clone selection and process optimization.

    Science.gov (United States)

    Popp, Oliver; Müller, Dirk; Didzus, Katharina; Paul, Wolfgang; Lipsmeier, Florian; Kirchner, Florian; Niklas, Jens; Mauch, Klaus; Beaucamp, Nicola

    2016-09-01

    In-depth characterization of high-producer cell lines and bioprocesses is vital to ensure robust and consistent production of recombinant therapeutic proteins in high quantity and quality for clinical applications. This requires applying appropriate methods during bioprocess development to enable meaningful characterization of CHO clones and processes. Here, we present a novel hybrid approach for supporting comprehensive characterization of metabolic clone performance. The approach combines metabolite profiling with multivariate data analysis and fluxomics to enable a data-driven mechanistic analysis of key metabolic traits associated with desired cell phenotypes. We applied the methodology to quantify and compare metabolic performance in a set of 10 recombinant CHO-K1 producer clones and a host cell line. The comprehensive characterization enabled us to derive an extended set of clone performance criteria that not only captured growth and product formation, but also incorporated information on intracellular clone physiology and on metabolic changes during the process. These criteria served to establish a quantitative clone ranking and allowed us to identify metabolic differences between high-producing CHO-K1 clones yielding comparably high product titers. Through multivariate data analysis of the combined metabolite and flux data we uncovered common metabolic traits characteristic of high-producer clones in the screening setup. This included high intracellular rates of glutamine synthesis, low cysteine uptake, reduced excretion of aspartate and glutamate, and low intracellular degradation rates of branched-chain amino acids and of histidine. Finally, the above approach was integrated into a workflow that enables standardized high-content selection of CHO producer clones in a high-throughput fashion. In conclusion, the combination of quantitative metabolite profiling, multivariate data analysis, and mechanistic network model simulations can identify metabolic

  13. Patient- and Family-Identified Problems of Traumatic Brain Injury: Value and Utility of a Target Outcome Approach to Identifying the Worst Problems

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    Laraine Winter

    2016-01-01

    Full Text Available Purpose: This study aimed to identify the sequelae of traumatic brain injury (TBI that are most troubling to veterans with TBI and their families and identify veteran-family differences in content and ranking. Instead of standardized measures of symptom frequency or severity, which may be insensitive to change or intervention effects, we used a target outcome measure for veterans with TBI and their key family members, which elicited open-ended reports concerning the three most serious TBI-related problems. This was followed by Likert-scaled ratings of difficulty in managing the problem. Methods: In this cross-sectional study, interviews were conducted in veterans’ homes. Participants included 83 veterans with TBI diagnosed at a Veterans Affairs medical rehabilitation service and a key family member of each veteran. We utilized open-ended questions to determine the problems caused by TBI within the last month. Sociodemographic characteristics of veterans and family members, and veterans’ military and medical characteristics were collected. A coding scheme was developed to categorize open-ended responses. Results: Families identified nearly twice as many categories of problems as did veterans, and veterans and families ranked problem categories very differently. Veterans ranked cognitive and physical problems worst; families ranked emotional and interpersonal problems worst. Conclusions: Easily administered open-ended questions about the most troubling TBI-related problems yield novel insights and reveal important veteran-family discrepancies.

  14. Identifying Obstacles and Research Gaps of Telemedicine Projects: Approach for a State-of-the-Art Analysis.

    Science.gov (United States)

    Harst, Lorenz; Timpel, Patrick; Otto, Lena; Wollschlaeger, Bastian; Richter, Peggy; Schlieter, Hannes

    2018-01-01

    This paper presents an approach for an evaluation of finished telemedicine projects using qualitative methods. Telemedicine applications are said to improve the performance of health care systems. While there are countless telemedicine projects, the vast majority never makes the threshold from testing to implementation and diffusion. Projects were collected from German project databases in the area of telemedicine following systematically developed criteria. In a testing phase, ten projects were subject to a qualitative content analysis to identify limitations, need for further research, and lessons learned. Using Mayring's method of inductive category development, six categories of possible future research were derived. Thus, the proposed method is an important contribution to diffusion and translation research regarding telemedicine, as it is applicable to a systematic research of databases.

  15. A Dynamic Combinatorial Approach for Identifying Side Groups that Stabilize DNA-Templated Supramolecular Self-Assemblies

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    Delphine Paolantoni

    2015-02-01

    Full Text Available DNA-templated self-assembly is an emerging strategy for generating functional supramolecular systems, which requires the identification of potent multi-point binding ligands. In this line, we recently showed that bis-functionalized guanidinium compounds can interact with ssDNA and generate a supramolecular complex through the recognition of the phosphodiester backbone of DNA. In order to probe the importance of secondary interactions and to identify side groups that stabilize these DNA-templated self-assemblies, we report herein the implementation of a dynamic combinatorial approach. We used an in situ fragment assembly process based on reductive amination and tested various side groups, including amino acids. The results reveal that aromatic and cationic side groups participate in secondary supramolecular interactions that stabilize the complexes formed with ssDNA.

  16. Design of future municipal wastewater treatment plants: A mathematical approach to manage complexity and identify optimal solutions

    DEFF Research Database (Denmark)

    Bozkurt, Hande; Quaglia, Alberto; Gernaey, Krist

    The increasing number of alternative wastewater treatment (WWT) technologies and stricter effluent requirements imposed by regulations make the early stage decision making for WWTP layout design, which is currently based on expert decisions and previous experiences, much harder. This paper...... therefore proposes a new approach based on mathematical programming to manage the complexity of the problem and generate/identify novel and optimal WWTP layouts for municipal/domestic wastewater treatment. Towards this end, after developing a database consisting of primary, secondary and tertiary WWT...... solved to obtain the optimal WWT network and the optimal wastewater and sludge flow through the network. The tool is evaluated on a case study, which was chosen as the Benchmark Simulation Model no.1 (BSM1) and many retrofitting options for obtaining a cost-effective treatment were investigated...

  17. A combined structural dynamics approach identifies a putative switch in factor VIIa employed by tissue factor to initiate blood coagulation

    DEFF Research Database (Denmark)

    Olsen, Ole H; Rand, Kasper D; Østergaard, Henrik

    2007-01-01

    Coagulation factor VIIa (FVIIa) requires tissue factor (TF) to attain full catalytic competency and to initiate blood coagulation. In this study, the mechanism by which TF allosterically activates FVIIa is investigated by a structural dynamics approach that combines molecular dynamics (MD......) simulations and hydrogen/deuterium exchange (HX) mass spectrometry on free and TF-bound FVIIa. The differences in conformational dynamics from MD simulations are shown to be confined to regions of FVIIa observed to undergo structural stabilization as judged by HX experiments, especially implicating activation...... in the presence of TF or an active-site inhibitor. Based on MD simulations, a key switch of the TF-induced structural changes is identified as the interacting pair Leu305{163} and Phe374{225} in FVIIa, whose mutual conformations are guided by the presence of TF and observed to be closely linked to the structural...

  18. General Approach to Identifying Potential Targets for Cancer Imaging by Integrated Bioinformatics Analysis of Publicly Available Genomic Profiles

    Directory of Open Access Journals (Sweden)

    Yongliang Yang

    2011-03-01

    Full Text Available Molecular imaging has moved to the forefront of drug development and biomedical research. The identification of appropriate imaging targets has become the touchstone for the accurate diagnosis and prognosis of human cancer. Particularly, cell surface- or membrane-bound proteins are attractive imaging targets for their aberrant expression, easily accessible location, and unique biochemical functions in tumor cells. Previously, we published a literature mining of potential targets for our in-house enzyme-mediated cancer imaging and therapy technology. Here we present a simple and integrated bioinformatics analysis approach that assembles a public cancer microarray database with a pathway knowledge base for ascertaining and prioritizing upregulated genes encoding cell surface- or membrane-bound proteins, which could serve imaging targets. As examples, we obtained lists of potential hits for six common and lethal human tumors in the prostate, breast, lung, colon, ovary, and pancreas. As control tests, a number of well-known cancer imaging targets were detected and confirmed by our study. Further, by consulting gene-disease and protein-disease databases, we suggest a number of significantly upregulated genes as promising imaging targets, including cell surface-associated mucin-1, prostate-specific membrane antigen, hepsin, urokinase plasminogen activator receptor, and folate receptors. By integrating pathway analysis, we are able to organize and map “focused” interaction networks derived from significantly dysregulated entity pairs to reflect important cellular functions in disease processes. We provide herein an example of identifying a tumor cell growth and proliferation subnetwork for prostate cancer. This systematic mining approach can be broadly applied to identify imaging or therapeutic targets for other human diseases.

  19. Performance scores in general practice: a comparison between the clinical versus medication-based approach to identify target populations.

    Directory of Open Access Journals (Sweden)

    Olivier Saint-Lary

    Full Text Available CONTEXT: From one country to another, the pay-for-performance mechanisms differ on one significant point: the identification of target populations, that is, populations which serve as a basis for calculating the indicators. The aim of this study was to compare clinical versus medication-based identification of populations of patients with diabetes and hypertension over the age of 50 (for men or 60 (for women, and any consequences this may have on the calculation of P4P indicators. METHODS: A comparative, retrospective, observational study was carried out with clinical and prescription data from a panel of general practitioners (GPs, the Observatory of General Medicine (OMG for the year 2007. Two indicators regarding the prescription for statins and aspirin in these populations were calculated. RESULTS: We analyzed data from 21.690 patients collected by 61 GPs via electronic medical files. Following the clinical-based approach, 2.278 patients were diabetic, 8,271 had hypertension and 1.539 had both against respectively 1.730, 8.511 and 1.304 following the medication-based approach (% agreement = 96%, kappa = 0.69. The main reasons for these differences were: forgetting to code the morbidities in the clinical approach, not taking into account the population of patients who were given life style and diet rules only or taking into account patients for whom morbidities other than hypertension could justify the use of antihypertensive drugs in the medication-based approach. The mean (confidence interval per doctor was 33.7% (31.5-35.9 for statin indicator and 38.4% (35.4-41.4 for aspirin indicator when the target populations were identified on the basis of clinical criteria whereas they were 37.9% (36.3-39.4 and 43.8% (41.4-46.3 on the basis of treatment criteria. CONCLUSION: The two approaches yield very "similar" scores but these scores cover different realities and offer food for thought on the possible usage of these indicators in the

  20. Using a community-driven approach to identify local forest and climate change priorities in Teslin, Yukon

    Directory of Open Access Journals (Sweden)

    Joleen Timko

    2015-12-01

    Full Text Available The likelihood of addressing the complex environmental, economic, and social/cultural issues associated with local climate change impacts is enhanced when collaborative partnerships with local people are established. Using a community-centered approach in the Teslin region of Canada’s Yukon Territory, we utilized our research skills to respond to local needs for information by facilitating both an internal community process to clarify traditional and local knowledge, values, and perceptions on locally identified priorities, while gathering external information to enable local people to make sound decisions. Specifically, we sought to clarify local perceptions surrounding climate change impacts on fire risk and wildlife habitat, and the potential adaptation strategies appropriate and feasible within the Teslin Tlingit Traditional Territory. This paper provides a characterization of the study region and our project team; provides background on the interview and data collection process; presents our key results; and discusses the importance of our findings and charts a way forward for our continued work with the people in the Teslin region. This approach presents an excellent opportunity to help people holistically connect a range of local values, including fire risk mitigation, habitat enhancement, economic development, and enhanced social health.

  1. Using a service sector segmented approach to identify community stakeholders who can improve access to suicide prevention services for veterans.

    Science.gov (United States)

    Matthieu, Monica M; Gardiner, Giovanina; Ziegemeier, Ellen; Buxton, Miranda

    2014-04-01

    Veterans in need of social services may access many different community agencies within the public and private sectors. Each of these settings has the potential to be a pipeline for attaining needed health, mental health, and benefits services; however, many service providers lack information on how to conceptualize where Veterans go for services within their local community. This article describes a conceptual framework for outreach that uses a service sector segmented approach. This framework was developed to aid recruitment of a provider-based sample of stakeholders (N = 70) for a study on improving access to the Department of Veterans Affairs and community-based suicide prevention services. Results indicate that although there are statistically significant differences in the percent of Veterans served by the different service sectors (F(9, 55) = 2.71, p = 0.04), exposure to suicidal Veterans and providers' referral behavior is consistent across the sectors. Challenges to using this framework include isolating the appropriate sectors for targeted outreach efforts. The service sector segmented approach holds promise for identifying and referring at-risk Veterans in need of services. Reprint & Copyright © 2014 Association of Military Surgeons of the U.S.

  2. Integrated Bioinformatics, Environmental Epidemiologic and Genomic Approaches to Identify Environmental and Molecular Links between Endometriosis and Breast Cancer

    Directory of Open Access Journals (Sweden)

    Deodutta Roy

    2015-10-01

    Full Text Available We present a combined environmental epidemiologic, genomic, and bioinformatics approach to identify: exposure of environmental chemicals with estrogenic activity; epidemiologic association between endocrine disrupting chemical (EDC and health effects, such as, breast cancer or endometriosis; and gene-EDC interactions and disease associations. Human exposure measurement and modeling confirmed estrogenic activity of three selected class of environmental chemicals, polychlorinated biphenyls (PCBs, bisphenols (BPs, and phthalates. Meta-analysis showed that PCBs exposure, not Bisphenol A (BPA and phthalates, increased the summary odds ratio for breast cancer and endometriosis. Bioinformatics analysis of gene-EDC interactions and disease associations identified several hundred genes that were altered by exposure to PCBs, phthalate or BPA. EDCs-modified genes in breast neoplasms and endometriosis are part of steroid hormone signaling and inflammation pathways. All three EDCs–PCB 153, phthalates, and BPA influenced five common genes—CYP19A1, EGFR, ESR2, FOS, and IGF1—in breast cancer as well as in endometriosis. These genes are environmentally and estrogen responsive, altered in human breast and uterine tumors and endometriosis lesions, and part of Mitogen Activated Protein Kinase (MAPK signaling pathways in cancer. Our findings suggest that breast cancer and endometriosis share some common environmental and molecular risk factors.

  3. A systems genetics approach identifies CXCL14, ITGAX, and LPCAT2 as novel aggressive prostate cancer susceptibility genes.

    Directory of Open Access Journals (Sweden)

    Kendra A Williams

    2014-11-01

    Full Text Available Although prostate cancer typically runs an indolent course, a subset of men develop aggressive, fatal forms of this disease. We hypothesize that germline variation modulates susceptibility to aggressive prostate cancer. The goal of this work is to identify susceptibility genes using the C57BL/6-Tg(TRAMP8247Ng/J (TRAMP mouse model of neuroendocrine prostate cancer. Quantitative trait locus (QTL mapping was performed in transgene-positive (TRAMPxNOD/ShiLtJ F2 intercross males (n = 228, which facilitated identification of 11 loci associated with aggressive disease development. Microarray data derived from 126 (TRAMPxNOD/ShiLtJ F2 primary tumors were used to prioritize candidate genes within QTLs, with candidate genes deemed as being high priority when possessing both high levels of expression-trait correlation and a proximal expression QTL. This process enabled the identification of 35 aggressive prostate tumorigenesis candidate genes. The role of these genes in aggressive forms of human prostate cancer was investigated using two concurrent approaches. First, logistic regression analysis in two human prostate gene expression datasets revealed that expression levels of five genes (CXCL14, ITGAX, LPCAT2, RNASEH2A, and ZNF322 were positively correlated with aggressive prostate cancer and two genes (CCL19 and HIST1H1A were protective for aggressive prostate cancer. Higher than average levels of expression of the five genes that were positively correlated with aggressive disease were consistently associated with patient outcome in both human prostate cancer tumor gene expression datasets. Second, three of these five genes (CXCL14, ITGAX, and LPCAT2 harbored polymorphisms associated with aggressive disease development in a human GWAS cohort consisting of 1,172 prostate cancer patients. This study is the first example of using a systems genetics approach to successfully identify novel susceptibility genes for aggressive prostate cancer. Such

  4. Labeling surface epitopes to identify Cryptosporidium life stages using a scanning electron microscopy-based immunogold approach.

    Science.gov (United States)

    Edwards, Hanna; Thompson, R C Andrew; Koh, Wan H; Clode, Peta L

    2012-02-01

    The Apicomplexan parasite Cryptosporidium parvum is responsible for the widespread disease cryptosporidiosis, in both humans and livestock. The nature of C. parvum infection is far from understood and many questions remain in regard to host-parasite interactions, limiting successful treatment of the disease. To definitively identify a range of C. parvum stages in cell culture and to begin to investigate host cell interactions in some of the lesser known life stages, we have utilized a combined scanning electron microscopy and immunolabeling approach, correlating high resolution microstructural information with definitive immunogold labeling of Cryptosporidium stages. Several life cycle stages, including oocysts, merozoites I, trophozoites, gamonts and microgametocytes, were successfully immunolabeled in an in vitro model system. Developing oocysts were clearly immunolabeled, but this did not persist once excystation had occurred. Immunolabeling visualized on the host cell surface adjacent to invasive merozoites is likely to be indicative of receptor shedding, with merozoites also initiating host responses that manifested as abnormal microvilli on the host cell surface. Small sub-micron stages such as microgametocytes, which were impossible to identify as single entities without immunolabeling, were readily visualized and observed to attach to host cells via novel membranous projections. Epicellular parasites also expressed Cryptosporidium-derived epitopes within their encapsulating membrane. These data have allowed us to confidently identify a variety of C. parvum stages in cell culture at high resolution. With this, we provide new insight into C. parvum - host cell interactions and highlight future opportunities for investigating and targeting receptor-mediated interactions between Cryptosporidium life cycle stages and host cells. Copyright © 2011 Elsevier Ltd. All rights reserved.

  5. In-Silico Integration Approach to Identify a Key miRNA Regulating a Gene Network in Aggressive Prostate Cancer

    Science.gov (United States)

    Colaprico, Antonio; Bontempi, Gianluca; Castiglioni, Isabella

    2018-01-01

    Like other cancer diseases, prostate cancer (PC) is caused by the accumulation of genetic alterations in the cells that drives malignant growth. These alterations are revealed by gene profiling and copy number alteration (CNA) analysis. Moreover, recent evidence suggests that also microRNAs have an important role in PC development. Despite efforts to profile PC, the alterations (gene, CNA, and miRNA) and biological processes that correlate with disease development and progression remain partially elusive. Many gene signatures proposed as diagnostic or prognostic tools in cancer poorly overlap. The identification of co-expressed genes, that are functionally related, can identify a core network of genes associated with PC with a better reproducibility. By combining different approaches, including the integration of mRNA expression profiles, CNAs, and miRNA expression levels, we identified a gene signature of four genes overlapping with other published gene signatures and able to distinguish, in silico, high Gleason-scored PC from normal human tissue, which was further enriched to 19 genes by gene co-expression analysis. From the analysis of miRNAs possibly regulating this network, we found that hsa-miR-153 was highly connected to the genes in the network. Our results identify a four-gene signature with diagnostic and prognostic value in PC and suggest an interesting gene network that could play a key regulatory role in PC development and progression. Furthermore, hsa-miR-153, controlling this network, could be a potential biomarker for theranostics in high Gleason-scored PC. PMID:29562723

  6. Integrative microRNA and proteomic approaches identify novel osteoarthritis genes and their collaborative metabolic and inflammatory networks.

    Directory of Open Access Journals (Sweden)

    Dimitrios Iliopoulos

    Full Text Available BACKGROUND: Osteoarthritis is a multifactorial disease characterized by destruction of the articular cartilage due to genetic, mechanical and environmental components affecting more than 100 million individuals all over the world. Despite the high prevalence of the disease, the absence of large-scale molecular studies limits our ability to understand the molecular pathobiology of osteoathritis and identify targets for drug development. METHODOLOGY/PRINCIPAL FINDINGS: In this study we integrated genetic, bioinformatic and proteomic approaches in order to identify new genes and their collaborative networks involved in osteoarthritis pathogenesis. MicroRNA profiling of patient-derived osteoarthritic cartilage in comparison to normal cartilage, revealed a 16 microRNA osteoarthritis gene signature. Using reverse-phase protein arrays in the same tissues we detected 76 differentially expressed proteins between osteoarthritic and normal chondrocytes. Proteins such as SOX11, FGF23, KLF6, WWOX and GDF15 not implicated previously in the genesis of osteoarthritis were identified. Integration of microRNA and proteomic data with microRNA gene-target prediction algorithms, generated a potential "interactome" network consisting of 11 microRNAs and 58 proteins linked by 414 potential functional associations. Comparison of the molecular and clinical data, revealed specific microRNAs (miR-22, miR-103 and proteins (PPARA, BMP7, IL1B to be highly correlated with Body Mass Index (BMI. Experimental validation revealed that miR-22 regulated PPARA and BMP7 expression and its inhibition blocked inflammatory and catabolic changes in osteoarthritic chondrocytes. CONCLUSIONS/SIGNIFICANCE: Our findings indicate that obesity and inflammation are related to osteoarthritis, a metabolic disease affected by microRNA deregulation. Gene network approaches provide new insights for elucidating the complexity of diseases such as osteoarthritis. The integration of microRNA, proteomic

  7. The CARPEDIEM Algorithm: A Rule-Based System for Identifying Heart Failure Phenotype with a Precision Public Health Approach

    Directory of Open Access Journals (Sweden)

    Michela Franchini

    2018-01-01

    Full Text Available Modern medicine remains dependent on the accurate evaluation of a patient’s health state, recognizing that disease is a process that evolves over time and interacts with many factors unique to that patient. The CARPEDIEM project represents a concrete attempt to address these issues by developing reproducible algorithms to support the accuracy in detection of complex diseases. This study aims to establish and validate the CARPEDIEM approach and algorithm for identifying those patients presenting with or at risk of heart failure (HF by studying 153,393 subjects in Italy, based on patient information flow databases and is not reliant on the electronic health record to accomplish its goals. The resulting algorithm has been validated in a two-stage process, comparing predicted results with (1 HF diagnosis as identified by general practitioners (GPs among the reference cohort and (2 HF diagnosis as identified by cardiologists within a randomly sampled subpopulation of 389 patients. The sources of data used to detect HF cases are numerous and were standardized for this study. The accuracy and the predictive values of the algorithm with respect to the GPs and the clinical standards are highly consistent with those from previous studies. In particular, the algorithm is more efficient in detecting the more severe cases of HF according to the GPs’ validation (specificity increases according to the number of comorbidities and external validation (NYHA: II–IV; HF severity index: 2, 3. Positive and negative predictive values reveal that the CARPEDIEM algorithm is most consistent with clinical evaluation performed in the specialist setting, while it presents a greater ability to rule out false-negative HF cases within the GP practice, probably as a consequence of the different HF prevalence in the two different care settings. Further development includes analyzing the clinical features of false-positive and -negative predictions, to explore the natural

  8. A Systems Approach to Identifying and Managing Opportunities and Constraints to Delivering Innovation Policy for Agriculture: An Analysis of the Australian Cooperative Research Centres (CRC) Program

    Science.gov (United States)

    Sandall, Jean; Cooksey, Ray; Wright, Vic

    2011-01-01

    In this paper we outline an analytical approach to identifying points in the policy process where management intervention to adjust organizational design could enhance delivery of innovation policy over time. We illustrate this approach using an example from native vegetation policy in the state of Victoria, Australia. We then use this approach to…

  9. Identifying important and feasible policies and actions for health at community sports clubs: a consensus-generating approach.

    Science.gov (United States)

    Kelly, Bridget; King, Lesley; Bauman, Adrian E; Baur, Louise A; Macniven, Rona; Chapman, Kathy; Smith, Ben J

    2014-01-01

    Children's high participation in organised sport in Australia makes sport an ideal setting for health promotion. This study aimed to generate consensus on priority health promotion objectives for community sports clubs, based on informed expert judgements. Delphi survey using three structured questionnaires. Forty-six health promotion, nutrition, physical activity and sport management/delivery professionals were approached to participate in the survey. Questionnaires used an iterative process to determine aspects of sports clubs deemed necessary for developing healthy sporting environments for children. Initially, participants were provided with a list of potential standards for a range of health promotion areas and asked to rate standards based on their importance and feasibility, and any barriers to implementation. Subsequently, participants were provided with information that summarised ratings for each standard to indicate convergence of the group, and asked to review and potentially revise their responses where they diverged. In a third round, participants ranked confirmed standards by priority. 26 professionals completed round 1, 21 completed round 2, and 18 completed round 3. The highest ranked standards related to responsible alcohol practices, availability of healthy food and drinks at sports canteens, smoke-free club facilities, restricting the sale and consumption of alcohol during junior sporting activities, and restricting unhealthy food and beverage company sponsorship. Identifying and prioritising health promotion areas that are relevant to children's sports clubs assists in focusing public health efforts and may guide future engagement of sports clubs. Approaches for providing informational and financial support to clubs to operationalise these standards are proposed. Copyright © 2013 Sports Medicine Australia. Published by Elsevier Ltd. All rights reserved.

  10. Identifying postpartum intervention approaches to prevent type 2 diabetes in women with a history of gestational diabetes

    Directory of Open Access Journals (Sweden)

    Abdul-Rahim Zainab S

    2011-03-01

    Full Text Available Abstract Background Women who develop gestational diabetes mellitus (GDM have an increased risk for the development of type 2 diabetes. Despite this "window of opportunity," few intervention studies have targeted postpartum women with a history of GDM. We sought perspectives of women with a history of GDM to identify a barriers and facilitators to healthy lifestyle changes postpartum, and b specific intervention approaches that would facilitate participation in a postpartum lifestyle intervention program. Methods We used mixed methods to gather data from women with a prior history of GDM, including focus groups and informant interviews. Analysis of focus groups relied on grounded theory and used open-coding to categorize data by themes, while frequency distributions were used for the informant interviews. Results Of 38 women eligible to participate in focus groups, only ten women were able to accommodate their schedules to attend a focus group and 15 completed informant interviews by phone. We analyzed data from 25 women (mean age 35, mean pre-pregnancy BMI 28, 52% Caucasian, 20% African American, 12% Asian, 8% American Indian, 8% refused to specify. Themes from the focus groups included concern about developing type 2 diabetes, barriers to changing diet, and barriers to increasing physical activity. In one focus group, women expressed frustration about feeling judged by their physicians during their GDM pregnancy. Cited barriers to lifestyle change were identified from both methods, and included time and financial constraints, childcare duties, lack of motivation, fatigue, and obstacles at work. Informants suggested facilitators for lifestyle change, including nutrition education, accountability, exercise partners/groups, access to gyms with childcare, and home exercise equipment. All focus group and informant interview participants reported access to the internet, and the majority expressed interest in an intervention program delivered

  11. Identifying postpartum intervention approaches to prevent type 2 diabetes in women with a history of gestational diabetes.

    Science.gov (United States)

    Nicklas, Jacinda M; Zera, Chloe A; Seely, Ellen W; Abdul-Rahim, Zainab S; Rudloff, Noelle D; Levkoff, Sue E

    2011-03-24

    Women who develop gestational diabetes mellitus (GDM) have an increased risk for the development of type 2 diabetes. Despite this "window of opportunity," few intervention studies have targeted postpartum women with a history of GDM. We sought perspectives of women with a history of GDM to identify a) barriers and facilitators to healthy lifestyle changes postpartum, and b) specific intervention approaches that would facilitate participation in a postpartum lifestyle intervention program. We used mixed methods to gather data from women with a prior history of GDM, including focus groups and informant interviews. Analysis of focus groups relied on grounded theory and used open-coding to categorize data by themes, while frequency distributions were used for the informant interviews. Of 38 women eligible to participate in focus groups, only ten women were able to accommodate their schedules to attend a focus group and 15 completed informant interviews by phone. We analyzed data from 25 women (mean age 35, mean pre-pregnancy BMI 28, 52% Caucasian, 20% African American, 12% Asian, 8% American Indian, 8% refused to specify). Themes from the focus groups included concern about developing type 2 diabetes, barriers to changing diet, and barriers to increasing physical activity. In one focus group, women expressed frustration about feeling judged by their physicians during their GDM pregnancy. Cited barriers to lifestyle change were identified from both methods, and included time and financial constraints, childcare duties, lack of motivation, fatigue, and obstacles at work. Informants suggested facilitators for lifestyle change, including nutrition education, accountability, exercise partners/groups, access to gyms with childcare, and home exercise equipment. All focus group and informant interview participants reported access to the internet, and the majority expressed interest in an intervention program delivered primarily via the internet that would include the

  12. A genomic approach to identify regulatory nodes in the transcriptional network of systemic acquired resistance in plants.

    Directory of Open Access Journals (Sweden)

    Dong Wang

    2006-11-01

    Full Text Available Many biological processes are controlled by intricate networks of transcriptional regulators. With the development of microarray technology, transcriptional changes can be examined at the whole-genome level. However, such analysis often lacks information on the hierarchical relationship between components of a given system. Systemic acquired resistance (SAR is an inducible plant defense response involving a cascade of transcriptional events induced by salicylic acid through the transcription cofactor NPR1. To identify additional regulatory nodes in the SAR network, we performed microarray analysis on Arabidopsis plants expressing the NPR1-GR (glucocorticoid receptor fusion protein. Since nuclear translocation of NPR1-GR requires dexamethasone, we were able to control NPR1-dependent transcription and identify direct transcriptional targets of NPR1. We show that NPR1 directly upregulates the expression of eight WRKY transcription factor genes. This large family of 74 transcription factors has been implicated in various defense responses, but no specific WRKY factor has been placed in the SAR network. Identification of NPR1-regulated WRKY factors allowed us to perform in-depth genetic analysis on a small number of WRKY factors and test well-defined phenotypes of single and double mutants associated with NPR1. Among these WRKY factors we found both positive and negative regulators of SAR. This genomics-directed approach unambiguously positioned five WRKY factors in the complex transcriptional regulatory network of SAR. Our work not only discovered new transcription regulatory components in the signaling network of SAR but also demonstrated that functional studies of large gene families have to take into consideration sequence similarity as well as the expression patterns of the candidates.

  13. Peptidomic approach identifies cruzioseptins, a new family of potent antimicrobial peptides in the splendid leaf frog, Cruziohyla calcarifer.

    Science.gov (United States)

    Proaño-Bolaños, Carolina; Zhou, Mei; Wang, Lei; Coloma, Luis A; Chen, Tianbao; Shaw, Chris

    2016-09-02

    Phyllomedusine frogs are an extraordinary source of biologically active peptides. At least 8 families of antimicrobial peptides have been reported in this frog clade, the dermaseptins being the most diverse. By a peptidomic approach, integrating molecular cloning, Edman degradation sequencing and tandem mass spectrometry, a new family of antimicrobial peptides has been identified in Cruziohyla calcarifer. These 15 novel antimicrobial peptides of 20-32 residues in length are named cruzioseptins. They are characterized by having a unique shared N-terminal sequence GFLD- and the sequence motifs -VALGAVSK- or -GKAAL(N/G/S) (V/A)V- in the middle of the peptide. Cruzioseptins have a broad spectrum of antimicrobial activity and low haemolytic effect. The most potent cruzioseptin was CZS-1 that had a MIC of 3.77μM against the Gram positive bacterium, Staphylococcus aureus and the yeast Candida albicans. In contrast, CZS-1 was 3-fold less potent against the Gram negative bacterium, Escherichia coli (MIC 15.11μM). CZS-1 reached 100% haemolysis at 120.87μM. Skin secretions from unexplored species such as C. calcarifer continue to demonstrate the enormous molecular diversity hidden in the amphibian skin. Some of these novel peptides may provide lead structures for the development of a new class of antibiotics and antifungals of therapeutic use. Through the combination of molecular cloning, Edman degradation sequencing, tandem mass spectrometry and MALDI-TOF MS we have identified a new family of 15 antimicrobial peptides in the skin secretion of Cruziohyla calcarifer. The novel family is named "Cruzioseptins" and contains cationic amphipathic peptides of 20-32 residues. They have a broad range of antimicrobial activity that also includes effective antifungals with low haemolytic activity. Therefore, C. calcarifer has proven to be a rich source of novel peptides, which could become leading structures for the development of novel antibiotics and antifungals of clinical

  14. A functional glycoproteomics approach identifies CD13 as a novel E-selectin ligand in breast cancer.

    Science.gov (United States)

    Carrascal, M A; Silva, M; Ferreira, J A; Azevedo, R; Ferreira, D; Silva, A M N; Ligeiro, D; Santos, L L; Sackstein, R; Videira, P A

    2018-05-17

    The glycan moieties sialyl-Lewis-X and/or -A (sLe X/A ) are the primary ligands for E-selectin, regulating subsequent tumor cell extravasation into distant organs. However, the nature of the glycoprotein scaffolds displaying these glycans in breast cancer remains unclear and constitutes the focus of the present investigation. We isolated glycoproteins that bind E-selectin from the CF1_T breast cancer cell line, derived from a patient with ductal carcinoma. Proteins were identified using bottom-up proteomics approach by nanoLC-orbitrap LTQ-MS/MS. Data were curated using bioinformatics tools to highlight clinically relevant glycoproteins, which were validated by flow cytometry, Western blot, immunohistochemistry and in-situ proximity ligation assays in clinical samples. We observed that the CF1_T cell line expressed sLe X , but not sLe A and the E-selectin reactivity was mainly on N-glycans. MS and bioinformatics analysis of the targeted glycoproteins, when narrowed down to the most clinically relevant species in breast cancer, identified CD44 glycoprotein (HCELL) and CD13 as key E-selectin ligands. Additionally, the co-expression of sLe X -CD44 and sLe X -CD13 was confirmed in clinical breast cancer tissue samples. Both CD44 and CD13 glycoforms display sLe X in breast cancer and bind E-selectin, suggesting a key role in metastasis development. Such observations provide a novel molecular rationale for developing targeted therapeutics. While HCELL expression in breast cancer has been previously reported, this is the first study indicating that CD13 functions as an E-selectin ligand in breast cancer. This observation supports previous associations of CD13 with metastasis and draws attention to this glycoprotein as an anti-cancer target. Copyright © 2018 Elsevier B.V. All rights reserved.

  15. Innovative new technologies to identify and treat traumatic brain injuries: crossover technologies and approaches between military and civilian applications.

    Science.gov (United States)

    Doarn, Charles R; McVeigh, Francis; Poropatich, Ronald

    2010-04-01

    Traumatic brain injury (TBI) has become the signature injury of Operation Iraqi Freedom and Operation Enduring Freedom. The use of improvised explosive devices has seen an exponential increase in both Iraq and Afghanistan. In previous conflicts prior to Iraq, survivability of such an injury was far less. Today, technological improvements in trauma care have increased an injured warfighter's chance of survival. A reduction in severe TBI has been achieved but an increase in mild or moderate TBI has been observed. The consequences of this kind of injury can be both physical and mental and can often be hidden or even misdiagnosed. The U.S. Army is interested in pursuing technological solutions for early detection and treatment of TBI to reduce its lasting impact on the warfighter. Such technological breakthroughs have benefit beyond the military, as TBI is a high probable event in nonmilitary settings as well. To gauge what technologies or methods are currently available, the U.S. Army's Telemedicine and Advanced Technology Research Center partnered with the American Telemedicine Association to organize and conduct a discipline-specific symposium entitled "Innovative New Technologies to Identify and Treat Traumatic Brain Injuries: Crossover Technologies and Approaches Between Military and Civilian Applications." This symposium was held in Palm Springs, CA, in September 2009. The purpose of the meeting was to provide a unique opportunity for leaders from disparate organizations involved in telemedicine and related other activities to meet and explore opportunities to collaborate in new partnership models. The meeting was designed to help Telemedicine and Advanced Technology Research Center identify opportunities to expand strategic operations and form new alliances. This report summarizes this symposium while raising awareness for collaboration into better ways of adapting and adopting technologies to address this growing health issue.

  16. Multipronged approach to identify and validate a novel upstream regulator of Sncg in mouse retinal ganglion cells.

    Science.gov (United States)

    Chintalapudi, Sumana R; Morales-Tirado, Vanessa M; Williams, Robert W; Jablonski, Monica M

    2016-02-01

    Loss of retinal ganglion cells (RGCs) is one of the hallmarks of retinal neurodegenerative diseases, glaucoma being one of the most common. Mechanistic studies on RGCs are hindered by the lack of sufficient primary cells and consensus regarding their signature markers. Recently, γ-synuclein (SNCG) has been shown to be highly expressed in the somas and axons of RGCs. In various mouse models of glaucoma, downregulation of Sncg gene expression correlates with RGC loss. To investigate the role of Sncg in RGCs, we used a novel systems genetics approach to identify a gene that modulates Sncg expression, followed by confirmatory studies in both healthy and diseased retinae. We found that chromosome 1 harbors an expression quantitative trait locus that modulates Sncg expression in the mouse retina, and identified the prefoldin-2 (PFDN2) gene as the candidate upstream modulator of Sncg expression. Our immunohistochemical analyses revealed similar expression patterns in both mouse and human healthy retinae, with PFDN2 colocalizing with SNCG in RGCs and their axons. In contrast, in retinae from glaucoma subjects, SNCG levels were significantly reduced, although PFDN2 levels were maintained. Using a novel flow cytometry-based RGC isolation method, we obtained viable populations of murine RGCs. Knocking down Pfdn2 expression in primary murine RGCs significantly reduced Sncg expression, confirming that Pfdn2 regulates Sncg expression in murine RGCs. Gene Ontology analysis indicated shared mitochondrial function associated with Sncg and Pfdn2. These data solidify the relationship between Sncg and Pfdn2 in RGCs, and provide a novel mechanism for maintaining RGC health. © 2015 FEBS.

  17. A Collaborative Approach to Identifying Social Media Markers of Schizophrenia by Employing Machine Learning and Clinical Appraisals.

    Science.gov (United States)

    Birnbaum, Michael L; Ernala, Sindhu Kiranmai; Rizvi, Asra F; De Choudhury, Munmun; Kane, John M

    2017-08-14

    Linguistic analysis of publicly available Twitter feeds have achieved success in differentiating individuals who self-disclose online as having schizophrenia from healthy controls. To date, limited efforts have included expert input to evaluate the authenticity of diagnostic self-disclosures. This study aims to move from noisy self-reports of schizophrenia on social media to more accurate identification of diagnoses by exploring a human-machine partnered approach, wherein computational linguistic analysis of shared content is combined with clinical appraisals. Twitter timeline data, extracted from 671 users with self-disclosed diagnoses of schizophrenia, was appraised for authenticity by expert clinicians. Data from disclosures deemed true were used to build a classifier aiming to distinguish users with schizophrenia from healthy controls. Results from the classifier were compared to expert appraisals on new, unseen Twitter users. Significant linguistic differences were identified in the schizophrenia group including greater use of interpersonal pronouns (P<.001), decreased emphasis on friendship (P<.001), and greater emphasis on biological processes (P<.001). The resulting classifier distinguished users with disclosures of schizophrenia deemed genuine from control users with a mean accuracy of 88% using linguistic data alone. Compared to clinicians on new, unseen users, the classifier's precision, recall, and accuracy measures were 0.27, 0.77, and 0.59, respectively. These data reinforce the need for ongoing collaborations integrating expertise from multiple fields to strengthen our ability to accurately identify and effectively engage individuals with mental illness online. These collaborations are crucial to overcome some of mental illnesses' biggest challenges by using digital technology. ©Michael L Birnbaum, Sindhu Kiranmai Ernala, Asra F Rizvi, Munmun De Choudhury, John M Kane. Originally published in the Journal of Medical Internet Research (http

  18. Gait disorders in the elderly and dual task gait analysis: a new approach for identifying motor phenotypes.

    Science.gov (United States)

    Auvinet, Bernard; Touzard, Claude; Montestruc, François; Delafond, Arnaud; Goeb, Vincent

    2017-01-31

    Gait disorders and gait analysis under single and dual-task conditions are topics of great interest, but very few studies have looked for the relevance of gait analysis under dual-task conditions in elderly people on the basis of a clinical approach. An observational study including 103 patients (mean age 76.3 ± 7.2, women 56%) suffering from gait disorders or memory impairment was conducted. Gait analysis under dual-task conditions was carried out for all patients. Brain MRI was performed in the absence of contra-indications. Three main gait variables were measured: walking speed, stride frequency, and stride regularity. For each gait variable, the dual task cost was computed and a quartile analysis was obtained. Nonparametric tests were used for all the comparisons (Wilcoxon, Kruskal-Wallis, Fisher or Chi 2 tests). Four clinical subgroups were identified: gait instability (45%), recurrent falls (29%), memory impairment (18%), and cautious gait (8%). The biomechanical severity of these subgroups was ordered according to walking speed and stride regularity under both conditions, from least to most serious as follows: memory impairment, gait instability, recurrent falls, cautious gait (p < 0.01 for walking speed, p = 0.05 for stride regularity). According to the established diagnoses of gait disorders, 5 main pathological subgroups were identified (musculoskeletal diseases (n = 11), vestibular diseases (n = 6), mild cognitive impairment (n = 24), central nervous system pathologies, (n = 51), and without diagnosis (n = 8)). The dual task cost for walking speed, stride frequency and stride regularity were different among these subgroups (p < 0.01). The subgroups mild cognitive impairment and central nervous system pathologies both showed together a higher dual task cost for each variable compared to the other subgroups combined (p = 0.01). The quartile analysis of dual task cost for stride frequency and stride regularity

  19. A systems immunology approach identifies the collective impact of 5 miRs in Th2 inflammation.

    Science.gov (United States)

    Kılıç, Ayşe; Santolini, Marc; Nakano, Taiji; Schiller, Matthias; Teranishi, Mizue; Gellert, Pascal; Ponomareva, Yuliya; Braun, Thomas; Uchida, Shizuka; Weiss, Scott T; Sharma, Amitabh; Renz, Harald

    2018-06-07

    Allergic asthma is a chronic inflammatory disease dominated by a CD4+ T helper 2 (Th2) cell signature. The immune response amplifies in self-enforcing loops, promoting Th2-driven cellular immunity and leaving the host unable to terminate inflammation. Posttranscriptional mechanisms, including microRNAs (miRs), are pivotal in maintaining immune homeostasis. Since an altered expression of various miRs has been associated with T cell-driven diseases, including asthma, we hypothesized that miRs control mechanisms ensuring Th2 stability and maintenance in the lung. We isolated murine CD4+ Th2 cells from allergic inflamed lungs and profiled gene and miR expression. Instead of focusing on the magnitude of miR differential expression, here we addressed the secondary consequences for the set of molecular interactions in the cell, the interactome. We developed the Impact of Differential Expression Across Layers, a network-based algorithm to prioritize disease-relevant miRs based on the central role of their targets in the molecular interactome. This method identified 5 Th2-related miRs (mir27b, mir206, mir106b, mir203, and mir23b) whose antagonization led to a sharp reduction of the Th2 phenotype. Overall, a systems biology tool was developed and validated, highlighting the role of miRs in Th2-driven immune response. This result offers potentially novel approaches for therapeutic interventions.

  20. Metabolomic approach to human brain spectroscopy identifies associations between clinical features and the frontal lobe metabolome in multiple sclerosis

    Science.gov (United States)

    Vingara, Lisa K.; Yu, Hui Jing; Wagshul, Mark E.; Serafin, Dana; Christodoulou, Christopher; Pelczer, István; Krupp, Lauren B.; Maletić-Savatić, Mirjana

    2013-01-01

    Proton magnetic resonance spectroscopy (1H-MRS) is capable of noninvasively detecting metabolic changes that occur in the brain tissue in vivo. Its clinical utility has been limited so far, however, by analytic methods that focus on independently evaluated metabolites and require prior knowledge about which metabolites to examine. Here, we applied advanced computational methodologies from the field of metabolomics, specifically partial least squares discriminant analysis and orthogonal partial least squares, to in vivo 1H-MRS from frontal lobe white matter of 27 patients with relapsing–remitting multiple sclerosis (RRMS) and 14 healthy controls. We chose RRMS, a chronic demyelinating disorder of the central nervous system, because its complex pathology and variable disease course make the need for reliable biomarkers of disease progression more pressing. We show that in vivo MRS data, when analyzed by multivariate statistical methods, can provide reliable, distinct profiles of MRS-detectable metabolites in different patient populations. Specifically, we find that brain tissue in RRMS patients deviates significantly in its metabolic profile from that of healthy controls, even though it appears normal by standard MRI techniques. We also identify, using statistical means, the metabolic signatures of certain clinical features common in RRMS, such as disability score, cognitive impairments, and response to stress. This approach to human in vivo MRS data should promote understanding of the specific metabolic changes accompanying disease pathogenesis, and could provide biomarkers of disease progression that would be useful in clinical trials. PMID:23751863

  1. A System-Wide Approach to Identify the Mechanisms of Barnacle Attachment: Toward the Discovery of New Antifouling Compounds

    KAUST Repository

    Al-Aqeel, Sarah

    2015-11-01

    Biofouling is a significant economic problem, particularly for marine and offshore oil industries. The acorn barnacle (Amphibalanus (Balanus) amphitrite) is the main biofouling organism in marine environments. Environmental conditions, the physiology of the biofouling organism, the surrounding microbial community, and the properties of the substratum can all influence the attachment of biofouling organisms to substrates. My dissertation investigated the biological processes involved in B. amphitrite development and attachment in the unique environment of the Red Sea, where the average water surface temperature is 34°C and the salinity reaches 41‰. I profiled the transcriptome and proteome of B. amphitrite at different life stages (nauplius II, nauplius VI, and cyprid) and identified 65,784 expressed contigs and 1387 expressed proteins by quantitative proteomics. During the planktonic stage, genes related to osmotic stress, salt stress, the hyperosmotic response, and the Wnt signaling pathway were strongly up-regulated, hereas genes related to the MAPK pathway, lipid metabolism, and cuticle development were down-regulated. In the transition from the nauplius VI to cyprid stages, there was up-regulation of genes involved in blood coagulation, cuticle development, and eggshell formation, and down-regulation of genes in the nitric oxide pathway, which stimulates the swimming and feeding responses of marine invertebrates. This system-wide integrated approach elucidated the development and attachment pathways important in B. amphitrite. Enzymes and metabolites in these pathways are potential molecular targets for the development of new antifouling compounds.

  2. Multiplatform Mass Spectrometry-Based Approach Identifies Extracellular Glycolipids of the Yeast Rhodotorula babjevae UCDFST 04-877.

    Science.gov (United States)

    Cajka, Tomas; Garay, Luis A; Sitepu, Irnayuli R; Boundy-Mills, Kyria L; Fiehn, Oliver

    2016-10-28

    A multiplatform mass spectrometry-based approach was used for elucidating extracellular lipids with biosurfactant properties produced by the oleaginous yeast Rhodotorula babjevae UCDFST 04-877. This strain secreted 8.6 ± 0.1 g/L extracellular lipids when grown in a benchtop bioreactor fed with 100 g/L glucose in medium without addition of hydrophobic substrate, such as oleic acid. Untargeted reversed-phase liquid chromatography-quadrupole/time-of-flight mass spectrometry (QTOFMS) detected native glycolipid molecules with masses of 574-716 Da. After hydrolysis into the fatty acid and sugar components and hydrophilic interaction chromatography-QTOFMS analysis, the extracellular lipids were found to consist of hydroxy fatty acids and sugar alcohols. Derivatization and chiral separation gas chromatography-mass spectrometry (GC-MS) identified these components as d-arabitol, d-mannitol, (R)-3-hydroxymyristate, (R)-3-hydroxypalmitate, and (R)-3-hydroxystearate. In order to assemble these substructures back into intact glycolipids that were detected in the initial screen, potential structures were in-silico acetylated to match the observed molar masses and subsequently characterized by matching predicted and observed MS/MS fragmentation using the Mass Frontier software program. Eleven species of acetylated sugar alcohol esters of hydroxy fatty acids were characterized for this yeast strain.

  3. 4-Chlorotetrazolo[1,5-a]quinoxaline inhibits activation of Syk kinase to suppress mast cells in vitro and mast cell-mediated passive cutaneous anaphylaxis in mice

    Energy Technology Data Exchange (ETDEWEB)

    Park, Kui Lea [Center for Drug Development Assistance, National Institute of Food Drug Safety Evaluation (NIFDS), KFDA, Cheongwon-gun (Korea, Republic of); Ko, Na Young; Lee, Jun Ho; Kim, Do Kyun; Kim, Hyuk Soon; Kim, A-Ram; Her, Erk; Kim, Bokyung [Department of Immunology and physiology, College of Medicine, Konkuk University, Chungju (Korea, Republic of); Kim, Hyung Sik [College of Pharmacy, Pusan National University, Busan (Korea, Republic of); Moon, Eun-Yi [Department of Bioscience and Biotechnology, College of Biological Science, Sejong University, Seoul (Korea, Republic of); Kim, Young Mi [College of Pharmacy, Duksung Women' s University, Seoul (Korea, Republic of); Kim, Hang-Rae, E-mail: hangrae2@snu.ac.kr [Department of Anatomy, Seoul National University College of Medicine, Seoul (Korea, Republic of); Choi, Wahn Soo, E-mail: wahnchoi@kku.ac.kr [Department of Immunology and physiology, College of Medicine, Konkuk University, Chungju (Korea, Republic of)

    2011-12-15

    4-Chlorotetrazolo[1,5-a]quinoxaline is a quinoxaline derivative. We aimed to study the effects of 4-chlorotetrazolo[1,5-a]quinoxaline on activation of mast cells in vitro and in mice. 4-Chlorotetrazolo[1,5-a]quinoxaline reversibly inhibited degranulation of mast cells in a dose-dependent manner, and also suppressed the expression and secretion of TNF-{alpha} and IL-4 in mast cells. Mechanistically, 4-chlorotetrazolo[1,5-a]quinoxaline inhibited activating phosphorylation of Syk and LAT, which are crucial for early Fc{epsilon}RI-mediated signaling events, as well as Akt and MAP kinases, which play essential roles in the production of various pro-inflammatory cytokines in mast cells. Notably, although 4-chlorotetrazolo[1,5-a]quinoxaline inhibited the activation of Fyn and Syk, minimal inhibition was observed in mast cells in the case of Lyn. Furthermore, consistent with its in vitro activity, 4-chlorotetrazolo[1,5-a]quinoxaline significantly suppressed mast cell-mediated passive cutaneous anaphylaxis in mice. In summary, the results from this study demonstrate that 4-chlorotetrazolo[1,5-a]quinoxaline shows an inhibitory effect on mast cells in vitro and in vivo, and that this is mediated by inhibiting the activation of Syk in mast cells. Therefore, 4-chlorotetrazolo[1,5-a]quinoxaline could be useful in the treatment of mast cell-mediated allergic diseases. -- Highlights: Black-Right-Pointing-Pointer 4-chlorotetrazolo[1,5-a]quinoxaline is a quinoxaline derivative. Black-Right-Pointing-Pointer The effect of 4-chlorotetrazolo[1,5-a]quinoxaline on mast cells was investigated. Black-Right-Pointing-Pointer 4-chlorotetrazolo[1,5-a]quinoxaline reversibly inhibited Syk activation. Black-Right-Pointing-Pointer 4-chlorotetrazolo[1,5-a]quinoxaline could be useful for IgE-mediated allergy.

  4. 4-Chlorotetrazolo[1,5-a]quinoxaline inhibits activation of Syk kinase to suppress mast cells in vitro and mast cell-mediated passive cutaneous anaphylaxis in mice

    International Nuclear Information System (INIS)

    Park, Kui Lea; Ko, Na Young; Lee, Jun Ho; Kim, Do Kyun; Kim, Hyuk Soon; Kim, A-Ram; Her, Erk; Kim, Bokyung; Kim, Hyung Sik; Moon, Eun-Yi; Kim, Young Mi; Kim, Hang-Rae; Choi, Wahn Soo

    2011-01-01

    4-Chlorotetrazolo[1,5-a]quinoxaline is a quinoxaline derivative. We aimed to study the effects of 4-chlorotetrazolo[1,5-a]quinoxaline on activation of mast cells in vitro and in mice. 4-Chlorotetrazolo[1,5-a]quinoxaline reversibly inhibited degranulation of mast cells in a dose-dependent manner, and also suppressed the expression and secretion of TNF-α and IL-4 in mast cells. Mechanistically, 4-chlorotetrazolo[1,5-a]quinoxaline inhibited activating phosphorylation of Syk and LAT, which are crucial for early FcεRI-mediated signaling events, as well as Akt and MAP kinases, which play essential roles in the production of various pro-inflammatory cytokines in mast cells. Notably, although 4-chlorotetrazolo[1,5-a]quinoxaline inhibited the activation of Fyn and Syk, minimal inhibition was observed in mast cells in the case of Lyn. Furthermore, consistent with its in vitro activity, 4-chlorotetrazolo[1,5-a]quinoxaline significantly suppressed mast cell-mediated passive cutaneous anaphylaxis in mice. In summary, the results from this study demonstrate that 4-chlorotetrazolo[1,5-a]quinoxaline shows an inhibitory effect on mast cells in vitro and in vivo, and that this is mediated by inhibiting the activation of Syk in mast cells. Therefore, 4-chlorotetrazolo[1,5-a]quinoxaline could be useful in the treatment of mast cell-mediated allergic diseases. -- Highlights: ► 4-chlorotetrazolo[1,5-a]quinoxaline is a quinoxaline derivative. ► The effect of 4-chlorotetrazolo[1,5-a]quinoxaline on mast cells was investigated. ► 4-chlorotetrazolo[1,5-a]quinoxaline reversibly inhibited Syk activation. ► 4-chlorotetrazolo[1,5-a]quinoxaline could be useful for IgE-mediated allergy.

  5. Using a distribution and conservation status weighted hotspot approach to identify areas in need of conservation action to benefit Idaho bird species

    Science.gov (United States)

    Haines, Aaron M.; Leu, Matthias; Svancara, Leona K.; Wilson, Gina; Scott, J. Michael

    2010-01-01

    Identification of biodiversity hotspots (hereafter, hotspots) has become a common strategy to delineate important areas for wildlife conservation. However, the use of hotspots has not often incorporated important habitat types, ecosystem services, anthropogenic activity, or consistency in identifying important conservation areas. The purpose of this study was to identify hotspots to improve avian conservation efforts for Species of Greatest Conservation Need (SGCN) in the state of Idaho, United States. We evaluated multiple approaches to define hotspots and used a unique approach based on weighting species by their distribution size and conservation status to identify hotspot areas. All hotspot approaches identified bodies of water (Bear Lake, Grays Lake, and American Falls Reservoir) as important hotspots for Idaho avian SGCN, but we found that the weighted approach produced more congruent hotspot areas when compared to other hotspot approaches. To incorporate anthropogenic activity into hotspot analysis, we grouped species based on their sensitivity to specific human threats (i.e., urban development, agriculture, fire suppression, grazing, roads, and logging) and identified ecological sections within Idaho that may require specific conservation actions to address these human threats using the weighted approach. The Snake River Basalts and Overthrust Mountains ecological sections were important areas for potential implementation of conservation actions to conserve biodiversity. Our approach to identifying hotspots may be useful as part of a larger conservation strategy to aid land managers or local governments in applying conservation actions on the ground.

  6. Neuroproteomics and Systems Biology Approach to Identify Temporal Biomarker Changes Post Experimental Traumatic Brain Injury in Rats

    Directory of Open Access Journals (Sweden)

    Firas H Kobeissy

    2016-11-01

    Full Text Available Traumatic brain injury (TBI represents a critical health problem of which diagnosis, management and treatment remain challenging. TBI is a contributing factor in approximately 1/3 of all injury-related deaths in the United States. The Centers for Disease Control and Prevention (CDC estimate that 1.7 million TBI people suffer a TBI in the United States annually. Efforts continue to focus on elucidating the complex molecular mechanisms underlying TBI pathophysiology and defining sensitive and specific biomarkers that can aid in improving patient management and care. Recently, the area of neuroproteomics-systems biology is proving to be a prominent tool in biomarker discovery for central nervous system (CNS injury and other neurological diseases. In this work, we employed the controlled cortical impact (CCI model of experimental TBI in rat model to assess the temporal-global proteome changes after acute (1 day and for the first time, subacute (7 days, post-injury time frame using the established CAX-PAGE LC-MS/MS platform for protein separation combined with discrete systems biology analyses to identify temporal biomarker changes related to this rat TBI model. Rather than focusing on any one individual molecular entities, we used in silico systems biology approach to understand the global dynamics that govern proteins that are differentially altered post-injury. In addition, gene ontology analysis of the proteomic data was conducted in order to categorize the proteins by molecular function, biological process, and cellular localization. Results show alterations in several proteins related to inflammatory responses and oxidative stress in both acute (1 day and subacute (7 days periods post TBI. Moreover, results suggest a differential upregulation of neuroprotective proteins at 7-days post-CCI involved in cellular functions such as neurite growth, regeneration, and axonal guidance. Our study is amongst the first to assess temporal neuroproteome

  7. Identifying Where REDD+ Financially Out-Competes Oil Palm in Floodplain Landscapes Using a Fine-Scale Approach.

    Science.gov (United States)

    Abram, Nicola K; MacMillan, Douglas C; Xofis, Panteleimon; Ancrenaz, Marc; Tzanopoulos, Joseph; Ong, Robert; Goossens, Benoit; Koh, Lian Pin; Del Valle, Christian; Peter, Lucy; Morel, Alexandra C; Lackman, Isabelle; Chung, Robin; Kler, Harjinder; Ambu, Laurentius; Baya, William; Knight, Andrew T

    2016-01-01

    + competitiveness in tropical floodplain landscapes; and, providing a robust approach for identifying and targeting limited REDD+ funds.

  8. Identifying Where REDD+ Financially Out-Competes Oil Palm in Floodplain Landscapes Using a Fine-Scale Approach.

    Directory of Open Access Journals (Sweden)

    Nicola K Abram

    : highlighting REDD+ competitiveness in tropical floodplain landscapes; and, providing a robust approach for identifying and targeting limited REDD+ funds.

  9. A multicopy suppressor screening approach as a means to identify antibiotic resistance determinant candidates in Yersinia pestis

    Directory of Open Access Journals (Sweden)

    Moy Richard L

    2008-07-01

    Full Text Available Abstract Background Yersinia pestis is the causative agent of plague and a potential agent of bioterrorism and biowarfare. The plague biothreat and the emergence of multidrug-resistant plague underscore the need to increase our understanding of the intrinsic potential of Y. pestis for developing antimicrobial resistance and to anticipate the mechanisms of resistance that may emerge in Y. pestis. Identification of Y. pestis genes that, when overexpressed, are capable of reducing antibiotic susceptibility is a useful strategy to expose genes that this pathogen may rely upon to evolve antibiotic resistance via a vertical modality. In this study, we explored the use of a multicopy suppressor, Escherichia coli host-based screening approach as a means to expose antibiotic resistance determinant candidates in Y. pestis. Results We constructed a multicopy plasmid-based, Y. pestis genome-wide expression library of nearly 16,000 clones in E. coli and screened the library for suppressors of the antimicrobial activity of ofloxacin, a fluoroquinolone antibiotic. The screen permitted the identification of a transcriptional regulator-encoding gene (robAYp that increased the MIC99 of ofloxacin by 23-fold when overexpressed from a multicopy plasmid in Y. pestis. Additionally, we found that robAYp overexpression in Y. pestis conferred low-level resistance to many other antibiotics and increased organic solvent tolerance. Overexpression of robAYp also upregulated the expression of several efflux pumps in Y. pestis. Conclusion Our study provides proof of principle for the use of multicopy suppressor screening based on the tractable and easy-to-manipulate E. coli host as a means to identify antibiotic resistance determinant candidates of Y. pestis.

  10. A concept mapping approach to identifying the barriers to implementing an evidence-based sports injury prevention programme.

    Science.gov (United States)

    Donaldson, Alex; Callaghan, Aisling; Bizzini, Mario; Jowett, Andrew; Keyzer, Patrick; Nicholson, Matthew

    2018-01-20

    Understanding the barriers to programme use is important to facilitate implementation of injury prevention programmes in real-word settings. This study investigated the barriers to coaches of adolescent female soccer teams, in Victoria, Australia, implementing the evidence-based FIFA 11+ injury prevention programme. Concept mapping with data collected from 19 soccer coaches and administrators. Brainstorming generated 65 statements as barriers to 11+ implementation. After the statements were synthesised and edited, participants sorted 59 statements into groups (mean, 6.2 groups; range, 3-10 groups). Multidimensional scaling and hierarchical cluster analysis identified a six-cluster solution: Lack of 11+ knowledge among coaches (15 statements), Lack of player enjoyment and engagement (14), Lack of link to football-related goals (11), Lack of facilities and resources (8), Lack of leadership (6) and Lack of time at training (5). Statements in the 'Lack of 11+ knowledge among coaches' cluster received the highest mean importance (3.67 out of 5) and feasibility for the Football Federation to address (3.20) rating. Statements in the 'Lack of facilities and resources' cluster received the lowest mean importance rating (2.23), while statements in the 'Lack of time at training' cluster received the lowest mean feasibility rating (2.19). A multistrategy, ecological approach to implementing the 11+-with specific attention paid to improving coach knowledge about the 11+ and how to implement it, linking the 11+ to the primary goal of soccer training, and organisational leadership-is required to improve the uptake of the 11+ among the targeted coaches. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  11. Demonstration of statistical approaches to identify component's ageing by operational data analysis-A case study for the ageing PSA network

    International Nuclear Information System (INIS)

    Rodionov, Andrei; Atwood, Corwin L.; Kirchsteiger, Christian; Patrik, Milan

    2008-01-01

    The paper presents some results of a case study on 'Demonstration of statistical approaches to identify the component's ageing by operational data analysis', which was done in the frame of the EC JRC Ageing PSA Network. Several techniques: visual evaluation, nonparametric and parametric hypothesis tests, were proposed and applied in order to demonstrate the capacity, advantages and limitations of statistical approaches to identify the component's ageing by operational data analysis. Engineering considerations are out of the scope of the present study

  12. Mapping industrial networks as an approach to identify inter-organisational collaborative potential in new product development

    DEFF Research Database (Denmark)

    Parraguez, Pedro; Maier, Anja

    2012-01-01

    . Consequently, identifying and selecting potential partners to establish collaboration agreements can be a key activity in the new product development process. This paper explores the implications of mapping industrial networks with the purpose of identifying inter-organisational collaborative potential...

  13. A novel approach to identify optimal metabotypes of elongase and desaturase activities in prevention of acute coronary syndrome

    Science.gov (United States)

    Both metabolomic and genomic approaches are valuable for risk analysis, however typical approaches evaluating differences in means do not model the changes well. Gene polymorphisms that alter function would appear as distinct populations, or metabotypes, from the predominant one, in which case risk...

  14. Identifying interactions in the time and frequency domains in local and global networks - A Granger Causality Approach.

    Science.gov (United States)

    Zou, Cunlu; Ladroue, Christophe; Guo, Shuixia; Feng, Jianfeng

    2010-06-21

    Reverse-engineering approaches such as Bayesian network inference, ordinary differential equations (ODEs) and information theory are widely applied to deriving causal relationships among different elements such as genes, proteins, metabolites, neurons, brain areas and so on, based upon multi-dimensional spatial and temporal data. There are several well-established reverse-engineering approaches to explore causal relationships in a dynamic network, such as ordinary differential equations (ODE), Bayesian networks, information theory and Granger Causality. Here we focused on Granger causality both in the time and frequency domain and in local and global networks, and applied our approach to experimental data (genes and proteins). For a small gene network, Granger causality outperformed all the other three approaches mentioned above. A global protein network of 812 proteins was reconstructed, using a novel approach. The obtained results fitted well with known experimental findings and predicted many experimentally testable results. In addition to interactions in the time domain, interactions in the frequency domain were also recovered. The results on the proteomic data and gene data confirm that Granger causality is a simple and accurate approach to recover the network structure. Our approach is general and can be easily applied to other types of temporal data.

  15. Identifying interactions in the time and frequency domains in local and global networks - A Granger Causality Approach

    Directory of Open Access Journals (Sweden)

    Guo Shuixia

    2010-06-01

    Full Text Available Abstract Background Reverse-engineering approaches such as Bayesian network inference, ordinary differential equations (ODEs and information theory are widely applied to deriving causal relationships among different elements such as genes, proteins, metabolites, neurons, brain areas and so on, based upon multi-dimensional spatial and temporal data. There are several well-established reverse-engineering approaches to explore causal relationships in a dynamic network, such as ordinary differential equations (ODE, Bayesian networks, information theory and Granger Causality. Results Here we focused on Granger causality both in the time and frequency domain and in local and global networks, and applied our approach to experimental data (genes and proteins. For a small gene network, Granger causality outperformed all the other three approaches mentioned above. A global protein network of 812 proteins was reconstructed, using a novel approach. The obtained results fitted well with known experimental findings and predicted many experimentally testable results. In addition to interactions in the time domain, interactions in the frequency domain were also recovered. Conclusions The results on the proteomic data and gene data confirm that Granger causality is a simple and accurate approach to recover the network structure. Our approach is general and can be easily applied to other types of temporal data.

  16. A System-Wide Approach to Identify the Mechanisms of Barnacle Attachment: Toward the Discovery of New Antifouling Compounds

    KAUST Repository

    Al-Aqeel, Sarah

    2015-01-01

    , cuticle development, and eggshell formation, and down-regulation of genes in the nitric oxide pathway, which stimulates the swimming and feeding responses of marine invertebrates. This system-wide integrated approach elucidated the development

  17. Students' Perceptions about Online Teaching Effectiveness: A Bottom-Up Approach for Identifying Online Instructors' Roles

    Science.gov (United States)

    Gómez-Rey, Pilar; Barbera, Elena; Fernández-Navarro, Francisco

    2018-01-01

    The topic of online instructors' roles has been of interest to the educational community since the late twentieth century. In previous studies, the identification of online instructors' roles was done using a top-down (deductive) approach. This study applied a bottom-up (inductive) procedure to examine not only the roles of online instructors from…

  18. To Be or Not to Be Associated: Power study of four statistical modeling approaches to identify parasite associations in cross-sectional studies

    Directory of Open Access Journals (Sweden)

    Elise eVaumourin

    2014-05-01

    Full Text Available A growing number of studies are reporting simultaneous infections by parasites in many different hosts. The detection of whether these parasites are significantly associated is important in medicine and epidemiology. Numerous approaches to detect associations are available, but only a few provide statistical tests. Furthermore, they generally test for an overall detection of association and do not identify which parasite is associated with which other one. Here, we developed a new approach, the association screening approach, to detect the overall and the detail of multi-parasite associations. We studied the power of this new approach and of three other known ones (i.e. the generalized chi-square, the network and the multinomial GLM approaches to identify parasite associations either due to parasite interactions or to confounding factors. We applied these four approaches to detect associations within two populations of multi-infected hosts: 1 rodents infected with Bartonella sp., Babesia microti and Anaplasma phagocytophilum and 2 bovine population infected with Theileria sp. and Babesia sp.. We found that the best power is obtained with the screening model and the generalized chi-square test. The differentiation between associations, which are due to confounding factors and parasite interactions was not possible. The screening approach significantly identified associations between Bartonella doshiae and B. microti, and between T. parva, T. mutans and T. velifera. Thus, the screening approach was relevant to test the overall presence of parasite associations and identify the parasite combinations that are significantly over- or under-represented. Unravelling whether the associations are due to real biological interactions or confounding factors should be further investigated. Nevertheless, in the age of genomics and the advent of new technologies, it is a considerable asset to speed up researches focusing on the mechanisms driving interactions

  19. Identifying Multi-Level Culturally Appropriate Smoking Cessation Strategies for Aboriginal Health Staff: A Concept Mapping Approach

    Science.gov (United States)

    Dawson, Anna P.; Cargo, Margaret; Stewart, Harold; Chong, Alwin; Daniel, Mark

    2013-01-01

    Aboriginal Australians, including Aboriginal Health Workers (AHWs), smoke at rates double the non-Aboriginal population. This study utilized concept mapping methodology to identify and prioritize culturally relevant strategies to promote smoking cessation in AHWs. Stakeholder participants included AHWs, other health service employees and tobacco…

  20. Identifying and Quantifying Cultural Factors That Matter to the IT Workforce: An Approach Based on Automated Content Analysis

    DEFF Research Database (Denmark)

    Schmiedel, Theresa; Müller, Oliver; Debortoli, Stefan

    2016-01-01

    builds on 112,610 online reviews of Fortune 500 IT companies collected from Glassdoor, an online platform on which current and former employees can anonymously review companies and their management. We perform an automated content analysis to identify cultural factors that employees emphasize...

  1. Identifying and Applying the Communicative and the Constructivist Approaches To Facilitate Transfer of Knowledge in the Bilingual Classroom.

    Science.gov (United States)

    Olivares, Rafael A.; Lemberger, Nancy

    2002-01-01

    Provides recommendations for the implementation of the communication, constructivism, and transference of knowledge (CCT) model in the education of English language learners (ELLS). Describes how the CCT model is identified in research studies and suggests specific recommendations to facilitate the implementation of the model in the education of…

  2. Identifying Students' Expectancy-Value Beliefs: A Latent Class Analysis Approach to Analyzing Middle School Students' Science Self-Perceptions

    Science.gov (United States)

    Phelan, Julia; Ing, Marsha; Nylund-Gibson, Karen; Brown, Richard S.

    2017-01-01

    This study extends current research by organizing information about students' expectancy-value achievement motivation, in a way that helps parents and teachers identify specific entry points to encourage and support students' science aspirations. This study uses latent class analysis to describe underlying differences in ability beliefs, task…

  3. Non-destructive inspection approach using ultrasound to identify the material state for amorphous and semi-crystalline materials

    Science.gov (United States)

    Jost, Elliott; Jack, David; Moore, David

    2018-04-01

    At present, there are many methods to identify the temperature and phase of a material using invasive techniques. However, most current methods require physical contact or implicit methods utilizing light reflectance of the specimen. This work presents a nondestructive inspection method using ultrasonic wave technology that circumvents these disadvantages to identify phase change regions and infer the temperature state of a material. In the present study an experiment is performed to monitor the time of flight within a wax as it undergoes melting and the subsequent cooling. Results presented in this work show a clear relationship between a material's speed of sound and its temperature. The phase change transition of the material is clear from the time of flight results, and in the case of the investigated material, this change in the material state occurs over a range of temperatures. The range of temperatures over which the wax material melts is readily identified by speed of sound represented as a function of material temperature. The melt temperature, obtained acoustically, is validated using Differential Scanning Calorimetry (DSC), which uses shifts in heat flow rates to identify phase transition temperature ranges. The investigated ultrasonic NDE method has direct applications in many industries, including oil and gas, food and beverage, and polymer composites, in addition to many implications for future capabilities of nondestructive inspection of multi-phase materials.

  4. A novel in vitro toxicological approach to identify chemicals with a prostate-mediated effect on male reproduction

    Directory of Open Access Journals (Sweden)

    S. Lorenzetti

    2011-01-01

    Full Text Available Prostate, an overlooked target in in vitro alternative methods, is critical for male fertility. Within the EU project ReProTect, the LNCaP cell line was used as a model system to screen chemicals affecting prostate by a tiered approach integrating two toxicological endpoints: cell viability and PSA secretion. A ReProTect training set of (anti androgenic chemicals affecting reproductive tissues were used. Androgens, and unexpectedly glufosinate ammonium, markedly increased PSA, whereas anti-androgens also increased PSA, but at a much lower magnitude than androgens. Our tiered approach properly discriminated androgenic compounds as well as yielded no false positives, as based on available toxicological evidences. The PSA secretion assay is directly linked to the prostate physiological function and it may integrate the information provided by mechanistic-based assays (i.e. AR binding and gene expression.

  5. A genome-wide approach accounting for body mass index identifies genetic variants influencing fasting glycemic traits and insulin resistance

    DEFF Research Database (Denmark)

    Manning, Alisa K; Hivert, Marie-France; Scott, Robert A

    2012-01-01

    pathways might be uncovered by accounting for differences in body mass index (BMI) and potential interactions between BMI and genetic variants. We applied a joint meta-analysis approach to test associations with fasting insulin and glucose on a genome-wide scale. We present six previously unknown loci...... associated with fasting insulin at P triglyceride and lower high-density lipoprotein (HDL) cholesterol levels, suggesting a role for these loci...

  6. A bottom-up approach to identifying the maximum operational adaptive capacity of water resource systems to a changing climate

    Science.gov (United States)

    Culley, S.; Noble, S.; Yates, A.; Timbs, M.; Westra, S.; Maier, H. R.; Giuliani, M.; Castelletti, A.

    2016-09-01

    Many water resource systems have been designed assuming that the statistical characteristics of future inflows are similar to those of the historical record. This assumption is no longer valid due to large-scale changes in the global climate, potentially causing declines in water resource system performance, or even complete system failure. Upgrading system infrastructure to cope with climate change can require substantial financial outlay, so it might be preferable to optimize existing system performance when possible. This paper builds on decision scaling theory by proposing a bottom-up approach to designing optimal feedback control policies for a water system exposed to a changing climate. This approach not only describes optimal operational policies for a range of potential climatic changes but also enables an assessment of a system's upper limit of its operational adaptive capacity, beyond which upgrades to infrastructure become unavoidable. The approach is illustrated using the Lake Como system in Northern Italy—a regulated system with a complex relationship between climate and system performance. By optimizing system operation under different hydrometeorological states, it is shown that the system can continue to meet its minimum performance requirements for more than three times as many states as it can under current operations. Importantly, a single management policy, no matter how robust, cannot fully utilize existing infrastructure as effectively as an ensemble of flexible management policies that are updated as the climate changes.

  7. An Integrated Approach Identifies Nhlh1 and Insm1 as Sonic Hedgehog-regulated Genes in Developing Cerebellum and Medulloblastoma

    Directory of Open Access Journals (Sweden)

    Enrico De Smaele

    2008-01-01

    Full Text Available Medulloblastoma (MB is the most common malignant brain tumor of childhood arising from deregulated cerebellar development. Sonic Hedgehog (Shh pathway plays a critical role in cerebellar development and its aberrant expression has been identified in MB. Gene expression profiling of cerebella from 1- to 14-day-old mice unveiled a cluster of genes whose expression correlates with the levels of Hedgehog (HH activity. From this cluster, we identified Insm1 and Nhlh1/NSCL1 as novel HH targets induced by Shh treatment in cultured cerebellar granule cell progenitors. Nhlh1 promoter was found to be bound and activated by Gli1 transcription factor. Remarkably, the expression of these genes is also upregulated in mouse and human HH-dependent MBs, suggesting that they may be either a part of the HH-induced tumorigenic process or a specific trait of HH-dependent tumor cells.

  8. Rational approach to identify newer caspase-1 inhibitors using pharmacophore based virtual screening, docking and molecular dynamic simulation studies.

    Science.gov (United States)

    Patel, Shivani; Modi, Palmi; Chhabria, Mahesh

    2018-05-01

    Caspase-1 is a key endoprotease responsible for the post-translational processing of pro-inflammatory cytokines IL-1β, 18 & 33. Excessive secretion of IL-1β leads to numerous inflammatory and autoimmune diseases. Thus caspase-1 inhibition would be considered as an important therapeutic strategy for development of newer anti-inflammatory agents. Here we have employed an integrated virtual screening by combining pharmacophore mapping and docking to identify small molecules as caspase-1 inhibitors. The ligand based 3D pharmacophore model was generated having the essential structural features of (HBA, HY & RA) using a data set of 27 compounds. A validated pharmacophore hypothesis (Hypo 1) was used to screen ZINC and Minimaybridge chemical databases. The retrieved virtual hits were filtered by ADMET properties and molecular docking analysis. Subsequently, the cross-docking study was also carried out using crystal structure of caspase-1, 3, 7 and 8 to identify the key residual interaction for specific caspase-1 inhibition. Finally, the best mapped and top scored (ZINC00885612, ZINC72003647, BTB04175 and BTB04410) molecules were subjected to molecular dynamics simulation for accessing the dynamic structure of protein after ligand binding. This study identifies the most promising hits, which can be leads for the development of novel caspase-1 inhibitors as anti-inflammatory agents. Copyright © 2018 Elsevier Inc. All rights reserved.

  9. Evaluation of direct and indirect ethanol biomarkers using a likelihood ratio approach to identify chronic alcohol abusers for forensic purposes.

    Science.gov (United States)

    Alladio, Eugenio; Martyna, Agnieszka; Salomone, Alberto; Pirro, Valentina; Vincenti, Marco; Zadora, Grzegorz

    2017-02-01

    The detection of direct ethanol metabolites, such as ethyl glucuronide (EtG) and fatty acid ethyl esters (FAEEs), in scalp hair is considered the optimal strategy to effectively recognize chronic alcohol misuses by means of specific cut-offs suggested by the Society of Hair Testing. However, several factors (e.g. hair treatments) may alter the correlation between alcohol intake and biomarkers concentrations, possibly introducing bias in the interpretative process and conclusions. 125 subjects with various drinking habits were subjected to blood and hair sampling to determine indirect (e.g. CDT) and direct alcohol biomarkers. The overall data were investigated using several multivariate statistical methods. A likelihood ratio (LR) approach was used for the first time to provide predictive models for the diagnosis of alcohol abuse, based on different combinations of direct and indirect alcohol biomarkers. LR strategies provide a more robust outcome than the plain comparison with cut-off values, where tiny changes in the analytical results can lead to dramatic divergence in the way they are interpreted. An LR model combining EtG and FAEEs hair concentrations proved to discriminate non-chronic from chronic consumers with ideal correct classification rates, whereas the contribution of indirect biomarkers proved to be negligible. Optimal results were observed using a novel approach that associates LR methods with multivariate statistics. In particular, the combination of LR approach with either Principal Component Analysis (PCA) or Linear Discriminant Analysis (LDA) proved successful in discriminating chronic from non-chronic alcohol drinkers. These LR models were subsequently tested on an independent dataset of 43 individuals, which confirmed their high efficiency. These models proved to be less prone to bias than EtG and FAEEs independently considered. In conclusion, LR models may represent an efficient strategy to sustain the diagnosis of chronic alcohol consumption

  10. Using complementary approaches to identify trans-domain nuclear gene transfers in the extremophile Galdieria sulphuraria (Rhodophyta).

    Science.gov (United States)

    Pandey, Ravi S; Saxena, Garima; Bhattacharya, Debashish; Qiu, Huan; Azad, Rajeev K

    2017-02-01

    Identification of horizontal gene transfers (HGTs) has primarily relied on phylogenetic tree based methods, which require a rich sampling of sequenced genomes to ensure a reliable inference. Because the success of phylogenetic approaches depends on the breadth and depth of the database, researchers usually apply stringent filters to detect only the most likely gene transfers in the genomes of interest. One such study focused on a highly conservative estimate of trans-domain gene transfers in the extremophile eukaryote, Galdieria sulphuraria (Galdieri) Merola (Rhodophyta), by applying multiple filters in their phylogenetic pipeline. This led to the identification of 75 inter-domain acquisitions from Bacteria or Archaea. Because of the evolutionary, ecological, and potential biotechnological significance of foreign genes in algae, alternative approaches and pipelines complementing phylogenetics are needed for a more comprehensive assessment of HGT. We present here a novel pipeline that uncovered 17 novel foreign genes of prokaryotic origin in G. sulphuraria, results that are supported by multiple lines of evidence including composition-based, comparative data, and phylogenetics. These genes encode a variety of potentially adaptive functions, from metabolite transport to DNA repair. © 2016 Phycological Society of America.

  11. Participatory approach to identify interventions to improve the health, safety, and work productivity of smallholder women vegetable farmers in the Gambia.

    Science.gov (United States)

    Vanderwal, Londa; Rautiainen, Risto; Ramirez, Marizen; Kuye, Rex; Peek-Asa, Corinne; Cook, Thomas; Culp, Kennith; Donham, Kelley

    2011-03-01

    This paper describes the qualitative, community-based participatory approach used to identify culturally-acceptable and sustainable interventions to improve the occupational health, safety, and productivity of smallholder women vegetable farmers in The Gambia (West Africa). This approach was used to conduct: 1) analysis of the tasks and methods traditionally used in vegetable production, and 2) selection of interventions. The most arduous garden tasks that were amenable to interventions were identified, and the interventions were selected through a participatory process for further evaluation. Factors contributing to the successful implementation of the participatory approach used in this study included the following: 1) ensuring that cultural norms were respected and observed; 2) working closely with the existing garden leadership structure; and 3) research team members working with the subjects for an extended period of time to gain first-hand understanding of the selected tasks and to build credibility with the subjects.

  12. Aggregator: a machine learning approach to identifying MEDLINE articles that derive from the same underlying clinical trial.

    Science.gov (United States)

    Shao, Weixiang; Adams, Clive E; Cohen, Aaron M; Davis, John M; McDonagh, Marian S; Thakurta, Sujata; Yu, Philip S; Smalheiser, Neil R

    2015-03-01

    It is important to identify separate publications that report outcomes from the same underlying clinical trial, in order to avoid over-counting these as independent pieces of evidence. We created positive and negative training sets (comprised of pairs of articles reporting on the same condition and intervention) that were, or were not, linked to the same clinicaltrials.gov trial registry number. Features were extracted from MEDLINE and PubMed metadata; pairwise similarity scores were modeled using logistic regression. Article pairs from the same trial were identified with high accuracy (F1 score=0.843). We also created a clustering tool, Aggregator, that takes as input a PubMed user query for RCTs on a given topic, and returns article clusters predicted to arise from the same clinical trial. Although painstaking examination of full-text may be needed to be conclusive, metadata are surprisingly accurate in predicting when two articles derive from the same underlying clinical trial. Copyright © 2014 Elsevier Inc. All rights reserved.

  13. IDENTIFYING AND SELECTING THE STRATEGIC PROCESS USING THE CROSS-EFFICIENCY APPROACH BASED ON SATISFACTION LEVEL AND EXTENDDED BALANCED SCORECARD

    Directory of Open Access Journals (Sweden)

    Ardeshir Bazrkar

    2018-03-01

    Full Text Available The strategy is a macro and strategic plan, and will only be implemented when it is defined in the form of various projects. In order to exploit the benefits of lean six sigma projects, these projects should be in line with the strategic goals of the organization. Organizations should select projects which are compatible with the organization overall goals and fulfill the strategic requirements of the organization. The purpose of this study is to identify the strategic process among the bank facility processes to use it in lean six sigma methodology in order to improve process performance and efficiency using a combination of cross-efficiency and extended balanced scorecard methods. In the first step, the criteria for selecting the strategic process were identified using the six measures of the balanced scorecard method. In the second step, after collecting information using the cross-efficiency model based on satisfaction level, the bank facility processes are ranked based on the efficiency score. The results show that the ranking of the processes under consideration is carried out without any interference, and one of the processes (process 3 is considered as the strategic process to use in the six sigma methodology.

  14. A novel ex vivo immunoproteomic approach characterising Fasciola hepatica tegumental antigens identified using immune antibody from resistant sheep.

    Science.gov (United States)

    Cameron, Timothy C; Cooke, Ira; Faou, Pierre; Toet, Hayley; Piedrafita, David; Young, Neil; Rathinasamy, Vignesh; Beddoe, Travis; Anderson, Glenn; Dempster, Robert; Spithill, Terry W

    2017-08-01

    A more thorough understanding of the immunological interactions between Fasciola spp. and their hosts is required if we are to develop new immunotherapies to control fasciolosis. Deeper knowledge of the antigens that are the target of the acquired immune responses of definitive hosts against both Fasciola hepatica and Fasciola gigantica will potentially identify candidate vaccine antigens. Indonesian Thin Tail sheep express a high level of acquired immunity to infection by F. gigantica within 4weeks of infection and antibodies in Indonesian Thin Tail sera can promote antibody-dependent cell-mediated cytotoxicity against the surface tegument of juvenile F. gigantica in vitro. Given the high protein sequence similarity between F. hepatica and F. gigantica, we hypothesised that antibody from F. gigantica-infected sheep could be used to identify the orthologous proteins in the tegument of F. hepatica. Purified IgG from the sera of F. gigantica-infected Indonesian Thin Tail sheep collected pre-infection and 4weeks p.i. were incubated with live adult F. hepatica ex vivo and the immunosloughate (immunoprecipitate) formed was isolated and analysed via liquid chromatography-electrospray ionisation-tandem mass spectrometry to identify proteins involved in the immune response. A total of 38 proteins were identified at a significantly higher abundance in the immunosloughate using week 4 IgG, including eight predicted membrane proteins, 20 secreted proteins, nine proteins predicted to be associated with either the lysosomes, the cytoplasm or the cytoskeleton and one protein with an unknown cellular localization. Three of the membrane proteins are transporters including a multidrug resistance protein, an amino acid permease and a glucose transporter. Interestingly, a total of 21 of the 38 proteins matched with proteins recently reported to be associated with the proposed small exosome-like extracellular vesicles of adult F. hepatica, suggesting that the Indonesian Thin Tail week

  15. A COMBINED FUZZY MCDM APPROACH FOR IDENTIFYING THE SUITABLE LANDS FOR URBAN DEVELOPMENT: AN EXAMPLE FROM BANDAR ABBS, IRAN

    Directory of Open Access Journals (Sweden)

    Mohsen Dadras

    2014-01-01

    Full Text Available This study aims at identifying the suitable lands for urban dev elopment in Bandar Abbas city based on its real world use regarding specific crite ria and sub-criteria. The city of Bandar Abbas is considered as the most important commer cial and economic city of Iran. It is also considered as one of the major cities of Iran which has played a pivotal role in the country's development and progress in recen t years especially after the end of Iran-Iraq war owing to its embracing the country's m ain commercial ports. This process has caused the immigration rate into the city to rise significantly over the past 20 years. Thus, the development of the city is meanwhile c onsidered as a high priority. Bandar Abbas city does not have a rich capacity for g rowth and development due to its special geographical situation being located in coastal border. Among the limitations placed in the city's development way, natural limit ations (heights and sea shore in the northern and southern parts of the city and struc tural limitations (military centers in the east and west sides of the city may be referred . Therefore, identifying the suitable lands for urban development within Bandar Abbas city l imits is becoming an essential priority. Therefore, d ifferent quantitative and quali tative criteria have been studied in order to select and identify these lands. The struct ures of qualitative criteria for most parts involve ambiguities and vagueness. This leads us to use Fuzzy logic in this study as a natural method for determining the solutions fo r problems of Multi- criteria decision making (MCDM. In the current research, a com bination of MCDM methods has been presented for analysis. To assignee weights of the criteria Fuzzy AHP (analytic hierarchy process is used for land selection and Fuzzy TOPSIS (method for order priority by similarity to ideal solution is utilized to choose the alternative that is the most appropriate through these criteria weights. The

  16. Multiproxies (benthic foraminifera, ostracods and biopolymers approach applied to identify the environmental partitioning of the Guadiana River Estuary (Iberian Peninsula

    Directory of Open Access Journals (Sweden)

    Lazaro Luiz Mattos Laut

    2016-04-01

    Full Text Available The Guadiana River is the fourth longest river in Europe and is a natural frontier between southern Portugal and Spain. This river was historically used to transport minerals exploited in the region since the Roman Empire and therefore suffered human interventions that have been intensified after the industrial revolution. The Guadiana River has in its limits the Guadiana Valley Natural Park, which is of great value for the Conservation of Geobiodiversity. This study mainly aims to identify zones with the environmental characteristics in the estuarine area of the Guadiana River based on the distribution and ecology of microorganisms (ostracods and foraminifera associated with physicochemical parameters and sedimentological and geochemical (carbohydrate, lipid, protein, total organic carbon and total sulfur data. Fifty-five foraminifera taxa were identified along the estuary with dominance of Ammonia tepida and Miliammina fusca and 13 ostracods taxa with dominance Leptocythere lacertosa and Loxoconcha elliptica. Detrended correspondence analysis (DCA performed using biotic and abiotic variables indicated that pH, grain size, total organic carbon (TOC and lipids were the most influent factors in the distribution of these organisms. Four zones were identified in the Guadiana River estuary: i Low estuary - region with the largest marine influence with sandy sediment, higher salinity and total sulfur and mainly represented by the dominance of estuarine species of foraminifera (Ammonia tepida and Cribroelphidium vadescens and by the ostracods (Darwinula stevensoni, Semicytherura sulcata and Urocythereis oblonga; ii Intermediate estuary - region characterized by neutral pH and sandy sediment enriched in carbohydrates; this region is characterized by the presence of the ostracods species Cytherois fischeri and Neocytherideis subulata and by calcareous and agglutinated species in foraminiferal assemblages; iii Upper estuary - silt, high TOC, proteins and

  17. Identifying patients suitable for palliative care - a descriptive analysis of enquiries using a Case Management Process Model approach

    Directory of Open Access Journals (Sweden)

    Kuhn Ulrike

    2012-11-01

    Full Text Available Abstract Background In Germany, case management in a palliative care unit was first implemented in 2005 at the Department of Palliative Medicine at the University Hospital Cologne. One of the purposes of this case management is to deal with enquiries from patients and their relatives as well as medical professionals. Using the Case Management Process Model of the Case Management Society of America as a reference, this study analysed (a how this case management was used by different enquiring groups and (b how patients were identified for case management and for palliative care services. The first thousand enquiries were analysed considering patient variables, properties of the enquiring persons and the content of the consultations. Results Most enquiries to the case management were made by telephone. The majority of requests regarded patients with oncological disease (84.3 %. The largest enquiring group was composed of patients and relatives (40.8 %, followed by internal professionals of the hospital (36.1 %. Most of the enquiring persons asked for a patient’s admission to the palliative care ward (46.4 %. The second most frequent request was for consultation and advice (30.9 %, followed by requests for the palliative home care service (13.3 %. Frequent reasons for actual admissions were the need for the treatment of pain, the presence of symptoms and the need for nursing care. More than half of the enquiries concerning admission to the palliative care ward were followed by an admission. Conclusions Case management has been made public among the relevant target groups. Case management as described by the Case Management Process Model helps to identify patients likely to benefit from case management and palliative care services. In addition, with the help of case management palliative patients may be allocated to particular health care services.

  18. A Microbial Signature Approach to Identify Fecal Pollution in the Waters Off an Urbanized Coast of Lake Michigan

    Science.gov (United States)

    Newton, Ryan J.; Bootsma, Melinda J.; Morrison, Hilary G.; Sogin, Mitchell L.

    2014-01-01

    Urban coasts receive watershed drainage from ecosystems that include highly developed lands with sewer and stormwater infrastructure. In these complex ecosystems, coastal waters are often contaminated with fecal pollution, where multiple delivery mechanisms that often contain multiple fecal sources make it difficult to mitigate the pollution. Here, we exploit bacterial community sequencing of the V6 and V6V4 hypervariable regions of the bacterial 16S rRNA gene to identify bacterial distributions that signal the presence of sewer, fecal, and human fecal pollution. The sequences classified to three sewer infrastructure-associated bacterial genera, Acinetobacter, Arcobacter, and Trichococcus, and five fecal-associated bacterial families, Bacteroidaceae, Porphyromonadaceae, Clostridiaceae, Lachnospiraceae, and Ruminococcaceae, served as signatures of sewer and fecal contamination, respectively. The human fecal signature was determined with the Bayesian source estimation program SourceTracker, which we applied to a set of 40 sewage influent samples collected in Milwaukee, WI, USA to identify operational taxonomic units (≥97 % identity) that were most likely of human fecal origin. During periods of dry weather, the magnitudes of all three signatures were relatively low in Milwaukee's urban rivers and harbor and nearly zero in Lake Michigan. However, the relative contribution of the sewer and fecal signature frequently increased to >2 % of the measured surface water communities following sewer overflows. Also during combined sewer overflows, the ratio of the human fecal pollution signature to the fecal pollution signature in surface waters was generally close to that of sewage, but this ratio decreased dramatically during dry weather and rain events, suggesting that nonhuman fecal pollution was the dominant source during these weather-driven scenarios. The qPCR detection of two human fecal indicators, human Bacteroides and Lachno2, confirmed the urban fecal footprint in

  19. Multimorbidity Patterns in the Elderly: A New Approach of Disease Clustering Identifies Complex Interrelations between Chronic Conditions

    Science.gov (United States)

    Schäfer, Ingmar; von Leitner, Eike-Christin; Schön, Gerhard; Koller, Daniela; Hansen, Heike; Kolonko, Tina; Kaduszkiewicz, Hanna; Wegscheider, Karl; Glaeske, Gerd; van den Bussche, Hendrik

    2010-01-01

    Objective Multimorbidity is a common problem in the elderly that is significantly associated with higher mortality, increased disability and functional decline. Information about interactions of chronic diseases can help to facilitate diagnosis, amend prevention and enhance the patients' quality of life. The aim of this study was to increase the knowledge of specific processes of multimorbidity in an unselected elderly population by identifying patterns of statistically significantly associated comorbidity. Methods Multimorbidity patterns were identified by exploratory tetrachoric factor analysis based on claims data of 63,104 males and 86,176 females in the age group 65+. Analyses were based on 46 diagnosis groups incorporating all ICD-10 diagnoses of chronic diseases with a prevalence ≥ 1%. Both genders were analyzed separately. Persons were assigned to multimorbidity patterns if they had at least three diagnosis groups with a factor loading of 0.25 on the corresponding pattern. Results Three multimorbidity patterns were found: 1) cardiovascular/metabolic disorders [prevalence female: 30%; male: 39%], 2) anxiety/depression/somatoform disorders and pain [34%; 22%], and 3) neuropsychiatric disorders [6%; 0.8%]. The sampling adequacy was meritorious (Kaiser-Meyer-Olkin measure: 0.85 and 0.84, respectively) and the factors explained a large part of the variance (cumulative percent: 78% and 75%, respectively). The patterns were largely age-dependent and overlapped in a sizeable part of the population. Altogether 50% of female and 48% of male persons were assigned to at least one of the three multimorbidity patterns. Conclusion This study shows that statistically significant co-occurrence of chronic diseases can be subsumed in three prevalent multimorbidity patterns if accounting for the fact that different multimorbidity patterns share some diagnosis groups, influence each other and overlap in a large part of the population. In recognizing the full complexity of

  20. Multimorbidity patterns in the elderly: a new approach of disease clustering identifies complex interrelations between chronic conditions.

    Directory of Open Access Journals (Sweden)

    Ingmar Schäfer

    Full Text Available OBJECTIVE: Multimorbidity is a common problem in the elderly that is significantly associated with higher mortality, increased disability and functional decline. Information about interactions of chronic diseases can help to facilitate diagnosis, amend prevention and enhance the patients' quality of life. The aim of this study was to increase the knowledge of specific processes of multimorbidity in an unselected elderly population by identifying patterns of statistically significantly associated comorbidity. METHODS: Multimorbidity patterns were identified by exploratory tetrachoric factor analysis based on claims data of 63,104 males and 86,176 females in the age group 65+. Analyses were based on 46 diagnosis groups incorporating all ICD-10 diagnoses of chronic diseases with a prevalence ≥ 1%. Both genders were analyzed separately. Persons were assigned to multimorbidity patterns if they had at least three diagnosis groups with a factor loading of 0.25 on the corresponding pattern. RESULTS: Three multimorbidity patterns were found: 1 cardiovascular/metabolic disorders [prevalence female: 30%; male: 39%], 2 anxiety/depression/somatoform disorders and pain [34%; 22%], and 3 neuropsychiatric disorders [6%; 0.8%]. The sampling adequacy was meritorious (Kaiser-Meyer-Olkin measure: 0.85 and 0.84, respectively and the factors explained a large part of the variance (cumulative percent: 78% and 75%, respectively. The patterns were largely age-dependent and overlapped in a sizeable part of the population. Altogether 50% of female and 48% of male persons were assigned to at least one of the three multimorbidity patterns. CONCLUSION: This study shows that statistically significant co-occurrence of chronic diseases can be subsumed in three prevalent multimorbidity patterns if accounting for the fact that different multimorbidity patterns share some diagnosis groups, influence each other and overlap in a large part of the population. In recognizing the

  1. Identifying Effective Design Approaches to Allocate Genotypes in Two-Phase Designs: A Case Study in Pelargonium zonale

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    Heike Molenaar

    2018-01-01

    Full Text Available Robust phenotypic data allow adequate statistical analysis and are crucial for any breeding purpose. Such data is obtained from experiments laid out to best control local variation. Additionally, experiments frequently involve two phases, each contributing environmental sources of variation. For example, in a former experiment we conducted to evaluate production related traits in Pelargonium zonale, there were two consecutive phases, each performed in a different greenhouse. Phase one involved the propagation of the breeding strains to obtain the stem cutting count, and phase two involved the assessment of root formation. The evaluation of the former study raised questions regarding options for improving the experimental layout: (i Is there a disadvantage to using exactly the same design in both phases? (ii Instead of generating a separate layout for each phase, can the design be optimized across both phases, such that the mean variance of a pair-wise treatment difference (MVD can be decreased? To answer these questions, alternative approaches were explored to generate two-phase designs either in phase-wise order (Option 1 or across phases (Option 2. In Option 1 we considered the scenarios (i using in both phases the same experimental design and (ii randomizing each phase separately. In Option 2, we considered the scenarios (iii generating a single design with eight replicates and splitting these among the two phases, (iv separating the block structure across phases by dummy coding, and (v design generation with optimal alignment of block units in the two phases. In both options, we considered the same or different block structures in each phase. The designs were evaluated by the MVD obtained by the intra-block analysis and the joint inter-block–intra-block analysis. The smallest MVD was most frequently obtained for designs generated across phases rather than for each phase separately, in particular when both phases of the design were

  2. Identifying Effective Design Approaches to Allocate Genotypes in Two-Phase Designs: A Case Study in Pelargonium zonale.

    Science.gov (United States)

    Molenaar, Heike; Boehm, Robert; Piepho, Hans-Peter

    2017-01-01

    Robust phenotypic data allow adequate statistical analysis and are crucial for any breeding purpose. Such data is obtained from experiments laid out to best control local variation. Additionally, experiments frequently involve two phases, each contributing environmental sources of variation. For example, in a former experiment we conducted to evaluate production related traits in Pelargonium zonale , there were two consecutive phases, each performed in a different greenhouse. Phase one involved the propagation of the breeding strains to obtain the stem cutting count, and phase two involved the assessment of root formation. The evaluation of the former study raised questions regarding options for improving the experimental layout: (i) Is there a disadvantage to using exactly the same design in both phases? (ii) Instead of generating a separate layout for each phase, can the design be optimized across both phases, such that the mean variance of a pair-wise treatment difference (MVD) can be decreased? To answer these questions, alternative approaches were explored to generate two-phase designs either in phase-wise order (Option 1) or across phases (Option 2). In Option 1 we considered the scenarios (i) using in both phases the same experimental design and (ii) randomizing each phase separately. In Option 2, we considered the scenarios (iii) generating a single design with eight replicates and splitting these among the two phases, (iv) separating the block structure across phases by dummy coding, and (v) design generation with optimal alignment of block units in the two phases. In both options, we considered the same or different block structures in each phase. The designs were evaluated by the MVD obtained by the intra-block analysis and the joint inter-block-intra-block analysis. The smallest MVD was most frequently obtained for designs generated across phases rather than for each phase separately, in particular when both phases of the design were separated with a

  3. A New Approach to Identify Optimal Properties of Shunting Elements for Maximum Damping of Structural Vibration Using Piezoelectric Patches

    Science.gov (United States)

    Park, Junhong; Palumbo, Daniel L.

    2004-01-01

    The use of shunted piezoelectric patches in reducing vibration and sound radiation of structures has several advantages over passive viscoelastic elements, e.g., lower weight with increased controllability. The performance of the piezoelectric patches depends on the shunting electronics that are designed to dissipate vibration energy through a resistive element. In past efforts most of the proposed tuning methods were based on modal properties of the structure. In these cases, the tuning applies only to one mode of interest and maximum tuning is limited to invariant points when based on den Hartog's invariant points concept. In this study, a design method based on the wave propagation approach is proposed. Optimal tuning is investigated depending on the dynamic and geometric properties that include effects from boundary conditions and position of the shunted piezoelectric patch relative to the structure. Active filters are proposed as shunting electronics to implement the tuning criteria. The developed tuning methods resulted in superior capabilities in minimizing structural vibration and noise radiation compared to other tuning methods. The tuned circuits are relatively insensitive to changes in modal properties and boundary conditions, and can applied to frequency ranges in which multiple modes have effects.

  4. A genome-wide approach accounting for body mass index identifies genetic variants influencing fasting glycemic traits and insulin resistance

    Science.gov (United States)

    Manning, Alisa K.; Hivert, Marie-France; Scott, Robert A.; Grimsby, Jonna L.; Bouatia-Naji, Nabila; Chen, Han; Rybin, Denis; Liu, Ching-Ti; Bielak, Lawrence F.; Prokopenko, Inga; Amin, Najaf; Barnes, Daniel; Cadby, Gemma; Hottenga, Jouke-Jan; Ingelsson, Erik; Jackson, Anne U.; Johnson, Toby; Kanoni, Stavroula; Ladenvall, Claes; Lagou, Vasiliki; Lahti, Jari; Lecoeur, Cecile; Liu, Yongmei; Martinez-Larrad, Maria Teresa; Montasser, May E.; Navarro, Pau; Perry, John R. B.; Rasmussen-Torvik, Laura J.; Salo, Perttu; Sattar, Naveed; Shungin, Dmitry; Strawbridge, Rona J.; Tanaka, Toshiko; van Duijn, Cornelia M.; An, Ping; de Andrade, Mariza; Andrews, Jeanette S.; Aspelund, Thor; Atalay, Mustafa; Aulchenko, Yurii; Balkau, Beverley; Bandinelli, Stefania; Beckmann, Jacques S.; Beilby, John P.; Bellis, Claire; Bergman, Richard N.; Blangero, John; Boban, Mladen; Boehnke, Michael; Boerwinkle, Eric; Bonnycastle, Lori L.; Boomsma, Dorret I.; Borecki, Ingrid B.; Böttcher, Yvonne; Bouchard, Claude; Brunner, Eric; Budimir, Danijela; Campbell, Harry; Carlson, Olga; Chines, Peter S.; Clarke, Robert; Collins, Francis S.; Corbatón-Anchuelo, Arturo; Couper, David; de Faire, Ulf; Dedoussis, George V; Deloukas, Panos; Dimitriou, Maria; Egan, Josephine M; Eiriksdottir, Gudny; Erdos, Michael R.; Eriksson, Johan G.; Eury, Elodie; Ferrucci, Luigi; Ford, Ian; Forouhi, Nita G.; Fox, Caroline S; Franzosi, Maria Grazia; Franks, Paul W; Frayling, Timothy M; Froguel, Philippe; Galan, Pilar; de Geus, Eco; Gigante, Bruna; Glazer, Nicole L.; Goel, Anuj; Groop, Leif; Gudnason, Vilmundur; Hallmans, Göran; Hamsten, Anders; Hansson, Ola; Harris, Tamara B.; Hayward, Caroline; Heath, Simon; Hercberg, Serge; Hicks, Andrew A.; Hingorani, Aroon; Hofman, Albert; Hui, Jennie; Hung, Joseph; Jarvelin, Marjo Riitta; Jhun, Min A.; Johnson, Paul C.D.; Jukema, J Wouter; Jula, Antti; Kao, W.H.; Kaprio, Jaakko; Kardia, Sharon L. R.; Keinanen-Kiukaanniemi, Sirkka; Kivimaki, Mika; Kolcic, Ivana; Kovacs, Peter; Kumari, Meena; Kuusisto, Johanna; Kyvik, Kirsten Ohm; Laakso, Markku; Lakka, Timo; Lannfelt, Lars; Lathrop, G Mark; Launer, Lenore J.; Leander, Karin; Li, Guo; Lind, Lars; Lindstrom, Jaana; Lobbens, Stéphane; Loos, Ruth J. F.; Luan, Jian’an; Lyssenko, Valeriya; Mägi, Reedik; Magnusson, Patrik K. E.; Marmot, Michael; Meneton, Pierre; Mohlke, Karen L.; Mooser, Vincent; Morken, Mario A.; Miljkovic, Iva; Narisu, Narisu; O’Connell, Jeff; Ong, Ken K.; Oostra, Ben A.; Palmer, Lyle J.; Palotie, Aarno; Pankow, James S.; Peden, John F.; Pedersen, Nancy L.; Pehlic, Marina; Peltonen, Leena; Penninx, Brenda; Pericic, Marijana; Perola, Markus; Perusse, Louis; Peyser, Patricia A; Polasek, Ozren; Pramstaller, Peter P.; Province, Michael A.; Räikkönen, Katri; Rauramaa, Rainer; Rehnberg, Emil; Rice, Ken; Rotter, Jerome I.; Rudan, Igor; Ruokonen, Aimo; Saaristo, Timo; Sabater-Lleal, Maria; Salomaa, Veikko; Savage, David B.; Saxena, Richa; Schwarz, Peter; Seedorf, Udo; Sennblad, Bengt; Serrano-Rios, Manuel; Shuldiner, Alan R.; Sijbrands, Eric J.G.; Siscovick, David S.; Smit, Johannes H.; Small, Kerrin S.; Smith, Nicholas L.; Smith, Albert Vernon; Stančáková, Alena; Stirrups, Kathleen; Stumvoll, Michael; Sun, Yan V.; Swift, Amy J.; Tönjes, Anke; Tuomilehto, Jaakko; Trompet, Stella; Uitterlinden, Andre G.; Uusitupa, Matti; Vikström, Max; Vitart, Veronique; Vohl, Marie-Claude; Voight, Benjamin F.; Vollenweider, Peter; Waeber, Gerard; Waterworth, Dawn M; Watkins, Hugh; Wheeler, Eleanor; Widen, Elisabeth; Wild, Sarah H.; Willems, Sara M.; Willemsen, Gonneke; Wilson, James F.; Witteman, Jacqueline C.M.; Wright, Alan F.; Yaghootkar, Hanieh; Zelenika, Diana; Zemunik, Tatijana; Zgaga, Lina; Wareham, Nicholas J.; McCarthy, Mark I.; Barroso, Ines; Watanabe, Richard M.; Florez, Jose C.; Dupuis, Josée; Meigs, James B.; Langenberg, Claudia

    2013-01-01

    Recent genome-wide association studies have described many loci implicated in type 2 diabetes (T2D) pathophysiology and beta-cell dysfunction, but contributed little to our understanding of the genetic basis of insulin resistance. We hypothesized that genes implicated in insulin resistance pathways may be uncovered by accounting for differences in body mass index (BMI) and potential interaction between BMI and genetic variants. We applied a novel joint meta-analytical approach to test associations with fasting insulin (FI) and glucose (FG) on a genome-wide scale. We present six previously unknown FI loci at P<5×10−8 in combined discovery and follow-up analyses of 52 studies comprising up to 96,496non-diabetic individuals. Risk variants were associated with higher triglyceride and lower HDL cholesterol levels, suggestive of a role for these FI loci in insulin resistance pathways. The localization of these additional loci will aid further characterization of the role of insulin resistance in T2D pathophysiology. PMID:22581228

  5. Community landscapes: an integrative approach to determine overlapping network module hierarchy, identify key nodes and predict network dynamics.

    Directory of Open Access Journals (Sweden)

    István A Kovács

    Full Text Available BACKGROUND: Network communities help the functional organization and evolution of complex networks. However, the development of a method, which is both fast and accurate, provides modular overlaps and partitions of a heterogeneous network, has proven to be rather difficult. METHODOLOGY/PRINCIPAL FINDINGS: Here we introduce the novel concept of ModuLand, an integrative method family determining overlapping network modules as hills of an influence function-based, centrality-type community landscape, and including several widely used modularization methods as special cases. As various adaptations of the method family, we developed several algorithms, which provide an efficient analysis of weighted and directed networks, and (1 determine persvasively overlapping modules with high resolution; (2 uncover a detailed hierarchical network structure allowing an efficient, zoom-in analysis of large networks; (3 allow the determination of key network nodes and (4 help to predict network dynamics. CONCLUSIONS/SIGNIFICANCE: The concept opens a wide range of possibilities to develop new approaches and applications including network routing, classification, comparison and prediction.

  6. A robust approach to identifying tissue-specific gene expression regulatory variants using personalized human induced pluripotent stem cells.

    Directory of Open Access Journals (Sweden)

    Je-Hyuk Lee

    2009-11-01

    Full Text Available Normal variation in gene expression due to regulatory polymorphisms is often masked by biological and experimental noise. In addition, some regulatory polymorphisms may become apparent only in specific tissues. We derived human induced pluripotent stem (iPS cells from adult skin primary fibroblasts and attempted to detect tissue-specific cis-regulatory variants using in vitro cell differentiation. We used padlock probes and high-throughput sequencing for digital RNA allelotyping and measured allele-specific gene expression in primary fibroblasts, lymphoblastoid cells, iPS cells, and their differentiated derivatives. We show that allele-specific expression is both cell type and genotype-dependent, but the majority of detectable allele-specific expression loci remains consistent despite large changes in the cell type or the experimental condition following iPS reprogramming, except on the X-chromosome. We show that our approach to mapping cis-regulatory variants reduces in vitro experimental noise and reveals additional tissue-specific variants using skin-derived human iPS cells.

  7. The Compositional HJ-Biplot—A New Approach to Identifying the Links among Bioactive Compounds of Tomatoes

    Directory of Open Access Journals (Sweden)

    Marcos Hernández Suárez

    2016-11-01

    Full Text Available Tomatoes have been described as a functional food because of their particular composition of different bioactive compounds. In this study, the proximate composition, minerals and trace elements, and antioxidant compounds were determined in two tomato cultivars (Mariana and Dunkan that were grown in Gran Canaria (Spain either conventionally or hydroponically. Although compositional data of this type require being subjected to the specific statistical techniques of compositional analysis, this approach has not usually been considered in this context. In the present case, a compositional Mann–Whitney U test of the data showed significant differences for each factor (cultivar and cultivation system in several of the compositional variables studied. For the differences between cultivars, these parameters were the protein, Mg, lycopene, ascorbic acid, citric acid, and fumaric acid contents. For the differences between cultivation systems, they were mainly those of the mineral and trace elements group. Although one-year data are insufficient to make clear relationship among compounds because more repetitions in several localities and years are necessary, the compositional HJ-biplot (in which the links provide estimates of the linear relationship among variables results agreed with other scientific results about linear relationship among some compounds analyzed.

  8. Identifying ecological "sweet spots" underlying cyanobacteria functional group dynamics from long-term observations using a statistical machine learning approach

    Science.gov (United States)

    Nelson, N.; Munoz-Carpena, R.; Phlips, E. J.

    2017-12-01

    Diversity in the eco-physiological adaptations of cyanobacteria genera creates challenges for water managers who are tasked with developing appropriate actions for controlling not only the intensity and frequency of cyanobacteria blooms, but also reducing the potential for blooms of harmful taxa (e.g., toxin producers, N2 fixers). Compounding these challenges, the efficacy of nutrient management strategies (phosphorus-only versus nitrogen-and-phosphorus) for cyanobacteria bloom abatement is the subject of an ongoing debate, which increases uncertainty associated with bloom mitigation decision-making. In this work, we analyze a unique long-term (17-year) dataset composed of monthly observations of cyanobacteria genera abundances, zooplankton abundances, water quality, and flow from Lake George, a bloom-impacted flow-through lake of the St. Johns River (FL, USA). Using the Random Forests machine learning algorithm, an assumption-free ensemble modeling approach, the dataset was evaluated to quantify and characterize relationships between environmental conditions and seven cyanobacteria groupings: five genera (Anabaena, Cylindrospermopsis, Lyngbya, Microcystis, and Oscillatoria) and two functional groups (N2 fixers and non-fixers). Results highlight the selectivity of nitrogen in describing genera and functional group dynamics, and potential for physical effects to limit the efficacy of nutrient management as a mechanism for cyanobacteria bloom mitigation.

  9. How do new dams impact downstream countries? - A screening approach to identify the best compromise assets and negotiate their designs

    Science.gov (United States)

    Geressu, Robel; Harou, Julien

    2015-04-01

    Water use rights are disputed in many transboundary basins. Even when water projects can benefit all, agreeing on cost and benefit sharing can be difficult where stakeholders have conflicting preferences on the designs and use of proposed water infrastructures. This study suggests a combination of many objective optimization and multi-criteria ranking methods to support negotiations regarding designs of new assets. The method allows competing users to assess development options based on their individual perspectives and agree on designs by incorporating coordination strategies into multi-reservoir system designs. We demonstrate a hypothetical negotiation on proposed Blue Nile reservoirs. The result form a set of Pareto-optimal designs i.e., reservoirs, storage capacity and their operating rules, and power trade, cost sharing and/or financing coordination strategies, which maximize benefit to all countries and show which trade-offs are implied by which designs. The approach fulfils decision-maker's desire to understand a) the critical design parameters that affect various objectives and b) how coordination mechanisms would enable them to incur benefits from proposed new dams.

  10. Geomfinder: a multi-feature identifier of similar three-dimensional protein patterns: a ligand-independent approach.

    Science.gov (United States)

    Núñez-Vivanco, Gabriel; Valdés-Jiménez, Alejandro; Besoaín, Felipe; Reyes-Parada, Miguel

    2016-01-01

    Since the structure of proteins is more conserved than the sequence, the identification of conserved three-dimensional (3D) patterns among a set of proteins, can be important for protein function prediction, protein clustering, drug discovery and the establishment of evolutionary relationships. Thus, several computational applications to identify, describe and compare 3D patterns (or motifs) have been developed. Often, these tools consider a 3D pattern as that described by the residues surrounding co-crystallized/docked ligands available from X-ray crystal structures or homology models. Nevertheless, many of the protein structures stored in public databases do not provide information about the location and characteristics of ligand binding sites and/or other important 3D patterns such as allosteric sites, enzyme-cofactor interaction motifs, etc. This makes necessary the development of new ligand-independent methods to search and compare 3D patterns in all available protein structures. Here we introduce Geomfinder, an intuitive, flexible, alignment-free and ligand-independent web server for detailed estimation of similarities between all pairs of 3D patterns detected in any two given protein structures. We used around 1100 protein structures to form pairs of proteins which were assessed with Geomfinder. In these analyses each protein was considered in only one pair (e.g. in a subset of 100 different proteins, 50 pairs of proteins can be defined). Thus: (a) Geomfinder detected identical pairs of 3D patterns in a series of monoamine oxidase-B structures, which corresponded to the effectively similar ligand binding sites at these proteins; (b) we identified structural similarities among pairs of protein structures which are targets of compounds such as acarbose, benzamidine, adenosine triphosphate and pyridoxal phosphate; these similar 3D patterns are not detected using sequence-based methods; (c) the detailed evaluation of three specific cases showed the versatility

  11. A systems toxicology approach identifies Lyn as a key signaling phosphoprotein modulated by mercury in a B lymphocyte cell model

    Energy Technology Data Exchange (ETDEWEB)

    Caruso, Joseph A.; Stemmer, Paul M. [Institute of Environmental Health Sciences, Wayne State University, Detroit, MI (United States); Dombkowski, Alan [Department of Pediatrics, Wayne State University, Detroit, MI (United States); Caruthers, Nicholas J. [Institute of Environmental Health Sciences, Wayne State University, Detroit, MI (United States); Gill, Randall [Department of Immunology and Microbiology, Wayne State University, Detroit, MI (United States); Rosenspire, Allen J., E-mail: arosenspire@wayne.edu [Department of Immunology and Microbiology, Wayne State University, Detroit, MI (United States)

    2014-04-01

    Network and protein–protein interaction analyses of proteins undergoing Hg{sup 2+}-induced phosphorylation and dephosphorylation in Hg{sup 2+}-intoxicated mouse WEHI-231 B cells identified Lyn as the most interconnected node. Lyn is a Src family protein tyrosine kinase known to be intimately involved in the B cell receptor (BCR) signaling pathway. Under normal signaling conditions the tyrosine kinase activity of Lyn is controlled by phosphorylation, primarily of two well known canonical regulatory tyrosine sites, Y-397 and Y-508. However, Lyn has several tyrosine residues that have not yet been determined to play a major role under normal signaling conditions, but are potentially important sites for phosphorylation following mercury exposure. In order to determine how Hg{sup 2+} exposure modulates the phosphorylation of additional residues in Lyn, a targeted MS assay was developed. Initial mass spectrometric surveys of purified Lyn identified 7 phosphorylated tyrosine residues. A quantitative assay was developed from these results using the multiple reaction monitoring (MRM) strategy. WEHI-231 cells were treated with Hg{sup 2+}, pervanadate (a phosphatase inhibitor), or anti-Ig antibody (to stimulate the BCR). Results from these studies showed that the phosphoproteomic profile of Lyn after exposure of the WEHI-231 cells to a low concentration of Hg{sup 2+} closely resembled that of anti-Ig antibody stimulation, whereas exposure to higher concentrations of Hg{sup 2+} led to increases in the phosphorylation of Y-193/Y-194, Y-501 and Y-508 residues. These data indicate that mercury can disrupt a key regulatory signal transduction pathway in B cells and point to phospho-Lyn as a potential biomarker for mercury exposure. - Highlights: • Inorganic mercury (Hg{sup 2+}) induces changes in the WEHI-231 B cell phosphoproteome. • The B cell receptor (BCR) signaling pathway was the pathway most affected by Hg{sup 2+}. • The Src family phosphoprotein kinase Lyn was the

  12. A metagenomic viral discovery approach identifies potential zoonotic and novel mammalian viruses in Neoromicia bats within South Africa.

    Science.gov (United States)

    Geldenhuys, Marike; Mortlock, Marinda; Weyer, Jacqueline; Bezuidt, Oliver; Seamark, Ernest C J; Kearney, Teresa; Gleasner, Cheryl; Erkkila, Tracy H; Cui, Helen; Markotter, Wanda

    2018-01-01

    Species within the Neoromicia bat genus are abundant and widely distributed in Africa. It is common for these insectivorous bats to roost in anthropogenic structures in urban regions. Additionally, Neoromicia capensis have previously been identified as potential hosts for Middle East respiratory syndrome (MERS)-related coronaviruses. This study aimed to ascertain the gastrointestinal virome of these bats, as viruses excreted in fecal material or which may be replicating in rectal or intestinal tissues have the greatest opportunities of coming into contact with other hosts. Samples were collected in five regions of South Africa over eight years. Initial virome composition was determined by viral metagenomic sequencing by pooling samples and enriching for viral particles. Libraries were sequenced on the Illumina MiSeq and NextSeq500 platforms, producing a combined 37 million reads. Bioinformatics analysis of the high throughput sequencing data detected the full genome of a novel species of the Circoviridae family, and also identified sequence data from the Adenoviridae, Coronaviridae, Herpesviridae, Parvoviridae, Papillomaviridae, Phenuiviridae, and Picornaviridae families. Metagenomic sequencing data was insufficient to determine the viral diversity of certain families due to the fragmented coverage of genomes and lack of suitable sequencing depth, as some viruses were detected from the analysis of reads-data only. Follow up conventional PCR assays targeting conserved gene regions for the Adenoviridae, Coronaviridae, and Herpesviridae families were used to confirm metagenomic data and generate additional sequences to determine genetic diversity. The complete coding genome of a MERS-related coronavirus was recovered with additional amplicon sequencing on the MiSeq platform. The new genome shared 97.2% overall nucleotide identity to a previous Neoromicia-associated MERS-related virus, also from South Africa. Conventional PCR analysis detected diverse adenovirus and

  13. A GIS-based approach for identifying potential runoff harvesting sites in the Thukela River basin, South Africa

    Science.gov (United States)

    de Winnaar, G.; Jewitt, G. P. W.; Horan, M.

    Water scarce countries such as South Africa are subject to various hydrological constraints which can often be attributed to poor rainfall partitioning, particularly within resource poor farming communities that are reliant on rainfed agriculture. Recent initiatives to address this have shifted focus to explore more efficient alternatives to water supply and the recognition of numerous opportunities to implement runoff harvesting as a means to supplement water availability. However, increasing the implementation of runoff harvesting, without encountering unintended impacts on downstream hydrological and ecological systems, requires better understanding of the hydrologic and environmental impacts at catchment scale. In this paper the representation of spatial variations in landscape characteristics such as soil, land use, rainfall and slope information is shown to be an important step in identifying potential runoff harvesting sites, after which modelling the hydrological response in catchments where extensive runoff harvesting is being considered can be performed and likely impacts assessed. Geographic information systems (GIS) was utilised as an integrating tool to store, analyse and manage spatial information and when linked to hydrological response models, provided a rational means to facilitate decision making by providing catchment level identification, planning and assessment of runoff harvesting sites as illustrated by a case study at the Potshini catchment, a small sub-catchment in the Thukela River basin, South Africa. Through the linked GIS, potential runoff harvesting sites are identified relative to areas that concentrate runoff and where the stored water will be appropriately distributed. Based on GIS analysis it was found that 17% percent of the Potshini catchment area has a high potential for generating surface runoff, whereas an analysis of all factors which influence the location of such systems, shows that 18% is highly suitable for runoff

  14. Identifying a clinical signature of suicidality among patients with mood disorders: A pilot study using a machine learning approach.

    Science.gov (United States)

    Passos, Ives Cavalcante; Mwangi, Benson; Cao, Bo; Hamilton, Jane E; Wu, Mon-Ju; Zhang, Xiang Yang; Zunta-Soares, Giovana B; Quevedo, Joao; Kauer-Sant'Anna, Marcia; Kapczinski, Flávio; Soares, Jair C

    2016-03-15

    A growing body of evidence has put forward clinical risk factors associated with patients with mood disorders that attempt suicide. However, what is not known is how to integrate clinical variables into a clinically useful tool in order to estimate the probability of an individual patient attempting suicide. A total of 144 patients with mood disorders were included. Clinical variables associated with suicide attempts among patients with mood disorders and demographic variables were used to 'train' a machine learning algorithm. The resulting algorithm was utilized in identifying novel or 'unseen' individual subjects as either suicide attempters or non-attempters. Three machine learning algorithms were implemented and evaluated. All algorithms distinguished individual suicide attempters from non-attempters with prediction accuracy ranging between 65% and 72% (pdisorder (PTSD) comorbidity. Risk for suicide attempt among patients with mood disorders can be estimated at an individual subject level by incorporating both demographic and clinical variables. Future studies should examine the performance of this model in other populations and its subsequent utility in facilitating selection of interventions to prevent suicide. Copyright © 2015 Elsevier B.V. All rights reserved.

  15. Redox regulation of cell proliferation: Bioinformatics and redox proteomics approaches to identify redox-sensitive cell cycle regulators.

    Science.gov (United States)

    Foyer, Christine H; Wilson, Michael H; Wright, Megan H

    2018-03-29

    Plant stem cells are the foundation of plant growth and development. The balance of quiescence and division is highly regulated, while ensuring that proliferating cells are protected from the adverse effects of environment fluctuations that may damage the genome. Redox regulation is important in both the activation of proliferation and arrest of the cell cycle upon perception of environmental stress. Within this context, reactive oxygen species serve as 'pro-life' signals with positive roles in the regulation of the cell cycle and survival. However, very little is known about the metabolic mechanisms and redox-sensitive proteins that influence cell cycle progression. We have identified cysteine residues on known cell cycle regulators in Arabidopsis that are potentially accessible, and could play a role in redox regulation, based on secondary structure and solvent accessibility likelihoods for each protein. We propose that redox regulation may function alongside other known posttranslational modifications to control the functions of core cell cycle regulators such as the retinoblastoma protein. Since our current understanding of how redox regulation is involved in cell cycle control is hindered by a lack of knowledge regarding both which residues are important and how modification of those residues alters protein function, we discuss how critical redox modifications can be mapped at the molecular level. Crown Copyright © 2018. Published by Elsevier Inc. All rights reserved.

  16. A Cost Benefit Analysis Approach to Identify Improvements in Merchant Navy Deck Officers’ HELM (Human Element Leadership and Management Training

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    Farhan Saeed

    2016-12-01

    Full Text Available A review of maritime accidents conducted over the last decade confirms that human error is the main contributing factor in these incidents. Well-developed Non-Technical Skills (NTS can reduce the effects of human error. NTS include both interpersonal and cognitive skills such as situation awareness, teamwork, decision-making, leadership, managerial skills, communication and language skills. In a crisis situation good NTS allow a deck officer to recognise the problem quickly, take action to manage the situation, and utilise the available team members safely and effectively. This paper identifies the importance of NTS training for merchant navy deck officers. It also highlights room for improvement in the existing HELM training. Research has shown that at present the structure of HELM training is not very effective. The other safety critical domains’ efforts into NTS developments are investigated and examples of best practice are adapted into the maritime domain’s NTS training. Suggestions are given for improvements to the HELM course based on proven successful methods in other safety critical domains (aviation and anaesthesia. A subsequent Cost Benefit Analysis for improving deck officers’ NTS is also carried out through the use of Bayesian Networks and Decision Tree Modelling.

  17. Glycemic Excursions in Type 1 Diabetes in Pregnancy: A Semiparametric Statistical Approach to Identify Sensitive Time Points during Gestation

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    Resmi Gupta

    2017-01-01

    Full Text Available Aim. To examine the gestational glycemic profile and identify specific times during pregnancy that variability in glucose levels, measured by change in velocity and acceleration/deceleration of blood glucose fluctuations, is associated with delivery of a large-for-gestational-age (LGA baby, in women with type 1 diabetes. Methods. Retrospective analysis of capillary blood glucose levels measured multiple times daily throughout gestation in women with type 1 diabetes was performed using semiparametric mixed models. Results. Velocity and acceleration/deceleration in glucose levels varied across gestation regardless of delivery outcome. Compared to women delivering LGA babies, those delivering babies appropriate for gestational age exhibited significantly smaller rates of change and less variation in glucose levels between 180 days of gestation and birth. Conclusions. Use of innovative statistical methods enabled detection of gestational intervals in which blood glucose fluctuation parameters might influence the likelihood of delivering LGA baby in mothers with type 1 diabetes. Understanding dynamics and being able to visualize gestational changes in blood glucose are a potentially useful tool to assist care providers in determining the optimal timing to initiate continuous glucose monitoring.

  18. Identifying Predictors of Central Sleep Apnea/Cheyne-Stokes Breathing in Chronic Heart Failure: a Pathophysiological Approach

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    Draganova Aneliya I.

    2016-12-01

    Full Text Available Chronic heart failure (CHF is a major health problem associated with increased mortality, despite modern treatment options. Central sleep apnea (CSA/Cheyne-Stokes breathing (CSB is a common and yet largely under-diagnosed co-morbidity, adding significantly to the poor prognosis in CHF because of a number of acute and chronic effects, including intermittent hypoxia, sympathetic overactivation, disturbed sleep architecture and impaired physical tolerance. It is characterized by repetitive periods of crescendo-decrescendo ventilatory pattern, alternating with central apneas and hypopneas. The pathogenesis of CSA/CSB is based on the concept of loop gain, comprising three major components: controller gain, plant gain and feedback gain. Laboratory polysomnography, being the golden standard for diagnosing sleep-disordered breathing (SDB at present, is a costly and highly specialized procedure unable to meet the vast diagnostic demand. Unlike obstructive sleep apnea, CSA/CSB has a low clinical profile. Therefore, a reliable predictive system is needed for identifying CHF patients who are most likely to suffer from CSA/CSB, optimizing polysomnography use. The candidate predictors should be standardized, easily accessible and low-priced in order to be applied in daily medical routine.

  19. Using a network-based approach to identify interactions structure for innovation in a low-technology intensive sector

    Energy Technology Data Exchange (ETDEWEB)

    Aouinait, C.; Lepori, B.; Christen, D.; Carlen, C.; Foray, D.

    2016-07-01

    Knowledge transfer in the agricultural network is realized through interactions between stakeholders, inducing innovation development and diffusion. The aim of the paper was to trace interactions in the Swiss apricot sector. Identification of collaborations using face-toface interviews of knowledge producers and knowledge users were conducted. The study showed that informal collaborations are exclusively used to transfer knowledge and create innovation. Personal ties have been established between internal actors of the value chain (e.g. professionals like producers, transformers and wholesalers). External partners like public research organizations have created strong ties with agricultural stakeholders. However, the spatial proximity does not guarantee higher rate of collaborations. The links with the Universities of Applied Sciences, closely located, are sparse. Hence, in order to warrant innovation success, spatial proximity has to be balanced with organizational proximity. Despite the educational background of producers, there are a few connections with universities. Human capital formation and education in the agricultural sector should be examined to design innovation policy. Besides, the public research center for agriculture catalyzes knowledge transfer and facilitates innovation adoption. A suitable ecology of actors through the value chain from research to application is necessary. Furthermore, productive interactions should be investigated to identify the efficiency of knowledge and innovation transfer mechanisms and potential gaps in this process. (Author)

  20. A non-targeted metabolomic approach to identify food markers to support discrimination between organic and conventional tomato crops.

    Science.gov (United States)

    Martínez Bueno, María Jesús; Díaz-Galiano, Francisco José; Rajski, Łukasz; Cutillas, Víctor; Fernández-Alba, Amadeo R

    2018-04-20

    In the last decade, the consumption trend of organic food has increased dramatically worldwide. However, the lack of reliable chemical markers to discriminate between organic and conventional products makes this market susceptible to food fraud in products labeled as "organic". Metabolomic fingerprinting approach has been demonstrated as the best option for a full characterization of metabolome occurring in plants, since their pattern may reflect the impact of both endogenous and exogenous factors. In the present study, advanced technologies based on high performance liquid chromatography-high-resolution accurate mass spectrometry (HPLC-HRAMS) has been used for marker search in organic and conventional tomatoes grown in greenhouse under controlled agronomic conditions. The screening of unknown compounds comprised the retrospective analysis of all tomato samples throughout the studied period and data processing using databases (mzCloud, ChemSpider and PubChem). In addition, stable nitrogen isotope analysis (δ 15 N) was assessed as a possible indicator to support discrimination between both production systems using crop/fertilizer correlations. Pesticide residue analyses were also applied as a well-established way to evaluate the organic production. Finally, the evaluation by combined chemometric analysis of high-resolution accurate mass spectrometry (HRAMS) and δ 15 N data provided a robust classification model in accordance with the agricultural practices. Principal component analysis (PCA) showed a sample clustering according to farming systems and significant differences in the sample profile was observed for six bioactive components (L-tyrosyl-L-isoleucyl-L-threonyl-L-threonine, trilobatin, phloridzin, tomatine, phloretin and echinenone). Copyright © 2018 Elsevier B.V. All rights reserved.

  1. Human Leptospirosis Infection in Fiji: An Eco-epidemiological Approach to Identifying Risk Factors and Environmental Drivers for Transmission.

    Science.gov (United States)

    Lau, Colleen L; Watson, Conall H; Lowry, John H; David, Michael C; Craig, Scott B; Wynwood, Sarah J; Kama, Mike; Nilles, Eric J

    2016-01-01

    Leptospirosis is an important zoonotic disease in the Pacific Islands. In Fiji, two successive cyclones and severe flooding in 2012 resulted in outbreaks with 576 reported cases and 7% case-fatality. We conducted a cross-sectional seroprevalence study and used an eco-epidemiological approach to characterize risk factors and drivers for human leptospirosis infection in Fiji, and aimed to provide an evidence base for improving the effectiveness of public health mitigation and intervention strategies. Antibodies indicative of previous or recent infection were found in 19.4% of 2152 participants (81 communities on the 3 main islands). Questionnaires and geographic information systems data were used to assess variables related to demographics, individual behaviour, contact with animals, socioeconomics, living conditions, land use, and the natural environment. On multivariable logistic regression analysis, variables associated with the presence of Leptospira antibodies included male gender (OR 1.55), iTaukei ethnicity (OR 3.51), living in villages (OR 1.64), lack of treated water at home (OR 1.52), working outdoors (1.64), living in rural areas (OR 1.43), high poverty rate (OR 1.74), living Fiji are complex and multifactorial, with environmental factors playing crucial roles. With global climate change, severe weather events and flooding are expected to intensify in the South Pacific. Population growth could also lead to more intensive livestock farming; and urbanization in developing countries is often associated with urban and peri-urban slums where diseases of poverty proliferate. Climate change, flooding, population growth, urbanization, poverty and agricultural intensification are important drivers of zoonotic disease transmission; these factors may independently, or potentially synergistically, lead to enhanced leptospirosis transmission in Fiji and other similar settings.

  2. Identifying food deserts and swamps based on relative healthy food access: a spatio-temporal Bayesian approach.

    Science.gov (United States)

    Luan, Hui; Law, Jane; Quick, Matthew

    2015-12-30

    Obesity and other adverse health outcomes are influenced by individual- and neighbourhood-scale risk factors, including the food environment. At the small-area scale, past research has analysed spatial patterns of food environments for one time period, overlooking how food environments change over time. Further, past research has infrequently analysed relative healthy food access (RHFA), a measure that is more representative of food purchasing and consumption behaviours than absolute outlet density. This research applies a Bayesian hierarchical model to analyse the spatio-temporal patterns of RHFA in the Region of Waterloo, Canada, from 2011 to 2014 at the small-area level. RHFA is calculated as the proportion of healthy food outlets (healthy outlets/healthy + unhealthy outlets) within 4-km from each small-area. This model measures spatial autocorrelation of RHFA, temporal trend of RHFA for the study region, and spatio-temporal trends of RHFA for small-areas. For the study region, a significant decreasing trend in RHFA is observed (-0.024), suggesting that food swamps have become more prevalent during the study period. For small-areas, significant decreasing temporal trends in RHFA were observed for all small-areas. Specific small-areas located in south Waterloo, north Kitchener, and southeast Cambridge exhibited the steepest decreasing spatio-temporal trends and are classified as spatio-temporal food swamps. This research demonstrates a Bayesian spatio-temporal modelling approach to analyse RHFA at the small-area scale. Results suggest that food swamps are more prevalent than food deserts in the Region of Waterloo. Analysing spatio-temporal trends of RHFA improves understanding of local food environment, highlighting specific small-areas where policies should be targeted to increase RHFA and reduce risk factors of adverse health outcomes such as obesity.

  3. A biology-driven approach identifies the hypoxia gene signature as a predictor of the outcome of neuroblastoma patients

    Directory of Open Access Journals (Sweden)

    Fardin Paolo

    2010-07-01

    Full Text Available Abstract Background Hypoxia is a condition of low oxygen tension occurring in the tumor microenvironment and it is related to poor prognosis in human cancer. To examine the relationship between hypoxia and neuroblastoma, we generated and tested an in vitro derived hypoxia gene signature for its ability to predict patients' outcome. Results We obtained the gene expression profile of 11 hypoxic neuroblastoma cell lines and we derived a robust 62 probesets signature (NB-hypo taking advantage of the strong discriminating power of the l1-l2 feature selection technique combined with the analysis of differential gene expression. We profiled gene expression of the tumors of 88 neuroblastoma patients and divided them according to the NB-hypo expression values by K-means clustering. The NB-hypo successfully stratifies the neuroblastoma patients into good and poor prognosis groups. Multivariate Cox analysis revealed that the NB-hypo is a significant independent predictor after controlling for commonly used risk factors including the amplification of MYCN oncogene. NB-hypo increases the resolution of the MYCN stratification by dividing patients with MYCN not amplified tumors in good and poor outcome suggesting that hypoxia is associated with the aggressiveness of neuroblastoma tumor independently from MYCN amplification. Conclusions Our results demonstrate that the NB-hypo is a novel and independent prognostic factor for neuroblastoma and support the view that hypoxia is negatively correlated with tumors' outcome. We show the power of the biology-driven approach in defining hypoxia as a critical molecular program in neuroblastoma and the potential for improvement in the current criteria for risk stratification.

  4. A state space approach for piecewise-linear recurrent neural networks for identifying computational dynamics from neural measurements.

    Directory of Open Access Journals (Sweden)

    Daniel Durstewitz

    2017-06-01

    Full Text Available The computational and cognitive properties of neural systems are often thought to be implemented in terms of their (stochastic network dynamics. Hence, recovering the system dynamics from experimentally observed neuronal time series, like multiple single-unit recordings or neuroimaging data, is an important step toward understanding its computations. Ideally, one would not only seek a (lower-dimensional state space representation of the dynamics, but would wish to have access to its statistical properties and their generative equations for in-depth analysis. Recurrent neural networks (RNNs are a computationally powerful and dynamically universal formal framework which has been extensively studied from both the computational and the dynamical systems perspective. Here we develop a semi-analytical maximum-likelihood estimation scheme for piecewise-linear RNNs (PLRNNs within the statistical framework of state space models, which accounts for noise in both the underlying latent dynamics and the observation process. The Expectation-Maximization algorithm is used to infer the latent state distribution, through a global Laplace approximation, and the PLRNN parameters iteratively. After validating the procedure on toy examples, and using inference through particle filters for comparison, the approach is applied to multiple single-unit recordings from the rodent anterior cingulate cortex (ACC obtained during performance of a classical working memory task, delayed alternation. Models estimated from kernel-smoothed spike time data were able to capture the essential computational dynamics underlying task performance, including stimulus-selective delay activity. The estimated models were rarely multi-stable, however, but rather were tuned to exhibit slow dynamics in the vicinity of a bifurcation point. In summary, the present work advances a semi-analytical (thus reasonably fast maximum-likelihood estimation framework for PLRNNs that may enable to recover

  5. Lipidomic approach to identify patterns in phospholipid profiles and define class differences in mammary epithelial and breast cancer cells.

    Science.gov (United States)

    Dória, M Luísa; Cotrim, Zita; Macedo, Bárbara; Simões, Cláudia; Domingues, Pedro; Helguero, Luisa; Domingues, M Rosário

    2012-06-01

    Breast cancer is the leading cause of cancer-related deaths in women. Altered cellular functions of cancer cells lead to uncontrolled cellular growth and morphological changes. Cellular biomembranes are intimately involved in the regulation of cell signaling; however, they remain largely understudied. Phospholipids (PLs) are the main constituents of biological membranes and play important functional, structural and metabolic roles. The aim of this study was to establish if patterns in the PL profiles of mammary epithelial cells and breast cancer cells differ in relation to degree of differentiation and metastatic potential. For this purpose, PLs were analyzed using a lipidomic approach. In brief, PLs were extracted using Bligh and Dyer method, followed by a separation of PL classes by thin layer chromatography, and subsequent analysis by mass spectrometry (MS). Differences and similarities were found in the relative levels of PL content between mammary epithelial and breast cancer cells and between breast cancer cells with different levels of aggressiveness. When compared to the total PL content, phosphatidylcholine levels were reduced and lysophosphatydilcholines increased in the more aggressive cancer cells; while phosphatidylserine levels remained unchanged. MS analysis showed alterations in the classes of phosphatidylcholine, lysophosphatidylcholine, sphingomyelin, and phosphatidylinositides. In particular, the phosphatidylinositides, which are signaling molecules that affect proliferation, survival, and migration, showed dramatic alterations in their profile, where an increase of phosphatdylinositides saturated fatty acids chains and a decrease in C20 fatty acids in cancer cells compared with mammary epithelial cells was observed. At present, information about PL changes in cancer progression is lacking. Therefore, these data will be useful as a starting point to define possible PLs with prospective as biomarkers and disclose metabolic pathways with potential

  6. A machine learning approach to identify clinical trials involving nanodrugs and nanodevices from ClinicalTrials.gov.

    Science.gov (United States)

    de la Iglesia, Diana; García-Remesal, Miguel; Anguita, Alberto; Muñoz-Mármol, Miguel; Kulikowski, Casimir; Maojo, Víctor

    2014-01-01

    Clinical Trials (CTs) are essential for bridging the gap between experimental research on new drugs and their clinical application. Just like CTs for traditional drugs and biologics have helped accelerate the translation of biomedical findings into medical practice, CTs for nanodrugs and nanodevices could advance novel nanomaterials as agents for diagnosis and therapy. Although there is publicly available information about nanomedicine-related CTs, the online archiving of this information is carried out without adhering to criteria that discriminate between studies involving nanomaterials or nanotechnology-based processes (nano), and CTs that do not involve nanotechnology (non-nano). Finding out whether nanodrugs and nanodevices were involved in a study from CT summaries alone is a challenging task. At the time of writing, CTs archived in the well-known online registry ClinicalTrials.gov are not easily told apart as to whether they are nano or non-nano CTs-even when performed by domain experts, due to the lack of both a common definition for nanotechnology and of standards for reporting nanomedical experiments and results. We propose a supervised learning approach for classifying CT summaries from ClinicalTrials.gov according to whether they fall into the nano or the non-nano categories. Our method involves several stages: i) extraction and manual annotation of CTs as nano vs. non-nano, ii) pre-processing and automatic classification, and iii) performance evaluation using several state-of-the-art classifiers under different transformations of the original dataset. The performance of the best automated classifier closely matches that of experts (AUC over 0.95), suggesting that it is feasible to automatically detect the presence of nanotechnology products in CT summaries with a high degree of accuracy. This can significantly speed up the process of finding whether reports on ClinicalTrials.gov might be relevant to a particular nanoparticle or nanodevice, which is

  7. Chassis organism from Corynebacterium glutamicum--a top-down approach to identify and delete irrelevant gene clusters.

    Science.gov (United States)

    Unthan, Simon; Baumgart, Meike; Radek, Andreas; Herbst, Marius; Siebert, Daniel; Brühl, Natalie; Bartsch, Anna; Bott, Michael; Wiechert, Wolfgang; Marin, Kay; Hans, Stephan; Krämer, Reinhard; Seibold, Gerd; Frunzke, Julia; Kalinowski, Jörn; Rückert, Christian; Wendisch, Volker F; Noack, Stephan

    2015-02-01

    For synthetic biology applications, a robust structural basis is required, which can be constructed either from scratch or in a top-down approach starting from any existing organism. In this study, we initiated the top-down construction of a chassis organism from Corynebacterium glutamicum ATCC 13032, aiming for the relevant gene set to maintain its fast growth on defined medium. We evaluated each native gene for its essentiality considering expression levels, phylogenetic conservation, and knockout data. Based on this classification, we determined 41 gene clusters ranging from 3.7 to 49.7 kbp as target sites for deletion. 36 deletions were successful and 10 genome-reduced strains showed impaired growth rates, indicating that genes were hit, which are relevant to maintain biological fitness at wild-type level. In contrast, 26 deleted clusters were found to include exclusively irrelevant genes for growth on defined medium. A combinatory deletion of all irrelevant gene clusters would, in a prophage-free strain, decrease the size of the native genome by about 722 kbp (22%) to 2561 kbp. Finally, five combinatory deletions of irrelevant gene clusters were investigated. The study introduces the novel concept of relevant genes and demonstrates general strategies to construct a chassis suitable for biotechnological application. © 2014 The Authors. Biotechnology Journal published by Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim. This is an open access article under the terms of the Creative Commons Attribution-Non-Commercial-NoDerivs Licence, which permits use and distribution in any medium, provided the original work is properly cited, the use is non- commercial and no modifications or adaptations are made.

  8. Identifying the determinants of South Africa’s extensive and intensive trade margins: A gravity model approach

    Directory of Open Access Journals (Sweden)

    Marianne Matthee

    2017-03-01

    Full Text Available Background: The significance of the paper is twofold. Firstly, it adds to the small but growing body of literature focusing on the decomposition of South Africa’s export growth. Secondly, it identifies the determinants of the intensive and extensive margins of South Africa’s exports – a topic that (as far as the authors are concerned has not been explored before. Aim: This paper aims to investigate a wide range of market access determinants that affect South Africa’s export growth along the intensive and extensive margins. Setting: Export diversification has been identified as one of the critical pillars of South Africa’s much-hoped-for economic revival. Although recent years have seen the country’s export product mix evolving, there is still insufficient diversification into new markets with high value-added products. This is putting a damper on export performance as a whole and, in turn, hindering South Africa’s economic growth. Methods: A Heckman selection gravity model is applied using highly disaggregated data. The first stage of the process revealed the factors affecting the probability of South Africa exporting to a particular destination (extensive margin. The second stage, which modelled trade flows, revealed the variables that affect export volumes (intensive margin. Results: The results showed that South Africa’s export product mix is relatively varied, but the number of export markets is limited. In terms of the extensive margin (or the probability of exporting, economic variables such as the importing country’s GDP and population have a positive impact on firms’ decision to export. Other factors affecting the extensive margin are distance to the market (negative impact, cultural or language fit (positive impact, presence of a South African embassy abroad (positive impact, existing free trade agreement with Southern African Development Community (positive impact and trade regulations and costs (negative

  9. Virtual screening approach to identifying influenza virus neuraminidase inhibitors using molecular docking combined with machine-learning-based scoring function.

    Science.gov (United States)

    Zhang, Li; Ai, Hai-Xin; Li, Shi-Meng; Qi, Meng-Yuan; Zhao, Jian; Zhao, Qi; Liu, Hong-Sheng

    2017-10-10

    In recent years, an epidemic of the highly pathogenic avian influenza H7N9 virus has persisted in China, with a high mortality rate. To develop novel anti-influenza therapies, we have constructed a machine-learning-based scoring function (RF-NA-Score) for the effective virtual screening of lead compounds targeting the viral neuraminidase (NA) protein. RF-NA-Score is more accurate than RF-Score, with a root-mean-square error of 1.46, Pearson's correlation coefficient of 0.707, and Spearman's rank correlation coefficient of 0.707 in a 5-fold cross-validation study. The performance of RF-NA-Score in a docking-based virtual screening of NA inhibitors was evaluated with a dataset containing 281 NA inhibitors and 322 noninhibitors. Compared with other docking-rescoring virtual screening strategies, rescoring with RF-NA-Score significantly improved the efficiency of virtual screening, and a strategy that averaged the scores given by RF-NA-Score, based on the binding conformations predicted with AutoDock, AutoDock Vina, and LeDock, was shown to be the best strategy. This strategy was then applied to the virtual screening of NA inhibitors in the SPECS database. The 100 selected compounds were tested in an in vitro H7N9 NA inhibition assay, and two compounds with novel scaffolds showed moderate inhibitory activities. These results indicate that RF-NA-Score improves the efficiency of virtual screening for NA inhibitors, and can be used successfully to identify new NA inhibitor scaffolds. Scoring functions specific for other drug targets could also be established with the same method.

  10. Black mother's intention to vaccinate daughters against HPV: A mixed methods approach to identify opportunities for targeted communication.

    Science.gov (United States)

    Cunningham-Erves, Jennifer; Forbes, Laura; Ivankova, Nataliya; Mayo-Gamble, Tilicia; Kelly-Taylor, Kendria; Deakings, Jason

    2018-03-24

    The cervical cancer disparity continues to exist and has widened between Black and non-Hispanic White women. Human Papillomavirus (HPV) vaccines could potentially reduce this disparity, yet remain underused among Black female adolescents. We investigated psychosocial and cultural factors associated with Black mothers' intentions to vaccinate their daughters against HPV, and explored views toward a HPV vaccine mandate. In this quantitative dominant, mixed methods study, cross sectional surveys (n=237) and follow-up semi-structured interviews (n=9) were conducted with Black mothers of daughters. A 2-step logistic regression determined factors associated with Black mothers' intention. Thematic content analysis determined emerging themes. Perceived susceptibility (p=.044), perceived barriers (pHPV vaccination intentions. Follow-up interviews provided insight into factors influencing mothers' intentions. Mothers with low intentions did not perceive their daughter to be currently sexually active or in near future, thus, not at HPV risk. Pediatricians were identified as the most influential person on maternal decision-making if there was a pre-existing relationship. However, many mothers had not received a pediatricians' recommendation for their daughters. Barriers influencing mother's decision-making include knowledge, daughters' age, and mistrust in pharmaceutical companies and physicians. Mothers were not in favor of the HPV vaccine mandate. Findings demonstrate the need to develop and evaluate physician-led interventions on HPV and vaccine importance, and engage these mothers in intervention development to build trust between physicians, researchers, and Black mothers to improve HPV vaccine uptake in Black female adolescents. Published by Elsevier Inc.

  11. Regional Differences of Proteins Expressing in Adipose Depots Isolated from Cows, Steers and Bulls as Identified by a Proteomic Approach

    Directory of Open Access Journals (Sweden)

    Jin Hyoung Cho

    2016-08-01

    Full Text Available Adipose tissue in the loin muscle area of beef cattle as a marbling factor is directly associated with beef quality. To elucidate whether properties of proteins involved in depot specific adipose tissue were sex-dependent, we analyzed protein expression of intramuscular adipose tissue (IMAT and omental adipose tissue (OMAT from Hanwoo cows, steers, and bulls of Korean native beef cattle by liquid chromatography-tandem mass spectrometry (LC-MS/MS–based proteomic analysis, quantitative polymerase chain reaction (PCR and western blot analysis. Two different adipose depots (i.e. intramuscular and omental were collected from cows (n = 7, steers (n = 7, or bulls (n = 7. LC-MS/MS revealed a total of 55 and 35 proteins in IMAT and OMAT, respectively. Of the 55 proteins identified, 44, 40, and 42 proteins were confirmed to be differentially expressed in IMAT of cows, steers, and bulls, respectively. In OMAT of cows, steers, and bulls, 33, 33, and 22 were confirmed to be differentially expressed, respectively. Tropomyosin (TPM 1, TPM 2, and TPM3 were subjected to verification by quantitative PCR and western blot analysis in IMAT and OMAT of Hanwoo cows, steers, and bulls as key factors closely associated with muscle development. Both mRNA levels and protein levels of TPM1, TPM2, and TPM3 in IMAT were lower in bulls compared to in cows or steers suggesting that they were positively correlated with marbling score and quality grade. Our results may aid the regulation of marbling development and improvement of meat quality grades in beef cattle.

  12. Inhibitors of MyD88-dependent proinflammatory cytokine production identified utilizing a novel RNA interference screening approach.

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    John S Cho

    2009-09-01

    Full Text Available The events required to initiate host defenses against invading pathogens involve complex signaling cascades comprised of numerous adaptor molecules, kinases, and transcriptional elements, ultimately leading to the production of proinflammatory cytokines, such as tumor necrosis factor alpha (TNF-alpha. How these signaling cascades are regulated, and the proteins and regulatory elements participating are still poorly understood.We report here the development a completely random short-hairpin RNA (shRNA library coupled with a novel forward genetic screening strategy to identify inhibitors of Toll-like receptor (TLR dependent proinflammatory responses. We developed a murine macrophage reporter cell line stably transfected with a construct expressing diphtheria toxin-A (DT-A under the control of the TNF-alpha-promoter. Stimulation of the reporter cell line with the TLR ligand lipopolysaccharide (LPS resulted in DT-A induced cell death, which could be prevented by the addition of an shRNA targeting the TLR adaptor molecule MyD88. Utilizing this cell line, we screened a completely random lentiviral short hairpin RNA (shRNA library for sequences that inhibited TLR-mediated TNF-alpha production. Recovery of shRNA sequences from surviving cells led to the identification of unique shRNA sequences that significantly inhibited TLR4-dependent TNF-alpha gene expression. Furthermore, these shRNA sequences specifically blocked TLR2 but not TLR3-dependent TNF-alpha production.Thus, we describe the generation of novel tools to facilitate large-scale forward genetic screens in mammalian cells and the identification of potent shRNA inhibitors of TLR2 and TLR4- dependent proinflammatory responses.

  13. Integrated Healthcare Delivery: A Qualitative Research Approach to Identifying and Harmonizing Perspectives of Integrated Neglected Tropical Disease Programs.

    Directory of Open Access Journals (Sweden)

    Arianna Rubin Means

    2016-10-01

    Full Text Available While some evidence supports the beneficial effects of integrating neglected tropical disease (NTD programs to optimize coverage and reduce costs, there is minimal information regarding when or how to effectively operationalize program integration. The lack of systematic analyses of integration experiences and of integration processes may act as an impediment to achieving more effective NTD programming. We aimed to learn about the experiences of NTD stakeholders and their perceptions of integration.We evaluated differences in the definitions, roles, perceived effectiveness, and implementation experiences of integrated NTD programs among a variety of NTD stakeholder groups, including multilateral organizations, funding partners, implementation partners, national Ministry of Health (MOH teams, district MOH teams, volunteer rural health workers, and community members participating in NTD campaigns. Semi-structured key informant interviews were conducted. Coding of themes involved a mix of applying in-vivo open coding and a priori thematic coding from a start list.In total, 41 interviews were conducted. Salient themes varied by stakeholder, however dominant themes on integration included: significant variations in definitions, differential effectiveness of specific integrated NTD activities, community member perceptions of NTD programs, the influence of funders, perceived facilitators, perceived barriers, and the effects of integration on health system strength. In general, stakeholder groups provided unique perspectives, rather than contrarian points of view, on the same topics. The stakeholders identified more advantages to integration than disadvantages, however there are a number of both unique facilitators and challenges to integration from the perspective of each stakeholder group.Qualitative data suggest several structural, process, and technical opportunities that could be addressed to promote more effective and efficient integrated NTD

  14. Do maize models capture the impacts of heat and drought stresses on yield? Using algorithm ensembles to identify successful approaches.

    Science.gov (United States)

    Jin, Zhenong; Zhuang, Qianlai; Tan, Zeli; Dukes, Jeffrey S; Zheng, Bangyou; Melillo, Jerry M

    2016-09-01

    Stresses from heat and drought are expected to increasingly suppress crop yields, but the degree to which current models can represent these effects is uncertain. Here we evaluate the algorithms that determine impacts of heat and drought stress on maize in 16 major maize models by incorporating these algorithms into a standard model, the Agricultural Production Systems sIMulator (APSIM), and running an ensemble of simulations. Although both daily mean temperature and daylight temperature are common choice of forcing heat stress algorithms, current parameterizations in most models favor the use of daylight temperature even though the algorithm was designed for daily mean temperature. Different drought algorithms (i.e., a function of soil water content, of soil water supply to demand ratio, and of actual to potential transpiration ratio) simulated considerably different patterns of water shortage over the growing season, but nonetheless predicted similar decreases in annual yield. Using the selected combination of algorithms, our simulations show that maize yield reduction was more sensitive to drought stress than to heat stress for the US Midwest since the 1980s, and this pattern will continue under future scenarios; the influence of excessive heat will become increasingly prominent by the late 21st century. Our review of algorithms in 16 crop models suggests that the impacts of heat and drought stress on plant yield can be best described by crop models that: (i) incorporate event-based descriptions of heat and drought stress, (ii) consider the effects of nighttime warming, and (iii) coordinate the interactions among multiple stresses. Our study identifies the proficiency with which different model formulations capture the impacts of heat and drought stress on maize biomass and yield production. The framework presented here can be applied to other modeled processes and used to improve yield predictions of other crops with a wide variety of crop models. © 2016 John

  15. A multicomponent approach to identify predictors of hospital outcomes in older in-patients: a multicentre, observational study.

    Directory of Open Access Journals (Sweden)

    Stefanie L De Buyser

    Full Text Available BACKGROUND: The identification of older patients at risk of poor hospital outcomes (e.g. longer hospital stay, in-hospital mortality, and institutionalisation is important to provide an effective healthcare service. OBJECTIVE: To identify factors related to older patients' clinical, nutritional, functional and socio-demographic profiles at admission to an acute care ward that can predict poor hospital outcomes. DESIGN AND SETTING: The CRiteria to assess appropriate Medication use among Elderly complex patients project was a multicentre, observational study performed in geriatric and internal medicine acute care wards of seven Italian hospitals. SUBJECTS: One thousand one hundred twenty-three consecutively admitted patients aged 65 years or older. METHODS: Hospital outcomes were length of stay, in-hospital mortality, and institutionalisation. RESULTS: Mean age of participants was 81 years, 56% were women. Median length of stay was 10 (7-14 days, 41 patients died during hospital stay and 37 were newly institutionalised. Number of drugs before admission, metastasized cancer, renal failure or dialysis, infection, falls at home during the last year, pain, and walking speed were independent predictors of LoS. Total dependency in activities of daily living and inability to perform grip strength test were independent predictors of in-hospital mortality. Malnutrition and total dependency in activities of daily living were independent predictors of institutionalisation. CONCLUSIONS: Our results confirm that not only diseases, but also multifaceted aspects of ageing such as physical function and malnutrition are strong predictors of hospital outcomes and suggest that these variables should be systematically recorded.

  16. Survivorship care planning in skin cancer: An unbiased statistical approach to identifying patterns of care-plan use.

    Science.gov (United States)

    Benci, Joseph L; Minn, Andy J; Vachani, Carolyn C; Bach, Christina; Arnold-Korzeniowski, Karen; Hampshire, Margaret K; Metz, James M; Hill-Kayser, Christine E

    2018-01-01

    Nearly 1 in 5 Americans will develop skin cancer, and as a result, survivors of skin cancer compose one of the largest groups of cancer survivors. Survivorship care plans (SCPs) are an important tool for improving patient outcomes and provide critical information to both survivors and health care professionals. Recent efforts have been made to expand SCP utilization; however, which patients currently receive SCPs is poorly understood. This study used 596 individuals with a diagnosis of melanoma (n = 391) or nonmelanoma skin cancer (n = 205) who had used an Internet-based SCP tool from May 2010 to December 2016 to model the patient and provider characteristics that determine SCP utilization. Survivors were predominantly white (95.3%) and female (56.5%). Survivors who received a treatment summary were more likely to also receive an SCP. University and nonuniversity cancer centers used SCPs at a higher rate than other care settings. Survivors whose care was managed by a team rather than just an individual physician were also more likely to receive an SCP. Survivors older than 70 years at diagnosis were almost twice as likely to receive a plan as survivors who were diagnosed at a younger age. With a convenience sample of skin cancer survivors, it is possible to model factors that predict the receipt of SCPs. Important variables include the diagnosis age, treatment setting, physician type, and treatment-summary utilization. A closer examination of these variables identified several disparities in care-plan use and, therefore, opportunities to improve the distribution of SCPs. Further validation in additional cohorts of survivors is necessary to confirm these conclusions. Cancer 2018;124:183-91. © 2017 American Cancer Society. © 2017 American Cancer Society.

  17. A machine learning approach to identify clinical trials involving nanodrugs and nanodevices from ClinicalTrials.gov.

    Directory of Open Access Journals (Sweden)

    Diana de la Iglesia

    Full Text Available Clinical Trials (CTs are essential for bridging the gap between experimental research on new drugs and their clinical application. Just like CTs for traditional drugs and biologics have helped accelerate the translation of biomedical findings into medical practice, CTs for nanodrugs and nanodevices could advance novel nanomaterials as agents for diagnosis and therapy. Although there is publicly available information about nanomedicine-related CTs, the online archiving of this information is carried out without adhering to criteria that discriminate between studies involving nanomaterials or nanotechnology-based processes (nano, and CTs that do not involve nanotechnology (non-nano. Finding out whether nanodrugs and nanodevices were involved in a study from CT summaries alone is a challenging task. At the time of writing, CTs archived in the well-known online registry ClinicalTrials.gov are not easily told apart as to whether they are nano or non-nano CTs-even when performed by domain experts, due to the lack of both a common definition for nanotechnology and of standards for reporting nanomedical experiments and results.We propose a supervised learning approach for classifying CT summaries from ClinicalTrials.gov according to whether they fall into the nano or the non-nano categories. Our method involves several stages: i extraction and manual annotation of CTs as nano vs. non-nano, ii pre-processing and automatic classification, and iii performance evaluation using several state-of-the-art classifiers under different transformations of the original dataset.The performance of the best automated classifier closely matches that of experts (AUC over 0.95, suggesting that it is feasible to automatically detect the presence of nanotechnology products in CT summaries with a high degree of accuracy. This can significantly speed up the process of finding whether reports on ClinicalTrials.gov might be relevant to a particular nanoparticle or nanodevice

  18. [Muscle and bone health as a risk factor of fall among the elderly. An approach to identify high-risk fallers by risk assessment].

    Science.gov (United States)

    Kikuchi, Reiko; Kozaki, Koichi; Nakamura, Tetsuro; Toba, Kenji

    2008-06-01

    Fall-induced hip fracture is one of the major causes rendering the elderly to be in a low ADL or bed-ridden status. Fall is not only the cause for fractures, but it lowers elderly peoples'ADL. History of fall, age, decline of motor function, orthostatic hypotension, balance deficit, dementia, drug and environmental factors were raised as possible risk factor for falls. We created a fall predicting score which consist of 21 risk factors and a history of falls. We found that the score is useful to identify high-risk fallers. It would be necessary to identify high-risk fallers early and give an appropriate individual approach.

  19. GIS and Multi Criteria Decision Method Based Approach of Identifying Appropriate Landfill Sites for the City Of Chittagong

    Directory of Open Access Journals (Sweden)

    M. Ali Ashraf

    2015-02-01

    were identified initially. Out of these sites four were found to be most appropriate and suitable for use as landfill. DOI: http://dx.doi.org/10.3126/ije.v4i1.12174International Journal of Environment Volume-4, Issue-1, Dec-Feb 2014/15, page: 1-15  

  20. An original phylogenetic approach identified mitochondrial haplogroup T1a1 as inversely associated with breast cancer risk in BRCA2 mutation carriers

    DEFF Research Database (Denmark)

    Blein, Sophie; Bardel, Claire; Danjean, Vincent

    2015-01-01

    of Investigators of Modifiers of BRCA1/2 for 129 mitochondrial polymorphisms using the iCOGS array. Haplogroup inference and association detection were performed using a phylogenetic approach. ALTree was applied to explore the reference mitochondrial evolutionary tree and detect subclades enriched in affected......, H and T clades), the T1a1 haplogroup has a HR of 0.62 (95% CI, 0.40 to 0.95; P = 0.03). We also identified three potential susceptibility loci, including G13708A/rs28359178, which has demonstrated an inverse association with familial breast cancer risk. CONCLUSIONS: This study illustrates how...... original approaches such as the phylogeny-based method we used can empower classical molecular epidemiological studies aimed at identifying association or risk modification effects....