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Sample records for consensus non-canonical signaling

  1. Evidence of non-canonical NOTCH signaling

    DEFF Research Database (Denmark)

    Traustadóttir, Gunnhildur Ásta; Jensen, Charlotte H; Thomassen, Mads

    2016-01-01

    Dlk1(+/+) and Dlk1(-/-) mouse tissues at E16.5, we demonstrated that several NOTCH signaling pathways indeed are affected by DLK1 during tissue development, and this was supported by a lower activation of NOTCH1 protein in Dlk1(+/+) embryos. Likewise, but using a distinct Dlk1-manipulated (si...

  2. Both canonical and non-canonical Wnt signaling independently promote stem cell growth in mammospheres.

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    Alexander M Many

    Full Text Available The characterization of mammary stem cells, and signals that regulate their behavior, is of central importance in understanding developmental changes in the mammary gland and possibly for targeting stem-like cells in breast cancer. The canonical Wnt/β-catenin pathway is a signaling mechanism associated with maintenance of self-renewing stem cells in many tissues, including mammary epithelium, and can be oncogenic when deregulated. Wnt1 and Wnt3a are examples of ligands that activate the canonical pathway. Other Wnt ligands, such as Wnt5a, typically signal via non-canonical, β-catenin-independent, pathways that in some cases can antagonize canonical signaling. Since the role of non-canonical Wnt signaling in stem cell regulation is not well characterized, we set out to investigate this using mammosphere formation assays that reflect and quantify stem cell properties. Ex vivo mammosphere cultures were established from both wild-type and Wnt1 transgenic mice and were analyzed in response to manipulation of both canonical and non-canonical Wnt signaling. An increased level of mammosphere formation was observed in cultures derived from MMTV-Wnt1 versus wild-type animals, and this was blocked by treatment with Dkk1, a selective inhibitor of canonical Wnt signaling. Consistent with this, we found that a single dose of recombinant Wnt3a was sufficient to increase mammosphere formation in wild-type cultures. Surprisingly, we found that Wnt5a also increased mammosphere formation in these assays. We confirmed that this was not caused by an increase in canonical Wnt/β-catenin signaling but was instead mediated by non-canonical Wnt signals requiring the receptor tyrosine kinase Ror2 and activity of the Jun N-terminal kinase, JNK. We conclude that both canonical and non-canonical Wnt signals have positive effects promoting stem cell activity in mammosphere assays and that they do so via independent signaling mechanisms.

  3. IFN signaling: how a non-canonical model led to the development of IFN mimetics

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    Howard M Johnson

    2013-07-01

    Full Text Available The classical model of cytokine signaling dominates our view of specific gene activation by cytokines such as the interferons (IFNs. The importance of the model extends beyond cytokines and applies to hormones such as growth hormone (GH and insulin, and growth factors such as epidermal growth factor (EGF and fibroblast growth factor (FGF. According to this model, ligand activates the cell via interaction with the extracellular domain of the receptor. This results in activation of receptor or receptor-associated tyrosine kinases, primarily of the Janus kinase (JAK family, phosphorylation and dimerization of the STAT transcription factors, which dissociate from the receptor cytoplasmic domain and translocate to the nucleus. This view ascribes no further role to the ligand, JAK kinase, or receptor in either specific gene activation or the associated epigenetic events. The presence of dimeric STATs in the nucleus essentially explains it all. Our studies have resulted in the development of a non-canonical, more complex model of IFNγ signaling that is akin to that of steroid hormone/steroid receptor signaling. We have shown that ligand, receptor, activated JAKs and STATs are associated with specific gene activation, where the receptor subunit IFNGR1 functions as a co-transcription factor and the JAKs are involved in associated epigenetic events. We found that the type I IFN system functions similarly. The fact that GH receptor, insulin receptor, EGF receptor, and FGF receptor undergo nuclear translocation upon ligand binding suggests that they may also function similarly. The steroid hormone/steroid receptor nature of type I and II IFN signaling provides insight into the specificity of signaling by members of cytokine families. The non-canonical model could also provide better understanding to more complex cytokine families such as those of IL-2 and IL-12, whose members often use the same JAKs and STATs, but also have different functions and

  4. Alteration of canonical and non-canonical WNT-signaling by crystalline silica in human lung epithelial cells

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    Perkins, Timothy N.; Dentener, Mieke A.; Stassen, Frank R.; Rohde, Gernot G.; Mossman, Brooke T.; Wouters, Emiel F.M.; Reynaert, Niki L.

    2016-01-01

    Growth and development of the mature lung is a complex process orchestrated by a number of intricate developmental signaling pathways. Wingless-type MMTV-integration site (WNT) signaling plays critical roles in controlling branching morphogenesis cell differentiation, and formation of the conducting and respiratory airways. In addition, WNT pathways are often re-activated in mature lungs during repair and regeneration. WNT- signaling has been elucidated as a crucial contributor to the development of idiopathic pulmonary fibrosis as well as other hyper-proliferative lung diseases. Silicosis, a detrimental occupational lung disease caused by excessive inhalation of crystalline silica dust, is hallmarked by repeated cycles of damaging inflammation, epithelial hyperplasia, and formation of dense, hyalinized nodules of whorled collagen. However, mechanisms of epithelial cell hyperplasia and matrix deposition are not well understood, as most research efforts have focused on the pronounced inflammatory response. Microarray data from our previous studies has revealed a number of WNT-signaling and WNT-target genes altered by crystalline silica in human lung epithelial cells. In the present study, we utilize pathway analysis to designate connections between genes altered by silica in WNT-signaling networks. Furthermore, we confirm microarray findings by QRT-PCR and demonstrate both activation of canonical (β-catenin) and down-regulation of non-canonical (WNT5A) signaling in immortalized (BEAS-2B) and primary (PBEC) human bronchial epithelial cells. These findings suggest that WNT-signaling and cross-talk with other pathways (e.g. Notch), may contribute to proliferative, fibrogenic and inflammatory responses to silica in lung epithelial cells. - Highlights: • Pathway analysis reveals silica-induced WNT-signaling in lung epithelial cells. • Silica-induced canonical WNT-signaling is mediated by autocrine/paracrine signals. • Crystalline silica decreases non-canonical WNT

  5. Alteration of canonical and non-canonical WNT-signaling by crystalline silica in human lung epithelial cells

    Energy Technology Data Exchange (ETDEWEB)

    Perkins, Timothy N.; Dentener, Mieke A. [Department of Respiratory Medicine, Maastricht University Medical Centre +, Maastricht University Maastricht (Netherlands); Stassen, Frank R. [Department of Medical Microbiology, Maastricht University Medical Centre +, Maastricht University Maastricht (Netherlands); Rohde, Gernot G. [Department of Respiratory Medicine, Maastricht University Medical Centre +, Maastricht University Maastricht (Netherlands); Mossman, Brooke T. [Department of Pathology, University of Vermont College of Medicine, Burlington, VT (United States); Wouters, Emiel F.M. [Department of Respiratory Medicine, Maastricht University Medical Centre +, Maastricht University Maastricht (Netherlands); Reynaert, Niki L., E-mail: n.reynaert@maastrichtuniversity.nl [Department of Respiratory Medicine, Maastricht University Medical Centre +, Maastricht University Maastricht (Netherlands)

    2016-06-15

    Growth and development of the mature lung is a complex process orchestrated by a number of intricate developmental signaling pathways. Wingless-type MMTV-integration site (WNT) signaling plays critical roles in controlling branching morphogenesis cell differentiation, and formation of the conducting and respiratory airways. In addition, WNT pathways are often re-activated in mature lungs during repair and regeneration. WNT- signaling has been elucidated as a crucial contributor to the development of idiopathic pulmonary fibrosis as well as other hyper-proliferative lung diseases. Silicosis, a detrimental occupational lung disease caused by excessive inhalation of crystalline silica dust, is hallmarked by repeated cycles of damaging inflammation, epithelial hyperplasia, and formation of dense, hyalinized nodules of whorled collagen. However, mechanisms of epithelial cell hyperplasia and matrix deposition are not well understood, as most research efforts have focused on the pronounced inflammatory response. Microarray data from our previous studies has revealed a number of WNT-signaling and WNT-target genes altered by crystalline silica in human lung epithelial cells. In the present study, we utilize pathway analysis to designate connections between genes altered by silica in WNT-signaling networks. Furthermore, we confirm microarray findings by QRT-PCR and demonstrate both activation of canonical (β-catenin) and down-regulation of non-canonical (WNT5A) signaling in immortalized (BEAS-2B) and primary (PBEC) human bronchial epithelial cells. These findings suggest that WNT-signaling and cross-talk with other pathways (e.g. Notch), may contribute to proliferative, fibrogenic and inflammatory responses to silica in lung epithelial cells. - Highlights: • Pathway analysis reveals silica-induced WNT-signaling in lung epithelial cells. • Silica-induced canonical WNT-signaling is mediated by autocrine/paracrine signals. • Crystalline silica decreases non-canonical WNT

  6. Canonical and Non-Canonical NF-κB Signaling Promotes Breast Cancer Tumor-Initiating Cells

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    Kendellen, Megan F.; Bradford, Jennifer W.; Lawrence, Cortney L.; Clark, Kelly S.; Baldwin, Albert S.

    2014-01-01

    Tumor-initiating cells (TICs) are a sub-population of cells that exhibit a robust ability to self-renew and contribute to the formation of primary tumors, the relapse of previously treated tumors, and the development of metastases. TICs have been identified in various tumors, including those of the breast, and are particularly enriched in the basal-like and claudin-low subtypes of breast cancer. The signaling pathways that contribute to the function and maintenance of TICs are under intense study. We explored the potential involvement of the NF-κB family of transcription factors in TICs in cell lines that are representative of basal-like and claudin-low breast cancer. NF-κB was found to be activated in breast cancer cells that form tumorspheres efficiently. Moreover, both canonical and non-canonical NF-κB signaling is required for these cells to self-renew in vitro and to form xenograft tumors efficiently in vivo using limiting dilutions of cells. Consistent with this, canonical and non-canonical NF-κB signaling is activated in TICs isolated from breast cancer cell lines. Experimental results indicate that NF-κB promotes the function of TICs by stimulating epithelial-to-mesenchymal transition (EMT) and by upregulating the expression of the inflammatory cytokines IL-1β and IL-6. The results suggest the use of NF-κB inhibitors for clinical therapy of certain breast cancers. PMID:23474754

  7. Canonical and Non-Canonical Aspects of JAK-STAT Signaling: Lessons from Interferons for Cytokine Responses.

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    Majoros, Andrea; Platanitis, Ekaterini; Kernbauer-Hölzl, Elisabeth; Rosebrock, Felix; Müller, Mathias; Decker, Thomas

    2017-01-01

    Janus kinase (JAK)-signal transducer and activator of transcription (STAT) signal transduction mediates cytokine responses. Canonical signaling is based on STAT tyrosine phosphorylation by activated JAKs. Downstream of interferon (IFN) receptors, activated JAKs cause the formation of the transcription factors IFN-stimulated gene factor 3 (ISGF3), a heterotrimer of STAT1, STAT2 and interferon regulatory factor 9 (IRF9) subunits, and gamma interferon-activated factor (GAF), a STAT1 homodimer. In recent years, several deviations from this paradigm were reported. These include kinase-independent JAK functions as well as extra- and intranuclear activities of U-STATs without phosphotyrosines. Additionally, transcriptional control by STAT complexes resembling neither GAF nor ISGF3 contributes to transcriptome changes in IFN-treated cells. Our review summarizes the contribution of non-canonical JAK-STAT signaling to the innate antimicrobial immunity imparted by IFN. Moreover, we touch upon functions of IFN pathway proteins beyond the IFN response. These include metabolic functions of IRF9 as well as the regulation of natural killer cell activity by kinase-dead TYK2 and different phosphorylation isoforms of STAT1.

  8. Canonical and Non-Canonical Aspects of JAK–STAT Signaling: Lessons from Interferons for Cytokine Responses

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    Majoros, Andrea; Platanitis, Ekaterini; Kernbauer-Hölzl, Elisabeth; Rosebrock, Felix; Müller, Mathias; Decker, Thomas

    2017-01-01

    Janus kinase (JAK)–signal transducer and activator of transcription (STAT) signal transduction mediates cytokine responses. Canonical signaling is based on STAT tyrosine phosphorylation by activated JAKs. Downstream of interferon (IFN) receptors, activated JAKs cause the formation of the transcription factors IFN-stimulated gene factor 3 (ISGF3), a heterotrimer of STAT1, STAT2 and interferon regulatory factor 9 (IRF9) subunits, and gamma interferon-activated factor (GAF), a STAT1 homodimer. In recent years, several deviations from this paradigm were reported. These include kinase-independent JAK functions as well as extra- and intranuclear activities of U-STATs without phosphotyrosines. Additionally, transcriptional control by STAT complexes resembling neither GAF nor ISGF3 contributes to transcriptome changes in IFN-treated cells. Our review summarizes the contribution of non-canonical JAK–STAT signaling to the innate antimicrobial immunity imparted by IFN. Moreover, we touch upon functions of IFN pathway proteins beyond the IFN response. These include metabolic functions of IRF9 as well as the regulation of natural killer cell activity by kinase-dead TYK2 and different phosphorylation isoforms of STAT1. PMID:28184222

  9. Interrelationship of canonical and non-canonical Wnt signalling pathways in chronic metabolic diseases.

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    Ackers, Ian; Malgor, Ramiro

    2018-01-01

    Chronic diseases account for approximately 45% of all deaths in developed countries and are particularly prevalent in countries with the most sophisticated and robust public health systems. Chronic metabolic diseases, specifically lifestyle-related diseases pertaining to diet and exercise, continue to be difficult to treat clinically. The most prevalent of these chronic metabolic diseases include obesity, diabetes, non-alcoholic fatty liver disease, chronic kidney disease and cardiovascular disease and will be the focus of this review. Wnt proteins are highly conserved glycoproteins best known for their role in development and homeostasis of tissues. Given the importance of Wnt signalling in homeostasis, aberrant Wnt signalling likely regulates metabolic processes and may contribute to the development of chronic metabolic diseases. Expression of Wnt proteins and dysfunctional Wnt signalling has been reported in multiple chronic diseases. It is interesting to speculate about an interrelationship between the Wnt signalling pathways as a potential pathological mechanism in chronic metabolic diseases. The aim of this review is to summarize reported findings on the contrasting roles of Wnt signalling in lifestyle-related chronic metabolic diseases; specifically, the contribution of Wnt signalling to lipid accumulation, fibrosis and chronic low-grade inflammation.

  10. Non-canonical Opioid Signaling Inhibits Itch Transmission in the Spinal Cord of Mice

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    Admire Munanairi

    2018-04-01

    Full Text Available Summary: Chronic itch or pruritus is a debilitating disorder that is refractory to conventional anti-histamine treatment. Kappa opioid receptor (KOR agonists have been used to treat chronic itch, but the underlying mechanism remains elusive. Here, we find that KOR and gastrin-releasing peptide receptor (GRPR overlap in the spinal cord, and KOR activation attenuated GRPR-mediated histamine-independent acute and chronic itch in mice. Notably, canonical KOR-mediated Gαi signaling is not required for desensitizing GRPR function. In vivo and in vitro studies suggest that KOR activation results in the translocation of Ca2+-independent protein kinase C (PKCδ from the cytosol to the plasma membrane, which in turn phosphorylates and inhibits GRPR activity. A blockade of phospholipase C (PLC in HEK293 cells prevented KOR-agonist-induced PKCδ translocation and GRPR phosphorylation, suggesting a role of PLC signaling in KOR-mediated GRPR desensitization. These data suggest that a KOR-PLC-PKCδ-GRPR signaling pathway in the spinal cord may underlie KOR-agonists-induced anti-pruritus therapies. : Munanairi et al. show that the kappa opioid receptor (KOR agonists inhibit nonhistaminergic itch transmission by attenuating the function of the gastrin-releasing peptide receptor (GRPR, an itch receptor in the spinal cord. KOR activation causes the translocation of PKCδ from plasma to membrane, which phosphorylates GRPR to dampen itch transmission. Keywords: KOR, GRPR, itch, PKC, phosphorylation, GPCR cross-signaling, spinal cord, mouse

  11. Wnt3a regulates proliferation and migration of HUVEC via canonical and non-canonical Wnt signaling pathways

    International Nuclear Information System (INIS)

    Samarzija, Ivana; Sini, Patrizia; Schlange, Thomas; MacDonald, Gwen; Hynes, Nancy E.

    2009-01-01

    Untangling the signaling pathways involved in endothelial cell biology is of central interest for the development of antiangiogenesis based therapies. Here we report that Wnt3a induces the proliferation and migration of HUVECs, but does not affect their survival. Wnt3a-induced proliferation was VEGFR signaling independent, but reduced upon CamKII inhibition. In a search for the downstream mediators of Wnt3a's effects on HUVEC biology, we found that Wnt3a treatment leads to phosphorylation of DVL3 and stabilization of β-catenin. Moreover, under the same conditions we observed an upregulation in c-MYC, TIE-2 and GJA1 mRNA transcripts. Although treatment of HUVECs with Wnt5a induced DVL3 phosphorylation, we did not observe any of the other effects seen upon Wnt3a stimulation. Taken together, our data indicate that Wnt3a induces canonical and non-canonical Wnt signaling in HUVECs, and stimulates their proliferation and migration.

  12. CAPE suppresses migration and invasion of prostate cancer cells via activation of non-canonical Wnt signaling.

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    Tseng, Jen-Chih; Lin, Ching-Yu; Su, Liang-Chen; Fu, Hsiao-Hui; Yang, Shiaw-Der; Chuu, Chih-Pin

    2016-06-21

    Prostate cancer (PCa) was the fifth most common cancer overall in the world. More than 80% of patients died from PCa developed bone metastases. Caffeic acid phenethyl ester (CAPE) is a main bioactive component of honeybee hive propolis. Transwell and wound healing assays demonstrated that CAPE treatment suppressed the migration and invasion of PC-3 and DU-145 PCa cells. Gelatin zymography and Western blotting indicated that CAPE treatment reduced the abundance and activity of MMP-9 and MMP-2. Analysis using Micro-Western Array (MWA), a high-throughput antibody-based proteomics platform with 264 antibodies detecting signaling proteins involved in important pathways indicated that CAPE treatment induced receptor tyrosine kinase-like orphan receptor 2 (ROR2) in non-canonical Wnt signaling pathway but suppressed abundance of β-catenin, NF-κB activity, PI3K-Akt signaling, and epithelial-mesenchymal transition (EMT). Overexpression or knockdown of ROR2 suppressed or enhanced cell migration of PC-3 cells, respectively. TCF-LEF promoter binding assay revealed that CAPE treatment reduced canonical Wnt signaling. Intraperitoneal injection of CAPE reduced the metastasis of PC-3 xenografts in tail vein injection nude mice model. Immunohistochemical staining demonstrated that CAPE treatment increased abundance of ROR2 and Wnt5a but decreased protein expression of Ki67, Frizzle 4, NF-κB p65, MMP-9, Snail, β-catenin, and phosphorylation of IκBα. Clinical evidences suggested that genes affected by CAPE treatment (CTNNB1, RELA, FZD5, DVL3, MAPK9, SNAl1, ROR2, SMAD4, NFKBIA, DUSP6, and PLCB3) correlate with the aggressiveness of PCa. Our study suggested that CAPE may be a potential therapeutic agent for patients with advanced PCa.

  13. Non-Canonical Hedgehog Signaling Is a Positive Regulator of the WNT Pathway and Is Required for the Survival of Colon Cancer Stem Cells

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    Joseph L. Regan

    2017-12-01

    Full Text Available Summary: Colon cancer is a heterogeneous tumor driven by a subpopulation of cancer stem cells (CSCs. To study CSCs in colon cancer, we used limiting dilution spheroid and serial xenotransplantation assays to functionally define the frequency of CSCs in a panel of patient-derived cancer organoids. These studies demonstrated cancer organoids to be enriched for CSCs, which varied in frequency between tumors. Whole-transcriptome analysis identified WNT and Hedgehog signaling components to be enhanced in CSC-enriched tumors and in aldehyde dehydrogenase (ALDH-positive CSCs. Canonical GLI-dependent Hedgehog signaling is a negative regulator of WNT signaling in normal intestine and intestinal tumors. Here, we show that Hedgehog signaling in colon CSCs is autocrine SHH-dependent, non-canonical PTCH1 dependent, and GLI independent. In addition, using small-molecule inhibitors and RNAi against SHH-palmitoylating Hedgehog acyltransferase (HHAT, we demonstrate that non-canonical Hedgehog signaling is a positive regulator of WNT signaling and required for colon CSC survival. : Colon cancer is a heterogeneous tumor driven by a subpopulation(s of therapy-resistant cancer stem cells (CSCs. Regan et al. use 3D culture models to demonstrate that CSC survival is regulated by non-canonical, SHH-dependent, PTCH1-dependent Hedgehog signaling, which acts as a positive regulator of WNT signaling to block CSC differentiation. Keywords: WNT pathway, non-canonical Hedgehog signaling, cancer stem cell, colon cancer, cancer organoid, PTCH1, HHAT, SHH

  14. Induction of CXC chemokines in human mesenchymal stem cells by stimulation with secreted frizzled-related proteins through non-canonical Wnt signaling.

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    Bischoff, David S; Zhu, Jian-Hua; Makhijani, Nalini S; Yamaguchi, Dean T

    2015-12-26

    To investigate the effect of secreted frizzled-related proteins (sFRPs) on CXC chemokine expression in human mesenchymal stem cells (hMSCs). CXC chemokines such as CXCL5 and CXCL8 are induced in hMSCs during differentiation with osteogenic differentiation medium (OGM) and may be involved in angiogenic stimulation during bone repair. hMSCs were treated with conditioned medium (CM) from L-cells expressing non-canonical Wnt5a protein, or with control CM from wild type L-cells, or directly with sFRPs for up to 10 d in culture. mRNA expression levels of both CXCL5 and CXCL8 were quantitated by real-time reverse transcriptase-polymerase chain reaction and secreted protein levels of these proteins determined by ELISA. Dose- (0-500 ng/mL) and time-response curves were generated for treatment with sFRP1. Signal transduction pathways were explored by western blot analysis with pan- or phosphorylation-specific antibodies, through use of specific pathway inhibitors, and through use of siRNAs targeting specific frizzled receptors (Fzd)-2 and 5 or the receptor tyrosine kinase-like orphan receptor-2 (RoR2) prior to treatment with sFRPs. CM from L-cells expressing Wnt5a, a non-canonical Wnt, stimulated an increase in CXCL5 mRNA expression and protein secretion in comparison to control L-cell CM. sFRP1, which should inhibit both canonical and non-canonical Wnt signaling, surprisingly enhanced the expression of CXCL5 at 7 and 10 d. Dickkopf1, an inhibitor of canonical Wnt signaling prevented the sFRP-stimulated induction of CXCL5 and actually inhibited basal levels of CXCL5 expression at 7 but not at 10 d post treatment. In addition, all four sFRPs isoforms induced CXCL8 expression in a dose- and time-dependent manner with maximum expression at 7 d with treatment at 150 ng/mL. The largest increases in CXCL5 expression were seen from stimulation with sFRP1 or sFRP2. Analysis of mitogen-activated protein kinase signaling pathways in the presence of OGM showed sFRP1-induced

  15. Prediction of non-canonical polyadenylation signals in human genomic sequences based on a novel algorithm using a fuzzy membership function.

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    Kamasawa, Masami; Horiuchi, Jun-Ichi

    2009-05-01

    Computational prediction of polyadenylation signals (PASes) is essential for analysis of alternative polyadenylation that plays crucial roles in gene regulations by generating heterogeneity of 3'-UTR of mRNAs. To date, several algorithms that are mostly based on machine learning methods have been developed to predict PASes. Accuracies of predictions by those algorithms have improved significantly for the last decade. However, they are designed primarily for prediction of the most canonical AAUAAA and its common variant AUUAAA whereas other variants have been ignored in their predictions despite recent studies indicating that non-canonical variants of AAUAAA are more important in the polyadenylation process than commonly recognized. Here we present a new algorithm "PolyF" employing fuzzy logic to confer an advance in computational PAS prediction--enable prediction of the non-canonical variants, and improve the accuracies for the canonical A(A/U)UAAA prediction. PolyF is a simple computational algorithm that is composed of membership functions defining sequence features of downstream sequence element (DSE) and upstream sequence element (USE), together with an inference engine. As a result, PolyF successfully identified the 10 single-nucleotide variants with approximately the same or higher accuracies compared to those for A(A/U)UAAA. PolyF also achieved higher accuracies for A(A/U)UAAA prediction than those by commonly known PAS finder programs, Polyadq and Erpin. Incorporating the USE into the PolyF algorithm was found to enhance prediction accuracies for all the 12 PAS hexamers compared to those using only the DSE, suggesting an important contribution of the USE in the polyadenylation process.

  16. β2-Adrenergic receptor activation mobilizes intracellular calcium via a non-canonical cAMP-independent signaling pathway.

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    Galaz-Montoya, Monica; Wright, Sara J; Rodriguez, Gustavo J; Lichtarge, Olivier; Wensel, Theodore G

    2017-06-16

    Beta adrenergic receptors (βARs) are G-protein-coupled receptors essential for physiological responses to the hormones/neurotransmitters epinephrine and norepinephrine which are found in the nervous system and throughout the body. They are the targets of numerous widely used drugs, especially in the case of the most extensively studied βAR, β 2 AR, whose ligands are used for asthma and cardiovascular disease. βARs signal through Gα s G-proteins and via activation of adenylyl cyclase and cAMP-dependent protein kinase, but some alternative downstream pathways have also been proposed that could be important for understanding normal physiological functioning of βAR signaling and its disruption in disease. Using fluorescence-based Ca 2+ flux assays combined with pharmacology and gene knock-out methods, we discovered a previously unrecognized endogenous pathway in HEK-293 cells whereby β 2 AR activation leads to robust Ca 2+ mobilization from intracellular stores via activation of phospholipase C and opening of inositol trisphosphate (InsP 3 ) receptors. This pathway did not involve cAMP, Gα s , or Gα i or the participation of the other members of the canonical β 2 AR signaling cascade and, therefore, constitutes a novel signaling mechanism for this receptor. This newly uncovered mechanism for Ca 2+ mobilization by β 2 AR has broad implications for adrenergic signaling, cross-talk with other signaling pathways, and the effects of βAR-directed drugs. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

  17. Celecoxib Ameliorates Non-Alcoholic Steatohepatitis in Type 2 Diabetic Rats via Suppression of the Non-Canonical Wnt Signaling Pathway Expression

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    Tian, Feng; Zhang, Ya Jie; Li, Yu; Xie, Ying

    2014-01-01

    Our aim was to test whether pharmacological inhibition of cycloxygenase-2 (COX-2) reverses non-alcoholic steatohepatitis (NASH) in type 2 diabetes mellitus (T2DM) rats via suppression of the non-canonical Wnt signaling pathway expression. Twenty-four male Sprague-Dawley rats were randomly distributed to two groups and were fed with a high fat and sucrose (HF-HS) diet or a normal chow diet, respectively. After four weeks, rats fed with a HF-HS diet were made diabetic with low-dose streptozotocin. At the 9th week the diabetic rats fed with a HF-HS diet or the non-diabetic rats fed with a normal chow diet were further divided into two subgroups treated with vehicle or celecoxib (a selective COX-2 inhibitor, 10 mg/Kg/day, gavage) for the last 4 weeks, respectively. At the end of the 12th week, rats were anesthetized. NASH was assessed by histology. Related cytokine expression was measured at both the protein and gene levels through immunohistochemistry (IHC), Western blot and real-time PCR. T2DM rats fed with a HF-HS diet developed steatohepatitis and insulin resistance associated with elevated serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), insulin levels and the non-alcoholic fatty liver disease (NAFLD) activity score (NAS). The expression of Wnt5a, JNK1, NF-κB p65, and COX-2 were all significantly increased in the T2DM-NASH group compared with the control and control-cele group. Hepatic injury was improved by celecoxib in T2DM-NASH-Cele group indicated by reduced serum ALT and AST levels and hepatic inflammation was reduced by celecoxib showed by histology and the NAFLD activity score (NAS). Serum related metabolic parameters, HOMA-IR and insulin sensitivity index were all improved by celecoxib. The expression of Wnt5a, JNK1, NF-κB p65, and COX-2 expression were all suppressed by celecoxib in T2DM-NASH-Cele group. The results of the present study indicated that celecoxib ameliorated NASH in T2DM rats via suppression of the non-canonical Wnt

  18. Characterization of a Non-Canonical Signal Peptidase Cleavage Site in a Replication Protein from Tomato Ringspot Virus.

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    Ting Wei

    Full Text Available The NTB-VPg polyprotein from tomato ringspot virus is an integral membrane replication protein associated with endoplasmic reticulum membranes. A signal peptidase (SPase cleavage was previously detected in the C-terminal region of NTB-VPg downstream of a 14 amino acid (aa-long hydrophobic region (termed TM2. However, the exact location of the cleavage site was not determined. Using in vitro translation assays, we show that the SPase cleavage site is conserved in the NTB-VPg protein from various ToRSV isolates, although the rate of cleavage varies from one isolate to another. Systematic site-directed mutagenesis of the NTB-VPg SPase cleavage sites of two ToRSV isolates allowed the identification of sequences that affect cleavage efficiency. We also present evidence that SPase cleavage in the ToRSV-Rasp2 isolate occurs within a GAAGG sequence likely after the AAG (GAAG/G. Mutation of a downstream MAAV sequence to AAAV resulted in SPase cleavage at both the natural GAAG/G and the mutated AAA/V sequences. Given that there is a distance of seven aa between the two cleavage sites, this indicates that there is flexibility in the positioning of the cleavage sites relative to the inner surface of the membrane and the SPase active site. SPase cleavage sites are typically located 3-7 aa downstream of the hydrophobic region. However, the NTB-VPg GAAG/G cleavage site is located 17 aa downstream of the TM2 hydrophobic region, highlighting unusual features of the NTB-VPg SPase cleavage site. A putative 11 aa-long amphipathic helix was identified immediately downstream of the TM2 region and five aa upstream of the GAAG/G cleavage site. Based on these results, we present an updated topology model in which the hydrophobic and amphipathic domains form a long tilted helix or a bent helix in the membrane lipid bilayer, with the downstream cleavage site(s oriented parallel to the membrane inner surface.

  19. Canonical and non-canonical WNT signaling in cancer stem cells and their niches: Cellular heterogeneity, omics reprogramming, targeted therapy and tumor plasticity (Review)

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    Katoh, Masaru

    2017-01-01

    Cancer stem cells (CSCs), which have the potential for self-renewal, differentiation and de-differentiation, undergo epigenetic, epithelial-mesenchymal, immunological and metabolic reprogramming to adapt to the tumor microenvironment and survive host defense or therapeutic insults. Intra-tumor heterogeneity and cancer-cell plasticity give rise to therapeutic resistance and recurrence through clonal replacement and reactivation of dormant CSCs, respectively. WNT signaling cascades cross-talk with the FGF, Notch, Hedgehog and TGFβ/BMP signaling cascades and regulate expression of functional CSC markers, such as CD44, CD133 (PROM1), EPCAM and LGR5 (GPR49). Aberrant canonical and non-canonical WNT signaling in human malignancies, including breast, colorectal, gastric, lung, ovary, pancreatic, prostate and uterine cancers, leukemia and melanoma, are involved in CSC survival, bulk-tumor expansion and invasion/metastasis. WNT signaling-targeted therapeutics, such as anti-FZD1/2/5/7/8 monoclonal antibody (mAb) (vantictumab), anti-LGR5 antibody-drug conjugate (ADC) (mAb-mc-vc-PAB-MMAE), anti-PTK7 ADC (PF-06647020), anti-ROR1 mAb (cirmtuzumab), anti-RSPO3 mAb (rosmantuzumab), small-molecule porcupine inhibitors (ETC-159, WNT-C59 and WNT974), tankyrase inhibitors (AZ1366, G007-LK, NVP-TNKS656 and XAV939) and β-catenin inhibitors (BC2059, CWP232228, ICG-001 and PRI-724), are in clinical trials or preclinical studies for the treatment of patients with WNT-driven cancers. WNT signaling-targeted therapeutics are applicable for combination therapy with BCR-ABL, EGFR, FLT3, KIT or RET inhibitors to treat a subset of tyrosine kinase-driven cancers because WNT and tyrosine kinase signaling cascades converge to β-catenin for the maintenance and expansion of CSCs. WNT signaling-targeted therapeutics might also be applicable for combination therapy with immune checkpoint blockers, such as atezolizumab, avelumab, durvalumab, ipilimumab, nivolumab and pembrolizumab, to treat cancers

  20. A novel role for ecdysone in Drosophila conditioned behavior: linking GPCR-mediated non-canonical steroid action to cAMP signaling in the adult brain.

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    Ishimoto, Hiroshi; Wang, Zhe; Rao, Yi; Wu, Chun-Fang; Kitamoto, Toshihiro

    2013-01-01

    The biological actions of steroid hormones are mediated primarily by their cognate nuclear receptors, which serve as steroid-dependent transcription factors. However, steroids can also execute their functions by modulating intracellular signaling cascades rapidly and independently of transcriptional regulation. Despite the potential significance of such "non-genomic" steroid actions, their biological roles and the underlying molecular mechanisms are not well understood, particularly with regard to their effects on behavioral regulation. The major steroid hormone in the fruit fly Drosophila is 20-hydroxy-ecdysone (20E), which plays a variety of pivotal roles during development via the nuclear ecdysone receptors. Here we report that DopEcR, a G-protein coupled receptor for ecdysteroids, is involved in activity- and experience-dependent plasticity of the adult central nervous system. Remarkably, a courtship memory defect in rutabaga (Ca²⁺/calmodulin-responsive adenylate cyclase) mutants was rescued by DopEcR overexpression or acute 20E feeding, whereas a memory defect in dunce (cAMP-specific phosphodiestrase) mutants was counteracted when a loss-of-function DopEcR mutation was introduced. A memory defect caused by suppressing dopamine synthesis was also restored through enhanced DopEcR-mediated ecdysone signaling, and rescue and phenocopy experiments revealed that the mushroom body (MB)--a brain region central to learning and memory in Drosophila--is critical for the DopEcR-dependent processing of courtship memory. Consistent with this finding, acute 20E feeding induced a rapid, DopEcR-dependent increase in cAMP levels in the MB. Our multidisciplinary approach demonstrates that DopEcR mediates the non-canonical actions of 20E and rapidly modulates adult conditioned behavior through cAMP signaling, which is universally important for neural plasticity. This study provides novel insights into non-genomic actions of steroids, and opens a new avenue for genetic

  1. A novel role for ecdysone in Drosophila conditioned behavior: linking GPCR-mediated non-canonical steroid action to cAMP signaling in the adult brain.

    Directory of Open Access Journals (Sweden)

    Hiroshi Ishimoto

    Full Text Available The biological actions of steroid hormones are mediated primarily by their cognate nuclear receptors, which serve as steroid-dependent transcription factors. However, steroids can also execute their functions by modulating intracellular signaling cascades rapidly and independently of transcriptional regulation. Despite the potential significance of such "non-genomic" steroid actions, their biological roles and the underlying molecular mechanisms are not well understood, particularly with regard to their effects on behavioral regulation. The major steroid hormone in the fruit fly Drosophila is 20-hydroxy-ecdysone (20E, which plays a variety of pivotal roles during development via the nuclear ecdysone receptors. Here we report that DopEcR, a G-protein coupled receptor for ecdysteroids, is involved in activity- and experience-dependent plasticity of the adult central nervous system. Remarkably, a courtship memory defect in rutabaga (Ca²⁺/calmodulin-responsive adenylate cyclase mutants was rescued by DopEcR overexpression or acute 20E feeding, whereas a memory defect in dunce (cAMP-specific phosphodiestrase mutants was counteracted when a loss-of-function DopEcR mutation was introduced. A memory defect caused by suppressing dopamine synthesis was also restored through enhanced DopEcR-mediated ecdysone signaling, and rescue and phenocopy experiments revealed that the mushroom body (MB--a brain region central to learning and memory in Drosophila--is critical for the DopEcR-dependent processing of courtship memory. Consistent with this finding, acute 20E feeding induced a rapid, DopEcR-dependent increase in cAMP levels in the MB. Our multidisciplinary approach demonstrates that DopEcR mediates the non-canonical actions of 20E and rapidly modulates adult conditioned behavior through cAMP signaling, which is universally important for neural plasticity. This study provides novel insights into non-genomic actions of steroids, and opens a new avenue for

  2. A non-canonical Flt3ITD/NF-κB signaling pathway represses DAPK1 in acute myeloid leukemia (AML)

    Science.gov (United States)

    Shanmugam, Rajasubramaniam; Sayar, Hamid; Suvannasankha, Attaya; Goswami, Chirayu; Li, Lang; Gupta, Sushil; Cardoso, Angelo A.; Baghdadi, Tareq Al; Sargent, Katie J.; Cripe, Larry D.; Kalvakolanu, Dhananjaya V.; Boswell, H. Scott

    2014-01-01

    Purpose DAPK1, a tumor suppressor, is a rate-limiting effector in an ER stress-dependent apoptotic pathway. Its expression is epigenetically suppressed in several tumors. A mechanistic basis for epigenetic/transcriptional repression of DAPK1 was investigated in certain forms of AML with poor prognosis, which lacked ER stress-induced apoptosis. Experimental Design Heterogeneous primary AMLs were screened to identify a subgroup with Flt3ITD in which repression of DAPK1, among NF-κB- and c- jun-responsive genes, was studied. RNAi knockdown studies were performed in Flt3ITD+ve cell line, MV-4-11, to establish genetic epistasis in the pathway Flt3ITD-TAK1-DAPK1 repression, and chromatin immunoprecipitations were performed to identify proximate effector proteins, including TAK1-activated p52NF-κB, at the DAPK1 locus. Results AMLs characterized by normal karyotype with Flt3ITD were found to have 10-100-fold lower DAPK1 transcripts normalized to the expression of c-jun, a transcriptional activator of DAPK1, as compared to a heterogeneous cytogenetic category. Meis1, a c-jun-responsive adverse AML prognostic gene signature was also measured as control. These Flt3ITD+ve AMLs over-express relB, a transcriptional repressor, which forms active heterodimers with p52NF-κB. Chromatin immunoprecipitation assays identified p52NF-κB binding to the DAPK1 promoter along with HDAC2 and HDAC6 in the Flt3ITD+ve human AML cell line MV-4-11. Knockdown of p52NF-κB or its upstream regulator, NIK, de-repressed DAPK1. DAPK1-repressed primary Flt3ITD+ve AMLs had selective nuclear activation of p52NF-κB. Conclusions Flt3ITD promotes a non-canonical pathway via TAK1 and p52NF-κB to suppress DAPK1 in association with HDACs, which explains DAPK1 repression in Flt3ITD+ve AML. PMID:22096027

  3. Tyrosine phosphorylation and proteolytic cleavage of Notch are required for non-canonical Notch/Abl signaling in Drosophila axon guidance.

    Science.gov (United States)

    Kannan, Ramakrishnan; Cox, Eric; Wang, Lei; Kuzina, Irina; Gu, Qun; Giniger, Edward

    2018-01-17

    Notch signaling is required for the development and physiology of nearly every tissue in metazoans. Much of Notch signaling is mediated by transcriptional regulation of downstream target genes, but Notch controls axon patterning in Drosophila by local modulation of Abl tyrosine kinase signaling, via direct interactions with the Abl co-factors Disabled and Trio. Here, we show that Notch-Abl axonal signaling requires both of the proteolytic cleavage events that initiate canonical Notch signaling. We further show that some Notch protein is tyrosine phosphorylated in Drosophila , that this form of the protein is selectively associated with Disabled and Trio, and that relevant tyrosines are essential for Notch-dependent axon patterning but not for canonical Notch-dependent regulation of cell fate. Based on these data, we propose a model for the molecular mechanism by which Notch controls Abl signaling in Drosophila axons. © 2018. Published by The Company of Biologists Ltd.

  4. Peracetylated hydroxytyrosol, a new hydroxytyrosol derivate, attenuates LPS-induced inflammatory response in murine peritoneal macrophages via regulation of non-canonical inflammasome, Nrf2/HO1 and JAK/STAT signaling pathways.

    Science.gov (United States)

    Montoya, Tatiana; Aparicio-Soto, Marina; Castejón, María Luisa; Rosillo, María Ángeles; Sánchez-Hidalgo, Marina; Begines, Paloma; Fernández-Bolaños, José G; Alarcón-de-la-Lastra, Catalina

    2018-03-18

    The present study was designed to investigate the anti-inflammatory effects of a new derivative of hydroxytyrosol (HTy), peracetylated hydroxytyrosol (Per-HTy), compared with its parent, HTy, on lipopolysaccharide (LPS)-stimulated murine macrophages as well as potential signaling pathways involved. In particular, we attempted to characterize the role of the inflammasome underlying Per-HTy possible anti-inflammatory effects. Isolated murine peritoneal macrophages were treated with HTy or its derivative in the presence or absence of LPS (5 μg/ml) for 18 h. Cell viability was determined using sulforhodamine B (SRB) assay. Nitric oxide (NO) production was analyzed by Griess method. Production of pro-inflammatory cytokines was evaluated by enzyme-linked immunosorbent assay (ELISA) and inducible nitric oxide synthase (iNOS) and cyclooxygenase (COX)-2, janus kinase/signal transducer and activator of transcription (JAK/STAT) pathway (STAT3), haem oxigenase 1 (HO1), nuclear factor (erythroid-derived 2)-like 2 (Nrf2) expression and mitogen-activated protein kinases (MAPKs) activation was determined by Western blot. Per-HTy significantly reduced the levels of NO and pro-inflammatory cytokines as well as both COX-2 and iNOS expressions. Furthermore, Per-HTy treatment inhibited STAT3 and increased Nrf2 and HO1 protein levels in murine macrophages exposed to LPS. In addition, Per-HTy anti-inflammatory activity was related with an inhibition of non-canonical nucleotide binding domain (NOD)-like receptor (NLRP3) inflammasome pathways by decreasing pro-inflammatory interleukin (IL)-1β and IL-18 cytokine levels as consequence of regulation of cleaved caspase-11 enzyme. These results support that this new HTy derivative may offer a new promising nutraceutical therapeutic strategy in the management of inflammatory-related pathologies. Copyright © 2018. Published by Elsevier Inc.

  5. Relations between canonical and non-canonical inflation

    Energy Technology Data Exchange (ETDEWEB)

    Gwyn, Rhiannon [Max-Planck-Institut fuer Gravitationsphysik (Albert-Einstein-Institut), Potsdam (Germany); Rummel, Markus [Hamburg Univ. (Germany). 2. Inst. fuer Theoretische Physik; Westphal, Alexander [Deutsches Elektronen-Synchrotron (DESY), Hamburg (Germany). Theory Group

    2012-12-15

    We look for potential observational degeneracies between canonical and non-canonical models of inflation of a single field {phi}. Non-canonical inflationary models are characterized by higher than linear powers of the standard kinetic term X in the effective Lagrangian p(X,{phi}) and arise for instance in the context of the Dirac-Born-Infeld (DBI) action in string theory. An on-shell transformation is introduced that transforms non-canonical inflationary theories to theories with a canonical kinetic term. The 2-point function observables of the original non-canonical theory and its canonical transform are found to match in the case of DBI inflation.

  6. Chimeric Vaccine Stimulation of Human Dendritic Cell Indoleamine 2, 3-Dioxygenase Occurs via the Non-Canonical NF-κB Pathway.

    Directory of Open Access Journals (Sweden)

    Nan-Sun Kim

    Full Text Available A chimeric protein vaccine composed of the cholera toxin B subunit fused to proinsulin (CTB-INS was shown to suppress type 1 diabetes onset in NOD mice and upregulate biosynthesis of the tryptophan catabolic enzyme indoleamine 2, 3-dioxygenase (IDO1 in human dendritic cells (DCs. Here we demonstrate siRNA inhibition of the NF-κB-inducing kinase (NIK suppresses vaccine-induced IDO1 biosynthesis as well as IKKα phosphorylation. Chromatin immunoprecipitation (ChIP analysis of CTB-INS inoculated DCs showed that RelB bound to NF-κB consensus sequences in the IDO1 promoter, suggesting vaccine stimulation of the non-canonical NF-κB pathway activates IDO1 expression in vivo. The addition of Tumor Necrosis Factor Associated Factors (TRAF TRAF 2, 3 and TRAF6 blocking peptides to vaccine inoculated DCs was shown to inhibit IDO1 biosynthesis. This experimental outcome suggests vaccine activation of the TNFR super-family receptor pathway leads to upregulation of IDO1 biosynthesis in CTB-INS inoculated dendritic cells. Together, our experimental data suggest the CTB-INS vaccine uses a TNFR-dependent signaling pathway of the non-canonical NF-κB signaling pathway resulting in suppression of dendritic cell mediated type 1 diabetes autoimmunity.

  7. Intermediate inflation from a non-canonical scalar field

    Energy Technology Data Exchange (ETDEWEB)

    Rezazadeh, K.; Karami, K. [Department of Physics, University of Kurdistan, Pasdaran St., Sanandaj (Iran, Islamic Republic of); Karimi, P., E-mail: rezazadeh86@gmail.com, E-mail: KKarami@uok.ac.ir, E-mail: parvin.karimi67@yahoo.com [Center for Excellence in Astronomy and Astrophysics (CEAA-RIAAM), P.O. Box 55134-441, Maragha (Iran, Islamic Republic of)

    2015-09-01

    We study the intermediate inflation in a non-canonical scalar field framework with a power-like Lagrangian. We show that in contrast with the standard canonical intermediate inflation, our non-canonical model is compatible with the observational results of Planck 2015. Also, we estimate the equilateral non-Gaussianity parameter which is in well agreement with the prediction of Planck 2015. Then, we obtain an approximation for the energy scale at the initial time of inflation and show that it can be of order of the Planck energy scale, i.e. M{sub P} ∼ 10{sup 18}GeV. We will see that after a short period of time, inflation enters in the slow-roll regime that its energy scale is of order M{sub P}/100 ∼ 10{sup 16}GeV and the horizon exit takes place in this energy scale. We also examine an idea in our non-canonical model to overcome the central drawback of intermediate inflation which is the fact that inflation never ends. We solve this problem without disturbing significantly the nature of the intermediate inflation until the time of horizon exit.

  8. The degeneracy problem in non-canonical inflation

    International Nuclear Information System (INIS)

    Easson, Damien A.; Powell, Brian A.

    2013-01-01

    While attempting to connect inflationary theories to observational physics, a potential difficulty is the degeneracy problem: a single set of observables maps to a range of different inflaton potentials. Two important classes of models affected by the degeneracy problem are canonical and non-canonical models, the latter marked by the presence of a non-standard kinetic term that generates observables beyond the scalar and tensor two-point functions on CMB scales. The degeneracy problem is manifest when these distinguishing observables go undetected. We quantify the size of the resulting degeneracy in this case by studying the most well-motivated non-canonical theory having Dirac-Born-Infeld Lagrangian. Beyond the scalar and tensor two-point functions on CMB scales, we then consider the possible detection of equilateral non-Gaussianity at Planck-precision and a measurement of primordial gravitational waves from prospective space-based laser interferometers. The former detection breaks the degeneracy with canonical inflation but results in poor reconstruction prospects, while the latter measurement enables a determination of n T which, while not breaking the degeneracy, can be shown to greatly improve the non-canonical reconstruction

  9. Non-Canonical Cell Death Induced by p53

    Directory of Open Access Journals (Sweden)

    Atul Ranjan

    2016-12-01

    Full Text Available Programmed cell death is a vital biological process for multicellular organisms to maintain cellular homeostasis, which is regulated in a complex manner. Over the past several years, apart from apoptosis, which is the principal mechanism of caspase-dependent cell death, research on non-apoptotic forms of programmed cell death has gained momentum. p53 is a well characterized tumor suppressor that controls cell proliferation and apoptosis and has also been linked to non-apoptotic, non-canonical cell death mechanisms. p53 impacts these non-canonical forms of cell death through transcriptional regulation of its downstream targets, as well as direct interactions with key players involved in these mechanisms, in a cell type- or tissue context-dependent manner. In this review article, we summarize and discuss the involvement of p53 in several non-canonical modes of cell death, including caspase-independent apoptosis (CIA, ferroptosis, necroptosis, autophagic cell death, mitotic catastrophe, paraptosis, and pyroptosis, as well as its role in efferocytosis which is the process of clearing dead or dying cells.

  10. XEDAR activates the non-canonical NF-κB pathway

    International Nuclear Information System (INIS)

    Verhelst, Kelly; Gardam, Sandra; Borghi, Alice; Kreike, Marja; Carpentier, Isabelle; Beyaert, Rudi

    2015-01-01

    Members of the tumor necrosis factor receptor (TNFR) superfamily are involved in a number of physiological and pathological responses by activating a wide variety of intracellular signaling pathways. The X-linked ectodermal dysplasia receptor (XEDAR; also known as EDA2R or TNFRSF27) is a member of the TNFR superfamily that is highly expressed in ectodermal derivatives during embryonic development and binds to ectodysplasin-A2 (EDA-A2), a member of the TNF family that is encoded by the anhidrotic ectodermal dysplasia (EDA) gene. Although XEDAR was first described in the year 2000, its function and molecular mechanism of action is still largely unclear. XEDAR has been reported to activate canonical nuclear factor κB (NF-κB) signaling and mitogen-activated protein (MAP) kinases. Here we report that XEDAR is also able to trigger the non-canonical NF-κB pathway, characterized by the processing of p100 (NF-κB2) into p52, followed by nuclear translocation of p52 and RelB. We provide evidence that XEDAR-induced p100 processing relies on the binding of XEDAR to TRAF3 and TRAF6, and requires the kinase activity of NIK and IKKα. We also show that XEDAR stimulation results in NIK accumulation and that p100 processing is negatively regulated by TRAF3, cIAP1 and A20. - Highlights: • XEDAR activates the non-canonical NF-κB pathway. • XEDAR-induced processing of p100 depends on XEDAR interaction with TRAF3 and TRAF6. • XEDAR-induced processing of p100 depends on NIK and IKKα activity. • Overexpression of XEDAR leads to NIK accumulation. • XEDAR-induced processing of p100 is negatively regulated by TRAF3 cIAP1 and A20

  11. XEDAR activates the non-canonical NF-κB pathway

    Energy Technology Data Exchange (ETDEWEB)

    Verhelst, Kelly, E-mail: Kelly.Verhelst@irc.VIB-UGent.be [Inflammation Research Center, Unit of Molecular Signal Transduction in Inflammation, VIB, Ghent (Belgium); Department of Biomedical Molecular Biology, Ghent University, Ghent (Belgium); Gardam, Sandra, E-mail: s.gardam@garvan.org.au [Inflammation Research Center, Unit of Molecular Signal Transduction in Inflammation, VIB, Ghent (Belgium); Department of Biomedical Molecular Biology, Ghent University, Ghent (Belgium); Borghi, Alice, E-mail: Alice.Borghi@irc.VIB-UGent.be [Inflammation Research Center, Unit of Molecular Signal Transduction in Inflammation, VIB, Ghent (Belgium); Department of Biomedical Molecular Biology, Ghent University, Ghent (Belgium); Kreike, Marja, E-mail: Marja.Kreike@irc.VIB-UGent.be [Inflammation Research Center, Unit of Molecular Signal Transduction in Inflammation, VIB, Ghent (Belgium); Department of Biomedical Molecular Biology, Ghent University, Ghent (Belgium); Carpentier, Isabelle, E-mail: Isabelle.Carpentier@irc.VIB-UGent.be [Inflammation Research Center, Unit of Molecular Signal Transduction in Inflammation, VIB, Ghent (Belgium); Department of Biomedical Molecular Biology, Ghent University, Ghent (Belgium); Beyaert, Rudi, E-mail: Rudi.Beyaert@irc.VIB-UGent.be [Inflammation Research Center, Unit of Molecular Signal Transduction in Inflammation, VIB, Ghent (Belgium); Department of Biomedical Molecular Biology, Ghent University, Ghent (Belgium)

    2015-09-18

    Members of the tumor necrosis factor receptor (TNFR) superfamily are involved in a number of physiological and pathological responses by activating a wide variety of intracellular signaling pathways. The X-linked ectodermal dysplasia receptor (XEDAR; also known as EDA2R or TNFRSF27) is a member of the TNFR superfamily that is highly expressed in ectodermal derivatives during embryonic development and binds to ectodysplasin-A2 (EDA-A2), a member of the TNF family that is encoded by the anhidrotic ectodermal dysplasia (EDA) gene. Although XEDAR was first described in the year 2000, its function and molecular mechanism of action is still largely unclear. XEDAR has been reported to activate canonical nuclear factor κB (NF-κB) signaling and mitogen-activated protein (MAP) kinases. Here we report that XEDAR is also able to trigger the non-canonical NF-κB pathway, characterized by the processing of p100 (NF-κB2) into p52, followed by nuclear translocation of p52 and RelB. We provide evidence that XEDAR-induced p100 processing relies on the binding of XEDAR to TRAF3 and TRAF6, and requires the kinase activity of NIK and IKKα. We also show that XEDAR stimulation results in NIK accumulation and that p100 processing is negatively regulated by TRAF3, cIAP1 and A20. - Highlights: • XEDAR activates the non-canonical NF-κB pathway. • XEDAR-induced processing of p100 depends on XEDAR interaction with TRAF3 and TRAF6. • XEDAR-induced processing of p100 depends on NIK and IKKα activity. • Overexpression of XEDAR leads to NIK accumulation. • XEDAR-induced processing of p100 is negatively regulated by TRAF3 cIAP1 and A20.

  12. Integration of oxygen signaling at the consensus HRE.

    Science.gov (United States)

    Wenger, Roland H; Stiehl, Daniel P; Camenisch, Gieri

    2005-10-18

    The hypoxia-inducible factor 1 (HIF-1) was initially identified as a transcription factor that regulated erythropoietin gene expression in response to a decrease in oxygen availability in kidney tissue. Subsequently, a family of oxygen-dependent protein hydroxylases was found to regulate the abundance and activity of three oxygen-sensitive HIFalpha subunits, which, as part of the HIF heterodimer, regulated the transcription of at least 70 different effector genes. In addition to responding to a decrease in tissue oxygenation, HIF is proactively induced, even under normoxic conditions, in response to stimuli that lead to cell growth, ultimately leading to higher oxygen consumption. The growing cell thus profits from an anticipatory increase in HIF-dependent target gene expression. Growth stimuli-activated signaling pathways that influence the abundance and activity of HIFs include pathways in which kinases are activated and pathways in which reactive oxygen species are liberated. These pathways signal to the HIF protein hydroxylases, as well as to HIF itself, by means of covalent or redox modifications and protein-protein interactions. The final point of integration of all of these pathways is the hypoxia-response element (HRE) of effector genes. Here, we provide comprehensive compilations of the known growth stimuli that promote increases in HIF abundance, of protein-protein interactions involving HIF, and of the known HIF effector genes. The consensus HRE derived from a comparison of the HREs of these HIF effectors will be useful for identification of novel HIF target genes, design of oxygen-regulated gene therapy, and prediction of effects of future drugs targeting the HIF system.

  13. Non-canonical autophagy: an exception or an underestimated form of autophagy?

    Science.gov (United States)

    Scarlatti, Francesca; Maffei, Roberta; Beau, Isabelle; Ghidoni, Riccardo; Codogno, Patrice

    2008-11-01

    Macroautophagy (hereafter called autophagy) is a dynamic and evolutionarily conserved process used to sequester and degrade cytoplasm and entire organelles in a sequestering vesicle with a double membrane, known as the autophagosome, which ultimately fuses with a lysosome to degrade its autophagic cargo. Recently, we have unraveled two distinct forms of autophagy in cancer cells, which we term canonical and non-canonical autophagy. In contrast to classical or canonical autophagy, non-canonical autophagy is a process that does not require the entire set of autophagy-related (Atg) proteins in particular Beclin 1, to form the autophagosome. Non-canonical autophagy is therefore not blocked by the knockdown of Beclin 1 or of its binding partner hVps34. Moreover overexpression of Bcl-2, which is known to block canonical starvation-induced autophagy by binding to Beclin 1, is unable to reverse the non-canonical autophagy triggered by the polyphenol resveratrol in the breast cancer MCF-7 cell line. In MCF-7 cells, at least, non-canonical autophagy is involved in the caspase-independent cell death induced by resveratrol.

  14. Base pair probability estimates improve the prediction accuracy of RNA non-canonical base pairs.

    Directory of Open Access Journals (Sweden)

    Michael F Sloma

    2017-11-01

    Full Text Available Prediction of RNA tertiary structure from sequence is an important problem, but generating accurate structure models for even short sequences remains difficult. Predictions of RNA tertiary structure tend to be least accurate in loop regions, where non-canonical pairs are important for determining the details of structure. Non-canonical pairs can be predicted using a knowledge-based model of structure that scores nucleotide cyclic motifs, or NCMs. In this work, a partition function algorithm is introduced that allows the estimation of base pairing probabilities for both canonical and non-canonical interactions. Pairs that are predicted to be probable are more likely to be found in the true structure than pairs of lower probability. Pair probability estimates can be further improved by predicting the structure conserved across multiple homologous sequences using the TurboFold algorithm. These pairing probabilities, used in concert with prior knowledge of the canonical secondary structure, allow accurate inference of non-canonical pairs, an important step towards accurate prediction of the full tertiary structure. Software to predict non-canonical base pairs and pairing probabilities is now provided as part of the RNAstructure software package.

  15. Base pair probability estimates improve the prediction accuracy of RNA non-canonical base pairs.

    Science.gov (United States)

    Sloma, Michael F; Mathews, David H

    2017-11-01

    Prediction of RNA tertiary structure from sequence is an important problem, but generating accurate structure models for even short sequences remains difficult. Predictions of RNA tertiary structure tend to be least accurate in loop regions, where non-canonical pairs are important for determining the details of structure. Non-canonical pairs can be predicted using a knowledge-based model of structure that scores nucleotide cyclic motifs, or NCMs. In this work, a partition function algorithm is introduced that allows the estimation of base pairing probabilities for both canonical and non-canonical interactions. Pairs that are predicted to be probable are more likely to be found in the true structure than pairs of lower probability. Pair probability estimates can be further improved by predicting the structure conserved across multiple homologous sequences using the TurboFold algorithm. These pairing probabilities, used in concert with prior knowledge of the canonical secondary structure, allow accurate inference of non-canonical pairs, an important step towards accurate prediction of the full tertiary structure. Software to predict non-canonical base pairs and pairing probabilities is now provided as part of the RNAstructure software package.

  16. Generalized second law of thermodynamics for non-canonical scalar field model with corrected-entropy

    International Nuclear Information System (INIS)

    Das, Sudipta; Mamon, Abdulla Al; Debnath, Ujjal

    2015-01-01

    In this work, we have considered a non-canonical scalar field dark energy model in the framework of flat FRW background. It has also been assumed that the dark matter sector interacts with the non-canonical dark energy sector through some interaction term. Using the solutions for this interacting non-canonical scalar field dark energy model, we have investigated the validity of generalized second law (GSL) of thermodynamics in various scenarios using first law and area law of thermodynamics. For this purpose, we have assumed two types of horizons viz apparent horizon and event horizon for the universe and using first law of thermodynamics, we have examined the validity of GSL on both apparent and event horizons. Next, we have considered two types of entropy-corrections on apparent and event horizons. Using the modified area law, we have examined the validity of GSL of thermodynamics on apparent and event horizons under some restrictions of model parameters. (orig.)

  17. Unifying Dark Matter and Dark Energy with non-Canonical Scalars

    OpenAIRE

    Mishra, Swagat S.; Sahni, Varun

    2018-01-01

    Non-canonical scalar fields with the Lagrangian ${\\cal L} = X^\\alpha - V(\\phi)$, possess the attractive property that the speed of sound, $c_s^{2} = (2\\,\\alpha - 1)^{-1}$, can be exceedingly small for large values of $\\alpha$. This allows a non-canonical field to cluster and behave like warm/cold dark matter on small scales. We demonstrate that simple potentials such as $V = V_0\\coth^2{\\phi}$ and the Starobinsky-type potential $V(\\phi) = V_0 \\left ( 1 - e^{-{\\phi}}\\right )^{2}$ can unify dark...

  18. Non-canonical programmed cell death mechanisms triggered by natural compounds.

    Science.gov (United States)

    Diederich, Marc; Cerella, Claudia

    2016-10-01

    Natural compounds are the fundament of pharmacological treatments and more than 50% of all anticancer drugs are of natural origins or at least derived from scaffolds present in Nature. Over the last 25 years, molecular mechanisms triggered by natural anticancer compounds were investigated. Emerging research showed that molecules of natural origins are useful for both preventive and therapeutic purposes by targeting essential hallmarks and enabling characteristics described by Hanahan and Weinberg. Moreover, natural compounds were able to change the differentiation status of selected cell types. One of the earliest response of cells treated by pharmacologically active compounds is the change of its morphology leading to ultra-structural perturbations: changes in membrane composition, cytoskeleton integrity, alterations of the endoplasmic reticulum, mitochondria and of the nucleus lead to formation of morphological alterations that are a characteristic of both compound and cancer type preceding cell death. Apoptosis and autophagy were traditionally considered as the most prominent cell death or cell death-related mechanisms. By now multiple other cell death modalities were described and most likely involved in response to chemotherapeutic treatment. It can be hypothesized that especially necrosis-related phenotypes triggered by various treatments or evolving from apoptotic or autophagic mechanisms, provide a more efficient therapeutic outcome depending on cancer type and genetic phenotype of the patient. In fact, the recent discovery of multiple regulated forms of necrosis and the initial elucidation of the corresponding cell signaling pathways appear nowadays as important tools to clarify the immunogenic potential of non-canonical forms of cell death induction. Copyright © 2016 Elsevier Ltd. All rights reserved.

  19. Machine Learning Reveals a Non-Canonical Mode of Peptide Binding to MHC class II Molecules

    DEFF Research Database (Denmark)

    Andreatta, Massimo; Jurtz, Vanessa Isabell; Kaever, Thomas

    2017-01-01

    binding motif with a non-canonical binding core of length different from nine. This previously undescribed mode of peptide binding to MHCII molecules gives a more complete picture of peptide presentation by MHCII and allows us to model more accurately this event. This article is protected by copyright...

  20. Signature and Pathophysiology of Non-canonical Pores in Voltage-Dependent Cation Channels.

    Science.gov (United States)

    Held, Katharina; Voets, Thomas; Vriens, Joris

    2016-01-01

    Opening and closing of voltage-gated cation channels allows the regulated flow of cations such as Na(+), K(+), and Ca(2+) across cell membranes, which steers essential physiological processes including shaping of action potentials and triggering Ca(2+)-dependent processes. Classical textbooks describe the voltage-gated cation channels as membrane proteins with a single, central aqueous pore. In recent years, however, evidence has accumulated for the existence of additional ion permeation pathways in this group of cation channels, distinct from the central pore, which here we collectively name non-canonical pores. Whereas the first non-canonical pores were unveiled only after making specific point mutations in the voltage-sensor region of voltage-gated Na(+) and K(+) channels, recent evidence indicates that they may also be functional in non-mutated channels. Moreover, several channelopathies have been linked to mutations that cause the appearance of a non-canonical ion permeation pathway as a new pathological mechanism. This review provides an integrated overview of the biophysical properties of non-canonical pores described in voltage-dependent cation channels (KV, NaV, Cav, Hv1, and TRPM3) and of the (patho)physiological impact of opening of such pores.

  1. Horizon-preserving dualities and perturbations in non-canonical scalar field cosmologies

    International Nuclear Information System (INIS)

    Geshnizjani, Ghazal; Kinney, William H.; Dizgah, Azadeh Moradinezhad

    2012-01-01

    We generalize the cosmological duality between inflation and cyclic contraction under the interchange a↔H to the case of non-canonical scalar field theories with varying speed of sound. The single duality in the canonical case generalizes to a family of three dualities constructed to leave the cosmological acoustic horizon invariant. We find three classes of models: (I) DBI inflation, (II) the non-canonical generalization of cyclic contraction, and (III) a new cosmological solution with rapidly decreasing speed of sound and relatively slowly growing scale factor, which we dub stalled cosmology. We construct dual analogs to the inflationary slow roll approximation, and solve for the curvature perturbation in all three cases. Both cyclic contraction and stalled cosmology predict a strongly blue spectrum for the curvature perturbations inconsistent with observations

  2. Non-Canonical Roles of Dengue Virus Non-Structural Proteins

    Directory of Open Access Journals (Sweden)

    Julianna D. Zeidler

    2017-03-01

    Full Text Available The Flaviviridae family comprises a number of human pathogens, which, although sharing structural and functional features, cause diseases with very different outcomes. This can be explained by the plurality of functions exerted by the few proteins coded by viral genomes, with some of these functions shared among members of a same family, but others being unique for each virus species. These non-canonical functions probably have evolved independently and may serve as the base to the development of specific therapies for each of those diseases. Here it is discussed what is currently known about the non-canonical roles of dengue virus (DENV non-structural proteins (NSPs, which may account for some of the effects specifically observed in DENV infection, but not in other members of the Flaviviridae family. This review explores how DENV NSPs contributes to the physiopathology of dengue, evasion from host immunity, metabolic changes, and redistribution of cellular components during infection.

  3. The dark sector from interacting canonical and non-canonical scalar fields

    International Nuclear Information System (INIS)

    De Souza, Rudinei C; Kremer, Gilberto M

    2010-01-01

    In this work general models with interactions between two canonical scalar fields and between one non-canonical (tachyon type) and one canonical scalar field are investigated. The potentials and couplings to the gravity are selected through the Noether symmetry approach. These general models are employed to describe interactions between dark energy and dark matter, with the fields being constrained by the astronomical data. The cosmological solutions of some cases are compared with the observed evolution of the late Universe.

  4. Search for the non-canonical Ising spin glass on rewired square lattices

    Science.gov (United States)

    Surungan, Tasrief

    2018-03-01

    A spin glass (SG) of non-canonical type is a purely antiferromagnetic (AF) system, exemplified by the AF Ising model on a scale free network (SFN), studied by Bartolozzi et al. [ Phys. Rev. B73, 224419 (2006)]. Frustration in this new type of SG is rendered by topological factor and its randomness is caused by random connectivity. As an SFN corresponds to a large dimensional lattice, finding non-canonical SG in lattice with physical dimension is desireable. However, a regular lattice can not have random connectivity. In order to obtain lattices with random connection and preserving the notion of finite dimension, we costructed rewired lattices. We added some extra bonds randomly connecting each site of a regular lattice to its next-nearest neighbors. Very recently, Surungan et al., studied AF Heisenberg system on rewired square lattice and found no SG behavior [AIP Conf. Proc. 1719, 030006 (2016)]. Due to the importance of discrete symmetry for phase transition, here we study similar structure for the Ising model (Z 2 symmetry). We used Monte Carlo simulation with Replica Exchange algorithm. Two types of structures were studied, firstly, the rewired square lattices with one extra bonds added to each site, and secondly, two bonds added to each site. We calculated the Edwards-Anderson paremeter, the commonly used parameter in searching for SG phase. The non-canonical SG is clearly observed in the rewired square lattice with two extra bonds added.

  5. Non-canonical transcription initiation: the expanding universe of transcription initiating substrates

    Czech Academy of Sciences Publication Activity Database

    Barvík, I.; Rejman, Dominik; Panova, Natalya; Šanderová, Hana; Krásný, Libor

    2017-01-01

    Roč. 41, č. 2 (2017), s. 131-138 ISSN 0168-6445 R&D Projects: GA ČR GA15-05228S; GA ČR GA15-11711S Institutional support: RVO:61388963 ; RVO:61388971 Keywords : RNA polymerase * non-canonical transcription initiation * transcription initiating substrate * nicotinamide adenine dinucleotide (NAD(+)) * coenzymes * RNA stability Subject RIV: EB - Genetics ; Molecular Biology; EE - Microbiology, Virology (MBU-M) OBOR OECD: Biochemistry and molecular biology; Microbiology (MBU-M) Impact factor: 12.198, year: 2016

  6. A Chern-Simons gauge-fixed Lagrangian in a 'non-canonical' BRST approach

    International Nuclear Information System (INIS)

    Constantinescu, R; Ionescu, C

    2009-01-01

    This paper presents a possible path which starts from the extended BRST Hamiltonian formalism and ends with a covariant Lagrangian action, using the equivalence between the two formalisms. The approach allows a simple account of the form of the master equation and offers a natural identification of some 'non-canonical' operators and variables. These are the main items which solve the major difficulty of the extended BRST Lagrangian formalism, i.e., the gauge-fixing problem. The algorithm we propose applies to a non-Abelian Chern-Simons model coupled with Dirac fields

  7. Non-canonical CRL4A/4B(CDT2 interacts with RAD18 to modulate post replication repair and cell survival.

    Directory of Open Access Journals (Sweden)

    Sarah Sertic

    Full Text Available The Cullin-4(CDT2 E3 ubiquitin ligase plays an essential role in DNA replication origin licensing directing degradation of several licensing factors at the G1/S transition in order to prevent DNA re-replication. Recently a RAD18-independent role of Cullin-4(CDT2 in PCNA monoubiquitylation has been proposed. In an effort to better understand the function of Cullin-4(CDT2 E3 ubiquitin ligase in mammalian Post-Replication Repair during an unperturbed S-phase, we show that down-regulation of Cullin-4(CDT2 leads to two distinguishable independent phenotypes in human cells that unveil at least two independent roles of Cullin-4(CDT2 in S-phase. Apart from the re-replication preventing activity, we identified a non-canonical Cullin-4(CDT2 complex, containing both CUL4A and CUL4B, associated to the COP9 signalosome, that controls a RAD18-dependent damage avoidance pathway essential during an unperturbed S-phase. Indeed, we show that the non-canonical Cullin-4A/4B(CDT2 complex binds to RAD18 and it is required to modulate RAD18 protein levels onto chromatin and the consequent dynamics of PCNA monoubiquitylation during a normal S-phase. This function prevents replication stress, ATR hyper-signaling and, ultimately, apoptosis. A very similar PRR regulatory mechanism has been recently described for Spartan. Our findings uncover a finely regulated process in mammalian cells involving Post-Replication Repair factors, COP9 signalosome and a non-canonical Cullin4-based E3 ligase which is essential to tolerate spontaneous damage and for cell survival during physiological DNA replication.

  8. Gossypol induces pyroptosis in mouse macrophages via a non-canonical inflammasome pathway

    International Nuclear Information System (INIS)

    Lin, Qiu-Ru; Li, Chen-Guang; Zha, Qing-Bing; Xu, Li-Hui; Pan, Hao; Zhao, Gao-Xiang; Ouyang, Dong-Yun; He, Xian-Hui

    2016-01-01

    Gossypol, a polyphenolic compound isolated from cottonseeds, has been reported to possess many pharmacological activities, but whether it can influence inflammasome activation remains unclear. In this study, we found that in mouse macrophages, gossypol induced cell death characterized by rapid membrane rupture and robust release of HMGB1 and pro-caspase-11 comparable to ATP treatment, suggesting an induction of pyroptotic cell death. Unlike ATP, gossypol induced much low levels of mature interleukin-1β (IL-1β) secretion from mouse peritoneal macrophages primed with LPS, although it caused pro-IL-1β release similar to that of ATP. Consistent with this, activated caspase-1 responsible for pro-IL-1β maturation was undetectable in gossypol-treated peritoneal macrophages. Besides, RAW 264.7 cells lacking ASC expression and caspase-1 activation also underwent pyroptotic cell death upon gossypol treatment. In further support of pyroptosis induction, both pan-caspase inhibitor and caspase-1 subfamily inhibitor, but not caspase-3 inhibitor, could sharply suppress gossypol-induced cell death. Other canonical pyroptotic inhibitors, including potassium chloride and N-acetyl-L-cysteine, could suppress ATP-induced pyroptosis but failed to inhibit or even enhanced gossypol-induced cell death, whereas nonspecific pore-formation inhibitor glycine could attenuate this process, suggesting involvement of a non-canonical pathway. Of note, gossypol treatment eliminated thioglycollate-induced macrophages in the peritoneal cavity with recruitment of other leukocytes. Moreover, gossypol administration markedly decreased the survival of mice in a bacterial sepsis model. Collectively, these results suggested that gossypol induced pyroptosis in mouse macrophages via a non-canonical inflammasome pathway, which raises a concern for its in vivo cytotoxicity to macrophages. - Highlights: • Gossypol induces pyroptosis in mouse peritoneal and RAW 264.7 macrophages. • In LPS

  9. Gossypol induces pyroptosis in mouse macrophages via a non-canonical inflammasome pathway

    Energy Technology Data Exchange (ETDEWEB)

    Lin, Qiu-Ru; Li, Chen-Guang [Department of Immunobiology, College of Life Science and Technology, Jinan University, Guangzhou 510632 (China); Zha, Qing-Bing [Department of Fetal Medicine, The First Affiliated Hospital of Jinan University, Guangzhou 510632 (China); Xu, Li-Hui [Department of Cell Biology, College of Life Science and Technology, Jinan University, Guangzhou 510632 (China); Pan, Hao; Zhao, Gao-Xiang [Department of Immunobiology, College of Life Science and Technology, Jinan University, Guangzhou 510632 (China); Ouyang, Dong-Yun, E-mail: dongyun1967@aliyun.com [Department of Immunobiology, College of Life Science and Technology, Jinan University, Guangzhou 510632 (China); He, Xian-Hui, E-mail: thexh@jnu.edu.cn [Department of Immunobiology, College of Life Science and Technology, Jinan University, Guangzhou 510632 (China)

    2016-02-01

    Gossypol, a polyphenolic compound isolated from cottonseeds, has been reported to possess many pharmacological activities, but whether it can influence inflammasome activation remains unclear. In this study, we found that in mouse macrophages, gossypol induced cell death characterized by rapid membrane rupture and robust release of HMGB1 and pro-caspase-11 comparable to ATP treatment, suggesting an induction of pyroptotic cell death. Unlike ATP, gossypol induced much low levels of mature interleukin-1β (IL-1β) secretion from mouse peritoneal macrophages primed with LPS, although it caused pro-IL-1β release similar to that of ATP. Consistent with this, activated caspase-1 responsible for pro-IL-1β maturation was undetectable in gossypol-treated peritoneal macrophages. Besides, RAW 264.7 cells lacking ASC expression and caspase-1 activation also underwent pyroptotic cell death upon gossypol treatment. In further support of pyroptosis induction, both pan-caspase inhibitor and caspase-1 subfamily inhibitor, but not caspase-3 inhibitor, could sharply suppress gossypol-induced cell death. Other canonical pyroptotic inhibitors, including potassium chloride and N-acetyl-L-cysteine, could suppress ATP-induced pyroptosis but failed to inhibit or even enhanced gossypol-induced cell death, whereas nonspecific pore-formation inhibitor glycine could attenuate this process, suggesting involvement of a non-canonical pathway. Of note, gossypol treatment eliminated thioglycollate-induced macrophages in the peritoneal cavity with recruitment of other leukocytes. Moreover, gossypol administration markedly decreased the survival of mice in a bacterial sepsis model. Collectively, these results suggested that gossypol induced pyroptosis in mouse macrophages via a non-canonical inflammasome pathway, which raises a concern for its in vivo cytotoxicity to macrophages. - Highlights: • Gossypol induces pyroptosis in mouse peritoneal and RAW 264.7 macrophages. • In LPS

  10. Complement factor H family proteins in their non-canonical role as modulators of cellular functions.

    Science.gov (United States)

    Józsi, Mihály; Schneider, Andrea E; Kárpáti, Éva; Sándor, Noémi

    2018-01-04

    Complement factor H is a major regulator of the alternative pathway of the complement system. The factor H-related proteins are less characterized, but recent data indicate that they rather promote complement activation. These proteins have some common ligands with factor H and have both overlapping and distinct functions depending on domain composition and the degree of conservation of amino acid sequence. Factor H and some of the factor H-related proteins also appear in a non-canonical function that is beyond their role in the modulation of complement activation. This review covers our current understanding on this emerging role of factor H family proteins in modulating the activation and function of various cells by binding to receptors or receptor ligands. Copyright © 2018 Elsevier Ltd. All rights reserved.

  11. A non-canonical landscape of the microRNA system

    Directory of Open Access Journals (Sweden)

    Gabriel Adelman Cipolla

    2014-09-01

    Full Text Available Microribonucleic acids, best known as microRNAs or miRNAs, are small, non-coding RNAs with important regulatory roles in eukaryotic cells. Here, I present a broad review about highly relevant but generally non-depicted features of miRNAs, among which stand out the non-conventional miRNA seed sites, the unusual messenger RNA (mRNA target regions, the non-canonical miRNA-guided mechanisms of gene expression regulation and the recently identified new class of miRNA ligands. Furthermore, I address the miRNA uncommon genomic location, transcription, and subcellular localization. Altogether, these unusual features and roles place the miRNA system as a very diverse, complex and intriguing biological mechanism.

  12. The Meckel-Gruber syndrome protein TMEM67 controls basal body positioning and epithelial branching morphogenesis in mice via the non-canonical Wnt pathway

    Directory of Open Access Journals (Sweden)

    Zakia A. Abdelhamed

    2015-06-01

    Full Text Available Ciliopathies are a group of developmental disorders that manifest with multi-organ anomalies. Mutations in TMEM67 (MKS3 cause a range of human ciliopathies, including Meckel-Gruber and Joubert syndromes. In this study we describe multi-organ developmental abnormalities in the Tmem67tm1Dgen/H1 knockout mouse that closely resemble those seen in Wnt5a and Ror2 knockout mice. These include pulmonary hypoplasia, ventricular septal defects, shortening of the body longitudinal axis, limb abnormalities, and cochlear hair cell stereociliary bundle orientation and basal body/kinocilium positioning defects. The basal body/kinocilium complex was often uncoupled from the hair bundle, suggesting aberrant basal body migration, although planar cell polarity and apical planar asymmetry in the organ of Corti were normal. TMEM67 (meckelin is essential for phosphorylation of the non-canonical Wnt receptor ROR2 (receptor-tyrosine-kinase-like orphan receptor 2 upon stimulation with Wnt5a-conditioned medium. ROR2 also colocalises and interacts with TMEM67 at the ciliary transition zone. Additionally, the extracellular N-terminal domain of TMEM67 preferentially binds to Wnt5a in an in vitro binding assay. Cultured lungs of Tmem67 mutant mice failed to respond to stimulation of epithelial branching morphogenesis by Wnt5a. Wnt5a also inhibited both the Shh and canonical Wnt/β-catenin signalling pathways in wild-type embryonic lung. Pulmonary hypoplasia phenotypes, including loss of correct epithelial branching morphogenesis and cell polarity, were rescued by stimulating the non-canonical Wnt pathway downstream of the Wnt5a-TMEM67-ROR2 axis by activating RhoA. We propose that TMEM67 is a receptor that has a main role in non-canonical Wnt signalling, mediated by Wnt5a and ROR2, and normally represses Shh signalling. Downstream therapeutic targeting of the Wnt5a-TMEM67-ROR2 axis might, therefore, reduce or prevent pulmonary hypoplasia in ciliopathies and other congenital

  13. Non-canonical spectral decomposition of random functions of the traction voltage and current in electric transportation systems

    Directory of Open Access Journals (Sweden)

    N.A. Kostin

    2015-03-01

    Full Text Available The paper proposes the non-canonical spectral decomposition of random functions of the traction voltages and currents. This decomposition is adapted for the electric transportation systems. The numerical representation is carried out for the random function of voltage on the pantograph of electric locomotives VL8 and DE1.

  14. Canonical and non-canonical barriers facing antimiR cancer therapeutics.

    Science.gov (United States)

    Cheng, Christopher J; Saltzman, W Mark; Slack, Frank J

    2013-01-01

    Once considered genetic "oddities", microRNAs (miRNAs) are now recognized as key epigenetic regulators of numerous biological processes, including some with a causal link to the pathogenesis, maintenance, and treatment of cancer. The crux of small RNA-based therapeutics lies in the antagonism of potent cellular targets; the main shortcoming of the field in general, lies in ineffective delivery. Inhibition of oncogenic miRNAs is a relatively nascent therapeutic concept, but as with predecessor RNA-based therapies, success hinges on delivery efficacy. This review will describes the canonical (e.g. pharmacokinetics and clearance, cellular uptake, endosome escape, etc.) and non-canonical (e.g. spatial localization and accessibility of miRNA, technical limitations of miRNA inhibition, off-target impacts, etc.) challenges to the delivery of antisense-based anti-miRNA therapeutics (i.e. antimiRs) for the treatment of cancer. Emphasis will be placed on how the current leading antimiR platforms-ranging from naked chemically modified oligonucleotides to nanoscale delivery vehicles-are affected by and overcome these barriers. The perplexity of antimiR delivery presents both engineering and biological hurdles that must be overcome in order to capitalize on the extensive pharmacological benefits of antagonizing tumor-associated miRNAs.

  15. A non-canonical transferred DNA insertion at the BRI1 locus in Arabidopsis thaliana.

    Science.gov (United States)

    Zhao, Zhong; Zhu, Yan; Erhardt, Mathieu; Ruan, Ying; Shen, Wen-Hui

    2009-04-01

    Agrobacterium-mediated transformation is widely used in transgenic plant engineering and has been proven to be a powerful tool for insertional mutagenesis of the plant genome. The transferred DNA (T-DNA) from Agrobacterium is integrated into the plant genome through illegitimate recombination between the T-DNA and the plant DNA. Contrasting to the canonical insertion, here we report on a locus showing a complex mutation associated with T-DNA insertion at the BRI1 gene in Arabidopsis thaliana. We obtained a mutant line, named salade for its phenotype of dwarf stature and proliferating rosette. Molecular characterization of this mutant revealed that in addition to T-DNA a non-T-DNA-localized transposon from bacteria was inserted in the Arabidopsis genome and that a region of more than 11.5 kb of the Arabidopsis genome was deleted at the insertion site. The deleted region contains the brassinosteroid receptor gene BRI1 and the transcription factor gene WRKY13. Our finding reveals non-canonical T-DNA insertion, implicating horizontal gene transfer and cautioning the use of T-DNA as mutagen in transgenic research.

  16. Far-red fluorescent probes for canonical and non-canonical nucleic acid structures: current progress and future implications.

    Science.gov (United States)

    Suseela, Y V; Narayanaswamy, Nagarjun; Pratihar, Sumon; Govindaraju, Thimmaiah

    2018-02-05

    The structural diversity and functional relevance of nucleic acids (NAs), mainly deoxyribonucleic acid (DNA) and ribonucleic acid (RNA), are indispensable for almost all living organisms, with minute aberrations in their structure and function becoming causative factors in numerous human diseases. The standard structures of NAs, termed canonical structures, are supported by Watson-Crick hydrogen bonding. Under special physiological conditions, NAs adopt distinct spatial organisations, giving rise to non-canonical conformations supported by hydrogen bonding other than the Watson-Crick type; such non-canonical structures have a definite function in controlling gene expression and are considered as novel diagnostic and therapeutic targets. Development of molecular probes for these canonical and non-canonical DNA/RNA structures has been an active field of research. Among the numerous probes studied, probes with turn-on fluorescence in the far-red (600-750 nm) region are highly sought-after due to minimal autofluorescence and cellular damage. Far-red fluorescent probes are vital for real-time imaging of NAs in live cells as they provide good resolution and minimal perturbation of the cell under investigation. In this review, we present recent advances in the area of far-red fluorescent probes of DNA/RNA and non-canonical G-quadruplex structures. For the sake of continuity and completeness, we provide a brief overview of visible fluorescent probes. Utmost importance is given to design criteria, characteristic properties and biological applications, including in cellulo imaging, apart from critical discussion on limitations of the far-red fluorescent probes. Finally, we offer current and future prospects in targeting canonical and non-canonical NAs specific to cellular organelles, through sequence- and conformation-specific far-red fluorescent probes. We also cover their implications in chemical and molecular biology, with particular focus on decoding various disease

  17. The TOPCONS web server for consensus prediction of membrane protein topology and signal peptides.

    Science.gov (United States)

    Tsirigos, Konstantinos D; Peters, Christoph; Shu, Nanjiang; Käll, Lukas; Elofsson, Arne

    2015-07-01

    TOPCONS (http://topcons.net/) is a widely used web server for consensus prediction of membrane protein topology. We hereby present a major update to the server, with some substantial improvements, including the following: (i) TOPCONS can now efficiently separate signal peptides from transmembrane regions. (ii) The server can now differentiate more successfully between globular and membrane proteins. (iii) The server now is even slightly faster, although a much larger database is used to generate the multiple sequence alignments. For most proteins, the final prediction is produced in a matter of seconds. (iv) The user-friendly interface is retained, with the additional feature of submitting batch files and accessing the server programmatically using standard interfaces, making it thus ideal for proteome-wide analyses. Indicatively, the user can now scan the entire human proteome in a few days. (v) For proteins with homology to a known 3D structure, the homology-inferred topology is also displayed. (vi) Finally, the combination of methods currently implemented achieves an overall increase in performance by 4% as compared to the currently available best-scoring methods and TOPCONS is the only method that can identify signal peptides and still maintain a state-of-the-art performance in topology predictions. © The Author(s) 2015. Published by Oxford University Press on behalf of Nucleic Acids Research.

  18. Telomerase variant A279T induces telomere dysfunction and inhibits non-canonical telomerase activity in esophageal carcinomas.

    Directory of Open Access Journals (Sweden)

    Yuwei Zhang

    exposure, as well as Li Fraumeni fibroblasts in the absence of pharmacologically-induced DNA damage.A279T induces telomere dysfunction and inhibits non-canonical telomerase activity in esophageal cancer cells. These findings warrant further analysis of A279T expression in esophageal cancers and premalignant esophageal lesions.

  19. Translation system engineering in Escherichia coli enhances non-canonical amino acid incorporation into proteins.

    Science.gov (United States)

    Gan, Rui; Perez, Jessica G; Carlson, Erik D; Ntai, Ioanna; Isaacs, Farren J; Kelleher, Neil L; Jewett, Michael C

    2017-05-01

    The ability to site-specifically incorporate non-canonical amino acids (ncAAs) into proteins has made possible the study of protein structure and function in fundamentally new ways, as well as the bio synthesis of unnatural polymers. However, the task of site-specifically incorporating multiple ncAAs into proteins with high purity and yield continues to present a challenge. At the heart of this challenge lies the lower efficiency of engineered orthogonal translation system components compared to their natural counterparts (e.g., translation elements that specifically use a ncAA and do not interact with the cell's natural translation apparatus). Here, we show that evolving and tuning expression levels of multiple components of an engineered translation system together as a whole enhances ncAA incorporation efficiency. Specifically, we increase protein yield when incorporating multiple p-azido-phenylalanine(pAzF) residues into proteins by (i) evolving the Methanocaldococcus jannaschii p-azido-phenylalanyl-tRNA synthetase anti-codon binding domain, (ii) evolving the elongation factor Tu amino acid-binding pocket, and (iii) tuning the expression of evolved translation machinery components in a single vector. Use of the evolved translation machinery in a genomically recoded organism lacking release factor one enabled enhanced multi-site ncAA incorporation into proteins. We anticipate that our approach to orthogonal translation system development will accelerate and expand our ability to site-specifically incorporate multiple ncAAs into proteins and biopolymers, advancing new horizons for synthetic and chemical biotechnology. Biotechnol. Bioeng. 2017;114: 1074-1086. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  20. Explicit high-order non-canonical symplectic particle-in-cell algorithms for Vlasov-Maxwell systems

    International Nuclear Information System (INIS)

    Xiao, Jianyuan; Liu, Jian; He, Yang; Zhang, Ruili; Qin, Hong; Sun, Yajuan

    2015-01-01

    Explicit high-order non-canonical symplectic particle-in-cell algorithms for classical particle-field systems governed by the Vlasov-Maxwell equations are developed. The algorithms conserve a discrete non-canonical symplectic structure derived from the Lagrangian of the particle-field system, which is naturally discrete in particles. The electromagnetic field is spatially discretized using the method of discrete exterior calculus with high-order interpolating differential forms for a cubic grid. The resulting time-domain Lagrangian assumes a non-canonical symplectic structure. It is also gauge invariant and conserves charge. The system is then solved using a structure-preserving splitting method discovered by He et al. [preprint http://arxiv.org/abs/arXiv:1505.06076 (2015)], which produces five exactly soluble sub-systems, and high-order structure-preserving algorithms follow by combinations. The explicit, high-order, and conservative nature of the algorithms is especially suitable for long-term simulations of particle-field systems with extremely large number of degrees of freedom on massively parallel supercomputers. The algorithms have been tested and verified by the two physics problems, i.e., the nonlinear Landau damping and the electron Bernstein wave

  1. Explicit high-order non-canonical symplectic particle-in-cell algorithms for Vlasov-Maxwell systems

    Energy Technology Data Exchange (ETDEWEB)

    Xiao, Jianyuan [School of Nuclear Science and Technology and Department of Modern Physics, University of Science and Technology of China, Hefei, Anhui 230026, China; Key Laboratory of Geospace Environment, CAS, Hefei, Anhui 230026, China; Qin, Hong [School of Nuclear Science and Technology and Department of Modern Physics, University of Science and Technology of China, Hefei, Anhui 230026, China; Plasma Physics Laboratory, Princeton University, Princeton, New Jersey 08543, USA; Liu, Jian [School of Nuclear Science and Technology and Department of Modern Physics, University of Science and Technology of China, Hefei, Anhui 230026, China; Key Laboratory of Geospace Environment, CAS, Hefei, Anhui 230026, China; He, Yang [School of Nuclear Science and Technology and Department of Modern Physics, University of Science and Technology of China, Hefei, Anhui 230026, China; Key Laboratory of Geospace Environment, CAS, Hefei, Anhui 230026, China; Zhang, Ruili [School of Nuclear Science and Technology and Department of Modern Physics, University of Science and Technology of China, Hefei, Anhui 230026, China; Key Laboratory of Geospace Environment, CAS, Hefei, Anhui 230026, China; Sun, Yajuan [LSEC, Academy of Mathematics and Systems Science, Chinese Academy of Sciences, P.O. Box 2719, Beijing 100190, China

    2015-11-01

    Explicit high-order non-canonical symplectic particle-in-cell algorithms for classical particle-field systems governed by the Vlasov-Maxwell equations are developed. The algorithms conserve a discrete non-canonical symplectic structure derived from the Lagrangian of the particle-field system, which is naturally discrete in particles. The electromagnetic field is spatially discretized using the method of discrete exterior calculus with high-order interpolating differential forms for a cubic grid. The resulting time-domain Lagrangian assumes a non-canonical symplectic structure. It is also gauge invariant and conserves charge. The system is then solved using a structure-preserving splitting method discovered by He et al. [preprint arXiv: 1505.06076 (2015)], which produces five exactly soluble sub-systems, and high-order structure-preserving algorithms follow by combinations. The explicit, high-order, and conservative nature of the algorithms is especially suitable for long-term simulations of particle-field systems with extremely large number of degrees of freedom on massively parallel supercomputers. The algorithms have been tested and verified by the two physics problems, i.e., the nonlinear Landau damping and the electron Bernstein wave. (C) 2015 AIP Publishing LLC.

  2. Stepping towards new parameterizations for non-canonical atmospheric surface-layer conditions

    Science.gov (United States)

    Calaf, M.; Margairaz, F.; Pardyjak, E.

    2017-12-01

    -dynamics parameter is introduced to differentiate dispersive fluxes driven by surface thermal heterogeneities from those induced by surface shear. We believe that results from this research are a first step in developing new parameterizations appropriate for non-canonical ASL conditions.

  3. Defining a conformational consensus motif in cotransin-sensitive signal sequences: a proteomic and site-directed mutagenesis study.

    Directory of Open Access Journals (Sweden)

    Wolfgang Klein

    Full Text Available The cyclodepsipeptide cotransin was described to inhibit the biosynthesis of a small subset of proteins by a signal sequence-discriminatory mechanism at the Sec61 protein-conducting channel. However, it was not clear how selective cotransin is, i.e. how many proteins are sensitive. Moreover, a consensus motif in signal sequences mediating cotransin sensitivity has yet not been described. To address these questions, we performed a proteomic study using cotransin-treated human hepatocellular carcinoma cells and the stable isotope labelling by amino acids in cell culture technique in combination with quantitative mass spectrometry. We used a saturating concentration of cotransin (30 micromolar to identify also less-sensitive proteins and to discriminate the latter from completely resistant proteins. We found that the biosynthesis of almost all secreted proteins was cotransin-sensitive under these conditions. In contrast, biosynthesis of the majority of the integral membrane proteins was cotransin-resistant. Cotransin sensitivity of signal sequences was neither related to their length nor to their hydrophobicity. Instead, in the case of signal anchor sequences, we identified for the first time a conformational consensus motif mediating cotransin sensitivity.

  4. Defining a Conformational Consensus Motif in Cotransin-Sensitive Signal Sequences: A Proteomic and Site-Directed Mutagenesis Study

    Science.gov (United States)

    Klein, Wolfgang; Westendorf, Carolin; Schmidt, Antje; Conill-Cortés, Mercè; Rutz, Claudia; Blohs, Marcus; Beyermann, Michael; Protze, Jonas; Krause, Gerd; Krause, Eberhard; Schülein, Ralf

    2015-01-01

    The cyclodepsipeptide cotransin was described to inhibit the biosynthesis of a small subset of proteins by a signal sequence-discriminatory mechanism at the Sec61 protein-conducting channel. However, it was not clear how selective cotransin is, i.e. how many proteins are sensitive. Moreover, a consensus motif in signal sequences mediating cotransin sensitivity has yet not been described. To address these questions, we performed a proteomic study using cotransin-treated human hepatocellular carcinoma cells and the stable isotope labelling by amino acids in cell culture technique in combination with quantitative mass spectrometry. We used a saturating concentration of cotransin (30 micromolar) to identify also less-sensitive proteins and to discriminate the latter from completely resistant proteins. We found that the biosynthesis of almost all secreted proteins was cotransin-sensitive under these conditions. In contrast, biosynthesis of the majority of the integral membrane proteins was cotransin-resistant. Cotransin sensitivity of signal sequences was neither related to their length nor to their hydrophobicity. Instead, in the case of signal anchor sequences, we identified for the first time a conformational consensus motif mediating cotransin sensitivity. PMID:25806945

  5. RNAHelix: computational modeling of nucleic acid structures with Watson-Crick and non-canonical base pairs.

    Science.gov (United States)

    Bhattacharyya, Dhananjay; Halder, Sukanya; Basu, Sankar; Mukherjee, Debasish; Kumar, Prasun; Bansal, Manju

    2017-02-01

    Comprehensive analyses of structural features of non-canonical base pairs within a nucleic acid double helix are limited by the availability of a small number of three dimensional structures. Therefore, a procedure for model building of double helices containing any given nucleotide sequence and base pairing information, either canonical or non-canonical, is seriously needed. Here we describe a program RNAHelix, which is an updated version of our widely used software, NUCGEN. The program can regenerate duplexes using the dinucleotide step and base pair orientation parameters for a given double helical DNA or RNA sequence with defined Watson-Crick or non-Watson-Crick base pairs. The original structure and the corresponding regenerated structure of double helices were found to be very close, as indicated by the small RMSD values between positions of the corresponding atoms. Structures of several usual and unusual double helices have been regenerated and compared with their original structures in terms of base pair RMSD, torsion angles and electrostatic potentials and very high agreements have been noted. RNAHelix can also be used to generate a structure with a sequence completely different from an experimentally determined one or to introduce single to multiple mutation, but with the same set of parameters and hence can also be an important tool in homology modeling and study of mutation induced structural changes.

  6. 4-Hydroxynonenal activates Src through a non-canonical pathway that involves EGFR/PTP1B

    Science.gov (United States)

    Zhang, Hongqiao; Forman, Henry Jay

    2015-01-01

    Src, a non-receptor protein tyrosine kinase involved in many biological processes, can be activated through both redox-dependent and independent mechanisms. 4-Hydroxy-2-nonenal (HNE) is a lipid peroxidation product that is increased in pathophysiological conditions associated with Src activation. This study examined how HNE activates human c-Src. In the canonical pathway Src activation is initiated by dephosphorylation of pTyr530 followed by conformational change that causes Src auto-phosphorylation at Tyr419 and its activation. HNE increased Src activation in both dose- and time-dependent manner, while it also increased Src phosphorylation at Tyr530 (pTyr530 Src), suggesting that HNE activated Src via a non-canonical mechanism. Protein tyrosine phosphatase 1B inhibitor (539741), at concentrations that increased basal pTyr530 Src, also increased basal Src activity and significantly reduced HNE-mediated Src activation. The EGFR inhibitor, AG1478, and EGFR silencing, abrogated HNE-mediated EGFR activation and inhibited basal and HNE-induced Src activity. In addition, AG1478 also eliminated the increase of basal Src activation by a PTP1B inhibitor. Taken together these data suggest that HNE can activate Src partly through a non-canonical pathway involving activation of EGFR and inhibition of PTP1B. PMID:26453921

  7. Neferine augments therapeutic efficacy of cisplatin through ROS- mediated non-canonical autophagy in human lung adenocarcinoma (A549 cells).

    Science.gov (United States)

    Kalai Selvi, Sivalingam; Vinoth, Amirthalingam; Varadharajan, Thiyagarajan; Weng, Ching Feng; Vijaya Padma, Viswanadha

    2017-05-01

    Combination of dietary components with chemotherapy drugs is an emerging new strategy for cancer therapy to increase antitumor responses. Neferine, major bisbenzylisoquinoline alkaloid isolated from the seed embryo of Nelumbo nucifera (Lotus). In the present study, we investigated the efficacy of the combinatorial regimen of neferine and cisplatin compared to cisplatin high dose in human lung adenocarcinoma (A549) cells. Co-treatment with neferine enhanced cisplatin-induced autophagy in A549 cells was accompanied by Acidic vesicular accumulation (AVO), enhanced generation of reactive oxygen species (ROS) and depletion of intracellular glutathione (GSH), down regulation of PI3K/AKT/mTOR pathway, conversion of LC3B-I to LC3B-II. This enhanced autophagy developed via a non-canonical mechanism that did not require Beclin-1, PI3KCIII. In conclusion, these results suggest that neferine enhances cisplatin -induced autophagic cancer cell death through downregulation of PI3K/Akt/mTOR signaling pro-survival pathway and ROS- mediated Beclin-1 and PI3K CIII independent autophagy in human lung adenocarcinoma (A549 cells). Copyright © 2017 Elsevier Ltd. All rights reserved.

  8. Non-canonical dorsoventral patterning in the moth midge Clogmia albipunctata

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    Karl R. Wotton

    2017-11-01

    Full Text Available Abstract Background Bone morphogenetic proteins (BMPs are of central importance for dorsal–ventral (DV axis specification. They are core components of a signalling cascade that includes the BMP ligand decapentaplegic (DPP and its antagonist short gastrulation (SOG in Drosophila melanogaster. These components are very ancient, with orthologs involved in DV patterning in both protostomes and deuterostomes. Despite such strong conservation, recent comparative work in insects has revealed interesting differences in the way the patterning function of the DV system is achieved in different species. Results In this paper, we characterise the expression patterns of the principal components of the BMP DV patterning system, as well as its signalling outputs and downstream targets, in the non-cyclorrhaphan moth midge Clogmia albipunctata (Diptera: Psychodidae. We previously reported ventral expression patterns of dpp in the pole regions of C. albipunctata blastoderm embryos. Strikingly, we also find ventral sog and posteriorly restricted tkv expression, as well as expanded polar activity of pMad. We use our results from gene knock-down by embryonic RNA interference to propose a mechanism of polar morphogen shuttling in C. albipunctata. We compare these results to available data from other species and discuss scenarios for the evolution of DV signalling in the holometabolan insects. Conclusions A comparison of gene expression patterns across hemipteran and holometabolan insects reveals that expression of upstream signalling factors in the DV system is very variable, while signalling output is highly conserved. This has two major implications: first, as long as ligand shuttling and other upstream regulatory mechanisms lead to an appropriately localised activation of BMP signalling at the dorsal midline, it is of less importance exactly where the upstream components of the DV system are expressed. This, in turn, explains why the early-acting components of

  9. The relevance of the non-canonical PTS1 of peroxisomal catalase

    NARCIS (Netherlands)

    Williams, Chris; Aksam, Eda Bener; Gunkel, Katja; Veenhuis, Marten; van der Klei, Ida J.

    Catalase is sorted to peroxisomes via a C-terminal peroxisomal targeting signal 1 (PTS1), which binds to the receptor protein Pex5. Analysis of the C-terminal sequences of peroxisomal catalases from various species indicated that catalase never contains the typical C-terminal PTS1 tripeptide-SKL,

  10. Intracrine prostaglandin E2 pro-tumoral actions in prostate epithelial cells originate from non-canonical pathways.

    Science.gov (United States)

    Madrigal-Martínez, Antonio; Fernández-Martínez, Ana B; Lucio Cazaña, Francisco J

    2018-04-01

    Prostaglandin E 2 (PGE 2 ) increases cell proliferation and stimulates migratory and angiogenic abilities in prostate cancer cells. However, the effects of PGE 2 on non-transformed prostate epithelial cells are unknown, despite the fact that PGE 2 overproduction has been found in benign hyperplastic prostates. In the present work we studied the effects of PGE 2 in immortalized, non-malignant prostate epithelial RWPE-1 cells and found that PGE 2 increased cell proliferation, cell migration, and production of vascular endothelial growth factor-A, and activated in vitro angiogenesis. These actions involved a non-canonic intracrine mechanism in which the actual effector was intracellular PGE 2 (iPGE 2 ) instead of extracellular PGE 2 : inhibition of the prostaglandin uptake transporter (PGT) or antagonism of EP receptors prevented the effects of PGE 2 , which indicated that PGE 2 activity depended on its carrier-mediated translocation from the outside to the inside of cells and that EP receptors located intracellularly (iEP) mediated the effects of PGE 2 . iPGE 2 acted through transactivation of epidermal growth factor-receptor (EGFR) by iEP, leading to increased expression and activity of hypoxia-inducible factor-1α (HIF-1α). Interestingly, iPGE 2 also mediates the effects of PGE 2 on prostate cancer PC3 cells through the axis iPGE 2 -iEP receptors-EGFR-HIF-1α. Thus, this axis might be responsible for the growth-stimulating effects of PGE 2 on prostate epithelial cells, thereby contributing to prostate proliferative diseases associated with chronic inflammation. Since this PGT-dependent non-canonic intracrine mechanism of PGE 2 action operates in both benign and malignant prostate epithelial cells, PGT inhibitors should be tested as a novel therapeutic modality to treat prostate proliferative disease. © 2017 Wiley Periodicals, Inc.

  11. New insights into transcription fidelity: thermal stability of non-canonical structures in template DNA regulates transcriptional arrest, pause, and slippage.

    Science.gov (United States)

    Tateishi-Karimata, Hisae; Isono, Noburu; Sugimoto, Naoki

    2014-01-01

    The thermal stability and topology of non-canonical structures of G-quadruplexes and hairpins in template DNA were investigated, and the effect of non-canonical structures on transcription fidelity was evaluated quantitatively. We designed ten template DNAs: A linear sequence that does not have significant higher-order structure, three sequences that form hairpin structures, and six sequences that form G-quadruplex structures with different stabilities. Templates with non-canonical structures induced the production of an arrested, a slipped, and a full-length transcript, whereas the linear sequence produced only a full-length transcript. The efficiency of production for run-off transcripts (full-length and slipped transcripts) from templates that formed the non-canonical structures was lower than that from the linear. G-quadruplex structures were more effective inhibitors of full-length product formation than were hairpin structure even when the stability of the G-quadruplex in an aqueous solution was the same as that of the hairpin. We considered that intra-polymerase conditions may differentially affect the stability of non-canonical structures. The values of transcription efficiencies of run-off or arrest transcripts were correlated with stabilities of non-canonical structures in the intra-polymerase condition mimicked by 20 wt% polyethylene glycol (PEG). Transcriptional arrest was induced when the stability of the G-quadruplex structure (-ΔG°37) in the presence of 20 wt% PEG was more than 8.2 kcal mol(-1). Thus, values of stability in the presence of 20 wt% PEG are an important indicator of transcription perturbation. Our results further our understanding of the impact of template structure on the transcription process and may guide logical design of transcription-regulating drugs.

  12. Salicylic acid receptors activate jasmonic acid signalling through a non-canonical pathway to promote effector-triggered immunity.

    Science.gov (United States)

    Liu, Lijing; Sonbol, Fathi-Mohamed; Huot, Bethany; Gu, Yangnan; Withers, John; Mwimba, Musoki; Yao, Jian; He, Sheng Yang; Dong, Xinnian

    2016-10-11

    It is an apparent conundrum how plants evolved effector-triggered immunity (ETI), involving programmed cell death (PCD), as a major defence mechanism against biotrophic pathogens, because ETI-associated PCD could leave them vulnerable to necrotrophic pathogens that thrive on dead host cells. Interestingly, during ETI, the normally antagonistic defence hormones, salicylic acid (SA) and jasmonic acid (JA) associated with defence against biotrophs and necrotrophs respectively, both accumulate to high levels. In this study, we made the surprising finding that JA is a positive regulator of RPS2-mediated ETI. Early induction of JA-responsive genes and de novo JA synthesis following SA accumulation is activated through the SA receptors NPR3 and NPR4, instead of the JA receptor COI1. We provide evidence that NPR3 and NPR4 may mediate this effect by promoting degradation of the JA transcriptional repressor JAZs. This unique interplay between SA and JA offers a possible explanation of how plants can mount defence against a biotrophic pathogen without becoming vulnerable to necrotrophic pathogens.

  13. Beta-Arrestin and casein kinase 1/2 define distinct branches of non-canonical WNT signalling pathways

    Czech Academy of Sciences Publication Activity Database

    Bryja, Vítězslav; Schambony, A.; Čajánek, L.; Dominguez, I.; Arenas, E.; Schulte, G.

    2008-01-01

    Roč. 9, č. 12 (2008), s. 1244-1250 ISSN 1469-221X Institutional research plan: CEZ:AV0Z50040507; CEZ:AV0Z50040702 Keywords : convergent extension movements * RAC-1 * RHO-like GTPases Subject RIV: BO - Biophysics Impact factor: 7.099, year: 2008

  14. Effects of histamine H1 receptor signaling on glucocorticoid receptor activity. Role of canonical and non-canonical pathways

    NARCIS (Netherlands)

    Zappia, C.D.; Granja-Galeano, G.; Fernández, N.; Shayo, C.; Davio, C.; Fitzsimons, C.P.; Monczor, F.

    2015-01-01

    Histamine H1 receptor (H1R) antagonists and glucocorticoid receptor (GR) agonists are used to treat inflammatory conditions such as allergic rhinitis, atopic dermatitis and asthma. Consistent with the high morbidity levels of such inflammatory conditions, these receptors are the targets of a vast

  15. Non-canonical microRNAs miR-320 and miR-702 promote proliferation in Dgcr8-deficient embryonic stem cells

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Byeong-Moo [Department of Medicine/GI Unit, Massachusetts General Hospital, Boston, MA 02114 (United States); Department of Medicine, Harvard Medical School, Boston, MA 02115 (United States); Choi, Michael Y., E-mail: mchoi@partners.org [Department of Medicine/GI Unit, Massachusetts General Hospital, Boston, MA 02114 (United States); Department of Medicine, Harvard Medical School, Boston, MA 02115 (United States); Harvard Stem Cell Institute, Boston, MA 02114 (United States)

    2012-09-21

    Highlights: Black-Right-Pointing-Pointer Embryonic stem cells (ESCs) lacking non-canonical miRNAs proliferate slower. Black-Right-Pointing-Pointer miR-320 and miR-702 are two non-canonical miRNAs expressed in ESCs. Black-Right-Pointing-Pointer miR-320 and miR-702 promote proliferation of Dgcr8-deficient ESCs. Black-Right-Pointing-Pointer miR-320 targets p57 and helps to release Dgcr8-deficient ESCs from G1 arrest. Black-Right-Pointing-Pointer miR-702 targets p21 and helps to release Dgcr8-deficient ESCs from G1 arrest. -- Abstract: MicroRNAs are known to contribute significantly to stem cell phenotype by post-transcriptionally regulating gene expression. Most of our knowledge of microRNAs comes from the study of canonical microRNAs that require two sequential cleavages by the Drosha/Dgcr8 heterodimer and Dicer to generate mature products. In contrast, non-canonical microRNAs bypass the cleavage by the Drosha/Dgcr8 heterodimer within the nucleus but still require cytoplasmic cleavage by Dicer. The function of non-canonical microRNAs in embryonic stem cells (ESCs) remains obscure. It has been hypothesized that non-canonical microRNAs have important roles in ESCs based upon the phenotypes of ESC lines that lack these specific classes of microRNAs; Dicer-deficient ESCs lacking both canonical and non-canonical microRNAs have much more severe proliferation defect than Dgcr8-deficient ESCs lacking only canonical microRNAs. Using these cell lines, we identified two non-canonical microRNAs, miR-320 and miR-702, that promote proliferation of Dgcr8-deficient ESCs by releasing them from G1 arrest. This is accomplished by targeting the 3 Prime -untranslated regions of the cell cycle inhibitors p57 and p21 and thereby inhibiting their expression. This is the first report of the crucial role of non-canonical microRNAs in ESCs.

  16. Non-canonical microRNAs miR-320 and miR-702 promote proliferation in Dgcr8-deficient embryonic stem cells

    International Nuclear Information System (INIS)

    Kim, Byeong-Moo; Choi, Michael Y.

    2012-01-01

    Highlights: ► Embryonic stem cells (ESCs) lacking non-canonical miRNAs proliferate slower. ► miR-320 and miR-702 are two non-canonical miRNAs expressed in ESCs. ► miR-320 and miR-702 promote proliferation of Dgcr8-deficient ESCs. ► miR-320 targets p57 and helps to release Dgcr8-deficient ESCs from G1 arrest. ► miR-702 targets p21 and helps to release Dgcr8-deficient ESCs from G1 arrest. -- Abstract: MicroRNAs are known to contribute significantly to stem cell phenotype by post-transcriptionally regulating gene expression. Most of our knowledge of microRNAs comes from the study of canonical microRNAs that require two sequential cleavages by the Drosha/Dgcr8 heterodimer and Dicer to generate mature products. In contrast, non-canonical microRNAs bypass the cleavage by the Drosha/Dgcr8 heterodimer within the nucleus but still require cytoplasmic cleavage by Dicer. The function of non-canonical microRNAs in embryonic stem cells (ESCs) remains obscure. It has been hypothesized that non-canonical microRNAs have important roles in ESCs based upon the phenotypes of ESC lines that lack these specific classes of microRNAs; Dicer-deficient ESCs lacking both canonical and non-canonical microRNAs have much more severe proliferation defect than Dgcr8-deficient ESCs lacking only canonical microRNAs. Using these cell lines, we identified two non-canonical microRNAs, miR-320 and miR-702, that promote proliferation of Dgcr8-deficient ESCs by releasing them from G1 arrest. This is accomplished by targeting the 3′-untranslated regions of the cell cycle inhibitors p57 and p21 and thereby inhibiting their expression. This is the first report of the crucial role of non-canonical microRNAs in ESCs.

  17. Defying the stereotype: non-canonical roles of the peptide hormones guanylin and uroguanylin

    Directory of Open Access Journals (Sweden)

    Nirmalya eBasu

    2011-06-01

    Full Text Available The peptide hormones uroguanylin and guanylin have been traditionally thought to be mediators of fluid-ion homeostasis in the vertebrate intestine. They serve as ligands for receptor guanylyl cyclase C (GC-C, and both receptor and ligands are expressed predominantly in the intestine. Ligand binding to GC-C results in increased cGMP production in the cell which governs downstream signaling. In the last decade, a significant amount of research has unraveled novel functions for this class of peptide hormones, in addition to their action as intestinal secretagogues. An additional receptor for uroguanylin, receptor guanylyl cyclase D, has also been identified. Thus, unconventional roles of these peptides in regulating renal filtration, olfaction, reproduction and cell proliferation have begun to be elucidated in detail. These varied effects suggest that these peptide hormones act in an autocrine, paracrine as well as endocrine manner to regulate diverse cellular processes.

  18. Regulation of natural competence by the orphan two-component system sensor kinase ChiS involves a non-canonical transmembrane regulator in Vibrio cholerae.

    Science.gov (United States)

    Yamamoto, Shouji; Mitobe, Jiro; Ishikawa, Takahiko; Wai, Sun Nyunt; Ohnishi, Makoto; Watanabe, Haruo; Izumiya, Hidemasa

    2014-01-01

    In Vibrio cholerae, 41 chitin-inducible genes, including the genes involved in natural competence for DNA uptake, are governed by the orphan two-component system (TCS) sensor kinase ChiS. However, the mechanism by which ChiS controls the expression of these genes is currently unknown. Here, we report the involvement of a novel transcription factor termed 'TfoS' in this process. TfoS is a transmembrane protein that contains a large periplasmic domain and a cytoplasmic AraC-type DNA-binding domain, but lacks TCS signature domains. Inactivation of tfoS abolished natural competence as well as transcription of the tfoR gene encoding a chitin-induced small RNA essential for competence gene expression. A TfoS fragment containing the DNA-binding domain specifically bound to and activated transcription from the tfoR promoter. Intracellular TfoS levels were unaffected by disruption of chiS and coexpression of TfoS and ChiS in Escherichia coli recovered transcription of the chromosomally integrated tfoR::lacZ gene, suggesting that TfoS is post-translationally modulated by ChiS during transcriptional activation; however, this regulation persisted when the canonical phosphorelay residues of ChiS were mutated. The results presented here suggest that ChiS operates a chitin-induced non-canonical signal transduction cascade through TfoS, leading to transcriptional activation of tfoR. © 2013 John Wiley & Sons Ltd.

  19. NES consensus redefined by structures of PKI-type and Rev-type nuclear export signals bound to CRM1.

    Science.gov (United States)

    Güttler, Thomas; Madl, Tobias; Neumann, Piotr; Deichsel, Danilo; Corsini, Lorenzo; Monecke, Thomas; Ficner, Ralf; Sattler, Michael; Görlich, Dirk

    2010-11-01

    Classic nuclear export signals (NESs) confer CRM1-dependent nuclear export. Here we present crystal structures of the RanGTP-CRM1 complex alone and bound to the prototypic PKI or HIV-1 Rev NESs. These NESs differ markedly in the spacing of their key hydrophobic (Φ) residues, yet CRM1 recognizes them with the same rigid set of five Φ pockets. The different Φ spacings are compensated for by different conformations of the bound NESs: in the case of PKI, an α-helical conformation, and in the case of Rev, an extended conformation with a critical proline docking into a Φ pocket. NMR analyses of CRM1-bound and CRM1-free PKI NES suggest that CRM1 selects NES conformers that pre-exist in solution. Our data lead to a new structure-based NES consensus, and explain why NESs differ in their affinities for CRM1 and why supraphysiological NESs bind the exportin so tightly.

  20. TWEAK activates the non-canonical NFkappaB pathway in murine renal tubular cells: modulation of CCL21.

    Directory of Open Access Journals (Sweden)

    Ana B Sanz

    2010-01-01

    Full Text Available TWEAK is a member of the TNF superfamily of cytokines that contribute to kidney tubulointerstitial injury. It has previously been reported that TWEAK induces transient nuclear translocation of RelA and expression of RelA-dependent cytokines in renal tubular cells. Additionally, TWEAK induced long-lasting NFkappaB activation suggestive of engagement of the non-canonical NFkappaB pathway. We now explore TWEAK-induced activation of NFkappaB2 and RelB, as well as expression of CCL21, a T-cell chemotactic factor, in cultured murine tubular epithelial cells and in healthy kidneys in vivo. In cultured tubular cells, TWEAK and TNFalpha activated different DNA-binding NFkappaB complexes. TWEAK-induced sustained NFkappaB activation was associated with NFkappaB2 p100 processing to p52 via proteasome and nuclear translocation and DNA-binding of p52 and RelB. TWEAK, but not TNFalpha used as control, induced a delayed increase in CCL21a mRNA (3.5+/-1.22-fold over control and CCL21 protein (2.5+/-0.8-fold over control, which was prevented by inhibition of the proteasome, or siRNA targeting of NIK or RelB, but not by RelA inhibition with parthenolide. A second NFkappaB2-dependent chemokine, CCL19, was upregulates by TWEAK, but not by TNFalpha. However, both cytokines promoted chemokine RANTES expression (3-fold mRNA at 24 h. In vivo, TWEAK induced nuclear NFkappaB2 and RelB translocation and CCL21a mRNA (1.5+/-0.3-fold over control and CCL21 protein (1.6+/-0.5-fold over control expression in normal kidney. Increased tubular nuclear RelB and tubular CCL21 expression in acute kidney injury were decreased by neutralization (2+/-0.9 vs 1.3+/-0.6-fold over healthy control or deficiency of TWEAK (2+/-0.9 vs 0.8+/-0.6-fold over healthy control. Moreover, anti-TWEAK treatment prevented the recruitment of T cells to the kidney in this model (4.1+/-1.4 vs 1.8+/-1-fold over healthy control. Our results thus identify TWEAK as a regulator of non-canonical NFkappa

  1. Structure-based non-canonical amino acid design to covalently crosslink an antibody–antigen complex

    Science.gov (United States)

    Xu, Jianqing; Tack, Drew; Hughes, Randall A.; Ellington, Andrew D.; Gray, Jeffrey J.

    2014-01-01

    Engineering antibodies to utilize non-canonical amino acids (NCAA) should greatly expand the utility of an already important biological reagent. In particular, introducing crosslinking reagents into antibody complementarity determining regions (CDRs) should provide a means to covalently crosslink residues at the antibody–antigen interface. Unfortunately, finding the optimum position for crosslinking two proteins is often a matter of iterative guessing, even when the interface is known in atomic detail. Computer-aided antibody design can potentially greatly restrict the number of variants that must be explored in order to identify successful crosslinking sites. We have therefore used Rosetta to guide the introduction of an oxidizable crosslinking NCAA, l-3,4-dihydroxyphenylalanine (l-DOPA), into the CDRs of the anti-protective antigen scFv antibody M18, and have measured crosslinking to its cognate antigen, domain 4 of the anthrax protective antigen. Computed crosslinking distance, solvent accessibility, and interface energetics were three factors considered that could impact the efficiency of l-DOPA-mediated crosslinking. In the end, 10 variants were synthesized, and crosslinking efficiencies were generally 10% or higher, with the best variant crosslinking to 52% of the available antigen. The results suggest that computational analysis can be used in a pipeline for engineering crosslinking antibodies. The rules learned from l-DOPA crosslinking of antibodies may also be generalizable to the formation of other crosslinked interfaces and complexes. PMID:23680795

  2. Monitoring Replication Protein A (RPA) dynamics in homologous recombination through site-specific incorporation of non-canonical amino acids.

    Science.gov (United States)

    Pokhrel, Nilisha; Origanti, Sofia; Davenport, Eric Parker; Gandhi, Disha; Kaniecki, Kyle; Mehl, Ryan A; Greene, Eric C; Dockendorff, Chris; Antony, Edwin

    2017-09-19

    An essential coordinator of all DNA metabolic processes is Replication Protein A (RPA). RPA orchestrates these processes by binding to single-stranded DNA (ssDNA) and interacting with several other DNA binding proteins. Determining the real-time kinetics of single players such as RPA in the presence of multiple DNA processors to better understand the associated mechanistic events is technically challenging. To overcome this hurdle, we utilized non-canonical amino acids and bio-orthogonal chemistry to site-specifically incorporate a chemical fluorophore onto a single subunit of heterotrimeric RPA. Upon binding to ssDNA, this fluorescent RPA (RPAf) generates a quantifiable change in fluorescence, thus serving as a reporter of its dynamics on DNA in the presence of multiple other DNA binding proteins. Using RPAf, we describe the kinetics of facilitated self-exchange and exchange by Rad51 and mediator proteins during various stages in homologous recombination. RPAf is widely applicable to investigate its mechanism of action in processes such as DNA replication, repair and telomere maintenance. © The Author(s) 2017. Published by Oxford University Press on behalf of Nucleic Acids Research.

  3. Inhibition of Non Canonical HIV-1 Tat Secretion Through the Cellular Na+,K+-ATPase Blocks HIV-1 Infection

    Directory of Open Access Journals (Sweden)

    Silvia Agostini

    2017-07-01

    Full Text Available Besides its essential role in the activation of HIV-1 gene expression, the viral Tat protein has the unusual property of trafficking in and out of cells. In contrast to Tat internalization, the mechanism involved in extracellular Tat release has so far remained elusive. Here we show that Tat secretion occurs through a Golgi-independent pathway requiring binding of Tat with three short, non-consecutive intracytoplasmic loops at the C-terminus of the cellular Na+,K+-ATPase pump alpha subunit. Ouabain, a pump inhibitor, blocked this interaction and prevented Tat secretion; virions produced in the presence of this drug were less infectious, consistent the capacity of virion-associated Tat to increase HIV-1 infectivity. Treatment of CD4+ T-cells with short peptides corresponding to the Tat-binding regions of the pump alpha subunit impaired extracellular Tat release and blocked HIV-1 replication. Thus, non canonical, extracellular Tat secretion is essential for viral infectivity.

  4. Role of non-canonical Beclin 1-independent autophagy in cell death induced by resveratrol in human breast cancer cells.

    Science.gov (United States)

    Scarlatti, F; Maffei, R; Beau, I; Codogno, P; Ghidoni, R

    2008-08-01

    Resveratrol, a polyphenol found in grapes and other fruit and vegetables, is a powerful chemopreventive and chemotherapeutic molecule potentially of interest for the treatment of breast cancer. The human breast cancer cell line MCF-7, which is devoid of caspase-3 activity, is refractory to apoptotic cell death after incubation with resveratrol. Here we show that resveratrol arrests cell proliferation, triggers death and decreases the number of colonies of cells that are sensitive to caspase-3-dependent apoptosis (MCF-7 casp-3) and also those that are unresponsive to it (MCF-7vc). We demonstrate that resveratrol (i) acts via multiple pathways to trigger cell death, (ii) induces caspase-dependent and caspase-independent cell death in MCF-7 casp-3 cells, (iii) induces only caspase-independent cell death in MCF-7vc cells and (iv) stimulates macroautophagy. Using BECN1 and hVPS34 (human vacuolar protein sorting 34) small interfering RNAs, we demonstrate that resveratrol activates Beclin 1-independent autophagy in both cell lines, whereas cell death via this uncommon form of autophagy occurs only in MCF-7vc cells. We also show that this variant form of autophagic cell death is blocked by the expression of caspase-3, but not by its enzymatic activity. In conclusion, this study reveals that non-canonical autophagy induced by resveratrol can act as a caspase-independent cell death mechanism in breast cancer cells.

  5. From Flies to Mice: The Emerging Role of Non-Canonical PRC1 Members in Mammalian Development

    Directory of Open Access Journals (Sweden)

    Izabella Bajusz

    2018-02-01

    Full Text Available Originally two types of Polycomb Repressive Complexes (PRCs were described, canonical PRC1 (cPRC1 and PRC2. Recently, a versatile set of complexes were identified and brought up several dilemmas in PRC mediated repression. These new class of complexes were named as non-canonical PRC1s (ncPRC1s. Both cPRC1s and ncPRC1s contain Ring finger protein (RING1, RNF2 and Polycomb group ring finger catalytic (PCGF core, but in ncPRCs, RING and YY1 binding protein (RYBP, or YY1 associated factor 2 (YAF2, replaces the Chromobox (CBX and Polyhomeotic (PHC subunits found in cPRC1s. Additionally, ncPRC1 subunits can associate with versatile accessory proteins, which determine their functional specificity. Homozygous null mutations of the ncPRC members in mice are often lethal or cause infertility, which underlines their essential functions in mammalian development. In this review, we summarize the mouse knockout phenotypes of subunits of the six major ncPRCs. We highlight several aspects of their discovery from fly to mice and emerging role in target recognition, embryogenesis and cell-fate decision making. We gathered data from stem cell mediated in vitro differentiation assays and genetically engineered mouse models. Accumulating evidence suggests that ncPRC1s play profound role in mammalian embryogenesis by regulating gene expression during lineage specification of pluripotent stem cells.

  6. Metabolic engineering of monoterpene biosynthesis in tomato fruits via introduction of the non-canonical substrate neryl diphosphate.

    Science.gov (United States)

    Gutensohn, Michael; Nguyen, Thuong T H; McMahon, Richard D; Kaplan, Ian; Pichersky, Eran; Dudareva, Natalia

    2014-07-01

    Recently it was shown that monoterpenes in tomato trichomes (Solanum lycopersicum) are synthesized by phellandrene synthase 1 (PHS1) from the non-canonical substrate neryl diphosphate (NPP), the cis-isomer of geranyl diphosphate (GPP). As PHS1 accepts both NPP and GPP substrates forming different monoterpenes, it was overexpressed in tomato fruits to test if NPP is also available in a tissue highly active in carotenoid production. However, transgenic fruits overexpressing PHS1 produced only small amounts of GPP-derived PHS1 monoterpene products, indicating the absence of endogenous NPP. Therefore, NPP formation was achieved by diverting the metabolic flux from carotenoids via expression of tomato neryl diphosphate synthase 1 (NDPS1). NDPS1 transgenic fruits produced NPP-derived monoterpenes, including nerol, neral and geranial, while displaying reduced lycopene content. NDPS1 co-expression with PHS1 resulted in a monoterpene blend, including β-phellandrene, similar to that produced from NPP by PHS1 in vitro and in trichomes. Unexpectedly, PHS1×NDPS1 fruits showed recovery of lycopene levels compared to NDPS1 fruits, suggesting that redirection of metabolic flux is only partially responsible for the reduction in carotenoids. In vitro assays demonstrated that NPP serves as an inhibitor of geranylgeranyl diphosphate synthase, thus its consumption by PHS1 leads to recovery of lycopene levels. Monoterpenes produced in PHS1×NDPS1 fruits contributed to direct plant defense negatively affecting feeding behavior of the herbivore Helicoverpa zea and displaying antifungal activity against Botrytis cinerea. These results show that NPP-derived terpenoids can be produced in plant tissues; however, NPP has to be consumed to avoid negative impacts on plant metabolism. Copyright © 2014 International Metabolic Engineering Society. Published by Elsevier Inc. All rights reserved.

  7. A non-canonical RNA degradation pathway suppresses RNAi-dependent epimutations in the human fungal pathogen Mucor circinelloides.

    Science.gov (United States)

    Calo, Silvia; Nicolás, Francisco E; Lee, Soo Chan; Vila, Ana; Cervantes, Maria; Torres-Martinez, Santiago; Ruiz-Vazquez, Rosa M; Cardenas, Maria E; Heitman, Joseph

    2017-03-01

    Mucorales are a group of basal fungi that includes the casual agents of the human emerging disease mucormycosis. Recent studies revealed that these pathogens activate an RNAi-based pathway to rapidly generate drug-resistant epimutant strains when exposed to stressful compounds such as the antifungal drug FK506. To elucidate the molecular mechanism of this epimutation pathway, we performed a genetic analysis in Mucor circinelloides that revealed an inhibitory role for the non-canonical RdRP-dependent Dicer-independent silencing pathway, which is an RNAi-based mechanism involved in mRNA degradation that was recently identified. Thus, mutations that specifically block the mRNA degradation pathway, such as those in the genes r3b2 and rdrp3, enhance the production of drug resistant epimutants, similar to the phenotype previously described for mutation of the gene rdrp1. Our genetic analysis also revealed two new specific components of the epimutation pathway related to the quelling induced protein (qip) and a Sad-3-like helicase (rnhA), as mutations in these genes prevented formation of drug-resistant epimutants. Remarkably, drug-resistant epimutant production was notably increased in M. circinelloides f. circinelloides isolates from humans or other animal hosts. The host-pathogen interaction could be a stressful environment in which the phenotypic plasticity provided by the epimutant pathway might provide an advantage for these strains. These results evoke a model whereby balanced regulation of two different RNAi pathways is determined by the activation of the RNAi-dependent epimutant pathway under stress conditions, or its repression when the regular maintenance of the mRNA degradation pathway operates under non-stress conditions.

  8. Molecular cloning and characterization of a novel isoform of the non-canonical poly(A) polymerase PAPD7

    Energy Technology Data Exchange (ETDEWEB)

    Ogami, Koichi; Cho, Rihe [Department of Biological Chemistry, Graduate School of Pharmaceutical Sciences, Nagoya City University, Nagoya 467-8603 (Japan); Hoshino, Shin-ichi, E-mail: hoshino@phar.nagoya-cu.ac.jp [Department of Biological Chemistry, Graduate School of Pharmaceutical Sciences, Nagoya City University, Nagoya 467-8603 (Japan)

    2013-03-01

    Highlights: ► So far, only an enzymatically inactive isoform of PAPD7 was reported. ► The novel isoform: PAPD7 l shows robust nucleotidyl transferase activity. ► The newly identified amino terminal region is required for the activity. ► PAPD7 l localizes to the nucleoplasm. ► The N terminal region identified is also required for the nuclear localization. - Abstract: Non-canonical poly(A) polymerases (ncPAPs) catalyze the addition of poly(A) tail to the 3′ end of RNA to play pivotal roles in the regulation of gene expression and also in quality control. Here we identified a novel isoform of the 7th member of ncPAPs: PAPD7 (PAPD7 l), which contains 230 extra amino acids at the amino terminus of the previously identified PAPD7 (PAPD7 s). In sharp contrast to the inactive PAPD7 s, PAPD7 l showed robust nucleotidyl transferase activity when tethered to an RNA. A region required for the activity was localized to 187–219 aa, and this region was also required for the nuclear retention of PAPD7 l. Western blot analysis revealed that 94 kDa band (corresponding to PAPD7 l) but not 62 kDa band (corresponding to PAPD7 s) detected by PAPD7 antibody was specifically depleted by treatment with PAPD7 siRNA in both HeLa and U2OS cells. These results suggest that PAPD7 l is the major and active isoform of PAPD7 expressed in cells.

  9. A novel non-canonical mechanism of regulation of MST3 (mammalian Sterile20-related kinase 3).

    Science.gov (United States)

    Fuller, Stephen J; McGuffin, Liam J; Marshall, Andrew K; Giraldo, Alejandro; Pikkarainen, Sampsa; Clerk, Angela; Sugden, Peter H

    2012-03-15

    The canonical pathway of regulation of the GCK (germinal centre kinase) III subgroup member, MST3 (mammalian Sterile20-related kinase 3), involves a caspase-mediated cleavage between N-terminal catalytic and C-terminal regulatory domains with possible concurrent autophosphorylation of the activation loop MST3(Thr(178)), induction of serine/threonine protein kinase activity and nuclear localization. We identified an alternative 'non-canonical' pathway of MST3 activation (regulated primarily through dephosphorylation) which may also be applicable to other GCKIII (and GCKVI) subgroup members. In the basal state, inactive MST3 co-immunoprecipitated with the Golgi protein GOLGA2/gm130 (golgin A2/Golgi matrix protein 130). Activation of MST3 by calyculin A (a protein serine/threonine phosphatase 1/2A inhibitor) stimulated (auto)phosphorylation of MST3(Thr(178)) in the catalytic domain with essentially simultaneous cis-autophosphorylation of MST3(Thr(328)) in the regulatory domain, an event also requiring the MST3(341-376) sequence which acts as a putative docking domain. MST3(Thr(178)) phosphorylation increased MST3 kinase activity, but this activity was independent of MST3(Thr(328)) phosphorylation. Interestingly, MST3(Thr(328)) lies immediately C-terminal to a STRAD (Sterile20-related adaptor) pseudokinase-like site identified recently as being involved in binding of GCKIII/GCKVI members to MO25 scaffolding proteins. MST3(Thr(178)/Thr(328)) phosphorylation was concurrent with dissociation of MST3 from GOLGA2/gm130 and association of MST3 with MO25, and MST3(Thr(328)) phosphorylation was necessary for formation of the activated MST3-MO25 holocomplex.

  10. A non-canonical RNA degradation pathway suppresses RNAi-dependent epimutations in the human fungal pathogen Mucor circinelloides.

    Directory of Open Access Journals (Sweden)

    Silvia Calo

    2017-03-01

    Full Text Available Mucorales are a group of basal fungi that includes the casual agents of the human emerging disease mucormycosis. Recent studies revealed that these pathogens activate an RNAi-based pathway to rapidly generate drug-resistant epimutant strains when exposed to stressful compounds such as the antifungal drug FK506. To elucidate the molecular mechanism of this epimutation pathway, we performed a genetic analysis in Mucor circinelloides that revealed an inhibitory role for the non-canonical RdRP-dependent Dicer-independent silencing pathway, which is an RNAi-based mechanism involved in mRNA degradation that was recently identified. Thus, mutations that specifically block the mRNA degradation pathway, such as those in the genes r3b2 and rdrp3, enhance the production of drug resistant epimutants, similar to the phenotype previously described for mutation of the gene rdrp1. Our genetic analysis also revealed two new specific components of the epimutation pathway related to the quelling induced protein (qip and a Sad-3-like helicase (rnhA, as mutations in these genes prevented formation of drug-resistant epimutants. Remarkably, drug-resistant epimutant production was notably increased in M. circinelloides f. circinelloides isolates from humans or other animal hosts. The host-pathogen interaction could be a stressful environment in which the phenotypic plasticity provided by the epimutant pathway might provide an advantage for these strains. These results evoke a model whereby balanced regulation of two different RNAi pathways is determined by the activation of the RNAi-dependent epimutant pathway under stress conditions, or its repression when the regular maintenance of the mRNA degradation pathway operates under non-stress conditions.

  11. Identification of genome-wide non-canonical spliced regions and analysis of biological functions for spliced sequences using Read-Split-Fly.

    Science.gov (United States)

    Bai, Yongsheng; Kinne, Jeff; Ding, Lizhong; Rath, Ethan C; Cox, Aaron; Naidu, Siva Dharman

    2017-10-03

    It is generally thought that most canonical or non-canonical splicing events involving U2- and U12 spliceosomes occur within nuclear pre-mRNAs. However, the question of whether at least some U12-type splicing occurs in the cytoplasm is still unclear. In recent years next-generation sequencing technologies have revolutionized the field. The "Read-Split-Walk" (RSW) and "Read-Split-Run" (RSR) methods were developed to identify genome-wide non-canonical spliced regions including special events occurring in cytoplasm. As the significant amount of genome/transcriptome data such as, Encyclopedia of DNA Elements (ENCODE) project, have been generated, we have advanced a newer more memory-efficient version of the algorithm, "Read-Split-Fly" (RSF), which can detect non-canonical spliced regions with higher sensitivity and improved speed. The RSF algorithm also outputs the spliced sequences for further downstream biological function analysis. We used open access ENCODE project RNA-Seq data to search spliced intron sequences against the U12-type spliced intron sequence database to examine whether some events could occur as potential signatures of U12-type splicing. The check was performed by searching spliced sequences against 5'ss and 3'ss sequences from the well-known orthologous U12-type spliceosomal intron database U12DB. Preliminary results of searching 70 ENCODE samples indicated that the presence of 5'ss with U12-type signature is more frequent than U2-type and prevalent in non-canonical junctions reported by RSF. The selected spliced sequences have also been further studied using miRBase to elucidate their functionality. Preliminary results from 70 samples of ENCODE datasets show that several miRNAs are prevalent in studied ENCODE samples. Two of these are associated with many diseases as suggested in the literature. Specifically, hsa-miR-1273 and hsa-miR-548 are associated with many diseases and cancers. Our RSF pipeline is able to detect many possible junctions

  12. Lineage-Specific Viral Hijacking of Non-canonical E3 Ubiquitin Ligase Cofactors in the Evolution of Vif Anti-APOBEC3 Activity

    Directory of Open Access Journals (Sweden)

    Joshua R. Kane

    2015-05-01

    Full Text Available HIV-1 encodes the accessory protein Vif, which hijacks a host Cullin-RING ubiquitin ligase (CRL complex as well as the non-canonical cofactor CBFβ, to antagonize APOBEC3 antiviral proteins. Non-canonical cofactor recruitment to CRL complexes by viral factors, to date, has only been attributed to HIV-1 Vif. To further study this phenomenon, we employed a comparative approach combining proteomic, biochemical, structural, and virological techniques to investigate Vif complexes across the lentivirus genus, including primate (HIV-1 and simian immunodeficiency virus macaque [SIVmac] and non-primate (FIV, BIV, and MVV viruses. We find that CBFβ is completely dispensable for the activity of non-primate lentiviral Vif proteins. Furthermore, we find that BIV Vif requires no cofactor and that MVV Vif requires a novel cofactor, cyclophilin A (CYPA, for stable CRL complex formation and anti-APOBEC3 activity. We propose modular conservation of Vif complexes allows for potential exaptation of functions through the acquisition of non-CRL-associated host cofactors while preserving anti-APOBEC3 activity.

  13. Deep sequencing of small RNAs identifies canonical and non-canonical miRNA and endogenous siRNAs in mammalian somatic tissues.

    Science.gov (United States)

    Castellano, Leandro; Stebbing, Justin

    2013-03-01

    MicroRNAs (miRNAs) are small RNA molecules that regulate gene expression. They are characterized by specific maturation processes defined by canonical and non-canonical biogenic pathways. Analysis of ∼0.5 billion sequences from mouse data sets derived from different tissues, developmental stages and cell types, partly characterized by either ablation or mutation of the main proteins belonging to miRNA processor complexes, reveals 66 high-confidence new genomic loci coding for miRNAs that could be processed in a canonical or non-canonical manner. A proportion of the newly discovered miRNAs comprises mirtrons, for which we define a new sub-class. Notably, some of these newly discovered miRNAs are generated from untranslated and open reading frames of coding genes, and we experimentally validate these. We also show that many annotated miRNAs do not present miRNA-like features, as they are neither processed by known processing complexes nor loaded on AGO2; this indicates that the current miRNA miRBase database list should be refined and re-defined. Accordingly, a group of them map on ribosomal RNA molecules, whereas others cannot undergo genuine miRNA biogenesis. Notably, a group of annotated miRNAs are Dgcr8 independent and DICER dependent endogenous small interfering RNAs that derive from a unique hairpin formed from a short interspersed nuclear element.

  14. Wnt signaling in triple-negative breast cancer

    Science.gov (United States)

    Pohl, SÖ-G; Brook, N; Agostino, M; Arfuso, F; Kumar, A P; Dharmarajan, A

    2017-01-01

    Wnt signaling regulates a variety of cellular processes, including cell fate, differentiation, proliferation and stem cell pluripotency. Aberrant Wnt signaling is a hallmark of many cancers. An aggressive subtype of breast cancer, known as triple-negative breast cancer (TNBC), demonstrates dysregulation in canonical and non-canonical Wnt signaling. In this review, we summarize regulators of canonical and non-canonical Wnt signaling, as well as Wnt signaling dysfunction that mediates the progression of TNBC. We review the complex molecular nature of TNBC and the emerging therapies that are currently under investigation for the treatment of this disease. PMID:28368389

  15. Read-Split-Run: an improved bioinformatics pipeline for identification of genome-wide non-canonical spliced regions using RNA-Seq data.

    Science.gov (United States)

    Bai, Yongsheng; Kinne, Jeff; Donham, Brandon; Jiang, Feng; Ding, Lizhong; Hassler, Justin R; Kaufman, Randal J

    2016-08-22

    Most existing tools for detecting next-generation sequencing-based splicing events focus on generic splicing events. Consequently, special types of non-canonical splicing events of short mRNA regions (IRE1α targeted) have not yet been thoroughly addressed at a genome-wide level using bioinformatics approaches in conjunction with next-generation technologies. During endoplasmic reticulum (ER) stress, the gene encoding the RNase Ire1α is known to splice out a short 26 nt region from the mRNA of the transcription factor Xbp1 non-canonically within the cytosol. This causes an open reading frame-shift that induces expression of many downstream genes in reaction to ER stress as part of the unfolded protein response (UPR). We previously published an algorithm termed "Read-Split-Walk" (RSW) to identify non-canonical splicing regions using RNA-Seq data and applied it to ER stress-induced Ire1α heterozygote and knockout mouse embryonic fibroblast cell lines. In this study, we have developed an improved algorithm "Read-Split-Run" (RSR) for detecting genome-wide Ire1α-targeted genes with non-canonical spliced regions at a faster speed. We applied the RSR algorithm using different combinations of several parameters to the previously RSW tested mouse embryonic fibroblast cells (MEF) and the human Encyclopedia of DNA Elements (ENCODE) RNA-Seq data. We also compared the performance of RSR with two other alternative splicing events identification tools (TopHat (Trapnell et al., Bioinformatics 25:1105-1111, 2009) and Alt Event Finder (Zhou et al., BMC Genomics 13:S10, 2012)) utilizing the context of the spliced Xbp1 mRNA as a positive control in the data sets we identified it to be the top cleavage target present in Ire1α (+/-) but absent in Ire1α (-/-) MEF samples and this comparison was also extended to human ENCODE RNA-Seq data. Proof of principle came in our results by the fact that the 26 nt non-conventional splice site in Xbp1 was detected as the top hit by our new RSR

  16. β-agonists selectively modulate proinflammatory gene expression in skeletal muscle cells via non-canonical nuclear crosstalk mechanisms.

    Directory of Open Access Journals (Sweden)

    Krzysztof Kolmus

    Full Text Available The proinflammatory cytokine Tumour Necrosis Factor (TNF-α is implicated in a variety of skeletal muscle pathologies. Here, we have investigated how in vitro cotreatment of skeletal muscle C2C12 cells with β-agonists modulates the TNF-α-induced inflammatory program. We observed that C2C12 myotubes express functional TNF receptor 1 (TNF-R1 and β2-adrenoreceptors (β2-ARs. TNF-α activated the canonical Nuclear Factor-κB (NF-κB pathway and Mitogen-Activated Protein Kinases (MAPKs, culminating in potent induction of NF-κB-dependent proinflammatory genes. Cotreatment with the β-agonist isoproterenol potentiated the expression of inflammatory mediators, including Interleukin-6 (IL-6 and several chemokines. The enhanced production of chemotactic factors upon TNF-α/isoproterenol cotreatment was also suggested by the results from migrational analysis. Whereas we could not explain our observations by cytoplasmic crosstalk, we found that TNF-R1-and β2-AR-induced signalling cascades cooperate in the nucleus. Using the IL-6 promoter as a model, we demonstrated that TNF-α/isoproterenol cotreatment provoked phosphorylation of histone H3 at serine 10, concomitant with enhanced promoter accessibility and recruitment of the NF-κB p65 subunit, cAMP-response element-binding protein (CREB, CREB-binding protein (CBP and RNA polymerase II. In summary, we show that β-agonists potentiate TNF-α action, via nuclear crosstalk, that promotes chromatin relaxation at selected gene promoters. Our data warrant further study into the mode of action of β-agonists and urge for caution in their use as therapeutic agents for muscular disorders.

  17. A complex relationship between TRAF3 and non-canonical NF-κB2 activation in B lymphocytes

    Directory of Open Access Journals (Sweden)

    Wai Wai Lin

    2013-12-01

    Full Text Available The adaptor protein TRAF3 restrains BAFF receptor (BAFFR and CD40-mediated activation of the NF-κB2 pathway in B cells. Mice lacking TRAF3 specifically in B cells revealed the critical role of TRAF3 in restraining homeostatic B cell survival. Furthermore, loss- of-function mutations of the traf3 gene have been associated with human B cell malignancies, especially multiple myeloma (MM. It has been proposed that receptor-induced TRAF3 degradation leads to stabilization of the NF-B inducing kinase NIK, and subsequent NF-κB2 activation. However, it is unclear how receptor-mediated TRAF3 degradation or loss of function contributes to B cell-specific NF-κB2 activation. In the current study, we employed two complementary models to address this question. One utilized a mutant traf3 gene found in a human MM-derived cell line called LP1. The LP1 mutant TRAF3 protein lacks the TRAF-N and TRAF-C domains. Consistent with the paradigm described, expression of LP1 TRAF3 in B cells promoted higher basal levels of NF-κB2 activation compared to Wt TRAF3. However, LP1 did not associate with TRAF2, CD40, or BAFFR, and no LP1 degradation was observed following receptor engagement. Interestingly, LP1 showed enhanced NIK association. Thus, TRAF3 degradation becomes dispensable to activate NF-κB2 when it is unable to associate with TRAF2. In a second model, we examined several mutant forms of BAFFR that are unable to induce NF-κB2 activation in B cells. Signaling to B cells by each of these BAFFR mutants, however, induced levels of TRAF3 degradation similar to those induced by Wt BAFFR. Thus, in B cells, receptor-mediated TRAF3 degradation is not sufficient to promote NF-B2 activation. We thus conclude that there is not a simple linear relationship in B lymphocytes between relative levels of cellular TRAF3, induced TRAF3 degradation, NIK activation and NF-B2 activation.

  18. Non-canonical Wnt signaling through Wnt5a/b and a novel Wnt11 gene, Wnt11b, regulates cell migration during avian gastrulation

    OpenAIRE

    Hardy, Katharine M.; Garriock, Robert J.; Yatskievych, Tatiana A.; D'Agostino, Susan L.; Antin, Parker B.; Krieg, Paul A.

    2008-01-01

    Knowledge of the molecular mechanisms regulating cell ingression, epithelial-mesenchymal transition and migration movements during amniote gastrulation is steadily improving. In the frog and fish embryo, Wnt5 and Wnt11 ligands are expressed around the blastopore and play an important role in regulating cell movements associated with gastrulation. In the chicken embryo, although Wnt5a and Wnt5b are expressed in the primitive streak, the known Wnt11 gene is expressed in paraxial and intermediat...

  19. Non-canonical regulation of glutathione and trehalose biosynthesis characterizes non-Saccharomyces wine yeasts with poor performance in active dry yeast production

    Directory of Open Access Journals (Sweden)

    Esther Gamero-Sandemetrio

    2018-01-01

    Full Text Available Several yeast species, belonging to Saccharomyces and non-Saccharomyces genera, play fundamental roles during spontaneous must grape fermentation, and recent studies have shown that mixed fermentations, co-inoculated with S. cerevisiae and non-Saccharomyces strains, can improve wine organoleptic properties. During active dry yeast (ADY production, antioxidant systems play an essential role in yeast survival and vitality as both biomass propagation and dehydration cause cellular oxidative stress and negatively affect technological performance. Mechanisms for adaptation and resistance to desiccation have been described for S. cerevisiae, but no data are available on the physiology and oxidative stress response of non-Saccharomyces wine yeasts and their potential impact on ADY production. In this study we analyzed the oxidative stress response in several non-Saccharomyces yeast species by measuring the activity of reactive oxygen species (ROS scavenging enzymes, e.g., catalase and glutathione reductase, accumulation of protective metabolites, e.g., trehalose and reduced glutathione (GSH, and lipid and protein oxidation levels. Our data suggest that non-canonical regulation of glutathione and trehalose biosynthesis could cause poor fermentative performance after ADY production, as it corroborates the corrective effect of antioxidant treatments, during biomass propagation, with both pure chemicals and food-grade argan oil.

  20. An amino acid depleted cell-free protein synthesis system for the incorporation of non-canonical amino acid analogs into proteins.

    Science.gov (United States)

    Singh-Blom, Amrita; Hughes, Randall A; Ellington, Andrew D

    2014-05-20

    Residue-specific incorporation of non-canonical amino acids into proteins is usually performed in vivo using amino acid auxotrophic strains and replacing the natural amino acid with an unnatural amino acid analog. Herein, we present an efficient amino acid depleted cell-free protein synthesis system that can be used to study residue-specific replacement of a natural amino acid by an unnatural amino acid analog. This system combines a simple methodology and high protein expression titers with a high-efficiency analog substitution into a target protein. To demonstrate the productivity and efficacy of a cell-free synthesis system for residue-specific incorporation of unnatural amino acids in vitro, we use this system to show that 5-fluorotryptophan and 6-fluorotryptophan substituted streptavidin retain the ability to bind biotin despite protein-wide replacement of a natural amino acid for the amino acid analog. We envisage this amino acid depleted cell-free synthesis system being an economical and convenient format for the high-throughput screening of a myriad of amino acid analogs with a variety of protein targets for the study and functional characterization of proteins substituted with unnatural amino acids when compared to the currently employed in vivo methodologies. Copyright © 2014 Elsevier B.V. All rights reserved.

  1. Systemic combinatorial peptide selection yields a non-canonical iron-mimicry mechanism for targeting tumors in a mouse model of human glioblastoma

    Science.gov (United States)

    Staquicini, Fernanda I.; Ozawa, Michael G.; Moya, Catherine A.; Driessen, Wouter H.P.; Barbu, E. Magda; Nishimori, Hiroyuki; Soghomonyan, Suren; Flores, Leo G.; Liang, Xiaowen; Paolillo, Vincenzo; Alauddin, Mian M.; Basilion, James P.; Furnari, Frank B.; Bogler, Oliver; Lang, Frederick F.; Aldape, Kenneth D.; Fuller, Gregory N.; Höök, Magnus; Gelovani, Juri G.; Sidman, Richard L.; Cavenee, Webster K.; Pasqualini, Renata; Arap, Wadih

    2010-01-01

    The management of CNS tumors is limited by the blood-brain barrier (BBB), a vascular interface that restricts the passage of most molecules from the blood into the brain. Here we show that phage particles targeted with certain ligand motifs selected in vivo from a combinatorial peptide library can cross the BBB under normal and pathological conditions. Specifically, we demonstrated that phage clones displaying an iron-mimic peptide were able to target a protein complex of transferrin and transferrin receptor (TfR) through a non-canonical allosteric binding mechanism and that this functional protein complex mediated transport of the corresponding viral particles into the normal mouse brain. We also showed that, in an orthotopic mouse model of human glioblastoma, a combination of TfR overexpression plus extended vascular permeability and ligand retention resulted in remarkable brain tumor targeting of chimeric adeno-associated virus/phage particles displaying the iron-mimic peptide and carrying a gene of interest. As a proof of concept, we delivered the HSV thymidine kinase gene for molecular-genetic imaging and targeted therapy of intracranial xenografted tumors. Finally, we established that these experimental findings might be clinically relevant by determining through human tissue microarrays that many primary astrocytic tumors strongly express TfR. Together, our combinatorial selection system and results may provide a translational avenue for the targeted detection and treatment of brain tumors. PMID:21183793

  2. Non-canonical PRC1.1 Targets Active Genes Independent of H3K27me3 and Is Essential for Leukemogenesis

    Directory of Open Access Journals (Sweden)

    Vincent van den Boom

    2016-01-01

    Full Text Available Polycomb proteins are classical regulators of stem cell self-renewal and cell lineage commitment and are frequently deregulated in cancer. Here, we find that the non-canonical PRC1.1 complex, as identified by mass-spectrometry-based proteomics, is critically important for human leukemic stem cells. Downmodulation of PRC1.1 complex members, like the DNA-binding subunit KDM2B, strongly reduces cell proliferation in vitro and delays or even abrogates leukemogenesis in vivo in humanized xenograft models. PRC1.1 components are significantly overexpressed in primary AML CD34+ cells. Besides a set of genes that is targeted by PRC1 and PRC2, ChIP-seq studies show that PRC1.1 also binds a distinct set of genes that are devoid of H3K27me3, suggesting a gene-regulatory role independent of PRC2. This set encompasses genes involved in metabolism, which have transcriptionally active chromatin profiles. These data indicate that PRC1.1 controls specific genes involved in unique cell biological processes required for leukemic cell viability.

  3. Dengue Virus Uses a Non-Canonical Function of the Host GBF1-Arf-COPI System for Capsid Protein Accumulation on Lipid Droplets.

    Science.gov (United States)

    Iglesias, Nestor G; Mondotte, Juan A; Byk, Laura A; De Maio, Federico A; Samsa, Marcelo M; Alvarez, Cecilia; Gamarnik, Andrea V

    2015-09-01

    Dengue viruses cause the most important human viral disease transmitted by mosquitoes. In recent years, a great deal has been learned about molecular details of dengue virus genome replication; however, little is known about genome encapsidation and the functions of the viral capsid protein. During infection, dengue virus capsid progressively accumulates around lipid droplets (LDs) by an unknown mechanism. Here, we examined the process by which the viral capsid is transported from the endoplasmic reticulum (ER) membrane, where the protein is synthesized, to LDs. Using different methods of intervention, we found that the GBF1-Arf1/Arf4-COPI pathway is necessary for capsid transport to LDs, while the process is independent of both COPII components and Golgi integrity. The transport was sensitive to Brefeldin A, while a drug resistant form of GBF1 was sufficient to restore capsid subcellular distribution in infected cells. The mechanism by which LDs gain or lose proteins is still an open question. Our results support a model in which the virus uses a non-canonical function of the COPI system for capsid accumulation on LDs, providing new ideas for antiviral strategies. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  4. Crafting consensus

    Czech Academy of Sciences Publication Activity Database

    Zápal, Jan

    2017-01-01

    Roč. 173, 1–2 (2017), s. 169-200 ISSN 0048-5829 R&D Projects: GA ČR(CZ) GP14-27902P Institutional support: Progres-Q24 Keywords : consensus building * agenda setting * vote buying Subject RIV: AH - Economics OBOR OECD: Economic Theory Impact factor: 0.788, year: 2016

  5. Why Consensus?

    Directory of Open Access Journals (Sweden)

    Francesca Polletta

    2016-05-01

    Full Text Available Activists have long justified their egalitarian organizational forms in prefigurative terms. Making decisions by consensus, decentralizing organization, and rotating leadership serves to model the radically democratic society that activists hope to bring into being. Our comparison of consensus-based decision-making in three historical periods, however, shows that activists have understood the purposes of prefiguration in very different ways. Whereas radical pacifists in the 1940s saw their cooperative organizations as sustaining movement stalwarts in a period of political repression, new left activists in the 1960s imagined that their radically democratic practices would be adopted by ever-widening circles. Along with the political conditions in which they have operated, activists’ distinctive understandings of equality have also shaped the way they have made decisions. Our interviews with 30 leftist activists today reveal a view of decision-making as a place to work through inequalities that are informal, unacknowledged, and pervasive.

  6. Efficient replication, and evolution of Sindbis virus genomes with non-canonical 3'A/U-rich elements (NC3ARE) in neonatal mice.

    Science.gov (United States)

    James, Frederick D; Hietala, Katie A; Eldar, Dganit; Guess, Tiffany E; Cone, Cecil; Mundell, Nathan A; Mundall, Nathan; Barnett, Joey V; Raju, Ramaswamy

    2007-12-01

    Sindbis virus (SIN) is a mosquito-transmitted animal RNA virus. We previously reported that SIN genomes lacking a canonical 19 nt 3'CSE undergo novel repair processes in BHK cells to generate a library of stable atypical SIN genomes with non-canonical 3'A/U-rich elements (NC3AREs) adjacent to the 3' poly(A) tail [1]. To determine the stability and evolutionary pressures on the SIN genomes with NC3AREs to regain a 3'CSE, five representative SIN isolates and a wild type SIN were tested in newborn mice. The key findings of this study are: (a) all six SIN isolates, including those that have extensive NC3AREs in the 3'NTRs, replicate well and produce high titer viremia in newborn mice; (b) 7-9 successive passages of these isolates in newborn mice produced comparable levels of viremia; (c) while all isolates produced only small-sized plaques during primary infection in animals, both small- and large-sized plaques were generated in all other passages; (d) polymerase stuttering occurs on select 3' oligo(U) motifs to add more U residues within the NC3AREs; (e) the S3-8 isolate with an internal UAUUU motif in the 3'poly(A) tail maintains this element even after 9 passages in animals; (f) despite differences in 3'NTRs and variable tissue distribution, all SIN isolates appear to produce similar tissue pathology in infected animals. Competition experiments with wt SIN and atypical SIN isolates in BHK cells show dominance of wt SIN. As shown for BHK cells in culture, the 3'CSE of the SIN genome is not required for virus replication and genome stability in live animals. Since the NC3AREs of atypical SIN genomes are not specific to SIN replicases, alternate RNA motifs of alphavirus genome must confer specificity in template selection. These studies fulfill the need to confirm the long-term viability of atypical SIN genomes in newborn mice and offer a basis for exploring the use of atypical SIN genomes in biotechnology.

  7. Some recent work on lattice structures for digital signal processing

    Indian Academy of Sciences (India)

    Digital signal processing (DSP); lattice structures; finite impulse ... fascinated this author for a long time, and for the known non-canonical ...... where M

  8. Consensus standard requirements and guidance

    International Nuclear Information System (INIS)

    Putman, V.L.

    1995-01-01

    This report presents information from the ANS Criticality Alarm System Workshop relating to the consensus standard requirements and guidance. Topics presented include: definition; nomenclature; requirements and recommendations; purpose of criticality alarms; design criteria; signal characteristics; reliability, dependability and durability; tests; and emergency preparedness and planning

  9. Comparative analysis of seven viral nuclear export signals (NESs reveals the crucial role of nuclear export mediated by the third NES consensus sequence of nucleoprotein (NP in influenza A virus replication.

    Directory of Open Access Journals (Sweden)

    Nopporn Chutiwitoonchai

    Full Text Available The assembly of influenza virus progeny virions requires machinery that exports viral genomic ribonucleoproteins from the cell nucleus. Currently, seven nuclear export signal (NES consensus sequences have been identified in different viral proteins, including NS1, NS2, M1, and NP. The present study examined the roles of viral NES consensus sequences and their significance in terms of viral replication and nuclear export. Mutation of the NP-NES3 consensus sequence resulted in a failure to rescue viruses using a reverse genetics approach, whereas mutation of the NS2-NES1 and NS2-NES2 sequences led to a strong reduction in viral replication kinetics compared with the wild-type sequence. While the viral replication kinetics for other NES mutant viruses were also lower than those of the wild-type, the difference was not so marked. Immunofluorescence analysis after transient expression of NP-NES3, NS2-NES1, or NS2-NES2 proteins in host cells showed that they accumulated in the cell nucleus. These results suggest that the NP-NES3 consensus sequence is mostly required for viral replication. Therefore, each of the hydrophobic (Φ residues within this NES consensus sequence (Φ1, Φ2, Φ3, or Φ4 was mutated, and its viral replication and nuclear export function were analyzed. No viruses harboring NP-NES3 Φ2 or Φ3 mutants could be rescued. Consistent with this, the NP-NES3 Φ2 and Φ3 mutants showed reduced binding affinity with CRM1 in a pull-down assay, and both accumulated in the cell nucleus. Indeed, a nuclear export assay revealed that these mutant proteins showed lower nuclear export activity than the wild-type protein. Moreover, the Φ2 and Φ3 residues (along with other Φ residues within the NP-NES3 consensus were highly conserved among different influenza A viruses, including human, avian, and swine. Taken together, these results suggest that the Φ2 and Φ3 residues within the NP-NES3 protein are important for its nuclear export function

  10. Activation of non-canonical Wnt/JNK pathway by Wnt3a is associated with differentiation fate determination of human bone marrow stromal (mesenchymal) stem cells

    DEFF Research Database (Denmark)

    Qiu, Weimin; Chen, Li; Kassem, Moustapha

    2011-01-01

    The canonical Wnt signaling pathway can determine human bone marrow stromal (mesenchymal) stem cell (hMSC) differentiation fate into osteoblast or adipocyte lineages. However, its downstream targets in MSC are not well characterized. Thus, using DNA microarrays, we compared global gene expression...

  11. Non-canonical binding interactions of the RNA recognition motif (RRM) domains of P34 protein modulate binding within the 5S ribonucleoprotein particle (5S RNP).

    Science.gov (United States)

    Kamina, Anyango D; Williams, Noreen

    2017-01-01

    RNA binding proteins are involved in many aspects of RNA metabolism. In Trypanosoma brucei, our laboratory has identified two trypanosome-specific RNA binding proteins P34 and P37 that are involved in the maturation of the 60S subunit during ribosome biogenesis. These proteins are part of the T. brucei 5S ribonucleoprotein particle (5S RNP) and P34 binds to 5S ribosomal RNA (rRNA) and ribosomal protein L5 through its N-terminus and its RNA recognition motif (RRM) domains. We generated truncated P34 proteins to determine these domains' interactions with 5S rRNA and L5. Our analyses demonstrate that RRM1 of P34 mediates the majority of binding with 5S rRNA and the N-terminus together with RRM1 contribute the most to binding with L5. We determined that the consensus ribonucleoprotein (RNP) 1 and 2 sequences, characteristic of canonical RRM domains, are not fully conserved in the RRM domains of P34. However, the aromatic amino acids previously described to mediate base stacking interactions with their RNA target are conserved in both of the RRM domains of P34. Surprisingly, mutation of these aromatic residues did not disrupt but instead enhanced 5S rRNA binding. However, we identified four arginine residues located in RRM1 of P34 that strongly impact L5 binding. These mutational analyses of P34 suggest that the binding site for 5S rRNA and L5 are near each other and specific residues within P34 regulate the formation of the 5S RNP. These studies show the unique way that the domains of P34 mediate binding with the T. brucei 5S RNP.

  12. The extracellular domain of Lrp5/6 inhibits noncanonical Wnt signaling in vivo

    Czech Academy of Sciences Publication Activity Database

    Bryja, Vítězslav; Andersson, E.R.; Schambony, A.; Esner, M.; Bryjová, Lenka; Biris, K.K.; Hall, A.C.; Kraft, B.; Čajánek, L.; Yamaguchi, T.P.; Buckingham, M.; Arenas, E.

    2009-01-01

    Roč. 20, č. 3 (2009), s. 924-936 ISSN 1059-1524 Institutional research plan: CEZ:AV0Z50040507; CEZ:AV0Z50040702 Keywords : non-canonical Wnt signaling * Lrp5/6 * mouse Subject RIV: BO - Biophysics Impact factor: 5.979, year: 2009

  13. Non-Smad pathways in TGF-β signaling

    OpenAIRE

    Zhang, Ying E

    2009-01-01

    Transforming growth factor-β utilizes a multitude of intracellular signaling pathways in addition to Smads to regulate a wide array of cellular functions. These non-canonical, non-Smad pathways are activated directly by ligand-occupied receptors to reinforce, attenuate, or otherwise modulate downstream cellular responses. These non-Smad pathways include various branches of MAP kinase pathways, Rho-like GTPase signaling pathways, and phosphatidylinositol-3-kinase/AKT pathways. This review focu...

  14. De Novo Assembly of Human Herpes Virus Type 1 (HHV-1) Genome, Mining of Non-Canonical Structures and Detection of Novel Drug-Resistance Mutations Using Short- and Long-Read Next Generation Sequencing Technologies.

    Science.gov (United States)

    Karamitros, Timokratis; Harrison, Ian; Piorkowska, Renata; Katzourakis, Aris; Magiorkinis, Gkikas; Mbisa, Jean Lutamyo

    2016-01-01

    Human herpesvirus type 1 (HHV-1) has a large double-stranded DNA genome of approximately 152 kbp that is structurally complex and GC-rich. This makes the assembly of HHV-1 whole genomes from short-read sequencing data technically challenging. To improve the assembly of HHV-1 genomes we have employed a hybrid genome assembly protocol using data from two sequencing technologies: the short-read Roche 454 and the long-read Oxford Nanopore MinION sequencers. We sequenced 18 HHV-1 cell culture-isolated clinical specimens collected from immunocompromised patients undergoing antiviral therapy. The susceptibility of the samples to several antivirals was determined by plaque reduction assay. Hybrid genome assembly resulted in a decrease in the number of contigs in 6 out of 7 samples and an increase in N(G)50 and N(G)75 of all 7 samples sequenced by both technologies. The approach also enhanced the detection of non-canonical contigs including a rearrangement between the unique (UL) and repeat (T/IRL) sequence regions of one sample that was not detectable by assembly of 454 reads alone. We detected several known and novel resistance-associated mutations in UL23 and UL30 genes. Genome-wide genetic variability ranged from genomes will be useful in determining genetic determinants of drug resistance, virulence, pathogenesis and viral evolution. The numerous, complex repeat regions of the HHV-1 genome currently remain a barrier towards this goal.

  15. The Limits of Consensus.

    Science.gov (United States)

    Poster, John B.

    Dynamics in the education policy arena suggest that, despite two generations of researchers extolling democratic leadership styles and consensus building over autocratic techniques, wide participation in policymaking and the broadest possible consensus are not always productive: American society has not yet agreed on what schools should…

  16. Model-based consensus

    NARCIS (Netherlands)

    Boumans, M.; Martini, C.; Boumans, M.

    2014-01-01

    The aim of the rational-consensus method is to produce "rational consensus", that is, "mathematical aggregation", by weighing the performance of each expert on the basis of his or her knowledge and ability to judge relevant uncertainties. The measurement of the performance of the experts is based on

  17. A role for the non-canonical Wnt-ß-Catenin and TGF-ß signaling pathways in the induction of tolerance during the establishment of a Salmonella enterica serovar Enteritidis persistent cecal infection in chickens

    Science.gov (United States)

    Non-typhoidal Salmonella enterica induce an early pro-inflammatory response in chickens. However, the response is short-lived, asymptomatic of disease, resulting in a persistent colonization of the ceca, and fecal shedding of bacteria. The underlying mechanisms that control this persistent infecti...

  18. ESCMID Study Group for Infections in Compromised Hosts (ESGICH) Consensus Document on the safety of targeted and biological therapies: an infectious diseases perspective (Intracellular signaling pathways: tyrosine kinase and mTOR inhibitors).

    Science.gov (United States)

    Reinwald, M; Silva, J T; Mueller, N J; Fortún, J; Garzoni, C; de Fijter, J W; Fernández-Ruiz, M; Grossi, P; Aguado, J M

    2018-06-01

    The present review is part of the European Society of Clinical Microbiology and Infectious Diseases (ESCMID) Study Group for Infections in Compromised Hosts (ESGICH) Consensus Document on the safety of targeted and biologic therapies. To review, from an infectious diseases perspective, the safety profile of therapies targeting different intracellular signaling pathways and to suggest preventive recommendations. Computer-based Medline searches with MeSH terms pertaining to each agent or therapeutic family. Although BCR-ABL tyrosine kinase inhibitors modestly increase the overall risk of infection, dasatinib has been associated with cytomegalovirus and hepatitis B virus reactivation. BRAF/MEK kinase inhibitors do not significantly affect infection susceptibility. The effect of Bruton tyrosine kinase inhibitors (ibrutinib) among patients with B-cell malignancies is difficult to distinguish from that of previous immunosuppression. However, cases of Pneumocystis jirovecii pneumonia (PCP), invasive fungal infection and progressive multifocal leukoencephalopathy have been occasionally reported. Because phosphatidylinositol-3-kinase inhibitors (idelalisib) may predispose to opportunistic infections, anti-Pneumocystis prophylaxis and prevention strategies for cytomegalovirus are recommended. No increased rates of infection have been observed with venetoclax (antiapoptotic protein Bcl-2 inhibitor). Therapy with Janus kinase inhibitors markedly increases the incidence of infection. Pretreatment screening for chronic hepatitis B virus and latent tuberculosis infection must be performed, and anti-Pneumocystis prophylaxis should be considered for patients with additional risk factors. Cancer patients receiving mTOR inhibitors face an increased incidence of overall infection, especially those with additional risk factors (prior therapies or delayed wound healing). Specific preventive approaches are warranted in view of the increased risk of infection associated with some of the

  19. Informed consent -- Building consensus

    International Nuclear Information System (INIS)

    Lovenheim, R.

    1990-01-01

    The author shares his observations and offers an approach to 'building consensus' for what he believes is the only environmentally sound option, i.e., safe, permanent disposal of low-level radioactive waste (LLRW). Consensus does not mean unanimity, acceptance, or harmony. The low-level radioactive waste disposal issue is fraught with fear and hysteria. The paper discusses major emotions that fracture public opinion regarding this issue. The author defines consensus as the informed consent of LLRW disposal strategies by a majority of citizens whose cooperation is required to achieve the goals of environmentally sound solution. The political aspects are reviewed. The need for US Department of Energy to fulfill its importance technical assistance role is discussed

  20. Continuity and consensus

    DEFF Research Database (Denmark)

    Abrahamson, Peter

    2010-01-01

    maternal leave. These changes can be explained as adjustments to post-industrial conditions within a political culture relying on class compromises and a broad consensus informed by expert advice coming from civil servants and ad hoc policy commissions. The paper concludes that changes in Danish family...... policy reflect changing conditions for employment and the minding of children and that there has been a high degree of continuity and consensus about the change, as indicated by the strong increase in female labour market involvement....

  1. A new inhibitor of the ?-arrestin/AP2 endocytic complex reveals interplay between GPCR internalization and signalling

    OpenAIRE

    Beautrait, Alexandre; Paradis, Justine S.; Zimmerman, Brandon; Giubilaro, Jenna; Nikolajev, Ljiljana; Armando, Sylvain; Kobayashi, Hiroyuki; Yamani, Lama; Namkung, Yoon; Heydenreich, Franziska M.; Khoury, Etienne; Audet, Martin; Roux, Philippe P.; Veprintsev, Dmitry B.; Laporte, St?phane A.

    2017-01-01

    In addition to G protein-coupled receptor (GPCR) desensitization and endocytosis, ?-arrestin recruitment to ligand-stimulated GPCRs promotes non-canonical signalling cascades. Distinguishing the respective contributions of ?-arrestin recruitment to the receptor and ?-arrestin-promoted endocytosis in propagating receptor signalling has been limited by the lack of selective analytical tools. Here, using a combination of virtual screening and cell-based assays, we have identified a small molecul...

  2. Inhibition of adipocytogenesis by canonical WNT signaling in human mesenchymal stem cells

    International Nuclear Information System (INIS)

    Shen, Longxiang; Glowacki, Julie; Zhou, Shuanhu

    2011-01-01

    The WNT signaling pathway plays important roles in the self-renewal and differentiation of mesenchymal stem cells (MSCs). Little is known about WNT signaling in adipocyte differentiation of human MSCs. In this study, we tested the hypothesis that canonical and non-canonical WNTs differentially regulate in vitro adipocytogenesis in human MSCs. The expression of adipocyte gene PPARγ2, lipoprotein lipase, and adipsin increased during adipocytogenesis of hMSCs. Simultaneously, the expression of canonical WNT2, 10B, 13, and 14 decreased, whereas non-canonical WNT4 and 11 increased, and WNT5A was unchanged. A small molecule WNT mimetic, SB-216763, increased accumulation of β-catenin protein, inhibited induction of WNT4 and 11 and inhibited adipocytogenesis. In contrast, knockdown of β-catenin with siRNA resulted in spontaneous adipocytogenesis. These findings support the view that canonical WNT signaling inhibits and non-canonical WNT signaling promotes adipocytogenesis in adult human marrow-derived mesenchymal stem cells.

  3. Model-based consensus

    NARCIS (Netherlands)

    Boumans, Marcel

    2014-01-01

    The aim of the rational-consensus method is to produce “rational consensus”, that is, “mathematical aggregation”, by weighing the performance of each expert on the basis of his or her knowledge and ability to judge relevant uncertainties. The measurement of the performance of the experts is based on

  4. Achieving diagnosis by consensus

    LENUS (Irish Health Repository)

    Kane, Bridget

    2009-08-01

    This paper provides an analysis of the collaborative work conducted at a multidisciplinary medical team meeting, where a patient’s definitive diagnosis is agreed, by consensus. The features that distinguish this process of diagnostic work by consensus are examined in depth. The current use of technology to support this collaborative activity is described, and experienced deficiencies are identified. Emphasis is placed on the visual and perceptual difficulty for individual specialities in making interpretations, and on how, through collaboration in discussion, definitive diagnosis is actually achieved. The challenge for providing adequate support for the multidisciplinary team at their meeting is outlined, given the multifaceted nature of the setting, i.e. patient management, educational, organizational and social functions, that need to be satisfied.

  5. Spanish Consensus Statement

    Science.gov (United States)

    Rey, Guillermo Álvarez; Cuesta, Jordi Ardevol; Loureda, Rafael Arriaza; España, Fernando Ávila; Matas, Ramón Balius; Pazos, Fernando Baró; de Dios Beas Jiménez, Juan; Rosell, Jorge Candel; Fernandez, César Cobián; Ros, Francisco Esparza; Colmenero, Josefina Espejo; de Prado, Jorge Fernández; Cota, Juan José García; González, Jose Ignacio Garrido; Santander, Manuela González; Munilla, Miguel Ángel Herrador; Ruiz, Francisco Ivorra; Díaz, Fernando Jiménez; Marqueta, Pedro Manonelles; Fernandez, Antonio Maestro; Benito, Juan José Muñoz; Vilás, Ramón Olivé; Teres, Xavier Peirau; Amaro, José Peña; Roque, Juan Pérez San; Parenteu, Christophe Ramírez; Serna, Juan Ribas; Álvarez, Mikel Sánchez; Marchori, Carlos Sanchez; Soto, Miguel del Valle; Alonso, José María Villalón; García, Pedro Guillen; de la Iglesia, Nicolas Hugo; Alcorocho, Juan Manuel Lopez

    2015-01-01

    On the 21st of March, 2015, experts met at Clínica CEMTRO in Madrid, Spain, under the patronage of The Spanish Society for Sports Traumatology (SETRADE), The Spanish Federation of Sports Medicine (FEMEDE), The Spanish Association of Medical Services for Football Clubs (AEMEF), and The Spanish Association of Medical Services for Basketball Clubs (AEMB) with the aim of establishing a round table that would allow specialists to consider the most appropriate current general actions to be taken when treating muscle tears in sport, based on proven scientific data described in the medical literature. Each expert received a questionnaire prior to the aforementioned meeting comprising a set of questions concerning therapeutic indications generally applied in the different stages present during muscle repair. The present Consensus Document is the result of the answers to the questionnaire and resulting discussion and consensus over which are the best current indications in the treatment of muscle tears in sport. Avoiding immobilization, not taking nonsteroidal anti-inflammatory drugs (NSAIDs) randomly, fostering early mobilization, increasing vascularization of injured, site and regulating inflammatory mechanisms—without inhibiting these from the early stages of the recovery period—all stood out as main points of the Consensus Document. Additionally, there is controversy concerning cell stimulation techniques and the use of growth factors or cell inhibitors. The decision concerning discharge was unanimous, as was the criteria considered when it came to performing sport techniques without pain. PMID:27213161

  6. Wnt5a Signaling in Cancer

    Directory of Open Access Journals (Sweden)

    Marwa S. Asem

    2016-08-01

    Full Text Available Wnt5a is involved in activating several non-canonical WNT signaling pathways, through binding to different members of the Frizzled- and Ror-family receptors. Wnt5a signaling is critical for regulating normal developmental processes, including proliferation, differentiation, migration, adhesion and polarity. However, the aberrant activation or inhibition of Wnt5a signaling is emerging as an important event in cancer progression, exerting both oncogenic and tumor suppressive effects. Recent studies show the involvement of Wnt5a in regulating cancer cell invasion, metastasis, metabolism and inflammation. In this article, we review findings regarding the molecular mechanisms and roles of Wnt5a signaling in various cancer types, and highlight Wnt5a in ovarian cancer.

  7. Achieving consensus in environmental programs

    International Nuclear Information System (INIS)

    Kurstedt, H.A.; Jones, R.M.; Walker, J.A.; Middleman, L.I.

    1989-01-01

    In this paper, the authors describe a research effort on consensus tied to the Environmental Restoration Program (ERP) within the U.S. Department of Energy's Office of Defense Waste and Transportation Management (DWTM). They define consensus and explain why consensus decisions are not merely desirable but necessary in furthering ERP activities. As examples of their planned applied research, the authors first discuss nominal group technique as a representative consensus-generating tool, and conclude by describing the consensus-related mission of the Waste Management Review Group, established to conduct independent, third-party review of DWTM/ERP plans and activities

  8. Achieving consensus in environmental programs

    Energy Technology Data Exchange (ETDEWEB)

    Kurstedt, Jr., H. A.; Jones, R. M.; Walker, J. A.; Middleman, L. I.

    1989-01-01

    In this paper, we describe a new research effort on consensus tied to the Environmental Restoration Program (ERP) within the US Department of Energy's Office of Defense Waste and Transportation Management (DWTM). We define consensus and explain why consensus decisions are not merely desirable but necessary in furthering ERP activities. As examples of our planned applied research, we first discuss Nominal Group Technique as a representative consensus-generating tool, and we conclude by describing the consensus-related mission of the Waste Management Review Group, established at Virginia Tech to conduct independent, third-party review of DWTM/ERP plans and activities. 10 refs.

  9. Microscopic enteritis: Bucharest consensus.

    Science.gov (United States)

    Rostami, Kamran; Aldulaimi, David; Holmes, Geoffrey; Johnson, Matt W; Robert, Marie; Srivastava, Amitabh; Fléjou, Jean-François; Sanders, David S; Volta, Umberto; Derakhshan, Mohammad H; Going, James J; Becheanu, Gabriel; Catassi, Carlo; Danciu, Mihai; Materacki, Luke; Ghafarzadegan, Kamran; Ishaq, Sauid; Rostami-Nejad, Mohammad; Peña, A Salvador; Bassotti, Gabrio; Marsh, Michael N; Villanacci, Vincenzo

    2015-03-07

    Microscopic enteritis (ME) is an inflammatory condition of the small bowel that leads to gastrointestinal symptoms, nutrient and micronutrient deficiency. It is characterised by microscopic or sub-microscopic abnormalities such as microvillus changes and enterocytic alterations in the absence of definite macroscopic changes using standard modern endoscopy. This work recognises a need to characterize disorders with microscopic and submicroscopic features, currently regarded as functional or non-specific entities, to obtain further understanding of their clinical relevance. The consensus working party reviewed statements about the aetiology, diagnosis and symptoms associated with ME and proposes an algorithm for its investigation and treatment. Following the 5(th) International Course in Digestive Pathology in Bucharest in November 2012, an international group of 21 interested pathologists and gastroenterologists formed a working party with a view to formulating a consensus statement on ME. A five-step agreement scale (from strong agreement to strong disagreement) was used to score 21 statements, independently. There was strong agreement on all statements about ME histology (95%-100%). Statements concerning diagnosis achieved 85% to 100% agreement. A statement on the management of ME elicited agreement from the lowest rate (60%) up to 100%. The remaining two categories showed general agreement between experts on clinical presentation (75%-95%) and pathogenesis (80%-90%) of ME. There was strong agreement on the histological definition of ME. Weaker agreement on management indicates a need for further investigations, better definitions and clinical trials to produce quality guidelines for management. This ME consensus is a step toward greater recognition of a significant entity affecting symptomatic patients previously labelled as non-specific or functional enteropathy.

  10. Consensus Convolutional Sparse Coding

    KAUST Repository

    Choudhury, Biswarup; Swanson, Robin; Heide, Felix; Wetzstein, Gordon; Heidrich, Wolfgang

    2017-01-01

    In this paper, we propose a new approach to solving CSC as a consensus optimization problem, which lifts these limitations. By learning CSC features from large-scale image datasets for the first time, we achieve significant quality improvements in a number of imaging tasks. Moreover, the proposed method enables new applications in high dimensional feature learning that has been intractable using existing CSC methods. This is demonstrated for a variety of reconstruction problems across diverse problem domains, including 3D multispectral demosaickingand 4D light field view synthesis.

  11. Primary Cilia, Signaling Networks and Cell Migration

    DEFF Research Database (Denmark)

    Veland, Iben Rønn

    Primary cilia are microtubule-based, sensory organelles that emerge from the centrosomal mother centriole to project from the surface of most quiescent cells in the human body. Ciliary entry is a tightly controlled process, involving diffusion barriers and gating complexes that maintain a unique...... this controls directional cell migration as a physiological response. The ciliary pocket is a membrane invagination with elevated activity of clathrin-dependent endocytosis (CDE). In paper I, we show that the primary cilium regulates TGF-β signaling and the ciliary pocket is a compartment for CDE...... on formation of the primary cilium and CDE at the pocket region. The ciliary protein Inversin functions as a molecular switch between canonical and non-canonical Wnt signaling. In paper II, we show that Inversin and the primary cilium control Wnt signaling and are required for polarization and cell migration...

  12. Expert consensus document

    DEFF Research Database (Denmark)

    Boehm, Ulrich; Bouloux, Pierre-Marc; Dattani, Mehul T

    2015-01-01

    Congenital hypogonadotropic hypogonadism (CHH) is a rare disorder caused by the deficient production, secretion or action of gonadotropin-releasing hormone (GnRH), which is the master hormone regulating the reproductive axis. CHH is clinically and genetically heterogeneous, with >25 different...... migration of GnRH-synthesizing neurons. CHH can be challenging to diagnose, particularly when attempting to differentiate it from constitutional delay of puberty. A timely diagnosis and treatment to induce puberty can be beneficial for sexual, bone and metabolic health, and might help minimize some...... of the psychological effects of CHH. In most cases, fertility can be induced using specialized treatment regimens and several predictors of outcome have been identified. Patients typically require lifelong treatment, yet ∼10-20% of patients exhibit a spontaneous recovery of reproductive function. This Consensus...

  13. American Burn Association Consensus Statements

    Science.gov (United States)

    2013-08-01

    quality consensus conference was underwrit- ten in part by unrestricted educational grants from Molnlycke Health Care and Baxter Health Care. Address... nutrition , psychological outcomes, resuscitation, and wound repair. After reviewing the literature, debating the issues at the consensus conference and...need for intubation, concomitant trauma. 3. Resuscitation characteristics: Lab values (base defi- cit, lactate, hemoglobin /hematocrit, blood urea

  14. Attitude extremity, consensus and diagnosticity

    NARCIS (Netherlands)

    van der Pligt, J.; Ester, P.; van der Linden, J.

    1983-01-01

    Studied the effects of attitude extremity on perceived consensus and willingness to ascribe trait terms to others with either pro- or antinuclear attitudes. 611 Ss rated their attitudes toward nuclear energy on a 5-point scale. Results show that attitude extremity affected consensus estimates. Trait

  15. Political Consensus and Fiscal Outcomes

    DEFF Research Database (Denmark)

    Houlberg, Kurt; Holm Pedersen, Lene

    2015-01-01

    It is becoming difficult to maintain consensus in a period of economic austerity, and this possibly challenges the ability of democratic institutions to take decisions on tough economic questions. In order to find out how political consensus influences fiscal outcomes, this article sets out...

  16. Identification and characterization of multiple conserved nuclear localization signals within adenovirus E1A

    Energy Technology Data Exchange (ETDEWEB)

    Marshall, Kris S.; Cohen, Michael J.; Fonseca, Greg J.; Todorovic, Biljana; King, Cason R. [Department of Microbiology and Immunology, Western University, London Regional Cancer Program, London, ON, Canada N6A 4L6 (Canada); Yousef, Ahmed F. [Department of Chemical and Environmental Engineering, Masdar Institute, Abu Dhabi (United Arab Emirates); Zhang, Zhiying [College of Animal Science and Technologies, Northwest A and F University, Yangling, Shaanxi 712100 (China); Mymryk, Joe S., E-mail: jmymryk@uwo.ca [Department of Microbiology and Immunology, Western University, London Regional Cancer Program, London, ON, Canada N6A 4L6 (Canada); Department of Oncology, Western University, London Regional Cancer Program, London, ON, Canada N6A 4L6 (Canada)

    2014-04-15

    The human adenovirus 5 (HAdV-5) E1A protein has a well defined canonical nuclear localization signal (NLS) located at its C-terminus. We used a genetic assay in the yeast Saccharomyces cerevisiae to demonstrate that the canonical NLS is present and functional in the E1A proteins of each of the six HAdV species. This assay also detects a previously described non-canonical NLS within conserved region 3 and a novel active NLS within the N-terminal/conserved region 1 portion of HAdV-5 E1A. These activities were also present in the E1A proteins of each of the other five HAdV species. These results demonstrate that, despite substantial differences in primary sequence, HAdV E1A proteins are remarkably consistent in that they contain one canonical and two non-canonical NLSs. By utilizing independent mechanisms, these multiple NLSs ensure nuclear localization of E1A in the infected cell. - Highlights: • HAdV E1A uses multiple mechanisms for nuclear import. • We identified an additional non-canonical NLS in the N-terminal/CR1 portion of E1A. • The new NLS does not contact importin-alpha directly. • All NLSs are functionally conserved in the E1A proteins of all 6 HAdV species.

  17. Consensus Convolutional Sparse Coding

    KAUST Repository

    Choudhury, Biswarup

    2017-12-01

    Convolutional sparse coding (CSC) is a promising direction for unsupervised learning in computer vision. In contrast to recent supervised methods, CSC allows for convolutional image representations to be learned that are equally useful for high-level vision tasks and low-level image reconstruction and can be applied to a wide range of tasks without problem-specific retraining. Due to their extreme memory requirements, however, existing CSC solvers have so far been limited to low-dimensional problems and datasets using a handful of low-resolution example images at a time. In this paper, we propose a new approach to solving CSC as a consensus optimization problem, which lifts these limitations. By learning CSC features from large-scale image datasets for the first time, we achieve significant quality improvements in a number of imaging tasks. Moreover, the proposed method enables new applications in high-dimensional feature learning that has been intractable using existing CSC methods. This is demonstrated for a variety of reconstruction problems across diverse problem domains, including 3D multispectral demosaicing and 4D light field view synthesis.

  18. Between consensus and contestation.

    Science.gov (United States)

    Weale, Albert

    2016-08-15

    Purpose - Noting that discussions of public participation and priority setting typically presuppose certain political theories of democracy, the purpose of this paper is to discuss two theories: the consensual and the agonistic. The distinction is illuminating when considering the difference between institutionalized public participation and contestatory participation. Design/methodology/approach - The approach is a theoretical reconstruction of two ways of thinking about public participation in relation to priority setting in health care, drawing on the work of Habermas, a deliberative theorist, and Mouffe, a theorist of agonism. Findings - The different theoretical approaches can be associated with different ways of understanding priority setting. In particular, agonistic democratic theory would understand priority setting as system of inclusions and exclusions rather than the determination of a consensus of social values, which is the typical deliberative way of thinking about the issues. Originality/value - The paper shows the value of drawing out explicitly the tacit assumptions of practices of political participation in order to reveal their scope and limitations. It suggests that making such theoretical presuppositions explicit has value for health services management in recognizing these implicit choices.

  19. Consensus Convolutional Sparse Coding

    KAUST Repository

    Choudhury, Biswarup

    2017-04-11

    Convolutional sparse coding (CSC) is a promising direction for unsupervised learning in computer vision. In contrast to recent supervised methods, CSC allows for convolutional image representations to be learned that are equally useful for high-level vision tasks and low-level image reconstruction and can be applied to a wide range of tasks without problem-specific retraining. Due to their extreme memory requirements, however, existing CSC solvers have so far been limited to low-dimensional problems and datasets using a handful of low-resolution example images at a time. In this paper, we propose a new approach to solving CSC as a consensus optimization problem, which lifts these limitations. By learning CSC features from large-scale image datasets for the first time, we achieve significant quality improvements in a number of imaging tasks. Moreover, the proposed method enables new applications in high dimensional feature learning that has been intractable using existing CSC methods. This is demonstrated for a variety of reconstruction problems across diverse problem domains, including 3D multispectral demosaickingand 4D light field view synthesis.

  20. Brazilian Consensus on Photoprotection

    Science.gov (United States)

    Schalka, Sérgio; Steiner, Denise; Ravelli, Flávia Naranjo; Steiner, Tatiana; Terena, Aripuanã Cobério; Marçon, Carolina Reato; Ayres, Eloisa Leis; Addor, Flávia Alvim Sant'anna; Miot, Helio Amante; Ponzio, Humberto; Duarte, Ida; Neffá, Jane; da Cunha, José Antônio Jabur; Boza, Juliana Catucci; Samorano, Luciana de Paula; Corrêa, Marcelo de Paula; Maia, Marcus; Nasser, Nilton; Leite, Olga Maria Rodrigues Ribeiro; Lopes, Otávio Sergio; Oliveira, Pedro Dantas; Meyer, Renata Leal Bregunci; Cestari, Tânia; dos Reis, Vitor Manoel Silva; Rego, Vitória Regina Pedreira de Almeida

    2014-01-01

    Brazil is a country of continental dimensions with a large heterogeneity of climates and massive mixing of the population. Almost the entire national territory is located between the Equator and the Tropic of Capricorn, and the Earth axial tilt to the south certainly makes Brazil one of the countries of the world with greater extent of land in proximity to the sun. The Brazilian coastline, where most of its population lives, is more than 8,500 km long. Due to geographic characteristics and cultural trends, Brazilians are among the peoples with the highest annual exposure to the sun. Epidemiological data show a continuing increase in the incidence of non-melanoma and melanoma skin cancers. Photoprotection can be understood as a set of measures aimed at reducing sun exposure and at preventing the development of acute and chronic actinic damage. Due to the peculiarities of Brazilian territory and culture, it would not be advisable to replicate the concepts of photoprotection from other developed countries, places with completely different climates and populations. Thus the Brazilian Society of Dermatology has developed the Brazilian Consensus on Photoprotection, the first official document on photoprotection developed in Brazil for Brazilians, with recommendations on matters involving photoprotection. PMID:25761256

  1. Consensus Convolutional Sparse Coding

    KAUST Repository

    Choudhury, Biswarup; Swanson, Robin; Heide, Felix; Wetzstein, Gordon; Heidrich, Wolfgang

    2017-01-01

    Convolutional sparse coding (CSC) is a promising direction for unsupervised learning in computer vision. In contrast to recent supervised methods, CSC allows for convolutional image representations to be learned that are equally useful for high-level vision tasks and low-level image reconstruction and can be applied to a wide range of tasks without problem-specific retraining. Due to their extreme memory requirements, however, existing CSC solvers have so far been limited to low-dimensional problems and datasets using a handful of low-resolution example images at a time. In this paper, we propose a new approach to solving CSC as a consensus optimization problem, which lifts these limitations. By learning CSC features from large-scale image datasets for the first time, we achieve significant quality improvements in a number of imaging tasks. Moreover, the proposed method enables new applications in high-dimensional feature learning that has been intractable using existing CSC methods. This is demonstrated for a variety of reconstruction problems across diverse problem domains, including 3D multispectral demosaicing and 4D light field view synthesis.

  2. Consensus on consensus: a synthesis of consensus estimates on human-caused global warming

    Science.gov (United States)

    Cook, John; Oreskes, Naomi; Doran, Peter T.; Anderegg, William R. L.; Verheggen, Bart; Maibach, Ed W.; Carlton, J. Stuart; Lewandowsky, Stephan; Skuce, Andrew G.; Green, Sarah A.; Nuccitelli, Dana; Jacobs, Peter; Richardson, Mark; Winkler, Bärbel; Painting, Rob; Rice, Ken

    2016-04-01

    The consensus that humans are causing recent global warming is shared by 90%-100% of publishing climate scientists according to six independent studies by co-authors of this paper. Those results are consistent with the 97% consensus reported by Cook et al (Environ. Res. Lett. 8 024024) based on 11 944 abstracts of research papers, of which 4014 took a position on the cause of recent global warming. A survey of authors of those papers (N = 2412 papers) also supported a 97% consensus. Tol (2016 Environ. Res. Lett. 11 048001) comes to a different conclusion using results from surveys of non-experts such as economic geologists and a self-selected group of those who reject the consensus. We demonstrate that this outcome is not unexpected because the level of consensus correlates with expertise in climate science. At one point, Tol also reduces the apparent consensus by assuming that abstracts that do not explicitly state the cause of global warming (‘no position’) represent non-endorsement, an approach that if applied elsewhere would reject consensus on well-established theories such as plate tectonics. We examine the available studies and conclude that the finding of 97% consensus in published climate research is robust and consistent with other surveys of climate scientists and peer-reviewed studies.

  3. Mexican consensus on dyspepsia

    Directory of Open Access Journals (Sweden)

    R. Carmona-Sánchez

    2017-10-01

    Full Text Available Since the publication of the 2007 dyspepsia guidelines of the Asociación Mexicana de Gastroenterología, there have been significant advances in the knowledge of this disease. A systematic search of the literature in PubMed (01/2007 to 06/2016 was carried out to review and update the 2007 guidelines and to provide new evidence-based recommendations. All high-quality articles in Spanish and English were included. Statements were formulated and voted upon using the Delphi method. The level of evidence and strength of recommendation of each statement were established according to the GRADE system. Thirty-one statements were formulated, voted upon, and graded. New definition, classification, epidemiology, and pathophysiology data were provided and include the following information: Endoscopy should be carried out in cases of uninvestigated dyspepsia when there are alarm symptoms or no response to treatment. Gastric and duodenal biopsies can confirm Helicobacter pylori infection and rule out celiac disease, respectively. Establishing a strong doctor-patient relationship, as well as dietary and lifestyle changes, are useful initial measures. H2-blockers, proton-pump inhibitors, prokinetics, and antidepressants are effective pharmacologic therapies. H. pylori eradication may be effective in a subgroup of patients. There is no evidence that complementary and alternative therapies are beneficial, with the exception of Iberogast and rikkunshito, nor is there evidence on the usefulness of prebiotics, probiotics, or psychologic therapies. The new consensus statements on dyspepsia provide guidelines based on up-to-date evidence. A discussion, level of evidence, and strength of recommendation are presented for each statement. Resumen: Desde la publicación de las guías de dispepsia 2007 de la Asociación Mexicana de Gastroenterología ha habido avances significativos en el conocimiento de esta enfermedad. Se realizó una revisión sistemática de la

  4. NIH Consensus Conference. Acupuncture.

    Science.gov (United States)

    1998-11-04

    To provide clinicians, patients, and the general public with a responsible assessment of the use and effectiveness of acupuncture to treat a variety of conditions. A nonfederal, nonadvocate, 12-member panel representing the fields of acupuncture, pain, psychology, psychiatry, physical medicine and rehabilitation, drug abuse, family practice, internal medicine, health policy, epidemiology, statistics, physiology, biophysics, and the representatives of the public. In addition, 25 experts from these same fields presented data to the panel and a conference audience of 1200. Presentations and discussions were divided into 3 phases over 2 1/2 days: (1) presentations by investigators working in areas relevant to the consensus questions during a 2-day public session; (2) questions and statements from conference attendees during open discussion periods that were part of the public session; and (3) closed deliberations by the panel during the remainder of the second day and morning of the third. The conference was organized and supported by the Office of Alternative Medicine and the Office of Medical Applications of Research, National Institutes of Health, Bethesda, Md. The literature, produced from January 1970 to October 1997, was searched through MEDLINE, Allied and Alternative Medicine, EMBASE, and MANTIS, as well as through a hand search of 9 journals that were not indexed by the National Library of Medicine. An extensive bibliography of 2302 references was provided to the panel and the conference audience. Expert speakers prepared abstracts of their own conference presentations with relevant citations from the literature. Scientific evidence was given precedence over clinical anecdotal experience. The panel, answering predefined questions, developed their conclusions based on the scientific evidence presented in the open forum and scientific literature. The panel composed a draft statement, which was read in its entirety and circulated to the experts and the audience

  5. Is There a Consensus on Consensus Methodology? Descriptions and Recommendations for Future Consensus Research.

    Science.gov (United States)

    Waggoner, Jane; Carline, Jan D; Durning, Steven J

    2016-05-01

    The authors of this article reviewed the methodology of three common consensus methods: nominal group process, consensus development panels, and the Delphi technique. The authors set out to determine how a majority of researchers are conducting these studies, how they are analyzing results, and subsequently the manner in which they are reporting their findings. The authors conclude with a set of guidelines and suggestions designed to aid researchers who choose to use the consensus methodology in their work.Overall, researchers need to describe their inclusion criteria. In addition to this, on the basis of the current literature the authors found that a panel size of 5 to 11 members was most beneficial across all consensus methods described. Lastly, the authors agreed that the statistical analyses done in consensus method studies should be as rigorous as possible and that the predetermined definition of consensus must be included in the ultimate manuscript. More specific recommendations are given for each of the three consensus methods described in the article.

  6. On consensus through communication without a commonly known protocol

    OpenAIRE

    Tsakas Elias; Voorneveld Mark

    2010-01-01

    The present paper extends the standard model of pairwise communication among Bayesianagents to cases where the structure of the communication protocol is not commonly known.We show that, even under strict conditions on the structure of the protocols and the nature of the transmitted signals, a consensus may never be reached if very little asymmetric information about the protocol is introduced.

  7. CD147 regulates extrinsic apoptosis in spermatocytes by modulating NFκB signaling pathways.

    Science.gov (United States)

    Wang, Chaoqun; Fok, Kin Lam; Cai, Zhiming; Chen, Hao; Chan, Hsiao Chang

    2017-01-10

    CD147 null mutant male mice are infertile with arrested spermatogenesis and increased apoptotic germ cells. Our previous studies have shown that CD147 prevents apoptosis in mouse spermatocytes but not spermatogonia. However, the underlying mechanism remains elusive. In the present study, we aim to determine the CD147-regulated apoptotic pathway in mouse spermatocytes. Our results showed that immunodepletion of CD147 triggered apoptosis through extrinsic apoptotic pathway in mouse testis and spermatocyte cell line (GC-2 cells), accompanied by activation of non-canonical NFκB signaling and suppression of canonical NFκB signaling. Furthermore, CD147 was found to interact with TRAF2, a factor known to regulate NFκB and extrinsic apoptotic signaling, and interfering CD147 led to the decrease of TRAF2. Consistently, depletion of CD147 by CRISPR/Cas9 technique in GC-2 cells down-regulated TRAF2 and resulted in cell death with suppressed canonical NFκB and activated non-canonical NFκB signaling. On the contrary, interfering of CD147 had no effect on NFκB signaling pathways as well as TRAF2 protein level in mouse spermatogonia cell line (GC-1 cells). Taken together, these results suggested that CD147 plays a key role in reducing extrinsic apoptosis in spermatocytes, but not spermatogonia, through modulating NFκB signaling pathway.

  8. Objective consensus from decision trees

    International Nuclear Information System (INIS)

    Putora, Paul Martin; Panje, Cedric M; Papachristofilou, Alexandros; Pra, Alan Dal; Hundsberger, Thomas; Plasswilm, Ludwig

    2014-01-01

    Consensus-based approaches provide an alternative to evidence-based decision making, especially in situations where high-level evidence is limited. Our aim was to demonstrate a novel source of information, objective consensus based on recommendations in decision tree format from multiple sources. Based on nine sample recommendations in decision tree format a representative analysis was performed. The most common (mode) recommendations for each eventuality (each permutation of parameters) were determined. The same procedure was applied to real clinical recommendations for primary radiotherapy for prostate cancer. Data was collected from 16 radiation oncology centres, converted into decision tree format and analyzed in order to determine the objective consensus. Based on information from multiple sources in decision tree format, treatment recommendations can be assessed for every parameter combination. An objective consensus can be determined by means of mode recommendations without compromise or confrontation among the parties. In the clinical example involving prostate cancer therapy, three parameters were used with two cut-off values each (Gleason score, PSA, T-stage) resulting in a total of 27 possible combinations per decision tree. Despite significant variations among the recommendations, a mode recommendation could be found for specific combinations of parameters. Recommendations represented as decision trees can serve as a basis for objective consensus among multiple parties

  9. Objective consensus from decision trees.

    Science.gov (United States)

    Putora, Paul Martin; Panje, Cedric M; Papachristofilou, Alexandros; Dal Pra, Alan; Hundsberger, Thomas; Plasswilm, Ludwig

    2014-12-05

    Consensus-based approaches provide an alternative to evidence-based decision making, especially in situations where high-level evidence is limited. Our aim was to demonstrate a novel source of information, objective consensus based on recommendations in decision tree format from multiple sources. Based on nine sample recommendations in decision tree format a representative analysis was performed. The most common (mode) recommendations for each eventuality (each permutation of parameters) were determined. The same procedure was applied to real clinical recommendations for primary radiotherapy for prostate cancer. Data was collected from 16 radiation oncology centres, converted into decision tree format and analyzed in order to determine the objective consensus. Based on information from multiple sources in decision tree format, treatment recommendations can be assessed for every parameter combination. An objective consensus can be determined by means of mode recommendations without compromise or confrontation among the parties. In the clinical example involving prostate cancer therapy, three parameters were used with two cut-off values each (Gleason score, PSA, T-stage) resulting in a total of 27 possible combinations per decision tree. Despite significant variations among the recommendations, a mode recommendation could be found for specific combinations of parameters. Recommendations represented as decision trees can serve as a basis for objective consensus among multiple parties.

  10. Ocular allergy latin american consensus

    Directory of Open Access Journals (Sweden)

    Myrna Serapião dos Santos

    2011-12-01

    Full Text Available PURPOSE: To establish current definition, classification and staging, and to develop diagnosis and treatment recommendations for ocular allergy, by using Delphi approach. METHODS: Ten Latin American experts on ocular allergy participated in a 4-round Delphi panel approach. Four surveys were constructed and answered by panelists. A two-thirds majority was defined as consensus. Definition, classification, staging and diagnosis and treatment recommendations were the main outcomes. RESULTS: "Ocular allergy" was proposed as the general term to describe ocular allergic diseases. Consensus regarding classification was not reached. Signs and symptoms were considered extremely important for the diagnosis. It was consensus that a staging system should be proposed based on the disease severity. Environmental control, avoidance of allergens and the use of artificial tears were recommended as first line treatment. The secondary treatment should include topical anti-histamines, mast cell stabilizers and multi actions drugs. Topical non-steroidal anti-inflammatory and vasoconstrictors were not recommended. Topical corticosteroids were recommended as third line of treatment for the most severe keratoconjunctivitis. Consensus was not reached regarding the use of systemic corticosteroids or immunosuppressant. Surgical approach and unconventional treatments were not recommended as routine. CONCLUSION: The task of creating guidelines for ocular allergies showed to be very complex. Many controversial topics remain unsolved. A larger consensus including experts from different groups around the world may be needed to further improve the current recommendations for several aspects of ocular allergy.

  11. Dynamical organization towards consensus in the Axelrod model on complex networks

    Science.gov (United States)

    Guerra, Beniamino; Poncela, Julia; Gómez-Gardeñes, Jesús; Latora, Vito; Moreno, Yamir

    2010-05-01

    We analyze the dynamics toward cultural consensus in the Axelrod model on scale-free networks. By looking at the microscopic dynamics of the model, we are able to show how culture traits spread across different cultural features. We compare the diffusion at the level of cultural features to the growth of cultural consensus at the global level, finding important differences between these two processes. In particular, we show that even when most of the cultural features have reached macroscopic consensus, there are still no signals of globalization. Finally, we analyze the topology of consensus clusters both for global culture and at the feature level of representation.

  12. Multi-Optimisation Consensus Clustering

    Science.gov (United States)

    Li, Jian; Swift, Stephen; Liu, Xiaohui

    Ensemble Clustering has been developed to provide an alternative way of obtaining more stable and accurate clustering results. It aims to avoid the biases of individual clustering algorithms. However, it is still a challenge to develop an efficient and robust method for Ensemble Clustering. Based on an existing ensemble clustering method, Consensus Clustering (CC), this paper introduces an advanced Consensus Clustering algorithm called Multi-Optimisation Consensus Clustering (MOCC), which utilises an optimised Agreement Separation criterion and a Multi-Optimisation framework to improve the performance of CC. Fifteen different data sets are used for evaluating the performance of MOCC. The results reveal that MOCC can generate more accurate clustering results than the original CC algorithm.

  13. The Copenhagen Consensus Conference 2016

    DEFF Research Database (Denmark)

    Bangsbo, Jens; Krustrup, Peter; Duda, Joan

    2016-01-01

    that consists of many structured and unstructured forms within school and out-of-school-time contexts, including organised sport, physical education, outdoor recreation, motor skill development programmes, recess, and active transportation such as biking and walking. This consensus statement presents the accord......From 4 to 7 April 2016, 24 researchers from 8 countries and from a variety of academic disciplines gathered in Snekkersten, Denmark, to reach evidence-based consensus about physical activity in children and youth, that is, individuals between 6 and 18 years. Physical activity is an overarching term...... on the effects of physical activity on children’s and youth’s fitness, health, cognitive functioning, engagement, motivation, psychological well-being and social inclusion, as well as presenting educational and physical activity implementation strategies. The consensus was obtained through an iterative process...

  14. Quantitative Non-canonical Amino Acid Tagging (QuaNCAT) Proteomics Identifies Distinct Patterns of Protein Synthesis Rapidly Induced by Hypertrophic Agents in Cardiomyocytes, Revealing New Aspects of Metabolic Remodeling*

    Science.gov (United States)

    Liu, Rui; Kenney, Justin W.; Manousopoulou, Antigoni; Johnston, Harvey E.; Kamei, Makoto; Woelk, Christopher H.; Xie, Jianling; Schwarzer, Michael; Proud, Christopher G.

    2016-01-01

    Cardiomyocytes undergo growth and remodeling in response to specific pathological or physiological conditions. In the former, myocardial growth is a risk factor for cardiac failure and faster protein synthesis is a major factor driving cardiomyocyte growth. Our goal was to quantify the rapid effects of different pro-hypertrophic stimuli on the synthesis of specific proteins in ARVC and to determine whether such effects are caused by alterations on mRNA abundance or the translation of specific mRNAs. Cardiomyocytes have very low rates of protein synthesis, posing a challenging problem in terms of studying changes in the synthesis of specific proteins, which also applies to other nondividing primary cells. To study the rates of accumulation of specific proteins in these cells, we developed an optimized version of the Quantitative Noncanonical Amino acid Tagging LC/MS proteomic method to label and selectively enrich newly synthesized proteins in these primary cells while eliminating the suppressive effects of pre-existing and highly abundant nonisotope-tagged polypeptides. Our data revealed that a classical pathologic (phenylephrine; PE) and the recently identified insulin stimulus that also contributes to the development of pathological cardiac hypertrophy (insulin), both increased the synthesis of proteins involved in, e.g. glycolysis, the Krebs cycle and beta-oxidation, and sarcomeric components. However, insulin increased synthesis of many metabolic enzymes to a greater extent than PE. Using a novel validation method, we confirmed that synthesis of selected candidates is indeed up-regulated by PE and insulin. Synthesis of all proteins studied was up-regulated by signaling through mammalian target of rapamycin complex 1 without changes in their mRNA levels, showing the key importance of translational control in the rapid effects of hypertrophic stimuli. Expression of PKM2 was up-regulated in rat hearts following TAC. This isoform possesses specific regulatory

  15. Functional Divergence in the Role of N-Linked Glycosylation in Smoothened Signaling.

    Directory of Open Access Journals (Sweden)

    Suresh Marada

    2015-08-01

    Full Text Available The G protein-coupled receptor (GPCR Smoothened (Smo is the requisite signal transducer of the evolutionarily conserved Hedgehog (Hh pathway. Although aspects of Smo signaling are conserved from Drosophila to vertebrates, significant differences have evolved. These include changes in its active sub-cellular localization, and the ability of vertebrate Smo to induce distinct G protein-dependent and independent signals in response to ligand. Whereas the canonical Smo signal to Gli transcriptional effectors occurs in a G protein-independent manner, its non-canonical signal employs Gαi. Whether vertebrate Smo can selectively bias its signal between these routes is not yet known. N-linked glycosylation is a post-translational modification that can influence GPCR trafficking, ligand responsiveness and signal output. Smo proteins in Drosophila and vertebrate systems harbor N-linked glycans, but their role in Smo signaling has not been established. Herein, we present a comprehensive analysis of Drosophila and murine Smo glycosylation that supports a functional divergence in the contribution of N-linked glycans to signaling. Of the seven predicted glycan acceptor sites in Drosophila Smo, one is essential. Loss of N-glycosylation at this site disrupted Smo trafficking and attenuated its signaling capability. In stark contrast, we found that all four predicted N-glycosylation sites on murine Smo were dispensable for proper trafficking, agonist binding and canonical signal induction. However, the under-glycosylated protein was compromised in its ability to induce a non-canonical signal through Gαi, providing for the first time evidence that Smo can bias its signal and that a post-translational modification can impact this process. As such, we postulate a profound shift in N-glycan function from affecting Smo ER exit in flies to influencing its signal output in mice.

  16. Building consensus in the community

    International Nuclear Information System (INIS)

    Bishop, J.

    1994-01-01

    The importance for the development of UK renewable energy projects of building consensus in the community is discussed. After outlining the benefits of such an approach, some of the likely concerns and questions from a developer's viewpoint are explored. The key principles of good practice are considered and an example from a wind project examined. (UK)

  17. Non-canonical insights into the evolution of stars. 2

    International Nuclear Information System (INIS)

    Harmanec, P.

    1987-01-01

    Simple arguments are presented to show that the interpretation of the observed semi-periodic light or radial-velocity variations of supergiants in terms of non-radial pulsations of these objects is not as straightforward as often believed. It is demonstrated that the observed semi-period luminosity-colour relation can also be derived under the assumption of rotational modulation or orbital motion in a binary system. Both these alternatives are investigated in some detail. The working hypothesis that at least some of the variable supergiants are in fact contacts or near-contacts of more massive components of unrecognized binary systems of low mass ratio seems to be worthy of a further study. (author). 2 figs., 2 tabs., 25 refs

  18. The Danish Reportive Passive as a Non-Canonical Passive

    DEFF Research Database (Denmark)

    Ørsnes, Bjarne

    2013-01-01

    Danish passive utterance and cognitive verbs allow a construction where the subject of an infinitival complement is raised: Peter siges at være bortrejst (‘Peter is said to be out of town’). Contrary to English, these verbs are not ECM-verbs or subject-to-object raising verbs in the active...

  19. Possibilities of consensus: toward democratic moral discourse.

    Science.gov (United States)

    Jennings, B

    1991-08-01

    The concept of consensus is often appealed to in discussions of biomedical ethics and applied ethics, and it plays an important role in many influential ethical theories. Consensus is an especially influential notion among theorists who reject ethical realism and who frame ethics as a practice of discourse rather than a body of objective knowledge. It is also a practically important notion when moral decision making is subject to bureaucratic organization and oversight, as is increasingly becoming the case in medicine. Two models of consensus are examined and criticized: pluralistic consensus and overlapping consensus. As an alternative to these models, the paper argues that consensus refers to the dialogic aspects of a broader normative conception of democratic moral agency. When the preconditions for that dialogic democratic practice are met, consensus has a justificatory role in ethics; when they are not, consensus, as distinct from mere agreement, does not emerge and can have no moral authority.

  20. Implicit Consensus: Blockchain with Unbounded Throughput

    OpenAIRE

    Ren, Zhijie; Cong, Kelong; Pouwelse, Johan; Erkin, Zekeriya

    2017-01-01

    Recently, the blockchain technique was put in the spotlight as it introduced a systematic approach for multiple parties to reach consensus without needing trust. However, the application of this technique in practice is severely restricted due to its limitations in throughput. In this paper, we propose a novel consensus model, namely the implicit consensus, with a distinctive blockchain-based distributed ledger in which each node holds its individual blockchain. In our system, the consensus i...

  1. Trust, values and false consensus

    OpenAIRE

    Butler, Jeffrey V.; Giuliano, Paola; Guiso, Luigi

    2012-01-01

    Trust beliefs are heterogeneous across individuals and, at the same time, persistent across generations. We investigate one mechanism yielding these dual patterns: false consensus. In the context of a trust game experiment, we show that individuals extrapolate from their own type when forming trust beliefs about the same pool of potential partners – i.e., more (less) trustworthy individuals form more optimistic (pessimistic) trust beliefs - and that this tendency continues to color trust beli...

  2. Endodontic retreatment decisions: no consensus.

    Science.gov (United States)

    Aryanpour, S; Van Nieuwenhuysen, J P; D'Hoore, W

    2000-05-01

    The objectives of the present study were to: (i) evaluate the consensus, if any, amongst dental schools, students and their instructors managing the same clinical cases, all of which involved endodontically treated teeth; and (ii) determine the predominant proposed treatment option. Final year students, endodontic staff members and instructors of 10 European dental schools were surveyed as decision makers. Fourteen different radiographic cases of root canal treated teeth accompanied by a short clinical history were presented to them in a uniform format. For each case the decision makers were requested to: (i) choose only one out of nine treatment alternatives proposed, from 'no treatment' to 'extraction' via 'retreatment' and 'surgery' (ii) assess on two 5-point scales: the difficulty of making a decision, and the technical complexity of the retreatment procedure. The results indicate wide inter- and also intra-school disagreements in the clinical management of root canal treated teeth. Analysis of variance showed that the main source of variation was the 'school effect', explaining 1.8% (NS) to 18.6% (P < 0.0001) of the treatment variations. No other factor explained as much variance. Decision difficulty was moderately correlated to technical complexity (Pearsons' r ranging from 0.19 to 0.35, P < 0.0001). No clear consensus occurred amongst and within dental schools concerning the clinical management of the 14 cases. The lack of consensus amongst schools seems to be due mainly to chance or uncertainty, but can be partly explained by the 'school effect'.

  3. Laparoscopic adhesiolysis: consensus conference guidelines.

    Science.gov (United States)

    Vettoretto, N; Carrara, A; Corradi, A; De Vivo, G; Lazzaro, L; Ricciardelli, L; Agresta, F; Amodio, C; Bergamini, C; Borzellino, G; Catani, M; Cavaliere, D; Cirocchi, R; Gemini, S; Mirabella, A; Palasciano, N; Piazza, D; Piccoli, M; Rigamonti, M; Scatizzi, M; Tamborrino, E; Zago, M

    2012-05-01

    Laparoscopic adhesiolysis has been demonstrated to be technically feasible in small bowel obstruction and carries advantages in terms of post-surgical course. The increasing dissemination of laparoscopic surgery in the emergency setting and the lack of concrete evidence in the literature have called for a consensus conference to draw recommendations for clinical practice. A literature search was used to outline the evidence, and a consensus conference was held between experts in the field. A survey of international experts added expertise to the debate. A public jury of surgeons discussed and validated the statements, and the entire process was reviewed by three external experts. Recommendations concern the diagnostic evaluation, the timing of the operation, the selection of patients, the induction of the pneumoperitoneum, the removal of the cause of obstructions, the criteria for conversion, the use of adhesion-preventing agents, the need for high-technology dissection instruments and behaviour in the case of misdiagnosed hernia or the need for bowel resection. Evidence of this kind of surgery is scanty because of the absence of randomized controlled trials. Nevertheless laparoscopic skills in emergency are widespread. The recommendations given with the consensus process might be a useful tool in the hands of surgeons. © 2012 The Authors. Colorectal Disease © 2012 The Association of Coloproctology of Great Britain and Ireland.

  4. International consensus on safety principles

    International Nuclear Information System (INIS)

    Warnecke, E.

    1993-01-01

    The International Atomic Energy Agency (IAEA) has been regularly requested by its Member States to provide evidence that radioactive waste can be managed safely and to help demonstrate a harmonization of approach at the international level by providing safety documents. In response, IAEA established a special series of safety documents devoted to radioactive waste management. These documents will be elaborated within the Radioactive Waste Safety Standards (RADWASS) programme [1,2] which covers all aspects of radioactive waste management. The RADWASS programme develops a series of international consensus documents on all parts of the safe management of radioactive waste, including disposal. The purpose of the RADWASS programme is to (i) document existing international consensus in the approaches and methodologies for safe radioactive waste management, (ii) create a mechanism to establish consensus where it does not exist and (iii) provide Member States with a comprehensive series of internationally agreed upon documents to complement national standards and criteria. This paper describes the RADWASS programme, and covers the structure, implementation plans and status of documents under preparation

  5. Attitude Importance and the False Consensus Effect.

    Science.gov (United States)

    Fabrigar, Leandre R.; Krosnick, Jon A.

    1995-01-01

    Explores the possibility that importance may regulate the magnitude of the false consensus effect. Analysis revealed a strong false consensus effect but no reliable relation between its magnitude and attitude importance. Results contradict assumptions that the false consensus effect arises from attitudes that directly or indirectly influence…

  6. CUX1/Wnt signaling regulates Epithelial Mesenchymal Transition in EBV infected epithelial cells

    International Nuclear Information System (INIS)

    Malizia, Andrea P.; Lacey, Noreen; Walls, Dermot; Egan, Jim J.; Doran, Peter P.

    2009-01-01

    Idiopathic pulmonary fibrosis (IPF) is a refractory and lethal interstitial lung disease characterized by alveolar epithelial cells apoptosis, fibroblast proliferation and extra-cellular matrix protein deposition. EBV, localised to alveolar epithelial cells of pulmonary fibrosis patients is associated with a poor prognosis. A strategy based on microarray-differential gene expression analysis to identify molecular drivers of EBV-associated lung fibrosis was utilized. Alveolar epithelial cells were infected with EBV to identify genes whose expression was altered following TGFβ1-mediated lytic phase. EBV lytic reactivation by TGFβ1 drives a selective alteration in CUX1 variant (a) (NCBI accession number NM 1 81552) expression, inducing activation of non-canonical Wnt pathway mediators, implicating it in Epithelial Mesenchymal Transition (EMT), the molecular event underpinning scar production in tissue fibrosis. The role of EBV in EMT can be attenuated by antiviral strategies and inhibition of Wnt signaling by using All-Trans Retinoic Acids (ATRA). Activation of non-canonical Wnt signaling pathway by EBV in epithelial cells suggests a novel mechanism of EMT via CUX1 signaling. These data present a framework for further description of the link between infectious agents and fibrosis, a significant disease burden.

  7. CUX1/Wnt signaling regulates Epithelial Mesenchymal Transition in EBV infected epithelial cells

    Energy Technology Data Exchange (ETDEWEB)

    Malizia, Andrea P.; Lacey, Noreen [Clinical Research Centre, School of Medicine and Medical Science, University College Dublin. 21, Nelson Street. Dublin, 7. Ireland (Ireland); Walls, Dermot [School of Biotechnology, Dublin City University. Dublin, 9. Ireland (Ireland); Egan, Jim J. [Advanced Lung Disease and Lung Transplant Program, Mater Misericordiae University Hospital. 44, Eccles Street. Dublin, 7. Ireland (Ireland); Doran, Peter P., E-mail: peter.doran@ucd.ie [Clinical Research Centre, School of Medicine and Medical Science, University College Dublin. 21, Nelson Street. Dublin, 7. Ireland (Ireland)

    2009-07-01

    Idiopathic pulmonary fibrosis (IPF) is a refractory and lethal interstitial lung disease characterized by alveolar epithelial cells apoptosis, fibroblast proliferation and extra-cellular matrix protein deposition. EBV, localised to alveolar epithelial cells of pulmonary fibrosis patients is associated with a poor prognosis. A strategy based on microarray-differential gene expression analysis to identify molecular drivers of EBV-associated lung fibrosis was utilized. Alveolar epithelial cells were infected with EBV to identify genes whose expression was altered following TGF{beta}1-mediated lytic phase. EBV lytic reactivation by TGF{beta}1 drives a selective alteration in CUX1 variant (a) (NCBI accession number NM{sub 1}81552) expression, inducing activation of non-canonical Wnt pathway mediators, implicating it in Epithelial Mesenchymal Transition (EMT), the molecular event underpinning scar production in tissue fibrosis. The role of EBV in EMT can be attenuated by antiviral strategies and inhibition of Wnt signaling by using All-Trans Retinoic Acids (ATRA). Activation of non-canonical Wnt signaling pathway by EBV in epithelial cells suggests a novel mechanism of EMT via CUX1 signaling. These data present a framework for further description of the link between infectious agents and fibrosis, a significant disease burden.

  8. Kinome profiling of Arabidopsis using arrays of kinase consensus substrates

    Directory of Open Access Journals (Sweden)

    Pieterse Corné MJ

    2007-02-01

    Full Text Available Abstract Background Kinome profiling aims at the parallel analysis of kinase activities in a cell. Novel developed arrays containing consensus substrates for kinases are used to assess those kinase activities. The arrays described in this paper were already used to determine kinase activities in mammalian systems, but since substrates from many organisms are present we decided to test these arrays for the determination of kinase activities in the model plant species Arabidopsis thaliana. Results Kinome profiling using Arabidopsis cell extracts resulted in the labelling of many consensus peptides by kinases from the plant, indicating the usefulness of this kinome profiling tool for plants. Method development showed that fresh and frozen plant material could be used to make cell lysates containing active kinases. Dilution of the plant extract increased the signal to noise ratio and non-radioactive ATP enhances full development of spot intensities. Upon infection of Arabidopsis with an avirulent strain of the bacterial pathogen Pseudomonas syringae pv. tomato, we could detect differential kinase activities by measuring phosphorylation of consensus peptides. Conclusion We show that kinome profiling on arrays with consensus substrates can be used to monitor kinase activities in plants. In a case study we show that upon infection with avirulent P. syringae differential kinase activities can be found. The PepChip can for example be used to purify (unknown kinases that play a role in P. syringae infection. This paper shows that kinome profiling using arrays of consensus peptides is a valuable new tool to study signal-transduction in plants. It complements the available methods for genomics and proteomics research.

  9. Phenylalanine ammonia lyase from Arabidopsis thaliana (AtPAL2): A potent MIO-enzyme for the synthesis of non-canonical aromatic alpha-amino acids: Part I: Comparative characterization to the enzymes from Petroselinum crispum (PcPAL1) and Rhodosporidium toruloides (RtPAL).

    Science.gov (United States)

    Dreßen, Alana; Hilberath, Thomas; Mackfeld, Ursula; Billmeier, Arne; Rudat, Jens; Pohl, Martina

    2017-09-20

    Phenylalanine ammonia lyase (PAL) from Arabidopsis thaliana (AtPAL2) was comparatively characterized to the well-studied enzyme from parsley (PcPAL1) and Rhodosporidium toruloides (RtPAL) with respect to kinetic parameters for the deamination and the amination reaction, pH- and temperature optima and the substrate range of the amination reaction. Whereas both plant enzymes are specific for phenylalanine, the bifunctional enzyme from Rhodosporidium toruloides shows K M -values for L-Phe and L-Tyr in the same order of magnitude and, compared to both plant enzymes, a 10-15-fold higher activity. At 30°C all enzymes were sufficiently stable with half-lives of 3.4days (PcPAL1), 4.6days (AtPAL2) and 9.7days (RtPAL/TAL). Very good results for the amination of various trans-cinnamic acid derivatives were obtained using E. coli cells as whole cell biocatalysts in ammonium carbonate buffer. Investigation of the substrate ranges gave interesting results for the newly tested enzymes from A. thaliana and R. toruloides. Only the latter accepts besides 4-hydroxy-CA also 3-methoxy-4-hydroxy-CA as a substrate, which is an interesting intermediate for the formation of pharmaceutically relevant L-Dopa. AtPAL2 is a very good catalyst for the formation of (S)-3-F-Phe, (S)-4-F-Phe and (S)-2-Cl-Phe. Such non-canonical amino acids are valuable building blocks for the formation of various drug molecules. Copyright © 2017 Elsevier B.V. All rights reserved.

  10. Flanking signal and mature peptide residues influence signal peptide cleavage

    Directory of Open Access Journals (Sweden)

    Ranganathan Shoba

    2008-12-01

    Full Text Available Abstract Background Signal peptides (SPs mediate the targeting of secretory precursor proteins to the correct subcellular compartments in prokaryotes and eukaryotes. Identifying these transient peptides is crucial to the medical, food and beverage and biotechnology industries yet our understanding of these peptides remains limited. This paper examines the most common type of signal peptides cleavable by the endoprotease signal peptidase I (SPase I, and the residues flanking the cleavage sites of three groups of signal peptide sequences, namely (i eukaryotes (Euk (ii Gram-positive (Gram+ bacteria, and (iii Gram-negative (Gram- bacteria. Results In this study, 2352 secretory peptide sequences from a variety of organisms with amino-terminal SPs are extracted from the manually curated SPdb database for analysis based on physicochemical properties such as pI, aliphatic index, GRAVY score, hydrophobicity, net charge and position-specific residue preferences. Our findings show that the three groups share several similarities in general, but they display distinctive features upon examination in terms of their amino acid compositions and frequencies, and various physico-chemical properties. Thus, analysis or prediction of their sequences should be separated and treated as distinct groups. Conclusion We conclude that the peptide segment recognized by SPase I extends to the start of the mature protein to a limited extent, upon our survey of the amino acid residues surrounding the cleavage processing site. These flanking residues possibly influence the cleavage processing and contribute to non-canonical cleavage sites. Our findings are applicable in defining more accurate prediction tools for recognition and identification of cleavage site of SPs.

  11. Loss of FTO antagonises Wnt signaling and leads to developmental defects associated with ciliopathies.

    Directory of Open Access Journals (Sweden)

    Daniel P S Osborn

    Full Text Available Common intronic variants in the Human fat mass and obesity-associated gene (FTO are found to be associated with an increased risk of obesity. Overexpression of FTO correlates with increased food intake and obesity, whilst loss-of-function results in lethality and severe developmental defects. Despite intense scientific discussions around the role of FTO in energy metabolism, the function of FTO during development remains undefined. Here, we show that loss of Fto leads to developmental defects such as growth retardation, craniofacial dysmorphism and aberrant neural crest cells migration in Zebrafish. We find that the important developmental pathway, Wnt, is compromised in the absence of FTO, both in vivo (zebrafish and in vitro (Fto(-/- MEFs and HEK293T. Canonical Wnt signalling is down regulated by abrogated β-Catenin translocation to the nucleus whilst non-canonical Wnt/Ca(2+ pathway is activated via its key signal mediators CaMKII and PKCδ. Moreover, we demonstrate that loss of Fto results in short, absent or disorganised cilia leading to situs inversus, renal cystogenesis, neural crest cell defects and microcephaly in Zebrafish. Congruently, Fto knockout mice display aberrant tissue specific cilia. These data identify FTO as a protein-regulator of the balanced activation between canonical and non-canonical branches of the Wnt pathway. Furthermore, we present the first evidence that FTO plays a role in development and cilia formation/function.

  12. Validation of consensus panel diagnosis in dementia.

    Science.gov (United States)

    Gabel, Matthew J; Foster, Norman L; Heidebrink, Judith L; Higdon, Roger; Aizenstein, Howard J; Arnold, Steven E; Barbas, Nancy R; Boeve, Bradley F; Burke, James R; Clark, Christopher M; Dekosky, Steven T; Farlow, Martin R; Jagust, William J; Kawas, Claudia H; Koeppe, Robert A; Leverenz, James B; Lipton, Anne M; Peskind, Elaine R; Turner, R Scott; Womack, Kyle B; Zamrini, Edward Y

    2010-12-01

    The clinical diagnosis of dementing diseases largely depends on the subjective interpretation of patient symptoms. Consensus panels are frequently used in research to determine diagnoses when definitive pathologic findings are unavailable. Nevertheless, research on group decision making indicates that many factors can adversely affect panel performance. To determine conditions that improve consensus panel diagnosis. Comparison of neuropathologic diagnoses with individual and consensus panel diagnoses based on clinical scenarios only, fludeoxyglucose F 18 positron emission tomography images only, and scenarios plus images. Expert and trainee individual and consensus panel deliberations using a modified Delphi method in a pilot research study of the diagnostic utility of fludeoxyglucose F 18 positron emission tomography. Forty-five patients with pathologically confirmed Alzheimer disease or frontotemporal dementia. Statistical measures of diagnostic accuracy, agreement, and confidence for individual raters and panelists before and after consensus deliberations. The consensus protocol using trainees and experts surpassed the accuracy of individual expert diagnoses when clinical information elicited diverse judgments. In these situations, consensus was 3.5 times more likely to produce positive rather than negative changes in the accuracy and diagnostic certainty of individual panelists. A rule that forced group consensus was at least as accurate as majority and unanimity rules. Using a modified Delphi protocol to arrive at a consensus diagnosis is a reasonable substitute for pathologic information. This protocol improves diagnostic accuracy and certainty when panelist judgments differ and is easily adapted to other research and clinical settings while avoiding the potential pitfalls of group decision making.

  13. Subclinical hypothyroidism: Controversies to consensus

    Directory of Open Access Journals (Sweden)

    Syed Abbas Raza

    2013-01-01

    Full Text Available Diagnoses of subclinicaal hypothyroidism (SCH is biochemically made, when serum thyroid stimulating hormone (TSH levels is elevated while free thyroid hormone levels are within normal reference range. SCH is diagnosed after excluding all other causes of elevated TSH levels. Symptoms of SCH may vary from being asymptomatic to having mild nonspecific symptoms. The risk of progression to overt hypothyroidism is related to number of factors including initial serum TSH concentration, presence of auto antibodies, family history and presence goiter. Various screening recommendations for thyroid function assessment are in practice. There are still controversies surrounding SCH and associated risk of various cardiovascular diseases (CVDs, pregnancy outcomes, neuropsychiatric issues, metabolic syndrome, and dyslipidemia. Consensus will require more large randomized clinical studies involving various age groups and medical condition, especially in developing countries. All these efforts will definitely improve our understanding of disease and ultimately patient outcomes.

  14. Learning consensus in adversarial environments

    Science.gov (United States)

    Vamvoudakis, Kyriakos G.; García Carrillo, Luis R.; Hespanha, João. P.

    2013-05-01

    This work presents a game theory-based consensus problem for leaderless multi-agent systems in the presence of adversarial inputs that are introducing disturbance to the dynamics. Given the presence of enemy components and the possibility of malicious cyber attacks compromising the security of networked teams, a position agreement must be reached by the networked mobile team based on environmental changes. The problem is addressed under a distributed decision making framework that is robust to possible cyber attacks, which has an advantage over centralized decision making in the sense that a decision maker is not required to access information from all the other decision makers. The proposed framework derives three tuning laws for every agent; one associated with the cost, one associated with the controller, and one with the adversarial input.

  15. Hilar cholangiocarcinoma: expert consensus statement.

    Science.gov (United States)

    Mansour, John C; Aloia, Thomas A; Crane, Christopher H; Heimbach, Julie K; Nagino, Masato; Vauthey, Jean-Nicolas

    2015-08-01

    An American Hepato-Pancreato-Biliary Association (AHPBA)-sponsored consensus meeting of expert panellists met on 15 January 2014 to review current evidence on the management of hilar cholangiocarcinoma in order to establish practice guidelines and to agree consensus statements. It was established that the treatment of patients with hilar cholangiocarcinoma requires a coordinated, multidisciplinary approach to optimize the chances for both durable survival and effective palliation. An adequate diagnostic and staging work-up includes high-quality cross-sectional imaging; however, pathologic confirmation is not required prior to resection or initiation of a liver transplant trimodal treatment protocol. The ideal treatment for suitable patients with resectable hilar malignancy is resection of the intra- and extrahepatic bile ducts, as well as resection of the involved ipsilateral liver. Preoperative biliary drainage is best achieved with percutaneous transhepatic approaches and may be indicated for patients with cholangitis, malnutrition or hepatic insufficiency. Portal vein embolization is a safe and effective strategy for increasing the future liver remnant (FLR) and is particularly useful for patients with an FLR of hilar cholangiocarcinoma should be evaluated for a standard trimodal protocol incorporating external beam and endoluminal radiation therapy, systemic chemotherapy and liver transplantation. Post-resection chemoradiation should be offered to patients who show high-risk features on surgical pathology. Chemoradiation is also recommended for patients with locally advanced, unresectable hilar cancers. For patients with locally recurrent or metastatic hilar cholangiocarcinoma, first-line chemotherapy with gemcitabine and cisplatin is recommended based on multiple Phase II trials and a large randomized controlled trial including a heterogeneous population of patients with biliary cancers. © 2015 International Hepato-Pancreato-Biliary Association.

  16. International Consensus on drug allergy.

    Science.gov (United States)

    Demoly, P; Adkinson, N F; Brockow, K; Castells, M; Chiriac, A M; Greenberger, P A; Khan, D A; Lang, D M; Park, H-S; Pichler, W; Sanchez-Borges, M; Shiohara, T; Thong, B Y- H

    2014-04-01

    When drug reactions resembling allergy occur, they are called drug hypersensitivity reactions (DHRs) before showing the evidence of either drug-specific antibodies or T cells. DHRs may be allergic or nonallergic in nature, with drug allergies being immunologically mediated DHRs. These reactions are typically unpredictable. They can be life-threatening, may require or prolong hospitalization, and may necessitate changes in subsequent therapy. Both underdiagnosis (due to under-reporting) and overdiagnosis (due to an overuse of the term ‘allergy’) are common. A definitive diagnosis of such reactions is required in order to institute adequate treatment options and proper preventive measures. Misclassification based solely on the DHR history without further testing may affect treatment options, result in adverse consequences, and lead to the use of more-expensive or less-effective drugs, in contrast to patients who had undergone a complete drug allergy workup. Several guidelines and/or consensus documents on general or specific drug class-induced DHRs are available to support the medical decision process. The use of standardized systematic approaches for the diagnosis and management of DHRs carries the potential to improve outcomes and should thus be disseminated and implemented. Consequently, the International Collaboration in Asthma, Allergy and Immunology (iCAALL), formed by the European Academy of Allergy and Clinical Immunology (EAACI), the American Academy of Allergy, Asthma and Immunology (AAAAI), the American College of Allergy, Asthma and Immunology (ACAAI), and the World Allergy Organization (WAO), has decided to issue an International CONsensus (ICON) on drug allergy. The purpose of this document is to highlight the key messages that are common to many of the existing guidelines, while critically reviewing and commenting on any differences and deficiencies of evidence, thus providing a comprehensive reference document for the diagnosis and management of

  17. Indispensable role of Notch ligand-dependent signaling in the proliferation and stem cell niche maintenance of APC-deficient intestinal tumors

    International Nuclear Information System (INIS)

    Nakata, Toru; Shimizu, Hiromichi; Nagata, Sayaka; Ito, Go; Fujii, Satoru; Suzuki, Kohei; Kawamoto, Ami; Ishibashi, Fumiaki; Kuno, Reiko; Anzai, Sho; Murano, Tatsuro; Mizutani, Tomohiro; Oshima, Shigeru; Tsuchiya, Kiichiro; Nakamura, Tetsuya; Hozumi, Katsuto; Watanabe, Mamoru; Okamoto, Ryuichi

    2017-01-01

    Ligand-dependent activation of Notch signaling is required to maintain the stem-cell niche of normal intestinal epithelium. However, the precise role of Notch signaling in the maintenance of the intestinal tumor stem cell niche and the importance of the RBPJ-independent non-canonical pathway in intestinal tumors remains unknown. Here we show that Notch signaling was activated in LGR5 +ve cells of APC-deficient mice intestinal tumors. Accordingly, Notch ligands, including Jag1, Dll1, and Dll4, were expressed in these tumors. In vitro studies using tumor-derived organoids confirmed the intrinsic Notch activity-dependent growth of tumor cells. Surprisingly, the targeted deletion of Jag1 but not RBPJ in LGR5 +ve tumor-initiating cells resulted in the silencing of Hes1 expression, disruption of the tumor stem cell niche, and dramatic reduction in the proliferation activity of APC-deficient intestinal tumors in vivo. Thus, our results highlight the importance of ligand-dependent non-canonical Notch signaling in the proliferation and maintenance of the tumor stem cell niche in APC-deficient intestinal adenomas. - Highlights: • Notch signaling is activated in LGR5 +ve cells of APC-deficient intestinal tumors. • Lack of Jag1 but not RBPJ disrupts stem cell niche formation in those tumors. • Lack of Jag1 reduces the proliferation activity of APC-deficient intestinal tumors.

  18. Delay-Induced Consensus and Quasi-Consensus in Multi-Agent Dynamical Systems

    NARCIS (Netherlands)

    Yu, Wenwu; Chen, Guanrong; Cao, Ming; Ren, Wei

    2013-01-01

    This paper studies consensus and quasi-consensus in multi-agent dynamical systems. A linear consensus protocol in the second-order dynamics is designed where both the current and delayed position information is utilized. Time delay, in a common perspective, can induce periodic oscillations or even

  19. Construction of barley consensus map showing chromosomal ...

    African Journals Online (AJOL)

    In the past, it has been difficult to accurately determine the location of many types of barley molecular markers due to the lack of commonality between international barley linkage maps. In this study, a consensus map of barley was constructed from five different maps (OWB, VxHs, KxM, barley consensus 2 and barley ...

  20. Bruxism defined and graded: an international consensus

    NARCIS (Netherlands)

    Lobbezoo, F.; Ahlberg, J.; Glaros, A.G.; Kato, T.; Koyano, K.; Lavigne, G.J.; de Leeuw, R.; Manfredini, D.; Svensson, P.; Winocur, E.

    2013-01-01

    To date, there is no consensus about the definition and diagnostic grading of bruxism. A written consensus discussion was held among an international group of bruxism experts as to formulate a definition of bruxism and to suggest a grading system for its operationalisation. The expert group defined

  1. Limited consensus around ARM information protection practices ...

    African Journals Online (AJOL)

    An existing enterprise IP SoP was adapted to ARM through literature analysis and produced a draft ARM SoP. The draft ARM SoP was applied in a rote fashion to a small sample of government-operated archives to identify likely areas of consensus and lack of consensus surrounding the various elements of the SoP.

  2. Veto-Consensus Multiple Kernel Learning

    NARCIS (Netherlands)

    Zhou, Y.; Hu, N.; Spanos, C.J.

    2016-01-01

    We propose Veto-Consensus Multiple Kernel Learning (VCMKL), a novel way of combining multiple kernels such that one class of samples is described by the logical intersection (consensus) of base kernelized decision rules, whereas the other classes by the union (veto) of their complements. The

  3. Automated consensus contour building for prostate MRI.

    Science.gov (United States)

    Khalvati, Farzad

    2014-01-01

    Inter-observer variability is the lack of agreement among clinicians in contouring a given organ or tumour in a medical image. The variability in medical image contouring is a source of uncertainty in radiation treatment planning. Consensus contour of a given case, which was proposed to reduce the variability, is generated by combining the manually generated contours of several clinicians. However, having access to several clinicians (e.g., radiation oncologists) to generate a consensus contour for one patient is costly. This paper presents an algorithm that automatically generates a consensus contour for a given case using the atlases of different clinicians. The algorithm was applied to prostate MR images of 15 patients manually contoured by 5 clinicians. The automatic consensus contours were compared to manual consensus contours where a median Dice similarity coefficient (DSC) of 88% was achieved.

  4. Consensus statement on genetic research in dementia

    DEFF Research Database (Denmark)

    Rikkert, M.G. Olde; der, V van; Burns, A.

    2008-01-01

    In this article, the authors describe how the European Dementia Consensus Network developed a consensus on research ethics in dementia, taking into account the questions posed by the era of genetic research and its new research methods. The consensus process started with a Delphi procedure...... to analyze relevant stakeholders' positions by describing their statements on the possibilities and limitations of research into genetic determinants of Alzheimer disease and to describe and analyze the moral desirability of genetic research on Alzheimer disease. The conclusions drawn from the Delphi...... procedure fuelled the development of the consensus statement, which is presented in this paper. The consensus statement aims to stimulate ethically acceptable research in the field of dementia and the protection of vulnerable elderly patients with dementia from application of inadequate research methods...

  5. [Spanish consensus on infantile haemangioma].

    Science.gov (United States)

    Baselga Torres, Eulalia; Bernabéu Wittel, José; van Esso Arbolave, Diego L; Febrer Bosch, María Isabel; Carrasco Sanz, Ángel; de Lucas Laguna, Raúl; Del Pozo Losada, Jesús; Hernández Martín, Ángela; Jiménez Montañés, Lorenzo; López Gutiérrez, Juan Carlos; Martín-Santiago, Ana; Redondo Bellón, Pedro; Ruíz-Canela Cáceres, Juan; Torrelo Fernández, Antonio; Vera Casaño, Ángel; Vicente Villa, María Asunción

    2016-11-01

    Infantile haemangiomas are benign tumours produced by the proliferation of endothelial cells of blood vessels, with a high incidence in children under the age of one year (4-10%). It is estimated that 12% of them require treatment. This treatment must be administered according to clinical practice guidelines, expert experience, patient characteristics and parent preferences. The consensus process was performed by using scientific evidence on the diagnosis and treatment of infantile haemangiomas, culled from a systematic review of the literature, together with specialist expert opinions. The recommendations issued were validated by the specialists, who also provided their level of agreement. This document contains recommendations on the classification, associations, complications, diagnosis, treatment, and follow-up of patients with infantile haemangioma. It also includes action algorithms, and addresses multidisciplinary management and referral criteria between the different specialities involved in the clinical management of this type of patient. The recommendations and the diagnostic and therapeutic algorithms of infantile haemangiomas contained in this document are a useful tool for the proper management of these patients. Copyright © 2015 Asociación Española de Pediatría. Publicado por Elsevier España, S.L.U. All rights reserved.

  6. Consensus Paper: Cerebellum and Emotion.

    Science.gov (United States)

    Adamaszek, M; D'Agata, F; Ferrucci, R; Habas, C; Keulen, S; Kirkby, K C; Leggio, M; Mariën, P; Molinari, M; Moulton, E; Orsi, L; Van Overwalle, F; Papadelis, C; Priori, A; Sacchetti, B; Schutter, D J; Styliadis, C; Verhoeven, J

    2017-04-01

    Over the past three decades, insights into the role of the cerebellum in emotional processing have substantially increased. Indeed, methodological refinements in cerebellar lesion studies and major technological advancements in the field of neuroscience are in particular responsible to an exponential growth of knowledge on the topic. It is timely to review the available data and to critically evaluate the current status of the role of the cerebellum in emotion and related domains. The main aim of this article is to present an overview of current facts and ongoing debates relating to clinical, neuroimaging, and neurophysiological findings on the role of the cerebellum in key aspects of emotion. Experts in the field of cerebellar research discuss the range of cerebellar contributions to emotion in nine topics. Topics include the role of the cerebellum in perception and recognition, forwarding and encoding of emotional information, and the experience and regulation of emotional states in relation to motor, cognitive, and social behaviors. In addition, perspectives including cerebellar involvement in emotional learning, pain, emotional aspects of speech, and neuropsychiatric aspects of the cerebellum in mood disorders are briefly discussed. Results of this consensus paper illustrate how theory and empirical research have converged to produce a composite picture of brain topography, physiology, and function that establishes the role of the cerebellum in many aspects of emotional processing.

  7. Database proton NMR chemical shifts for RNA signal assignment and validation

    Energy Technology Data Exchange (ETDEWEB)

    Barton, Shawn; Heng Xiao [University of Maryland, Baltimore County, Howard Hughes Medical Institute (United States); Johnson, Bruce A., E-mail: bruce@onemoonscientific.com [University of Maryland, Baltimore County, Department of Chemistry and Biochemistry (United States); Summers, Michael F., E-mail: summers@hhmi.umbc.edu [University of Maryland, Baltimore County, Howard Hughes Medical Institute (United States)

    2013-01-15

    The Biological Magnetic Resonance Data Bank contains NMR chemical shift depositions for 132 RNAs and RNA-containing complexes. We have analyzed the {sup 1}H NMR chemical shifts reported for non-exchangeable protons of residues that reside within A-form helical regions of these RNAs. The analysis focused on the central base pair within a stretch of three adjacent base pairs (BP triplets), and included both Watson-Crick (WC; G:C, A:U) and G:U wobble pairs. Chemical shift values were included for all 4{sup 3} possible WC-BP triplets, as well as 137 additional triplets that contain one or more G:U wobbles. Sequence-dependent chemical shift correlations were identified, including correlations involving terminating base pairs within the triplets and canonical and non-canonical structures adjacent to the BP triplets (i.e. bulges, loops, WC and non-WC BPs), despite the fact that the NMR data were obtained under different conditions of pH, buffer, ionic strength, and temperature. A computer program (RNAShifts) was developed that enables convenient comparison of RNA {sup 1}H NMR assignments with database predictions, which should facilitate future signal assignment/validation efforts and enable rapid identification of non-canonical RNA structures and RNA-ligand/protein interaction sites.

  8. International Veterinary Epilepsy Task Force consensus proposal

    DEFF Research Database (Denmark)

    Bhatti, Sofie F M; De Risio, Luisa; Muñana, Karen

    2015-01-01

    with the initial drug is unsatisfactory, and 4) when treatment changes should be considered. In this consensus proposal, an overview is given on the aim of AED treatment, when to start long-term treatment in canine epilepsy and which veterinary AEDs are currently in use for dogs. The consensus proposal for drug...... treatment protocols, 1) is based on current published evidence-based literature, 2) considers the current legal framework of the cascade regulation for the prescription of veterinary drugs in Europe, and 3) reflects the authors' experience. With this paper it is aimed to provide a consensus...

  9. testing a consensus conference method by discussing

    African Journals Online (AJOL)

    hi-tech

    2000-10-10

    Oct 10, 2000 ... Objectives: To test the recommended consensus conference methods in Tanzania by discussing the management ... “wrong”, based on recommendations advocated in western ..... future scenarios sponsored the conference.

  10. OGC Consensus: How Successful Standards Are Made

    Directory of Open Access Journals (Sweden)

    Carl Reed

    2015-09-01

    Full Text Available This paper describes the history, background, and current status of the Open Geospatial Consortium (OGC standards development consensus process. The roots of the formation of the OGC lie in the early 1990s when a very strong market requirement for exchanging GIS data content was clearly stated. At that time, each GIS vendor had their own formats for publishing and/or exchanging their GIS data. There was no mechanism or organization that provided a forum for the GIS vendors and GIS data users to collaborate and agree on how to share GIS data. That requirement, along with the vision of a few individuals, led to the formation of the OGC. This paper describes the early development of the consensus process in the OGC, how this process has evolved over time, why consensus is so important for defining open standards that are implemented in the marketplace, and the future of the OGC consensus process.

  11. Overlapping community detection using weighted consensus ...

    Indian Academy of Sciences (India)

    2016-09-21

    Sep 21, 2016 ... Complex networks; overlapping community; consensus clustering. PACS Nos 89.75 ... networks, a person may be in several social groups like family, friends ..... the social interactions between individuals in a karate club in an.

  12. The emergence of consensus: a primer

    Science.gov (United States)

    Baronchelli, Andrea

    2018-02-01

    The origin of population-scale coordination has puzzled philosophers and scientists for centuries. Recently, game theory, evolutionary approaches and complex systems science have provided quantitative insights on the mechanisms of social consensus. However, the literature is vast and widely scattered across fields, making it hard for the single researcher to navigate it. This short review aims to provide a compact overview of the main dimensions over which the debate has unfolded and to discuss some representative examples. It focuses on those situations in which consensus emerges `spontaneously' in the absence of centralized institutions and covers topics that include the macroscopic consequences of the different microscopic rules of behavioural contagion, the role of social networks and the mechanisms that prevent the formation of a consensus or alter it after it has emerged. Special attention is devoted to the recent wave of experiments on the emergence of consensus in social systems.

  13. Statistical Inference for Cultural Consensus Theory

    Science.gov (United States)

    2014-02-24

    Social Network Conference XXXII , Redondo Beach, California, March 2012. Agrawal, K. (Presenter), and Batchelder, W. H. Cultural Consensus Theory...Aggregating Complete Signed Graphs Under a Balance Constraint -- Part 2. International Sunbelt Social Network Conference XXXII , Redondo Beach

  14. Blockchain Consensus Protocols in the Wild

    OpenAIRE

    Cachin, Christian; Vukolić, Marko

    2017-01-01

    A blockchain is a distributed ledger for recording transactions, maintained by many nodes without central authority through a distributed cryptographic protocol. All nodes validate the information to be appended to the blockchain, and a consensus protocol ensures that the nodes agree on a unique order in which entries are appended. Consensus protocols for tolerating Byzantine faults have received renewed attention because they also address blockchain systems. This work discusses the process o...

  15. Judicial Deference Allows European Consensus to Emerge

    DEFF Research Database (Denmark)

    Dothan, Shai

    2018-01-01

    jurisdiction. But the ECHR sometimes defers to countries, even if their policies fall short of the standard accepted by most of the countries in Europe. This deference is accomplished by using the so-called "margin of appreciation" doctrine. Naturally, emerging consensus and margin of appreciation are often......, the paper demonstrates that a correct application of the margin of appreciation doctrine actually helps emerging consensus reach optimal results, by giving countries an incentive to make their policies independently....

  16. Crosstalk between autophagy and inflammatory signalling pathways: balancing defence and homeostasis.

    Science.gov (United States)

    Cadwell, Ken

    2016-11-01

    Autophagy has broad functions in immunity, ranging from cell-autonomous defence to coordination of complex multicellular immune responses. The successful resolution of infection and avoidance of autoimmunity necessitates efficient and timely communication between autophagy and pathways that sense the immune environment. The recent literature indicates that a variety of immune mediators induce or repress autophagy. It is also becoming increasingly clear that immune signalling cascades are subject to regulation by autophagy, and that a return to homeostasis following a robust immune response is critically dependent on this pathway. Importantly, examples of non-canonical forms of autophagy in mediating immunity are pervasive. In this article, the progress in elucidating mechanisms of crosstalk between autophagy and inflammatory signalling cascades is reviewed. Improved mechanistic understanding of the autophagy machinery offers hope for treating infectious and inflammatory diseases.

  17. Skeletal (stromal) stem cells: an update on intracellular signaling pathways controlling osteoblast differentiation.

    Science.gov (United States)

    Abdallah, Basem M; Jafari, Abbas; Zaher, Walid; Qiu, Weimin; Kassem, Moustapha

    2015-01-01

    Skeletal (marrow stromal) stem cells (BMSCs) are a group of multipotent cells that reside in the bone marrow stroma and can differentiate into osteoblasts, chondrocytes and adipocytes. Studying signaling pathways that regulate BMSC differentiation into osteoblastic cells is a strategy for identifying druggable targets for enhancing bone formation. This review will discuss the functions and the molecular mechanisms of action on osteoblast differentiation and bone formation; of a number of recently identified regulatory molecules: the non-canonical Notch signaling molecule Delta-like 1/preadipocyte factor 1 (Dlk1/Pref-1), the Wnt co-receptor Lrp5 and intracellular kinases. This article is part of a Special Issue entitled: Stem Cells and Bone. Copyright © 2014 Elsevier Inc. All rights reserved.

  18. Pragmatism and Political Pluralism - Consensus and Pluralism

    Directory of Open Access Journals (Sweden)

    Michele Marsonet

    2015-07-01

    In our day the German philosopher Jürgen Habermas has in a way revived these Peircean insights, putting forward an influential theory to the effect that consensus indeed plays a key role in human praxis, so that the primary task of philosophy is to foster it by eliminating the disagreement which we constantly have to face in the course of our daily life. In his “communicative theory of consensus,” furthermore, he claims that human communication rests on an implicit commitment to a sort of “ideal speech situation” which is the normative foundation of agreement in linguistic matters. Consequently, the quest for consensus is a constitutive feature of our nature of (rational human beings: rationality and consensus are tied together. A very strong consequence derives from Habermas’ premises: were we to abandon the search for consensus we would lose rationality, too, and this makes us understand that he views the pursuit of consensus as a regulative principle (rather than as a merely practical objective. Rescher opposes both Peirce’s eschatological view and Habermas’ regulative and idealized one.

  19. The Role of Hedgehog Signaling in Tumor Induced Bone Disease

    Directory of Open Access Journals (Sweden)

    Shellese A. Cannonier

    2015-08-01

    Full Text Available Despite significant progress in cancer treatments, tumor induced bone disease continues to cause significant morbidities. While tumors show distinct mutations and clinical characteristics, they behave similarly once they establish in bone. Tumors can metastasize to bone from distant sites (breast, prostate, lung, directly invade into bone (head and neck or originate from the bone (melanoma, chondrosarcoma where they cause pain, fractures, hypercalcemia, and ultimately, poor prognoses and outcomes. Tumors in bone secrete factors (interleukins and parathyroid hormone-related protein that induce RANKL expression from osteoblasts, causing an increase in osteoclast mediated bone resorption. While the mechanisms involved varies slightly between tumor types, many tumors display an increase in Hedgehog signaling components that lead to increased tumor growth, therapy failure, and metastasis. The work of multiple laboratories has detailed Hh signaling in several tumor types and revealed that tumor establishment in bone can be controlled by both canonical and non-canonical Hh signaling in a cell type specific manner. This review will explore the role of Hh signaling in the modulation of tumor induced bone disease, and will shed insight into possible therapeutic interventions for blocking Hh signaling in these tumors.

  20. The Role of Hedgehog Signaling in Tumor Induced Bone Disease

    Energy Technology Data Exchange (ETDEWEB)

    Cannonier, Shellese A.; Sterling, Julie A., E-mail: Julie.sterling@vanderbilt.edu [Department of Veterans Affairs, Tennessee Valley Healthcare System, Nashville, TN 37235 (United States); Vanderbilt Center for Bone Biology, Department of Medicine, Division of Clinical Pharmacology Vanderbilt University, Nashville, TN 372335 (United States); Department of Cancer Biology, Vanderbilt University, Nashville, TN 37235 (United States)

    2015-08-26

    Despite significant progress in cancer treatments, tumor induced bone disease continues to cause significant morbidities. While tumors show distinct mutations and clinical characteristics, they behave similarly once they establish in bone. Tumors can metastasize to bone from distant sites (breast, prostate, lung), directly invade into bone (head and neck) or originate from the bone (melanoma, chondrosarcoma) where they cause pain, fractures, hypercalcemia, and ultimately, poor prognoses and outcomes. Tumors in bone secrete factors (interleukins and parathyroid hormone-related protein) that induce RANKL expression from osteoblasts, causing an increase in osteoclast mediated bone resorption. While the mechanisms involved varies slightly between tumor types, many tumors display an increase in Hedgehog signaling components that lead to increased tumor growth, therapy failure, and metastasis. The work of multiple laboratories has detailed Hh signaling in several tumor types and revealed that tumor establishment in bone can be controlled by both canonical and non-canonical Hh signaling in a cell type specific manner. This review will explore the role of Hh signaling in the modulation of tumor induced bone disease, and will shed insight into possible therapeutic interventions for blocking Hh signaling in these tumors.

  1. Regulation of Wnt signaling by nociceptive input in animal models

    Directory of Open Access Journals (Sweden)

    Shi Yuqiang

    2012-06-01

    Full Text Available Abstract Background Central sensitization-associated synaptic plasticity in the spinal cord dorsal horn (SCDH critically contributes to the development of chronic pain, but understanding of the underlying molecular pathways is still incomplete. Emerging evidence suggests that Wnt signaling plays a crucial role in regulation of synaptic plasticity. Little is known about the potential function of the Wnt signaling cascades in chronic pain development. Results Fluorescent immunostaining results indicate that β-catenin, an essential protein in the canonical Wnt signaling pathway, is expressed in the superficial layers of the mouse SCDH with enrichment at synapses in lamina II. In addition, Wnt3a, a prototypic Wnt ligand that activates the canonical pathway, is also enriched in the superficial layers. Immunoblotting analysis indicates that both Wnt3a a β-catenin are up-regulated in the SCDH of various mouse pain models created by hind-paw injection of capsaicin, intrathecal (i.t. injection of HIV-gp120 protein or spinal nerve ligation (SNL. Furthermore, Wnt5a, a prototypic Wnt ligand for non-canonical pathways, and its receptor Ror2 are also up-regulated in the SCDH of these models. Conclusion Our results suggest that Wnt signaling pathways are regulated by nociceptive input. The activation of Wnt signaling may regulate the expression of spinal central sensitization during the development of acute and chronic pain.

  2. The Role of Hedgehog Signaling in Tumor Induced Bone Disease

    International Nuclear Information System (INIS)

    Cannonier, Shellese A.; Sterling, Julie A.

    2015-01-01

    Despite significant progress in cancer treatments, tumor induced bone disease continues to cause significant morbidities. While tumors show distinct mutations and clinical characteristics, they behave similarly once they establish in bone. Tumors can metastasize to bone from distant sites (breast, prostate, lung), directly invade into bone (head and neck) or originate from the bone (melanoma, chondrosarcoma) where they cause pain, fractures, hypercalcemia, and ultimately, poor prognoses and outcomes. Tumors in bone secrete factors (interleukins and parathyroid hormone-related protein) that induce RANKL expression from osteoblasts, causing an increase in osteoclast mediated bone resorption. While the mechanisms involved varies slightly between tumor types, many tumors display an increase in Hedgehog signaling components that lead to increased tumor growth, therapy failure, and metastasis. The work of multiple laboratories has detailed Hh signaling in several tumor types and revealed that tumor establishment in bone can be controlled by both canonical and non-canonical Hh signaling in a cell type specific manner. This review will explore the role of Hh signaling in the modulation of tumor induced bone disease, and will shed insight into possible therapeutic interventions for blocking Hh signaling in these tumors

  3. Democracy-based consensus in medicine.

    Science.gov (United States)

    Greco, Massimiliano; Zangrillo, Alberto; Mucchetti, Marta; Nobile, Leda; Landoni, Paolo; Bellomo, Rinaldo; Landoni, Giovanni

    2015-04-01

    High-quality evidence and derived guidelines, as typically published in major academic journals, are a major process that shapes physician decision-making worldwide. However, for many aspects of medical practice, there is a lack of High-quality evidence or an overload of somewhat contradictory low-quality information, which makes decision-making a difficult, uncertain, and unpredictable process. When the issues in question are important and evidence limited or controversial, the medical community seeks to establish common ground for "best practice" through consensus conferences and consensus statements or guidelines. Such consensus statements are seen as a useful tool to establish expert agreement, define the boundaries of acceptable practice, provide priorities for the research agenda, and obtain opinions from different countries and healthcare systems. This standard approach, however, can be criticized for being elitist, noninclusive, and poorly representative of the community of clinicians who will have to make decisions about the implementation of such recommendations. Accordingly, the authors propose a new model based on a combination of a local core meeting (detailed review and expert input) followed by a worldwide web-based network assessment (democracy-based consensus). The authors already have applied this approach to develop consensus on all nonsurgical interventions that increase or reduce perioperative mortality in critically ill patients and in those with acute kidney injury. The methodology was based on 5 sequential local and web-based steps. Both a panel of experts and a large number of professionals from all over the world were involved, giving birth to a new type of "democracy-based consensus." This new type of "democracy-based consensus" has the potential to increase grass-root clinician involvement, expand the reach to less-developed countries, provide a more global perspective on proposed interventions, and perhaps more importantly, increase

  4. Asian Consensus Report on Functional Dyspepsia

    Science.gov (United States)

    Miwa, Hiroto; Ghoshal, Uday C; Gonlachanvit, Sutep; Gwee, Kok-Ann; Ang, Tiing-Leong; Chang, Full-Young; Fock, Kwong Ming; Hongo, Michio; Hou, Xiaohua; Kachintorn, Udom; Ke, Meiyun; Lai, Kwok-Hung; Lee, Kwang Jae; Lu, Ching-Liang; Mahadeva, Sanjiv; Miura, Soichiro; Park, Hyojin; Rhee, Poong-Lyul; Sugano, Kentaro; Vilaichone, Ratha-korn; Wong, Benjamin CY

    2012-01-01

    Background/Aims Environmental factors such as food, lifestyle and prevalence of Helicobacter pylori infection are widely different in Asian countries compared to the West, and physiological functions and genetic factors of Asians may also be different from those of Westerners. Establishing an Asian consensus for functional dyspepsia is crucial in order to attract attention to such data from Asian countries, to articulate the experience and views of Asian experts, and to provide a relevant guide on management of functional dyspepsia for primary care physicians working in Asia. Methods Consensus team members were selected from Asian experts and consensus development was carried out using a modified Delphi method. Consensus teams collected published papers on functional dyspepsia especially from Asia and developed candidate consensus statements based on the generated clinical questions. At the first face-to-face meeting, each statement was reviewed and e-mail voting was done twice. At the second face-to-face meeting, final voting on each statement was done using keypad voting system. A grade of evidence and a strength of recommendation were applied to each statement according to the method of the GRADE Working Group. Results Twenty-nine consensus statements were finalized, including 7 for definition and diagnosis, 5 for epidemiology, 9 for pathophysiology and 8 for management. Algorithms for diagnosis and management of functional dyspepsia were added. Conclusions This consensus developed by Asian experts shows distinctive features of functional dyspepsia in Asia and will provide a guide to the diagnosis and management of functional dyspepsia for Asian primary care physicians. PMID:22523724

  5. 43 CFR 46.110 - Incorporating consensus-based management.

    Science.gov (United States)

    2010-10-01

    ... 43 Public Lands: Interior 1 2010-10-01 2010-10-01 false Incorporating consensus-based management... § 46.110 Incorporating consensus-based management. (a) Consensus-based management incorporates direct... carry out those plans and activities. For the purposes of this Part, consensus-based management involves...

  6. Dynamic Average Consensus and Consensusability of General Linear Multiagent Systems with Random Packet Dropout

    Directory of Open Access Journals (Sweden)

    Wen-Min Zhou

    2013-01-01

    Full Text Available This paper is concerned with the consensus problem of general linear discrete-time multiagent systems (MASs with random packet dropout that happens during information exchange between agents. The packet dropout phenomenon is characterized as being a Bernoulli random process. A distributed consensus protocol with weighted graph is proposed to address the packet dropout phenomenon. Through introducing a new disagreement vector, a new framework is established to solve the consensus problem. Based on the control theory, the perturbation argument, and the matrix theory, the necessary and sufficient condition for MASs to reach mean-square consensus is derived in terms of stability of an array of low-dimensional matrices. Moreover, mean-square consensusable conditions with regard to network topology and agent dynamic structure are also provided. Finally, the effectiveness of the theoretical results is demonstrated through an illustrative example.

  7. [SECOT consensus on medial femorotibial osteoarthritis].

    Science.gov (United States)

    Moreno, A; Silvestre, A; Carpintero, P

    2013-01-01

    A consensus, prepared by SECOT, is presented on the management of medial knee compartment osteoarthritis, in order to establish clinical criteria and recommendations directed at unifying the criteria in its management, dealing with the factors involved in the pathogenesis of medial femorotibial knee osteoarthritis, the usefulness of diagnostic imaging techniques, and the usefulness of arthroscopy. Conservative and surgical treatments are also analysed. The experts consulted showed a consensus (agreed or disagreed) in 65.8% of the items considered, leaving 14items where no consensus was found, which included the aetiopathogenesis of the osteoarthritis, the value of NMR in degenerative disease, the usefulness of COX-2 and the chondroprotective drugs, as well as on the ideal valgus tibial osteotomy technique. © 2013 SECOT. Published by Elsevier Espana. All rights reserved.

  8. Lack of consensus in social systems

    Science.gov (United States)

    Benczik, I. J.; Benczik, S. Z.; Schmittmann, B.; Zia, R. K. P.

    2008-05-01

    We propose an exactly solvable model for the dynamics of voters in a two-party system. The opinion formation process is modeled on a random network of agents. The dynamical nature of interpersonal relations is also reflected in the model, as the connections in the network evolve with the dynamics of the voters. In the infinite time limit, an exact solution predicts the emergence of consensus, for arbitrary initial conditions. However, before consensus is reached, two different metastable states can persist for exponentially long times. One state reflects a perfect balancing of opinions, the other reflects a completely static situation. An estimate of the associated lifetimes suggests that lack of consensus is typical for large systems.

  9. Eastern Canadian Gastrointestinal Cancer Consensus Conference 2016.

    Science.gov (United States)

    Bossé, D; Ng, T; Ahmad, C; Alfakeeh, A; Alruzug, I; Biagi, J; Brierley, J; Chaudhury, P; Cleary, S; Colwell, B; Cripps, C; Dawson, L A; Dorreen, M; Ferland, E; Galiatsatos, P; Girard, S; Gray, S; Halwani, F; Kopek, N; Mahmud, A; Martel, G; Robillard, L; Samson, B; Seal, M; Siddiqui, J; Sideris, L; Snow, S; Thirwell, M; Vickers, M; Goodwin, R; Goel, R; Hsu, T; Tsvetkova, E; Ward, B; Asmis, T

    2016-12-01

    The annual Eastern Canadian Gastrointestinal Cancer Consensus Conference 2016 was held in Montreal, Quebec, 5-7 February. Experts in radiation oncology, medical oncology, surgical oncology, and infectious diseases involved in the management of patients with gastrointestinal malignancies participated in presentations and discussion sessions for the purpose of developing the recommendations presented here. This consensus statement addresses multiple topics: ■ Follow-up and survivorship of patients with resected colorectal cancer■ Indications for liver metastasectomy■ Treatment of oligometastases by stereotactic body radiation therapy■ Treatment of borderline resectable and unresectable pancreatic cancer■ Transarterial chemoembolization in hepatocellular carcinoma■ Infectious complications of antineoplastic agents.

  10. Consensus among Economists--An Update

    Science.gov (United States)

    Fuller, Dan; Geide-Stevenson, Doris

    2014-01-01

    In this article, the authors explore consensus among economists on specific propositions based on a fall 2011 survey of American Economic Association members. Results are based on 568 responses and provide evidence of changes in opinion over time by including propositions from earlier studies in 2000 (Fuller and Geide-Stevenson 2003) and 1992…

  11. Health Promoting Schools: Consensus, Strategies, and Potential

    Science.gov (United States)

    Macnab, Andrew J.; Gagnon, Faith A.; Stewart, Donald

    2014-01-01

    Purpose: The purpose of this paper is to summarize a consensus statement generated on the current challenges, strategies, and potential of health promoting schools (HPS) at a 2011 colloquium at the Stellenbosch Institute for Advanced Study where 40 people from five continents came together to share their global and regional experience surrounding…

  12. Consensus and Cognitivism in Habermas's Discourse | Moellendorf ...

    African Journals Online (AJOL)

    Habermas asserts that his discourse ethics rests on two main commitments: 1) Moral judgements have cognitive content analogous to truth value; and 2) moral justification requires real- life discourse. Habermas elaborates on the second claim by making actual consensus a necessary condition of normative validity. I argue ...

  13. Construction of barley consensus map showing chromosomal ...

    African Journals Online (AJOL)

    GRACE

    2006-02-02

    Feb 2, 2006 ... the purpose of this consensus map (containing QTL) is to provide a tool for scientists to accurately locate molecular markers to ... community with powerful tools for comparative genomics. (Gai et al., 2000; Mekhdov et al., ...... and controlled by almost the same loci (Marquez et al.,. 2000). In the present study ...

  14. Consensus over peri-implantaire infecties

    NARCIS (Netherlands)

    van Winkelhoff, A J

    2010-01-01

    In 2008, in a workshop of the European Federation on Periodontology, a consensus was reached concerning oral peri-implant infections on the basis of the state of the art in the relevant sciences. Important conclusions were that peri-implant mucositis occurs in 80% of subjects with oral implants, and

  15. 3rd BRAZILIAN CONSENSUS ON Helicobacter pylori

    Directory of Open Access Journals (Sweden)

    Luiz Gonzaga Coelho

    2013-04-01

    Full Text Available Significant progress has been obtained since the Second Brazilian Consensus Conference on Helicobacter pylori Infection held in 2004, in São Paulo, SP, Brazil, and justify a third meeting to establish updated guidelines on the current management of H. pylori infection. The Third Brazilian Consensus Conference on H pylori Infection was organized by the Brazilian Nucleus for the Study of Helicobacter, a Department of the Brazilian Federation of Gastroenterology and took place on April 12-15, 2011, in Bento Gonçalves, RS, Brazil. Thirty-one delegates coming from the five Brazilian regions and one international guest, including gastroenterologists, pathologists, epidemiologists, and pediatricians undertook the meeting. The participants were allocated in one of the five main topics of the meeting: H pylori, functional dyspepsia and diagnosis; H pylori and gastric cancer; H pylori and other associated disorders; H pylori treatment and retreatment; and, epidemiology of H pylori infection in Brazil. The results of each subgroup were submitted to a final consensus voting to all participants. Relevant data were presented, and the quality of evidence, strength of recommendation, and level of consensus were graded. Seventy per cent and more votes were considered as acceptance for the final statement. This article presents the main recommendations and conclusions to guide Brazilian doctors involved in the management of H pylori infection.

  16. 2016 updated MASCC/ESMO consensus recommendations

    DEFF Research Database (Denmark)

    Roila, Fausto; Warr, David; Hesketh, Paul J

    2017-01-01

    PURPOSE: An update of the recommendations for the prophylaxis of acute and delayed emesis induced by moderately emetogenic chemotherapy published after the last MASCC/ESMO antiemetic consensus conference in 2009 has been carried out. METHODS: A systematic literature search using PubMed from Janua...

  17. Consensus among Economics Teachers from Transition Economies

    Science.gov (United States)

    Leet, Don R.; Lang, Nancy A.

    2010-01-01

    The authors analyze the economic opinions of teachers and economists from the former Soviet Union who participated in economic education programs sponsored by the U.S. Department of Education under the auspices of the National Council on Economic Education from 1995-2001. They sought to determine the level of consensus on economic topics among the…

  18. Prostate cancer: ESMO Consensus Conference Guidelines 2012

    NARCIS (Netherlands)

    Horwich, A.; Hugosson, J.; de Reijke, T.; Wiegel, T.; Fizazi, K.; Kataja, V.; Parker, Chris; Bellmunt, Joaquim; Berthold, Dominik; Bill-Axelson, Anna; Carlsson, Sigrid; Daugaard, Gedske; de Meerleer, Gert; Dearnaley, David; Fizazi, Karim; Fonteyne, Valérie; Gillessen, Silke; Heinrich, Daniel; Horwich, Alan; Hugosson, Jonas; Kataja, Vesa; Kwiatkowski, Maciej; Nilsson, Sten; Padhani, Anwar; Papandreou, Christos; Roobol, Monique; Sella, Avishay; Valdagni, Riccardo; van der Kwast, Theo; Verhagen, Paul; Wiegel, Thomas

    2013-01-01

    The first ESMO Consensus Conference on prostate cancer was held in Zurich, Switzerland, on 17-19 November 2011, with the participation of a multidisciplinary panel of leading professionals including experts in methodological aspects. Before the conference, the expert panel prepared clinically

  19. A consensus view on liquidity risk

    NARCIS (Netherlands)

    Acharya, V.; Krishnamurthy, A.; Perotti, E.

    2011-01-01

    Liquidity risk - which was at the heart of the September 2008 financial meltdown and explains regulatory concerns about a Greek default today - remains an open issue in financial regulatory reform. This column presents a consensus view of several leading academics on what more needs to be done to

  20. Adult Asthma Consensus Guidelines Update 2003

    Directory of Open Access Journals (Sweden)

    Catherine Lemière

    2004-01-01

    Full Text Available BACKGROUND: Several sets of Canadian guidelines for the diagnosis and management of asthma have been published over the past 15 years. Since the last revision of the 1999 Canadian Asthma Consensus Report, important new studies have highlighted the need to incorporate new information into the asthma guidelines.

  1. ACTIVITY OF CANONICAL WNT SIGNAL SYSTEM IN HYALINE CARTILAGE ARTICULAR CHONDROCYTES IN PROCESS OF SYNOVIAL JOINT DEVELOPMENT

    Directory of Open Access Journals (Sweden)

    A.O. Molotkov

    2009-03-01

    Full Text Available Canonical and non-canonical Wnt systems are essential regulators of chondrogenesis and bone development. However, the roles of these systems in synovial joint development are not well studied. To determine if canonical Wnt system is active in developing articular chondrocytes we used immunohistochemistry for в-galactosidase and doublecortin (cell-type specific marker for articular chondrocytes to double label sections through joint regions of E14.5, E18.5, P10 and adult mice. Here the following results are presented. Canonical Wnt signal system does not work in developing articular chondrocytes at early embryonic stages (E14.5; it is active in the articular chondrocytes at late embryonic stages (E16.5-E18.5 and during postnatal development (P7-P10, but is turned off again in the adult articular chondrocytes. These results suggest that canonical Wnt signaling is being regulated during articular chondrocytes differentiation and joint formation.

  2. Building consensus in developing radioactive waste management systems

    International Nuclear Information System (INIS)

    Terrell, R.; Philpott, R.; Smith, S.L.; Gibson, J.

    1991-01-01

    To successfully develop radioactive waste management systems, national authorities must work to establish consensus on numerous complex issues among many affected and interested parties. This paper explores the meaning of consensus in waste management, with special attention to the different arenas in which consensus is established and how DOE can respond if consensus is withheld. Highlights of other national waste management programs are introduced to provide a broader perspective on consensus. It is suggested that the US waste management program has reached a point where Congress needs to act to reaffirm consensus on the direction of the US program

  3. The Consensus of Strategic Consensus: A Study of the State of the Art about the Theme

    Directory of Open Access Journals (Sweden)

    Marcelo Curth

    2018-04-01

    Full Text Available This paper aims to present the state of the art regarding the strategic consensus, emphasizing the approaches and the nature of the research methods used, the results obtained and the future agenda for this theme studies. Analyzing beyond the last four decades of publications, it was understood that relating the strategic consensus only with the performance and strategic levels can be seen as something limited, suggesting the need to bring to the researching field new aspects and backgrounds as innovation, the methods for generating new ideas, the occurrence beyond the Top Management Team level (TMT, among others. Moreover, concludes that the predominant approach the strategic consensus is a process and the methodology used is based on quantitative techniques. As a suggestion for future studies, this study indicates the investigation of situations in which the strategic consensus is not positive.

  4. Consensus statement update on posttraumatic stress disorder from the international consensus group on depression and anxiety.

    Science.gov (United States)

    Ballenger, James C; Davidson, Jonathan R T; Lecrubier, Yves; Nutt, David J; Marshall, Randall D; Nemeroff, Charles B; Shalev, Arieh Y; Yehuda, Rachel

    2004-01-01

    To provide an update to the "Consensus Statement on Posttraumatic Stress Disorder From the International Consensus Group on Depression and Anxiety" that was published in a supplement to The Journal of Clinical Psychiatry (2000) by presenting important developments in the field, the latest recommendations for patient care, and suggestions for future research. The 4 members of the International Consensus Group on Depression and Anxiety were James C. Ballenger (chair), Jonathan R. T. Davidson, Yves Lecrubier, and David J. Nutt. Other faculty who were invited by the chair were Randall D. Marshall, Charles B. Nemeroff, Arieh Y. Shalev, and Rachel Yehuda. The consensus statement is based on the 7 review articles in this supplement and the related scientific literature. Group meetings were held over a 2-day period. On day 1, the group discussed topics to be represented by the 7 review articles in this supplement, and the chair identified key issues for further debate. On day 2, the group discussed these issues to arrive at a consensus view. After the group meetings, the consensus statement was drafted by the chair and approved by all faculty. There have been advancements in the science and treatment of posttraumatic stress disorder. Attention to this disorder has increased with recent world events; however, continued efforts are needed to improve diagnosis, treatment, and prevention of posttraumatic stress disorder.

  5. Consensus statement on social anxiety disorder from the International Consensus Group on Depression and Anxiety.

    Science.gov (United States)

    Ballenger, J C; Davidson, J R; Lecrubier, Y; Nutt, D J; Bobes, J; Beidel, D C; Ono, Y; Westenberg, H G

    1998-01-01

    The goal of this consensus statement is to provide primary care clinicians with a better understanding of management issues in social anxiety disorder (social phobia) and guide clinical practice with recommendations for appropriate pharmacotherapy. The 4 members of the International Consensus Group on Depression and Anxiety were James C. Ballenger (chair), Jonathan R. T. Davidson, Yves Lecrubier, and David J. Nutt. Other faculty invited by the chair were Julio Bobes, Deborah C. Beidel, Yukata Ono, and Herman G. M. Westenberg. The consensus statement is based on the 7 review papers published in this supplement and on the scientific literature relevant to the issues reviewed in these papers. The group met over a 2-day period. On day 1, the group discussed each review paper, and the chair identified key issues for further debate. On day 2, the group discussed these issues to arrive at a consensus view. After the group meetings, the consensus statement was drafted by the chair and approved by all attendees. The consensus statement underlines the importance of recognizing social anxiety disorder and provides recommendations on how it may be distinguished from other anxiety disorders. It proposes definitions for response and remission and considers appropriate management strategies. Selective serotonin reuptake inhibitors are recommended as first-line therapy, and effective treatment should be continued for at least 12 months. Long-term treatment is indicated if symptoms are unresolved, the patient has a comorbid condition or a history of relapse, or there was an early onset of the disorder.

  6. The basic chemistry of exercise-induced DNA oxidation: oxidative damage, redox signalling and their interplay

    Directory of Open Access Journals (Sweden)

    James Nathan Cobley

    2015-06-01

    Full Text Available Acute exercise increases reactive oxygen and nitrogen species generation. This phenomenon is associated with two major outcomes: (1 redox signalling and (2 macromolecule damage. Mechanistic knowledge of how exercise-induced redox signalling and macromolecule damage are interlinked is limited. This review focuses on the interplay between exercise-induced redox signalling and DNA damage, using hydroxyl radical (·OH and hydrogen peroxide (H2O2 as exemplars. It is postulated that the biological fate of H2O2 links the two processes and thus represents a bifurcation point between redox signalling and damage. Indeed, H2O2 can participate in two electron signalling reactions but its diffusion and chemical properties permit DNA oxidation following reaction with transition metals and ·OH generation. It is also considered that the sensing of DNA oxidation by repair proteins constitutes a non-canonical redox signalling mechanism. Further layers of interaction are provided by the redox regulation of DNA repair proteins and their capacity to modulate intracellular H2O2 levels. Overall, exercise-induced redox signalling and DNA damage may be interlinked to a greater extent than was previously thought but this requires further investigation.

  7. Managing Carious Lesions: Consensus Recommendations on Carious Tissue Removal

    NARCIS (Netherlands)

    Schwendicke, F.; Frencken, J.E.; Bjorndal, L.; Maltz, M.; Manton, D.J.; Ricketts, D.; Van Landuyt, K.; Banerjee, A.; Campus, G.; Domejean, S.; Fontana, M.; Leal, S.; Lo, E.; Machiulskiene, V.; Schulte, A.; Splieth, C.; Zandona, A.F.; Innes, N.P.

    2016-01-01

    The International Caries Consensus Collaboration undertook a consensus process and here presents clinical recommendations for carious tissue removal and managing cavitated carious lesions, including restoration, based on texture of demineralized dentine. Dentists should manage the disease dental

  8. Consensus Through Conversation How to Achieve High-Commitment Decisions

    CERN Document Server

    Dressler, Larry

    2006-01-01

    Facilitation expert Larry Dressler's Consensus Through Conversation is a guide for the effective facilitation and practice of one of business's most popular - but most widely misunderstood - decision-making models: consensus.

  9. 76 FR 45647 - Consensus Standards, Light-Sport Aircraft

    Science.gov (United States)

    2011-07-29

    ... DEPARTMENT OF TRANSPORTATION Federal Aviation Administration Consensus Standards, Light-Sport... previously accepted consensus standards relating to the provisions of the Sport Pilot and Light-Sport... Light Sport Aircraft developed the revised standards with Federal Aviation Administration (FAA...

  10. [Experts consensus of dental esthetic photography].

    Science.gov (United States)

    2017-05-09

    Clinical photography in esthetic dentistry is an essential skill in clinical practice. It is widely applied clinically in multiple fields related to esthetic dentistry. Society of Esthetic Dentistry of Chinese Stomatological Association established a consensus for clinical photography and standards for images in esthetic dentistry in order to standardize domestic dental practitioners' procedure, and meet the demands of diagnosis and design in modern esthetic dentistry. It was also developed to facilitate domestic and international academic communication. Sixteen commonly used images in practice, which are of apparent importance in guiding esthetic analysis, design and implementation, are proposed in the standards. This consensus states the clinical significance of these images and the standard protocol of acquiring them.

  11. Bruxism defined and graded: an international consensus.

    Science.gov (United States)

    Lobbezoo, F; Ahlberg, J; Glaros, A G; Kato, T; Koyano, K; Lavigne, G J; de Leeuw, R; Manfredini, D; Svensson, P; Winocur, E

    2013-01-01

    To date, there is no consensus about the definition and diagnostic grading of bruxism. A written consensus discussion was held among an international group of bruxism experts as to formulate a definition of bruxism and to suggest a grading system for its operationalisation. The expert group defined bruxism as a repetitive jaw-muscle activity characterised by clenching or grinding of the teeth and/or by bracing or thrusting of the mandible. Bruxism has two distinct circadian manifestations: it can occur during sleep (indicated as sleep bruxism) or during wakefulness (indicated as awake bruxism). For the operationalisation of this definition, the expert group proposes a diagnostic grading system of 'possible', 'probable' and 'definite' sleep or awake bruxism. The proposed definition and grading system are suggested for clinical and research purposes in all relevant dental and medical domains. © 2012 Blackwell Publishing Ltd.

  12. ESMO consensus conference on malignant lymphoma

    DEFF Research Database (Denmark)

    Ladetto, M; Buske, C; Hutchings, M

    2016-01-01

    The European Society for Medical Oncology (ESMO) consensus conference on mature B-cell lymphomas and chronic lymphocytic leukaemia (CLL) was held on 20 June 2015 in Lugano, Switzerland, and included a multidisciplinary panel of 25 leading experts. The aim of the conference was to develop recommen......The European Society for Medical Oncology (ESMO) consensus conference on mature B-cell lymphomas and chronic lymphocytic leukaemia (CLL) was held on 20 June 2015 in Lugano, Switzerland, and included a multidisciplinary panel of 25 leading experts. The aim of the conference was to develop...... to their potentially high prognostic value, at least in some lymphoma entities, implementation of interim PET, COO and MRD was highly recommended in the context of clinical trials. All expert panel members approved this final article....

  13. Consensus on Exercise Reporting Template (CERT)

    DEFF Research Database (Denmark)

    Slade, Susan C; Dionne, Clermont E; Underwood, Martin

    2016-01-01

    the reporting of exercise programs in all evaluative study designs and contains 7 categories: materials, provider, delivery, location, dosage, tailoring, and compliance. The CERT will encourage transparency, improve trial interpretation and replication, and facilitate implementation of effective exercise......BACKGROUND: Exercise interventions are often incompletely described in reports of clinical trials, hampering evaluation of results and replication and implementation into practice. OBJECTIVE: The aim of this study was to develop a standardized method for reporting exercise programs in clinical...... trials: the Consensus on Exercise Reporting Template (CERT). DESIGN AND METHODS: Using the EQUATOR Network's methodological framework, 137 exercise experts were invited to participate in a Delphi consensus study. A list of 41 items was identified from a meta-epidemiologic study of 73 systematic reviews...

  14. Using consensus building to improve utility regulation

    International Nuclear Information System (INIS)

    Raab, J.

    1994-01-01

    The utility industry and its regulatory environment are at a crossroads. Utilities, intervenors and even public utility commissions are no longer able to initiate and sustain changes unilaterally. Traditional approaches to regulation are often contentious and costly, producing results that are not perceived as legitimate or practical. Consensus building and alternative dispute resolution have the potential to help utilities, intervenors and regulators resolve a host of regulatory issues. This book traces the decline of consensus in utility regulation and delineates current controversies. It presents the theory and practice of alternative dispute resolution in utility regulation and offers a framework for evaluating the successes and failures of attempts to employ these processes. Four regulatory cases are analyzed in detail: the Pilgrim nuclear power plant outage settlement, the use of DSM collaboratives, the New Jersey resource bidding policy and the formation of integrated resource management rules in Massachusetts

  15. Lone ranger decision making versus consensus decision making: Descriptive analysis

    OpenAIRE

    Maite Sara Mashego

    2015-01-01

    Consensus decision making, concerns group members make decisions together with the requirement of reaching a consensus that is all members abiding by the decision outcome. Lone ranging worked for sometime in a autocratic environment. Researchers are now pointing to consensus decision-making in organizations bringing dividend to many organizations. This article used a descriptive analysis to compare the goodness of consensus decision making and making lone ranging decision management. This art...

  16. IAEA Director General welcomes NPT consensus

    International Nuclear Information System (INIS)

    2000-01-01

    The document informs that the Director General of the IAEA welcomed the adoption with consensus by the Review Conference of the Parties to the Treaty on the Non-Proliferation of Nuclear Weapons of the final document on the review and operation of the Treaty, and that he was pleased by the vote of confidence shown in the IAEA and its role in the implementation of the Treaty

  17. Consensus in the Age of Blockchains

    OpenAIRE

    Bano, Shehar; Sonnino, Alberto; Al-Bassam, Mustafa; Azouvi, Sarah; McCorry, Patrick; Meiklejohn, Sarah; Danezis, George

    2017-01-01

    The blockchain initially gained traction in 2008 as the technology underlying bitcoin, but now has been employed in a diverse range of applications and created a global market worth over $150B as of 2017. What distinguishes blockchains from traditional distributed databases is the ability to operate in a decentralized setting without relying on a trusted third party. As such their core technical component is consensus: how to reach agreement among a group of nodes. This has been extensively s...

  18. The Mexican consensus on irritable bowel syndrome.

    Science.gov (United States)

    Carmona-Sánchez, R; Icaza-Chávez, M E; Bielsa-Fernández, M V; Gómez-Escudero, O; Bosques-Padilla, F; Coss-Adame, E; Esquivel-Ayanegui, F; Flores-Rendón, Á R; González-Martínez, M A; Huerta-Iga, F; López-Colombo, A; Méndez-Gutiérrez, T H; Noble-Lugo, A; Nogueira-de Rojas, J R; Raña-Garibay, R H; Remes-Troche, J M; Roesch-Dietlen, F; Schmulson, M J; Soto-Pérez, J C; Tamayo, J L; Uscanga, L F; Valdovinos, M Á; Valerio-Ureña, J; Zavala-Solares, M R

    2016-01-01

    Since the publication in 2009 of the Guidelines on the Diagnosis and Treatment of Irritable Bowel Syndrome of the Asociación Mexicana de Gastroenterología (2009 Guidelines), there have been significant advances in our knowledge of the epidemiology, pathophysiology, diagnosis, and treatment of this disease. To present a consensus review of the most current knowledge of IBS, updating the 2009 Guidelines by incorporating new internationally published scientific evidence, with a special interest in Mexican studies. The PubMed literature from January 2009 to March 2015 was reviewed and complemented through a manual search. Articles in English and Spanish were included and preference was given to consensuses, guidelines, systematic reviews, and meta-analyses. Statements referring to the different aspects of the disease were formulated and voted upon by 24 gastroenterologists employing the Delphi method. Once a consensus on each statement was reached, the quality of evidence and strength of recommendation were determined through the GRADE system. Forty-eight statements were formulated, updating the information on IBS and adding the complementary data that did not appear in the 2009 Guidelines regarding the importance of exercise and diet, diagnostic strategies, and current therapy alternatives that were analyzed with more stringent scientific vigor or that emerged within the last 5 years. We present herein a consensus review of the most relevant advances in the study of IBS, updating and complementing the 2009 Guidelines. Several studies conducted in Mexico were included. Copyright © 2016 Asociación Mexicana de Gastroenterología. Publicado por Masson Doyma México S.A. All rights reserved.

  19. UK national consensus conference on radwaste management

    International Nuclear Information System (INIS)

    Craven-Howe, Andrew

    2000-01-01

    UK CEED organised a consensus conference to debate radwaste disposal. It lasted from 21-24 May 1999. Among the witnesses called to give evidence were UKAEA, BNFL, Nuclear Industries' Inspectorate, Department of the Environment, Transport and the Regions, Friends of the Earth and Greenpeace. The end result was a report produced by the panel of members of the public, recording their views and recommendations. Conclusions are presented. (author)

  20. International Consensus for ultrasound lesions in gout

    DEFF Research Database (Denmark)

    Gutierrez, Marwin; Schmidt, Wolfgang A; Thiele, Ralf G

    2015-01-01

    OBJECTIVE: To produce consensus-based definitions of the US elementary lesions in gout and to test their reliability in a web-based exercise. METHODS: The process consisted of two steps. In the first step a written Delphi questionnaire was developed from a systematic literature review and expert...... lesions in gout, demonstrated good reliability overall. It constitutes an essential step in developing a core outcome measurement that permits a higher degree of homogeneity and comparability between multicentre studies....

  1. The Mexican consensus on probiotics in gastroenterology

    OpenAIRE

    M.A. Valdovinos; E. Montijo; A.T. Abreu; S. Heller; A. González-Garay; D. Bacarreza; M. Bielsa-Fernández; M.C. Bojórquez-Ramos; F. Bosques-Padilla; A.I. Burguete-García; R. Carmona-Sánchez; A. Consuelo-Sánchez; E. Coss-Adame; J.A. Chávez-Barrera; M. de Ariño

    2017-01-01

    Introduction: Probiotics are frequently prescribed in clinical practice. Their efficacy in treating gastrointestinal disorders is supported by a significant number of clinical trials. However, the correct prescription of these agents is hampered due to a lack of knowledge of the scientific evidence and to the different presentations and microbial compositions of the probiotics that are currently available. Aim: To provide the clinician with a consensus review of probiotics and recommendati...

  2. Applying consensus standards to cask development

    International Nuclear Information System (INIS)

    Leatham, J.; Abbott, D.G.; Warrant, M.M.

    1987-01-01

    The Department of Energy's (DOE's) Office of Civilian Radioactive Waste Management is procuring cask systems for transporting commercial spent nuclear fuel and is encouraging development of innovative cask designs and materials to improve system efficiency. New designs and innovative materials require that consensus standards be established so that cask designers and regulators have criteria for determining acceptability. Recent DOE experience in certifying three spent fuel shipping casks, NUPAC-125B, TN-BRP, and TN-REG, is discussed. Certification of the NUPAC-125B was expedited because it was made of conventional American Society for Testing and Materials (ASTM) materials and complied with the American Society of Mechanical Engineers (ASME) Code and Nuclear Regulatory Commission Regulatory Guides. The TN-BRP and TN-REG cask designs are still being reviewed because baskets included in the casks are made of borated stainless steel, which has no ASTM Specification or ASME Code approval. The process of developing and approving consensus standards is discussed, including the role of ANSI and ANSI N14. Specific procedures for ASTM and ASME are described. A draft specification or standard must be prepared and then approved by the appropriate body. For new material applications to the ASME Code, an existing ASTM Specification is needed. These processes may require several years. The status of activities currently in progress to develop consensus standards for spent fuel casks is discussed, including (1) ASME NUPAC, and (2) ASTM Specifications for ductile cast iron and borated stainless steel

  3. ESMO Consensus Conference on malignant lymphoma

    DEFF Research Database (Denmark)

    Buske, C; Hutchings, M; Ladetto, M

    2018-01-01

    The European Society for Medical Oncology (ESMO) consensus conference on mature B cell lymphomas and chronic lymphocytic leukaemia (CLL) was held on 20 June 2015 in Lugano, Switzerland, and included a multidisciplinary panel of 25 leading experts. The aim of the conference was to develop recommen......The European Society for Medical Oncology (ESMO) consensus conference on mature B cell lymphomas and chronic lymphocytic leukaemia (CLL) was held on 20 June 2015 in Lugano, Switzerland, and included a multidisciplinary panel of 25 leading experts. The aim of the conference was to develop...... of the three key areas identified. This manuscript presents the consensus recommendations regarding the clinical management of elderly patients diagnosed with malignant lymphoma. Four clinically-relevant topics identified by the panel were: 1) how to define patient fitness, 2) assessing quality of life, 3......) diagnostic work-up and 4) clinical management of elderly patients with lymphoma. Each of these key topics is addressed in the context of five different lymphoma entities, namely: CLL, follicular lymphoma, mantle cell lymphoma, peripheral T-cell lymphoma and diffuse large B-cell lymphoma. Results, including...

  4. A Self-Categorization Explanation for Opinion Consensus Perceptions

    Science.gov (United States)

    Zhang, Jinguang; Reid, Scott A.

    2013-01-01

    The public expression of opinions (and related communicative activities) hinges upon the perception of opinion consensus. Current explanations for opinion consensus perceptions typically focus on egocentric and other biases, rather than functional cognitions. Using self-categorization theory we showed that opinion consensus perceptions flow from…

  5. Consensus statement on panic disorder from the International Consensus Group on Depression and Anxiety.

    Science.gov (United States)

    Ballenger, J C; Davidson, J R; Lecrubier, Y; Nutt, D J; Baldwin, D S; den Boer, J A; Kasper, S; Shear, M K

    1998-01-01

    To provide primary care clinicians with a better understanding of management issues in panic disorder and guide clinical practice with recommendations for appropriate pharmacotherapy. The 4 members of the International Consensus Group on Depression and Anxiety were James C. Ballenger (chair), Jonathan R. T. Davidson, Yves Lecrubier, and David J. Nutt. Four faculty invited by the chairman also participated: David S. Baldwin, Johan A. den Boer, Siegfried Kasper, and M. Katherine Shear. The consensus statement is based on the 6 review papers that are published in this supplement and on the scientific literature relevant to these issues. There were group meetings held during a 2-day period. On day 1, the group discussed each review paper and the chairman and discussant (Dr. Kasper) identified key issues for further debate. On day 2, the group discussed these key issues to arrive at a consensus view. After the group meetings, the consensus statement was drafted by the chairman and approved by all attendees. The consensus statement provides standard definitions for response and remission and identifies appropriate strategy for the management of panic disorder in a primary care setting. Serotonin selective reuptake inhibitors are recommended as drugs of first choice with a treatment period of 12 to 24 months. Pharmacotherapy should be discontinued slowly over a period of 4 to 6 months.

  6. ‘WNT-er is coming’: WNT signalling in chronic lung diseases

    Science.gov (United States)

    Baarsma, H A

    2017-01-01

    Chronic lung diseases represent a major public health problem with only limited therapeutic options. An important unmet need is to identify compounds and drugs that target key molecular pathways involved in the pathogenesis of chronic lung diseases. Over the last decade, there has been extensive interest in investigating Wingless/integrase-1 (WNT) signalling pathways; and WNT signal alterations have been linked to pulmonary disease pathogenesis and progression. Here, we comprehensively review the cumulative evidence for WNT pathway alterations in chronic lung pathologies, including idiopathic pulmonary fibrosis, pulmonary arterial hypertension, asthma and COPD. While many studies have focused on the canonical WNT/β-catenin signalling pathway, recent reports highlight that non-canonical WNT signalling may also significantly contribute to chronic lung pathologies; these studies will be particularly featured in this review. We further discuss recent advances uncovering the role of WNT signalling early in life, the potential of pharmaceutically modulating WNT signalling pathways and highlight (pre)clinical studies describing promising new therapies for chronic lung diseases. PMID:28416592

  7. International Spine Radiosurgery Consortium Consensus Guidelines for Target Volume Definition in Spinal Stereotactic Radiosurgery

    International Nuclear Information System (INIS)

    Cox, Brett W.; Spratt, Daniel E.; Lovelock, Michael; Bilsky, Mark H.; Lis, Eric; Ryu, Samuel; Sheehan, Jason; Gerszten, Peter C.; Chang, Eric; Gibbs, Iris; Soltys, Scott; Sahgal, Arjun; Deasy, Joe; Flickinger, John; Quader, Mubina; Mindea, Stefan

    2012-01-01

    Purpose: Spinal stereotactic radiosurgery (SRS) is increasingly used to manage spinal metastases. However, target volume definition varies considerably and no consensus target volume guidelines exist. This study proposes consensus target volume definitions using common scenarios in metastatic spine radiosurgery. Methods and Materials: Seven radiation oncologists and 3 neurological surgeons with spinal radiosurgery expertise independently contoured target and critical normal structures for 10 cases representing common scenarios in metastatic spine radiosurgery. Each set of volumes was imported into the Computational Environment for Radiotherapy Research. Quantitative analysis was performed using an expectation maximization algorithm for Simultaneous Truth and Performance Level Estimation (STAPLE) with kappa statistics calculating agreement between physicians. Optimized confidence level consensus contours were identified using histogram agreement analysis and characterized to create target volume definition guidelines. Results: Mean STAPLE agreement sensitivity and specificity was 0.76 (range, 0.67-0.84) and 0.97 (range, 0.94-0.99), respectively, for gross tumor volume (GTV) and 0.79 (range, 0.66-0.91) and 0.96 (range, 0.92-0.98), respectively, for clinical target volume (CTV). Mean kappa agreement was 0.65 (range, 0.54-0.79) for GTV and 0.64 (range, 0.54-0.82) for CTV (P<.01 for GTV and CTV in all cases). STAPLE histogram agreement analysis identified optimal consensus contours (80% confidence limit). Consensus recommendations include that the CTV should include abnormal marrow signal suspicious for microscopic invasion and an adjacent normal bony expansion to account for subclinical tumor spread in the marrow space. No epidural CTV expansion is recommended without epidural disease, and circumferential CTVs encircling the cord should be used only when the vertebral body, bilateral pedicles/lamina, and spinous process are all involved or there is extensive metastatic

  8. The Toll-like receptor 1/2 agonists Pam(3) CSK(4) and human β-defensin-3 differentially induce interleukin-10 and nuclear factor-κB signalling patterns in human monocytes.

    Science.gov (United States)

    Funderburg, Nicholas T; Jadlowsky, Julie K; Lederman, Michael M; Feng, Zhimin; Weinberg, Aaron; Sieg, Scott F

    2011-10-01

    Human β-defensin 3 (hBD-3) activates antigen-presenting cells through Toll-like receptors (TLRs) 1/2. Several TLR1/2 agonists have been identified but little is known about how they might differentially affect cellular activation. We compared the effects of hBD-3 with those of another TLR1/2 agonist, Pam(3) CSK(4) , in human monocytes. Monocytes incubated with hBD-3 or Pam(3) CSK(4) produced interleukin-6 (IL-6), IL-8 and IL-1β, but only Pam(3) CSK(4) induced IL-10. The IL-10 induction by Pam(3) CSK(4) caused down-modulation of the co-stimulatory molecule, CD86, whereas CD86 expression was increased in monocytes exposed to hBD-3. Assessment of signalling pathways linked to IL-10 induction indicated that mitogen-activated protein kinases were activated similarly by hBD-3 or Pam(3) CSK(4) , whereas the non-canonical nuclear factor-κB pathway was only induced by Pam(3) CSK(4) . Our data suggest that the lack of non-canonical nuclear factor-κB signalling by hBD-3 could contribute to the failure of this TLR agonist to induce production of the anti-inflammatory cytokine, IL-10, in human monocytes. © 2011 The Authors. Immunology © 2011 Blackwell Publishing Ltd.

  9. Constructive conflict and staff consensus in substance abuse treatment.

    Science.gov (United States)

    Melnick, Gerald; Wexler, Harry K; Chaple, Michael; Cleland, Charles M

    2009-03-01

    Previous studies demonstrated the relationship between consensus among both staff and clients with client engagement in treatment and between client consensus and 1-year treatment outcomes. The present article explores the correlates of staff consensus, defined as the level of agreement among staff as to the importance of treatment activities in their program, using a national sample of 80 residential substance abuse treatment programs. Constructive conflict resolution had the largest effect on consensus. Low client-to-staff ratios, staff education, and staff experience in substance abuse treatment were also significantly related to consensus. Frequency of training, an expected correlate of consensus, was negatively associated with consensus, whereas frequency of supervision was not a significant correlate. The implications of the findings for future research and program improvement are discussed.

  10. New ICRP recommendations 2005: without full consensus?

    International Nuclear Information System (INIS)

    Novakovic, M.

    2005-01-01

    Ionising radiation is viewed as one of the most studied of all known carcinogens. Over the last 50 years Recommendations of International Commission for Radiological Protection (ICRP) have been changed regularly every 10 years. At the beginning these changes were significant, sometimes even radical, according to quick acquiring of new scientific evidence on physical, biological and health effects of radiation. In order to handle each new situation evolution of the radiation protection system has been extended and new portions have been added (the ubiquitous exposure of public to radon gas and its progeny, and the need to develop an appropriate response to emergency situations, increasing social desire to participate in decision making processes, concern for the protection of non-human species and environment), that resulted in a system that is increasingly complicated. Over the last few years very broad discussions of major radiation protection concepts have been encouraged by the ICRP in order to achieve consensus on a more operational and coherent system of radiation protection elaborated in a transparent fashion, and presented in readily understandable terms. This process for the first time involves a broad spectrum of stake holders in these discussions. It is further assumed that these debates will eventually result in consensus on the basis for the next round of ICRP general recommendations, probably in the 2005. While now it is certain that the consensus is not yet reached within the international community and the discussion of these issues will continue for some time the new recommendations should be seen as a consolidation of recommendations from 1990 to give a single unified set that can be simply and coherently expressed. The paper presents essential issues of the outcome of the Commission discussions and improvement of the current system of radiation protection.(author)

  11. II Brazilian consensus statement on endoscopic ultrasonography.

    Science.gov (United States)

    Maluf-Filho, Fauze; de Oliveira, Joel Fernandez; Mendonça, Ernesto Quaresma; Carbonari, Augusto; Maciente, Bruno Antônio; Salomão, Bruno Chaves; Medrado, Bruno Frederico; Dotti, Carlos Marcelo; Lopes, César Vivian; Braga, Cláudia Utsch; M Dutra, Daniel Alencar; Retes, Felipe; Nakao, Frank; de Sousa, Giovana Biasia; de Paulo, Gustavo Andrade; Ardengh, Jose Celso; Dos Santos, Juliana Bonfim; Sampaio, Luciana Moura; Okawa, Luciano; Rossini, Lucio; de Brito Cardoso, Manoel Carlos; Ribeiro Camunha, Marco Antonio; Clarêncio, Marcos; Lera Dos Santos, Marcos Eduardo; Franco, Matheus; Schneider, Nutianne Camargo; Mascarenhas, Ramiro; Roda, Rodrigo; Matuguma, Sérgio; Guaraldi, Simone; Figueiredo, Viviane

    2017-01-01

    At the time of its introduction in the early 80s, endoscopic ultrasonography (EUS) was indicated for diagnostic purposes. Recently, EUS has been employed to assist or to be the main platform of complex therapeutic interventions. From a series of relevant new topics in the literature and based on the need to complement the I Brazilian consensus on EUS, twenty experienced endosonographers identified and reviewed the pertinent literature in databases. The quality of evidence, strength of recommendations, and level of consensus were graded and voted on. Consensus was reached for eight relevant topics: treatment of gastric varices, staging of nonsmall cell lung cancer, biliary drainage, tissue sampling of subepithelial lesions (SELs), treatment of pancreatic fluid collections, tissue sampling of pancreatic solid lesions, celiac neurolysis, and evaluation of the incidental pancreatic cysts. There is a high level of evidence for staging of nonsmall cell lung cancer; biopsy of SELs as the safest method; unilateral and bilateral injection techniques are equivalent for EUS-guided celiac neurolysis, and in patients with visible ganglia, celiac ganglia neurolysis appears to lead to better results. There is a moderate level of evidence for: yield of tissue sampling of pancreatic solid lesions is not influenced by the needle shape, gauge, or employed aspiration technique; EUS-guided and percutaneous biliary drainage present similar clinical success and adverse event rates; plastic and metallic stents are equivalent in the EUS-guided treatment of pancreatic pseudocyst. There is a low level of evidence in the routine use of EUS-guided treatment of gastric varices.

  12. Wireless sensor networks distributed consensus estimation

    CERN Document Server

    Chen, Cailian; Guan, Xinping

    2014-01-01

    This SpringerBrief evaluates the cooperative effort of sensor nodes to accomplish high-level tasks with sensing, data processing and communication. The metrics of network-wide convergence, unbiasedness, consistency and optimality are discussed through network topology, distributed estimation algorithms and consensus strategy. Systematic analysis reveals that proper deployment of sensor nodes and a small number of low-cost relays (without sensing function) can speed up the information fusion and thus improve the estimation capability of wireless sensor networks (WSNs). This brief also investiga

  13. Energy consensus talks collapse over nuclear issues

    International Nuclear Information System (INIS)

    Anon.

    1993-01-01

    Germany's energy consensus talks, ongoing since March 1993, were brought to unsuccessful end on October 26. Representatives from the Social Democratic Party (SDP), led by Lower Saxony's prime minister, Gerhard Schroeder, failed to get approval from party leaders on continued development of advanced reactors with enhanced safety - notably the Siemens/Framatome-designed 1500-MWe European pressurized water reactor (EPR) plan, for which the prospective schedule envisages a construction start in 1998. Nor would the SDP leadership accept the continued operation of existing nuclear plans to the end of their design life (some 20 to 25 years)

  14. The Mexican consensus on probiotics in gastroenterology

    Directory of Open Access Journals (Sweden)

    M.A. Valdovinos

    2017-04-01

    Results and conclusions: Eleven statements on the general concepts of probiotics and 27 statements on the use of probiotics in gastrointestinal diseases in both adults and children were formulated. The consensus group recommends the use of probiotics under the following clinical conditions: the prevention of diarrhea associated with antibiotics, the treatment of acute infectious diarrhea, the prevention of Clostridium difficile infection and necrotizing enterocolitis, the reduction of adverse events from Helicobacter pylori eradication therapy, relief from irritable bowel syndrome symptoms, the treatment of functional constipation in the adult, and the induction and maintenance of remission in patients with ulcerative colitis (UC and pouchitis, and the treatment of covert and overt hepatic encephalopathy.

  15. International consensus and States non-Parties

    International Nuclear Information System (INIS)

    Kellman, B.

    1996-01-01

    It is significant to recognize the contribution that international law can make to the promotion of consensus for arms control. Issues surface with a constancy that demand consistent, codified responses. International law should be more powerful, especially in addressing non-members and non-complying states. Successful negotiation of a multilateral treaty is not an end but a means to establish a law enforcement system capable of promoting important global interests. Accordingly arms control should generate the development of authoritative legal doctrines and institutions that can meet the challenge

  16. Methodological Quality of Consensus Guidelines in Implant Dentistry.

    Science.gov (United States)

    Faggion, Clovis Mariano; Apaza, Karol; Ariza-Fritas, Tania; Málaga, Lilian; Giannakopoulos, Nikolaos Nikitas; Alarcón, Marco Antonio

    2017-01-01

    Consensus guidelines are useful to improve clinical decision making. Therefore, the methodological evaluation of these guidelines is of paramount importance. Low quality information may guide to inadequate or harmful clinical decisions. To evaluate the methodological quality of consensus guidelines published in implant dentistry using a validated methodological instrument. The six implant dentistry journals with impact factors were scrutinised for consensus guidelines related to implant dentistry. Two assessors independently selected consensus guidelines, and four assessors independently evaluated their methodological quality using the Appraisal of Guidelines for Research & Evaluation (AGREE) II instrument. Disagreements in the selection and evaluation of guidelines were resolved by consensus. First, the consensus guidelines were analysed alone. Then, systematic reviews conducted to support the guidelines were included in the analysis. Non-parametric statistics for dependent variables (Wilcoxon signed rank test) was used to compare both groups. Of 258 initially retrieved articles, 27 consensus guidelines were selected. Median scores in four domains (applicability, rigour of development, stakeholder involvement, and editorial independence), expressed as percentages of maximum possible domain scores, were below 50% (median, 26%, 30.70%, 41.70%, and 41.70%, respectively). The consensus guidelines and consensus guidelines + systematic reviews data sets could be compared for 19 guidelines, and the results showed significant improvements in all domain scores (p dentistry journals is needed. The findings of the present study may help researchers to better develop consensus guidelines in implant dentistry, which will improve the quality and trust of information needed to make proper clinical decisions.

  17. Stabilizing IkappaBalpha by "consensus" design.

    Science.gov (United States)

    Ferreiro, Diego U; Cervantes, Carla F; Truhlar, Stephanie M E; Cho, Samuel S; Wolynes, Peter G; Komives, Elizabeth A

    2007-01-26

    IkappaBalpha is the major regulator of transcription factor NF-kappaB function. The ankyrin repeat region of IkappaBalpha mediates specific interactions with NF-kappaB dimers, but ankyrin repeats 1, 5 and 6 display a highly dynamic character when not in complex with NF-kappaB. Using chemical denaturation, we show here that IkappaBalpha displays two folding transitions: a non-cooperative conversion under weak perturbation, and a major cooperative folding phase upon stronger insult. Taking advantage of a native Trp residue in ankyrin repeat (AR) 6 and engineered Trp residues in AR2, AR4 and AR5, we show that the cooperative transition involves AR2 and AR3, while the non-cooperative transition involves AR5 and AR6. The major structural transition can be affected by single amino acid substitutions converging to the "consensus" ankyrin repeat sequence, increasing the native state stability significantly. We further characterized the structural and dynamic properties of the native state ensemble of IkappaBalpha and the stabilized mutants by H/(2)H exchange mass spectrometry and NMR. The solution experiments were complemented with molecular dynamics simulations to elucidate the microscopic origins of the stabilizing effect of the consensus substitutions, which can be traced to the fast conformational dynamics of the folded ensemble.

  18. Dialogic Consensus In Clinical Decision-Making.

    Science.gov (United States)

    Walker, Paul; Lovat, Terry

    2016-12-01

    This paper is predicated on the understanding that clinical encounters between clinicians and patients should be seen primarily as inter-relations among persons and, as such, are necessarily moral encounters. It aims to relocate the discussion to be had in challenging medical decision-making situations, including, for example, as the end of life comes into view, onto a more robust moral philosophical footing than is currently commonplace. In our contemporary era, those making moral decisions must be cognizant of the existence of perspectives other than their own, and be attuned to the demands of inter-subjectivity. Applicable to clinical practice, we propose and justify a Habermasian approach as one useful means of achieving what can be described as dialogic consensus. The Habermasian approach builds around, first, his discourse theory of morality as universalizable to all and, second, communicative action as a cooperative search for truth. It is a concrete way to ground the discourse which must be held in complex medical decision-making situations, in its actual reality. Considerations about the theoretical underpinnings of the application of dialogic consensus to clinical practice, and potential difficulties, are explored.

  19. Consensus for the brain metastases treatment

    International Nuclear Information System (INIS)

    Rabadan, Alejandra; Diez, Blanca; Martinez, Ana M.; Antico, Julio; Saidon, Patricia; Christiansen, Silvia; Rojas, Galeno

    2006-01-01

    The advancement in oncology therapies has made brain metastases treatment a major factor influencing the survival time and quality of life of patients with cancer. Although there are numerous publications on the issue, there is not yet to be consensus regarding the best strategy for treatment, which is probably due to population heterogeneity in terms of functional status, type of neoplasia, control of the systemic disease, and the number and localization of the lesions in the central nervous system. Our objective is to present general recommendations based on rational analysis in order to guide the practical management of brain metastases. With this purpose, a multidisciplinary team composed by neurosurgeons, neuro-oncologists, neuro-pathologist, radio therapist and neurologists was brought together, conducting a thorough search, in english and spanish, for publications in Pub- Med from 1980 to July 2006 (the starting period was set at the beginning of use of RM in medical practice). Review and original articles with n= or >20 were selected. Also, book chapters of renowned authors in the different consulted areas were included. The assessment of the literature, in addition to the experience of the authors allowed for the development of the 'Consensus for the brain metastases treatment'. Finally, the authors expect the present work will contribute to the multidisciplinary approach for the management of brain metastases with simple and practical recommendations, and probably stimulating future developments in this field. (author)

  20. Calcium hydroxylapatite for jawline rejuvenation: consensus recommendations.

    Science.gov (United States)

    Dallara, Jean-Marie; Baspeyras, Martine; Bui, Patrick; Cartier, Hugues; Charavel, Marie-Hélène; Dumas, Laurent

    2014-03-01

    Age-associated volume loss is now known to play an important role in the structural changes of the aging face. In the lower face, this manifests as drooping of the corners of the mouth and jowl leading to a loss of the oval jawline of youth. Jawline reshaping by replacing volume has therefore become an indispensable component of modern facial rejuvenation. Calcium hydroxylapatite (CaHA; Radiesse® , Merz Pharmaceuticals GmbH, Frankfurt, Germany) is an injectable filler with a cosmetic indication for tissue augmentation. The ability of calcium hydroxylapatite to provide immediate and long-lasting volume enhancement makes it an ideal agent for restoring an oval jawline. This consensus statement has been developed to assist clinicians who would like to gain more experience in the use of volumizing agents to achieve an optimal outcome with this procedure. Using the recently developed Merz Aesthetics Scale® for jawline, the consensus provides a treatment protocol for individuals at each stage of oval loss and presents a series of before and after images to illustrate the improvements that can be achieved. Specific recommendations for calcium hydroxylapatite including type of anesthesia, injection techniques, volume for injection, use in combination with other procedures, and expected duration of corrections are provided. Techniques for minimizing and managing expected problems and potential complications are also described. Calcium hydroxylapatite is appropriate for treating patients at any stage of oval loss. © 2014 Wiley Periodicals, Inc.

  1. International Consensus (ICON): allergic reactions to vaccines.

    Science.gov (United States)

    Dreskin, Stephen C; Halsey, Neal A; Kelso, John M; Wood, Robert A; Hummell, Donna S; Edwards, Kathryn M; Caubet, Jean-Christoph; Engler, Renata J M; Gold, Michael S; Ponvert, Claude; Demoly, Pascal; Sanchez-Borges, Mario; Muraro, Antonella; Li, James T; Rottem, Menachem; Rosenwasser, Lanny J

    2016-01-01

    Routine immunization, one of the most effective public health interventions, has effectively reduced death and morbidity due to a variety of infectious diseases. However, allergic reactions to vaccines occur very rarely and can be life threatening. Given the large numbers of vaccines administered worldwide, there is a need for an international consensus regarding the evaluation and management of allergic reactions to vaccines. Following a review of the literature, and with the active participation of representatives from the World Allergy Organization (WAO), the European Academy of Allergy and Clinical Immunology (EAACI), the American Academy of Allergy, Asthma, and Immunology (AAAAI), and the American College of Allergy, Asthma, and Immunology (ACAAI), the final committee was formed with the purpose of having members who represented a wide-range of countries, had previously worked on vaccine safety, and included both allergist/immunologists as well as vaccinologists. Consensus was reached on a variety of topics, including: definition of immediate allergic reactions, including anaphylaxis, approaches to distinguish association from causality, approaches to patients with a history of an allergic reaction to a previous vaccine, and approaches to patients with a history of an allergic reaction to components of vaccines. This document provides comprehensive and internationally accepted guidelines and access to on-line documents to help practitioners around the world identify allergic reactions following immunization. It also provides a framework for the evaluation and further management of patients who present either following an allergic reaction to a vaccine or with a history of allergy to a component of vaccines.

  2. Maastricht consensus-5: analytical review of statements

    Directory of Open Access Journals (Sweden)

    Yu.M. Stepanov

    2017-02-01

    Full Text Available This article analyzes the statements of Maastricht consensus-5 on H. pylori infection studying. There was shown the changes in approaches to diagnostics and treatment of H. pylori infection in previous Maastricht consensuses. H. pylori associated gastritis was considered to be an infection disease. There was also analyzed the relation between this infection and gatroduodenal pathology including functional dyspepsia, NSAID-gastropathy and others. The paper deals with up-to-date approaches to diagnostics of H. pylori infection with determination of the most optimal diagnostic method in different situations. The approaches to antihelicobacter therapy were analyzed. The special attention was paid to dependence of modern therapeutic schemes of helicobacteriosis therapy on H. pylori resistance to key antibiotics. There was confirmed the importance of H. pylori eradication for prevention of precancerous changes in the stomach. The increased interest of researchers to non-helicobacter flora in the stomach was shown. There was regarded an important role of probiotics in antihelicobacter therapy.

  3. [SECOT consensus on painful knee replacement].

    Science.gov (United States)

    Vaquero, J; Macule, F; Bello, S; Chana, F; Forriol, F

    2013-01-01

    The opinions of 21 experts in knee surgery were evaluated in this study, using a DELPHI questionnaire method in two successive rounds, on 64 controversial scenarios that covered both the diagnosis and possible treatment of painful knee replacements. The level of consensus was significantly unanimous in 42 items and of the design in 5, with no agreement in 17 of the questions presented. light of the published scientific evidence, the surgeons who took part showed to have a notable level of information on the most effective diagnostic tests, although, it should be pointed out that there was a lack of confidence in the possibility of ruling out an infection when the erythrocyte sedimentation rate and the C-reactive protein were within normal values, which have been demonstrated in the literature to have a high negative predictive value As regards the treatments to employ in the different situations, the responses of the expert panel were mainly in agreement with the data in the literature. The conclusions of this consensus may help other surgeons when they are faced with a painful knee prosthesis. Copyright © 2013 SECOT. Published by Elsevier Espana. All rights reserved.

  4. TGF-β/Smad signaling in renal fibrosis

    Directory of Open Access Journals (Sweden)

    Xiao-Ming eMeng

    2015-03-01

    Full Text Available TGF-β (transforming growth factor-β is well identified as a central mediator in renal fibrosis. TGF-β initiates canonical and non-canonical pathways to exert multiple biological effects. Among them, Smad signaling is recognized as a major pathway of TGF- signaling in progressive renal fibrosis. During fibrogenesis, Smad3 is highly activated, which is associated with the down-regulation of an inhibitory Smad7 via an ubiquitin E3-ligases-dependent degradation mechanism. The equilibrium shift between Smad3 and Smad7 leads to accumulation and activation of myofibroblasts, overproduction of ECM (extracellular matrix, and reduction in ECM degradation in the diseased kidney. Therefore, overexpression of Smad7 has been shown to be a therapeutic agent for renal fibrosis in various models of kidney diseases. In contrast, another downstream effecter of TGF-β/Smad signaling pathway, Smad2, exerts its renal protective role by counter-regulating the Smad3. Furthermore, recent studies demonstrated that Smad3 mediates renal fibrosis by down-regulating miR-29 and miR-200 but up-regulating miR-21 and miR-192. Thus, overexpression of miR-29 and miR-200 or down-regulation of miR-21 and miR-192 is capable of attenuating Smad3-mediated renal fibrosis in various mouse models of chronic kidney diseases. Taken together, TGF-/Smad signaling plays an important role in renal fibrosis. Targeting TGF-β/Smad3 signaling may represent a specific and effective therapy for chronic kidney diseases associated with renal fibrosis.

  5. Consensus statement on panic disorder from the International Consensus Group on Depression and Anxiety

    NARCIS (Netherlands)

    Ballenger, JC; Lecrubier, Y; Nutt, DJ; Baldwin, DS; den Boer, JA; Kasper, S; Shear, MK

    1998-01-01

    Objective: To provide primary care clinicians with a better understanding of management issues in panic disorder and guide clinical practice with recommendations for appropriate pharmacotherapy. Participants: The 4 members of the International Consensus Group on Depression and Anxiety were James C.

  6. Consensus statement on posttraumatic stress disorder from the International Consensus Group on Depression and Anxiety.

    Science.gov (United States)

    Ballenger, J C; Davidson, J R; Lecrubier, Y; Nutt, D J; Foa, E B; Kessler, R C; McFarlane, A C; Shalev, A Y

    2000-01-01

    To provide primary care clinicians with a better understanding of management issues in posttraumatic stress disorder (PTSD) and guide clinical practice with recommendations on the appropriate management strategy. The 4 members of the International Consensus Group on Depression and Anxiety were James C. Ballenger (chair), Jonathan R. T. Davidson, Yves Lecrubier, and David J. Nutt. Other faculty invited by the chair were Edna B. Foa, Ronald C. Kessler, Alexander C. McFarlane, and Arieh Y. Shalev. The consensus statement is based on the 6 review articles that are published in this supplement and the scientific literature relevant to the issues reviewed in these articles. Group meetings were held over a 2-day period. On day 1, the group discussed the review articles and the chair identified key issues for further debate. On day 2, the group discussed these issues to arrive at a consensus view. After the group meetings, the consensus statement was drafted by the chair and approved by all attendees. PTSD is often a chronic and recurring condition associated with an increased risk of developing secondary comorbid disorders, such as depression. Selective serotonin reuptake inhibitors are generally the most appropriate choice of first-line medication for PTSD, and effective therapy should be continued for 12 months or longer. The most appropriate psychotherapy is exposure therapy, and it should be continued for 6 months, with follow-up therapy as needed.

  7. The Mexican consensus on chronic constipation

    Directory of Open Access Journals (Sweden)

    J.M. Remes-Troche

    2018-04-01

    Full Text Available Introduction: Significant advances have been made in the knowledge and understanding of the epidemiology, pathophysiology, diagnosis, and treatment of chronic constipation, since the publication of the 2011 guidelines on chronic constipation diagnosis and treatment in Mexico from the Asociación Mexicana de Gastroenterología. Aims: To present a consensus review of the current state of knowledge about chronic constipation, providing updated information and integrating the new scientific evidence. Methods: Three general coordinators reviewed the literature published within the time frame of January 2011 and January 2017. From that information, 62 initial statements were formulated and then sent to 12 national experts for their revision. The statements were voted upon, using the Delphi system in 3 voting rounds (2 electronic and one face-to-face. The statements were classified through the GRADE system and those that reached agreement > 75% were included in the consensus. Results and conclusions: The present consensus is made up of 42 final statements that provide updated knowledge, supplementing the information that had not been included in the previous guidelines. The strength of recommendation and quality (level of evidence were established for each statement. The current definitions of chronic constipation, functional constipation, and opioid-induced constipation are given, and diagnostic strategies based on the available diagnostic methods are described. The consensus treatment recommendations were established from evidence on the roles of diet and exercise, fiber, laxatives, new drugs (such as prucalopride, lubiprostone, linaclotide, plecanatide, biofeedback therapy, and surgery. Resumen: Introducción: Desde la publicación de las guías de diagnóstico y tratamiento del estreñimiento crónico (EC en México de la Asociación Mexicana de Gastroenterología en el 2011 se han producido avances significativos en el conocimiento de la

  8. Signal Words

    Science.gov (United States)

    SIGNAL WORDS TOPIC FACT SHEET NPIC fact sheets are designed to answer questions that are commonly asked by the ... making decisions about pesticide use. What are Signal Words? Signal words are found on pesticide product labels, ...

  9. Hyaluronan activates Hyal-2/WWOX/Smad4 signaling and causes bubbling cell death when the signaling complex is overexpressed

    Science.gov (United States)

    Hsu, Li-Jin; Hong, Qunying; Chen, Shur-Tzu; Kuo, Hsiang-Lin; Schultz, Lori; Heath, John; Lin, Sing-Ru; Lee, Ming-Hui; Li, Dong-Zhang; Li, Zih-Ling; Cheng, Hui-Ching; Armand, Gerard; Chang, Nan-Shan

    2017-01-01

    Malignant cancer cells frequently secrete significant amounts of transforming growth factor beta (TGF-β), hyaluronan (HA) and hyaluronidases to facilitate metastasizing to target organs. In a non-canonical signaling, TGF-β binds membrane hyaluronidase Hyal-2 for recruiting tumor suppressors WWOX and Smad4, and the resulting Hyal-2/WWOX/Smad4 complex is accumulated in the nucleus to enhance SMAD-promoter dependent transcriptional activity. Yeast two-hybrid analysis showed that WWOX acts as a bridge to bind both Hyal-2 and Smad4. When WWOX-expressing cells were stimulated with high molecular weight HA, an increased formation of endogenous Hyal-2/WWOX/Smad4 complex occurred rapidly, followed by relocating to the nuclei in 20-40 min. In WWOX-deficient cells, HA failed to induce Smad2/3/4 relocation to the nucleus. To prove the signaling event, we designed a real time tri-molecular FRET analysis and revealed that HA induces the signaling pathway from ectopic Smad4 to WWOX and finally to p53, as well as from Smad4 to Hyal-2 and then to WWOX. An increased binding of the Smad4/Hyal-2/WWOX complex occurs with time in the nucleus that leads to bubbling cell death. In contrast, HA increases the binding of Smad4/WWOX/p53, which causes membrane blebbing but without cell death. In traumatic brain injury-induced neuronal death, the Hyal-2/WWOX complex was accumulated in the apoptotic nuclei of neurons in the rat brains in 24 hr post injury, as determined by immunoelectron microscopy. Together, HA activates the Hyal-2/WWOX/Smad4 signaling and causes bubbling cell death when the signaling complex is overexpressed. PMID:27845895

  10. Hyaluronan activates Hyal-2/WWOX/Smad4 signaling and causes bubbling cell death when the signaling complex is overexpressed.

    Science.gov (United States)

    Hsu, Li-Jin; Hong, Qunying; Chen, Shur-Tzu; Kuo, Hsiang-Lin; Schultz, Lori; Heath, John; Lin, Sing-Ru; Lee, Ming-Hui; Li, Dong-Zhang; Li, Zih-Ling; Cheng, Hui-Ching; Armand, Gerard; Chang, Nan-Shan

    2017-03-21

    Malignant cancer cells frequently secrete significant amounts of transforming growth factor beta (TGF-β), hyaluronan (HA) and hyaluronidases to facilitate metastasizing to target organs. In a non-canonical signaling, TGF-β binds membrane hyaluronidase Hyal-2 for recruiting tumor suppressors WWOX and Smad4, and the resulting Hyal-2/WWOX/Smad4 complex is accumulated in the nucleus to enhance SMAD-promoter dependent transcriptional activity. Yeast two-hybrid analysis showed that WWOX acts as a bridge to bind both Hyal-2 and Smad4. When WWOX-expressing cells were stimulated with high molecular weight HA, an increased formation of endogenous Hyal-2/WWOX/Smad4 complex occurred rapidly, followed by relocating to the nuclei in 20-40 min. In WWOX-deficient cells, HA failed to induce Smad2/3/4 relocation to the nucleus. To prove the signaling event, we designed a real time tri-molecular FRET analysis and revealed that HA induces the signaling pathway from ectopic Smad4 to WWOX and finally to p53, as well as from Smad4 to Hyal-2 and then to WWOX. An increased binding of the Smad4/Hyal-2/WWOX complex occurs with time in the nucleus that leads to bubbling cell death. In contrast, HA increases the binding of Smad4/WWOX/p53, which causes membrane blebbing but without cell death. In traumatic brain injury-induced neuronal death, the Hyal-2/WWOX complex was accumulated in the apoptotic nuclei of neurons in the rat brains in 24 hr post injury, as determined by immunoelectron microscopy. Together, HA activates the Hyal-2/WWOX/Smad4 signaling and causes bubbling cell death when the signaling complex is overexpressed.

  11. Distributed Estimation using Bayesian Consensus Filtering

    Science.gov (United States)

    2014-06-06

    Convergence rate analysis of distributed gossip (linear parameter) estimation: Fundamental limits and tradeoffs,” IEEE J. Sel. Topics Signal Process...Dimakis, S. Kar, J. Moura, M. Rabbat, and A. Scaglione, “ Gossip algorithms for distributed signal processing,” Proc. of the IEEE, vol. 98, no. 11, pp

  12. On the Control of Consensus Networks: Theory and Applications

    Science.gov (United States)

    Hudoba de Badyn, Mathias

    Signed networks allow the study of positive and negative interactions between agents. In this thesis, three papers are presented that address controllability of networked dynamics. First, controllability of signed consensus networks is approached from a symmetry perspective, for both linear and nonlinear consensus protocols. It is shown that the graph-theoretic property of signed networks known as structural balance renders the consensus protocol uncontrollable when coupled with a certain type of symmetry. Stabilizability and output controllability of signed linear consensus is also examined, as well as a data-driven approach to finding bipartite consensus stemming from structural balance for signed nonlinear consensus. Second, an algorithm is constructed that allows one to grow a network while preserving controllability, and some generalizations of this algorithm are presented. Submodular optimization is used to analyze a second algorithm that adds nodes to a network to maximize the network connectivity.

  13. Operationalising emergency care delivery in sub-Saharan Africa: consensus-based recommendations for healthcare facilities.

    Science.gov (United States)

    Calvello, Emilie J B; Tenner, Andrea G; Broccoli, Morgan C; Skog, Alexander P; Muck, Andrew E; Tupesis, Janis P; Brysiewicz, Petra; Teklu, Sisay; Wallis, Lee; Reynolds, Teri

    2016-08-01

    A major barrier to successful integration of acute care into health systems is the lack of consensus on the essential components of emergency care within resource-limited environments. The 2013 African Federation of Emergency Medicine Consensus Conference was convened to address the growing need for practical solutions to further implementation of emergency care in sub-Saharan Africa. Over 40 participants from 15 countries participated in the working group that focused on emergency care delivery at health facilities. Using the well-established approach developed in the WHO's Monitoring Emergency Obstetric Care, the workgroup identified the essential services delivered-signal functions-associated with each emergency care sentinel condition. Levels of emergency care were assigned based on the expected capacity of the facility to perform signal functions, and the necessary human, equipment and infrastructure resources identified. These consensus-based recommendations provide the foundation for objective facility capacity assessment in developing emergency health systems that can bolster strategic planning as well as facilitate monitoring and evaluation of service delivery. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

  14. Consensus of Heterogeneous Multiagent Systems with Arbitrarily Bounded Communication Delay

    Directory of Open Access Journals (Sweden)

    Xue Li

    2017-01-01

    Full Text Available This paper focuses on the consensus problem of high-order heterogeneous multiagent systems with arbitrarily bounded communication delays. Through the method of nonnegative matrices, we get a sufficient consensus condition for the systems with dynamically changing topology. The results of this paper show, even when there are arbitrarily bounded communication delays in the systems, all agents can reach a consensus no matter whether there are spanning trees for the corresponding communication graphs at any time.

  15. Consensus states of local majority rule in stochastic process

    Energy Technology Data Exchange (ETDEWEB)

    Luo, Yu-Pin [Department of Electronic Engineering, National Formosa University, Huwei, 63201, Taiwan (China); Tang, Chia-Wei; Xu, Hong-Yuan [Department of Physics, Chung-Yuan Christian University, Chungli, 32023, Taiwan (China); Wu, Jinn-Wen [Department of Applied Mathematics, Chung-Yuan Christian University, Chungli, 32023, Taiwan (China); Huang, Ming-Chang, E-mail: mchuang@cycu.edu.tw [Center for Theoretical Science and Department of Physics, Chung-Yuan Christian University, Chungli, 32023, Taiwan (China)

    2015-04-03

    A sufficient condition for a network system to reach a consensus state of the local majority rule is shown. The influence of interpersonal environment on the occurrence probability of consensus states for Watts–Strogatz and scale-free networks with random initial states is analyzed by numerical method. We also propose a stochastic local majority rule to study the mean first passage time from a random state to a consensus and the escape rate from a consensus state for systems in a noisy environment. Our numerical results show that there exists a window of fluctuation strengths for which the mean first passage time from a random to a consensus state reduces greatly, and the escape rate of consensus states obeys the Arrhenius equation in the window. - Highlights: • A sufficient condition for reaching a consensus. • The relation between the geometry of networks and the reachability of a consensus. • Stochastic local majority rule. • The mean first-passage time and the escape rate of consensus states.

  16. Consensus states of local majority rule in stochastic process

    International Nuclear Information System (INIS)

    Luo, Yu-Pin; Tang, Chia-Wei; Xu, Hong-Yuan; Wu, Jinn-Wen; Huang, Ming-Chang

    2015-01-01

    A sufficient condition for a network system to reach a consensus state of the local majority rule is shown. The influence of interpersonal environment on the occurrence probability of consensus states for Watts–Strogatz and scale-free networks with random initial states is analyzed by numerical method. We also propose a stochastic local majority rule to study the mean first passage time from a random state to a consensus and the escape rate from a consensus state for systems in a noisy environment. Our numerical results show that there exists a window of fluctuation strengths for which the mean first passage time from a random to a consensus state reduces greatly, and the escape rate of consensus states obeys the Arrhenius equation in the window. - Highlights: • A sufficient condition for reaching a consensus. • The relation between the geometry of networks and the reachability of a consensus. • Stochastic local majority rule. • The mean first-passage time and the escape rate of consensus states

  17. Cultural Consensus Theory for the ordinal data case.

    Science.gov (United States)

    Anders, Royce; Batchelder, William H

    2015-03-01

    A Cultural Consensus Theory approach for ordinal data is developed, leading to a new model for ordered polytomous data. The model introduces a novel way of measuring response biases and also measures consensus item values, a consensus response scale, item difficulty, and informant knowledge. The model is extended as a finite mixture model to fit both simulated and real multicultural data, in which subgroups of informants have different sets of consensus item values. The extension is thus a form of model-based clustering for ordinal data. The hierarchical Bayesian framework is utilized for inference, and two posterior predictive checks are developed to verify the central assumptions of the model.

  18. Rooted triple consensus and anomalous gene trees

    Directory of Open Access Journals (Sweden)

    Schmidt Heiko A

    2008-04-01

    Full Text Available Abstract Background Anomalous gene trees (AGTs are gene trees with a topology different from a species tree that are more probable to observe than congruent gene trees. In this paper we propose a rooted triple approach to finding the correct species tree in the presence of AGTs. Results Based on simulated data we show that our method outperforms the extended majority rule consensus strategy, while still resolving the species tree. Applying both methods to a metazoan data set of 216 genes, we tested whether AGTs substantially interfere with the reconstruction of the metazoan phylogeny. Conclusion Evidence of AGTs was not found in this data set, suggesting that erroneously reconstructed gene trees are the most significant challenge in the reconstruction of phylogenetic relationships among species with current data. The new method does however rule out the erroneous reconstruction of deep or poorly resolved splits in the presence of lineage sorting.

  19. Using Network Dynamical Influence to Drive Consensus

    Science.gov (United States)

    Punzo, Giuliano; Young, George F.; MacDonald, Malcolm; Leonard, Naomi E.

    2016-05-01

    Consensus and decision-making are often analysed in the context of networks, with many studies focusing attention on ranking the nodes of a network depending on their relative importance to information routing. Dynamical influence ranks the nodes with respect to their ability to influence the evolution of the associated network dynamical system. In this study it is shown that dynamical influence not only ranks the nodes, but also provides a naturally optimised distribution of effort to steer a network from one state to another. An example is provided where the “steering” refers to the physical change in velocity of self-propelled agents interacting through a network. Distinct from other works on this subject, this study looks at directed and hence more general graphs. The findings are presented with a theoretical angle, without targeting particular applications or networked systems; however, the framework and results offer parallels with biological flocks and swarms and opportunities for design of technological networks.

  20. [First Mexican Consensus of Vaccination in Adults].

    Science.gov (United States)

    Gutiérrez-Robledo, Luis Miguel; Caro-López, Elizabeth; Guerrero-Almeida, María de Lourdes; Dehesa-Violante, Margarita; Rodríguez-Noriega, Eduardo; García-Lara, Juan Miguel; Medina-López, Zaira; Báez-Saldaña, Renata; Díaz-López, Elsa; Avila-Fematt, Flor Maria de Guadalupe; Betancourt-Cravioto, Miguel; Garcia-Garcia, Lourdes

    2017-03-01

    For years our efforts have been focused on vaccination during childhood. Today we know that this is not enough to ensure health in the rest of the life. Childhood is as important as any other stage and, therefore, vaccination must be permanent and differentiated, according to our age, throughout life. Introducing a life course perspective in vaccination programs, with emphasis on adult vaccination, particularly in older adults, offers us the opportunity to review the performance of health programs, actions, and services in the field of immunization, as well as strengthening health promotion actions. In this context, the first Mexican Consensus on Adult Vaccination was carried out in a joint effort of the National Institute of Geriatrics, bringing together a group of specialists who worked on three central objectives: establishing vaccination guidelines throughout the life course, with emphasis on new vaccines; defining priority groups according to their risk factors; and contributing to the effort to promote healthy aging.

  1. Consensus and new improvements of disability glare

    Directory of Open Access Journals (Sweden)

    Yu-Wei Zheng

    2014-12-01

    Full Text Available Patients with early cataract may have normal visual acuity(VAbut complain that they have problems in driving at night, like seeing things through a veil. This phenomenon is defined as disability glare which maybe caused by growing stray light. Patients with intraocular lens following cataract surgery may complain about glare, halos and shadows in visual field, which are also resulted from dysphotopia. Disability glare is the VA loss due to disturbing luminance in visual field. In other words, it's the retinal contrast sensitivity reduction because of the straylight. This article contains the consensus and new progress of disability glare. It provides solutions according to its effect factors and offers clues for further study.

  2. Achieving Consensus Through Professionalized Head Nods

    DEFF Research Database (Denmark)

    Oshima, Sae

    2014-01-01

    of nodding in a particular professional-client setting, namely, hair salon interactions. My interest specifically lies in the frequent occurrence of synchronized head nods during the “service-assessment sequence,” where both service provider and customer inspect and determine whether the completed work...... is adequate. I pursue mechanisms of synchronized head nods by revealing exactly how participants collaborate in producing a nod, and how their verbal actions may at times be designed accordingly. In doing so, the study provides insight into what consensus may look like at service encounters in Japan......While the interactional functions of head nodding in everyday Japanese conversation have been frequently studied, a discourse on head nodding as a professional communicative practice has yet to be explored. With the method of multimodal conversation analysis, the current study examines the role...

  3. Distributed consensus and fault tolerance - Lecture 2

    CERN Multimedia

    CERN. Geneva

    2017-01-01

    In a world where clusters with thousands of nodes are becoming commonplace, we are often faced with the task of having them coordinate and share state. As the number of machines goes up, so does the probability that something goes wrong: a node could temporarily lose connectivity, crash because of some race condition, or have its hard drive fail. What are the challenges when designing fault-tolerant distributed systems, where a cluster is able to survive the loss of individual nodes? In this lecture, we will discuss some basics on this topic (consistency models, CAP theorem, failure modes, byzantine faults), detail the raft consensus algorithm, and showcase an interesting example of a highly resilient distributed system, bitcoin.

  4. Distributed consensus and fault tolerance - Lecture 1

    CERN Multimedia

    CERN. Geneva

    2017-01-01

    In a world where clusters with thousands of nodes are becoming commonplace, we are often faced with the task of having them coordinate and share state. As the number of machines goes up, so does the probability that something goes wrong: a node could temporarily lose connectivity, crash because of some race condition, or have its hard drive fail. What are the challenges when designing fault-tolerant distributed systems, where a cluster is able to survive the loss of individual nodes? In this lecture, we will discuss some basics on this topic (consistency models, CAP theorem, failure modes, byzantine faults), detail the raft consensus algorithm, and showcase an interesting example of a highly resilient distributed system, bitcoin.

  5. Consensus strategy in genes prioritization and combined bioinformatics analysis for preeclampsia pathogenesis.

    Science.gov (United States)

    Tejera, Eduardo; Cruz-Monteagudo, Maykel; Burgos, Germán; Sánchez, María-Eugenia; Sánchez-Rodríguez, Aminael; Pérez-Castillo, Yunierkis; Borges, Fernanda; Cordeiro, Maria Natália Dias Soeiro; Paz-Y-Miño, César; Rebelo, Irene

    2017-08-08

    Preeclampsia is a multifactorial disease with unknown pathogenesis. Even when recent studies explored this disease using several bioinformatics tools, the main objective was not directed to pathogenesis. Additionally, consensus prioritization was proved to be highly efficient in the recognition of genes-disease association. However, not information is available about the consensus ability to early recognize genes directly involved in pathogenesis. Therefore our aim in this study is to apply several theoretical approaches to explore preeclampsia; specifically those genes directly involved in the pathogenesis. We firstly evaluated the consensus between 12 prioritization strategies to early recognize pathogenic genes related to preeclampsia. A communality analysis in the protein-protein interaction network of previously selected genes was done including further enrichment analysis. The enrichment analysis includes metabolic pathways as well as gene ontology. Microarray data was also collected and used in order to confirm our results or as a strategy to weight the previously enriched pathways. The consensus prioritized gene list was rationally filtered to 476 genes using several criteria. The communality analysis showed an enrichment of communities connected with VEGF-signaling pathway. This pathway is also enriched considering the microarray data. Our result point to VEGF, FLT1 and KDR as relevant pathogenic genes, as well as those connected with NO metabolism. Our results revealed that consensus strategy improve the detection and initial enrichment of pathogenic genes, at least in preeclampsia condition. Moreover the combination of the first percent of the prioritized genes with protein-protein interaction network followed by communality analysis reduces the gene space. This approach actually identifies well known genes related with pathogenesis. However, genes like HSP90, PAK2, CD247 and others included in the first 1% of the prioritized list need to be further

  6. Consensus classification of posterior cortical atrophy.

    Science.gov (United States)

    Crutch, Sebastian J; Schott, Jonathan M; Rabinovici, Gil D; Murray, Melissa; Snowden, Julie S; van der Flier, Wiesje M; Dickerson, Bradford C; Vandenberghe, Rik; Ahmed, Samrah; Bak, Thomas H; Boeve, Bradley F; Butler, Christopher; Cappa, Stefano F; Ceccaldi, Mathieu; de Souza, Leonardo Cruz; Dubois, Bruno; Felician, Olivier; Galasko, Douglas; Graff-Radford, Jonathan; Graff-Radford, Neill R; Hof, Patrick R; Krolak-Salmon, Pierre; Lehmann, Manja; Magnin, Eloi; Mendez, Mario F; Nestor, Peter J; Onyike, Chiadi U; Pelak, Victoria S; Pijnenburg, Yolande; Primativo, Silvia; Rossor, Martin N; Ryan, Natalie S; Scheltens, Philip; Shakespeare, Timothy J; Suárez González, Aida; Tang-Wai, David F; Yong, Keir X X; Carrillo, Maria; Fox, Nick C

    2017-08-01

    A classification framework for posterior cortical atrophy (PCA) is proposed to improve the uniformity of definition of the syndrome in a variety of research settings. Consensus statements about PCA were developed through a detailed literature review, the formation of an international multidisciplinary working party which convened on four occasions, and a Web-based quantitative survey regarding symptom frequency and the conceptualization of PCA. A three-level classification framework for PCA is described comprising both syndrome- and disease-level descriptions. Classification level 1 (PCA) defines the core clinical, cognitive, and neuroimaging features and exclusion criteria of the clinico-radiological syndrome. Classification level 2 (PCA-pure, PCA-plus) establishes whether, in addition to the core PCA syndrome, the core features of any other neurodegenerative syndromes are present. Classification level 3 (PCA attributable to AD [PCA-AD], Lewy body disease [PCA-LBD], corticobasal degeneration [PCA-CBD], prion disease [PCA-prion]) provides a more formal determination of the underlying cause of the PCA syndrome, based on available pathophysiological biomarker evidence. The issue of additional syndrome-level descriptors is discussed in relation to the challenges of defining stages of syndrome severity and characterizing phenotypic heterogeneity within the PCA spectrum. There was strong agreement regarding the definition of the core clinico-radiological syndrome, meaning that the current consensus statement should be regarded as a refinement, development, and extension of previous single-center PCA criteria rather than any wholesale alteration or redescription of the syndrome. The framework and terminology may facilitate the interpretation of research data across studies, be applicable across a broad range of research scenarios (e.g., behavioral interventions, pharmacological trials), and provide a foundation for future collaborative work. Copyright © 2017 The Authors

  7. The Mexican consensus on probiotics in gastroenterology.

    Science.gov (United States)

    Valdovinos, M A; Montijo, E; Abreu, A T; Heller, S; González-Garay, A; Bacarreza, D; Bielsa-Fernández, M; Bojórquez-Ramos, M C; Bosques-Padilla, F; Burguete-García, A I; Carmona-Sánchez, R; Consuelo-Sánchez, A; Coss-Adame, E; Chávez-Barrera, J A; de Ariño, M; Flores-Calderón, J; Gómez-Escudero, O; González-Huezo, M S; Icaza-Chávez, M E; Larrosa-Haro, A; Morales-Arámbula, M; Murata, C; Ramírez-Mayans, J A; Remes-Troche, J M; Rizo-Robles, T; Peláez-Luna, M; Toro-Monjaraz, E M; Torre, A; Urquidi-Rivera, M E; Vázquez, R; Yamamoto-Furusho, J K; Guarner, F

    Probiotics are frequently prescribed in clinical practice. Their efficacy in treating gastrointestinal disorders is supported by a significant number of clinical trials. However, the correct prescription of these agents is hampered due to a lack of knowledge of the scientific evidence and to the different presentations and microbial compositions of the probiotics that are currently available. To provide the clinician with a consensus review of probiotics and recommendations for their use in gastroenterology. Controlled clinical trials, meta-analyses, and systematic reviews published up to 2015 were selected, using the MESH terms: probiotics, gastrointestinal diseases, humans, adults, AND children. The Delphi method was employed. Eighteen gastroenterologists treating adult patients and 14 pediatric gastroenterologists formulated statements that were voted on until agreement>70% was reached. The level of evidence based on the GRADE system was evaluated for each statement. Eleven statements on the general concepts of probiotics and 27 statements on the use of probiotics in gastrointestinal diseases in both adults and children were formulated. The consensus group recommends the use of probiotics under the following clinical conditions: the prevention of diarrhea associated with antibiotics, the treatment of acute infectious diarrhea, the prevention of Clostridium difficile infection and necrotizing enterocolitis, the reduction of adverse events from Helicobacter pylori eradication therapy, relief from irritable bowel syndrome symptoms, the treatment of functional constipation in the adult, and the induction and maintenance of remission in patients with ulcerative colitis and pouchitis, and the treatment of covert and overt hepatic encephalopathy. Copyright © 2016 Asociación Mexicana de Gastroenterología. Publicado por Masson Doyma México S.A. All rights reserved.

  8. Consensus for the management of IPMN

    International Nuclear Information System (INIS)

    Tanaka, Masao

    2012-01-01

    International Consensus Guidelines for management of intraductal papillary mucious neoplasms (IPMIN) and mucious cystic neoplasms (MCN) of the pancreas defined their difference in 2006 Sendai Conference, and this paper describes about their still remaining problem in the consensus by referring related literatures. The author explains the macroscopic classification of IPMIN in types of brunch duct (BD), main duct (MD) and their mixture. Guidelines are obscure concerning which of the histology or preoperative imaging is appropriate for diagnosis of the mixed type and the author considers that the latter imaging is better as the method used has influence on indication of surgery thereafter. MD-IPMIN is easily diagnosed differentially from chronic pantreatitis, but differential diagnosis of BD-IPMIN and other cystic lesion is rather complex, particularly, for MCN tending to malignancy and macrocystic serous CN (SCN). For this, analysis of the intraductal mucious liquid obtained by endoscopic ultrasonography-fine needle aspiration biopsy (EUS-FNA) is useful but its safety to see the grade of malignancy for extending the indication leading to resection is not established. Diagnosis of the malignancy of BD-IPMIN can be done best based on the presence of mural nodules, and other markers are of low reliability. In fact, cysts with >3 cm, when resected, are found mostly (80%) benign, indicating the necessity of a more reliable sign and of detailed classification of sub-tissue type. The purpose of progress observation involves diagnoses of changing to malignancy, of concurrent cancer and of recurrence of resected lesion, and an author's case report of this is given with MR cholangiopancreatography (MRCP), CT and MRI images. Observatory approach, interval and period of the disease progression are yet unestablished. (T.T.)

  9. 2003 Canadian Asthma Consensus Guidelines Executive Summary

    Directory of Open Access Journals (Sweden)

    Becker Allan

    2006-03-01

    Full Text Available Abstract Background Guidelines for the diagnosis and management of asthma have been published over the last 15 years; however, there has been little focus on issues relating to asthma in childhood. Since the last revision of the 1999 Canadian Asthma Consensus Report, important new studies, particularly in children, have highlighted the need to incorporate new information into the asthma guidelines. The objectives of this article are to review the literature on asthma published between January 2000 and June 2003 and to evaluate the influence of new evidence on the recommendations made in the 1999 Canadian Asthma Consensus Report and its 2001 update, with a major focus on pediatric issues. Methods The diagnosis of asthma in young children and prevention strategies, pharmacotherapy, inhalation devices, immunotherapy, and asthma education were selected for review by small expert resource groups. The reviews were discussed in June 2003 at a meeting under the auspices of the Canadian Network For Asthma Care and the Canadian Thoracic Society. Data published through December 2004 were subsequently reviewed by the individual expert resource groups. Results This report evaluates early-life prevention strategies and focuses on treatment of asthma in children, emphasizing the importance of early diagnosis and preventive therapy, the benefits of additional therapy, and the essential role of asthma education. Conclusion We generally support previous recommendations and focus on new issues, particularly those relevant to children and their families. This document is a guide for asthma management based on the best available published data and the opinion of health care professionals, including asthma experts and educators.

  10. Robust point matching via vector field consensus.

    Science.gov (United States)

    Jiayi Ma; Ji Zhao; Jinwen Tian; Yuille, Alan L; Zhuowen Tu

    2014-04-01

    In this paper, we propose an efficient algorithm, called vector field consensus, for establishing robust point correspondences between two sets of points. Our algorithm starts by creating a set of putative correspondences which can contain a very large number of false correspondences, or outliers, in addition to a limited number of true correspondences (inliers). Next, we solve for correspondence by interpolating a vector field between the two point sets, which involves estimating a consensus of inlier points whose matching follows a nonparametric geometrical constraint. We formulate this a maximum a posteriori (MAP) estimation of a Bayesian model with hidden/latent variables indicating whether matches in the putative set are outliers or inliers. We impose nonparametric geometrical constraints on the correspondence, as a prior distribution, using Tikhonov regularizers in a reproducing kernel Hilbert space. MAP estimation is performed by the EM algorithm which by also estimating the variance of the prior model (initialized to a large value) is able to obtain good estimates very quickly (e.g., avoiding many of the local minima inherent in this formulation). We illustrate this method on data sets in 2D and 3D and demonstrate that it is robust to a very large number of outliers (even up to 90%). We also show that in the special case where there is an underlying parametric geometrical model (e.g., the epipolar line constraint) that we obtain better results than standard alternatives like RANSAC if a large number of outliers are present. This suggests a two-stage strategy, where we use our nonparametric model to reduce the size of the putative set and then apply a parametric variant of our approach to estimate the geometric parameters. Our algorithm is computationally efficient and we provide code for others to use it. In addition, our approach is general and can be applied to other problems, such as learning with a badly corrupted training data set.

  11. Distributed Consensus of Stochastic Delayed Multi-agent Systems Under Asynchronous Switching.

    Science.gov (United States)

    Wu, Xiaotai; Tang, Yang; Cao, Jinde; Zhang, Wenbing

    2016-08-01

    In this paper, the distributed exponential consensus of stochastic delayed multi-agent systems with nonlinear dynamics is investigated under asynchronous switching. The asynchronous switching considered here is to account for the time of identifying the active modes of multi-agent systems. After receipt of confirmation of mode's switching, the matched controller can be applied, which means that the switching time of the matched controller in each node usually lags behind that of system switching. In order to handle the coexistence of switched signals and stochastic disturbances, a comparison principle of stochastic switched delayed systems is first proved. By means of this extended comparison principle, several easy to verified conditions for the existence of an asynchronously switched distributed controller are derived such that stochastic delayed multi-agent systems with asynchronous switching and nonlinear dynamics can achieve global exponential consensus. Two examples are given to illustrate the effectiveness of the proposed method.

  12. An adaptive critic-based scheme for consensus control of nonlinear multi-agent systems

    Science.gov (United States)

    Heydari, Ali; Balakrishnan, S. N.

    2014-12-01

    The problem of decentralised consensus control of a network of heterogeneous nonlinear systems is formulated as an optimal tracking problem and a solution is proposed using an approximate dynamic programming based neurocontroller. The neurocontroller training comprises an initial offline training phase and an online re-optimisation phase to account for the fact that the reference signal subject to tracking is not fully known and available ahead of time, i.e., during the offline training phase. As long as the dynamics of the agents are controllable, and the communication graph has a directed spanning tree, this scheme guarantees the synchronisation/consensus even under switching communication topology and directed communication graph. Finally, an aerospace application is selected for the evaluation of the performance of the method. Simulation results demonstrate the potential of the scheme.

  13. A Requirement for ZAK Kinase Activity in Canonical TGF-β Signaling

    Directory of Open Access Journals (Sweden)

    Shyam Nyati

    2016-12-01

    Full Text Available The sterile alpha motif and leucine zipper containing kinase ZAK (AZK, MLT, MLK7, is a MAPK-kinase kinase (MKKK. Like most MAPKKKs which are known to activate the c-Jun. amino-terminal kinase (JNK pathway, ZAK has been shown to participate in the transduction of Transforming growth factor-β (TGF-β-mediated non-canonical signaling. A role for ZAK in SMAD-dependent, canonical TGF-β signaling has not been previously appreciated. Using a combination of functional genomics and biochemical techniques, we demonstrate that ZAK regulates canonical TGFβRI/II signaling in lung and breast cancer cell lines and may serve as a key node in the regulation of TGFBR kinase activity. Remarkably, we demonstrate that siRNA mediated depletion of ZAK strongly inhibited TGF-β dependent SMAD2/3 activation and subsequent promoter activation (SMAD binding element driven luciferase expression; SBE4-Luc. A ZAK specific inhibitor (DHP-2, dose-dependently activated the bioluminescent TGFBR-kinase activity reporter (BTR, blocked TGF-β induced SMAD2/3 phosphorylation and SBE4-Luc activation and cancer cell-invasion. In aggregate, these findings identify a novel role for the ZAK kinase in canonical TGF-β signaling and an invasive cancer cell phenotype thus providing a novel target for TGF-β inhibition.

  14. CCTOP: a Consensus Constrained TOPology prediction web server.

    Science.gov (United States)

    Dobson, László; Reményi, István; Tusnády, Gábor E

    2015-07-01

    The Consensus Constrained TOPology prediction (CCTOP; http://cctop.enzim.ttk.mta.hu) server is a web-based application providing transmembrane topology prediction. In addition to utilizing 10 different state-of-the-art topology prediction methods, the CCTOP server incorporates topology information from existing experimental and computational sources available in the PDBTM, TOPDB and TOPDOM databases using the probabilistic framework of hidden Markov model. The server provides the option to precede the topology prediction with signal peptide prediction and transmembrane-globular protein discrimination. The initial result can be recalculated by (de)selecting any of the prediction methods or mapped experiments or by adding user specified constraints. CCTOP showed superior performance to existing approaches. The reliability of each prediction is also calculated, which correlates with the accuracy of the per protein topology prediction. The prediction results and the collected experimental information are visualized on the CCTOP home page and can be downloaded in XML format. Programmable access of the CCTOP server is also available, and an example of client-side script is provided. © The Author(s) 2015. Published by Oxford University Press on behalf of Nucleic Acids Research.

  15. A consensus definition of cataplexy in mouse models of narcolepsy.

    Science.gov (United States)

    Scammell, Thomas E; Willie, Jon T; Guilleminault, Christian; Siegel, Jerome M

    2009-01-01

    People with narcolepsy often have episodes of cataplexy, brief periods of muscle weakness triggered by strong emotions. Many researchers are now studying mouse models of narcolepsy, but definitions of cataplexy-like behavior in mice differ across labs. To establish a common language, the International Working Group on Rodent Models of Narcolepsy reviewed the literature on cataplexy in people with narcolepsy and in dog and mouse models of narcolepsy and then developed a consensus definition of murine cataplexy. The group concluded that murine cataplexy is an abrupt episode of nuchal atonia lasting at least 10 seconds. In addition, theta activity dominates the EEG during the episode, and video recordings document immobility. To distinguish a cataplexy episode from REM sleep after a brief awakening, at least 40 seconds of wakefulness must precede the episode. Bouts of cataplexy fitting this definition are common in mice with disrupted orexin/hypocretin signaling, but these events almost never occur in wild type mice. It remains unclear whether murine cataplexy is triggered by strong emotions or whether mice remain conscious during the episodes as in people with narcolepsy. This working definition provides helpful insights into murine cataplexy and should allow objective and accurate comparisons of cataplexy in future studies using mouse models of narcolepsy.

  16. CD137 is induced by the CD40 signal on chronic lymphocytic leukemia B cells and transduces the survival signal via NF-κB activation.

    Directory of Open Access Journals (Sweden)

    Yukana Nakaima

    Full Text Available CD137 is a member of the tumor necrosis factor receptor family that is expressed on activated T cells. This molecule provides a co-stimulatory signal that enhances the survival, and differentiation of cells, and has a crucial role in the development of CD8 cytotoxic T cells and anti-tumor immunity. Here we report that CD137 expression is also induced on normal or malignant human B cells by CD40 ligation by its ligand CD154. This CD137 induction was more prominent in chronic lymphocytic leukemia (CLL cells than in other types of B cells. CD137 stimulation on B cells by its ligand induced the nuclear translocation of p52 (a non-canonical NF-κB factor. In agreement with this finding, expression of the survival factor BCL-XL was upregulated. Consequently, the CD137 signal augmented the survival of CD154-stimulated CLL B cells in vitro. This unexpected induction of CD137 on B cells by CD40 signal may influence the clinical course of CLL.

  17. Distributed Data-aggregation Consensus for Sensor Networks: Relaxation of Consensus Concept and Convergence Property

    Science.gov (United States)

    2014-08-01

    consensus algorithm called randomized gossip is more suitable [7, 8]. In asynchronous randomized gossip algorithms, pairs of neighboring nodes exchange...messages and perform updates in an asynchronous and unattended manner, and they also 1 The class of broadcast gossip algorithms [9, 10, 11, 12] are...dynamics [2] and asynchronous pairwise randomized gossip [7, 8], broadcast gossip algorithms do not require that nodes know the identities of their

  18. Consensus statement on generalized anxiety disorder from the International Consensus Group on Depression and Anxiety.

    Science.gov (United States)

    Ballenger, J C; Davidson, J R; Lecrubier, Y; Nutt, D J; Borkovec, T D; Rickels, K; Stein, D J; Wittchen, H U

    2001-01-01

    To provide primary care clinicians with a better understanding of management issues in generalized anxiety disorder (GAD) and guide clinical practice with recommendations on the appropriate treatment strategy. The 4 members of the International Consensus Group on Depression and Anxiety were James C. Ballenger (chair), Jonathan R.T. Davidson, Yves Lecrubier, and David J. Nutt. Four additional faculty members invited by the chair were Karl Rickels, Hans-Ulrich Wittchen, Dan J. Stein, and Thomas D. Borkovec. The consensus statement is based on the 6 review articles that are published in this supplement and the scientific literature relevant to the issues reviewed in these articles. Group meetings were held over a 2-day period. On day 1, the group discussed the review articles and the chair identified key issues for further debate. On day 2, the group discussed these issues to arrive at a consensus view. After the group meetings, the consensus statement was drafted by the chair and approved by all attendees. GAD is the most common anxiety disorder in primary care and is highly debilitating. Furthermore, it is frequently comorbid with depression and other anxiety disorders, which exacerbates functional impairment. Antidepressants (serotonin reuptake inhibitors, serotonin-norepinephrine reuptake inhibitors, and nonsedating tricyclic antidepressants) are generally the most appropriate first-line pharmacotherapy for GAD, since they are also effective against comorbid psychiatric disorders and are suitable for long-term use. Cognitive-behavioral therapy is the preferred form of psychotherapy for GAD, although when GAD is comorbid with depression, pharmacotherapy is increasingly indicated.

  19. Kyoto global consensus report on Helicobacter pylori gastritis

    NARCIS (Netherlands)

    K. Sugano (Kentaro); J. Tack (Jan); E.J. Kuipers (Ernst); D.Y. Graham (David Y.); E. El-Omar; S. Miura (Soichiro); K. Haruma (Ken); M. Asaka (Masahiro); N. Uemura (Naomi); P. Malfertheiner

    2015-01-01

    textabstractObjective To present results of the Kyoto Global Consensus Meeting, which was convened to develop global consensus on (1) classification of chronic gastritis and duodenitis, (2) clinical distinction of dyspepsia caused by Helicobacter pylori from functional dyspepsia, (3) appropriate

  20. Treatment of adrenocorticotropin-dependent cushing's syndrome: A consensus statement

    NARCIS (Netherlands)

    B.M.K. Biller; A. Grossman (Ashley Barry); P.M. Stewart; S. Melmed (Shlomo); X. Bertagna; J. Bertherat (Jerome); M. Buchfelder; A. Colao (Annamaria); A.R.M.M. Hermus (Ad); L.J. Hofland (Leo); A. Klibanski; A. Lacroix; J.R. Lindsay; J. Newell-Price (John); L.K. Nieman; S. Petersenn; N. Sonino; G.K. Stalla (Günter); B. Swearingen; M.L. Vance; J.A.H. Wass (John); M. Boscaro

    2008-01-01

    textabstractObjective: Our objective was to evaluate the published literature and reach a consensus on the treatment of patients with ACTH-dependent Cushing's syndrome, because there is no recent consensus on the management of this rare disorder. Participants: Thirty-two leading endocrinologists,

  1. Treatment of adrenocorticotropin-dependent Cushing's syndrome: a consensus statement.

    NARCIS (Netherlands)

    Biller, B.M.; Grossman, A.B.; Stewart, P.M.; Melmed, S.; Bertagna, X.; Bertherat, J.; Buchfelder, M.; Colao, A.; Hermus, A.R.M.M.; Hofland, L.J.; Klibanski, A.; Lacroix, A.; Lindsay, J.R.; Newell-Price, J.; Nieman, L.K.; Petersenn, S.; Sonino, N.; Stalla, G.K.; Swearingen, B.; Vance, M.L.; Wass, J.A.; Boscaro, M.

    2008-01-01

    OBJECTIVE: Our objective was to evaluate the published literature and reach a consensus on the treatment of patients with ACTH-dependent Cushing's syndrome, because there is no recent consensus on the management of this rare disorder. PARTICIPANTS: Thirty-two leading endocrinologists, clinicians,

  2. Communitarian Consensus: A New Social Philosophy for Good ...

    African Journals Online (AJOL)

    ... and discuss the communitarian consensus as a new social philosophy of development and reconstruction for Africa. The notion of consensus as first canvassed by Kwasi Wiredu, is an important element in traditional African societies. It revolves around the view that African should be able to speak with one voice on issues ...

  3. 75 FR 70074 - Consensus Standards, Light-Sport Aircraft

    Science.gov (United States)

    2010-11-16

    ... DEPARTMENT OF TRANSPORTATION Federal Aviation Administration Consensus Standards, Light-Sport... accepted consensus standards relating to the provisions of the Sport Pilot and Light-Sport Aircraft rule issued July 16, 2004, and effective September 1, 2004. ASTM International Committee F37 on Light Sport...

  4. Power, conflict and consensus building in Africa: Ideology revisited ...

    African Journals Online (AJOL)

    This paper interrogates and rejects the effectiveness of consensus building as a mechanism for conflict resolution in Africa. Drawing from the conflict/consensus theoretical debates of the 1960s, the paper argues that because of the inherent character of power, and considering the nature of the state in Africa which is ...

  5. Insulin Signaling in the Aging of Healthy and Proteotoxically Stressed Mechanosensory Neurons

    Directory of Open Access Journals (Sweden)

    Courtney eScerbak

    2014-07-01

    Full Text Available Insulin signaling is central to cellular metabolism and organismal aging. However, the role of insulin signaling in natural and proteotoxically stressed aging neurons has yet to be fully described. We studied aging of Caenorbaditis elegans mechanosensory neurons expressing a neurotoxic expanded polyglutamine transgene (polyQ128, or lacking this proteotoxicity stressor (polyQ0, under conditions in which the insulin signaling pathway was disrupted by RNA interference (RNAi. We describe specific changes in lifespan, mechanosensory neuronal morphologies, and mechansensory function following RNAi treatment targeting the insulin signaling pathway. Overall, we confirmed that transcription factor DAF-16 is neuroprotective in the proteotoxically stressed model, though not strikingly in the naturally aging model. Decreased insulin signaling through daf-2 RNAi improved mechanosensory function in both models and decreased protein aggregation load in polyQ128, yet showed opposing effects on accumulation of neuronal aberrations in both strains. Decreased daf-2 signaling slightly enhanced mechanosensation while greatly enhancing branching of the mechanosensory neuron axons and dendrites in polyQ0 animals, suggesting that branching is an adaptive response in natural aging. These effects in polyQ0 did not appear to involve DAF-16, suggesting the existence of a non-canonical DAF-2 pathway for the modulation of morphological adaptation. However, in polyQ128 animals, decreased daf-2 signaling significantly enhanced mechanosensation while decreasing neuronal aberrations. Unlike other interventions that reduce the strength of insulin signaling, daf-2 RNAi dramatically redistributed large polyQ128 aggregates to the cell body, away from neuronal processes. Our results suggest that insulin signaling strength can differentially affect specific neurons aging naturally or under proteotoxic stress.

  6. Model of Decision Making through Consensus in Ranking Case

    Science.gov (United States)

    Tarigan, Gim; Darnius, Open

    2018-01-01

    The basic problem to determine ranking consensus is a problem to combine some rankings those are decided by two or more Decision Maker (DM) into ranking consensus. DM is frequently asked to present their preferences over a group of objects in terms of ranks, for example to determine a new project, new product, a candidate in a election, and so on. The problem in ranking can be classified into two major categories; namely, cardinal and ordinal rankings. The objective of the study is to obtin the ranking consensus by appying some algorithms and methods. The algorithms and methods used in this study were partial algorithm, optimal ranking consensus, BAK (Borde-Kendal)Model. A method proposed as an alternative in ranking conssensus is a Weighted Distance Forward-Backward (WDFB) method, which gave a little difference i ranking consensus result compare to the result oethe example solved by Cook, et.al (2005).

  7. Structure of the Regulator of G Protein Signaling 8 (RGS8)-Gαq Complex: MOLECULAR BASIS FOR Gα SELECTIVITY.

    Science.gov (United States)

    Taylor, Veronica G; Bommarito, Paige A; Tesmer, John J G

    2016-03-04

    Regulator of G protein signaling (RGS) proteins interact with activated Gα subunits via their RGS domains and accelerate the hydrolysis of GTP. Although the R4 subfamily of RGS proteins generally accepts both Gαi/o and Gαq/11 subunits as substrates, the R7 and R12 subfamilies select against Gαq/11. In contrast, only one RGS protein, RGS2, is known to be selective for Gαq/11. The molecular basis for this selectivity is not clear. Previously, the crystal structure of RGS2 in complex with Gαq revealed a non-canonical interaction that could be due to interfacial differences imposed by RGS2, the Gα subunit, or both. To resolve this ambiguity, the 2.6 Å crystal structure of RGS8, an R4 subfamily member, was determined in complex with Gαq. RGS8 adopts the same pose on Gαq as it does when bound to Gαi3, indicating that the non-canonical interaction of RGS2 with Gαq is due to unique features of RGS2. Based on the RGS8-Gαq structure, residues in RGS8 that contact a unique α-helical domain loop of Gαq were converted to those typically found in R12 subfamily members, and the reverse substitutions were introduced into RGS10, an R12 subfamily member. Although these substitutions perturbed their ability to stimulate GTP hydrolysis, they did not reverse selectivity. Instead, selectivity for Gαq seems more likely determined by whether strong contacts can be maintained between α6 of the RGS domain and Switch III of Gαq, regions of high sequence and conformational diversity in both protein families. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

  8. ATP signals

    DEFF Research Database (Denmark)

    Novak, Ivana

    2016-01-01

    The Department of Biology at the University of Copenhagen explains the function of ATP signalling in the pancreas......The Department of Biology at the University of Copenhagen explains the function of ATP signalling in the pancreas...

  9. [Mexican National Consensus on Assisted Reproduction Treatment].

    Science.gov (United States)

    Kably Ambe, Alberto; López Ortiz, Carlos Salazar; Serviere Zaragoza, Claudio; Velázquez Cornejo, Gerardo; Pérez Peña, Efrain; Santos Haliscack, Roberto; Luna Rojas, Martha; Valerio, Emilio; Santana, Héctor; Gaviño Gaviño, Fernando

    2012-09-01

    It is estimated that 15% of couples living in industrialized countries are infertile, ie have failed to conceive, reproductive age, after 12 months ormore of regular intercourse without contraception. During the past decade has increased the demand for fertility treatments because they believe are moreeffective now. To unify the therapeutic approach and service to patients and set a precedent for a Mexican Official Standard respect and support for the legislation of these procedures. Consensus by technical experts group panel with the participation of 34 national centers accredited for use in assisted reproduction. He organized seven workshops with the following themes: 1) selection of patients for assisted reproduction treatment, 2) schemes controlled ovarian stimulation for assisted reproduction techniques of high complexity, 3) preparation and egg retrieval technique, 4) transferembryo; 5) luteal phase supplementation; 6) indications and techniques of cryopreservation and 7) informed consent. Each table had a coordinator who wrote and presented the findings to the full, it made a number of observations until they reached unanimity of criteria, which are reflected in this document. Patient selection for assisted reproduction techniques is the first step of the process. Proper selection lead to success, in the same way that a bad pick up for failure. In the case of egg donation the most important recommendation is that only one to two embryos transferred in order to reduce multiple pregnancy rates and maintaining high pregnancy rates.

  10. The Revised Academic Consensus Definition of Terrorism

    Directory of Open Access Journals (Sweden)

    Alex P. Schmid

    2012-05-01

    Full Text Available Terrorism is a contested concept. While there are many national and regional definitions, there is no universal legal definition approved by the General Assembly of the United Nations (the one proposed by the Security Council in Res. 1566 (2004 is non-binding, lacking legal authority in international law. The Ad Hoc Committee on Terrorism of the 6th (legal Committee of the General Assembly has, with some interruptions, been trying to reach a legal definition since 1972 - but in vain. In the absence of a legal definition, attempts have been made since the 1980s to reach agreement on an academic consensus definition. The latest outcome is the revised definition reprinted below. It is the result of three rounds of consultations among academics and other professionals. A description how it was arrived at can be found on pp. 39 - 98 of Alex P. Schmid (Ed.. The Routledge Handbook of Terrorism Research. London and New York: Routledge, 2011. The same volume also contains 260 other definitions compiled by Joseph J. Easson and Alex P. Schmid on pp. 99 -200.

  11. Consensus conference on irradiation of foodstuffs

    International Nuclear Information System (INIS)

    1989-01-01

    The Danish government is obliged to define its attitude to a proposal made by the European Communities regarding common regulations for the irradiation of food (May 1989). Denmark, in comparison to some other European countries, tends to show reserve on this issue. At the consensus conference a panel discussed related questions. The participants reached the conclusion that as yet disagreement and uncertainty about the subjects of safety, public health and food quality is so significant that they were not able to recommend that sanctions for irradiation of food should be given in Denmark. It was also agreed that problems related to control and determination of radiation content were too serious to allow this method of food preservation. The panel felt that there were many areas of research, such as long-term biological effects, that had not been investigated satisfactorily. Experiments carried out in India and China did not encourage confidence, as the people tested had recommenced eating food preserved by other methods, so that long term effects could not be measured. The specialists claim that Danish standards in relation to the food industry are very high so that alternative methods of preservation to those already used do not appear to be necessary. The only applications to the National Food Agency for authorization to irradiate food had come from producers of spices and in relation to educative acitivites. (AB)

  12. The Delphi Technique: Making Sense of Consensus

    Directory of Open Access Journals (Sweden)

    Chia-Chien Hsu

    2007-08-01

    Full Text Available The Delphi technique is a widely used and accepted method for gathering data from respondents within their domain of expertise. The technique is designed as a group communication process which aims to achieve a convergence of opinion on a specific real-world issue. The Delphi process has been used in various fields of study such as program planning, needs assessment, policy determination, and resource utilization to develop a full range of alternatives, explore or expose underlying assumptions, as well as correlate judgments on a topic spanning a wide range of disciplines. The Delphi technique is well suited as a method for consensus-building by using a series of questionnaires delivered using multiple iterations to collect data from a panel of selected subjects. Subject selection, time frames for conducting and completing a study, the possibility of low response rates, and unintentionally guiding feedback from the respondent group are areas which should be considered when designing and implementing a Delphi study.

  13. [National consensus on the ketogenic diet].

    Science.gov (United States)

    Armeno, Marisa; Caraballo, Roberto; Vaccarezza, María; Alberti, M Julia; Ríos, Viviana; Galicchio, Santiago; de Grandis, Elizabeth S; Mestre, Graciela; Escobal, Nidia; Matarrese, Pablo; Viollaz, Rocío; Agostinho, Ariela; Díez, Cecilia; Cresta, Araceli; Cabrera, Analía; Blanco, Virginia; Ferrero, Hilario; Gambarini, Victoria; Sosa, Patricia; Bouquet, Cecilia; Caramuta, Luciana; Guisande, Silvina; Gamboni, Beatriz; Hassan, Amal; Pesce, Laura; Argumedo, Laura; Dlugoszewski, Corina; DeMartini, Martha G; Panico, Luis

    2014-09-01

    Epilepsy is a chronic disease with onset in infancy affecting 0.5-1% of the population. One third of the patients is refractory to antiepileptic drugs and they pose a challenge for the health care team. The ketogenic diet is an effective, non-pharmacological, alternative treatment for the management of refractory epilepsy. There is a need to establish guidelines for the adequate and increased use of the ketogenic diet in Spanish-speaking countries. The National Committee on the Ketogenic Diet, consisting of paediatric neurologists, clinical nutritionists, and dietitians, of the Argentine Society of Child Neurology has developed this consensus statement to standardize the use of the ketogenic diet based on the literature and clinical experience. Patient selection, pre-treatment family counseling, drug interactions, micronutrient supplementation, adverse effects, and discontinuation of the diet are discussed. The ketogenic diet is an effective treatment for children with refractory epilepsy. Education and collaboration of the patient and their family is essential. The patient should be managed by an experienced multidisciplinary team using a protocol. The formation of a national multidisciplinary team and the publication of this document provide possibilities for new centers to integrate the ketogenic diet into their treatment options.

  14. Recovery and Performance in Sport: Consensus Statement.

    Science.gov (United States)

    Kellmann, Michael; Bertollo, Maurizio; Bosquet, Laurent; Brink, Michel; Coutts, Aaron J; Duffield, Rob; Erlacher, Daniel; Halson, Shona L; Hecksteden, Anne; Heidari, Jahan; Kallus, K Wolfgang; Meeusen, Romain; Mujika, Iñigo; Robazza, Claudio; Skorski, Sabrina; Venter, Ranel; Beckmann, Jürgen

    2018-02-01

    The relationship between recovery and fatigue and its impact on performance has attracted the interest of sport science for many years. An adequate balance between stress (training and competition load, other life demands) and recovery is essential for athletes to achieve continuous high-level performance. Research has focused on the examination of physiological and psychological recovery strategies to compensate external and internal training and competition loads. A systematic monitoring of recovery and the subsequent implementation of recovery routines aims at maximizing performance and preventing negative developments such as underrecovery, nonfunctional overreaching, the overtraining syndrome, injuries, or illnesses. Due to the inter- and intraindividual variability of responses to training, competition, and recovery strategies, a diverse set of expertise is required to address the multifaceted phenomena of recovery, performance, and their interactions to transfer knowledge from sport science to sport practice. For this purpose, a symposium on Recovery and Performance was organized at the Technical University Munich Science and Study Center Raitenhaslach (Germany) in September 2016. Various international experts from many disciplines and research areas gathered to discuss and share their knowledge of recovery for performance enhancement in a variety of settings. The results of this meeting are outlined in this consensus statement that provides central definitions, theoretical frameworks, and practical implications as a synopsis of the current knowledge of recovery and performance. While our understanding of the complex relationship between recovery and performance has significantly increased through research, some important issues for future investigations are also elaborated.

  15. Consensus and Synchronization in Complex Networks

    CERN Document Server

    2013-01-01

    Synchronization in complex networks is one of the most captivating cooperative phenomena in nature and has been shown to be of fundamental importance in such varied circumstances as the continued existence of species, the functioning of heart pacemaker cells, epileptic seizures, neuronal firing in the feline visual cortex and cognitive tasks in humans. E.g. coupled visual and acoustic interactions make fireflies flash, crickets chirp, and an audience clap in unison. On the other hand, in distributed systems and networks, it is often necessary for some or all of the nodes to calculate some function of certain parameters, e.g. sink nodes in sensor networks being tasked with calculating the average measurement value of all the sensors or multi-agent systems in which all agents are required to coordinate their speed and direction. When all nodes calculate the same function of the initial values in the system, they are said to reach consensus. Such concepts - sometimes also called state agreement, rendezvous, and ...

  16. Notching on cancer’s door: Notch signaling in brain tumors

    Directory of Open Access Journals (Sweden)

    Marcin eTeodorczyk

    2015-01-01

    Full Text Available Notch receptors play an essential role in the regulation of central cellular processes during embryonic and postnatal development. The mammalian genome encodes for four Notch paralogs (Notch 1-4, which are activated by three Delta-like (Dll1/3/4 and two Serrate-like (Jagged1/2 ligands. Further, non-canonical Notch ligands such as EGFL7 have been identified and serve mostly as antagonists of Notch signaling. The Notch pathway prevents neuronal differentiation in the central nervous system by driving neural stem cell maintenance and commitment of neural progenitor cells into the glial lineage. Notch is therefore often implicated in the development of brain tumors, as tumor cells share various characteristics with neural stem and progenitor cells. Notch receptors are overexpressed in gliomas and their oncogenicity has been confirmed by gain- and loss-of-function studies in vitro and in vivo. To this end, special attention is paid to the impact of Notch signaling on stem-like brain tumor-propagating cells as these cells contribute to growth, survival, invasion and recurrence of brain tumors. Based on the outcome of ongoing studies in vivo, Notch-directed therapies such as γ secretase inhibitors and blocking antibodies have entered and completed various clinical trials. This review summarizes the current knowledge on Notch signaling in brain tumor formation and therapy.

  17. R-spondin1 Controls Muscle Cell Fusion through Dual Regulation of Antagonistic Wnt Signaling Pathways

    Directory of Open Access Journals (Sweden)

    Floriane Lacour

    2017-03-01

    Full Text Available Wnt-mediated signals are involved in many important steps in mammalian regeneration. In multiple cell types, the R-spondin (Rspo family of secreted proteins potently activates the canonical Wnt/β-catenin pathway. Here, we identify Rspo1 as a mediator of skeletal muscle tissue repair. First, we show that deletion of Rspo1 results in global alteration of muscle regeneration kinetics following acute injury. We find that muscle progenitor cells lacking Rspo1 show delayed differentiation due to reduced activation of Wnt/β-catenin target genes. Furthermore, muscle cells lacking Rspo1 have a fusion phenotype leading to larger myotubes containing supernumerary nuclei both in vitro and in vivo. The increase in muscle fusion was dependent on downregulation of Wnt/β-catenin and upregulation of non-canonical Wnt7a/Fzd7/Rac1 signaling. We conclude that reciprocal control of antagonistic Wnt signaling pathways by Rspo1 in muscle stem cell progeny is a key step ensuring normal tissue architecture restoration following acute damage.

  18. Indian hedgehog signaling triggers Nkx3.2 protein degradation during chondrocyte maturation

    Science.gov (United States)

    Choi, Seung-Won; Jeong, Da-Un; Kim, Jeong-Ah; Lee, Boyoung; Joeng, Kyu Sang; Long, Fanxin; Kim, Dae-Won

    2015-01-01

    The Indian hedgehog (Ihh) pathway plays an essential role in facilitating chondrocyte hypertrophy and bone formation during skeletal development. Nkx3.2 is initially induced in chondrocyte precursor cells, maintained in early-stage chondrocytes, and down-regulated in terminal-stage chondrocytes. Consistent with these expression patterns, Nkx3.2 has been shown to enhance chondrocyte differentiation and cell survival, while inhibiting chondrocyte hypertrophy and apoptosis. Thus, in this work, we investigate whether Nkx3.2, an early stage chondrogenic factor, can be regulated by Ihh, a key regulator for chondrocyte hypertrophy. Here, we show that Ihh signaling can induce proteasomal degradation of Nkx3.2. In addition, we found that Ihh can suppress levels of Lrp (Wnt co-receptor) and Sfrp (Wnt antagonist) expression, which, in turn, may selectively enhance Lrp-independent non-canonical Wnt pathways in chondrocyte. In agreement with these findings, Ihh-induced Nkx3.2 degradation requires Wnt5a, which is capable of triggering Nkx3.2 degradation. Finally, we found that Nkx3.2 protein levels in chondrocytes are remarkably elevated in mice defective in Ihh signaling by deletion of either Ihh or Smoothened. Thus, these results suggest that Ihh/Wnt5a signaling may play a role in negative regulation of Nkx3.2 for appropriate progression of chondrocyte hypertrophy during chondrogenesis. PMID:22507129

  19. Fuz regulates craniofacial development through tissue specific responses to signaling factors.

    Directory of Open Access Journals (Sweden)

    Zichao Zhang

    Full Text Available The planar cell polarity effector gene Fuz regulates ciliogenesis and Fuz loss of function studies reveal an array of embryonic phenotypes. However, cilia defects can affect many signaling pathways and, in humans, cilia defects underlie several craniofacial anomalies. To address this, we analyzed the craniofacial phenotype and signaling responses of the Fuz(-/- mice. We demonstrate a unique role for Fuz in regulating both Hedgehog (Hh and Wnt/β-catenin signaling during craniofacial development. Fuz expression first appears in the dorsal tissues and later in ventral tissues and craniofacial regions during embryonic development coincident with cilia development. The Fuz(-/- mice exhibit severe craniofacial deformities including anophthalmia, agenesis of the tongue and incisors, a hypoplastic mandible, cleft palate, ossification/skeletal defects and hyperplastic malformed Meckel's cartilage. Hh signaling is down-regulated in the Fuz null mice, while canonical Wnt signaling is up-regulated revealing the antagonistic relationship of these two pathways. Meckel's cartilage is expanded in the Fuz(-/- mice due to increased cell proliferation associated with the up-regulation of Wnt canonical target genes and decreased non-canonical pathway genes. Interestingly, cilia development was decreased in the mandible mesenchyme of Fuz null mice, suggesting that cilia may antagonize Wnt signaling in this tissue. Furthermore, expression of Fuz decreased expression of Wnt pathway genes as well as a Wnt-dependent reporter. Finally, chromatin IP experiments demonstrate that β-catenin/TCF-binding directly regulates Fuz expression. These data demonstrate a new model for coordination of Hh and Wnt signaling and reveal a Fuz-dependent negative feedback loop controlling Wnt/β-catenin signaling.

  20. The CARE guidelines: consensus-based clinical case report guideline development.

    Science.gov (United States)

    Gagnier, Joel J; Kienle, Gunver; Altman, Douglas G; Moher, David; Sox, Harold; Riley, David

    2014-01-01

    A case report is a narrative that describes, for medical, scientific, or educational purposes, a medical problem experienced by one or more patients. Case reports written without guidance from reporting standards are insufficiently rigorous to guide clinical practice or to inform clinical study design. Develop, disseminate, and implement systematic reporting guidelines for case reports. We used a three-phase consensus process consisting of (1) pre-meeting literature review and interviews to generate items for the reporting guidelines, (2) a face-to-face consensus meeting to draft the reporting guidelines, and (3) post-meeting feedback, review, and pilot testing, followed by finalization of the case report guidelines. This consensus process involved 27 participants and resulted in a 13-item checklist-a reporting guideline for case reports. The primary items of the checklist are title, key words, abstract, introduction, patient information, clinical findings, timeline, diagnostic assessment, therapeutic interventions, follow-up and outcomes, discussion, patient perspective, and informed consent. We believe the implementation of the CARE (CAse REport) guidelines by medical journals will improve the completeness and transparency of published case reports and that the systematic aggregation of information from case reports will inform clinical study design, provide early signals of effectiveness and harms, and improve healthcare delivery. Copyright © 2014 Reproduced with permission of Global Advances in Health and Medicine. Published by Elsevier Inc. All rights reserved.

  1. Distributed adaptive asymptotically consensus tracking control of uncertain Euler-Lagrange systems under directed graph condition.

    Science.gov (United States)

    Wang, Wei; Wen, Changyun; Huang, Jiangshuai; Fan, Huijin

    2017-11-01

    In this paper, a backstepping based distributed adaptive control scheme is proposed for multiple uncertain Euler-Lagrange systems under directed graph condition. The common desired trajectory is allowed totally unknown by part of the subsystems and the linearly parameterized trajectory model assumed in currently available results is no longer needed. To compensate the effects due to unknown trajectory information, a smooth function of consensus errors and certain positive integrable functions are introduced in designing virtual control inputs. Besides, to overcome the difficulty of completely counteracting the coupling terms of distributed consensus errors and parameter estimation errors in the presence of asymmetric Laplacian matrix, extra information transmission of local parameter estimates are introduced among linked subsystem and adaptive gain technique is adopted to generate distributed torque inputs. It is shown that with the proposed distributed adaptive control scheme, global uniform boundedness of all the closed-loop signals and asymptotically output consensus tracking can be achieved. Copyright © 2017 ISA. Published by Elsevier Ltd. All rights reserved.

  2. Transatlantic Multispecialty Consensus on Fundamental Endovascular Skills: Results of a Delphi Consensus Study.

    Science.gov (United States)

    Maertens, H; Aggarwal, R; Macdonald, S; Vermassen, F; Van Herzeele, I

    2016-01-01

    The aim of this study was to establish a consensus on Fundamental Endovascular Skills (FES) for educational purposes and development of training curricula for endovascular procedures. The term "Fundamental Endovascular Skills" is widely used; however, the current literature does not explicitly describe what skills are included in this concept. Endovascular interventions are performed by several specialties that may have opposing perspectives on these skills. A two round Delphi questionnaire approach was used. Experts from interventional cardiology, interventional radiology, and vascular surgery from the United States and Europe were invited to participate. An electronic questionnaire was generated by endovascular therapists with an appropriate educational background but who would not participate in subsequent rounds. The questionnaire consisted of 50 statements describing knowledge, technical, and behavioral skills during endovascular procedures. Experts received the questionnaires by email. They were asked to rate the importance of each skill on a Likert scale from 1 to 5. A statement was considered fundamental when more than 90% of the experts rated it 4 or 5 out of 5. Twenty-three of 53 experts invited agreed to participate: six interventional radiologists (2 USA, 4 Europe), 10 vascular surgeons (4 USA, 6 Europe), and seven interventional cardiologists (4 USA, 3 Europe). There was a 100% response rate in the first round and 87% in the second round. Results showed excellent consensus among responders (Cronbach's alpha = .95 first round; .93 second round). Ninety percent of all proposed skills were considered fundamental. The most critical skills were determined. A transatlantic multispecialty consensus was achieved about the content of "FES" among interventional radiologists, interventional cardiologists, and vascular surgeons from Europe and the United States. These results can serve as directive principles for developing endovascular training curricula

  3. Status of conversion of NE standards to national consensus standards

    International Nuclear Information System (INIS)

    Jennings, S.D.

    1990-06-01

    One major goal of the Nuclear Standards Program is to convert existing NE standards into national consensus standards (where possible). This means that an NE standard in the same subject area using the national consensus process. This report is a summary of the activities that have evolved to effect conversion of NE standards to national consensus standards, and the status of current conversion activities. In some cases, all requirements in an NE standard will not be incorporated into the published national consensus standard because these requirements may be considered too restrictive or too specific for broader application by the nuclear industry. If these requirements are considered necessary for nuclear reactor program applications, the program standard will be revised and issued as a supplement to the national consensus standard. The supplemental program standard will contain only those necessary requirements not reflected by the national consensus standard. Therefore, while complete conversion of program standards may not always be realized, the standards policy has been fully supported in attempting to make maximum use of the national consensus standard. 1 tab

  4. Developing syndrome definitions based on consensus and current use

    Science.gov (United States)

    Dowling, John N; Baer, Atar; Buckeridge, David L; Cochrane, Dennis; Conway, Michael A; Elkin, Peter; Espino, Jeremy; Gunn, Julia E; Hales, Craig M; Hutwagner, Lori; Keller, Mikaela; Larson, Catherine; Noe, Rebecca; Okhmatovskaia, Anya; Olson, Karen; Paladini, Marc; Scholer, Matthew; Sniegoski, Carol; Thompson, David; Lober, Bill

    2010-01-01

    Objective Standardized surveillance syndromes do not exist but would facilitate sharing data among surveillance systems and comparing the accuracy of existing systems. The objective of this study was to create reference syndrome definitions from a consensus of investigators who currently have or are building syndromic surveillance systems. Design Clinical condition–syndrome pairs were catalogued for 10 surveillance systems across the United States and the representatives of these systems were brought together for a workshop to discuss consensus syndrome definitions. Results Consensus syndrome definitions were generated for the four syndromes monitored by the majority of the 10 participating surveillance systems: Respiratory, gastrointestinal, constitutional, and influenza-like illness (ILI). An important element in coming to consensus quickly was the development of a sensitive and specific definition for respiratory and gastrointestinal syndromes. After the workshop, the definitions were refined and supplemented with keywords and regular expressions, the keywords were mapped to standard vocabularies, and a web ontology language (OWL) ontology was created. Limitations The consensus definitions have not yet been validated through implementation. Conclusion The consensus definitions provide an explicit description of the current state-of-the-art syndromes used in automated surveillance, which can subsequently be systematically evaluated against real data to improve the definitions. The method for creating consensus definitions could be applied to other domains that have diverse existing definitions. PMID:20819870

  5. Expert surgical consensus for prenatal counseling using the Delphi method.

    Science.gov (United States)

    Berman, Loren; Jackson, Jordan; Miller, Kristen; Kowalski, Rebecca; Kolm, Paul; Luks, Francois I

    2017-11-28

    Pediatric surgeons frequently offer prenatal consultation for congenital pulmonary airway malformation (CPAM) and congenital diaphragmatic hernia (CDH); however, there is no evidence-based consensus to guide prenatal decision making and counseling for these conditions. Eliciting feedback from experts is integral to defining best practice regarding prenatal counseling and intervention. A Delphi consensus process was undertaken using a panel of pediatric surgeons identified as experts in fetal therapy to address current limitations. Areas of discrepancy in the literature on CPAM and CDH were identified and used to generate a list of content and intervention questions. Experts were invited to participate in an online Delphi survey. Items that did not reach first-round consensus were broken down into additional questions, and consensus was achieved in the second round. Fifty-four surgeons (69%) responded to at least one of the two survey rounds. During round one, consensus was reached on 54 of 89 survey questions (61%), and 45 new questions were developed. During round two, consensus was reached on 53 of 60 survey questions (88%). We determined expert consensus to establish guidelines regarding perinatal management of CPAM and CDH. Our results can help educate pediatric surgeons participating in perinatal care of these patients. V. Copyright © 2017 Elsevier Inc. All rights reserved.

  6. A collaborative platform for consensus sessions in pathology over Internet.

    Science.gov (United States)

    Zapletal, Eric; Le Bozec, Christel; Degoulet, Patrice; Jaulent, Marie-Christine

    2003-01-01

    The design of valid databases in pathology faces the problem of diagnostic disagreement between pathologists. Organizing consensus sessions between experts to reduce the variability is a difficult task. The TRIDEM platform addresses the issue to organize consensus sessions in pathology over the Internet. In this paper, we present the basis to achieve such collaborative platform. On the one hand, the platform integrates the functionalities of the IDEM consensus module that alleviates the consensus task by presenting to pathologists preliminary computed consensus through ergonomic interfaces (automatic step). On the other hand, a set of lightweight interaction tools such as vocal annotations are implemented to ease the communication between experts as they discuss a case (interactive step). The architecture of the TRIDEM platform is based on a Java-Server-Page web server that communicate with the ObjectStore PSE/PRO database used for the object storage. The HTML pages generated by the web server run Java applets to perform the different steps (automatic and interactive) of the consensus. The current limitations of the platform is to only handle a synchronous process. Moreover, improvements like re-writing the consensus workflow with a protocol such as BPML are already forecast.

  7. Public Awareness of the Scientific Consensus on Climate

    Directory of Open Access Journals (Sweden)

    Lawrence C. Hamilton

    2016-11-01

    Full Text Available Questions about climate change elicit some of the widest political divisions of any items on recent U.S. surveys. Severe polarization affects even basic questions about the reality of anthropogenic climate change (ACC, or whether most scientists agree that humans are changing the Earth’s climate. Statements about scientific consensus have been contentious among social scientists, with some arguing for consensus awareness as a “gateway cognition” that leads to greater public acceptance of ACC, but others characterizing consensus messaging (deliberate communication about the level of scientific agreement as a counterproductive tactic that exacerbates polarization. A series of statewide surveys, with nationwide benchmarks, repeated questions about the reality of ACC and scientific consensus many times over 2010 to 2016. These data permit tests for change in beliefs and polarization. ACC and consensus beliefs have similar trends and individual background predictors. Both rose gradually by about 10 points over 2010 to 2016, showing no abrupt shifts that might correspond to events such as scientific reports, leadership statements, or weather. Growing awareness of the scientific consensus, whether from deliberate messaging or the cumulative impact of many studies and publicly engaged scientists, provides the most plausible explanation for this rise in both series. In state-level data, the gap between liberal and conservative views on the reality of ACC did not widen over this period, whereas the liberal–conservative gap regarding existence of a scientific consensus narrowed.

  8. Improving consensus structure by eliminating averaging artifacts

    Directory of Open Access Journals (Sweden)

    KC Dukka B

    2009-03-01

    Full Text Available Abstract Background Common structural biology methods (i.e., NMR and molecular dynamics often produce ensembles of molecular structures. Consequently, averaging of 3D coordinates of molecular structures (proteins and RNA is a frequent approach to obtain a consensus structure that is representative of the ensemble. However, when the structures are averaged, artifacts can result in unrealistic local geometries, including unphysical bond lengths and angles. Results Herein, we describe a method to derive representative structures while limiting the number of artifacts. Our approach is based on a Monte Carlo simulation technique that drives a starting structure (an extended or a 'close-by' structure towards the 'averaged structure' using a harmonic pseudo energy function. To assess the performance of the algorithm, we applied our approach to Cα models of 1364 proteins generated by the TASSER structure prediction algorithm. The average RMSD of the refined model from the native structure for the set becomes worse by a mere 0.08 Å compared to the average RMSD of the averaged structures from the native structure (3.28 Å for refined structures and 3.36 A for the averaged structures. However, the percentage of atoms involved in clashes is greatly reduced (from 63% to 1%; in fact, the majority of the refined proteins had zero clashes. Moreover, a small number (38 of refined structures resulted in lower RMSD to the native protein versus the averaged structure. Finally, compared to PULCHRA 1, our approach produces representative structure of similar RMSD quality, but with much fewer clashes. Conclusion The benchmarking results demonstrate that our approach for removing averaging artifacts can be very beneficial for the structural biology community. Furthermore, the same approach can be applied to almost any problem where averaging of 3D coordinates is performed. Namely, structure averaging is also commonly performed in RNA secondary prediction 2, which

  9. In control? IQC consensus and statutory regulation.

    Science.gov (United States)

    Lee, Graham R; Fitzgibbon, Maria C; O'Shea, Paula

    2016-06-13

    have provided a template to potentially harmonise IQC practice nationally. Given the central and critical role that IQC practice plays in ensuring the quality of patient results' importance, the authors contend that the time has come for international consensus and statutory regulation regarding the minimally acceptable criteria for its implementation, monitoring and review.

  10. Consensus statement on diabetes in children

    Directory of Open Access Journals (Sweden)

    K M Prasanna Kumar

    2014-01-01

    Full Text Available While T1DM has been traditionally seen as a minor concern in the larger picture of pediatric ailments, new data reveals that the incidence of T1DM has assumed alarming proportions. It has long been clear that while the disease may be diagnosed at an early age, its impact is not isolated to afflicted children. The direct impact of the disease on the patient is debilitating due to the nature of the disease and lack of proper access to treatment in India. But this impact is further compounded by the utter apathy and often times antipathy, which patients withT1DM have to face. Lack of awareness of the issue in all stakeholders, low access to quality healthcare, patient, physician, and system level barriers to the delivery of optimal diabetes care are some of the factors which hinder successful management of T1DM. The first international consensus meet on diabetes in children was convened with the aim of providing a common platform to all the stakeholders in the management of T1DM, to discuss the academic, administrative and healthcare system related issues. The ultimate aim was to articulate the problems faced by children with diabetes in a way that centralized their position and focused on creating modalities of management sensitive to their needs and aspirations. It was conceptualized to raise a strong voice of advocacy for improving the management of T1DM and ensuring that "No child should die of diabetes". The unique clinical presentations of T1DM coupled with ignorance on the part of the medical community and society in general results in outcomes that are far worse than that seen with T2DM. So there is a need to substantially improve training of HCPs at all levels on this neglected aspect of healthcare.

  11. A formal concept analysis approach to consensus clustering of multi-experiment expression data

    Science.gov (United States)

    2014-01-01

    Background Presently, with the increasing number and complexity of available gene expression datasets, the combination of data from multiple microarray studies addressing a similar biological question is gaining importance. The analysis and integration of multiple datasets are expected to yield more reliable and robust results since they are based on a larger number of samples and the effects of the individual study-specific biases are diminished. This is supported by recent studies suggesting that important biological signals are often preserved or enhanced by multiple experiments. An approach to combining data from different experiments is the aggregation of their clusterings into a consensus or representative clustering solution which increases the confidence in the common features of all the datasets and reveals the important differences among them. Results We propose a novel generic consensus clustering technique that applies Formal Concept Analysis (FCA) approach for the consolidation and analysis of clustering solutions derived from several microarray datasets. These datasets are initially divided into groups of related experiments with respect to a predefined criterion. Subsequently, a consensus clustering algorithm is applied to each group resulting in a clustering solution per group. These solutions are pooled together and further analysed by employing FCA which allows extracting valuable insights from the data and generating a gene partition over all the experiments. In order to validate the FCA-enhanced approach two consensus clustering algorithms are adapted to incorporate the FCA analysis. Their performance is evaluated on gene expression data from multi-experiment study examining the global cell-cycle control of fission yeast. The FCA results derived from both methods demonstrate that, although both algorithms optimize different clustering characteristics, FCA is able to overcome and diminish these differences and preserve some relevant biological

  12. Consensus Making in Requirements Negotiation: the communication perspective

    Directory of Open Access Journals (Sweden)

    Jenny Price

    2005-11-01

    Full Text Available When developing an Information System (IS, organizational goals of various stakeholders are commonly in direct conflict. Furthermore, individuals often rank their private objectives well over their management's directions. Recognising and reconciling all these diverse goals, and reaching agreement among the stakeholders, are prerequisite to establishing project cooperation and collaboration. This paper focuses, in particular, on the negotiation and consensus making during requirements elicitation - the earliest stages of the IS development process. As requirements elicitation involves rich communication between project stakeholders, we therefore explore negotiation and consensus making from the communication perspective. The resulting model assists our understanding of the communication factors that influence the consensus process during requirements negotiation.

  13. Inferring gene and protein interactions using PubMed citations and consensus Bayesian networks.

    Science.gov (United States)

    Deeter, Anthony; Dalman, Mark; Haddad, Joseph; Duan, Zhong-Hui

    2017-01-01

    The PubMed database offers an extensive set of publication data that can be useful, yet inherently complex to use without automated computational techniques. Data repositories such as the Genomic Data Commons (GDC) and the Gene Expression Omnibus (GEO) offer experimental data storage and retrieval as well as curated gene expression profiles. Genetic interaction databases, including Reactome and Ingenuity Pathway Analysis, offer pathway and experiment data analysis using data curated from these publications and data repositories. We have created a method to generate and analyze consensus networks, inferring potential gene interactions, using large numbers of Bayesian networks generated by data mining publications in the PubMed database. Through the concept of network resolution, these consensus networks can be tailored to represent possible genetic interactions. We designed a set of experiments to confirm that our method is stable across variation in both sample and topological input sizes. Using gene product interactions from the KEGG pathway database and data mining PubMed publication abstracts, we verify that regardless of the network resolution or the inferred consensus network, our method is capable of inferring meaningful gene interactions through consensus Bayesian network generation with multiple, randomized topological orderings. Our method can not only confirm the existence of currently accepted interactions, but has the potential to hypothesize new ones as well. We show our method confirms the existence of known gene interactions such as JAK-STAT-PI3K-AKT-mTOR, infers novel gene interactions such as RAS- Bcl-2 and RAS-AKT, and found significant pathway-pathway interactions between the JAK-STAT signaling and Cardiac Muscle Contraction KEGG pathways.

  14. Risk communication strategies : achieving a multidisciplinary consensus; La communication des risques : un consensus multidisciplinaire

    Energy Technology Data Exchange (ETDEWEB)

    Robert, B.; Cloutier, I. [Ecole Polytechnique, Montreal, PQ (Canada). Dept. de Mathematiques et de Genie Industriel; Sabourin, J.P. [Ville de Quebec, Quebec, PQ (Canada)

    2006-07-01

    Risk management related to floods and dam failures requires input from a variety of stakeholders from both the private and the public sector. This paper provided details of a risk management communication strategy based on a consequence approach that established work sequence modes to achieve a multidisciplinary consensus of opinion. The communication of risk was considered as a bilateral exchange of information between concerned parties, who were divided into 2 spheres: (1) a public sphere which included interest groups, government agencies, individuals and the media; and (2) a technical sphere comprised of industry members, scientific experts, and government agencies. Divided between the 2 spheres, government agencies play a distinct role in both the communication and understanding of risk. In Quebec, municipal agencies are required to identify risk and develop plans that ensure public safety. Risk management plans developed by industry members are a valuable source of information for municipal authorities, who can identify vulnerabilities in their own risk communication strategies. In addition, members of the public play an important role in eliciting further risk communications to improve areas of vulnerability. Interest groups can demand further analyses from impartial sources on sensitive issues. Conflicting results offer a plurality of opinions that must be considered to obtain a consensus in risk assessment, which is the ultimate aim of all risk analyses and communications strategies. It was concluded that risk communication strategies benefit from the engagement of a variety of often conflicting views. 8 refs., 3 figs.

  15. The development of a consensus definition for healthcare improvement science (HIS) in seven European countries: A consensus methods approach.

    Science.gov (United States)

    Skela-Savič, Brigita; Macrae, Rhoda; Lillo-Crespo, Manuel; Rooney, Kevin D

    2017-06-01

    There is a limited body of research in the field of healthcare improvement science (HIS). Quality improvement and 'change making' should become an intrinsic part of everyone's job, every day in all parts of the healthcare system. The lack of theoretical grounding may partly explain the minimal transfer of health research into health policy. This article seeks to present the development of the definition for healthcare improvement science. A consensus method approach was adopted with a two-stage Delphi process, expert panel and consensus group techniques. A total of 18 participants were involved in the expert panel and consensus group, and 153 answers were analysed as a part of the Delphi survey. Participants were researchers, educators and healthcare professionals from Scotland, Slovenia, Spain, Italy, England, Poland, and Romania. A high level of consensus was achieved for the broad definition in the 2nd Delphi iteration (86%). The final definition was agreed on by the consensus group: 'Healthcare improvement science is the generation of knowledge to cultivate change and deliver person-centred care that is safe, effective, efficient, equitable and timely. It improves patient outcomes, health system performance and population health.' The process of developing a consensus definition revealed different understandings of healthcare improvement science between the participants. Having a shared consensus definition of healthcare improvement science is an important step forward, bringing about a common understanding in order to advance the professional education and practice of healthcare improvement science.

  16. Signaling aggression.

    Science.gov (United States)

    van Staaden, Moira J; Searcy, William A; Hanlon, Roger T

    2011-01-01

    From psychological and sociological standpoints, aggression is regarded as intentional behavior aimed at inflicting pain and manifested by hostility and attacking behaviors. In contrast, biologists define aggression as behavior associated with attack or escalation toward attack, omitting any stipulation about intentions and goals. Certain animal signals are strongly associated with escalation toward attack and have the same function as physical attack in intimidating opponents and winning contests, and ethologists therefore consider them an integral part of aggressive behavior. Aggressive signals have been molded by evolution to make them ever more effective in mediating interactions between the contestants. Early theoretical analyses of aggressive signaling suggested that signals could never be honest about fighting ability or aggressive intentions because weak individuals would exaggerate such signals whenever they were effective in influencing the behavior of opponents. More recent game theory models, however, demonstrate that given the right costs and constraints, aggressive signals are both reliable about strength and intentions and effective in influencing contest outcomes. Here, we review the role of signaling in lieu of physical violence, considering threat displays from an ethological perspective as an adaptive outcome of evolutionary selection pressures. Fighting prowess is conveyed by performance signals whose production is constrained by physical ability and thus limited to just some individuals, whereas aggressive intent is encoded in strategic signals that all signalers are able to produce. We illustrate recent advances in the study of aggressive signaling with case studies of charismatic taxa that employ a range of sensory modalities, viz. visual and chemical signaling in cephalopod behavior, and indicators of aggressive intent in the territorial calls of songbirds. Copyright © 2011 Elsevier Inc. All rights reserved.

  17. The non-canonical roles of clathrin and actin in pathogen internalization, egress and spread.

    Science.gov (United States)

    Humphries, Ashley C; Way, Michael

    2013-08-01

    The role of clathrin in pathogen entry has received much attention and has highlighted the adaptability of clathrin during internalization. Recent studies have now uncovered additional roles for clathrin and have put the spotlight on its role in pathogen spread. Here, we discuss the manipulation of clathrin by pathogens, with specific attention to the processes that occur at the plasma membrane. In the majority of cases, both clathrin and the actin cytoskeleton are hijacked, so we also examine the interplay between these two systems and their role during pathogen internalization, egress and spread.

  18. Non-canonical WOX11-mediated root branching contributes to plasticity in Arabidopsis root system architecture.

    Science.gov (United States)

    Sheng, Lihong; Hu, Xiaomei; Du, Yujuan; Zhang, Guifang; Huang, Hai; Scheres, Ben; Xu, Lin

    2017-09-01

    Lateral roots (LRs), which originate from the growing root, and adventitious roots (ARs), which are formed from non-root organs, are the main contributors to the post-embryonic root system in Arabidopsis However, our knowledge of how formation of the root system is altered in response to diverse inductive cues is limited. Here, we show that WOX11 contributes to root system plasticity. When seedlings are grown vertically on medium, WOX11 is not expressed in LR founder cells. During AR initiation, WOX11 is expressed in AR founder cells and activates LBD16 LBD16 also functions in LR formation and is activated in that context by ARF7 / 19 and not by WOX11 This indicates that divergent initial processes that lead to ARs and LRs may converge on a similar mechanism for primordium development. Furthermore, we demonstrated that when plants are grown in soil or upon wounding on medium, the primary root is able to produce both WOX11 -mediated and non- WOX11 -mediated roots. The discovery of WOX11 -mediated root-derived roots reveals a previously uncharacterized pathway that confers plasticity during the generation of root system architecture in response to different inductive cues. © 2017. Published by The Company of Biologists Ltd.

  19. A non-canonical function of Ezh2 preserves immune homeostasis.

    Science.gov (United States)

    Vasanthakumar, Ajithkumar; Xu, Dakang; Lun, Aaron Tl; Kueh, Andrew J; van Gisbergen, Klaas Pjm; Iannarella, Nadia; Li, Xiaofang; Yu, Liang; Wang, Die; Williams, Bryan Rg; Lee, Stanley Cw; Majewski, Ian J; Godfrey, Dale I; Smyth, Gordon K; Alexander, Warren S; Herold, Marco J; Kallies, Axel; Nutt, Stephen L; Allan, Rhys S

    2017-04-01

    Enhancer of zeste 2 (Ezh2) mainly methylates lysine 27 of histone-H3 (H3K27me3) as part of the polycomb repressive complex 2 (PRC2) together with Suz12 and Eed. However, Ezh2 can also modify non-histone substrates, although it is unclear whether this mechanism has a role during development. Here, we present evidence for a chromatin-independent role of Ezh2 during T-cell development and immune homeostasis. T-cell-specific depletion of Ezh2 induces a pronounced expansion of natural killer T (NKT) cells, although Ezh2-deficient T cells maintain normal levels of H3K27me3. In contrast, removal of Suz12 or Eed destabilizes canonical PRC2 function and ablates NKT cell development completely. We further show that Ezh2 directly methylates the NKT cell lineage defining transcription factor PLZF, leading to its ubiquitination and subsequent degradation. Sustained PLZF expression in Ezh2-deficient mice is associated with the expansion of a subset of NKT cells that cause immune perturbation. Taken together, we have identified a chromatin-independent function of Ezh2 that impacts on the development of the immune system. © 2017 The Authors.

  20. A non-canonical function of Ezh2 preserves immune homeostasis

    NARCIS (Netherlands)

    Vasanthakumar, Ajithkumar; Xu, Dakang; Lun, Aaron Tl; Kueh, Andrew J.; van Gisbergen, Klaas Pjm; Iannarella, Nadia; Li, Xiaofang; Yu, Liang; Wang, Die; Williams, Bryan Rg; Lee, Stanley Cw; Majewski, Ian J.; Godfrey, Dale I.; Smyth, Gordon K.; Alexander, Warren S.; Herold, Marco J.; Kallies, Axel; Nutt, Stephen L.; Allan, Rhys S.

    2017-01-01

    Enhancer of zeste 2 (Ezh2) mainly methylates lysine 27 of histoneH3 (H3K27me3) as part of the polycomb repressive complex 2 (PRC2) together with Suz12 and Eed. However, Ezh2 can also modify non-histone substrates, although it is unclear whether this mechanism has a role during development. Here, we

  1. Non-canonical TAF complexes regulate active promoters in human embryonic stem cells.

    Science.gov (United States)

    Maston, Glenn A; Zhu, Lihua Julie; Chamberlain, Lynn; Lin, Ling; Fang, Minggang; Green, Michael R

    2012-11-13

    The general transcription factor TFIID comprises the TATA-box-binding protein (TBP) and approximately 14 TBP-associated factors (TAFs). Here we find, unexpectedly, that undifferentiated human embryonic stem cells (hESCs) contain only six TAFs (TAFs 2, 3, 5, 6, 7 and 11), whereas following differentiation all TAFs are expressed. Directed and global chromatin immunoprecipitation analyses reveal an unprecedented promoter occupancy pattern: most active genes are bound by only TAFs 3 and 5 along with TBP, whereas the remaining active genes are bound by TBP and all six hESC TAFs. Consistent with these results, hESCs contain a previously undescribed complex comprising TAFs 2, 6, 7, 11 and TBP. Altering the composition of hESC TAFs, either by depleting TAFs that are present or ectopically expressing TAFs that are absent, results in misregulated expression of pluripotency genes and induction of differentiation. Thus, the selective expression and use of TAFs underlies the ability of hESCs to self-renew.DOI:http://dx.doi.org/10.7554/eLife.00068.001.

  2. Analytical functions in non-canonical two dimensional algebras; Funzioni analitiche nelle algebre a due componenti

    Energy Technology Data Exchange (ETDEWEB)

    Catoni, Francesco; Zampetti, Paolo [ENEA, Centro Ricerche Casaccia, Rome (Italy). Dipt. Energia; Cannata, Roberto [ENEA, Centro Ricerche Casaccia, Rome (Italy). Funzione Centrale INFO; Nichelatti, Enrico [ENEA, Centro Ricerche Casaccia, Rome (Italy). Dipt. Innovazione

    1997-10-01

    Systems of two-dimensional hypercomplex numbers are usually studied in their canonical form, i.e. according to the multiplicative rule for the ``imaginary``versor i{sup 2} = {+-} 1, 0. In this report those systems for which i{sup 2} = {alpha} + {beta}i are studied and expressions are derived for functions given by series expansion as well as for some elementary functions. The results obtained for systems which can be decomposed are then extended to all systems.

  3. Non-canonical ribosomal DNA segments in the human genome, and nucleoli functioning.

    Science.gov (United States)

    Kupriyanova, Natalia S; Netchvolodov, Kirill K; Sadova, Anastasia A; Cherepanova, Marina D; Ryskov, Alexei P

    2015-11-10

    Ribosomal DNA (rDNA) in the human genome is represented by tandem repeats of 43 kb nucleotide sequences that form nucleoli organizers (NORs) on each of five pairs of acrocentric chromosomes. RDNA-similar segments of different lengths are also present on (NOR)(-) chromosomes. Many of these segments contain nucleotide substitutions, supplementary microsatellite clusters, and extended deletions. Recently, it was shown that, in addition to ribosome biogenesis, nucleoli exhibit additional functions, such as cell-cycle regulation and response to stresses. In particular, several stress-inducible loci located in the ribosomal intergenic spacer (rIGS) produce stimuli-specific noncoding nucleolus RNAs. By mapping the 5'/3' ends of the rIGS segments scattered throughout (NOR)(-) chromosomes, we discovered that the bonds in the rIGS that were most often susceptible to disruption in the rIGS were adjacent to, or overlapped with stimuli-specific inducible loci. This suggests the interconnection of the two phenomena - nucleoli functioning and the scattering of rDNA-like sequences on (NOR)(-) chromosomes. Copyright © 2015 Elsevier B.V. All rights reserved.

  4. A Non-canonical Voltage-Sensing Mechanism Controls Gating in K2P K(+) Channels.

    Science.gov (United States)

    Schewe, Marcus; Nematian-Ardestani, Ehsan; Sun, Han; Musinszki, Marianne; Cordeiro, Sönke; Bucci, Giovanna; de Groot, Bert L; Tucker, Stephen J; Rapedius, Markus; Baukrowitz, Thomas

    2016-02-25

    Two-pore domain (K2P) K(+) channels are major regulators of excitability that endow cells with an outwardly rectifying background "leak" conductance. In some K2P channels, strong voltage-dependent activation has been observed, but the mechanism remains unresolved because they lack a canonical voltage-sensing domain. Here, we show voltage-dependent gating is common to most K2P channels and that this voltage sensitivity originates from the movement of three to four ions into the high electric field of an inactive selectivity filter. Overall, this ion-flux gating mechanism generates a one-way "check valve" within the filter because outward movement of K(+) induces filter opening, whereas inward movement promotes inactivation. Furthermore, many physiological stimuli switch off this flux gating mode to convert K2P channels into a leak conductance. These findings provide insight into the functional plasticity of a K(+)-selective filter and also refine our understanding of K2P channels and the mechanisms by which ion channels can sense voltage. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

  5. Planck limits on non-canonical generalizations of large-field inflation models

    Energy Technology Data Exchange (ETDEWEB)

    Stein, Nina K.; Kinney, William H., E-mail: ninastei@buffalo.edu, E-mail: whkinney@buffalo.edu [Dept. of Physics, University at Buffalo, the State University of New York, Buffalo, NY 14260-1500 (United States)

    2017-04-01

    In this paper, we consider two case examples of Dirac-Born-Infeld (DBI) generalizations of canonical large-field inflation models, characterized by a reduced sound speed, c {sub S} < 1. The reduced speed of sound lowers the tensor-scalar ratio, improving the fit of the models to the data, but increases the equilateral-mode non-Gaussianity, f {sup equil.}{sub NL}, which the latest results from the Planck satellite constrain by a new upper bound. We examine constraints on these models in light of the most recent Planck and BICEP/Keck results, and find that they have a greatly decreased window of viability. The upper bound on f {sup equil.}{sub NL} corresponds to a lower bound on the sound speed and a corresponding lower bound on the tensor-scalar ratio of r ∼ 0.01, so that near-future Cosmic Microwave Background observations may be capable of ruling out entire classes of DBI inflation models. The result is, however, not universal: infrared-type DBI inflation models, where the speed of sound increases with time, are not subject to the bound.

  6. A Non-canonical Melanin Biosynthesis Pathway Protects Aspergillus terreus Conidia from Environmental Stress.

    Science.gov (United States)

    Geib, Elena; Gressler, Markus; Viediernikova, Iuliia; Hillmann, Falk; Jacobsen, Ilse D; Nietzsche, Sandor; Hertweck, Christian; Brock, Matthias

    2016-05-19

    Melanins are ubiquitous pigments found in all kingdoms of life. Most organisms use them for protection from environmental stress, although some fungi employ melanins as virulence determinants. The human pathogenic fungus Aspergillus fumigatus and related Ascomycetes produce dihydroxynaphthalene- (DHN) melanin in their spores, the conidia, and use it to inhibit phagolysosome acidification. However, biosynthetic origin of melanin in a related fungus, Aspergillus terreus, has remained a mystery because A. terreus lacks genes for synthesis of DHN-melanin. Here we identify genes coding for an unusual NRPS-like enzyme (MelA) and a tyrosinase (TyrP) that A. terreus expressed under conidiation conditions. We demonstrate that MelA produces aspulvinone E, which is activated for polymerization by TyrP. Functional studies reveal that this new pigment, Asp-melanin, confers resistance against UV light and hampers phagocytosis by soil amoeba. Unexpectedly, Asp-melanin does not inhibit acidification of phagolysosomes, thus likely contributing specifically to survival of A. terreus conidia in acidic environments. Copyright © 2016 Elsevier Ltd. All rights reserved.

  7. Structural Basis for the Canonical and Non-canonical PAM Recognition by CRISPR-Cpf1.

    Science.gov (United States)

    Yamano, Takashi; Zetsche, Bernd; Ishitani, Ryuichiro; Zhang, Feng; Nishimasu, Hiroshi; Nureki, Osamu

    2017-08-17

    The RNA-guided Cpf1 (also known as Cas12a) nuclease associates with a CRISPR RNA (crRNA) and cleaves the double-stranded DNA target complementary to the crRNA guide. The two Cpf1 orthologs from Acidaminococcus sp. (AsCpf1) and Lachnospiraceae bacterium (LbCpf1) have been harnessed for eukaryotic genome editing. Cpf1 requires a specific nucleotide sequence, called a protospacer adjacent motif (PAM), for target recognition. Besides the canonical TTTV PAM, Cpf1 recognizes suboptimal C-containing PAMs. Here, we report four crystal structures of LbCpf1 in complex with the crRNA and its target DNA containing either TTTA, TCTA, TCCA, or CCCA as the PAM. These structures revealed that, depending on the PAM sequences, LbCpf1 undergoes conformational changes to form altered interactions with the PAM-containing DNA duplexes, thereby achieving the relaxed PAM recognition. Collectively, the present structures advance our mechanistic understanding of the PAM-dependent, crRNA-guided DNA cleavage by the Cpf1 family nucleases. Copyright © 2017 Elsevier Inc. All rights reserved.

  8. Non-canonical transcription initiation: the expanding universe of transcription initiating substrates.

    Science.gov (United States)

    Barvík, Ivan; Rejman, Dominik; Panova, Natalya; Šanderová, Hana; Krásný, Libor

    2017-03-01

    RNA polymerase (RNAP) is the central enzyme of transcription of the genetic information from DNA into RNA. RNAP recognizes four main substrates: ATP, CTP, GTP and UTP. Experimental evidence from the past several years suggests that, besides these four NTPs, other molecules can be used to initiate transcription: (i) ribooligonucleotides (nanoRNAs) and (ii) coenzymes such as NAD+, NADH, dephospho-CoA and FAD. The presence of these molecules at the 5΄ ends of RNAs affects the properties of the RNA. Here, we discuss the expanding portfolio of molecules that can initiate transcription, their mechanism of incorporation, effects on RNA and cellular processes, and we present an outlook toward other possible initiation substrates. © FEMS 2016. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  9. Towards a New Democracy: Consensus Through Quantum Parliament

    OpenAIRE

    Aerts, Diederik

    2005-01-01

    We compare different actual forms of democracy and analyse in which way they are variations of a 'natural consensus decision process'. We analyse how 'consensus decision followed by majority voting' is open to 'false play' by the majority, and investigate how other types of false play appear in alternative types of democratic decision procedures. We introduce the combined notion of 'quantum parliament' and 'quantum decision procedure', and prove it to be the only one, when applied after conse...

  10. Blockchain Consensus Protocols in the Wild (Keynote Talk)

    OpenAIRE

    Cachin, Christian; Vukolic, Marko

    2017-01-01

    A blockchain is a distributed ledger for recording transactions, maintained by many nodes without central authority through a distributed cryptographic protocol. All nodes validate the information to be appended to the blockchain, and a consensus protocol ensures that the nodes agree on a unique order in which entries are appended. Consensus protocols for tolerating Byzantine faults have received renewed attention because they also address blockchain systems. This work discusses the process o...

  11. Consensus algorithm in smart grid and communication networks

    Science.gov (United States)

    Alfagee, Husain Abdulaziz

    On a daily basis, consensus theory attracts more and more researches from different areas of interest, to apply its techniques to solve technical problems in a way that is faster, more reliable, and even more precise than ever before. A power system network is one of those fields that consensus theory employs extensively. The use of the consensus algorithm to solve the Economic Dispatch and Load Restoration Problems is a good example. Instead of a conventional central controller, some researchers have explored an algorithm to solve the above mentioned problems, in a distribution manner, using the consensus algorithm, which is based on calculation methods, i.e., non estimation methods, for updating the information consensus matrix. Starting from this point of solving these types of problems mentioned, specifically, in a distribution fashion, using the consensus algorithm, we have implemented a new advanced consensus algorithm. It is based on the adaptive estimation techniques, such as the Gradient Algorithm and the Recursive Least Square Algorithm, to solve the same problems. This advanced work was tested on different case studies that had formerly been explored, as seen in references 5, 7, and 18. Three and five generators, or agents, with different topologies, correspond to the Economic Dispatch Problem and the IEEE 16-Bus power system corresponds to the Load Restoration Problem. In all the cases we have studied, the results met our expectations with extreme accuracy, and completely matched the results of the previous researchers. There is little question that this research proves the capability and dependability of using the consensus algorithm, based on the estimation methods as the Gradient Algorithm and the Recursive Least Square Algorithm to solve such power problems.

  12. Voting experiments: Bandwagon voting or false-consensus effect?

    OpenAIRE

    Ivo Bischoff; Henrik Egbert

    2008-01-01

    In an experiment designed to test for expressive voting, Tyran (JPubEc 2004) found a strong positive correlation between the participants' approval for a proposal to donate money for charity and their expected approval rate for fellow voters. This phenomenon can be due to bandwagon voting or a false consensus effect. The social science literature reports both effects for voting decisions. Replicating Tyran's experiment and adding new treatments, we provide evidence for a false consensus effec...

  13. Consensus formation in science modeled by aggregated bibliographic coupling

    DEFF Research Database (Denmark)

    Nicolaisen, Jeppe; Frandsen, Tove Faber

    2012-01-01

    as their unit of analysis. To produce a more fine grained citation analysis one needs to study consensusformation on an even more detailed level – i.e. the scientific document or article. To do so, we have developed a new technique that measures consensus by aggregatedbibliographiccouplings (ABC) between...... documents. The advantages of the ABC-technique are demonstrated in a study of two selected disciplines in which the levels of consensus are measured using the propopsed technique....

  14. Deriving consensus rankings via multicriteria decision making methodology

    OpenAIRE

    Amy Poh Ai Ling; Mohamad Nasir Saludin; Masao Mukaidono

    2012-01-01

    Purpose - This paper seeks to take a cautionary stance to the impact of the marketing mix on customer satisfaction, via a case study deriving consensus rankings for benchmarking on selected retail stores in Malaysia. Design/methodology/approach - The ELECTRE I model is used in deriving consensus rankings via multicriteria decision making method for benchmarking base on the marketing mix model 4P's. Descriptive analysis is used to analyze best practice among the four marketing tactics. Finding...

  15. Wnt3a Promotes the Vasculogenic Mimicry Formation of Colon Cancer via Wnt/β-Catenin Signaling.

    Science.gov (United States)

    Qi, Lisha; Song, Wangzhao; Liu, Zhiyong; Zhao, Xiulan; Cao, Wenfeng; Sun, Baocun

    2015-08-10

    Our previous study provided evidence that non-canonical Wnt signaling is involved in regulating vasculogenic mimicry (VM) formation. However, the functions of canonical Wnt signaling in VM formation have not yet been explored. In this study, we found the presence of VM was related to colon cancer histological differentiation (p colon cancer samples showed increased Wnt3a expression (p colon cancer cells promoted the capacity to form tube-like structures in the three-dimensional (3-D) culture together with increased expression of endothelial phenotype-associated proteins such as VEGFR2 and VE-cadherin. The mouse xenograft model showed that Wnt3a-overexpressing cells grew into larger tumor masses and formed more VM than the control cells. In addition, the Wnt/β-catenin signaling antagonist Dickkopf-1(Dkk1) can reverse the capacity to form tube-like structures and can decrease the expressions of VEGFR2 and VE-cadherin in Wnt3a-overexpressing cells. Taken together, our results suggest that Wnt/β-catenin signaling is involved in VM formation in colon cancer and might contribute to the development of more accurate treatment modalities aimed at VM.

  16. Consensus clustering approach to group brain connectivity matrices

    Directory of Open Access Journals (Sweden)

    Javier Rasero

    2017-10-01

    Full Text Available A novel approach rooted on the notion of consensus clustering, a strategy developed for community detection in complex networks, is proposed to cope with the heterogeneity that characterizes connectivity matrices in health and disease. The method can be summarized as follows: (a define, for each node, a distance matrix for the set of subjects by comparing the connectivity pattern of that node in all pairs of subjects; (b cluster the distance matrix for each node; (c build the consensus network from the corresponding partitions; and (d extract groups of subjects by finding the communities of the consensus network thus obtained. Different from the previous implementations of consensus clustering, we thus propose to use the consensus strategy to combine the information arising from the connectivity patterns of each node. The proposed approach may be seen either as an exploratory technique or as an unsupervised pretraining step to help the subsequent construction of a supervised classifier. Applications on a toy model and two real datasets show the effectiveness of the proposed methodology, which represents heterogeneity of a set of subjects in terms of a weighted network, the consensus matrix.

  17. Stiffness-dependent cellular internalization of matrix-bound BMP-2 and its relation to Smad and non-Smad signaling.

    Science.gov (United States)

    Gilde, Flora; Fourel, Laure; Guillot, Raphael; Pignot-Paintrand, Isabelle; Okada, Takaharu; Fitzpatrick, Vincent; Boudou, Thomas; Albiges-Rizo, Corinne; Picart, Catherine

    2016-12-01

    Surface coatings delivering BMP are a promising approach to render biomaterials osteoinductive. In contrast to soluble BMPs which can interact with their receptors at the dorsal side of the cell, BMPs presented as an insoluble cue physically bound to a biomimetic matrix, called here matrix-bound (bBMP-2), are presented to cells by their ventral side. To date, BMP-2 internalization and signaling studies in cell biology have always been performed by adding soluble (sBMP-2) to cells adhered on cell culture plates or glass slides, which will be considered here as a "reference" condition. However, whether and how matrix-bound BMP-2 can be internalized by cells and its relation to canonical (SMAD) and non-canonical signaling (ALP) remain open questions. In this study, we investigated the uptake and processing of BMP-2 by C2C12 myoblasts. This BMP-2 was presented either embedded in polyelectrolyte multilayer films (matrix-bound presentation) or as soluble form. Using fluorescently labeled BMP-2, we showed that the amount of matrix-bound BMP-2 internalized is dependent on the level of crosslinking of the polyelectrolyte films. Cav-1-mediated internalization is related to both SMAD and ALP signaling, while clathrin-mediated is only related to ALP signaling. BMP-2 internalization was independent of the presentation mode (sBMP-2 versus bBMP-2) for low crosslinked films (soft, EDC10) in striking contrast with high crosslinked (stiff, EDC70) films where internalization was much lower and slower for bBMP-2. As anticipated, internalization of sBMP-2 barely depended on the underlying matrix. Taken together, these results indicate that BMP-2 internalization can be tuned by the underlying matrix and activates downstream BMP-2 signaling, which is key for the effective formation of bone tissue. The presentation of growth factors from material surfaces currently presents significant challenges in academic research, clinics and industry. Being able to deliver efficiently these growth

  18. Signal detection

    International Nuclear Information System (INIS)

    Tholomier, M.

    1985-01-01

    In a scanning electron microscope, whatever is the measured signal, the same set is found: incident beam, sample, signal detection, signal amplification. The resulting signal is used to control the spot luminosity with the observer cathodoscope. This is synchronized with the beam scanning on the sample; on the cathodoscope, the image in secondary electrons, backscattered electrons,... of the sample surface is reconstituted. The best compromise must be found between a register time low enough to remove eventual variations (under the incident beam) of the nature of the observed phenomenon, and a good spatial resolution of the image and a signal-to-noise ratio high enough. The noise is one of the basic limitations of the scanning electron microscope performance. The whose measurement line must be optimized to reduce it [fr

  19. Alcohol use and pregnancy consensus clinical guidelines.

    Science.gov (United States)

    Carson, George; Cox, Lori Vitale; Crane, Joan; Croteau, Pascal; Graves, Lisa; Kluka, Sandra; Koren, Gideon; Martel, Marie-Jocelyne; Midmer, Deana; Nulman, Irena; Poole, Nancy; Senikas, Vyta; Wood, Rebecca

    2010-08-01

    to establish national standards of care for the screening and recording of alcohol use and counselling on alcohol use of women of child-bearing age and pregnant women based on the most up-to-date evidence. published literature was retrieved through searches of PubMed, CINAHL, and the Cochrane Library in May 2009 using appropriate controlled vocabulary (e.g., pregnancy complications, alcohol drinking, prenatal care) and key words (e.g., pregnancy, alcohol consumption, risk reduction). Results were restricted to literature published in the last five years with the following research designs: systematic reviews, randomized control trials/controlled clinical trials, and observational studies. There were no language restrictions. Searches were updated on a regular basis and incorporated in the guideline to May 2010. Grey (unpublished) literature was identified through searching the websites of health technology assessment (HTA) and HTA-related agencies, national and international medical specialty societies, clinical practice guideline collections, and clinical trial registries. Each article was screened for relevance and the full text acquired if determined to be relevant. The evidence obtained was reviewed and evaluated by the members of the Expert Workgroup established by the Society of Obstetricians and Gynaecologists of Canada. The quality of evidence was evaluated and recommendations were made according to guidelines developed by the Canadian Task Force on Preventive Health Care. the quality of evidence was rated using the criteria described by the Canadian Task Force on Preventive Health Care (Table 1). the Public Health Agency of Canada and the Society of Obstetricians and Gynaecologists of Canada. these consensus guidelines have been endorsed by the Association of Obstetricians and Gynecologists of Quebec; the Canadian Association of Midwives; the Canadian Association of Perinatal, Women's Health and Neonatal Nurses (CAPWHN); the College of Family Physicians of

  20. EURECCA colorectal: multidisciplinary management: European consensus conference colon & rectum.

    Science.gov (United States)

    van de Velde, Cornelis J H; Boelens, Petra G; Borras, Josep M; Coebergh, Jan-Willem; Cervantes, Andres; Blomqvist, Lennart; Beets-Tan, Regina G H; van den Broek, Colette B M; Brown, Gina; Van Cutsem, Eric; Espin, Eloy; Haustermans, Karin; Glimelius, Bengt; Iversen, Lene H; van Krieken, J Han; Marijnen, Corrie A M; Henning, Geoffrey; Gore-Booth, Jola; Meldolesi, Elisa; Mroczkowski, Pawel; Nagtegaal, Iris; Naredi, Peter; Ortiz, Hector; Påhlman, Lars; Quirke, Philip; Rödel, Claus; Roth, Arnaud; Rutten, Harm; Schmoll, Hans J; Smith, Jason J; Tanis, Pieter J; Taylor, Claire; Wibe, Arne; Wiggers, Theo; Gambacorta, Maria A; Aristei, Cynthia; Valentini, Vincenzo

    2014-01-01

    Care for patients with colon and rectal cancer has improved in the last 20years; however considerable variation still exists in cancer management and outcome between European countries. Large variation is also apparent between national guidelines and patterns of cancer care in Europe. Therefore, EURECCA, which is the acronym of European Registration of Cancer Care, is aiming at defining core treatment strategies and developing a European audit structure in order to improve the quality of care for all patients with colon and rectal cancer. In December 2012, the first multidisciplinary consensus conference about cancer of the colon and rectum was held. The expert panel consisted of representatives of European scientific organisations involved in cancer care of patients with colon and rectal cancer and representatives of national colorectal registries. The expert panel had delegates of the European Society of Surgical Oncology (ESSO), European Society for Radiotherapy & Oncology (ESTRO), European Society of Pathology (ESP), European Society for Medical Oncology (ESMO), European Society of Radiology (ESR), European Society of Coloproctology (ESCP), European CanCer Organisation (ECCO), European Oncology Nursing Society (EONS) and the European Colorectal Cancer Patient Organisation (EuropaColon), as well as delegates from national registries or audits. Consensus was achieved using the Delphi method. For the Delphi process, multidisciplinary experts were invited to comment and vote three web-based online voting rounds and to lecture on the subjects during the meeting (13th-15th December 2012). The sentences in the consensus document were available during the meeting and a televoting round during the conference by all participants was performed. This manuscript covers all sentences of the consensus document with the result of the voting. The consensus document represents sections on diagnostics, pathology, surgery, medical oncology, radiotherapy, and follow-up where

  1. Inhibition of Wnt Signaling Pathways Impairs Chlamydia trachomatis Infection in Endometrial Epithelial Cells.

    Science.gov (United States)

    Kintner, Jennifer; Moore, Cheryl G; Whittimore, Judy D; Butler, Megan; Hall, Jennifer V

    2017-01-01

    Chlamydia trachomatis infections represent the predominant cause of bacterial sexually transmitted infections. As an obligate intracellular bacterium, C. trachomatis is dependent on the host cell for survival, propagation, and transmission. Thus, factors that affect the host cell, including nutrition, cell cycle, and environmental signals, have the potential to impact chlamydial development. Previous studies have demonstrated that activation of Wnt/β-catenin signaling benefits C. trachomatis infections in fallopian tube epithelia. In cervical epithelial cells chlamydiae sequester β-catenin within the inclusion. These data indicate that chlamydiae interact with the Wnt signaling pathway in both the upper and lower female genital tract (FGT). However, hormonal activation of canonical and non-canonical Wnt signaling pathways is an essential component of cyclic remodeling in another prominent area of the FGT, the endometrium. Given this information, we hypothesized that Wnt signaling would impact chlamydial infection in endometrial epithelial cells. To investigate this hypothesis, we analyzed the effect of Wnt inhibition on chlamydial inclusion development and elementary body (EB) production in two endometrial cell lines, Ishikawa (IK) and Hec-1B, in nonpolarized cell culture and in a polarized endometrial epithelial (IK)/stromal (SHT-290) cell co-culture model. Inhibition of Wnt by the small molecule inhibitor (IWP2) significantly decreased inclusion size in IK and IK/SHT-290 cultures ( p Wnt inhibition caused chlamydiae to become aberrant in morphology. EB formation was also impaired in IK, Hec-1B and IK/SHT-290 cultures regardless of whether Wnt inhibition occurred throughout, in the middle (24 hpi) or late (36 hpi) during the development cycle. Overall, these data lead us to conclude that Wnt signaling in the endometrium is a key host pathway for the proper development of C. trachomatis .

  2. TRAF1 Coordinates Polyubiquitin Signaling to Enhance Epstein-Barr Virus LMP1-Mediated Growth and Survival Pathway Activation.

    Directory of Open Access Journals (Sweden)

    Hannah Greenfeld

    2015-05-01

    Full Text Available The Epstein-Barr virus (EBV encoded oncoprotein Latent Membrane Protein 1 (LMP1 signals through two C-terminal tail domains to drive cell growth, survival and transformation. The LMP1 membrane-proximal TES1/CTAR1 domain recruits TRAFs to activate MAP kinase, non-canonical and canonical NF-kB pathways, and is critical for EBV-mediated B-cell transformation. TRAF1 is amongst the most highly TES1-induced target genes and is abundantly expressed in EBV-associated lymphoproliferative disorders. We found that TRAF1 expression enhanced LMP1 TES1 domain-mediated activation of the p38, JNK, ERK and canonical NF-kB pathways, but not non-canonical NF-kB pathway activity. To gain insights into how TRAF1 amplifies LMP1 TES1 MAP kinase and canonical NF-kB pathways, we performed proteomic analysis of TRAF1 complexes immuno-purified from cells uninduced or induced for LMP1 TES1 signaling. Unexpectedly, we found that LMP1 TES1 domain signaling induced an association between TRAF1 and the linear ubiquitin chain assembly complex (LUBAC, and stimulated linear (M1-linked polyubiquitin chain attachment to TRAF1 complexes. LMP1 or TRAF1 complexes isolated from EBV-transformed lymphoblastoid B cell lines (LCLs were highly modified by M1-linked polyubiqutin chains. The M1-ubiquitin binding proteins IKK-gamma/NEMO, A20 and ABIN1 each associate with TRAF1 in cells that express LMP1. TRAF2, but not the cIAP1 or cIAP2 ubiquitin ligases, plays a key role in LUBAC recruitment and M1-chain attachment to TRAF1 complexes, implicating the TRAF1:TRAF2 heterotrimer in LMP1 TES1-dependent LUBAC activation. Depletion of either TRAF1, or the LUBAC ubiquitin E3 ligase subunit HOIP, markedly impaired LCL growth. Likewise, LMP1 or TRAF1 complexes purified from LCLs were decorated by lysine 63 (K63-linked polyubiqutin chains. LMP1 TES1 signaling induced K63-polyubiquitin chain attachment to TRAF1 complexes, and TRAF2 was identified as K63-Ub chain target. Co-localization of M1- and K63

  3. A consensus statement on how to conduct inclusive health research.

    Science.gov (United States)

    Frankena, T K; Naaldenberg, J; Cardol, M; Garcia Iriarte, E; Buchner, T; Brooker, K; Embregts, P; Joosa, E; Crowther, F; Fudge Schormans, A; Schippers, A; Walmsley, J; O'Brien, P; Linehan, C; Northway, R; van Schrojenstein Lantman-de Valk, H; Leusink, G

    2018-04-11

    The active involvement of people with intellectual disabilities in research, or inclusive research, is relatively common. However, inclusive health research is less common, even though it is expected to lead to appropriate healthcare and increased quality of life. Inclusive health research can build upon lessons learned from inclusive research. A total of 17 experts on inclusive (health) research without intellectual disabilities and 40 experts with intellectual disabilities collaborated in this consensus statement. The consensus statement was developed in three consecutive rounds: (1) an initial feedback round; (2) a roundtable discussion at the 2016 International Association for the Scientific Study of Intellectual and Developmental Disabilities World Congress; and (3) a final feedback round. This consensus statement provides researchers with guidelines, agreed upon by experts in the field, regarding attributes, potential outcomes, reporting and publishing, and future research directions, for designing and conducting inclusive health research. Consensus was reached on how to design and conduct inclusive health research. However, this statement should be continuously adapted to incorporate recent knowledge. The focus of this consensus statement is largely on inclusive health research, but the principles can also be applied to other areas. © 2018 MENCAP and International Association of the Scientific Study of Intellectual and Developmental Disabilities and John Wiley & Sons Ltd.

  4. ncRNA consensus secondary structure derivation using grammar strings.

    Science.gov (United States)

    Achawanantakun, Rujira; Sun, Yanni; Takyar, Seyedeh Shohreh

    2011-04-01

    Many noncoding RNAs (ncRNAs) function through both their sequences and secondary structures. Thus, secondary structure derivation is an important issue in today's RNA research. The state-of-the-art structure annotation tools are based on comparative analysis, which derives consensus structure of homologous ncRNAs. Despite promising results from existing ncRNA aligning and consensus structure derivation tools, there is a need for more efficient and accurate ncRNA secondary structure modeling and alignment methods. In this work, we introduce a consensus structure derivation approach based on grammar string, a novel ncRNA secondary structure representation that encodes an ncRNA's sequence and secondary structure in the parameter space of a context-free grammar (CFG) and a full RNA grammar including pseudoknots. Being a string defined on a special alphabet constructed from a grammar, grammar string converts ncRNA alignment into sequence alignment. We derive consensus secondary structures from hundreds of ncRNA families from BraliBase 2.1 and 25 families containing pseudoknots using grammar string alignment. Our experiments have shown that grammar string-based structure derivation competes favorably in consensus structure quality with Murlet and RNASampler. Source code and experimental data are available at http://www.cse.msu.edu/~yannisun/grammar-string.

  5. Negative-pressure wound therapy with instillation: international consensus guidelines.

    Science.gov (United States)

    Kim, Paul J; Attinger, Christopher E; Steinberg, John S; Evans, Karen K; Lehner, Burkhard; Willy, Christian; Lavery, Larry; Wolvos, Tom; Orgill, Dennis; Ennis, William; Lantis, John; Gabriel, Allen; Schultz, Gregory

    2013-12-01

    Negative-pressure wound therapy with instillation is increasingly utilized as an adjunct therapy for a wide variety of wounds. Despite its growing popularity, there is a paucity of evidence and lack of guidance to provide effective use of this therapy. A panel of experts was convened to provide guidance regarding the appropriate use of negative-pressure wound therapy with instillation. A face-to-face meeting was held where the available evidence was discussed and individual clinical experience with this therapy was shared. Follow-up communication among the panelists continued until consensus was achieved. The final consensus recommendations were derived through more than 80 percent agreement among the panelists. Nine consensus statements were generated that address the appropriate use of negative-pressure wound therapy with instillation. The question of clinical effectiveness of this therapy was not directly addressed by the consensus panel. This document serves as preliminary guidelines until more robust evidence emerges that will support or modify these consensus recommendations.

  6. Consensus guidelines on management of childhood convulsive status epilepticus.

    Science.gov (United States)

    Mishra, Devendra; Sharma, Suvasini; Sankhyan, Naveen; Konanki, Ramesh; Kamate, Mahesh; Kanhere, Sujata; Aneja, Satinder

    2014-12-01

    Status epilepticus has a wide etiological spectrum, and significant morbidity and mortality. Management using a pre-determined uniform protocol leads to better outcomes. Multiple protocols for management of childhood status epilepticus are available, without much consensus. A 'Multi-disciplinary Consensus Development Workshop on Management of Status Epilepticus in Children in India' was organized. The invited experts included Pediatricians, Pediatric neurologists, Neurologists, Epileptologists, and Pediatric intensive care specialists from India, with experience in the relevant field. Experts had previously been divided into focus groups and had interacted on telephone and e-mail regarding their group recommendations, and developed consensus on the topic. During the meeting, each group presented their recommendations, which were deliberated upon by the house and a consensus was reached on various issues; the document was finalized after incorporating suggestions of experts on the draft document. To provide consensus guidelines on evaluation and management of convulsive status epilepticus in children in India (excluding neonatal and super-refractory status epilepticus). Each institution should use a pre-determined protocol for management of status epilepticus; pre-hospital management and early stabilization is the key to a satisfactory outcome of status epilepticus. Pharmacotherapy should not be delayed for any investigations; the initial management should consist of a parenteral benzodiazepine by any route feasible. Subsequent management has been detailed. The group also felt the need for more epidemiological research on status epilepticus from India, and identified certain research areas for the purpose.

  7. Weighted voting-based consensus clustering for chemical structure databases

    Science.gov (United States)

    Saeed, Faisal; Ahmed, Ali; Shamsir, Mohd Shahir; Salim, Naomie

    2014-06-01

    The cluster-based compound selection is used in the lead identification process of drug discovery and design. Many clustering methods have been used for chemical databases, but there is no clustering method that can obtain the best results under all circumstances. However, little attention has been focused on the use of combination methods for chemical structure clustering, which is known as consensus clustering. Recently, consensus clustering has been used in many areas including bioinformatics, machine learning and information theory. This process can improve the robustness, stability, consistency and novelty of clustering. For chemical databases, different consensus clustering methods have been used including the co-association matrix-based, graph-based, hypergraph-based and voting-based methods. In this paper, a weighted cumulative voting-based aggregation algorithm (W-CVAA) was developed. The MDL Drug Data Report (MDDR) benchmark chemical dataset was used in the experiments and represented by the AlogP and ECPF_4 descriptors. The results from the clustering methods were evaluated by the ability of the clustering to separate biologically active molecules in each cluster from inactive ones using different criteria, and the effectiveness of the consensus clustering was compared to that of Ward's method, which is the current standard clustering method in chemoinformatics. This study indicated that weighted voting-based consensus clustering can overcome the limitations of the existing voting-based methods and improve the effectiveness of combining multiple clusterings of chemical structures.

  8. A new inhibitor of the β-arrestin/AP2 endocytic complex reveals interplay between GPCR internalization and signalling

    Science.gov (United States)

    Beautrait, Alexandre; Paradis, Justine S.; Zimmerman, Brandon; Giubilaro, Jenna; Nikolajev, Ljiljana; Armando, Sylvain; Kobayashi, Hiroyuki; Yamani, Lama; Namkung, Yoon; Heydenreich, Franziska M.; Khoury, Etienne; Audet, Martin; Roux, Philippe P.; Veprintsev, Dmitry B.; Laporte, Stéphane A.; Bouvier, Michel

    2017-04-01

    In addition to G protein-coupled receptor (GPCR) desensitization and endocytosis, β-arrestin recruitment to ligand-stimulated GPCRs promotes non-canonical signalling cascades. Distinguishing the respective contributions of β-arrestin recruitment to the receptor and β-arrestin-promoted endocytosis in propagating receptor signalling has been limited by the lack of selective analytical tools. Here, using a combination of virtual screening and cell-based assays, we have identified a small molecule that selectively inhibits the interaction between β-arrestin and the β2-adaptin subunit of the clathrin adaptor protein AP2 without interfering with the formation of receptor/β-arrestin complexes. This selective β-arrestin/β2-adaptin inhibitor (Barbadin) blocks agonist-promoted endocytosis of the prototypical β2-adrenergic (β2AR), V2-vasopressin (V2R) and angiotensin-II type-1 (AT1R) receptors, but does not affect β-arrestin-independent (transferrin) or AP2-independent (endothelin-A) receptor internalization. Interestingly, Barbadin fully blocks V2R-stimulated ERK1/2 activation and blunts cAMP accumulation promoted by both V2R and β2AR, supporting the concept of β-arrestin/AP2-dependent signalling for both G protein-dependent and -independent pathways.

  9. Cultural Consensus Theory: Aggregating Continuous Responses in a Finite Interval

    Science.gov (United States)

    Batchelder, William H.; Strashny, Alex; Romney, A. Kimball

    Cultural consensus theory (CCT) consists of cognitive models for aggregating responses of "informants" to test items about some domain of their shared cultural knowledge. This paper develops a CCT model for items requiring bounded numerical responses, e.g. probability estimates, confidence judgments, or similarity judgments. The model assumes that each item generates a latent random representation in each informant, with mean equal to the consensus answer and variance depending jointly on the informant and the location of the consensus answer. The manifest responses may reflect biases of the informants. Markov Chain Monte Carlo (MCMC) methods were used to estimate the model, and simulation studies validated the approach. The model was applied to an existing cross-cultural dataset involving native Japanese and English speakers judging the similarity of emotion terms. The results sharpened earlier studies that showed that both cultures appear to have very similar cognitive representations of emotion terms.

  10. Consensus and stratification in the affective meaning of human sociality.

    Science.gov (United States)

    Ambrasat, Jens; von Scheve, Christian; Conrad, Markus; Schauenburg, Gesche; Schröder, Tobias

    2014-06-03

    We investigate intrasocietal consensus and variation in affective meanings of concepts related to authority and community, two elementary forms of human sociality. Survey participants (n = 2,849) from different socioeconomic status (SES) groups in German society provided ratings of 909 social concepts along three basic dimensions of affective meaning. Results show widespread consensus on these meanings within society and demonstrate that a meaningful structure of socially shared knowledge emerges from organizing concepts according to their affective similarity. The consensus finding is further qualified by evidence for subtle systematic variation along SES differences. In relation to affectively neutral words, high-status individuals evaluate intimacy-related and socially desirable concepts as less positive and powerful than middle- or low-status individuals, while perceiving antisocial concepts as relatively more threatening. This systematic variation across SES groups suggests that the affective meaning of sociality is to some degree a function of social stratification.

  11. The importance of assessing and communicating scientific consensus

    Science.gov (United States)

    Maibach, Edward W.; van der Linden, Sander L.

    2016-09-01

    The spread of influential misinformation, such as conspiracy theories about the existence of a secret, large-scale atmospheric spraying program (SLAP), is contributing to the politicization of science. In an important recent study, Shearer et al (2016 Environ. Res. Lett. 11 084011) employ a novel methodology to quantify the expert consensus of popular SLAP assertions. The authors find that 99% (76/77) of surveyed experts have not encountered any evidence that would support the existence of such a program. Here we argue that this finding is important because a growing body of research has shown that the public’s perception of expert consensus on key societal issues acts an important ‘gateway’ to science acceptance. Furthermore, communicating normative agreement among experts, such as the strong scientific consensus against the existence of a SLAP, can help limit the spread of misinformation and promote more effective public decision-making about science and society.

  12. Stem cell research ethics: consensus statement on emerging issues.

    Science.gov (United States)

    Caulfield, Timothy; Ogbogu, Ubaka; Nelson, Erin; Einsiedel, Edna; Knoppers, Bartha; McDonald, Michael; Brunger, Fern; Downey, Robin; Fernando, Kanchana; Galipeau, Jacques; Geransar, Rose; Griener, Glenn; Grenier, Glenn; Hyun, Insoo; Isasi, Rosario; Kardel, Melanie; Knowles, Lori; Kucic, Terrence; Lotjonen, Salla; Lyall, Drew; Magnus, David; Mathews, Debra J H; Nisbet, Matthew; Nisker, Jeffrey; Pare, Guillaume; Pattinson, Shaun; Pullman, Daryl; Rudnicki, Michael; Williams-Jones, Bryn; Zimmerman, Susan

    2007-10-01

    This article is a consensus statement by an international interdisciplinary group of academic experts and Canadian policy-makers on emerging ethical, legal and social issues in human embryonic stem cells (hESC) research in Canada. The process of researching consensus included consultations with key stakeholders in hESC research (regulations, stem cell researchers, and research ethics experts), preparation and distribution of background papers, and an international workshop held in Montreal in February 2007 to discuss the papers and debate recommendations. The recommendations provided in the consensus statement focus on issues of immediate relevance to Canadian policy-makers, including informed consent to hESC research, the use of fresh embryos in research, management of conflicts of interest, and the relevance of public opinion research to policy-making.

  13. Neural mechanisms underlying human consensus decision-making.

    Science.gov (United States)

    Suzuki, Shinsuke; Adachi, Ryo; Dunne, Simon; Bossaerts, Peter; O'Doherty, John P

    2015-04-22

    Consensus building in a group is a hallmark of animal societies, yet little is known about its underlying computational and neural mechanisms. Here, we applied a computational framework to behavioral and fMRI data from human participants performing a consensus decision-making task with up to five other participants. We found that participants reached consensus decisions through integrating their own preferences with information about the majority group members' prior choices, as well as inferences about how much each option was stuck to by the other people. These distinct decision variables were separately encoded in distinct brain areas-the ventromedial prefrontal cortex, posterior superior temporal sulcus/temporoparietal junction, and intraparietal sulcus-and were integrated in the dorsal anterior cingulate cortex. Our findings provide support for a theoretical account in which collective decisions are made through integrating multiple types of inference about oneself, others, and environments, processed in distinct brain modules. Copyright © 2015 Elsevier Inc. All rights reserved.

  14. Acceptance, acceptability, and energy consensus. Can there still be a consensus on nuclear energy?

    International Nuclear Information System (INIS)

    Renn, O.

    1995-01-01

    The question of public acceptance of nuclear energy has for years fueled the discussion on social issues. Denial of this acceptance has without doubt delayed, if not altogether prevented, the further development of nuclear energy during the past two decades. Public perception of nuclear energy is still dominated by resent. In the eyes of the German public it is a dangerous and unacceptable technology that deserves to be substituted as soon as possible. The necessity of this is widely agreed, the only unsettled question being how fast it must happen. Sociologists are often reproached for having only created the acceptance problems they purport to analyse. All sociology can do is describe our reality and make suggestions how to cope with social problems more effectively. The sociologist is the herald of social reality: he should neither gloss over nor dramatise things but rather present a real picture of what is happening. With this premise in mind the author attempts to point out possibilities of and limits to a consensus on the valuation of energy systems, particularly that of nuclear energy. (orig./UA) [de

  15. Kyoto global consensus report on Helicobacter pylori gastritis.

    Science.gov (United States)

    Sugano, Kentaro; Tack, Jan; Kuipers, Ernst J; Graham, David Y; El-Omar, Emad M; Miura, Soichiro; Haruma, Ken; Asaka, Masahiro; Uemura, Naomi; Malfertheiner, Peter

    2015-09-01

    To present results of the Kyoto Global Consensus Meeting, which was convened to develop global consensus on (1) classification of chronic gastritis and duodenitis, (2) clinical distinction of dyspepsia caused by Helicobacter pylori from functional dyspepsia, (3) appropriate diagnostic assessment of gastritis and (4) when, whom and how to treat H. pylori gastritis. Twenty-three clinical questions addressing the above-mentioned four domains were drafted for which expert panels were asked to formulate relevant statements. A Delphi method using an anonymous electronic system was adopted to develop the consensus, the level of which was predefined as ≥80%. Final modifications of clinical questions and consensus were achieved at the face-to-face meeting in Kyoto. All 24 statements for 22 clinical questions after extensive modifications and omission of one clinical question were achieved with a consensus level of >80%. To better organise classification of gastritis and duodenitis based on aetiology, a new classification of gastritis and duodenitis is recommended for the 11th international classification. A new category of H. pylori-associated dyspepsia together with a diagnostic algorithm was proposed. The adoption of grading systems for gastric cancer risk stratification, and modern image-enhancing endoscopy for the diagnosis of gastritis, were recommended. Treatment to eradicate H. pylori infection before preneoplastic changes develop, if feasible, was recommended to minimise the risk of more serious complications of the infection. A global consensus for gastritis was developed for the first time, which will be the basis for an international classification system and for further research on the subject. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

  16. Pediatric psycho-oncology care: standards, guidelines, and consensus reports.

    Science.gov (United States)

    Wiener, Lori; Viola, Adrienne; Koretski, Julia; Perper, Emily Diana; Patenaude, Andrea Farkas

    2015-02-01

    The aim of this study was to identify existing guidelines, standards, or consensus-based reports for psychosocial care of children with cancer and their families. Psychosocial standards of care for children with cancer can systematize the approach to care and create a replicable model that can be utilized in pediatric hospitals around the world. Determining gaps in existing standards in pediatric psycho-oncology can guide development of useful evidence-based and consensus-based standards. The MEDLINE and PubMed databases were searched by investigators at two major pediatric oncology centers for existing guidelines, consensus-based reports, or standards for psychosocial care of patients with pediatric cancer and their families published in peer-reviewed journals in English between 1980 and 2013. We located 27 articles about psychosocial care that met inclusion criteria: 5 set forth standards, 19 were guidelines, and 3 were consensus-based reports. None was sufficiently up to date, comprehensive, specific enough, or evidence- or consensus-based to serve as a current standard for psychosocial care for children with cancer and their families. Despite calls by a number of international pediatric oncology and psycho-oncology professional organizations about the urgency of addressing the psychosocial needs of the child with cancer to reduce suffering, there remains a need for development of a widely acceptable, evidence-based and consensus-based, comprehensive standard of care to guide provision of essential psychosocial services to all patients with pediatric cancer. Published 2014. This article is a U.S. Government work and is in the public domain in the USA.

  17. ConStruct: Improved construction of RNA consensus structures

    Directory of Open Access Journals (Sweden)

    Steger Gerhard

    2008-04-01

    Full Text Available Abstract Background Aligning homologous non-coding RNAs (ncRNAs correctly in terms of sequence and structure is an unresolved problem, due to both mathematical complexity and imperfect scoring functions. High quality alignments, however, are a prerequisite for most consensus structure prediction approaches, homology searches, and tools for phylogeny inference. Automatically created ncRNA alignments often need manual corrections, yet this manual refinement is tedious and error-prone. Results We present an extended version of CONSTRUCT, a semi-automatic, graphical tool suitable for creating RNA alignments correct in terms of both consensus sequence and consensus structure. To this purpose CONSTRUCT combines sequence alignment, thermodynamic data and various measures of covariation. One important feature is that the user is guided during the alignment correction step by a consensus dotplot, which displays all thermodynamically optimal base pairs and the corresponding covariation. Once the initial alignment is corrected, optimal and suboptimal secondary structures as well as tertiary interaction can be predicted. We demonstrate CONSTRUCT's ability to guide the user in correcting an initial alignment, and show an example for optimal secondary consensus structure prediction on very hard to align SECIS elements. Moreover we use CONSTRUCT to predict tertiary interactions from sequences of the internal ribosome entry site of CrP-like viruses. In addition we show that alignments specifically designed for benchmarking can be easily be optimized using CONSTRUCT, although they share very little sequence identity. Conclusion CONSTRUCT's graphical interface allows for an easy alignment correction based on and guided by predicted and known structural constraints. It combines several algorithms for prediction of secondary consensus structure and even tertiary interactions. The CONSTRUCT package can be downloaded from the URL listed in the Availability and

  18. Consensus stability testing protocols for organic photovoltaic materials and devices

    DEFF Research Database (Denmark)

    Reese, Matthew O.; Gevorgyan, Suren; Jørgensen, Mikkel

    2011-01-01

    Procedures for testing organic solar cell devices and modules with respect to stability and operational lifetime are described. The descriptions represent a consensus of the discussion and conclusions reached during the first 3 years of the international summit on OPV stability (ISOS). The proced......Procedures for testing organic solar cell devices and modules with respect to stability and operational lifetime are described. The descriptions represent a consensus of the discussion and conclusions reached during the first 3 years of the international summit on OPV stability (ISOS...

  19. Acute pancreatitis: reflections through the history of the Atlanta Consensus

    OpenAIRE

    Torres López, Ana María; Hoyos Duque, Sergio Iván

    2014-01-01

    Acute pancreatitis is an inflammatory process with systemic and local repercussions. Most cases are mild with low mortality rate, but 20% of the patients have severe pancreatitis with a mortality rate up to 30%. Through the years the medical community has tried to reach consensus about this disease in order to better understand, classify and treat it. The most important of these has been known as the Atlanta Consensus 1992, in use for many years. However, it has been recently the subject of v...

  20. Consensus paper on post-operative pediatric cerebellar mutism syndrome

    DEFF Research Database (Denmark)

    Gudrunardottir, Thora; Morgan, Angela T; Lux, Andrew L

    2016-01-01

    -operative pediatric CMS" was formed, preliminary recommendations for diagnostic and follow-up procedures were created, two working groups on a new scoring scale and risk prediction and prevention were established, and areas were identified where further information is needed. DISCUSSION: The consensus process...... to provide a more solid foundation for future clinical and research work. It is thought as a consensus for moving forward and hopefully paves the way to developing a standard approach to this challenging problem with the advent of better scoring methods and ultimate goal of reducing the risk of CMS....

  1. [GEITDAH consensus on conduct disorders in children and adolescents].

    Science.gov (United States)

    Sasot-Llevadot, Jordi; Ibáñez-Bordas, Rosa M; Soto-López, Antonio; Montañés-Rada, Francisco; Gastaminza-Pérez, Xavier; Alda-Díez, José A; Cantó-Díez, Tomás; Catalá, Miguel A; Ferrin-Erdozáin, Maite; García-Giral, Marta; Graell-Bernal, Montserrat; Granada-Jiménez, Olvido; Herreros-Rodríguez, Óscar; Mardomingo-Sanz, María J; Mojarro-Práxedes, Dolores; Morey-Canyelles, Jaume; Ortiz-Guerra, Juan; Pàmies-Massana, Montserrat; Rey-Sánchez, Francisco; Romera-Torrens, María; Rubio-Morell, Belén; Ruiz-Lázaro, Pedro M; Ruiz-Sanz, Francisco

    2015-08-16

    In this paper, the Special Interest Group on Attention Deficit Hyperactivity Disorder (GEITDAH, from its name in Spanish) presents a consensus reached by experts from all over Spain on conduct disorders in children and adolescents. Following the initial work by the team at the Pedopsychiatry Unit at the Quiron-Teknon Hospital in Barcelona, agreements have been reached on a number of basic aspects that could be the starting point for future consensuses. A top priority aim of the work was also to update the criteria in the Diagnostic and statistical manual of mental disorders, fifth edition, for conduct disorders in children and adolescents, together with their comorbidity with attention deficit hyperactivity disorder.

  2. Acute pancreatitis: reflections through the history of the Atlanta Consensus

    Directory of Open Access Journals (Sweden)

    Torres López, Ana María

    2014-10-01

    Full Text Available Acute pancreatitis is an inflammatory process with systemic and local repercussions. Most cases are mild with low mortality rate, but 20% of the patients have severe pancreatitis with a mortality rate up to 30%. Through the years the medical community has tried to reach consensus about this disease in order to better understand, classify and treat it. The most important of these has been known as the Atlanta Consensus 1992, in use for many years. However, it has been recently the subject of various proposals for changes and updates, which are discussed in this review article.

  3. Consensus Based Nuclear Public-Hearing System Model

    International Nuclear Information System (INIS)

    Young Wook Lee; Suk Hoon Kim; Young Ho Cho; Hyun Seok Ko; Dong Hoon Shin; Chang Sun Kang; Joo Hyun Moon

    2006-01-01

    Although the government admit the benefit of construction of a nuclear facility for national electric source, related policy could be developed and carried out only if the public, especially who have some stake on it, recognize the benefit and accept the policy. For public participation, Korea has a system of public-hearing in accordance with the law. Because of the absence of the detailed way for public opinion aggregation and for the reflection of the aggregated opinion, Korean public-hearing system is only a conceptual model. Therefore, some specific system for Korean Public-Hearing should be developed and applied. In this study, to share the right of decision making, which is an ultimate concept for public participation, decision making components and the characteristics of each phase are analyzed. The criteria weight for assessment and comparison with alternatives are founded as a valuation factor of the decision making components, which should be based on the social consensus. On these foundations, a system for aggregation and reflection of the public opinion was proposed. The system named 'CPDM' (Consensus based Participatory Decision Making) has three authority groups for decision making. At first, 'advisory experts group' play a role for the technical assessment and the serve utility value on the criteria for each alternatives. Next, 'participatory deliberation group' play a role for consensus building on the relative-importance (weight) between the criteria by feedback to promote degree of consensus. Lastly including gentlemen of the long robe, 'expert group for decision making' play a role to reflect the utility and weight and make a decision with agreement for performance of it. Also, in this study, a mathematical model for the quantification of the degree of consensus was conceptualized using Ordered Weighted Averaging (OWA) aggregation operator and fuzzy similarity theory, which is a comparison concept. Since this model enables influence of each

  4. Linear motif atlas for phosphorylation-dependent signaling

    DEFF Research Database (Denmark)

    Miller, Martin Lee; Jensen, LJ; Diella, F

    2008-01-01

    bind to them remains a challenge. NetPhorest is an atlas of consensus sequence motifs that covers 179 kinases and 104 phosphorylation-dependent binding domains [Src homology 2 (SH2), phosphotyrosine binding (PTB), BRCA1 C-terminal (BRCT), WW, and 14-3-3]. The atlas reveals new aspects of signaling...

  5. Consensus statement on transcultural issues in depression and anxiety from the International Consensus Group on Depression and Anxiety.

    Science.gov (United States)

    Ballenger, J C; Davidson, J R; Lecrubier, Y; Nutt, D J; Kirmayer, L J; Lépine, J P; Lin, K M; Tajima, O; Ono, Y

    2001-01-01

    To provide primary care physicians with a better understanding of transcultural issues in depression and anxiety. The 4 members of the International Consensus Group on Depression and Anxiety were James C. Ballenger (chair), Jonathan R. T. Davidson, Yves Lecrubier, and David J. Nutt. Five faculty invited by the chair also participated: Laurence J. Kirmayer, Jean-Pierre Lepine, Keh-Ming Lin, Osamu Tajima, and Yutaka Ono. The consensus statement is based on the 5 review articles that are published in this supplement and the scientific literature relevant to the issues reviewed in these articles. Group meetings were held over a 2-day period. On day 1, the group discussed the review articles, and the chair identified key issues for further debate. On day 2, the group discussed these issues to arrive at a consensus view. After the group meetings, the consensus statement was drafted by the chair and approved by all attendees. The consensus statement underlines the prevalence of depression and anxiety disorders across all cultures and nations while recognizing that cultural differences exist in symptom presentation and prevalence estimates. In all countries, the recognition of depression by clinicians in the primary care setting is low (generally less than 50%), and the consensus group recommends a 2-step process to aid the recognition and diagnosis of depression. In line with the low recognition of depression and anxiety disorders is the finding that only a small proportion of patients with depression or anxiety are receiving appropriate treatments for their condition. Biological diversity across ethnic groups may account for the differential sensitivity of some groups to psychotropic medication, but this area requires further investigation.

  6. Signal Processing

    International Nuclear Information System (INIS)

    Anon.

    1992-01-01

    Signal processing techniques, extensively used nowadays to maximize the performance of audio and video equipment, have been a key part in the design of hardware and software for high energy physics detectors since pioneering applications in the UA1 experiment at CERN in 1979

  7. Identification of Phosphorylation Consensus Sequences and Endogenous Neuronal Substrates of the Psychiatric Risk Kinase TNIK.

    Science.gov (United States)

    Wang, Qi; Amato, Stephen P; Rubitski, David M; Hayward, Matthew M; Kormos, Bethany L; Verhoest, Patrick R; Xu, Lan; Brandon, Nicholas J; Ehlers, Michael D

    2016-02-01

    Traf2- and Nck-interacting kinase (TNIK) is a serine/threonine kinase highly expressed in the brain and enriched in the postsynaptic density of glutamatergic synapses in the mammalian brain. Accumulating genetic evidence and functional data have implicated TNIK as a risk factor for psychiatric disorders. However, the endogenous substrates of TNIK in neurons are unknown. Here, we describe a novel selective small molecule inhibitor of the TNIK kinase family. Using this inhibitor, we report the identification of endogenous neuronal TNIK substrates by immunoprecipitation with a phosphomotif antibody followed by mass spectrometry. Phosphorylation consensus sequences were defined by phosphopeptide sequence analysis. Among the identified substrates were members of the delta-catenin family including p120-catenin, δ-catenin, and armadillo repeat gene deleted in velo-cardio-facial syndrome (ARVCF), each of which is linked to psychiatric or neurologic disorders. Using p120-catenin as a representative substrate, we show TNIK-induced p120-catenin phosphorylation in cells requires intact kinase activity and phosphorylation of TNIK at T181 and T187 in the activation loop. Addition of the small molecule TNIK inhibitor or knocking down TNIK by two shRNAs reduced endogenous p120-catenin phosphorylation in cells. Together, using a TNIK inhibitor and phosphomotif antibody, we identify endogenous substrates of TNIK in neurons, define consensus sequences for TNIK, and suggest signaling pathways by which TNIK influences synaptic development and function linked to psychiatric and neurologic disorders. Copyright © 2016 by The American Society for Pharmacology and Experimental Therapeutics.

  8. Analysis and prediction of leucine-rich nuclear export signals

    DEFF Research Database (Denmark)

    La Cour, T.; Kiemer, Lars; Mølgaard, Anne

    2004-01-01

    We present a thorough analysis of nuclear export signals and a prediction server, which we have made publicly available. The machine learning prediction method is a significant improvement over the generally used consensus patterns. Nuclear export signals (NESs) are extremely important regulators...... this analysis is that the most important properties of NESs are accessibility and flexibility allowing relevant proteins to interact with the signal. Furthermore, we show that not only the known hydrophobic residues are important in defining a nuclear export signals. We employ both neural networks and hidden...

  9. The ''Article Act'' - a substitute for the miscarried energy consensus?

    International Nuclear Information System (INIS)

    Knott, G.

    1994-01-01

    A prerequisite for arriving at a long-term energy policy is that all political parties come to an energy consensus. This paper reviews the chronology of the energy consensus negatiations, their failure, and the consequent energy-political rerouting which is to be realised by an act securing hard coal a share in electricity generation and amending the Atomic Energy Act (termed 'Article Act'). The Article Act is an attempt at a binding definition of central issues of the energy consensus talks even in the absence of an all-party agreement. It is particularly noteworthy that the bill makes mention of both coal and nuclear energy, reviving this link-up between the two energy sources already decined lost. The German electricity industry considers the provisions on atomic energy law contained in the Article Act insufficient for securing already existing power plants an untroubled future and for providing the investment climate needed by the manufacturing industry. To the electricity industry the main problems lie in the execution deficits at the Laender level, but these are not affected by the Article Act. It is concluded that an all-party consensus on an answerable nuclear energy utilisation will have to be found by 1995 at the latest in order to give the manufacturing industry the go-alread for continuing research and provide electricity producers with a sound basis for investment decisions. (orig./HSCH) [de

  10. Yes, But...Creating a Consensus for Educational Change.

    Science.gov (United States)

    Hampel, Robert L.

    1991-01-01

    Maintains that the division of opinions in a staff can determine an educational innovation's success or failure. Teacher empowerment can help forge widespread agreement and consensus for the innovation. These principles are exemplified by the Sizer initiative in the Delaware schools, which is described. (BB)

  11. Forging Consensus for Implementing Youth Socialization Policy in Northwest China

    Science.gov (United States)

    Fairbrother, Gregory P.

    2011-01-01

    The goal of this article is to examine how the provincial education media in China play a role of forging consensus among local actors responsible for the implementation of new centrally-promulgated youth socialization policy. In doing so, it also explores the tension among three of the Chinese state's claims to legitimacy: economic development,…

  12. Global Consensus Recommendations on Prevention and Management of Nutritional Rickets.

    Science.gov (United States)

    Munns, Craig F; Shaw, Nick; Kiely, Mairead; Specker, Bonny L; Thacher, Tom D; Ozono, Keiichi; Michigami, Toshimi; Tiosano, Dov; Mughal, M Zulf; Mäkitie, Outi; Ramos-Abad, Lorna; Ward, Leanne; DiMeglio, Linda A; Atapattu, Navoda; Cassinelli, Hamilton; Braegger, Christian; Pettifor, John M; Seth, Anju; Idris, Hafsatu Wasagu; Bhatia, Vijayalakshmi; Fu, Junfen; Goldberg, Gail; Sävendahl, Lars; Khadgawat, Rajesh; Pludowski, Pawel; Maddock, Jane; Hyppönen, Elina; Oduwole, Abiola; Frew, Emma; Aguiar, Magda; Tulchinsky, Ted; Butler, Gary; Högler, Wolfgang

    2016-02-01

    Vitamin D and calcium deficiencies are common worldwide, causing nutritional rickets and osteomalacia, which have a major impact on health, growth, and development of infants, children, and adolescents; the consequences can be lethal or can last into adulthood. The goals of this evidence-based consensus document are to provide health care professionals with guidance for prevention, diagnosis, and management of nutritional rickets and to provide policy makers with a framework to work toward its eradication. A systematic literature search examining the definition, diagnosis, treatment, and prevention of nutritional rickets in children was conducted. Evidence-based recommendations were developed using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) system that describe the strength of the recommendation and the quality of supporting evidence. Thirty-three nominated experts in pediatric endocrinology, pediatrics, nutrition, epidemiology, public health, and health economics evaluated the evidence on specific questions within five working groups. The consensus group, representing 11 international scientific organizations, participated in a multiday conference in May 2014 to reach a global evidence-based consensus. This consensus document defines nutritional rickets and its diagnostic criteria and describes the clinical management of rickets and osteomalacia. Risk factors, particularly in mothers and infants, are ranked, and specific prevention recommendations including food fortification and supplementation are offered for both the clinical and public health contexts. Rickets, osteomalacia, and vitamin D and calcium deficiencies are preventable global public health problems in infants, children, and adolescents. Implementation of international rickets prevention programs, including supplementation and food fortification, is urgently required.

  13. If Not Consensus, at Least Coherence and Transparency.

    Science.gov (United States)

    Phillips, June K.

    1995-01-01

    Suggests that consensus is the result of intellectual inquiry among scholars for some common purpose. External and internal forces impel the academic community to move beyond argumentation about what students should be able to achieve as they progress. Legislatures and boards of regents are exercising increasing oversight over public and private…

  14. When goals diverge: Staff consensus and the organizational climate.

    Science.gov (United States)

    Melnick, Gerald; Ulaszek, Wendy R; Lin, Hsiu-Ju; Wexler, Harry K

    2009-08-01

    A sample of correctional officers and prison substance abuse treatment staff collected by the National Criminal Justice Treatment Practices Survey is used to provide an exploratory study of an aspect of organizational culture consisting of consensus (agreement) among prison personnel regarding their beliefs about rehabilitation in the presence of conflicting organizational goals and aspects of the organizational climate important to change. Findings show that among those staff members responding to the survey, the belief in rehabilitation scale mean score was associated with higher levels of organizational commitment, and interdepartmental coordination. However, an hierarchical linear modeling (HLM) analysis that used an index score derived from the standard deviation for staff consensus regarding these same beliefs about rehabilitation produced a different pattern of results, showing that high levels of consensus were associated with job frustration, cynicism towards the ability of the institution to change, and lower levels of organizational commitment. The authors conclude that, although the sample may not express the beliefs of corrections officers or prison-based treatment staff at large, within the sample, consensus appeared to play a unique role in evaluating the effect of divergent goals on organizational climate as it relates to change, and warrants consideration when considering the effects of organizational climate.

  15. False consensus in situational judgment tests : What would others do?

    NARCIS (Netherlands)

    Oostrom, J.K.; Köbis, N.C.; Ronay, R.; Cremers, M.

    2017-01-01

    We introduce an alternative response instruction to reduce the fakability of situational judgment tests. This novel instruction is based on the false consensus effect, a robust social psychological bias whereby people infer that the majority of other people’s thoughts, attitudes, and behaviors are

  16. The False Consensus Bias as Applied to Psychologically Disturbed Adolescents.

    Science.gov (United States)

    Range, Lillian M.; And Others

    1991-01-01

    Twelve adolescents who described themselves as depressed or suicidal and 43 nondisturbed adolescents read article about child's suicidal or viral illness death. Both groups viewed suicidal child and family more negatively than family and child with viral illness. Consistent with false consensus hypothesis, psychologically disturbed adolescents…

  17. Attributions, false consensus and valence: two field studies

    NARCIS (Netherlands)

    van der Pligt, J.

    1984-01-01

    Two studies, with 1,056 Ss, investigated attitudes, knowledge, and behavior with regard to several environmental issues. Findings demonstrate that observers tend to perceive a false consensus with respect to the relative commonness of their own behavioral choices. This phenomenon was replicated

  18. A Computerized Demonstration of the False Consensus Effect.

    Science.gov (United States)

    Clement, Russell W.; And Others

    1997-01-01

    Replicates a classic psychology laboratory experiment where students either endorsed or refuted personal statements and estimated how other people would respond. Students always overestimated an affirmative response on the statements they endorsed, thus illustrating the false consensus effect. Includes a list of the statements and statistical…

  19. Power, conflict and consensus building in Africa: Ideology revisited

    African Journals Online (AJOL)

    As presently applied in Africa, consensus building seems to be a product of knowledge ... Often international professional negotiators and .... The conflict model views individual or group relationships in all structures of power as a ..... for political parties to win and maintain power, Weber states that 'parties live in the house of ...

  20. Consensus in the network with uniform constant communication delay

    NARCIS (Netherlands)

    Wang, Xu; Saberi, Ali; Stoorvogel, Antonie Arij; Grip, H°avard Fjær; Yang, Tao

    2013-01-01

    This paper studies consensus among identical agents that are at most critically unstable and coupled through networks with uniform constant communication delay. An upper bound for delay tolerance is obtained which explicitly depends on agent dynamics and network topology. The dependence on network

  1. Implants and/or teeth: consensus statements and recommendations

    DEFF Research Database (Denmark)

    Gotfredsen, K; Carlsson, G E; Jokstad, A

    2008-01-01

    In August 23-25, 2007, the Scandinavian Society for Prosthetic Dentistry in collaboration with the Danish Society of Oral Implantology arranged a consensus conference on the topic 'Implants and/or teeth'. It was preceded by a workshop in which eight focused questions were raised and answered in e...

  2. Helicobacter pylori management in ASEAN: The Bangkok consensus report.

    Science.gov (United States)

    Mahachai, Varocha; Vilaichone, Ratha-Korn; Pittayanon, Rapat; Rojborwonwitaya, Jarin; Leelakusolvong, Somchai; Maneerattanaporn, Monthira; Chotivitayatarakorn, Peranart; Treeprasertsuk, Sombat; Kositchaiwat, Chomsri; Pisespongsa, Pises; Mairiang, Pisaln; Rani, Aziz; Leow, Alex; Mya, Swe Mon; Lee, Yi-Chia; Vannarath, Sengdao; Rasachak, Bouachanh; Chakravuth, Oung; Aung, Moe Myint; Ang, Tiing-Leong; Sollano, Jose D; Trong Quach, Duc; Sansak, Inchaya; Wiwattanachang, Olarn; Harnsomburana, Piyathida; Syam, Ari Fahrial; Yamaoka, Yoshio; Fock, Kwong-Ming; Goh, Khean-Lee; Sugano, Kentaro; Graham, David

    2018-01-01

    Helicobacter pylori (H. pylori) infection remains to be the major cause of important upper gastrointestinal diseases such as chronic gastritis, peptic ulcer, gastric adenocarcinoma, and mucosa-associated lymphoid tissue lymphoma. H. pylori management in ASEAN: the Bangkok consensus report gathered key opinion leaders for the region to review and evaluate clinical aspects of H. pylori infection and to develop consensus statements, rationales, and grades of recommendation for the management of H. pylori infection in clinical practice in ASEAN countries. This ASEAN Consensus consisted of 34 international experts from 10 ASEAN countries, Japan, Taiwan, and the United States. The meeting mainly focused on four issues: (i) epidemiology and disease association; (ii) diagnostic tests; (iii) management; and (iv) follow-up after eradication. The final results of each workshop were presented for consensus voting by all participants. Statements, rationale, and recommendations were developed from the available current evidence to help clinicians in the diagnosis and treatment of H. pylori and its clinical diseases. © 2017 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.

  3. A consensus linkage map of the chicken genome

    NARCIS (Netherlands)

    Groenen, M.A.M.; Cheng, H.H.; Bumstead, N.; Benkel, B.; Briles, E.; Burt, D.W.; Burke, T.; Dodgson, J.; Hillel, J.; Lamont, S.; Ponce, de F.A.; Soller, M.

    2000-01-01

    A consensus linkage map has been developed in the chicken that combines all of the genotyping data from the three available chicken mapping populations. Genotyping data were contributed by the laboratories that have been using the East Lansing and Compton reference populations and from the Animal

  4. Consensus double reading of mammograms in private practice

    International Nuclear Information System (INIS)

    Pacher, B.; Tscherney, R.; Litmann-Rowenta, B.; Liskutin, J.; Mazewski, I.; Leitner, H.; Tscholakoff, D.

    2004-01-01

    Purpose: To evaluate retrospectively the results of consensus double reading of mammograms in a private practice for a period of 1.5 years (November 2001 to March 2003). Materials and Method: Two independent experts with dedicated training read all mammograms on a weekly basis. All mammograms including sonographic examinations were evaluated independently and categorized using the Bl-RADS classification. The achieved consensus included a possible recommendation for recall or therapy. A total of 3936 mammograms and 1912 sonography studies were evaluated. All cases with BI-RADS 4 and 5 categories were compared with the histologic results. For a period of three months, the acceptance of double reading including a delay of the final report by one week was tested with a questionnaire and informed consent sheet. Results: BI-RADS categories 4 and 5 were found in 57 cases, with 41 consensus results by two independent readers and 26 carcinomas verified by histology. No consensus could be reached in 16 patients, of which 10 had a final histologic result, with 5 benign lesions and 5 carcinomas of less than 1 cm in diameter. Clinical symptoms or alterations were absent in all patients. The 5 carcinomas were discovered by the double reading procedure. The result of the questionnaire (695 questionnaires) showed a refusal rate of 0.7%, with only 5 women refusing the opportunity of double reading their mammograms. Conclusion: Double reading of mammograms by independent experts is feasible, shows a measurable increase in quality and is accepted by almost all women. (orig.)

  5. Recommendations for Probiotic Use--2015 Update: Proceedings and Consensus Opinion

    NARCIS (Netherlands)

    Floch, Martin H.; Walker, W. Allan; Sanders, Mary Ellen; Nieuwdorp, Max; Kim, Adam S.; Brenner, David A.; Qamar, Amir A.; Miloh, Tamir A.; Guarino, Alfredo; Guslandi, Mario; Dieleman, Levinus A.; Ringel, Yehuda; Quigley, Eamonn M. M.; Brandt, Lawrence J.

    2015-01-01

    This paper describes the consensus opinion of the participants in the 4th Triennial Yale/Harvard Workshop on Probiotic Recommendations. The recommendations update those of the first 3 meetings that were published in 2006, 2008, and 2011. Recommendations for the use of probiotics in necrotizing

  6. 78 FR 35085 - Consensus Standards, Light-Sport Aircraft

    Science.gov (United States)

    2013-06-11

    ... DEPARTMENT OF TRANSPORTATION Federal Aviation Administration Consensus Standards, Light-Sport... to the provisions of the Sport Pilot and Light-Sport Aircraft rule issued July 16, 2004, and effective September 1, 2004. ASTM International Committee F37 on Light Sport Aircraft developed the new and...

  7. 77 FR 24251 - Consensus Standards, Light-Sport Aircraft

    Science.gov (United States)

    2012-04-23

    ... DEPARTMENT OF TRANSPORTATION Federal Aviation Administration Consensus Standards, Light-Sport... relating to the provisions of the Sport Pilot and Light-Sport Aircraft rule issued July 16, 2004, and effective September 1, 2004. ASTM International Committee F37 on Light Sport Aircraft developed the new and...

  8. Functional Analysis of HIV/AIDS Stigma: Consensus or Divergence?

    Science.gov (United States)

    Hosseinzadeh, Hassan; Hossain, Syeda Zakia

    2011-01-01

    Functional theory proposes that attitudes may serve a variety of purposes for individuals. This study aimed to determine whether stigmatized attitudes toward HIV/AIDS serve the same function for all (consensus function) or serve different functions for different individuals (divergence function) by assessing various aspects of HIV/AIDS stigma…

  9. Expert Consensus on Characteristics of Wisdom: A Delphi Method Study

    Science.gov (United States)

    Jeste, Dilip V.; Ardelt, Monika; Blazer, Dan; Kraemer, Helena C.; Vaillant, George; Meeks, Thomas W.

    2010-01-01

    Purpose: Wisdom has received increasing attention in empirical research in recent years, especially in gerontology and psychology, but consistent definitions of wisdom remain elusive. We sought to better characterize this concept via an expert consensus panel using a 2-phase Delphi method. Design and Methods: A survey questionnaire comprised 53…

  10. Recurrence of Dupuytren's contracture: A consensus-based definition.

    Directory of Open Access Journals (Sweden)

    Hester J Kan

    Full Text Available One of the major determinants of Dupyutren disease (DD treatment efficacy is recurrence of the contracture. Unfortunately, lack of agreement in the literature on what constitutes recurrence makes it nearly impossible to compare the multiple treatments alternatives available today. The aim of this study is to bring an unbiased pool of experts to agree upon what would be considered a recurrence of DD after treatment; and from that consensus establish a much-needed definition for DD recurrence.To reach an expert consensus on the definition of recurrence we used the Delphi method and invited 43 Dupuytren's research and treatment experts from 10 countries to participate by answering a series of questionnaire rounds. After each round the answers were analyzed and the experts received a feedback report with another questionnaire round to further hone in of the definition. We defined consensus when at least 70% of the experts agreed on a topic.Twenty-one experts agreed to participate in this study. After four consensus rounds, we agreed that DD recurrence should be defined as "more than 20 degrees of contracture recurrence in any treated joint at one year post-treatment compared to six weeks post-treatment". In addition, "recurrence should be reported individually for every treated joint" and afterwards measurements should be repeated and reported yearly.This study provides the most comprehensive to date definition of what should be considered recurrence of DD. These standardized criteria should allow us to better evaluate the many treatment alternatives.

  11. Building consensus on clinical procedural skills for South African ...

    African Journals Online (AJOL)

    Background: The development of registrar training as part of the newly created speciality of family medicine in South Africa requires the development of a national consensus on the clinical procedural skills outcomes that should be expected of training programmes. Methods: This study utilized a Delphi technique to ...

  12. Differential diagnosis of suspected multiple sclerosis: a consensus approach

    NARCIS (Netherlands)

    Miller, D. H.; Weinshenker, B.G.; Filippi, M.; Banwell, B.L.; Cohen, J.A.; Freedman, M.S.; Galetta, S.L.; Hutchinson, M.; Johnson, R.T.; Kappos, L.; Kira, J.; Lublin, F.D.; McFarland, H.F.; Montalban, X.; Panitch, H.; Richert, J.R.; Reingold, S.C.; Polman, C.H.

    2008-01-01

    Background and objectives: Diagnosis of multiple sclerosis (MS) requires exclusion of diseases that could better explain the clinical and paraclinical findings. A systematic process for exclusion of alternative diagnoses has not been defined. An International Panel of MS experts developed consensus

  13. Effects of heterogeneous convergence rate on consensus in opinion dynamics

    Science.gov (United States)

    Huang, Changwei; Dai, Qionglin; Han, Wenchen; Feng, Yuee; Cheng, Hongyan; Li, Haihong

    2018-06-01

    The Deffuant model has attracted much attention in the study of opinion dynamics. Here, we propose a modified version by introducing into the model a heterogeneous convergence rate which is dependent on the opinion difference between interacting agents and a tunable parameter κ. We study the effects of heterogeneous convergence rate on consensus by investigating the probability of complete consensus, the size of the largest opinion cluster, the number of opinion clusters, and the relaxation time. We find that the decrease of the convergence rate is favorable to decreasing the confidence threshold for the population to always reach complete consensus, and there exists optimal κ resulting in the minimal bounded confidence threshold. Moreover, we find that there exists a window before the threshold of confidence in which complete consensus may be reached with a nonzero probability when κ is not too large. We also find that, within a certain confidence range, decreasing the convergence rate will reduce the relaxation time, which is somewhat counterintuitive.

  14. An updated Asia Pacific Consensus Recommendations on colorectal cancer screening.

    Science.gov (United States)

    Sung, J J Y; Ng, S C; Chan, F K L; Chiu, H M; Kim, H S; Matsuda, T; Ng, S S M; Lau, J Y W; Zheng, S; Adler, S; Reddy, N; Yeoh, K G; Tsoi, K K F; Ching, J Y L; Kuipers, E J; Rabeneck, L; Young, G P; Steele, R J; Lieberman, D; Goh, K L

    2015-01-01

    Since the publication of the first Asia Pacific Consensus on Colorectal Cancer (CRC) in 2008, there are substantial advancements in the science and experience of implementing CRC screening. The Asia Pacific Working Group aimed to provide an updated set of consensus recommendations. Members from 14 Asian regions gathered to seek consensus using other national and international guidelines, and recent relevant literature published from 2008 to 2013. A modified Delphi process was adopted to develop the statements. Age range for CRC screening is defined as 50-75 years. Advancing age, male, family history of CRC, smoking and obesity are confirmed risk factors for CRC and advanced neoplasia. A risk-stratified scoring system is recommended for selecting high-risk patients for colonoscopy. Quantitative faecal immunochemical test (FIT) instead of guaiac-based faecal occult blood test (gFOBT) is preferred for average-risk subjects. Ancillary methods in colonoscopy, with the exception of chromoendoscopy, have not proven to be superior to high-definition white light endoscopy in identifying adenoma. Quality of colonoscopy should be upheld and quality assurance programme should be in place to audit every aspects of CRC screening. Serrated adenoma is recognised as a risk for interval cancer. There is no consensus on the recruitment of trained endoscopy nurses for CRC screening. Based on recent data on CRC screening, an updated list of recommendations on CRC screening is prepared. These consensus statements will further enhance the implementation of CRC screening in the Asia Pacific region. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

  15. Consensus pursuit of heterogeneous multi-agent systems under a directed acyclic graph

    Science.gov (United States)

    Yan, Jing; Guan, Xin-Ping; Luo, Xiao-Yuan

    2011-04-01

    This paper is concerned with the cooperative target pursuit problem by multiple agents based on directed acyclic graph. The target appears at a random location and moves only when sensed by the agents, and agents will pursue the target once they detect its existence. Since the ability of each agent may be different, we consider the heterogeneous multi-agent systems. According to the topology of the multi-agent systems, a novel consensus-based control law is proposed, where the target and agents are modeled as a leader and followers, respectively. Based on Mason's rule and signal flow graph analysis, the convergence conditions are provided to show that the agents can catch the target in a finite time. Finally, simulation studies are provided to verify the effectiveness of the proposed approach.

  16. Reliability of a consensus-based ultrasound score for tenosynovitis in rheumatoid arthritis

    DEFF Research Database (Denmark)

    Naredo, Esperanza; D'Agostino, Maria Antonietta; Wakefield, Richard J

    2013-01-01

    OBJECTIVE: To produce consensus-based scoring systems for ultrasound (US) tenosynovitis and to assess the intraobserver and interobserver reliability of these scoring systems in rheumatoid arthritis (RA). METHODS: We undertook a Delphi process on US-defined tenosynovitis and US scoring system...... recruited. Ten rheumatologists expert in MSUS blindly, independently and consecutively scored for tenosynovitis in B-mode and PD mode three wrist extensor compartments, two finger flexor tendons and two ankle tendons of each patient in two rounds in a blinded fashion. Intraobserver reliability was assessed...... Doppler signal within the synovial sheath. The intraobserver reliability for tenosynovitis scoring on B-mode and PD mode was good (κ value 0.72 for B-mode; κ value 0.78 for PD mode). Interobserver reliability assessment showed good κ values for PD tenosynovitis scoring (first round, 0.64; second round, 0...

  17. World Endometriosis Society consensus on the classification of endometriosis.

    Science.gov (United States)

    Johnson, Neil P; Hummelshoj, Lone; Adamson, G David; Keckstein, Jörg; Taylor, Hugh S; Abrao, Mauricio S; Bush, Deborah; Kiesel, Ludwig; Tamimi, Rulla; Sharpe-Timms, Kathy L; Rombauts, Luk; Giudice, Linda C

    2017-02-01

    What is the global consensus on the classification of endometriosis that considers the views of women with endometriosis? We have produced an international consensus statement on the classification of endometriosis through systematic appraisal of evidence and a consensus process that included representatives of national and international, medical and non-medical societies, patient organizations, and companies with an interest in endometriosis. Classification systems of endometriosis, developed by several professional organizations, traditionally have been based on lesion appearance, pelvic adhesions, and anatomic location of disease. One system predicts fertility outcome and none predicts pelvic pain, response to medications, disease recurrence, risks for associated disorders, quality of life measures, and other endpoints important to women and health care providers for guiding appropriate therapeutic options and prognosis. A consensus meeting, in conjunction with pre- and post-meeting processes, was undertaken. A consensus meeting was held on 30 April 2014 in conjunction with the World Endometriosis Society's 12th World Congress on Endometriosis. Rigorous pre- and post-meeting processes, involving 55 representatives of 29 national and international, medical and non-medical organizations from a range of disciplines, led to this consensus statement. A total of 28 consensus statements were made. Of all, 10 statements had unanimous consensus, however none of the statements was made without expression of a caveat about the strength of the statement or the statement itself. Two statements did not achieve majority consensus. The statements covered women's priorities, aspects of classification, impact of low resources, as well as all the major classification systems for endometriosis. Until better classification systems are developed, we propose a classification toolbox (that includes the revised American Society for Reproductive Medicine and, where appropriate, the

  18. Consensus on Recording Deep Endometriosis Surgery: the CORDES statement.

    Science.gov (United States)

    Vanhie, A; Meuleman, C; Tomassetti, C; Timmerman, D; D'Hoore, A; Wolthuis, A; Van Cleynenbreugel, B; Dancet, E; Van den Broeck, U; Tsaltas, J; Renner, S P; Ebert, A D; Carmona, F; Abbott, J; Stepniewska, A; Taylor, H; Saridogan, E; Mueller, M; Keckstein, J; Pluchino, N; Janik, G; Zupi, E; Minelli, L; Cooper, M; Dunselman, G; Koh, C; Abrao, M S; Chapron, C; D'Hooghe, T

    2016-06-01

    Which essential items should be recorded before, during and after endometriosis surgery and in clinical outcome based surgical trials in patients with deep endometriosis (DE)? A DE surgical sheet (DESS) was developed for standardized reporting of the surgical treatment of DE and an international expert consensus proposal on relevant items that should be recorded in surgical outcome trials in women with DE. Surgery is an important treatment for symptomatic DE. So far, data have been reported in such a way that comparison of different surgical techniques is impossible. Therefore, we present an international expert proposal for standardized reporting of surgical treatment and surgical outcome trials in women with DE. International expert consensus based on a systematic review of literature. Taking into account recommendations from Consolidated Standards of Reporting Trials (CONSORT), the Innovation Development Exploration Assessment and Long-term Study (IDEAL), the Initiative on Methods, Measurement and Pain Assessment in Clinical trials (IMMPACT) and the World Endometriosis Research Foundation Phenome and Biobanking Harmonisation Project (WERF EPHect), a systematic literature review on surgical treatment of DE was performed and resulted in a proposal for standardized reporting, adapted by contributions from eight members of the multidisciplinary Leuven University Hospitals Endometriosis Care Program, from 18 international experts and from audience feedback during three international meetings. We have developed the DESS to record in detail the surgical procedures for DE, and an international consensus on pre-, intra- and post-operative data that should be recorded in surgical outcome trials on DE. The recommendations in this paper represent a consensus among international experts based on a systematic review of the literature. For several items and recommendations, high-quality RCTs were not available. Further research is needed to validate and evaluate the

  19. Integrin Signalling

    OpenAIRE

    Schelfaut, Roselien

    2005-01-01

    Integrins are receptors presented on most cells. By binding ligand they can generate signalling pathways inside the cell. Those pathways are a linkage to proteins in the cytosol. It is known that tumor cells can survive and proliferate in the absence of a solid support while normal cells need to be bound to ligand. To understand why tumour cells act that way, we first have to know how ligand-binding to integrins affect the cell. This research field includes studies on activation of proteins b...

  20. Learning Gene Regulatory Networks Computationally from Gene Expression Data Using Weighted Consensus

    KAUST Repository

    Fujii, Chisato

    2015-01-01

    the performance of the consensus. The linear programming- based consensus method is evaluated and it had the best performance on in silico and Saccharomyces cerevisiae networks, and the second best on the Escherichia coli network outperformed by Inferelator

  1. Secondary Coordinated Control of Islanded Microgrids Based on Consensus Algorithms

    DEFF Research Database (Denmark)

    Wu, Dan; Dragicevic, Tomislav; Vasquez, Juan Carlos

    2014-01-01

    systems. Nevertheless, the conventional decentralized secondary control, although does not need to be implemented in a microgrid central controller (MGCC), it has the limitation that all decentralized controllers must be mutually synchronized. In a clear cut contrast, the proposed secondary control......This paper proposes a decentralized secondary control for islanded microgrids based on consensus algorithms. In a microgrid, the secondary control is implemented in order to eliminate the frequency changes caused by the primary control when coordinating renewable energy sources and energy storage...... requires only a more simplified communication protocol and a sparse communication network. Moreover, the proposed approach based on dynamic consensus algorithms is able to achieve the coordinated secondary performance even when all units are initially out-of-synchronism. The control algorithm implemented...

  2. Consensus, Polarization, and Alignment in the Economics Profession

    Directory of Open Access Journals (Sweden)

    Tod S. Van Gunten

    2016-12-01

    Full Text Available Scholars interested in the political influence of the economics profession debate whether the discipline is unified by policy consensus or divided among competing schools or factions. We address this question by reanalyzing a unique recent survey of elite economists. We present a theoretical framework based on a formal sociological approach to the structure of belief systems and propose alignment, rather than consensus or polarization, as a model for the structure of belief in the economics profession. Moreover, we argue that social clustering in a heterogeneous network topology is a better model for disciplinary social structure than discrete factionalization. Results show that there is a robust latent ideological dimension related to economists’ departmental affiliations and political partisanship. Furthermore, we show that economists closer to one another in informal social networks also share more similar ideologies.

  3. Automating the expert consensus paradigm for robust lung tissue classification

    Science.gov (United States)

    Rajagopalan, Srinivasan; Karwoski, Ronald A.; Raghunath, Sushravya; Bartholmai, Brian J.; Robb, Richard A.

    2012-03-01

    Clinicians confirm the efficacy of dynamic multidisciplinary interactions in diagnosing Lung disease/wellness from CT scans. However, routine clinical practice cannot readily accomodate such interactions. Current schemes for automating lung tissue classification are based on a single elusive disease differentiating metric; this undermines their reliability in routine diagnosis. We propose a computational workflow that uses a collection (#: 15) of probability density functions (pdf)-based similarity metrics to automatically cluster pattern-specific (#patterns: 5) volumes of interest (#VOI: 976) extracted from the lung CT scans of 14 patients. The resultant clusters are refined for intra-partition compactness and subsequently aggregated into a super cluster using a cluster ensemble technique. The super clusters were validated against the consensus agreement of four clinical experts. The aggregations correlated strongly with expert consensus. By effectively mimicking the expertise of physicians, the proposed workflow could make automation of lung tissue classification a clinical reality.

  4. Multilevel stake holder consensus building in radioactive waste management

    International Nuclear Information System (INIS)

    Dreimanis, Andrejs

    2008-01-01

    Full text: The increased demand of our society to its quality of life, global security and environmental safety as well as to observing a basic ethical principle of equity have advanced our attitude towards the recent proposals to develop shared multinational projects in the use of nuclear energy technologies, in particular, to: a) Siting of shared deep repositories for high-level radioactive waste (RW) and spent nuclear fuel safe disposal. In turn, arrangement of multinational facilities requires to gain more complex consensus between all involved parties. Method: We propose an interdisciplinary synergetic approach to multilevel consensus building for siting and construction of shared multinational repositories for RW deep disposal, based on self-organization (SO) of various stake holders, chaos and fuzziness concepts as well as Ashby principle of requisite variety. In the siting of a multi-national repository there appears an essential novel component of stake holder consensus building, namely: to reach consent - political, social, economic, ecological - among international partners, in addition to solving the whole set of intra-national consensus building items. An entire partnering country is considered as a national stake holder, represented by the national government, being faced to simultaneous seeking an upward (international) and a downward (intra-national) consensus in a psychologically stressed environment, having possibly diverse political, economic and social interests. Main Results: Following inferences about building of multilevel consensus are developed: 1) The basis of synergetic approach to stake holder interaction - informational SO, by forming a knowledge-creating stake holder community via cooperation and competition among individuals, public bodies/groups, companies, institutions; 2) Building of international stake holder consensus could be promoted by activating and diversifying multilateral interactions between intra- and international stake

  5. A case study of consensus modelling for tracking oil spills

    International Nuclear Information System (INIS)

    King, Brian; Brushett, Ben; Lemckert, Charles

    2010-01-01

    Metocean forecast datasets are essential for the timely response to marine incidents and pollutant spill mitigation at sea. To effectively model the likely drift pattern and the area of impact for a marine spill, both wind and ocean current forecast datasets are required. There are two ocean current forecast models and two wind forecast models currently used operationally in the Australia and Asia Pacific region. The availability of several different forecast models provides a unique opportunity to compare the outcome of a particular modelling exercise with the outcome of another using a different model and determining whether there is consensus in the results. Two recent modelling exercises, the oil spill resulting from the damaged Pacific Adventurer (in Queensland) and the oil spill from the Montara well blowout (in Western Australia) are presented as case studies to examine consensus modelling.

  6. [Neuroendocrine dysfunction and brain damage. A consensus statement].

    Science.gov (United States)

    Leal-Cerro, Alfonso; Rincón, María Dolores; Domingo, Manel Puig

    2009-01-01

    This consensus statement aims to enhance awareness of the incidence and risks of hypopituitarism in patients with traumatic brain injury (TBI) and/or brain hemorrhages among physicians treating patients with brain damage. The importance of this problem is related not only to the frequency of TBI but also to its prevalence in younger populations. The consequences of TBI are characterized by a series of symptoms that depend on the type of sequels related to neuroendocrine dysfunction. The signs and symptoms of hypopituitarism are often confused with those of other sequels of TBI. Consequently, patients with posttraumatic hypopituitarism may receive suboptimal rehabilitation unless the underlying hormone deficiency is identified and treated. This consensus is based on the recommendation supported by expert opinion that patients with a TBI and/or brain hemorrhage should undergo endocrine evaluation in order to assess pituitary function and, if deficiency is detected, should receive hormone replacement therapy.

  7. Highlights of the international consensus statement on major depressive disorder.

    Science.gov (United States)

    Nutt, David J

    2011-06-01

    The International Consensus Group on Depression gathered to outline a universal treatment algorithm for depression with the purpose of merging the evidence base and standards of clinical practice from various countries, including the United States, Europe, the Middle East, China, and Japan. This brief summary includes the following recommendations made by the consensus group: periodically screen all patients for depression, use measurement-based tools and full psychiatric assessments to complete differential diagnoses, refer patients to psychiatric specialists when appropriate, establish a therapeutic alliance with patients and their families, begin treatment with an antidepressant for moderate or severe depression, treat patients to remission, and continually monitor patients' symptomatic improvement. © Copyright 2011 Physicians Postgraduate Press, Inc.

  8. Engineering large-scale agent-based systems with consensus

    Science.gov (United States)

    Bokma, A.; Slade, A.; Kerridge, S.; Johnson, K.

    1994-01-01

    The paper presents the consensus method for the development of large-scale agent-based systems. Systems can be developed as networks of knowledge based agents (KBA) which engage in a collaborative problem solving effort. The method provides a comprehensive and integrated approach to the development of this type of system. This includes a systematic analysis of user requirements as well as a structured approach to generating a system design which exhibits the desired functionality. There is a direct correspondence between system requirements and design components. The benefits of this approach are that requirements are traceable into design components and code thus facilitating verification. The use of the consensus method with two major test applications showed it to be successful and also provided valuable insight into problems typically associated with the development of large systems.

  9. Improving consensus contact prediction via server correlation reduction.

    Science.gov (United States)

    Gao, Xin; Bu, Dongbo; Xu, Jinbo; Li, Ming

    2009-05-06

    Protein inter-residue contacts play a crucial role in the determination and prediction of protein structures. Previous studies on contact prediction indicate that although template-based consensus methods outperform sequence-based methods on targets with typical templates, such consensus methods perform poorly on new fold targets. However, we find out that even for new fold targets, the models generated by threading programs can contain many true contacts. The challenge is how to identify them. In this paper, we develop an integer linear programming model for consensus contact prediction. In contrast to the simple majority voting method assuming that all the individual servers are equally important and independent, the newly developed method evaluates their correlation by using maximum likelihood estimation and extracts independent latent servers from them by using principal component analysis. An integer linear programming method is then applied to assign a weight to each latent server to maximize the difference between true contacts and false ones. The proposed method is tested on the CASP7 data set. If the top L/5 predicted contacts are evaluated where L is the protein size, the average accuracy is 73%, which is much higher than that of any previously reported study. Moreover, if only the 15 new fold CASP7 targets are considered, our method achieves an average accuracy of 37%, which is much better than that of the majority voting method, SVM-LOMETS, SVM-SEQ, and SAM-T06. These methods demonstrate an average accuracy of 13.0%, 10.8%, 25.8% and 21.2%, respectively. Reducing server correlation and optimally combining independent latent servers show a significant improvement over the traditional consensus methods. This approach can hopefully provide a powerful tool for protein structure refinement and prediction use.

  10. Improving consensus contact prediction via server correlation reduction

    Directory of Open Access Journals (Sweden)

    Xu Jinbo

    2009-05-01

    Full Text Available Abstract Background Protein inter-residue contacts play a crucial role in the determination and prediction of protein structures. Previous studies on contact prediction indicate that although template-based consensus methods outperform sequence-based methods on targets with typical templates, such consensus methods perform poorly on new fold targets. However, we find out that even for new fold targets, the models generated by threading programs can contain many true contacts. The challenge is how to identify them. Results In this paper, we develop an integer linear programming model for consensus contact prediction. In contrast to the simple majority voting method assuming that all the individual servers are equally important and independent, the newly developed method evaluates their correlation by using maximum likelihood estimation and extracts independent latent servers from them by using principal component analysis. An integer linear programming method is then applied to assign a weight to each latent server to maximize the difference between true contacts and false ones. The proposed method is tested on the CASP7 data set. If the top L/5 predicted contacts are evaluated where L is the protein size, the average accuracy is 73%, which is much higher than that of any previously reported study. Moreover, if only the 15 new fold CASP7 targets are considered, our method achieves an average accuracy of 37%, which is much better than that of the majority voting method, SVM-LOMETS, SVM-SEQ, and SAM-T06. These methods demonstrate an average accuracy of 13.0%, 10.8%, 25.8% and 21.2%, respectively. Conclusion Reducing server correlation and optimally combining independent latent servers show a significant improvement over the traditional consensus methods. This approach can hopefully provide a powerful tool for protein structure refinement and prediction use.

  11. The False Consensus Effect: Deconstruction and Reconstruction of an Anomaly

    OpenAIRE

    Dirk Engelmann; Martin Strobel

    2004-01-01

    We present a striking example of the deconstruction and reconstruction or an anomaly. In line with previous experiments we show in a one-shot setting that the allegedly robust false consensus effect disappears if representative information is readily available. But the effect reappears if a small cognitive effort is required to retrieve the information. Most subjects apparently ignore valuable information if it is not handed to them on a silver platter. We conclude that the relevance of the f...

  12. To Create a Consensus on Malnutrition Diagnostic Criteria.

    Science.gov (United States)

    Cederholm, Tommy; Jensen, Gordon L

    2017-03-01

    During the European Society for Clinical Nutrition and Metabolism (ESPEN) Congress in Copenhagen, Denmark (September 2016), representatives of the 4 largest global parenteral and enteral nutrition (PEN) societies from Europe (ESPEN), the United States (American Society for Parenteral and Enteral Nutrition [ASPEN]), Asia (Parenteral and Enteral Nutrition Society of Asia [PENSA]), and Latin America (Latin American Federation of Parenteral and Enteral Nutrition [FELANPE]) and from national PEN societies around the world met to continue the conversation on how to diagnose malnutrition that started during the Clinical Nutrition Week, Austin, Texas (February 2016). Current thinking on diagnostic approaches was shared; ESPEN suggested a grading approach that could encompass various types of signs, symptoms, and etiologies to support diagnosis. ASPEN emphasized where the parties agree; that is, that the 3 major published approaches (ESPEN, ASPEN-Academy of Nutrition and Dietetics, and Subjective Global Assessment [SGA]) all propose weight loss as a key indicator for malnutrition. FELANPE suggested that the anticipated consensus approach needs to prioritize a diagnostic method that is available for everybody since resources differ globally. PENSA highlighted that body mass index varies by ethnicity/race and that sarcopenia/muscle mass evaluation is important for the diagnosis of malnutrition. A Core Working Committee of the Global Leadership Initiative on Malnutrition has been established (comprising 2 representatives each from the 4 largest PEN societies) that will lead consensus development in collaboration with a larger working group with broad global representation, using e-mail, telephone conferences, and face-to-face meetings during the upcoming ASPEN and ESPEN congresses. Transparency and external input will be sought. Objectives include (1) consensus development around evidence-based criteria for broad application, (2) promotion of global dissemination of the

  13. Cooperation and Consensus Seeking for Teams of Unmanned Air Vehicles

    Science.gov (United States)

    2007-06-30

    border, a spreading forest fire, a growing toxic plume, or a group of fleeing enemy combatants. Our recent work on the development of consensus seeking...shows the airframes used for the flight tests reported in this section. The airframe is a 1.1 m wingspan Unicorn EPP foam flying wing, which was...fail-safe mechanism to facilitate safe operations. Figure 34: (a) Kestrel autopilot, (b) Unicorn airframes, (c) ground station components. Cooperative

  14. Solida: A Blockchain Protocol Based on Reconfigurable Byzantine Consensus

    OpenAIRE

    Abraham, Ittai; Malkhi, Dahlia; Nayak, Kartik; Ren, Ling; Spiegelman, Alexander

    2018-01-01

    The decentralized cryptocurrency Bitcoin has experienced great success but also encountered many challenges. One of the challenges has been the long confirmation time. Another chal- lenge is the lack of incentives at certain steps of the protocol, raising concerns for transaction withholding, selfish mining, etc. To address these challenges, we propose Solida, a decentralized blockchain protocol based on reconfigurable Byzantine consensus augmented by proof-of-work. Solida improves on Bitcoin...

  15. Solida: A Blockchain Protocol Based on Reconfigurable Byzantine Consensus

    OpenAIRE

    Abraham, Ittai; Malkhi, Dahlia; Nayak, Kartik; Ren, Ling; Spiegelman, Alexander

    2016-01-01

    The decentralized cryptocurrency Bitcoin has experienced great success but also encountered many challenges. One of the challenges has been the long confirmation time. Another challenge is the lack of incentives at certain steps of the protocol, raising concerns for transaction withholding, selfish mining, etc. To address these challenges, we propose Solida, a decentralized blockchain protocol based on reconfigurable Byzantine consensus augmented by proof-of-work. Solida improves on Bitcoin i...

  16. A new consensus measure based on Pearson correlation coefficient

    OpenAIRE

    Chiclana, Francisco; Gonzalez-Arteaga, Teresa; de Andres Calle, Rocio

    2016-01-01

    Obtaining consensual solutions is an important issue in decision making processes. It depends on several factors such as experts’ opinions, principles, knowledge, experience, etc. In the literature we can find a considerable amount of consensus measurement from different research areas (from a Social Choice perspective: Alcalde-Unzu and Vorsatz [1], Alcantud, de Andres Calle and Cascon [2] and Bosch [3], among others and from Decision Making Theory: Gonzalez-Arteaga, Alcantud and ...

  17. Interdisciplinary consensus document for the treatment of fibromyalgia.

    Science.gov (United States)

    de Miquel, C Alegre; Campayo, J García; Flórez, M Tomás; Arguelles, J M Gómez; Tarrio, E Blanco; Montoya, M Gobbo; Martin, Á Pérez; Salio, A Martínez; Fuentes, J Vidal; Alberch, E Altarriba; de la Cámara, A Gómez

    2010-01-01

    Backgrounds. The elevated prevalence and enormous clinical and social impact of fibromyalgia, together with the complexity of its treatment, require action consensuses that guide health care professionals. Although there are some similar documents in our language, most have been made from the perspective of a single discipline.Objective. To develop a consensus on the treatment of fibromyalgia made by selected representatives and supported by the principal medical associations that intervene in its treatment (rheumatology, neurology, psychiatry,rehabilitation and family medicine) and representatives of the associations of patients. On the other hand, understanding the disease not as a homogenous disorders but also as the sum of different clinical subtypes,having specific symptomatic characteristics and different therapeutic needs is stressed. This approach represented a need perceived by the clinicians and a novelty regarding previous consensuses.Methods. The different clinical classifications proposed in fibromyalgia and the scientific evidence of the treatments used in this disease were reviewed. For the selection of the classification used and performance of the therapeutic recommendations, some of the usual techniques to obtain the consensus (nominal group and brainstorming) were used.Conclusion. The classification of Giesecke of fibromyalgia into 3 subgroups seems to have the greatest scientific evidence and the most useful for the clinician. The guide offers a series of general recommendations for all the patients with fibromyalgia. However, in addition, for each subgroup, there are a series of specific pharmacological and psychological-type recommendations and those of modification of the environment, which will make it possible to have a personalized approach to the patient with fibromyalgia in accordance with their individual clinical characteristics (pain, catastrophizing levels, etc.).

  18. Development of Consensus Treatment Plans for Juvenile Localized Scleroderma

    Science.gov (United States)

    Li, Suzanne C.; Torok, Kathryn S.; Pope, Elena; Dedeoglu, Fatma; Hong, Sandy; Jacobe, Heidi T.; Rabinovich, C. Egla; Laxer, Ronald M.; Higgins, Gloria C.; Ferguson, Polly J.; Lasky, Andrew; Baszis, Kevin; Becker, Mara; Campillo, Sarah; Cartwright, Victoria; Cidon, Michael; Inman, Christi J; Jerath, Rita; O'Neil, Kathleen M.; Vora, Sheetal; Zeft, Andrew; Wallace, Carol A.; Ilowite, Norman T.; Fuhlbrigge, Robert C

    2013-01-01

    Objective To develop standardized treatment plans, clinical assessments, and response criteria for active, moderate to high severity juvenile localized scleroderma (jLS). Background jLS is a chronic inflammatory skin disorder associated with substantial morbidity and disability. Although a wide range of therapeutic strategies have been reported in the literature, a lack of agreement on treatment specifics and accepted methods for clinical assessment of have made it difficult to compare approaches and identify optimal therapy. Methods A core group of pediatric rheumatologists, dermatologists and a lay advisor was engaged by the Childhood Arthritis and Rheumatology Research Alliance (CARRA) to develop standardized treatment plans and assessment parameters for jLS using consensus methods/nominal group techniques. Recommendations were validated in two face-to-face conferences with a larger group of practitioners with expertise in jLS and with the full membership of CARRA, which encompasses the majority of pediatric rheumatologists in the U.S and Canada. Results Consensus was achieved on standardized treatment plans that reflect the prevailing treatment practices of CARRA members. Standardized clinical assessment methods and provisional treatment response criteria were also developed. Greater than 90% of pediatric rheumatologists responding to a survey (67% of CARRA membership) affirmed the final recommendations and agreed to utilize these consensus plans to treat patients with jLS. Conclusions Using consensus methodology, we have developed standardized treatment plans and assessment methods for jLS. The high level of support among pediatric rheumatologists will support future comparative effectiveness studies and enable the development of evidence-based guidelines for the treatment of jLS. PMID:22505322

  19. Semi-supervised consensus clustering for gene expression data analysis

    OpenAIRE

    Wang, Yunli; Pan, Youlian

    2014-01-01

    Background Simple clustering methods such as hierarchical clustering and k-means are widely used for gene expression data analysis; but they are unable to deal with noise and high dimensionality associated with the microarray gene expression data. Consensus clustering appears to improve the robustness and quality of clustering results. Incorporating prior knowledge in clustering process (semi-supervised clustering) has been shown to improve the consistency between the data partitioning and do...

  20. Use of expert consensus to improve atherogenic dyslipidemia management.

    Science.gov (United States)

    Millán Núñez-Cortés, Jesús; Pedro-Botet, Juan; Brea-Hernando, Ángel; Díaz-Rodríguez, Ángel; González-Santos, Pedro; Hernández-Mijares, Antonio; Mantilla-Morató, Teresa; Pintó-Sala, Xavier; Simó, Rafael

    2014-01-01

    Although atherogenic dyslipidemia is a recognized cardiovascular risk factor, it is often underassessed and thus undertreated and poorly controlled in clinical practice. The objective of this study was to reach a multidisciplinary consensus for the establishment of a set of clinical recommendations on atherogenic dyslipidemia to optimize its prevention, early detection, diagnostic evaluation, therapeutic approach, and follow-up. After a review of the scientific evidence, a scientific committee formulated 87 recommendations related to atherogenic dyslipidemia, which were grouped into 5 subject areas: general concepts (10 items), impact and epidemiology (4 items), cardiovascular risk (32 items), detection and diagnosis (19 items), and treatment (22 items). A 2-round modified Delphi method was conducted to compare the opinions of a panel of 65 specialists in cardiology (23%), endocrinology (24.6%), family medicine (27.7%), and internal medicine (24.6%) on these issues. After the first round, the panel reached consensus on 65 of the 87 items discussed, and agreed on 76 items by the end of the second round. Insufficient consensus was reached on 3 items related to the detection and diagnosis of atherogenic dyslipidemia and 3 items related to the therapeutic goals to be achieved in these patients. The external assessment conducted by experts on atherogenic dyslipidemia showed a high level of professional agreement with the proposed clinical recommendations. These recommendations represent a useful tool for improving the clinical management of patients with atherogenic dyslipidemia. A detailed analysis of the current scientific evidence is required for those statements that eluded consensus. Copyright © 2013 Sociedad Española de Cardiología. Published by Elsevier Espana. All rights reserved.

  1. Group consensus peer review in radiation oncology: commitment to quality.

    Science.gov (United States)

    Duggar, W Neil; Bhandari, Rahul; Yang, Chunli Claus; Vijayakumar, Srinivasan

    2018-03-27

    Peer review, especially prospective peer review, has been supported by professional organizations as an important element in optimal Radiation Oncology practice based on its demonstration of efficacy at detecting and preventing errors prior to patient treatment. Implementation of peer review is not without barriers, but solutions do exist to mitigate or eliminate some of those barriers. Peer review practice at our institution involves three key elements: new patient conference, treatment planning conference, and chart rounds. The treatment planning conference is an adaptation of the group consensus peer review model from radiology which utilizes a group of peers reviewing each treatment plan prior to implementation. The peer group in radiation oncology includes Radiation Oncologists, Physician Residents, Medical Physicists, Dosimetrists, and Therapists. Thus, technical and clinical aspects of each plan are evaluated simultaneously. Though peer review is held in high regard in Radiation Oncology, many barriers commonly exist preventing optimal implementation such as time intensiveness, repetition, and distraction from clinic time with patients. Through the use of automated review tools and commitment by individuals and administration in regards to staffing, scheduling, and responsibilities, these barriers have been mitigated to implement this Group Consensus Peer Review model into a Radiation Oncology Clinic. A Group Consensus Peer Review model has been implemented with strategies to address common barriers to effective and efficient peer review.

  2. Probabilistic consensus scoring improves tandem mass spectrometry peptide identification.

    Science.gov (United States)

    Nahnsen, Sven; Bertsch, Andreas; Rahnenführer, Jörg; Nordheim, Alfred; Kohlbacher, Oliver

    2011-08-05

    Database search is a standard technique for identifying peptides from their tandem mass spectra. To increase the number of correctly identified peptides, we suggest a probabilistic framework that allows the combination of scores from different search engines into a joint consensus score. Central to the approach is a novel method to estimate scores for peptides not found by an individual search engine. This approach allows the estimation of p-values for each candidate peptide and their combination across all search engines. The consensus approach works better than any single search engine across all different instrument types considered in this study. Improvements vary strongly from platform to platform and from search engine to search engine. Compared to the industry standard MASCOT, our approach can identify up to 60% more peptides. The software for consensus predictions is implemented in C++ as part of OpenMS, a software framework for mass spectrometry. The source code is available in the current development version of OpenMS and can easily be used as a command line application or via a graphical pipeline designer TOPPAS.

  3. Assessment and management of agitation in psychiatry: Expert consensus.

    Science.gov (United States)

    Garriga, Marina; Pacchiarotti, Isabella; Kasper, Siegfried; Zeller, Scott L; Allen, Michael H; Vázquez, Gustavo; Baldaçara, Leonardo; San, Luis; McAllister-Williams, R Hamish; Fountoulakis, Konstantinos N; Courtet, Philippe; Naber, Dieter; Chan, Esther W; Fagiolini, Andrea; Möller, Hans Jürgen; Grunze, Heinz; Llorca, Pierre Michel; Jaffe, Richard L; Yatham, Lakshmi N; Hidalgo-Mazzei, Diego; Passamar, Marc; Messer, Thomas; Bernardo, Miquel; Vieta, Eduard

    2016-01-01

    Psychomotor agitation is associated with different psychiatric conditions and represents an important issue in psychiatry. Current recommendations on agitation in psychiatry are not univocal. Actually, an improper assessment and management may result in unnecessary coercive or sedative treatments. A thorough and balanced review plus an expert consensus can guide assessment and treatment decisions. An expert task force iteratively developed consensus using the Delphi method. Initial survey items were based on systematic review of the literature. Subsequent surveys included new, re-worded or re-rated items. Out of 2175 papers assessing psychomotor agitation, 124 were included in the review. Each component was assigned a level of evidence. Integrating the evidence and the experience of the task force members, a consensus was reached on 22 statements on this topic. Recommendations on the assessment of agitation emphasise the importance of identifying any possible medical cause. For its management, experts agreed in considering verbal de-escalation and environmental modification techniques as first choice, considering physical restraint as a last resort strategy. Regarding pharmacological treatment, the "ideal" medication should calm without over-sedate. Generally, oral or inhaled formulations should be preferred over i.m. routes in mildly agitated patients. Intravenous treatments should be avoided.

  4. The functional neuroanatomy of bipolar disorder: a consensus model

    Science.gov (United States)

    Strakowski, Stephen M; Adler, Caleb M; Almeida, Jorge; Altshuler, Lori L; Blumberg, Hilary P; Chang, Kiki D; DelBello, Melissa P; Frangou, Sophia; McIntosh, Andrew; Phillips, Mary L; Sussman, Jessika E; Townsend, Jennifer D

    2013-01-01

    Objectives Functional neuroimaging methods have proliferated in recent years, such that functional magnetic resonance imaging, in particular, is now widely used to study bipolar disorder. However, discrepant findings are common. A workgroup was organized by the Department of Psychiatry, University of Cincinnati (Cincinnati, OH, USA) to develop a consensus functional neuroanatomic model of bipolar I disorder based upon the participants’ work as well as that of others. Methods Representatives from several leading bipolar disorder neuroimaging groups were organized to present an overview of their areas of expertise as well as focused reviews of existing data. The workgroup then developed a consensus model of the functional neuroanatomy of bipolar disorder based upon these data. Results Among the participants, a general consensus emerged that bipolar I disorder arises from abnormalities in the structure and function of key emotional control networks in the human brain. Namely, disruption in early development (e.g., white matter connectivity, prefrontal pruning) within brain networks that modulate emotional behavior leads to decreased connectivity among ventral prefrontal networks and limbic brain regions, especially amygdala. This developmental failure to establish healthy ventral prefrontal–limbic modulation underlies the onset of mania and ultimately, with progressive changes throughout these networks over time and with affective episodes, a bipolar course of illness. Conclusions This model provides a potential substrate to guide future investigations and areas needing additional focus are identified. PMID:22631617

  5. Delayed Consensus Problem for Single and Double Integrator Systems

    Directory of Open Access Journals (Sweden)

    Martín Velasco-Villa

    2015-01-01

    Full Text Available This work deals with the analysis of the consensus problem for networks of agents constituted by single and double integrator systems. It is assumed that the communication among agents is affected by a constant time-delay. Previous and numerous analysis of the problem shows that the maximum communication time-delay that can be introduced to the network without affecting the consensus of the group of the agents depends on the considered topology. In this work, a control scheme that is based on the estimation of future states of the agents and that allows increasing the magnitude of a possible time-delay affecting the communication channels is proposed. How the proposed delay compensation strategy is independent of the network topology in the sense that the maximum allowable time-delay that could be supported by the network depends on a design parameter and not on the maximum eigenvalue of the corresponding Laplacian matrix is shown. It is formally proven that, under the proposed prediction scheme, the consensus of the group can be achieved by improving the maximum time-delay bounds previously reported in the literature. Numerical simulations show the effectiveness of the proposed solution.

  6. Taiwan consensus of pharmacological treatment for bipolar disorder

    Directory of Open Access Journals (Sweden)

    Ya-Mei Bai

    2013-10-01

    Full Text Available Bipolar disorder is an important psychiatric disorder with different disease phases. The pharmacological treatment is complicated, and is updated frequently as new research evidence emerges. For the purpose of international collaboration, research, and education, the Taiwan consensus of pharmacological treatment for bipolar disorders was initiated by the Taiwanese Society of Biological Psychiatry and Neuropsychopharmacology (TSBPN – the Bipolar Chapter, which was established in August 2010 and approved as a member of International Society of Bipolar Disorder. TSBPN is the country member of the World Federation of Societies of Biological Psychiatry (WFSBP. The development of the Taiwan consensus for bipolar disorder was mainly based on the template of WFSBP Guidelines, with references to other international guidelines including the Canadian Network for Mood and Anxiety Treatments, and British Association for Psychopharmacology. We have also added Taiwanese experts’ experience, Taiwan national health insurance data, and the indications for the pharmacological treatment of bipolar disorder given by the Taiwan Department of Health, to emphasize the balance between efficacy and safety, and to make this consensus a concise, empirical, and important reference for clinical psychiatric practice.

  7. Lack of international consensus in low-risk drinking guidelines.

    Science.gov (United States)

    Furtwaengler, Nina A F F; de Visser, Richard O

    2013-01-01

    To encourage moderate alcohol consumption, many governments have developed guidelines for alcohol intake, guidelines for alcohol consumption during pregnancy and legislation relating to blood alcohol limits when driving. The aim of this study was to determine the degree of international consensus within such guidelines. Official definitions of standard drinks and consumption guidelines were searched for on government websites, including all 27 European Union Member States and countries from all global geographic regions. There was a remarkable lack of agreement about what constitutes harmful or excessive alcohol consumption on a daily basis, a weekly basis and when driving, with no consensus about the ratios of consumption guidelines for men and women. International consensus in low-risk drinking guidelines is an important--and achievable--goal. Such agreement would facilitate consistent labelling of packaged products and could help to promote moderate alcohol consumption. However, there are some paradoxes related to alcohol content labelling and people's use of such information: although clearer information could increase people's capacity to monitor and regulate their alcohol consumption, not all drinkers are motivated to drink moderately or sensibly, and drinkers who intend to get drunk may use alcohol content labelling to select more alcoholic products. © 2012 Australasian Professional Society on Alcohol and other Drugs.

  8. European consensus on the histopathology of inflammatory bowel disease.

    Science.gov (United States)

    Magro, F; Langner, C; Driessen, A; Ensari, A; Geboes, K; Mantzaris, G J; Villanacci, V; Becheanu, G; Borralho Nunes, P; Cathomas, G; Fries, W; Jouret-Mourin, A; Mescoli, C; de Petris, G; Rubio, C A; Shepherd, N A; Vieth, M; Eliakim, R

    2013-11-01

    The histologic examination of endoscopic biopsies or resection specimens remains a key step in the work-up of affected inflammatory bowel disease (IBD) patients and can be used for diagnosis and differential diagnosis, particularly in the differentiation of UC from CD and other non-IBD related colitides. The introduction of new treatment strategies in inflammatory bowel disease (IBD) interfering with the patients' immune system may result in mucosal healing, making the pathologists aware of the impact of treatment upon diagnostic features. The European Crohn's and Colitis Organisation (ECCO) and the European Society of Pathology (ESP) jointly elaborated a consensus to establish standards for histopathology diagnosis in IBD. The consensus endeavors to address: (i) procedures required for a proper diagnosis, (ii) features which can be used for the analysis of endoscopic biopsies, (iii) features which can be used for the analysis of surgical samples, (iv) criteria for diagnosis and differential diagnosis, and (v) special situations including those inherent to therapy. Questions that were addressed include: how many features should be present for a firm diagnosis? What is the role of histology in patient management, including search for dysplasia? Which features if any, can be used for assessment of disease activity? The statements and general recommendations of this consensus are based on the highest level of evidence available, but significant gaps remain in certain areas. Copyright © 2013 European Crohn's and Colitis Organisation. All rights reserved.

  9. Distributed Optimal Consensus Control for Multiagent Systems With Input Delay.

    Science.gov (United States)

    Zhang, Huaipin; Yue, Dong; Zhao, Wei; Hu, Songlin; Dou, Chunxia; Huaipin Zhang; Dong Yue; Wei Zhao; Songlin Hu; Chunxia Dou; Hu, Songlin; Zhang, Huaipin; Dou, Chunxia; Yue, Dong; Zhao, Wei

    2018-06-01

    This paper addresses the problem of distributed optimal consensus control for a continuous-time heterogeneous linear multiagent system subject to time varying input delays. First, by discretization and model transformation, the continuous-time input-delayed system is converted into a discrete-time delay-free system. Two delicate performance index functions are defined for these two systems. It is shown that the performance index functions are equivalent and the optimal consensus control problem of the input-delayed system can be cast into that of the delay-free system. Second, by virtue of the Hamilton-Jacobi-Bellman (HJB) equations, an optimal control policy for each agent is designed based on the delay-free system and a novel value iteration algorithm is proposed to learn the solutions to the HJB equations online. The proposed adaptive dynamic programming algorithm is implemented on the basis of a critic-action neural network (NN) structure. Third, it is proved that local consensus errors of the two systems and weight estimation errors of the critic-action NNs are uniformly ultimately bounded while the approximated control policies converge to their target values. Finally, two simulation examples are presented to illustrate the effectiveness of the developed method.

  10. The Oslo consensus conference on protection of the environment

    International Nuclear Information System (INIS)

    Oughton, D.H.; Strand, P.

    2004-01-01

    A number of international organisations are focussing on a revision of radiation protection policy from the existing system which addresses only effects on man, to one which also addresses effects on the wider environment. These developments are expected to effect a wide range of stakeholders, including industry, regulators, scientists, users and the public. With this in mind a 'Consensus Conference on Protection of the Environment' was arranged as part of an International Seminar on 'Radiation Protection in the 21st Century: Ethical, Philosophical and Environmental Issues' held at the Norwegian Academy of Science and Letters. The conference attracted 46 international experts representing various disciplines and affiliations including Environmental Science, Health Physics, Radioecology, Ethics and Philosophy and a wide spectrum of perspectives bearing on the question of radiation protection of the environment. The conference was novel in that the participants were professionals rather than laypersons, and the purpose of the consensus procedure was to identify areas of agreement as an input to the ongoing regulatory developments. The success and innovation of the model is reflected in the significant areas of agreement identified in the final consensus statement, and the subsequent interest at an international level. Participants also noted the need for furthering the debate through ongoing work. Notable issues were the harmonisation of standards for radiation with other environmental stressors, guidance for balancing different interests and values within practical management, and the need for assessment criteria

  11. Spanish Consensus Statement: The Treatment of Muscle Tears in Sport.

    Science.gov (United States)

    Fernandez-Jaén, Tomas F; Rey, Guillermo Álvarez; Cuesta, Jordi Ardevol; Loureda, Rafael Arriaza; España, Fernando Ávila; Matas, Ramón Balius; Pazos, Fernando Baró; de Dios Beas Jiménez, Juan; Rosell, Jorge Candel; Fernandez, César Cobián; Ros, Francisco Esparza; Colmenero, Josefina Espejo; de Prado, Jorge Fernández; Cota, Juan José García; González, Jose Ignacio Garrido; Santander, Manuela González; Munilla, Miguel Ángel Herrador; Ruiz, Francisco Ivorra; Díaz, Fernando Jiménez; Marqueta, Pedro Manonelles; Fernandez, Antonio Maestro; Benito, Juan José Muñoz; Vilás, Ramón Olivé; Teres, Xavier Peirau; Amaro, José Peña; Roque, Juan Pérez San; Parenteu, Christophe Ramírez; Serna, Juan Ribas; Álvarez, Mikel Sánchez; Marchori, Carlos Sanchez; Soto, Miguel Del Valle; Alonso, José María Villalón; García, Pedro Guillen; de la Iglesia, Nicolas Hugo; Alcorocho, Juan Manuel Lopez

    2015-12-01

    On the 21st of March, 2015, experts met at Clínica CEMTRO in Madrid, Spain, under the patronage of The Spanish Society for Sports Traumatology (SETRADE), The Spanish Federation of Sports Medicine (FEMEDE), The Spanish Association of Medical Services for Football Clubs (AEMEF), and The Spanish Association of Medical Services for Basketball Clubs (AEMB) with the aim of establishing a round table that would allow specialists to consider the most appropriate current general actions to be taken when treating muscle tears in sport, based on proven scientific data described in the medical literature. Each expert received a questionnaire prior to the aforementioned meeting comprising a set of questions concerning therapeutic indications generally applied in the different stages present during muscle repair. The present Consensus Document is the result of the answers to the questionnaire and resulting discussion and consensus over which are the best current indications in the treatment of muscle tears in sport. Avoiding immobilization, not taking nonsteroidal anti-inflammatory drugs (NSAIDs) randomly, fostering early mobilization, increasing vascularization of injured, site and regulating inflammatory mechanisms-without inhibiting these from the early stages of the recovery period-all stood out as main points of the Consensus Document. Additionally, there is controversy concerning cell stimulation techniques and the use of growth factors or cell inhibitors. The decision concerning discharge was unanimous, as was the criteria considered when it came to performing sport techniques without pain.

  12. Time for a neonatal-specific consensus definition for sepsis.

    Science.gov (United States)

    Wynn, James L; Wong, Hector R; Shanley, Thomas P; Bizzarro, Matthew J; Saiman, Lisa; Polin, Richard A

    2014-07-01

    To review the accuracy of the pediatric consensus definition of sepsis in term neonates and to determine the definition of neonatal sepsis used. The review focused primarily on pediatric literature relevant to the topic of interest. Neonatal sepsis is variably defined based on a number of clinical and laboratory criteria that make the study of this common and devastating condition very difficult. Diagnostic challenges and uncertain disease epidemiology necessarily result from a variable definition of disease. In 2005, intensivists caring for children recognized that as new drugs became available, children would be increasingly studied and thus, pediatric-specific consensus definitions were needed. Pediatric sepsis criteria are not accurate for term neonates and have not been examined in preterm neonates for whom the developmental stage influences aberrations associated with host immune response. Thus, specific consensus definitions for both term and preterm neonates are needed. Such definitions are critical for the interpretation of observational studies, future training of scientists and practitioners, and implementation of clinical trials in neonates.

  13. Consensus Based Definition of Growth Restriction in the Newborn.

    Science.gov (United States)

    Beune, Irene M; Bloomfield, Frank H; Ganzevoort, Wessel; Embleton, Nicholas D; Rozance, Paul J; van Wassenaer-Leemhuis, Aleid G; Wynia, Klaske; Gordijn, Sanne J

    2018-05-01

    To develop a consensus definition of growth restriction in the newborn that can be used clinically to identify newborn infants at risk and in research to harmonize reporting and definition in the current absence of a gold standard. An international panel of pediatric leaders in the field of neonatal growth were invited to participate in an electronic Delphi procedure using standardized methods and predefined consensus rules. Responses were fed back at group-level and the list of participants was provided. Nonresponders were excluded from subsequent rounds. In the first round, variables were scored on a 5-point Likert scale; in subsequent rounds, inclusion of variables and cut-offs were determined with a 70% level of agreement. In the final round participants selected the ultimate algorithm. In total, 57 experts participated in the first round; 79% completed the procedure. Consensus was reached on the following definition: birth weight less than the third percentile, or 3 out of the following: birth weight definition for growth restriction in the newborn. This definition recognizes that infants with birth weights 10th percentile can be growth restricted. This definition can be adopted in clinical practice and in clinical trials to better focus on newborns at risk, and is complementary to the previously determined definition of fetal growth restriction. Copyright © 2017 Elsevier Inc. All rights reserved.

  14. Consensus-based training and assessment model for general surgery.

    Science.gov (United States)

    Szasz, P; Louridas, M; de Montbrun, S; Harris, K A; Grantcharov, T P

    2016-05-01

    Surgical education is becoming competency-based with the implementation of in-training milestones. Training guidelines should reflect these changes and determine the specific procedures for such milestone assessments. This study aimed to develop a consensus view regarding operative procedures and tasks considered appropriate for junior and senior trainees, and the procedures that can be used as technical milestone assessments for trainee progression in general surgery. A Delphi process was followed where questionnaires were distributed to all 17 Canadian general surgery programme directors. Items were ranked on a 5-point Likert scale, with consensus defined as Cronbach's α of at least 0·70. Items rated 4 or above on the 5-point Likert scale by 80 per cent of the programme directors were included in the models. Two Delphi rounds were completed, with 14 programme directors taking part in round one and 11 in round two. The overall consensus was high (Cronbach's α = 0·98). The training model included 101 unique procedures and tasks, 24 specific to junior trainees, 68 specific to senior trainees, and nine appropriate to all. The assessment model included four procedures. A system of operative procedures and tasks for junior- and senior-level trainees has been developed along with an assessment model for trainee progression. These can be used as milestones in competency-based assessments. © 2016 BJS Society Ltd Published by John Wiley & Sons Ltd.

  15. Food Security: The Elaboration of Contested Claims to a Consensus Frame

    Science.gov (United States)

    Mooney, Patrick H.; Hunt, Scott A.

    2009-01-01

    This article demonstrates Gamson's claim that behind the apparent agreement implied by "consensus frames" lies considerable dissensus. Ironically, the very potency of consensus frames may generate contested claims to the ownership of a social problem. Food security is a potent consensus frame that has generated at least three distinct collective…

  16. 30 CFR Appendix I to Subpart M of... - National Consensus Standards

    Science.gov (United States)

    2010-07-01

    ... 30 Mineral Resources 1 2010-07-01 2010-07-01 false National Consensus Standards I Appendix I to... Machinery and Equipment Pt. 56, Subpt. M, App. I Appendix I to Subpart M of Part 56—National Consensus... object protective structures (FOPS) may consult the following national consensus standards, as applicable...

  17. 29 CFR Appendix B to Subpart L of... - National Consensus Standards

    Science.gov (United States)

    2010-07-01

    ... 29 Labor 5 2010-07-01 2010-07-01 false National Consensus Standards B Appendix B to Subpart L of... Appendix B to Subpart L of Part 1910—National Consensus Standards The following table contains a cross-reference listing of those current national consensus standards which contains information and guidelines...

  18. Second-Order Consensus for Multiagent Systems With Directed Topologies and Nonlinear Dynamics

    NARCIS (Netherlands)

    Yu, Wenwu; Chen, Guanrong; Cao, Ming; Kurths, Juergen; Kurths, Jürgen

    This paper considers a second-order consensus problem for multiagent systems with nonlinear dynamics and directed topologies where each agent is governed by both position and velocity consensus terms with a time-varying asymptotic velocity. To describe the system's ability for reaching consensus, a

  19. Wnt and β-Catenin Signaling and Skeletal Muscle Myogenesis in Response to Muscle Damage and Resistance Exercise and Training

    Directory of Open Access Journals (Sweden)

    Dan Newmire

    2015-10-01

    Full Text Available The factors that regulate skeletal muscle hypertrophy in human adults in response to resistance training (RT has largely focused on endogenous endocrine responses. However, the endocrine response to RT as having an obligatory role in muscle hypertrophy has come under scrutiny, as other mechanisms and pathways seem to also be involved in up-regulating muscle protein synthesis (MPS. Skeletal muscle myogenesis is a multifactorial process of tissue growth and repair in response to resistance training is regulated by many factors.  As a result, satellite cell-fused myogenesis is a possible factor in skeletal muscle regeneration and hypertrophy in response to RT.  The Wnt family ligands interact with various receptors and activate different downstream signaling pathways and have been classified as either canonical (β-catenin dependent or non-canonical (β-catenin independent.  Wnt is secreted from numerous tissues in a paracrine fashion. The Wnt/β-catenin signaling pathway is a highly-regulated and intricate pathway that is essential to skeletal muscle myogenesis.  The canonical Wnt/β-catenin pathway may influence satellite cells to myogenic commitment, differentiation, and fusion into muscle fibers in response to injury or trauma, self-renewal, and normal basal turnover.  The current literature has shown that, in response mechanical overload from acute resistance exercise and chronic resistance training, that the Wnt/β-catenin signaling pathway is stimulated which may actuate the process of muscle repair and hypertrophy in response to exercise-induced muscle damage. The purpose of this review is to elaborate on the Wnt/β-catenin signaling  pathway, the current literature investigating the relationship of the Wnt/β-catenin pathway and its effects on myogenesis is response to muscle damage and resistance exercise and training.      Keywords: skeletal muscle, hypertrophy, myogenesis, cell signaling, protein synthesis, resistance

  20. The late endosomal HOPS complex anchors active G-protein signaling essential for pathogenesis in magnaporthe oryzae.

    Directory of Open Access Journals (Sweden)

    Ravikrishna Ramanujam

    Full Text Available In Magnaporthe oryzae, the causal ascomycete of the devastating rice blast disease, the conidial germ tube tip must sense and respond to a wide array of requisite cues from the host in order to switch from polarized to isotropic growth, ultimately forming the dome-shaped infection cell known as the appressorium. Although the role for G-protein mediated Cyclic AMP signaling in appressorium formation was first identified almost two decades ago, little is known about the spatio-temporal dynamics of the cascade and how the signal is transmitted through the intracellular network during cell growth and morphogenesis. In this study, we demonstrate that the late endosomal compartments, comprising of a PI3P-rich (Phosphatidylinositol 3-phosphate highly dynamic tubulo-vesicular network, scaffold active MagA/GαS, Rgs1 (a GAP for MagA, Adenylate cyclase and Pth11 (a non-canonical GPCR in the likely absence of AKAP-like anchors during early pathogenic development in M. oryzae. Loss of HOPS component Vps39 and consequently the late endosomal function caused a disruption of adenylate cyclase localization, cAMP signaling and appressorium formation. Remarkably, exogenous cAMP rescued the appressorium formation defects associated with VPS39 deletion in M. oryzae. We propose that sequestration of key G-protein signaling components on dynamic late endosomes and/or endolysosomes, provides an effective molecular means to compartmentalize and control the spatio-temporal activation and rapid downregulation (likely via vacuolar degradation of cAMP signaling amidst changing cellular geometry during pathogenic development in M. oryzae.

  1. Perceptions of a fluid consensus: uniqueness bias, false consensus, false polarization, and pluralistic ignorance in a water conservation crisis.

    Science.gov (United States)

    Monin, Benoît; Norton, Michael I

    2003-05-01

    A 5-day field study (N = 415) during and right after a shower ban demonstrated multifaceted social projection and the tendency to draw personality inferences from simple behavior in a time of drastic consensus change. Bathers thought showering was more prevalent than did non-bathers (false consensus) and respondents consistently underestimated the prevalence of the desirable and common behavior--be it not showering during the shower ban or showering after the ban (uniqueness bias). Participants thought that bathers and non-bathers during the ban differed greatly in their general concern for the community, but self-reports demonstrated that this gap was illusory (false polarization). Finally, bathers thought other bathers cared less than they did, whereas non-bathers thought other non-bathers cared more than they did (pluralistic ignorance). The study captures the many biases at work in social perception in a time of social change.

  2. Towards global consensus on core outcomes for hidradenitis suppurativa research: an update from the HISTORIC consensus meetings I and II*

    Science.gov (United States)

    Thorlacius, L.; Garg, A.; Ingram, J.R.; Villumsen, B.; Riis, P. Theut; Gottlieb, A.B.; Merola, J.F.; Dellavalle, R.; Ardon, C.; Baba, R.; Bechara, F.G.; Cohen, A.D.; Daham, N.; Davis, M.; Emtestam, L.; Fernández-Peñas, P.; Filippelli, M.; Gibbons, A.; Grant, T.; Guilbault, S.; Gulliver, S.; Harris, C; Harvent, C.; Houston, K.; Kirby, J.S.; Matusiak, L.; Mehdizadeh, A.; Mojica, T.; Okun, M.; Orgill, D.; Pallack, L.; Parks-Miller, A.; Prens, E.P.; Randell, S.; Rogers, C.; Rosen, C.F.; Choon, S.E.; van der Zee, H.H.; Christensen, R.; Jemec, G.B.E.

    2018-01-01

    Summary Background A core outcomes set (COS) is an agreed minimum set of outcomes that should be measured and reported in all clinical trials for a specific condition. Hidradenitis suppurativa (HS) has no agreed-upon COS. A central aspect in the COS development process is to identify a set of candidate outcome domains from a long list of items. Our long list had been developed from patient interviews, a systematic review of the literature and a healthcare professional survey, and initial votes had been cast in two e-Delphi surveys. In this manuscript, we describe two in-person consensus meetings of Delphi participants designed to ensure an inclusive approach to generation of domains from related items. Objectives To consider which items from a long list of candidate items to exclude and which to cluster into outcome domains. Methods The study used an international and multistakeholder approach, involving patients, dermatologists, surgeons, the pharmaceutical industry and medical regulators. The study format was a combination of formal presentations, small group work based on nominal group theory and a subsequent online confirmation survey. Results Forty-one individuals from 13 countries and four continents participated. Nine items were excluded and there was consensus to propose seven domains: disease course, physical signs, HS-specific quality of life, satisfaction, symptoms, pain and global assessments. Conclusions The HISTORIC consensus meetings I and II will be followed by further e-Delphi rounds to finalize the core domain set, building on the work of the in-person consensus meetings. PMID:29080368

  3. IncobotulinumtoxinA in aesthetics: Russian multidisciplinary expert consensus recommendations

    Directory of Open Access Journals (Sweden)

    Yutskovskaya Y

    2015-06-01

    Full Text Available Yana Yutskovskaya,1 Elena Gubanova,2 Irina Khrustaleva,3 Vasiliy Atamanov,4 Anastasiya Saybel,5 Elena Parsagashvili,6 Irina Dmitrieva,7 Elena Sanchez,8 Natalia Lapatina,9 Tatiana Korolkova,10 Alena Saromytskaya,11 Elena Goltsova,12 Elmira Satardinova13 1Department of Dermatovenereology and Cosmetology, Pacific State Medical University, Vladivostock, 2Department of Skin and Venereal Diseases, Postgraduate Medical Institute, Moscow National University of Food Production, Moscow, 3Department of Plastic Surgery, IP Pavlov Medical State University, St Petersburg, 4Department of Reconstructive and Plastic Surgery, SN Fedorova, Federal State Institution, Novosibirsk, 5Clinic Ideal, Laser Technologies Center, Moscow, 6Aestima-clinic, 7Clinic “Academy”, St Petersburg, 8Eklan Medical Center of Cosmetological Correction, 9Clinic of Aesthetic Medicine and Plastic Surgery, Moscow, 10Department of Cosmetology, II Mechnikov North-Western State Medical University, St Petersburg, 11Plastic Surgery Clinic, Center of Aesthetic Medicine and Beauty Cosmetology, 12“Neo-Clinic,” Tyumen, 13Botulinum Toxin Therapy Department, Diagnostic Center of the Irkutsk State Medical Academy of Postgraduate Education, Irkutsk, Russia Background: Although there are various international consensus recommendations on the use of botulinum neurotoxin type A (BoNT/A in facial aesthetics, there are no global or Russian guidelines on the optimal dose of incobotulinumtoxinA, free from complexing proteins, within specific aesthetic indications. This article reports the outcomes of two expert consensus meetings, conducted to review and analyze efficacy and tolerability data for incobotulinumtoxinA in various facial aesthetic indications and to give expert consensus recommendations to ensure best clinical practice among Russian clinicians. Methods: Thirteen dermatology and/or plastic surgery experts attended meetings held in Paris, France (November 2013, and Moscow, Russia (March 2014

  4. Non-consensus Opinion Models on Complex Networks

    Science.gov (United States)

    Li, Qian; Braunstein, Lidia A.; Wang, Huijuan; Shao, Jia; Stanley, H. Eugene; Havlin, Shlomo

    2013-04-01

    Social dynamic opinion models have been widely studied to understand how interactions among individuals cause opinions to evolve. Most opinion models that utilize spin interaction models usually produce a consensus steady state in which only one opinion exists. Because in reality different opinions usually coexist, we focus on non-consensus opinion models in which above a certain threshold two opinions coexist in a stable relationship. We revisit and extend the non-consensus opinion (NCO) model introduced by Shao et al. (Phys. Rev. Lett. 103:01870, 2009). The NCO model in random networks displays a second order phase transition that belongs to regular mean field percolation and is characterized by the appearance (above a certain threshold) of a large spanning cluster of the minority opinion. We generalize the NCO model by adding a weight factor W to each individual's original opinion when determining their future opinion (NCO W model). We find that as W increases the minority opinion holders tend to form stable clusters with a smaller initial minority fraction than in the NCO model. We also revisit another non-consensus opinion model based on the NCO model, the inflexible contrarian opinion (ICO) model (Li et al. in Phys. Rev. E 84:066101, 2011), which introduces inflexible contrarians to model the competition between two opinions in a steady state. Inflexible contrarians are individuals that never change their original opinion but may influence the opinions of others. To place the inflexible contrarians in the ICO model we use two different strategies, random placement and one in which high-degree nodes are targeted. The inflexible contrarians effectively decrease the size of the largest rival-opinion cluster in both strategies, but the effect is more pronounced under the targeted method. All of the above models have previously been explored in terms of a single network, but human communities are usually interconnected, not isolated. Because opinions propagate not

  5. Consensus-based perspectives of pediatric inpatient eating disorder services.

    Science.gov (United States)

    O'Brien, Amy; McCormack, Julie; Hoiles, Kimberley J; Watson, Hunna J; Anderson, Rebecca A; Hay, Phillipa; Egan, Sarah J

    2018-03-14

    There are few evidence-based guidelines for inpatient pediatric eating disorders. The aim was to gain perspectives from those providing and receiving inpatient pediatric eating disorder care on the essential components treatment. A modified Delphi technique was used to develop consensus-based opinions. Participants (N = 74) were recruited for three panels: clinicians (n = 24), carers (n = 31), and patients (n = 19), who endorsed three rounds of statements online. A total of 167 statements were rated, 79 were accepted and reached a consensus level of at least 75% across all panels, and 87 were rejected. All agreed that families should be involved in treatment, and thatpsychological therapy be offered in specialist inpatient units. Areas of disagreement included that patients expressed a desire for autonomy in sessions being available without carers, and that weight gain should be gradual and admissions longer, in contrast to carers and clinicians. Carers endorsed that legal frameworks should be used to retain patients if required, and that inpatients are supervised at all times, in contrast to patients and clinicians. Clinicians endorsed that food access should be restricted outside meal times, in contrast to patients and carers. The findings indicate areas of consensus in admission criteria, and that families should be involved in treatment, family involvement in treatment, while there was disagreement across groups on topics including weight goals and nutrition management. Perspectives from patients, carers, and clinicians may be useful to consider during future revisions of best practice guidelines. © 2018 Wiley Periodicals, Inc.

  6. Radiology curriculum for undergraduate medical studies—A consensus survey

    International Nuclear Information System (INIS)

    Mirsadraee, S.; Mankad, K.; McCoubrie, P.; Roberts, T.; Kessel, D.

    2012-01-01

    Aim: To establish an expert consensus of what, when, and how the teaching of radiology should be incorporated into the core undergraduate medical curriculum. Methods and materials: This Delphi survey consisted of four iterative rounds, with feedback given at the start of each successive round in the form of the results of the previous round. The participants consisted of both radiologists and non-radiologists with significant interest and involvement in radiology and undergraduate/Foundation training. The study addressed the questions of how, where, when, and by whom radiology should be taught. Results: The number of responses in rounds 1–4 was 20, 23, 41, and 25 (25, 22, 31, and 61% response rate, respectively). There was good consensus amongst the responders on the following: radiology teaching must be delivered in conjunction with anatomy and clinical case-based teaching, if possible in the department of radiology on picture archiving and communication system (PACS) workstations, and the teaching should be delivered by a competent and credentialled individual. Case-based assessment was the most agreed method of assessment. The majority of the responders concurred that the curriculum should include general indications for commonly requested radiological investigations, consent and safety issues around radiological tests, and their basic interpretation. Conclusion: The consensus points reached by the present study not only serve as directive principles for developing a more comprehensive radiology curriculum, but also places emphasis on a broader range of knowledge required to promote the best use of a department of radiology by junior doctors in an attempt to improve patient experiences and care.

  7. Standard operating procedures for ESPEN guidelines and consensus papers.

    Science.gov (United States)

    Bischoff, Stephan C; Singer, Pierre; Koller, Michael; Barazzoni, Rocco; Cederholm, Tommy; van Gossum, André

    2015-12-01

    The ESPEN Guideline standard operating procedures (SOP) is based on the methodology provided by the Association of Scientific Medical Societies of Germany (AWMF), the Scottish Intercollegiate Guidelines Network (SIGN), and the Centre for Evidence-based Medicine at the University of Oxford. The SOP is valid and obligatory for all future ESPEN-sponsored guideline projects aiming to generate high-quality guidelines on a regular basis. The SOP aims to facilitate the preparation of guideline projects, to streamline the consensus process, to ensure quality and transparency, and to facilitate the dissemination and publication of ESPEN guidelines. To achieve this goal, the ESPEN Guidelines Editorial board (GEB) has been established headed by two chairmen. The GEB will support and supervise the guideline processes and is responsible for the strategic planning of ESPEN guideline activities. Key elements of the SOP are the generation of well-built clinical questions according to the PICO system, a systemic literature search, a classification of the selected literature according to the SIGN evidence levels providing an evidence table, and a clear and straight-forward consensus procedure consisting of online voting's and a consensus conference. Only experts who meet the obligation to disclosure any potential conflict of interests and who are not employed by the Industry can participate in the guideline process. All recommendations will be graded according to the SIGN grading and novel outcome models besides biomedical endpoints. This approach will further extent the leadership of ESPEN in creating up-to-date and suitable for implementation guidelines and in sharing knowledge on malnutrition and clinical nutrition. Copyright © 2015 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.

  8. The impact of individual biases on consensus formation.

    Directory of Open Access Journals (Sweden)

    Marta Sales-Pardo

    Full Text Available Social groups of interacting agents display an ability to coordinate in the absence of a central authority, a phenomenon that has been recently amplified by the widespread availability of social networking technologies. Models of opinion formation in a population of agents have proven a very useful tool to investigate these phenomena that arise independently of the heterogeneities across individuals and can be used to identify the factors that determine whether widespread consensus on an initial small majority is reached. Recently, we introduced a model in which individual agents can have conservative and partisan biases. Numerical simulations for finite populations showed that while the inclusion of conservative agents in a population enhances the population's efficiency in reaching consensus on the initial majority opinion, even a small fraction of partisans leads the population to converge on the opinion initially held by a minority. To further understand the mechanisms leading to our previous numerical results, we investigate analytically the noise driven transition from a regime in which the population reaches a majority consensus (efficient, to a regime in which the population settles in deadlock (non-efficient. We show that the mean-field solution captures what we observe in model simulations. Populations of agents with no opinion bias show a continuous transition to a deadlock regime, while populations with an opinion bias, show a discontinuous transition between efficient and partisan regimes. Furthermore, the analytical solution reveals that populations with an increasing fraction of conservative agents are more robust against noise than a population of naive agents because in the efficient regime there are relatively more conservative than naive agents holding the majority opinion. In contrast, populations with partisan agents are less robust to noise with an increasing fraction of partisans, because in the efficient regime there are

  9. Complications to evaluate adult trauma care: An expert consensus study.

    Science.gov (United States)

    Moore, Lynne; Lauzier, François; Stelfox, Henry Thomas; Le Sage, Natalie; Bourgeois, Gilles; Clément, Julien; Shemilt, Michèle; Turgeon, Alexis F

    2014-08-01

    Complications affect up to 37% of patients hospitalized for injury and increase mortality, morbidity, and costs. One of the keys to controlling complications for injury admissions is to monitor in-hospital complication rates. However, there is no consensus on which complications should be used to evaluate the quality of trauma care. The objective of this study was to develop a consensus-based list of complications that can be used to assess the acute phase of adult trauma care. We used a three-round Web-based Delphi survey among experts in the field of trauma care quality with a broad range of clinical expertise and geographic diversity. The main outcome measure was median importance rating on a 5-point Likert scale (very low to very high); complications with a median of 4 or greater and no disagreement were retained. A secondary measure was the perceived quality of information on each complication available in patient files. Of 19 experts invited to participate, 17 completed the first (brainstorming) round and 16 (84%) completed all rounds. Of 73 complications generated in Round 1, a total of 25 were retained including adult respiratory distress syndrome, hospital-acquired pneumonia, sepsis, acute renal failure, deep vein thrombosis, pulmonary embolism, wound infection, decubitus ulcers, and delirium. Of these, 19 (76%) were perceived to have high-quality or very high-quality information in patient files by more than 50% of the panel members. This study proposes a consensus-based list of 25 complications that can be used to evaluate the quality of acute adult trauma care. These complications can be used to develop an informative and actionable quality indicator to evaluate trauma care with the goal of decreasing rates of hospital complications and thus improving patient outcomes and resource use. DRG International Classification of Diseases codes are provided.

  10. Consensus on Changing Trends, Attitudes, and Concepts of Asian Beauty.

    Science.gov (United States)

    Liew, Steven; Wu, Woffles T L; Chan, Henry H; Ho, Wilson W S; Kim, Hee-Jin; Goodman, Greg J; Peng, Peter H L; Rogers, John D

    2016-04-01

    Asians increasingly seek non-surgical facial esthetic treatments, especially at younger ages. Published recommendations and clinical evidence mostly reference Western populations, but Asians differ from them in terms of attitudes to beauty, structural facial anatomy, and signs and rates of aging. A thorough knowledge of the key esthetic concerns and requirements for the Asian face is required to strategize appropriate facial esthetic treatments with botulinum toxin and hyaluronic acid (HA) fillers. The Asian Facial Aesthetics Expert Consensus Group met to develop consensus statements on concepts of facial beauty, key esthetic concerns, facial anatomy, and aging in Southeastern and Eastern Asians, as a prelude to developing consensus opinions on the cosmetic facial use of botulinum toxin and HA fillers in these populations. Beautiful and esthetically attractive people of all races share similarities in appearance while retaining distinct ethnic features. Asians between the third and sixth decades age well compared with age-matched Caucasians. Younger Asians' increasing requests for injectable treatments to improve facial shape and three-dimensionality often reflect a desire to correct underlying facial structural deficiencies or weaknesses that detract from ideals of facial beauty. Facial esthetic treatments in Asians are not aimed at Westernization, but rather the optimization of intrinsic Asian ethnic features, or correction of specific underlying structural features that are perceived as deficiencies. Thus, overall facial attractiveness is enhanced while retaining esthetic characteristics of Asian ethnicity. Because Asian patients age differently than Western patients, different management and treatment planning strategies are utilized. This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to Table of Contents or the online Instructions to Authors www

  11. European consensus conference on diagnosis and treatment of germ cell cancer: a report of the second meeting of the European Germ Cell Cancer Consensus Group (EGCCCG): part II

    DEFF Research Database (Denmark)

    Krege, Susanne; Beyer, Jörg; Souchon, Rainer

    2007-01-01

    OBJECTIVES: The first consensus report that had been presented by the European Germ Cell Cancer Consensus Group (EGCCCG) in 2004 has found widespread approval by many colleagues throughout the world. In November 2006, the group met a second time under the auspices of the Department of Urology of ...

  12. European consensus conference on diagnosis and treatment of germ cell cancer: a report of the second meeting of the European Germ Cell Cancer Consensus group (EGCCCG): part I

    DEFF Research Database (Denmark)

    Krege, Susanne; Beyer, Jörg; Souchon, Rainer

    2007-01-01

    OBJECTIVES: The first consensus report presented by the European Germ Cell Cancer Consensus Group (EGCCCG) in the year 2004 has found widespread approval by many colleagues throughout the world. In November 2006, the group met a second time under the auspices of the Department of Urology of the A...

  13. SEPAR-ALAT Consensus Document on Antipneumoccal Vaccination in Smokers.

    Science.gov (United States)

    Jiménez Ruiz, Carlos A; Buljubasich, Daniel; Sansores, Raúl; Riesco Miranda, Juan Antonio; Guerreros Benavides, Alfredo; Luhning, Susana; Chatkin, José Miguel; Zabert, Gustavo; de Granda Orive, José Ignacio; Solano Reina, Segismundo; Casas Herrera, Alejandro; de Lucas Ramos, Pilar

    2015-07-01

    Streptococcus pneumoniae is responsible for several clinical syndromes, such as community-acquired pneumonia, sinusitis, otitis media, and others. The most severe clinical entity caused by this bacteria is undoubtedly invasive pneumococcal disease. Certain factors are known to increase the risk of presenting invasive pneumococcal disease, the most important being smoking habit and underlying concomitant diseases. This article comprises a consensus document on antipneumococcal vaccination in smokers, drawn up by a Smoking Expert Group from the Spanish Society of Pulmonology and Thoracic Surgery and the Latin American Chest Association. Copyright © 2014 SEPAR. Published by Elsevier Espana. All rights reserved.

  14. Global consensus for discrete-time competitive systems

    International Nuclear Information System (INIS)

    Shih, C.-W.; Tseng, J.-P.

    2009-01-01

    Grossberg established a remarkable convergence theorem for a class of competitive systems without knowing and using Lyapunov function for the systems. We present the parallel investigations for the discrete-time version of the Grossberg's model. Through developing an extended component-competing analysis for the coupled system, without knowing a Lyapunov function and applying the LaSalle's invariance principle, the global pattern formation or the so-called global consensus for the system can be achieved. A numerical simulation is performed to illustrate the present theory.

  15. Consensus recommendations on training and competing in the heat

    DEFF Research Database (Denmark)

    Racinais, Sebastien; Alonso, J M; Coutts, A J

    2015-01-01

    Exercising in the heat induces thermoregulatory and other physiological strain that can lead to impairments in endurance exercise capacity. The purpose of this consensus statement is to provide up-to-date recommendations to optimise performance during sporting activities undertaken in hot ambient...... and minimise dehydration during exercise. Following the development of commercial cooling systems (eg, cooling-vest), athletes can implement cooling strategies to facilitate heat loss or increase heat storage capacity before training or competing in the heat. Moreover, event organisers should plan for large...

  16. Consensus recommendations on training and competing in the heat

    DEFF Research Database (Denmark)

    Racinais, Sébastien; Alonso, Juan-Manuel; Coutts, Aaron J

    2015-01-01

    Exercising in the heat induces thermoregulatory and other physiological strain that can lead to impairments in endurance exercise capacity. The purpose of this consensus statement is to provide up-to-date recommendations to optimize performance during sporting activities undertaken in hot ambient...... and minimize dehydration during exercise. Following the development of commercial cooling systems (e.g., cooling vests), athletes can implement cooling strategies to facilitate heat loss or increase heat storage capacity before training or competing in the heat. Moreover, event organizers should plan for large...

  17. Consensus recommendations on training and competing in the heat

    DEFF Research Database (Denmark)

    Racinais, S; Alonso, J M; Coutts, A J

    2015-01-01

    Exercising in the heat induces thermoregulatory and other physiological strain that can lead to impairments in endurance exercise capacity. The purpose of this consensus statement is to provide up-to-date recommendations to optimize performance during sporting activities undertaken in hot ambient...... and minimize dehydration during exercise. Following the development of commercial cooling systems (e.g., cooling vest), athletes can implement cooling strategies to facilitate heat loss or increase heat storage capacity before training or competing in the heat. Moreover, event organizers should plan for large...

  18. Core Outcomes for Colorectal Cancer Surgery: A Consensus Study.

    Directory of Open Access Journals (Sweden)

    Angus G K McNair

    2016-08-01

    Full Text Available Colorectal cancer (CRC is a major cause of worldwide morbidity and mortality. Surgical treatment is common, and there is a great need to improve the delivery of such care. The gold standard for evaluating surgery is within well-designed randomized controlled trials (RCTs; however, the impact of RCTs is diminished by a lack of coordinated outcome measurement and reporting. A solution to these issues is to develop an agreed standard "core" set of outcomes to be measured in all trials to facilitate cross-study comparisons, meta-analysis, and minimize outcome reporting bias. This study defines a core outcome set for CRC surgery.The scope of this COS includes clinical effectiveness trials of surgical interventions for colorectal cancer. Excluded were nonsurgical oncological interventions. Potential outcomes of importance to patients and professionals were identified through systematic literature reviews and patient interviews. All outcomes were transcribed verbatim and categorized into domains by two independent researchers. This informed a questionnaire survey that asked stakeholders (patients and professionals from United Kingdom CRC centers to rate the importance of each domain. Respondents were resurveyed following group feedback (Delphi methods. Outcomes rated as less important were discarded after each survey round according to predefined criteria, and remaining outcomes were considered at three consensus meetings; two involving international professionals and a separate one with patients. A modified nominal group technique was used to gain the final consensus. Data sources identified 1,216 outcomes of CRC surgery that informed a 91 domain questionnaire. First round questionnaires were returned from 63 out of 81 (78% centers, including 90 professionals, and 97 out of 267 (35% patients. Second round response rates were high for all stakeholders (>80%. Analysis of responses lead to 45 and 23 outcome domains being retained after the first and

  19. Fitness voter model: Damped oscillations and anomalous consensus.

    Science.gov (United States)

    Woolcock, Anthony; Connaughton, Colm; Merali, Yasmin; Vazquez, Federico

    2017-09-01

    We study the dynamics of opinion formation in a heterogeneous voter model on a complete graph, in which each agent is endowed with an integer fitness parameter k≥0, in addition to its + or - opinion state. The evolution of the distribution of k-values and the opinion dynamics are coupled together, so as to allow the system to dynamically develop heterogeneity and memory in a simple way. When two agents with different opinions interact, their k-values are compared, and with probability p the agent with the lower value adopts the opinion of the one with the higher value, while with probability 1-p the opposite happens. The agent that keeps its opinion (winning agent) increments its k-value by one. We study the dynamics of the system in the entire 0≤p≤1 range and compare with the case p=1/2, in which opinions are decoupled from the k-values and the dynamics is equivalent to that of the standard voter model. When 0≤psystem approaches exponentially fast to the consensus state of the initial majority opinion. The mean consensus time τ appears to grow logarithmically with the number of agents N, and it is greatly decreased relative to the linear behavior τ∼N found in the standard voter model. When 1/2system initially relaxes to a state with an even coexistence of opinions, but eventually reaches consensus by finite-size fluctuations. The approach to the coexistence state is monotonic for 1/2oscillations around the coexistence value. The final approach to coexistence is approximately a power law t^{-b(p)} in both regimes, where the exponent b increases with p. Also, τ increases respect to the standard voter model, although it still scales linearly with N. The p=1 case is special, with a relaxation to coexistence that scales as t^{-2.73} and a consensus time that scales as τ∼N^{β}, with β≃1.45.

  20. Consensus based Nuclear Public-Hearing system Model

    International Nuclear Information System (INIS)

    Lee, Young Wook; Cho, Young Ho; Shin, Dong Hoon; Ko, Hyun Seok; Kim, Suk Hoon; Kang, Chang Sun

    2006-01-01

    For public participation, Korea has a system of Public-Hearing in accordance with the law. Because of the absence of the detailed way for public opinion aggregation and for the reflection of the aggregated opinion, Korean Public-Hearing system is only a concept model. In this study, to share the right of decision making, which is an ultimate concept for public participation, components of decision making and the characteristics of each phase are analyzed. It could be said that the relative weight of attributes for assessment and comparison with alternatives are founded as a valuation factor of the decision making, which should be based on the social consensus

  1. Consensus based scheduling of storage capacities in a virtual microgrid

    DEFF Research Database (Denmark)

    Brehm, Robert; Top, Søren; Mátéfi-Tempfli, Stefan

    2017-01-01

    We present a distributed, decentralized method for coordinated scheduling of charge/discharge intervals of storage capacities in a utility grid integrated microgrid. The decentralized algorithm is based on a consensus scheme and solves an optimisation problem with the objective of minimising......, by use of storage capacities, the power flow over a transformer substation from/to the utility grid integrated microgrid. It is shown that when using this coordinated scheduling algorithm, load profile flattening (peak-shaving) for the utility grid is achieved. Additionally, mutual charge...

  2. Consensus on Intermediate Scale Salt Field Test Design

    Energy Technology Data Exchange (ETDEWEB)

    Kuhlman, Kristopher L; Mills, Melissa Marie; Matteo, Edward N

    2017-03-01

    This report summarizes the first stage in a collaborative effort by Sandia, Los Alamos, and Lawrence Berkeley National Laboratories to design a small-diameter borehole heater test in salt at the Waste Isolation Pilot Plant (WIPP) for the US Department of Energy Office of Nuclear Energy (DOE-NE). The intention is to complete test design during the remainder of fiscal year 2017 (FY17), and the implementation of the test will begin in FY18. This document is the result of regular meetings between the three national labs and the DOE-NE, and is intended to represent a consensus of these meetings and discussions.

  3. [Consensus on the legibility criteria of health education leaflets].

    Science.gov (United States)

    Barrio-Cantalejo, I; Simón-Lorda, P; Jiménez, M Melguizo; Ruiz, A Molina

    2011-01-01

    To identify the most relevant aspects that guarantee the readability, clarity and simplicity of written health education materials. Delphi methodology in order to reach a state of consensus among health education experts on criteria of legibility in the design and publication of informative material and literature. Seventeen experts reached agreement on the principal recommendations for ensuring the legibility of health education materials. They were as follows: a) text content and layout: to structure the text using a title or subtitle, message explanation and conclusion; b) text construction: to use simple and concise sentences, diagrams and examples, and graphically highlighting the principal ideas; c) lexical comprehension: to use simple words and avoid technical language and abbreviations; d) typography: to use an easy-to-read font. There is a high degree of consensus regarding the way health education materials should be drawn up. This list of recommendations could be used as an instrument for reviewing and improving the design of health education materials. In general, it is recommended to identify the users of the leaflets and involve them in the writing and design.

  4. Canadian Paediatric Neurology Workforce Survey and Consensus Statement.

    Science.gov (United States)

    Doja, Asif; Orr, Serena L; McMillan, Hugh J; Kirton, Adam; Brna, Paula; Esser, Michael; Tang-Wai, Richard; Major, Philippe; Poulin, Chantal; Prasad, Narayan; Selby, Kathryn; Weiss, Shelly K; Yeh, E Ann; Callen, David Ja

    2016-05-01

    Little knowledge exists on the availability of academic and community paediatric neurology positions. This knowledge is crucial for making workforce decisions. Our study aimed to: 1) obtain information regarding the availability of positions for paediatric neurologists in academic centres; 2) survey paediatric neurology trainees regarding their perceptions of employment issues and career plans; 3) survey practicing community paediatric neurologists 4) convene a group of paediatric neurologists to develop consensus regarding how to address these workforce issues. Surveys addressing workforce issues regarding paediatric neurology in Canada were sent to: 1) all paediatric neurology program directors in Canada (n=9) who then solicited information from division heads and from paediatric neurologists in surrounding areas; 2) paediatric neurology trainees in Canada (n=57) and; 3) community paediatric neurologists (n=27). A meeting was held with relevant stakeholders to develop a consensus on how to approach employment issues. The response rate was 100% from program directors, 57.9% from residents and 44% from community paediatric neurologists. We found that the number of projected positions in academic paediatric neurology is fewer than the number of paediatric neurologists that are being trained over the next five to ten years, despite a clinical need for paediatric neurologists. Paediatric neurology residents are concerned about job availability and desire more career counselling. There is a current and projected clinical demand for paediatric neurologists despite a lack of academic positions. Training programs should focus on community neurology as a viable career option.

  5. Phenomenology and classification of dystonia: a consensus update.

    Science.gov (United States)

    Albanese, Alberto; Bhatia, Kailash; Bressman, Susan B; Delong, Mahlon R; Fahn, Stanley; Fung, Victor S C; Hallett, Mark; Jankovic, Joseph; Jinnah, Hyder A; Klein, Christine; Lang, Anthony E; Mink, Jonathan W; Teller, Jan K

    2013-06-15

    This report describes the consensus outcome of an international panel consisting of investigators with years of experience in this field that reviewed the definition and classification of dystonia. Agreement was obtained based on a consensus development methodology during 3 in-person meetings and manuscript review by mail. Dystonia is defined as a movement disorder characterized by sustained or intermittent muscle contractions causing abnormal, often repetitive, movements, postures, or both. Dystonic movements are typically patterned and twisting, and may be tremulous. Dystonia is often initiated or worsened by voluntary action and associated with overflow muscle activation. Dystonia is classified along 2 axes: clinical characteristics, including age at onset, body distribution, temporal pattern and associated features (additional movement disorders or neurological features); and etiology, which includes nervous system pathology and inheritance. The clinical characteristics fall into several specific dystonia syndromes that help to guide diagnosis and treatment. We provide here a new general definition of dystonia and propose a new classification. We encourage clinicians and researchers to use these innovative definition and classification and test them in the clinical setting on a variety of patients with dystonia. © 2013 Movement Disorder Society. © 2013 Movement Disorder Society.

  6. Consensus in Gestational Diabetes MELLITUS: Looking for the Holy Grail.

    Science.gov (United States)

    Agarwal, Mukesh M

    2018-05-28

    The world's pre-eminent diabetes, obstetric, endocrine, and health organizations advocate a plethora of diverse algorithms for the screening, diagnosis, management, and follow-up of gestational diabetes mellitus (GDM). Additionally, there are regional recommendations of local health societies. Several of these proposals for GDM are contentious because some of them were developed from unscientific studies, based on expert-opinion, catered to preserve resources, and subjectively modified for convenience. Due to the wide variety of choices available, the approach to GDM can be extremely diverse even within the same hospital. This lack of consensus creates major problems in addressing prevalence, complications, efficacy of treatment, and follow-up of GDM. Moreover, it becomes nearly impossible to compare the numerous studies. Furthermore, the lack of consensus confuses the health care providers of obstetric health who look to the experts for guidance. Therefore, a clear, objective, "evidence-based" global approach, which is simple, easy to follow, and validated by corroborative research, is crucial. We contend that, despite decades of research, a single acceptable global guideline is not yet on the horizon.

  7. Domestic and International Nuclear Energy Voluntary Consensus Standards Needs

    International Nuclear Information System (INIS)

    Hopper, Calvin Mitchell

    2013-01-01

    This report introduces the reader to the domestic and international standards development organizations (SDOs) and their structures and operations. It also identifies some of the support and subject matter needs for the development of standards on the subject of nuclear energy. The support needs are described with regard to organizational structure and subject-matter-expert (SME) participation that is required for producing voluntary consensus standards. The subject matter needs are described with regard to growing technologies and objectives that approach the boundaries of existing standards; implementation of knowledge; and safety of people, facilities, and the environment. Standards are proposed, developed, and produced by SMEs with the support of industry and government organizations. The voluntary consensus standards development process is, as its name implies, a voluntary effort. The problem in today's competitive market, impacted by global economic uncertainty, is that the voluntary participation is shifting from a collaborative industry and SME effort to a nearly SME-only one. This shift places a financial and/or time burden on the SMEs to the point that they are purposely withdrawing from the standards development process, both domestically and internationally. The standards development process desperately needs participation from more and younger SMEs. The report includes several suggestions on how this can be addressed.

  8. The UK shielding Forum. Best Practice through consensus

    International Nuclear Information System (INIS)

    Hobson, J.; Gunston, K.; Gunston, K.

    2000-01-01

    The UK national shielding Forum has been established to represent all key industry groups in the UK (including the Nuclear Installations Inspectorate (NII), the national regulatory authority). The Forum's aim is to increase awareness and confidence in the range of professional practice within the UK shielding community, with a view to having a coherent and dynamic role within the international shielding community. In the past, no comprehensive representative body covering the whole UK nuclear industry has existed, and the different industry shielding groups have developed local ways of working to address their particular requirements. Inevitably, there are common issues arising from these requirements which benefit from a wider consensus. As a result of the formation of the Forum (initiated by the NII and subsequently chaired by BNFL as an industry key player), expertise, experience and best working practice are now being actively shared between shielding professionals, and there has been a strong and successful drive to achieving consensus on key issues, which is also reflected in the increasing quality of industry-regulator relationships. (author)

  9. A conceptualisation framework for building consensus on environmental sensitivity.

    Science.gov (United States)

    González Del Campo, Ainhoa

    2017-09-15

    Examination of the intrinsic attributes of a system that render it more or less sensitive to potential stressors provides further insight into the baseline environment. In impact assessment, sensitivity of environmental receptors can be conceptualised on the basis of their: a) quality status according to statutory indicators and associated thresholds or targets; b) statutory protection; or c) inherent risk. Where none of these considerations are pertinent, subjective value judgments can be applied to determine sensitivity. This pragmatic conceptual framework formed the basis of a stakeholder consultation process for harmonising degrees of sensitivity of a number of environmental criteria. Harmonisation was sought to facilitate their comparative and combined analysis. Overall, full or wide agreement was reached on relative sensitivity values for the large majority of the reviewed criteria. Consensus was easier to reach on some themes (e.g. biodiversity, water and cultural heritage) than others (e.g. population and soils). As anticipated, existing statutory measures shaped the outcomes but, ultimately, knowledge-based values prevailed. The agreed relative sensitivities warrant extensive consultation but the conceptual framework provides a basis for increasing stakeholder consensus and objectivity of baseline assessments. This, in turn, can contribute to improving the evidence-base for characterising the significance of potential impacts. Copyright © 2017 Elsevier Ltd. All rights reserved.

  10. Prediction of antigenic epitopes on protein surfaces by consensus scoring

    Directory of Open Access Journals (Sweden)

    Zhang Chi

    2009-09-01

    Full Text Available Abstract Background Prediction of antigenic epitopes on protein surfaces is important for vaccine design. Most existing epitope prediction methods focus on protein sequences to predict continuous epitopes linear in sequence. Only a few structure-based epitope prediction algorithms are available and they have not yet shown satisfying performance. Results We present a new antigen Epitope Prediction method, which uses ConsEnsus Scoring (EPCES from six different scoring functions - residue epitope propensity, conservation score, side-chain energy score, contact number, surface planarity score, and secondary structure composition. Applied to unbounded antigen structures from an independent test set, EPCES was able to predict antigenic eptitopes with 47.8% sensitivity, 69.5% specificity and an AUC value of 0.632. The performance of the method is statistically similar to other published methods. The AUC value of EPCES is slightly higher compared to the best results of existing algorithms by about 0.034. Conclusion Our work shows consensus scoring of multiple features has a better performance than any single term. The successful prediction is also due to the new score of residue epitope propensity based on atomic solvent accessibility.

  11. Consensus Paper: Pathological Role of the Cerebellum in Autism

    Science.gov (United States)

    Fatemi, S. Hossein; Aldinger, Kimberly A.; Ashwood, Paul; Bauman, Margaret L.; Blaha, Charles D.; Blatt, Gene J.; Chauhan, Abha; Chauhan, Ved; Dager, Stephen R.; Dickson, Price E.; Estes, Annette M.; Goldowitz, Dan; Heck, Detlef H.; Kemper, Thomas L.; King, Bryan H.; Martin, Loren A.; Millen, Kathleen J.; Mittleman, Guy; Mosconi, Matthew W.; Persico, Antonio M.; Sweeney, John A.; Webb, Sara J.; Welsh, John P.

    2013-01-01

    There has been significant advancement in various aspects of scientific knowledge concerning the role of cerebellum in the etiopathogenesis of autism. In the current consensus paper, we will observe the diversity of opinions regarding the involvement of this important site in the pathology of autism. Recent emergent findings in literature related to cerebellar involvement in autism are discussed, including: cerebellar pathology, cerebellar imaging and symptom expression in autism, cerebellar genetics, cerebellar immune function, oxidative stress and mitochondrial dysfunction, GABAergic and glutamatergic systems, cholinergic, dopaminergic, serotonergic, and oxytocin related changes in autism, motor control and cognitive deficits, cerebellar coordination of movements and cognition, gene-environment interactions, therapeutics in autism and relevant animal models of autism. Points of consensus include presence of abnormal cerebellar anatomy, abnormal neurotransmitter systems, oxidative stress, cerebellar motor and cognitive deficits, and neuroinflammation in subjects with autism. Undefined areas or areas requiring further investigation include lack of treatment options for core symptoms of autism, vermal hypoplasia and other vermal abnormalities as a consistent feature of autism, mechanisms underlying cerebellar contributions to cognition, and unknown mechanisms underlying neuroinflammation. PMID:22370873

  12. Distributed consensus with visual perception in multi-robot systems

    CERN Document Server

    Montijano, Eduardo

    2015-01-01

    This monograph introduces novel responses to the different problems that arise when multiple robots need to execute a task in cooperation, each robot in the team having a monocular camera as its primary input sensor. Its central proposition is that a consistent perception of the world is crucial for the good development of any multi-robot application. The text focuses on the high-level problem of cooperative perception by a multi-robot system: the idea that, depending on what each robot sees and its current situation, it will need to communicate these things to its fellows whenever possible to share what it has found and keep updated by them in its turn. However, in any realistic scenario, distributed solutions to this problem are not trivial and need to be addressed from as many angles as possible. Distributed Consensus with Visual Perception in Multi-Robot Systems covers a variety of related topics such as: ·         distributed consensus algorithms; ·         data association and robustne...

  13. International consensus diagnostic criteria for neuromyelitis optica spectrum disorders

    Science.gov (United States)

    Banwell, Brenda; Bennett, Jeffrey L.; Cabre, Philippe; Carroll, William; Chitnis, Tanuja; de Seze, Jérôme; Fujihara, Kazuo; Greenberg, Benjamin; Jacob, Anu; Jarius, Sven; Lana-Peixoto, Marco; Levy, Michael; Simon, Jack H.; Tenembaum, Silvia; Traboulsee, Anthony L.; Waters, Patrick; Wellik, Kay E.

    2015-01-01

    Neuromyelitis optica (NMO) is an inflammatory CNS syndrome distinct from multiple sclerosis (MS) that is associated with serum aquaporin-4 immunoglobulin G antibodies (AQP4-IgG). Prior NMO diagnostic criteria required optic nerve and spinal cord involvement but more restricted or more extensive CNS involvement may occur. The International Panel for NMO Diagnosis (IPND) was convened to develop revised diagnostic criteria using systematic literature reviews and electronic surveys to facilitate consensus. The new nomenclature defines the unifying term NMO spectrum disorders (NMOSD), which is stratified further by serologic testing (NMOSD with or without AQP4-IgG). The core clinical characteristics required for patients with NMOSD with AQP4-IgG include clinical syndromes or MRI findings related to optic nerve, spinal cord, area postrema, other brainstem, diencephalic, or cerebral presentations. More stringent clinical criteria, with additional neuroimaging findings, are required for diagnosis of NMOSD without AQP4-IgG or when serologic testing is unavailable. The IPND also proposed validation strategies and achieved consensus on pediatric NMOSD diagnosis and the concepts of monophasic NMOSD and opticospinal MS. PMID:26092914

  14. International consensus for a definition of disease flare in lupus.

    Science.gov (United States)

    Ruperto, N; Hanrahan, L M; Alarcón, G S; Belmont, H M; Brey, R L; Brunetta, P; Buyon, J P; Costner, M I; Cronin, M E; Dooley, M A; Filocamo, G; Fiorentino, D; Fortin, P R; Franks, A G; Gilkeson, G; Ginzler, E; Gordon, C; Grossman, J; Hahn, B; Isenberg, D A; Kalunian, K C; Petri, M; Sammaritano, L; Sánchez-Guerrero, J; Sontheimer, R D; Strand, V; Urowitz, M; von Feldt, J M; Werth, V P; Merrill, J T

    2011-04-01

    The Lupus Foundation of America (LFA) convened an international working group to obtain a consensus definition of disease flare in lupus. With help from the Paediatric Rheumatology International Trials Organization (PRINTO), two web-based Delphi surveys of physicians were conducted. Subsequently, the LFA held a second consensus conference followed by a third Delphi survey to reach a community-wide agreement for flare definition. Sixty-nine of the 120 (57.5%) polled physicians responded to the first survey. Fifty-nine of the responses were available to draft 12 preliminary statements, which were circulated in the second survey. Eighty-seven of 118 (74%) physicians completed the second survey, with an agreement of 70% for 9/12 (75%) statements. During the second conference, three alternative flare definitions were consolidated and sent back to the international community. One hundred and sixteen of 146 (79.5%) responded, with agreement by 71/116 (61%) for the following definition: "A flare is a measurable increase in disease activity in one or more organ systems involving new or worse clinical signs and symptoms and/or laboratory measurements. It must be considered clinically significant by the assessor and usually there would be at least consideration of a change or an increase in treatment." The LFA proposes this definition for lupus flare on the basis of its high face validity.

  15. Starling flock networks manage uncertainty in consensus at low cost.

    Directory of Open Access Journals (Sweden)

    George F Young

    Full Text Available Flocks of starlings exhibit a remarkable ability to maintain cohesion as a group in highly uncertain environments and with limited, noisy information. Recent work demonstrated that individual starlings within large flocks respond to a fixed number of nearest neighbors, but until now it was not understood why this number is seven. We analyze robustness to uncertainty of consensus in empirical data from multiple starling flocks and show that the flock interaction networks with six or seven neighbors optimize the trade-off between group cohesion and individual effort. We can distinguish these numbers of neighbors from fewer or greater numbers using our systems-theoretic approach to measuring robustness of interaction networks as a function of the network structure, i.e., who is sensing whom. The metric quantifies the disagreement within the network due to disturbances and noise during consensus behavior and can be evaluated over a parameterized family of hypothesized sensing strategies (here the parameter is number of neighbors. We use this approach to further show that for the range of flocks studied the optimal number of neighbors does not depend on the number of birds within a flock; rather, it depends on the shape, notably the thickness, of the flock. The results suggest that robustness to uncertainty may have been a factor in the evolution of flocking for starlings. More generally, our results elucidate the role of the interaction network on uncertainty management in collective behavior, and motivate the application of our approach to other biological networks.

  16. Starling Flock Networks Manage Uncertainty in Consensus at Low Cost

    Science.gov (United States)

    Young, George F.; Scardovi, Luca; Cavagna, Andrea; Giardina, Irene; Leonard, Naomi E.

    2013-01-01

    Flocks of starlings exhibit a remarkable ability to maintain cohesion as a group in highly uncertain environments and with limited, noisy information. Recent work demonstrated that individual starlings within large flocks respond to a fixed number of nearest neighbors, but until now it was not understood why this number is seven. We analyze robustness to uncertainty of consensus in empirical data from multiple starling flocks and show that the flock interaction networks with six or seven neighbors optimize the trade-off between group cohesion and individual effort. We can distinguish these numbers of neighbors from fewer or greater numbers using our systems-theoretic approach to measuring robustness of interaction networks as a function of the network structure, i.e., who is sensing whom. The metric quantifies the disagreement within the network due to disturbances and noise during consensus behavior and can be evaluated over a parameterized family of hypothesized sensing strategies (here the parameter is number of neighbors). We use this approach to further show that for the range of flocks studied the optimal number of neighbors does not depend on the number of birds within a flock; rather, it depends on the shape, notably the thickness, of the flock. The results suggest that robustness to uncertainty may have been a factor in the evolution of flocking for starlings. More generally, our results elucidate the role of the interaction network on uncertainty management in collective behavior, and motivate the application of our approach to other biological networks. PMID:23382667

  17. European Consensus on Primary Prevention of Coronary Heart Disease.

    Science.gov (United States)

    Assmann, G

    1988-07-01

    The European Consensus on Primary Prevention of Coronary Heart Disease has recommended that providing care for individuals at particular risk for coronary artery disease (CAD) requires case finding through medical examinations in primary care, hospital and employment health examination settings. Decisions concerning management of elevated lipid levels should be based on overall cardiovascular risk. The goal of reducing cholesterol levels through risk reduction can ultimately be accomplished only with the implementation of health education efforts directed toward all age groups and actions by government and supranational agencies, including adequate food labelling to identify fat content, selective taxation to encourage healthful habits and wider availability of exercise facilities. Only measures directed at the overall population can eventually reach the large proportion of individuals at mildly to moderately increased risk for CAD. The European Policy Statement on the Prevention of Coronary Heart Disease recognizes that the question of lipid elevation as a risk factor for CAD involves assessment, not only of cholesterol level alone, but also of triglycerides and the HDL cholesterol lipid fraction. Five specific categories of dyslipidemia have been identified, with individualized screening and treatment strategies advised for each. It is the consensus of the study group panel members that these procedures are both practical and feasible. They begin the necessary long term process to reduce the unacceptably high levels of morbidity and mortality due to CAD throughout the European community.

  18. Consensus paper: pathological role of the cerebellum in autism.

    Science.gov (United States)

    Fatemi, S Hossein; Aldinger, Kimberly A; Ashwood, Paul; Bauman, Margaret L; Blaha, Charles D; Blatt, Gene J; Chauhan, Abha; Chauhan, Ved; Dager, Stephen R; Dickson, Price E; Estes, Annette M; Goldowitz, Dan; Heck, Detlef H; Kemper, Thomas L; King, Bryan H; Martin, Loren A; Millen, Kathleen J; Mittleman, Guy; Mosconi, Matthew W; Persico, Antonio M; Sweeney, John A; Webb, Sara J; Welsh, John P

    2012-09-01

    There has been significant advancement in various aspects of scientific knowledge concerning the role of cerebellum in the etiopathogenesis of autism. In the current consensus paper, we will observe the diversity of opinions regarding the involvement of this important site in the pathology of autism. Recent emergent findings in literature related to cerebellar involvement in autism are discussed, including: cerebellar pathology, cerebellar imaging and symptom expression in autism, cerebellar genetics, cerebellar immune function, oxidative stress and mitochondrial dysfunction, GABAergic and glutamatergic systems, cholinergic, dopaminergic, serotonergic, and oxytocin-related changes in autism, motor control and cognitive deficits, cerebellar coordination of movements and cognition, gene-environment interactions, therapeutics in autism, and relevant animal models of autism. Points of consensus include presence of abnormal cerebellar anatomy, abnormal neurotransmitter systems, oxidative stress, cerebellar motor and cognitive deficits, and neuroinflammation in subjects with autism. Undefined areas or areas requiring further investigation include lack of treatment options for core symptoms of autism, vermal hypoplasia, and other vermal abnormalities as a consistent feature of autism, mechanisms underlying cerebellar contributions to cognition, and unknown mechanisms underlying neuroinflammation.

  19. Consensus-based methodology for detection communities in multilayered networks

    Science.gov (United States)

    Karimi-Majd, Amir-Mohsen; Fathian, Mohammad; Makrehchi, Masoud

    2018-03-01

    Finding groups of network users who are densely related with each other has emerged as an interesting problem in the area of social network analysis. These groups or so-called communities would be hidden behind the behavior of users. Most studies assume that such behavior could be understood by focusing on user interfaces, their behavioral attributes or a combination of these network layers (i.e., interfaces with their attributes). They also assume that all network layers refer to the same behavior. However, in real-life networks, users' behavior in one layer may differ from their behavior in another one. In order to cope with these issues, this article proposes a consensus-based community detection approach (CBC). CBC finds communities among nodes at each layer, in parallel. Then, the results of layers should be aggregated using a consensus clustering method. This means that different behavior could be detected and used in the analysis. As for other significant advantages, the methodology would be able to handle missing values. Three experiments on real-life and computer-generated datasets have been conducted in order to evaluate the performance of CBC. The results indicate superiority and stability of CBC in comparison to other approaches.

  20. [Consensus statement for accreditation of multidisciplinary thyroid cancer units].

    Science.gov (United States)

    Díez, Juan José; Galofré, Juan Carlos; Oleaga, Amelia; Grande, Enrique; Mitjavila, Mercedes; Moreno, Pablo

    2016-03-01

    Thyroid cancer is the leading endocrine system tumor. Great advances have recently been made in understanding of the origin of these tumors and the molecular biology that makes them grow and proliferate, which have been associated to improvements in diagnostic procedures and increased availability of effective local and systemic treatments. All of the above makes thyroid cancer a paradigm of how different specialties should work together to achieve the greatest benefit for the patients. Coordination of all the procedures and patient flows should continue throughout diagnosis, treatment, and follow-up, and is essential for further optimization of resources and time. This manuscript was prepared at the request of the Working Group on Thyroid Cancer of the Spanish Society of Endocrinology and Nutrition, and is aimed to provide a consensus document on the definition, composition, requirements, structure, and operation of a multidisciplinary team for the comprehensive care of patients with thyroid cancer. For this purpose, we have included contributions by several professionals from different specialties with experience in thyroid cancer treatment at centers where multidisciplinary teams have been working for years, with the aim of developing a practical consensus applicable in clinical practice. Copyright © 2015 SEEN. Published by Elsevier España, S.L.U. All rights reserved.