497 research outputs found

    Low-latitude Scintillation weakening during sudden stratospheric warming events

    Get PDF
    Global Positioning System (GPS) L1-frequency (1.575 GHz) amplitude scintillations at São José dos Campos (23.1°S, 45.8°W, dip latitude 17.3°S), located under the southern crest of the equatorial ionization anomaly, are analyzed during the Northern Hemisphere winter sudden stratospheric warming (SSW) events of 2001/2002, 2002/2003, and 2012/2013. The events occurred during a period when moderate to strong scintillations are normally observed in the Brazilian longitude sector. The selected SSW events were of moderate and major categories and under low Kp conditions. The most important result of the current study is the long-lasting (many weeks) weakening of scintillation amplitudes at this low-latitude station, compared to their pre-SSW periods. Ionosonde-derived evening vertical plasma drifts and meridional neutral wind effects inferred from total electron content measurements are consistent with the observed weakening of GPS scintillations during these SSW events. This work provides strong evidence of SSW effects on ionospheric scintillations and the potential consequences of such SSW events on Global Navigation Satellite System-based applications

    Kinase Inhibitor Profile For Human Nek1, Nek6, And Nek7 And Analysis Of The Structural Basis For Inhibitor Specificity

    Get PDF
    Human Neks are a conserved protein kinase family related to cell cycle progression and cell division and are considered potential drug targets for the treatment of cancer and other pathologies. We screened the activation loop mutant kinases hNek1 and hNek2, wild-type hNek7, and five hNek6 variants in different activation/phosphorylation statesand compared them against 85 compounds using thermal shift denaturation. We identified three compounds with significant Tm shifts: JNK Inhibitor II for hNek1(Ä262-1258)-(T162A), Isogranulatimide for hNek6(S206A), and GSK-3 Inhibitor XIII for hNek7wt. Each one of these compounds was also validated by reducing the kinases activity by at least 25%. The binding sites for these compounds were identified by in silico docking at the ATP-binding site of the respective hNeks. Potential inhibitors were first screened by thermal shift assays, had their efficiency tested by a kinase assay, and were finally analyzed by molecular docking. Our findings corroborate the idea of ATP-competitive inhibition for hNek1 and hNek6 and suggest a novel non-competitive inhibition for hNek7 in regard to GSK-3 Inhibitor XIII. Our results demonstrate that our approach is useful for finding promising general and specific hNekscandidate inhibitors, which may also function as scaffolds to design more potent and selective inhibitors.20111761191Rubin, G.M., Yandell, M.D., Wortman, J.R., Gabor Miklos, G.L., Nelson, C.R., Hariharan, I.K., Fortini, M.E., Fleischmann, W., Comparative genomics of the eukaryotes (2000) Science, 287, pp. 2204-2215Johnson, L.N., Lowe, E.D., Noble, M.E., Owen, D.J., The Eleventh Datta Lecture. The structural basis for substrate recognition and control by protein kinases (1998) FEBS Lett., 430, pp. 1-11Hanks, S.K., Eukaryotic protein kinases (1991) Curr. Opin. Struct. Biol., 1, pp. 369-383Jeffrey, P.D., Russo, A.A., Polyak, K., Gibbs, E., Hurwitz, J., Massagué, J., Pavletich, N.P., Mechanism of CDK activation revealed by the structure of a cyclinA-CDK2 complex (1995) Nature, 376, pp. 313-320Yamaguchi, H., Hendrickson, W.A., Structural basis for activation of human lymphocyte kinase Lck upon tyrosine phosphorylation (1996) Nature, 384, pp. 484-489Canagarajah, B.J., Khokhlatchev, A., Cobb, M.H., Goldsmith, E.J., Activation mechanism of the MAP kinase ERK2 by dual phosphorylation (1997) Cell, 90, pp. 859-869Hubbard, S.R., Crystal structure of the activated insulin receptor tyrosine kinase in complex with peptide substrate and ATP analog (1997) EMBO J, 16, pp. 5572-5581Fry, A.M., O'Regan, L., Sabir, S.R., Bayliss, R., Cell cycle regulation by the NEK family of protein kinases (2012) J. Cell Sci., 125, pp. 4423-4433Meirelles, G.V., Perez, A.M., Souza, E.E., Basei, F.L., Papa, P.F., Melo Hanchuk, T.D., Cardoso, V.B., Kobarg, J., "Stop Ne(c)king around": How systems biology can help to characterize the functions of Nek family kinases from cell cycle regulation to DNA damage response (2014) World J. Biol. Chem., 5, pp. 141-160Fry, A.M., Mayor, T., Meraldi, P., Stierhof, Y.D., Tanaka, K., Nigg, E.A., C-Nap1, a novel centrosomal coiled-coil protein and candidate substrate of the cell cycle-regulated protein kinase Nek2 (1998) J. Cell Biol., 141, pp. 1563-1574Quarmby, L.M., Mahjoub, M.R., Caught nek-ing: Cilia and centrioles (2005) J. Cell Sci., 118, pp. 5161-5169Meirelles, G.V., Silva, J.C., Mendonça, Y.A., Ramos, C.H., Torriani, I.L., Kobarg, J., Human Nek6 is a monomeric mostly globular kinase with an unfolded short N-terminal domain (2011) BMC Struct. Biol., 11, p. 12Belham, C., Roig, J., Caldwell, J.A., Aoyama, Y., Kemp, B.E., Comb, M., Avruch, J., A mitotic cascade of NIMA family kinases. Nercc1/Nek9 activates the Nek6 and Nek7 kinases (2003) J. Biol. Chem., 278, pp. 34897-34909Yin, M.J., Shao, L., Voehringer, D., Smeal, T., Jallal, B., The serine/threonine kinase Nek6 is required for cell cycle progression through mitosis (2003) J. Biol. Chem., 278, pp. 52454-52460Yissachar, N., Salem, H., Tennenbaum, T., Motro, B., Nek7 kinase is enriched at the centrosome, and is required for proper spindle assembly and mitotic progression (2006) FEBS Lett., 580, pp. 6489-6495Kim, S., Lee, K., Rhee, K., NEK7 is a centrosomal kinase critical for microtubule nucleation (2007) Biochem. Biophys. Res.Commun., 360, pp. 56-62Roig, J., Mikhailov, A., Belham, C., Avruch, J., Nercc1, a mammalian NIMA-family kinase, binds the Ran GTPase and regulates mitotic progression (2002) Genes Dev., 16, pp. 1640-1658Upadhya, P., Birkenmeier, E.H., Birkenmeier, C.S., Barker, J.E., Mutations in a NIMA-related kinase gene, Nek1, cause pleiotropic effects including a progressive polycystic kidney disease in mice (2000) Proc. Natl. Acad. Sci. USA, 97, pp. 217-221Liu, S., Lu, W., Obara, T., Kuida, S., Lehoczky, J., Dewar, K., Drummond, I.A., Beier, D.R., A defect in a novel Nek-family kinase causes cystic kidney disease in the mouse and in zebrafish (2002) Development, 129, pp. 5839-5846Chen, J., Li, L., Zhang, Y., Yang, H., Wei, Y., Zhang, L., Liu, X., Yu, L., Interaction of Pin1 with Nek6 and characterization of their expression correlation in Chinese hepatocellular carcinoma patients (2006) Biochem. Biophys. Res. Commun., 341, pp. 1059-1065Chen, Y., Chen, P.L., Chen, C.F., Jiang, X., Riley, D.J., Never-in mitosis related kinase 1 functions in DNA damage response and checkpoint control (2008) Cell Cycle, 7, pp. 3194-3201Lee, M.Y., Kim, H.J., Kim, M.A., Jee, H.J., Kim, A.J., Bae, Y.S., Park, J.I., Yun, J., Nek6 is involved in G2/M phase cell cycle arrest through DNA damage induced phosphorylation (2008) Cell Cycle, 7, pp. 2705-2709Innocenti, P., Cheung, K.M., Solanki, S., Mas-Droux, C., Rowan, F., Yeoh, S., Boxall, K., Hardy, T., Design of potent and selective hybrid inhibitors of the mitotic kinase Nek2: Structure-activity relationship, structural biology, and cellular activity (2012) J. Med. Chem., 55, pp. 3228-3241Solanki, S., Innocenti, P., Mas-Droux, C., Boxall, K., Barillari, C., Van Montfort, R.L., Aherne, G.W., Hoelder, S., Benzimidazole inhibitors induce a DFG-out conformation of never in mitosis gene A-related kinase 2 (Nek2) without binding to the back pocket and reveal a nonlinear structure-activity relationship (2011) J. Med. Chem., 54, pp. 1626-1639Whelligan, D.K., Solanki, S., Taylor, D., Thomson, D.W., Cheung, K.M., Boxall, K., Mas-Droux, C., Grummitt, C.G., Aminopyrazine inhibitors binding to an unusual inactive conformation of the mitotic kinase Nek2: SAR and structural characterization (2010) J. Med. Chem., 53, pp. 7682-7698Srinivasan, P., ChellaPerumal, P., Sudha, A., Discovery of novel inhibitors for Nek6 protein through homology model assisted structure based virtual screening and molecular docking approaches (2014) Sci. World J., 2014. , ID: 967873Rellos, P., Ivins, F.J., Baxter, J.E., Pike, A., Nott, T.J., Parkinson, D.M., Das, S., Shen, Q.Y., Structure and regulation of the human Nek2 centrosomal kinase (2007) J. Biol. Chem., 282, pp. 6833-6842Westwood, I., Cheary, D.M., Baxter, J.E., Richards, M.W., Van Montfort, R.L., Fry, A.M., Bayliss, R., Insights into the conformational variability and regulation of human Nek2 kinase (2009) J. Mol. Biol, 386, pp. 476-485Richards, M.W., O'Regan, L., Mas-Droux, C., Blot, J.M., Cheung, J., Hoelder, S., Fry, A.M., Bayliss, R., An autoinhibitory tyrosine motif in the cell-cycleregulated Nek7 kinase is released through binding of Nek9 (2009) Mol. Cell, 36, pp. 560-570Geromichalos, G.D., Importance of molecular computer modeling in anticancer drug development (2007) J. Buon., 12, pp. S101-S118Vedadi, M., Niesen, F.H., Allali-Hassani, A., Fedorov, O.Y., Finerty, P.J., Jr., Wasney, G.A., Yeung, R., Berglund, H., Chemical screening methods to identify ligands that promote protein stability, protein crystallization, and structure determination (2006) Proc. Natl. Acad. Sci. USA, 103, pp. 15835-15840Lengauer, T., Rarey, M., Computational methods for biomolecular docking (1996) Curr. Opin. Struct. Biol., 6, pp. 402-406Fedorov, O., Marsden, B., Pogacic, V., Rellos, P., Müller, S., Bullock, A.N., Schwaller, J., Knapp, S., A systematic interaction map of validated kinase inhibitors with Ser/Thr kinases (2007) Proc. Natl. Acad. Sci. USA, 104, pp. 20523-20528Roberge, M., Berlinck, R.G., Xu, L., Anderson, H.J., Lim, L.Y., Curman, D., Stringer, C.M., Vincent, I., High-throughput assay for G2 checkpoint inhibitors and identification of the structurally novel compound isogranulatimide (1998) Cancer Res, 58, pp. 5701-5706Jiang, X., Zhao, B., Britton, R., Lim, L.Y., Leong, D., Sanghera, J.S., Zhou, B.B., Roberge, M., Inhibition of Chk1 by the G2 DNA damage checkpoint inhibitor isogranulatimide (2004) Mol. Cancer Ther., 3, pp. 1221-1227De Castro, E., Sigrist, C.J.A., Gattiker, A., Bulliard, V., Langendijk-Genevaux, P.S., Gasteiger, E., Bairoch, A., Hulo, N., ScanProsite: Detection of PROSITE signature matches and ProRule-associated functional and structural residues in proteins (2006) Nucleic Acids Res., 34, pp. W362-W365Gavrin, L.K., Saiah, E., Approaches to discover non-ATP site kinase inhibitors (2013) Med. Chem. Commun., 4, pp. 41-51Oliveira, S.H., Ferraz, F.A., Honorato, R.V., Xavier-Neto, J., Sobreira, T.J., De Oliveira, P.S., KVFinder: Steered identification of protein cavities as a PyMOL plugin (2014) BMC Bioinform., 15, p. 197Meirelles, G.V., Lanza, D.C.F., Silva, J.C., Bernachi, J.S., Leme, A.F.P., Kobarg, J., Characterization of hNek6 Interactome Reveals an Important Role for Its Short N-Terminal Domain and Colocalization with Proteins at the Centrosome (2010) J. Proteome Res., 9, pp. 6298-6316Trott, O., Olson, A.J., AutoDockVina: Improving the speed and accuracy of docking with a new scoring function, efficient optimization and multithreading (2010) J. Comput. Chem., 31, pp. 455-46

    Corrosion behaviour of micro-plasma arc welded stainless steels in H3PO4 under flowing conditions at different temperatures

    Full text link
    [EN] This paper studies the general corrosion behaviour of the micro-plasma arc welded AISI 316L stainless steel in phosphoric acid at different temperatures (25-60°C) and at a Reynolds number of 1456. Galvanic corrosion has been studied using zero-resistance ammeter (ZRA) measurements and polarization curves (by the mixed potential theory). Results show that the microstructure of the stainless steel is modified due to the micro-plasma arc welding procedure. Coupled current density values obtained from polarization curves increase with temperature. ZRA tests present the highest iG values at 60°C; however, the values are very close to zero for all the temperatures studied. This is in agreement with the low value of the compatibility limit and of the parameter which evaluates the importance of the galvanic phenomenon. Both techniques present the most positive potentials at the highest temperature. This study reveals that micro-plasma arc welded AISI 316L stainless steels are appropriated working in the studied H3PO4 media from a corrosion point of view for all the temperatures analysedThe authors would like to express their gratitude to the Spanish MAEC (PCI Mediterráneo C/8196/07, C/018046/08, D/023608/09) and to Asuncion Jaime for her translation assistance.Sánchez Tovar, R.; Montañés Sanjuan, MT.; García Antón, J.; Guenbour, A.; Ben Bachir, A. (2011). Corrosion behaviour of micro-plasma arc welded stainless steels in H3PO4 under flowing conditions at different temperatures. Corrosion Science. 53(4):1237-1246. https://doi.org/10.1016/j.corsci.2010.12.017S1237124653

    Search for direct production of charginos and neutralinos in events with three leptons and missing transverse momentum in √s = 7 TeV pp collisions with the ATLAS detector

    Get PDF
    A search for the direct production of charginos and neutralinos in final states with three electrons or muons and missing transverse momentum is presented. The analysis is based on 4.7 fb−1 of proton–proton collision data delivered by the Large Hadron Collider and recorded with the ATLAS detector. Observations are consistent with Standard Model expectations in three signal regions that are either depleted or enriched in Z-boson decays. Upper limits at 95% confidence level are set in R-parity conserving phenomenological minimal supersymmetric models and in simplified models, significantly extending previous results

    Jet size dependence of single jet suppression in lead-lead collisions at sqrt(s(NN)) = 2.76 TeV with the ATLAS detector at the LHC

    Get PDF
    Measurements of inclusive jet suppression in heavy ion collisions at the LHC provide direct sensitivity to the physics of jet quenching. In a sample of lead-lead collisions at sqrt(s) = 2.76 TeV corresponding to an integrated luminosity of approximately 7 inverse microbarns, ATLAS has measured jets with a calorimeter over the pseudorapidity interval |eta| < 2.1 and over the transverse momentum range 38 < pT < 210 GeV. Jets were reconstructed using the anti-kt algorithm with values for the distance parameter that determines the nominal jet radius of R = 0.2, 0.3, 0.4 and 0.5. The centrality dependence of the jet yield is characterized by the jet "central-to-peripheral ratio," Rcp. Jet production is found to be suppressed by approximately a factor of two in the 10% most central collisions relative to peripheral collisions. Rcp varies smoothly with centrality as characterized by the number of participating nucleons. The observed suppression is only weakly dependent on jet radius and transverse momentum. These results provide the first direct measurement of inclusive jet suppression in heavy ion collisions and complement previous measurements of dijet transverse energy imbalance at the LHC.Comment: 15 pages plus author list (30 pages total), 8 figures, 2 tables, submitted to Physics Letters B. All figures including auxiliary figures are available at http://atlas.web.cern.ch/Atlas/GROUPS/PHYSICS/PAPERS/HION-2011-02

    Search for displaced vertices arising from decays of new heavy particles in 7 TeV pp collisions at ATLAS

    Get PDF
    We present the results of a search for new, heavy particles that decay at a significant distance from their production point into a final state containing charged hadrons in association with a high-momentum muon. The search is conducted in a pp-collision data sample with a center-of-mass energy of 7 TeV and an integrated luminosity of 33 pb^-1 collected in 2010 by the ATLAS detector operating at the Large Hadron Collider. Production of such particles is expected in various scenarios of physics beyond the standard model. We observe no signal and place limits on the production cross-section of supersymmetric particles in an R-parity-violating scenario as a function of the neutralino lifetime. Limits are presented for different squark and neutralino masses, enabling extension of the limits to a variety of other models.Comment: 8 pages plus author list (20 pages total), 8 figures, 1 table, final version to appear in Physics Letters
    corecore