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Volumn 5, Issue 5, 2010, Pages

An agent-based model of signal transduction in bacterial chemotaxis

Author keywords

[No Author keywords available]

Indexed keywords

BACTERIAL PROTEIN; CHEA KINASE; CHEW PROTEIN; CHEY PROTEIN; CYTOPLASM PROTEIN; LIGAND; PROTEIN CHEB; PROTEIN CHER; PROTEIN CHEZ; UNCLASSIFIED DRUG; ESCHERICHIA COLI PROTEIN; TAR PROTEIN, E COLI;

EID: 77956283729     PISSN: None     EISSN: 19326203     Source Type: Journal    
DOI: 10.1371/journal.pone.0009454     Document Type: Article
Times cited : (14)

References (62)
  • 1
    • 33748058888 scopus 로고    scopus 로고
    • Bistability in bacteria
    • Dubnau D, Losick R (2006) Bistability in bacteria. Mol Microbiol 61: 564-572.
    • (2006) Mol Microbiol , vol.61 , pp. 564-572
    • Dubnau, D.1    Losick, R.2
  • 2
    • 2542516200 scopus 로고    scopus 로고
    • Agent-based modeling in the social and behavioral sciences
    • Elliott E, Kiel LD (2004) Agent-based modeling in the social and behavioral sciences. Nonlinear Dynamics Psychol Life Sci 8: 121-130.
    • (2004) Nonlinear Dynamics Psychol Life Sci , vol.8 , pp. 121-130
    • Elliott, E.1    Kiel, L.D.2
  • 4
    • 85020216227 scopus 로고    scopus 로고
    • The re-emergence of "emergence": A venerable concept in search of a theory
    • Corning PA (2002) The re-emergence of "emergence": a venerable concept in search of a theory. Complexity 7: 18-30.
    • (2002) Complexity , vol.7 , pp. 18-30
    • Corning, P.A.1
  • 5
    • 0016345728 scopus 로고
    • Change in direction of flagellar rotation is the basis of the chemotactic response in Escherichia coli
    • Larsen SH, Reader RW, Kort EN, Tso WW, Adler J (1974) Change in direction of flagellar rotation is the basis of the chemotactic response in Escherichia coli. Nature 249: 74-77.
    • (1974) Nature , vol.249 , pp. 74-77
    • Larsen, S.H.1    Reader, R.W.2    Kort, E.N.3    Tso, W.W.4    Adler, J.5
  • 6
    • 0015526205 scopus 로고
    • Chemotaxis in Escherichia coli analyzed by threedimensional tracking
    • Berg HC, Brown DA (1972) Chemotaxis in Escherichia coli analyzed by threedimensional tracking. Nature 239: 500-504.
    • (1972) Nature , vol.239 , pp. 500-504
    • Berg, H.C.1    Brown, D.A.2
  • 8
    • 0037039434 scopus 로고    scopus 로고
    • Bacterial chemotaxis and the question of gain
    • Bray D (2002) Bacterial chemotaxis and the question of gain. Proc Natl Acad Sci U S A 99: 7-9.
    • (2002) Proc Natl Acad Sci U S A , vol.99 , pp. 7-9
    • Bray, D.1
  • 9
    • 0037965621 scopus 로고    scopus 로고
    • A sensitive, versatile microfluidic assay for bacterial chemotaxis
    • Mao H, Cremer PS, Manson MD (2003) A sensitive, versatile microfluidic assay for bacterial chemotaxis. Proc Natl Acad Sci U S A 100: 5449-5454.
    • (2003) Proc Natl Acad Sci U S A , vol.100 , pp. 5449-5454
    • Mao, H.1    Cremer, P.S.2    Manson, M.D.3
  • 10
    • 7944221332 scopus 로고    scopus 로고
    • Receptor clustering and signal processing in E. coli chemotaxis
    • Sourjik V (2004) Receptor clustering and signal processing in E. coli chemotaxis. Trends Microbiol 12: 569-576.
    • (2004) Trends Microbiol , vol.12 , pp. 569-576
    • Sourjik, V.1
  • 12
    • 37749029507 scopus 로고    scopus 로고
    • Bacterial chemoreceptors: Highperformance signaling in networked arrays
    • Hazelbauer GL, Falke JJ, Parkinson JS (2008) Bacterial chemoreceptors: highperformance signaling in networked arrays. Trends Biochem Sci 33: 9-19.
    • (2008) Trends Biochem Sci , vol.33 , pp. 9-19
    • Hazelbauer, G.L.1    Falke, J.J.2    Parkinson, J.S.3
  • 13
    • 0001690764 scopus 로고    scopus 로고
    • Four-helical-bundle structure of the cytoplasmic domain of a serine chemotaxis receptor
    • Kim KK, Yokota H, Kim SH (1999) Four-helical-bundle structure of the cytoplasmic domain of a serine chemotaxis receptor. Nature 400: 787-792.
    • (1999) Nature , vol.400 , pp. 787-792
    • Kim, K.K.1    Yokota, H.2    Kim, S.H.3
  • 14
    • 27344455900 scopus 로고    scopus 로고
    • Insights into the organization and dynamics of bacterial chemoreceptor clusters through in vivo crosslinking studies
    • Studdert CA, Parkinson JS (2005) Insights into the organization and dynamics of bacterial chemoreceptor clusters through in vivo crosslinking studies. Proc Natl Acad Sci U S A 102: 15623-15628.
    • (2005) Proc Natl Acad Sci U S A , vol.102 , pp. 15623-15628
    • Studdert, C.A.1    Parkinson, J.S.2
  • 15
    • 0034009901 scopus 로고    scopus 로고
    • An ultrasensitive bacterial motor revealed by monitoring signaling proteins in single cells
    • Cluzel P, Surette M, Leibler S (2000) An ultrasensitive bacterial motor revealed by monitoring signaling proteins in single cells. Science 287: 1652-1655.
    • (2000) Science , vol.287 , pp. 1652-1655
    • Cluzel, P.1    Surette, M.2    Leibler, S.3
  • 16
    • 0037039384 scopus 로고    scopus 로고
    • Receptor sensitivity in bacterial chemotaxis
    • Sourjik V, Berg HC (2002) Receptor sensitivity in bacterial chemotaxis. Proc Natl Acad Sci U S A 99: 123-127.
    • (2002) Proc Natl Acad Sci U S A , vol.99 , pp. 123-127
    • Sourjik, V.1    Berg, H.C.2
  • 17
    • 1842473065 scopus 로고    scopus 로고
    • Functional interactions between receptors in bacterial chemotaxis
    • Sourjik V, Berg HC (2004) Functional interactions between receptors in bacterial chemotaxis. Nature 428: 437-441.
    • (2004) Nature , vol.428 , pp. 437-441
    • Sourjik, V.1    Berg, H.C.2
  • 18
    • 0037011939 scopus 로고    scopus 로고
    • Inter-receptor communication through arrays of bacterial chemoreceptors
    • Gestwicki JE, Kiessling LL (2002) Inter-receptor communication through arrays of bacterial chemoreceptors. Nature 415: 81-84.
    • (2002) Nature , vol.415 , pp. 81-84
    • Gestwicki, J.E.1    Kiessling, L.L.2
  • 19
    • 0037015003 scopus 로고    scopus 로고
    • Dynamic and clustering model of bacterial chemotaxis receptors: Structural basis for signaling and high sensitivity
    • Kim SH, Wang W, Kim KK (2002) Dynamic and clustering model of bacterial chemotaxis receptors: structural basis for signaling and high sensitivity. Proc Natl Acad Sci U S A 99: 11611-11615.
    • (2002) Proc Natl Acad Sci U S A , vol.99 , pp. 11611-11615
    • Kim, S.H.1    Wang, W.2    Kim, K.K.3
  • 21
    • 0038399793 scopus 로고    scopus 로고
    • A spatially extended stochastic model of the bacterial chemotaxis signaling pathway
    • Shimizu TS, Aksenov SV, Bray D (2003) A spatially extended stochastic model of the bacterial chemotaxis signaling pathway. J Mol Biol 329: 291-309.
    • (2003) J Mol Biol , vol.329 , pp. 291-309
    • Shimizu, T.S.1    Aksenov, S.V.2    Bray, D.3
  • 22
    • 0001180444 scopus 로고
    • Transient response to chemotactic stimuli in Escherichia coli
    • Berg HC, Tedesco PM (1975) Transient response to chemotactic stimuli in Escherichia coli. Proc Natl Acad Sci U S A 72: 3235-3239.
    • (1975) Proc Natl Acad Sci U S A , vol.72 , pp. 3235-3239
    • Berg, H.C.1    Tedesco, P.M.2
  • 23
    • 0024347198 scopus 로고
    • Phosphorylation of an N-terminal regulatory domain activates the CheB methylesterase in bacterial chemotaxis
    • Lupas A, Stock J (1989) Phosphorylation of an N-terminal regulatory domain activates the CheB methylesterase in bacterial chemotaxis. J Biol Chem 264: 17337-17342.
    • (1989) J Biol Chem , vol.264 , pp. 17337-17342
    • Lupas, A.1    Stock, J.2
  • 24
    • 0032492852 scopus 로고    scopus 로고
    • Receptor clustering as a cellular mechanism to control sensitivity
    • Bray D, Levin MD, Morton-Firth CJ (1998) Receptor clustering as a cellular mechanism to control sensitivity. Nature 393: 85-88.
    • (1998) Nature , vol.393 , pp. 85-88
    • Bray, D.1    Levin, M.D.2    Morton-Firth, C.J.3
  • 25
    • 77449157985 scopus 로고    scopus 로고
    • Active signaling complexes of bacterial chemoreceptors do not contain proposed receptor-receptor contacts observed in crystal structures
    • [Epub ahead of print]
    • Fowler DJ, Weis RM, Thompson LK (2010) Active signaling complexes of bacterial chemoreceptors do not contain proposed receptor-receptor contacts observed in crystal structures. Biochemistry;[Epub ahead of print].
    • (2010) Biochemistry
    • Fowler, D.J.1    Weis, R.M.2    Thompson, L.K.3
  • 26
    • 33751213049 scopus 로고    scopus 로고
    • Spatial organization of the bacterial chemotaxis system
    • Kentner D, Sourjik V (2006) Spatial organization of the bacterial chemotaxis system. Curr Opin Microbiol 9: 1-6.
    • (2006) Curr Opin Microbiol , vol.9 , pp. 1-6
    • Kentner, D.1    Sourjik, V.2
  • 27
    • 0033778277 scopus 로고    scopus 로고
    • Molecular model of a lattice of signaling proteins involved in bacterial chemotaxis
    • Shimizu TS, Le Novere N, Levin MD, Beavil AJ, Sutton BJ, et al. (2000) Molecular model of a lattice of signaling proteins involved in bacterial chemotaxis. Nat Cell Biol 2: 792-796.
    • (2000) Nat Cell Biol , vol.2 , pp. 792-796
    • Shimizu, T.S.1    Le Novere, N.2    Levin, M.D.3    Beavil, A.J.4    Sutton, B.J.5
  • 29
    • 33748486238 scopus 로고    scopus 로고
    • Determinants of chemoreceptor cluster formation in Escherichia coli
    • Kentner D, Thiem S, Hildenbeutel M, Sourjik V (2006) Determinants of chemoreceptor cluster formation in Escherichia coli. Mol Microbiol 61: 407-417.
    • (2006) Mol Microbiol , vol.61 , pp. 407-417
    • Kentner, D.1    Thiem, S.2    Hildenbeutel, M.3    Sourjik, V.4
  • 30
    • 72949123244 scopus 로고    scopus 로고
    • Signal amplification in a lattice of coupled protein kinases
    • Goldman JP, Levin MD, Bray D (2009) Signal amplification in a lattice of coupled protein kinases. Mol Biosyst 5: 1853-1859.
    • (2009) Mol Biosyst , vol.5 , pp. 1853-1859
    • Goldman, J.P.1    Levin, M.D.2    Bray, D.3
  • 31
    • 77956556167 scopus 로고    scopus 로고
    • Adaptational assistance in clusters of bacterial chemoreceptors
    • Li M, Hazelbauer GL (2005) Adaptational assistance in clusters of bacterial chemoreceptors. Mol Microbiol 61: 407-417.
    • (2005) Mol Microbiol , vol.61 , pp. 407-417
    • Li, M.1    Hazelbauer, G.L.2
  • 32
    • 0027231876 scopus 로고
    • Computer simulation of the phosphorylation cascade controlling bacterial chemotaxis
    • Bray D, Bourret RB, Simon MI (1993) Computer simulation of the phosphorylation cascade controlling bacterial chemotaxis. Mol Biol Cell 4: 469-482.
    • (1993) Mol Biol Cell , vol.4 , pp. 469-482
    • Bray, D.1    Bourret, R.B.2    Simon, M.I.3
  • 33
    • 0028853660 scopus 로고
    • Computer analysis of the binding reactions leading to a transmembrane receptor-linked multiprotein complex involved in bacterial chemotaxis
    • Bray D, Bourret RB (1995) Computer analysis of the binding reactions leading to a transmembrane receptor-linked multiprotein complex involved in bacterial chemotaxis. Mol Biol Cell 6: 1367-1380.
    • (1995) Mol Biol Cell , vol.6 , pp. 1367-1380
    • Bray, D.1    Bourret, R.B.2
  • 34
    • 33845909561 scopus 로고    scopus 로고
    • The chemotactic behavior of computerbased surrogate bacteria
    • Bray D, Levin MD, Lipkow K (2007) The chemotactic behavior of computerbased surrogate bacteria. Curr Biol 17: 12-19.
    • (2007) Curr Biol , vol.17 , pp. 12-19
    • Bray, D.1    Levin, M.D.2    Lipkow, K.3
  • 36
    • 34047125290 scopus 로고    scopus 로고
    • Co-expression of signaling proteins improves robustness of the bacterial chemotaxis pathway
    • Lovdok L, Kollmann M, Sourjik V (2007) Co-expression of signaling proteins improves robustness of the bacterial chemotaxis pathway. J Biotechnol.
    • (2007) J Biotechnol
    • Lovdok, L.1    Kollmann, M.2    Sourjik, V.3
  • 37
    • 2942610579 scopus 로고    scopus 로고
    • Cellular stoichiometry of the components of the chemotaxis signaling complex
    • Li M, Hazelbauer GL (2004) Cellular stoichiometry of the components of the chemotaxis signaling complex. J Bacteriol 186: 3687-3694.
    • (2004) J Bacteriol , vol.186 , pp. 3687-3694
    • Li, M.1    Hazelbauer, G.L.2
  • 39
    • 0026344818 scopus 로고
    • Estimation of macromolecule concentrations and excluded volume effects for the cytoplasm of Escherichia coli
    • Zimmerman SB, Trach SO (1991) Estimation of macromolecule concentrations and excluded volume effects for the cytoplasm of Escherichia coli. J Mol Biol 222: 599-620.
    • (1991) J Mol Biol , vol.222 , pp. 599-620
    • Zimmerman, S.B.1    Trach, S.O.2
  • 40
    • 11144261882 scopus 로고    scopus 로고
    • Myriad molecules in motion: Simulated diffusion as a new tool to study molecular movement and interaction in a living cell
    • Hazelbauer GL (2005) Myriad molecules in motion: simulated diffusion as a new tool to study molecular movement and interaction in a living cell. J Bacteriol 187: 23-25.
    • (2005) J Bacteriol , vol.187 , pp. 23-25
    • Hazelbauer, G.L.1
  • 41
    • 77956550000 scopus 로고    scopus 로고
    • Levin MD (2008) Rate tables. http://www.pdn.cam.ac.uk/groups/comp-cell/Rates.html.
    • (2008) Rate tables
    • Levin, M.D.1
  • 42
    • 0035815743 scopus 로고    scopus 로고
    • The influence of macromolecular crowding and macromolecular confinement on biochemical reactions in physiological media
    • Minton AP (2001) The influence of macromolecular crowding and macromolecular confinement on biochemical reactions in physiological media. J Biol Chem 276: 10577-10580.
    • (2001) J Biol Chem , vol.276 , pp. 10577-10580
    • Minton, A.P.1
  • 43
    • 2442543316 scopus 로고    scopus 로고
    • Reaction kinetics in intracellular environments with macromolecular crowding: Simulations and rate laws
    • Schnell S, Turner TE (2004) Reaction kinetics in intracellular environments with macromolecular crowding: simulations and rate laws. Prog Biophys Mol Biol 85: 235-260.
    • (2004) Prog Biophys Mol Biol , vol.85 , pp. 235-260
    • Schnell, S.1    Turner, T.E.2
  • 45
    • 38149125617 scopus 로고    scopus 로고
    • Kinetic characterization of catalysis by the chemotaxis phosphatase CheZ. Modulation of activity by the phosphorylated CheY substrate
    • Silversmith RE, Levin MD, Schilling E, Bourret RB (2008) Kinetic characterization of catalysis by the chemotaxis phosphatase CheZ. Modulation of activity by the phosphorylated CheY substrate. J Biol Chem 283: 756-765.
    • (2008) J Biol Chem , vol.283 , pp. 756-765
    • Silversmith, R.E.1    Levin, M.D.2    Schilling, E.3    Bourret, R.B.4
  • 46
    • 2142753979 scopus 로고    scopus 로고
    • Dynamic receptor team formation can explain the high signal transduction gain in Escherichia coli
    • Albert R, Chiu YW, Othmer HG (2004) Dynamic receptor team formation can explain the high signal transduction gain in Escherichia coli. Biophys J 86: 2650-2659.
    • (2004) Biophys J , vol.86 , pp. 2650-2659
    • Albert, R.1    Chiu, Y.W.2    Othmer, H.G.3
  • 47
    • 1242274351 scopus 로고    scopus 로고
    • Crosslinking snapshots of bacterial chemoreceptor squads
    • Studdert CA, Parkinson JS (2004) Crosslinking snapshots of bacterial chemoreceptor squads. Proc Natl Acad Sci U S A 101: 2117-2122.
    • (2004) Proc Natl Acad Sci U S A , vol.101 , pp. 2117-2122
    • Studdert, C.A.1    Parkinson, J.S.2
  • 48
    • 4644278216 scopus 로고    scopus 로고
    • An allosteric model for transmembrane signaling in bacterial chemotaxis
    • Rao CV, Frenklach M, Arkin AP (2004) An allosteric model for transmembrane signaling in bacterial chemotaxis. J Mol Biol 343: 291-303.
    • (2004) J Mol Biol , vol.343 , pp. 291-303
    • Rao, C.V.1    Frenklach, M.2    Arkin, A.P.3
  • 49
    • 33744798728 scopus 로고    scopus 로고
    • Receptor-receptor coupling in bacterial chemotaxis: Evidence for strongly coupled clusters
    • Skoge ML, Endres RG, Wingreen NS (2006) Receptor-receptor coupling in bacterial chemotaxis: evidence for strongly coupled clusters. Biophys J 90: 4317-4326.
    • (2006) Biophys J , vol.90 , pp. 4317-4326
    • Skoge, M.L.1    Endres, R.G.2    Wingreen, N.S.3
  • 50
    • 0037816259 scopus 로고    scopus 로고
    • Quantitative modeling of sensitivity in bacterial chemotaxis: The role of coupling among different chemoreceptor species
    • Mello BA, Tu Y (2003) Quantitative modeling of sensitivity in bacterial chemotaxis: the role of coupling among different chemoreceptor species. Proc Natl Acad Sci U S A 100: 8223-8228.
    • (2003) Proc Natl Acad Sci U S A , vol.100 , pp. 8223-8228
    • Mello, B.A.1    Tu, Y.2
  • 51
    • 4444270835 scopus 로고    scopus 로고
    • Effects of receptor interaction in bacterial chemotaxis
    • Mello BA, Shaw L, Tu Y (2004) Effects of receptor interaction in bacterial chemotaxis. Biophys J 87: 1578-1595.
    • (2004) Biophys J , vol.87 , pp. 1578-1595
    • Mello, B.A.1    Shaw, L.2    Tu, Y.3
  • 52
    • 0034961694 scopus 로고    scopus 로고
    • STOCHSIM: Modelling of stochastic biomolecular processes
    • Le Novere N, Shimizu TS (2001) STOCHSIM: modelling of stochastic biomolecular processes. Bioinformatics 17: 575-576.
    • (2001) Bioinformatics , vol.17 , pp. 575-576
    • Le Novere, N.1    Shimizu, T.S.2
  • 53
    • 11144264728 scopus 로고    scopus 로고
    • Simulated diffusion of phosphorylated CheY through the cytoplasm of Escherichia coli
    • Lipkow K, Andrews SS, Bray D (2005) Simulated diffusion of phosphorylated CheY through the cytoplasm of Escherichia coli. J Bacteriol 187: 45-53.
    • (2005) J Bacteriol , vol.187 , pp. 45-53
    • Lipkow, K.1    Andrews, S.S.2    Bray, D.3
  • 55
    • 0037076308 scopus 로고    scopus 로고
    • Overcoming design and development challenges in agent-based modeling using ASCAPE
    • Inchiosa ME, Parker MT (2002) Overcoming design and development challenges in agent-based modeling using ASCAPE. Proc Natl Acad Sci U S A 99: 7304-7308.
    • (2002) Proc Natl Acad Sci U S A , vol.99 , pp. 7304-7308
    • Inchiosa, M.E.1    Parker, M.T.2
  • 56
    • 0012993281 scopus 로고    scopus 로고
    • Electron microscopic analysis of membrane assemblies formed by the bacterial chemotaxis receptor Tsr
    • Weis RM, Hirai T, Chalah A, Kessel M, Peters PJ, et al. (2003) Electron microscopic analysis of membrane assemblies formed by the bacterial chemotaxis receptor Tsr. J Bacteriol 185: 3636-3643.
    • (2003) J Bacteriol , vol.185 , pp. 3636-3643
    • Weis, R.M.1    Hirai, T.2    Chalah, A.3    Kessel, M.4    Peters, P.J.5
  • 57
    • 0028260372 scopus 로고
    • Attractant- and disulfide-induced conformational changes in the ligand binding domain of the chemotaxis aspartate receptor: A 19F NMR study
    • Danielson MA, Biemann HP, Koshland DEJ, Falke JJ (1994) Attractant- and disulfide-induced conformational changes in the ligand binding domain of the chemotaxis aspartate receptor: a 19F NMR study. Biochemistry 33: 6100-6109.
    • (1994) Biochemistry , vol.33 , pp. 6100-6109
    • Danielson, M.A.1    Biemann, H.P.2    Koshland, D.E.J.3    Falke, J.J.4
  • 58
    • 0033525474 scopus 로고    scopus 로고
    • A free-energy-based stochastic simulation of the Tar receptor complex
    • Morton-Firth CJ, Shimizu TS, Bray D (1999) A free-energy-based stochastic simulation of the Tar receptor complex. J Mol Biol 286: 1059-1074.
    • (1999) J Mol Biol , vol.286 , pp. 1059-1074
    • Morton-Firth, C.J.1    Shimizu, T.S.2    Bray, D.3
  • 59
    • 0027476771 scopus 로고
    • Polar location of the chemoreceptor complex in the Escherichia coli cell
    • Maddock JR, Shapiro L (1993) Polar location of the chemoreceptor complex in the Escherichia coli cell. Science 259: 1717-1723.
    • (1993) Science , vol.259 , pp. 1717-1723
    • Maddock, J.R.1    Shapiro, L.2
  • 60
    • 0026664405 scopus 로고
    • Attenuation of sensory receptor signaling by covalent modification
    • Borkovich KA, Alex LA, Simon MI (1992) Attenuation of sensory receptor signaling by covalent modification. Proc Natl Acad Sci U S A 89: 6756-6760.
    • (1992) Proc Natl Acad Sci U S A , vol.89 , pp. 6756-6760
    • Borkovich, K.A.1    Alex, L.A.2    Simon, M.I.3
  • 61
    • 0035195796 scopus 로고    scopus 로고
    • Evidence that both ligand binding and covalent adaptation drive a two-state equilibrium in the aspartate receptor signaling complex
    • Bornhorst JA, Falke JJ (2001) Evidence that both ligand binding and covalent adaptation drive a two-state equilibrium in the aspartate receptor signaling complex. J Gen Physiol 118: 693-710.
    • (2001) J Gen Physiol , vol.118 , pp. 693-710
    • Bornhorst, J.A.1    Falke, J.J.2
  • 62
    • 0037184003 scopus 로고    scopus 로고
    • Organization of the receptor-kinase signaling array that regulates Escherichia coli chemotaxis
    • Levit MN, Grebe TW, Stock JB (2002) Organization of the receptor-kinase signaling array that regulates Escherichia coli chemotaxis. J Biol Chem 277: 36748-36754.
    • (2002) J Biol Chem , vol.277 , pp. 36748-36754
    • Levit, M.N.1    Grebe, T.W.2    Stock, J.B.3


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