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Volumn 378, Issue 6, 1997, Pages 445-456

Selectively infective phages (SIP)

Author keywords

Gene3protein; Libraries; Molecular evolution; Phage infectivity; Phage libraries; Screening

Indexed keywords

AMINO TERMINAL SEQUENCE; BACTERIAL INFECTION; BACTERIOPHAGE; LIBRARY; LIGAND BINDING; MOLECULAR INTERACTION; NONHUMAN; PRIORITY JOURNAL; PROTEIN BINDING; REVIEW;

EID: 0030849223     PISSN: 14316730     EISSN: None     Source Type: Journal    
DOI: None     Document Type: Review
Times cited : (32)

References (58)
  • 1
    • 0028962883 scopus 로고
    • Characterization of phage that bind plastic from phage-displayed random peptide libraries
    • Adey, N.B., Mataragnon, A.H., Rider, J.E., Carter, J.M., and Kay, B.K. (1995). Characterization of phage that bind plastic from phage-displayed random peptide libraries. Gene 156, 27-31.
    • (1995) Gene , vol.156 , pp. 27-31
    • Adey, N.B.1    Mataragnon, A.H.2    Rider, J.E.3    Carter, J.M.4    Kay, B.K.5
  • 2
    • 0019841225 scopus 로고
    • Domain structure of bacteriophage fd adsorption protein
    • Armstrong, J., Perham, R.N., and Walker, J.E. (1981). Domain structure of bacteriophage fd adsorption protein. FEBS Lett. 135, 167-172.
    • (1981) FEBS Lett. , vol.135 , pp. 167-172
    • Armstrong, J.1    Perham, R.N.2    Walker, J.E.3
  • 3
    • 0029842096 scopus 로고    scopus 로고
    • Gene identification using the yeast two-hybrid system
    • Bai, C., and Elledge, S.J. (1996). Gene identification using the yeast two-hybrid system. Methods Enzymol. 273, 331-347.
    • (1996) Methods Enzymol. , vol.273 , pp. 331-347
    • Bai, C.1    Elledge, S.J.2
  • 4
    • 0019832250 scopus 로고
    • Nucleotide sequence and genome organization of filamentous bacteriophages f1 and fd
    • Beck, E., and Zink, B. (1981). Nucleotide sequence and genome organization of filamentous bacteriophages f1 and fd. Gene 16, 35-58.
    • (1981) Gene , vol.16 , pp. 35-58
    • Beck, E.1    Zink, B.2
  • 5
    • 0027193060 scopus 로고
    • Evolutionary relationship of uptake systems for biopolymers in Escherichia coli: Cross-complementation between the TonB-ExbB-ExbD and the TolA-TolQ-TolR proteins
    • Braun, V., and Herrmann, C. (1993). Evolutionary relationship of uptake systems for biopolymers in Escherichia coli: cross-complementation between the TonB-ExbB-ExbD and the TolA-TolQ-TolR proteins. Mol. Microbiol. 8, 261-268.
    • (1993) Mol. Microbiol. , vol.8 , pp. 261-268
    • Braun, V.1    Herrmann, C.2
  • 7
    • 0028223378 scopus 로고
    • In vitro selection from protein and peptide libraries
    • Clackson, T., and Wells, J.A. (1994). In vitro selection from protein and peptide libraries. Trends Biotechnol. 72, 173-184.
    • (1994) Trends Biotechnol. , vol.72 , pp. 173-184
    • Clackson, T.1    Wells, J.A.2
  • 8
    • 0027723182 scopus 로고
    • Display of biologically active proteins on the surface of filamentous phages: cDNA cloning system for selection of funcional gene products linked to the genetic information responsible for their production
    • Crameri, R., and Suter, M. (1993). Display of biologically active proteins on the surface of filamentous phages: cDNA cloning system for selection of funcional gene products linked to the genetic information responsible for their production. Gene 137, 69-75.
    • (1993) Gene , vol.137 , pp. 69-75
    • Crameri, R.1    Suter, M.2
  • 9
    • 0021352584 scopus 로고
    • Gene-III protein of filamentous phages: Evidence for a carboxy-terminal domain with a role in morphogenesis
    • Crissman, J.W., and Smith, G.P. (1984). Gene-III protein of filamentous phages: evidence for a carboxy-terminal domain with a role in morphogenesis. Virology 132, 445-455.
    • (1984) Virology , vol.132 , pp. 445-455
    • Crissman, J.W.1    Smith, G.P.2
  • 10
    • 0026546880 scopus 로고
    • Screening for receptor ligands using large libraries of peptides linked to the C terminus of the lac repressor
    • Cull, M.G., Miller, J.F., and Schatz, P.J. (1992). Screening for receptor ligands using large libraries of peptides linked to the C terminus of the lac repressor. Proc. Natl. Acad. Sci. USA 89, 1865-1869.
    • (1992) Proc. Natl. Acad. Sci. USA , vol.89 , pp. 1865-1869
    • Cull, M.G.1    Miller, J.F.2    Schatz, P.J.3
  • 11
    • 0022358219 scopus 로고
    • Fine structure of a membrane anchor domain
    • Davis, N.G., Boeke, J.D., and Model, P. (1985). Fine structure of a membrane anchor domain. J. Mol. Biol. 181, 111-121.
    • (1985) J. Mol. Biol. , vol.181 , pp. 111-121
    • Davis, N.G.1    Boeke, J.D.2    Model, P.3
  • 12
    • 0027933750 scopus 로고
    • Clonal selection and amplification of phage displayed antibodies by linking antigen recognition and phage replication
    • Duenas, M., and Borrebaeck, C.A.K. (1994). Clonal selection and amplification of phage displayed antibodies by linking antigen recognition and phage replication. Bio/Technology 12, 999-1002.
    • (1994) Bio/Technology , vol.12 , pp. 999-1002
    • Duenas, M.1    Borrebaeck, C.A.K.2
  • 13
    • 0028985654 scopus 로고
    • Novel helper phage design: Intergenic region affects the assembly of bacteriophages and the size of antibody libraries
    • Duenas, M., and Borrebaeck, C.A.K. (1995). Novel helper phage design: intergenic region affects the assembly of bacteriophages and the size of antibody libraries. FEMS Lett. 125, 317-321.
    • (1995) FEMS Lett. , vol.125 , pp. 317-321
    • Duenas, M.1    Borrebaeck, C.A.K.2
  • 15
    • 0029843718 scopus 로고    scopus 로고
    • In vitro immunization of naive human B cells yields high affinity immunoglobulin G antibodies as illustrated by phage display
    • Duenas, M., Chin, L.-T., Malmborg, A.-C., Casalvilla, R., Ohlin, M., and Borrebaeck, C.A.K. (1996b). In vitro immunization of naive human B cells yields high affinity immunoglobulin G antibodies as illustrated by phage display. Immunology 89, 1-7.
    • (1996) Immunology , vol.89 , pp. 1-7
    • Duenas, M.1    Chin, L.-T.2    Malmborg, A.-C.3    Casalvilla, R.4    Ohlin, M.5    Borrebaeck, C.A.K.6
  • 16
    • 0030271501 scopus 로고    scopus 로고
    • Phage display of proteins
    • Dunn, I.S. (1996). Phage display of proteins. Curr. Opin. Biotechnol. 7, 547-553.
    • (1996) Curr. Opin. Biotechnol. , vol.7 , pp. 547-553
    • Dunn, I.S.1
  • 17
    • 0029087064 scopus 로고
    • Location of filamentous phage minor coat proteins in phage and in infected cells
    • Endemann, H., and Model, P. (1995). Location of filamentous phage minor coat proteins in phage and in infected cells. J. Mol. Biol. 250, 496-506.
    • (1995) J. Mol. Biol. , vol.250 , pp. 496-506
    • Endemann, H.1    Model, P.2
  • 18
    • 0026582682 scopus 로고
    • The adsorption protein of phage IKe. Localization by deletion mutagenesis of domains involved in infectivity
    • Endemann, H., Bross, P., and Rasched, I. (1992). The adsorption protein of phage IKe. Localization by deletion mutagenesis of domains involved in infectivity. Mol. Microbiol. 6, 471-478.
    • (1992) Mol. Microbiol. , vol.6 , pp. 471-478
    • Endemann, H.1    Bross, P.2    Rasched, I.3
  • 19
    • 0027238126 scopus 로고
    • Interchange-ability of the adsorption proteins of bacteriophages Ff and IKe
    • Endemann, H., Gailus, V., and Rasched, I. (1993). Interchange-ability of the adsorption proteins of bacteriophages Ff and IKe. J. Wol. 67, 3332-3337.
    • (1993) J. Wol. , vol.67 , pp. 3332-3337
    • Endemann, H.1    Gailus, V.2    Rasched, I.3
  • 20
    • 0028217913 scopus 로고
    • The adsorption protein of bacteriophage fd and its neighbour minor coat protein build a structural entity
    • Gailus, V., and Rasched, I. (1994) The adsorption protein of bacteriophage fd and its neighbour minor coat protein build a structural entity. Eur. J. Biochem. 222, 927-931.
    • (1994) Eur. J. Biochem. , vol.222 , pp. 927-931
    • Gailus, V.1    Rasched, I.2
  • 21
    • 0028130487 scopus 로고
    • The role of the adsorption complex in the termination of filamentous phage assembly
    • Gailus, V., Ramsperger, U., Johner, C., Kramer, H., and Rasched, I. (1994). The role of the adsorption complex in the termination of filamentous phage assembly. Res. Microbiol. 145, 699-709.
    • (1994) Res. Microbiol. , vol.145 , pp. 699-709
    • Gailus, V.1    Ramsperger, U.2    Johner, C.3    Kramer, H.4    Rasched, I.5
  • 22
    • 0028670306 scopus 로고
    • Direct interaction rescue, a novel filamentous phage technique to study protein-protein interactions
    • Gramatikoff, K., Georgiev, O., and Schaffner, W. (1994). Direct interaction rescue, a novel filamentous phage technique to study protein-protein interactions. Nucl. Acids Res. 22, 5761-5762.
    • (1994) Nucl. Acids Res. , vol.22 , pp. 5761-5762
    • Gramatikoff, K.1    Georgiev, O.2    Schaffner, W.3
  • 23
    • 0029294706 scopus 로고
    • The leucin-zipper of c-Jun binds to ribosomal protein L18a: A role in Jun protein regulation?
    • Gramatikoff, K., Schaffner, W., and Georgiev, O. (1995). The leucin-zipper of c-Jun binds to ribosomal protein L18a: a role in Jun protein regulation? Biol. Chem. 376, 321-325.
    • (1995) Biol. Chem. , vol.376 , pp. 321-325
    • Gramatikoff, K.1    Schaffner, W.2    Georgiev, O.3
  • 25
    • 0030974119 scopus 로고    scopus 로고
    • In vitro selection and diversification of functional proteins using ribosome display
    • Hanes, J., and Plückthun, A. (1997). In vitro selection and diversification of functional proteins using ribosome display. Proc. Natl. Acad. Sci. USA, 94, 4937-4942.
    • (1997) Proc. Natl. Acad. Sci. USA , vol.94 , pp. 4937-4942
    • Hanes, J.1    Plückthun, A.2
  • 26
    • 0026699293 scopus 로고
    • Selection of phage antibodies by binding affinity. Mimicking affinity maturation
    • Hawkins, R.E., Russell, S.J., and Winter, G. (1992). Selection of phage antibodies by binding affinity. Mimicking affinity maturation. J. Mol. Biol. 226, 889-896.
    • (1992) J. Mol. Biol. , vol.226 , pp. 889-896
    • Hawkins, R.E.1    Russell, S.J.2    Winter, G.3
  • 27
    • 0031568809 scopus 로고    scopus 로고
    • A conserved infection pathway for filamentous bacteriophages is suggested by the structure of the membrane penetration domain of the minor coat protein g3p from phage fd
    • Holliger, P., and Riechmann, L. (1997). A conserved infection pathway for filamentous bacteriophages is suggested by the structure of the membrane penetration domain of the minor coat protein g3p from phage fd. Structure 5, 265-275.
    • (1997) Structure , vol.5 , pp. 265-275
    • Holliger, P.1    Riechmann, L.2
  • 28
    • 0019320778 scopus 로고
    • Synthesis, assembly into the cytoplasmic membrane, and proteolytic processing of the precursor of coliphage M13 coat protein
    • Ito, K., Date T., and Wickner, W. (1980). Synthesis, assembly into the cytoplasmic membrane, and proteolytic processing of the precursor of coliphage M13 coat protein. J. Biol. Chem. 255, 2123-2130.
    • (1980) J. Biol. Chem. , vol.255 , pp. 2123-2130
    • Ito, K.1    Date, T.2    Wickner, W.3
  • 29
    • 0023697146 scopus 로고
    • A hybrid toxin from bacteriophage f1 attachment protein and colicin E3 has altered cell receptor specificity
    • Jakes, K.S., Davis, G.D., and Zinder, N.D. (1988). A hybrid toxin from bacteriophage f1 attachment protein and colicin E3 has altered cell receptor specificity. J. Bacteriol. 170, 4231-4238.
    • (1988) J. Bacteriol. , vol.170 , pp. 4231-4238
    • Jakes, K.S.1    Davis, G.D.2    Zinder, N.D.3
  • 30
    • 0343561675 scopus 로고    scopus 로고
    • Krebber, C., Moroney, S., Plückthun, A., and Schneider, C. (1993). European Patent Application EP 93102484
    • Krebber, C., Moroney, S., Plückthun, A., and Schneider, C. (1993). European Patent Application EP 93102484.
  • 31
    • 0029585566 scopus 로고
    • Co-selection of cognate antibody-antigen pairs by selectively-infective phages
    • Krebber, C., Spada, S., Desplancq, D., and Plückthun, A. (1995). Co-selection of cognate antibody-antigen pairs by selectively-infective phages. FEBS Lett. 377, 227-231.
    • (1995) FEBS Lett. , vol.377 , pp. 227-231
    • Krebber, C.1    Spada, S.2    Desplancq, D.3    Plückthun, A.4
  • 32
    • 0031560775 scopus 로고    scopus 로고
    • Selectively-infective phage (SIP): A mechanistic dissection of a novel in vivo selection for protein-ligand interactions
    • Krebber, C., Spada, S., Desplancq, D., Krebber, A., Ge, L., and Plückthun, A. (1997). Selectively-infective phage (SIP): a mechanistic dissection of a novel in vivo selection for protein-ligand interactions. J. Mol. Biol. 268, 619-630.
    • (1997) J. Mol. Biol. , vol.268 , pp. 619-630
    • Krebber, C.1    Spada, S.2    Desplancq, D.3    Krebber, A.4    Ge, L.5    Plückthun, A.6
  • 33
    • 0020619299 scopus 로고
    • Morphogenesis of filamentous bacteriophage f1 : Orientation of extrusion and production of polyphage
    • Lopez, J., and Webster, R.E. (1983). Morphogenesis of filamentous bacteriophage f1 : orientation of extrusion and production of polyphage. Virology 127, 177-193.
    • (1983) Virology , vol.127 , pp. 177-193
    • Lopez, J.1    Webster, R.E.2
  • 34
    • 0026343486 scopus 로고
    • Selecting high-affinity binding proteins by monovalent phage display
    • Lowman, H.B., Bass, S.H., Simpson, N., and Wells, J.A. (1991). Selecting high-affinity binding proteins by monovalent phage display. Biochemistry 30, 10832-10838.
    • (1991) Biochemistry , vol.30 , pp. 10832-10838
    • Lowman, H.B.1    Bass, S.H.2    Simpson, N.3    Wells, J.A.4
  • 35
    • 0028168581 scopus 로고
    • Lambda too: A lambda phage vector for the expression of foreign proteins
    • Maruyama, I.N., Maruyama, H.I., and Brenner, S. (1994). Lambda too: a lambda phage vector for the expression of foreign proteins. Proc. Natl. Acad. Sci. USA 91, 8273-8277.
    • (1994) Proc. Natl. Acad. Sci. USA , vol.91 , pp. 8273-8277
    • Maruyama, I.N.1    Maruyama, H.I.2    Brenner, S.3
  • 36
    • 0031031766 scopus 로고    scopus 로고
    • Extending filamentous phage host range by the grafting of a heterologous receptor binding domain
    • Marzari, R., Sblattero, D., Righi, M., and Bradbury, A. (1997) Extending filamentous phage host range by the grafting of a heterologous receptor binding domain. Gene 185, 27-33.
    • (1997) Gene , vol.185 , pp. 27-33
    • Marzari, R.1    Sblattero, D.2    Righi, M.3    Bradbury, A.4
  • 37
    • 0028592703 scopus 로고
    • An in vitro polysome display system for identifying ligands from very large peptidelibraries
    • Mattheakis, L.C., Bhatt, R.R., and Dower, W.J. (1994). An in vitro polysome display system for identifying ligands from very large peptidelibraries. Proc. Natl. Acad. Sci. USA 91, 9022-9026.
    • (1994) Proc. Natl. Acad. Sci. USA , vol.91 , pp. 9022-9026
    • Mattheakis, L.C.1    Bhatt, R.R.2    Dower, W.J.3
  • 38
    • 0025226085 scopus 로고
    • Phage antibodies: Filamentous phage displaying antibody variable domains
    • McCafferty, J., Griffiths, A.D., Winter G., and Chriswell, D.J. (1990). Phage antibodies: filamentous phage displaying antibody variable domains. Nature 348, 552-554.
    • (1990) Nature , vol.348 , pp. 552-554
    • McCafferty, J.1    Griffiths, A.D.2    Winter, G.3    Chriswell, D.J.4
  • 39
    • 0030272124 scopus 로고    scopus 로고
    • Genetic and biochemical probes for protein-protein interactions
    • McNabb, D.S., and Guarente, L. (1996). Genetic and biochemical probes for protein-protein interactions. Curr. Opin. Biotechnol. 7, 554-559.
    • (1996) Curr. Opin. Biotechnol. , vol.7 , pp. 554-559
    • McNabb, D.S.1    Guarente, L.2
  • 40
    • 0019351126 scopus 로고
    • Filamentous phage DNA cloning vectors: A non-infective mutant with a non-polar deletion in gene III
    • Nelson, F.K., Friedman, S.M., and Smith, G.P. (1981). Filamentous phage DNA cloning vectors: A non-infective mutant with a non-polar deletion in gene III. Virology 108, 338-350.
    • (1981) Virology , vol.108 , pp. 338-350
    • Nelson, F.K.1    Friedman, S.M.2    Smith, G.P.3
  • 41
    • 0029102175 scopus 로고
    • Phage display: Protein engineering by directed evolution
    • O'Neil, K.T., and Hoess, R.H. (1995). Phage display: protein engineering by directed evolution. Curr. Opin. Struct. Biol. 5, 443-449.
    • (1995) Curr. Opin. Struct. Biol. , vol.5 , pp. 443-449
    • O'Neil, K.T.1    Hoess, R.H.2
  • 42
    • 0028364259 scopus 로고
    • Energy transfer analysis of Fos-Jun dimerization and DNA binding
    • Patel, L.R., Curran, T., and Kerppola, T.K. (1994). Energy transfer analysis of Fos-Jun dimerization and DNA binding. Proc. Natl. Acad. Sci. USA 91, 7360-7364.
    • (1994) Proc. Natl. Acad. Sci. USA , vol.91 , pp. 7360-7364
    • Patel, L.R.1    Curran, T.2    Kerppola, T.K.3
  • 43
    • 0022397969 scopus 로고
    • Nucleotide sequence and genetic organization of the genome of the N-specific filamentous bacteriophage IKe. Comparison with the genome of the F-specific filamentous phages M13, fd and f1
    • Peeters, B.P., Peters, R.M., Schoenmakers, J.G., and Konings, R. N. (1985). Nucleotide sequence and genetic organization of the genome of the N-specific filamentous bacteriophage IKe. Comparison with the genome of the F-specific filamentous phages M13, fd and f1. J. Mol. Biol. 181, 27-39.
    • (1985) J. Mol. Biol. , vol.181 , pp. 27-39
    • Peeters, B.P.1    Peters, R.M.2    Schoenmakers, J.G.3    Konings, R.N.4
  • 44
    • 0027442673 scopus 로고
    • An efficient screening assay for the rapid and precise determination of affinities between leucine-zipper domains
    • Pernelle, C., Clerc, F.F., Dureuil, C., Bracco, L., and Tocque, B. (1993). An efficient screening assay for the rapid and precise determination of affinities between leucine-zipper domains. Biochemistry 32, 11682-11687.
    • (1993) Biochemistry , vol.32 , pp. 11682-11687
    • Pernelle, C.1    Clerc, F.F.2    Dureuil, C.3    Bracco, L.4    Tocque, B.5
  • 45
    • 0028926048 scopus 로고
    • Protein-protein interactions: Methods for detection and analysis
    • Phizicky, E.M., and Fields, S. (1995). Protein-protein interactions: methods for detection and analysis. Microbiol. Rev. 59, 94-123.
    • (1995) Microbiol. Rev. , vol.59 , pp. 94-123
    • Phizicky, E.M.1    Fields, S.2
  • 49
    • 0021818675 scopus 로고
    • Filamentous fusion phage: Novel expression vectors that display cloned antigens on the virion surface
    • Smith, G.P. (1985). Filamentous fusion phage: novel expression vectors that display cloned antigens on the virion surface. Science 228, 1315-1317.
    • (1985) Science , vol.228 , pp. 1315-1317
    • Smith, G.P.1
  • 50
    • 0028050350 scopus 로고
    • Rapid evolution of a protein in vitro by DNA shuffling
    • Stemmer, W.P. (1994). Rapid evolution of a protein in vitro by DNA shuffling. Nature 370, 389-391.
    • (1994) Nature , vol.370 , pp. 389-391
    • Stemmer, W.P.1
  • 51
    • 0025273561 scopus 로고
    • Dissection of functional domains in phage fd adsorption protein
    • Stengele, I., Bross, P., Garces, X., Giray, J., and Rasched, I. (1990). Dissection of functional domains in phage fd adsorption protein. J. Mol. Biol. 212, 143-149.
    • (1990) J. Mol. Biol. , vol.212 , pp. 143-149
    • Stengele, I.1    Bross, P.2    Garces, X.3    Giray, J.4    Rasched, I.5
  • 52
    • 0028907327 scopus 로고
    • Display of peptides and proteins on the surface of bacteriophage lambda
    • Sternberg, N., and Hoess, R.H. (1995). Display of peptides and proteins on the surface of bacteriophage lambda. Proc. Natl. Acad. Sci. USA 92, 1609-1613.
    • (1995) Proc. Natl. Acad. Sci. USA , vol.92 , pp. 1609-1613
    • Sternberg, N.1    Hoess, R.H.2
  • 53
    • 0023225017 scopus 로고
    • Nucleotide sequence of a gene cluster involved in entry of E colicins and single-stranded DNA of infecting filamentous bacteriophages into Escherichia coli
    • Sun, T.-P. and Webster, R.E. (1987). Nucleotide sequence of a gene cluster involved in entry of E colicins and single-stranded DNA of infecting filamentous bacteriophages into Escherichia coli. J. Bacteriol. 169, 2667-2674.
    • (1987) J. Bacteriol. , vol.169 , pp. 2667-2674
    • Sun, T.-P.1    Webster, R.E.2
  • 55
    • 0028559783 scopus 로고
    • Trinucleotide phosphoramidites: Ideal reagents for the synthesis of mixed oligonucleotides for random mutagenesis
    • Virnekäs, B., Ge, L., Plückthun, A., Schneider, K.C., Wellnhofer, G., and Moroney, S.E. (1994). Trinucleotide phosphoramidites: ideal reagents for the synthesis of mixed oligonucleotides for random mutagenesis. Nucleic Acids Res. 22, 5600-5607.
    • (1994) Nucleic Acids Res. , vol.22 , pp. 5600-5607
    • Virnekäs, B.1    Ge, L.2    Plückthun, A.3    Schneider, K.C.4    Wellnhofer, G.5    Moroney, S.E.6
  • 56
    • 0025897173 scopus 로고
    • The tol gene products and the import of macromolecules into Escherichia coli
    • Webster, R.E. (1991). The tol gene products and the import of macromolecules into Escherichia coli. Mol. Microbiol. 5, 1005-1011.
    • (1991) Mol. Microbiol. , vol.5 , pp. 1005-1011
    • Webster, R.E.1
  • 58
    • 0018888903 scopus 로고
    • A new filamentous phage cloning vector: Fd-tet
    • Zacher, A.N., Stock, C.A., Golden, J.W., and Smith, G.P. (1980). A new filamentous phage cloning vector: fd-tet. Gene 9, 127-140.
    • (1980) Gene , vol.9 , pp. 127-140
    • Zacher, A.N.1    Stock, C.A.2    Golden, J.W.3    Smith, G.P.4


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