Precursor forms of vitamin D reduce HIV-1 infection in vitro

Artículo Científico

Autores:
Aguilar Jiménez, Wbeimar
Villegas Ospina, Simón
Gonzalez, Sandra
Zapata Builes, Wildeman
Saulle, Irma
Garziano, Micaela
Biasin, Mara
Clerici, Mario
Rugeles López, María Teresa
Tipo de recurso:
Article of journal
Fecha de publicación:
2016
Institución:
Universidad Cooperativa de Colombia
Repositorio:
Repositorio UCC
Idioma:
OAI Identifier:
oai:repository.ucc.edu.co:20.500.12494/1327
Acceso en línea:
https://hdl.handle.net/20.500.12494/1327
Palabra clave:
HIV-1
Vitamin D
Immune activation
Infection susceptibility
Rights
embargoedAccess
License
Licencia CC
id COOPER2_4ddb2ac88acfbc2d159490fff9d088a1
oai_identifier_str oai:repository.ucc.edu.co:20.500.12494/1327
network_acronym_str COOPER2
network_name_str Repositorio UCC
repository_id_str
dc.title.spa.fl_str_mv Precursor forms of vitamin D reduce HIV-1 infection in vitro
title Precursor forms of vitamin D reduce HIV-1 infection in vitro
spellingShingle Precursor forms of vitamin D reduce HIV-1 infection in vitro
HIV-1
Vitamin D
Immune activation
Infection susceptibility
title_short Precursor forms of vitamin D reduce HIV-1 infection in vitro
title_full Precursor forms of vitamin D reduce HIV-1 infection in vitro
title_fullStr Precursor forms of vitamin D reduce HIV-1 infection in vitro
title_full_unstemmed Precursor forms of vitamin D reduce HIV-1 infection in vitro
title_sort Precursor forms of vitamin D reduce HIV-1 infection in vitro
dc.creator.fl_str_mv Aguilar Jiménez, Wbeimar
Villegas Ospina, Simón
Gonzalez, Sandra
Zapata Builes, Wildeman
Saulle, Irma
Garziano, Micaela
Biasin, Mara
Clerici, Mario
Rugeles López, María Teresa
dc.contributor.author.none.fl_str_mv Aguilar Jiménez, Wbeimar
Villegas Ospina, Simón
Gonzalez, Sandra
Zapata Builes, Wildeman
Saulle, Irma
Garziano, Micaela
Biasin, Mara
Clerici, Mario
Rugeles López, María Teresa
dc.subject.spa.fl_str_mv HIV-1
Vitamin D
Immune activation
Infection susceptibility
topic HIV-1
Vitamin D
Immune activation
Infection susceptibility
description Artículo Científico
publishDate 2016
dc.date.issued.none.fl_str_mv 2016-12-15
dc.date.accessioned.none.fl_str_mv 2017-08-23T22:33:35Z
dc.date.available.none.fl_str_mv 2017-08-23T22:33:35Z
2018-01
dc.type.none.fl_str_mv Artículo
dc.type.coar.fl_str_mv http://purl.org/coar/resource_type/c_2df8fbb1
dc.type.coar.none.fl_str_mv http://purl.org/coar/resource_type/c_6501
dc.type.coarversion.none.fl_str_mv http://purl.org/coar/version/c_970fb48d4fbd8a85
dc.type.driver.none.fl_str_mv info:eu-repo/semantics/article
dc.type.version.none.fl_str_mv info:eu-repo/semantics/publishedVersion
format http://purl.org/coar/resource_type/c_6501
status_str publishedVersion
dc.identifier.uri.none.fl_str_mv https://hdl.handle.net/20.500.12494/1327
dc.identifier.bibliographicCitation.spa.fl_str_mv Aguilar Jimenez, W., Villegas Ospina, S., Gonzalez, S., Zapata, W., Saulle, I., Garziano, M., … Rugeles, M. T. (2016). Precursor Forms of Vitamin D Reduce HIV-1 Infection In Vitro. JAIDS Journal of Acquired Immune Deficiency Syndromes, 73(5). Retrieved from http://journals.lww.com/jaids/Fulltext/2016/12150/Precursor_Forms_of_Vitamin_D_Reduce_HIV_1.2.aspx
url https://hdl.handle.net/20.500.12494/1327
identifier_str_mv Aguilar Jimenez, W., Villegas Ospina, S., Gonzalez, S., Zapata, W., Saulle, I., Garziano, M., … Rugeles, M. T. (2016). Precursor Forms of Vitamin D Reduce HIV-1 Infection In Vitro. JAIDS Journal of Acquired Immune Deficiency Syndromes, 73(5). Retrieved from http://journals.lww.com/jaids/Fulltext/2016/12150/Precursor_Forms_of_Vitamin_D_Reduce_HIV_1.2.aspx
dc.relation.isversionof.spa.fl_str_mv https://insights.ovid.com/pubmed?pmid=27509245
dc.relation.isversionof.none.fl_str_mv http://journals.lww.com/jaids/Abstract/2016/12150/Precursor_Forms_of_Vitamin_D_Reduce_HIV_1.2.aspx
dc.rights.cc.none.fl_str_mv Licencia CC
dc.rights.accessrights.none.fl_str_mv info:eu-repo/semantics/embargoedAccess
dc.rights.coar.none.fl_str_mv http://purl.org/coar/access_right/c_f1cf
rights_invalid_str_mv Licencia CC
http://purl.org/coar/access_right/c_f1cf
eu_rights_str_mv embargoedAccess
dc.publisher.spa.fl_str_mv Universidad Cooperativa de Colombia, Facultad de Ciencias de la Salud, Programa de Medicina, Medellín y Envigado, Colombia, 00000
dc.publisher.program.spa.fl_str_mv Medicina
dc.publisher.place.spa.fl_str_mv Medellín
institution Universidad Cooperativa de Colombia
bitstream.url.fl_str_mv https://repository.ucc.edu.co/bitstreams/b5be0cb8-2679-430a-932a-c7dfb4dd47eb/download
https://repository.ucc.edu.co/bitstreams/e0dc0480-9052-4f34-969c-39c5e5fb1086/download
https://repository.ucc.edu.co/bitstreams/e96e8f81-0ee4-40bc-86ef-6f0e3cf9d540/download
https://repository.ucc.edu.co/bitstreams/aa4a7e16-6807-429c-a9a1-6a564f3230a6/download
bitstream.checksum.fl_str_mv 7cff87f1409b7a0ea2c8e3166379f346
5c0455ee701229ed2890dbf97da55ab0
efd6e8797d31357446d5e73d6b1c3c65
cb8f4d9b72d863ad6737f22af442cc82
bitstream.checksumAlgorithm.fl_str_mv MD5
MD5
MD5
MD5
repository.name.fl_str_mv Repositorio Institucional Universidad Cooperativa de Colombia
repository.mail.fl_str_mv bdigital@metabiblioteca.com
_version_ 1814246833954750464
spelling Aguilar Jiménez, WbeimarVillegas Ospina, SimónGonzalez, SandraZapata Builes, WildemanSaulle, IrmaGarziano, MicaelaBiasin, MaraClerici, MarioRugeles López, María Teresa2017-08-23T22:33:35Z2018-012017-08-23T22:33:35Z2016-12-15https://hdl.handle.net/20.500.12494/1327Aguilar Jimenez, W., Villegas Ospina, S., Gonzalez, S., Zapata, W., Saulle, I., Garziano, M., … Rugeles, M. T. (2016). Precursor Forms of Vitamin D Reduce HIV-1 Infection In Vitro. JAIDS Journal of Acquired Immune Deficiency Syndromes, 73(5). Retrieved from http://journals.lww.com/jaids/Fulltext/2016/12150/Precursor_Forms_of_Vitamin_D_Reduce_HIV_1.2.aspxArtículo CientíficoBackground: Although the anti-HIV-1 effects of vitamin D (VitD) have been reported, mechanisms behind such protection remain largely unexplored. Methods: The effects of two precursor forms (cholecalciferol/calciol at 0.01, 1 and 100 nM and calcidiol at 100 and 250 nM) on HIV-1 infection, immune activation, and gene expression were analyzed in vitro in cells of Colombian and Italian healthy donors. We quantified levels of released p24 by enzyme-linked immunosorbent assay, of intracellular p24 and cell-surface expression of CD38 and HLA-DR by flow cytometry, and mRNA expression of antiviral and immunoregulatory genes by real-time reverse transcriptionpolymerase chain reaction. Results: Cholecalciferol decreased the frequency of HIV-1-infected p24+CD4+ T cells and levels of p24 in supernatants in a dosedependent manner. Moreover, the CD4+CD38+HLA-DR+ and CD4+CD382HLA-DR+ subpopulations were more susceptible to infection but displayed the greatest cholecalciferol-induced decreases in infection rate by an X4-tropic strain. Likewise, cholecalciferol at its highest concentration decreased the frequency of CD382HLA-DR+ but not of CD38+HLA-DR+ T-cell subsets. Analyzing the effects of calcidiol, the main VitD source for immune cells and an R5-tropic strain as the most frequently transmitted virus, a reduction in HIV-1 productive infection was also observed. In addition, an increase in mRNA expression of APOBEC3G and PI3 and a reduction of TRIM22 and CCR5 expression, this latter positively correlated with p24 levels, was noted. Conclusions: VitD reduces HIV-1 infection in T cells possibly by inducing antiviral gene expression, reducing the viral co-receptor CCR5 and, at least at the highest holecalciferol concentration, by promoting an HIV-1-restrictive CD38+HLA-DR2 immunophenotype.wildeman.zapatab@campusucc.edu.coUniversidad Cooperativa de Colombia, Facultad de Ciencias de la Salud, Programa de Medicina, Medellín y Envigado, Colombia, 00000MedicinaMedellínhttps://insights.ovid.com/pubmed?pmid=27509245http://journals.lww.com/jaids/Abstract/2016/12150/Precursor_Forms_of_Vitamin_D_Reduce_HIV_1.2.aspxHIV-1Vitamin DImmune activationInfection susceptibilityPrecursor forms of vitamin D reduce HIV-1 infection in vitroArtículohttp://purl.org/coar/resource_type/c_6501http://purl.org/coar/resource_type/c_2df8fbb1http://purl.org/coar/version/c_970fb48d4fbd8a85info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionLicencia CCinfo:eu-repo/semantics/embargoedAccesshttp://purl.org/coar/access_right/c_f1cfPublicationORIGINAL2016_Abstract_Precursor_VitaminD_ReduceHIV.pdf2016_Abstract_Precursor_VitaminD_ReduceHIV.pdfapplication/pdf158368https://repository.ucc.edu.co/bitstreams/b5be0cb8-2679-430a-932a-c7dfb4dd47eb/download7cff87f1409b7a0ea2c8e3166379f346MD53TEXT2016_Abstract_Precursor_VitaminD_ReduceHIV.pdf.txt2016_Abstract_Precursor_VitaminD_ReduceHIV.pdf.txtExtracted texttext/plain3339https://repository.ucc.edu.co/bitstreams/e0dc0480-9052-4f34-969c-39c5e5fb1086/download5c0455ee701229ed2890dbf97da55ab0MD54THUMBNAIL2016_Abstract_Precursor_VitaminD_ReduceHIV.pdf.jpg2016_Abstract_Precursor_VitaminD_ReduceHIV.pdf.jpgIM Thumbnailimage/jpeg4652https://repository.ucc.edu.co/bitstreams/e96e8f81-0ee4-40bc-86ef-6f0e3cf9d540/downloadefd6e8797d31357446d5e73d6b1c3c65MD55LICENSElicense.txtlicense.txttext/plain; charset=utf-84553https://repository.ucc.edu.co/bitstreams/aa4a7e16-6807-429c-a9a1-6a564f3230a6/downloadcb8f4d9b72d863ad6737f22af442cc82MD5220.500.12494/1327oai:repository.ucc.edu.co:20.500.12494/13272024-08-10 22:40:29.412open.accesshttps://repository.ucc.edu.coRepositorio Institucional Universidad Cooperativa de Colombiabdigital@metabiblioteca.comVU5JVkVSU0lEQUQgQ09PUEVSQVRJVkEgREUgQ09MT01CSUEKUkVQT1NJVE9SSU9TIElOU1RJVFVDSU9OQUxFUwpMSUNFTkNJQSBERSBVU08KClBvciBtZWRpbyBkZWwgcHJlc2VudGUgZG9jdW1lbnRvLCBlbCBBdXRvcihlcyksIG1heW9yIChlcykgZGUgZWRhZCwgcXVpZW4gZW4gYWRlbGFudGUgc2UgZGVub21pbmFyw6EgZWwgQVVUT1IsIGNvbmZpZXJlIGEgbGEgVU5JVkVSU0lEQUQgQ09PUEVSQVRJVkEgREUgQ09MT01CSUEsIGNvbiBOSVQuIDg2MC0wMjk5MjQtNywgdW5hIExJQ0VOQ0lBIERFIFVTTyBkZSBvYnJhLCBiYWpvIGxhcyBzaWd1aWVudGVzIGNvbmRpY2lvbmVzLgoKQ0zDgVVTVUxBUwoKUFJJTUVSQS4gT2JqZXRvLiBFTCBBVVRPUiBwb3IgZXN0ZSBhY3RvIGF1dG9yaXphIGxhIHV0aWxpemFjacOzbiBkZSBsYSBvYnJhLCBkZSBjb25mb3JtaWRhZCBjb24gbG8gZXN0aXB1bGFkbyBhIGNvbnRpbnVhY2nDs246IAoKKGEpIFBhcmEgZWZlY3RvcyBkZSBsYSBwcmVzZW50ZSBsaWNlbmNpYSBzZSBhdXRvcml6YSBsYSByZXByb2R1Y2Npw7NuIGRlIGxhIG9icmEgYW50ZXJpb3JtZW50ZSBjaXRhZGEsIGxhIGN1YWwgc2UgYWxvamFyw6EgZW4gZm9ybWF0byBkaWdpdGFsIGVuIGxhcyBwbGF0YWZvcm1hcyBvIHJlcG9zaXRvcmlvcyBhZG1pbmlzdHJhZG9zIHBvciBsYSBVTklWRVJTSURBRCBvIGVuIG90cm8gdGlwbyBkZSByZXBvc2l0b3Jpb3MgZXh0ZXJub3MgbyBww6FnaW5hcyB3ZWIgZXNjb2dpZG9zIHBvciBsYSBVTklWRVJTSURBRCwgcGFyYSBmaW5lcyBkZSBkaWZ1c2nDs24geSBkaXZ1bGdhY2nDs24uIEFkaWNpb25hbG1lbnRlLCBzZSBhdXRvcml6YSBhIHF1ZSBsb3MgdXN1YXJpb3MgaW50ZXJub3MgeSBleHRlcm5vcyBkZSBkaWNoYXMgcGxhdGFmb3JtYXMgbyByZXBvc2l0b3Jpb3MgcmVwcm9kdXpjYW4gbyBkZXNjYXJndWVuIGxhIG9icmEsIHNpbiDDoW5pbW8gZGUgbHVjcm8sIHBhcmEgZmluZXMgcHJpdmFkb3MsIGVkdWNhdGl2b3MgbyBhY2Fkw6ltaWNvczsgc2llbXByZSB5IGN1YW5kbyBubyBzZSB2aW9sZW4gYWN1ZXJkb3MgY29uIGVkaXRvcmVzLCBwZXJpb2RvcyBkZSBlbWJhcmdvIG8gYWN1ZXJkb3MgZGUgY29uZmlkZW5jaWFsaWRhZCBxdWUgYXBsaXF1ZW4uCgooYikgU2UgYXV0b3JpemEgbGEgY29tdW5pY2FjacOzbiBww7pibGljYSB5IGxhIHB1ZXN0YSBhIGRpc3Bvc2ljacOzbiBkZSBsYSBvYnJhIG1lbmNpb25hZGEsIGVuIGFjY2VzbyBhYmllcnRvLCBwYXJhIHN1IHV0aWxpemFjacOzbiBlbiBsYXMgcGxhdGFmb3JtYXMgbyByZXBvc2l0b3Jpb3MgYWRtaW5pc3RyYWRvcyBwb3IgbGEgVU5JVkVSU0lEQUQuCgooYykgTG8gYW50ZXJpb3IgZXN0YXLDoSBzdWpldG8gYSBsYXMgZGVmaW5pY2lvbmVzIGNvbnRlbmlkYXMgZW4gbGEgRGVjaXNpw7NuIEFuZGluYSAzNTEgZGUgMTk5MyB5IGxhIExleSAyMyBkZSAxOTgyLgoKClNFR1VOREEuIE9yaWdpbmFsaWRhZCB5IHJlY2xhbWFjaW9uZXMuIEVsIEFVVE9SIGRlY2xhcmEgcXVlIGxhIE9CUkEgZXMgb3JpZ2luYWwgeSBxdWUgZXMgZGUgc3UgY3JlYWNpw7NuIGV4Y2x1c2l2YSwgbm8gZXhpc3RpZW5kbyBpbXBlZGltZW50byBkZSBjdWFscXVpZXIgbmF0dXJhbGV6YSAoZW1iYXJnb3MsIHVzbyBkZSBtYXRlcmlhbCBwcm90ZWdpZG8gcG9yIGRlcmVjaG9zIGRlIGF1dG9yKSBwYXJhIGxhIGNvbmNlc2nDs24gZGUgbG9zIGRlcmVjaG9zIHByZXZpc3RvcyBlbiBlc3RlIGNvbnRyYXRvLiBFbCBBVVRPUiByZXNwb25kZXLDoSBwb3IgY3VhbHF1aWVyIGFjY2nDs24gZGUgcmVpdmluZGljYWNpw7NuLCBwbGFnaW8gdSBvdHJhIGNsYXNlIGRlIHJlY2xhbWFjacOzbiBxdWUgYWwgcmVzcGVjdG8gcHVkaWVyYSBzb2JyZXZlbmlyLgoKVEVSQ0VSQS4gQ29udHJhcHJlc3RhY2nDs24uIEVsIEFVVE9SIGF1dG9yaXphIGEgcXVlIHN1IG9icmEgc2VhIHV0aWxpemFkYSBkZSBjb25mb3JtaWRhZCBjb24gbGEgY2zDoXVzdWxhIFBSSU1FUkEgZGUgZm9ybWEgZ3JhdHVpdGEsIGVzIGRlY2lyLCBxdWUgbGEgdXRpbGl6YWNpw7NuIGRlIGxhIG1pc21hIG5vIGdlbmVyYSBuaW5nw7puIHBhZ28gbyByZWdhbMOtYXMgZW4gZmF2b3IgZGUgZXN0ZS4KCkNVQVJUQS4gVGl0dWxhcmlkYWQgZGUgZGVyZWNob3MuIEVsIHByZXNlbnRlIGNvbnRyYXRvIG5vIHRyYW5zZmllcmUgbGEgdGl0dWxhcmlkYWQgZGUgbG9zIGRlcmVjaG9zIHBhdHJpbW9uaWFsZXMgc29icmUgbGFzIG9icmFzIGFudGVyaW9ybWVudGUgbWVuY2lvbmFkYXMgYSBsYSBVTklWRVJTSURBRC4gw5puaWNhbWVudGUgaGFjZSByZWxhY2nDs24gYSB1bmEgbGljZW5jaWEgbm8gZXhjbHVzaXZhIGVuIGxvcyB0w6lybWlub3MgeSBjb25kaWNpb25lcyBhbnRlcmlvcm1lbnRlIHBhY3RhZG9zLgoKUVVJTlRBLiBDcsOpZGl0b3MuIExhIFVOSVZFUlNJREFEIHNlIGNvbXByb21ldGUgYSBkYXIgYWwgQVVUT1IsIGVsIHJlY29ub2NpbWllbnRvIGRlbnRybyBjYWRhIGZvcm1hIGRlIHV0aWxpemFjacOzbiBlbiBsYSBvYnJhLiBMb3MgY3LDqWRpdG9zIGRlYmVuIGZpZ3VyYXIgZW4gY2FkYSB1bm8gZGUgbG9zIGZvcm1hdG9zIG8gcmVnaXN0cm9zIGRlIHB1YmxpY2FjacOzbi4gTm8gY29uc3RpdHVpcsOhIHVuYSB2aW9sYWNpw7NuIGEgbG9zIGRlcmVjaG9zIG1vcmFsZXMgZGVsIGF1dG9yIGxhIG5vIHJlcHJvZHVjY2nDs24sIGNvbXVuaWNhY2nDs24gbyBkZW3DoXMgdXRpbGl6YWNpb25lcyBkZSBsYSBvYnJhLiBMYSB1dGlsaXphY2nDs24gbyBubyBkZSBsYSBvYnJhLCBhc8OtIGNvbW8gc3UgZm9ybWEgZGUgdXRpbGl6YWNpw7NuIHNlcsOhIGZhY3VsdGFkIGV4Y2x1c2l2YSBkZSBsYSBVTklWRVJTSURBRC4KIApTRVhUQS4gRHVyYWNpw7NuIHkgdGVycml0b3Jpby4gTGEgcHJlc2VudGUgbGljZW5jaWEgZGUgdXNvIHF1ZSBzZSBvdG9yZ2EgYSBmYXZvciBkZSBsYSBVTklWRVJTSURBRCB0ZW5kcsOhIHVuYSBkdXJhY2nDs24gZXF1aXZhbGVudGUgYWwgdMOpcm1pbm8gZGUgcHJvdGVjY2nDs24gbGVnYWwgZGUgbGEgb2JyYSB5IHBhcmEgdG9kb3MgbG9zIHBhw61zZXMgZGVsIG11bmRvLgoKU8OJUFRJTUEuIFVzbyBkZSBDcmVhdGl2ZSBDb21tb25zLiBFbCBBVVRPUiBhdXRvcml6YXLDoSBsYSBkaWZ1c2nDs24gZGUgc3Ugb2JyYSBiYWpvIHVuYSBsaWNlbmNpYSBkZSBDcmVhdGl2ZSBDb21tb25zIEJZIE5DIE5EIChBdHJpYnVjacOzbiAtIE5vIGNvbWVyY2lhbCDigJMgTm8gRGVyaXZhZGEpLCBsbyBjdWFsIHNlIHBvZHLDoSBpbmNsdWlyIGVuIGxhIE9CUkEsIHNpIGxhIFVOSVZFUlNJREFEIGNvbnNpZGVyYSBuZWNlc2FyaW8gaGFjZXJsbyBleHBsw61jaXRvLCBhbCBtb21lbnRvIGRlIGxhIHB1YmxpY2FjacOzbiwgYXJjaGl2byBvIHJlZ2lzdHJvIGVuIGxhcyBwbGF0YWZvcm1hcyBvIHJlcG9zaXRvcmlvcywgcG9yIHNlciB1bmEgY29udmVuY2nDs24gbWF5b3JpdGFyaWFtZW50ZSByZWNvbm9jaWRhLiAKCk9DVEFWQS4gRGVyZWNobyBkZSBleGNsdXNpw7NuLiBDYWRhIGF1dG9yIHB1ZWRlIGluZGljYXIgZW4gZWwgbW9tZW50byBkZSBkZXDDs3NpdG8gZGVsIGNvbnRlbmlkbyBxdWUgZWwgdGV4dG8gY29tcGxldG8gZGUgbGEgcHJvZHVjY2nDs24gYWNhZMOpbWljYSBvIGNpZW50w61maWNhIG5vIGVzdGUgY29uIGFjY2VzbyBhYmllcnRvIGVuIGVsIFJlcG9zaXRvcmlvIEluc3RpdHVjaW9uYWwgcG9yIG1vdGl2b3MgZGUgY29uZmlkZW5jaWFsaWRhZCwgcG9ycXVlIHNlIGVuY3VlbnRyZSBlbiB2w61hcyBkZSBvYnRlbmVyIHVuIGRlcmVjaG8gZGUgcHJvcGllZGFkIGluZHVzdHJpYWwgbyBleGlzdGlyIGFjdWVyZG9zIHByZXZpb3MgY29uIHRlcmNlcm9zIChlZGl0b3JpYWxlcywgcmV2aXN0YXMgY2llbnTDrWZpY2FzLCBvdHJhcyBpbnN0aXR1Y2lvbmVzKS4gRWwgYXV0b3Igc2UgY29tcHJvbWV0ZSBhIGRlcG9zaXRhciBsb3MgbWV0YWRhdG9zIGUgaW5mb3JtYXIgZWwgdGllbXBvIGRlIGVtYmFyZ28gZHVyYW50ZSBlbCBjdWFsIGVsIHRleHRvIGNvbXBsZXRvIHRlbmRyw6EgYWNjZXNvIHJlc3RyaW5naWRvLiAKCk5PVkVOQS4gRWwgQVVUT1IgYWwgYWNlcHRhciBlc3RhIGxpY2VuY2lhIGFkdWNlIHF1ZSBlc3RhIHByb2R1Y2Npw7NuIHNlIGRlc2Fycm9sbMOzIGVuIGVsIHBlcmlvZG8gZW4gcXVlIHNlIGVuY3VlbnRyYSBjb24gdsOtbmN1bG9zIGNvbiBMYSBVbml2ZXJzaWRhZC4KCkTDiUNJTUEuIE5vcm1hcyBhcGxpY2FibGVzLiBQYXJhIGxhIGludGVycHJldGFjacOzbiB5IGN1bXBsaW1pZW50byBkZWwgcHJlc2VudGUgY29udHJhdG8gbGFzIHBhcnRlcyBzZSBzb21ldGVuIGEgbGEgRGVjaXNpw7NuIEFuZGluYSAzNTEgZGUgMTk5MywgbGEgTGV5IDIzIGRlIDE5ODIgeSBkZW3DoXMgbm9ybWFzIGFwbGljYWJsZXMgZGUgQ29sb21iaWEuIEFkZW3DoXMsIGEgbGFzIG5vcm1hcyBJbnN0aXR1Y2lvbmFsZXMgcXVlIGFwbGlxdWVuLgoKTGEgcHJlc2VudGUgbGljZW5jaWEgc2UgYXV0b3JpemEgZW4gbGEgZmVjaGEgZGUgcHVibGljYWNpw7NuIGVuIGxvcyByZXBvc2l0b3Jpb3MgaW5zdGl0dWNpb25hbGVzLgo=