Síntesis, actividad antibacteriana e interacción del ADN con complejos de inclusión entre compuestos lantánidos y β-ciclodextrina
1 recurso en línea (páginas 99-117).
- Autores:
-
Mayor Rivera, Angélica María
Aragón Muriel, Alberto
Polo Cerón, Dorian
- Tipo de recurso:
- Article of journal
- Fecha de publicación:
- 2018
- Institución:
- Universidad Pedagógica y Tecnológica de Colombia
- Repositorio:
- RiUPTC: Repositorio Institucional UPTC
- Idioma:
- spa
- OAI Identifier:
- oai:repositorio.uptc.edu.co:001/2366
- Acceso en línea:
- http://repositorio.uptc.edu.co/handle/001/2366
- Palabra clave:
- Actividad antibacteriana
Complejos de inclusión
Complejos lantánidos
Interacción con ADN
- Rights
- openAccess
- License
- Copyright (c) 2018 Universidad Pedagógica y Tecnológica de Colombia
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Síntesis, actividad antibacteriana e interacción del ADN con complejos de inclusión entre compuestos lantánidos y β-ciclodextrina |
| dc.title.alternative.eng.fl_str_mv |
Synthesis, antibacterial activity and interaction of DNA with lanthanide-β-cyclodextrin inclusion complexes |
| title |
Síntesis, actividad antibacteriana e interacción del ADN con complejos de inclusión entre compuestos lantánidos y β-ciclodextrina |
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Síntesis, actividad antibacteriana e interacción del ADN con complejos de inclusión entre compuestos lantánidos y β-ciclodextrina Actividad antibacteriana Complejos de inclusión Complejos lantánidos Interacción con ADN |
| title_short |
Síntesis, actividad antibacteriana e interacción del ADN con complejos de inclusión entre compuestos lantánidos y β-ciclodextrina |
| title_full |
Síntesis, actividad antibacteriana e interacción del ADN con complejos de inclusión entre compuestos lantánidos y β-ciclodextrina |
| title_fullStr |
Síntesis, actividad antibacteriana e interacción del ADN con complejos de inclusión entre compuestos lantánidos y β-ciclodextrina |
| title_full_unstemmed |
Síntesis, actividad antibacteriana e interacción del ADN con complejos de inclusión entre compuestos lantánidos y β-ciclodextrina |
| title_sort |
Síntesis, actividad antibacteriana e interacción del ADN con complejos de inclusión entre compuestos lantánidos y β-ciclodextrina |
| dc.creator.fl_str_mv |
Mayor Rivera, Angélica María Aragón Muriel, Alberto Polo Cerón, Dorian |
| dc.contributor.author.none.fl_str_mv |
Mayor Rivera, Angélica María Aragón Muriel, Alberto Polo Cerón, Dorian |
| dc.subject.proposal.spa.fl_str_mv |
Actividad antibacteriana Complejos de inclusión Complejos lantánidos Interacción con ADN |
| topic |
Actividad antibacteriana Complejos de inclusión Complejos lantánidos Interacción con ADN |
| description |
1 recurso en línea (páginas 99-117). |
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2018 |
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2018-07-04 |
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2019-01-31T20:39:28Z |
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2019-01-31T20:39:28Z |
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Artículo de revista |
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Mayor Rivera, A. M., Aragón Muriel, A. & Polo Cerón, D. (2018). Síntesis, actividad antibacteriana e interacción del ADN con complejos de inclusión entre compuestos lantánidos y β-ciclodextrina. Ciencia en Desarrollo, 9(2), 99-117. DOI: https://doi.org/10.19053/01217488.v9.n2.2018.7365. http://repositorio.uptc.edu.co/handle/001/2366 |
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10.19053/01217488.v9.n2.2018.7365 |
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Mayor Rivera, A. M., Aragón Muriel, A. & Polo Cerón, D. (2018). Síntesis, actividad antibacteriana e interacción del ADN con complejos de inclusión entre compuestos lantánidos y β-ciclodextrina. Ciencia en Desarrollo, 9(2), 99-117. DOI: https://doi.org/10.19053/01217488.v9.n2.2018.7365. http://repositorio.uptc.edu.co/handle/001/2366 2462-7658 10.19053/01217488.v9.n2.2018.7365 |
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Enriz, “Structure-antifungal activity relationship of cinnamic acid derivatives”, J. Agr. Food Chem., vol. 55, no. 26, pp. 10635–10640, Nov. 2007. http://pubs.acs. org/doi/abs/10.1021/jf0729098. N. J. Bello-Vieda, H. F. Pastrana, M. F. Garavito, A. G. Ávila, A. M. Celis, A. Muñoz-Castro, S. Restrepo, J. J. Hurtado, “Antibacterial Activities of Azole Complexes Combined with Silver Nanoparticles”, Molecules, vol. 23, no. 2, pp. 361, 1-17, Feb. 2018. https://doi. org/10.3390/molecules23020361. K. F. Castillo, N. J. Bello-Vieda, N. G. Nuñez-Dallos, H. F. Pastrana, A. M. Celis, S. Restrepo, J. J. Hurtado, A. G. Ávila, “Metal Complex Derivatives of Azole: a Study on Their Synthesis, Characterization, and Antibacterial and Antifungal Activities”, J. Braz. Chem. Soc., vol. 27, no. 12, pp. 2334-2347, Dec. 2016. http://dx.doi. org/10.5935/0103-5053.20160130. N. K. Singh, S. B. Singh, D. K. Singh, V. B. Chauhan, “Synthesis, characterization and biological properties of N-nicotinoyl-N’-thiobenzoyl-hydrazine complexes of cobalt(II), nickel(II), copper(II) and zinc(II), Indian J. Chem., vol. 42A, pp. 2767-2771, Nov. 2003. http://nopr.niscair.res. in/bitstream/123456789/20791/1/IJCA%20 42A(11)%202767-2771.pdf. A. Aragon-Muriel, D. Polo-Cerón, “Synthesis, characterization, thermal behavior, and antifungal activity of La(III) complexes with cinnamates and 4-methoxyphenylacetate”, J. Rare Earths, vol. 31, no. 11, pp. 1106-1113, Nov. 2013. https://doi.org/10.1016/ S1002-0721(12)60412-8. A. Aragon-Muriel, Y. Upegui, J. A. Muñoz, S. M. Robledo, D. Polo-Ceron, “Synthesis, characterization and biological evaluation of rare earth complexes against tropical diseases Leishmaniasis, Malaria and Trypanosomiasis”, Avances en Química, vol. 11, no. 2, pp. 53-61, Aug. 2016. http://erevistas. saber.ula.ve/index.php/avancesenquímica/ article/view/7863/7806. E. M. Martin Del Valle, “Cyclodextrins and their uses: a review”. Process Biochem., vol. 39, no. 9, pp. 1033–1046, May 2004. https:// doi.org/10.1016/S0032-9592(03)00258-9. E. Santos, J. Kamimura, L. Hill, C. Gomes, “Characterization of carvacrol beta-cyclodextrin inclusion complexes as delivery systems for antibacterial and antioxidant applications”, Food Sci. Technol., vol. 60, no. 1, pp. 583-592, Jan. 2015. https://doi. org/10.1016/j.lwt.2014.08.046. K. Uekama, F. Hirayama, T. Irie, “Cyclodextrin Drug Carrier Systems”, Chem. Rev., vol. 98, no. 5, pp. 2045-2076, Jul. 1998. http:// pubs.acs.org/doi/abs/10.1021/cr970025p C. Demicheli, R. Ochoa, J. Da Silva, C. Falcao, B. Rossi-Bergmann, A. De Melo, R. Sinisterra, F. Frézard, “Oral Delivery of Meglumine Antimoniate-β-Cyclodextrin Complex for Treatment of Leishmaniasis”, Antimicrob. Agents Chemother., vol. 48, no. 1, pp. 100-103, Jan. 2004. https://dx.doi. org/10.1128%2FAAC.48.1.100-103.2004. G. Deacon, M. Forsyth, P. Junk, S. Leary, W. Lee, “Synthesis and characterisation of rare earth complexes supported by para-substituted cinnamate ligands”, Z. Anorg. Allg. Chem., vol. 635, no. 6-7, pp. 833-839, May 2009. http://dx.doi.org/10.1002/zaac. 200801379. Performance Standards for Antimicrobial Disk and Dilution Susceptibility Tests for Bacterial Isolated from Animals, CLSI M31-A3. 3 ed., 2008. G. Deacon, F. Huber, R. Phillips, “Diagnosis of the nature of carboxylate coordination from the direction of shifts of carbón-oxygen stretching frequencies”, Inorg. Chim. Acta., vol. 104, no. 1, pp. 41-45, Oct. 1985. https:// doi.org/10.1016/S0020-1693(00)83783-4. A. Aragón-Muriel, M. Camprubi, E. Gonzalez, A. Salinas, A. Rodriguez, S. Gomez, D. Polo-Cerón, “Dual investigation of lanthanide complexes with cinnamate and phenylacetate ligands: study of the cytotoxic properties and the catalytic oxidation of styrene”, Polyhedron, vol. 80, pp. 117–128, Sep. 2014. https://doi.org/10.1016/j. poly.2014.02.040. N. Roik, L. Belyakova, “Infrared spectroscopy, x-ray diffraction and thermal analysis studies of solid b-cyclodextrin - para-aminobenzoic acid inclusion complex”, PCSS, vol. 12, no. 1, pp. 168-173, 2011. http:// www.pu.if.ua/inst/phys_che/start/pcss/ vol12/1201-26.pdf A. Kokkinou, S. Makedonopoulou, D. Mentzafos, “The cristal structure of the 1:1 complex of β-cyclodextrin with trans-cinnamic acid”, Carbohydr. Res., vol. 328, no. 2, pp. 135-140, Sep. 2000. https://doi.org/10.1016/ S0008-6215(00)00091-4. H. Schneider, F. Hacket, V. Rüdiger, I. Ikeda, “NMR studies of cyclodextrins and cyclodextrin complexes”, Chem. Rev., vol. 98, no. 5, pp. 1755-1786, Jul. 1998. http:// pubs.acs.org/doi/abs/10.1021/cr970019t. F. Giordano, C. Novak, J. Moyano, “Thermal analysis of cyclodextrins and their inclusion compounds”, Thermochim. Acta, vol. 380, no. 2, pp. 123-151, Dec. 2001. https://doi. org/10.1016/S0040-6031(01)00665-7. K. Chandrul, “Role of Macromolecules in Chromatography: Cyclodextrines”, J. Chem. 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Acta A., vol. 131, pp. 388-397, Oct. 2014. https://doi.org/10.1016/j. saa.2014.04.134. T. Abbs, A. Pearl, B. Rosy, “Synthesis, characterization, cytotoxicity, DNA cleavage and antimicrobial activity of homodinuclear lanthanide complexes of phenylthioacetic acid”, J. Rare Earths, vol. 31, no. 10, pp. 1009-1016. Oct. 2013. https://doi.org/10.1016/ S1002-0721(13)60022-8. J. Calvo, L. Martínez-Martínez, “Mecanismo de acción de los antimicrobianos”, Enferm. Infecc. Microbiol. Clin., vol. 27, no. 1, pp. 44–52, Jan. 2009. http://dx.doi. org/10.1016/j.eimc.2008.11.001. A. Deredjian, C. Colinon, S. Brothier, S. Favre-Bonte, B. Cournoyer, S. Nazaret, “Antibiotic and metal resistance among hospital and outdoor strains of Pseudomonas aeruginosa”, Res. Microbiol., vol. 162, no. 7, pp. 689-700, Sep. 2011. https://doi. org/10.1016/j.resmic.2011.06.007. K. Suntharalingam, O. Mendoza, A. Duarte, D. Mann, R. Vilar, “A platinum complex that binds non-covalently to DNA and induces cell death via a different mechanism than cisplatin”, Metallomics., vol. 5, pp. 514-523, Feb. 2013. https://doi.org/10.1039/ C3MT20252F. Y. Sun, F. Dong, D. Wang, Y. Lib, “Crystal Structure, Supramolécular Self-Assembly and Interaction with DNA of a Mixed Ligand Manganese(II) Complex”, J. Braz. Chem. Soc., vol. 22, no. 6, pp. 1089- 1095, Jun. 2011. http://dx.doi.org/10.1590/ S0103-50532011000600013. N. Sohrabi, “Binding and uv/vis spectral investigation of interaction of ni(ii) piroxicam complex with calf thymus deoxyribonucleic acid (Ct-DNA): a thermodynamic approach”, J. Pharm. Sci. & Res., vol. 7, no. 8, pp. 533-537, Aug. 2015. http://www. jpsr.pharmainfo.in/Documents/Volumes/ vol7Issue08/jpsr07081507.pdf A. Jamali, A. Tavakoli, J. Nazhad, “Analytical overview of DNA interaction with Morin and its metal complexes”, Eur. Food Res. Technol., vol. 235, no. 3, pp 367–373, Sep. 2012. https://doi.org/10.1007/ s00217-012-1778-8. A. Sigel, H. Sigel, R. Sigel, Interplay between metal ions and nucleic acids. New York: Springer, 2012. A. Kresel, J. Lisowski, “Enantioselective cleavage of supercoiled plasmid DNA catalyzed by chiral macrocyclic lanthanide(III) complexes”, J. Inorg. Biochem., vol. 107, no. 1, pp. 1–5, Feb. 2012. https://doi.org/10.1016/j. jinorgbio.2011.10.011 M. Komiyama, N. Takeda, H. Shigekawa, “Hydrolysis of DNA and RNA by lanthanide ions: mechanistic studies leading to new applications”, Chem. Commun., vol. 16, pp. 1443–1451, 1999. https://doi.org/10.1039/ A901621J. S. Tabassum, G. Sharma, F. Arjmand, “New modulated design and synthesis of chiral CuII/SnIV bimetallic potential anticancer drug entity: In vitro DNA binding and pBR322 DNA cleavage activity”, Spectrochim. Acta Part A., vol. 90, pp. 208-217, May 2012. https://doi.org/10.1016/j. saa.2012.01.020. |
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Mayor Rivera, Angélica MaríaAragón Muriel, AlbertoPolo Cerón, Dorian2019-01-31T20:39:28Z2019-01-31T20:39:28Z2018-07-04Mayor Rivera, A. M., Aragón Muriel, A. & Polo Cerón, D. (2018). Síntesis, actividad antibacteriana e interacción del ADN con complejos de inclusión entre compuestos lantánidos y β-ciclodextrina. Ciencia en Desarrollo, 9(2), 99-117. DOI: https://doi.org/10.19053/01217488.v9.n2.2018.7365. http://repositorio.uptc.edu.co/handle/001/23662462-7658http://repositorio.uptc.edu.co/handle/001/236610.19053/01217488.v9.n2.2018.73651 recurso en línea (páginas 99-117).En este trabajo se han sintetizado complejos de lantánidos a partir de los cloruros de La(III), Ce(III), Sm (III) e Yb(III) con ligandos cinamato, presentando coordinación bidentada entre el grupo carboxilo del ligando y el metal lantánido. Estos compuestos se utilizaron como huéspedes de la β-ciclodextrina con el fin de obtener nuevos complejos de inclusión mediante el método de co-precipitación, utilizando N,N-dimetilformamida como disolvente. Los productos de inclusión obtenidos fueron caracterizados mediante espectroscopía IR-ATR, Raman, UV-vis, RMN 1H y 13C, DRX, TGA, DSC, análisis elemental y complexometría con EDTA. Se realizaron pruebas de actividad antibacteriana empleando 6 cepas ATTC (S. aureus ATCC 25923, S. aureus ATCC 29213, E. coli ATCC 25922, P. aeruginosa ATCC 27853, S. Typhimurium ATCC 14028 y K. pneumoniae ATCC BAA-2146) mediante el método de microdilución con caldo Mueller-Hinton; los resultados de actividad biológica para los complejos lantánidos permitieron evidenciar el efecto sinérgico entre el catión lantánido y el ligando cinamato. Igualmente, para los complejos de inclusión se observó una disminución de la concentración mínima inhibitoria (CMI) respecto a los complejos lantánidos iniciales. Los resultados obtenidos con el ADN de timo de ternera y el ADN plasmídico pBR322 permiten proponer una interacción electrostática entre los complejos evaluados y la estructura molécular del ADN.In this work, lanthanide complexes were synthesized starting from the corresponding La (III), Ce (III), Sm (III) and Yb (III) chlorides and cinnamate ligands which present bidentate coordination between the carboxyl group of the ligand and the lanthanide metal. These compounds were used as hosts of β-cyclodextrin to obtain new inclusion complexes by a co-precipitation method using N,N-dimethylformamide as solvent. The inclusion products were characterized by IR-ATR spectroscopy, Raman, UV-vis, 1H and 13C NMR,XRD, TGA-DSC, elemental analysis and EDTA complexometry. Antibacterial activity tests were performed using six ATTC strains (S. aureus ATCC 25923, S. aureus ATCC 29213, E. coli ATCC 25922, P. aeruginosa ATCC 27853, S. Typhimurium ATCC 14028 and K. pneumoniae ATCC BAA-2146) by the microdilution method with Mueller-Hinton broth. The results of the biological activity for the lanthanide complexes showed the synergistic effect between the lanthanide cation and the cinnamate ligand. For the inclusion complexes, a decrease of the minimum inhibitory concentration (MIC) was observed with respect to the initial lanthanide complexes. The results obtained with the bovine thymus DNA and the plasmid pBR322 DNA allow to propose an electrostatic interaction between the evaluated complexes and the molécular structure of the DNA.Bibliografía y webgrafía: páginas 114-117.application/pdfspaUniversidad Pedagógica y Tecnológica de ColombiaCopyright (c) 2018 Universidad Pedagógica y Tecnológica de Colombiahttps://creativecommons.org/licenses/by-nc/4.0/info:eu-repo/semantics/openAccessAtribución-NoComercial 4.0 Internacional (CC BY-NC 4.0)http://purl.org/coar/access_right/c_abf2https://revistas.uptc.edu.co/index.php/ciencia_en_desarrollo/article/view/7365/7263Síntesis, actividad antibacteriana e interacción del ADN con complejos de inclusión entre compuestos lantánidos y β-ciclodextrinaSynthesis, antibacterial activity and interaction of DNA with lanthanide-β-cyclodextrin inclusion complexesArtículo de revistahttp://purl.org/coar/resource_type/c_6501http://purl.org/coar/resource_type/c_2df8fbb1info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionTexthttps://purl.org/redcol/resource_type/ARThttp://purl.org/coar/version/c_970fb48d4fbd8a85G. 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Acta Part A., vol. 90, pp. 208-217, May 2012. https://doi.org/10.1016/j. saa.2012.01.020.Ciencia en Desarrollo;Volumen 9, número 2 (Julio-Diciembre 2018)Actividad antibacterianaComplejos de inclusiónComplejos lantánidosInteracción con ADNORIGINALPPS_975_Sintesis_actividad_antibacteriana.pdfPPS_975_Sintesis_actividad_antibacteriana.pdfArchivo principalapplication/pdf2323658https://repositorio.uptc.edu.co/bitstreams/73ef40be-0d87-4ac6-bba7-1cbf7bf7cfd3/downloade35613df9d80cd0bc2ab12015a40a618MD51LICENSElicense.txtlicense.txttext/plain; charset=utf-814798https://repositorio.uptc.edu.co/bitstreams/fbe37d85-56d2-43af-b9a1-f9b421f70e7e/download88794144ff048353b359a3174871b0d5MD52TEXTPPS-975.pdf.txtPPS-975.pdf.txtExtracted texttext/plain63476https://repositorio.uptc.edu.co/bitstreams/a82380f7-5101-44b2-ac7f-2dbe2496350d/downloadc620ecc6f66b19887d946abd61ff8041MD53PPS_975_Sintesis_actividad_antibacteriana.pdf.txtPPS_975_Sintesis_actividad_antibacteriana.pdf.txtExtracted 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BlbCBub21icmUgZGUgbGEgcGFydGUgbyBsYXMgcGFydGVzIHF1ZSBlbCBBdXRvciBPcmlnaW5hbCB5L28gZWwgTGljZW5jaWFudGUgaHViaWVyZW4gZGVzaWduYWRvIHBhcmEgbGEgYXRyaWJ1Y2nDs24gKHYuZy4sIHVuIGluc3RpdHV0byBwYXRyb2NpbmFkb3IsIGVkaXRvcmlhbCwgcHVibGljYWNpw7NuKSBlbiBsYSBpbmZvcm1hY2nDs24gZGUgbG9zIGRlcmVjaG9zIGRlIGF1dG9yIGRlbCBMaWNlbmNpYW50ZSwgdMOpcm1pbm9zIGRlIHNlcnZpY2lvcyBvIGRlIG90cmFzIGZvcm1hcyByYXpvbmFibGVzOyBlbCB0w610dWxvIGRlIGxhIE9icmEgc2kgZXN0w6EgcHJvdmlzdG87IGVuIGxhIG1lZGlkYSBkZSBsbyByYXpvbmFibGVtZW50ZSBmYWN0aWJsZSB5LCBzaSBlc3TDoSBwcm92aXN0bywgZWwgSWRlbnRpZmljYWRvciBVbmlmb3JtZSBkZSBSZWN1cnNvcyAoVW5pZm9ybSBSZXNvdXJjZSBJZGVudGlmaWVyKSBxdWUgZWwgTGljZW5jaWFudGUgZXNwZWNpZmljYSBwYXJhIHNlciBhc29jaWFkbyBjb24gbGEgT2JyYSwgc2Fsdm8gcXVlIHRhbCBVUkkgbm8gc2UgcmVmaWVyYSBhIGxhIG5vdGEgc29icmUgbG9zIGRlcmVjaG9zIGRlIGF1dG9yIG8gYSBsYSBpbmZvcm1hY2nDs24gc29icmUgZWwgbGljZW5jaWFtaWVudG8gZGUgbGEgT2JyYTsgeSBlbiBlbCBjYXNvIGRlIHVuYSBPYnJhIERlcml2YWRhLCBhdHJpYnVpciBlbCBjcsOpZGl0byBpZGVudGlmaWNhbmRvIGVsIHVzbyBkZSBsYSBPYnJhIGVuIGxhIE9icmEgRGVyaXZhZGEgKHYuZy4sICJUcmFkdWNjacOzbiBGcmFuY2VzYSBkZSBsYSBPYnJhIGRlbCBBdXRvciBPcmlnaW5hbCwiIG8gIkd1acOzbiBDaW5lbWF0b2dyw6FmaWNvIGJhc2FkbyBlbiBsYSBPYnJhIG9yaWdpbmFsIGRlbCBBdXRvciBPcmlnaW5hbCIpLiBUYWwgY3LDqWRpdG8gcHVlZGUgc2VyIGltcGxlbWVudGFkbyBkZSBjdWFscXVpZXIgZm9ybWEgcmF6b25hYmxlOyBlbiBlbCBjYXNvLCBzaW4gZW1iYXJnbywgZGUgT2JyYXMgRGVyaXZhZGFzIHUgT2JyYXMgQ29sZWN0aXZhcywgdGFsIGNyw6lkaXRvIGFwYXJlY2Vyw6EsIGNvbW8gbcOtbmltbywgZG9uZGUgYXBhcmVjZSBlbCBjcsOpZGl0byBkZSBjdWFscXVpZXIgb3RybyBhdXRvciBjb21wYXJhYmxlIHkgZGUgdW5hIG1hbmVyYSwgYWwgbWVub3MsIHRhbiBkZXN0YWNhZGEgY29tbyBlbCBjcsOpZGl0byBkZSBvdHJvIGF1dG9yIGNvbXBhcmFibGUuCmQuCVBhcmEgZXZpdGFyIHRvZGEgY29uZnVzacOzbiwgZWwgTGljZW5jaWFudGUgYWNsYXJhIHF1ZSwgY3VhbmRvIGxhIG9icmEgZXMgdW5hIGNvbXBvc2ljacOzbiBtdXNpY2FsOgppLglSZWdhbMOtYXMgcG9yIGludGVycHJldGFjacOzbiB5IGVqZWN1Y2nDs24gYmFqbyBsaWNlbmNpYXMgZ2VuZXJhbGVzLiBFbCBMaWNlbmNpYW50ZSBzZSByZXNlcnZhIGVsIGRlcmVjaG8gZXhjbHVzaXZvIGRlIGF1dG9yaXphciBsYSBlamVjdWNpw7NuIHDDumJsaWNhIG8gbGEgZWplY3VjacOzbiBww7pibGljYSBkaWdpdGFsIGRlIGxhIG9icmEgeSBkZSByZWNvbGVjdGFyLCBzZWEgaW5kaXZpZHVhbG1lbnRlIG8gYSB0cmF2w6lzIGRlIHVuYSBzb2NpZWRhZCBkZSBnZXN0acOzbiBjb2xlY3RpdmEgZGUgZGVyZWNob3MgZGUgYXV0b3IgeSBkZXJlY2hvcyBjb25leG9zIChwb3IgZWplbXBsbywgU0FZQ08pLCBsYXMgcmVnYWzDrWFzIHBvciBsYSBlamVjdWNpw7NuIHDDumJsaWNhIG8gcG9yIGxhIGVqZWN1Y2nDs24gcMO6YmxpY2EgZGlnaXRhbCBkZSBsYSBvYnJhIChwb3IgZWplbXBsbyBXZWJjYXN0KSBsaWNlbmNpYWRhIGJham8gbGljZW5jaWFzIGdlbmVyYWxlcywgc2kgbGEgaW50ZXJwcmV0YWNpw7NuIG8gZWplY3VjacOzbiBkZSBsYSBvYnJhIGVzdMOhIHByaW1vcmRpYWxtZW50ZSBvcmllbnRhZGEgcG9yIG8gZGlyaWdpZGEgYSBsYSBvYnRlbmNpw7NuIGRlIHVuYSB2ZW50YWphIGNvbWVyY2lhbCBvIHVuYSBjb21wZW5zYWNpw7NuIG1vbmV0YXJpYSBwcml2YWRhLgppaS4JUmVnYWzDrWFzIHBvciBGb25vZ3JhbWFzLiBFbCBMaWNlbmNpYW50ZSBzZSByZXNlcnZhIGVsIGRlcmVjaG8gZXhjbHVzaXZvIGRlIHJlY29sZWN0YXIsIGluZGl2aWR1YWxtZW50ZSBvIGEgdHJhdsOpcyBkZSB1bmEgc29jaWVkYWQgZGUgZ2VzdGnDs24gY29sZWN0aXZhIGRlIGRlcmVjaG9zIGRlIGF1dG9yIHkgZGVyZWNob3MgY29uZXhvcyAocG9yIGVqZW1wbG8sIGxvcyBjb25zYWdyYWRvcyBwb3IgbGEgU0FZQ08pLCB1bmEgYWdlbmNpYSBkZSBkZXJlY2hvcyBtdXNpY2FsZXMgbyBhbGfDum4gYWdlbnRlIGRlc2lnbmFkbywgbGFzIHJlZ2Fsw61hcyBwb3IgY3VhbHF1aWVyIGZvbm9ncmFtYSBxdWUgVXN0ZWQgY3JlZSBhIHBhcnRpciBkZSBsYSBvYnJhICjigJx2ZXJzacOzbiBjb3ZlcuKAnSkgeSBkaXN0cmlidXlhLCBlbiBsb3MgdMOpcm1pbm9zIGRlbCByw6lnaW1lbiBkZSBkZXJlY2hvcyBkZSBhdXRvciwgc2kgbGEgY3JlYWNpw7NuIG8gZGlzdHJpYnVjacOzbiBkZSBlc2EgdmVyc2nDs24gY292ZXIgZXN0w6EgcHJpbW9yZGlhbG1lbnRlIGRlc3RpbmFkYSBvIGRpcmlnaWRhIGEgb2J0ZW5lciB1bmEgdmVudGFqYSBjb21lcmNpYWwgbyB1bmEgY29tcGVuc2FjacOzbiBtb25ldGFyaWEgcHJpdmFkYS4KZS4JR2VzdGnDs24gZGUgRGVyZWNob3MgZGUgQXV0b3Igc29icmUgSW50ZXJwcmV0YWNpb25lcyB5IEVqZWN1Y2lvbmVzIERpZ2l0YWxlcyAoV2ViQ2FzdGluZykuIFBhcmEgZXZpdGFyIHRvZGEgY29uZnVzacOzbiwgZWwgTGljZW5jaWFudGUgYWNsYXJhIHF1ZSwgY3VhbmRvIGxhIG9icmEgc2VhIHVuIGZvbm9ncmFtYSwgZWwgTGljZW5jaWFudGUgc2UgcmVzZXJ2YSBlbCBkZXJlY2hvIGV4Y2x1c2l2byBkZSBhdXRvcml6YXIgbGEgZWplY3VjacOzbiBww7pibGljYSBkaWdpdGFsIGRlIGxhIG9icmEgKHBvciBlamVtcGxvLCB3ZWJjYXN0KSB5IGRlIHJlY29sZWN0YXIsIGluZGl2aWR1YWxtZW50ZSBvIGEgdHJhdsOpcyBkZSB1bmEgc29jaWVkYWQgZGUgZ2VzdGnDs24gY29sZWN0aXZhIGRlIGRlcmVjaG9zIGRlIGF1dG9yIHkgZGVyZWNob3MgY29uZXhvcyAocG9yIGVqZW1wbG8sIEFDSU5QUk8pLCBsYXMgcmVnYWzDrWFzIHBvciBsYSBlamVjdWNpw7NuIHDDumJsaWNhIGRpZ2l0YWwgZGUgbGEgb2JyYSAocG9yIGVqZW1wbG8sIHdlYmNhc3QpLCBzdWpldGEgYSBsYXMgZGlzcG9zaWNpb25lcyBhcGxpY2FibGVzIGRlbCByw6lnaW1lbiBkZSBEZXJlY2hvIGRlIEF1dG9yLCBzaSBlc3RhIGVqZWN1Y2nDs24gcMO6YmxpY2EgZGlnaXRhbCBlc3TDoSBwcmltb3JkaWFsbWVudGUgZGlyaWdpZGEgYSBvYnRlbmVyIHVuYSB2ZW50YWphIGNvbWVyY2lhbCBvIHVuYSBjb21wZW5zYWNpw7NuIG1vbmV0YXJpYSBwcml2YWRhLgo1LiBSZXByZXNlbnRhY2lvbmVzLCBHYXJhbnTDrWFzIHkgTGltaXRhY2lvbmVzIGRlIFJlc3BvbnNhYmlsaWRhZC4KQSBNRU5PUyBRVUUgTEFTIFBBUlRFUyBMTyBBQ09SREFSQU4gREUgT1RSQSBGT1JNQSBQT1IgRVNDUklUTywgRUwgTElDRU5DSUFOVEUgT0ZSRUNFIExBIE9CUkEgKEVOIEVMIEVTVEFETyBFTiBFTCBRVUUgU0UgRU5DVUVOVFJBKSDigJxUQUwgQ1VBTOKAnSwgU0lOIEJSSU5EQVIgR0FSQU5Uw41BUyBERSBDTEFTRSBBTEdVTkEgUkVTUEVDVE8gREUgTEEgT0JSQSwgWUEgU0VBIEVYUFJFU0EsIElNUEzDjUNJVEEsIExFR0FMIE8gQ1VBTFFVSUVSQSBPVFJBLCBJTkNMVVlFTkRPLCBTSU4gTElNSVRBUlNFIEEgRUxMQVMsIEdBUkFOVMONQVMgREUgVElUVUxBUklEQUQsIENPTUVSQ0lBQklMSURBRCwgQURBUFRBQklMSURBRCBPIEFERUNVQUNJw5NOIEEgUFJPUMOTU0lUTyBERVRFUk1JTkFETywgQVVTRU5DSUEgREUgSU5GUkFDQ0nDk04sIERFIEFVU0VOQ0lBIERFIERFRkVDVE9TIExBVEVOVEVTIE8gREUgT1RSTyBUSVBPLCBPIExBIFBSRVNFTkNJQSBPIEFVU0VOQ0lBIERFIEVSUk9SRVMsIFNFQU4gTyBOTyBERVNDVUJSSUJMRVMgKFBVRURBTiBPIE5PIFNFUiBFU1RPUyBERVNDVUJJRVJUT1MpLiBBTEdVTkFTIEpVUklTRElDQ0lPTkVTIE5PIFBFUk1JVEVOIExBIEVYQ0xVU0nDk04gREUgR0FSQU5Uw41BUyBJTVBMw41DSVRBUywgRU4gQ1VZTyBDQVNPIEVTVEEgRVhDTFVTScOTTiBQVUVERSBOTyBBUExJQ0FSU0UgQSBVU1RFRC4KNi4gTGltaXRhY2nDs24gZGUgcmVzcG9uc2FiaWxpZGFkLgpBIE1FTk9TIFFVRSBMTyBFWElKQSBFWFBSRVNBTUVOVEUgTEEgTEVZIEFQTElDQUJMRSwgRUwgTElDRU5DSUFOVEUgTk8gU0VSw4EgUkVTUE9OU0FCTEUgQU5URSBVU1RFRCBQT1IgREHDkU8gQUxHVU5PLCBTRUEgUE9SIFJFU1BPTlNBQklMSURBRCBFWFRSQUNPTlRSQUNUVUFMLCBQUkVDT05UUkFDVFVBTCBPIENPTlRSQUNUVUFMLCBPQkpFVElWQSBPIFNVQkpFVElWQSwgU0UgVFJBVEUgREUgREHDkU9TIE1PUkFMRVMgTyBQQVRSSU1PTklBTEVTLCBESVJFQ1RPUyBPIElORElSRUNUT1MsIFBSRVZJU1RPUyBPIElNUFJFVklTVE9TIFBST0RVQ0lET1MgUE9SIEVMIFVTTyBERSBFU1RBIExJQ0VOQ0lBIE8gREUgTEEgT0JSQSwgQVVOIENVQU5ETyBFTCBMSUNFTkNJQU5URSBIQVlBIFNJRE8gQURWRVJUSURPIERFIExBIFBPU0lCSUxJREFEIERFIERJQ0hPUyBEQcORT1MuIEFMR1VOQVMgTEVZRVMgTk8gUEVSTUlURU4gTEEgRVhDTFVTScOTTiBERSBDSUVSVEEgUkVTUE9OU0FCSUxJREFELCBFTiBDVVlPIENBU08gRVNUQSBFWENMVVNJw5NOIFBVRURFIE5PIEFQTElDQVJTRSBBIFVTVEVELgo3LiBUw6lybWluby4KYS4JRXN0YSBMaWNlbmNpYSB5IGxvcyBkZXJlY2hvcyBvdG9yZ2Fkb3MgZW4gdmlydHVkIGRlIGVsbGEgdGVybWluYXLDoW4gYXV0b23DoXRpY2FtZW50ZSBzaSBVc3RlZCBpbmZyaW5nZSBhbGd1bmEgY29uZGljacOzbiBlc3RhYmxlY2lkYSBlbiBlbGxhLiBTaW4gZW1iYXJnbywgbG9zIGluZGl2aWR1b3MgbyBlbnRpZGFkZXMgcXVlIGhhbiByZWNpYmlkbyBPYnJhcyBEZXJpdmFkYXMgbyBDb2xlY3RpdmFzIGRlIFVzdGVkIGRlIGNvbmZvcm1pZGFkIGNvbiBlc3RhIExpY2VuY2lhLCBubyB2ZXLDoW4gdGVybWluYWRhcyBzdXMgbGljZW5jaWFzLCBzaWVtcHJlIHF1ZSBlc3RvcyBpbmRpdmlkdW9zIG8gZW50aWRhZGVzIHNpZ2FuIGN1bXBsaWVuZG8gw61udGVncmFtZW50ZSBsYXMgY29uZGljaW9uZXMgZGUgZXN0YXMgbGljZW5jaWFzLiBMYXMgU2VjY2lvbmVzIDEsIDIsIDUsIDYsIDcsIHkgOCBzdWJzaXN0aXLDoW4gYSBjdWFscXVpZXIgdGVybWluYWNpw7NuIGRlIGVzdGEgTGljZW5jaWEuCmIuCVN1amV0YSBhIGxhcyBjb25kaWNpb25lcyB5IHTDqXJtaW5vcyBhbnRlcmlvcmVzLCBsYSBsaWNlbmNpYSBvdG9yZ2FkYSBhcXXDrSBlcyBwZXJwZXR1YSAoZHVyYW50ZSBlbCBwZXLDrW9kbyBkZSB2aWdlbmNpYSBkZSBsb3MgZGVyZWNob3MgZGUgYXV0b3IgZGUgbGEgb2JyYSkuIE5vIG9ic3RhbnRlIGxvIGFudGVyaW9yLCBlbCBMaWNlbmNpYW50ZSBzZSByZXNlcnZhIGVsIGRlcmVjaG8gYSBwdWJsaWNhciB5L28gZXN0cmVuYXIgbGEgT2JyYSBiYWpvIGNvbmRpY2lvbmVzIGRlIGxpY2VuY2lhIGRpZmVyZW50ZXMgbyBhIGRlamFyIGRlIGRpc3RyaWJ1aXJsYSBlbiBsb3MgdMOpcm1pbm9zIGRlIGVzdGEgTGljZW5jaWEgZW4gY3VhbHF1aWVyIG1vbWVudG87IGVuIGVsIGVudGVuZGlkbywgc2luIGVtYmFyZ28sIHF1ZSBlc2EgZWxlY2Npw7NuIG5vIHNlcnZpcsOhIHBhcmEgcmV2b2NhciBlc3RhIGxpY2VuY2lhIG8gcXVlIGRlYmEgc2VyIG90b3JnYWRhICwgYmFqbyBsb3MgdMOpcm1pbm9zIGRlIGVzdGEgbGljZW5jaWEpLCB5IGVzdGEgbGljZW5jaWEgY29udGludWFyw6EgZW4gcGxlbm8gdmlnb3IgeSBlZmVjdG8gYSBtZW5vcyBxdWUgc2VhIHRlcm1pbmFkYSBjb21vIHNlIGV4cHJlc2EgYXRyw6FzLiBMYSBMaWNlbmNpYSByZXZvY2FkYSBjb250aW51YXLDoSBzaWVuZG8gcGxlbmFtZW50ZSB2aWdlbnRlIHkgZWZlY3RpdmEgc2kgbm8gc2UgbGUgZGEgdMOpcm1pbm8gZW4gbGFzIGNvbmRpY2lvbmVzIGluZGljYWRhcyBhbnRlcmlvcm1lbnRlLgo4LiBWYXJpb3MuCmEuCUNhZGEgdmV6IHF1ZSBVc3RlZCBkaXN0cmlidXlhIG8gcG9uZ2EgYSBkaXNwb3NpY2nDs24gcMO6YmxpY2EgbGEgT2JyYSBvIHVuYSBPYnJhIENvbGVjdGl2YSwgZWwgTGljZW5jaWFudGUgb2ZyZWNlcsOhIGFsIGRlc3RpbmF0YXJpbyB1bmEgbGljZW5jaWEgZW4gbG9zIG1pc21vcyB0w6lybWlub3MgeSBjb25kaWNpb25lcyBxdWUgbGEgbGljZW5jaWEgb3RvcmdhZGEgYSBVc3RlZCBiYWpvIGVzdGEgTGljZW5jaWEuCmIuCVNpIGFsZ3VuYSBkaXNwb3NpY2nDs24gZGUgZXN0YSBMaWNlbmNpYSByZXN1bHRhIGludmFsaWRhZGEgbyBubyBleGlnaWJsZSwgc2Vnw7puIGxhIGxlZ2lzbGFjacOzbiB2aWdlbnRlLCBlc3RvIG5vIGFmZWN0YXLDoSBuaSBsYSB2YWxpZGV6IG5pIGxhIGFwbGljYWJpbGlkYWQgZGVsIHJlc3RvIGRlIGNvbmRpY2lvbmVzIGRlIGVzdGEgTGljZW5jaWEgeSwgc2luIGFjY2nDs24gYWRpY2lvbmFsIHBvciBwYXJ0ZSBkZSBsb3Mgc3VqZXRvcyBkZSBlc3RlIGFjdWVyZG8sIGFxdcOpbGxhIHNlIGVudGVuZGVyw6EgcmVmb3JtYWRhIGxvIG3DrW5pbW8gbmVjZXNhcmlvIHBhcmEgaGFjZXIgcXVlIGRpY2hhIGRpc3Bvc2ljacOzbiBzZWEgdsOhbGlkYSB5IGV4aWdpYmxlLgpjLglOaW5nw7puIHTDqXJtaW5vIG8gZGlzcG9zaWNpw7NuIGRlIGVzdGEgTGljZW5jaWEgc2UgZXN0aW1hcsOhIHJlbnVuY2lhZGEgeSBuaW5ndW5hIHZpb2xhY2nDs24gZGUgZWxsYSBzZXLDoSBjb25zZW50aWRhIGEgbWVub3MgcXVlIGVzYSByZW51bmNpYSBvIGNvbnNlbnRpbWllbnRvIHNlYSBvdG9yZ2FkbyBwb3IgZXNjcml0byB5IGZpcm1hZG8gcG9yIGxhIHBhcnRlIHF1ZSByZW51bmNpZSBvIGNvbnNpZW50YS4KZC4JRXN0YSBMaWNlbmNpYSByZWZsZWphIGVsIGFjdWVyZG8gcGxlbm8gZW50cmUgbGFzIHBhcnRlcyByZXNwZWN0byBhIGxhIE9icmEgYXF1w60gbGljZW5jaWFkYS4gTm8gaGF5IGFycmVnbG9zLCBhY3VlcmRvcyBvIGRlY2xhcmFjaW9uZXMgcmVzcGVjdG8gYSBsYSBPYnJhIHF1ZSBubyBlc3TDqW4gZXNwZWNpZmljYWRvcyBlbiBlc3RlIGRvY3VtZW50by4gRWwgTGljZW5jaWFudGUgbm8gc2UgdmVyw6EgbGltaXRhZG8gcG9yIG5pbmd1bmEgZGlzcG9zaWNpw7NuIGFkaWNpb25hbCBxdWUgcHVlZGEgc3VyZ2lyIGVuIGFsZ3VuYSBjb211bmljYWNpw7NuIGVtYW5hZGEgZGUgVXN0ZWQuIEVzdGEgTGljZW5jaWEgbm8gcHVlZGUgc2VyIG1vZGlmaWNhZGEgc2luIGVsIGNvbnNlbnRpbWllbnRvIG11dHVvIHBvciBlc2NyaXRvIGRlbCBMaWNlbmNpYW50ZSB5IFVzdGVkLgo= 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