Industrial-Scale bioprocess simulation of polyphenol production using superpro designer
Polyphenols are molecules with antioxidant potential for several diseases. In this research, an analysis of polyphenols production costs from Theobroma cacao L suspension cell culture was evaluated. The latter proposing different scenarios based on a large-scale plant production using the SuperPro D...
- Autores:
-
Niño, Lilibeth
Gelves, German
Hernandez, Shannon
- Tipo de recurso:
- Article of journal
- Fecha de publicación:
- 2021
- Institución:
- UNIVERSIDAD FRANCISCO DE PAULA SANTANDER
- Repositorio:
- Repositorio Digital UFPS
- Idioma:
- eng
- OAI Identifier:
- oai:repositorio.ufps.edu.co:ufps/300
- Acceso en línea:
- http://repositorio.ufps.edu.co/handle/ufps/300
- Palabra clave:
- Bioprocess simulation
Elicitation
Gasification
Phenolic compounds
Plant design
Software
- Rights
- openAccess
- License
- CC BY-NC-ND
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Industrial-Scale bioprocess simulation of polyphenol production using superpro designer |
| title |
Industrial-Scale bioprocess simulation of polyphenol production using superpro designer |
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Industrial-Scale bioprocess simulation of polyphenol production using superpro designer Bioprocess simulation Elicitation Gasification Phenolic compounds Plant design Software |
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Industrial-Scale bioprocess simulation of polyphenol production using superpro designer |
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Industrial-Scale bioprocess simulation of polyphenol production using superpro designer |
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Industrial-Scale bioprocess simulation of polyphenol production using superpro designer |
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Industrial-Scale bioprocess simulation of polyphenol production using superpro designer |
| title_sort |
Industrial-Scale bioprocess simulation of polyphenol production using superpro designer |
| dc.creator.fl_str_mv |
Niño, Lilibeth Gelves, German Hernandez, Shannon |
| dc.contributor.author.none.fl_str_mv |
Niño, Lilibeth Gelves, German Hernandez, Shannon |
| dc.subject.proposal.eng.fl_str_mv |
Bioprocess simulation Elicitation Gasification Phenolic compounds Plant design Software |
| topic |
Bioprocess simulation Elicitation Gasification Phenolic compounds Plant design Software |
| description |
Polyphenols are molecules with antioxidant potential for several diseases. In this research, an analysis of polyphenols production costs from Theobroma cacao L suspension cell culture was evaluated. The latter proposing different scenarios based on a large-scale plant production using the SuperPro Designer software. Two strategies for bioprocess improvement were proposed based on information from a traditional suspension cell culture (Strategy I). These improvements are firstly based on adding elicitors (Strategy II) for increasing polyphenol production and secondly, energetic use of cane bagasse and rice bran (Strategy III) by adding a gasifier. Results showed that the percentage of losses decreases from 19 % to only 5.8 % applying a recirculation system in losses lines product regarding Strategy II. Also, adding Methyl Jasmonate (MJ) elicitor increased the Y p / s yield up to 0.08 kg polyphenols/kg glucose. Gasification proposed in Strategy III achieved supplying 37 % of energy requirements using only 1.14 % of bagasse. One essential finding refers to the decreased cost of producing a 100 mg tablet formulated at 50 % of the active substance. Therefore, the latter resulted in 0.23 USD / tablet: promising data compared to 1.0-2.0 USD / tablet corresponding to the average value in the market. Thus, this research demonstrates that the increase of polyphenols by adding elicitors positively influences the operating costs. |
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2021 |
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2021-10-13T15:38:59Z |
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2021-10-13T15:38:59Z |
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2021-06 |
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Artículo de revista |
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http://purl.org/coar/resource_type/c_2df8fbb1 |
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http://purl.org/coar/version/c_970fb48d4fbd8a85 |
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Text |
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eng |
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eng |
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Journal of Engineering Science and Technology ISSN: 1823-4690, 2021 vol:16 fasc: 3 págs: 2100 - 2113 |
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Vol. 16, No. 3 (2021) |
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2113 |
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3 (2021) |
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2100 |
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16 |
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Journal of Engineering Science and Technology |
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CC BY-NC-ND |
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13 páginas |
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Journal of Engineering Science and Technology |
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Malasia |
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Journal of Engineering Science and Technology |
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Niño, Lilibeth5bf9116c56f582543d90ee6339f46664Gelves, Germanebd05026ba6120b1b66ca5e1b1ce8875Hernandez, Shannon9fabca7894d860e9d345a6c49b80c5294002021-10-13T15:38:59Z2021-10-13T15:38:59Z2021-06http://repositorio.ufps.edu.co/handle/ufps/300Polyphenols are molecules with antioxidant potential for several diseases. In this research, an analysis of polyphenols production costs from Theobroma cacao L suspension cell culture was evaluated. The latter proposing different scenarios based on a large-scale plant production using the SuperPro Designer software. Two strategies for bioprocess improvement were proposed based on information from a traditional suspension cell culture (Strategy I). These improvements are firstly based on adding elicitors (Strategy II) for increasing polyphenol production and secondly, energetic use of cane bagasse and rice bran (Strategy III) by adding a gasifier. Results showed that the percentage of losses decreases from 19 % to only 5.8 % applying a recirculation system in losses lines product regarding Strategy II. Also, adding Methyl Jasmonate (MJ) elicitor increased the Y p / s yield up to 0.08 kg polyphenols/kg glucose. Gasification proposed in Strategy III achieved supplying 37 % of energy requirements using only 1.14 % of bagasse. One essential finding refers to the decreased cost of producing a 100 mg tablet formulated at 50 % of the active substance. Therefore, the latter resulted in 0.23 USD / tablet: promising data compared to 1.0-2.0 USD / tablet corresponding to the average value in the market. Thus, this research demonstrates that the increase of polyphenols by adding elicitors positively influences the operating costs.13 páginasapplication/pdfengJournal of Engineering Science and TechnologyMalasiaJournal of Engineering Science and Technology ISSN: 1823-4690, 2021 vol:16 fasc: 3 págs: 2100 - 2113Vol. 16, No. 3 (2021)21133 (2021)210016Journal of Engineering Science and TechnologyCC BY-NC-NDhttps://creativecommons.org/licenses/by-nc-nd/4.0/info:eu-repo/semantics/openAccesshttp://purl.org/coar/access_right/c_abf2https://jestec.taylors.edu.my/Vol%2016%20issue%203%20June%202021/16_3_18.pdfIndustrial-Scale bioprocess simulation of polyphenol production using superpro designerArtículo de revistahttp://purl.org/coar/resource_type/c_6501http://purl.org/coar/resource_type/c_2df8fbb1Textinfo:eu-repo/semantics/articlehttp://purl.org/redcol/resource_type/ARTinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/version/c_970fb48d4fbd8a85Bioprocess simulationElicitationGasificationPhenolic compoundsPlant designSoftwareSingh, S.; Pandey, S.S.; Shanker, K.; and Kalra, A. (2020). Endophytes enhance the production of root alkaloids ajmalicine and serpentine by modulating the terpenoid indole alkaloid pathway in Catharanthus roseus roots. Journal of Applied Microbiology, 128(4), 1128-1142.Rafińska, K.; Pomastowski, P.; Wrona, O.; Górecki, R.; and Buszewski, B. (2017). Medicago sativa as a source of secondary metabolites for agriculture and pharmaceutical industry. Phytochemistry Letters, 20, 520-539.Rojas-Padilla, C.; and Vásquez-Villalobos, V. (2016). Phenolic compounds with antioxidant capacity of the native Andean potato (Solanum tuberosum L.) Huagalina variety in La Libertad-Peru. Scientia Agropecuaria, 7(3), 333-340.Nova-López, C.J.; Muñoz-Pérez, J.M.; Granger-Serrano, L.F.; Arias-Zabala, M.E.; and Arango-Isaza, R.E. (2017). Expression of recombinant Cry 1Ac protein in potato plant cell suspension culture: Establishment of culture and optimization of biomass and protein production by nitrogen supply. DYNA, 84(201), 34-41.Ljekočević, M.; Jadranin, M.; Stanković, J.; Popović, B.; Nikićević, N.; Petrović, A.; and Tešević, V. (2019). Phenolic composition and DPPH radical scavenging activity of plum wine produced from three plum cultivars. Journal of the Serbian Chemical Society, 84(2), 141-151.Saini, S.S.; Teotia, D.; Gaid, M.; Thakur, A.; Beerhues, L.; and Sircar, D. (2017). Benzaldehyde dehydrogenase-driven phytoalexin biosynthesis in elicitor-treated Pyrus pyrifolia cell cultures. Journal of Plant Physiology, 215, 154-162.Flórez, C.; Rojas, L.F.; Londoño, J.; and Atehortúa, L. (2011). Efecto del metil jasmonato sobre la producción de polifenoles totales en cultivos celulares de Theobroma cacao. XIV National Congress of Biotechnology and Bioengineering, Juriquilla, Queretaro, 14, 53Med, N.C.; and Rodríguez, M.D. (2019). Polifenoles y vitaminas en la protección del daño genético inducido por metales con potencial cancerígeno. Nutricion Clinica en Medicina, 13(3),129-139García, A.Á.; and Carril, E.P. (2011). Metabolismo secundario de plantas. REDUCA (biology), 2(3) 119-145Ploeg, M.; Aben, K.K.H.; and Kiemeney, L.A. (2009). The present and future burden of urinary bladder cancer in the world. World Journal of Urology, 27(3), 289-293.Zabala, M.A.; Velásquez, M.J.A.; Cardona, A.M.A.; Flórez, J.M.R.; and Vallejo, C.M. (2009). Estrategias para incrementar la producción de metabolitos secundarios en cultivos de células vegetales. Revista Facultad Nacional de Agronomía-Medellín, 62(1) 4881-4895.Dmitrović , S.; Škoric, M.; Boljević, J.; Aničić, N.; Božić, D.; Mišić, D.; and Opsenica, D. (2016). Elicitation effects of a synthetic 1, 2, 4, 5-tetraoxane and a 2, 5-diphenylthiophene in shoot cultures of two nepeta species. Journal of the Serbian Chemical Society, 81(9), 999-1012Jiao, J.; Gai, Q.Y.; Wang, W.; Luo, M.; Zu, Y.G.; Fu, Y.J.; and Ma, W. (2016). Enhanced astragaloside production and transcriptional responses of biosynthetic genes in astragalus membranaceus hairy root cultures by elicitation with methyl jasmonate. Biochemical engineering journal, 105, 339-346.Campos-Ramirez, L.; Pérez-Sánchez, A.; Benítez-Legra, A.; and Benítez, I. (2020). Estudio técnico-económico de dos tecnologías de producción de biodiesel a partir de aceite de soya empleando el simulador superpro designer. TecnoLógicas, 23(48), 119-141.Villamizar-Jaimes, A.R.V.; and López-Giraldo, L.J. (2017). Cocoa husk source of polyphenol and fiber: simulation of a pilot plant for their extraction. Respuestas, 22(1), 75-83.Rouf, S.A.; Douglas, P.L.; Moo-Young, M.; and Scharer, J.M. (2001). Computer simulation for large scale bioprocess design. Biochemical Engineering Journal, 8(3), 229-234.Ontiveros, G.A. (2015). Evaluación de tratamientos para aguas residuales contaminadas con fármacos y productos de higiene personal. Universidad Nacional del Litoral, 213-217.Vidal, H. R. (2017). Regulación de la producción de taxanos y otros metabolitos secundarios en cultivos de células y órganos vegetales. Doctoral dissertation, Universitat de Barcelona, 47-62.Gallego, A.M.; Rojas, L.F.; Rodriguez, H.A.; Mora, C.; Atehortúa, L.; Urrea, A.I.; Guiltinan, M.J.; Maximova, S.N.; Gaquerel, E.; Zuluaga, M. and Pabón, N. (2019). Metabolomic profile of cacao cell suspensions growing in blue light / dark conditions with potential in food biotechnology. Plant Cell, Tissue and Organ Culture, 139, 275-294.Wu, C.H.; Tang, J.; Jin, Z.X.; Wang, M.; Liu, Z.Q.; Huang, T.; and Lian, M.L. (2018). Optimizing co-culture conditions of adventitious roots of echinacea pallida and echinacea purpurea in air-lift bioreactor systems. Biochemical engineering journal, 132, 206-216.Garcia, C.; Marelli, J.P.; Motamayor, J.C.; and Villela, C. (2018). Somatic Embryogenesis in Theobroma cacao L. Plant Cell Culture Protocols. Humana Press (4th ed.), New York: Loyola-Vargas V, Ochoa-Alejo N,1815, 227-245.Villafuerte, L. (2011). Los excipientes y su funcionalidad en productos farmacéuticos sólidos. Revista mexicana de ciencias farmacéuticas, 42(1), 18-36.Petrides, D.; Carmichael, D.; Charles, C.; and Koulouris, A. (2014). Biopharmaceutical Process Optimization with Simulation and Scheduling Tools. Bioengineering 1, 154-187.. Nazario, O.; Ordoñez, E.; Mandujano, Y.; and Arévalo, J. (2018). Polifenoles totales, antocianinas, capacidad antioxidante de granos secos y análisis sensorial del licor de cacao (Theobroma cacao L.) criollo y siete clonesInvestigación y Amazonía, 3(1), 51-59.ORIGINALINDUSTRIAL-SCALE BIOPROCESS SIMULATION OF POLYPHENOL PRODUCTION USING SUPERPRO DESIGNER.pdfINDUSTRIAL-SCALE BIOPROCESS SIMULATION OF POLYPHENOL PRODUCTION USING SUPERPRO DESIGNER.pdfapplication/pdf444505https://repositorio.ufps.edu.co/bitstream/ufps/300/1/INDUSTRIAL-SCALE%20BIOPROCESS%20SIMULATION%20OF%20POLYPHENOL%20PRODUCTION%20USING%20SUPERPRO%20DESIGNER.pdf63709f9ca3893883acbe922898b867dbMD51open accessLICENSElicense.txtlicense.txttext/plain; charset=utf-814828https://repositorio.ufps.edu.co/bitstream/ufps/300/2/license.txt2f9959eaf5b71fae44bbf9ec84150c7aMD52open accessTEXTINDUSTRIAL-SCALE BIOPROCESS SIMULATION OF POLYPHENOL PRODUCTION USING SUPERPRO DESIGNER.pdf.txtINDUSTRIAL-SCALE BIOPROCESS SIMULATION OF POLYPHENOL PRODUCTION USING SUPERPRO DESIGNER.pdf.txtExtracted 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 incorporada en las Obras Colectivas.

b.	Distribuir copias o fonogramas de las Obras, exhibirlas públicamente, ejecutarlas públicamente y/o ponerlas a disposición pública, incluyéndolas como incorporadas en Obras Colectivas, según corresponda.

c.	Distribuir copias de las Obras Derivadas que se generen, exhibirlas públicamente, ejecutarlas públicamente y/o ponerlas a disposición pública.
Los derechos mencionados anteriormente pueden ser ejercidos en todos los medios y formatos, actualmente conocidos o que se inventen en el futuro. Los derechos antes mencionados incluyen el derecho a realizar dichas modificaciones en la medida que sean técnicamente necesarias para ejercer los derechos en otro medio o formatos, pero de otra manera usted no está autorizado para realizar obras derivadas. Todos los derechos no otorgados expresamente por el Licenciante quedan por este medio reservados, incluyendo pero sin limitarse a aquellos que se mencionan en las secciones 4(d) y 4(e).

4. Restricciones.
La licencia otorgada en la anterior Sección 3 está expresamente sujeta y limitada por las siguientes restricciones:

a.	Usted puede distribuir, exhibir públicamente, ejecutar públicamente, o poner a disposición pública la Obra sólo bajo las condiciones de esta Licencia, y Usted debe incluir una copia de esta licencia o del Identificador Universal de Recursos de la misma con cada copia de la Obra que distribuya, exhiba públicamente, ejecute públicamente o ponga a disposición pública. No es posible ofrecer o imponer ninguna condición sobre la Obra que altere o limite las condiciones de esta Licencia o el ejercicio de los derechos de los destinatarios otorgados en este documento. No es posible sublicenciar la Obra. Usted debe mantener intactos todos los avisos que hagan referencia a esta Licencia y a la cláusula de limitación de garantías. Usted no puede distribuir, exhibir públicamente, ejecutar públicamente, o poner a disposición pública la Obra con alguna medida tecnológica que controle el acceso o la utilización de ella de una forma que sea inconsistente con las condiciones de esta Licencia. Lo anterior se aplica a la Obra incorporada a una Obra Colectiva, pero esto no exige que la Obra Colectiva aparte de la obra misma quede sujeta a las condiciones de esta Licencia. Si Usted crea una Obra Colectiva, previo aviso de cualquier Licenciante debe, en la medida de lo posible, eliminar de la Obra Colectiva cualquier referencia a dicho Licenciante o al Autor Original, según lo solicitado por el Licenciante y conforme lo exige la cláusula 4(c).

b.	Usted no puede ejercer ninguno de los derechos que le han sido otorgados en la Sección 3 precedente de modo que estén principalmente destinados o directamente dirigidos a conseguir un provecho comercial o una compensación monetaria privada. El intercambio de la Obra por otras obras protegidas por derechos de autor, ya sea a través de un sistema para compartir archivos digitales (digital file-sharing) o de cualquier otra manera no será considerado como estar destinado principalmente o dirigido directamente a conseguir un provecho comercial o una compensación monetaria privada, siempre que no se realice un pago mediante una compensación monetaria en relación con el intercambio de obras protegidas por el derecho de autor.

c.	Si usted distribuye, exhibe públicamente, ejecuta públicamente o ejecuta públicamente en forma digital la Obra o cualquier Obra Derivada u Obra Colectiva, Usted debe mantener intacta toda la información de derecho de autor de la Obra y proporcionar, de forma razonable según el medio o manera que Usted esté utilizando: (i) el nombre del Autor Original si está provisto (o seudónimo, si fuere aplicable), y/o (ii) el nombre de la parte o las partes que el Autor Original y/o el Licenciante hubieren designado para la atribución (v.g., un instituto patrocinador, editorial, publicación) en la información de los derechos de autor del Licenciante, términos de servicios o de otras formas razonables; el título de la Obra si está provisto; en la medida de lo razonablemente factible y, si está provisto, el Identificador Uniforme de Recursos (Uniform Resource Identifier) que el Licenciante especifica para ser asociado con la Obra, salvo que tal URI no se refiera a la nota sobre los derechos de autor o a la información sobre el licenciamiento de la Obra; y en el caso de una Obra Derivada, atribuir el crédito identificando el uso de la Obra en la Obra Derivada (v.g., "Traducción Francesa de la Obra del Autor Original," o "Guión Cinematográfico basado en la Obra original del Autor Original"). Tal crédito puede ser implementado de cualquier forma razonable; en el caso, sin embargo, de Obras Derivadas u Obras Colectivas, tal crédito aparecerá, como mínimo, donde aparece el crédito de cualquier otro autor comparable y de una manera, al menos, tan destacada como el crédito de otro autor comparable.

d.	Para evitar toda confusión, el Licenciante aclara que, cuando la obra es una composición musical:

i.	Regalías por interpretación y ejecución bajo licencias generales. El Licenciante se reserva el derecho exclusivo de autorizar la ejecución pública o la ejecución pública digital de la obra y de recolectar, sea individualmente o a través de una sociedad de gestión colectiva de derechos de autor y derechos conexos (por ejemplo, SAYCO), las regalías por la ejecución pública o por la ejecución pública digital de la obra (por ejemplo Webcast) licenciada bajo licencias generales, si la interpretación o ejecución de la obra está primordialmente orientada por o dirigida a la obtención de una ventaja comercial o una compensación monetaria privada.

ii.	Regalías por Fonogramas. El Licenciante se reserva el derecho exclusivo de recolectar, individualmente o a través de una sociedad de gestión colectiva de derechos de autor y derechos conexos (por ejemplo, los consagrados por la SAYCO), una agencia de derechos musicales o algún agente designado, las regalías por cualquier fonograma que Usted cree a partir de la obra (“versión cover”) y distribuya, en los términos del régimen de derechos de autor, si la creación o distribución de esa versión cover está primordialmente destinada o dirigida a obtener una ventaja comercial o una compensación monetaria privada.

e.	Gestión de Derechos de Autor sobre Interpretaciones y Ejecuciones Digitales (WebCasting). Para evitar toda confusión, el Licenciante aclara que, cuando la obra sea un fonograma, el Licenciante se reserva el derecho exclusivo de autorizar la ejecución pública digital de la obra (por ejemplo, webcast) y de recolectar, individualmente o a través de una sociedad de gestión colectiva de derechos de autor y derechos conexos (por ejemplo, ACINPRO), las regalías por la ejecución pública digital de la obra (por ejemplo, webcast), sujeta a las disposiciones aplicables del régimen de Derecho de Autor, si esta ejecución pública digital está primordialmente dirigida a obtener una ventaja comercial o una compensación monetaria privada.

5. Representaciones, Garantías y Limitaciones de Responsabilidad.
A MENOS QUE LAS PARTES LO ACORDARAN DE OTRA FORMA POR ESCRITO, EL LICENCIANTE OFRECE LA OBRA (EN EL ESTADO EN EL QUE SE ENCUENTRA) “TAL CUAL”, SIN BRINDAR GARANTÍAS DE CLASE ALGUNA RESPECTO DE LA OBRA, YA SEA EXPRESA, IMPLÍCITA, LEGAL O CUALQUIERA OTRA, INCLUYENDO, SIN LIMITARSE A ELLAS, GARANTÍAS DE TITULARIDAD, COMERCIABILIDAD, ADAPTABILIDAD O ADECUACIÓN A PROPÓSITO DETERMINADO, AUSENCIA DE INFRACCIÓN, DE AUSENCIA DE DEFECTOS LATENTES O DE OTRO TIPO, O LA PRESENCIA O AUSENCIA DE ERRORES, SEAN O NO DESCUBRIBLES (PUEDAN O NO SER ESTOS DESCUBIERTOS). ALGUNAS JURISDICCIONES NO PERMITEN LA EXCLUSIÓN DE GARANTÍAS IMPLÍCITAS, EN CUYO CASO ESTA EXCLUSIÓN PUEDE NO APLICARSE A USTED.

6. Limitación de responsabilidad.
A MENOS QUE LO EXIJA EXPRESAMENTE LA LEY APLICABLE, EL LICENCIANTE NO SERÁ RESPONSABLE ANTE USTED POR DAÑO ALGUNO, SEA POR RESPONSABILIDAD EXTRACONTRACTUAL, PRECONTRACTUAL O CONTRACTUAL, OBJETIVA O SUBJETIVA, SE TRATE DE DAÑOS MORALES O PATRIMONIALES, DIRECTOS O INDIRECTOS, PREVISTOS O IMPREVISTOS PRODUCIDOS POR EL USO DE ESTA LICENCIA O DE LA OBRA, AUN CUANDO EL LICENCIANTE HAYA SIDO ADVERTIDO DE LA POSIBILIDAD DE DICHOS DAÑOS. ALGUNAS LEYES NO PERMITEN LA EXCLUSIÓN DE CIERTA RESPONSABILIDAD, EN CUYO CASO ESTA EXCLUSIÓN PUEDE NO APLICARSE A USTED.

7. Término.

a.	Esta Licencia y los derechos otorgados en virtud de ella terminarán automáticamente si Usted infringe alguna condición establecida en ella. Sin embargo, los individuos o entidades que han recibido Obras Derivadas o Colectivas de Usted de conformidad con esta Licencia, no verán terminadas sus licencias, siempre que estos individuos o entidades sigan cumpliendo íntegramente las condiciones de estas licencias. Las Secciones 1, 2, 5, 6, 7, y 8 subsistirán a cualquier terminación de esta Licencia.

b.	Sujeta a las condiciones y términos anteriores, la licencia otorgada aquí es perpetua (durante el período de vigencia de los derechos de autor de la obra). No obstante lo anterior, el Licenciante se reserva el derecho a publicar y/o estrenar la Obra bajo condiciones de licencia diferentes o a dejar de distribuirla en los términos de esta Licencia en cualquier momento; en el entendido, sin embargo, que esa elección no servirá para revocar esta licencia o que deba ser otorgada , bajo los términos de esta licencia), y esta licencia continuará en pleno vigor y efecto a menos que sea terminada como se expresa atrás. La Licencia revocada continuará siendo plenamente vigente y efectiva si no se le da término en las condiciones indicadas anteriormente.

8. Varios.

a.	Cada vez que Usted distribuya o ponga a disposición pública la Obra o una Obra Colectiva, el Licenciante ofrecerá al destinatario una licencia en los mismos términos y condiciones que la licencia otorgada a Usted bajo esta Licencia.

b.	Si alguna disposición de esta Licencia resulta invalidada o no exigible, según la legislación vigente, esto no afectará ni la validez ni la aplicabilidad del resto de condiciones de esta Licencia y, sin acción adicional por parte de los sujetos de este acuerdo, aquélla se entenderá reformada lo mínimo necesario para hacer que dicha disposición sea válida y exigible.

c.	Ningún término o disposición de esta Licencia se estimará renunciada y ninguna violación de ella será consentida a menos que esa renuncia o consentimiento sea otorgado por escrito y firmado por la parte que renuncie o consienta.

d.	Esta Licencia refleja el acuerdo pleno entre las partes respecto a la Obra aquí licenciada. No hay arreglos, acuerdos o declaraciones respecto a la Obra que no estén especificados en este documento. El Licenciante no se verá limitado por ninguna disposición adicional que pueda surgir en alguna comunicación emanada de Usted. Esta Licencia no puede ser modificada sin el consentimiento mutuo por escrito del Licenciante y Usted.
 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