Meta-heurística ACO (Ant Colony Optimization) para la resolución de problemas en líneas de producción

La meta -heurística ACO (Ant Colony Optimization) es un procedimiento heurístico para la resolución de problemas de optimización di screta basado en el comportamiento de las hormigas. Sus principales características son: (1) la utilización de "feed -back" positivo, (2) computación distribuida (la estructura de estos algoritmos permite su paralelización de forma muy simple y natural), y (3) el uso de heurísticas Greedy constructivas (ayuda a encontrar soluciones aceptables en las primeras etapas del proceso de exploración). En este artículo se presenta la aplicación de dichas meta -heurísticas a la resolución de problemas de producción co mo equilibrado de líneas de montaje o la secuenciación de unidades en un sistema que no permite esperasPostprint (published version

Comportamiento aerodinámico de barreras cortavientos 1

El trabajo presenta resultados de la exploración del campo de velocidades en estelas de distintos modelos de barreras porosas, con vistas a suposible utilización para proteger plantaciones o zonas habitadas de los efectos perniciosos del viento. Los ensayos se han hecho en túnel aerodinámico y, para las medidas, se ha utilizado un anemómetro de hilo caliente. Se ha medido: la velocidad media temporal, el nivel de turbulencia y, en algunos casos, el transporte turbulento y la inclinación del vector velocidad, en cuatro secciones distintas corriente abajo de cada barrera. El trabajo está dividido en ocho capítulos. En el primero se discute la posible utilidad de las barreras en agricultura. En el segundo se revisan ciertas características de las estelas turbulentas de diferentes obstáculos,con el fin de contrastar los resultados obtenidos con otros análogos. En el capítulo tercero se describen los métodos de medida. El cuarto presenta el grueso de los resultados, y los cuatro siguientes: la influencia del número de Reynolds, rugosidad del suelo, perfil del viento incidente y presencia de las paredes y techo del túnel, respectivamente. Los ensayos muestran que los perfiles de velocidades correspondientes a secciones situadas a cierta distancia de la barrera (mayor de seis a ocho veces la altura de ésta) se asemejan a los de un semichorro de baja velocidad que descarga paralelamente a una corriente más rápida. Los perfiles próximos y las condiciones iniciales del semichorro dependen de la configuración de la barrera. El modelo del semichorro equivalente permite calcular las características de la estela a distancias mayores que las que es posible reproducir en los experimentos. Por otra parte, sugiere ciertas modificaciones de la forma de la barrera para aumentar la longitud de la zona protegida del viento. La rugosidad del suelo y la existencia de perfiles de viento distintos del uniforme y más ajustados a la realidad, contribuyen a disminuir la longitud de la zona protegida. Esta observación está de acuerdo con los resultados de otros autores. Se observa que el nivel de turbulencia es muy sensible a las características geométricas de la barrera, lo que sugiere la posibilidad de controlar la capa límite sobre el terreno y, por tanto, el transporte de calor y masa en provecho de la productividad de cultivo. El trabajo que se presenta es parte de un programa más amplio, que tiene por objeto transmitir tecnología avanzada a ciertos dominios de interés para la agricultura y la industria

Respiratory complexes III and IV can each bind two molecules of cytochrome c at low ionic strength

The transient interactions of respiratory cytochrome c with complexes III and IV is herein investigated by using heterologous proteins, namely human cytochrome c, the soluble domain of plant cytochrome c1 and bovine cytochrome c oxidase. The binding molecular mechanisms of the resulting cross-complexes have been analyzed by Nuclear Magnetic Resonance and Isothermal Titration Calorimetry. Our data reveal that the two cytochrome c-involving adducts possess a 2:1 stoichiometry – that is, two cytochrome c molecules per adduct – at low ionic strength. We conclude that such extra binding sites at the surfaces of complexes III and IV can facilitate the turnover and sliding of cytochrome c molecules and, therefore, the electron transfer within respiratory supercomplexes.España, MINECO Grant Nos. BFU2010-19451/BMC and BFU2012-31670/BMCJunta de Andalucía Grant PAI, BIO198España Ministerio de Educación, y European Social Fund-ERDF AP2009-409

Structural basis of mitochondrial dysfunction in response to cytochrome c phosphorylation at tyrosine 48

Regulation of mitochondrial activity allows cells to adapt to changing conditions and to control oxidative stress, and its dysfunction can lead to hypoxia-dependent pathologies such as ischemia and cancer. Although cytochrome c phosphorylation—in particular, at tyrosine 48—is a key modulator of mitochondrial signaling, its action and molecular basis remain unknown. Here we mimic phosphorylation of cytochrome c by replacing tyrosine 48 with p-carboxy-methylL-phenylalanine (pCMF). The NMR structure of the resulting mutant reveals significant conformational shifts and enhanced dynamics around pCMF that could explain changes observed in its functionality: The phosphomimetic mutation impairs cytochrome c diffusion between respiratory complexes, enhances hemeprotein peroxidase and reactive oxygen species scavenging activities, and hinders caspase-dependent apoptosis. Our findings provide a framework to further investigate the modulation of mitochondrial activity by phosphorylated cytochrome c and to develop novel therapeutic approaches based on its prosurvival effects.España, MINECO BFU2015-71017-P/BMC and BFU2015- 19451/BMCUnión Europea, Bio-NMR-00130 and CALIPSO-312284España, Ministerio de Educación AP2009-409

Structural basis of mitochondrial dysfunction in response to cytochrome c phosphorylation at tyrosine 48

Regulation of mitochondrial activity allows cells to adapt to changing conditions and to control oxidative stress, and its dysfunction can lead to hypoxia-dependent pathologies such as ischemia and cancer. Although cytochrome c phosphorylation—in particular, at tyrosine 48—is a key modulator of mitochondrial signaling, its action and molecular basis remain unknown. Here we mimic phosphorylation of cytochrome c by replacing tyrosine 48 with p-carboxy-methyl-L-phenylalanine (pCMF). The NMR structure of the resulting mutant reveals significant conformational shifts and enhanced dynamics around pCMF that could explain changes observed in its functionality: The phosphomimetic mutation impairs cytochrome c diffusion between respiratory complexes, enhances hemeprotein peroxidase and reactive oxygen species scavenging activities, and hinders caspase-dependent apoptosis. Our findings provide a framework to further investigate the modulation of mitochondrial activity by phosphorylated cytochrome c and to develop novel therapeutic approaches based on its prosurvival effects.Financial support was provided by the Spanish Ministry of Economy and Competitiveness (Grants BFU2015-71017-P/BMC and BFU2015-19451/BMC, cofounded by FEDER EU), European Union (Bio-MR-00130 and CALIPSO-312284), Ramon Areces Foundation, and Andalusian Government (BIO198). B.M.-B. was awarded a PhD fellowship from the Spanish Ministry of Education (AP2009-4092) and a short-term traveling fellowship from the European Bio-NMR Project. A.G.-C. was awarded a PhD fellowship from the CSIC (JaePre-2011-01248).Peer reviewe

Computational and Experimental Evaluation of the Immune Response of Neoantigens for Personalized Vaccine Design

In the last few years, the importance of neoantigens in the development of personalized antitumor vaccines has increased remarkably. In order to study whether bioinformatic tools are effective in detecting neoantigens that generate an immune response, DNA samples from patients with cutaneous melanoma in different stages were obtained, resulting in a total of 6048 potential neoantigens gathered. Thereafter, the immunological responses generated by some of those neoantigens ex vivo were tested, using a vaccine designed by a new optimization approach and encapsulated in nanoparticles. Our bioinformatic analysis indicated that no differences were found between the number of neoantigens and that of non-mutated sequences detected as potential binders by IEDB tools. However, those tools were able to highlight neoantigens over non-mutated peptides in HLA-II recognition (p-value 0.03). However, neither HLA-I binding affinity (p-value 0.08) nor Class I immunogenicity values (p-value 0.96) indicated significant differences for the latter parameters. Subsequently, the new vaccine, using aggregative functions and combinatorial optimization, was designed. The six best neoantigens were selected and formulated into two nanoparticles, with which the immune response ex vivo was evaluated, demonstrating a specific activation of the immune response. This study reinforces the use of bioinformatic tools in vaccine development, as their usefulness is proven both in silico and ex vivo.This work was supported by Basque Government funding (IT456-22; IT1448-22, IT693-22 and IT1524-22; ONKOVAC 2021111042), as well as by the UPV/EHU (GIU20/035; US21/27; US18/21; PIF18/295) and Basque Center of Applied Mathematics (US21/27 and US18/21)