Arginase as a new concern in blood transfusion

Letter to the editor.-- et al.This work was supported in part from the Junta de Castilla y León (Biomedicine project 2011-2012, and CSI221A12-2), Red Temática de Investigación Cooperativa en Cáncer, Instituto de Salud Carlos III, co-funded by the Fondo Europeo de Desarrollo Regional of the European Union (RD06/0020/1037 and RD12/0036/0065), and the Spanish Ministerio de Economia y Competitividad (SAF2011-30518).Peer Reviewe

A place-based policy for promoting Industry 4.0: the case of the Castellon ceramic tile district

This is an Author's Accepted Manuscript of an article published in Jose-Luis Hervas-Oliver, Sofia Estelles-Miguel, Gustavo Mallol-Gasch & Juan Boix-Palomero (2019) A place-based policy for promoting Industry 4.0: the case of the Castellon ceramic tile district, European Planning Studies, 27:9, 1838-1856, DOI: 10.1080/09654313.2019.1642855 [copyright Taylor & Francis], available online at: http://www.tandfonline.com/10.1080/09654313.2019.1642855[EN] Digitization and its impact on regions and clusters remains overlooked in the literature, and constitute this present paper's goal. How does an industrial district transit collectively to the adoption of new radical changes brought about by Industry 4.0? This study explores the role of collective actors and innovation platforms during the early stages of a pilot policy to stimulate a collective transition of an entire MID (Marshallian Industrial District) into Industry 4.0. We posit that institutional isomorphism and the existent social capital in MIDs is a double-sword phenomenon that can also positively constitute an enabler for fostering change on a collective-basis. Technology transitions, such as Industry 4.0, can be supported and led by collective actors that are central in facilitating the adoption of Industry 4.0 in MIDs, enticing innovative firms to engage in that transition, establishing, legitimizing, and embedding a new set of processes, practices and inter-firm arrangements for digitizing and then promoting imitation: the positive leverage of isomorphism. Thus, MID transition is facilitated through capitalizing on the MID logic of cooperation-competition and isomorphism, by developing and promoting a collective understanding of the new paradigm, building a supportive infrastructure, educating in the new technology and avoiding cognitive inertia.This work was supported by Ministerio de Ciencia, Innovacion y Universidades [grant number RTI2018-095739-B-100].Hervás Oliver, JL.; Estelles Miguel, S.; Mallol-Gasch, G.; Boix-Palomero, J. (2019). A place-based policy for promoting Industry 4.0: the case of the Castellon ceramic tile district. European Planning Studies. 27(9):1838-1856. https://doi.org/10.1080/09654313.2019.1642855S18381856279Aldrich, H. E., & Fiol, C. M. (1994). Fools Rush in? The Institutional Context of Industry Creation. Academy of Management Review, 19(4), 645-670. doi:10.5465/amr.1994.9412190214Alvedalen, J., & Boschma, R. (2017). A critical review of entrepreneurial ecosystems research: towards a future research agenda. 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Cambridge Journal of Regions, Economy and Society, 11(2), 335-351. doi:10.1093/cjres/rsy011Foray, D. (2016). On the policy space of smart specialization strategies. European Planning Studies, 24(8), 1428-1437. doi:10.1080/09654313.2016.1176126Gabaldón-Estevan, D., Manjarrés-Henríquez, L., & Molina-Morales, F. X. (2018). An analysis of the Spanish ceramic tile industry research contracts and patents. European Planning Studies, 26(5), 895-914. doi:10.1080/09654313.2018.1427701Gilbert, B. A. (2012). Creative destruction: Identifying its geographic origins. Research Policy, 41(4), 734-742. doi:10.1016/j.respol.2011.11.005Glasmeier, A. (1991). Technological discontinuities and flexible production networks: The case of Switzerland and the world watch industry. Research Policy, 20(5), 469-485. doi:10.1016/0048-7333(91)90070-7Hervás-Oliver, J. L., & Albors-Garrigós, J. (2007). Do clusters capabilities matter? An empirical application of the resource-based view in clusters. Entrepreneurship & Regional Development, 19(2), 113-136. doi:10.1080/08985620601137554Hervas-Oliver, J.-L., & Albors-Garrigos, J. (2008). The role of the firm’s internal and relational capabilities in clusters: when distance and embeddedness are not enough to explain innovation. Journal of Economic Geography, 9(2), 263-283. doi:10.1093/jeg/lbn033Hervas-Oliver, J.-L., & Albors-Garrigos, J. (2014). Are technology gatekeepers renewing clusters? Understanding gatekeepers and their dynamics across cluster life cycles. Entrepreneurship & Regional Development, 26(5-6), 431-452. doi:10.1080/08985626.2014.933489Hervás-Oliver, J.-L., Albors-Garrigos, J., Estelles-Miguel, S., & Boronat-Moll, C. (2017). Radical innovation in Marshallian industrial districts. Regional Studies, 52(10), 1388-1397. doi:10.1080/00343404.2017.1390311Hervas-Oliver, J.-L., Lleo, M., & Cervello, R. (2017). The dynamics of cluster entrepreneurship: Knowledge legacy from parents or agglomeration effects? The case of the Castellon ceramic tile district. Research Policy, 46(1), 73-92. doi:10.1016/j.respol.2016.10.006Hervas-Oliver, J.-L., Sempere-Ripoll, F., Estelles-Miguel, S., & Rojas-Alvarado, R. (2019). Radical vs incremental innovation in Marshallian Industrial Districts in the Valencian Region: what prevails? European Planning Studies, 27(10), 1924-1939. doi:10.1080/09654313.2019.1638887Hervas-Oliver, J.-L., Sempere-Ripoll, F., Rojas Alvarado, R., & Estelles-Miguel, S. (2017). Agglomerations and firm performance: who benefits and how much? Regional Studies, 52(3), 338-349. doi:10.1080/00343404.2017.1297895Liao, Y., Loures, E. R., Deschamps, F., Brezinski, G., & Venâncio, A. (2018). The impact of the fourth industrial revolution: a cross-country/region comparison. Production, 28(0). doi:10.1590/0103-6513.20180061Robertson, P. L., & Langlois, R. N. (1995). Innovation, networks, and vertical integration. Research Policy, 24(4), 543-562. doi:10.1016/s0048-7333(94)00786-1Saxenian, A. 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La cubierta como estrategia sostenible. Materia y forma en la obra de Glenn Murcutt

En Australia, el “Genius Loci“ emana necesariamente del paisaje natural, que aún prevalece al urbano. No ajeno a ello, Glenn Murcutt es conocido por proyectar desde el lugar, teniendo en cuenta la naturaleza y respetándola por encima de cualquier cosa, usando todo lo que ella nos da en su beneficio. El reniega de los debates contemporáneos sobre la sostenibilidad al considerarlos comerciales o hasta bromas, abogando por un punto de vista más pragmático y más romántico a un tiempo, con una arquitectura que responde de manera muy prosaica a los condicionantes climáticos del lugar, pero que atiende prominentemente a las necesidades del paisaje australiano. Todo gira en torno al lugar. Posarse de puntillas, construir de forma que la casa se pueda desmontar y montar en otro sitio con los mismos materiales, adaptándose al nuevo medio. La importancia que cobran en este arquitecto las experiencias vividas en su infancia, en Papua Nueva Guinea y Sydney, sus intereses desde una temprana edad y la influencia de su padre, que le instaba a estudiar artículos de revistas como Architectural Record sobre las Case Study Houses o la casa Farnsworth, entre otros es de tal magnitud que no podemos comprender las inquietudes y soluciones de este arquitecto sin su previa investigación y análisis. De esta manera, hasta 1975 cuando construye la casa para su suegra, Marie Short, la obra de Murcutt bebe enormemente de sus influencias tempranas, caracterizándose por su rigor en planta y su pragmatismo constructivo. Esta casa resulta un punto de inflexión en su obra, siendo la primera vez que abandona la cubierta plana. El proyecto pasa de focalizarse en el rigor en planta para hacerlo en la sección. A partir de entonces la obra de Murcutt se entiende como una sección extrusionada. Manteniendo siempre unas dimensiones reducidas en sección, los proyectos se formalizan a base de cuerpos longitudinales; varios, si si la amplitud del programa así lo requiere. Por ello, la cubierta pasa a tener una importancia capital en su arquitectura y no solo centra la atención por su expresividad formal, algo que no preocupa a Murcutt, sino que es el elemento que funciona como catalizador de todos los demás, en el que se centran las soluciones a todos los problemas que nos da el entorno. Este trabajo se centra en entender los razonamientos y estrategias de proyecto que hay detrás de esas cubiertas, cuál es la importancia del contexto, tanto suyo como el de su país, (todas sus obras están en Australia al negarse Murcutt a construir fuera por falta de conocimiento del lugar), que papel juega el material y, en un último término como todo ello se engloba dentro de su particular método. Como premio Pritzker en 2002, la obra de Glenn Murcutt ha sido ampliamente difundida, escapando de su contexto nacional para convertirlo en una figura de importancia internacional. Por ello, el estudio busca analizar su método, y a la vez rastrear su influencia tanto en el contexto australiano como en la esfera internacional, evaluando la validez de sus principios más allá de su capacidad de producir una obra con un indiscutible sello personal

Zn-Mg and Zn-Cu alloys for stenting applications: From nanoscale mechanical characterization to in vitro degradation and biocompatibility

Reproducció del document publicat a: https://doi.org/10.1016/j.bioactmat.2021.04.015In the recent decades, zinc (Zn) and its alloys have been drawing attention as promising candidates for bioresorbable cardiovascular stents due to its degradation rate more suitable than magnesium (Mg) and iron (Fe) alloys. However, its mechanical properties need to be improved in order to meet the criteria for vascular stents. This work investigates the mechanical properties, biodegradability and biocompatibility of Zn-Mg and Zn-Cu alloys in order to determine a proper alloy composition for optimal stent performance. Nanoindentation measurements are performed to characterize the mechanical properties at the nanoscale as a function of the Zn microstructure variations induced by alloying. The biodegradation mechanisms are discussed and correlated to microstructure, mechanical performance and bacterial/cell response. Addition of Mg or Cu alloying elements refined the microstructure of Zn and enhanced yield strength (YS) and ultimate tensile strength (UTS) proportional to the volume fraction of secondary phases. Zn-1Mg showed the higher YS and UTS and better performance in terms of degradation stability in Hanks’ solution. Zn-Cu alloys presented an antibacterial effect for S. aureus controlled by diffusion mechanisms and by contact. Biocompatibility was dependent on the degradation rate and the nature of the corrosion products.Financial support was received from Spanish Government, MINECO/FEDER, (RTI2018-098075-B-C21) and the Agency for Administration of University and Research Grants of the Government of Catalonia (2017SGR-1165). L.C.C. thanks COFUND scheme (GA 712754) and SEV-2014-0425 (2015–2019) for the financial support. Support for the research of M-P.G. was received through the prize “ICREA Academia” for excellence in research, funded by the Generalitat de Catalunya. Authors acknowledge Dr. Daniel Rodríguez-Rius for helping in the corrosion studies and measurement setup

Tumor expression of cyclin-dependent kinase 5 (Cdk5) is a prognostic biomarker and predicts outcome of oxaliplatin-treated metastatic colorectal cancer patients

Colorectal cancer; Cyclin-dependent kinase 5 (Cdk5); Prognostic and predictive biomarkerCáncer colorrectal; Quinasa dependiente de ciclina 5 (Cdk5); Biomarcador pronóstico y predictivoCàncer colorectal; Quinasa dependent de ciclina 5 (CDK5); Biomarcador pronòstic i predictiuIn recent years, an increasing number of studies have shown that elevated expression of cyclin dependent kinase (Cdk5) contributes to the oncogenic initiation and progression of many types of cancers. In this study, we investigated the expression pattern of Cdk5 in colorectal cancer (CRC) cell lines and in a large number of tumor samples in order to evaluate its relevance in this pathogenesis and possible use as a prognostic marker. We found that Cdk5 is highly expressed and activated in CRC cell lines and that silencing of the kinase decreases their migration ability. In tumor tissues, Cdk5 is overexpressed compared to normal tissues due to a copy number gain. In patients with localized disease, we found that high Cdk5 levels correlate with poor prognosis, while in the metastatic setting, this was only the case for patients receiving an oxaliplatin-based treatment. When exploring the Cdk5 levels in the consensus molecular subtypes (CMS), we found the lowest levels in subtype 1, where high Cdk5 again was associated with a poorer prognosis. In conclusion, we confirm that Cdk5 is involved in CRC and disease progression and that it could serve as a prognostic and predictive biomarker in this disease.This work has been funded by the ISCIII grants from the Spanish Government, project numbers PI09/01334 and PI12/02228, and the Departament d’Innovació, Universitats i Empresa, Generalitat de Catalunya, project numbers 2014-SGR-1494, 2017-SGR-1705 and 2017-SGR-723. The group from Eva Martinez Balibrea is furthermore funded by the PIE16/00011 and the group from Diego Arango by the PI16/00540 and AC15/00066 grants

Disease networks identify specific conditions and pleiotropy influencing multimorbidity in the general population

Multimorbidity is an emerging topic in public health policy because of its increasing prevalence and socio-economic impact. However, the age- and gender-dependent trends of disease associations at fine resolution, and the underlying genetic factors, remain incompletely understood. Here, by analyzing disease networks from electronic medical records of primary health care, we identify key conditions and shared genetic factors influencing multimorbidity. Three types of diseases are outlined: "central", which include chronic and non-chronic conditions, have higher cumulative risks of disease associations; "community roots" have lower cumulative risks, but inform on continuing clustered disease associations with age; and "seeds of bursts", which most are chronic, reveal outbreaks of disease associations leading to multimorbidity. The diseases with a major impact on multimorbidity are caused by genes that occupy central positions in the network of human disease genes. Alteration of lipid metabolism connects breast cancer, diabetic neuropathy and nutritional anemia. Evaluation of key disease associations by a genome-wide association study identifies shared genetic factors and further supports causal commonalities between nervous system diseases and nutritional anemias. This study also reveals many shared genetic signals with other diseases. Collectively, our results depict novel population-based multimorbidity patterns, identify key diseases within them, and highlight pleiotropy influencing multimorbidity

Industria 4.0 en el cluster cerámico de Castellón

[ES] Se presentan los resultados del Informe, basado en una encuesta a 62 empresas del sector cerámico de Castellón, "La industria 4.0 en el clúster cerámico de Castellón" que ratifican la amplia aceptación de la Industria 4.0 como una línea “estratégica y de futuro” y además se reconoce la existencia de conocimiento en el territorio-cluster para lograr este objetivo. Los esfuerzos de CEBRA+, con el ITC a la cabeza, así como el papel impulsor de los proveedores de maquinaria existentes en el territorio, están impulsado el reconocimiento y adopción de dichas tecnologías. La gran mayoría de las empresas reconocen grandes oportunidades de mejora con la adopción de la Industria 4.0, en producto, en proceso, control de costes y flexibilidad de procesos y algo menos en sostenibilidad. El sector se encuentra en una fase de crecimiento en la adopción de la Industria 4.0, mostrando una clara tendencia positiva que ya ha propiciado el salto cultural necesario para el cambio hacia la digitalización. Los sistemas de información son muy importantes, ya que constituyen la base para digitalizar. Así, el estudio demuestra que las empresas más digitalizadas, aquellas que tienen el proyecto de digitalización más avanzado, son aquellas que tienen implantados más sistemas de información.[EN] The results of the report, based on a survey of 62 companies in the ceramic sector in Castellón, "Industry 4.0 in the ceramic cluster of Castellón" are presented, ratifying the wide acceptance of Industry 4.0 as a "strategic and future" line and also recognizing the existence of knowledge in the cluster-territory to reach this goal. The efforts of CEBRA+, with the leadership of ITC, as well as the driving role of existing machinery suppliers in the territory, are promoting the recognition and adoption of these technologies. The vast majority of companies recognize great opportunities for improvement with the adoption of Industry 4.0, in product, process, cost control and process flexibility, and somewhat less in sustainability. The sector is in a phase of growth in the adoption of Industry 4.0, showing a clear positive trend that has already led to the cultural leap necessary for the change towards digitalization. Information systems are very important, as they form the basis for digitization. Thus, the study shows that the most digitized companies (those with the most advanced digitization project), are those that have implemented more information systems.Hervás Oliver, JL. (2021). Industria 4.0 en el cluster cerámico de Castellón. Universitat Politècnica de València. http://hdl.handle.net/10251/18274

Tumor Expression of Cyclin-Dependent Kinase 5 (Cdk5) Is a Prognostic Biomarker and Predicts Outcome of Oxaliplatin-Treated Metastatic Colorectal Cancer Patients

In recent years, an increasing number of studies have shown that elevated expression of cyclin dependent kinase (Cdk5) contributes to the oncogenic initiation and progression of many types of cancers. In this study, we investigated the expression pattern of Cdk5 in colorectal cancer (CRC) cell lines and in a large number of tumor samples in order to evaluate its relevance in this pathogenesis and possible use as a prognostic marker. We found that Cdk5 is highly expressed and activated in CRC cell lines and that silencing of the kinase decreases their migration ability. In tumor tissues, Cdk5 is overexpressed compared to normal tissues due to a copy number gain. In patients with localized disease, we found that high Cdk5 levels correlate with poor prognosis, while in the metastatic setting, this was only the case for patients receiving an oxaliplatin-based treatment. When exploring the Cdk5 levels in the consensus molecular subtypes (CMS), we found the lowest levels in subtype 1, where high Cdk5 again was associated with a poorer prognosis. In conclusion, we confirm that Cdk5 is involved in CRC and disease progression and that it could serve as a prognostic and predictive biomarker in this disease

DNA polymerase λ, a novel DNA repair enzyme in human cells

DNA polymerase lambda (pol λ) is a novel family X DNA polymerase that has been suggested to play a role in meiotic recombination and DNA repair. The recent demonstration of an intrinsic 5′-deoxyribose-5-phosphate lyase activity in pol λ supports a function of this enzyme in base excision repair. However, the biochemical properties of the polymerization activity of this enzyme are still largely unknown. We have cloned and purified human pol λ to homogeneity in a soluble and active form, and we present here a biochemical description of its polymerization features. In support of a role in DNA repair, pol λ inserts nucleotides in a DNA template-dependent manner and is processive in small gaps containing a 5′-phosphate group. These properties, together with its nucleotide insertion fidelity parameters and lack of proofreading activity, indicate that pol λ is a novel β-like DNA polymerase. However, the high affinity of pol λ for dNTPs (37-fold over pol β) is consistent with its possible involvement in DNA transactions occurring under low cellular levels of dNTPs. This suggests that, despite their similarities, pol β and pol λ have nonredundant in vivo functions.This work was supported by Ministerio de Ciencia y Tecnologı´a Grant BMC2000-1138, Comunidad Auto´noma de Madrid Grant 08.5/0063/2000 (to L. B.) and by an institutional grant from Fundacio´n Ramo´n Areces