Las barreras a la integración interfuncional y su relación con el rendimiento de los nuevos productos en las empresas innovadoras españolas

[ES] En este trabajo se analiza la relación entre la integración interfuncional y el rendimiento de los nuevos productos en una muestra de empresas innovadoras españolas. Las percepciones de los directivos de I+D, marketing, producción y otras áreas permiten comprobar que la falta de apoyo de la alta dirección y la distancia física entre áreas son dos barreras significativas a la integración interfuncional. Además, los directivos perciben que la integración interfuncional está relacionada con el rendimiento del programa de desarrollo de nuevos productos. Los resultados apoyan la mayoría de las hipótesis planteadas y son coherentes con las investigaciones previas sobre el tema. También se plantean las implicaciones que para la dirección tienen estos resultados y algunas líneas de investigación futuras.

The Loss of Functional Caspase-12 in Europe Is a Pre-Neolithic Event

6 p.

Early Functional Deficit and Microglial Disturbances in a Mouse Model of Amyotrophic Lateral Sclerosis

11 p.

The study of film adaptation: a state of the art and some "new" functional proposals

Eguíluz, Federico; Merino, Raquel; Olsen, Vickie; Pajares, Eterio; Santamaría, José Miguel (eds.)

Fine mapping and functional analysis of the multiple sclerosis risk gene CD6

CD6 has recently been identified and validated as risk gene for multiple sclerosis (MS), based on the association of a single nucleotide polymorphism (SNP), rs17824933, located in intron 1. CD6 is a cell surface scavenger receptor involved in T-cell activation and proliferation, as well as in thymocyte differentiation. In this study, we performed a haptag SNP screen of the CD6 gene locus using a total of thirteen tagging SNPs, of which three were non-synonymous SNPs, and replicated the recently reported GWAS SNP rs650258 in a Spanish-Basque collection of 814 controls and 823 cases. Validation of the six most strongly associated SNPs was performed in an independent collection of 2265 MS patients and 2600 healthy controls. We identified association of haplotypes composed of two non-synonymous SNPs [rs11230563 (R225W) and rs2074225 (A257V)] in the 2nd SRCR domain with susceptibility to MS (Pmax(T) permutation=161024). The effect of these haplotypes on CD6 surface expression and cytokine secretion was also tested. The analysis showed significantly different CD6 expression patterns in the distinct cell subsets, i.e. – CD4+ naı¨ve cells, P = 0.0001; CD8+ naı¨ve cells, P,0.0001; CD4+ and CD8+ central memory cells, P = 0.01 and 0.05, respectively; and natural killer T (NKT) cells, P = 0.02; with the protective haplotype (RA) showing higher expression of CD6. However, no significant changes were observed in natural killer (NK) cells, effector memory and terminally differentiated effector memory T cells. Our findings reveal that this new MS-associated CD6 risk haplotype significantly modifies expression of CD6 on CD4+ and CD8+ T cells.

Functional analysis of cancer-associated EGFR mutants using a cellular assay with YFP-tagged EGFR intracellular domain

Background: The presence of EGFR kinase domain mutations in a subset of NSCLC patients correlates with the response to treatment with the EGFR tyrosine kinase inhibitors gefitinib and erlotinib. Although most EGFR mutations detected are short deletions in exon 19 or the L858R point mutation in exon 21, more than 75 different EGFR kinase domain residues have been reported to be altered in NSCLC patients. The phenotypical consequences of different EGFR mutations may vary dramatically, but the majority of uncommon EGFR mutations have never been functionally evaluated. Results: We demonstrate that the relative kinase activity and erlotinib sensitivity of different EGFR mutants can be readily evaluated using transfection of an YFP-tagged fragment of the EGFR intracellular domain (YFP-EGFR-ICD), followed by immunofluorescence microscopy analysis. Using this assay, we show that the exon 20 insertions Ins770SVD and Ins774HV confer increased kinase activity, but no erlotinib sensitivity. We also show that, in contrast to the common L858R mutation, the uncommon exon 21 point mutations P848L and A859T appear to behave like functionally silent polymorphisms. Conclusion: The ability to rapidly obtain functional information on EGFR variants of unknown relevance using the YFP-EGFR-ICD assay might prove important in the future for the management of NSCLC patients bearing uncommon EGFR mutations. In addition, our assay may be used to determine the response of resistant EGFR mutants to novel second-generation TKIs.

EAE eta Irlanda, Hezkuntza Bereziaren bi ikuspegi

Aniztasun funtzionala duten pertsonen hezkuntzaren inguruko GALa da hau. Hezkuntzak arlo honetan izan duen ibilbidea ezagutu ostean, EAE eta Irlandako hezkuntza sistemak aztertzen dituena. Ikerketa lana da hau eta gaiaren inguruko azterketa bibliografiko sakona izateaz gain bi herrialdeetan datu bilketa egin izan da, bi herrialdeetako irakasleak betetako galdetegien bitartez. Tresna hauen helburua batzuen zein besteen jarrerak ezagutzea eta konparatzea zen, hauen garrantziaz jabetuz. Ikerketa lanaren ostean bi herrialdeek heziketa berezia ulertzeko bi modu desberdin dituztela azaleratzen da: EAEn integraziotik inklusiora bidean gauden bitartean, Irlandan kontraesan ugari daude; izan ere, inklusioa bultzatu nahi da, baina eskola bereziak mantenduz. Irlandan badute zer aldatu, baina bertan ere badugu. Inklusioa da jarraitu beharreko bidea; ez da erraza izango, baina aniztasun funtzionala duten haurrekin elkar bizitzea aukera bat da eta guztiok izan gaitezke irabazle.

DEVELOPMENT AND APPLICATIONS OF TIME-DEPENDENT DENSITY MATRIX FUNCTIONAL THEORY

En esta tesis estudiamos las teorías sobre la Matriz Densidad Reducida (MDR) como un marco prometedor. Nos enfocamos sobre esta teorías desde dos aspectos: Primero, usamos algunos modelos sencillos hechos con dos partículas las cuales estan armónicamente confinadas como una base para ilustrar la utilidad de la matriz densidad. Para tales sistemas, usamos la MDR de un cuerpo para calcular algunas cantidades de interés tales como densidad de momentum. Posteriormente obtenemos los orbitales naturales y su número de ocupación para algunos de los modelos, y en uno de los casos expresamos la MDR de dos cuerpos de manera exacta en términos de la MDR de un cuerpo. También usamos el teorema diferencial del virial para establecer una descripción unificada de la familia entera de estos sistemas modelo en términos de la densidad. En la seguna parte cambiamos a casos fuera del equilibrio y analizamos la así llamada jerarquía BBGKY de ecuaciones para describir la evolución temporal de un sistema de muchos cuerpos en términos de sus MDRs (a todos los órdenes). Proveemos un exhaustivo estudio de los desafíos y problemas abiertos ligados a la truncación de tales jerarquías de ecuaciones para hacerlas aplicables. Restringimos nuestro análisis a la evolución acoplada de la MDR de uno y dos cuerpos, donde los efectos de correlación de alto orden estan embebidos dentro de la aproximación usada para cerrar las ecuaciones. Probamos que dentro de esta aproximación, el número de electrones y la energía total se conservan, sin importar la aproximación usada. Luego, demostramos que aplicando los esquemas de truncación de estado base para llevar los electrones a comportamientos indeseables y no físicos, tales como la violación e incluso la divergencia en la densidad electrónica local, tanto en regímenes correlacionados débiles y fuertes.

Compliance verification methodology for renewable generation integration. Application to island power grids

261 p.

Eurasian integration as a way to respond to global challenges

510 p.

Modular integration and on-chip sensing approaches for tunable fluid control polymer microdevices

228 p.

Specific Interaction with Cardiolipin Triggers Functional Activation of Dynamin-Related Protein 1

Dynamin-Related Protein 1 (Drp1), a large GTPase of the dynamin superfamily, is required for mitochondrial fission in healthy and apoptotic cells. Drp1 activation is a complex process that involves translocation from the cytosol to the mitochondrial outer membrane (MOM) and assembly into rings/spirals at the MOM, leading to membrane constriction/division. Similar to dynamins, Drp1 contains GTPase (G), bundle signaling element (BSE) and stalk domains. However, instead of the lipid-interacting Pleckstrin Homology (PH) domain present in the dynamins, Drp1 contains the so-called B insert or variable domain that has been suggested to play an important role in Drp1 regulation. Different proteins have been implicated in Drp1 recruitment to the MOM, although how MOM-localized Drp1 acquires its fully functional status remains poorly understood. We found that Drp1 can interact with pure lipid bilayers enriched in the mitochondrion-specific phospholipid cardiolipin (CL). Building on our previous study, we now explore the specificity and functional consequences of this interaction. We show that a four lysine module located within the B insert of Drp1 interacts preferentially with CL over other anionic lipids. This interaction dramatically enhances Drp1 oligomerization and assembly-stimulated GTP hydrolysis. Our results add significantly to a growing body of evidence indicating that CL is an important regulator of many essential mitochondrial functions.

Density-potential mapping in the standard and quantum electrodynamical time-dependent density functional theory

131 p.

Hyers-Ulam-Rassias Stability of Functional Differential Systems with Point and Distributed Delays

This paper investigates stability and asymptotic properties of the error with respect to its nominal version of a nonlinear time-varying perturbed functional differential system subject to point, finite-distributed, and Volterra-type distributed delays associated with linear dynamics together with a class of nonlinear delayed dynamics. The boundedness of the error and its asymptotic convergence to zero are investigated with the results being obtained based on the Hyers-Ulam-Rassias analysis.

Fiscal Integration in the European Union : assessment of different proposals

This paper explores the fiscal situation of the European Union as well as the different approaches proposed for achieving fiscal policy coordination among the member states. Furthermore, it works through the need of fiscal integration as a pressing matter in order for the European Union to achieve its aim of functioning as an efficient single market and economic unit. In order to do so, it analyzes the theoretical lines of the Modern Money Theory as a possible framework for further integration, and it evaluates the different proposals made for fiscal integration so that it can give an assessment regarding their compatibility with this theory.