THE RELEVANCE OF INTERACTIONS IN INNOVATION SYSTEMS: HOW TO CONSOLIDATE THE FRAMEWORK

Innovation Systems constitute an analysis framework which tries to identify the agents, and the interactions produced among them within an innovation system, endowing thus authorities of a tool for the definition of innovation policies. Accordingly, cooperation or interaction related practices become crucial. However, there is a need for the development and implementation of a more sophisticated measures and indicators as regards these interactive patterns, both from a theoretical and a quantitative approach. This papers aims at empirically contributing to highlight the relevance of these interactions. In order to do that, we first start by offering a clear taxonomy of the Spanish regions concerning R&D and innovation activities, to then analyse the extent to which interactions are relevant or not by considering in this case Spain as the unit of analysis between 1995-2002.Innovation Systems, Interactions, Innovation Networks, Measures

Blended Learning in University Education: Activities, Results and Quality

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Calidad de vida en pacientes españoles con trastorno mental grave

Los Trastornos Mentales Graves (TMG) afectan a la calidad de vida (CDV) de los pacientes. El objetivo de este estudio fue analizar la CDV de pacientes con TMG del Centro de Rehabilitación Psicosocial Rey Ardid en Zaragoza (España), con el fin de conocer qué aspectos de su vida estaban más afectados. La muestra estuvo compuesta por 35 pacientes del Centro y 35 sujetos de población general, quienes completaron el cuestionario Calidad de Vida de Sevilla. Tras utilizar el programa SPSS® para una prueba T de medias para muestras independientes, se encontró que una de las áreas más afectadas fue la ocupación (el trabajo o estudio que realizaban), además de una baja puntuación en satisfacción general con la vida. En resumen, medir la CDV de estos pacientes y conocer qué áreas se ven más afectadas, puede mejorar las posibles intervenciones en su tratamiento. Severe Mental Disorders (SMD) affect patient's quality of life (QOL). The aim of this study was to analyze the QOL of patients with SMD at the Rey Ardid Psychosocial Rehabilitation Center in Zaragoza (Spain), in order to know which aspects of their lives were most affected. The sample consisted of 35 patients from the Center and 35 subjects from the general population, who completed the questionnaire Quality of Life of Seville. After using the SPSS (R) program for a T-test of means for independent samples, it was found that one of the areas most affected was occupation (the work or study they performed), in addition to a low score in general satisfaction with life. In summary, measuring the QOL of these patients and knowing which areas are most affected, may improve the possible interventions in their treatment

Directed Evolution of (R)-2-Hydroxyglutarate Dehydrogenase Improves 2-Oxoadipate Reduction by 2 Orders of Magnitude

Pathway engineering is commonly employed to improve the production of various metabolites but may incur in bottlenecks due to the low catalytic activity of a particular reaction step. The reduction of 2-oxoadipate to (R)-2-hydroxyadipate is a key reaction in metabolic pathways that exploit 2-oxoadipate conversion via α-reduction to produce adipic acid, an industrially important platform chemical. Here, we engineered (R)-2-hydroxyglutarate dehydrogenase from Acidaminococcus fermentans (Hgdh) with the aim of improving 2-oxoadipate reduction. Using a combination of computational analysis, saturation mutagenesis, and random mutagenesis, three mutant variants with a 100-fold higher catalytic efficiency were obtained. As revealed by rational analysis of the mutations found in the variants, this improvement could be ascribed to a general synergistic effect where mutation A206V played a key role since it boosted the enzyme\u27s activity by 4.8-fold. The Hgdh variants with increased activity toward 2-oxoadipate generated within this study pave the way for the bio-based production of adipic acid

A comparative three-dimensional neutron depolarization study on RCrO4 oxides (R=Y, Er, Tm, Yb)

Three-dimensional neutron depolarization experiments have been performed on RCrO4 (R=Y, Er, Tm, Yb) powder samples in order to gain insight into their magnetic domain structure in the submicrometer range. The temperature evolution of both the average domain size and the net magnetization of each compound has been studied for different applied magnetic fields. The largest average domain size at zero external magnetic field was found in YbCrO4. The effect of an applied magnetic field on the magnetic domain structure is relatively small in ErCrO4 and TmCrO4, when compared to YCrO4 and YbCrO4 where the average domain size even surpasses the average particle size determined by Scanning Electron Microscopy studies.</p

Finite-element-model updating of civil engineering structures using a hybrid UKF-HS algorithm

This is the author accepted manuscript. The final version is available from Taylor & Francis via the DOI in this recordFinite-element-model updating allows reducing the discrepancies between the numerical and the experimental dynamic behaviour of civil engineering structures. Among the different methods to tackle the updating problem, the maximum likelihood method has been widely used for practical engineering applications. In this method, the updating problem is transformed into an optimization problem where the relative differences between the numerical and experimental modal properties of the structure are reduced via the modification of the most relevant physical parameters of the model. However, this method often presents the drawback of requiring high simulation times in order to perform the updating process when dealing with complex structures. To overcome this limitation, in this paper a novel hybrid Unscented Kalman Filter – Harmony Search (UKF-HS) algorithm is proposed and its implementation details are discussed. In order to validate such hybrid algorithm and further illustrate its performance, the finite-element-model updating of a benchmark footbridge is performed using two different approaches (single-objective and multi-objective) and three different computational algorithms, namely: (i) genetic algorithms; (ii) harmony search; and (iii) the novel UKF-HS hybrid algorithm. The obtained results reveal that the proposed hybrid algorithm may be considered as an adequate alternative tool to efficiently perform the finite-element-mMinisterio de Economía y Competitividad of SpainEuropean Regional Development Fund (ERDF)Universidad de Sevill

Structure-function investigation of 3-methylaspartate ammonia lyase reveals substrate molecular determinants for the deamination reaction

The enzymatic reactions leading to the deamination of β-lysine, lysine, or 2-aminoadipic acid are of great interest for the metabolic conversion of lysine to adipic acid. Enzymes able to carry out these reactions are not known, however ammonia lyases (EC 4.3.1.-) perform deamination on a wide range of substrates. We have studied 3-methylaspartate ammonia lyase (MAL, EC 4.3.1.2) as a potential candidate for protein engineering to enable deamination towards β-lysine, that we have shown to be a competitive inhibitor of MAL. We have characterized MAL activity, binding and inhibition properties on six different compounds that would allow to define the molecular determinants necessary for MAL to deaminate our substrate of interest. Docking calculations showed that β-lysine as well as the other compounds investigated could fit spatially into MAL catalytic pocket, although they probably are weak or very transient binders and we identified molecular determinants involved in the binding of the substrate. The hydrophobic interactions formed by the methyl group of 3-methylaspartic acid, together with the presence of the amino group on carbon 2, play an essential role in the appropriate binding of the substrate. The results showed that β-lysine is able to fit and bind in MAL catalytic pocket and can be potentially converted from inhibitor to substrate of MAL upon enzyme engineering. The characterization of the binding and inhibition properties of the substrates tested here provide the foundation for future and more extensive studies on engineering MAL that could lead to a MAL variant able to catalyse this challenging deamination reaction

Engineering ammonia-lyases for lysine transformation: first steps to green production of adipic acid

Adipic acid is one of the most important dicarboxylic acid for commercial purposes, mainly used as building block for nylon polymers. The current chemical production process has serious consequences for the environment. Therefore, the implementation of a by a bio-based process using renewable feedstocks would be highly beneficial for the society and the environment.\ua0The construction of a microbial metabolic pathway to produce adipic acid using L-lysine as precursor is a potential alternative. The first step of the proposed pathway converts L-lysine into 6-aminohex-2-enoic acid (6-AHEA) via removal of the α-amino group. Chemical methods for this deamination reaction are known; however, no enzymes able to carry out this reaction on L-lysine have been disclosed yet. The main goal of the current research is the generation a novel enzyme activity for the conversion of L-lysine to 6-AHEA.\ua0The enzymatic activity necessary to catalyze the required deamination is defined as ammonia lyase and results in the removal of the α-amino group. Histidine ammonia-lyase (HAL) and 3-methylaspartate-ammonia-lyase (MAL), enzymes acting on histidine and 3-methylaspartate, respectively, were selected to be engineered to catalyze the deamination of lysine.\ua0HAL from Pseudomonas putida and MAL from Clostridium tetanomorphum and Carboxydothermus hydrogenoformans were expressed in E.coli and purified. The capability of the enzymes to deaminate lysine was tested. No deamination activity was observed, while the inhibitory effect of L-lysine on HAL activity was shown.Computational structural biology methodologies were applied on MAL and combined with protein engineering techniques\ua0in order to design mutant enzyme variants potentially active on L-lysine. In-silico saturation mutagenesis tools were used to model all the possible mutations in the active site or its surroundings that are expected to increase affinity for the L-lysine substrate. Following the results obtained, the residues C361, M389 and L384 were mutagenized. The mutant variants were produced and purified, and the activity on L-lysine tested by monitoring the production of 6-AHEA and the release of ammonia