Ingeniería de máquinas : discurso de ingreso [en la Real Academia de Ingeniería] del Excmo. Sr. D. Jaime Domínguez Abascal y contestación del académico Excmo. Sr. D. Enrique Alarcón Álvarez

En el discurso se reivindica el papel actual de la ingeniería mecánica como impulsora del desarrollo de las máquinas. Comienza con una breve exposición de la evolución de las máquinas a lo largo de la historia y su influencia en el desarrollo económico y social. Igualmente, señala la importancia de otras áreas de la ingeniería en el desarrollo de las máquinas actuales y el carácter multidisciplinar del diseño y desarrollo de las máquinas actuales. Ante la nueva situación, el discurso analiza el papel que desempeña actualmente la ingeniería de máquinas. Asimismo, comprueba que la aportación de otras disciplinas ha llevado a la concepción de máquinas con soluciones, más eficientes y eficaces, que requieren nuevos avances de la ingeniería de máquinas. Finalmente, se muestran diversos ejemplos significativos de los avances requeridos para el diseño de las máquinas actuales, entre los que destacan los relativos al análisis dinámico y a la fatiga. Entre los problemas dinámicos, se analizan los casos del comportamiento de sistemas multicuerpos con holgura o sujetos a impactos, y la detección de grietas en rotores mediante la medida de vibraciones. Del análisis del comportamiento a fatiga, se destaca la importancia de la aplicación conjunta de la mecánica de la fractura y el método de las deformaciones locales, especialmente para el análisis del comportamiento de grietas microestructuralmente pequeñas

Construindo "Europolis" a partir da cooperação local “informal” nos espaços de fronteira da Europa: o caso da RIET

Transcurridos veinticinco años del inicio de la cooperación formal transfronteriza en Europa, con la puesta en marcha de la Iniciativa Comunitaria Interreg (1990), el presente análisis exploratorio plantea un modelo de análisis de la cooperación de “segunda generación” a través del estudio de la experiencia de la Red Ibérica de Entidades Transfronterizas (RIET), que desarrolla su actividad en el espacio de frontera de España y Portugal. El caso de la RIET nos permite constatar la construcción de un modelo de cooperación ampliado (formal-informal) y reforzado (isopoliteia y sympoliteia), denominado Europolis, basado en prácticas de gobernanza transfronteriza local, que contempla los procesos de cooperación transfronteriza desde ópticas de diversidad y flexibilidad. Para analizar el modelo se toma como ejemplo la construcción de la isopoliteia y la sympoliteia practicada por las ligas de ciudades en la Grecia clásica, y se aplica a la realidad de las redes de ciudades que ponen en marcha proyectos en las fronteras interiores de la Unión Europea, en nuestro caso, la RIET. Para ello, se estudia su path dependence desde el neoinstitucionalismo histórico, además de su influencia en la definición de problemas públicos transfonterizos y en la posterior conformación de las agendas públicas de las Cumbres Ibéricas, que España y Portugal celebraron los años 2013 y 2014.After twenty five years of cross-border formal cooperation in Europe with origins in the landmark launch of the Communitarian Initiative Interreg (1990), this exploratory analysis offers a model for the study of “second generation” cooperation based on the experience of the Red Ibérica de Entidades Transfronterizas (RIET) that operates in the border space between Spain and Portugal. The case of RIET enables the observation of a model of widened (formal-informal) and reinforced (isopoliteia and sympoliteia) cooperation. Under the name of Europolis, it is based on practices of cross-border local governance that address the processes of cross-border cooperation from diversity and flexibility standpoints. For the examination of the model, the construction of the isopoliteia and sympoliteia put in practice by the leagues of classical Greek cities is taken as an example; and, in turn, applied to the realities of the cities’ networks that boost the development of projects across the European Union’s inner borders ―in our case, the RIET. To this end, their path-dependence is explored from a historical neo-institutionalist perspective, as well as their influence in the definition of cross-border public issues and the political agendas of the Iberian Summits, which brought Spain and Portugal together in the years 2013 and 2014.Depois de vinte cinco anos do início da cooperação transfronteiriça formal na Europa, com o lançamento da Iniciativa Comunitária Interreg (1990), esta análise exploratória apresenta um modelo de análise da cooperação de “segunda geração”, através do estudo da experiência da Rede Ibérica Entidades Transfronteiriças (RIET), que opera na zona fronteiriça entre Espanha e Portugal. O caso da RIET nos permite observar a construção de um modelo de cooperação ampliado (formal‐informal) e reforçado (isopoliteia e sympoliteia), chamado Europolis, com base em práticas de governança local transfronteiriça, que inclui os processos de cooperação transfronteiriça na perspectiva de diversidade e flexibilidade. Para analisar o modelo é tomado como um exemplo a construção da isopoliteia e da sympoliteia praticada pelas ligas de cidades na Grécia clássica, e se aplica à realidade das redes de cidades que implementam projetos nas fronteiras internas da União Europeia, no nosso caso, a RIET. Para esse fim, estuda‐se seu path dependence na ótica do institucionalismo histórico, além de sua influência sobre a definição de problemas públicos transfronteiriços e a subsequente formação de agendas públicas das Cúpulas Ibéricas, que Espanha e Portugal celebraram nos anos de 2013 e 2014

Bioorganic Chemistry: Current and Future Perspectives

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Pounding force assessment in performance-based design of bridges

Bridges with deck supported on either sliding or elastomeric bearings are very common in mid-seismicity regions. Their main seismic vulnerabilities are related to the pounding of the deck against abutments or between the different deck elements. A simplified model of the longitudinal behavior of those bridges will allow to characterize the reaction forces developed during pounding using the Pacific Earthquake Engineering Research Center framework formula. In order to ensure the general applicability of the results obtained, a large number of system parameter combinations will be considered. The heart of the formula is the identification of suitable intermediate variables. First, the pseudo acceleration spectral value for the fundamental period of the system (Sa(Ts)) will be used as an intensity measure (IM). This IM will result in a very large non-explained variability of the engineering demand parameter. A portion of this variability will be proved to be related to the relative content of high-frequency energy in the input motion. Two vector-valued IMs including a second parameter taking this energy content into account will then be considered. For both of them, a suitable form for the conditional intensity dependence of the response will be obtained. The question of which one to choose will also be analyzed. Finally, additional issues related to the IM will be studied: its applicability to pulse-type records, the validity of scaling records and the sufficiency of the IM

Selenides and Diselenides: A Review of Their Anticancer and Chemopreventive Activity

Selenium and selenocompounds have attracted the attention and the efforts of scientists worldwide due to their promising potential applications in cancer prevention and/or treatment. Different organic selenocompounds, with diverse functional groups that contain selenium, have been reported to exhibit anticancer and/or chemopreventive activity. Among them, selenocyanates, selenoureas, selenoesters, selenium-containing heterocycles, selenium nanoparticles, selenides and diselenides have been considered in the search for efficiency in prevention and treatment of cancer and other related diseases. In this review, we focus our attention on the potential applications of selenides and diselenides in cancer prevention and treatment that have been reported so far. The around 80 selenides and diselenides selected herein as representative compounds include promising antioxidant, prooxidant, redox-modulating, chemopreventive, anticancer, cytotoxic and radioprotective compounds, among other activities. The aim of this work is to highlight the possibilities that these novel organic selenocompounds can offer in an effort to contribute to inspire medicinal chemists in their search of new promising derivatives

Analysis of the economic feasibility and reduction of a building’s energy consumption and emissions when integrating hybrid solar thermal/PV/micro-CHP systems

The aim of this paper is to assess the performance of several designs of hybrid systems composed of solar thermal collectors, photovoltaic panels and natural gas internal combustion engines. The software TRNSYS 17 has been used to perform all the calculations and data processing, as well as an optimisation of the tank volumes through an add-in coupled with the GENOPT® software. The study is carried out by analysing the behaviour of the designed systems and the conventional case in five different locations of Spain with diverse climatic characteristics, evaluating the same building in all cases. Regulators, manufacturers and energy service engineers are the most interested in these results. Two major contributions in this paper are the calculations of primary energy consumption and emissions and the inclusion of a Life Cycle Cost analysis. A table which shows the order of preference regarding those criteria for each considered case study is also included. This was fulfilled in the interest of comparing between the different configurations and climatic zones so as to obtain conclusions on each of them. The study also illustrates a sensibility analysis regarding energy prices. Finally, the exhaustive literature review, the novel electricity consumption profile of the building and the illustration of the influence of the cogeneration engine working hours are also valuable outputs of this paper, developed in order to address the knowledge gap and the ongoing challenges in the field of distributed generation

Effects of small conductance calcium activated potassium channels in atrial myocytes

Among the different potassium channels present in cardiac myocytes, the small conductance Ca2+ activated potassium channels (SK channels) are particular because they are affected by changes in intracellular calcium. The functional role of these channels in cardiac electrophysiology is still under intense debate. While they do not seem to play an important role in healthy hearts – their associated current, IKCa, is smaller than other potassium currents -, there is increasing evidence that they may become relevant under pathological conditions. In fact, both pro- and anti-arrhythmic effects have been assigned to these channels, depending on the clinical situation. In this work, we have incorporated the current through SK channels, IKCa, into an electrophysiological ionic model of human atria myocyte. This allows us to evaluate changes in the action potential under different parameters affecting the kinetics of these channels. We observe a large dependence of the action potential duration with the conductance and gate dynamics of the channel. The dependence of SK channels with changes in intracellular calcium dynamics helps decreasing the proarrhythmic effect of spontaneous calcium release eventsPeer ReviewedPostprint (published version

Nonlinearities due to refractoriness in SR Ca release

Calcium alternans is a pro-arrhytmic cardiac dysfunction related to beat-to-beat changes in the amplitude of intracellular calcium transient, that typically occurs at rapid pacing rates. Although oscillations in sarcoplasmic reticulum (SR) content have been related with calcium alternans, the experimental appearance of alternans without these oscillations suggests that another mechanism related with refractoriness of SR calcium release might be key, at least, under certain conditions. We investigate how RyR2 refractoriness modulates calcium handling on a beat-to-beat basis using a numerical rabbit cardiomyocyte model. We find that a slow recovery from inactivation of the RyR2 might be crucial. On one hand, a steep relation between sarcoplasmic reticulum (SR) load and calcium release makes regular calcium cycling unstable at high SR calcium load and/or fast pacing rates, in agreement with previous explanation when RyR2 inactivation is not important. On the other hand, we show that calcium release can also depend strongly on the number of RyR2 ready to open if an important number of RyR2s inactivate after the release. This gives rise to a steep nonlinear relation between the calcium release and the level of recovered RyR2, so that a small change in the later produces big changes in calcium release. A conclusion of this result is that RyR2 refractoriness can be the main nonlinearity behind alternans even when alternation in SR-Ca load is present.Peer ReviewedPostprint (published version

Reversal of Multidrug Resistance by Symmetrical Selenoesters in Colon Adenocarcinoma Cells

Recently, selenium containing derivatives have attracted more attention in medicinal chemistry. In the present work, the anticancer activity of symmetrical selenoesters was investigated by studying the reversal of efflux pump-related and apoptosis resistance in sensitive and resistant human colon adenocarcinoma cells expressing the ABCB1 protein. The combined effect of the compounds with doxorubicin was demonstrated with a checkerboard assay. The ABCB1 inhibitory and the apoptosis-inducing effects of the derivatives were measured with flow cytometry. Whole transcriptome sequencing was carried out on Illumina platform upon the treatment of resistant cells with the most potent derivatives. One ketone and three methyl ester selenoesters showed synergistic or weak synergistic interaction with doxorubicin, respectively. Ketone selenoesters were the most potent ABCB1 inhibitors and apoptosis inducers. Nitrile selenoesters could induce moderate early and late apoptotic processes that could be explained by their ABCB1 modulating properties. The transcriptome analysis revealed that symmetrical selenoesters may influence the redox state of the cells and interfere with metastasis formation. It can be assumed that these symmetrical selenocompounds possess toxic, DNA-damaging effects due to the presence of two selenium atoms in the molecule, which may be augmented by the presence of symmetrical groups