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Liver resection treats primary and secondary liver tumors, though clinical applicability is limited by the remnant liver mass and quality. Herein, major hepatic resections were performed in pigs to define changes associated with sufficient and insufficient remnants and improve liver-specific outcomes with somatostatin therapy. Three experimental groups were performed: 75% hepatectomy (75H), 90% hepatectomy (90H), and 90% hepatectomy + somatostatin (90H + SST). Animals were followed for 24 h (N = 6) and 5 d (N = 6). After hepatectomy, portal pressure gradient was higher in 90H versus 75H and 90H + SST (8 (3–13) mmHg vs. 4 (2–6) mmHg and 4 (2–6) mmHg, respectively, p < 0.001). After 24 h, changes were observed in 90H associated with stellate cell activation and collapse of sinusoidal lumen. Collagen chain type 1 alpha 1 mRNA expression was higher, extracellular matrix width less, and percentage of collagen-staining areas greater at 24 h in 90H versus 75H and 90H + SST. After 5 d, remnant liver mass was higher in 75H and 90H + SST versus 90H, and Ki-67 immunostaining was higher in 90H + SST versus 75H and 90H. As well, more TUNEL-staining cells were observed in 90H versus 75H and 90H + SST at 5 d. Perioperative somatostatin modified portal pressure, injury, apoptosis, and stellate cell activation, stemming changes related to hepatic fibrogenesis seen in liver remnants not receiving treatment.

Several studies have demonstrated that melanoma-derived extracellular vesicles (EVs) are involved in lymph node metastasis; however, the molecular mechanisms involved are not completely defined. Here, we found that EMILIN-1 is proteolyzed and secreted in small EVs (sEVs) as a novel mechanism to reduce its intracellular levels favoring metastasis in mouse melanoma lymph node metastatic cells. Interestingly, we observed that EMILIN-1 has intrinsic tumor and metastasis suppressive-like properties reducing effective migration, cell viability, primary tumor growth, and metastasis. Overall, our analysis suggests that the inactivation of EMILIN-1 by proteolysis and secretion in sEVs reduce its intrinsic tumor suppressive activities in melanoma favoring tumor progression and metastasis.

In this work, an evaluation and quantification of the impact of using mixtures based on supercritical carbon dioxide “s-CO2” (s-CO2/COS, s-CO2/H2S, s-CO2/NH3, s-CO2/SO2) are made as a working fluid in simple and complex recompression Brayton s-CO2 power cycle configurations that have pressure drops in their components. These cycles are coupled with a solar thermal plant with parabolic-trough collector (PTC) technology. The methodology used in the calculation performance is to establish values of the heat recuperator total conductance (UAtotal) between 5 and 25 MW/K. The main conclusion of this work is that the cycle’s efficiency has improved due to using s-CO2 mixtures as working fluid; this is significant compared to the results obtained using the standard fluid (pure s-CO2). Furthermore, a techno-economic analysis is carried out that compares each configuration’s costs using pure s-CO2 and a mixture of s-CO2/COS with a molar fraction (70/30), respectively, as working fluid where relevant results are obtained. These results show that the best configuration in terms of thermal efficiency and cost is the RCC-RH for pure sCO2 with values of 41.25% and 2811 $/kWe, while for the mixture sCO2/COS, the RCC-2RH configuration with values of 45.05% and 2621 $/kWe is optimal. Using the mixture costs 6.75% less than if it is used the standard fluid (s-CO2).

A new type of Fresnel array has been devised and constructed as an answer to the need to reduce the investment costs of solar thermal collectors, without jeopardizing their efficiency in capturing solar radiation at high temperatures. The array of mirror bands is fixed onto a horizontal platform, which rotates around a virtual vertical axis, so that the sun is in the extrapolated vertical plane of symmetry of the array. The receptor central line is also placed in said plane, and it is physically made of at least one tube at each side of the plane. The geometrical relation between the mirrors and the receptor is therefore fixed. The platform rotates with the same speed as that of the sunlight’s azimuthal component. On the contrary, the angle of incidence of the sunlight on the mirrors changes as the sun rises and declines in its daily apparent motion, but this effect does not disturb the radiation concentration kinematics, although it induces a shift along the receptor. This is a new configuration based on the use of simple and cheap flat mirrors to obtain circular cylindrical mirrors. These mirrors are made of originally flat mirrors that are bent by applying an inexpensive and simple bending technique patented by our research group. The radius of curvature of each mirror is tuned to the distance from the mirror to the receiver central line. The integration of different scientific domains (such as structural analysis) and elementary technologies (such as 3D printing) in this innovative solar radiation concentrator and receiver can lead to a large reduction in costs. Nevertheless, the first experimental campaign has shown additional problems in the receiver configuration, which should be addressed in a next stage of research. This paper explains the methodology used and procedures in the development of the first prototype of the Sundial.

Multi-UAV systems are attracting, especially in the last decade, the attention of researchers and companies of very different fields due to the great interest in developing systems capable of operating in a coordinated manner in complex scenarios and to cover and speed up applications that can be dangerous or tedious for people: search and rescue tasks, inspection of facilities, delivery of goods, surveillance, etc. Inspired by these needs, this work aims to design, implement and analyze a trajectory planning and collision avoidance strategy for multi-UAV systems in 3D environments. For this purpose, a study of the existing techniques for both problems is carried out and an innovative strategy based on Fast Marching Square—for the planning phase—and a simple priority-based speed control—as the method for conflict resolution—is proposed, together with prevention measures designed to try to limit and reduce the greatest number of conflicting situations that may occur between vehicles while they carry out their missions in a simulated 3D urban environment. The performance of the algorithm is evaluated successfully on the basis of certain conveniently chosen statistical measures that are collected throughout the simulation runs.

The human genome contains nearly 100 deubiquitinating enzymes (DUBs) responsible for removing ubiquitin moieties from a large variety of substrates. Which DUBs are responsible for targeting which substrates remain mostly unknown. Here we implement the bioUb approach to identify DUB substrates in a systematic manner, combining gene silencing and proteomics analyses. Silencing of individual DUB enzymes is used to reduce their ubiquitin deconjugating activity, leading to an increase of the ubiquitination of their substrates, which can then be isolated and identified. We report here quantitative proteomic data of the putative substrates of 5 human DUBs. Furthermore, we have built a novel interactive database of DUB substrates to provide easy access to our data and collect DUB proteome data from other groups as a reference resource in the DUB substrates research field.

The thermal management of magnetic components for power electronics is crucial to ensure their reliability. However, conventional thermal models for magnetic components are known to have either poor accuracy or excessive complexity. Contrary to these models, the use of Thermal Resistance Matrices is proposed in this paper instead, which combine both accuracy and simplicity. They are usually used to characterize semiconductor devices, but not for magnetic components. The guidelines to apply Thermal Resistance Matrices for magnetic components are discussed in detail. The accuracy of this model is validated by 3D FEA simulations and experimental results, showing an absolute error lower than 5 ∘C and a relative error between −6.4% and 3.9%, which is outstanding compared to the carried-out literature review.

Un adecuado desarrollo de la competencia científica en los alumnos de secundaria es una necesidad urgente para el futuro avance de cualquier sociedad.Por tanto, siendo el docente un participante activo en su proceso de formación, debe estar a la vanguardia de los requerimientos nacionales e internacionales sobre las habilidades científicas que debe potenciar en sus alumnos. Con este fin, se presenta una extensa base de ítems liberados de las pruebas internacionales PISA para dar a conocer y ejemplificar cada una de las tres competencias científicas que evalúan estas pruebas. Este trabajo hace parte de una investigación doctoral que busca la implementación de estos ítems como instrumento de evaluación diagnóstica en el aula para orientar las prácticas docentes a partir de la retroalimentación que pueda generar los resultados de su aplicación. Como producto inicial del proceso de investigación se hace una revisión bibliográfica, contrastando los ítems originales en inglés y en algunos casos la traducción completa de ellos, obteniendo como resultado una lista de 164 ítems liberados de PISA, categorizados de acuerdo a cada competencia, lo que permitió abordarlas mediante un gran número de ejemplos y reconocer las habilidades principales que caracterizan a cada competencia.

Management as a science is a relatively newcomer in the human repository. Some authors give the date of its birth in 1886 with Henry Robinson Towne’s lecture The engineer as an economist within the context of the Scientific Administration (George & Alvarez, 2005). Management theories developed and evolved since then and had been published in textbooks for the use of students. However, none of these textbooks offers a glimpse of Elliott Jaques’ (19172003) Requisite Organization. This article presents a Requisite Organization’s overview and makes a comparative analysis with other major scientific management theories developed in the past, following Glaser and Strauss (1967) method of continuous comparisons. The conclusion is that Jaques’ research of more than 60 years should be known in the academic world and taught in business schools.

El desarrollo de habilidades científicas requiere de un razonamiento adecuado que debe fundamentarse en un corpus de conocimientos de contenido, procedimentales y epistémicos de la ciencia. Sin embargo, actualmente es habitual que en la práctica docente se sigan enseñando y evaluando en el aula sólo conocimientos de contenido -al margen de los otros dos mencionados- desconectados de todo contexto que permita un verdadero desarrollo de la competencia científica. Para identificar estos conocimientos y favorecer la confluencia con sus habilidades en algunos contextos es necesario que el docente disponga de recursos que faciliten su comprensión. A partir de una extensa revisión bibliográfica, se generó una base de ítems PISA que fueron caracterizados y categorizados a partir de las habilidades específicas que evalúan y los tipos de conocimientos que utilizan. En este trabajo, se presenta el análisis de algunos de los ítems PISA liberados que se corresponden con la subcompetencia Evaluar y diseñar la investigación científica, con el fin de poder ser utilizados por el docente como herramienta de reconocimiento, autoaprendizaje y retroalimentación de los conocimientos y habilidades científicas que lo orienten a una mejor comprensión de la competencia científica y que a su vez se vean reflejados en los procesos de aprendizaje de sus estudiantes.

Summary: Senescence is a cellular phenotype present in health and disease, characterized by a stable cell-cycle arrest and an inflammatory response called senescence-associated secretory phenotype (SASP). The SASP is important in influencing the behavior of neighboring cells and altering the microenvironment; yet, this role has been mainly attributed to soluble factors. Here, we show that both the soluble factors and small extracellular vesicles (sEVs) are capable of transmitting paracrine senescence to nearby cells. Analysis of individual cells internalizing sEVs, using a Cre-reporter system, show a positive correlation between sEV uptake and senescence activation. We find an increase in the number of multivesicular bodies during senescence in vivo. sEV protein characterization by mass spectrometry (MS) followed by a functional siRNA screen identify interferon-induced transmembrane protein 3 (IFITM3) as being partially responsible for transmitting senescence to normal cells. We find that sEVs contribute to paracrine senescence. : Borghesan et al. show that the soluble fraction and small extracellular vesicles (sEVs) mediate paracrine senescence. RNA sequencing and loxP reporter systems confirm sEV-mediated paracrine senescence, while preventing sEV release averts senescence. Mass spectrometry and functional analysis show that the IFN protein, IFITM3, is partially responsible for this phenotype. Keywords: exosomes, small extracellular vesicles, EV, paracrine senescence, OIS, DDIS, aging, interferon, IFITM3, fragilis

La reconstrucción de una opinión pública tuvo, en el caso español, algunas características que la diferenciaron de las democracias surgidas de la derrota del fascismo. La larga duración y la evolución de la dictadura franquista posibilitaron la apertura de ciertos espacios de debate en su fase final, tras la aprobación de la Ley de Prensa e Imprenta en 1966. Sin embargo, esos espacios estuvieron lejos de constituir una opinión pública normalizada, y surgieron, sobre todo, de la resistencia de la sociedad civil. Además, hubo niveles de socialización distintos según los medios de comunicación: la prensa se dirigía a una minoría lectora, más movilizada en su apoyo u oposición a la dictadura, mientras que la televisión y la radio abarcaban a un público mucho más amplio, con un predominio de actitudes desmovilizadas. A diferencia de la construcción del welfare europeo de posguerra, donde el acceso al disfrute del ocio y la cultura se contemplaba como uno de los objetivos del bienestar económico, la modernización franquista trató deliberadamente de evitar la formación de una ciudadanía. Un modelo de dualización cultural que dejó como herencia la naciente democracia

Antimetastatic properties on both murine and human osteosarcoma cell lines (POS-1 and KHOS) have been evidenced using exopolysaccharide (EPS) derivatives, produced by Alteromonas infernus bacterium. These derivatives had no significant effect on the cell cycle neither a pro-apoptotic effect on osteosarcoma cells. Based on this observation, these EPSs could be employed as new drug delivery systems for therapeutic uses. A theranostic approach, i.e., combination of a predictive biomarker with a therapeutic agent, has been developed notably by combining with true pair of theranostic radionuclides, such as scandium 47Sc/44Sc. However, it is crucial to ensure that, once complexation is done, the biological properties of the vector remain intact, allowing the molecular tropism of the ligand to recognize its molecular target. It is important to assess if the biological properties of EPS evidenced on osteosarcoma cell lines remain when scandium is complexed to the polymers and can be extended to other cancer cell types. Scandium-EPS complexes were thus tested in vitro on human cell lines: MNNG/HOS osteosarcoma, A375 melanoma, A549 lung adenocarcinoma, U251 glioma, MDA231 breast cancer, and Caco2 colon cancer cells. An xCELLigence Real Cell Time Analysis (RTCA) technology assay was used to monitor for 160 h, the proliferation kinetics of the different cell lines. The tested complexes exhibited an anti-proliferative effect, this effect was more effective compared to EPS alone. This increase of the antiproliferative properties was explained by a change in conformation of EPS complexes due to their polyelectrolyte nature that was induced by complexation. Alterations of both growth factor-receptor signaling, and transmembrane protein interactions could be the principal cause of the antiproliferative effect. These results are very promising and reveal that EPS can be coupled to scandium for improving its biological effects and also suggesting that no major structural modification occurs on the ligand.

The single-phase matrix converter is an AC-AC power topology which consists of six bidirectional switches and it is considered the key unit in cascade or multilevel configurations. In this paper, a comparison between two control techniques is presented, one based on a proportional-integral-derivative control module with a pulse width modulator, and the other known as finite-state model predictive control. Simulation and experimental results are presented and discussed to demonstrate the feasibility and performance of both techniques.

Superconducting links are an innovative solution for bulk power transmission, distinguished by their compact dimensions, high efficiency and small environmental footprint. As with any new technology field, there is a large amount of design possibilities for such links, each of them having a profound impact on the system configuration. For instance, changing the material can imply a change in the working temperature from 20 to 70 K and has consequences on the maximum link length. This article presents the dichotomic decision possibilities for the optimized design of a high-power superconducting link, focusing on some of the key components of the cable system. The complex design optimization process is exemplified using the European project Best Paths, in which the first 3-gigawatt-class superconducting cable system was designed, optimized, manufactured, and successfully tested.

Specimens of the genus Promops (Chiroptera, Molossidae) are rare in Colombian scientific collections. Only one species, P. centralis, has been documented from the country. We report the first record of P.nasutus for Colombia, collected on the Eastern Cordillera of the Andes. External and cranial measurements, as well as morphological features in our specimen match those of P. nasutus. Our record of P. nasutus also represents a geographic extension in the distribution of the species of more than 755 km west from the closest known location in the Venezuelan Amazon.

Epithelial malignancies are effectively treated by antiangiogenics; however, acquired resistance is a major problem in cancer therapeutics. Epithelial tumors commonly have mutations in the MAPK/Pi3K-AKT pathways, which leads to high-rate aerobic glycolysis. Here, we show how multikinase inhibitor antiangiogenics (TKIs) induce hypoxia correction in spontaneous breast and lung tumor models. When this happens, the tumors downregulate glycolysis and switch to long-term reliance on mitochondrial respiration. A transcriptomic, metabolomic, and phosphoproteomic study revealed that this metabolic switch is mediated by downregulation of HIF1α and AKT and upregulation of AMPK, allowing uptake and degradation of fatty acids and ketone bodies. The switch renders mitochondrial respiration necessary for tumor survival. Agents like phenformin or ME344 induce synergistic tumor control when combined with TKIs, leading to metabolic synthetic lethality. Our study uncovers mechanistic insights in the process of tumor resistance to TKIs and may have clinical applicability.

In atherosclerosis, circulating angiogenic cells (CAC), also known as early endothelial progenitor cells (eEPC), are thought to participate mainly in a paracrine fashion by promoting the recruitment of other cell populations such as late EPC, or endothelial colony-forming cells (ECFC), to the injured areas. There, ECFC replace the damaged endothelium, promoting neovascularization. However, despite their regenerative role, the number and function of EPC are severely affected under pathological conditions, being essential to further understand how these cells react to such environments in order to implement their use in regenerative cell therapies. Herein, we evaluated the effect of direct incubation ex vivo of healthy CAC with the secretome of atherosclerotic arteries. By using a quantitative proteomics approach, 194 altered proteins were identified in the secretome of pre-conditioned CAC, many of them related to inhibition of angiogenesis (e.g., endostatin, thrombospondin-1, fibulins) and cell migration. Functional assays corroborated that healthy CAC released factors enhanced ECFC angiogenesis, but, after atherosclerotic pre-conditioning, the secretome of pre-stimulated CAC negatively affected ECFC migration, as well as their ability to form tubules on a basement membrane matrix assay. Overall, we have shown here, for the first time, the effect of atherosclerotic factors over the paracrine role of CAC ex vivo. The increased release of angiogenic inhibitors by CAC in response to atherosclerotic factors induced an angiogenic switch, by blocking ECFC ability to form tubules in response to pre-conditioned CAC. Thus, we confirmed here that the angiogenic role of CAC is highly affected by the atherosclerotic environment.

Despite significant efforts to improve pancreatic ductal adenocarcinoma (PDAC) clinical outcomes, overall survival remains dismal. The poor response to current therapies is partly due to the existence of pancreatic cancer stem cells (PaCSCs), which are efficient drivers of PDAC tumorigenesis, metastasis and relapse. To find new therapeutic agents that could efficiently kill PaCSCs, we screened a chemical library of 680 compounds for candidate small molecules with anti-CSC activity, and identified two compounds of a specific chemical series with potent activity in vitro and in vivo against patient-derived xenograft (PDX) cultures. The anti-CSC mechanism of action of this specific chemical series was found to rely on induction of lysosomal membrane permeabilization (LMP), which is likely associated with the increased lysosomal mass observed in PaCSCs. Using the well characterized LMP-inducer siramesine as a tool molecule, we show elimination of the PaCSC population in mice implanted with tumors from two PDX models. Collectively, our approach identified lysosomal disruption as a promising anti-CSC therapeutic strategy for PDAC.

Microgrids need control and management at different levels to allow the inclusion of renewable energy sources. In this paper, a comprehensive literature review is presented to analyse the latest trends in research and development referring to the applications of predictive control in microgrids. As a result of this review, it was found that the application of predictive control techniques on microgrids is performed for the three control levels and with adaptations of the models in order to include uncertainties to improve their performance and dynamics response. In addition, to ensure system stability, but also, at higher control levels, coordinated operation among the microgrid’s components and synchronised and optimised operation with utility grids and electric power markets. Predictive control appears as a very promising control scheme with several advantages for microgrid applications of different control levels.

Introducción: el cáncer de piel es considerado por expertos como una epidemia, constituye una es una de las patologías crónicas más frecuentes en el mundo, con reconocida influencia de factores ambientales, genéticos, infecciosos y sociales. Objetivo: evaluar la utilidad de fotoeducación para familiares cuidadores de niños y adolescentes con riesgo de cáncer cutáneo. Métodos: la Comisión Nacional de Xeroderma Pigmentoso desarrolló una estrategia de intervención educativa durante cinco años, destinada familiares cuidadores de niños y adolescentes cubanos con alto riesgo de cáncer cutáneo. Se realizó una evaluación de los hábitos y conocimientos de la población intervenida, mediante la realización de encuestas, comparándola con un grupo control. Resultados: el grupo cuidadores participantes en la escuela de verano y el grupo control presentaron características homogéneas, pero los participantes en la intervención educativa presentaron mejores conocimientos y hábitos relacionados con la fotoprotección. La mayoría de los cuidadores opinan que la escuela de verano siempre ha influido en su conducta personal y que los conocimientos adquiridos son de utilidad para desempeñar el cuidado de sus familiares con alto riesgo de cáncer de piel. Conclusión: el estudio realizado permitió llegar a la conclusión de que la fotoeducación es un instrumento válido para la incorporación de conocimientos y hábitos positivos en los cuidadores, y facilita el manejo de los enfermos a su cuidado.

The scarcity of primordial germ cells (PGCs) in the developing mammalian embryo hampers robust biochemical analysis of the processes that underlie early germ cell formation. Here, we demonstrate that DAZL, a germ cell-specific RNA binding protein, is a robust PGC marker during in vitro germ cell development. Using Dazl-GFP reporter ESCs, we demonstrate that DAZL plays a central role in a large mRNA/protein interactive network that blocks the translation of core pluripotency factors, including Sox2 and Sall4, as well as of Suz12, a polycomb family member required for differentiation of pluripotent cells. Thus, DAZL limits both pluripotency and somatic differentiation in nascent PGCs. In addition, we observed that DAZL associates with mRNAs of key Caspases and similarly inhibits their translation. This elegant fail-safe mechanism ensures that, whereas loss of DAZL results in prolonged expression of pluripotency factors, teratoma formation is avoided due to the concomitant activation of the apoptotic cascade.

The Anaphase-promoting complex/cyclosome (APC/C) cofactor Cdh1 modulates cell proliferation by targeting multiple cell-cycle regulators for ubiquitin-dependent degradation. Lack of Cdh1 results in structural and numerical chromosome aberrations, a hallmark of genomic instability. By using a proteomic approach in Cdh1-null cells and mouse tissues, we have identified kinesin Eg5 and topoisomerase 2α as Cdh1 targets involved in the maintenance of genomic stability. These proteins are ubiquitinated and degraded through specific KEN and D boxes in a Cdh1-dependent manner. Whereas Cdh1-null cells display partial resistance to Eg5 inhibitors such as monastrol, lack of Cdh1 results in a dramatic sensitivity to Top2α poisons as a consequence of increased levels of trapped Top2α-DNA complexes. Chemical inhibition of the APC/C in cancer cells results in increased sensitivity to Top2α poisons. This work identifies in vivo targets of the mammalian APC/C-Cdh1 complex and reveals synthetic lethal interactions of relevance in anticancer treatments.

DNA replication is facilitated by multiple factors that concentrate in the vicinity of replication forks. Here, we developed an approach that combines the isolation of proteins on nascent DNA chains with mass spectrometry (iPOND-MS), allowing a comprehensive proteomic characterization of the human replisome and replisome-associated factors. In addition to known replisome components, we provide a broad list of proteins that reside in the vicinity of the replisome, some of which were not previously associated with replication. For instance, our data support a link between DNA replication and the Williams-Beuren syndrome and identify ZNF24 as a replication factor. In addition, we reveal that SUMOylation is widespread for factors that concentrate near replisomes, which contrasts with lower UQylation levels at these sites. This resource provides a panoramic view of the proteins that concentrate in the surroundings of the replisome, which should facilitate future investigations on DNA replication and genome maintenance.

A mechanical spectroscopy study of Cu-Zr-Al bulk metallic glasses, was performed with two types of equipment: a Kê-type inverted torsion pendulum and an acoustic elastometer, working in the frequency ranges of Hz and kHz, respectively, with a heating rate of 1 K/min. The analysis of the anelastic relaxation shows similar spectra for both types of equipment resulting in internal friction patterns that vary with temperature and are not reproducible at each thermal cycle. The normalized of the square of the frequency changes from the first to later measurement cycles. These results indicate that the specimens of Cu-Zr-Al alloys were changing by mechanical relaxation, owing to the motion of atoms or clusters in the glassy state and possible "defects" produced during the processing of alloys.

During cell division, the mitotic spindle segregates replicated chromosomes to opposite poles of the cell, while the position of the spindle determines the plane of cleavage. Spindle positioning and chromosome segregation depend on pulling forces on microtubules extending from the centrosomes to the cell cortex. Critical in pulling force generation is the cortical anchoring of cytoplasmic dynein by a conserved ternary complex of Gα, GPR-1/2, and LIN-5 proteins in C. elegans (Gα-LGN-NuMA in mammals). Previously, we showed that the polarity kinase PKC-3 phosphorylates LIN-5 to control spindle positioning in early C. elegans embryos. Here, we investigate whether additional LIN-5 phosphorylations regulate cortical pulling forces, making use of targeted alteration of in vivo phosphorylated residues by CRISPR/Cas9-mediated genetic engineering. Four distinct in vivo phosphorylated LIN-5 residues were found to have critical functions in spindle positioning. Two of these residues form part of a 30 amino acid binding site for GPR-1, which we identified by reverse two-hybrid screening. We provide evidence for a dual-kinase mechanism, involving GSK3 phosphorylation of S659 followed by phosphorylation of S662 by casein kinase 1. These LIN-5 phosphorylations promote LIN-5-GPR-1/2 interaction and contribute to cortical pulling forces. The other two critical residues, T168 and T181, form part of a cyclin-dependent kinase consensus site and are phosphorylated by CDK1-cyclin B in vitro. We applied a novel strategy to characterize early embryonic defects in lethal T168,T181 knockin substitution mutants, and provide evidence for sequential LIN-5 N-terminal phosphorylation and dephosphorylation in dynein recruitment. Our data support that phosphorylation of multiple LIN-5 domains by different kinases contributes to a mechanism for spatiotemporal control of spindle positioning and chromosome segregation.

Las reflexiones sobre los límites de la democracia, su crisis y los medios para adaptarla a los nuevos tiempos ocuparon buena parte de los debates teóricos de los intelectuales franquistas, pero también de los antifranquistas. Al término de democracia se añadieron tantos calificativos como proyectos sociales se asociaron, de manera instrumental, al prestigio de su legitimidad como un principio insoslayable del ejercicio del poder en las sociedades contemporáneas. Como esos debates dieron por sentada la crisis de la democracia liberal, se buscaron las soluciones fuera de ella. La derecha mediante formas plebiscitarias, carismáticas, organicistas, semiautoritarias, presidencialistas o tecnocráticas. La izquierda recurriendo a formas socializantes o decididamente socialistas, aunque la derrota, la resistencia y el exilio hicieron que su aprendizaje democrático fuera mucho más rápido, pese al breve renacer de las utopías revolucionarias en la «nueva izquierda» de los años sesenta.

En la dictadura de Franco (1939-1975), la idea del «intelectual» fue mucho más allá de un individuo o colectivo social para convertirse en un imaginario cultural de profundo contenido político, por lo que permaneció en el centro de los conflictos dentro de la coalición en el poder. La figura de Antonio Machado centró como ninguna otra esos conflictos simbólicos y de legitimidad, tanto entre proyectos políticos dentro del régimen como entre este y la oposición antifranquista en el exilio, y, cada vez más, en el interior. De ahí el interés del régimen por la repatriación de los restos del poeta, enterrado en Francia, frustrada por la oposición familiar pero también por la propia ambigüedad de esos intentos de apropiación por parte del franquismo. En el presente texto, dichos intentos de traslado de los restos de Antonio Machado se analizan a través de documentación hasta ahora inédita.

En el conjunto de factores que se consideran para diseñar, proyectar y tomar decisiones dentro de la construcción, se propone la inclusión de los indicadores “huella ecológica” y “huella de carbono” en las bases de costes de construcción (BCC), ya que constituyen herramientas simples y fáciles de utilizar que permiten integrar el aspecto ambiental en los presupuestos de los proyectos. Con el fin de demostrar dicha posibilidad, se toma como caso particular la BCC de Andalucía, para el cual se calcula un presupuesto ambiental. El modelo propuesto se valida con el análisis de un proyecto de urbanización industrial en Écija (España), proporcionando resultados comparables con otras metodologías de huella en edificación.

Objetivo. Evaluar degradabilidad in situ en rumen de cuatro especies forrajeras: Acacia Roja (Delonix regia), pízamo (Eritryna glauca), Cratilia (Cratylia argentea) y casco de vaca (Bahuinia variegata), para determinar su calidad nutricional. Materiales y métodos. Cuatro hembras rumino-fistuladas en un diseño de sobrecambio simple, pastoreando en Brachiaria decumbens, suplementadas en la mañana con tres kg de hojas deshidratadas de las cuatro especies mencionadas, de un año de establecidas y podadas cada 3 meses. En las pruebas in situ se utilizaron bolsas de nylon, adicionando 5 g de MS de cada arbórea/bolsa, incluyendo braquiaria, en diferentes horas (6, 12, 24, 48 y 72). Se evaluó la degradabilidad de la materia seca (DMS), fibra detergente neutro (DFDN) fibra detergente ácido (DFDA), nitrógeno total (DNT) y nitrógeno adherido a FDN (DNFDN). En el líquido ruminal se midió nitrógeno amoniacal a las 0, 4, 8 y 12 y pH a las 0, 3, 6, 9 y 12 horas. Resultados. La DMS fue mayor (p>0.05) para casco de vaca (53.3%) y acacia roja (56.1%) con relación a pízamo y cratilia. La DMS de braquiaria fue mayor (p>0.05) en 18.6% suplementando con casco de vaca con relación a las otras arbóreas. La DFDN potencial fue menor (p>0.05) para pízamo (7.6%) en comparación con cratilia. La DFDN de braquiaria fue similar en todas las forrajeras. Conclusiones. Algunos componentes de las arbóreas tienen efecto asociativo en la cinética de la tasa de degradación de MS y FDA del pasto, siendo superiores (p>0.05) cuando se suplementó con casco de vaca.

Este artículo explora -en el contexto del enfrentamiento entre liberales e Iglesia Católica, por la secularización del estado en el siglo XIX- un elemento clave de todo conflicto: la subjetividad. Se rescatará a través del diario "El Estandarte Católico" la imagen que la Iglesia Católica se construye acerca del liberalismo y se explicarán sus principios. El artículo se divide en dos partes: primero, un marco general sobre los fundamentos del tema, el estado de la cuestión y las relaciones del periódico con el gobierno de Pinto. Finalmente, se buscará sintetizar el simbolismo conferido al liberalismo interpretando sus alcances.This article explores the notion of subjectivity the context of the securalization of the state in the nineteenth century and the clash between liberals and Catholic Church. Through the analysis of the newspaper "El Estandarte Católico",we will study the image that the Catholic Church generates about liberalism, and its principles. The article is divided two section. In the first one articulares, a general framework on the foundations of the subject, the state of the art and the connections between "El Estandarte Católico" and Pinto’s government. Finally, we eventually seek to summarize and explain the symbolism conferred to liberalism.

En el presente trabajo se enuncia la idea fundamental en la que se basan todos los métodos empleados para la estimación de los parámetros de fase de los motores de reluctancia conmutada. Se describe, además, un algoritmo de división con punto decimal fijo en lenguaje VHDL. El algoritmo descrito se utiliza posteriormente para la estimación de la inductancia de fase del motor de reluctancia conmutada MFR 132.1, mediante el empleo de la técnica invasiva de modulación de amplitud con señales de tensión pulsantes de tres estados. Se diseñó y construyó una instalación experimental sobre la base de un FPGA de Actel, de la familia ProASIC 3 modelo A3P250, para el procesamiento de las señales. Finalmente se exponen y comentan las características de inductancia de fase del motor de reluctancia MFR 132.1, obtenidas.In the present work is enunciated the fundamental idea of all the methods used for the estimation of phase parameters in the switched reluctance motors. The fixed point division algorithm employed to estimate the inactive phase inductance profile of the MFR 132.1 switched reluctance motor, is described in VHDL programming language. The algorithm implements the intrusive estimation technique of amplitude modulation with three states pulsating signals. The structure of the experimental set up for the digital signal processing, which is based on the Actel FPGA ProAsic 3 A3P250 development kit, is depicted. Finally, the inactive phase’s inductance profiles, which were experimentally obtained, are shown for different voltage values in the Direct Current converter link.

Los grafiti —como manifestación expresiva— subrayan la coexistencia de diversos parámetros sociolingüisticos que aportan datos intrínsecos sobre el emisor, el mundo que le rodea y su intención comunicativa. En el presente estudio analizamos los grafiti sobre mesas universitarias o in tabula; un tipo de grafiti que no ha sido objeto de un profundo estudio y que sin embargo posee características sociolingüisticas que lo distinguen del resto de manifestaciones similares. A lo largo del análisis veremos cómo se construye sobre una mesa un entorno icónico y verbal que determina y condiciona lingüisticamente la autoría, la temática y la intencionalidad del mensaje. Dichas características acentúan además la presencia de una serie de parámetros socioculturales compartidos por emisor y receptor que definen y delimitan su campo de actuación. Sobre la mesa —o canal transmisor— se recuperan asimismo las inquietudes socio-históricas de la época en la que se fija el mensaje y se confirma la relevancia comunicativa e interpretativa de los grafiti in tabula.

This paper compares the annual performance of Integrated Solar Combined Cycles (ISCCs) using different solar concentration technologies: parabolic trough collectors (PTC), linear Fresnel reflectors (LFR) and central tower receiver (CT). Each solar technology (i.e. PTC, LFR and CT) is proposed to integrate solar energy into the combined cycle in two different ways. The first one is based on the use of solar energy to evaporate water of the steam cycle by means of direct steam generation (DSG), increasing the steam production of the high pressure level of the steam generator. The other one is based on the use of solar energy to preheat the pressurized air at the exit of the gas turbine compressor before it is introduced in the combustion chamber, reducing the fuel consumption. Results show that ISCC with DSG increases the yearly production while solar air heating reduces it due to the incremental pressure drop. However, air heating allows significantly higher solar-to-electricity efficiencies and lower heat rates. Regarding the solar technologies, PTC provides the best thermal results.

Tras su muerte en 1939, Antonio Machado fue elevado a la categoría de mito literario, moral y político, disputado por los dos grandes proyectos ideológicos de la posguerra: el falangista y el comunista. La calidad de su obra y sus temas, dentro de la reflexión sobre España de la «generación del 98», llevaron a los intelectuales falangistas a tratar de «recuperarlo» para su proyecto de integración nacional en los años 40 y 50, depurándolo de circunstancias históricas concretas. En el exilio, en cambio, se reivindicó su magisterio ético, más que estético, el del poeta que había sabido ponerse al lado del pueblo en las circunstancias trágicas de la guerra. Los homenajes de 1959 sirvieron de encuentro al exilio y la oposición interior, un acontecimiento generacional impulsado por el Partido Comunista de España (PCE) que fructificó en ulteriores iniciativas político-culturales. En los años 60 el mito, contestado en su dimensión estrictamente literaria, funcionó en la cultura progresista como ejemplo del «intelectual comprometido», pero se asoció cada vez más a la idea de reconciliación entre las «dos Españas». Esta idea pasó a la transición a la democracia y su «espíritu de consenso», si bien el mito sigue enfrentando hoy a quienes reivindican su memoria prorrepublicana y quienes sólo ven en él el símbolo de «dos Españas» que ya no son.

Monocytes are bone marrow-derived leukocytes that are part of the innate immune system. Monocytes are divided into three subsets: classical, intermediate and non-classical, which can be differentiated by their expression of some surface antigens, mainly CD14 and CD16. These cells are key players in the inflammation process underlying the mechanism of many diseases. Thus, the molecular characterization of these cells may provide very useful information for understanding their biology in health and disease. We performed a multicentric proteomic study with pure classical and non-classical populations derived from 12 healthy donors. The robust workflow used provided reproducible results among the five participating laboratories. Over 5000 proteins were identified, and about half of them were quantified using a spectral counting approach. The results represent the protein abundance catalogue of pure classical and enriched non-classical blood peripheral monocytes, and could serve as a reference dataset of the healthy population. The functional analysis of the differences between cell subsets supports the consensus roles assigned to human monocytes.

La determinación de la posición angular instantánea del rotor es parte integral del control en los accionamientos de Motores de Reluctancia Conmutada. La medición directa de esta variable adiciona complejidad y costo al sistema y no siempre brinda buenos resultados, lo que ha motivado el desarrollo y prueba de algoritmos de estimación de la posición angular del rotor. En este trabajo se presenta el empleo de un Filtro Desaromatizado de Kalman para estimar la velocidad y la posición angular del rotor del motor MFR 132.5, basado en un modelo de caja gris de dicho motor que también es presentado en este trabajo. Los resultados demuestran que este estimador ofrece estimaciones satisfactorias del estado del motor, lo mismo durante el arranque que durante el funcionamiento regular, aún bajo la presencia de perturbaciones en el torque de la carga y errores en la estimación inicial de la posición angular del rotor. The measure of the instant angular position of the rotor is integral part of the control of Switching Reluctance Motors drivers. The direct measurement of this variable adds complexity and cost to the system and it doesn’t give good results sometimes. That has motivated the development and test of algorithms for estimating the rotor angular position of the motor. In this work is presented the use of an Unscented Kalman Filter for estimating the speed and rotor angular position of the motor MFR 132.5, based on a grey box model of the motor which is also presented in this work. The results show that this kind of estimator gives good estimations of the state of the motor, as well during the starting as during the regular operation, even under the presence of perturbations of the load torque and errors in the initial estimation of the angular position.

The biography of Joaquín Ruiz-Giménez is a virtual paradigm of two historical phenomena which distinguished the last two decades of the Franco regime and, to a large extent, paved the way for the future democracy: on the one hand, the rift between Catholic and Falangist intellectuals and the regime which they had enthusiastically helped to establish after the civil war; and on the other, the secularization of its political thinking and practice. Ruíz-Giménez, ambassador and minister under Franco, was an exception among the Catholic laity that collaborated with the dictatorship, in that he held high government positions and, despite all the reservations concerning his personal development, for many of his peers as well as many aspiring figures of the coming generations, he symbolized the definitive renunciation of all legitimacy of power based on victory in battle or on Catholic natural law, and the definitive adoption of the language of human rights and democracy. | La biografía de Joaquín Ruiz-Giménez representa casi de manera paradigmática dos fenómenos históricos que caracterizaron las dos últimas décadas del franquismo y sentaron, en buena medida las bases de la futura democracia: por un lado, el alejamiento de los intelectuales católicos y falangistas respecto al régimen que habían contribuido a levantar con entusiasmo tras la guerra civil; por otro, la secularización de su pensamiento y práctica política. Ruiz-Giménez, embajador y ministro de Franco, fue una excepción entre los seglares católicos que colaboraron con la dictadura desempeñando altas responsabilidades de gobierno y, pese a todas las cautelas de su evolución personal, simbolizó para bastantes compañeros de su generación, así como para muchos jóvenes alumnos de las nuevas generaciones, la renuncia definitiva a toda legitimación del poder basada en la victoria de las armas o en el iusnaturalismo católico y la adopción irreversible del lenguaje de los derechos humanos y la democracia.

A variety of genetic alterations are considered hallmarks of cancer development and progression. The Ikaros gene family, encoding for key transcription factors in hematopoietic development, provides several examples as genetic defects in these genes are associated with the development of different types of leukemia. However, the complex patterns of expression of isoforms in Ikaros family genes has prevented their use as clinical markers. In this study, we propose the use of the expression profiles of the Ikaros isoforms to classify various hematological tumor diseases. We have standardized a quantitative PCR protocol to estimate the expression levels of the Ikaros gene exons. Our analysis reveals that these levels are associated with specific types of leukemia and we have found differences in the levels of expression relative to five interexonic Ikaros regions for all diseases studied. In conclusion, our method has allowed us to precisely discriminate between B-ALL, CLL and MM cases. Differences between the groups of lymphoid and myeloid pathologies were also identified in the same way.

Ena glavnih zahtev gotskega žanra je izguba občutka za stvarnost. To značilnost, ki v veliko primerih vodi v strah ali celo grozo, je mogoče doseči predvsem z zatekanjem k čutom. V romanu Aura Carlosa Fuentesa opisovanje preseže meje percepcije čutov, saj bralec ni zgolj voden, ampak se, kot bi bil zapeljan, pusti voditi, očaran s čutno razvejanostjo, ki veje iz zapleta. V študiji bomo pokazali, kako kromatičnost in čutna zaznavnost potencirata splošen smisel romana, hkrati pa razkrivata številne slogovne značilnosti, ki potrjujejo hermenevtično relevantnost opisanega. Izhajajoč iz podrobne študije uporabe jezika, bomo analizirali tvorjenje pripovedi s tehniko kromatične progresije, ki uspešno združuje percepcijo čutov in psihologijo glavnega junaka ter strne celo vrsto bralcu razpoložljivih gotskih občutkov.

In an active, self-ubiquitinated state, the Ring1B ligase monoubiquitinates histone H2A playing a critical role in Polycomb-mediated gene silencing. Following ubiquitination by external ligases, Ring1B is targeted for proteosomal degradation. Using biochemical data and computational modeling, we show that the Ring1B ligase can exhibit abrupt switches, overshoot transitions and self-perpetuating oscillations between its distinct ubiquitination and activity states. These different Ring1B states display canonical or multiply branched, atypical polyubiquitin chains and involve association with the Polycomb-group protein Bmi1. Bistable switches and oscillations may lead to all-or-none histone H2A monoubiquitination rates and result in discrete periods of gene (in)activity. Switches, overshoots and oscillations in Ring1B catalytic activity and proteosomal degradation are controlled by the abundances of Bmi1 and Ring1B, and the activities and abundances of external ligases and deubiquitinases, such as E6-AP and USP7.

En el presente trabajo se enuncia la idea fundamental en la que se basan todos los métodos empleados para la estimación de los parámetros de fase de los motores de reluctancia conmutada. Se describe, además, un algoritmo de división con punto decimal fijo en lenguaje VHDL. El algoritmo descrito se utiliza posteriormente para la estimación de la inductancia de fase del motor de reluctancia conmutada MFR 132.1, mediante el empleo de la técnica invasiva de modulación de amplitud con señales de tensión pulsantes de tres estados. Se diseñó y construyó una instalación experimental sobre la base de un FPGA de Actel, de la familia ProASIC 3 modelo A3P250, para el procesamiento de las señales. Finalmente se exponen y comentan las características de inductancia de fase del motor de reluctancia MFR 132.1, obtenidas. In the present work is enunciated the fundamental idea of all the methods used for the estimation of phase parameters in the switched reluctance motors. The fixed point division algorithm employed to estimate the inactive phase inductance profile of the MFR 132.1 switched reluctance motor, is described in VHDL programming language. The algorithm implements the intrusive estimation technique of amplitude modulation with three states pulsating signals. The structure of the experimental set up for the digital signal processing, which is based on the Actel FPGA ProAsic 3 A3P250 development kit, is depicted. Finally, the inactive phase’s inductance profiles, which were experimentally obtained, are shown for different voltage values in the Direct Current converter link.